USP1 deubiquitinates ID proteins to preserve a mesenchymal stem cell program in osteosarcoma.

Inhibitors of DNA binding (IDs) antagonize basic-helix-loop-helix (bHLH) transcription factors to inhibit differentiation and maintain stem cell fate. ID ubiquitination and proteasomal degradation occur in differentiated tissues, but IDs in many neoplasms appear to escape degradation. We show that the deubiquitinating enzyme USP1 promotes ID protein stability and stem cell-like characteristics in osteosarcoma. USP1 bound, deubiquitinated, and thereby stabilized ID1, ID2, and ID3. A subset of primary human osteosarcomas coordinately overexpressed USP1 and ID proteins. USP1 knockdown in osteosarcoma cells precipitated ID protein destabilization, cell-cycle arrest, and osteogenic differentiation. Conversely, ectopic USP1 expression in mesenchymal stem cells stabilized ID proteins, inhibited osteoblastic differentiation, and enhanced proliferation. Consistent with USP1 functioning in normal mesenchymal stem cells, USP1-deficient mice were osteopenic. Our observations implicate USP1 in preservation of the stem cell state that characterizes osteosarcoma and identify USP1 as a target for differentiation therapy.

Gram-negative anaerobes elicit a robust keratinocytes immune response with potential insights into HS pathogenesis.

Hidradenitis Suppurativa (HS) is a chronic autoinflammatory skin disease with activated keratinocytes, tunnel formation and a complex immune infiltrate in tissue. The HS microbiome is polymicrobial with an abundance of commensal gram-positive facultative (GPs) Staphylococcus species and gram-negative anaerobic (GNA) bacteria like Prevotella, Fusobacterium and Porphyromonas with increasing predominance of GNAs with disease severity. We sought to define the keratinocyte response to bacteria commonly isolated from HS lesions to probe pathogenic relationships between HS and the microbiome. Type strains of Prevotella nigrescens, Prevotella melaninogenica, Prevotella intermedia, Prevotella asaccharolytica, Fusobacterium nucleatum, as well as Staphylococcus aureus and the normal skin commensal Staphylococcus epidermidis were heat-killed and co-incubated with normal human keratinocytes. RNA was collected and analysed using RNAseq and RT-qPCR. The supernatant was collected from cell culture for protein quantification. Transcriptomic profiles between HS clinical samples and stimulated keratinocytes were compared. Co-staining of patient HS frozen sections was used to localize bacteria in lesions. A mouse intradermal injection model was used to investigate early immune recruitment. TLR4 and JAK inhibitors were used to investigate mechanistic avenues of bacterial response inhibition. GNAs, especially F. nucleatum, stimulated vastly higher CXCL8, IL17C, CCL20, IL6, TNF and IL36γ transcription in normal skin keratinocytes than the GPs S. epidermidis and S. aureus. Using RNAseq, we found that F. nucleatum (and Prevotella) strongly induced the IL-17 pathway in keratinocytes and overlapped with transcriptome profiles of HS patient clinical samples. Bacteria were juxtaposed to activated keratinocytes in vivo, and F. nucleatum strongly recruited murine neutrophil and macrophage migration. Both the TLR4 and pan-JAK inhibitors reduced cytokine production. Detailed transcriptomic profiling of healthy skin keratinocytes exposed to GNAs prevalent in HS revealed a potent, extensive inflammatory response vastly stronger than GPs. GNAs stimulated HS-relevant genes, including many genes in the IL-17 response pathway, and were significantly associated with HS tissue transcriptomes. The close association of activated keratinocytes with bacteria in HS lesions and innate infiltration in murine skin cemented GNA pathogenic potential. These novel mechanistic insights could drive future targeted therapies.

Advanced HIV disease and associated factors among young people aged 15-24 years at a tertiary hospital in Sierra Leone: a cross-sectional study.

BACKGROUND: Advanced HIV disease (AHD) in young people living with HIV (PLHIV) is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many youths experience increased rates of HIV disease progression in sub-Saharan Africa. This study describes the burden, clinical manifestations, and factors for disease progression among young PLHIV aged 15 - 24 years seeking medical services at a major public hospital in Sierra Leone. METHODS: We performed a cross-sectional analysis of routinely collected data for PLHIV patients aged 15 to 24 seen at Connaught Hospital in Sierra Leone between September 2022 and March 2023. We estimated the proportion of AHD in young PLHIV and performed logistic regression modelling to explore predictors of AHD. The statistical significance level was set at 0.05 for all statistical tests. RESULTS: Of the 581 PLHIV that were reported, 238 (40.9%) were between the ages of 15 and 24 years, with a median age of 22 (20-24), and 151 (63.5%) were females. On review, 178 (74.8%) has initiated antiretroviral therapy regimen (ART); 117 (65.7%) were actively on ART for ≤ 6 months, while 114 (64%) had interruptions with their ART treatment. The overall prevalence of AHD was 41.6% (99/238); 46.7% (35/68) of young PLHIV at the HIV clinic, and 39.3% (64/163) of admission. Sex-Female (OR, 0.51; 95% CI, 0.28-0.94; p = 0.030), and Tertiary Education level (OR, 0.27; 95% CI, 0.10 - 0.78; p = 0.015) have significantly lower odds of AHD in the entire study population. While for inpatients, Age (young Adults) of PLHIV (OR, 1.23; 95% CI, 1.00-1.52; p = 0.047) had 1.23 times the odds of AHD compared to adolescents, and being female (OR, 0.27; 95% CI, 0.08-0.84; p = 0.024), Overweight-Body mass index (OR, 0.10; 95% CI, 0.01-0.77; p = 0.028), Tertiary Education level (OR, 0.08; 95% CI, 0.01-0.52; p = 0.008) have significantly lower odds of AHD. Common conditions reported for the AHD group in the medical wards are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and oesophagal candidiasis (2.45%). CONCLUSION: We reported a high prevalence of advanced HIV among young patients in a tertiary Hospital in Sierra Leone. One in two young PLHIV aged 15 to 24 years reported AHD, emphasizing the need to strengthen public health measures that address access to and retention of HIV services.

Tape strips detect molecular alterations and cutaneous biomarkers in skin of patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) has a high unmet need for better treatments. Biopsies are considered the gold standard for studying molecular alterations in skin. A reproducible, minimally invasive approach is needed for longitudinal monitoring in trials and in pediatric populations. OBJECTIVE: To determine whether skin tape strips can detect molecular alterations in HS and identify biomarkers of disease activity. METHODS: We performed RNA sequencing on tape strips collected from lesional and healthy-appearing (nonlesional) HS skin (n = 22) and healthy controls (n = 21). We correlated the expression of skin biomarkers between tape strips and a previously published gene-signature of HS biopsies. RESULTS: Tape strips detected upregulation of known HS biomarkers (eg, Interleukin[IL]-17A) in nonlesional and/or lesional skin and also identified novel clinically actionable targets, including OX40 and JAK3. The expression of Th17 and tumor necrosis factor-α pathways were highly correlated between tape strips and biopsies. HS clinical severity was significantly associated with expression of biomarkers (eg tumor necrosis factor-α , IL-17 A/F, OX40, JAK1-3, IL-4R) in HS lesional and/or nonlesional skin. LIMITATIONS: Sample size. Tape stripping is limited in depth. CONCLUSION: This study validates tape strips as a minimally-invasive approach to identify cutaneous biomarkers in HS. This provides a novel avenue for monitoring treatment efficacy and a potential step toward individualized therapy in HS.

Characterisation of skin barrier defects in atopic dermatitis patients using Infrared Spectroscopy.

INTRODUCTION: Atopic dermatitis (AD) is characterised by skin barrier defects often measured by biophysical tools that observe stratum corneum (SC) functional properties. OBJECTIVE: To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in chemical composition of the SC in relation to AD severity. METHODS: We conducted an observational cross-sectional cohort study where attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL) combined with tape stripping (STS) in a cohort of 75 participants; 55 AD patients stratified by phenotypic severity, compared to 20 healthy controls. Common filaggrin (FLG) variant alleles were genotyped. RESULTS: Reduced hydration, elevated TEWL and redness all associated with greater AD severity. Spectral analysis showed a reduction in 1465cm-1 (full width half maximum) and 1340 cm-1 peak areas indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups that correlated with clinical severity (lipid structure r=-0.59, carboxylate peak area r=-0.50). CONCLUSION: ATR-FTIR spectroscopy is a suitable tool for the characterisation of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatments based on chemical structural deficiencies.

A case of acute tubulointerstitial nephritis following administration of the Oxford-AstraZeneca COVID-19 vaccine: a case report.

BACKGROUND: More than 4 billion doses of the Coronavirus disease (COVID-19) vaccine have been administered worldwide but the relationship between the different vaccines and the development of renal disease is unknown. We present a case of tubulointerstitial nephritis following administration of the Oxford-AstraZeneca COVID-19 vaccine. CASE PRESENTATION: A previously fit and well 51-year-old female presented on 27th May 2021 with a one-month history of weight loss, fatigue, nausea, and a metallic taste. She had an acute kidney injury with a creatinine of 484 umol/L. She was on no regular medications and denied taking any over-the-counter or alternative medicines. She had received her first dose of the Oxford-AstraZeneca vaccine on 23rd March 2021 and her second dose on 20th May 2021. A renal biopsy was performed the following day. The 19 glomeruli appeared normal to light microscopy but the tubulointerstitial compartment contained a dense inflammatory infiltrate including many eosinophils. There was widespread acute tubular injury with tubulitis, but no established or longstanding atrophy. A diagnosis was made of an acute tubulointerstitial nephritis. She was commenced on oral prednisolone and her renal function improved. She did not require renal replacement therapy at any time. CONCLUSIONS: To our knowledge, this was the first described case of acute tubulointerstitial nephritis following administration of the Oxford-AstraZeneca COVID-19 vaccine, although a number of cases have emerged more recently. In our case the patient was very fit and well, had no previous past medical history and had not taken any recent prescribed, over-the-counter or alternative medications. The absence of these provoking factors in our case makes the vaccine the most likely explanation for the development of tubulointerstitial nephritis although the pathophysiology behind this remains unknown. Given the unprecedented number of vaccinations being delivered around the world, nephrologists should be aware of this possible link although more research into the topic is required.

International Dermatology Outcome Measures (IDEOM) - Report from the 2022 Annual Meeting.

BACKGROUND: The International Dermatology Outcome Measures (IDEOM) is a non-profit organization dedicated to the advancement of evidence-based, consensus-driven outcome measures in dermatological diseases. Researchers and stakeholders from various backgrounds collaborate to develop these objective benchmark metrics to further advance treatment and management of dermatological conditions. SUMMARY: The 2022 IDEOM Annual Meeting was held on June 17-18, 2022. Leaders and stakeholders from the hidradenitis suppurativa, acne, vitiligo, actinic keratosis, alopecia areata, itch, cutaneous lymphoma, and psoriatic disease workgroups discussed the progress of their respective outcome-measures research. This report summarizes each workgroup's updates from 2022 and their next steps as established during the 2022 IDEOM Annual Meeting. J Drugs Dermatol. 2023;22(12):1153-1159 doi:10.36849/JDD.7615.

Challenges in Developing a Real-Time Bee-Counting Radar.

Detailed within is an attempt to implement a real-time radar signal classification system to monitor and count bee activity at the hive entry. There is interest in keeping records of the productivity of honeybees. Activity at the entrance can be a good measure of overall health and capacity, and a radar-based approach could be cheap, low power, and versatile, beyond other techniques. Fully automated systems would enable simultaneous, large-scale capturing of bee activity patterns from multiple hives, providing vital data for ecological research and business practice improvement. Data from a Doppler radar were gathered from managed beehives on a farm. Recordings were split into 0.4 s windows, and Log Area Ratios (LARs) were computed from the data. Support vector machine models were trained to recognize flight behavior from the LARs, using visual confirmation recorded by a camera. Spectrogram deep learning was also investigated using the same data. Once complete, this process would allow for removing the camera and accurately counting the events by radar-based machine learning alone. Challenging signals from more complex bee flights hindered progress. System accuracy of 70% was achieved, but clutter impacted the overall results requiring intelligent filtering to remove environmental effects from the data.

Interleukin-17RA blockade by brodalumab decreases inflammatory pathways in hidradenitis suppurativa skin and serum.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory skin disease with dysregulation of the interleukin (IL)-17 axis. Recently, we reported the clinical benefit of brodalumab, a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody, in moderate-to-severe HS. OBJECTIVES: To characterize the molecular response to brodalumab in HS skin and serum, and to identify biomarkers of treatment response. METHODS: Ten participants, who received brodalumab 210 mg /1·5 mL subcutaneously at weeks 0, 1, 2, 4 and every 2 weeks thereafter, were included in this molecular profiling study (NCT03960268). RNA sequencing and immunohistochemistry of nonlesional, perilesional and lesional HS skin biopsies, and Olink high-throughput proteomics of serum at baseline, weeks 4 and 12 were assessed. RESULTS: At week 12, brodalumab led to a decrease of overall inflammation, and improvement of psoriasis-, keratinocyte- and neutrophil-related pathways. Despite perilesional and lesional skin exhibiting no differentially expressed genes at baseline, treatment response was best assessed in perilesional skin. In serum, brodalumab treatment decreased pathways involved in neutrophil inflammation. Patients with higher baseline expression of neutrophil-associated lipocalin-2 (LCN2) in the skin or IL-17A in the serum demonstrated greater decreases of HS-related inflammatory cytokines as measured in skin biopsies at week 12. CONCLUSIONS: IL-17RA inhibition by brodalumab decreases several pathogenic inflammatory axes in HS. Perilesional skin provides a valid and robust assessment of treatment response. Expression of LCN2 in skin or IL-17A in serum may be used as biomarkers to stratify patients that may have a superior molecular response to brodalumab.

Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone skin.

BACKGROUND: The skin of patients with atopic dermatitis is characterized by abnormal stratum corneum lipid levels. Consequently, the lamellar matrices are disrupted and skin barrier function is diminished, increasing skin sensitivity to irritants and allergens. OBJECTIVES: To determine whether a cream containing ceramides, triglycerides and cholesterol in a multivesicular emulsion can reinforce the skin barrier and protect against skin irritation. METHODS: A randomized observer-blind intrapatient-controlled study in 34 adults with dry, eczema-prone skin was conducted. Each participant underwent 4 weeks of treatment with the test cream on one forearm and lower leg and a reference emollient cream on the other. Skin properties were determined before and after treatment. Lipid structure was assessed by Fourier-transform infrared spectroscopy using a novel interface. RESULTS: Skin barrier integrity was greater at sites treated with the test cream [effect size for area under the transepidermal water loss curve -162, 95% confidence interval (CI) -206 to -118]. Skin sensitivity to sodium lauryl sulfate was reduced (-0·5 points visual redness, 97·57% CI -1·00 to -0·25), as was transepidermal water loss (-15·3 g m-2 h-1 , 95% CI -20·3 to -10·4) compared with the reference. Sites treated with the test cream displayed enhanced lipid chain ordering, which was significantly associated with skin barrier integrity (r = 0·61). Compared with the reference, treatment with the test cream increased hydration (8·61 capacitance units, 95% CI 6·61-10·6) and decreased signs of dryness. CONCLUSIONS: The test cream facilitates skin barrier restoration and protects the skin from dryness and irritation. Compared with a commonly prescribed emollient in the UK, the test cream is highly suited to the management of dry, sensitive skin.

Assessment of knowledge, attitude and practice on family planning among women of reproductive age at hospitals and clinic centers in the rural Western Sierra Leone.

Informed decisions about one's sexual and reproductive health can be made through family planning. Women of reproductive age in rural Sierra Leone's Western area were asked to participate in a survey to determine their attitudes and knowledge toward family planning and the use of contraceptives. A descriptive cross-sectional study survey was conducted in the Western Area Rural of Sierra Leone. Females in the range of 15 to 49 years old were included in the study. The research was conducted from November 2021 to December 2021. Using a pre-designed and pretested questionnaire, 180 women were assessed for their knowledge, attitudes, and practices regarding family planning. According to the study, all participants knew about family planning, but only 68.3% had used contraceptives. There were more than half who learned about it from the media. The study found that 95% of participants had a positive attitude towards contraceptives. Most commonly, contraceptives used were oral pills (31.6), injections (21.1%), implants (19.1%), lactational amenorrhea (13.8%), condoms (8.8%), and intrauterine devices (5%). In our study, the most common reasons given by participants for not using contraceptives were; not willing to disclose 52.6%, a desire for a child 19.2%, fear of side effects 15.7%, currently pregnant 8.7%, and against religious beliefs 3.5%. The study shows that even if people are aware and educated about contraceptives, they may not use them. Educating and motivating people and improving access to family planning services are still necessary to improve the effectiveness and appropriateness of contraceptive use and halt the population growth trend.

A systematic review and critical appraisal of metagenomic and culture studies in hidradenitis suppurativa.

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin disease with still largely unknown pathogenesis. While infectious organisms have been identified in lesions of the disease since the 1980s, questions remain over the role that bacteria and microbiome play. Recent studies using 16S ribosomal RNA gene sequencing and larger culture-based studies have begun to paint a clearer picture of the microbial world of HS. With this systematic review, we summarize all the work that has been done to date in HS bacteriology, analyse potential pitfalls and limitations of the current studies, and address future directions of investigation. This systematic review attempted to collate and analyse all bacteriology studies done to date. This review was prospectively registered with PROSPERO (1670769) performed in line with the PRISMA checklist. Twenty two studies were identified comprising 862 individual HS patients for culture studies and 206 HS patients for 16S rRNA gene sequencing studies. Methodology tended to be varied, with different sampling, culturing and sequencing methods as well as amount of analysis and stratification of patients. Bacteria identified as elevated in HS lesions in sequencing studies as well as grown from HS lesions in culture studies are identified and discussed. These primarily included the anerobic Gram-negative bacilli Prevotella, Porphyromonas and Fusibacterium, the Gram-positive bacilli Corynebacterium, and the Gram-positive cocci Staphylococcus, Streptococcus and Parvimonas. Potential interactions, as well as work in other disease models with related bacteria are also discussed. Areas of further investigation include in vitro studies of interactions between bacteria and keratinocytes, gut and oral microbiome studies and deep sequencing studies for virulence and phage factors.

Identifying shark species responsible for fisheries depredation off Southeast Queensland, Australia.

Anecdotal reports from fishers in Southeast Queensland, Australia suggest that shark depredation is a significant issue, however little is known about which species are responsible for depredating catches. This research aimed to identify depredating species in Southeast Queensland line based fisheries, by undertaking a genetic analysis of depredated samples collected by commercial, charter and recreational fishers. The genetic analysis successfully identified ten depredating sharks, all from the genus Carcharhinus (19.2% success). The species identified using mitochondrial DNA included five C. leucas (bull sharks), two C. plumbeus (sandbar sharks), one C. amboinensis (pigeye shark), one C. brevipinna (spinner shark) and one unconfirmed C. plumbeus/C. altimus (bignose shark). While many species of Carcharhinus have been found to depredate catches in Australia, C. leucas has not been highlighted until this research as a potential problematic species. The optimised protocol allowed for the confident identification of shark species responsible for depredation in fisheries using frozen fish samples donated by fishers.

Characterization of thiosulfate reductase from Pyrobaculum aerophilum heterologously produced in Pyrococcus furiosus.

The genome of the archaeon Pyrobaculum aerophilum (Topt ~ 100 °C) contains an operon (PAE2859-2861) encoding a putative pyranopterin-containing oxidoreductase of unknown function and metal content. These genes (with one gene modified to encode a His-affinity tag) were inserted into the fermentative anaerobic archaeon, Pyrococcus furiosus (Topt ~ 100 °C). Dye-linked assays of cytoplasmic extracts from recombinant P. furiosus show that the P. aerophilum enzyme is a thiosulfate reductase (Tsr) and reduces thiosulfate but not polysulfide. The enzyme (Tsr-Mo) from molybdenum-grown cells contains Mo (Mo:W = 9:1) while the enzyme (Tsr-W) from tungsten-grown cells contains mainly W (Mo:W = 1:6). Purified Tsr-Mo has over ten times the activity (Vmax = 1580 vs. 141 µmol min-1 mg-1) and twice the affinity for thiosulfate (Km = ~ 100 vs. ~ 200 µM) than Tsr-W and is reduced at a lower potential (Epeak = - 255 vs - 402 mV). Tsr-Mo and Tsr-W proteins are heterodimers lacking the membrane anchor subunit (PAE2861). Recombinant P. furiosus expressing P. aerophilum Tsr could not use thiosulfate as a terminal electron acceptor. P. furiosus contains five pyranopterin-containing enzymes, all of which utilize W. P. aerophilum Tsr-Mo is the first example of an active Mo-containing enzyme produced in P. furiosus.

Evaluation of PNU-159682 antibody drug conjugates (ADCs).

PNU-159682 is a highly potent secondary metabolite of nemorubicin belonging to the anthracycline class of natural products. Due to its extremely high potency and only partially understood mechanism of action, it was deemed an interesting starting point for the development of a new suite of linker drugs for antibody drug conjugates (ADCs). Structure activity relationships were explored on the small molecule which led to six linker drugs being developed for conjugation to antibodies. Herein we describe the synthesis of novel PNU-159682 derivatives and the subsequent linker drugs as well as the corresponding biological evaluations of the small molecules and ADCs.

Enhancing Access for Student Nurse Athletes: Office Hours on the Road.

The purpose of this education innovation was to facilitate office hour (OH) instruction for student nurse athletes due to training schedules and off-campus travel. Effective integration of technology, learning theory, and multimedia resources provide strategies to enhance student athlete access to faculty OH and associated learning opportunities. Explain Everything™ software, a digital interactive whiteboard space, enables students and faculty to collaborate and learn across distance. This innovative approach enriches learning, ensuring OH access among student athletes.

Population allocation at the housing unit level: estimates around underground natural gas storage wells in PA, OH, NY, WV, MI, and CA.

BACKGROUND: Spatially accurate population data are critical for determining health impacts from many known risk factors. However, the utility of the increasing spatial resolution of disease mapping and environmental exposures is limited by the lack of receptor population data at similar sub-census block spatial scales. METHODS: Here we apply an innovative method (Population Allocation by Occupied Domicile Estimation - ABODE) to disaggregate U.S. Census populations by allocating an average person per household to geospatially-identified residential housing units (RHU). We considered two possible sources of RHU location data: address point locations and building footprint centroids. We compared the performance of ABODE with the common proportional population allocation (PPA) method for estimating the nighttime residential populations within 200 m radii and setback areas (100 - 300 ft) around active underground natural gas storage (UGS) wells (n = 9834) in six U.S. states. RESULTS: Address location data generally outperformed building footprint data in predicting total counts of census residential housing units, with correlations ranging from 0.67 to 0.81 at the census block level. Using residentially-sited addresses only, ABODE estimated upwards of 20,000 physical households with between 48,126 and 53,250 people living within 200 m of active UGS wells - likely encompassing the size of a proposed UGS Wellhead Safety Zone. Across the 9834 active wells assessed, ABODE estimated between 5074 and 10,198 more people living in these areas compare to PPA, and the difference was significant at the individual well level (p = < 0.0001). By either population estimation method, OH exhibits a substantial degree of hyperlocal land use conflict between populations and UGS wells - more so than other states assessed. In some rare cases, population estimates differed by more than 100 people for the small 200 m2 well-areas. ABODE's explicit accounting of physical households confirmed over 50% of PPA predictions as false positives indicated by non-zero predictions in areas absent physical RHUs. CONCLUSIONS: Compared to PPA - in allocating identical population data at sub-census block spatial scales -ABODE provides a more precise population at risk (PAR) estimate with higher confidence estimates of populations at greatest risk. 65% of UGS wells occupy residential urban and suburban areas indicating the unique land use conflicts presented by UGS systems that likely continue to experience population encroachment. Overall, ABODE confirms tens of thousands of homes and residents are likely located within the proposed UGS Wellhead Safety Zone - and in some cases within state's oil and gas well surface setback distances - of active UGS wells.

Misidentification of istiophorid billfishes by fisheries observers raises uncertainty over stock status.

We investigated whether commercially landed black marlin Istiompax indica were being misidentified by fisheries observers operating throughout the Pacific Ocean. Of 83 samples reported by observers as I. indica, 77% were genetically identified to be blue marlin Makaira nigricans and 2% to be striped marlin Kajikia audax. The high rate of misidentification by observers places considerable uncertainty over historic catch ratios of Indo-Pacific marlin and stock assessments relying on the validity of these data.

Investigating Clinical Benefits of a Novel Sleep-Focused Mind-Body Program on Gulf War Illness Symptoms: A Randomized Controlled Trial.

OBJECTIVE: Mind-Body Bridging (MBB) has been shown to be effective for improving disturbed sleep. In this prospective randomized controlled trial, we evaluated the efficacy of sleep-focused MBB compared with sleep education control (SED) for improving sleep in previously deployed Gulf War veterans. METHODS: US military service members with sleep and physical health complaints who were deployed in 1990-1991 were randomized to receive three weekly sessions of either MBB (n = 33) or SED (n = 27) between 2012 and 2015. The primary outcome of Medical Outcomes Study Sleep Scale was completed at baseline, weekly during treatment, postintervention, and 3-month follow-up. Secondary outcome measures for posttraumatic stress disorder, depression, fatigue, quality of life, symptom severity, and mindfulness were completed at baseline, postintervention and 3-month follow-up. Salivary samples were collected at five time points per day at each visit for cortisol and α-amylase assessment. Clinician-administered assessments of sleep and co-occurring conditions were conducted at baseline and postintervention. RESULTS: MBB was significantly more efficacious than SED in reducing disturbed sleep at follow-up (F(1,180.54) = 4.04, p = .046). In addition, self-reported posttraumatic stress disorder (F(1,56.42) = 4.50, p = .038) for the treatment effect, depression (F(1,93.70) = 4.44, p = .038), and fatigue symptoms (F(1,68.58) = 3.90, p = .050) at follow-up improved in MBB compared with those in SED. Consistently higher percentages of veterans in MBB reported improvements of sleep, pain, and composite sleep/general co-occurring symptoms at the postclinical evaluation, as compared with veterans in SED. Finally, the mean waking level of salivary α-amylase in the MBB declined to a greater extent than that in the SED, at follow-up (F(1,88.99) = 3.78, p = .055), whereas no effects were found on cortisol. CONCLUSIONS: Sleep-focused MBB can improve sleep and possibly also co-occurring symptoms in Gulf War veterans. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT01543997.