A cluster-randomized trial of client and provider directed financial interventions to align incentives with appropriate case management in private medicine retailers: Results of the TESTsmART trial in Lagos, Nigeria.

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemisinin-based Combination Therapy (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that mRDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Trials registration: Clinical Trials Registration Number: NCT04428307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816435/ Correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476591/.

Promoting mental wellbeing in pregnant women living in Pakistan with the Safe Motherhood-Accessible Resilience Training (SM-ART) intervention: a randomized controlled trial.

BACKGROUND: The negative impact of adverse perinatal mental health extends beyond the mother and child; therefore, it is essential to make an early intervention for the management of mental illness during pregnancy. Resilience-building interventions are demonstrated to reduce depression and anxiety among expectant mothers, yet research in this field is limited. This study aims to examine the effect of the 'Safe Motherhood-Accessible Resilience Training (SM-ART)' on resilience, marital adjustment, depression, and pregnancy-related anxiety in a sample of pregnant women in Karachi, Pakistan. METHOD: In this single-blinded block randomized controlled study, 200 pregnant women were recruited and randomly assigned to either an intervention or a control group using computer-generated randomization and opaque sealed envelopes. The intervention group received the SM-ART intervention consisting of six, weekly sessions ranging from 60 to 90 min. Outcomes (Resilience, depression, pregnancy-related anxiety and marital harmony) were assessed through validated instruments at baseline and after six weeks of both intervention and control groups. RESULTS: The results revealed a significant increase in mean resilience scores (Difference:6.91, Effect size: 0.48, p-value < 0.05) and a decrease in depressive symptoms (Difference: -2.12, Effect size: 0.21, p-value < 0.05) in the intervention group compared to the control group. However, no significant change was observed in anxiety and marital adjustment scores. CONCLUSION: The SM-ART intervention has the potential to boost resilience scores and decrease depressive symptoms in pregnant women and offers a promising intervention to improve maternal psychological health. TRIAL REGISTRATION: NCT04694261, Date of first trial registration: 05/01/2021.

International Consensus Definition and Diagnostic Criteria for Generalized Pustular Psoriasis From the International Psoriasis Council.

Importance: Generalized pustular psoriasis (GPP) lacks internationally accepted definitions and diagnostic criteria, impeding timely diagnosis and treatment and hindering cross-regional clinical and epidemiological study comparisons. Objective: To develop an international consensus definition and diagnostic criteria for GPP using the modified Delphi method. Evidence Review: The rarity of GPP presents a challenge in acquiring comprehensive published clinical data necessary for developing standardized definition and criteria. Instead of relying on a literature search, 43 statements that comprehensively addressed the fundamental aspects of the definitions and diagnostic criteria for GPP were formulated based on expert reviews of 64 challenging GPP cases. These statements were presented to a panel of 33 global GPP experts for voting, discussion, and refinements in 2 virtual consensus meetings. Consensus during voting was defined as at least 80% agreement; the definition and diagnostic criteria were accepted by all panelists after voting and in-depth discussion. Findings: In the first and second modified Delphi round, 30 (91%) and 25 (76%) experts participated. In the initial Delphi round, consensus was achieved for 53% of the statements, leading to the approval of 23 statements that were utilized to develop the proposed definitions and diagnostic criteria for GPP. During the second Delphi round, the final definition established was, "Generalized Pustular Psoriasis is a systemic inflammatory disease characterized by cutaneous erythema and macroscopically visible sterile pustules." It can occur with or without systemic symptoms, other psoriasis types, and laboratory abnormalities. GPP may manifest as an acute form with widespread pustules or a subacute variant with an annular phenotype. The identified essential criterion was, "Macroscopically visible sterile pustules on erythematous base and not restricted to the acral region or within psoriatic plaques." Conclusions and Relevance: The achievement of international consensus on the definition and diagnostic criteria for GPP underscores the importance of collaboration, innovative methodology, and expert engagement to address rare diseases. Although further validation is needed, these criteria can serve as a reference point for clinicians, researchers, and patients, which may contribute to more accurate diagnosis and improved management of GPP.

Provider attitudes towards quality improvement for myocardial infarction care in northern Tanzania.

INTRODUCTION: Myocardial Infarction (MI) is a leading cause of death worldwide. In high income countries, quality improvement strategies have played an important role in increasing uptake of evidence-based MI care and improving MI outcomes. The incidence of MI in sub-Saharan Africa is rising, but uptake of evidence-based care in northern Tanzania is low. There are currently no published quality improvement interventions from the region. The objective of this study was to determine provider attitudes towards a planned quality improvement intervention for MI care in northern Tanzania. METHODS: This study was conducted at a zonal referral hospital in northern Tanzania. A 41-question survey, informed by the Theoretical Framework for Acceptability, was developed by an interdisciplinary team from Tanzania and the United States. The survey, which explored provider attitudes towards MI care improvement, was administered to key provider stakeholders (physicians, nurses, and hospital administrators) using convenience sampling. RESULTS: A total of 140 providers were enrolled, including 82 (58.6%) nurses, 56 (40.0%) physicians, and 2 (1.4%) hospital administrators. Most participants worked in the Emergency Department or inpatient medical ward. Providers were interested in participating in a quality improvement project to improve MI care at their facility, with 139 (99.3%) strongly agreeing or agreeing with this statement. All participants agreed or strongly agreed that improvements were needed to MI care pathways at their facility. Though their facility has an MI care protocol, only 88 (62.9%) providers were aware of it. When asked which intervention would be the single-most effective strategy to improve MI care, the two most common responses were provider training (n = 66, 47.1%) and patient education (n = 41, 29.3%). CONCLUSION: Providers in northern Tanzania reported strongly positive attitudes towards quality improvement interventions for MI care. Locally-tailored interventions to improve MI should include provider training and patient education strategies.

Risk Factors for Invasive Fungal Infection in Lung Transplant Recipients on Universal Antifungal Prophylaxis.

Background: Many centers use universal antifungal prophylaxis after lung transplant, but risk factors for invasive fungal infection (IFI) in this setting are poorly described. Methods: This retrospective, single-center cohort study including 603 lung transplant recipients assessed risk factors for early (within 90 days of transplant) invasive candidiasis (IC) and invasive mold infection (IMI) and late (90-365 days after transplant) IMI using Cox proportional hazard regression. Results: In this cohort, 159 (26.4%) patients had 182 IFIs. Growth of yeast on donor culture (hazard ratio [HR], 3.30; 95% CI, 1.89-5.75) and prolonged length of stay (HR, 1.02; 95% CI, 1.01-1.03) were associated with early IC risk, whereas transplantation in 2016 or 2017 (HR, 0.21; 95% CI, 0.06-0.70; HR, 0.25; 95% CI, 0.08-0.80, respectively) and female recipient sex (HR, 0.53; 95% CI, 0.30-0.93) were associated with reduced risk. Antimold therapy (HR, 0.21; 95% CI, 0.06-0.78) was associated with lower early IMI risk, and female donor sex (HR, 0.40; 95% CI, 0.22-0.72) was associated with lower late IMI risk. Recent rejection was a risk factor for late IMI (HR, 1.73; 95% CI, 1.02-2.95), and renal replacement therapy predisposed to early IC, early IMI, and late IMI (HR, 5.67; 95% CI, 3.01-10.67; HR, 7.54; 95% CI, 1.93-29.45; HR, 5.33; 95% CI, 1.46-19.49, respectively). Conclusions: In lung transplant recipients receiving universal antifungal prophylaxis, risk factors for early IC, early IMI, and late IMI differ.

Autogenous breast reconstruction for total mastectomies: a narrative review.

Background and Objective: Mastectomies have a significant socio-psychological impact, motivating patients to undergo breast reconstruction. Initially, silicone implants were used to reconstruct the breast. However, breast implants have been the subject of successive crises throughout the years. Indeed, rupture, silicone bleeding, and capsular contracture remain topical. In 2019, the BIOCELL textured breast implants was banned and recalled due to the discovery of the breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). More recently, the breast implant illness has been depicted in the media. To cope with these issues and to respond to some patients' expectations for a natural reconstruction, plastic surgeons have developed autogenous solutions for breast reconstruction. Since Taylor's research on angiosomes, the development of the microsurgery and more recently fat grafting, autogenous breast reconstruction has known a tremendous expansion. Autologous breast reconstruction allows a more natural feeling and texture. This narrative review aims to provide to the readers a comprehensive and updated evidence-based overview of state of the art about autologous breast reconstruction after total mastectomy. Methods: We conducted a narrative review of the literature searching for papers published between January 2010 and December 2022. The MeSH terms with different combinations were used to identify articles for inclusion. After screening article titles and abstracts independently by three authors, 66 papers were included in this review. Key Content and Findings: In this review, the authors describe and discuss the different autogenous techniques in breast reconstruction. Conclusions: Autologous reconstructions provide very satisfactory, durable, and reliable results with relatively low complication rates. Deep inferior epigastric perforator (DIEP) flaps, latissimus dorsi flaps and autologous fat grafting are the most common type of autogenous breast reconstructions.

Evaluating the performance of the HEART score in a Tanzanian emergency department.

OBJECTIVE: The HEART score successfully risk stratifies emergency department (ED) patients with chest pain in high-income settings. However, this tool has not been validated in low-income countries. METHODS: This is a secondary analysis of a prospective observational study that was conducted in a Tanzanian ED from January 2019 through January 2023. Adult patients with chest pain were consecutively enrolled, and their presenting symptoms and medical history were recorded. Electrocardiograms and point-of-care troponin assays were obtained for all participants. Thirty-day follow-up was conducted, assessing for major adverse cardiac events (MACEs), defined as death, myocardial infarction, or coronary revascularization (coronary artery bypass grafting or percutaneous coronary intervention). HEART scores were calculated for all participants. Likelihood ratios, sensitivity, specificity, and negative predictive values (NPVs) were calculated for each HEART cutoff score to predict 30-day MACEs, and area under the curve (AUC) was calculated from the receiver operating characteristic curve. RESULTS: Of 927 participants with chest pain, the median (IQR) age was 61 (45.5-74.0) years. Of participants, 216 (23.3%) patients experienced 30-day MACEs, including 163 (17.6%) who died, 48 (5.2%) with myocardial infarction, and 23 (2.5%) with coronary revascularization. The positive likelihood ratio for each cutoff score ranged from 1.023 (95% CI 1.004-1.042; cutoff ≥ 1) to 3.556 (95% CI 1.929-6.555; cutoff ≥ 7). The recommended cutoff of ≥4 to identify patients at high risk of MACEs yielded a sensitivity of 59.4%, specificity of 52.8%, and NPV of 74.7%. The AUC was 0.61. CONCLUSIONS: Among patients with chest pain in a Tanzanian ED, the HEART score did not perform as well as in high-income settings. Locally validated risk stratification tools are needed for ED patients with chest pain in low-income countries.

A cluster-randomized trial of client and provider-directed financial interventions to align incentives with appropriate case management in retail medicine outlets: Results of the TESTsmART Trial in western Kenya.

ACTs are responsible for a substantial proportion of the global reduction in malaria mortality over the last ten years, made possible by publicly-funded subsidies making these drugs accessible and affordable in the private sector. However, inexpensive ACTs available in retail outlets have contributed substantially to overconsumption. We test an innovative, scalable strategy to target ACT-subsidies to clients with a confirmatory diagnosis. We supported malaria testing(mRDTs) in 39 medicine outlets in western Kenya, randomized to three study arms; control arm offering subsidized mRDT testing (0.4USD), client-directed intervention where all clients who received a positive RDT at the outlet were eligible for a free (fully-subsidized) ACT, and a combined client and provider directed intervention where clients with a positive RDT were eligible for free ACT and outlets received 0.1USD for every RDT performed. Our primary outcome was the proportion of ACT dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients tested at the outlet and adherence to diagnostic test results. 43% of clients chose to test at the outlet. Test results informed treatment decisions, resulting in targeting of ACTs to confirmed malaria cases- 25.3% of test-negative clients purchased an ACT compared to 75% of untested clients. Client-directed and client+provider-directed interventions did not offer further improvements, compared to the control arm, in testing rates(RD = 0.09, 95%CI:-0.08,0.26) or dispensing of ACTs to test-positive clients(RD = 0.01,95% CI:-0.14, 0.16). Clients were often unaware of the price they paid for the ACT leading to uncertainty in whether the ACT subsidy was passed on to the client. This uncertainty undermines our ability to definitively conclude that client-directed subsidies are not effective for improving testing and appropriate treatment. We conclude that mRDTs could reduce ACT overconsumption in the private retail sector, but incentive structures are difficult to scale and their value to private providers is uncertain. Trial registration: ClinicalTrials.gov NCT04428307.

QSAR modelling, molecular docking, molecular dynamic and ADMET prediction of pyrrolopyrimidine derivatives as novel Bruton's tyrosine kinase (BTK) inhibitors.

In recent years, there has been a focus on developing and discovering novel Bruton's tyrosine kinase (BTK) inhibitors, as they offer an effective treatment strategy for B-cell malignancies. BTK plays a crucial role in B cell receptor (BCR)-mediated activation and proliferation by regulating downstream factors such as the NF-κB and MAP kinase pathways. To address this challenge and propose potential therapeutic options for B-cell lymphomas, researchers conducted 2D-QSAR and ADMET studies on pyrrolopyrimidine derivatives that act as inhibitors of the BCR site in cytochrome b. These studies aim to improve and identify new compounds that could serve as more potent potential BTK inhibitors, which would lead to the identification of new drug candidates in this field. In our study, we used 2D-QSAR (multiple linear regression, multiple nonlinear regression, and artificial neural networks), molecular docking, molecular dynamics, and ADMET properties to investigate the potential of 35 pyrrolopyrimidine derivatives as BTK inhibitors. A molecular docking study and molecular dynamics simulations of molecule 13 over 10 ns revealed that it establishes multiple hydrogen bonds with several residues and exhibits frequent stability throughout the simulation period. Based on the results obtained by molecular modeling, we proposed six new compounds (Pred1, Pred2, Pred3, Pred4, Pred5, and Pred6) with highly significant predicted activity by MLR models. A study based on the in silico evaluation of the predicted ADMET properties of the new candidate molecules is strongly recommended to classify these molecules as promising candidates for new anticancer agents specifically designed to target Bruton's tyrosine kinase (BTK) inhibition.

Development and Validation of Safe Motherhood-Accessible Resilience Training (SM-ART) Intervention to Improve Perinatal Mental Health.

Perinatal mental health issues in women can lead to a variety of health complications for both mother and child. Building resilience can strengthen coping mechanisms for pregnant women to improve their mental health and protect themselves and their children. The study aims to develop and validate the contextual and cultural appropriateness of the Safe Motherhood-Accessible Resilience Training (SM-ART) intervention for pregnant women in Pakistan. A three-phase approach was used to develop and validate an intervention that promotes resilience in pregnant women. Phase I comprised a needs assessment with stakeholders (pregnant women and key informants) to elicit opinions regarding module content. In Phase II, an intervention to build resilience was developed with the help of a literature review and formative assessment findings, and Phase III involved the validation of the intervention by eight mental health experts. The experts assessed the Content Validity Index (CVI) of the SM-ART intervention on a self-developed checklist. The resultant SM-ART intervention consists of six modules with strong to perfect CVI scores for each of the modules. Qualitative responses endorsed the strengths of the intervention as having innovative and engaging activities, contextual and cultural relevance, and a detailed, comprehensive facilitator guide. SM-ART was successfully developed and validated and is now ready for testing to promote the resilience of pregnant women at risk of perinatal mental illness.

The CaSR Modulator NPS-2143 Reduced UV-Induced DNA Damage in Skh:hr1 Hairless Mice but Minimally Inhibited Skin Tumours.

The calcium-sensing receptor (CaSR) is an important regulator of epidermal function. We previously reported that knockdown of the CaSR or treatment with its negative allosteric modulator, NPS-2143, significantly reduced UV-induced DNA damage, a key factor in skin cancer development. We subsequently wanted to test whether topical NPS-2143 could also reduce UV-DNA damage, immune suppression, or skin tumour development in mice. In this study, topical application of NPS-2143 (228 or 2280 pmol/cm2) to Skh:hr1 female mice reduced UV-induced cyclobutane pyrimidine dimers (CPD) (p < 0.05) and oxidative DNA damage (8-OHdG) (p < 0.05) to a similar extent as the known photoprotective agent 1,25(OH)2 vitamin D3 (calcitriol, 1,25D). Topical NPS-2143 failed to rescue UV-induced immunosuppression in a contact hypersensitivity study. In a chronic UV photocarcinogenesis protocol, topical NPS-2143 reduced squamous cell carcinomas for only up to 24 weeks (p < 0.02) but had no other effect on skin tumour development. In human keratinocytes, 1,25D, which protected mice from UV-induced skin tumours, significantly reduced UV-upregulated p-CREB expression (p < 0.01), a potential early anti-tumour marker, while NPS-2143 had no effect. This result, together with the failure to reduce UV-induced immunosuppression, may explain why the reduction in UV-DNA damage in mice with NPS-2143 was not sufficient to inhibit skin tumour formation.

Resilience and prenatal mental health in Pakistan: a qualitative inquiry.

BACKGROUND: Women in Pakistan suffer from a high rate of depression. The stress of low-income, illiteracy, exposure to violence and living in a patriarchal society are predisposing vulnerabilities for depression, particularly during and following pregnancy. The resilience of an individual plays a significant role in promoting prenatal mental health, but this has yet to be thoroughly researched. In this article, our objective is to identify the core characteristics of resilience among pregnant women, which will then help us in developing an intervention. METHODS: The exploratory-descriptive study was conducted over 6 months in five different antenatal hospitals in Sindh, Pakistan. A total of 17 semi-structured interviews were conducted with pregnant women, purposefully selected with heterogeneous characteristics to explore diverse perspectives, while symptoms of depression were quantified by the Edinburgh Postnatal Depression Scale before the interview. Verbatim transcriptions were coded openly and merged into categories and themes. RESULT: A total of six themes emerged from in-depth thematic analysis: 1) purpose of life, 2) dealing with emotions, 3) believing in yourself, 4) optimistic approach, 5) strengthening support and relationship and 6) spirituality and humanity. Women agreed that these characteristics could help them improve their mental health. CONCLUSION: In conclusion, these themes were the core components of pregnant women's resilience which ultimately could help to promote prenatal mental health. These pave a pathway towards developing culturally and contextually resilience interventions aimed at enhancing mental health of pregnant women which then may improve neonatal and family mental wellbeing.

Computational drug design of novel COVID-19 inhibitor.

Background: In 2003, the first case of severe acute respiratory syndrome coronavirus (SARS-CoV) was recorded. Coronaviruses (CoVs) have caused a major outbreak of human fatal pneumonia. Currently, there is no specific drug or treatment for diseases caused by SARS CoV 2. Computational approach that adopts dynamic models is widely accepted as indispensable tool in drug design but yet to be exploited in covid-19 in Zaria, Nigeria. In this study, steps were taken to advance on the successful achievements in the field of covid-19 drug, with the aid of in silico drug design technique, to create novel inhibitor drug candidates with better activity. In this study, one thousand human immunodeficiency virus (HIV1) antiviral chemical compounds from www.bindingBD.org were docked on the SARS CoV 2 main protease protein data bank identification number 6XBH (PDB ID: 6XBH) and the molecular docking score were ranked in order to identify the compounds with the highest inhibitory effects, and easy selection for future studies. Results: The docking studies showed some interesting results. Inhibitors with Index numbers 331, 741, and 819 had the highest binding affinity. Similarly, inhibitors with Index number 441, 847, and 46 had the lowest hydrogen bond energy. Inhibitor with index number 331 was reported with the lowest value (- 48.38kCal/mol). Five new compounds were designed from the selected six (6) compounds with the best binding score giving a total of thirty (30) novel compounds. The low binding energy of inhibitor with index no. 847b is unique, as most of the interaction energies are of H-bond type with amino acids (Thr26, Gly143, Ser144, Cys145, Glu166, Gln189, Hie164, Met49, Thr26, Thr25, Thr190, Asn142, Met165) resulting in an overall negative value (-16.31 kCal/mol) making it the best of all the newly designed inhibitors. Conclusions: The novel inhibitor is 2-(2-(5-amino-2-((((3-aminobenzyl)oxy)carbonyl)amino)-5-oxopentanamido)-4-(2-(tert-butyl)-4-oxo-4-(pentan-3-ylamino) butanamido)-3-hydroxybutyl) benzoic acid. The improvement it has over the parent inhibitor is from the primary amine group attached to meta position of first benzene ring and the carboxyl group attached to the ortho position of the second benzene ring. The molecular dynamics studies also show that the novel inhibitor remains stable after the study. This result makes it a better drug candidate against SARS CoV 2 main protease when compared with the co-crystallized inhibitor or any of the 1000 docked inhibitors. Supplementary Information: The online version contains supplementary material available at 10.1186/s42269-022-00892-z.

A new person-fit method based on machine learning in CDM in education.

Cognitive diagnosis models have become popular in educational assessment and are used to provide more individualized feedback about a student's specific strengths and weaknesses than traditional total scores. However, if the testing data are contaminated by certain biases or aberrant response patterns, such predictions may not be accurate. The current research objective is to develop a new person-fit method that is based on machine learning and improves the functionality of existing person-fit methods. Various simulations were designed under three aberrant conditions: cheating, sleeping and random guessing. Simulation results showed that the new method was more powerful and effective than previous methods, especially for short-length tests.

UV-induced DNA Damage in Skin is Reduced by CaSR Inhibition.

The epidermis maintains a cellular calcium gradient that supports keratinocyte differentiation from its basal layers (low) to outer layers (high) leading to the development of the stratum corneum, which resists penetration of UV radiation. The calcium-sensing receptor (CaSR) expressed in keratinocytes responds to the calcium gradient with signals that promote differentiation. In this study, we investigated whether the CaSR is involved more directly in protection from UV damage in studies of human keratinocytes in primary culture and in mouse skin studied in vivo. siRNA-directed reductions in CaSR protein levels in human keratinocytes significantly reduced UV-induced direct cyclobutane pyrimidine dimers (CPD) by ~80% and oxidative DNA damage (8-OHdG) by ~65% compared with control transfected cells. Similarly, in untransfected cells, the CaSR negative modulator, NPS-2143 (500 nm), reduced UV-induced CPD and 8-OHdG by ~70%. NPS-2143 also enhanced DNA repair and reduced reactive oxygen species (ROS) by ~35% in UV-exposed keratinocytes, consistent with reduced DNA damage after UV exposure. Topical application of NPS-2143 also protected hairless Skh:hr1 mice from UV-induced CPD, oxidative DNA damage and inflammation, similar to the reductions observed in response to the well-known photoprotection agent 1,25(OH)2 D3 (calcitriol). Thus, negative modulators of the CaSR offer a new approach to reducing UV-induced skin damage.

Computer-aided modeling of triazole analogues, docking studies of the compounds on DNA gyrase enzyme and design of new hypothetical compounds with efficient activities.

The increasing problem of multi-drug resistant-tuberculosis has focused attention on developing new drugs that are not only active against drug-resistant tuberculosis, but also shorten the lengthy therapy. Therefore, this work employs the application of modeling technique to predict the inhibition activities of some prominent compounds which been reported to be efficient against Mycobacterium tuberculosis. To accomplish the purpose of this work, multiple regression and genetic function approximation were adopted to create the model. The established model was swayed with topological descriptors; MATS7s, SpMin4_Bhv, TDB3v and RDF70v. More also, interactions between the compounds and the target protein 'DNA gyrase' were evaluated via molecular docking approach utilizing the PyRx and discovery studio simulation software. Based on the docking analysis, compound 20 has the most noticeable binding affinity of -16.5 kcal/mol. Therefore, compound 20 served as a reference structural template and insight to design fourteen novel hypothetical agents with more prominent anti-tubercular activities. More also, compound 20j was observed with the highest activity among the designed compounds with a prominent binding affinity of -24.3 kcal/mol. Therefore, this research recommends in-vivo, in-vitro screening and pharmacokinetic properties to be carried out in order to determine the toxicity of the designed compounds.Communicated by Ramaswamy H. Sarma.

speciesLink: rich data and novel tools for digital assessments of biodiversity / speciesLink: dados valiosos e ferramentas inovadoras para avaliações digitais da biodiversidade

Abstract speciesLink is a large-scale biodiversity information portal that exists thanks to a broad collaborative network of people and institutions. CRIA's involvement with the scientific community of Brazil and other countries is responsible for the significant results achieved, currently reaching more than 15 million primary biodiversity data records, 95% of which are associated with preserved specimens and about 25% with high-quality digital images. The network provides data on over 200,000 species, of which over 110,000 occur in Brazil. This article describes thematic networks within speciesLink, as well as some of the most useful tools developed. The importance and contributions of speciesLink are outlined, as are concerns about securing stable budgetary support for such biodiversity data e-infrastructures. Here we review the value of speciesLink as a major source of biodiversity information for research, education, informed decision-making, policy development, and bioeconomy.

Resumo speciesLink é um portal de informações em larga escala sobre biodiversidade, que existe graças a uma ampla rede colaborativa de pessoas e instituições. O envolvimento do CRIA com a comunidade científica do Brasil e de outros países é responsável pelos resultados expressivos alcançados, atingindo atualmente mais de 15 milhões de registros de dados primários de biodiversidade, sendo 95% associados a espécimes preservados e cerca de 25% a imagens digitais de alta qualidade. A rede fornece dados sobre mais de 200.000 espécies, das quais mais de 110.000 ocorrem no Brasil. Este artigo descreve as redes temáticas do speciesLink, bem como algumas das ferramentas mais úteis desenvolvidas. A importância e as contribuições do speciesLink são destacadas, assim como as preocupações em garantir um apoio financeiro estável para e-infraestruturas de dados sobre biodiversidade. Aqui revisamos o valor do speciesLink como uma das principais fontes de informação sobre biodiversidade para pesquisa, educação, tomada de decisão, desenvolvimento de políticas e bioeconomia.

Faster super-resolution ultrasound imaging with a deep learning model for tissue decluttering and contrast agent localization.

Super-resolution ultrasound (SR-US) imaging allows visualization of microvascular structures as small as tens of micrometers in diameter. However, use in the clinical setting has been impeded in part by ultrasound (US) acquisition times exceeding a breath-hold and by the need for extensive offline computation. Deep learning techniques have been shown to be effective in modeling the two more computationally intensive steps of microbubble (MB) contrast agent detection and localization. Performance gains by deep networks over conventional methods are more than two orders of magnitude and in addition the networks can localize overlapping MBs. The ability to separate overlapping MBs allows use of higher contrast agent concentrations and reduces US image acquisition time. Herein we propose a fully convolutional neural network (CNN) architecture to perform the operations of MB detection as well as localization in a single model. Termed SRUSnet, the network is based on the MobileNetV3 architecture modified for 3-D input data, minimal convergence time, and high-resolution data output using a flexible regression head. Also, we propose to combine linear B-mode US imaging and nonlinear contrast pulse sequencing (CPS) which has been shown to increase MB detection and further reduce the US image acquisition time. The network was trained within silicodata and tested onin vitrodata from a tissue-mimicking flow phantom, and onin vivodata from the rat hind limb (N = 3). Images were collected with a programmable US system (Vantage 256, Verasonics Inc., Kirkland, WA) using an L11-4v linear array transducer. The network exceeded 99.9% detection accuracy onin silicodata. The average localization accuracy was smaller than the resolution of a pixel (i.e.λ/8). The average processing time on a Nvidia GeForce 2080Ti GPU was 64.5 ms for a 128 × 128-pixel image.

A Systematic Review of the Biological Effects of Cordycepin.

We conducted a systematic review of the literature on the effects of cordycepin on cell survival and proliferation, inflammation, signal transduction and animal models. A total of 1204 publications on cordycepin were found by the cut-off date of 1 February 2021. After application of the exclusion criteria, 791 papers remained. These were read and data on the chosen subjects were extracted. We found 192 papers on the effects of cordycepin on cell survival and proliferation and calculated a median inhibitory concentration (IC50) of 135 µM. Cordycepin consistently repressed cell migration (26 papers) and cellular inflammation (53 papers). Evaluation of 76 papers on signal transduction indicated consistently reduced PI3K/mTOR/AKT and ERK signalling and activation of AMPK. In contrast, the effects of cordycepin on the p38 and Jun kinases were variable, as were the effects on cell cycle arrest (53 papers), suggesting these are cell-specific responses. The examination of 150 animal studies indicated that purified cordycepin has many potential therapeutic effects, including the reduction of tumour growth (37 papers), repression of pain and inflammation (9 papers), protecting brain function (11 papers), improvement of respiratory and cardiac conditions (8 and 19 papers) and amelioration of metabolic disorders (8 papers). Nearly all these data are consistent with cordycepin mediating its therapeutic effects through activating AMPK, inhibiting PI3K/mTOR/AKT and repressing the inflammatory response. We conclude that cordycepin has excellent potential as a lead for drug development, especially for age-related diseases. In addition, we discuss the remaining issues around the mechanism of action, toxicity and biodistribution of cordycepin.

The effect of a culturally sensitive mental well-being module on Pakistani nursing students' knowledge and beliefs regarding their own mental health and illness.

This study examined the effect of a mental well-being module on undergraduate nursing students' knowledge and beliefs regarding causes and treatment of mental health and illness, and explored the relationship between these variables and depression and anxiety. The one group design incorporated pre-intervention, intervention and post-intervention phases, in a consecutive sample of 246 students in a 4-year BScN programme in Pakistan. A culturally sensitive, interactive mental well-being module of four hours length was delivered to three groups of approximately 40 students per group. Repeated measures ANOVA was performed to assess the difference in the mean knowledge scores. Paired t-tests investigated between-group differences on the factor scores. A total of 112 students screened positive for anxiety and depression symptoms. Repeated measures ANOVA showed a significant difference in the mean knowledge scores regarding mental illness (P < 0.001). Factor analysis resulted in four factors for the aetiology items. Paired t-test showed significant differences (P < 0.001) between psycho-social and environmental factors, supernatural and religious beliefs, and neuro-genetics. For treatment, significant differences (P < 0.001) were found between all factors - Professional and Help from others, Religiosity and Socialization, and Alternative and Medical Treatment. There was a significant and positive change in students' mental health knowledge, beliefs and mental health-seeking behaviour and diminished stigmatized beliefs. Based on the findings, it is highly recommended to incorporate the mental well-being program in the curriculum.