I was like sh*t this is gonna hurt': Implementing Self-Sampling of Dried Blood Spots to Measure HIV Viral Load.

Background: Sexual minority men (SMM) with HIV who use stimulants may experience greater difficulties with antiretroviral therapy adherence which amplifies risk for unsuppressed HIV viral load (VL). Remote monitoring of VL could support efforts to rapidly respond to sub-optimal adherence. Methods: This qualitative study enrolled 24 SMM with HIV who use stimulants to examine experiences with two different dried blood spots (DBS) self-sampling devices (i.e., Tasso-M20 vs. HemaSpot HD) to measure VL. Participants were asked to complete self-sampling of DBS using both devices, and then participated in a 45-minute semi-structured interview. Interviews focused on ease of use, device preference, experiences with receiving and mailing kits, and barriers to participating in research. A thematic analysis was conducted to analyze interviews transcripts. Results: Twenty-two participants (92%) returned the Tasso-M20 and 21 (88%) returned the Hemaspot HD devices. Among the 22 participants that completed qualitative interviews, twenty-three codes were identified and collapsed within seven themes. Preferences for devices were based on convenience, pain and prior experiences with finger-pricking technology. Participants emphasized that clearer instructions with contingency plans for self-sampling of DBS would improve the user experience with self-sampling of DBS. Intersectional stigma (e.g., HIV, sexual minority status, and substance use) was noted as an important consideration in implementing self-sampling of DBS. Promoting decision making, or the option to choose sampling method based on personal preferences, may improve engagement and likelihood of DBS completion. Conclusions: Findings will guide the broader implementation of self-sampling of DBS to optimize VL monitoring in SMM with HIV who use stimulants.

Establishing community mental health clinics increased the number of patients receiving care in rural Western Uganda.

Background: Mental, neurological, and substance-use disorders cause medium to long term disability in all countries. They are amenable to treatment but often treatment is only available in hospitals, as few staff feel competent to give treatment. The WHO developed the "Mental Health GAP" (mhGAP) course to train non-specialist clinical staff in basic diagnosis and treatment. At Bwindi Community Hospital, in south-west Uganda, mental health care was initially only provided at the hospital. It was extended outside the hospital in two implementation phases, initially by establishing 17 clinics in the community, run by qualified mental health staff from the hospital. In the second implementation phase staff in 12 health centers were trained using mhGAP and ran their own clinics under supervision. Methods: Using routine data the defined data variables for the individuals attending the clinics was extracted. Results: A total of 2,617 people attended a mental health care clinic in the study period between January 2016 and March 2020. Of these 1,051 people attended more than once. The number of patients attending clinics increased from 288 during the baseline to 693 in the first implementation phase then to 839 patients in the second implementation phase. After mhGAP training, about 30% of patients were seen locally by mhGAP trained healthcare personnel. The average number of mental health patients seen each month increased from 12 to 65 over the time of the study. The number of patients living >20 km from the hospital increased from 69 in the baseline to 693 in the second implementation phase. The proportion of patients seen at the hospital clinic dropped from 100% to 27%. Conclusions: Providing mental health care in the community at a distance from the hospital substantially increased the number of people accessing mental health care. Training health center-based staff in mhGAP contributed to this. Not all patients could appropriately be managed by non-specialist clinical staff, who only had the five-day training in mhGAP. Supplies of basic medicines were not always adequate, which probably contributed to patients being lost to follow-up. About 50% of patients only attend the clinic once. Further work is required to understand the reasons.

The evolution of atmospheric particulate matter in an urban landscape since the Industrial Revolution.

Atmospheric particulate matter (PM) causes 3.7 million annual deaths worldwide and potentially damages every organ in the body. The cancer-causing potential of fine particulates (PM2.5) highlights the inextricable link between air quality and human health. With over half of the world's population living in cities, PM2.5 emissions are a major concern, however, our understanding of exposure to urban PM is restricted to relatively recent (post-1990) air quality monitoring programmes. To investigate how the composition and toxicity of PM has varied within an urban region, over timescales encompassing changing patterns of industrialisation and urbanisation, we reconstructed air pollution records spanning 200 years from the sediments of urban ponds in Merseyside (NW England), a heartland of urbanisation since the Industrial Revolution. These archives of urban environmental change across the region demonstrate a key shift in PM emissions from coarse carbonaceous 'soot' that peaked during the mid-twentieth century, to finer combustion-derived PM2.5 post-1980, mirroring changes in urban infrastructure. The evolution of urban pollution to a recent enhanced PM2.5 signal has important implications for understanding lifetime pollution exposures for urban populations over generational timescales.

The sinister story of a gauche deliverer and his corrie-fisted tribesmen: Ehud and the left-handed artillery.

Bias against left-handers is well-documented and seen in the etymology of "left" and "right" in most languages. The subject of this study, Ehud, lived between the exodus of the Hebrew slaves from Egypt and the establishment of the Israelite kingdom (c1200-1000 BC), at the transition between the Late Bronze Age and Iron Age 1. His left-handedness was crucial to his deliverance of the proto-nation from tyranny, recorded in Judges in the Hebrew Bible. The description of Ehud as left-handed ('itter yad-yεmînô) is used once more in the Hebrew Bible, also in Judges, to describe the artillery of Ehud's tribe. The words apparently mean "bound/restricted in the right hand", sometimes interpreted as "ambidextrous". This is unlikely: ambidexterity is uncommon. The artillery used the sling with either hand, but Ehud used his left (sεm'ol) hand to draw his sword. sεm'ol, used throughout the Hebrew Bible, means left, without bias or derogatory implications. We suggest that 'itter yad-yεmînô was a right-handed bias towards left-handed people, but Ehud's left-handed victory was recognized as significant. Significant enough that (a) the language changed and the biased description was dropped in favour of simple description, and (b) the army changed with the development of left-handed slingers (artillery).

"Old" and "new" contaminants and their management: learning from the past, looking to the future.

Within the 50 year lifetime of the Society for Environmental Geochemistry and Health (SEGH), we have seen a number of contaminants transfer from being the wonder chemical of their day through to becoming current contaminants of concern. This is also true for a variety of emerging contaminants such as plastic microbeads, pharmaceutical residues, and fire retardant chemicals, amongst others. This thought piece discusses the risk associated with a range of these emerging contaminants, their global nature, how existing models and frameworks can be applied to deal with their impacts, and research and management gaps and challenges.

Chickens, more than humans, focus the diversity of their immunoglobulin genes on the complementarity-determining region but utilise amino acids, indicative of a more cross-reactive antibody repertoire.

The mechanisms of B-cell diversification differ greatly between aves and mammals, but both produce B cells and antibodies capable of supporting an effective immune response. To see how differences in the generation of diversity might affect overall repertoire diversity, we have compared the diversity characteristics of immunoglobulin genes from domestic chickens to those from humans. Both use V(D)J gene rearrangement and somatic hypermutation, but only chickens use somatic gene conversion. A range of diversity analysis tools were used to investigate multiple aspects of amino acid diversity at both the germline and repertoire levels. The effect of differing amino acid usages on antibody characteristics was assessed. At both the germline and repertoire levels, chickens exhibited lower amino acid diversity in comparison to the human immunoglobulin genes, especially outside of the complementarity-determining region (CDR). Chickens were also found to possess much larger and more hydrophilic CDR3s with a higher predicted protein binding potential, suggesting that the antigen-binding site in chicken antibodies is more flexible and more polyreactive than that seen in human antibodies.

Untargeted saliva metabolomics by liquid chromatography-Mass spectrometry reveals markers of COVID-19 severity.

BACKGROUND: The COVID-19 pandemic is likely to represent an ongoing global health issue given the potential for new variants, vaccine escape and the low likelihood of eliminating all reservoirs of the disease. Whilst diagnostic testing has progressed at a fast pace, the metabolic drivers of outcomes-and whether markers can be found in different biofluids-are not well understood. Recent research has shown that serum metabolomics has potential for prognosis of disease progression. In a hospital setting, collection of saliva samples is more convenient for both staff and patients, and therefore offers an alternative sampling matrix to serum. METHODS: Saliva samples were collected from hospitalised patients with clinical suspicion of COVID-19, alongside clinical metadata. COVID-19 diagnosis was confirmed using RT-PCR testing, and COVID-19 severity was classified using clinical descriptors (respiratory rate, peripheral oxygen saturation score and C-reactive protein levels). Metabolites were extracted and analysed using high resolution liquid chromatography-mass spectrometry, and the resulting peak area matrix was analysed using multivariate techniques. RESULTS: Positive percent agreement of 1.00 between a partial least squares-discriminant analysis metabolomics model employing a panel of 6 features (5 of which were amino acids, one that could be identified by formula only) and the clinical diagnosis of COVID-19 severity was achieved. The negative percent agreement with the clinical severity diagnosis was also 1.00, leading to an area under receiver operating characteristics curve of 1.00 for the panel of features identified. CONCLUSIONS: In this exploratory work, we found that saliva metabolomics and in particular amino acids can be capable of separating high severity COVID-19 patients from low severity COVID-19 patients. This expands the atlas of COVID-19 metabolic dysregulation and could in future offer the basis of a quick and non-invasive means of sampling patients, intended to supplement existing clinical tests, with the goal of offering timely treatment to patients with potentially poor outcomes.

The Structured Operational Research and Training Initiative for Strengthening Health Systems to Tackle Antimicrobial Resistance and Improve Public Health in Low-and-Middle Income Countries.

If research is to have an impact and change health outcomes for the better, the findings of the research should be translated into recommendations and actions that can influence policy and/or practice [...].

Tracking sleep in the field: sleep quality and sleep behaviours of elite track and field athletes during preparation and competition.

Elite athletes are susceptible to inadequate sleep, which may peak during competition and be exacerbated by poor sleep behaviours. This study sought to characterise and compare the sleep quality and sleep behaviours of elite track and field athletes during preparation and major competitions. Forty elite international track and field athletes (50% female, aged 25.1 ± 3.9 years) completed the Athlete Sleep Screening Questionnaire and the Athlete Sleep Behaviour Questionnaire on three separate occasions: during habitual training, during a pre-meet training camp and during a major international competition. Overall, 62.5% of athletes reported at least mild sleep difficulty during competition. Athletes reported higher sleep difficulty and poorer sleep behaviour during major competitions and the pre-meet training camp compared to habitual training (P = .001-.025). No significant differences were observed between the training camp and major competition. Global sleep behaviour scores were underpinned by unique characteristics at each timepoint. Sleep behaviour (R2 = .330, P = .017), injury status (R2 = .253, P = .003) and major championship experience (R2 = .113, P = .034) were associated with sleep difficulty during competition. Sleep quality and behaviours vary according to stage of the track and field season, providing a foundation for targeted intervention.

Parasitic nematodes of the genus Syphacia Seurat, 1916 infecting Cricetidae in the British Isles: the enigmatic status of Syphacia nigeriana.

Oxyurid nematodes (Syphacia spp.) from bank (Myodes glareolus) and field/common (Microtus spp.) voles, from disparate geographical sites in the British Isles, were examined morphologically and genetically. The genetic signatures of 118 new isolates are provided, based primarily on the rDNA internal transcribed spacers (ITS1-5.8S-ITS2) region and for representative isolates also on the small subunit 18S rDNA region and cytochrome c oxidase subunit 1 (cox-1) gene locus. Genetic data on worms recovered from Microtus spp. from the European mainland and from other rodent genera from the Palaearctic, North America and West Africa are also included. We test historical hypotheses indicating that S. nigeriana is a generalist species, infecting a range of different rodent genera. Our results establish that S. nigeriana is a parasite of both bank and field voles in the British Isles. An identical genotype was also recorded from Hubert's multimammate mouse (Mastomys huberti) from Senegal, but Mastomys spp. from West Africa were additionally parasitized by a related, although genetically distinct Syphacia species. We found no evidence for S. petrusewiczi in voles from the British Isles but isolates from Russia and North America were genetically distinct and formed their own separate deep branch in maximum likelihood molecular phylogenetic trees.

Telomere Roles in Fungal Genome Evolution and Adaptation.

Telomeres form the ends of linear chromosomes and usually comprise protein complexes that bind to simple repeated sequence motifs that are added to the 3' ends of DNA by the telomerase reverse transcriptase (TERT). One of the primary functions attributed to telomeres is to solve the "end-replication problem" which, if left unaddressed, would cause gradual, inexorable attrition of sequences from the chromosome ends and, eventually, loss of viability. Telomere-binding proteins also protect the chromosome from 5' to 3' exonuclease action, and disguise the chromosome ends from the double-strand break repair machinery whose illegitimate action potentially generates catastrophic chromosome aberrations. Telomeres are of special interest in the blast fungus, Pyricularia, because the adjacent regions are enriched in genes controlling interactions with host plants, and the chromosome ends show enhanced polymorphism and genetic instability. Previously, we showed that telomere instability in some P. oryzae strains is caused by novel retrotransposons (MoTeRs) that insert in telomere repeats, generating interstitial telomere sequences that drive frequent, break-induced rearrangements. Here, we sought to gain further insight on telomeric involvement in shaping Pyricularia genome architecture by characterizing sequence polymorphisms at chromosome ends, and surrounding internalized MoTeR loci (relics) and interstitial telomere repeats. This provided evidence that telomere dynamics have played historical, and likely ongoing, roles in shaping the Pyricularia genome. We further demonstrate that even telomeres lacking MoTeR insertions are poorly preserved, such that the telomere-adjacent sequences exhibit frequent presence/absence polymorphism, as well as exchanges with the genome interior. Using TERT knockout experiments, we characterized chromosomal responses to failed telomere maintenance which suggested that much of the MoTeR relic-/interstitial telomere-associated polymorphism could be driven by compromised telomere function. Finally, we describe three possible examples of a phenomenon known as "Adaptive Telomere Failure," where spontaneous losses of telomere maintenance drive rapid accumulation of sequence polymorphism with possible adaptive advantages. Together, our data suggest that telomere maintenance is frequently compromised in Pyricularia but the chromosome alterations resulting from telomere failure are not as catastrophic as prior research would predict, and may, in fact, be potent drivers of adaptive polymorphism.

Environmental and human iodine and selenium status: lessons from Gilgit-Baltistan, North-East Pakistan.

Iodine and selenium deficiencies are common worldwide. We assessed the iodine and selenium status of Gilgit-Baltistan, Pakistan. We determined the elemental composition (ICP-MS) of locally grown crops (n = 281), drinking water (n = 82), urine (n = 451) and salt (n = 76), correcting urinary analytes for hydration (creatinine, specific gravity). We estimated dietary iodine, selenium and salt intake. Median iodine and selenium concentrations were 11.5 (IQR 6.01, 23.2) and 8.81 (IQR 4.03, 27.6) µg/kg in crops and 0.24 (IQR 0.12, 0.72) and 0.27 (IQR 0.11, 0.46) µg/L in water, respectively. Median iodised salt iodine was 4.16 (IQR 2.99, 10.8) mg/kg. Population mean salt intake was 13.0 g/day. Population median urinary iodine (uncorrected 78 µg/L, specific gravity-corrected 83 µg/L) was below WHO guidelines; creatinine-corrected median was 114 µg/L but was unreliable. Daily selenium intake (from urinary selenium concentration) was below the EAR in the majority (46-90%) of individuals. Iodine and selenium concentrations in all crops were low, but no health-related environmental standards exist. Iodine concentration in iodised salt was below WHO-recommended minimum. Estimated population average salt intake was above WHO-recommended daily intake. Locally available food and drinking water together provide an estimated 49% and 72% of EAR for iodine (95 µg/day) and selenium (45 µg/day), respectively. Low environmental and dietary iodine and selenium place Gilgit-Baltistan residents at risk of iodine deficiency disorders despite using iodised salt. Specific gravity correction of urine analysis for hydration is more consistent than using creatinine. Health-relevant environmental standards for iodine and selenium are needed.

Changes to the sebum lipidome upon COVID-19 infection observed via rapid sampling from the skin.

BACKGROUND: The COVID-19 pandemic has led to an unprecedented demand for testing - for diagnosis and prognosis - as well as for investigation into the impact of the disease on the host metabolism. Sebum sampling has the potential to support both needs by looking at what the virus does to us, rather than looking for the virus itself. METHODS: In this pilot study, sebum samples were collected from 67 hospitalised patients (30 COVID-19 positive and 37 COVID-19 negative) by gauze swab. Lipidomics analysis was carried out using liquid chromatography mass spectrometry, identifying 998 reproducible features. Univariate and multivariate statistical analyses were applied to the resulting feature set. FINDINGS: Lipid levels were depressed in COVID-19 positive participants, indicative of dyslipidemia; p-values of 0·022 and 0·015 were obtained for triglycerides and ceramides respectively, with effect sizes of 0·44 and 0·57. Partial Least Squares-Discriminant Analysis showed separation of COVID-19 positive and negative participants with sensitivity of 57% and specificity of 68%, improving to 79% and 83% respectively when controlled for confounding comorbidities. INTERPRETATION: COVID-19 dysregulates many areas of metabolism; in this work we show that the skin lipidome can be added to the list. Given that samples can be provided quickly and painlessly, we conclude that sebum is worthy of future consideration for clinical sampling. FUNDING: The authors acknowledge funding from the EPSRC Impact Acceleration Account for sample collection and processing, as well as EPSRC Fellowship Funding EP/R031118/1, the University of Surrey and BBSRC BB/T002212/1. Mass Spectrometry was funded under EP/P001440/1.

Science and agriculture: promoting beneficial symbiosis.

While fundamental research into key mechanisms and interactions is important, the practical investigations that scientists also undertake have additional considerations, since the results are applicable in the real world but need disseminating in a way that reaches the intended audience. Worldwide, rapid population growth produces multiple pressures on land, meaning agriculture must become more efficient and productive. Other pressures on farmers are also increasing: to meet environmental quality standards, to follow legislation about application of chemical products, to remain financially viable against uncertain markets, and more. Applied research addresses specific aspects, but often reports do not describe local contexts or are too restricted, lacking details that enable an understanding of their wider application. We illustrate from our experience within UK agriculture, with a particular focus on soil, the identification of current shortcomings in many research publications; provide examples of good practice; and make suggestions for how scientists can help agriculturalists use their work to address the global issues currently faced. Specifically, we recommend that communication between science and agricultural communities is nurtured, to improve mutual understanding and facilitate two-way flow of ideas. In scientific publications, provision of as much contextual information as possible, and consideration for climatic/temporal/location influences, will enable investigations and results to be used for maximum practical effect and should increase citations.

Mining is bad for health: a voyage of discovery.

Mining continues to be a dangerous activity, whether large-scale industrial mining or small-scale artisanal mining. Not only are there accidents, but exposure to dust and toxins, along with stress from the working environment or managerial pressures, give rise to a range of diseases that affect miners. I look at mining and health from various personal perspectives: that of the ordinary man (much of life depends on mined elements in the house, car and phone); as a member of the Society for Environmental Geochemistry and Health (environmental contamination and degradation leads to ill health in nearby communities); as a public health doctor (mining health is affected by many factors, usually acting in a mix, ranging from individual inheritance-genetic makeup, sex, age; personal choices-diet, lifestyle; living conditions-employment, war; social support-family, local community; environmental conditions-education, work; to national and international constraints-trade, economy, natural world); as a volunteer (mining health costs are not restricted to miners or industry but borne by everyone who partakes of mining benefits-all of us); and as a lay preacher (the current global economy concentrates on profit at the expense of the health of miners). Partnership working by academics with communities, government and industry should develop evidence-based solutions. Employment, health, economic stability and environmental protection need not be mutually exclusive. We all need to act.