Tag: nevin manimala

Eur J Pediatr. 2023 Dec 23. doi: 10.1007/s00431-023-05376-4. Online ahead of print.

ABSTRACT

Biotinidase deficiency (BD) is an autosomal recessive inherited metabolic disorder which results from the inability of biotin-dependent carboxylase enzymes to function due to the release and absorption of biotin, leading to neurological and cutaneous findings. In the present study, evaluation of demographic characteristics, clinical findings, laboratory results, molecular genetic characteristics, and genotype-phenotype correlations of cases with BD. Two hundred forty-seven cases were included in the study who were admitted to the Department of Pediatric Metabolism of Ankara Bilkent City Hospital after being identified with potential BD through the Newborn Screening Program (NBS), during family screening or based on suspicious clinical findings, or following the detection of a pathogenic variant in a BTD genetic analysis during the period of October 2020 and February 2022. The medical files of the cases were reviewed retrospectively. An analysis of the admission routes of all cases to our clinic revealed 89.5% NBS, 5.7% family screening, and 4.9% suspicious clinical findings suggestive of BD. Complete enzyme deficiency was identified in 19.8%, partial enzyme deficiency in 55.1%, and heterogenous enzyme deficiency in 9.7%. The most common pathogenic variants were c.1270G > C (p.Asp424His), c.410G > A (p.Arg137His), and c.38_44delGCGCTGinsTCC (p.Cys13Phefs*36) in BTD gene. The c.1270G > C variant was most common in patients with cutaneous symptoms. The c.410G > A and c.38_44delGCGCTGinsTCC variants were more common in the patients with neurological symptoms. The mean activity level in patients with the c.1270G > C homozygous variant was statistically significantly higher than the mean activity level in the c.1270G > C compound heterozygous patients and the activity level of patients without the c.1270G > C variant. The mean activity level in c.410G > A homozygous patients was statistically significantly lower than the mean activity level of the c.410G > A compound heterozygous patients and the activity level of patients without the c.410G > A variant. In the course of our study, four new pathogenic variants were detected, namely: c.190G > A (p.Glu64Lys), c.249 + 5G > T, c.228delA (p.Val77*), and c.682A > G (p.Ile228Val). Conclusions: The present study has determined the clinical and genetic spectrum of a large group of patients with BD in a single center. The frequent mutations in our study were similar to those reported in literature, and four novel variants were also described. What is Known: • Biotinidase deficiency is an autosomal recessive, treatable inborn error of metabolism. Two hundred ninety-four pathogenic variants in the BTD gene have been identified and the c.1270G > C variant is the most frequent BTD gene mutation in both Turkey and around the world. What is New: • Four new pathogenic variants (c.190G > A, p.Glu64Lys; c.249 + 5G > T; c.228delA, p.Val77*; and c.682A > G, p.Ile228Val) have been identified. It is believed that the c.38_44delGCGGCTGinsTCC variant is more commonly seen in individuals with ocular issues; however, further genotype-phenotype correlations are needed.

PMID:38141137 | DOI:10.1007/s00431-023-05376-4

J Neurol. 2023 Dec 23. doi: 10.1007/s00415-023-12128-9. Online ahead of print.

ABSTRACT

OBJECTIVE: The objective of this study was to investigate the factors influencing relapse and prognosis in patients with primary autoimmune cerebellar ataxia (PACA), an area previously not well understood.

METHODS: This prospective cohort study included patients who satisfied the modified diagnostic criteria of PACA. A modified Rankin scale score ≤ 2 at the last follow-up was defined as a favorable prognosis. Cox and Logistic regression were utilized to identify relapsing and prognostic factors, respectively.

RESULTS: A total of 68 patients were included and 35.3% were male. The median onset age was 42.9 years (IQR 22.1-54.0). Neuronal autoantibodies were detected in 33 (50.8%) patients. Of the 65 patients who received first-line immunotherapy, 55 (84.6%) were responsive and 10 (15.4%) were not. Responsiveness to first-line immunotherapy emerged as an independent factor for favorable prognosis (HR 16.762; 95% CI 2.877-97.655; p = 0.002), as did the absence of peripheral neuropathy/radiculopathy (HR 14.286; 95% CI 2.41-83.333; p = 0.003). Relapses occurred in 19 (27.9%) patients. Onset age ≤ 43 years (HR 5.245; 95% CI 1.499-18.35; p = 0.009), presence of peripheral neuropathy/radiculopathy (HR 4.280; 95% CI 1.622-11.298; p = 0.003) and elevated cerebrospinal fluid (CSF) protein concentration (HR 3.443; 95% CI 1.083-10.951; p = 0.036) were statistically significant relapsing factors.

CONCLUSION: This study identified younger onset age, presence of peripheral neuropathy/radiculopathy and elevated CSF protein concentration as relapsing factors, and absence of peripheral neuropathy/radiculopathy and responsiveness to first-line immunotherapy as independent factors for favorable prognosis in PACA patients. These findings may guide individualized treatment strategies and potentially improve patient outcomes.

PMID:38141127 | DOI:10.1007/s00415-023-12128-9

Appl Health Econ Health Policy. 2023 Dec 23. doi: 10.1007/s40258-023-00856-y. Online ahead of print.

NO ABSTRACT

PMID:38141116 | DOI:10.1007/s40258-023-00856-y

Clin Oral Investig. 2023 Dec 23;28(1):19. doi: 10.1007/s00784-023-05397-1.

ABSTRACT

OBJECTIVES: Low-frequency, low-intensity ultrasound is commonly utilized in various dental research fields to remove biofilms from surfaces, but no clear recommendation exists in dental studies so far. Therefore, this study aims to optimize the sonication procedure for the dental field to efficiently detach bacteria while preserving viability.

MATERIALS AND METHODS: Initial biofilm was formed in vivo on bovine enamel slabs (n = 6) which were worn by four healthy participants for 4 h and 24 h. The enamel slabs covered with biofilm were then ultrasonicated ex vivo for various time periods (0, 1, 2, 4, 6 min). Colony-forming units were determined for quantification, and bacteria were identified using MALDI-TOF. Scanning electron microscopic images were taken to also examine the efficiency of ultrasonications for different time periods.

RESULTS: Ultrasonication for 1 min resulted in the highest bacterial counts, with at least 4.5-fold number compared to the non-sonicated control (p < 0.05). Most bacteria were detached within the first 2 min of sonication, but there were still bacteria detached afterwards, although significantly fewer (p < 0.0001). The highest bacterial diversity was observed after 1 and 2 min of sonication (p < 0.03). Longer sonication periods negatively affected bacterial counts of anaerobes, Gram-negative bacteria, and bacilli. Scanning electron microscopic images demonstrated the ability of ultrasound to desorb microorganisms, as well as revealing cell damage and remaining bacteria.

CONCLUSIONS: With the use of low-frequency, low-intensity ultrasound, significantly higher bacterial counts and diversity can be reached. A shorter sonication time of 1 min shows the best results overall.

CLINICAL RELEVANCE: This standardization is recommended to study initial oral biofilms aged up to 24 h to maximize the outcome of experiments and lead to better comparability of studies.

PMID:38141103 | DOI:10.1007/s00784-023-05397-1

J Nephrol. 2023 Dec 23. doi: 10.1007/s40620-023-01818-2. Online ahead of print.

ABSTRACT

BACKGROUND: Sotagliflozin is a dual sodium-glucose co-transporter 1 and 2 inhibitor that increases glucosuria and natriuresis in patients with type 2 diabetes mellitus (T2DM). However, the safety and efficacy in patients with concomitant chronic kidney disease (CKD) remains unclear. Therefore, we aimed to conduct a meta-analysis to evaluate the current evidence in this regard.

METHODS: We searched PubMed, Embase, Cochrane, and Web of Science for randomized controlled clinical trials on the safety and efficacy of Sotagliflozin in patients with T2DM and CKD compared with placebo. Statistical analysis was performed using RevMan 5.4. Heterogeneity was assessed with I² statistics. The study was recorded in PROSPERO registry (CRD42023449631). RESULTS : We included three studies totaling 11,648 patients followed for 15.7 ± 5.9 months. Reduction in HbA₁C (mean difference – 0.33%; 95% CI [- 0.54, – 0.11]; p = 0.003; I² = 100%) and weight (mean difference – 1.01 kg; 95% CI [- 1.17, – 0.86]; p < 0.00001; I² = 96%) were significantly higher in the Sotagliflozin group compared with placebo. All-cause mortality (RR 0.98; 95% CI [0.81, 1.20]; p = 0.87; I² = 0%) and major adverse cardiovascular events (RR 0.70; 95% CI [0.40, 1.21]; p = 0.20; I² = 39%) were not significantly different between groups. However, estimated glomerular filtration rate reduction (mean difference – 0.95; 95% CI [- 1.32, – 0.58]; p < 0.00001; I² = 98%), genital mycotic infections (RR 2.73; 95% CI [1.96, 3.79]; p < 0.00001; I² = 0%), diarrhea (RR 1.42; 95% CI [1.24. 1.63]; p < 0.00001; I² = 0%) and volume depletion (RR 1.31; 95% CI [1.11, 1.56]; p = 0.002; I² = 0%) were more common with Sotagliflozin.

CONCLUSIONS: In patients with T2DM and CKD, Sotagliflozin appears to be effective for glycemic control and weight loss. Although the medication seemed safe concerning mortality and cardiovascular events, it induced estimated glomerular filtration rate reduction, and was associated with a higher risk of genital mycotic infections, diarrhea, and volume depletion.

PMID:38141092 | DOI:10.1007/s40620-023-01818-2

Mikrochim Acta. 2023 Dec 23;191(1):48. doi: 10.1007/s00604-023-06137-8.

ABSTRACT

The synergistic armor-etching (SAE) approach was proposed using natural organic weak acid (tannic acid, i.e., TA) for the controllable assembly of hollow and interpenetrated HZIF-8@MWCNTs hybrid nanomaterial (ZIF-8, zeolitic imidazolate framework-8; MWCNTs, multi-walled carbon nanotubes), which exhibited highly ordered crystal structure and unique morphological characteristics. The SAE strategy not only can rapidly etch solid ZIF- material into a hollow structure (~ 10 min), but also form the TA shell (~ 33 nm) on its surface. Then, the HZIF-8@MWCNTs electrochemical sensor was constructed for selective and sensitive detection of the target molecule (dopamine, DA). A sequence of studies indicated that the fabricated TA coating was capable of promoting the spread of DA into the reactive centers of hollow MOF and MWCNTs, which exhibited outstanding electroanalytical characteristics through the synergistic effect. The DPV oxidation peak of DA was strongest at 50 mV vs. Ag/AgCl reference electrode. Under the optimal conditions, there are two linear dynamic ranges of current response of 0.01 ~ 10 and 10 ~ 550 µmol L^{– 1} with a detection limit of 0.003 µmol·L^{– 1} (S/N = 3). Simultaneously, the HZIF-8@MWCNTs electrochemical sensor could detect low levels of DA in real products. The recoveries of the actual sample tests were between 98.2% and 102%, and the relative standard deviation (R.S.D.) of all studies was less than 3.0%. The statistical analyses (F-test and t-test) were employed to demonstrate the accuracy of method developed. This work will enlighten researchers operating in the domain of MOFs composites, accelerating the advancement of electrochemical sensing on the basis of hollow MOFs materials.

PMID:38141091 | DOI:10.1007/s00604-023-06137-8

Endocrine. 2023 Dec 23. doi: 10.1007/s12020-023-03637-8. Online ahead of print.

ABSTRACT

BACKGROUND: Machine learning is increasingly recognized as a viable approach for identifying risk factors associated with diabetic kidney disease (DKD). However, the current state of real-world research lacks a comprehensive systematic analysis of the predictive performance of machine learning (ML) models for DKD.

OBJECTIVES: The objectives of this study were to systematically summarize the predictive capabilities of various ML methods in forecasting the onset and the advancement of DKD, and to provide a basic outline for ML methods in DKD.

METHODS: We have searched mainstream databases, including PubMed, Web of Science, Embase, and MEDLINE databases to obtain the eligible studies. Subsequently, we categorized various ML techniques and analyzed the differences in their performance in predicting DKD.

RESULTS: Logistic regression (LR) was the prevailing ML method, yielding an overall pooled area under the receiver operating characteristic curve (AUROC) of 0.83. On the other hand, the non-LR models also performed well with an overall pooled AUROC of 0.80. Our t-tests showed no statistically significant difference in predicting ability between LR and non-LR models (t = 1.6767, p > 0.05).

CONCLUSION: All ML predicting models yielded relatively satisfied DKD predicting ability with their AUROCs greater than 0.7. However, we found no evidence that non-LR models outperformed the LR model. LR exhibits high performance or accuracy in practice, while it is known for algorithmic simplicity and computational efficiency compared to others. Thus, LR may be considered a cost-effective ML model in practice.

PMID:38141061 | DOI:10.1007/s12020-023-03637-8

Int J Geriatr Psychiatry. 2023 Dec;38(12):e6042. doi: 10.1002/gps.6042.

ABSTRACT

INTRODUCTION: HIV-associated neurocognitive disorders (HAND) are a spectrum of cognitive impairments in chronic HIV infection. HAND is common in sub-Saharan Africa (SSA), despite combination antiretroviral therapy (cART). Older people appear to be at increased risk. It is unknown if cognitive reserve (CR), which is protective in neurodegenerative dementias, protects against HAND.

OBJECTIVE: To evaluate the association of CR and risk of HAND in an older cART-treated population in SSA.

METHODS: Cross-sectional observational study completed in hospital outpatient clinics in Southwest Tanzania. We assessed HIV-positive participants aged ≥50 years established on cART using a neuropsychological test battery, functional assessment, informant history and depression screen. Control participants were HIV-negative individuals attending chronic disease clinics. We used operationalised Frascati criteria for HAND diagnosis. CR was measured using the Cognitive Reserve Index (CRI) and other proxy measures.

RESULTS: The prevalence of HAND was 64.4% (n = 219/343). Lower CRI score [odds ratio (OR) = 0.971, p = 0.009] and less formal education (OR = 4.364, p = 0.026) were independent risk factors for HAND but HIV-severity measures were not. Unemployment and low-skilled manual work were associated with increased risk of HAND in bivariate analysis but not in multivariable analysis.

CONCLUSIONS: Higher total CRI score and more formal education appeared to be protective against HAND, in this cohort. Potentially, cognitively and socially stimulating activities and exercise could increase cognitive reserve in later life. Cognitive reserve could possibly be more important than HIV-disease severity in risk of HAND in older people with treated HIV.

PMID:38141048 | DOI:10.1002/gps.6042

J Public Health (Oxf). 2023 Dec 21:fdad277. doi: 10.1093/pubmed/fdad277. Online ahead of print.

ABSTRACT

BACKGROUND: During the pandemic, countries utilized various forms of statistical estimations of coronavirus disease-2019 (COVID-19) impact. Differences between databases make direct comparisons and interpretations of data in different countries a challenge. We evaluated country-specific approaches to COVID-19 data and recommended changes that would improve future international collaborations.

METHODS: We compared the COVID-19 reports presented on official UK (National Health System), Israeli (Department of Health), Latvian (Center for Disease Prevention and Control) and USA (Centers for Disease Control and Prevention) health authorities’ websites.

RESULTS: Our analysis demonstrated critical differences in the ways COVID-19 statistics were made available to the general and scientific communities. Specifically, the differences in approaches were found in the presentation of the number of infected cases and tests, and percentage of positive cases, the number of severe cases, the number of vaccinated, and the number and percent of deaths.

CONCLUSION: Findability, Accessibility, Interoperability and Reusability principles could guide the development of essential global standards that provide a basis for communication within and outside of the scientific community.

PMID:38141038 | DOI:10.1093/pubmed/fdad277

Stress Health. 2023 Dec 23. doi: 10.1002/smi.3360. Online ahead of print.

ABSTRACT

The COVID-19 pandemic has led to economic turndowns, social restrictions, and family life alterations. The stress induced by the public health crisis and its consequences are beginning to be explored. This study examined stress experiences since the pandemic’sonset in work, financial, social, and health domainsamong a large sample of post-9/11, United States military veterans. The sample, who separated from active-duty service or deactivated from active status in a reserve component in 2016, completed an online survey (n = 3180) in 2020. Participants were 70% White non-Hispanic, 81% male, and had an average age of 38 years. Frequencies and descriptive statistics were calculated. Female veterans and veterans of colour reported significantly higher levels of stress across most life domains. The results suggest White, male, post-9/11 veterans may be somewhat protected from COVID-19 stress, but that the pandemic is exacerbatinghealth and social disparities experienced by post-9/11 veterans of colour and female veterans. Supports and comprehensive care, particularly targeted towardsat-risk populations, are likely needed to provide sufficient resources for resiliency during and after the pandemic.

PMID:38141014 | DOI:10.1002/smi.3360