Microinstability of Major Joints in Movement Disorders: The Hidden Challenge.

Microinstability, characterized by subtle and often painful disturbances in joint stability, significantly impacts individuals engaged in activities requiring extensive ranges of motion, such as dancing or gymnastics, and is particularly prevalent in young female athletes. This condition, resulting from progressive microtrauma, architectural and functional abnormalities, or iatrogenic factors, is challenging to diagnose and often underreported. Understanding the biomechanical nuances of microinstability is essential for accurate diagnosis and effective management. Upper limb joints, including the shoulder, elbow, wrist, and hand, each exhibit unique anatomical and functional characteristics that contribute to their susceptibility to microinstability. Movement disorders, such as Parkinson's disease, essential tremor, dystonia, and cerebral palsy, exacerbate joint instability due to impaired proprioception, altered muscle tone, and uncoordinated muscle contractions. Effective diagnosis involves physical examination techniques and advanced imaging modalities. Therapeutic interventions encompass physical therapy, pharmacological treatments, surgical procedures, and assistive devices, tailored to enhance joint stability and improve the quality of life for affected individuals.

Utilizing a portable magnetic resonance imaging (MRI) in the setting of an acute ischemic stroke in a patient with a cardiac implantable electronic device.

BACKGROUND: Cardiac implantable electronic device (CIED) generally excludes patients from undergoing fixed, high-field magnetic resonance imaging (MRI). Acute ischemic stroke patients undergo MRI as a standard part of an assessment of infarct burden. The use of a portable MRI scanner may be useful in patients who have contraindications to high-field MRI. We present the first case of a patient with a CIED who required an endovascular thrombectomy (EVT) for large vessel occlusion. She underwent a low-field MRI in the operating room with the Hyperfine portable system. CASE: The patient is an 80-year-old female status post-CIED, on Eliquis who presented with an acute ischemic stroke. Her National Institutes of Health Stroke Scale (NIHSS) of 8. Imaging demonstrated a left M2 occlusion on computed tomography angiogram (CTA) of the head and neck. No lytics were used due to concomitant gastrointestinal bleed. While, admitted, her NIHSS increased to 15. A subsequent CTA demonstrated a left internal carotid artery terminus and M1 occlusion. She underwent EVT with thrombolysis in cerebral infarction (TICI) 3 revascularization. An MRI was performed intraoperatively using a Hyperfine system, which is a low-field, portable MRI, to assess infarct volume. CONCLUSION: Hyperfine Swoop brain MRI may be safe for use in patients with contraindications to high-field MRI scans. Continued technological refinement will improve the quality of diffusion-weighted imaging. Larger studies will be required to generalize Hyperfine MRI-based imaging for patients with devices that exclude them from high-field imaging.

The impact of hypertension on clinical outcomes in moyamoya disease: a multicenter, propensity score-matched analysis.

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.

Engineered Amine-Functionalized Metal-Organic Framework to Fabricate a Composite for Next-Generation Asymmetric Supercapacitors with Ultrahigh Performance: Modulating the Energy Storage Barrier.

The present work summarizes the fabrication of an amine-functionalized cadmium-based metal-organic framework (MOF), {[Cd(AT)(BP)]·4DMF}n or Cd_AT-BP, by adopting a simple solvothermal approach using 2-aminoterephthalic acid (AT) as the main linker, while 4,4'-bipyridyl (BP) as an auxiliary linker. The structure of Cd_AT-BP was validated by the single-crystal X-ray diffraction technique that revealed the formation of an overall three-dimensional network with BP acting as a bridge between the 2D sheets of the MOF. The robust framework of Cd_AT-BP decorated with a free amine functional group was utilized for energy storage application. The electrochemical measurements of Cd_AT-BP revealed a maximum areal capacitance of 9.8 mF/cm2 at a scan rate of 5 mV/s. Further, to enhance the practical utility of Cd_AT-BP in energy storage devices, two composites of Cd_AT-BP with reduced graphene oxide (rGO) and multiwalled carbon nanotubes (CNTs), viz., Cd_AT-BP/rGO and Cd_AT-BP/CNT, were prepared by adopting a facile ultrasonication approach. The synthesized Cd_AT-BP/rGO and Cd_AT-BP/CNT composites displayed an impressive areal capacitance of 117 and 37 mF/cm2 (58.5 and 17.5 F/g) at a scan rate of 5 mV/s, respectively, and a capacitance retention of up to 118 and 100% after 5000 cycles at a constant current density of 5 mA/cm2. The highest energy density of about 4.23 mW h/cm2 (2.12 W h/kg) at a current density of 1 mA/cm2 was shown by Cd_AT-BP/rGO among all the three materials attributable to the layered structure of rGO, providing a larger surface area accessible for ion adsorption. Enticed by the remarkable outcomes exhibited by Cd_AT-BP/rGO, we fabricated a two-electrode asymmetric supercapacitor (ASC) device. The developed ASC device revealed energy and power densities of 26.7 mW h/cm2 (13.4 W h/kg) and 3760 mW/cm2 (1880 W/kg), respectively, with a galvanostatic charge-discharge stability of up to 10,000 cycles. The findings identify Cd_AT-BP/rGO as a potential contender for future-generation supercapacitors.

Efficient energy and memory storage capabilities in optimized BiFeO3/MnMoO4/NiFe2O4 triphasic composites for futuristic multistate devices.

The emergence of multiferroic materials particularly bismuth iron oxide (BiFeO3) with distinctive magnetoelectric, and high energy storage capabilities, present pivotal aspects for next-generation memory storage devices. However, intrinsically weak magnetoelectric coupling limits their widespread applications, that can be leap over by the integration of BiFeO3 with enriched ferroelectric, and ferro/ferrimagnetic materials. Here, a series (1 - x)[0.7BiFeO3 + 0.3MnMoO4] + xNiFe2O4 (x = 0.00, 0.03, 0.06, and 0.09) is synthesized via citrate-gel based self-ignition, and solid-state reaction routes. Phase purity and crystallinity of tri-phase composites with surfaces revealing random and arbitrarily shaped grains are assured by X-ray diffraction, and field emission scanning electron microscopy, respectively. Dielectric studies illustrated non-linear trend for broad range of frequencies as predicted by Maxwell-Wagner theory along with single semicircle arcs in Nyquist plots that exposes grain boundaries effect. An enriched 68.42% of ferroelectric efficiency is featured for x = 0.06 substitutional contents, while magnetic computations demonstrated improved saturation magnetization (M s), remanence magnetization (M r), and coercive applied magnetic field (H c) values as 5.87 emu g-1, 0.96 emu g-1, and 215.19 Oe, respectively for x = 0.09 phase-fraction. The intriguing linear trends of magnetoelectric coupling for all the compositions are corroborating them propitious contenders for futuristic multistate devices.

Graphene oxide nanoribbons conjugated with 1, 2-distearoyl-sn-glycero-3 phosphoethanolamine-poly (ethylene glycol)-transferrin enhanced targeted delivery and cytotoxicity of raloxifene against breast cancer.

The clinical utility of raloxifene (RLX), a selective estrogen receptor modulator (SERM), has been compromised by severe side effects and unfavorable drug properties. To address these, a transferrin (Tf) conjugated graphene oxide nanoribbon (GONR) platform was tried for RLX. The stability of GONRs in biological media was improved by surface modification with 1, 2-Distearoyl-sn-glycero-3 phosphoethanolamine-Poly (ethylene glycol) (DSPE-PEG). The Tf molecule was covalently attached to DSPE-PEG (DPT) using EDC-NHS chemistry. The surface of GONR was then modified with DSPE-PEG (DP) or DPT and loaded with RLX (GDP-RLX and GDPT-RLX). The final formulations were characterized for drug loading and stability. The anticancer activities of pure RLX, GDP-RLX, and GDPT-RLX were evaluated and compared in all the in vitro and in vivo studies. In vitro cell line studies showed that GDPT-RLX have significantly high cytotoxicity, cellular uptake, apoptosis induction, G2/M phase arrest, anti-migration properties, and apoptotic protein expression, followed by GDP-RLX and RLX. Pharmacokinetics and tumor biodistribution were also found to be excellent with GDPT-RLX. The in vivo tumor therapy and tumor evaluation outcomes were also consistent with the in vitro data. The Tf conjugated GDPT-RLX represents a promising approach for targeted and sustained delivery of RLX with enhanced therapeutic efficacy.

ROTEM and von Willebrand Factor in COVID patients presenting with acute ischemic stroke: A case series: ROTEM and von Willebrand Factor in COVID-19 Related Stroke.

OBJECTIVES: SARS-CoV-2 (COVID) induces systemic thrombotic complications including acute ischemic stroke. In this case series, we report markers of inflammation, coagulation factors including von Willebrand factor antigen, and rotational thromboelastometry (ROTEM) data. MATERIALS AND METHODS: Retrospective case series of COVID patients seen at a single comprehensive stroke center between 2020-2022. For patients undergoing mechanical thrombectomy (MT), ROTEM data was collected during the procedure and analyzed on ROTEM delta system. RESULTS: Fifteen patients (33.3% female) median age 65-years-old presented with COVID and acute ischemic stroke. Thirteen had LVO. The mean NIHSS was 15 (range 0-35) on admission and 18 (0-42) at discharge. Most were cryptogenic (N=7, 46.7%), followed by cardioembolic (N=6, 40%) and large artery-to-artery embolization (N=2, 13.3%). mRS was < 3 in 8 (53%) patients at discharge. None of the patients were on anticoagulation, and five were on antiplatelet therapy pre-hospitalization. Seven received thrombolytics with alteplase (tPA), and 10 had MT. Baseline platelet count was 102 K/uL (range 102-291 K/uL). vWF was measured in 12 patients, all elevated, with seven having levels >400 (180%). ROTEM data was collected in six patients. Three who received tPA had abnormal EXTEM and FIBTEM data (CT extem > 85secs, A10 EXTEM < 45mm, and A10 FIBTEM < 10mm). Notably, INTEM (CT INTEM >208secs) was abnormal in five of the six patients, two of whom did not receive tPA. CONCLUSIONS: Elevated vWF antigen levels with abnormal ROTEM data suggests that COVID induces changes in the clotting cascade. More robust research is needed to investigate these findings. Thrombolytics, MT, and antiplatelet agents should be utilized to treat COVID-related ischemic stroke based on current clinical guidelines.

Decompressive craniectomy in symptomatic intracerebral hemorrhage after ischemic stroke: a multicenter retrospective cohort study.

OBJECTIVE: Symptomatic intracerebral hemorrhage (sICH) after stroke is a devastating neurological complication. Current guidelines support a "possible benefit" of decompressive craniectomy (DC) for large supratentorial sICH with significant mass effect. METHODS: The authors conducted a retrospective study of 8 comprehensive stroke centers. They included all patients who sustained an sICH after acute ischemic stroke (AIS), as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), from January 2016 to December 2020. They compared patients who underwent DC to those who were treated with standard medical treatment to measure functional outcome at 90 days, primarily as defined by the modified Rankin Scale (mRS) and secondarily by the Glasgow Outcome Scale-Extended (GOS-E). RESULTS: Eighty-five patients were identified, 26 of whom (30.5%) underwent DC. Patients who underwent DC were younger (58 years [DC] vs 76 years [no DC], p < 0.001). No patient with a previous history of cancer underwent DC (n = 14, p = 0.004). Twenty-five patients (96.2%) in the DC group underwent thrombectomy versus 54 (91.5%) in the non-DC group (p = 0.443). Patients who underwent DC had a longer ICU stay (median [IQR] 240 [38-408] hours vs 24 [5-96] hours in non-DC patients, p = 0.002). At 90 days, 3 patients (4.1%) had obtained an mRS score of 0-2 and 10 patients (11.7%) an mRS score of 0-3. Patients who had improved functional outcome were younger (mRS score, OR 1.06, 95% CI 1.01-1.10, p = 0.012). Patients with a history of cancer had worse 90-day mRS scores (OR 8.49, 95% CI 1.54-159, p = 0.046). The rate of in-hospital mortality or discharge to hospice was significantly higher in the non-DC cohort (10 [38.5%] patients in the DC cohort vs 38 [64.4%] in the non-DC cohort, p = 0.026). Ninety days later, patients who underwent DC were more likely to have improved outcome (mRS mean rank 30.0 vs 40.0, p = 0.027). In multivariable analysis, history of cancer (OR 12.2, 95% CI 1.26-118, p = 0.031) and older age (OR 1.07, 95% CI 1.02-1.13, p = 0.011) increased the odds of worse mRS outcomes while DC did not (OR 1.34, 95% CI 0.357-5.03, p = 0.665). CONCLUSIONS: DC after sICH did not improve functional outcome at 90 days according to multivariable analysis, although younger age and absence of previous cancer history were associated with improved outcomes.

Expedited liver transplantation as first-line therapy for severe alcohol hepatitis: ELFSAH; deferring corticosteroids in the sickest subset of patients.

BACKGROUND & AIMS: Severe alcohol-associated hepatitis (SAH) represents a lethal subset of alcohol-associated liver disease. Although corticosteroids are recommended by guidelines, their efficacy and safety remain questionable and so liver transplantation (LT) has been increasingly utilized. The timing and indication of corticosteroid use, specifically in patients being considered for LT requires further clarification. METHODS: A retrospective analysis was conducted on 256 patients with SAH between 2018 and 2022 at a single US center. RESULTS: Twenty of these patients underwent LT. Of the 256 patients, 38% had what we termed "catastrophic" SAH, defined as a MELD-Na ≥35 and/or discriminant function (DF) ≥100, which carried a mortality of 90% without LT. Compared with 100 matched controls, patients undergoing LT exhibited a one-year survival rate of 100% versus 35% (p < .0005). LT provided an absolute risk reduction of 65%, with a number needed to treat of 1.5. Steroid utilization in the entire cohort was 19% with 60% developing severe complications. Patients administered steroids were younger with lower MELD and DF scores. Only 10% of those prescribed steroids derived a favorable response. Sustained alcohol use post-LT was 20%. CONCLUSIONS: We propose ELFSAH: Expedited LT as First Line Therapy for SAH; challenging the current paradigm with recommendations to defer steroids in patients with "catastrophic" SAH (defined as: MELD-Na ≥35 and/or DF ≥100). Patients should be seen urgently by hepatology, transplant surgery, psychiatry and social work. Patients without an absolute contraindication should be referred for LT as first-line therapy during their index admission.

Molecular investigation of vitamin D receptor (VDR) genetic variants and their impact on VDR mRNA and serum vitamin D levels in allergic rhinitis in an Indian population: A case-control study.

Vitamin D deficiency is widespread and poses a significant health concern, as emerging research links it to allergic diseases owing to its immunomodulatory functions. The optimal functioning of vitamin D and its activation depend on its nuclear receptor, vitamin D receptor (VDR). Genetic variants of VDR have been explored as potential factors in autoimmune and allergic diseases, with limited studies on their association with allergic rhinitis (AR). The present investigation aims to analyse the role of three VDR genetic variants - TaqI, FokI and BsmI - in AR susceptibility and their impact on VDR mRNA and serum vitamin D levels. A total of 550 subjects, consisting of 250 AR cases and 300 age- and gender-matched controls, underwent genotyping by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). VDR mRNA and vitamin D levels were determined by quantitative real-time PCR and chemiluminescence, respectively. Although TaqI did not exhibit significant differences, FokI demonstrated a noteworthy association with AR, particularly with the CC genotype (odds ratio [OR]: 3.34; confidence interval [CI]: 1.79-6.23). Similarly, BsmI revealed an increased risk for AR, with the GA + AA genotypes showing a 2.2-fold elevated risk (OR: 2.20; CI: 1.53-3.16). VDR mRNA expression was threefold lower in AR patients (p < .0001), accompanied by reduced serum vitamin D levels (p < .0001). In addition, CC (p = .01) and AA (p = .02) genotypes of FokI and BsmI were associated with reduced VDR mRNA levels, whereas TaqI showed no such association. Similarly, heterozygous genotypes of TaqI and FokI, as well as homozygous AA of BsmI, correlated with lower serum vitamin D levels (p < .001). This study emphasizes the intricate relationship among VDR genetic variations, altered VDR activity, immune modulation and vitamin D metabolism in AR. Further research involving diverse populations is crucial for confirming and generalizing these findings, paving the way for personalized therapeutic interventions in vitamin D-related disorders.

Diffusion-Weighted Imaging Fluid-Attenuated Inversion Recovery Mismatch on Portable, Low-Field Magnetic Resonance Imaging Among Acute Stroke Patients.

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.

The Brain Injury Guidelines (BIG) and emergency department observation and admission rates: A retrospective cohort study.

BACKGROUND: Emergency Department (ED) Observation Units (OU) can provide safe, effective care for low risk patients with intracranial hemorrhages. We compared current ED OU use for patients with subdural hematomas (SDH) to the validated Brain Injury Guidelines (BIG) to evaluate the potential impact of implementing this risk stratification tool. METHODS: Retrospective cohort of patients ≥18 years old with SDH of any cause from 2014 to 2020 to evaluate for potential missed OU cases. Missed OU cases were defined as patients with an initial Glasgow Coma Score (GCS) of 15 with hospital length of stays (LOS) <2 days, who did not meet the composite outcome and were not cared for in the OU or discharged from the ED. Composite outcome included in-hospital death or transition to hospice care, neurosurgical intervention, GCS decline, and worsening SDH size. Secondary outcomes were whether application of BIG would increase ED OU use or reduce CT use. RESULTS: 264 patients met inclusion criteria over 5.3 year study timeframe. Mean age was 61 years (range 19-93) and 61.4% were male. SDH were traumatic in 76.9% and 60.2% of the cohort had additional injuries. The admission rate was 81.4% (n = 215). Fourteen (6.5%) missed OU cases were identified (2.6/year). Retrospective application of BIG resulted in 82.6% (n = 217) at BIG 3, 10.2% (n = 27) at BIG 2 and 7.6% (n = 20) at BIG 1. Application of BIG would not have decreased admission rates (82.6% BIG 3) and BIG 1 and 2 admissions were often for medical co-morbidities. The composite outcome was met in 50% of BIG 3, 22% of BIG 2, and no BIG 1 patients. CONCLUSION: In a level 1 trauma center with an established observation unit, current clinical care processes missed very few patients who could be discharged or placed in ED OU for SDH. Hospital admissions in BIG 1/2 were driven by co-morbidities and/or injuries, limiting applicability of BIG to this population.

Optimization of switching charge and recoverable energy density mediated by structural transformation in Sr-substituted BaNiO3 perovskites.

Because of their distinctive characteristics, ferroelectric perovskites are considered among the most potent and auspicious candidates for energy storage and pulsed power devices. But their energy storage properties and switching capabilities need to be further enhanced which can be done by substitutions of appropriate cations. Hence, a series of lead-free Ba1-xSrxNiO3 (x = 0.00, 0.33, 0.67, and 1.00) ceramics was fabricated using a sol-gel auto combustion technique. Rietveld's refinement of X-ray diffraction plots verified the complete development of the required hexagonal perovskite structure. Scanning electron microscopy images revealed a gradual increase in average grain sizes and agglomeration with the increase in Sr-content. Moreover, the existence of all the constituent elements exactly in proportion to their stoichiometric ratios was verified by energy dispersive X-ray spectroscopy. The characteristic parameters of ferroelectric materials such as ferroelectric response, electrical conductivity, and switching charge density were also determined. The P-E loops indicated that with the increase in Sr-content, the coercive field, remanent polarization, and maximum polarization all decreased gradually, but the recoverable energy density (Wrec) increased as the loops became slimmer. The maximum value of Wrec was found in the Ba0.33Sr0.67NiO3 sample. Moreover, SrNiO3 exhibited minimum energy loss with the highest efficiency of ∼47.21%. The existence of a current barrier in all the samples was proved from the low leakage current values (∼10-7 A). In addition, the pure SrNiO3 showed a low electrical conductivity and minimum value of switching charge density. All these findings make SrNiO3 a promising candidate for fast switching and energy storage applications.

Biallelic loss-of-function variants of ZFTRAF1 cause neurodevelopmental disorder with microcephaly and hypotonia.

PURPOSE: Neurodevelopmental disorders exhibit clinical and genetic heterogeneity, ergo manifest dysfunction in components of diverse cellular pathways; the precise pathomechanism for the majority remains elusive. METHODS: We studied 5 affected individuals from 3 unrelated families manifesting global developmental delay, postnatal microcephaly, and hypotonia. We used exome sequencing and prioritized variants that were subsequently characterized using immunofluorescence, immunoblotting, pulldown assays, and RNA sequencing. RESULTS: We identified biallelic variants in ZFTRAF1, encoding a protein of yet unknown function. Four affected individuals from 2 unrelated families segregated 2 homozygous frameshift variants in ZFTRAF1, whereas, in the third family, an intronic splice site variant was detected. We investigated ZFTRAF1 at the cellular level and signified it as a nucleocytoplasmic protein in different human cell lines. ZFTRAF1 was completely absent in the fibroblasts of 2 affected individuals. We also identified 110 interacting proteins enriched in mRNA processing and autophagy-related pathways. Based on profiling of autophagy markers, patient-derived fibroblasts show irregularities in the protein degradation process. CONCLUSION: Thus, our findings suggest that biallelic variants of ZFTRAF1 cause a severe neurodevelopmental disorder.

Significance and implications of FHIT gene expression and promoter hypermethylation in acute lymphoblastic leukemia (ALL).

BACKGROUND: Fragile histidine triad (FHIT) has been documented to play a vital role in various cancers including acute lymphoblastic leukemia (ALL). Keeping in view the plausible role of FHIT gene, we aimed to examine DNA promoter hypermethylation and mRNA expression in ALL cases in Kashmir (North India). METHODS: A total of 66 cases of ALL were analyzed for FHIT mRNA expression and promoter methylation by qRT-PCR and Methylation Specific-PCR (MS-PCR) respectively. RESULTS: FHIT mRNA expression showed significantly decreased expression in ALL cases with mean fold change of 9.24 ± 5.44 as compared to healthy controls (p = 0.01). The pattern of FHIT deregulation in ALL cases differed significantly between decreased and increased expression (p < 0.0001). A threefold decreased expression was observed in 75% of ALL cases than healthy controls (- 3.58 ± 2.32). ALL patients with FHIT gene promoter hypermethylation presented significantly higher in 80% (53/66) of cases (p = 0.0005). The association of FHIT gene hypermethylation and its subsequent expression showed FHIT mRNA expression as significantly lower in ALL cases with hypermethylation (p = 0.0008). B-ALL cases exhibited a highly significant association between the methylation pattern and its mRNA expression (p = 0.000). In low range WBC group, a significant association was found between increased expression (26%) of the cases and methylated (4%)/unmethylated group 86% (p = 0.0006). CONCLUSION: The present study conclude that FHIT gene hypermethylation and its altered expression may be linked in the pathogenesis of ALL and provide an evidence for the role of FHIT in the development of ALL.

Facile synthesis of a three-dimensional Ln-MOF@FCNT composite for the fabrication of a symmetric supercapacitor device with ultra-high energy density: overcoming the energy storage barrier.

In order to quench the thirst for efficient energy storage devices, a novel praseodymium-based state-of-the-art three-dimensional metal-organic framework (MOF), {[Pr(pdc)2]Me2NH2}n (YK-1), has been synthesized by using a simple solvothermal method employing a readily available ligand. YK-1 was characterised by single-crystal XRD and crystallographic analysis. The electrochemical measurements of YK-1 show that it exhibits a specific capacitance of 363.5 F g-1 at a current density of 1.5 A g-1 with 83.8% retention after 5000 cycles. In order to enhance its electrochemical performance for practical application, two composites of YK-1 with graphene oxide (GO) and functionalised multi-walled carbon nanotubes (FCNTs), namely YK-1@GO and YK-1@FCNT, were fabricated by employing a facile ultrasonication technique. The as-synthesized MOF and the composites were characterized by PXRD, FTIR, SEM, and TEM techniques. YK-1@GO and YK-1@FCNT offer enhanced specific capacitances of 488.2 F g-1 and 730.2 F g-1 at the same current density with 93.8% and 97.7% capacity retention after 5000 cycles, respectively (at 16 A g-1). Fascinated by the outstanding results shown by YK-1@FCNT, a symmetric supercapacitor device (SSC) based on it was fabricated. The assembled SSC achieved a remarkable energy density (87.6 W h kg-1) and power density (750.2 W kg-1) at a current density of 1 A g-1, along with very good cycling stability of 91.4% even after 5000 GCD cycles. The SSC device was able to power up several LED lights and even operated a DC brushless fan for a significant amount of time. To the best of our knowledge, the assembled SSC device exhibits the highest energy density among the MOF composite-based SSCs reported so far.

Gastric Cancer: A Comprehensive Literature Review.

Gastric cancer stands as a significant global health concern, particularly prevalent in Eastern Asia, with high mortality rates urging urgent attention and research efforts. This article comprehensively explores the epidemiology, anatomy, risk factors, pathophysiology, clinical presentation, diagnosis, staging, treatment modalities, prevention strategies, and survival rates associated with gastric cancer. Notably, Helicobacter pylori infection, dietary choices, and intricate stomach anatomy play pivotal roles in disease development. Early detection, utilizing staging, grading, and genetic testing for personalized treatment approaches is emphasized. Treatment modalities encompass surgery, chemotherapy, radiation therapy, targeted therapy, and immunotherapy. Prevention strategies involve lifestyle changes, screening, and genetic counseling. Survival rates vary by stage, highlighting the need for individualized care. In conclusion, a collaborative global effort is essential to address the impact of gastric cancer and improve outcomes.

Regulatory role of miR-125a expression with respect to its target genes LIFR, ERBB2 and STAT3 in the pathogenesis of recurrent pregnancy losses.

OBJECTIVES: Studies have investigated miR-125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3. METHODS: The present study included 40 cases of women with at least two RPLs in ≤20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR-125a was conducted by quantitative real-time PCR (qPCR). RESULTS: The expression of miR-125a was significantly lower in the plasma of RPL cases (P = 0.0001) and showed a significantly increased mean expression level in product of conception (2.56-fold, P < 0.0001). Among the target gene of miR-125a, ERBB2 and STAT3 gene expression level was significantly increased (2.58-fold, P = 0.04; 1.87-fold, P = 0.025), respectively in RPL cases while the LIFR gene revealed comparable expression (P = 0.64). Furthermore, expression analysis of ERBB2 gene with respect to its regulatory miR-125a cases depicted a significant association (P = 0.0005). Kaplan-Meier survival analysis revealed cases with low miR-125a expression had significantly shorter time to miscarriages, (log-rank P = 0.02). Also, decreased expression of miR-125a significantly conferred >2-fold increased risk for RPL (HR = 2.34: P < 0.05). CONCLUSION: The overall conclusion of the study was that altered miR-125a expression may cause deregulation in target genes LIFR, ERBB2 and STAT3 resulting in adverse consequence in the outcome of pregnancy.