A RIPK1-specific PROTAC degrader achieves potent antitumor activity by enhancing immunogenic cell death.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a critical stress sentinel that coordinates cell survival, inflammation, and immunogenic cell death (ICD). Although the catalytic function of RIPK1 is required to trigger cell death, its non-catalytic scaffold function mediates strong pro-survival signaling. Accordingly, cancer cells can hijack RIPK1 to block necroptosis and evade immune detection. We generated a small-molecule proteolysis-targeting chimera (PROTAC) that selectively degraded human and murine RIPK1. PROTAC-mediated depletion of RIPK1 deregulated TNFR1 and TLR3/4 signaling hubs, accentuating the output of NF-κB, MAPK, and IFN signaling. Additionally, RIPK1 degradation simultaneously promoted RIPK3 activation and necroptosis induction. We further demonstrated that RIPK1 degradation enhanced the immunostimulatory effects of radio- and immunotherapy by sensitizing cancer cells to treatment-induced TNF and interferons. This promoted ICD, antitumor immunity, and durable treatment responses. Consequently, targeting RIPK1 by PROTACs emerges as a promising approach to overcome radio- or immunotherapy resistance and enhance anticancer therapies.

Emodepside for Trichuris trichiura and Hookworm Infection.

BACKGROUND: Current treatments for soil-transmitted helminth infections in humans have low efficacy against Trichuris trichiura. Emodepside - a drug in veterinary use and under development for the treatment of onchocerciasis in humans - is a leading therapeutic candidate for soil-transmitted helminth infection. METHODS: We conducted two phase 2a, dose-ranging, randomized, controlled trials to evaluate the efficacy and safety of emodepside against T. trichiura and hookworm infections. We randomly assigned, in equal numbers, adults 18 to 45 years of age in whom T. trichiura or hookworm eggs had been detected in stool samples to receive emodepside, at a single oral dose of 5, 10, 15, 20, 25, or 30 mg; albendazole, at a single oral dose of 400 mg; or placebo. The primary outcome was the percentage of participants who were cured of T. trichiura or hookworm infection (the cure rate) with emodepside 14 to 21 days after treatment, determined with the use of the Kato-Katz thick-smear technique. Safety was assessed 3, 24, and 48 hours after the receipt of treatment or placebo. RESULTS: A total of 266 persons were enrolled in the T. trichiura trial and 176 in the hookworm trial. The predicted cure rate against T. trichiura in the 5-mg emodepside group (85% [95% confidence interval {CI}, 69 to 93]; 25 of 30 participants) was higher than the predicted cure rate in the placebo group (10% [95% CI, 3 to 26]; 3 of 31 participants) and the observed cure rate in the albendazole group (17% [95% CI, 6 to 35]; 5 of 30 participants). A dose-dependent relationship was shown in participants with hookworm: the observed cure rate was 32% (95% CI, 13 to 57; 6 of 19 participants) in the 5-mg emodepside group and 95% (95% CI, 74 to 99.9; 18 of 19 participants) in the 30-mg emodepside group; the observed cure rates were 14% (95% CI, 3 to 36; 3 of 21 participants) in the placebo group and 70% (95% CI, 46 to 88; 14 of 20 participants) in the albendazole group. In the emodepside groups, headache, blurred vision, and dizziness were the most commonly reported adverse events 3 and 24 hours after treatment; the incidence of events generally increased in a dose-dependent fashion. Most adverse events were mild in severity and were self-limited; there were few moderate and no serious adverse events. CONCLUSIONS: Emodepside showed activity against T. trichiura and hookworm infections. (Funded by the European Research Council; ClinicalTrials.gov number, NCT05017194.).

HCMV Infection Reduces Nidogen-1 Expression, Contributing to Impaired Neural Rosette Development in Brain Organoids.

Human cytomegalovirus (HCMV) is a leading cause of birth defects in humans. These birth defects include microcephaly, sensorineural hearing loss, vision loss, and cognitive impairment. The process by which the developing fetus incurs these neurological defects is poorly understood. To elucidate some of these mechanisms, we have utilized HCMV-infected induced pluripotent stem cells (iPSCs) to generate in vitro brain organoids, modeling the first trimester of fetal brain development. Early during culturing, brain organoids generate neural rosettes. These structures are believed to model neural tube formation. Rosette formation was analyzed in HCMV-infected and mock-infected brain organoids at 17, 24, and 31 days postinfection. Histological analysis revealed fewer neural rosettes in HCMV-infected compared to mock-infected organoids. HCMV-infected organoid rosettes incurred multiple structural deficits, including increased lumen area, decreased ventricular zone depth, and decreased cell count. Immunofluorescent (IF) analysis found that nidogen-1 (NID1) protein expression in the basement membrane surrounding neural rosettes was greatly reduced by virus infection. IF analysis also identified a similar downregulation of laminin in basement membranes of HCMV-infected organoid rosettes. Knockdown of NID1 alone in brain organoids impaired their development, leading to the production of rosettes with increased lumen area, decreased structural integrity, and reduced laminin localization in the basement membrane, paralleling observations in HCMV-infected organoids. Our data strongly suggest that HCMV-induced downregulation of NID1 impairs neural rosette formation and integrity, likely contributing to many of HCMV's most severe birth defects. IMPORTANCE HCMV infection in pregnant women continues to be the leading cause of virus-induced neurologic birth defects. The mechanism through which congenital HCMV (cCMV) infection induces pathological changes to the developing fetal central nervous system (CNS) remains unclear. Our lab previously reproduced identified clinical defects in HCMV-infected infants using a three dimensional (3D) brain organoid model. In this new study, we have striven to discover very early HCMV-induced changes in developing brain organoids. We investigated the development of neural tube-like structures, neural rosettes. HCMV-infected rosettes displayed multiple structural abnormalities and cell loss. HCMV-infected rosettes displayed reduced expression of the key basement membrane protein, NID1. We previously found NID1 to be specifically targeted in HCMV-infected fibroblasts and endothelial cells. Brain organoids generated from NID1 knockdown iPSCs recapitulated the structural defects observed in HCMV-infected rosettes. Findings in this study revealed HCMV infection induced early and dramatic structural changes in 3D brain organoids. We believe our results suggest a major role for infection-induced NID1 downregulation in HCMV-induced CNS birth defects.

Consensus statement on the management of hyperkalaemia-An Asia-Pacific perspective.

Hyperkalaemia is an electrolyte imbalance that impairs muscle function and myocardial excitability, and can potentially lead to fatal arrhythmias and sudden cardiac death. The prevalence of hyperkalaemia is estimated to be 6%-7% worldwide and 7%-10% in Asia. Hyperkalaemia frequently affects patients with chronic kidney disease, heart failure, and diabetes mellitus, particularly those receiving treatment with renin-angiotensin-aldosterone system (RAAS) inhibitors. Both hyperkalaemia and interruption of RAAS inhibitor therapy are associated with increased risks for cardiovascular events, hospitalisations, and death, highlighting a clinical dilemma in high-risk patients. Conventional potassium-binding resins are widely used for the treatment of hyperkalaemia; however, caveats such as the unpalatable taste and the risk of gastrointestinal side effects limit their chronic use. Recent evidence suggests that, with a rapid onset of action and improved gastrointestinal tolerability, novel oral potassium binders (e.g., patiromer and sodium zirconium cyclosilicate) are alternative treatment options for both acute and chronic hyperkalaemia. To optimise the care for patients with hyperkalaemia in the Asia-Pacific region, a multidisciplinary expert panel was convened to review published literature, share clinical experiences, and ultimately formulate 25 consensus statements, covering three clinical areas: (i) risk factors of hyperkalaemia and risk stratification in susceptible patients; (ii) prevention of hyperkalaemia for at-risk individuals; and (iii) correction of hyperkalaemia for at-risk individuals with cardiorenal disease. These statements were expected to serve as useful guidance in the management of hyperkalaemia for health care providers in the region.

Open Surgical Therapy for Peripheral Artery Disease.

PURPOSE OF REVIEW: The surgical management of symptomatic peripheral artery disease (PAD) has changed in the last few decades. Improvement in endovascular technology has resulted in more complex lesion once reserved for open surgery being addressed in an endovascular fashion. Even with these advances, there are lesions and patients that are better managed with an open surgical procedure. The aim of this review is to describe the most commonly performed open surgical procedures for PAD. RECENT FINDINGS: The recently published Best Endovascular versus Best Surgical Therapy (BEST-CLI) trial was an international, prospective, randomized controlled trial that aimed to investigate which revascularization (endovascular vs. surgical bypass) approach was superior for limb salvage. The evidence supports an open surgical bypass as an initial approach. The advancements made in the surgical management of PAD have provided options for patients who were once deemed poor surgical candidates. The goal continues to be utilization of the best available tools to address patient disease. In this current era, it is important to be familiar with the open surgical therapies.

The Fragility of Statistical Findings in Cervical Disc Arthroplasty: a Systematic Review of Randomized Controlled Trials.

PURPOSE: This study employs both the fragility index (FI) and fragility quotient (FQ) to assess the level of robustness in the cervical disc arthroplasty (CDA) literature. We hypothesize that dichotomous outcomes involving CDA would exhibit statistical vulnerability. METHODS: A PubMed search was conducted to evaluate dichotomous data for randomized controlled trials (RCTs) in CDA literature from 2000 to 2023. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each fragility index by the study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 1561 articles screened, 111 met the search criteria, with 35 RCTs evaluating CDA included for analysis. Six hundred and ninety-three outcome events with 130 significant (P < 0.05) outcomes and 563 nonsignificant (P ≥ 0.05) outcomes were identified. The overall FI and FQ for all 693 outcomes were 5 (IQR 3-7) and 0.019 (IQR 0.011-0.043). Fragility analysis of statistically significant outcomes and nonsignificant outcomes both revealed an FI of 5. All of the studies reported loss to follow-up (LTF) data where 65.7% (23) did not report or reported an LTF greater or equal to 5. CONCLUSIONS: The literature regarding CDA RCTs lacks statistical robustness and may misrepresent the conclusions with the sole use of the P value. By implementing the FI and FQ along with the P value, we believe the interpretation and contextualization of the clinical data surrounding CDA will be better understood.

Notes on [post]human nursing: What It MIGHT Be, What it is Not.

With this paper, we walk out some central ideas about posthumanisms and the ways in which nursing is already deeply entangled with them. At the same time, we point to ways in which nursing might benefit from further entanglement with other ideas emerging from posthumanisms. We first offer up a brief history of posthumanisms, following multiple roots to several points of formation. We then turn to key flavors of posthuman thought to differentiate between them and clarify our collective understanding and use of the terms. This includes considerations of the threads of transhumanism, critical posthumanism, feminist new materialism, and the speculative, affirmative ethics that arise from critical posthumanism and feminist new materialism. These ideas are fruitful for nursing, and already in action in many cases, which is the matter we occupy ourselves with in the final third of the paper. We consider the ways nursing is already posthuman-sometimes even critically so-and the speculative worldbuilding of nursing as praxis. We conclude with visions for a critical posthumanist nursing that attends to humans and other/more/nonhumans, situated and material and embodied and connected, in relation.

Social Support as a Correlate of Depression and Quality of Life Among Nigerian Older Adults: a Cross-Sectional Study.

Reduced social support has been associated with presence of depression and reduced quality of life among older adults. The relationships may be better understood by exploring the interactions of individual domains among the constructs. This cross-sectional survey involved a consecutive sample of 206 (116 females and 90 males) older adults living in a Southern Nigeria community. The Multidimensional Scale of Perceived Social Support, Geriatric Depression Scale, and World Health Organization Quality of Life-OLD Questionnaire, were used to measure social support, depression, and quality of life respectively. Data was analyzed using frequency counts, percentages, mean, standard deviation, multiple regression and Spearman rank-order correlation coefficient, at 0.05 alpha level. Prevalence rate of depression among participants was 45.5%. Social support was perceived to be low by 37.4% of participants with the lowest mean social support score coming from friends domain. Participants' quality of life was generally fairly good (> 60%) with the lowest scores coming from the intimacy domain. Significant correlations between social support domains and each of quality of life (p < 0.05) and depression were respectively positive and negative; but weakest for the friend and strongest for significant others domains. All quality of life domains were significantly correlated with social support except the death and dying domain. All the domains of social support (family and significant other) were significant predictors of depression except the friend domain. Significant others around individual older adults particularly those with depression ought to be educated on the importance of their roles. Stakeholders including healthcare providers may create and support programmes for improved social networking for the older adults in order to enhance their general wellbeing and quality of life.

Engineered PROTAC-CID Systems for Mammalian Inducible Gene Regulation.

Gene regulation via chemically induced dimerization (CID) is useful for biomedical research. However, the number, type, versatility, and in vivo applications of CID tools remain limited. Here, we demonstrate the development of proteolysis-targeting chimera-based scalable CID (PROTAC-CID) platforms by systematically engineering the available PROTAC systems for inducible gene regulation and gene editing. Further, we show orthogonal PROTAC-CIDs that can fine-tune gene expression at gradient levels or multiplex biological signals with different logic gating operations. Coupling the PROTAC-CID platform with genetic circuits, we achieve digitally inducible expression of DNA recombinases, base- and prime-editors for transient genome manipulation. Finally, we package a compact PROTAC-CID system into adeno-associated viral vectors for inducible and reversible gene activation in vivo. This work provides a versatile molecular toolbox that expands the scope of chemically inducible gene regulation in human cells and mice.

Similar cortical morphometry trajectories from 5 to 9 years in children with perinatal HIV who started treatment before age 2 years and uninfected controls.

BACKGROUND: Life-long early ART (started before age 2 years), often with periods of treatment interruption, is now the standard of care in pediatric HIV infection. Although cross-sectional studies have investigated HIV-related differences in cortical morphology in the setting of early ART and ART interruption, the long-term impact on cortical developmental trajectories is unclear. This study compares the longitudinal trajectories of cortical thickness and folding (gyrification) from age 5 to 9 years in a subset of children perinatally infected with HIV (CPHIV) from the Children with HIV Early antiRetroviral therapy (CHER) trial to age-matched children without HIV infection. METHODS: 75 CHER participants in follow-up care at FAMCRU (Family Centre for Research with Ubuntu), as well as 66 age-matched controls, received magnetic resonance imaging (MRI) on a 3 T Siemens Allegra at ages 5, 7 and/or 9 years. MR images were processed, and cortical surfaces reconstructed using the FreeSurfer longitudinal processing stream. Vertex-wise linear mixed effects (LME) analyses were performed across the whole brain to compare the means and linear rates of change of cortical thickness and gyrification from 5 to 9 years between CPHIV and controls, as well as to examine effects of ART interruption. RESULTS: Children without HIV demonstrated generalized cortical thinning from 5 to 9 years, with the rate of thinning varying by region, as well as regional age-related gyrification increases. Overall, the means and developmental trajectories of cortical thickness and gyrification were similar in CPHIV. However, at an uncorrected p < 0.005, 6 regions were identified where the cortex of CPHIV was thicker than in uninfected children, namely bilateral insula, left supramarginal, lateral orbitofrontal and superior temporal, and right medial superior frontal regions. Planned ART interruption did not affect development of cortical morphometry. CONCLUSIONS: Although our results suggest that normal development of cortical morphometry between the ages of 5 and 9 years is preserved in CPHIV who started ART early, these findings require further confirmation with longitudinal follow-up through the vulnerable adolescent period.

SS31 Confers Cerebral Protection by Reversing Mitochondrial Dysfunction in Early Brain Injury Following Subarachnoid Hemorrhage, via the Nrf2- and PGC-1α-Dependent Pathways.

In early brain injury (EBI), oxidative stress occurs following subarachnoid hemorrhage (SAH), and mitochondria are intricately linked to this process. SS31, a mitochondria-targeting antioxidative peptide, has been demonstrated to be beneficial for multiple diseases because of its powerful antioxidant and neuroprotective properties. Although our previous study revealed that SS31 was involved in the powerful antioxidant effect following SAH, the underlying molecular mechanisms remained unclear. Thus, our study aimed to investigate the neuroprotective effects of SS31 by reversing mitochondrial dysfunction in EBI following SAH, via activating the Nrf2 signaling and PGC-1α pathways. Our findings confirmed that SS31 ameliorated SAH-triggered oxidative insult. SS31 administration decreased redundant reactive oxygen species, alleviated lipid peroxidation, and elevated the activities of antioxidant enzymes. Concomitant with the inhibited oxidative insult, SS31 dramatically attenuated neurological deficits, cerebral edema, neural apoptosis, and blood-brain barrier disruption following SAH. Moreover, SS31 remarkably promoted nuclear factor-erythroid 2 related factor 2 (Nrf2) nuclear shuttle and upregulated the expression levels of heme oxygenase-1 and NADPH: quinine oxidoreductase1. Additionally, SS31 enhanced the expression levels of PGC-1α and its target genes, and increased the mtDNA copy number, promoting mitochondrial function. However, PGC-1α-specific inhibitor SR-18292 pretreatment dramatically suppressed SS31-induced Nrf2 expression and PGC-1α activation. Furthermore, pretreatment with SR-18292 reversed the neuroprotective and antioxidant roles of SS31. These significant beneficial effects were associated with the activation of the Nrf2 signaling and PGC-1α pathways and were antagonized by SR-18292 administration. Our findings reveal that SS31 exhibits its neuroprotective activity by reversing mitochondrial dysfunction via activating the Nrf2 signaling pathway, which could be mediated through PGC-1α activation.

Cholera outbreak in some communities in North-East Nigeria, 2019: an unmatched case-control study.

BACKGROUND: Cholera, a diarrheal disease caused by the bacterium Vibrio cholerae, transmitted through fecal contamination of water or food remains an ever-present risk in many countries, especially where water supply, sanitation, food safety, and hygiene are inadequate. A cholera outbreak was reported in Bauchi State, North-eastern Nigeria. We investigated the outbreak to determine the extent and assess risk factors associated with the outbreak. METHODS: We conducted a descriptive analysis of suspected cholera cases to determine the fatality rate (CFR), attack rate (AR), and trends/patterns of the outbreak. We also conducted a 1:2 unmatched case-control study to assess risk factors amongst 110 confirmed cases and 220 uninfected individuals (controls). We defined a suspected case as any person > 5 years with acute watery diarrhea with/without vomiting; a confirmed case as any suspected case in which there was laboratory isolation of Vibrio cholerae O1 or O139 from the stool while control was any uninfected individual with close contact (same household) with a confirmed case. Children under 5 were not included in the case definition however, samples from this age group were collected where such symptoms had occurred and line-listed separately. Data were collected with an interviewer-administered questionnaire and analyzed using Epi-info and Microsoft excel for frequencies, proportions, bivariate and multivariate analysis at a 95% confidence interval. RESULTS: A total of 9725 cases were line-listed with a CFR of 0.3% in the state. Dass LGA had the highest CFR (14.3%) while Bauchi LGA recorded the highest AR of 1,830 cases per 100,000 persons. Factors significantly associated with cholera infection were attending social gatherings (aOR = 2.04, 95% CI = 1.16-3.59) and drinking unsafe water (aOR = 1.74, 95% CI = 1.07-2.83). CONCLUSION: Attending social gatherings and drinking unsafe water were risk factors for cholera infection. Public health actions included chlorination of wells and distribution of water guard (1% chlorine solution) bottles to households and public education on cholera prevention. We recommend the provision of safe drinking water by the government as well as improved sanitary and hygienic conditions for citizens of the state.

The Statistical Fragility of Orbital Fractures: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The P value has often been used as a tool to determine the statistical significance and evaluate the statistical robustness of study findings in orthopedic literature. The purpose of this study is to apply both the fragility index (FI) and the fragility quotient (FQ) to evaluate the degree of statistical fragility in orbital fracture literature. We hypothesized that the dichotomous outcomes within the orbital fracture literature will be vulnerable to a small number of outcome event reversals and will be statistically fragile. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the authors identified all dichotomous data for randomized controlled trials (RCTs) in orbital fracture literature and performed a PubMed search from 2000 to 2022. The FI of each outcome was calculated through the reversal of a single outcome event until significance was reversed. The FQ was calculated by dividing each FI by study sample size. The interquartile range (IQR) was also calculated for the FI and FQ. RESULTS: Of the 3,329 studies screened, 28 met the criteria with 10 RCTs evaluating orbital fractures included for analysis. A total of 58 outcome events with 22 significant (P < .05) outcomes and 36 nonsignificant (P ≥ .05) outcomes were identified. The overall FI and FQ for all 58 outcomes was 5 (IQR: 4 to 5) and 0.140 (IQR: 0.075 to 0.250), respectively. Fragility analysis of statistical significant outcomes and nonsignificant outcomes had an FI of 3.5 with no IQR and 5 (IQR 4-5), respectively. All of the studies reported a loss to follow-up data, where 20% (2) was greater than the overall FI of 5. CONCLUSION: The orbital fracture literature provides treatment guidance by relying on statistical significant results from RCTs. However, the RCTs in the orbital fracture peer-reviewed literature may not be statistically stable as previously thought. The sole reliance of the P value may depict misleading results. Thus, we recommend standardizing the reporting of the P value, FI, and FQ in the orbital fracture literature to aid readers in reliably drawing conclusions based on fragility outcome measures impacting clinical decision-making.

Examining the adequacy of preoperative informed consent in a developing country: Challenges in the era of surgical specialisation.

Preoperative informed consent is a legal and ethical requirement that ensures patients understand a procedure, its associated risks and benefits, alternative treatment options, and potential complications to make an informed decision about their care. This cross-sectional study evaluated the informed consent process for major orthopaedic surgeries at a tertiary hospital in Nigeria. A self-administered questionnaire was used to collect data from 120 adult participants. Results showed that many patients do not read the consent form before signing it, and surgeons do not adequately explain the alternatives to surgery, potential risks, and available anaesthetic options. Higher-educated patients are more likely to read the consent form. Surgeons performed well in explaining the nature of the condition and prognosis, the procedure's potential benefits, and answering patients' questions. The study emphasises the need to improve the informed consent process to ensure patients understand and can make rational decisions about their healthcare.

Vascular Access in Hemodialysis: Peculiarities in a Low-Income Setting, Pattern, Prevalence and Relationship with Intradialysis Events and Dialysis Dose.

OBJECTIVES: Dialysis vascular access has remained a major determinant of intra and inter-dialytic events and the dialysis dose, and this impacts the quality of life, morbidity and mortality of dialysis patients. Assessing the different access types would help minimize peri-dialytic events and improve outcome. METHODS: This was a retrospective, age and sex-matched, comparative study that assessed dialysis sessions with tunneled dialysis catheters (TDCs) with arteriovenous fistula (AVF). RESULTS: Two hundred and four participants with 1062 sessions were involved. The male participants had 66.7% of all sessions, 60.6% of sessions with TDCs and 87.3% of sessions with AVF, P=0.001. The elderly constituted 23.5% of all participants but 37.7% of sessions with AVF, P=0.04. The percentage of the health-insured was more in sessions with AVF compared to the study population, P<0.001. Diabetics were more likely to use the TDCs, P=0.06. Participants using AVF were more likely to receive full dialysis and erythropoietin treatment, P<0.001. Intradialytic hypotension and dialysis termination were commoner with AVF than TDCs, P=0.03 and P=0.04 respectively. The dialysis dose was higher with AVF than TDCs, P=0.02. Predictors of AVF as dialysis access were male gender, advancing age, health insurance and full treatment compliance. CONCLUSION: There is predominance of venous catheters in our dialysis population. The AVF gave better BP control, fluid and solute clearance, and dialysis dose, and was commoner with males, the health insured and older participants. Intradialytic hypotension was commoner with AVF as IDHT was commoner with TDCs.

OBJECTIFS: L'accès vasculaire à la dialyse reste un déterminant majeur des événements intra et inter-dialytiques et de la dose de dialyse, ce qui a un impact sur la qualité de vie, la morbidité et lamortalité des dialysés. L'évaluation des différents types d'accès permettrait de minimiser les événements péridialytiques et d'améliorer les résultats. MÉTHODES: Il s'agit d'une étude comparative rétrospective, appariée selon l'âge et le sexe, qui a évalué les séances de dialyse avec des cathéters de dialyse tunnellisés (CDT) et des fistules artérioveineuses (FAV). RÉSULTATS: Deux cent quatre participants ont participé à 1 062 séances. Les hommes représentaient 66,7 % de toutes les séances, 60,6 % des séances avec CDT et 87,3 % des séances avec FAV, P=0,001. Les personnes âgées représentaient 23,5 % de l'ensemble des participants, mais 37,7 % des séances avec FVA, P=0,04. Le pourcentage d'assurés sociaux était plus élevé dans les sessions avec AVF que dans la population étudiée, P<0.001. Les diabétiques étaient plus susceptibles d'utiliser les CDT, P=0,06. Les participants utilisant la FVA étaient plus susceptibles de recevoir une dialyse complète et un traitement à l'érythropoïétine, P<0,001. L'hypotension intradialytique et l'arrêt de la dialyse étaient plus fréquents avec l'AVF qu'avec les CDT, P=0,03 et P=0,04. La dose de dialyse était plus élevée en cas de FVA qu'en cas de CDT, P=0,02. Les facteurs prédictifs de l'utilisation de la FVA comme accès à la dialyse étaient le sexe masculin, l'âge avancé, l'assurance maladie et l'observance totale du traitement. CONCLUSION: Il y a une prédominance des cathéters veineux dans notre population de dialysés. Le FVA permet un meilleur contrôle de la PA, de la clairance des fluides et des solutés et de la dose de dialyse, et il est plus fréquent chez les hommes, les assurés sociaux et les participants plus âgés. L'hypotension intradialytique était plus fréquente avec le FVA que l'IDHT était plus fréquente avec les CDT. Mots-clés: Cathéters veineux centraux, fistule artério-veineuse, veine jugulaire interne tunnellisée.

Continent-wide patterns of song variation predicted by classical rules of biogeography.

Physiological constraints related to atmospheric temperature pose a limit to body and appendage size in endothermic animals. This relationship has been summarised by two classical principles of biogeography: Bergmann's and Allen's rules. Body size may also constrain other phenotypic traits important in ecology, evolution and behaviour, and such effects have seldom been investigated at a continental scale. Through a multilevel-modelling approach, we demonstrate that continent-wide morphology of related African barbets follows predictions of Bergmann's rule, and that body size mirrors variation in song pitch, an acoustic trait important in species recognition and sexual selection. Specifically, effects on song frequency in accordance with Bergmann's rule dwarf those of acoustic adaptation at a continental scale. Our findings suggest that macroecological patterns of body size can influence phenotypic traits important in ecology and evolution, and provide a baseline for further studies on the effects of environmental change on bird song.

Systematic review of surveillance systems for AMR in Africa.

AIMS: Surveillance is a useful tool for tracking antimicrobial resistance (AMR) trends, patterns, therapeutic and policy interventions. Proper correlation of surveillance data gives meaningful insight into the underlying epidemiology and facilitates development of rational interventions. This comprehensive review aims to identify, classify and assess gaps in Global Antimicrobial Resistance and Use Surveillance System (GLASS) reporting and national action plan (NAP) implementation in Africa. METHODS: Articles published in English were searched across five electronic databases (PubMed, Scopus, Embase, AJOL and Cochrane) and grey literature. Articles were screened against inclusion/exclusion criteria and data from eligible studies were retrieved and analysed. This systematic review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) on 31 July 2020 under protocol CRD42020192165. RESULTS: Of the 4304 records found, only 32 met the initial inclusion criteria (4 peer reviews and 28 were grey literature). From these records, 41 surveillance systems were identified (30 national and 11 transnational). After final review of reported outcomes, only 23 national surveillance systems met the inclusion criteria. Indicators recorded from these systems shows lack of external quality assessment (EQA) in some systems and limited reporting of parameters such as infection origin, patient population and pathogen types. CONCLUSIONS: The outcome of the review shows that although AMR surveillance has been implemented in 23 out of the 47 countries in the region, a number of limitations exist in the surveillance methods and reporting protocols that can impair the usefulness, validity and trustworthiness of data generated from these surveillance systems.

Comparative prospective study of early outcomes after osteosynthesis with locked intramedullary nailing or plating for closed femoral shaft fractures at the National Orthopaedic Hospital Enugu, Nigeria.

AIM OF THE STUDY: This was to compare the early outcome of closed femoral shaft fractures treated with locked intramedullary nailing and plating at the National Orthopaedic Hospital Enugu. METHODS: The study was a prospective study over 12-month period at the National Orthopaedic Hospital Enugu. Ethical clearance was obtained from the hospital ethical committee. Written informed consent was obtained from all prospectively recruited participants. Patients who met the inclusion criteria were randomly selected by simple balloting into either intramedullary nailing group or plating group. The patients were evaluated at presentation and postoperatively within 48 hours, then at two weeks, six weeks, 12 weeks and 18 weeks, respectively. Participants were evaluated using Thoresen criteria. RESULTS: A total of 52 femoral shaft fractures in 50 patients were included and analysed using SPSS version 20.0. Bone union was obtained in all the patients in the intramedullary nailing group at 12 weeks and in 84.6% patients in the plating group between 12 and 18 weeks. The overall wound infection rate was 11.5% in the locked intramedullary group and 7.7% in the plating group. Similarly, the overall limb length discrepancy was 11.5% in the locked intramedullary nailing group and 19.2% in the plating group. Based on the Thoresen criteria, good to excellent outcome was achieved in 65.4% of patients in the locked intramedullary nailing group. DISCUSSION: The patients in both groups were evaluated clinically, radiologically and functionally based on the Thoresen criteria and significantly higher number of patients in the intramedullary nailing group (17; 65.4%) than the plating group had good to excellent outcome (x2 = 9.734; p = 0.020). CONCLUSION: The early outcome of treatment of closed femoral shaft fractures in adults is significantly better following locked intramedullary nailing than plating.

A Review on the Molecular Mechanisms of Action of Natural Products in Preventing Bone Diseases.

The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs' adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/ß-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3ß), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conducted ex vivo and mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.

Prevalence and determinants of use of traditional methods of infertility treatment among women attending infertility clinic in Southeast Nigeria.

Infertility, an obstacle to healthy living, makes its victims patronize traditional methods of infertility treatment (TMIT) in spite of associated complications. They turn to hospitals when this method fails. This is actually a serious issue because the presence of contaminated herbal products and the relationship between the use of TMIT and noncompliance with biomedical treatment regimens constitutes a major concern in medical practice. And the use of traditional methods of infertility treatment has been correlated with severe and fatal consequences. Therefore, the study assessed prevalence/determinants of TMIT use among patients visiting the gynaecology clinic at Alex Ekwueme Federal University Teaching Hospital Abakaliki (AE-FUTHA). Descriptive cross-sectional design was adopted for the research. Only 263 women took part in the study. The research instrument was questionnaire. Data were analyzed using descriptive statistics. Findings revealed that 95.4% of these women have used traditional methods for infertility treatment and factors influencing infertile women's use of TMIT are demographic characteristics, infertility duration, husbands' relatives' pressure and cheap cost of traditional medical treatment. Again, inability of infertile women to disclose TMIT use to healthcare providers makes effective treatment difficult. Therefore, these impediments expose infertile women to use TMIT. The result is a guide to healthcare providers who are expected to know the extent of their parents' use of TMIT.