Narrow-linewidth Fano microcavities with resonant subwavelength grating mirror.

We report on the theoretical and experimental investigations of optical microcavities consisting in the plane-plane arrangement of a broadband high-reflectivity mirror and a suspended one-dimensional grating mirror possessing a high-quality factor Fano resonance. By varying the length of these cavities from the millimeter to the few-micron range, we observe at short lengths the reduction of the spectral linewidth predicted to occur for such a Fano cavity as compared to a conventional broadband mirror cavity with the same length and internal losses. Such narrow linewidth and small modevolume microcavities with high-mechanical quality ultrathin mirrors will be attractive for a wide range of applications within optomechanics and sensing.

Development and effect of a coordinated Community Health Worker (CHW) Intervention (C-CHW-I) model for the stroke survivors in Kerala, South India.

INTRODUCTION: Structured models for secondary prevention of stroke in community settings are scarce. We aimed to develop and evaluate a model for improving medication adherence and enhanced risk factor monitoring. METHODS: We developed a multimodal C-CHW-I model for stroke survivors. Following training, all patients received a minimum of three CHW home visits, and once in 3-month telephone-call and health education for six months by CHWs. Seven blocks from 16 blocks of the study area were randomised to additionally receive an SMS alert for six months to reinforce CHW involvement. The primary outcomes were medication adherence and risk factor monitoring, and the secondary outcome was risk factor control. RESULTS: The mean age of the study population was 64+12 years, 765(85%) had ischaemic stroke. In the overall study cohort receiving the CHW intervention, mean medication adherence significantly improved from 3.56(0.88) at baseline to 3.78(0.61) at 6 months; p<0.001. Overall risk factor monitoring improved from 42.7% to 49.7%, and mean (standard deviation) systolic blood pressure (SBP) significantly reduced from 138(21) mmHg to 132(15) mmHg at 6-months; p<0.001. In patients additionally receiving SMS-based intervention, a statistically significant improvement in medication adherence was seen at 3 months (3.76+0.64 versus 3.61+0.81; p=0.008) however no difference persisted at 6 months. The proportion of smokers and alcohol users reduced in both groups with a trend to greater reduction in the intervention group (smokers:5.9% versus 2.8% (p=0.446) and alcohol users: 1.6% versus 1.4%(p=0.474)). At six months, the SBP did not differ (SBP (132.1(16.2) in the SMS group versus 133.2(15.8) mmHg in the control group, p=0.409). CONCLUSION: Our model improved medication adherence and risk factor monitoring of stroke survivors in community settings, and this can reduce stroke burden in the community.

The effect of synthetic grass sports surfaces on the thermal environment: A systematic review.

There are concerns regarding high surface temperatures on synthetic grass sports surfaces influencing the surrounding thermal environment, potentially increasing heat stress and impacting athlete safety. As such, studies have investigated changes to the thermal environment surrounding synthetic grass surfaces in comparison to both natural grass, and synthetic surfaces with different features, but this body of research has not been systematically reviewed. Therefore, this systematic review aimed to (i) determine if there are differences in the thermal environment surrounding synthetic grass surfaces compared with natural grass surfaces, and (ii) determine if there are differences in the thermal environment between different types of synthetic grass surfaces. A systematic review adhering to the PRISMA guidelines was performed. The eligibility criteria required investigations to report at least one of the following environmental parameters on or directly above both a synthetic surface and a comparator group of either natural grass or an alternative synthetic grass surface used in sport: Air temperature, mean radiant temperature, humidity, wind velocity, unified heat stress indices (i.e. wet-bulb-globe temperature and heat index) and/or surface temperature. Twenty-three studies were identified. The only parameters that were consistently higher on synthetic grass compared to natural grass were the air temperature (range: 0.5-1.2 °C) and surface temperature (range: 9.4-33.7 °C), while the mean radiant temperature, humidity, wind velocity and wet-bulb-globe temperature remained similar or required more data to determine if any differences exist. Synthetic grass surfaces consisting of styrene butadiene rubber infill or a shock pad had increased surface temperatures, whereas surfaces with thermoplastic elastomer infill, Cool climate turf fibres or HydroChill had lower surface temperatures. This systematic review has demonstrated that air and surface temperatures can be increased on synthetic sports surfaces, compared to natural grass surfaces. However, it is uncertain whether the differences are enough to increase an individual's heat stress risk and cause concern for athlete safety. While modifications to the turf infill or fibres can reduce synthetic surface temperatures, the effect of these features on the thermal environment as a whole is unclear. This review was prospectively registered with the Open Science Framework (Open Science Framework registration   https://doi.org/10.17605/OSF.IO/BTKGE ).

TMQuery: a database of precomputed template modeling scores for assessment of protein structural similarity.

SUMMARY: Comparisons of protein structures are critical for developing novel protein designs, annotating protein functions and predicting protein structure. The template modeling score (TM-score) is a widely used but computationally expensive measure of protein similarity that is applicable to a wide variety of structural biology problems. We introduce TMQuery-a continuously updated database containing over eight billion pre-computed TM-score values for every pair of proteins in the Protein Data Bank, allowing researchers to quickly query and download TM-scores via a web interface. AVAILABILITY AND IMPLEMENTATION: Publicly available at https://tmquery.gsk.com/.

Sodium and potassium ion storage in cation substituted 2D MoWSe2: insights into the effects of upper voltage cut-off.

The superior properties, such as large interlayer spacing and the ability to host large alkali-metal ions, of two-dimensional (2D) materials based on transition metal di-chalcogenides (TMDs) enable next-generation battery development beyond lithium-ion rechargeable batteries. In addition, compelling but rarely inspected TMD alloys provide additional opportunities to tailor bandgap and enhance thermodynamic stability. This study explores the sodium-ion (Na-ion) and potassium-ion (K-ion) storage behavior of cation-substituted molybdenum tungsten diselenide (MoWSe2), a TMD alloy. This research also investigates upper potential suspension to overcome obstacles commonly associated with TMD materials, such as capacity fading at high current rates, prolonged cycling conditions, and voltage polarization during conversion reaction. The voltage cut-off was restricted to 1.5 V, 2.0 V, and 2.5 V to realize the material's Na+and K+ion storage behavior. Three-dimensional (3D) surface plots of differential capacity analysis up to prolonged cycles revealed the convenience of voltage suspension as a viable method for structural preservation. Moreover, the cells with higher potential cut-off values conveyed improved cycling stability, higher and stable coulombic efficiency for Na+and K+ion half-cells, and increased capacity retention for Na+ion half-cells, respectively, with half-cells cycled at higher voltage ranges.

Correlation of oral mucosa dose and volume parameters with Grade 3 mucositis, in patients treated with volumetric modulated arc radiotherapy for oropharyngeal cancer?

BACKGROUND: Oral mucositis is the dose-limiting toxicity of chemoradiation in oropharyngeal cancer patients, which can be minimized by giving constraints to oral mucosa. However, the constraints defined in literature are extrapolated from chemoradiation in head and neck cancers as a whole. This study aims to determine oral mucosa dose-volume parameters that can predict grade ≥ 3 acute oral mucositis in oropharyngeal cancer patients treated with volumetric modulated arc radiotherapy. METHODS: This prospective study was done in 52 patients of locally advanced oropharyngeal cancer treated with Volumetric modulated arc radiotherapy. Dose-volume histogram data were extracted and then acute oral mucosa toxicity was analysed. Receiver operating characteristic analysis and logistic regression were carried out to determine predictive factors for grade ≥ 3 mucositis. RESULTS: Grade ≥ 3 acute oral mucositis occurred in 57.6% (30/52) patients in the study. V30Gy > 53.35% (P = 0.005) was an independent dosimetric factor related to grade ≥ 3 acute toxicity. In the receiver operating characteristic curve, the area under V30Gy was 0.770 (P = 0.001); the cut-off value of V30 was 46.23% (sensitivity, 0.80; specificity, 0.91). CONCLUSIONS: Dose-volume histogram analysis predicts V30 > 53.35% as independent factors for grade ≥ 3 acute oral mucositis in patients with oropharyngeal cancers treated with Volumetric modulated arc radiotherapy. Studies in future with more patient number can further validate the above results.

Peptide Nucleic Acids: Recent Developments in the Synthesis and Backbone Modifications.

Nucleic acid represents the ideal drug candidate for protein targets that are hard to target or against which drug development is not easy. Peptide nucleic acids (PNAs) are synthesized by attaching modified peptide backbones generally derived from repetitive N-2-aminoethyl glycine units in place of the regular phosphodiester backbone and represent synthetic impersonator of nucleic acids that offers an exciting research field due to their fascinating spectrum of biotechnological, diagnostic and potential therapeutic applications. The semi-rigid peptide nucleic acid backbone serves as a nearly-perfect template for attaching complimentary base pairs on DNA or RNA in a sequence-dependent manner as described by Watson-Crick models. PNAs and their analogues are endowed with exceptionally high affinity and specificity for receptor sites, essentially due to their polyamide backbone's uncharged and flexible nature. The present review compiled various strategies to modify the polypeptide backbone for improving the target selectivity and stability of the PNAs in the body. The investigated biological activities carried out on PNAs have also been summarized in the present review.

Successive addition of rice straw biochar enhances carbon accumulation in soil irrigated with saline or non-saline water.

Biochar has been evaluated globally to improve soil fertility and mitigate climate change. However, the long-term effects of successive biochar application on carbon (C) accumulation in soil irrigated with saline versus non-saline water (canal water) has not been investigated. A field experiment was conducted to study the effects of rice straw biochar addition rates (0, 2, 4, 8 Mg ha-1) on C storage in soil irrigated with water of different electrical conductivity [EC, dS m-1]; 0.3 (non-saline canal irrigation water; CIW), 5 (saline irrigation water; SIW5), 10 (SIW10), and 15 (SIW15) in a cotton-wheat system. Long-term irrigation with saline water of variable EC levels adversely affected soil functions, reducing above-ground biomass in cotton (12-48%) and wheat (5-27%). In contrast, plots irrigated with saline water but amended with rice straw biochar showed significant improvement in aboveground biomass (both in cotton and wheat), possibly due to its beneficial effects on soil properties such as soil EC, organic carbon, microbial population, water and nutrient availability, bulk density, soil aggregation, and proliferation of roots. Interestingly, the change in total organic C (TOC) stocks (8.5, 17, and 27.5 Mg C ha-1) after 5 years were found to be almost double the amount of biochar C added (4.3, 8.6, 17.2 Mg ha-1), indicating stabilization of belowground C inputs from the root biomass by the applied biochar and also possibly through its physical interaction with aggregates and minerals. Even though biochar application to saline water irrigated plots increased the contribution of plant-derived C to overall soil TOC stocks, it was still lower compared with canal water irrigated plots. The study conclusively established that the long-term stabilization of biogenic C through biochar has essential implications for mitigating climate change by accumulating additional C beyond the recalcitrant C contained in biochar.

Astaxanthin as a King of Ketocarotenoids: Structure, Synthesis, Accumulation, Bioavailability and Antioxidant Properties.

Astaxanthin (3,3-dihydroxy-ß, ß-carotene-4,4-dione) is a ketocarotenoid synthesized by Haematococcus pluvialis/lacustris, Chromochloris zofingiensis, Chlorococcum, Bracteacoccus aggregatus, Coelastrella rubescence, Phaffia rhodozyma, some bacteria (Paracoccus carotinifaciens), yeasts, and lobsters, among others However, it is majorly synthesized by Haematococcus lacustris alone (about 4%). The richness of natural astaxanthin over synthetic astaxanthin has drawn the attention of industrialists to cultivate and extract it via two stage cultivation process. However, the cultivation in photobioreactors is expensive, and converting it in soluble form so that it can be easily assimilated by our digestive system requires downstream processing techniques which are not cost-effective. This has made the cost of astaxanthin expensive, prompting pharmaceutical and nutraceutical companies to switch over to synthetic astaxanthin. This review discusses the chemical character of astaxanthin, more inexpensive cultivating techniques, and its bioavailability. Additionally, the antioxidant character of this microalgal product against many diseases is discussed, which can make this natural compound an excellent drug to minimize inflammation and its consequences.

Comparison of 90-Day Adverse Events Associated With Aspirin and Potent Anticoagulation Use for Venous Thromboembolism Prophylaxis: A Cohort Study of 72,288 Total Knee and 35,142 Total Hip Arthroplasty Patients.

BACKGROUND: While aspirin is acceptable for venous thromboembolism (VTE) prophylaxis following total joint arthroplasty in most patients, more potent agents are used in patients considered higher risk for VTE. We evaluated the efficacy and safety of aspirin versus potent anticoagulation agents following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: A cohort study of 72,288 TKA and 35,142 THA from the Kaiser Permanente Total Joint Replacement Registry was performed (2009 to 2019). Identified medications were aspirin, factor Xa inhibitors, low-molecular-weight heparin (LMWH), and warfarin. A validated VTE risk score was assigned to each patient. Propensity score-weighted logistic regressions were used to evaluate 90-day VTEs. Noninferiority testing was performed with a margin of 1.25 using the upper bound (UB) of the 1-sided 95% CI. RESULTS: For TKA, aspirin was not inferior to LMWH (odds ratio [OR] = 0.77, UB = 1.09) and warfarin (OR = 0.64, UB = 0.90); there was no evidence to support noninferiority of aspirin compared to factor Xa inhibitors. Findings were consistent for THA (LMWH: OR = 0.59, UB = 0.75; warfarin: OR = 0.69, UB = 0.89). TKA was considered higher risk for VTE, whereas aspirin use demonstrated noninferiority compared to warfarin (OR = 0.54, UB = 0.81), we lacked evidence of noninferiority when compared to LMWH and factor Xa inhibitors. We lacked evidence of noninferiority of aspirin versus any potent anticoagulation in higher-risk THA. CONCLUSION: Aspirin was found to be effective and safe for VTE prevention in primary total joint arthroplasty, including in patients considered higher risk for VTE. LEVEL OF EVIDENCE: III.

Biomarkers predict hemorrhagic transformation and stroke severity after acute ischemic stroke.

OBJECTIVES: Hemorrhagic transformation (HT) is a complication occurring in patients with acute ischemic stroke (AIS) either spontaneously or post-thrombolysis leading to significant morbidity and mortality. We assessed circulating matrix metalloproteinase-9 (MMP-9), Claudin-5, and soluble serum stimulation-2 (sST2) in HT and stroke severity in AIS based on their temporal distribution. MATERIALS AND METHODS: We prospectively enrolled 111 AIS patients within 12 h from onset. Patient demographic, clinical, and imaging details were documented. Follow-up imaging was conducted 24-48 h after admission. Blood samples were taken at three time-points from stroke onset. HT was classified according to the European Co-operative Acute Stroke Study-III(ECASS-III). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Multiple logistic regression and receiver operating characteristic curve were conducted to determine the discriminative capacity. RESULTS: Mean age was 62.3 ± 11.7 years and median baseline NIHSS was 12[IQR 8.0-18.0]. HT was detected in 30(27%) patients. Biomarker levels at 12 h were elevated with median MMP-9 concentration of 153.9 ng/mL[IQR 110.6-309 ng/mL] indicating a trend toward significant positive correlation with HT(P = 0.05). Claudin-5 levels at 12 h was elevated but was not statistically significant (43.1 pg/mL[IQR:26.7-72.6 pg/mL] vs 59.4 pg/mL[IQR:24.5-100.8 pg/mL];P = 0.4). Multiple logistic regression indicated Claudin-5 levels at 12 h (OR 9.46;95% CI:1.97-64.6;P = 0.010) and baseline low ASPECTS score(OR 20.3;95% CI:3.46-193; P = 0.003) independently predicted HT. MMP-9 at 12 h was significantly elevated in patients with moderate to severe strokes (P = 0.04). CONCLUSIONS: Claudin-5 and low ASPECTS independently predicted HT. MMP-9 was positively correlated with baseline stroke severity.

Homeopathy as an Adjuvant to Standard Care in Moderate and Severe Cases of COVID-19: A Single-Blind, Randomized, Placebo-Controlled Study.

OBJECTIVES: This study aimed to evaluate whether individualized homeopathic medicines have a greater adjunctive effect than adjunctive placebos in the treatment of moderate and severe cases of coronavirus disease 2019 (COVID-19). METHODS: The study was a randomized, single-blind, prospective, placebo-controlled clinical trial set in the clinical context of standard care. INTERVENTION: Patients of either sex, admitted in a tertiary care hospital, suffering from moderate or severe COVID-19 and above 18 years of age were included. In total, 150 patients were recruited and then randomly divided into two groups to receive either individualized homeopathic medicines or placebos, in addition to the standard treatment of COVID-19. OUTCOME MEASURES: The primary outcome was time taken to achieve RT-PCR-confirmed virus clearance for COVID-19. Secondary outcomes were changes in the Clinical Ordinal Outcomes Scale (COOS) of the World Health Organization, the patient-reported MYMOP2 scale, and several biochemical parameters. Parametric data were analyzed using unpaired t-test. Non-parametric data were analyzed using the Wilcoxon signed rank test. Categorical data were analyzed using Chi-square test. RESULTS: In total, 72 participants of the add-on homeopathy (AoH) group showed conversion of RT-PCR status to negative, in an average time of 7.53 ± 4.76 days (mean ± SD), as compared with 11.65 ± 9.54 days in the add-on placebo (AoP) group (p = 0.001). The mean COOS score decreased from 4.26 ± 0.44 to 3.64 ± 1.50 and from 4.3 ± 0.46 to 4.07 ± 1.8 in the AoH and AoP groups respectively (p = 0.130). The mortality rate for the AoH group was 9.7% compared with 17.3% in the AoP group. The MYMOP2 scores between the two groups differed significantly (p = 0.001), in favor of AoH. Inter-group differences in the pre- and post- mean values of C-reactive protein, fibrinogen, total leukocyte count, platelet count and alkaline phosphatase were each found to be statistically significant (p <0.05), favoring AoH; six other biochemical parameters showed no statistically significant differences. CONCLUSION: The study suggests homeopathy may be an effective adjunct to standard care for treating moderate and severe COVID-19 patients. More rigorous, including double-blinded, studies should be performed to confirm or refute these initial findings.

Moderation of nitrogen availability through the application of pyrolyzed and unpyrolyzed organic materials in saline water irrigated soil.

Soil application of pyrolyzed biomass (biochar) has been proposed as an effective strategy for managing degraded land, but its limitations as a sole nutrient supplier discourage its widespread application as a soil amendment. Excessive use of saline water for irrigation leads to buildup of salts and other toxic ions, which cause a decline in the availability of essential nutrients due to negative effects on the mineralization process. Therefore, a long-term incubation experiment was conducted for 52 weeks to study the individual or combined impact of pyrolyzed [biochar derived from rice residue (RB)] and unpyrolyzed organic materials [rice residue (RR) and animal manure (AM)] on nitrogen (N) dynamics in soil irrigated with water of varying electrical conductivity (EC) (EC0.3 [non-saline canal water), EC10, and EC15 dS m-1 (saline)]. Increasing salinity had an adverse effect on N mineralization, reducing it by 20-70% during the incubation period. Irrespective of the EC, soil amended with AM showed greater and faster N mineralization than unamended control, while individual application of RB or RR showed immobilization of N during the early period of incubation. However, conjoint application of pyrolyzed (RB) and unpyrolyzed organic materials (RR or AM) showed enhanced mineralized N content (26-96%) compared with the sole biochar-amended soil irrigated with water of different EC levels. It was most likely due to the synergic effect of unpyrolyzed materials on the mineralization rate of biochar. On the other hand, the high cation exchange capacity, large surface area, and greater total porosity of the biochar may cause stronger adsorption of free NH4+-N released from the labile organic amendments, thereby moderating the N mineralization process under saline conditions. Therefore, it is recommended that biochar be used in conjunction with AM or RR to ensure the prolonged availability of N in a saline environment.

Core body temperature responses during competitive sporting events: A narrative review.

Due to the lack of research in real-world sports competitions, the International Olympic Committee, in 2012, called for data characterising athletes' sport and event-specific thermal profiles. Studies clearly demonstrate that elite athletes often attain a core body temperature (Tc) ≥ 40°C without heat-related medical issues during competition. However, practitioners, researchers and ethical review boards continue to cite a Tc ≥ 40°C (and lower) as a threshold where athlete health is impacted (an assumption from laboratory studies). Therefore, this narrative review aims to: (i) summarise and review published data on Tc responses during competitive sport and identify key considerations for practitioners; (ii) establish the incidence of athletes experiencing a Tc ≥ 40°C in competitive sport alongside the incidence of heat illness/heat stroke (EHI/EHS) symptoms; and (iii) discuss the evolution of Tc measurement during competition. The Tc response is primarily based on the physical demands of the sport, environmental conditions, competitive level, and athlete disability. In the reviewed research, 11.9% of athletes presented a Tc ≥ 40°C, with only 2.8% of these experiencing EHI/EHS symptoms, whilst a high Tc ≥ 40°C (n = 172; Tc range 40-41.5°C) occurred across a range of sports and environmental conditions (including some temperate environments). Endurance athletes experienced a Tc ≥ 40°C more than intermittent athletes, but EHI/EHS was similar. This review demonstrates that a Tc ≥ 40°C is not a consistently meaningful risk factor of EHI/EHS symptomology in this sample; therefore, Tc monitoring alongside secondary measures (i.e. general cognitive disturbance and gait disruption) should be incorporated to reduce heat-related injuries during competition.

Assessment of donor cell engraftment after hematopoietic stem cell transplantation for sickle cell disease: A review of current and future methods.

Hematopoietic stem cell transplantation (HSCT) is the only established curative treatment for sickle cell disease (SCD), a debilitating red blood cell (RBC) disorder with significant prevalence worldwide. Accurate assessment of RBC engraftment following HSCT is essential to evaluate the status of the graft and can enable early intervention to treat or prevent graft rejection. Currently, chimerism measurement is performed on whole blood samples, which mainly reflect white blood cell (WBC) chimerism. This approach has limitations in assessing engraftment in patients with SCD because RBCs engraft non-linearly with WBCs. Direct measures of RBC chimerism exist but are not routinely used. In this review, we critically examine the current methodologies for assessing donor engraftment; highlight the limitations of these different methods, and present emerging and novel technologies with the potential to improve clinical monitoring of RBC engraftment post-HSCT for SCD. Promising alternative methodologies include RBC-specific flow cytometry, RBC-specific RNA analysis, and quantification of plasma cell-free DNA derived specifically from nucleated RBCs.

Biomarkers in the Prediction of Hemorrhagic Transformation in Acute Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Hemorrhagic transformation (HT) is a complication that occurs spontaneously or after thrombolysis in acute ischemic stroke (AIS) and can increase morbidity and mortality. The association of biomarkers with the risk of HT has been variably reported. We conducted a systematic review of the literature and meta-analysis and sought to compare blood biomarkers associated with HT and its subtypes by evaluating its predictability and correlation with outcome in AIS. METHODS: The study protocol was registered in the PROSPERO database (CRD42020201334) and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among 2,230 articles identified from Cochrane Library, PubMed, and Web of Science databases, 30 quality-appraised articles were found eligible. Meta-analysis was conducted for matrix metalloproteinase-9 (MMP-9), cellular fibronectin (c-Fn), ferritin, S100 calcium-binding protein B (S100B), and neutrophil-lymphocyte ratio (NLR). We also reviewed biomarkers for correlation with the functional outcome at 90 days from stroke onset (poor outcome modified Rankin scale >2). RESULTS: The pooled diagnostic odds ratio (DORpooled) was the highest for baseline c-Fn levels (299.253 [95% CI, 20.508-4,366.709]), followed by MMP-9 (DORpooled, 29.571 [95% CI 17.750-49.267]) and ferritin (DORpooled, 24.032 [95% CI 2.557-225.871]). However, wide confidence intervals for ferritin and c-Fn suggested lesser reliability of the markers. Patients with MMP-9 levels ≥140 ng/mL were 29.5 times at higher risk of developing symptomatic HT after AIS (area under the curve = 0.881). S100B (DORpooled, 6.286 [95% CI, 1.861-21.230]) and NLR (DORpooled, 5.036 [95% CI, 2.898-8.749]) had lower diagnostic accuracies. Among the markers not included for meta-analysis, caveolin-1, thrombin-activated fibrinolysis inhibitor, plasminogen activator inhibitor-1, and soluble ST2 were highly sensitive. Elevated levels of MMP-9, ferritin, and NLR were found to be associated with poor functional outcomes and mortality. CONCLUSION: Of the 5 biomarkers, there was enough evidence that MMP-9 has higher diagnostic accuracy for predicting the risk of HT before thrombolysis. MMP-9, ferritin, and NLR also predicted poor short-term outcomes.

Neuropsychological, behavioral, and quality-of-life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series.

BACKGROUND/OBJECTIVES: Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT. DESIGN/METHODS: Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol. RESULTS: Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ = 92.1, SD 9.0; n = 8) and 2 years post-HCT (mean FSIQ = 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = -.54) and fine motor speed and dexterity (Cohen's d = -.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44). CONCLUSION: Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.

The medicinal perspective of 2,4-thiazolidinediones based ligands as antimicrobial, antitumor and antidiabetic agents: A review.

2,4-Thiazolidinedione (2,4-TZD), commonly known as glitazone, is a ubiquitous heterocyclic pharmacophore possessing a plethora of pharmacological activities and offering a vast opportunity for structural modification. The diverse range of biological activities endowed with a novel mode of action, low cost, and easy synthesis has attracted the attention of medicinal chemists. Several researchers have integrated the TZD core with different structural fragments to develop a wide range of lead molecules against various clinical disorders. The most common sites for structural modifications at the 2,4-TZD nucleus are the N-3 and the active methylene at C-5. The review covers the recent development of TZD derivatives such as antimicrobial, anticancer, and antidiabetic agents. Various 2,4-TZD based agents or drugs, which are either under clinical development or in the market, are discussed in the study. Different synthetic methodologies for synthesizing the 2,4-TZD core are also included in the manuscript. The importance of various substitutions at N-3 and C-5 and the mechanisms of action and structure-activity relationships are also discussed. We hope this study will serve as a valuable tool for the scientific community engaged in the structural exploitation of the 2,4-TZD core for developing novel drug m\olecules for life-threatening ailments.

Characterization of caspase-2 inhibitors based on specific sites of caspase-2-mediated proteolysis.

Since the discovery of the caspase-2 (Casp2)-mediated ∆tau314 cleavage product and its associated impact on tauopathies such as Alzheimer's disease, the design of selective Casp2 inhibitors has become a focus in medicinal chemistry research. In the search for new lead structures with respect to Casp2 selectivity and drug-likeness, we have taken an approach by looking more closely at the specific sites of Casp2-mediated proteolysis. Using seven selected protein cleavage sequences, we synthesized a peptide series of 53 novel molecules and studied them using in vitro pharmacology, molecular modeling, and crystallography. Regarding Casp2 selectivity, AcITV(Dab)D-CHO (23) and AcITV(Dap)D-CHO (26) demonstrated the best selectivity (1-6-fold), although these trends were only moderate. However, some analogous tetrapeptides, most notably AcDKVD-CHO (45), showed significantly increased Casp3 selectivities (>100-fold). Tetra- and tripeptides display decreased or no Casp2 affinity, supporting the assumption that a motif of five amino acids is required for efficient Casp2 inhibition. Overall, the results provide a reasonable basis for the development of both selective Casp2 and Casp3 inhibitors.

Adaptation of IoT with Blockchain in Food Supply Chain Management: An Analysis-Based Review in Development, Benefits and Potential Applications.

In today's scenario, blockchain technology is an emerging area and promising technology in the field of the food supply chain industry (FSCI). A literature survey comprising an analytical review of blockchain technology with the Internet of things (IoT) for food supply chain management (FSCM) is presented to better understand the associated research benefits, issues, and challenges. At present, with the concept of farm-to-fork gaining increasing popularity, food safety and quality certification are of critical concern. Blockchain technology provides the traceability of food supply from the source, i.e., the seeding factories, to the customer's table. The main idea of this paper is to identify blockchain technology with the Internet of things (IoT) devices to investigate the food conditions and various issues faced by transporters while supplying fresh food. Blockchain provides applications such as smart contracts to monitor, observe, and manage all transactions and communications among stakeholders. IoT technology provides approaches for verifying all transactions; these transactions are recorded and then stored in a centralized database system. Thus, IoT enables a safe and cost-effective FSCM system for stakeholders. In this paper, we contribute to the awareness of blockchain applications that are relevant to the food supply chain (FSC), and we present an analysis of the literature on relevant blockchain applications which has been conducted concerning various parameters. The observations in the present survey are also relevant to the application of blockchain technology with IoT in other areas.