Biotin-thiamine-responsive basal ganglia disease (BTBGD) is a rare autosomal recessive neurometabolic disorder that is caused by biallelic pathogenic SLC19A3 variants and is characterized by subacute ...encephalopathy associated with confusion, convulsions, dysphagia, dysarthria, or other neurological manifestations. A retrospective review of the data registry in Kuwait Medical Genetics Center for all cases diagnosed clinically and radiographically and confirmed genetically with BTBGD. Twenty one cases from 13 different families were diagnosed with BTBGD in Kuwait. Most cases (86%) presented with confusion, dystonia, convulsions, or dysarthria, while three individuals were diagnosed pre-symptomatically during familial targeted genetic screening. Symptoms resolved completely within 2-week of treatment in two-thirds of the symptomatic cases but progressed in six of them to a variety of severe symptoms including severe cogwheel rigidity, dystonia and quadriparesis due to delayed presentation and management. Neuroradiological findings of the symptomatic cases revealed bilateral central changes in the basal ganglia. Two novel homozygous missense SLC19A3 variants were detected in a Kuwaiti and a Jordanian individuals, in addition to the previously reported Saudi founder homozygous variant, c.1264A > G; p.(Thr422Ala) in the remaining cases. Age of diagnosis ranged from newborn to 32 years, with a median age of 2-3 years. All cases are still alive receiving high doses of biotin and thiamine. This is the first study reporting the phenotypic and genotypic spectrum of 21 individuals with BTBGD in Kuwait and describing two novel SLC19A3 variants. BTBGD is a treatable neurometabolic disease that requires early recognition and treatment initiation. This study highlights the importance of performing targeted molecular testing of the founder variant in patients presenting with acute encephalopathy in the region.
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•COSMO-RS calculations performed over more than 36,000 ILs.•Experiments show a strong correlation between PS solubility and battery performance.•Machine learning models developed ...using experiment-guided target solubility limits.•XGBoost models successfully predict the PS solubility and IL properties.•ARM and feature importance analysis show that anion descriptors are more dominant.
The polysulfide (PS) shuttle mechanism (PSM) is one of the most significant challenges of lithium-sulfur (Li-S) batteries in achieving high capacity and cyclability. One way to minimize the shuttle effect is to limit the PS solubilities in the battery electrolyte. Ionic liquids (IL) are particularly suited as electrolyte solvents because of their tunable physical and chemical properties. In this work, thousands of ILs are screened to narrow down potentially viable candidates to be used as electrolytes in Li-S batteries. To that end, the COnductor-like Screening Model for Realistic Solvents (COSMO-RS) calculations are performed over more than 36,000 ILs. An extensive database containing PS solubilities and other relevant properties is constructed at 25 °C. First, the effectiveness of the COSMO-RS calculations is experimentally tested with six different ILs having a wide range of solubility and viscosity values; a strong correlation between the PS solubility and battery performance is obtained. After specifying the target limits for promising ILs using the experimental battery performance data, machine learning (ML) tools are used to predict and identify the relationship between IL properties and PS solubilities and structural and molecular descriptors of ILs. The extreme gradient boosting (XGBoost) method successfully predicts the solubility and property values. Association rule mining (ARM) and the feature importance analysis show that anion descriptors are more dominant, whereas cations have less impact on the solubilities and properties of ILs. Finally, the imidazolium and pyridinium ILs with bis_imide and borate anion groups are identified as the most promising ones.
PPP1R21 encodes for a conserved protein that is involved in endosomal maturation. Biallelic pathogenic variants in PPP1R21 have been associated with a syndromic neurodevelopmental disorder from ...studying 13 affected individuals. In this report, we present 11 additional individuals from nine unrelated families and their clinical, radiological, and molecular findings. We identified eight different variants in PPP1R21, of which six were novel variants. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals. Common findings in 75% of individuals with available brain imaging include delays in myelination, wavy outline of the bodies of the lateral ventricles, and slight prominence of the bodies of the lateral ventricles. PPP1R21‐related neurodevelopmental disorder is associated with a consistent phenotype and should be considered in highly consanguineous individuals presenting with developmental delay/intellectual disability along with coarse facial features.
We present 11 individuals with PPP1R21‐related neurodevelopmental disorder. Global developmental delay and hypotonia are neurological features that were observed in all individuals. There is also a similar pattern of dysmorphic features with coarse faces as a gestalt observed in several individuals.
This work proposes general formulas for designing two different topologies of fractional-order relaxation oscillators. One topology contains an Operational Amplifier and the other one relies on an ...Operational Trans-Resistance Amplifier. The design procedure hinges on the general fractional-order natural and step responses of
RC
, which is proved in this work depending on Mittag Leffler function. The proposed topologies can be controlled to generate symmetrical and non-symmetrical square wave signals. They also benefit from the employment of fractional-order capacitors (FOCs), which makes it possible to obtain higher frequencies using simple components. Furthermore, these topologies are verified through numerical solutions, circuit simulations, and experimental implementations. This encourages the authors to build circuit emulators for the FOC, which is achieved by applying the Foster-I synthesizing technique to the Matsuda’s approximation of
s
α
.
Purpose
Weight reduction can effectively improve nonalcoholic fatty liver disease (NAFLD), which is a constant companion of severe obesity. This study aimed to determine the effect of one-anastomosis ...gastric bypass (OAGB) on pathological liver changes in severely obese cases with NAFLD.
Methods
The present prospective research comprised 67 subjects with morbid obesity scheduled for OAGB during the period from February 2015 to August 2018. Clinical, biological, and histologic data were evaluated pre and 15 months postoperatively.
Results
Fifteen months after surgery, a considerable reduction was noted in the grades of fat deposition, liver cell ballooning, and lobular inflammatory changes, in addition to the total NAS score. Fifteen months after surgery, nonalcoholic steatohepatitis (NASH) disappeared in 42% of the patients. A significant regression of fibrosis stage occurred after surgery in 79.1% of patients (
p
< 0.001). After surgery, patients had substantial reductions in aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, HbA1c, total cholesterol, and Low-density lipoprotein (
p
< 0.001, for all comparisons). Diabetes mellitus, hypertension, and dyslipidemia resolved in 54%, 59%, and 69% of the patients, respectively.
Conclusion
OAGB resolved NASH from nearly 42% of patients and reduced the histological features of NAFLD 15 months after surgery. Bariatric procedures might be adopted as a therapeutic modality in severely obese cases with NAFLD after the failure of lifestyle modifications.
Recently, increasing evidence showed that small-for-size syndrome (SFSS) is a multifactorial disease which is precipitated by various perioperative factors other than graft size. We conducted the ...current work to evaluate perioperative effectors, which can increase the risk of SFSS following adult living-donor liver transplantation (LDLT).
This is a retrospective study on 110 adult cirrhotic cases (mean age of 48.4 ± 6.9 years old) who underwent adult LDLT. Most cases were males (89%). Cases were categorized into two groups based on the occurrence of SFSS. The groups were compared regarding preoperative (gender, age, comorbidities, baseline investigations), intraoperative (mean blood pressure and glucose; mean operation time; number of packed red cells, plasma, platelets, and cryoprecipitate units; time of cold and warm ischemia, and anhepatic phase; preclamping and post-reperfusion portal pressures), and postoperative factors (relevant investigations, hospital stay).
Postoperatively, 23 patients developed SFSS (20.9%). SFSS group had significantly lower preoperative graft recipient weight ratio (GRWR) (0.76 ± 0.1% versus 1.03 ± 0.15, respectively; p < 0.001), and elevated MELD scores (19 ± 2.1 versus 17.9 ± 4; p = 0.024). Preclamping and post-reperfusion portal pressures of ≥22.5 and 17.5 mmHg, exhibited a sensitivity of 95.7% and 91.3% and specificity of 87.4% and 88.9% respectively, for SFSS prediction.
SFSS risk is significantly linked to GRWR, MELD score, and intraoperative portal haemodynamics. Intraoperative portal haemodynamics exhibited good diagnostic accuracy for SFSS prediction and represented promising indicators for the prediction of SFSS.
Introduction and Aim
Recently, the incidence of obesity has been rising exponentially. Clinical studies have demonstrated that different subtypes of pulmonary hypertension (PH) are linked to obesity. ...The current work mainly aims to assess the impact of laparoscopic sleeve gastrectomy (LSG) on PH in a cohort of obese cases.
Patients and Methods
The present prospective work included 37 obese cases with PH for whom LSG was done. Only cases with PH and presurgical right ventricular systolic pressure (RVSP) ≥ 35 mmHg using Doppler echocardiogram were enrolled. Fifteen months later, patients were reassessed regarding new weight and BMI in addition to changes in RVSP.
Results
At the end of follow-up, the average BMI improved from 45.8
+
3.9 to 33.8
+
2.5 Kg/m
2
(
p
value < 0.001). Improved right ventricular (RV) size compared to baseline echo was observed in 20 patients. RV size decreased from 2.68
+
0.44 cm to 2.34
+
0.36 cm (
p
value < 0.001). Notable decrease of PH to less than 30 mmHg occurred in 33 patients. Mean RVSP decreased from 39.62
+
2.1 to 31.81
+
3.1 mmHg (
p
value < 0.001). LSG significantly decreased the requirements for PH drugs and supplemental oxygen therapy.
Conclusion
The current work suggests that LSG-induced weight loss may result in a considerable decrease in pulmonary pressures as well as RV size with a concurrent resolution of other metabolic comorbidities.
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