sync

12136306.json

@@ -0,0 +1,8 @@
+{
+ "id": "12136306",
+ "label": 0,
+ "article": {
+  "id": "12136306",
+  "text": "We report an infant with geleophysic dysplasia (MIM 231050) who developed multiple trigger fingers. The condition was progressive and distinct from trigger thumb, which is generally seen in infants without any underlying metabolic disease."
+ }
+}

16105694.json

@@ -0,0 +1,8 @@
+{
+ "id": "16105694",
+ "label": 0,
+ "article": {
+  "id": "16105694",
+  "text": "Clinical evaluation of children with skeletal dysplasias is often concentrated on morphologic and radiographic assessments, but many of these patients also have disease processes of the ear, nose, and throat. We report a case of an 11-month-old girl with an unknown short-limbed dwarfism, similar to acromicric dysplasia, with grade II subglottic stenosis. Laryngotracheoplasty with anterior autologous costal cartilage graft and posterior cricoid split was performed at age 13 months, with subsequent improvement of her airway status. In cases of children with skeletal dysplasias and obstructive airway symptoms, formal otolaryngologic evaluation is warranted for definitive diagnosis and treatment."
+ }
+}

23027497.json

@@ -0,0 +1,8 @@
+{
+ "id": "23027497",
+ "label": 0,
+ "article": {
+  "id": "23027497",
+  "text": "Acromicric dysplasia is a skeletal dysplasia that is characterized by short stature, short hands and feet, typical facial dysmorphism, normal mental development, and characteristic hand radiology. Carpal tunnel syndrome may be seen in adults with acromicric dysplasia; however, to the authors' knowledge, it has not been reported in pediatric patients. This article describes a 9-year old boy with bilateral carpal tunnel syndrome and acromicric dysplasia treated operatively. No recurrences occurred during 1 year of postoperative follow-up.Carpal tunnel syndrome is a rare disease in childhood. The etiologic factors of carpal tunnel syndrome include trauma (especially distal radius epiphysealis), overuse, genetic or metabolic disorders, space-occupying lesions in the carpal tunnel, hemophilia, congenital anomalies, adverse effect of growth hormone replacement therapy, and idiopathic carpal tunnel syndrome. Acromicric dysplasia should be considered in the etiology of childhood carpal tunnel syndrome.The surgical outcome of carpal tunnel syndrome is good with early diagnosis and treatment. However, in the case of skeletal dysplasia, the diagnosis of carpal tunnel syndrome may be delayed due to anomalies of the hand and due to the child's difficulty in expressing symptoms. Because of the delay in diagnosis of carpal tunnel syndrome in patients with skeletal dysplasia, the treatment outcomes may not be promising. Electrophysiologic studies should be performed early when the clinical signs are positive."
+ }
+}

23514648.json

@@ -0,0 +1,8 @@
+{
+ "id": "23514648",
+ "label": 0,
+ "article": {
+  "id": "23514648",
+  "text": "In this case report, we present occurrence of bilateral angle closure glaucoma in a 9-year-old girl with geleophysic dysplasia. Bilateral YAG laser iridotomy was applied, but intraocular pressure (IOP) remained at high levels, necessitating bilateral trabeculectomy with mitomycin C. On her follow-up examinations for 3 years, IOP remained in the mid-20s with no need for further intervention or antiglaucoma medication. There are few reports describing the ocular findings of geleophysic dysplasia in literature. To our knowledge, this is the first case report describing an application of glaucoma surgery and its results at geleophysic dysplasia."
+ }
+}

24339047.json

@@ -0,0 +1,8 @@
+{
+ "id": "24339047",
+ "label": 0,
+ "article": {
+  "id": "24339047",
+  "text": "UNLABELLED:\nAcromicric dysplasia (AD) is an autosomal dominant disorder characterized by short stature, short extremities, stiff joint and skeleton features including brachymetacarpia, cone-shaped epiphyses, internal notch of the femoral head, and delayed bone age. Recently, we identified fibrillin 1 (FBN1) as the disease gene of AD. The aim of our study was to further describe the long-term follow up of AD patients with an emphasis on orthopedic management. Nine patients with FBN1 mutations were included in the study ranging in age from 5.5 to 64 years. For all, detailed clinical and radiological data were available.\n\nRESULTS:\nBirth parameters were always normal and patients progressively developed short stature \u003c-3 SD. Carpal tunnel syndrome was observed in four patients. We found discrepancy between the carpal bone age and the radius and ulna epiphysis bone ages, a variable severity of hip dysplasia with acetabular dysplasia, epiphyseal and metaphyseal femoral dysplasia resembling Legg-Perthes-Calvé disease and variable pelvic anteversion and hyperlordosis. Orthopedic surgery was required in two patients for hip dysplasia, in one for limb lengthening and in three for carpal tunnel syndrome. Our observations expand the AD phenotype and emphasize the importance of regular orthopedic survey."
+ }
+}

25762570.json

@@ -0,0 +1,8 @@
+{
+ "id": "25762570",
+ "label": 0,
+ "article": {
+  "id": "25762570",
+  "text": "Mutations in the secreted glycoprotein ADAMTSL2 cause recessive geleophysic dysplasia (GD) in humans and Musladin-Lueke syndrome (MLS) in dogs. GD is a severe, often lethal, condition presenting with short stature, brachydactyly, stiff skin, joint contractures, tracheal-bronchial stenosis and cardiac valve anomalies, whereas MLS is non-lethal and characterized by short stature and severe skin fibrosis. Although most mutations in fibrillin-1 (FBN1) cause Marfan syndrome (MFS), a microfibril disorder leading to transforming growth factor-β (TGFβ) dysregulation, domain-specific FBN1 mutations result in dominant GD. ADAMTSL2 has been previously shown to bind FBN1 and latent TGFβ-binding protein-1 (LTBP1). Here, we investigated mice with targeted Adamtsl2 inactivation as a new model for GD (Adamtsl2(-/-) mice). An intragenic lacZ reporter in these mice showed that ADAMTSL2 was produced exclusively by bronchial smooth muscle cells during embryonic lung development. Adamtsl2(-/-) mice, which died at birth, had severe bronchial epithelial dysplasia with abnormal glycogen-rich inclusions in bronchial epithelium resembling the cellular anomalies described previously in GD. An increase in microfibrils in the bronchial wall was associated with increased FBN2 and microfibril-associated glycoprotein-1 (MAGP1) staining, whereas LTBP1 staining was increased in bronchial epithelium. ADAMTSL2 was shown to bind directly to FBN2 with an affinity comparable to FBN1. The observed extracellular matrix (ECM) alterations were associated with increased bronchial epithelial TGFβ signaling at 17.5 days of gestation; however, treatment with TGFβ-neutralizing antibody did not correct the epithelial dysplasia. These investigations reveal a new function of ADAMTSL2 in modulating microfibril formation, and a previously unsuspected association with FBN2. Our studies suggest that the bronchial epithelial dysplasia accompanying microfibril dysregulation in Adamtsl2(-/-) mice cannot be reversed by TGFβ neutralization, and thus might be mediated by other mechanisms."
+ }
+}

27078247.json

@@ -0,0 +1,8 @@
+{
+ "id": "27078247",
+ "label": 0,
+ "article": {
+  "id": "27078247",
+  "text": "HISTORY AND CLINICAL PRESENTATION:\nA 53-year old woman with recurrent polyarthralgias, negative test results in a recent rheumatologic work-up and an unmeasurably low uric acid serum concentration presented for suspected IgM paraproteinemia.\n\nINVESTIGATIONS:\nPhysical examination, abdominal ultrasound and routine laboratory test results were unremarkable. Repeat determination confirmed a markedly decreased uric acid (UA) serum concentration. Urinary xanthine and hypoxanthine concentrations were increased by 14-fold and 7.5-fold, respectively. Fractional urinary UA excretion was not increased and the allopurinol loading test was normal. Sequencing of the xanthine dehydrogenase (XDH) gene revealed the pathogenic deletion c.641delC in the homozygous state. Segregation analysis showed that the patient's mother and her two adult sons were carriers of the mutation but not a half-sister and a half-brother of her deceased father. There was no evidence of parental consanguinity. These results established xanthinuria type 1 as the cause of the patient's recurrent polyarthralgias due to a previously unreported homozygosity for the known mutation c.641delC of the XDH gene.\n\nTREATMENT AND COURSE:\nThe patient was advised to adhere to a low-purine diet and to ensure an increased daily fluid-intake of at least 2.5 l. She has since remained symptom free.\n\nCONCLUSION:\nMarkedly lowered serum uric acid concentrations are a hallmark of xanthinuria and of hereditary renal hypouricemia, and in the absence of severe hepatic failure or evidence of an untoward drug effect should raise suspicion of these diseases. A targeted diagnostic work-up should then be initiated and factitious hypouricemia due to IgM paraproteinemia considered only in the case of equivocal test results. Molecular-genetic characterization and segregation analysis will ultimately establish the underlying genotype."
+ }
+}

27112522.json

@@ -0,0 +1,8 @@
+{
+ "id": "27112522",
+ "label": 0,
+ "article": {
+  "id": "27112522",
+  "text": "OBJECTIVE:\nThe objective of this study was to describe the adverse effects of allopurinol on the urinary system during treatment of canine leishmaniasis.\n\nMETHODS:\nRetrospective case series of 42 dogs that developed xanthinuria while receiving allopurinol treatment for leishmaniasis.\n\nRESULTS:\nOf 320 dogs diagnosed with leishmaniasis, 42 (13%) developed adverse urinary effects. Thirteen (of 42) dogs (31%) developed xanthinuria, renal mineralisation and urolithiasis; 11 (26·2%) showed xanthinuria with renal mineralisation; 9 (21·4%) had xanthinuria with urolithiasis and 9 (21·4%) developed xanthinuria alone. Urinary clinical signs developed in 19 dogs (45·2%).\n\nCLINICAL SIGNIFICANCE:\nThis study demonstrates that urolithiasis and renal mineralisation can occur in dogs receiving allopurinol therapy. Dogs receiving therapy should be monitored for the development of urinary adverse effects from the beginning of treatment."
+ }
+}

28495197.json

@@ -0,0 +1,8 @@
+{
+ "id": "28495197",
+ "label": 0,
+ "article": {
+  "id": "28495197",
+  "text": "First-line treatment for canine leishmaniosis (CanL) is N-methylglucamine antimoniate (MGA) combined with allopurinol. However, in some dogs allopurinol may induce hyperxanthinuria leading to urolithiasis. Moreover, allopurinol resistance has recently been described in Leishmania infantum isolates from treated dogs with a relapse of the disease. Alternative treatments are thus needed. Since the type of host immune response strongly influences CanL progression and prognosis, dogs could benefit from treatments targeted at modulating such response, such as nucleotides and active hexose correlated compound (AHCC). The aim of this study was to evaluate the effects of an oral combination of nucleotides and AHCC in dogs with clinical leishmaniosis. Sixty-nine dogs with naturally-occurring clinical leishmaniosis were included in this multicenter, open-label, positively-controlled clinical trial and randomized to receive 10mg/kg allopurinol PO BID (allopurinol group) or 17mg/kg AHCC plus 32mg/kg nucleotides PO SID (supplement group) for 180 days. All dogs were also given 50mg/kg MGA SC BID during the first 28 days. At the time points 0, 30, and 180 days of the trial, dogs underwent a clinical examination, and blood, urine, and bone marrow samples were submitted for analytical tests. Final data analyses (allopurinol group: n=29; supplement group: n=24) revealed a significant improvement in both groups in clinical scores and ELISA-determined antibody titers after treatment. However, the supplement group showed a significantly lower clinical score (P=0.005) and significantly higher antibody titers (P=0.032) after 180 days, compared to the allopurinol group. RT-PCR parasite loads were reduced in groups (mean±SD supplement: 0.38±0.56 vs 5.23±18.9; allopurinol: 0.45±1.47 vs 3.09±8.36 parasites/ng of DNA), but there were no significant differences over time or between groups. During the study, 12 dogs in the allopurinol group developed xanthinuria (41%) compared to no dogs (0%) in the supplement group (P=0.000). Both treatments led to significantly increased CD4+/CD8+ ratio, and improvements in protein electrophoretic pattern and acute phase response. In conclusion, 6-month oral treatment with nucleotides and AHCC in addition to MGA showed similar efficacy to the current first-line treatment for CanL, without producing xanthinuria. This combination could be a good alternative to MGA-allopurinol combination treatment for CanL, especially for dogs suffering allopurinol-related adverse events."
+ }
+}

28587840.json

@@ -0,0 +1,8 @@
+{
+ "id": "28587840",
+ "label": 0,
+ "article": {
+  "id": "28587840",
+  "text": "The chewing lice (Mallophaga) are common parasites of different animals. Most of them infest terrestrial and marine birds, including pigeons, doves, swans, cormorants and penguins. Mallophaga have not been found on marine mammals but only on terrestrial ones, including livestock and pets. Their bites damage cattle, sheep, goats, horses and poultry, causing itch and scratch and arousing phthiriasis and dermatitis. Notably, Mallophaga can vector important parasites, such as the filarial heartworm Sarconema eurycerca. Livestock losses due to chewing lice are often underestimated, maybe because farmers notice the presence of the biting lice only when the infestation is too high. In this review, we examined current knowledge on the various strategies available for Mallophaga control. The effective management of their populations has been obtained through the employ of several synthetic insecticides. However, pesticide overuse led to serious concerns for human health and the environment. Natural enemies of Mallophaga are scarcely studied. Their biological control with predators and parasites has not been explored yet. However, the entomopathogenic fungus Metarhizium anisopliae has been reported as effective in vitro and in vivo experiments against Damalinia bovis infestation on cattle. Furthermore, different Bacillus thuringiensis preparations have been tested against Mallophaga, the most effective were B. thuringiensis var. kurstaki, kenyae and morrisoni. Lastly, plant-borne insecticides have been evaluated against Mallophaga. Tested products mainly contained bioactive principles from two Meliaceae, Azadirachta indica, and Carapa guianensis. High efficacy of neem-borne preparations was reported, leading to the development of several products currently marketed. Overall, our review highlighted that our knowledge about Mallophaga vector activity and control is extremely patchy. Their control still relied on the employ of chemical pesticides widely used to fight other primary pests and vectors of livestock, such as ticks, while the development of eco-friendly control tool is scarce. Behavior-based control of Mallophaga, using pheromone-based lures or even the Sterile Insect Technique (SIT) may also represent a potential route for their control, but our limited knowledge on their behavioral ecology and chemical communication strongly limit any possible approach."
+ }
+}

28917829.json

@@ -0,0 +1,8 @@
+{
+ "id": "28917829",
+ "label": 0,
+ "article": {
+  "id": "28917829",
+  "text": "Geleophysic dysplasia, belonging to the group of acromelic dysplasia, is a rare genetic disease. Two genes, FBN1 and ADAMTSL2, were known to be linked to this disorder. The disorder presents as extreme short stature, short limbs, small hands and feet, stubby fingers and toes, joint stiffness, toe walking, skin thickening, progressive cardiac valvular thickening and characteristic facial features, including a round face with full cheeks. Here, we report the first Chinese case with geleophysic dysplasia type 1 based on clinical and genetic features. The boy was admitted because of severe physical growth retardation and mild motor retardation. Comprehensive medical evaluations were performed including metabolic studies, endocrine function examination, bone X-rays and echocardiography. Much delayed bone age and geleophysic dysplasia were found. Targeted next-generation sequencing was used to detect genetic mutations associated with skeletal dysplasia. Sanger sequencing was used to confirm the mutations in the patient. PCR amplification, cloing, and sequencing was used to determine the de novo mutation origin. Two compound heterozygous mutations were confirmed in the ADAMTSL2 gene of the patient. The c.340G \u003e A (p.Glu114Lys) mutation was a de novo heterozygous mutation, and our results suggested that it was located on the paternal allele. While the c.234-2A \u003e G inherited from his mother was a novel pathogenic heterozygous splicing mutation. Growth hormone deficiency had been observed in the patient. His growth velocity was improved by growth hormone supplementation. In conclusion, we have identified a novel splicing mutation of ADAMTSL2 carried by a Chinese boy with geleophysic dysplasia type 1. The patient was treated effectively with growth hormone supplementation."
+ }
+}

29432500.json

@@ -0,0 +1,8 @@
+{
+ "id": "29432500",
+ "label": 0,
+ "article": {
+  "id": "29432500",
+  "text": "Many animal models in different species have been developed for mental and behavioral disorders. This review presents large animals (dog, ovine, swine, horse) as potential models of this disorders. The article was based on the researches that were published in the peer-reviewed journals. Aliterature research was carried out using the PubMed database. The above issues were discussed in the several problem groups in accordance with the WHO International Statistical Classification of Diseases and Related Health Problems 10thRevision (ICD-10), in particular regarding: organic, including symptomatic, disorders; mental disorders (Alzheimer's disease and Huntington's disease, pernicious anemia and hepatic encephalopathy, epilepsy, Parkinson's disease, Creutzfeldt-Jakob disease); behavioral disorders due to psychoactive substance use (alcoholic intoxication, abuse of morphine); schizophrenia and other schizotypal disorders (puerperal psychosis); mood (affective) disorders (depressive episode); neurotic, stress-related and somatoform disorders (posttraumatic stress disorder, obsessive-compulsive disorder); behavioral syndromes associated with physiological disturbances and physical factors (anxiety disorders, anorexia nervosa, narcolepsy); mental retardation (Cohen syndrome, Down syndrome, Hunter syndrome); behavioral and emotional disorders (attention deficit hyperactivity disorder). This data indicates many large animal disorders which can be models to examine the above human mental and behavioral disorders."
+ }
+}

29599887.json

@@ -0,0 +1,8 @@
+{
+ "id": "29599887",
+ "label": 0,
+ "article": {
+  "id": "29599887",
+  "text": "Pepper's syndrome is a neuroblastoma that metastasizes to the liver. It affects infants younger than six months of age. It can regress spontaneously and is associated with a favorable prognosis in 80% of cases. Given its rarity, we here report two cases of Pepper's syndrome observed at the Charles de Gaulle university pediatric hospital center, Ouagadougou (Burkina Faso). Our study involved two female infants in whom the disease manifested as an increase in abdominal volume, hepatomegaly and signs of respiratory distress. Ultrasound enabled diagnosis, which was based on the nodular appearance of the liver in both cases and determination of the primary tumor in one case. Urinary catecholamine test confirmed the diagnosis in one case. Both patients died from complications related to liver compression, chemotherapy (in one of the cases) and lack of treatment (in the other case)."
+ }
+}

29758347.json

@@ -0,0 +1,8 @@
+{
+ "id": "29758347",
+ "label": 0,
+ "article": {
+  "id": "29758347",
+  "text": "Cohen syndrome is a rare, genetic, connective-tissue disorder, which is caused by mutations in the gene COH1 (VPS13B, Vacuolar Protein Sorting 13 Homolog B) at the chromosome 8q22. The disease is rare reported, which major clinical features include postnatal microcephaly, obesity, short stature, intellectual disability, progressive retinal dystrophy, intermittent neutropenia and many other unusual facial feature. We report four patients in China who were diagnosed with Cohen syndrome by genetic testing and clinical manifestations. At the same time, we review the related literature, and further expound the molecular mechanism of the disease, a variety of clinical manifestations, treatment and prognosis."
+ }
+}

29780020.json

@@ -0,0 +1,8 @@
+{
+ "id": "29780020",
+ "label": 0,
+ "article": {
+  "id": "29780020",
+  "text": "A six-year-old male patient was admitted to our hospital due to itching and scalding crusts that persisted 10-15 days in both eyes. Upon biomicroscopic examination, 5-6 semi-translucent, yellowish brown living lice attached to the upper eyelashes and a large number of eggs were observed. Following application of pilocarpine hydrochloride (Pilomann 2%, Bausch-Lomb) and topical proparacaine hydrochloride (Alcaine 0.5%, Alcon), the paralyzed parasites and eggs were manually removed by pulling with forceps. The lice were identified as adult forms of pubic louse, Pthirus pubis, and its eggs. The patient was treated with pilocarpine hydrochloride, which was applied thrice a day combined with pure vaseline. One week later, no lice or eggs were seen on the eyelashes."
+ }
+}

29875990.json

@@ -0,0 +1,8 @@
+{
+ "id": "29875990",
+ "label": 0,
+ "article": {
+  "id": "29875990",
+  "text": "We report the imaging appearances of a case of pathologically proven, neonatal neuroblastoma 4S with diffuse hepatic metastatic involvement at presentation. Patient had an abnormal appearing liver both by ultrasound and MR. There was no evidence for associated adrenal tumor by imaging. Lack of an associated adrenal mass led to initial misinterpretation of diffuse hepatic accumulation of MIBG seen with radionuclide scintigraphy. To the best our knowledge, this is the first report of metastatic neonatal 4S neuroblastoma without an adrenal (or extra-adrenal) primary identified either on pre- or post-natal imaging."
+ }
+}

29935280.json

@@ -0,0 +1,8 @@
+{
+ "id": "29935280",
+ "label": 0,
+ "article": {
+  "id": "29935280",
+  "text": "BACKGROUND:\nThe aim of our study was to identify the genetic background of thiopurine-induced toxicity in a patient with a wild-type thiopurine methyltransferase genotype and activity. A 38-year-old Caucasian woman presented with cutaneous necrotizing vasculitis pancytopenia one month after starting azathioprine therapy.\n\nMETHODS:\nDuring a routine biochemical follow-up of the patient, undetectable serum uric acid (\u003c10 μl) was observed. A high performance liquid chromatography analysis of urinary purines revealed increased levels of xanthine (137 mmol/mol creatinine). The suspected diagnosis of hereditary xanthinuria, a rare autosomal recessive disorder of the last two steps of purine metabolism, was confirmed by sequence analysis.\n\nRESULTS:\nAn analysis of XDH/XO and AOX1 revealed common polymorphisms, while analysis of the MOCOS gene identified a rare homozygous variant c.362C \u003e T. Dysfunction of this variant was confirmed by significantly decreased xanthine dehydrogenase/oxidase activity in the patient's plasma (\u003c2% of control mean activity).\n\nCONCLUSIONS:\nWe present a biochemical, enzymatic, and molecular genetic case study suggesting an important association between a hitherto undescribed dysfunction variant in the MOCOS gene and thiopurine-induced toxicity. The identified variant c.362C \u003e T results in slower thiopurine metabolism caused by inhibition of 6-mercaptopurine oxidation (catabolism) to 6-thioxanthine and 6-thiouric acid, which increases the formation of the nucleotide 6-thioguanine, which is toxic. This is the first clinical case to identify the crucial role of the MOCOS gene in thiopurine intolerance and confirm the impact of genetic variability of purine enzymes on different therapeutic outcomes in patients undergoing thiopurine treatment."
+ }
+}

30057829.json

@@ -0,0 +1,8 @@
+{
+ "id": "30057829",
+ "label": 0,
+ "article": {
+  "id": "30057829",
+  "text": "BACKGROUND:\nGeleophysic dysplasia is a rare multisystem disorder that principally affects the bones, joints, heart, and skin. This condition is inherited either in an autosomal dominant pattern due to mutations or in an autosomal recessive pattern due to mutations. Two patients with unaffected parents from unrelated families presented to their endocrinologist with severe short stature, resistant to growth hormone treatment. Routine endocrine tests did not reveal an underlying etiology. Exome sequencing was performed in each family. Our two patients, harboring heterozygous mutations p.Tyr1696Asp and p.Cys1748Ser, had common clinical symptoms such as severe short stature, characteristic facial features, short hands and feet, and limitation of joint movement. However, one patient had severe cardiac involvement whereas the other patient had tracheal stenosis requiring tracheostomy placement.\n\nCONCLUSIONS:\nPatients with severe dwarfism, skeletal anomalies, and other specific syndromic features (e.g., tracheal stenosis and cardiac valvulopathy) should undergo genetic testing to exclude acromelic dysplasia syndromes."
+ }
+}

30157195.json

@@ -0,0 +1,8 @@
+{
+ "id": "30157195",
+ "label": 0,
+ "article": {
+  "id": "30157195",
+  "text": "OBJECTIVE:\nTo identify in vitro inhibitors of xanthine crystallization that have potential for inhibiting the formation of xanthine crystals in urine and preventing the development of the renal calculi in patients with xanthinuria.\n\nMETHODS:\nThe formation of xanthine crystals in synthetic urine and the effects of 10 potential crystallization inhibitors were assessed using a kinetic turbidimetric system with a photometer. The maximum concentration tested for each compound was: 20 mg/L for 3-methylxanthine (3-MX); 40 mg/L for 7-methylxanthine (7-MX), 1-methylxanthine (1-MX), theobromine (TB), theophylline, paraxanthine, and caffeine; 45 mg/L for 1-methyluric acid; 80 mg/L for 1,3-dimethyluric acid; and 200 mg/L for hypoxanthine. Scanning electron microscopy was used to examine the morphology of the crystals formed when inhibitory effects were observed.\n\nRESULTS:\nOnly 7-MX, 3-MX, and 1-MX significantly inhibited xanthine crystallization at the tested concentrations. Mixtures of inhibitors had an additive effect rather than a synergistic effect on crystallization.\n\nCONCLUSION:\nTwo of the inhibitors identified here-7-MX and 3-MX-are major metabolites of TB. In particular, after TB consumption, 20% is excreted in the urine as TB, 21.5% as 3-MX, and 36% as 7-MX. Thus, consumption of theobromine could protect patients with xanthinuria from the development of renal xanthine calculi. Clinical trials are necessary to demonstrate these effects in vivo."
+ }
+}

31350823.json

@@ -0,0 +1,8 @@
+{
+ "id": "31350823",
+ "label": 0,
+ "article": {
+  "id": "31350823",
+  "text": "BACKGROUND:\nGeleophysic dysplasia (GPHYSD) is a disorder characterized by dysmorphic features, stiff joints and cardiac involvement due to defects of TGF-β signaling. GPHYSD can be caused by mutations in FBN1, ADAMTLS2, and LTBP3 genes.\n\nMETHODS AND RESULTS:\nConsistent with previous reports, we found intracellular inclusions of unknown material by electron microscopy (EM) in skin fibroblasts of two GPHYSD individuals carrying FBN1 mutations. Moreover, we found that the storage material is enclosed within lysosomes and is associated with the upregulation of several lysosomal genes. Treatment of GPHYSD fibroblasts carrying FBN1 mutations with the angiotensin II receptor type 1 inhibitor losartan that inhibits TGF-β signaling did not reduce the storage but improved the extracellular deposition of fibrillin-1 microfibrils.\n\nCONCLUSION:\nLosartan is a promising candidate drug for treatment of GPHYSD due to FBN1 defects."
+ }
+}

31745037.json

@@ -0,0 +1,8 @@
+{
+ "id": "31745037",
+ "label": 0,
+ "article": {
+  "id": "31745037",
+  "text": "Phthiriasis palpebrarum (PP) is the infestation of eyelids caused by the ectoparasite Phthirus pubis, frequently misdiagnosed as allergic conjunctivitis, blepharitis or dermatitis. There is no standard treatment of choice although various treatment modalities have been described. A 6-year-old male child with PP was successfully treated with local application of 20% fluorescein solution over the eyelashes and eyebrows of both the eyes, followed by the mechanical removal of all parasites and trimming of the eyelashes from the base and application of ophthalmic ointment."
+ }
+}

31943017.json

@@ -0,0 +1,8 @@
+{
+ "id": "31943017",
+ "label": 0,
+ "article": {
+  "id": "31943017",
+  "text": "Mutations in each of the four human VPS13 (VPS13A-D) proteins are associated with distinct neurological disorders: chorea-acanthocytosis, Cohen syndrome, early-onset Parkinson's disease and spastic ataxia. Recent evidence suggests that the different VPS13 paralogs transport lipids between organelles at different membrane contact sites. How each VPS13 isoform is targeted to organelles is not known. We have shown that the localization of yeast Vps13 protein to membranes requires a conserved six-repeat region, the Vps13 Adaptor Binding (VAB) domain, which binds to organelle-specific adaptors. Here, we use a systematic mutagenesis strategy to determine the role of each repeat in recognizing each known adaptor. Our results show that mutation of invariant asparagines in repeats 1 and 6 strongly impacts the binding of all adaptors and blocks Vps13 membrane recruitment. However, we find that repeats 5-6 are sufficient for localization and interaction with adaptors. This supports a model where a single adaptor-binding site is found in the last two repeats of the VAB domain, while VAB domain repeat 1 may influence domain conformation. Importantly, a disease-causing mutation in VPS13D, which maps to the highly conserved asparagine residue in repeat 6, blocks adaptor binding and Vps13 membrane recruitment when modeled in yeast. Our findings are consistent with a conserved adaptor binding role for the VAB domain and suggest the presence of as-yet-unidentified adaptors in both yeast and humans."
+ }
+}

32316042.json

@@ -0,0 +1,8 @@
+{
+ "id": "32316042",
+ "label": 0,
+ "article": {
+  "id": "32316042",
+  "text": "BACKGROUND:\nPatients who have undergone Roux-en-Y gastric bypass (RYGB) are at increased risk of biliary disease necessitating endoscopic retrograde cholangiopancreatography (ERCP). The most widely used approaches to perform ERCP after RYGB are laparoscopy-assisted ERCP (LA-ERCP) and balloon enteroscopy-assisted ERCP (BEA-ERCP). There are few studies comparing these procedures. We aimed to compare the performance, benefits, and harms of LA-ERCP and BEA-ERCP in RYGB patients.\n\nMETHODS:\nWe identified all RYGB patients who underwent ERCP at two tertiary care endoscopy centers in Oslo, Norway between May 2013 and December 2017. One center performed BEA-ERCP, the other LA-ERCP. Procedure success was defined as fulfillment of the therapeutic or diagnostic aim, according to the procedure description. Adverse events were classified according to the Clavien-Dindo grading system.\n\nRESULTS:\nDuring the study period, 40 BEA-ERCP and 39 LA-ERCP procedures were performed in 68 patients. Procedure success rate was 72.5 % for BEA-ERCP and 87.2 % for LA-ERCP ( = 0.14). Adverse events occurred in 18 % of BEA-ERCP and 28 % of LA-ERCP ( = 0.23). Serious adverse events (Clavien-Dindo grade ≥ 3b) occurred in 2.5 % of BEA-ERCP and 7.7 % of LA-ERCP procedures ( = 0.36). Concomitant cholecystectomy was performed in 25 of the 39 LA-ERCP procedures. The median procedure times for LA-ERCP performed with and without concomitant cholecystectomy were 201 minutes and 140 minutes, respectively, and for BEA-ERCP was 125 minutes.\n\nCONCLUSIONS:\nIn experienced hands, both LA-ERCP and BEA-ERCP have high success rates after RYGB. The choice of approach should be individualized according to patient characteristics and available physician competence."
+ }
+}

32447120.json

@@ -0,0 +1,8 @@
+{
+ "id": "32447120",
+ "label": 0,
+ "article": {
+  "id": "32447120",
+  "text": "INTRODUCTION:\nParasitic infections of the eye are a major cause of ocular-surface diseases globally. While most infections are treatable, parasites can cause varying levels of damage mostly due to late diagnosis or misdiagnosis as a result of doctors' unfamiliarity with their characteristics of latency and crypsis, as well as lack of awareness by the patients.\n\nCASE REPORTS:\nIn this study, we present three cases of phthiriasis palpebrarum, thelaziasis, and ophthalmomyiasis, respectively. Two of the cases were treated at the clinic and did not recur. One patient refused treatment and was lost to follow-up.\n\nDISCUSSION:\nBy evaluating the natural histories, morphology, symptoms, clinical findings, and treatment of these parasitic diseases, we systematically analyzed several distinct and unique parasite characteristics, especially latency and crypsis. Furthermore, we have proposed specific examination techniques and methods as well as prevention and treatment strategies from these specific perspectives, aiming to prompt timely diagnoses and early interventions for these diseases by health care workers and improve the public's awareness of parasitic infections.\n\nCONCLUSION:\nParasitosis on the ocular surface is a global infectious disease, and prevention strategies include maintaining personal and environmental hygiene and limiting contact with animals. We recommend that health care workers should enhance their ability to detect and diagnose these diseases while promoting the public's awareness of them in the context of our new perspectives."
+ }
+}

32478318.json

@@ -0,0 +1,8 @@
+{
+ "id": "32478318",
+ "label": 0,
+ "article": {
+  "id": "32478318",
+  "text": "Prompt diagnosis in the emergency department in the case of a patient with emesis may be difficult due to the increasing prevalence of diseases which manifest with emesis. Furthermore, in the case of chronic symptomatology, management and therapy are even more complicated. One episode of emesis rarely causes complications, but severe or repetitive episodes of emesis can cause life-threatening complications. For this reason, the diagnosis of the underlying disease which manifests with emesis is mandatory to be established in a short time in order to choose the correct therapeutic option. In order to systemize the process of diagnosis, this clinical narrative review will discuss only rare causes of emesis."
+ }
+}

32605629.json

@@ -0,0 +1,8 @@
+{
+ "id": "32605629",
+ "label": 0,
+ "article": {
+  "id": "32605629",
+  "text": "BACKGROUND:\nCohen syndrome, an autosomal recessive syndrome, is a rare syndrome with diverse clinical manifestations including failure to thrive, hypotonia, hypermobile joints, microcephaly, intellectual disabilities, craniofacial and limb anomalies, neutropenia and a friendly character. It is associated with mutations of the vacuolar protein sorting 13 homolog B (VPS13B) gene, which is involved in the development of the ocular, hematological and central nervous systems. This gene encodes a transmembrane protein playing a crucial role in preserving the integrity of the Golgi complex. To date, more than 150 mutations of VPS13B have been reported in over 200 Cohen syndrome patients. Missense or nonsense mutations are the most common mutations.\n\nCASE PRESENTATION:\nA 4-year-old girl, born to consanguineous parents, was referred to the pediatric clinical immunology outpatient clinic for investigation of recurrent neutropenia with a history of recurrent infections in the past year. On physical examination, she had the characteristic facial features of Cohen syndrome, developmental delay and speech disorder. She had a cheerful disposition, and her mother gave a history of feeding difficulties in her first months of life. She did not present any ophthalmologic or cardiac abnormalities. Her lab results revealed moderate neutropenia. Serum IgG, IgM, IgA and IgE levels were normal. She fulfilled the clinical diagnostic criteria for Cohen syndrome. WES revealed a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49). Currently, she is not experiencing any severe problem, and she undergoes irregular medical treatment once her neutrophil count decreases under the normal limit. Her verbal and motor abilities have improved as a result of speech and occupational therapies.\n\nCONCLUSION:\nWe reported a novel homozygous frameshift variant in VPS13B (LRG_351t1: c.7095del; p.Ser2366AlafsTer49) in a 4-year-old girl with Cohen syndrome. Cohen syndrome should be considered in differential diagnosis of any child with intellectual disability and neutropenia."
+ }
+}

32642357.json

@@ -0,0 +1,8 @@
+{
+ "id": "32642357",
+ "label": 0,
+ "article": {
+  "id": "32642357",
+  "text": "Cohen syndrome is an extremely rare disease with characteristic somatic and multi-system features that severely affect vision. Ophthalmologists must consider Cohen syndrome when developmental delay, high-grade myopia, and retinal dystrophy are present in a child. Here we report a case of Cohen syndrome in a 10-year-old boy presenting with cystoid macular edema (CME), only the second reported case of its kind. This case illustrates the phenotypic variability that can occur in Cohen syndrome, with rare features in addition to CME including trace posterior subcapsular cataracts, growth hormone deficiency, mild vermian hypoplasia, a nasolacrimal cyst, hearing loss, and high-functioning intelligence quotient (IQ). Our patient did not have an identifiable second mutation even after extensive genetic testing, which raises questions about whether the patient has a novel gene variant for the disease or an autosomal dominant mode of inheritance exists for Cohen syndrome. In addition to peripheral vision loss, the rare appearance of macular edema can threaten the remaining vision and requires intervention. This case also demonstrates that, without a high index of suspicion, there can be considerable delay in diagnosing Cohen syndrome. Though little is known about the prevalence of many of the clinical features seen in our case in the Cohen syndrome population, this case raises awareness of the syndrome and the need to recognize various clinical features, perform genetic testing, and direct appropriate treatment to prevent complications and help improve quality of life."
+ }
+}

32773395.json

@@ -0,0 +1,8 @@
+{
+ "id": "32773395",
+ "label": 0,
+ "article": {
+  "id": "32773395",
+  "text": "BACKGROUND:\nHereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.\n\nOBJECTIVE:\nWe collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.\n\nMETHODS:\nWe searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale.\n\nRESULTS:\nOf the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH).\n\nCONCLUSIONS:\nThe 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies."
+ }
+}

32904930.json

@@ -0,0 +1,8 @@
+{
+ "id": "32904930",
+ "label": 0,
+ "article": {
+  "id": "32904930",
+  "text": "Refsum disease is a rare inherited metabolic disorder arising from a defect in peroxisomal metabolism. Patients lack the functional enzyme phytanoyl-CoA hydroxylase, resulting in perturbed alpha oxidation of fatty acids. Phytanic acid accumulates in nervous and adipose tissue and leads to several disease phenotypes including early-onset retinal degeneration, hearing loss, peripheral neuropathy, anosmia, and cerebellar ataxia, among others. Currently, restricting dietary phytanic acid is the only means of altering the chronic sequelae and the disease course. While dietary intervention has been demonstrated to improve peripheral neuropathy, ichthyosis, and ataxia, there have been no reports of improved retinal function in patients with Refsum disease. We describe the case of a 51-year-old patient with molecularly and biochemically confirmed Refsum disease who underwent electroretinography before and after beginning a phytanic acid-restricted diet. His post-intervention 30 Hz flicker electroretinogram demonstrated significantly improved waveform amplitudes and implicit times, suggesting improved retinal function. Thus, we propose that the possibility exists for some visual recovery in these patients and we highlight the utility of performing standardized electroretinography to assess treatment response in Refsum disease."
+ }
+}

33025479.json

@@ -0,0 +1,8 @@
+{
+ "id": "33025479",
+ "label": 0,
+ "article": {
+  "id": "33025479",
+  "text": "Cohen syndrome (CS) is an autosomal recessive congenital disorder characterized by mutation in the vacuolar protein sorting 13 homolog B (VPS13B; formerly COH1) gene. In the current study, a Chinese family has two young sibling cases having a developmental delay, physical obesity, high myopia, and a special face, which suspected to be CS. The purpose of the study was to identify variants and further analyze their pathogenicity for CS. Next-generation sequencing (NGS) revealed a compound heterozygous mutation in VPS13B gene in the proband, which comprises a frameshift mutation in NM_017890.4: c.10076_10077delCA (p.T3359fs*29) and a putative splice site mutation in c.6940 + 1G \u003e T. Both Minigene assay in vitro and splicing assay in vivo confirmed that the splicing mutation in c.6940 + 1G \u003e T generates a frameshift transcript with whole exon 38 skipping. Eventually, quantitative real-time PCR demonstrated that either of the two mutations can lead to degradation of the VPS13B gene at the transcriptional level. Functional studies of variants identified in CS patients are essential for their subsequent genetic counseling and prenatal diagnoses and could also be the start point for new therapeutic approaches, currently based only on symptomatic treatment."
+ }
+}

33381333.json

@@ -0,0 +1,8 @@
+{
+ "id": "33381333",
+ "label": 0,
+ "article": {
+  "id": "33381333",
+  "text": "Portal hypertension caused by cirrhosis is the most common etiology of esophageal varices. However, abnormalities of the splenoportal axis in the absence of liver disease may also cause portal hypertension resulting in varices. We report a rare case of esophageal variceal bleed in a noncirrhotic patient with isolated splenomegaly secondary to chronic granulocyte colony stimulating factor (G-CSF) therapy. The patient is a 26-year-old male with Cohen syndrome who required long-term G-CSF treatment for chronic neutropenia. He presented with large volume hematemesis and pancytopenia in the setting of known splenomegaly with no evidence of cirrhosis. An urgent EGD revealed active variceal bleeding and portal hypertensive gastropathy. The patient was appropriately resuscitated and underwent a successful transjugular intrahepatic portosystemic shunt and CT-guided coil placement for the bleeding varices. We are the first to report variceal bleed as a complication of long-term G-CSF use, a life-threatening consequence that requires urgent intervention."
+ }
+}

33427631.json

@@ -0,0 +1,8 @@
+{
+ "id": "33427631",
+ "label": 0,
+ "article": {
+  "id": "33427631",
+  "text": "Calpainopathies are inherited limb-girdle muscular dystrophies, most often following an autosomal recessive (AR) transmission. Autosomal dominant (AD) forms with less severe presentation are increasingly reported. Calpainopathies with autosomal recessive (AR) mutations of the calpain3 gene (CAPN3) are associated with limb girdle muscular dystrophy type R1 (LGMD-R1, OMIM 253600) also referred to as LGMD-2A according to the old nomenclature. LGMD-R1 is the commonest form of all LGMDs, with an estimated prevalence of 10 to 70 cases per million inhabitants, that is a cohort of between 670 and 4,200 patients in France theoritically. Patients present a symmetrical proximal axial myopathy manifesting itself between the first and second decade. The clinical course is variable. The level of Creatine- Kinase (CK) is usually high and there is no cardiac involvement. From a therapeutic perspective, the autosomal recessive form of calpainopathy is quite suitable to gene replacement strategies; the viability of recombinant AAV-mediated calpain 3 transfer has been demonstrated in animal models and clinical trials are expected in the coming years. Meanwhile, natural history studies are needed to prepare for future clinical trials."
+ }
+}

33502714.json

@@ -0,0 +1,8 @@
+{
+ "id": "33502714",
+ "label": 0,
+ "article": {
+  "id": "33502714",
+  "text": "Molybdenum cofactor is essential for the activity of multiple enzymes including xanthine dehydrogenase. Molybdenum cofactor deficiencies are rare inborn errors of metabolism. Clinically, they present with intractable seizures, axial hypotonia, and hyperekplexia. They further develop cerebral atrophy, microcephaly, global developmental delay and ectopia lentis. We report a 5-year-old female with clinically, biochemically and genetically confirmed molybdenum cofactor deficiency type B due to compound heterozygous pathogenic variants in the molybdenum cofactor synthesis 2 gene found on whole exome sequencing. The xanthine stones were a key clue towards diagnosis. No mutation was detected in XDH gene. Implementation of a low-purine diet, urine alkalization and hydration lead to a near complete decrease in stone burden. The patient received pyridoxine supplementation with improvement in energy levels and attentiveness. Despite reports of high mortality at a young age, our patient was 9 years old at the time of this writing. Molybdenum cofactor deficiencies should be considered in neonates with early-onset seizures, hypotonia, and feeding difficulties. Screening with serum uric acid levels and empiric treatment may be considered while awaiting genetic results."
+ }
+}

33548958.json

@@ -0,0 +1,8 @@
+{
+ "id": "33548958",
+ "label": 0,
+ "article": {
+  "id": "33548958",
+  "text": "To explore the phenotypes and genotypes of molybdenum cofactor deficiency type B (MoCD-B) manifested as Leigh-like syndrome. The clinical data, laboratory tests, neuroimaging and gene results of one patient diagnosed as MoCD-B at Beijing Children's Hospital and Hebei Children's Hospital in December 2018 were collected. Related literature was searched and reviewed at Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed (up to September 2020) by using terms \"MOCS2\" \"molybdenum cofactor deficiency\" \"Leigh-like syndrome,MOCS2\" \"molybdenum cofactor deficiency, Leigh-like syndrome\". The phenotypes and genotypes of MoCD-B were summarized. A 7 months and 14 days old boy with the chief complaint of \"cough for 6 days, abnormal posture for 4 days and fever for 2 days\" was admitted to Hebei Children' Hospital on December 2018. His abnormal posture presented as opisthotonos accompanied with dysphagia, without seizures. His previous psychomotor development was described as normal. He was born at term after an uneventful pregnancy to non-consanguineous parents. Blood test showed a slightly increased lactic acid and a significantly decreased uric acid. Urine metabolism test showed an obviously increased xanthine and hypoxanthine. Brain magnetic resonance imaging showed hyperintense signal on T2 weighted image and fluid attenuated inversion recovery in bilateral globus pallidus and pedunculus cerebri. The patient was diagnosed with Leigh-like syndrome. No obvious improvement was achieved after cocktail therapy and symptomatic treatment. The whole exome sequencing showed that the patient carried a homozygous variant of MOCS2 gene, c.19G\u003eT(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B. His parents carried a heterozygous variant respectively. A total of 41 MoCD-B cases with MOCS2 gene variants were collected through literature review and our study, among which 30 cases had full medical records. The onset ages of 23 (77%) cases were in neonate, manifesting with severe encephalopathy, including neonatal-onset intractable seizures, developmental delay, laboratory abnormalities included very low levels of serum and urinary uric acid, increased urinary levels of xanthine and hypoxanthine. Cranial imaging showed cerebral atrophy, cystic encephalomalacia, etc. The onset ages of 7 patients varied from 5 months to 23 years. Four cases had normal psychomotor development before disease onset. Neurological disorders appeared acutely or exacerbated after external triggers and all of them had basal ganglia involvement. Among the 30 cases, 3 cases had a relatively milder phenotype with the ability of brief communication and walking without or with support. Molybdenum cofactor deficiency is a rare disease. Most cases had severe phenotypes and poor outcomes, but some cases may have mild phenotype. MoCD-B caused by MOCS2 gene variants may manifest as Leigh-like syndrome with a normal psychomotor development before the trigger of infection strike. Hypouricemia, xanthinuria and hypoxanthinuria can be indicators of the disease. The presence of MOCS2 gene variants would confirm a final diagnosis."
+ }
+}

33660358.json

@@ -0,0 +1,8 @@
+{
+ "id": "33660358",
+ "label": 0,
+ "article": {
+  "id": "33660358",
+  "text": "We have reviewed the literature and have identified more than 100 diseases or conditions that are associated with raised concentrations of plasma total homocysteine. The commonest associations are with cardiovascular diseases and diseases of the central nervous system, but a large number of developmental and age-related conditions are also associated. Few other disease biomarkers have so many associations. The clinical importance of these associations becomes especially relevant if lowering plasma total homocysteine by B vitamin treatment can prevent disease and so improve health. Five diseases can at least in part be prevented by lowering total homocysteine: neural tube defects, impaired childhood cognition, macular degeneration, primary stroke, and cognitive impairment in the elderly. We conclude from our review that total homocysteine values in adults of 10 μmol/L or below are probably safe, but that values of 11 μmol/L or above may justify intervention. Homocysteine is more than a disease biomarker: it is a guide for the prevention of disease."
+ }
+}

33676434.json

@@ -0,0 +1,8 @@
+{
+ "id": "33676434",
+ "label": 0,
+ "article": {
+  "id": "33676434",
+  "text": "BACKGROUND:\nPhthirus pubis is an obligate parasite of human beings. Demodex spp. is a much more common parasite of human beings. However, P. pubis infestation accompanied by Demodex mite infestation in eye has not been reported.\n\nCASE PRESENTATION:\nWe report the first case of Phthirus pubis and Demodex co-infestation on a 48-years-old woman. She presented to the hospital with itching and burning at her right eye for 2 weeks. Slit lamp examination revealed multiple nits and adults of P. pubis anchored to both upper and lower eyelashes. Eyelashes were trimmed, moxifloxacin eye ointment and fluorometholone eye drops were initiated daily. However, itching didn't improve after 2 weeks of treatment. Light microscopy examination of eyelashes revealed infestation with Demodex. The patient was treated with lid scrubs with 25% tea tree oil daily for 4 weeks and was completely cured.\n\nCONCLUSION:\nOur report shows the importance of an early and comprehensive diagnosis, because both phthiriasis palpebrarum and demodicosis can be confused with blepharitis."
+ }
+}

33685072.json

@@ -0,0 +1,8 @@
+{
+ "id": "33685072",
+ "label": 0,
+ "article": {
+  "id": "33685072",
+  "text": "Phthiriasis palpebrarum is a rare eyelid infestation caused by (pubic lice) that is often confused with other causes of blepharoconjunctivitis. In this study, we report the case of a 49-year-old male patient with phthiriasis palpebrarum who presented with itching and eye irritation in the left eye and had undergone treatment for conjunctivitis in the past month. Biomicroscopic examination revealed a dense population of motile and translucent lice and eggs, more intensely on the upper lid. For treatment, the lice were first cleaned mechanically, eyelashes were cut from the bottom, and eggs and lice were removed from the eye, after which petrolatum jelly (vsaseline) was applied to the lids for 10 days. In the control examination, no lice and eggs were observed."
+ }
+}

33809364.json

@@ -0,0 +1,8 @@
+{
+ "id": "33809364",
+ "label": 0,
+ "article": {
+  "id": "33809364",
+  "text": "The conserved VPS13 proteins constitute a new family of lipid transporters at membrane contact sites. These large proteins are suspected to bridge membranes and form a direct channel for lipid transport between organelles. Mutations in the 4 human homologs () are associated with a number of neurological disorders, but little is known about their precise functions or the relevant contact sites affected in disease. In contrast, yeast has a single Vps13 protein which is recruited to multiple organelles and contact sites. The yeast model system has proved useful for studying the function of Vps13 at different organelles and identifying the localization determinants responsible for its membrane targeting. In this review we describe recent advances in our understanding of VPS13 proteins with a focus on yeast research."
+ }
+}

33816764.json

@@ -0,0 +1,8 @@
+{
+ "id": "33816764",
+ "label": 0,
+ "article": {
+  "id": "33816764",
+  "text": "INTRODUCTION:\nElevated homocysteine (Hcy) and related metabolites accelerate Alzheimer's disease. Hcy-lowering B vitamins slow brain atrophy/cognitive decline in mild cognitive impairment (MCI). Modification with Hcy-thiolactone generates auto-immunogenic -Hcy-protein. We tested a hypothesis that anti--Hcy-protein autoantibodies predict cognition in individuals with MCI participating in a randomized, double-blind, placebo-controlled VITACOG trial of B vitamins.\n\nMETHODS:\nParticipants with MCI (n = 196, 76.8 years old, 60% women) were randomly assigned to receive a daily dose of folic acid (0.8 mg), vitamin B (0.5 mg), and B (20 mg) (n = 98) or placebo (n = 98) for 2 years. Cognition was analyzed by neuropsychological tests. Brain atrophy was quantified in a subset of patients (n = 167) by magnetic resonance imaging. Anti -Hcy-protein auto-antibodies were quantified by enzyme-linked immunosorbent assay. Associations among anti--Hcy-protein autoantibodies, cognition, and brain atrophy were examined by multiple regression analysis.\n\nRESULTS:\nAt baseline, anti--Hcy-protein autoantibodies were significantly associated with impaired global cognition (Mini-Mental State Examination [MMSE]), episodic memory (Hopkins Verbal Learning Test-revised), and attention/processing speed (Map Search). At the end of the study, anti--Hcy-protein autoantibodies were associated with impaired global cognition (MMSE) and attention/processing speed (Trail Making A). In the placebo group, baseline anti--Hcy-protein autoantibodies predicted, independently of Hcy, global cognition (Telephone Inventory for Cognitive Status modified [TICS-m]; MMSE) and attention/processing speed (Trail Making A) but not brain atrophy, at the end of study. B-vitamin treatment abrogated association of anti--Hcy-protein autoantibodies with cognition.\n\nDISCUSSION:\nThese findings suggest that anti--Hcy-protein autoantibodies can impair functional (attention/processing speed and global cognition), but not structural (brain atrophy), aspects of cognition. Anti--Hcy-protein autoantibodies are a new factor associated with impaired cognition, which could be ameliorated by B vitamins."
+ }
+}

33823207.json

@@ -0,0 +1,8 @@
+{
+ "id": "33823207",
+ "label": 0,
+ "article": {
+  "id": "33823207",
+  "text": "We report the anesthetic management with combined spinal-epidural in a patient with limb-girdle muscular dystrophy type 2A, submitted to abdominoplasty and liposuction. The patient had onset of symptoms at 8 years old, diagnosed by muscular biopsy, presenting muscle weakness in the scapular and pelvic girdles, with reduced mobility. We performed monitorization with noninvasive blood pressure, oximeter, thermometer, and electrocardiogram. In the postoperative period, she showed no clinical signs of rhabdomyolysis, myotonia, or adverse effects, maintaining hemodynamic stability. The anesthesia technique allowed spontaneous ventilation, monitoring of clinical parameters close to physiological conditions and used smaller doses of medication, reducing related risks."
+ }
+}

33908178.json

@@ -0,0 +1,8 @@
+{
+ "id": "33908178",
+ "label": 0,
+ "article": {
+  "id": "33908178",
+  "text": "Sleep-disordered breathing (SDB) is common in patients with skeletal dysplasias. The aim of our study was to analyze SDB and respiratory management in children with rare skeletal dysplasias. We performed a retrospective analysis of patients with spondyloepiphyseal dysplasia congenita (SEDC), metatropic dysplasia (MD), spondyloepimetaphyseal dysplasia (SEMD), acrodysostosis (ADO), geleophysic dysplasia (GD), acromicric dysplasia (AD), and spondylocostal dysplasia (SCD) between April 2014 and October 2020. Polygraphic data, clinical management, and patients' outcome were analyzed. Thirty-one patients were included (8 SEDC, 3 MD, 4 SEMD, 1 ADO, 4 GD, 3 AD, and 8 SCD). Sixteen patients had obstructive sleep apnea (OSA): 11 patients (2 with SEDC, 1 with SEMD, 1 with ADO, 1 with GD, 2 with AD, and 4 with SCD) had mild OSA, 2 (1 SEMD and 1 GD) had moderate OSA, and 3 (1 SEDC, 1 MD, 1 SEMD) had severe OSA. Adenotonsillectomy was performed in one patient with SCD and mild OSA, and at a later age in two other patients with ADO and AD. The two patients with moderate OSA were treated with noninvasive ventilation (NIV) because of nocturnal hypoxemia. The three patients with severe OSA were treated with adenotonsillectomy (1 SEDC), adeno-turbinectomy and continuous positive airway pressure (CPAP; 1 MD), and with NIV (1 SEMD) because of nocturnal hypoventilation. OSA and/or alveolar hypoventilation is common in patients with skeletal dysplasias, underlining the importance of systematic screening for SDB. CPAP and NIV are effective treatments for OSA and nocturnal hypoventilation/hypoxemia."
+ }
+}

33974487.json

@@ -0,0 +1,8 @@
+{
+ "id": "33974487",
+ "label": 0,
+ "article": {
+  "id": "33974487",
+  "text": ": Cohen Syndrome (CS) is an autosomal recessive multisystemic disorder characterized by various ophthalmologic findings, including retinal dystrophy and associated cystoid macular edema (CME), in which there was no known effective treatment approach. We describe a CS patient with a homozygous c.62 T \u003e G, p.(Leu21*) mutation in the gene with a topical carbonic anhydrase inhibitor (CAI; brinzolamide %1, thrice daily) responding CME. A seven-year-old girl with an established diagnosis of CS was referred with a primary complaint of nyctalopia. On ophthalmologic examination, bilateral decreased visual acuity and normal-appearing macula with mild optic disc pallor were present. However, the detailed evaluation revealed bilateral blunted foveal reflexes, barely visible foveal pigmentation, and slightly attenuated retinal vessels without any peripheral retinal pigmentary changes in dilated fundus examination, and CME on optical coherence tomography. Bilateral topical brinzolamide thrice daily was initiated for CME. Visual acuity increased, and CME was resolved except for minimal schisis at the inner nuclear layer level at the third-month follow-up visit and remained stable up to one-year follow-up. CME reappeared after five months of self-discontinuation of the patient's therapy but resolved again with treatment resumption. We report the first case of CME secondary to rod-cone dystrophy associated with CS showing improvement in anatomy and visual acuity with a topical CAI."
+ }
+}

34105174.json

@@ -0,0 +1,8 @@
+{
+ "id": "34105174",
+ "label": 0,
+ "article": {
+  "id": "34105174",
+  "text": "INTRODUCTION/AIMS:\nIn this study, we examined the social and health impacts of the coronavirus disease 2019 (COVID-19) pandemic and social guidelines on people with muscular dystrophies.\n\nMETHODS:\nA prospective de-identified electronic survey was distributed to adults with self-reported facioscapulohumeral muscular dystrophy (FSHD), myotonic dystrophy (DM), and limb-girdle muscular dystrophy (LGMD) enrolled in national registries or with patient advocacy groups. The COVID-19 Impact Survey was developed by muscular dystrophy experts in association with patient collaborators and advocacy groups. The Perceived Stress Scale was used to measure perceived stress.\n\nRESULTS:\nRespondents (n = 774: 56% FSHD; 35% DM, and 9% LGMD) were mostly women and middle-aged (range 19-87 y). Rates of COVID-19 infections were low (\u003c1%), compliance with local social distancing guidelines and policies high (98%). Major challenges reported during the pandemic included: obtaining treatment (40%), managing stress (37%), social distancing (36%), and obtaining essentials (34%). The majority reported a slight worsening in their disease state. Respondents reported moderate stress levels (stress score = 15.4; range = 0-35), with higher stress levels reported by women and those under age 30 y. Three-quarters of participants who participated in telemedicine visits were satisfied with the encounters; however, most reported a preference for in-person visits.\n\nDISCUSSION:\nPeople with muscular dystrophy reported moderate stress and challenges during the COVID-19 pandemic. Interventions such as exercise and stress-coping strategies, including strategies specific to women or individuals \u003c30 y, may be important. Further investigation is needed into the role of telemedicine in the care of individuals with muscular dystrophy."
+ }
+}

34110586.json

@@ -0,0 +1,8 @@
+{
+ "id": "34110586",
+ "label": 0,
+ "article": {
+  "id": "34110586",
+  "text": "The limb-girdle muscular dystrophies (LGMD) are a collection of genetic diseases united in their phenotypical expression of pelvic and shoulder area weakness and wasting. More than 30 subtypes have been identified, five dominant and 26 recessive. The increase in the characterization of new genotypes in the family of LGMDs further adds to the heterogeneity of the disease. Meanwhile, better understanding of the phenotype led to the reconsideration of the disease definition, which resulted in eight old subtypes to be no longer recognized officially as LGMD and five new diseases to be added to the LGMD family. The unique variabilities of LGMD stem from genetic mutations, which then lead to protein and ultimately muscle dysfunction. Herein, we review the LGMD pathway, starting with the genetic mutations that encode proteins involved in muscle maintenance and repair, and including the genotype-phenotype relationship of the disease, the epidemiology, disease progression, burden of illness, and emerging treatments."
+ }
+}

34385517.json

@@ -0,0 +1,8 @@
+{
+ "id": "34385517",
+ "label": 0,
+ "article": {
+  "id": "34385517",
+  "text": "Cohen syndrome (CS) is a rare syndromic form of rod-cone dystrophy. Recent case reports have suggested that cystoid maculopathy (CM) could affect CS patients with an early onset and high prevalence. Our study aims at improving our understanding and management of CM in CS patients through a retrospective case series of ten CS patients with identified pathogenic variants in VPS13B. Longitudinal optical coherence tomography (OCT) imaging was performed and treatment with carbonic anhydrase inhibitors (CAI) was provided to reduce the volume of cystoid spaces. CM affected eight out of ten patients in our cohort. The youngest patient showed a strong progression of macular cysts from the age of 4.5 to 5 years despite oral CAI medication. Other teenage and young adult patients showed stable macular cysts with and without treatment. One patient showed a moderate decrease of cystoid spaces in the absence of treatment at 22 years of age. Through a correlative analysis we found that the volume of cystoid spaces was positively correlated to the thickness of peripheral and macular photoreceptor-related layers. This study suggests that CAI treatments may not suffice to improve CM in CS patients, and that CM may resolve spontaneously during adulthood as photoreceptor dystrophy progresses."
+ }
+}

34472379.json

@@ -0,0 +1,8 @@
+{
+ "id": "34472379",
+ "label": 0,
+ "article": {
+  "id": "34472379",
+  "text": "Limb-girdle muscular dystrophies (LGMDs) represent a major group of muscle disorders. Treatment is sorely needed and currently expanding based on safety and efficacy adopting principles of single-dosing gene therapy for monogenic autosomal recessive disorders. Gene therapy has made in-roads for LGMD and this review describes progress that has been achieved for these conditions. This review first provides a background on the definition and classification of LGMDs. The major effort focuses on progress in LGMD gene therapy, from experimental studies to clinical trials. The disorders discussed include the LGMDs where the most work has been done including calpainopathies (LGMD2A/R1), dysferlinopathies (LGMD2B/R2) and sarcoglycanopathies (LGMD2C/R5, LGMD2D/R3, LGMD2E/R4). Early success in clinical trials provides a template to move the field forward and potentially apply emerging technology like CRISPR/Cas9 that may enhance the scope and efficacy of gene therapy applied to patient care."
+ }
+}

34513757.json

@@ -0,0 +1,8 @@
+{
+ "id": "34513757",
+ "label": 0,
+ "article": {
+  "id": "34513757",
+  "text": "Zellweger spectrum disorder (ZSD) is a heterogeneous group of autosomal recessive disorders characterized by a defect in peroxisome formation and attributable to mutations in the gene family. Patients with ZSD have profound neurologic impairments, including seizures, severe retardation, and dysmorphic features, and poor prognosis. Currently, there is no specific, effective treatment. Here, we investigated the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on -related ZSD. The suspected clinical proband was first diagnosed at the Department of Neurology of our hospital. The proband died soon after diagnosis, and his family was studied. We found that a brother had the same genetic alterations, and he was diagnosed with Infantile Refsum disease (IRD) as the mildest form of ZSD. We implemented treatment with allo-HSCT, at the request of the child's parents. After transplantation, we observed significant improvements in the clinical manifestations, very-long-chain fatty acids, and brain MRI. The patient has recovered well and not showed any abnormal clinical manifestations after 2 years of follow-up. We have achieved satisfactory short-term results in the treatment of ZSD-IRD with allo-HSCT. Long-term follow-up and observation will be performed to determine the long-term prognosis."
+ }
+}

34514031.json

@@ -0,0 +1,8 @@
+{
+ "id": "34514031",
+ "label": 0,
+ "article": {
+  "id": "34514031",
+  "text": "Limb girdle muscular dystrophy (LGMD) 2A/R1, caused by mutations in the gene and CAPN3 loss of function, is known to play a role in disease pathogenicity. In this study, AAVrh74.tMCK.CAPN3 was delivered systemically to two different age groups of CAPN3 knockout (KO) mice; each group included two treatment cohorts receiving low (1.17 × 10 vg/kg) and high (2.35 × 10 vg/kg) doses of the vector and untreated controls. Treatment efficacy was tested 20 weeks after gene delivery using functional (treadmill), physiological ( muscle contractility assay), and histopathological outcomes. AAV.CAPN3 gene therapy resulted in significant, robust improvements in functional outcomes and muscle physiology at low and high doses in both age groups. Histological analyses of skeletal muscle showed remodeling of muscle, a switch to fatigue-resistant oxidative fibers in females, and fiber size increases in both sexes. Safety studies revealed no organ tissue abnormalities; specifically, there was no histopathological evidence of cardiotoxicity. These results show that gene replacement therapy improved the phenotype in the CAPN3 KO mouse model at both doses independent of age at the time of vector administration. The improvements were supported by an absence of cardiotoxicity, showing the efficacy and safety of the AAV.CAPN3 vector as a potential gene therapy for LGMDR1."
+ }
+}

34593652.json

@@ -0,0 +1,8 @@
+{
+ "id": "34593652",
+ "label": 0,
+ "article": {
+  "id": "34593652",
+  "text": "A teenage girl had the rare combined phenotype of xeroderma pigmentosum and trichothiodystrophy, resulting from mutations in the XPD (ERCC2) gene involved in nucleotide excision repair (NER). After treatment with antibiotics, including metronidazole for recurrent infections, she showed signs of acute and severe hepatotoxicity, which gradually resolved after withdrawal of the treatment. Cultured skin fibroblasts from the patient revealed cellular sensitivity to killing by metronidazole compared with cells from a range of other donors. This reveals that the metronidazole sensitivity was an intrinsic property of her cells. It is well recognized that patients with Cockayne syndrome, another NER disorder, are at high risk of metronidazole-induced hepatotoxicity, but this had not been reported in individuals with other NER disorders. We would urge extreme caution in the use of metronidazole in the management of individuals with the xeroderma pigmentosum and trichothiodystrophy overlap or trichothiodystrophy phenotypes."
+ }
+}