3HP preventive treatment among children and adolescents with HIV and child household contacts of TB patients.

INTRODUCTION: India's National TB Elimination Programme plans to roll out short-course TB preventive therapy (TPT) using 3 months of rifapentine and isoniazid (3HP). Understanding the feasibility and safety of children in programmatic settings is critical for widespread implementation. We present the findings of a targeted scale-up of 3HP among children and adolescents living with HIV (CALHIV) and child household contacts (>2 to <6 years) of pulmonary TB patients (CHHC). METHODS: Between December 2021 and July 2023, eligible CALHIV and CHHC participants were given weekly dosages of 3HP for 3 months at antiretroviral therapy (ART) and TB clinics, respectively, of a public hospital in Pune, India. RESULTS: Of 97 children screened, 91 initiated 3HP (32 CALHIV and 59 CHHC). The median age of CALHIV was 14 years; 66% were male and on dolutegravir-based ART. The median age of CHHC was 4 years; 47% were males. Thirty-one (97%) CALHIV and 56 (95%) CHHC completed 3HP without dolutegravir dose adjustment. None of the child participants discontinued 3HP due to adverse events. No child participant developed TB during 1 year of follow-up post-3HP. CONCLUSION: Our study provides evidence of the uptake and feasibility of the planned nationwide rollout of 3HP.

INTRODUCTION: Le programme national indien d'élimination de la tuberculose prévoit de mettre en place un traitement préventif de courte durée contre la tuberculose (TPT) en utilisant trois mois de rifapentine et d'isoniazide (3HP). Il est essentiel de comprendre la faisabilité et la sécurité des enfants dans le cadre des programmes pour pouvoir les mettre en œuvre à grande échelle. Nous présentons les résultats d'une extension ciblée de la 3HP parmi les enfants et les adolescents vivant avec le VIH (CALHIV, pour l'anglais « children and adolescents living with HIV ¼) et les enfants contacts familiaux (>2 à <6 ans) de patients atteints de tuberculose pulmonaire (CHHC, pour l'anglais « child household contacts ¼). MÉTHODES: Des doses hebdomadaires de 3HP ont été administrées pendant 3 mois aux participants éligibles CALHIV et CHHC dans les cliniques de thérapie antirétrovirale (ART) et de tuberculose, respectivement, d'un hôpital public de Pune, en Inde, entre décembre 2021 et juillet 2023. RÉSULTATS: Sur 97 enfants dépistés, 91 ont initié 3HP (32 CALHIV et 59 CHHC). L'âge médian des CALHIV était de 14 ans ; 66% étaient de sexe masculin et sous ART à base de dolutegravir. L'âge médian des CHHC était de 4 ans ; 47% étaient des hommes. Trente et un (97%) CALHIV et 56 (95%) CHHC ont terminé l'étude 3HP sans ajustement de la dose de dolutégravir. Aucun des enfants participants n'a interrompu le traitement 3HP en raison d'effets indésirables. Aucun enfant participant n'a développé de tuberculose au cours de l'année de suivi post-3HP. CONCLUSION: Notre étude fournit des preuves de l'adoption et de la faisabilité de la mise en œuvre prévue de 3HP à l'échelle nationale.

Three months of weekly rifapentine plus isoniazid for TB prevention among people with HIV.

BACKGROUND: Evidence on implementation of three months of weekly isoniazid (H, INH) and rifapentine (P, RPT) (3HP) as a TB preventive therapy (TPT) for at-risk groups in Indian programmatic conditions is limited. METHODS: A prospective demonstration study assessing scale-up, safety, and effectiveness of 3HP TPT among people living with HIV (PLHIV) in Indian programmatic settings was conducted. RESULTS: Of 656 screened PLHIV, 502 (77%) received 3HP. Of these, 20 (4%) discontinued TPT due to toxicity,17 (3.8%) lost to follow-up, one (0.2%) had breakthrough rifampicin-sensitive TB, and 464 (92%) completed 3 HP TPT. Of 288 (57%) overall adverse events (AEs), 46 (9%) had Grade 2 or above AEs. The median time to AE was 14 days (IQR 7-42). Serious adverse events (SAEs) were reported in 9 (2%) participants; of these, 7 (78%) were not related to 3HP. No TB episodes occurred during the 1-year follow-up period. CONCLUSION: 3HP TPT completion rate of 92%, with few adverse events leading to 3HP discontinuation, providing evidence of the scalability and safety of 3HP TPT among PLHIV in Indian health program settings.

CONTEXTE: Les données probantes sur la mise en œuvre de 3 mois de traitement hebdomadaire d'isoniazide (H, INH) et de rifapentine (P, RPT) (3HP) en tant que traitement préventif de la TB (TPT) pour les groupes à risque dans les conditions programmatiques indiennes sont limitées. MÉTHODES: Une étude de démonstration prospective évaluant la mise à l'échelle, l'innocuité et l'efficacité de la TPT 3HP chez les personnes vivant avec le VIH (PVVIH) dans des contextes programmatiques indiens a été menée. RÉSULTATS: Sur les 656 PVVIH dépistés, 502 (77%) ont reçu le traitement 3HP. Parmi eux, 20 (4%) ont interrompu le TPT en raison de toxicité, 17 (3,8%) ont été perdus de vue, un (0,2%) a développé une TB sensible à la rifampicine et 464 (92%) ont terminé le TPT 3HP. Parmi les 288 (57%) événements indésirables (AE, pour l'anglais, « adverse events ¼) en tout, 46 (9%) ont présenté des AE de Grade 2 ou supérieur. Le délai médian jusqu'à l'apparition d'un AE était de 14 jours (IQR 7­42). Des événements indésirables graves ont été rapportés chez 9 (2%) participants ; parmi eux, 7 (78%) n'étaient pas liés au traitement 3HP. Aucun épisode de TB n'a été observé pendant la période de suivi d'un an. CONCLUSION: Le taux d'achèvement du TPT 3HP est de 92%, avec peu d'événements indésirables conduisant à l'arrêt du TPT 3HP, fournissant des preuves de l'évolutivité et de l'innocuité du TPT 3HP chez les PVVIH dans le cadre de programmes de santé indiens.

Additional use of extrinsic warmer for intravenous CT contrast media and its impact on incidence of contrast extravasations and allergic like reactions: a prospective observational case control study.

AIMS: To prospectively determine whether extrinsic warming of the low-osmolality CT contrast media (Iohexol 350, Iodixanol 320, Iopromide 300, and Iopamidol 300) to 37°C prior to intravenous administration affects extravasation and allergic-like reaction rates. MATERIALS AND METHODS: This large scale prospective case control study of adverse events included all the patients between the age group of 15-80 years undergoing routine contrast-enhanced computed tomographic (CECT) examinations from April 2018 to March 2020 at our institute. Ex vivo experiments were also performed to demonstrate change in contrast viscosity and fluid dynamics in relation to temperature. RESULTS: A total of 24,379 CECTs were conducted during the study period. Extrinsic warming showed a significant decrease in extravasation rates for Iohexol 350 at flow rates <3.5 mL/sec (P=0.037). No significant difference was observed with Iopromide 300 (P=0.432). Overall, a significant decrease in allergic reactions and overall contrast-related reactions (excluding physiologic reactions) was noted (P<0.001), with Iohexol 350. However, no significant difference was found with Iopromide 300. The most common physiological reaction was a sense of warmth, more prevalent in the warmed group, aligning with ex-vivo experiments demonstrating decreased viscosity with contrast warming. CONCLUSIONS: Extrinsic warming of contrast helps reduce the incidence of allergic-like reactions and extravasations for Iohexol 350, but no significant difference was noted with Iopromide 300 even at low injection rates (<3.5 mL/sec).

An adapted scale to measure perceived TB and HIV stigma during household contact investigation.

Measuring stigma for TB and HIV in households undergoing contact investigation for TB is critical for understanding its impacts on health behaviours and identifying opportunities for intervention. However, standardised measurements for TB-HIV stigma in household contact investigations are limited.We adapted and validated a household stigma scale in Uganda. This involved field testing measures from another setting with 163 household contacts of newly diagnosed TB patients, conducting cognitive interviews with seven household contacts, adapting scale items using cognitive interview data, and retesting the adapted scales in a random sample of 60 contacts. We assessed inter-item covariance and performed factor analysis to select the final scale items.In whole-scale factor analysis, no cross-loading of items with scores ≥0.32 was found after the elimination of items based on covariance and symmetry. All TB items were loaded onto a single factor with scores ≥0.5, and all but one HIV item was loaded onto a second factor with scores ≥0.5. The final subscale internal consistency (Cronbach's alpha) was 0.92 for TB and 0.89 for HIV.The adapted TB-HIV stigma scale demonstrated acceptable psychometric properties and is substantially shorter and easier to administer than previous scales, making it suitable for programmatic research and evaluation..

Savings from the introduction of BPaL and BPaLM regimens at the country level.

BACKGROUND: In 2022, the WHO recommended the 6-month regimens BPaL (bedaquiline + pretomanid + linezolid) and BPaLM (BPaL + moxifloxacin) as treatment options for most forms of drug-resistant TB. SLASH-TB estimates the cost-saving and cost-effectiveness for the healthcare system and patients when a country switches from current standard-of-care treatment regimens to BPaL/BPaLM. METHODOLOGY: Country data from national TB programmes (NTP) are used to calculate the costs for all regimens and treatment outcomes. Where BPaL/BPaLM is not currently used, clinical trial outcomes data are used to estimate cost-effectiveness. DALYs are calculated using the Global Burden of Disease (GBD) database. RESULTS: We present the results of four countries that have used the tool and shared their data. When shorter and longer regimens are replaced with BPaL/BPaLM, the savings per patient treated in Pakistan, the Philippines, South Africa, and Ukraine are $746, $478, $757, and $2,636, respectively. An increased number of patients would be successfully treated with BPaL/BPaLM regimens, with 411, 1,025, 1,371 and 829 lives saved and 20,179, 27,443, 33,384 and 21,924 DALYs averted annually in the four countries, respectively. CONCLUSION: Through BPaL/BPaLM regimens, drug-resistant TB treatment has become more effective, shorter, less burdensome for patients, cheaper for both health systems and patients, and saves more lives.

CONTEXTE: En 2022, l'OMS a préconisé l'utilisation des schémas thérapeutiques (bedaquiline + pretomanid + linezolid) et BPaLM (BPaL + moxifloxacin), d'une durée de 6 mois, comme alternatives pour traiter la plupart des formes de TB résistante aux médicaments. SLASH-TB a réalisé une estimation des économies et de la rentabilité pour le système de santé et les patients lorsqu'un pays décide de passer des schémas thérapeutiques standards actuels au BPaL/BPaLM. MÉTHODOLOGIE: Les programmes nationaux de lutte contre la TB (NTP) utilisent les données nationales pour évaluer les coûts des différents schémas thérapeutiques et des résultats des traitements. Si le BPaL/BPaLM n'est pas utilisé actuellement, les données des essais cliniques sont utilisées pour estimer le rapport coût-efficacité. Les années de vie ajustées sur l'incapacité (DALYs, pour l'anglais « disability-adjusted life-years ¼) sont calculées à l'aide de la base de données Global Burden of Disease (GBD). RÉSULTATS: Nous présentons les résultats de quatre pays qui ont utilisé l'outil et partagé leurs données. Lorsque les schémas plus courts et plus longs sont remplacés par BPaL/BPaLM, les économies par patient traité au Pakistan, aux Philippines, en Afrique du Sud et en Ukraine sont respectivement de 746, 478, 757 et 2 636 dollars. L'utilisation des schémas BPaL/BPaLM permettrait de traiter un plus grand nombre de patients avec succès, ce qui sauverait respectivement 411, 1 025, 1 371 et 829 vies et éviterait 20 179, 27 443, 33 384 et 21 924 DALYs par an dans les quatre pays. CONCLUSION: Les schémas BPaL/BPaLM ont révolutionné le traitement de la tuberculose pharmacorésistante en le rendant plus efficace, plus rapide, moins contraignant pour les patients, plus économique pour les systèmes de santé et les patients, et en sauvant un plus grand nombre de vies.

Cost and cost-effectiveness of BPaL regimen used in drug-resistant TB treatment in the Philippines.

BACKGROUND: In 2022, the WHO announced that the 6-month BPaL/M regimen should be used for drug-resistant TB (DR-TB). We estimate the patient and provider costs of BPaL compared to current standard-of-care treatment in the Philippines. METHODS: Patients on BPaL under operational research, or 9-11-month standard short oral regimen (SSOR) and 18-21-month standard long oral regimen (SLOR) under programmatic conditions were interviewed using the WHO cross-sectional TB patient cost tool. Provider costs were assessed through a bottom-up and top-down costing analysis. RESULTS: Total patient costs per treatment episode were lowest with BPaL (USD518.0) and increased with use of SSOR (USD825.8) and SLOR (USD1,023.0). Total provider costs per successful treatment were lowest with BPaL (USD1,994.5) and increased with SSOR (USD3,121.5) and SLOR (USD10,032.4). Compared to SSOR, BPaL treatment was cost-effective at even the lowest willingness to pay threshold. As expected, SLOR was the costliest and least effective regimen. CONCLUSIONS: Costs incurred by patients on BPaL were 37% (95% CI 22-56) less than SSOR and 50% (95% CI 32-68) less than SLOR, while providers could save 36% (95% CI 21-56) to 80% (95% CI 64-93) per successful treatment, respectively. The study shows that treatment of DR-TB with BPaL was cost-saving for patients and cost-effective for the health system.

CONTEXTE: En 2022, l'OMS a annoncé que le traitement BPaL/M de 6 mois devrait être utilisé pour la TB pharmacorésistante (DR-TB). Nous estimons les coûts du BPaL pour les patients et les prestataires par rapport au traitement standard actuel aux Philippines. MÉTHODES: Des patients sous BPaL dans le cadre d'une recherche opérationnelle, ou un régime oral court standard de 9 à 11 mois (SSOR, pour l'anglais « standard short oral regimen ¼) et un régime oral long standard de 18 à 21 mois (SLOR, pour l'anglais « standard long oral regimen ¼) dans des conditions programmatiques ont été interrogés à l'aide de l'outil transversal de l'OMS sur le coût pour les patients atteints de TB. Les coûts des fournisseurs ont été évalués par une analyse ascendante et descendante des coûts. RÉSULTATS: Les coûts totaux pour les patients par épisode de traitement étaient les plus bas avec BPaL (518,0 USD) et augmentaient avec l'utilisation de SSOR (825,8 USD) et SLOR (1 023,0 USD). Les coûts totaux des prestataires par traitement réussi étaient les plus bas avec BPaL (1 994,5 USD) et ont augmenté avec SSOR (3 121,5 USD) et SLOR (10 032,4 USD). Comparé à SSOR, le traitement BPaL était rentable même au seuil de volonté de payer le plus bas. Comme prévu, le SLOR était le régime le plus coûteux et le moins efficace. CONCLUSIONS: Les coûts encourus par les patients sous BPaL étaient inférieurs de 37% (IC à 95% 22­56) à ceux du SSOR et de 50% (IC à 95% 32­68) à ceux du SLOR, tandis que les prestataires pouvaient économiser respectivement 36 % (IC à 95% 21­56) à 80% (IC à 95% 64­93) par traitement réussi. L'étude montre que le traitement de la DR-TB par BPaL a permis de réaliser des économies pour les patients et pour le système de santé.

Prevalence of depression in hypertensive patients and its associated factors in India: A systematic review and meta-analysis.

BACKGROUND: Hypertension is a prevalent health challenge in India, with a bidirectional link to depression. Recognizing the prevalence of depression among hypertensive patients and associated factors are important for better health outcomes. METHODS: A comprehensive search was conducted in PubMed, Embase, Scopus, and Google Scholar databases to identify relevant studies. R software was used for analysis, employing a random effects model with a 95% confidence interval. Subgroup analyses were done to explore sources of heterogeneity within the included studies. RESULTS: The prevalence of depression among hypertensive patients in India was 39.8% (95% CI: 28.6; 52.1). Despite a higher prevalence observed in South region (44.7%) compared to North (26.9%), the difference was not significant (p=0.39). Studies utilizing different assessment scales and varying sample sizes yielded similar prevalence. However, a temporal trend analysis indicated a higher prevalence in studies published between 2020 and 2023 (52.6%) compared to those published between 2016 and 2019 (35.5%) (p=0.03). Major factors associated with depression included lower socioeconomic status, low education level, female gender, uncontrolled hypertension, and COVID-19 related factors. CONCLUSIONS: A significant proportion of hypertensive patients suffer from depression. Therefore, screening for depression in hypertensive patients is essential to improve hypertension management in India.

Bioinformatic Prediction and High Throughput In Vivo Screening to Identify Cis-Regulatory Elements for the Development of Algal Synthetic Promoters.

Algae biotechnology holds immense promise for revolutionizing the bioeconomy through the sustainable and scalable production of various bioproducts. However, their development has been hindered by the lack of advanced genetic tools. This study introduces a synthetic biology approach to develop such tools, focusing on the construction and testing of synthetic promoters. By analyzing conserved DNA motifs within the promoter regions of highly expressed genes across six different algal species, we identified cis-regulatory elements (CREs) associated with high transcriptional activity. Combining the algorithms POWRS, STREME, and PhyloGibbs, we predicted 1511 CREs and inserted them into a minimal synthetic promoter sequence in 1, 2, or 3 copies, resulting in 4533 distinct synthetic promoters. These promoters were evaluated in vivo for their capacity to drive the expression of a transgene in a high-throughput manner through next-generation sequencing post antibiotic selection and fluorescence-activated cell sorting. To validate our approach, we sequenced hundreds of transgenic lines showing high levels of GFP expression. Further, we individually tested 14 identified promoters, revealing substantial increases in GFP expression─up to nine times higher than the baseline synthetic promoter, with five matching or even surpassing the performance of the native AR1 promoter. As a result of this study, we identified a catalog of CREs that can now be used to build superior synthetic algal promoters. More importantly, here we present a validated pipeline to generate building blocks for innovative synthetic genetic tools applicable to any algal species with a sequenced genome and transcriptome data set.

Postoperative pain, recovery and discharge after robot-assisted laparoscopic prostatectomy: A multicentre, single blinded, randomised controlled trial.

BACKGROUND: General anaesthesia is standard of care for patients undergoing robot assisted laparoscopic prostatectomy (RALP). However, postoperative pain and bladder discomfort remains an issue, and optimising pain management could improve recovery and promote earlier home discharge. The main objective of this trial was to evaluate if patients receiving spinal anaesthesia are more frequently home ready at 8 pm on the same day compared with multimodal pain management following RALP under general anaesthesia. METHODS: This pragmatic, randomised controlled, multicentre trial was performed between January 2019 to December 2021. Patients undergoing RALP under general anaesthesia were randomised to either multimodal analgesia using parecoxib and morphine intra-operatively (Group GM) or spinal anaesthesia with bupivacaine and sufentanil (Group GS). The primary aim, home readiness, was assessed using a post-anaesthesia discharge scoring system. RESULTS: Of 202 patients analysed, 27% patients reached home readiness criteria after 12 h, 46% after 24 h and 79% after 48 h, without differences between the groups. Urge to pass urine was greater in group GM than in group GS (p ⟨0.001) and lasted for a median of two hours in both groups. More patients expressed satisfaction with postoperative care in group GS (p ⟨0.001). No other significant differences were found between the groups. DISCUSSION: We found no difference in time to home readiness between the groups. Approximately one-fourth of the patients achieved home readiness the same day after surgery without difference between the groups. Fewer patients had urge, and patient satisfaction was greater in group GS.

Plasmons in the Kagome metal CsV3Sb5.

Plasmon polaritons, or plasmons, are coupled oscillations of electrons and electromagnetic fields that can confine the latter into deeply subwavelength scales, enabling novel polaritonic devices. While plasmons have been extensively studied in normal metals or semimetals, they remain largely unexplored in correlated materials. In this paper, we report infrared (IR) nano-imaging of thin flakes of CsV3Sb5, a prototypical layered Kagome metal. We observe propagating plasmon waves in real-space with wavelengths tunable by the flake thickness. From their frequency-momentum dispersion, we infer the out-of-plane dielectric function ϵ c that is generally difficult to obtain in conventional far-field optics, and elucidate signatures of electronic correlations when compared to density functional theory (DFT). We propose correlation effects might have switched the real part of ϵ c from negative to positive values over a wide range of middle-IR frequencies, transforming the surface plasmons into hyperbolic bulk plasmons, and have dramatically suppressed their dissipation.

Biodiversity of endosymbiont fungi associated with a marine sponge Lamellodysidea herbacea and their potential as antioxidant producers.

This study aims to isolate endosymbiontic fungi from the marine sponge Lamellodysidea herbacea and to explore their antioxidant potential. Marine-derived fungi, with their vast biodiversity, are considered a promising source of novel antioxidants which can replace synthetic ones. Marine sponges have previously reported bioactive properties that could ameliorate oxidative stress, particularly their associated fungi, producing high-frequency bioactive molecules (adaptogenic molecules) in response to stressors. 19 endosymbiont fungi associated with marine sponges were isolated, and their extracts were evaluated for their antioxidant capacities. Extract of an endosymbiont fungus, isolate SPG6, identified as Alternaria destruens, through surface electron microscopy (SEM) and ITS gene sequencing, showed broad range antioxidant activities (EC50 values) (free radical scavenging 32.54 mg L-1, Hydroxyl radical scavenging activity < 0.078 g L-1, total reducing power 0.114 g L-1, Chelating power 0.262 g L-1, H2O2 scavenging activity < 0.078 g L-1, and Superoxide radical scavenging activity > 5.0 g L-1). The extract of isolate SPG6 was fractioned and analyzed through GC-MS. Marine sponge-associated endosymbiont fungi are a rich source of antioxidant molecules. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03972-1.

3-Tesla cardiac magnetic resonance imaging in primary dilated cardiomyopathy.

Background: Cardiac magnetic resonance imaging (CMR) is an excellent non-invasive imaging tool in the assessment of patients with dilated cardiomyopathy (DCM). Few studies have analysed the findings in primary (idiopathic) DCM. Objectives: To study the CMR features in primary DCM. Methods: We conducted a descriptive observational study on 20 adult patients with suspected or confirmed primary DCM. Each patient underwent a dedicated 3-Tesla CMR scan, and the findings were evaluated. Results: Seventeen patients had systolic dysfunction with a reduced ejection fraction and elevated end-diastolic volume, 19 patients had contractile dysfunction in the form of global left ventricular hypokinesia, 13 patients showed no abnormal delayed contrast enhancement with gadolinium administration, and 7 patients showed abnormal late gadolinium enhancement patterns. Conclusion: In patients with primary DCM, CMR is a powerful diagnostic tool that can definitively establish the diagnosis, assess the severity of the disease, predict the risk of future adverse cardiovascular outcomes, check for complications, and assist in future follow-ups. Study synopsis: What the study adds. Cardiac magnetic resonance imaging (CMR) is an excellent non-invasive imaging tool in the assessment of patients with primary dilated cardiomyopathy (DCM). Findings include global ventricular enlargement, systolic dysfunction (ejection fraction <40%), and elevated end-diastolic (≥140 mL) and end-systolic volumes. Global abnormal wall contractility is often seen. In DCM there is either no abnormal gadolinium enhancement or curvilinear mid-myocardial or subepicardial late gadolinium enhancement, unrelated to a coronary artery distribution.Implications of the findings. In patients with primary DCM, CMR provides powerful diagnostic and prognostic information. Enhanced awareness and understanding of this relatively uncommon condition among clinicians and radiologists would be of benefit in patient management and treatment.

Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Current perspective in research and industrial applications of microbial cellulases.

The natural interactions between various bacteria, fungi, and other cellulolytic microorganisms destroy lignocellulosic polymers. The efficacy of this process is determined by the combined action of three main enzymes: endoglucanases, exo-glucanases, and ß-glucosidase. The enzyme attacks the polymeric structure's ß-1,4-linkages during the cellulose breakdown reaction. This mechanism is crucial for the environment as it recycles cellulose in the biosphere. However, there are problems with enzymatic cellulose breakdown, including complex cellulase structure, insufficient degradation efficacy, high production costs, and post-translational alterations, many of which are closely related to certain unidentified cellulase properties. These issues impede the practical use of cellulases. A developing area of research is the application of this similar paradigm for industrial objectives. Cellulase enzyme exhibits greater promise in many critical industries, including biofuel manufacture, textile smoothing and finishing, paper and pulp manufacturing, and farming. However, the study on cellulolytic enzymes must move forward in various directions, including increasing the activity of cellulase as well as designing peptides to give biocatalysts their desired attributes. This manuscript includes an overview of current research on different sources of cellulases, their production, and biochemical characterization.

Signatures of Correlated Defects in an Ultraclean Wigner Crystal in the Extreme Quantum Limit.

Low-disorder two-dimensional electron systems in the presence of a strong, perpendicular magnetic field terminate at very small Landau level filling factors in a Wigner crystal (WC), where the electrons form an ordered array to minimize the Coulomb repulsion. The nature of this exotic, many-body, quantum phase is yet to be fully understood and experimentally revealed. Here we probe one of WC's most fundamental parameters, namely, the energy gap that determines its low-temperature conductivity, in record mobility, ultrahigh-purity, two-dimensional electrons confined to GaAs quantum wells. The WC domains in these samples contain ≃1000 electrons. The measured gaps are a factor of three larger than previously reported for lower quality samples, and agree remarkably well with values predicted for the lowest-energy, intrinsic, hypercorrelated bubble defects in a WC made of flux-electron composite fermions, rather than bare electrons. The agreement is particularly noteworthy, given that the calculations are done for disorder-free composite fermion WCs, and there are no adjustable parameters. The results reflect the exceptionally high quality of the samples, and suggest that composite fermion WCs are indeed more stable compared to their electron counterparts.

Abdominal wall reconstruction (AWR) for post-trauma laparotomy ventral hernia and follow-up assessment of functional quality of life (QOL): experience of a level-1 trauma centre in India.

PURPOSE: The aim of this study was to examine the postoperative outcomes and follow-up QOL of patients after AWR at a level-1 trauma centre in India. METHODS: The study cohort included AWR patients treated between January 2011 and July 2022. The Activities Assessment Scale (AAS) was used to measure QOL, and the Ventral Hernia Recurrence Inventory (VHRI) was used to determine the occurrence of recurrence. In patients suspected of having recurrence, thorough clinical examination and relevant imaging were performed to confirm or rule out recurrence. RESULTS: Out of 89 patients, 35 patients whose complete perioperative and follow-up data were available were enrolled. The mean age of the patients was 28 (SD, 9) years. The mean defect size was 14. 9 (SD, 7) cm. The mean time from laparotomy to AWR surgery was 21 months. During the postoperative course, 37% of patients developed complications, such as SSI and seroma. The mean follow-up time was 53 (SD, 43) months. Upon comparing procedures involving the mesh placed in the sublay position with procedures involving the mesh placed in other positions, no statistically significant difference in the recurrence rate (one in each group, p = 0.99), surgical complication rate (33% v/s 66%, p = 0.6), or mean AAS QOL score (94.7 v/s 98, p = 0.4) was observed. The specificity of the VHRI for diagnosing recurrence was 79%. CONCLUSION: Overall, the recurrence rate was low in these patients despite the presence of large hernia defects. Long-term QOL was not affected by the specific procedure used. Timely planning and execution are more important than the specific repair approach for post-trauma laparotomy ventral hernia.

Mandibular reconstruction using an iliac bone flap with perforator-supported external oblique abdominal muscle island: a pilot study.

The deep circumflex iliac artery (DCIA) flap is one of the bone flaps commonly used for mandibular reconstruction. Observation of the skin paddle and Doppler ultrasound are methods that are usually used to monitor DCIA flaps after mandibular reconstruction surgery. The aim of this study was to introduce a novel DCIA flap with a perforator-supported external oblique abdominal muscle (EOAM) island for postoperative flap monitoring. This study included five patients who underwent mandibular reconstruction using this modified technique. The DCIA flap and the EOAM island supplied by the ascending branch of the DCIA were harvested during the surgery. After mandibular reconstruction, the EOAM island was placed in the submandibular region to monitor the blood supply to the DCIA flap after surgery. The blood supply to the DCIA flap was monitored by observing the colour, texture, and bleeding condition of the EOAM island. After the monitoring period, the EOAM was removed and the ascending branch of the DCIA was ligated. The outcome was successful in all patients. The EOAM island supported by the ascending branch of the DCIA is reliable and safe, thus providing a robust option to monitor the blood supply to the DCIA flap.

Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Differential impact of COVID-19 on mental health and burnout.

BACKGROUND: There may be differential impact of the COVID-19 pandemic on mental health and burnout rates of healthcare professionals (HCPs) performing different roles. AIMS: To examine mental health and burnout rates, and possible drivers for any disparities between professional roles. METHODS: In this cohort study, online surveys were distributed to HCPs in July-September 2020 (baseline) and re-sent 4 months later (follow-up; December 2020) assessing for probable major depressive disorder (MDD), generalized anxiety disorder (GAD), insomnia, mental well-being and burnout (emotional exhaustion and depersonalization). Separate logistic regression models (at both phases) compared the risk of outcomes between roles: healthcare assistants (HCAs), nurses and midwives (nurses), allied health professionals (AHPs) and doctors (reference group). Separate linear regression models were also developed relating the change in scores to professional role. RESULTS: At baseline (n = 1537), nurses had a 1.9-fold and 2.5-fold increased risk of MDD and insomnia, respectively. AHPs had a 1.7-fold and 1.4-fold increased risk of MDD and emotional exhaustion, respectively. At follow-up (n = 736), the disproportionate risk between doctors and others worsened: nurses and HCAs were at 3.7-fold and 3.6-fold increased risk of insomnia, respectively. Nurses also had a significantly increased risk of MDD, GAD, poor mental well-being and burnout. Nurses also had significantly worsened anxiety, mental well-being and burnout scores over time, relative to doctors. CONCLUSIONS: Nurses and AHPs had excess risk of adverse mental health and burnout during the pandemic, and this difference worsened over time (in nurses especially). Our findings support adoption of targeted strategies accounting for different HCP roles.

Perioperative myocardial injury is associated with increased postoperative non-cardiac complications in patients undergoing vascular surgery: a post hoc analysis of a randomised clinical pilot trial.

BACKGROUND: Elevated cardiac biomarkers, such as high-sensitivity cardiac Troponin T and N-terminal pro-B-type natriuretic peptide improve the prediction of major adverse cardiac events. However, very few trials have investigated the association between perioperative cardiac injury and non-cardiac complications. The primary aim of this study was to determine the association between peri-operative myocardial injury and non-cardiac complications in patients undergoing vascular surgery. Additionally, the association between elevated pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide and non-cardiac complications was explored. METHODS: This study is a post hoc analysis of a multicentre randomised controlled trial. Patients were recruited from three centres in Sweden between 2016 and 2019. Cardiac troponin level was measured pre-operatively and at 4, 24, and 48 h after the start of surgery in patients undergoing vascular surgery. N-terminal pro-B-type natriuretic peptide was measured pre-operatively. The primary outcome was a composite of major postoperative non-cardiac complications assessed at 30 days. RESULTS: A total of 184 patients undergoing peripheral or aortic vascular surgery were included in this study. The primary endpoint occurred in 67 (36%) patients. Perioperative myocardial injury was significantly associated with non-cardiac complications, with an adjusted odds ratio (OR) of 2.71 (95% confidence interval 1.33-5.55, P = 0.01). Sensitivity and specificity were 0.40 and 0.81, respectively. No association was found between pre-operative hs-cTnT or NT-proBNP and non-cardiac complications. CONCLUSION: In this pilot study, we found that new peri-operative myocardial injury is associated with an increased risk of non-cardiac complications within 30 days after index surgery in patients undergoing vascular surgery. Pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide did not appear to predict non-cardiac complications. Larger studies are needed to confirm our findings. TRIAL REGISTRATION: EudraCT database: 2016-001584-36.