Tracking the sources of Leptospira and nutrient flows in two urban watersheds of Puerto Rico.

This study investigated the relationship between nutrient levels, source of fecal contamination, and pathogenic Leptospira in Puerto Rico's northern coast and San Juan Bay Estuary (SJBE) aquatic ecosystems. Microbial source tracking (MST) was also used to investigate the connections between sources of feces contamination and the presence of Leptospira. Eighty-seven water samples were collected during the June (n=44) and August (n=43) in 2020. To quantify phosphorus and nitrogen concentrations, standard USEPA protocols were utilized, specifically Methods 365.4 for total and dissolved phosphorus, 351.2 for total Kjeldahl nitrogen and ammonium, and 353.2 for nitrate. Lipl32 gene-specific quantitative polymerase chain reaction (qPCR) was used to detect the presence of Leptospira. Human (HF183), canine (BacCan-UCD), and equine (HoF597) MST assays were utilized to trace the origins of fecal contamination. Forty one percent of the locations exceeded Puerto Rico's authorized total phosphorus limit of 160 g L-1, while 34% exceeded the total nitrogen limit of 1700 g L-1. Nearly half of the streams examined are affected by eutrophication. The MST analysis identified human and canine feces as the most prevalent contaminants, affecting approximately 50% of the sites. In addition, Leptospira was detected in 32% of the June samples. There was a significant correlation (r = 0.79) between the incidence of pathogenic Leptospira and the human bacterial marker (HF183). This study illuminates the central role of anthropogenic inputs in nutrient enrichment and pathogen proliferation in Puerto Rico's aquatic ecosystems.

A Systematic Review of Inequalities in the Mental Health Experiences of Black African, Black Caribbean and Black-mixed UK Populations: Implications for Action.

BACKGROUND: Measurable differences in the experience and treatment of mental health conditions have been found to exist between different racial categories of community groups. The objective of this research was to review the reported mental health of Black African-Caribbean communities in the UK, determinants of mental health, and interventions to enhance their experiences of mental health services. METHOD: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement was applied. To be included, papers must be published in a peer reviewed journal; report on adult populations (over 18) from any of Black African, Black Caribbean or Black mixed people in the UK; and assess (quantitative), or discuss (qualitative) mental health experiences, determinants of mental health, or interventions intended to enhance experiences of mental health services among the target population. The aims, inclusion criteria, data extraction, and data quality evaluation were specified in advance. Searches were conducted using EBSCO (PsychInfo; MEDLINE; CINAHL Plus; psychology and behavioural sciences collection). The search strategy included search terms relating to the aim. Risk of bias was assessed using a standard tool, records were organised using Endnote, and data were extracted and synthesised using Microsoft Excel. RESULTS: Thirty-six studies were included, of which 26 were quantitative and six reported exclusively on Black participants. Black populations were less likely to access mental health support via traditional pathways due to stigma and mistrust of mental health services. Black Africans especially, sought alternative help from community leaders, which increased the likelihood of accessing treatment at the point of crisis or breakdown, which in turn increased risk of being detained under the Mental Health Act and via the criminal justice system. DISCUSSION: Findings suggest a cycle of poor mental health, coercive treatment, stigma, and mistrust of services as experienced by Black communities. Evidence was limited by poorly defined ethnic categories, especially where Black populations were subsumed into one category. It is recommended that mental health services work collaboratively with cultural and faith communities in supporting Black people to cope with mental illness, navigate mental health pathways, and provide culturally appropriate advice. Protocol Registration Number PROSPERO CRD42021261510.

Pestilence, Plague and Pandemics: A Troubled History.

Humankind has lived with the danger of endemic, epidemic and pandemic disease for thousands of years. The effects of these outbreaks have often devastated human populations. Sixteen pandemic events causing an estimated 147 million deaths have occurred since the eighth century, The Black Death and the influenza pandemic of 1918-1920 probably having the greatest impact. Animal populations, both wild and domestic, have similarly suffered devastating outbreaks of disease which, on occasions, have translated into serious effects on human health. The deliberate or accidental introduction of animals into virgin areas has given rise to unforeseen disease events occasionally leading to extinction. Similarly, human intent or negligence and the vagaries of nature itself has resulted in ill health and loss of life. This paper describes the history of pandemics, epidemics and disasters, and the attempts to bring them under control.

A SHORT HISTORY OF OCCUPATIONAL DISEASE: 2. ASBESTOS, CHEMICALS, RADIUM AND BEYOND.

Historically, the weighing out and manipulation of dangerous chemicals frequently occurred without adequate protection from inhalation or accidental ingestion. The use of gloves, eye protection using goggles, masks or visors was scant. From Canary Girls and chimney sweeps to miners, stone cutters and silo fillers, these are classic exemplars of the subtle (and in some cases not so subtle) effects that substances, environments and practices can have on individual health.

A SHORT HISTORY OF OCCUPATIONAL DISEASE: 1. LABORATORY-ACQUIRED INFECTIONS.

Laboratory-acquired infections are as old as laboratories themselves. As soon as the culture of microorganisms was introduced, so too was their transfer to laboratory workers. It is only in relatively recent history that such infections have been fully understood, and methods of spread and their prevention or avoidance developed. This paper endeavours to provide an overview of the history of laboratory-acquired infection and the steps taken, particularly in the UK, for its prevention.

A SHORT HISTORY OF OCCUPATIONAL DISEASE: 3. LEISURE CAN MAKE YOU SICK.

The risk of infection associated with occupations can, and does, extend to certain leisure and sports activities. Generally, such pastimes are regarded as important for human health and mental wellbeing. However, infections may, rarely, be acquired during leisure activities that include water sports and water-related relaxation, and certain sports.

The eyespot resistance genes Pch1 and Pch2 of wheat are not homoeoloci.

KEY MESSAGE: Phenotyping and mapping data reveal that chromosome intervals containing eyespot resistance genes Pch1 and Pch2 on 7D and 7A, respectively, do not overlap, and thus, these genes are not homoeloci. Eyespot is a stem-base fungal disease of cereals growing in temperate regions. Two main resistances are currently available for use in wheat. Pch1 is a potent single major gene transferred to wheat from Aegilops ventricosa and located on the distal end of chromosome 7D. Pch2, a moderate resistance deriving from Cappelle Desprez, is located at the end of 7AL. The relative positions of Pch1 and Pch2 on 7D and 7A, respectively, suggest that they are homoeoloci. A single seed decent recombinant F7 population was used to refine the position of Pch2 on 7A. New markers designed to 7D also allowed the position of Pch1 to be further defined. We exploited the syntenic relationship between Brachypodium distachyon and wheat to develop 7A and 7D specific KASP markers tagging inter-varietal and interspecific SNPs and allow the comparison of the relative positions of Pch1 and Pch2 on 7D and 7A. Together, phenotyping and mapping data reveal that the intervals containing Pch1 and Pch2 do not overlap, and thus, they cannot be considered homoeloci. Using this information, we analysed two durum wheat lines carrying Pch1 on 7A to determine whether the Ae.ventricosa introgression extended into the region associated with Pch2. This identified that the introgression is distal to Pch2 on 7A, providing further evidence that the genes are not homoeoloci. However, it is feasible to use this material to pyramid Pch1 and Pch2 on 7A in a tetraploid background and also to increase the copy number of Pch1 in combination with Pch2 in a hexaploid background.

The use of a negative pressure wound management system in perineal wound closure after extralevator abdominoperineal excision (ELAPE) for low rectal cancer.

BACKGROUND: Perineal wound healing is a significant challenge after extralevator abdominoperineal excision (ELAPE) due to a high rate of wound breakdown. Negative pressure therapy has proven benefits in open wounds, and recently a negative pressure system has been developed for use on closed wounds at high risk of breakdown, such as apronectomy and hysterectomy. The aim of the present study was to determine whether negative pressure therapy applied to closed perineal wounds after ELAPE improved wound healing and compare outcomes to the published literature and outcomes from a historical cohort of patients who had undergone 'standard' abdominoperineal resection (APR) and primary closure of the perineal wounds. METHODS: Prospective data on consecutive patients having ELAPE in the period from November 2012 to April 2015 were collected. The pelvic floor defect was reconstructed with biologic mesh. The adipose tissue layer was closed with vicryl sutures, a suction drain was left in the deep layer, the subcuticular layer and skin were closed, and the negative pressure system was applied. Any wound breakdown within the first 30 days postoperatively was recorded. RESULTS: Of the 32 consecutive ELAPE patients whose perineal wounds were closed within 30 days with the use of the negative pressure system, there was 1 patient with major perineal wound breakdown and 2 patients with a 1 cm superficial wound defect, which needed no further treatment. In the remaining 29 (90 %) patients, the perineal wounds healed fully without complications. Twenty-five patients underwent standard APR in 2010-2011 with primary closure of their perineal wounds. Ten out of 25(40 %) of patients who had undergone standard APR and primary closure of perineal wounds had major wound complications (p = 0.01). CONCLUSIONS: Our results suggest that after ELAPE the application of a negative pressure system to the perineal wound closed with biologic mesh may reduce perineal wound complications and may reduce the need for major perineal reconstruction.

Mapping a Type 1 FHB resistance on chromosome 4AS of Triticum macha and deployment in combination with two Type 2 resistances.

Markers closely flanking a Type 1 FHB resistance have been produced and the potential of combining this with Type 2 resistances to improve control of FHB has been demonstrated. Two categories of resistance to Fusarium head blight (FHB) in wheat are generally recognised: resistance to initial infection (Type 1) and resistance to spread within the head (Type 2). While numerous sources of Type 2 resistance have been reported, relatively fewer Type 1 resistances have been characterised. Previous study identified a Type 1 FHB resistance (QFhs.jic-4AS) on chromosome 4A in Triticum macha. Little is known about the effect of combining Type 1 and Type 2 resistances on overall FHB symptoms or accumulation of the mycotoxin deoxynivalenol (DON). QFhs.jic-4AS was combined independently with two Type 2 FHB resistances (Fhb1 and one associated with the 1BL/1RS translocation). While combining Type 1 and Type 2 resistances generally reduced visual symptom development, the effect on DON accumulation was marginal. A lack of polymorphic markers and a limited number of recombinants had originally prevented accurate mapping of the QFhs.jic-4AS resistance. Using an array of recently produced markers in combination with new populations, the position of QFhs.jic-4AS has been determined to allow this resistance to be followed in breeding programmes.

In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors.

The effect on survival of including HLA-DPB1 in a 12-allele matching strategy was retrospectively evaluated in 130 patients with acute leukaemia and myelodysplasia undergoing T-cell-depleted PBSC transplantation using unrelated donors. Patients received alemtuzumab in vivo T-cell depletion as part of a myeloablative (MA; n=61) or reduced-intensity conditioning regimen (n=69). No difference in OS was seen with single-locus mismatching (mm) when 10 conventional alleles (HLA-A, B, C, DRB1 and DQB1) were considered. However, the addition of HLA-DPB1 matching data proved highly discriminatory. Mismatches were identified in 87% of patients previously considered fully matched (1DPmm=49pts: 2DPmm=28pts), and in the 9/10 group 22 patients were reclassified as double and 16 as triple mismatches. In 10/10 transplants, there was a distinct trend to poorer OS with double DPB1 mm. If all 12 loci were considered, 98% of single mm were at HLA-DPB1. Furthermore, cumulative mm at two or more loci was associated with significantly poorer 3-year OS (34% vs 48%, P=0.013: hazard ratio 1.8 (95% confidence interval 1.14-3.06; P=0.017), although his detrimental effect was only apparent using MA conditioning, in which reduced OS was associated with increased chronic GVHD (61% vs 16%, P=0.018) and nonrelapse mortality (30% vs 9%, P=0.039).

Brachypodium distachyon exhibits compatible interactions with Oculimacula spp. and Ramularia collo-cygni, providing the first pathosystem model to study eyespot and ramularia leaf spot diseases.

Brachypodium distachyon (Bd) has established itself as an essential tool for comparative genomic studies in cereals and increasing attention is being paid to its potential as a model pathosystem. Eyespot and ramularia leaf spot (RLS) are important diseases of wheat, barley and other small-grain cereals for which very little is known about the mechanisms of host resistance despite urgent requirements for plant breeders to develop resistant varieties. This work aimed to test the compatibility of interaction of two Bd accessions with the cereal pathogens Oculimacula spp. and Ramularia collo-cygni, the causal agents of eyespot and RLS diseases, respectively. Results showed that both Bd accessions developed symptoms similar to those on the natural host for all pathogen species tested. Microscopy images demonstrated that R. collo-cygni produced secondary conidia and both Oculimacula spp. formed characteristic infection structures on successive tissue layers. Visual disease assessment revealed that quantitative differences in disease severity exist between the two Bd accessions. The results presented here provide the first evidence that Bd is compatible with the main causal agents of eyespot and RLS diseases, and suggest that future functional genetic studies can be undertaken to investigate the mechanisms of eyespot and RLS disease resistance using Bd.

HLA-A, -B, -DR allele group frequencies in 7007 kidney transplant list patients in 27 UK centres.

This observational study aims to determine the HLA specificity frequencies of patients on the UK renal transplant list, which can be used as a resource for those laboratories that support the UK renal transplant programme. Whilst the HLA specificity frequencies may differ from that of the general population, it is the individuals on the transplant list who are in need of a new kidney, which has to be provided from the general population. Any differences in protein allele frequencies between this patient population and the general population are likely to be minimal because of the very large number of patients included. The HLA-A, -B and -DR allele group frequencies from 7007 patients on the UK kidney transplant list (August, 2009) were analysed. HLA types had been submitted to NHSBT to register patients on the UK deceased donor kidney waiting list. The data were submitted from 27 different registering centres throughout the UK. Within this data set, 25 different HLA-A, 50 HLA-B and 18 HLA-DR allele groups were present. The most common allele groups at each locus were -A2 (phenotype frequency 42.6%), -B44 (phenotype frequency 23.3%) and -DR4 (phenotype frequency 29.8%). The least common allele groups at each locus were -A19, - A43, -B16, -B21, -B22, -B83 and -DR5. Reports of HLA frequency (protein allotype) data from populations as large as this are not readily available adding value to this observational study.

The 'Green Revolution' dwarfing genes play a role in disease resistance in Triticum aestivum and Hordeum vulgare.

The Green Revolution dwarfing genes, Rht-B1b and Rht-D1b, encode mutant forms of DELLA proteins and are present in most modern wheat varieties. DELLA proteins have been implicated in the response to biotic stress in the model plant, Arabidopsis thaliana. Using defined wheat Rht near-isogenic lines and barley Sln1 gain of function (GoF) and loss of function (LoF) lines, the role of DELLA in response to biotic stress was investigated in pathosystems representing contrasting trophic styles (biotrophic, hemibiotrophic, and necrotrophic). GoF mutant alleles in wheat and barley confer a resistance trade-off with increased susceptibility to biotrophic pathogens and increased resistance to necrotrophic pathogens whilst the converse was conferred by a LoF mutant allele. The polyploid nature of the wheat genome buffered the effect of single Rht GoF mutations relative to barley (diploid), particularly in respect of increased susceptibility to biotrophic pathogens. A role for DELLA in controlling cell death responses is proposed. Similar to Arabidopsis, a resistance trade-off to pathogens with contrasting pathogenic lifestyles has been identified in monocotyledonous cereal species. Appreciation of the pleiotropic role of DELLA in biotic stress responses in cereals has implications for plant breeding.

Exploiting co-linearity among grass species to map the Aegilops ventricosa-derived Pch1 eyespot resistance in wheat and establish its relationship to Pch2.

Introgressions into wheat from related species have been widely used as a source of agronomically beneficial traits. One such example is the introduction of the potent eyespot resistance gene Pch1 from the wild relative Aegilops ventricosa onto chromosome 7DL of wheat. In common with genes carried on many other such introgressions, the use of Pch1 in commercial wheat varieties has been hindered by linkage drag with yield-limiting traits. Attempts to break this linkage have been frustrated by a lack of co-dominant PCR markers suitable for identifying heterozygotes in F(2) populations. We developed conserved orthologous sequence (COS) markers, utilising the Brachypodium distachyon (Brachypodium) genome sequence, to provide co-dominant markers in the Pch1 region. These were supplemented with previously developed sequence-tagged site (STS) markers and simple sequence repeat (SSR) markers. Markers were applied to a panel of varieties and to a BC(6) F(2) population, segregating between wheat and Ae. ventricosa over the distal portion of 7DL, to identify recombinants in the region of Pch1. By exploiting co-linearity between wheat chromosome 7D, Brachypodium chromosome 1, rice chromosome 6 and sorghum chromosome 10, Pch1 was located to an interval between the flanking markers Xwg7S and Xcos7-9. Furthermore candidate gene regions were identified in Brachypodium (364 Kb), rice (178 Kb) and sorghum (315 Kb) as a prelude to the map-based cloning of the gene. In addition, using homoeologue transferable markers, we obtained evidence that the eyespot resistances Pch1 and Pch2 on chromosomes 7D and 7A, respectively, are potentially homoeoloci. It is anticipated that the COS marker methodology could be used for the identification of recombinants in other introgressions into wheat from wild relatives. This would assist the mapping of genes of interest and the breaking of deleterious linkages to enable greater use of these introgressions in commercial varieties.

Identification of a QTL conferring seedling and adult plant resistance to eyespot on chromosome 5A of Cappelle Desprez.

Eyespot is an economically important fungal disease of wheat and other cereals caused by two fungal species: Oculimacula yallundae and Oculimacula acuformis. However, only two eyespot resistance genes have been characterised and molecular markers made available to plant breeders. These resistances are Pch1, introduced into wheat from the relative Aegilops ventricosa, and Pch2, originally identified in the cultivar Cappelle Desprez (CD). There are drawbacks associated with both resistances; Pch1 is linked to deleterious traits carried on the Ae. ventricosa introgression and Pch2 has been shown to have limited effectiveness. An additional resistance has been reported on chromosome 5A of CD that confers resistance to eyespot in adult plants. In the present study, we demonstrate that resistance on this chromosome is effective against both O. yallundae and O. acuformis eyespot pathogens and confers resistance at both seedling and adult plant stages. This resistance was mapped in both seedling bioassays and field trials in a 5A recombinant population derived from a cross between CD and a CD single chromosome substitution line carrying 5A from the susceptible line Bezostaya. The resistance was also mapped using seedling bioassays in a 5A recombinant population derived from a cross between the susceptible line Chinese Spring (CS) and a single chromosome substitution line carrying 5A from CD. A single major QTL on the long arm of chromosome 5A was detected in all experiments. Furthermore, the SSR marker Xgwm639 was found to be closely associated with the resistance and could be used for marker-assisted selection of the eyespot resistance by plant breeders.

Randomized clinical trial of metronidazole ointment versus placebo in perianal Crohn's disease.

BACKGROUND: The potential for metronidazole 10 per cent ointment to exert therapeutic benefit in perianal Crohn's disease, while minimizing the adverse effects found with oral metronidazole, was evaluated in a randomized placebo-controlled study. METHODS: Subjects with perianal Crohn's disease were randomized to metronidazole 10 per cent ointment, 0.7 g applied perianally three times daily, or placebo ointment. The Perianal Crohn's Disease Activity Index (PCDAI) was scored at baseline and after 4 weeks of treatment. Perianal pain was assessed on a visual analogue scale. RESULTS: Seventy-four subjects (33 metronidazole, 41 placebo) were evaluated. The mean(s.e.m.) reduction in PCDAI score at 4 weeks was 2.4(0.5) in the metronidazole group and 2.2(0.4) in the placebo group (P = 0.660). More subjects in the metronidazole group than the placebo group showed a reduction in PCDAI score of at least 5 points (10 of 27 versus 4 of 34; P = 0.031). Perianal discharge was reduced significantly in metronidazole-treated subjects (P = 0.012). A greater reduction in perianal pain was seen in the metronidazole group, which approached statistical significance (P = 0.059). No serious adverse events were reported. CONCLUSION: Metronidazole 10 per cent ointment was not effective in the reduction of PDCAI score, but some secondary outcomes showed improvement suggestive of a treatment effect. It is well tolerated, with minimal adverse effects, and has potential as treatment for pain and discharge associated with perianal Crohn's disease. REGISTRATION NUMBER: NCT00509639 (http://www.clinicaltrials.gov).

The development of PCR-based markers for the selection of eyespot resistance genes Pch1 and Pch2.

Two eyespot resistance genes (Pch1 and Pch2) have been characterised in wheat. The potent resistance gene Pch1, transferred from Aegilops ventricosa, is located on the distal end of the long arm of chromosome 7D (7DL). Pch2 derives from the variety Cappelle Desprez and is located at the distal end of chromosome 7AL. The RFLP marker Xpsr121 and the endopeptidase isozyme allele Ep-D1b, are very closely linked to Pch1, probably due to reduced recombination in the region of the introgressed A. ventricosa segment. Pch2 is less closely linked to these markers but is thought to be closer to Xpsr121 than to Ep-A1b. In the present study simple sequence repeat (SSR) markers were integrated into the genetic map of a single chromosome (7D) recombinant (RVPM) population segregating for Pch1. Sequence-tagged-site (STS)-based assays were developed for Xpsp121 and a 7DL wheat EST containing a SSR. SSR markers Xwmc14 and Xbarc97 and the Xpsr121-derived marker co-segregated with Pch1 in the RVPM population. A single chromosome (7A) recombinant population segregating for Pch2 was screened for eyespot resistance and mapped using SSRs. QTL interval mapping closely associated Pch2 with the SSR marker Xwmc525.

Developing a long-term surviving piglet model of neonatal hypoxic-ischemic encephalopathy.

OBJECTIVE: This study was designed to develop a piglet model of neonatal hypoxic-ischemic encephalopathy, which would allow for serial assessments of long-term neurodevelopmental impairment. METHODS: In 12 newborn piglets, we produced hypoxia by 8% oxygen breathing for 5-91 minutes. We combined ischemia by reversible bilateral common carotid artery occlusion for varying times. Outcome measures were clinical neurological evaluation, magnetic resonance spectroscopy studies and brain histology. RESULTS: Those animals which received intravenous sedation and no mechanical ventilation showed poor tolerance to hypoxia-ischemia and died early in the course of the experiments. The use of inhalation anesthesia during surgical procedures and mechanical ventilation during hypoxia-ischemia was associated with long-term survival. Seven of eight animals that survived > or = 48 hr showed clinical neurological abnormalities, that later resolved. Magnetic resonance spectroscopy measurements did not change significantly following hypoxia-ischemia. None of the animals had histopathological brain lesions. CONCLUSION: When subjected to acute hypoxia-ischemia, piglets were likely to survive only if they were given such supportive measures as anesthesia and mechanical ventilation. Even with hypoxic-ischemic injury sufficient to produce acute signs of neurological dysfunctions, longterm, stable survival with no evident brain histopathological abnormalities was possible.

Trends in hospital emergency department utilization: United States, 1992-99.

OBJECTIVES: This report describes trends in hospital emergency department (ED) visits in the United States. Statistics are presented for overall utilization, case mix of patients, services provided, and outcome measures. METHODS: The data presented in this report were collected from the National Hospital Ambulatory Medical Care Survey (NHAMCS) from 1992 through 1999. To make the data points more reliable for trend analysis, the data were combined to provide 2-year annual averages for 1993-94, 1995-96, and 1997-98. The survey in 1992 was especially large so it was used alone. The 1999 data are the most recent year available and are presented separately. RESULTS: The volume of ED visits in the United States increased by 14% from 1992 through 1999, from 89.8 million to 102.8 million annually. This increase is mainly due to an increase in visits for illness-related as opposed to injury-related conditions. Although the population rate for ED visits did not significantly increase over this time period (rates between 35.7 and 37.9 visits per 100 persons), the rate for illness-related visits rose from 21.0 to 24.0 visits per 100 persons (p < 0.01). The most dramatic increases were observed in the overall visit rate for black persons 65 years of age and over, which rose by 59% from 45.4 visits per 100 persons in 1992 to 72.2 in 1999. For black seniors, both illness and injury-related visit rates increased at a much higher rate compared with trends for white seniors. CONCLUSION: Increased volume of ED encounters for persons 45 years of age and over was associated with a greater proportion of illness conditions presenting to the ED and the use of more services, medications, and mid-level providers.