Comparative transcriptional analysis identifies genes associated with the attenuation of Theileria parva infected cells after long-term in vitro culture.

Autologous administration of attenuated Theileria parva-infected cells induces immunity to T. parva in cattle. The mechanism of attenuation, however, is largely unknown. Here, we used RNA sequencing of pathogenic and attenuated T. parva-infected T-cells to elucidate the transcriptional changes underpinning attenuation. We observed differential expression of several host genes, including TRAIL, PD-1, TGF-ß and granzymes that are known to regulate inflammation and proliferation of infected cells. Importantly, many genes linked with the attenuation of the related T. annulata-infected cells were not dysregulated in this study. Furthermore, known T. parva antigens were not dysregulated in attenuated relative to pathogenic cells, indicating that attenuation is not due to enhanced immunogenicity. Overall this study suggests that attenuation is driven by a decrease in proliferation and restoration of the inflammatory profile of T. parva-infected cells. Additionally, it provides a foundation for future mechanistic studies of the attenuation phenotype in Theileria-infected cells.

Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish Systemic Lupus Erythematosus patients.

OBJECTIVES: In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 interferon production, a hallmark of SLE. We measured antinuclear antibody (ANA) sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines. METHODS: We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N = 104 + 192). Autoantibodies targeting ANA-subspecificites: dsDNA, Sm, Sm/U1RNPcomplex, U1RNP, SSA/Ro52, SSA/Ro60, SSB/La, ribosomal P, PCNA and histones were quantified in all subjects, anti-nucleosome only in the Swedish patients, with a bead-based multiplex immunoassay. Levels of 72 plasma biomarkers were determined with Proximity Extension Assay technique or ELISA. RESULTS: Among Sudanese patients, the investigated antibodies significantly associated with 9/72 biomarkers. Anti-histone antibodies showed the strongest positive correlations with MCP-3 and S100A12 as well as with interferon I-inducible factors MCP-1 and CXCL10. Anti-dsDNA antibodies associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.Among Swedish patients, MCP-1, CXCL10, SA100A12 also demonstrated stronger associations to anti-histone and anti-nucleosome antibodies, compared with anti-dsDNA and other ANA sub-specificities. In multiple regression models, anti-histone/nucleosome retained the strongest associations. When excluding anti-histone or anti-nucleosome positive patients, the associations between MCP-1/CXCL10 and anti-dsDNA were lost. In contrast, when excluding anti-dsDNA positive patients, associations with anti-histone and anti-nucleosome remained significant. CONCLUSION: In two cohorts of different ethnical origin, autoantibodies targeting chromatin correlate stronger with IFN-induced inflammatory biomarkers than anti-dsDNA or other ANA sub-specificities. Our results suggest that anti-histone/nucleosome autoantibodies may be main drivers of type-1 interferon activity in SLE.

Antipsychotics-related hyperprolactinaemia among patients with schizophrenia in Maiduguri.

Background: Hyperprolactinaemia among patients on antipsychotic medications is generally overlooked due to lack of outwardly visible symptoms, patient resistance to reporting because the symptoms are perceived as shameful, or to clinician's insufficient knowledge. Aim: The study aimed to evaluate the patterns and correlates of hyperprolactinemia among patients with schizophrenia on antipsychotic medications. Setting: The study was conducted in a psychiatric facility in Maiduguri, Northeastern Nigeria. Methods: A total of 209 patients with schizophrenia were evaluated through a cross-sectional design and assayed for serum prolactin with ELISA Kits. Frequencies and percentages were tabulated for categorical variables. Variables with significant associations with hyperprolactinaemia on chi-square (p < 0.05) were subjected to logistic regression analysis. Results: The prevalence of hyperprolactinaemia was 45.9% in all patients on antipsychotic medication. The prevalence because of the use of typical and atypical antipsychotics was 51.5% and 25.0%, respectively. Hyperprolactinaemia was significantly associated with typical antipsychotics (ß = 0314, p = 0.002), high overall drug dosage (ß = 2.340, p = 0.003), high-dose typical antipsychotics (ß = 3.228, p = 0.000), twice daily dosing frequency (ß = 2.751, p = 0.001) and polypharmacy (ß = 1.828, p = 0.0024). Conclusion: The findings support that patients on typical, high-dose antipsychotic medications and polypharmacy have a high prevalence of hyperprolactinaemia. As hyperprolactinaemia is often undetectable, screening and patient psycho-education on the significance of the signs and symptoms of hyperprolactinaemia is required for necessary clinical intervention. Contribution: The study provides evidence for the rational use of antipsychotic medications in sub-Saharan Africa.

Effects of temperament during handling and social rank on the blood biochemical parameters of common eland (Taurotragus oryx).

Large herbivores are subject to handling and social stress in captivity. These may affect blood biochemical values, which motivated this research. Twelve healthy common eland (Taurotragus oryx) were monitored for 12 months. The animals were handled monthly, and blood samples were collected. Samples from every second month were analysed for 14 blood biochemical parameters. Temperament throughout the handling, as the summation of various behavioural responses, was calculated as a proxy of the stress generated during handling. Social behaviour was recorded each month, and the agonistic interactions were used to calculate the social rank, which was considered a proxy of social stress. Generalised Linear Mixed Models were designed to test the effects of temperament and social rank on the blood biochemical parameters while keeping sex, age, body condition, and body weight as covariates. The results show that the temperament during handling influences blood levels of albumin, alkaline phosphate, blood urea nitrogen, glucose, total bilirubin, and total protein; however, social rank has little influence, affecting just albumin. The ranges observed in the values of these biochemical parameters were still within their reference intervals, implying the absence of pathology or physiological problems during the study. The results suggest that blood biochemical values of physically restrained common eland should be carefully interpreted, even in animals already habituated to routine handling. On the contrary, social rank has low effects on the blood biochemical parameters.

Preliminary Study on Open Labelled Randomized Controlled Trial of the Safety and Efficacy of Hydroxychloroquine and Chloroquine Phosphate for the Treatment of Persons Infected with 2019 Coronavirus Disease in Nigeria.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a causative agent of COVID-19 is a leading cause of ill-health and deaths worldwide. Currently, COVID-19 has no known widely approved therapeutics. Thus, the need for effective treatment. OBJECTIVES: We investigated the safety and efficacy of two (2) therapeutic agents; chloroquine phosphate (CQ), 2- hydroxychloroquine (HCQ) and a control (standard supportive therapy) among hospitalized adults with COVID-19. METHODS: The clinical trial was done in accordance to the World Health Organization master protocol for investigational therapeutics for COVID-19. Atotal of 40 participants with laboratory-confirmed positive COVID-19 were enrolled. Blood samples and oropharyngeal (OP) swabs were obtained on days 1,3,15 and 29 for safety and efficacy assessments. RESULTS: The baseline demographics showed that the median ages in years (range) were 45 (31-57) in CQ, 45 (36.5-60.5) in HCQ, 43 (39.5-67.0) and 44.5 (25.3-51.3) in the control (P<0.042).At randomization, seven (7) participants were asymptomatic, thirty-three (33) had mild symptoms, eight (8) had moderate symptoms while three (3) had severe symptoms. The average day of conversion to negative COVID-19 was 15.5 days for CQ, 16 days for HCQ and 18 days for the control(P=0.036). CONCLUSION: The safety assessment revealed no adverse effect of the drugs in COVID-19 patients after treatment. These findings proved that chloroquine and hydroxychloroquine are effective for the treatment of COVID-19 among hospitalized adults. It also confirmed that they are safe.

CONTEXTE: Le coronavirus du syndrome respiratoire aigu sévère 2 (SARS-CoV-2),agentcausaldelaCOVID-19, est l'unedes principales causes demaladie et de décès dans le monde. À l'heure actuelle, il n'existe aucun traitement largement approuvé pour la COVID-19. Ainsi, ilya un besoin de traitement efficace. OBJECTIFS: Nous avons étudié l'innocuité et l'efficacité de deux (2) agents thérapeutiques, le phosphate de chloroquine (CQ) et l'hydroxychloroquine (HCQ), ainsi qu'un groupe témoin (traitement de soutien standard) chez des adultes hospitalisés atteints de la COVID-19.MÉTHODES: L'essai clinique a été mené conformément au protocole maître de l'Organisation mondiale de la santé pour les thérapeutiques à l'étude de la COVID-19. Au total, 40 participants atteints de la COVID-19, confirmée en laboratoire, ont été in scrits. Des échantillons de sang et des prélèvements oropharyngés (PO) ont été effectuésauxjours1,3,15et29pourévaluerl'innocuitéetl'efficacité. RÉSULTATS: Les données démographiques initiales ont révélé que l'âge médian en années (plage) était de 45 (31-57) pour le groupe CQ, de 45 (36,5-60,5) pour le groupe HCQ, de 43 (39,5-67,0) et de 44,5 (25,3-51,3) pour le groupe témoin (P<0,042). À la randomisation, sept (7) participants étaient asymptomatiques, trente-trois (33) présentaient des symptômes bénins, huit(8) avaient des symptômes modérés, tandis que trois(3) avaient des symptômes graves. Le jour moyende conversionentest COVID-19 négatif était de 15,5 jours pour le groupe CQ, de 16 jours pour le groupe HCQ et de 18 jours pourle groupe témoin (P=0,036). CONCLUSION: L'évaluation de la sécurité n'a révélé aucun effet indésirable des médicaments chez les patients atteints de la COVID-19 après le traitement. Ces conclusions ont prouvé que la chloroquine et l'hydroxychloroquine sont efficaces pour le traitement de la COVID-19 chez les adultes hospitalisés. Cela a également confirmé qu' ilssont sûrs. Mots-clés: COVID-19, SARS-CoV-2, essai clinique, innocuité, efficacité, thérapeutiques.

Synthesis of Silver(I) Complexes Containing 3-Oxo-3-phenyl-2-(2-phenylhydrazono)propanal-Based Ligands as a Multifunction Platform for Antimicrobial and Optoelectronic Applications.

Toward multifunctionality, including antimicrobial and optoelectronic applications, herein, we reported the synthesis of a novel Ag(I) complex with 3-oxo-3-phenyl-2-(2-phenylhydrazono)propanal-based ligands including 3-(4-chlorophenyl)-2-[2-(4-nitrophenyl)hydrazono]-3-oxopropanal (named as "4A"), 3-(4-chlorophenyl)-2-[2-(4-methylphenyl)hydrazono]-3-oxopropanal (named as "6A"), and 3-(4-chlorophenyl)-3-oxo-2-(2-phenylhydrazono)propanal (named as "9A"). The synthesized compounds were characterized through FTIR, 1H NMR, and density functional theory (DFT). The morphological features and thermal stability were evaluated through transmission electron microscopy (TEM) and TG/DTA analysis. The antimicrobial activity of the synthesized Ag complexes was tested against various pathogens, including Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia), Gram-positive bacteria (Staphylococcus aureus and Streptococcus mutans), and fungi (Candida albicans and Aspergillus niger). Results show that the synthesized complexes (Ag(4A), Ag(6A), and Ag(9A)) possess promising antimicrobial efficacy against various pathogens and are in good competition with several standard drugs as well. On the other hand, the optoelectronic features such as absorbance, band gap, and Urbach energy were examined by measuring the absorbance using a UV-vis spectrophotometer. The values of the band gap reflected the semiconducting nature of these complexes. The complexation with Ag resulted in a lowering band gap to match the apex of the solar spectrum. Such low band gap values are preferable for optoelectronic applications like dye-sensitized solar cells, photodiodes, and photocatalysis.

Implementing primary eye care in private practises in Malaysia: the challenges faced by optometrists.

OBJECTIVE: In Malaysia, optometrists' role in the private sector is limited compared to their counterparts elsewhere. Primary eye care (PEC) is still not widely offered in private practises despite its demand to reduce the public's eye morbidity. This study aims to explore the challenges perceived by the private sector optometrists in implementing PEC in Malaysia. MATERIALS AND METHODS: In-depth interview using semistructured open-ended questions were designed to explore the challenges of implementing PEC. Fifteen private optometrists across Malaysian were interviewed via purposive sampling until the data were saturated. The interviews were audio-recorded, transcribed and analysed. RESULTS: Four major themes emerged: working environment, support and recognition, self-sufficiency and customer influence. The first major theme identified a lack of time and equipment in the workplace as a barrier to PEC implementation. The second major theme acknowledges the lack of support and recognition for PEC practise from financial bodies, the government, Malaysian Optical Council (MOC) and other eye professionals. Meanwhile, some practising optometrists faced significant challenges due to their lack of self-sufficiency regarding skills, knowledge and confidence. The final major theme, customer influence, reflects the customer's role in shaping eye care delivery through their perception and acceptance of PEC. CONCLUSION: Each of the issues identified played a significant impact in impeding PEC implementation in Malaysia. This study is the first step toward developing tailored interventions to improve eye care delivery in Malaysia.

Understanding host response to infectious salmon anaemia virus in an Atlantic salmon cell line using single-cell RNA sequencing.

BACKGROUND: Infectious Salmon Anaemia Virus (ISAV) is an Orthomixovirus that represents a large problem for salmonid aquaculture worldwide. Current prevention and treatment methods are only partially effective. Genetic selection and genome engineering have the potential to develop ISAV resistant salmon stocks. Both strategies can benefit from an improved understanding of the genomic regulation of ISAV pathogenesis. Here, we used single-cell RNA sequencing of an Atlantic salmon cell line to provide the first high dimensional insight into the transcriptional landscape that underpins host-virus interaction during early ISAV infection. RESULTS: Salmon head kidney (SHK-1) cells were single-cell RNA sequenced at 24, 48 and 96 h post-ISAV challenge. At 24 h post infection, cells showed expression signatures consistent with viral entry, with genes such as PI3K, FAK or JNK being upregulated relative to uninfected cells. At 48 and 96 h, infected cells showed a clear anti-viral response, characterised by the expression of IFNA2 or IRF2. Uninfected bystander cells at 48 and 96 h also showed clear transcriptional differences, potentially suggesting paracrine signalling from infected cells. These bystander cells expressed pathways such as mRNA sensing, RNA degradation, ubiquitination or proteasome; and up-regulation of mitochondrial ribosome genes also seemed to play a role in the host response to the infection. Correlation between viral and host genes revealed novel genes potentially key for this fish-virus interaction. CONCLUSIONS: This study has increased our understanding of the cellular response of Atlantic salmon during ISAV infection and revealed host-virus interactions at the cellular level. Our results highlight various potential key genes in this host-virus interaction, which can be manipulated in future functional studies to increase the resistance of Atlantic salmon to ISAV.

Emphysematous pancreatitis with pulmonary embolism: A case report.

Background: Emphysematous pancreatitis is a severe systemic inflammatory process with reports of pulmonary embolism in the setting of acute pancreatitis rarely described. Case presentation: A 61-year-old woman presented with severe abdominal pain of 1 day duration. She was found to have acute interstitial pancreatitis. During her hospitalization, the patient developed worsening abdominal pain associated with increasing oxygen demands, requiring supplemental oxygen through nasal cannula. Workup showed pulmonary embolism in the posterior segmental branch of the left lower lobar artery and development of emphysematous pancreatitis was noted on imaging. The patient was started on intravenous antibiotics and therapeutic anticoagulation; her condition improved and was discharged home. Conclusion: Patients with severe acute pancreatitis may be at risk for pulmonary embolism due to immobilization and other inflammatory mechanisms. Mitigating individualized risk factors and anticoagulation use as prophylaxis should be considered in patients with pancreatitis to prevent embolism. Early detection by clinicians is critical to reduce misdiagnosis and mortality rates.

The Burden of Unsafe Abortion Six Years before the COVID-19 Era in a Nigerian Tertiary Hospital: An Analytical Retrospective Study.

BACKGROUND: Unsafe abortion remains a leading cause of maternal mortality and morbidity, especially in developing countries with restrictive abortion laws. Disease containment measures during the COVID-19 pandemic have reduced access to contraception and safe abortion care, potentially increasing rates of unintended pregnancies and unsafe abortion. OBJECTIVE: To evaluate the morbidity and mortality burden of unsafe abortion before the COVID-19 pandemic. METHODS: A six-year analytical retrospective study of unsafe abortion at the Federal Medical Centre, Lokoja, Nigeria. All case records of unsafe abortion managed within the study period were retrieved, and relevant data extracted using a purpose-designed proforma. Data obtained was analysed using the IBM SPSS Statistics for Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Associations between categorical independent and outcome variables were assessed using the Chi square test at 95% confidence level. A p-value of <0.05 was considered statistically significant. RESULTS: The prevalence of unsafe abortion was 8.6 per 1,000 deliveries. More than one-half (37, 52.9%) were medical abortions using misoprostol tablets. The mean age of the women was 23.15+ 3.96 years, and most of them were single (49, 70%), with primary/ secondary education (42, 60%), and of low socioeconomic status (67, 95.7%). Nearly one-half (33, 47.1%) had either never used any modern contraceptive (9, 12.9%) or only used emergency contraception (24, 34.3%). The predominant complications of unsafe abortion included retained product of conception (69, 98.6%), haemorrhagic shock (22,31.4%), and sepsis (19, 27.1%). There were two maternal deaths, giving a case fatality rate of 2.9%. CONCLUSION: Unsafe abortion remains a significant cause of maternal mortality and morbidity in our setting. Improving access to effective modern contraceptives and liberalizing our abortion laws may reduce maternal morbidity and mortality from unsafe abortion.

CONTEXTE: L'avortement à risque reste l'une des principales causes de mortalité et de morbidité maternelles, en particulier dans les pays en développement où les lois sur l'avortement sont restrictives. Les mesures de confinement de la maladie pendant la pandémie de COVID-19 ont réduit l'accès à la contraception et aux soins d'avortement sûrs, augmentant potentiellement les taux de grossesses non désirées et d'avortements à risque. OBJECTIF: Évaluer le fardeau de morbidité et de mortalité de l'avortement à risque avant la pandémie de COVID-19. METHODES: Une étude rétrospective analytique de six ans sur l'avortement à risque au Fédéral Médical Center, Lokoja, Nigeria. Tous les dossiers de tous les cas d'avortement à risque pris en charge au cours de la période d'étude ont été récupérés et les données pertinentes extraites à l'aide d'un formulaire conçu à cet effet. Les données obtenues ont été analysées à l'aide d'IBM SPSS Statistiques pour Windows, version 25 (IBM Corp., Armonk, N.Y., USA). Les associations entre les variables indépendantes catégorielles et les variables de résultat ont été évaluées à l'aide du test du chi carré à un niveau de confiance de 95 %. Une valeur de p <0,05 était considérée comme statistiquement significative. RESULTATS: L'prévalence des avortements à risque était de 8,6 pour 1000 accouchements. Plus de la moitié (37, 52,9%) étaient des avortements médicamenteux utilisant comprimés de misoprostol. L'âge moyen des femmes était de 23,15+ 3,96 ans, et la plupart d'entre elles étaient célibataires (49, 70%), avec une éducation primaire/secondaire (42, 60%) et de statut socio-économique bas (67, 95,7%). Près de la moitié (33, 47,1%) n'avaient jamais utilisé de contraceptif moderne (9,12,9%) ou n'avaient utilisé qu'une contraception d'urgence (24, 34,3%). Les complications prédominantes comprenaient la rétention du produit de conception (69, 98,6 %), le choc hémorragique (22, 31,4 %) et la septicémie (19, 27,1 %). Il y a eu deux décès maternels, soit un taux de létalité de 2,9 %. CONCLUSION: L'avortement à risque reste une cause importante de mortalité et de morbidité maternelles dans notre contexte. L'amélioration de l'accès à des contraceptifs modernes efficaces et la libéralisation de nos lois sur l'avortement réduiront la morbidité et la mortalité maternelles dues à l'avortement à risque. Mots-clés: Planification familiale, Avortement illégal/criminel, morbidité et mortalité maternelles, Produit de la conception retenu, Besoin non satisfait.

The anticancer and EGFR-TK/CDK-9 dual inhibitory potentials of new synthetic pyranopyrazole and pyrazolone derivatives: X-ray crystallography, in vitro, and in silico mechanistic investigations.

Treatment options for the management of breast cancer are still inadequate. This inadequacy is attributed to the lack of effective targeted medications, often resulting in the recurrence of metastatic disorders. Cumulative evidence suggests that epidermal growth factor receptor (EGFR-TK) and cyclin-dependent kinases-9 (CDK-9) overexpression correlates with worse overall survival in breast cancer patients. Pyranopyrazole and pyrazolone are privileged options for the development of anticancer agents. Inspired by this proven scientific fact, we report here the synthesis of two new series of suggested anticancer molecules incorporating both heterocycles together with their characterization by IR, 1H NMR, 13C NMR, 13C NMR-DEPT, and X-ray diffraction methods. An attempt to get the pyranopyrazole-gold complexes was conducted but unexpectedly yielded benzylidene-2,4-dihydro-3H-pyrazol-3-one instead. This unexpected result was confirmed by X-ray crystallographic analysis. All newly synthesized compounds were assessed for their anti-proliferative activity against two different human breast cancer cells, and the obtained results were compared with the reference drug Staurosporine. The target compounds revealed variable cytotoxicity with IC50 at a low micromolar range with superior selectivity indices. Target enzyme EGFR-TK and CDK-9 assays showed that compounds 22 and 23 effectively inhibited both biological targets with IC50 values of 0.143 and 0.121 µM, respectively. Molecular docking experiments and molecular dynamics simulation were also conducted to further rationalize the in vitro obtained results.Communicated by Ramaswamy H. Sarma.

Effectiveness and safety of membrane sweeping in the prevention of post-term pregnancy: a randomised controlled trial.

There is a rising concern with increasing rates of pharmacologically induced labour and its complications. Membrane sweeping is a simple and less invasive means of initiating spontaneous labour onset. We compared the safety and efficacy of membrane sweeping. A total of 186 women (62 in each arm) were recruited at the antenatal clinic at 39 weeks. The intervention groups had membrane sweeping once and twice weekly respectively while the control arm had no membrane sweeping. They were all monitored and followed up till delivery. The trial was registered with the South Africa registry www.pactr.org (PACTR202112841108933) The incidence of prolonged pregnancy was 32.3%, 19.4% and 11.7% among the control, once-weekly, and twice-weekly groups respectively. The sweeping to the delivery interval was significantly shorter for the twice-weekly group (7.4 days) compared to once weekly (8.8 days) and the control group (10.6 days). There were significantly higher odds of spontaneous labour onset in the twice-weekly group (HR 1.53, p = .029) compared to the control group (HR 0.65, p = .033) and the once-weekly group using once weekly as reference. Membrane sweeping is a safe and effective means of preventing prolonged pregnancy. Twice-weekly sweeping of foetal membranes is more effective than once-weekly or no sweeping without added adverse feto-maternal outcomes.IMPACT STATEMENTWhat is already known about the subject? There is no evidence supporting any increase in maternal or foetal morbidity suggesting that membrane sweeping is a safe procedure to offer to all low-risk pregnant women so as to initiate spontaneous labour onset.What do the results of the study add? Membrane sweeping twice weekly after 39weeks for low-risk pregnant women is more effective than once weekly or no sweep with no added adverse maternal or perinatal risks.What are the implications of these findings for clinical practice and or further research? Twice-weekly membrane sweeping is encouraged in selected patients to reduce the risks associated with post-term pregnancy.

Female Genital Tuberculosis Among Infertile Women and Its Contributions to Primary and Secondary Infertility: A systematic review and meta-analysis.

Female genital tuberculosis (FGTB) is a widespread infectious disease among young women. This meta-analysis aimed to investigate the prevalence of FGTB among infertile women and its contribution to primary and secondary infertility. PubMed, MEDLINE®, WorldCat, The Lens, direct Google search, Google Scholar and ResearchGate were searched from 1971 to July 17, 2021 using the following terms: "prevalence", "epidemiology", "urogenital tuberculosis", "FGTB", "infertile women", "infertility complaints" and "FGTB testing methods". Data were extracted and a meta-analysis was performed. A total of 42 studies were selected with a total of 30,918 infertile women. Of these, the pooled prevalence of FGTB was 20% (95% confidence interval: 15-25%, I2 = 99.94%) and the prevalence of overall infertility, primary infertility and secondary infertility among FGTB population were 88%, 66% and 34%, respectively. The proportion of FGTB is remarkable among infertile women globally. The biggest burden of the disease is present in low-income countries followed by lower-to-middle- and upper-to-middle-income countries.

Synthesis and greener pastures biological study of bis-thiadiazoles as potential Covid-19 drug candidates.

A novel series of bis- (Abdelhamid et al., 2017, Banerjee et al., 2018, Bharanidharan et al., 2022)thiadiazoles was synthesized from the reaction of precursor dimethyl 2,2'-(1,2-diphenylethane-1,2-diylidene)-bis(hydrazine-1-carbodithioate) and hydrazonyl chlorides in ethanol under ultrasonic irradiation. Spectral tools (IR. NMR, MS, elemental analyses, molecular dynamic simulation, DFT and LUMO and HOMO) were used to elucidate the structure of the isolated products. Molecular docking for the precursor, 3 and ligands 6a-i to two COVID-19 important proteins Mpro and RdRp was compared with two approved drugs, Remdesivir and Ivermectin. The binding affinity varied between the ligands and the drugs. The highest recorded binding affinity of 6c with Mpro was (-9.2 kcal/mol), followed by 6b and 6a, (-8.9 and -8.5 kcal/mol), respectively. The lowest recorded binding affinity was (-7.0 kcal/mol) for 6 g. In comparison, the approved drugs showed binding affinity (-7.4 and -7.7 kcal/mol), for Remdesivir and Ivermectin, respectively, which are within the range of the binding affinity of our ligands. The binding affinity of the approved drug Ivermectin against RdRp recoded the highest (-8.6 kcal/mol), followed by 6a, 6 h, and 6i are the same have (-8.2 kcal/mol). The lowest reading was found for compound 3 ligand (-6.3 kcal/mol). On the other side, the amino acids also differed between the compounds studied in this project for both the viral proteins. The ligand 6a forms three H-bonds with Thr 319(A), Sr 255(A) and Arg 457(A), whereas Ivermectin forms three H-bonds with His 41(A), Gly143(A) and Gln 18(A) for viral Mpro. The RdRp amino acids residues could be divided into four groups based on the amino acids that interact with hydrogen or hydrophobic interactions. The first group contained 6d, 6b, 6 g, and Remdesivir with 1-4 hydrogen bonds and hydrophobic interactions 1 to 10. Group 2 is 6a and 6f exhibited 1 and 3 hydrogen bonds and 15 and 14 hydrophobic interactions. Group 3 has 6e and Ivermectin shows 4 and 3 hydrogen bonds, respectively and 11 hydrophobic interactions for both compounds. The last group contains ligands 3, 6c, 6 h, and 6i gave 1-3 hydrogen bonds and 6c and 3 recorded the highest number of hydrophobic interactions, 14 for both 6c and 6 h. Pro Tox-II estimated compounds' activities as Hepatoxic, Carcinogenic and Mutagenic, revealing that 6f-h were inactive in all five similar to that found with Remdesivir and Ivermectin. The drug-likeness prediction was carried out by studying physicochemical properties, lipophilicity, size, polarity, insolubility, unsaturation, and flexibility. Generally, some properties of the ligands were comparable to that of the standards used in this study, Remdesivir and Ivermectin.

Quantum Phase Transition in the Spin Transport Properties of Ferromagnetic Metal-Insulator-Metal Hybrid Materials.

Perpendicular magnetic tunnel junctions provide a technologically important design platform for studying metal-insulator-metal heterostructure materials. Accurate characterization of the sensitivity of their electronic structure to proximity coupling effects based on first-principles calculations is key in the fundamental understanding of their emergent collective properties at macroscopic scales. Here, we use an effective field theory that combines ab initio calculations of the electronic structure within density functional theory with the plane waves calculation of the spin polarised conductance to gain insights into the proximity effect induced magnetoelectric couplings that arise in the transport of spin angular momentum when a monolayer tunnel barrier material is integrated into the magnetic tunnel junction. We find that the spin density of states exhibits a discontinuous change from half-metallic to the metallic character in the presence of monolayer hexagonal boron nitride when the applied electric field reaches a critical amplitude, and this signals a first order transition in the transport phase. This unravels an electric-field induced quantum phase transition in the presence of a monolayer hexagonal boron nitride tunnel barrier quite unlike molybdenum disulphide. The role of the applied electric field in the observed phase transition is understood in terms of the induced spin-flip transition and the charge transfer at the constituent interfaces. The results of this study show that the choice of the tunnel barrier layer material plays a nontrivial role in determining the magnetoelectric couplings during spin tunnelling under external field bias.

The Effects of Three and Six Sessions of Low Energy Extracorporeal Shockwave Therapy on Graft Incorporation and Knee Functions Post Anterior Cruciate Ligament Reconstruction.

Introduction: One session of high energy extracorporeal shockwave therapy (ESWT) was found to improve the healing of anterior cruciate ligament (ACL) after reconstruction in animal and human studies. This study investigated the effects of three and six sessions of low energy ESWT on graft incorporation and knee functions post ACL reconstruction in humans. Materials and methods: Thirty participants with ACL injuries were recruited and assigned equally into three groups with 10 participants per group (n=10). Participants in the control group received physiotherapy alone without low energy ESWT. Participants in the 3ESWT group underwent three sessions of low energy ESWT (one session per week) combined with physiotherapy, and participants in the 6ESWT group received six sessions of low energy ESWT (one session per week) combined with physiotherapy. However, five participants were lost to follow-up. Evaluations of graft incorporation of the tibial tunnel using magnetic resonance (MRI) and Lysholm score were carried out before ACL reconstruction and after six months post ACL reconstruction. Results: The number of grafts with partial incorporation in the tibia tunnel in 6ESWT was significantly higher compared with the number of grafts with non-incorporation at six months post-operatively, X2 (1, N=9) =5.44, p =0.02. However, there was no significant difference between frequencies of graft incorporation in tibia tunnel in the control and 3ESWT groups, X2 (1, N=7) =3.57, p =0.06 and X2 (1, N=9) =2.78, p =0.10, respectively at 6 months postoperatively. Lysholm scores were significantly higher at 6 months post ACL reconstruction compared to the baseline value for each group (p<0.002, respectively). However, there was no significant difference in the Lysholm score between each group (F = 2.798, p = 0.083). Conclusions: Six sessions of low energy ESWT improved graft incorporation in the tibial tunnel. Both three and six sessions of low energy of ESWT does not affect the knee function score at six months post ACL reconstruction.

Microalgae Bioactive Carbohydrates as a Novel Sustainable and Eco-Friendly Source of Prebiotics: Emerging Health Functionality and Recent Technologies for Extraction and Detection.

There is a global interest in the novel consumption, nutritional trends, and the market of new prebiotic sources and their potential functional impacts. Commercially available nutritional supplements based on microalgae that are approved to be edible by FDA, like Arthrospira platensis (Cyanobacteria) and Chlorella vulgaris (Chlorophyta) become widely attractive. Microalgae are rich in carbohydrates, proteins, and polyunsaturated fatty acids that have high bioactivity. Recently, scientists are studying the microalgae polysaccharides (PS) or their derivatives (as dietary fibers) for their potential action as a novel prebiotic source for functional foods. Besides, the microalgae prebiotic polysaccharides are used for medication due to their antioxidant, anticancer, and antihypertensive bioactivities. This review provides an overview of microalgae prebiotics and other macromolecules' health benefits. The phytochemistry of various species as alternative future sources of novel polysaccharides were mentioned. The application as well as the production constraints and multidisciplinary approaches for evaluating microalgae phytochemistry were discussed. Additionally, the association between this potential of combining techniques like spectroscopic, chromatographic, and electrochemical analyses for microalgae sensation and analysis novelty compared to the chemical methods was emphasized.

Barriers and solutions to effective mentorship in health research and training institutions in Nigeria: Mentors, mentees, and organizational perspectives.

Aims and Background: Mentoring relationships and programs have become a subject of global interest and their relevance is high in the ever-evolving health system. In Nigeria, informal system of mentoring is largely practiced. To be able to institutionalize mentoring program, there is need to explore the various challenges of mentoring process and suggest potential approaches for effective mentor-mentee relationship in health research institutions in Nigeria. Subjects and Methods: The study was designed to explore the barriers and solutions to mentoring process from the perspectives of the mentor, mentee, and organization in health research and training institutions in Nigeria. A cross-sectional descriptive design was employed and the study was conducted among 21 health researchers drawn from 24 health research institutions across the 6 regions of Nigeria. The nominal group technique was adopted in the data collection process. Results: The most frequently reported mentor challenges were "lack of understanding of mentorship process" (84.2%) and "lack of capacity for mentoring" (78.9%), while those of mentee were "mentor preference" (73.7%) and "lack of freedom of expression" (47.4%). "Culture of selfishness/individualism" (84.2%) and "lack of formal relationship" (63.2%) were the most mentioned systemic challenges. Training on mentoring process and relationship was mentioned as the most frequent approach to overcoming challenges for the three perspectives. Conclusion: Significant mentorship challenges exist in the Nigerian health, academic and research institution. Systematic approaches to finding and implementing the appropriate solutions are needed to circumvent these bottlenecks.

Potential COVID-19 Drug Candidates Based on Diazinyl-Thiazol-Imine Moieties: Synthesis and Greener Pastures Biological Study.

A novel series of 1-aryl-N-[4-phenyl-5-(arylazo)thiazol-2-yl)methanimines has been synthesized via the condensation of 2-amino-4-phenyl-5-arylazothiazole with various aromatic aldehydes. The synthesized imines were characterized by spectroscopic techniques, namely 1H and 13C-NMR, FTIR, MS, and Elemental Analysis. A molecular comparative docking study for 3a-f was calculated, with reference to two approved drugs, Molnupiravir and Remdesivir, using 7BQY (Mpro; PDB code 7BQY; resolution: 1.7 A°) under identical conditions. The binding scores against 7BQY were in the range of -7.7 to -8.7 kcal/mol for 3a-f. The high scores of the compounds indicated an enhanced binding affinity of the molecules to the receptor. This is due to the hydrophobic interactions and multi-hydrogen bonds between 3a-f ligands and the receptor's active amino acid residues. The main aim of using in silco molecular docking was to rank 3a-f with respect to the approved drugs, Molnupiravir and Remdesivir, using free energy methods as greener pastures. A further interesting comparison presented the laydown of the ligands before and after molecular docking. These results and other supporting statistical analyses suggested that ligands 3a-f deserve further investigation in the context of potential therapeutic agents for COVID-19. Free-cost, PASS, SwissADME, and Way2drug were used in this research paper to determine the possible biological activities and cytotoxicity of 3a-f.

Using machine learning to detect the differential usage of novel gene isoforms.

BACKGROUND: Differential isoform usage is an important driver of inter-individual phenotypic diversity and is linked to various diseases and traits. However, accurately detecting the differential usage of different gene transcripts between groups can be difficult, in particular in less well annotated genomes where the spectrum of transcript isoforms is largely unknown. RESULTS: We investigated whether machine learning approaches can detect differential isoform usage based purely on the distribution of reads across a gene region. We illustrate that gradient boosting and elastic net approaches can successfully identify large numbers of genes showing potential differential isoform usage between Europeans and Africans, that are enriched among relevant biological pathways and significantly overlap those identified by previous approaches. We demonstrate that diversity at the 3' and 5' ends of genes are primary drivers of these differences between populations. CONCLUSION: Machine learning methods can effectively detect differential isoform usage from read fraction data, and can provide novel insights into the biological differences between groups.