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Background: Retinoblastoma is associated with mortality in resource-poor nations due to disparities and poor access to treatment. The aim was to determine the relationships between patient-related factors and clinical outcomes of retinoblastoma in a tertiary hospital in Nigeria. Material and methods: It was a retrospective study of all children diagnosed and treated for retinoblastoma from January 2017 through December 2022. Information obtained from their records included bio-socioeconomic data, symptoms, lag time from initial symptoms, staging, treatment, and survival outcome. Results: Fifty-three patients, aged 6–88 months on first hospital presentation were recruited. There were 29 (54.7%) females. Twenty (37.7%) patients died. The majority were the last child of their parents (62.3%) with a low socioeconomic class (86.8%) and lived in rural areas (50.9%). The median (interquartile) age at diagnosis [24 (18–36) months, p = 0.005] and lag time [13 (6–20) months, p = 0.274] were lower in those who survived than in those who died. The prevalence of bilateral disease (20.8%, p = 0.002), brain metastasis (22.6%, p

Background: Dysregulation of adipocyte function occurs in obesity. Meteorin-like protein (Metrnl) is a newly discovered modulator of inflammation, metabolism, and differentiation of human adipocytes. The dietary supplement Chlorella Vulgaris (CV) reduces hyperlipidemia, hyperglycemia, and oxidative stress in clinical trials. Objectives: To explore the impact of 12 wks of interval resistance training (IRT) and CV supplementation on plasma levels of Metrnl and oxidative stress in males with obesity. Methods: Forty-four obese men (BMI: 32.0 ± 1.5 kg/m2, weight: 101.1 ± 2.2 kg, age: 23–35 years) were randomly assigned into 4 groups (n = 11/group): control (CON), CV supplement (CV), IRT, and CV + IRT (CVIRT). The IRT was performed for 12 wks (3 sessions per week). The treatment consisted of a daily intake of CV (1800 mg capsule) or placebo capsules. Blood samples were collected 48 hours before and after the interventions to analyze biomedical measurements. Results: The IRT and CVIRT groups had elevations in plasma Metrnl, superoxide dismutase, and total antioxidant capacity levels (all P < 0.0001), and reductions in malondialdehyde (P < 0.0001). Supplementation with CV significantly reduced malondialdehyde (P < 0.001) and increased total antioxidant capacity (P < 0.0001) but failed to alter superoxide dismutase or Metrnl (P > 0.05). Conclusions: Although IRT and its combination with CV hold promise for improving Metrnl levels and oxidative status in obesity, combining IRT and CV do not yield greater benefits than IRT alone. Although standalone CV supplementation could favorably impact certain markers of oxidative stress, the effectiveness of CV supplementation appears to have a relatively limited effect across assessed biomarkers and requires further investigation.

Sex differences are widespread during neurodevelopment and play a role in neuropsychiatric conditions such as autism, which is more prevalent in males than females. In humans, males have been shown to have larger brain volumes than females with development of the hippocampus and amygdala showing prominent sex differences. Mechanistically, sex steroids and sex chromosomes drive these differences in brain development, which seem to peak during prenatal and pubertal stages. Animal models have played a crucial role in understanding sex differences, but the study of human sex differences requires an experimental model that can recapitulate complex genetic traits. To fill this gap, human induced pluripotent stem cell–derived brain organoids are now being used to study how complex genetic traits influence prenatal brain development. For example, brain organoids from individuals with autism and individuals with X chromosome–linked Rett syndrome and fragile X syndrome have revealed prenatal differences in cell proliferation, a measure of brain volume differences, and excitatory-inhibitory imbalances. Brain organoids have also revealed increased neurogenesis of excitatory neurons due to androgens. However, despite growing interest in using brain organoids, several key challenges remain that affect its validity as a model system. In this review, we discuss how sex steroids and the sex chromosomes each contribute to sex differences in brain development. Then, we examine the role of X chromosome inactivation as a factor that drives sex differences. Finally, we discuss the combined challenges of modeling X chromosome inactivation and limitations of brain organoids that need to be taken into consideration when studying sex differences.

Aims: To evaluate the effects of 12-week chlorella vulgaris (CV) combined with interval resistance training (IRT) on plasma levels of leptin, adiponectin and neuregulin-4 (Nrg-4) in obese men. Methods: Obese men (n = 44, BMI of 32.1 ± 1.5 kg/m2) were randomly allocated to the following groups of 11 participants per group: Control Placebo group (CP), CV supplement group (CV), Interval Resistance Training group plus Placebo (IRT + P), and Interval Resistance Training plus CV supplement group (IRT + CV). IRT was performed three times a week for 12 weeks using three sets of 10 repetitions at 60 % 1RM, and integrating an active rest interval with 15 repetitions at 20 % 1RM. Participants consumed either CV (1800 mg daily) or a placebo. Pre- and post-intervention blood samples were obtained to assess adipokines which were measured by ELISA. Results: While CV or IRT separately did not alter plasma levels of leptin (p > 0.05), their combination reduced leptin levels (p = 0.007). IRT and IRT plus CV increased the plasma levels of adiponectin and Nrg-4 (p

Photovoltaic technology has been widely recognized as a means to advance green energy solutions in the sub-Saharan region. In the real-time operation of solar modules, temperature plays a crucial role, making it necessary to evaluate the thermal impact on the performance of the solar devices, especially in high-insolation environments. Hence, this paper investigates the effect of operating temperature on the performance of two types of organometallic halide perovskites (OHP) - formamidinium tin iodide (FASnI3) and methylammonium lead iodide (MAPbI3). The solar cells were evaluated under a typical Nigerian climate in two different cities before and after graphene passivation. Using a one-dimensional solar capacitance simulation software (SCAPS-1D) program, the simulation results show that graphene passivation improved the conversion efficiency of the solar cells by 0.51 % (FASnI3 device) and 3.11 % (MAPbI3 device). The presence of graphene played a vital role in resisting charge recombination and metal diffusion, which are responsible for the losses in OHP. Thermal analysis revealed that the MAPbI3 device exhibited an increased fill factor (FF) in the temperature range of 20–64 °C, increasing the power conversion efficiency (PCE). This ensured that the MAPbI3 solar cell performed better in the city and the season with harsher thermal conditions (Kaduna, dry season). Thus, MAPbI3 solar cells can thrive excellently in environments where the operating temperature is below 65 °C. Overall, this study shows that the application of OHP devices in sub-Saharan climatic conditions is empirically possible with the right material modification.

New therapies and vaccines based on nucleic acids combined with an efficient nanoparticle delivery vehicle have a broad applicability for different disease indications. An alternative delivery technology for the successfully applied lipid nanoparticles in mRNA SARS-CoV-2 vaccines are nanoparticles composed of biodegradable poly(amido)amine-based polymers with mRNA payload. To show that these polymeric nanoparticles can efficiently deliver influenza hemagglutinin mRNA to target tissues and elicit protective immune responses, a relevant ferret influenza challenge model was used. In this model, our nanoparticle-based vaccine elicited strong humoral and cellular immune responses in the absence of local and systemic reactogenicity. Upon virus challenge, vaccinated animals exhibited reduced clinical signs and virus load relative to unvaccinated control animals. Based on these findings, further investigation of the polymeric nanoparticles in the context of prophylactic vaccination is warranted. Future studies will focus on optimizing the payload, the nanoparticle stability, the efficacy in the context of pre-existing immunity, and the applicability of the technology to prevent other infectious diseases.

Summary: Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid carcinomas, even those arising in a single patient. Finally, we unambiguously demonstrate that anaplastic thyroid carcinomas share a genomic origin with co-occurring differentiated carcinomas and emerge from a common malignant field through acquisition of characteristic clonal driver mutations.

Notably, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19) have all had significant negative impact on global health and economy. COVID-19 alone, has resulted to millions of deaths with new cases and mortality still being reported in its various waves. The development and use of vaccines have not stopped the transmission of SARS coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19, even among vaccinated individuals. The use of vaccines and curative drugs should be supplemented with adoption of simple hygiene preventive measures in the fight against the spread of the virus, especially for healthcare workers. Several virucidal topical antiseptics, such as povidone-iodine (PVP-I), citrox, cyclodextrins among others, have been demonstrated to be efficacious in the inactivation of SARS-CoV-2 and other coronaviruses in both in vitro and in vivo studies. The strategic application of these virucidal formulations could provide the additional impetus needed to effectively control the spread of the virus. We have here presented a simple dimension towards curtailing the dissemination of COVID-19, and other coronaviruses, through the application of effective oral, nasal and eye antiseptics among patients and medical personnel. We have further discussed the mechanism of action of some of these commonly available virucidal solutions while also highlighting some essential controversies in their use.

Purpose: The aim of this study was to review, systematically, evidence concerning the link between the ACTN3 R577X polymorphism and the rates and severity of non-contact injuries and exercise-induced muscle damage in athletes and individuals enrolled in exercise training programs. Methods: A computerized literature search was performed in the electronic databases PubMed, Web of Science, and SPORTDiscus, from inception until November 2020. All included studies compared the epidemiological characteristics of non-contact injury between the different genotypes of the ACTN3 R577X polymorphism. Results: Our search identified 492 records. After the screening of titles, abstracts, and full texts, 13 studies examining the association between the ACTN3 genotypes and the rate and severity of non-contact injury were included in the analysis. These studies were performed in 6 different countries (Spain, Japan, Brazil, China, the Republic of Korea, and Italy) and involved a total participant pool of 1093 participants. Of the studies, 2 studies involved only women, 5 studies involved only men, and 6 studies involved both men and women. All the studies included were classified as high-quality studies (≥6 points in the Physiotherapy Evidence Database (PEDro) scale score). Overall, evidence suggests there is an association between the ACTN3 R577X genotype and non-contact injury in 12 investigations. Six studies observed a significant association between ACTN3 R577X polymorphism and exercise induced muscle damage: 2 with non-contact ankle injury, 3 with non-contact muscle injury, and 1 with overall non-contact injury. Conclusion: The present findings support the premise that possessing the ACTN3 XX genotype may predispose athletes to a higher probability of some non-contact injuries, such as muscle injury, ankle sprains, and higher levels of exercise-induced muscle damage.

The filtration performance of Chitosan/silver-nanoparticles/graphene oxide (CS/AgNP/GO) composite membranes modified with Dimethyl acetamide (DMAc) were investigated in relation to the impacts of cotton (CO) and polyester (PES) fabric support modules. The contact angle of the modified CS matrix decreased with proper blending of membrane composites, which improved fluid transport due to strongly bound water oxygen-containing functional groups present in the modified chitosan, according to the FTIR report. After the addition of DMAc to the CS matrix, the composite's thermal stability increased, and the water absorption of the CO fabric was 16.3 % higher than that of the polyester (PES), indicating enhanced wettability. The average permeation flux for the CO-supported CS/AgNP/GO membrane was 50.38 Lm−2h−1, while that of PES and unsupported membranes were 46.28 Lm−2h−1 and 38.8 Lm−2h−1 respectively. Additionally, all the membrane samples demonstrated acceptable tensile strength and antifouling characteristics against Bovine Serum Albumin (BSA), with the unsupported CS/AgNP/GO composite displaying the highest fouling inhibition of 97.3 %. Therefore, the 3D-printed modified CS membranes can effectively be used for inhibiting fouling in water treatment.

Objective: To identify the training needs of front-line aged care staff as perceived by senior clinicians and managers at selected residential aged care facilities (RACFs). Methods: A qualitative explorative designed study using semi-structured interviews with a convenience sample of RACF senior managers and nurses. A hybrid analysis approach using a framework deductive analysis followed by inductive analysis for sub-themes. Results: Four sub-themes emerged to sustain increased telehealth activity: technology knowledge and digital literacy skills, including understanding telehealth ecosystems and technical skills; evidence-based reviews and clinical frameworks for telehealth consultations to identify appropriate consultations and successful use cases; telehealth best practice guidelines and workflows including telehealth consultations protocols, communicating by videoconferencing, how to support families in attending telehealth consultations and optimal training models; and telehealth policy and legal guidance. Conclusion: Staff require comprehensive training to sustain and expand telehealth use in RACFs. Training should focus on knowledge, skills and competencies in using telehealth as well as the broad factors of policies and understanding ICT systems to support staffs’ abilities and confidence. Innovation: This study provides innovative findings that identify key components and associated activities and resources for training RACF staff to ensure they have sufficient knowledge, competency, skills and confidence to integrate telehealth into care provision.

Despite tremendous biotechnological and therapeutic advances, hepatitis B virus (HBV) and hepatitis C virus (HCV) still constitute a significant global health challenge. With Nigeria known to be a high HBV and HCV burden country, increasing knowledge about viral hepatitis in rural and urban settings, combined with testing and vaccination for unexposed individuals, could be an effective strategy to eliminate these viruses in Nigeria. Therefore, we undertook this prospective study to determine the level of knowledge and epidemiology of HBV and HCV in selected communities and towns in Enugu North geopolitical zone. In this study, 52.3 % of the participants admitted to having previously heard about hepatitis B and/or C. Also 71.2 % of the research participants had no prior vaccination against HBV. Based on our findings, the prevalence rate of HBV is 2.8 % and that of HCV is 0 %. With only the HBsAg marker detected using the five-panel test kits, five of our fourteen samples are designated as being in the acute phase. Another three had HBsAg and HBeAg present and were therefore classified as being either in the late acute or chronic phase. We also recorded a single case of waned immunity to HBV. Further studies to determine viral DNA levels and other new seromarkers is recommended along with vaccination of unvaccinated individuals.

Thoracic outlet syndrome is an umbrella term for compressive pathologies in the supraclavicular and infraclavicular fossae, with the vast majority being neurogenic in nature. These compressive neuropathies, such as pectoralis minor syndrome, can be challenging problems for both patients and physicians. Robust understanding of thoracic outlet anatomy and scapulothoracic biomechanics are necessary to distinguish neurogenic vs. vascular disorders and properly diagnose affected patients. Repetitive overhead activity, particularly when combined with scapular dyskinesia, leads to pectoralis minor shortening, decreased volume of the retropectoralis minor space, and subsequent brachial plexus compression causing neurogenic thoracic outlet syndrome. Combining a thorough history, physical examination, and diagnostic modalities including ultrasound-guided injections are necessary to arrive at the correct diagnosis. Rigorous attention must be paid to rule out alternate etiologies such as peripheral neuropathies, vascular disorders, cervical radiculopathy, and space-occupying lesions. Initial nonoperative treatment with pectoralis minor stretching, as well as periscapular and postural retraining, is successful in the majority of patients. For patients that fail nonoperative management, surgical release of the pectoralis minor may be performed through a variety of approaches. Both open and arthroscopic pectoralis minor release may be performed safely with effective resolution of neurogenic symptoms. When further indicated by the preoperative workup, this can be combined with suprascapular nerve release and brachial plexus neurolysis for complete infraclavicular thoracic outlet decompression.

Background: Therapeutic efficacy of artemether-lumefantrine is highly dependent on adequate systemic exposure to the partner drug lumefantrine particularly day 7 lumefantrine plasma concentration. There has been contradicting findings on the role of the cut-off values in predicting treatment outcomes among malaria patients in malaria endemic regions. This study assesses the day 3 and 7 lumefantrine plasma concentrations including related determinant factors and their influence on treatment outcomes among treated Tanzanian children and adults in uncontrolled conditions (real life condition). Methods: Data was nested from an efficacy study employing the WHO protocol, 2015 for monitoring antimalarial drug efficacy. Lumefantrine plasma concentration was measured by high performance liquid chromatography with ultraviolet (HPLC-UV). Results: Lumefantrine plasma concentrations below 175ng/ml and 200ng/ml on day 3 and 7 did not affect adequate clinical and parasitological response (ACPR) and recurrence of infection (p = 0.428 and 0.239 respectively). Age and baseline parasitemia were not associated to day 3 median lumefantrine plasma concentrations (p = 0.08 and 0.31 respectively) and day 7 lumefantrine plasma concentrations (p = 0.07 and 0.41 respectively). However, the day 3 and day 7 lumefantrine plasma concentrations were significantly higher in males compared to females (p = 0.03 and 0.042 respectively). Conclusion: Lumefantrine plasma concentrations below cut-off points (175ng/ml and 200ng/ml) on day 3 and 7 did not influence treatment outcomes.

Selection bias may arise when data have been chosen in a way that subsequent analysis does not account for. Such bias can arise in climate event attribution studies that are performed rapidly after a devastating “trigger event”, whose occurrence corresponds to a stopping rule. Intuition suggests that naïvely including the trigger event in a standard fit in which it is the final observation will bias its importance downwards, and that excluding it will have the opposite effect. In either case the stopping rule leads to bias recently discussed in the statistical literature (Barlow et al., 2020) and whose implications for climate event attribution we investigate. Simulations in a univariate setting show substantially lower relative bias and root mean squared error for estimation of the 200-year return level when the timing bias is accounted for. Simulations in a bivariate setting show that not accounting for the stopping rule can lead to both over- and under-estimation of return levels, but that bias can be reduced by more appropriate analysis. We also discuss biases arising when an extreme event occurs in one of several related time series but this is not accounted for in data analysis, and show that the estimated return period for the “trigger event” based on a dataset that contains this event can be both biased and very uncertain. The ideas are illustrated by analysis of rainfall data from Venezuela and temperature data from India and Canada.

In a Smart Home wireless module, the antenna generally occupies one-third of the total circuit advances in the Internet of Things (IoTs). Dipole antenna comes in various shapes, but the planar antenna is the most suitable and attractive design for the IoTs application in Smart Homes because it is smaller in size and has a thin profile, making it suitable for mounting on portable equipment. In this research, two antennae, Meandered Dipole and Wideband Planar Antenna, were designed using Advance Design System (ADS) software on a PCB size of 18.8 mm × 43.2 mm, FR4 substrate with 4.6 dielectric constant and 0.8 mm thickness using copper metal as the conducting element. The transmission line has designed width of 1.25 mm, resulting in a typical line impedance of 50 Ω. A comparison of the analysis of simulation and measurement results from feeding port 1 of the Meandered PIFA Antenna shows a better performance of 95.43% efficiency with a gain of 2.54391dBi and a return loss of −24.49 dB at resonant frequency of 2.4 GHz than that from feeding port 2 whose efficiency was only 73.99%. Whereas, the wideband planar antenna shows an average bandwidth of 93.91% from 1.3 to 2.4 GHz. This range covers the GPS applications, the 2.4 GHz ISM band, and the general WCDMA and the LTE 3GPP bands useable for smart home and IoT applications. The proposed antenna provides low power operation, extended range and compact, cost-effective designs to support vendor's customers, and make quality of life smarter and more economical with the use of the smart home device.

The paper studies randomization rules for a sequential two-treatment, two-site clinical trial in Parkinson’s disease. An important feature is that we have values of responses and five potential prognostic factors from a sample of 144 patients similar to those to be enrolled in the trial. Analysis of this sample provides a model for trial analysis. The comparison of allocation rules is made by simulation yielding measures of loss due to imbalance and of potential bias. A major novelty of the paper is the use of this sample, via a two-stage algorithm, to provide an empirical distribution of covariates for the simulation; sampling of a correlated multivariate normal distribution is followed by transformation to variables following the empirical marginal distributions. Six allocation rules are evaluated. The paper concludes with some comments on general aspects of the evaluation of such rules and provides a recommendation for two allocation rules, one for each site, depending on the target number of patients to be enrolled.

Ca and Mg have been implicated in causing hardness in beans resulting in relatively long cooking time. This study used potassium to replace the cations and determined the adsorption of potassium solution to bean seeds. Then, plantain peel, a natural source of potassium, was used to cook beans and its impact on the cooking time of beans was investigated. The adsorption experiments were performed using batch technique, while metal compositions of the bean seeds and plantain peel were determined by spectroscopy. Optimum removal conditions of potassium ion biosorption using bean seeds were observed at pH 10.2, 2 g bean seed dosage, 180 min agitation time, with 75 ppm as initial metal concentration. The kinetic model correlate with pseudo-second order reaction and the Langmuir adsorption model best fitted the adsorption. After cooking the beans with plantain peel, the concentration of Mg reduced in the bean seeds by about 48%, while the concentration of Ca reduced by about 22%, but the concentration of K increased by over 200% in the cooked bean seeds. Beans treated with plantain peel cooked earlier than the control experiment. This may be affected by pH, adsorbent dosage, metal concentration and contact time.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52–87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15–30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015–001,235–20NCT00123456.

Objective: To investigate structural relationships of latent constructs such as occupational wellbeing, resilience, work meaningfulness, and psychological empowerment with affective and cognitive clinical empathy among a community of physicians and advanced practice providers. Methods: We conducted a cross-sectional observational study. We gathered data by an anonymous self-administered multidimensional questionnaire disseminated electronically between March and May 2016. Participants were physicians and advanced practice providers belonging to the Health Texas Provider Network, a group private practice affiliated with the Baylor Scott and White Health system. We excluded allied health care staff (eg, nurses) and trainees (eg, residents, medical students). We pursued a 3-step strategy: (1) confirmatory factor analysis of a theory-driven measurement model, (2) a modified structural equation model from which pathways with nonsignificant path coefficients were deleted, and (3) multigroup analyses of the modified model. Results: Cognitive empathy was the strongest predictor of affective empathy. We observed modest positive associations of resilience with cognitive and affective empathy and of well-being and meaning with affective but not with cognitive empathy. Resilience, meaning, and psychological empowerment were surprisingly negatively associated with well-being, suggesting diminished self-care among practitioners. Effects of psychological empowerment on empathy and well-being were mediated by resilience and meaning. Conclusion: Cognitive empathy directly influenced affective empathy; well-being and meaningfulness exerted direct positive effects on affective but not on cognitive empathy, whereas resilience had direct positive associations with both empathy dimensions. Resilience and meaning manifested direct, negative associations with well-being, revealing clinicians’ disproportionate focus on patient care at the expense of self-care.

Summary: Background: There is significant interest in treatment de-escalation for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC) patients given the generally favourable prognosis. However, 15–30% of patients recur after primary treatment, reflecting a need for improved risk-stratification tools. We sought to develop a molecular test to risk stratify HPV+ OPSCC patients. Methods: We created an immune score (UWO3) associated with survival outcomes in six independent cohorts comprising 906 patients, including blinded retrospective and prospective external validations. Two aggressive radiation de-escalation cohorts were used to assess the ability of UWO3 to identify patients who recur. Multivariate Cox models were used to assess the associations between the UWO3 immune class and outcomes. Findings: A three-gene immune score classified patients into three immune classes (immune rich, mixed, or immune desert) and was strongly associated with disease-free survival in six datasets, including large retrospective and prospective datasets. Pooled analysis demonstrated that the immune rich group had superior disease-free survival compared to the immune desert (HR = 9.0, 95% CI: 3.2–25.5, P = 3.6 × 10−5) and mixed (HR = 6.4, 95% CI: 2.2–18.7, P = 0.006) groups after adjusting for age, sex, smoking status, and AJCC8 clinical stage. Finally, UWO3 was able to identify patients from two small treatment de-escalation cohorts who remain disease-free after aggressive de-escalation to 30 Gy radiation. Interpretation: With additional prospective validation, the UWO3 score could enable biomarker-driven clinical decision-making for patients with HPV+ OPSCC based on robust outcome prediction across six independent cohorts. Prospective de-escalation and intensification clinical trials are currently being planned. Funding: CIHR, European Union, and the NIH.

Protein tyrosine phosphatases (PTPs) are critical regulators of cellular signal transduction that catalyze the hydrolytic dephosphorylation of phosphotyrosine in substrate proteins. Among several conserved features in classical PTP domains are an active-site cysteine residue that is necessary for catalysis and a “backdoor” cysteine residue that can serve to protect the active-site cysteine from irreversible oxidation. Curiously, two biologically important phosphatases, Src homology domain-containing PTPs 2 and 1 (SHP2 and SHP1), each contain an additional backdoor cysteine residue at a position of the PTP domain that is occupied by proline in almost all other classical PTPs (position 333 in human SHP2 numbering). Here we show that the presence of cysteine 333 significantly destabilizes the fold of the PTP domains in the SHPs. We find that replacement of cysteine 333 with proline confers increased thermal stability on the SHP2 and SHP1 PTP domains, as measured by temperature-dependent activity assays and differential scanning fluorimetry. Conversely, we show that substantial destabilization of the PTP-domain fold is conferred by introduction of a non-natural cysteine residue in a non-SHP PTP that contains proline at the 333 position. It has previously been suggested that the extra backdoor cysteine of the SHP PTPs may work in tandem with the conserved backdoor cysteine to provide protection from irreversible oxidative enzyme inactivation. If so, our current results suggest that, during the course of mammalian evolution, the SHP proteins have developed extra protection from oxidation at the cost of the thermal instability that is conferred by the presence of their PTP domains’ second backdoor cysteine.

Phyto-mediated nanoparticles (NPs) have attracted great attention in recent times due to their unique properties such as high biocompatibility, eco-friendliness, and cost-effectiveness. In this study, silver- zinc oxide nanoparticles (Ag/ZnO-NPs) were prepared using the fruit extract of Capsicum Chinense. The results obtained from both structural, and optical characterization of the nanoparticles confirmed the purity of the composites and their high crystallinity. The nanoparticles exhibited two absorption peaks at 376 and 258 nm with a bang gap energy of 3.53 eV, and the nanoparticulate size of the materials exhibited antibacterial and cytotoxic activities. The Ag/ZnO-NPs exhibited better proliferative activity against HEK 293 cells than HeLa cells. The antibacterial study showed that both the pristine and the composite nanoparticles (ZnO and Ag/ZnO-NPs) have high bactericidal effect on all tested bacterial pathogens, with Ag/ZnO-NPs displaying better antibacterial activity. Cytotoxicity studies showed a dose-dependent proliferative relationship between Ag/ZnO-NPs and tested cancer cells (HEK 293 and HeLa). Antibacterial results showed significant zones of bactericidal inhibition for all tested bacterial pathogens using the biosynthesized ZnO and Ag/ZnO-NPs. These findings demonstrated two-fold applications of biosynthesized Ag/ZnO-NPs, as anticancer and antibacterial agents.

Background: Enzalutamide is an antiandrogen used to treat both metastatic and nonmetastatic prostate cancer. Here we present results from a phase 2 trial designed to determine the safety, tolerability, and efficacy of adding enzalutamide to standard androgen deprivation therapy with radiation therapy in high-risk localized or regional, nonmetastatic patients with prostate cancer. Methods and Materials: Enrollment criteria included at least 2 of the following: stage cT3a/b, prostate specific antigen (PSA) ≥20 ng/mL, Gleason grade 8 to 10, ≥33% core involvement on biopsy, or pelvic lymph node involvement on computed tomography or magnetic resonance imaging. Patients with metastatic disease were excluded. All patients received 24 months of leuprolide and enzalutamide, and 5 weeks of intensity modulated radiation therapy followed by a brachytherapy boost. Adverse events (AE), PSA, testosterone, and basic laboratory tests were then followed for up to 36 months. Primary outcomes were safety and tolerability and PSA complete response rate (PSA-CR, defined as PSA ≤0.3). Secondary outcomes included time to biochemical recurrence (BCR; nadir + 2 ng/mL). Results: Sixteen patients were enrolled; 2 were ineligible and 3 withdrew before starting treatment. Median age at enrollment was 69.0 years (interquartile range [IQR] 11.5). Median treatment duration was 24.0 months (IQR 11.9). Median follow-up time was 35.5 months (IQR 11.2), and 9 of 11 (81.8%) patients completed the 36 months of follow-up. One of 11 (9%) patients had grade 4 AE (seizure), and no grade 5 AE were reported. Four of 11 (36.4%) patients had grade 3 AE, such as erectile dysfunction and hot flashes. All patients achieved PSA-CR, and median time to PSA-CR was 4.2 months (IQR 1.4). At 24 months follow-up, 0 of 11 (0%) patients had a biochemical recurrence. At 36 months, 1 of 9 (11.1%) patient had a biochemical recurrence. Of note, this patient did not complete the full 24 months of enzalutamide and leuprolide due to AEs. Conclusions: Enzalutamide in combination with standard androgen deprivation therapy and radiation therapy was well-tolerated and effective warranting further study in a randomized controlled trial.

Summary: Reoccurring/high-risk neuroblastoma (NB) tumors have the enrichment of non-RAS/RAF mutations along the mitogen-activated protein kinase (MAPK) signaling pathway, suggesting that activation of MEK/ERK is critical for their survival. However, based on preclinical data, MEK inhibitors are unlikely to be active in NB and have demonstrated dose-limiting toxicities that limit their use. Here, we explore an alternative way to target the MAPK pathway in high-risk NB. We find that NB models are among the most sensitive among over 900 tumor-derived cell lines to the allosteric SHP2 inhibitor SHP099. Sensitivity to SHP099 in NB is greater in models with loss or low expression of the RAS GTPase activation protein (GAP) neurofibromin 1 (NF1). Furthermore, NF1 is lower in advanced and relapsed NB and NF1 loss is enriched in high-risk NB tumors regardless of MYCN status. SHP2 inhibition consistently blocks tumor growth in high-risk NB mouse models, revealing a new drug target in relapsed NB.

As public access to longitudinal developmental datasets like the Adolescent Brain Cognitive Development StudySM (ABCD Study®) increases, so too does the need for resources to benchmark time-dependent effects. Scan-to-scan changes observed with repeated imaging may reflect development but may also reflect practice effects, day-to-day variability in psychological states, and/or measurement noise. Resources that allow disentangling these time-dependent effects will be useful in quantifying actual developmental change. We present an accelerated adult equivalent of the ABCD Study dataset (a-ABCD) using an identical imaging protocol to acquire magnetic resonance imaging (MRI) structural, diffusion-weighted, resting-state and task-based data from eight adults scanned five times over five weeks. We report on the task-based imaging data (n = 7). In-scanner stop-signal (SST), monetary incentive delay (MID), and emotional n-back (EN-back) task behavioral performance did not change across sessions. Post-scan recognition memory for emotional n-back stimuli, however, did improve as participants became more familiar with the stimuli. Functional MRI analyses revealed that patterns of task-based activation reflecting inhibitory control in the SST, reward success in the MID task, and working memory in the EN-back task were more similar within individuals across repeated scan sessions than between individuals. Within-subject, activity was more consistent across sessions during the EN-back task than in the SST and MID task, demonstrating differences in fMRI data reliability as a function of task. The a-ABCD dataset provides a unique testbed for characterizing the reliability of brain function, structure, and behavior across imaging modalities in adulthood and benchmarking neurodevelopmental change observed in the open-access ABCD Study.

Background/Objective: The aim of this study was to examine the effects of two different sprint-training regimes on sprint and jump performances according to age in elite young male soccer players over the course of one soccer season. Methods: Players were randomly assigned to two training groups. Group 1 performed systematic change-of-direction sprints (CODST, U19 [n = 9], U17 [n = 9], U15 [n = 10]) while group 2 conducted systematic linear sprints (LST, U19 [n = 9], U17 [n = 9], U15 [n = 9]). Training volumes were similar between groups (40 sprints per week x 30 weeks = 1200 sprints per season). Pre and post training, all players performed tests for the assessment of linear and slalom sprint speed (5-m and 10-m), countermovement jump, and maximal aerobic speed performance. Results: For all physical fitness measures, the baseline-adjusted means data (ANCOVA) across the age groups showed no significant differences between LST and CODST at post (0.061

Study objective: Atrial fibrillation (AF) is the most common cardiac rhythm disorder, responsible for 15 % of strokes in the United States. Studies continue to document underuse of anticoagulation therapy in minority populations and women. Our objective was to compare the proportion of AF patients by race and sex who were receiving non-optimal anticoagulation as determined by an Atrial Fibrillation Decision Support Tool (AFDST). Design, setting, and participants: Retrospective cohort study including 14,942 patients within University of Cincinnati Health Care system. Data were analyzed between November 18, 2020, and November 20, 2021. Main outcomes and measures: Discordance between current therapy and that recommended by the AFDST. Results: In our two-category analysis 6107 (41 %) received non-optimal anticoagulation therapy, defined as current treatment category ≠ AFDST-recommended treatment category. Non-optimal therapy was highest in Black (42 % [n = 712]) and women (42 % [n = 2668]) and lower in White (39 % [n = 4748]) and male (40 % [n = 3439]) patients. Compared with White patients, unadjusted and adjusted odds ratios of receiving non-optimal anticoagulant therapy for Black patients were 1.13; 95 % CI, 1.02–1.30, p = 0.02; and 1.17; 95%CI, 1.04–1.31, p = 0.01; respectively, and 1.10; 95 % CI 1.03–1.18, p = 0.005; and 1.36; 95 % CI, 1.25–1.47, p

Study Region. Two areas in Minnesota, USA: Buffalo aquifer in Clay County and Jordan aquifer in Olmsted County. There are concerns about the long-term sustainability of groundwater resources in the two aquifers. Study Focus. Aquifer storage and recovery is an important tool for water resources management in various geographic and socio-economic contexts. However, practical guidelines regarding the assessment of injection capacity remain limited. In this study, we present a quantitative methodology which is based on the Theis solution. The methodology allows an efficient estimation of well-based injection capacity and generation of an aquifer-scale injection capacity map. We present a detailed workflow for applying the methodology and demonstrate its application to the two study areas. The tool developed in this study can be easily applied to other areas. New Hydrological Insights for the Region. The two study areas show significant spatial variability in injection capacity. In the Buffalo aquifer, the variability is mainly controlled by transmissivity, whereas in the Jordan aquifer, it is mainly controlled by maximum allowable hydraulic head change. Assuming an injection duration of one month and considering the 90-percentile value of the injection capacity at each site, we found that two and four wells are required to inject the volume of water equivalent to one month of domestic water requirements for the cities of Moorhead and Rochester, respectively.

Background: The Singapore GSDCS score was developed to enable clinicians predict the risk of nosocomial multidrug-resistant Gram-negative bacilli (RGNB) infection in critically ill patients. We aimed to validate this score in a UK setting. Method: A retrospective case–control study was conducted including patients who stayed for more than 24 h in intensive care units (ICUs) across two tertiary National Health Service hospitals in London, UK (April 2011–April 2016). Cases with RGNB and controls with sensitive Gram-negative bacilli (SGNB) infection were identified. Results: The derived GSDCS score was calculated from when there was a step change in antimicrobial therapy in response to clinical suspicion of infection as follows: prior Gram-negative organism, Surgery, Dialysis with end-stage renal disease, prior Carbapenem use and intensive care Stay of more than 5 days. A total of 110 patients with RGNB infection (cases) were matched 1:1 to 110 geotemporally chosen patients with SGNB infection (controls). The discriminatory ability of the prediction tool by receiver operating characteristic curve analysis in our validation cohort was 0.75 (95% confidence interval 0.65–0.81), which is comparable with the area under the curve of the derivation cohort (0.77). The GSDCS score differentiated between low- (0–1.3), medium- (1.4–2.3) and high-risk (2.4–4.3) patients for RGNB infection (P

A 25-year-old man with a venous malformation (VM) along the anterior and posterolateral aspects of the right chest wall presented with progressive enlargement of VM, chest wall pain, and physical disfigurement. Because of the complexity and size of the VM, a staged multidisciplinary team approach, ie percutaneous embolization, followed by surgical resection and tissue-skin grafting was used. The percutaneous embolization was achieved with a combination of liquid embolic agents including n-butyl cyanoacrylate for the superficial cutaneous component and ethylene vinyl alcohol copolymer for the deeper subcutaneous component of the VM. Such a combination can achieve safe occlusion of the VM, facilitate surgical resection without blood loss, and contribute to a cosmetically desirable result.

Fourty-seven-year-old woman with 5-year history of progressive decreased left eye vision. Optical coherence tomography showed optic nerve atrophy (left > right) and brain MRI revealed T2 hyperintense signal along the course of left optic radiations. We present a case of a trans-synaptic degeneration of the optic radiation in a patient with confirmed optic atrophy. Trans-synaptic degeneration of the optic radiation without associated infarct or inflammatory disease has not been reported before in patients with optic atrophy.

Summary: Identification of selective deubiquitinase (DUB) inhibitors is critical for probe development to further understand and explore DUB biological function. Here, we detail the optimization and deployment of an in vitro fluorogenic ubiquitin-rhodamine assay to conduct high-throughput screening of a small molecule library against a panel of DUBs. In screening the compound library against multiple DUBs in parallel, we describe an approach for identifying selective DUB inhibitors and provide a roadmap for enabling selective DUB inhibitor discovery.For complete details on the use and execution of this protocol, please refer to Varca et al. (2021).

Patients with chronic wounds often have associated cognitive dysfunction and depression with an as yet unknown mechanism for this association. To address the possible causality of skin wounding inducing these changes, behavior and cognitive functions of female C57BL/6 mice with an excisional skin wound were compared to unwounded animals. At six days post wounding, animals exhibited anxiety-like behaviors, impaired recognition memory, and impaired coping behavior. Wounded animals also had concomitant increased hippocampal expression of Tnfa, the pattern recognition receptor (PRR) Nod2, the glucocorticoid receptors GR/Nr3c1 and Nr3c2. Prefrontal cortex serotonin and dopamine turnover were increased on day six post-wounding. In contrast to the central nervous system (CNS) findings, day six post -wounding serum catecholamines did not differ between wounded and unwounded animals, nor did levels of the stress hormone corticosterone, TNFα, or TGFβ. Serum IL6 levels were, however elevated in the wounded animals. These findings provide evidence of skin-to-brain signaling, mediated either by elevated serum IL6 or a direct neuronal signaling from the periphery to the CNS, independent of systemic mediators. Wounding in the periphery is associated with an altered expression of inflammatory mediators and PRR genes in the hippocampus, which may be responsible for the observed behavioral deficits.

Disruptions in stress-sensitive biological systems, notably the immune system and hypothalamic-pituitary-adrenal axis, are strongly implicated in depression, and disturbances in these neuroendoimmune systems could reflect potential pathways through which experiences of stress are translated into depression. To characterize the links between stress and depression, the present study investigated whether neuroendoimmune activity mediates the relationship between perceived stress and depressive symptoms in 59 medically healthy adult females with varying levels of depression. Consistent with hypotheses, both greater perceived stress and higher concentrations of the proinflammatory immune marker, interleukin-6 (IL-6), were associated with greater depressive symptoms. Although neuroendoimmune activity did not significantly mediate the relationship between lifetime perceived stress and depressive symptoms, when considered together, elevated concentrations of IL-6 and lower free cortisol mediated the relationship between severity of childhood stress and current depressive symptoms. These findings shed light on how early life stress may be translated into adulthood depression.

Summary: Introduction: Familial hypercholesterolaemia (FH) is a common, heritable and preventable cause of premature coronary artery disease, with significant potential for positive impact on public health and healthcare savings. New clinical practice recommendations are presented in an abridged guidance to assist practitioners in enhancing the care of all patients with FH. Main recommendations: Core recommendations are made on the detection, diagnosis, assessment and management of adults, children and adolescents with FH. There is a key role for general practitioners (GPs) working in collaboration with specialists with expertise in lipidology. Advice is given on genetic and cholesterol testing and risk notification of biological relatives undergoing cascade testing for FH; all healthcare professionals should develop skills in genomic medicine. Management is under-pinned by the precepts of risk stratification, adherence to healthy lifestyles, treatment of non-cholesterol risk factors, and appropriate use of low-density lipoprotein (LDL)-cholesterol lowering therapies, including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Recommendations on service design are provided in the full guidance. Potential impact on care of FH: These recommendations need to be utilised using judicious clinical judgement and shared decision making with patients and families. Models of care need to be adapted to both local and regional needs and resources. In Australia new government funded schemes for genetic testing and use of PCSK9 inhibitors, as well as the National Health Genomics Policy Framework, will enable adoption of these recommendations. A broad implementation science strategy is, however, required to ensure that the guidance translates into benefit for all families with FH.

Rationale & Objective: Although end-stage kidney disease (ESKD) adversely affects fertility, pregnancies can occur among women receiving dialysis. ESKD increases the risk for adverse pregnancy outcomes and little is known about contraceptive use in women undergoing dialysis. Study Design: Retrospective cohort study. Setting & Participants: Using the US Renal Data System covering January 1, 2005, through December 31, 2014, we evaluated for each calendar year women who for the entire year were aged 15 to 44 years, receiving dialysis, and with Medicare as the primary payer. Predictors: Age, race/ethnicity, and calendar year of prevalent ESKD. Outcome: Contraceptive use. Analytic Approach: We determined rates of contraceptive use and used multivariable logistic regression to identify factors associated with contraceptive use. Results: The study cohort included 35,732 women and represented 115,713 person-years. The rate of contraceptive use was 5.30% of person-years (95% CI, 5.17%-5.42%). Overall, contraceptive use increased from 2005 to 2014 (4.21%; 95% CI, 3.84%-4.59% vs 6.54%, 95% CI, 6.10%-6.99%). Compared with women aged 25 to 29 years, contraceptive use was higher in women aged 15 to 24 years (OR, 1.30; 95% CI, 1.18-1.43) and lower in women aged 30 to 34 years (OR, 0.74; 95% CI, 0.68-0.81), 35 to 39 years (OR, 0.46; 95% CI, 0.42-0.50), and 40 to 44 years (OR, 0.30; 95% CI, 0.27-0.34). Compared with White women, contraceptive use was higher in Black (OR, 1.12; 95% CI, 1.02-1.24) and Native American women (OR, 1.60; 95% CI, 1.25-2.05). Women with ESKD due to glomerulonephritis had a higher likelihood of contraceptive use than women with ESKD due to diabetes (OR, 1.22; 95% CI, 1.06-1.42). Women receiving peritoneal dialysis had a lower likelihood of contraceptive use than women receiving hemodialysis (OR, 0.85; 95% CI, 0.78-0.93). Compared with women without predialysis nephrology care, contraceptive use was higher in women who received predialysis nephrology care for 12 or fewer months (OR, 1.22; 95% CI, 1.09-1.37) and more than 12 months (OR, 1.33; 95% CI, 1.20-1.47). Limitations: Retrospective design and use of administrative data. Conclusions: Among women with ESKD undergoing dialysis, contraceptive use remains low at 5.30%. Younger age, Native American and Black race/ethnicity, ESKD due to glomerulonephritis, hemodialysis, and predialysis nephrology care are associated with a higher likelihood of contraceptive use. The study highlights the importance of prepregnancy counseling for contraceptive use in women receiving dialysis.

Background: The present study is a prospective observational single arm clinical investigation, with parallel bench test interrogation, aimed at investigating the technical feasibility, safety and clinical outcomes with the cone flare crush modified-T (CFCT) bifurcation stenting technique. Bifurcation percutaneous coronary intervention (PCI) remains an area of ongoing procedural evolution. More widely applicable and reproducible techniques are required. Methods: From April 2018 until March 2019, 20 consecutive patients underwent bifurcation PCI using the CFCT technique with a Pt-Cr everolimus drug-eluting stent with a bioresorbable polymer. Exercise stress echocardiography was performed at 12-month follow-up. The primary outcome was a composite of cardiac related mortality, myocardial infarction, target lesion/vessel revascularization and stroke. Safety secondary endpoints included bleeding, all-cause mortality and stent thrombosis. Results: All patients underwent a successful CFCT bifurcation procedure with no complications to 30-day follow-up. One patient met the primary endpoint requiring target lesion revascularization at 9 months for stable angina. There were no other primary or secondary outcome events in the cohort. There were no strokes, deaths, stent thrombosis or myocardial infarction during the follow-up period. The mean CCS score improved from 2.25 to 0.25 (p

Summary: Antimicrobial resistance (AMR) is a global healthcare problem and therefore raising awareness within young learners is imperative. An AMR roadshow was designed to take key stage 4 students' learning ‘out of the classroom’, assess pre-existing knowledge of AMR and determine the impact of the roadshow on knowledge retention. Knowledge and subsequent retention were measured pre- and post-event through a standardised questionnaire. The roadshow significantly improved knowledge and understanding of AMR, which was retained for a minimum of twelve weeks. Engaging and interactive strategies addressing key health issues provide a positive learning experience which contributes to retained knowledge in young learners.

الملخص: أهداف البحث: أجريت هذه الدراسة لتحديد ما يفضله الطلاب في اختيار العلاج الطبيعي كخيار مهني والعوامل التي تلعب أدوارا رئيسة في اختيارهم. طرق البحث: أجريت دراسة مقطعية شملت ٢٩٧ شخصا بأعمار تتراوح بين ١٤-٢١ سنة بين طلاب جامعات محتملين. وقد تم استقطابهم من ٧ مدارس ثانوية في مناطق حكومية محلية مختارة من ولاية لاغوس باستخدام تقنية المعاينة الهادفة. تم تبني استبانة من الأدبيات المناسبة مكون من ١٤ بندا يبحث في العلاج الطبيعي مقارنة بـ ١١ مهنة مختارة على ستة أبعاد، هي مستويات الإجهاد البدني، والرواتب، والفائدة للمجتمع، والمسؤولية، والوضع الاجتماعي، والتعرف الشخصي، بالإضافة إلى التحقيق في عوامل تعتبر مهمة في اختيار المهنة. ولخصت البيانات باستخدام المتوسط والانحراف المعياري ومعامل كيندال للوفاق. النتائج: تم استقطاب ما يصل إلى ١٨٤ من الذكور (٦٢٪)، و١١٣ من الإناث (٣٨٪) في هذه الدراسة. صُنّف العلاج الطبيعي في المرتبة الرابعة على مستوى الإجهاد البدني، والثالثة على مستوى الراتب، والخامسة على مستوى الفائدة، والرابعة على مستوى المسؤولية، والرابعة على المكانة الاجتماعية والرابعة على الاعتراف الشخصي. وبصورة عامة، تم تصنيف العلاج الطبيعي رابع تخصص من ناحية الأكثر تفضيلا. وينظر طلاب الجامعات المحتملين إلى العلاج الطبيعي على أنه يحمل مكانة مهنية عالية وذلك بتصنيفه في المرتبة الرابعة بعد الأطباء والمهندسين والمحامين. الاستنتاجات: تُعتبر مهنة العلاج الطبيعي ذات تقديرعالٍ ويمكن أن ينظر إليها على أنها مهنة مرغوبة في المستقبل. Abstract: Objectives: This study was carried out to determine the preferences of students in selecting physiotherapy as a career choice and the factors that play key roles in their selection. Methods: A cross-sectional study involving 297 subjects ranging from 14 to 21 years of age was conducted among prospective university students. They were recruited from seven secondary schools in selected local government areas of Lagos state using a purposive sampling technique. A 14-item questionnaire, comparing physiotherapy to 11 selected occupations on six dimensions, that is, level of physical stress, salary, usefulness to society, responsibility, social status, and personal recognition as well as investigating factors considered important in selecting a career, was adapted from relevant literature. The data was analysed using mean, standard deviation, and Kendall's coefficient of concordance. Results and discussion: The responses of 184 males (62.0%) and 113 females (38.0%) were used in the data analysis of this study. Physiotherapy was ranked fourth in terms of level of physical stress, third in terms of salary, fifth in terms of usefulness, fourth in terms of responsibility, fourth in terms of social status, and fourth in terms of personal recognition. Overall, physiotherapy was rated as the fourth-most preferred occupation. Prospective university students perceived physiotherapy as having a high level of occupational prestige, rating it fourth after medicine, engineering, and law. Conclusions: The profession of physiotherapy is held in high esteem and is seen as a desirable career choice among Nigerian high school students. الكلمات المفتاحية: المكانة المهنية, طالب جامعي محتمل, العلاج الطبيعي, Keywords: Occupational prestige, Physiotherapy, Prospective university students

Summary: Acetyl-coenzyme A (CoA) is an abundant metabolite that can also alter protein function through non-enzymatic N-acetylation of protein lysines. This N-acetylation is greatly enhanced in vitro if an adjacent cysteine undergoes initial S-acetylation, as this can lead to S→N transfer of the acetyl moiety. Here, using modeled mouse structures of 619 proteins N-acetylated in mouse liver, we show lysine N-acetylation is greater in vivo if a cysteine is within ∼10 Å. Extension to the genomes of 52 other mammalian and bird species shows pairs of proximal cysteine and N-acetylated lysines are less conserved, implying most N-acetylation is detrimental. Supporting this, there is less conservation of cytosolic pairs of proximal cysteine and N-acetylated lysines in species with longer lifespans. As acetyl-CoA levels are linked to nutrient supply, these findings suggest how dietary restriction could extend lifespan and how pathologies resulting from dietary excess may occur. : Acetyl-CoA non-enzymatically N-acetylates protein lysines. Using proteins N-acetylated in mouse liver, James et al. show N-acetylation is greater if a cysteine is within ∼10 Å. These pairs of proximal cysteine and N-acetylated lysines are less conserved in species with longer lifespans. This might explain how dietary restriction extends lifespan.

Purpose: Dose-volume histogram (DVH) toxicity relationships are poorly defined in men who receive radiation after radical prostatectomy (RP). We evaluated Radiation Therapy Oncology Group (RTOG) study 0534 and institutional intact normal-tissue sparing guidelines, as well as dose to bladder trigone, for ability to minimize late toxicity. Methods and materials: 164 men received intensity modulated radiation therapy (RT) to a median prostate bed dose of 66.6 Gy at a median of 22 months after RP. 46% of men were prescribed androgen deprivation therapy and pelvic lymph node irradiation to a median dose of 50.4 Gy. DVH relationships for the rectum, bladder, trigone, and bladder excluding the clinical target volume (bladder-CTV) were analyzed against the Common Terminology Criteria for Adverse Events late grade 2 + (G2+) gastrointestinal (GI) and genitourinary (GU) toxicity by log-rank test. RTOG 0534 (rectum V65, 40 Gy ≤35, 55%, and bladder-CTV V65, 40 ≤50, 70%) and intact prostate RT institutional guidelines (rectum V70, 65, 40 ≤20, 40, 80% and bladder V70, 65, 40 ≤30, 60, 80%, respectively) guidelines were evaluated. Results: With a median follow-up time of of 33 months, the 4-year freedom from G2 + GI and GU toxicity were both 91%. G2 + GI (n = 12) and GU (n = 15) toxicity included 4% diarrhea (n = 6), 4% hemorrhage (n = 6), 1% proctitis (n = 1), and 4% urinary frequency (n = 7), 1% obstructive (n = 2), 2% cystitis (n = 3), and 3% incontinence (n = 5), respectively. RTOG 0534 rectum and bladder goals were not achieved in 65% and 41% of cases, while the institutional intact prostate goals were not achieved in 21% and 25% of cases, respectively. Neither dose to the bladder trigone nor any of the proposed normal tissue goals were associated with late toxicity (P > .1). In the univariate analysis, age, pelvic RT, RT dose, anticoagulation use, androgen deprivation therapy, time from RP to RT, and tobacco history were not associated with toxicity. Conclusions: More than 90% of men were free from late G2 + toxicity 4 years after post-RP intensity modulated RT. No tested parameters were associated with late toxicity. In the absence of established normal-tissue DVH guidelines in the postoperative setting, the use of intact guidelines is reasonable.

Enterocutaneous fistulas (ECFs) can be one of the complications found after surgical intervention for rectal cancer. Interventional modalities consisting of surgical, endoscopic, and radiological methods are often implemented to treat postoperative symptomatic complications. We present the case of 61-year-old Caucasian man who presented to us with a recent diagnosis of rectal cancer that had invaded the levators as well as anteriorly into the prostate, and who underwent low anterior resection with a diverting loop ileostomy. The patient was found to have a persistent presacral abscess due to an ECF tract. This case highlights the off-label use of ethylene-vinyl alcohol copolymer dissolved in dimethyl sulfoxide (Onyx 34) to seal an ECF. Keywords: Rectal cancer, Embolization, Onyx

Cowden disease is a rare autosomal dominant disorder first described by Rachel Cowden in 1963 as one of the phosphatase and tensin homolog (PTEN) gene hamartoma tumor syndromes. Commonly affecting multiple systems, patients typically have an increased risk of breast and thyroid cancers as well as macrocephaly and benign hamartomatous growths. Due to the benign nature of many of the symptoms, true prevalence is likely higher than reported rates. Malformations associated with PTEN gene lead to dysregulation of cell proliferation yielding increased risk of neoplasm and frequently benign growths. Associated dysregulation of angiogenesis may result in arteriovenous malformations (AVMs). Intracranial AVMs may be asymptomatic. These AVMs present a risk of rupture and subsequent morbidity and mortality. Those with Cowden disease must be monitored for development of intracranial AVMs. Patients should be made aware that treatment for intracranial AVMs may be invasive and include serial embolization.

Exercise has been well demonstrated to potentially reduce chemotherapy-induced side effects and possibly aid slowing down tumor growth in cancer patients but exercise training adherence is typically low. Thus, training regimens which are perceived less strenuous but do not compromise the training-induced beneficial adaptations will help to increase adherence to exercise and reduce attrition. This 4-armed study aims to investigate the effects of high intensity interval training (HIIT) in hyperoxia versus intermittent hyperoxia and hypoxia in cancer patients undergoing chemotherapy. Forty-eight cancer patients will be randomized into either of three intervention groups or a no-training control group. Patients in the intervention groups will perform twice weekly HIIT on a cycle ergometer in hyperoxia, intermittent hyperoxia and hypoxia or normoxia. Study outcomes will be assessed before and after 4 weeks of training, while selected measures will also be performed pre- and post the first and last training session. The primary aim of this study is to investigate the feasibility, compliance, tolerance and safety of the training. Secondary endpoints will include measures of quality of life, aerobic capacity, transcutaneous oxygen saturation, red blood cell deformability, as well as the assessment of anabolic and catabolic hormone concentrations, reactive oxygen species, cytokine profiles and NK-cell cytotoxicity. To the best of our knowledge, this is the first study investigating the combined effects of exercise with modified fraction of inspired O2 in cancer patients. As such, we provide a novel approach for exercise as an adjuvant therapy in cancer patients undergoing chemotherapy.

Purpose: To report a case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy. Observations: A 65-year-old Caucasian woman presented with acute respiratory distress syndrome and septic shock. After treatment with vasopressors and prolonged prone positioning, she was noted to be bilaterally completely blind on hospitalization day 12. Evaluation revealed evidence of bilateral central retinal artery occlusion and bilateral ischemic optic neuropathy. Magnetic resonance imaging of the orbits demonstrated severe restricted diffusion of both optic nerves consistent with ischemia. Both central retinal artery occlusion and ischemic optic neuropathy have been reported in cases of severe hypotension, blood loss, and prone positioning, most often postoperatively after spinal surgery. Conclusions and importance: To our knowledge, this is the first reported case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy, presumed due to the combination of severe systemic hypotension, hypoxemia due to the respiratory distress syndrome, and prolonged prone positioning.

Clinical features and investigations lack predictive value when diagnosing pneumonia, especially when patients are ventilated and when patients develop ventilator associated pneumonia (VAP). New tools to aid diagnosis are important to improve outcomes. This pilot study examines the potential for metabolic profiling to aid the diagnosis in critical care. In this prospective observational study ventilated patients with brain injuries or pneumonia were recruited in the intensive care unit and serum samples were collected soon after the start of ventilation. Metabolic profiles were produced using 1D 1H NMR spectra. Metabolic data were compared using multivariate statistical techniques including Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA). We recruited 15 patients with pneumonia and 26 with brain injuries, seven of whom went on to develop VAP. Comparison of metabolic profiles using OPLS-DA differentiated those with pneumonia from those with brain injuries (R2Y = 0.91, Q2Y = 0.28, p = 0.02) and those with VAP from those without (R2Y = 0.94, Q2Y = 0.27, p = 0.05). Metabolites that differentiated patients with pneumonia included lipid species, amino acids and glycoproteins. Metabolic profiling shows promise to aid in the diagnosis of pneumonia in ventilated patients and may allow a more timely diagnosis and better use of antibiotics.

Abstract Objective: To examine reported outcomes of health services delivered by telehealth to Indigenous Australians. Methods: Systematic review of the literature. Searches were conducted to identify articles that reported a telehealth service used to provide clinical services to Indigenous Australians. Articles were screened for inclusion using pre‐defined criteria. Findings were synthesised narratively and reported using the preferred reporting items for systematic reviews and meta‐analyses (PRISMA) guidelines. Results: 14 articles, describing 11 distinct telehealth services, were selected based on the inclusion criteria. Authors of included studies report that telehealth has improved social and emotional wellbeing, clinical outcomes and access to health services for Indigenous Australians. Further, it has reduced travel and improved screening rates. Indigenous people report positive perceptions of their telehealth interaction. Conclusion: Telehealth is used to address poor accessibility to health services and for targeted screening programs for at risk populations. Reported outcomes from existing services demonstrate the potential of telehealth for health service delivery for Indigenous Australians. Confidence in the findings of this review is reduced by the predominance of descriptive studies and small sample sizes in many of the included articles. Implications: Telehealth models of care facilitated through partnerships between Aboriginal community‐controlled health services and public hospitals may improve both patient outcomes and access to specialist services for Indigenous people.