Miracle-dz/UniFAR-FTUs huggingface dataset:
Ion torrent high throughput mitochondrial genome sequencing (HTMGS)

The implementation and popularity of next generation sequencing (NGS) has led to the development of various rapid whole mitochondrial genome sequencing techniques. We summarise an efficient and cost-effective NGS approach for mitochondrial genomic DNA in humans using the Ion Torrent platform, and further discuss our bioinformatics pipeline for streamlined variant calling. Ion 316 chips were utilised with the Ion Torrent semi-conductor platform Personal Genome Machine (PGM) to perform tandem sequencing of mitochondrial genomes from the core pedigree (n = 315) of the Norfolk Island Health Study. Key improvements from commercial methods focus on the initial PCR step, which currently requires extensive optimisation to ensure the accurate and reproducible elongation of each section of the complete mitochondrial genome. Dual-platform barcodes were incorporated into our protocol thereby extending its potential application onto Illumina-based systems. Our bioinformatics pipeline consists of a modified version of GATK best practices tailored for mitochondrial genomic data. When compared with current commercial methods, our method, termed high throughput mitochondrial genome sequencing (HTMGS), allows high multiplexing of samples and the use of alternate library preparation reagents at a lower cost per sample (~1.7 times) when compared to current commercial methodologies. Our HTMGS methodology also provides robust mitochondrial sequencing data (>450X average coverage) that can be applied and modified to suit various study designs. On average, we were able to identify ~30 variants per sample with 572 variants observed across 315 samples. We have developed a high throughput sequencing and analysis method targeting complete mitochondrial genomes; with the potential to be platform agnostic with analysis options that adhere to current best practices.
Hepatic MicroRNA Expression by PGC-1α and PGC-1β in the Mouse

The fine-tuning of liver metabolism is essential to maintain the whole-body homeostasis and to prevent the onset of diseases. The peroxisome proliferator-activated receptor-γ coactivators (PGC-1s) are transcriptional key players of liver metabolism, able to regulate mitochondrial function, gluconeogenesis and lipid metabolism. Their activity is accurately modulated by post-translational modifications. Here, we showed that specific PGC-1s expression can lead to the upregulation of different microRNAs widely implicated in liver physiology and diseases development and progression, thus offering a new layer of complexity in the control of hepatic metabolism.
Iodine status of non-pregnant women and availability of food vehicles for fortification with iodine in a remote community in Gulf province, Papua New Guinea

Adequate iodine status of women of childbearing age is essential for optimal growth and development of their offspring. The objectives of the current study were to assess the iodine status of non-pregnant women, availability and use of commercial salt, extent to which it is iodised, and availability of other industrially processed foods suitable for fortification with iodine. This prospective cross-sectional study was carried out in 2018 in a remote area in Gulf province, Papua New Guinea. Multistage cluster sampling was used to randomly select 300 women visiting local markets. Of these, 284 met study criteria of being non-pregnant and non-lactating. Single urine samples were collected from each of them. Discretionary salt intake was assessed; salt samples were collected from a sub-sample of randomly selected households. A semi-structured, pre-tested questionnaire to assess use and availability of commercial salt and other processed foods was modified and used. Salt was available on the interview day in 51.6% of households. Mean iodine content in household salt samples was 37.8 ± 11.8 ppm. Iodine content was below 30.0 ppm in 13.1% and below 15.0 ppm in 3.3% of salt samples. Mean iodine content of salt available at markets was 39.6 ± 0.52 ppm. Mean discretionary intake of salt per capita per day was 3.9 ± 1.21 g. Median UIC was 34.0 μg/L (95% CI, 30.0–38.0 ppm), indicating moderate iodine deficiency. For women with salt in the household, median UIC was 39.5 μg/L (95% CI, 32.0–47.0 μg/L), compared to median UIC of 29.0 μg/L (95% CI, 28.0–32.0 μg/L) for those without salt. This community has low consumption of iodised salt, likely due to limited access. Investigation of other industrially processed foods indicated salt is the most widely consumed processed food in this remote community, although 39.8% of households did use salty flavourings.
Evaluated interventions to prevent substance abuse among young South Africans

Introduction South Africa has one of the highest levels of drug use in the world (Rehm et al, 2003). Throughout the country, alcohol is the primary substance of abuse for those admitted for treatment, with the exception of the Western Cape, where methamphetamine is the primary substance of abuse (Pluddemann et al, 2008). A national study of student prevalence rates (in grades 8 to 11) of ‘ever having used’ a substance, revealed that 49.1% of students had drunk alcohol, 30.5% had used tobacco, and 12.8% had used marijuana (Reddy et al, 2003). In the Western Cape, consumption of methamphetamine (also known as ‘tik’) by young people under 20 years of age seems to be evolving into an epidemic, with rates of treatment for methamphetamine-related problems rising from 4% in 2003, to 57% in 2007 (Pluddemann et al, 2007). A cross-sectional study (Flisher et al, 2006), comparing risk-taking behaviours in Grade 8 students in Cape Town in 1997 and 2004, revealed increases for past-month use of cigarettes (23% to 31% for males) and marijuana (3.1% to 17.2% for males, 1.9% to 5.2% for females). Substance misuse has been associated with a number of adverse outcomes. Worldwide, 5% of all deaths of young people aged 15 to 29 years are attributed to alcohol abuse (Jernigan, 2001). In Cape Town, between the years 1999 and 2001, 31.8% of adolescents at trauma units tested positive for alcohol, 26.9% for marijuana, 15.4% for Mandrax (a sedative containing a mixture of methaqualone and diphenhydramine), 11.5% for opiates, and 1.9% tested positive for cocaine (Parry et al, 2004). Liang et al (2007) reported statistically significant relationships between alcohol and tobacco use on the one hand, and bullying and suicidal ideation on the other, among Grade 8 and Grade 11 students in Cape Town and Durban. In both KwaZulu-Natal and Cape Town, high school students who used alcohol and smoked cigarettes were more likely than non-users to be sexually active (Flisher et al, 1996; Taylor et al, 2003) (see also Chapter 14). Against the background of these high rates of substance use and the associated negative outcomes, the South African Department of Education introduced the mandatory Life Orientation learning area in 2001 for students from Grade 1 to Grade 12. Life Orientation encourages healthy lifestyles by promoting general health and wellbeing, but also targets drug use, sexuality, and socio-emotive skills development. Yet it has been noted that few schools prioritise Life Orientation, and teachers tend to implement its components in a personalised and unsystematic fashion (Smith et al, 2008). Relevant to this, researchers have initiated the development and application of substance use prevention programmes
Role of Non-Coding RNAs in the Progression of Liver Cancer: Evidence from Experimental Models

Liver cancer is a devastating cancer that ranges from relatively rare (around 2% of all cancers in the United States) to commonplace (up to 50% of cancers in underdeveloped countries). Depending upon the stage of pathogenesis, prognosis, or functional liver tissue present, transplantation or partial hepatectomy may be the only available treatment option. However, due to the rise in metabolic syndrome and the increasing demand for livers, patients often wait months or years for available organs. Due to this shortage, doctors must have other treatment options available. One promising area of cancer research lies in understanding the role of regulatory non-coding RNAs (ncRNAs) as oncogenic drivers and potential targets for prospective therapies. While the role of these ncRNAs was not initially clear, many of them have since been recognized to function as important players in the regulation of gene expression, epigenetic modification, and signal transduction in both normal and cancer cell cycles. Dysregulation of these different ncRNA subtypes has been implicated in the pathogenesis and progression of many major cancers including hepatocellular carcinoma. This review summarizes current findings on the roles noncoding RNAs play in the progression of liver cancer and the various animal models used in current research to elucidate those data.
Changes in anger and aggression after treatment for PTSD in active duty military.

OBJECTIVE To examine whether treating posttraumatic stress disorder (PTSD) reduces anger and aggression and if changes in PTSD symptoms are associated with changes in anger and aggression. METHOD Active duty service members (n = 374) seeking PTSD treatment in two randomized clinical trials completed a pretreatment assessment, 12 treatment sessions, and a posttreatment assessment. Outcomes included the Revised Conflict Tactics Scale and state anger subscale of the State-Trait Anger Expression Inventory. RESULTS Treatment groups were analyzed together. There were small to moderate pretreatment to posttreatment reductions in anger (standardized mean difference [SMD] = -0.25), psychological aggression (SMD = -0.43), and physical aggression (SMD = -0.25). The majority of participants continued to endorse anger and aggression at posttreatment. Changes in PTSD symptoms were mildly to moderately associated with changes in anger and aggression. CONCLUSIONS PTSD treatments reduced anger and aggression with effects similar to anger and aggression treatments; innovative psychotherapies are needed.
Acceptability of and treatment preferences for recurrent bacterial vaginosis—Topical lactic acid gel or oral metronidazole antibiotic: Qualitative findings from the VITA trial

Background Bacterial vaginosis (BV) is associated with an elevated vaginal pH and the presence of abnormal offensive discharge. It is common, often recurrent, and the most effective treatment regimen is unknown. ‘Metronidazole Versus lactic acId for Treating bacterial vAginosis’ (VITA) is a UK-based randomised controlled trial assessing clinical and cost-effectiveness of topical lactic acid gel compared to oral metronidazole antibiotic for treating second and subsequent BV episodes. Few BV trials report on women’s preferences for treatment in the context of their own experiences. Method This qualitative study investigated the acceptability and tolerability of the two treatments. During the trial, semi-structured telephone interviews were undertaken between January—May 2018. A total of 33 women diagnosed with BV were consecutively sampled then interviewed from six sites across England. Thematic analysis was guided by the acceptability of health interventions framework. Potential causes of BV and its impact on women’s lives were explored in addition to women’s treatment preference and perceived treatment effectiveness. Results Although women felt antibiotics treat BV effectively, and were associated with longer time periods between episodes, they generally preferred using the lactic acid gel because of ease of use, once daily application and less side-effects. Women would recommend the lactic acid gel to others for mild cases of BV but to take antibiotics when more severe. The risk of antibiotic drug resistance was a common concern. Self-help medicating or self-decision to not treat was also evident due to prior experience of poor outcomes from treatment. Triggers of BV were attributed to personal hygiene habits–soaps used to wash the vagina and sexual practices such as unprotected sex. Conclusion Acceptability and preference for topical lactic acid gel or oral metronidazole tablets in the treatment of recurrent BV was affected by personal choice relating to affective attitude, burden, ethicality, intervention coherence, opportunity costs, and self-efficacy. These differed depending on ease of use, tolerability and past experiences, but not necessarily based on perceived drug effectiveness. Knowledge of a patient preference for topical lactic acid gel therapy despite lower perceived effectiveness may be useful for clinicians when making treatment decisions.
Longterm Effect on Leisure Time Physical Activity Level in Individuals with Axial Spondyloarthritis: Secondary Analysis of a Randomized Controlled Trial

Objective. To explore the longterm effect of a 3-month exercise program on leisure time physical activity level in individuals with axial spondyloarthritis (axSpA). Methods. A secondary analysis was performed on data from 100 individuals with axSpA who were included in a randomized controlled trial. The exercise group (EG) participated in a 3-month exercise program while the control group (CG) received no intervention. Physical activity during leisure time was measured with a questionnaire (physically active: ≥ 1 h/week with moderate/vigorous intensity physical activity). Disease activity was measured with the Ankylosing Spondylitis Disease Activity Scale (ASDAS; higher score = worst). Statistical analyses were performed on an intention-to-treat basis using chi-square tests, logistic regression, and mixed models. Results. At the 12-month followup, significantly more individuals in the EG than in the CG were physically active [29 (67%) vs 13 (30%), p < 0.001] and exercised 2–3 times/week [25 (58%) vs 15 (34%), p = 0.02], and fewer exercised at light intensity [3 (8%) vs 14 (44%), p = 0.002]. “Participation in the EG” (OR 6.7, 95% CI 2.4–18.6, p < 0.001) and “being physically active at baseline” (OR 4.7, 95% CI 1.4–15.8, p = 0.01) were the factors most associated with being physically active. There were no differences between the groups in ASDAS (p = 0.79). Conclusion. A 3-month exercise program had a beneficial longterm effect on leisure time physical activity in individuals with axSpA, thus indicating a more beneficial health profile. Still, few individuals continued the intensive program, and there was no difference between the groups in disease activity after 12 months. (ClinicalTrials.gov: NCT02356874)
An Assessment of Dietary Diversity and Nutritional Status of Preschool Children

Dietary diversity is gaining prominence in assessing diet adequacy of individuals and households in developing countries. Dietary diversity or food variety is not known in Tobago. This study’s purpose therefore was to assess dietary diversity, food variety and its relationship to the nutritional status of preschool children. A cross-sectional descriptive study design was implemented and a structured, culturally sensitive questionnaire with a 24-hour recall procedure was used for data collection. A representative sample (n=423), stratified by parish, population density, gender and age, was recruited from public and private pre-schools. Less than half (48%) of the preschoolers met minimum dietary diversity. Approximately 33% consumed food items from 5 or more food groups and 19%had low dietary diversity scores (DDS). Mean scores were obtained for food variety (9.37 ± 2.4) and diversity (4.19 ± .83). Nutrient adequacy ratios (NAR) for eleven nutrients were calculated and correlated with DDS, food variety scores (FVS) and nutrition indices. Notable percentages (11.35%) of the children had acute malnutrition, while 10% were underweight and ~5% exhibited chronic malnutrition. NAR for various micronutrients were significantly (p ≤ 0.01) correlated with DDS. NAR for energy moderately predicted weight-for-age (WAZ) z-scores (r=0.437, p=0.000), height-for-age (HAZ) z-scores (r=0.413, p=0.001) and weight-for-height (WHZ) z-scores (r=0.466, p=0.000). With notable levels of malnutrition and minimum dietary diversity observed among this group of preschoolers, it is important that stakeholders work collaboratively in coming up with integrated approaches to health and nutrition, in order to improve the wellbeing of its children.
Determination of the number of RAD51 molecules in different human cell lines

ABSTRACT Knowledge about precise numbers of specific molecules is necessary for understanding and verification of biological pathways. The RAD51 protein is central in the repair of DNA double-strand breaks (DSBs) by homologous recombination repair and understanding its role in cellular pathways is crucial to design mechanistic DNA repair models. Here, we determined the number of RAD51 molecules in several human cell lines including primary fibroblasts. We showed that between 20000 to 100000 of RAD51 molecules are available per human cell that theoretically can be used for simultaneously loading at least 7 DSBs. Interestingly, the amount of RAD51 molecules does not significantly change after the induction of DNA damage using bleomycin or γ-irradiation in cells but an accumulation of RAD51 on the chromatin occurs. Furthermore, we generated an EGFP-RAD51 fusion under the control of HSV thymidine kinase promoter sequences yielding moderate protein expression levels comparable to endogenously expressed RAD51. Initial characterizations suggest that these low levels of ectopically expressed RAD51 are compatible with cell cycle progression of human cells. Hence, we provide parameters for the quantitative understanding and modeling of RAD51-involving processes.
Mycoredoxins Are Required for Redox Homeostasis and Intracellular Survival in the Actinobacterial Pathogen Rhodococcus equi

Rhodococcus equi is a facultative intracellular pathogen that can survive within macrophages of a wide variety of hosts, including immunosuppressed humans. Current antibiotherapy is often ineffective, and novel therapeutic strategies are urgently needed to tackle infections caused by this pathogen. In this study, we identified three mycoredoxin-encoding genes (mrx) in the genome of R. equi, and we investigated their role in virulence. Importantly, the intracellular survival of a triple mrx-null mutant (Δmrx1Δmrx2Δmrx3) in murine macrophages was fully impaired. However, each mycoredoxin alone could restore the intracellular proliferation rate of R. equi Δmrx1Δmrx2Δmrx3 to wild type levels, suggesting that these proteins could have overlapping functions during host cell infection. Experiments with the reduction-oxidation sensitive green fluorescent protein 2 (roGFP2) biosensor confirmed that R. equi was exposed to redox stress during phagocytosis, and mycoredoxins were involved in preserving the redox homeostasis of the pathogen. Thus, we studied the importance of each mycoredoxin for the resistance of R. equi to different oxidative stressors. Interestingly, all mrx genes did have overlapping roles in the resistance to sodium hypochlorite. In contrast, only mrx1 was essential for the survival against high concentrations of nitric oxide, while mrx3 was not required for the resistance to hydrogen peroxide. Our results suggest that all mycoredoxins have important roles in redox homeostasis, contributing to the pathogenesis of R. equi and, therefore, these proteins may be considered interesting targets for the development of new anti-infectives.
Bilateral Simultaneous Iliac Dislocation of the Hip

Traumatic anterior dislocation of the hip is an uncommon injury and bilateral anterior dislocation of the hip is still rare. A case is described of hitherto unreported simultaneous bilateral anterior iliac hip dislocation, complicated by fracture of the femoral head on one side. The extreme rarity of this fracture and the peculiar mechanism of injury (the treatment planning and the post reduction protocol) make this case worth reporting.
Bipolar versus Total Hip Arthroplasty in the Treatment of Avascular Necrosis of the Femoral Head in Young Patients

The authors evaluate medium-term results of bipolar and total hip arthroplasty as a treatment for avascular necrosis of the femoral head. Between 1990 and 2000, 57 hips (45 patients) were treated with a bipolar (BHA: 37 hips) or total hip arthroplasty (THA: 20 hips) depending on the radiographic and macroscopic aspect of the acetabulum. At surgery, all patients were under 65 years of age (average: 45.09 years). All had the same cementless hydroxylapatite coated femoral stem inserted through an anterolateral approach. The BHA were followed during a mean of 4.49 years. One BHA was lost to follow-up. Seven out of 36 hips (19.44%) were considered failures: three due to a poor functional result (Harris Hip Score (HHS) <70) and four which needed conversion to THA for groin pain. Two hips were revised for periprosthetic fracture. Twenty BHA (55.56%) had a good or excellent result (HHS 80). The THA were followed for a mean of 4.32 years. One THA was lost to follow-up. Four out of 19 hips (21.05%) were considered as failures. Three due to a poor functional result (HHS<70) and one which needed cup revision for recurrent dislocation. Fifteen THA (78.95%) had a good or excellent functional result (HHS80). BHA as a treatment of avascular necrosis of the femoral head in young patients preserves bone stock for later revisions and can lead to excellent results. But the outcome seems less predictable than after THA. Groin pain associated to BHA can be treated successfully with conversion to THA if necessary.
Hyperosmolar Solution Reduces Apoptosis in the Acute Spinal Cord Injury Model in Rats

Although the primary lesion caused by traumatic injury to the spinal cord is considered intractable, the secondary lesions and consequent clinical manifestations can be diminished considerably with early administration of steroids or by surgical decompression of the injured segment, removal of bony fragments and stabilization (1-3). The extent of the neurologic deficits caused by the lesion is determined by two main factors: the primary mechanical insult and the secondary insult caused by inflammation, compression and ischemia (4-6). The primary lesion is caused by the trauma itself and involves cellular death and tissue necrosis, independently of biological factors. The mechanisms underlying secondary lesions involve activation of inflammation, tissue ischemia, reperfusion deficits, edema, lipidic peroxidation, calcium influx, and particularly apoptosis. The secondary lesions constitute the main target for the development of novel therapeutic approaches (7-9). Among these novel strategies, new anti-apoptotic agents are being developed, in the hope that their administration might limit tissue damage and increase the potential for clinical recovery (10).