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Age-related endothelial dysfunction is a pivotal factor in the development of cardiovascular diseases, stemming, at least in part, from mitochondrial dysfunction and a consequential increase in oxidative stress. These alterations are central to the decline in vascular health seen with aging, underscoring the urgent need for interventions capable of restoring endothelial function for preventing cardiovascular diseases. Dietary interventions, notably time-restricted feeding (TRF), have been identified for their anti-aging effects on mitochondria, offering protection against age-associated declines in skeletal muscle and other organs. Motivated by these findings, our study aimed to investigate whether TRF could similarly exert protective effects on endothelial health in the vasculature, enhancing mitochondrial function and reducing oxidative stress. To explore this, 12-month-old C57BL/6 mice were placed on a TRF diet, with food access limited to a 6-h window daily for 12 months. For comparison, we included groups of young mice and age-matched controls with unrestricted feeding. We evaluated the impact of TRF on endothelial function by measuring acetylcholine-induced vasorelaxation of the aorta. Mitochondrial health was assessed using fluororespirometry, and vascular reactive oxygen species (ROS) production was quantified with the redox-sensitive dye dihydroethidium. We also quantified 4-hydroxynonenal (4-HNE) levels, a stable marker of lipid peroxidation, in the aorta using ELISA. Our findings demonstrated that aged mice on a standard diet exhibited significant impairments in aortic endothelial relaxation and mitochondrial function, associated with elevated vascular oxidative stress. Remarkably, the TRF regimen led to substantial improvements in these parameters, indicating enhanced endothelial vasorelaxation, better mitochondrial function, and reduced oxidative stress in the aortas of aged mice. This investigation establishes a vital foundation, paving the way for subsequent clinical research aimed at exploring the cardiovascular protective benefits of intermittent fasting.

Through an exploratory descriptive study, we examined school counselors' attitudes and beliefs about their role in HIV prevention, and their professional behaviors in addressing HIV in their schools. Participants reported strong support of youth's sexual health rights, moderate agreement with school counselors' role in HIV prevention, moderate to high comfort addressing HIV, and low engagement in HIV prevention behaviors. We discuss implications for school counselor training, supervision, and advocacy.

Fancy Yarns is a term that is given to yarns with special effects, this yarn may be single or plied, and these effects can be added during the spinning process, plying process, or after producing the yarn, i.e. during the painting or printing process.Producing fancy yarns aims to decorate the fabrics with which they are woven, and the use of fancy warns helps the designer to present the best fancy innovations for woven fabrics, whether they are clothing or furniture fabrics. The use of fancy warns helps acquiring the plain fabrics low cost fancy tactile effects.The research depended on producing samples on single circular knitting machines using the four methods (descriptive method, symbolic method, cartographic method, and pictorial method), and this was made using four structures derived from the single jersey, then carrying out statistical analysis of the results of the directed questionnaire to specialists using Weighted arithmetic.

Background: Cooperative inquiry gives a voice to marginalised groups and breaks down power imbalances which makes it suitable for researching practical issues at community level. Objectives: The objective of this article is to illustrate how cooperative inquiry can be utilised to empower members of marginalised communities in facilitating social change. Method: The study setting is in Paarl, Western Cape, South Africa. A cooperative inquiry methodology was used. The inquiry group consisted of wheelchair users (9), their care givers (8), taxi drivers (7) and stakeholders (4). Data collection comprised 16 sessions, alternating between action and reflection. Inductive thematic analysis of data of all the phases was done to ensure that cooperative inquiry gives voice to marginalised communities. Results: The four themes that is, practical arrangements, understanding process, purpose, bonding and a cohesive group were identified. The themes showed progress from logistics, through individual understanding, to the group becoming one, and working together. Each of these phases is important in the development of a cooperative inquiry. Conclusion: Cooperative inquiry methodology can bring people together in a positive way to facilitate social change, and developing practical solutions to challenges. Contribution: Making use of a cooperative inquiry methodology to bring social change, minibus taxi services can be made accessible for wheelchair users. Concepts of social justice and decolonisation were imbued in the methodology.

Health risk behaviour, as it pertains to adolescent behaviour, poses a massive challenge for many fields of medicine, not only due to developmental and psychological concerns but also its inevitable contribution to the burden of disease through trauma and non‑communicable diseases resulting from risky behavioural choices. The objective study is to explore the prevalence of health risk behavior engage‑ ment among grade 4‑7 learners at four primary schools in the Western Cape, South Africa, as well as establish a need for a prevention program starting at primary school level. An observational, descriptive, quantitative design was used to conduct this study. Non‑probability, heterogenous, purposive sampling was used to select the study population. A needs analysis assessment using a modified self‑administered Child Health Risk Behaviour survey was conducted using 7‑inch electronic tablets. Four primary schools agreed to participate yielding a total sample size of n=1147 learners in grades 4 to 7. Learners' age ranged from nine years old to fourteen years old with a mean age of 11.45 (SD 1.271). Riding a bicycle without a helmet, physical fight (86.1 and 64.1% among boys and girls respectively), ever smoked a cigarette (boys 36.3%; girls 28.3%) and consuming alcohol without permission (boys 28.7%; girls 23.8%) had the most engagement. Sexual curi‑ osity questions had by far the most positive engagement and consistency of engagement among both boys and girls. This evidence reaffirms the need that early, bespoke and scientific intervention/prevention programs are needed to combat health risk behaviour and subsequently reduce the burden of disease.

It is unclear whether mitochondrial dysfunction and redox stress contribute to impaired age-related muscle regenerative capacity. Here we characterized a novel compound, BI4500, that inhibits the release of reactive oxygen species (ROS) from the quinone site in mitochondrial complex I (site IQ). We tested the hypothesis that ROS release from site IQ contributes to impaired regenerative capacity in aging muscle. Electron transfer system site-specific ROS production was measured in adult and aged mouse isolated muscle mitochondria and permeabilized gastrocnemius fibers. BI4500 inhibited ROS production from site IQ in a concentration-dependent manner (IC50 = ∼985 nM) by inhibiting ROS release without impairing complex I-linked respiration. In vivo BI4500 treatment decreased ROS production from site IQ. Muscle injury and sham injury were induced using barium chloride or vehicle injection to the tibialis anterior (TA) muscle in adult and aged male mice. On the same day as injury, mice began a daily gavage of 30 mg/kg BI4500 (BI) or placebo (PLA). Muscle regeneration (H&E, Sirius Red, Pax7) was measured at 5 and 35 days after injury. Muscle injury increased centrally nucleated fibers (CNFs) and fibrosis with no treatment or age effect. There was a significant age by treatment interaction for CNFs at 5- and 35-days post injury with significantly more CNFs in BI adults compared to PLA adults. Muscle fiber cross-sectional area (CSA) recovered significantly more in adult BI mice (−89 ± 365 μm2) compared to old PLA (−599 ± 153 μm2) and old BI (−535 ± 222 μm2, mean ± SD). In situ TA force recovery was measured 35 days after injury and was not significantly different by age or treatment. Inhibition of site IQ ROS partially improves muscle regeneration in adult but not old muscle demonstrating a role for CI ROS in the response to muscle injury. Site IQ ROS does not contribute to impaired regenerative capacity in aging.

Objective: This study assessed traditional farmers' preferences for indigenous pigs and their awareness levels toward reproductive biotechnology. Materials and Methods: This cross-sectional, descriptive study employed a mixed-methods con¬current triangulation design with a pragmatic approach. For quantitative data collection, a ran¬domly selected sample size of 622 respondents was interviewed using a structured questionnaire. A semi-structured interview guide was used in seven focus group discussions (FGDs) for qualitative data. For quantitative data, descriptive statistics were used to find out how often something happened, and chi-square tests were used to look for relationships. For qualitative data, thematic analysis was used. Results: The majority (66.9%) of respondents were female, and they had largely (64.8%) attended a primary level of education. A slight majority (43.1%) of the respondents were 30–45 years old. Most respondents (65.1%) were low-income earners (below K500). Incidentally, the majority (74.1%) of respondents had low awareness of reproductive biotechnologies. Respondents' aware¬ness levels were associated with gender (p < 0.001), education (p < 0.001), income (p < 0.01), and not age (p > 0.05). With regard to trait preference, a total of seven indigenous pig traits were reportedly preferred, of which disease resistance (25.9%) and litter size (23.8%) were the most preferred. From FGDs, participants valued indigenous pigs, citing many preferred traits, of which disease resistance and litter size were the most emphasized traits. Some participants were aware of many reproductive biotechnologies and their perceived advantages. However, they were more familiar with artificial insemination, heat detection methods, and synchronization. Conclusions: The majority of respondents had low awareness of reproductive biotechnologies. Respondents' awareness was associated with sociodemographic characteristics. The identified indigenous pig traits preferred by traditional farmers included adaptive and productive traits. [J Adv Vet Anim Res 2022; 9(2.000): 255-266]

Background and Aim: Pig production remains crucial to the livelihood of farmers in Zambia. However, low production continues to undermine efforts to reduce animal protein deficit; hence, the need emerges to improve production through biotechnology. To contribute to the prediction of their acceptance, this study assessed the attitudes and preferences of traditional farmers toward reproductive biotechnologies by exploring the socio-demographic characteristics of farmers. Materials and Methods: The study conducted a cross-sectional descriptive survey that employed a mixed-methods design with a qualitative-quantitative methodological triangulation. Quantitative data were obtained from 622 respondents using a questionnaire, whereas seven focus group discussions (FGDs) were conducted to obtain qualitative data. Descriptive statistics and thematic analysis were used to analyze quantitative and qualitative data, respectively. Results: The majority (65.1%) of the respondents were low-income earners who mainly (64.8%) attained primary education. In addition, pig farming was dominated by middle-aged (43.7%) and elderly (40.7%) individuals. Moreover, most of the respondents owned (51.3% and 78.0%) more than 2 acres and six pigs, respectively. Furthermore, the respondents expressed a positive attitude (3.84±0.42) toward reproductive biotechnology application. However, despite supportive opinions (4.17±0.54) and favorable behavioral intentions (4.09±0.51), their feelings were generally neutral (3.10±0.89). In addition, the study observed various contrasting attitudes across socio-demographic factors. The respondents mainly preferred artificial insemination (AI; 66.2%). The results of the FGDs supported the survey findings. Nevertheless, the lack of information, knowledge and practical exposure, absence of peer influence, perceived beliefs and risks, poverty situations, and gender issues were pinpointed as the identified barriers to the biotechnology acceptance of the participants. Conclusion: The respondents generally supported reproductive biotechnology application and its contribution to improved production. However, further promotion of the favorable attitudes of the farmers will be required. In this case, interventions sensitive to their socio-demographic characteristics, perceived barriers, and identified contributing factors to favorable attitudes will be crucial. In addition, despite the overwhelming preference for AI, efforts to promote AI-supporting reproductive technologies are required because they contribute to AI success rate.

BackgroundSubstantial evidence supports an association between use of menopausal hormone therapy and decreased colorectal cancer (CRC) risk, indicating a role of exogenous sex hormones in CRC development. However, findings on endogenous oestrogen exposure and CRC are inconsistent.MethodsWe used a Mendelian randomisation approach to test for a causal effect of age at menarche and age at menopause as surrogates for endogenous oestrogen exposure on CRC risk. Weighted genetic risk scores based on 358 single-nucleotide polymorphisms associated with age at menarche and 51 single-nucleotide polymorphisms associated with age at menopause were used to estimate the association with CRC risk using logistic regression in 12,944 women diagnosed with CRC and 10,741 women without CRC from three consortia. Sensitivity analyses were conducted to address pleiotropy and possible confounding by body mass index.ResultsGenetic risk scores for age at menarche (odds ratio per year 0.98, 95% confidence interval: 0.95-1.02) and age at menopause (odds ratio 0.98, 95% confidence interval: 0.94-1.01) were not significantly associated with CRC risk. The sensitivity analyses yielded similar results.ConclusionsOur study does not support a causal relationship between genetic risk scores for age at menarche and age at menopause and CRC risk.

Abstract Background Ageing and cachexia cause a loss of muscle mass over time, indicating that protein breakdown exceeds protein synthesis. Deuterium oxide (D2O) is used for studies of protein turnover because of the advantages of long‐term labelling, but these methods introduce considerations that have been largely overlooked when studying conditions of protein gain or loss. The purpose of this study was to demonstrate the importance of accounting for a change in protein mass, a non‐steady state, during D2O labelling studies while also exploring the contribution of protein synthesis and breakdown to denervation‐induced muscle atrophy. Methods Adult (6 months) male C57BL/6 mice (n = 14) were labelled with D2O for a total of 7 days following unilateral sciatic nerve transection to induce denervation of hindlimb muscles. The contralateral sham limb and nonsurgical mice (n = 5) were used as two different controls to account for potential crossover effects of denervation. We calculated gastrocnemius myofibrillar and collagen protein synthesis and breakdown assuming steady‐state or using non‐steady‐state modelling. We measured RNA synthesis rates to further understand ribosomal turnover during atrophy. Results Gastrocnemius mass was less in denervated muscle (137 ± 9 mg) compared with sham (174 ± 15 mg; P

Neglecting the significant role played by family members in the post-rehabilitation trajectory of substance abusers can pose a significant challenge in supporting intervention programmes in the workplace. This paper reports on a small-scale qualitative investigation that used focus group interviews with family members to explore their perceptions and experiences of being confronted with family members with substance use disorders. The findings are presented through three themes: 1) emotional burden; 2) coping and avoidance strategies; and 3) support needs of family members. Recommendations highlight how employee assistance programmes can provide a comprehensive suite of holistic support systems.

Abstract Background Health risk behaviour among South African youth is a significant public health concern. Despite a societal mind shift to educating the public on the prevention of health risk behaviour, behavioural change is not progressing at the rate needed to influence health risk behaviour positively. The project aims to explore behavioural trends and willingness to engage in risky behaviour among senior primary school children. Secondly, to design a health risk behaviour prevention program which adequately equips senior primary school children with the necessary life skills to alter risk behaviour engagement. Methods The study will make use of an intervention mapping framework and a sequential, explanatory mixed methods design. Stratified random probability sampling will be used to select three primary schools in the region. Nonprobability purposive sampling will be used to select the stakeholders participating in the focus group sessions. Data collection consists of five phases with the results of each stage informing the structure and application of the next. Phase 1 - baseline data collection (needs analysis) using the child health risk behaviour survey. Phase 2 - focus group interviews. Phase 3 - a systematic review of the literature for result analysis triangulation. Phase 4 – the development of the child risk behaviour prevention program based on the outcomes of phases 1,2 and 3. Phase 5 - implementation of the program. Descriptive statistics will be used to analyse the quantitative data. Chi-square, ANOVA and multiple regression analyses will be used to predict health risk behaviour engagement. Thematic analysis will be used to analyse qualitative data. Discussion To our knowledge, this is the first study that would attempt to establish a health risk behaviour prevention program in youth and young people in South Africa. Overwhelming evidence exists that adolescents engage in risky health behaviour which may potentially negatively impact their lives. This study provides an opportunity to address a gap in the current strategy by developing a prevention program for young people which could later be supported by further booster programs through their adolescents. This project would serve as a baseline prevention program that could assist in the reduction of risky health behaviour among various communities.

Abstract Background Endothelial function is dependent on the balance between vasoconstrictive and vasodilatory substances. The endothelium ability to produce nitric oxide is one of the most crucial mechanisms in regulating vascular tone. An increase in inducible nitric oxide synthase contributes to endothelial dysfunction in overweight persons, while oxidative stress contributes to the conversion of nitric oxide to peroxynitrite (measured as nitrotyrosine in vivo) in underweight persons. The objective of this study was to elucidate the interaction of body composition and oxidative stress on vascular function and peroxynitrite. This was done through an experimental design with three weight groups (underweight, normal weight and overweight), with four treatment arms in each. Plasma nitrotyrosine levels were measured 15–20 h post lipopolysaccharide (LPS) treatment, as were aortic ring tension changes. Acetylcholine (ACh) and sodium nitroprusside (SNP) challenges were used to observe endothelial-dependent and endothelial-independent vascular relaxation after pre-constriction of aortic rings with phenylephrine. Results Nitrotyrosine levels in saline-treated rats were similar among the weight groups. There was a significant increase in nitrotyrosine levels between saline-treated rats and those treated with the highest lipopolysaccharide doses in each of the weight groups. In response to ACh challenge, R max (percentage reduction in aortic tension) was lowest in overweight rats (112%). In response to SNP, there was an insignificantly lower R max in the underweight rats (106%) compared to the normal weight rats (112%). Overweight rats had a significant decrease in R max (83%) in response to SNP, signifying involvement of a more chronic process in tension reduction changes. A lower R max accompanied an increase in peroxynitrite after acetylcholine challenge in all weight groups. Conclusions Endothelial dysfunction, observed as an impairment in the ability to reduce tension, is associated with increased plasma peroxynitrite levels across the spectrum of body mass. In higher-BMI rats, an additional role is played by vascular smooth muscle in the causation of endothelial dysfunction.

Abstract Background Mitochondrial bioenergetics are sensitive to adenosine diphosphate (ADP) concentration. Reactive oxygen species (ROS) production and respiration [oxygen consumption rate (OCR)] are altered at physiological ADP concentrations (i.e. ADP insensitivity) in aged human muscle. Here, we investigate ADP sensitivity in mouse muscle mitochondria. Methods We measured OCR and ROS production in permeabilized gastrocnemius fibres using an ADP titration protocol and the Oroboros O2k respirometer and fluorometer. We measured changes in ADP sensitivity in muscle from mice at different ages, after sciatic nerve transection (denervation), and in response to increased oxidative stress (Sod1−/− mice). Further, we asked whether the mitochondrial‐targeted peptide SS‐31 can modulate ADP insensitivity and contractile function in the Sod1−/− mouse model. Results Reduced ADP sensitivity is associated with increases in mitochondrial ROS production in aged (62%) and Sod1−/− (33%) mice. The maximal capacity to produce ROS does not increase with age, and there is no effect of age on ADP sensitivity for OCR in mouse gastrocnemii. Denervation does not induce ADP insensitivity for either ROS generation or OCR. Treatment of Sod1−/− mice with SS‐31 increases ADP sensitivity for both OCR and ROS, decreases maximal ROS production (~40%), and improves resistance to muscle fatigue. Conclusions Adenosine diphosphate sensitivity for ROS production decreases in aged mouse gastrocnemius muscle fibres, although aged mice do not exhibit a difference in OCR. Denervation does not induce ADP insensitivity; however, insensitivity to ADP is induced in a model of oxidative stress. ADP insensitivity could contribute to muscle fatigue, and SS‐31 may be the first drug capable of targeting this aging phenotype.

Cerebral ischemia is an acute disorder characterized by an abrupt reduction in blood flow that results in immediate deprivation of both glucose and oxygen. The main types of cerebral ischemia are ischemic and hemorrhagic stroke. When a stroke occurs, several signaling pathways are activated, comprising necrosis, apoptosis, and autophagy as well as glial activation and white matter injury, which leads to neuronal cell death. Current treatments for strokes include challenging mechanical thrombectomy or tissue plasminogen activator, which increase the danger of cerebral bleeding, brain edema, and cerebral damage, limiting their usage in clinical settings. Monoclonal antibody therapy has proven to be effective and safe in the treatment of a variety of neurological disorders. In contrast, the evidence for stroke therapy is minimal. Recently, Clone MTS510 antibody targeting toll-like receptor-4 (TLR4) protein, ASC06-IgG1 antibody targeting acid sensing ion channel-1a (ASIC1a) protein, Anti-GluN1 antibodies targeting N-methyl-D-aspartate (NMDA) receptor associated calcium influx, GSK249320 antibody targeting myelin-associated glycoprotein (MAG), anti-High Mobility Group Box-1 antibody targeting high mobility group box-1 (HMGB1) are currently under clinical trials for cerebral ischemia treatment. In this article, we review the current antibody-based pharmaceuticals for neurological diseases, the use of antibody drugs in stroke, strategies to improve the efficacy of antibody therapeutics in cerebral ischemia, and the recent advancement of antibody drugs in clinical practice. Overall, we highlight the need of enhancing blood–brain barrier (BBB) penetration for the improvement of antibody-based therapeutics in the brain, which could greatly enhance the antibody medications for cerebral ischemia in clinical practice.

Abstract Background Excess reactive oxygen species (ROS) and muscle weakness occur in parallel in multiple pathological conditions. However, the causative role of skeletal muscle mitochondrial ROS (mtROS) on neuromuscular junction (NMJ) morphology and function and muscle weakness has not been directly investigated. Methods We generated mice lacking skeletal muscle‐specific manganese‐superoxide dismutase (mSod2KO) to increase mtROS using a cre‐Lox approach driven by human skeletal actin. We determined primary functional parameters of skeletal muscle mitochondrial function (respiration, ROS, and calcium retention capacity) using permeabilized muscle fibres and isolated muscle mitochondria. We assessed contractile properties of isolated skeletal muscle using in situ and in vitro preparations and whole lumbrical muscles to elucidate the mechanisms of contractile dysfunction. Results The mSod2KO mice, contrary to our prediction, exhibit a 10–15% increase in muscle mass associated with an ~50% increase in central nuclei and ~35% increase in branched fibres (P

Background: Detecting pre-clinical bladder cancer (BC) using urinary biomarkers may provide a valuable opportunity for screening and management. Telomerase reverse transcriptase (TERT) promoter mutations detectable in urine have emerged as promising BC biomarkers. Methods: We performed a nested case-control study within the population-based prospective Golestan Cohort Study (50,045 participants, followed up to 14 years) and assessed TERT promoter mutations in baseline urine samples from 38 asymptomatic individuals who subsequently developed primary BC and 152 matched controls using a Next-Generation Sequencing-based single-plex assay (UroMuTERT) and droplet digital PCR assays. Findings: Results were obtained for 30 cases and 101 controls. TERT promoter mutations were detected in 14 pre-clinical cases (sensitivity 46·67%) and none of the controls (specificity 100·00%). At an estimated BC cumulative incidence of 0·09% in the cohort, the positive and negative predictive values were 100·00% and 99·95% respectively. The mutant allelic fractions decreased with the time interval from urine collection until BC diagnosis (p = 0·033) but the mutations were detectable up to 10 years prior to clinical diagnosis. Interpretation: Our results provide the first evidence from a population-based prospective cohort study of the potential of urinary TERT promoter mutations as promising non-invasive biomarkers for early detection of BC. Further studies should validate this finding and assess their clinical utility in other longitudinal cohorts. Funding: French Cancer League, World Cancer Research Fund International, Cancer Research UK, Tehran University of Medical Sciences, the International Agency for Research on Cancer, and the U.S. National Cancer Institute. Keywords: Early detection, TERT promoter mutations, Urinary biomarker, Bladder cancer, Prospective cohort

While GWAS have uncovered susceptibility loci for B-cell precursor acute lymphoblastic leukemia (BCP-ALL), much of the heritable risk remains undiscovered. Here, the authors perform a meta-analysis of two existing BCP-ALL GWAS together with an unpublished GWAS to identify risk loci at 8q24.21 and 2q22.3.

Objective: A decline in mitochondrial function and biogenesis as well as increased reactive oxygen species (ROS) are important determinants of aging. With advancing age, there is a concomitant reduction in circulating levels of insulin-like growth factor-1 (IGF-1) that is closely associated with neuronal aging and neurodegeneration. In this study, we investigated the effect of the decline in IGF-1 signaling with age on astrocyte mitochondrial metabolism and astrocyte function and its association with learning and memory. Methods: Learning and memory was assessed using the radial arm water maze in young and old mice as well as tamoxifen-inducible astrocyte-specific knockout of IGFR (GFAP-CreTAM/igfrf/f). The impact of IGF-1 signaling on mitochondrial function was evaluated using primary astrocyte cultures from igfrf/f mice using AAV-Cre mediated knockdown using Oroboros respirometry and Seahorse assays. Results: Our results indicate that a reduction in IGF-1 receptor (IGFR) expression with age is associated with decline in hippocampal-dependent learning and increased gliosis. Astrocyte-specific knockout of IGFR also induced impairments in working memory. Using primary astrocyte cultures, we show that reducing IGF-1 signaling via a 30–50% reduction IGFR expression, comparable to the physiological changes in IGF-1 that occur with age, significantly impaired ATP synthesis. IGFR deficient astrocytes also displayed altered mitochondrial structure and function and increased mitochondrial ROS production associated with the induction of an antioxidant response. However, IGFR deficient astrocytes were more sensitive to H2O2-induced cytotoxicity. Moreover, IGFR deficient astrocytes also showed significantly impaired glucose and Aβ uptake, both critical functions of astrocytes in the brain. Conclusions: Regulation of astrocytic mitochondrial function and redox status by IGF-1 is essential to maintain astrocytic function and coordinate hippocampal-dependent spatial learning. Age-related astrocytic dysfunction caused by diminished IGF-1 signaling may contribute to the pathogenesis of Alzheimer's disease and other age-associated cognitive pathologies. Keywords: Primary astrocytes, IGF-1, Amyloid, Mitochondria, ROS, Alzheimer's disease

The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.

Background: Pulmonary tuberculosis (PTB) remains a major concern worldwide. Albeit curable, PTB continues to negatively affect patients’ health-related quality of life (HRQoL) and functioning even after cure. Objectives: To describe the demographics, respiratory symptoms, pulmonary airflow patterns, HRQoL and exercise capacity of cured PTB patients, in the Breede Valley district of South Africa. Methods: A cross-sectional study conducted at five primary health care facilities included adult patients diagnosed with PTB, who had completed anti-tuberculosis treatment. Post-treatment bronchodilator lung function, HRQoL and 6-min walk distance (6MWD) were measured. Results: Three hundred and twenty-four patients were screened. Specific challenges resulted in 45 patients being included (male n = 25 [56%]; mean population age 39.9 [± 10.2]). HRQoL was assessed using the short-form 12v2, part of the burden of lung disease core questionnaire. In general, self-reported physical scores (physical health component summary score = 45) were higher than mental scores (mental health component summary score = 39). The mean 6MWD was 294.5 m (± 122.7) m (range 110 m – 600 m), which is well below normal reference values. Forty-eight percent (48%) of the sample presented with abnormal lung function, including obstructive (n = 9; 21%), restrictive (n = 11; 25%) and mixed (n = 1; 2%). Conclusions: This pilot study suggests that most cured PTB patients have decreased HRQoL, exercise capacity and abnormal lung function. This study is the first to describe the combination of these three outcomes in a South African population. Clinical implications: Clinicians must recognise that holistic management of PTB patients is required after cure.

Many Amyotrophic Lateral Sclerosis (ALS) patients experience hypermetabolism, or an increase in measured vs. calculated metabolic rate. The cause of hypermetabolism and the effects on neuronal metabolism in ALS are currently unknown, but the efficacy of dietary interventions shows promise for metabolism as an ALS therapeutic target. The goal of this study is to measure changes in metabolic pathways as a function of disease progression in spinal cords of the SOD1G93A mouse model of ALS. We conducted a comprehensive assessment of protein expression for metabolic pathways, antioxidants, chaperones, and proteases in lumbar spinal cord from male SOD1G93A mice at pre-onset, onset, and end-stages of the disease using targeted proteomic analysis. These results reveal that protein content of metabolic proteins including proteins involved in glycolysis, β-oxidation, and mitochondrial metabolism is altered in SOD1G93A mouse spinal cord well before disease onset. The changes in mitochondrial metabolism proteins are associated with decreased maximal respiration and glycolytic flux in SOD1G93A dermal fibroblasts and increased hydrogen peroxide and lipid hydroperoxide production in mitochondria from sciatic nerve and gastrocnemius muscle fibers at end stage of disease. Consistent with redox dysregulation, expression of the glutathione antioxidant system is decreased, and peroxiredoxins and catalase expression are increased. In addition, stress response proteases and chaperones, including those involved in the mitochondrial unfolded protein response (UPRmt), are induced before disease onset. In summary, we report that metabolic and stress response changes occur in SOD1G93A lumbar spinal cord before motor symptom onset, and are primarily caused by SOD1G93A expression and do not vary greatly as a function of disease course.

Mice deficient in the electron transport chain (ETC) complex IV assembly protein SURF1 have reduced assembly and activity of cytochrome c oxidase that is associated with an upregulation of components of the mitochondrial unfolded protein response (UPRMT) and increased mitochondrial number. We hypothesized that the upregulation of proteins associated with the UPRMT in response to reduced cytochrome c oxidase activity in Surf1−/− mice might contribute to increased stress resistance. To test this hypothesis we asked whether primary cultures of fibroblasts from Surf1−/− mice exhibit enhanced resistance to stressors compared to wild-type fibroblasts. Here we show that primary dermal fibroblasts isolated from Surf1−/− mice have increased expression of UPRMT components ClpP and Hsp60, and increased expression of Lon protease. Fibroblasts from Surf1−/− mice are significantly more resistant to cell death caused by oxidative stress induced by paraquat or tert-Butyl hydroperoxide compared to cells from wild-type mice. In contrast, Surf1−/− fibroblasts show no difference in sensitivity to hydrogen peroxide stress. The enhanced cell survival in response to paraquat or tert-Butyl hydroperoxide in Surf1−/− fibroblasts compared to wild-type fibroblasts is associated with induced expression of Lon, ClpP, and Hsp60, increased maximal respiration, and increased reserve capacity as measured using the Seahorse Extracellular Flux Analyzer. Overall these data support a protective role for the activation of the UPRMT in cell survival.

Alawite family Immaculate has suffered early seventh decade AH serious repercussions came as a result of its commitment to the principles of the Islamic religion, as those family felt led grandson of the Prophet Mustafa (peace be upon him and his family and him) Imam Hussein bin Ali bin Abi Talib (peace be upon him) that Islam as a religion and principles and the values ​​of its large importance in the details of the lives of Muslims began Anharomam negative hiring him by the leaders of Tbaa graduate Centers did not give it right, so Hussein's determination to combat these trends, including made available to him and his family from potential despite its simplicity, but it took way until the end, Hussein was a leader of that family, and his brother Imam Abbas ibn Ali (peace be upon him) associate him and holding a banner and committed to its principles and sacrificing Braanh and what has the strength, courage and Osama was the way one results and one murder in the end share everyone's courage details filled with noble principles, witnessed the land of Karbala in ten days reflected the the meanings of the tournament in clearer images, but Abbas, who was a leader and a wonderful human being was his receipts and tours in the fields of the right and the courage and selflessness and fulfillment we left off in the following lines recalling the tournament with great reverence and pride.

Traditional, horse-derived antivenin is currently the most efficient treatment against snake bites. However, it is costly and has unpredictable side effects. Thus, alternative, cost-effective strategies for producing antivenin are needed. In this study, we immunized hens with inactivated NNA venom proteins from the cobra Naja naja atra (NNA). Purified yolk IgY antibodies showed specific anti-NNA binding activity comparable to that of the equine-derived antivenin. We used phage display technology to generate two antibody libraries containing 9.0 × 108 and 8.4 × 108 clones with a short or long linker, respectively. The phage ELISA indicated that anti-NNA clones displaying single-chain variable fragments (scFv) were significantly enriched after biopanning. The nucleotide sequences of the light and heavy chain genes of 30 monoclonal scFv antibodies were determined and classified into six groups with the short linker and nine groups with the long linker. These scFv clones specifically bound to NNA proteins but not to venom proteins from other snakes. Their binding affinities were further determined by competitive ELISA. Animal model studies showed that anti-NNA IgY antibodies exhibited complete protective effects, while a combination of scFv antibodies raised the survival rates and times of mice challenged with lethal doses of NNA venom proteins.

A growing shift towards research and evidence based practice in academia is associated with requirements to disseminate research results in the form of publication in peer reviewed journals. Mentoring has been identified as an important component of developing young authors, as it increases confidence and competence, and facilitates professional development. This led to the formation of a support group to stimulate peer-review publication in the physiotherapy department at the University of the Western Cape. The Kirkpatrick Framework of Evaluation was used to evaluate the success of the mentoring process which made use of a participatory action research methodology. The writing group consisted of nine academic members of staff and took place over ten weeks. The programme included writing, giving feedback, discussion and peer review on a weekly basis. Focus group discussions were taped and transcribed in order to evaluate the mentoring process by identifying relationships within the data and categorising key concepts, which were shaped into a thematic framework. The findings indicated that participants experienced a variety of emotions throughout the programme, with an overall feeling of personal growth by the end. In addition, participants also reported improved writing, reviewing and communication skills. Six months following the programme, six participants had submitted at least one article to a peer reviewed journal. It is clear from this study that some academics still find the task of writing and reviewing articles daunting, and that guidance and support in the form of a writing programme can be useful.

Russell’s vipers containing hemotoxic and neurotoxic venom commonly cause snake envenomation. Horse-derived antivenom is a specific antidote, but its production is expensive and has side effects. Developing a cost-effective and more tolerable therapeutic strategy is favorable. In this study, using glutaraldehyde-attenuated Daboia russelii formosensis (DRF) venom proteins to immunize chickens, polyclonal yolk-immunoglobulin (IgY) antibodies were generated and showed a specific binding affinity. Phage display technology was used to generate two antibody libraries of single-chain variable fragments (scFvs) containing 3.4 × 107 and 5.5 × 107 transformants, respectively. Phage-based ELISA indicated that specific clones were enriched after bio-panning. The nucleotide sequences of scFv-expressing clones were analyzed and classified into six groups in the short linker and four groups in the long linker. These scFv antibodies specifically bound to DRF proteins, but not other venom proteins. Mass spectrometric data suggested that these scFv antibodies may recognize phospholipase A2 RV-4 or RV-7. In vivo studies showed that anti-DRF IgY exhibited complete protective effects and mixed scFv antibodies increased the survival rate and time of mice challenged with a lethal dose of DRF proteins. These antibodies can be potentially applied in a rapid diagnostic method or for treatment in the future.

Neglecting the significant role played by family members in the post-rehabilitation trajectory of substance abusers can pose a significant challenge in supporting intervention programmes in the workplace. This paper reports on a small-scale qualitative investigation that used focus group interviews with family members to explore their perceptions and experiences of being confronted with family members with substance use disorders. The findings are presented through three themes: 1) emotional burden; 2) coping and avoidance strategies; and 3) support needs of family members. Recommendations highlight how employee assistance programmes can provide a comprehensive suite of holistic support systems. [ABSTRACT FROM AUTHOR]