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Eighteen patients in a street-drug–induced stupor were seen in EDs on a single day in a New York City neighborhood. With rapid cooperative efforts among physicians, police, public health authorities, and toxicologists, the cannabinoid AMB-FUBINACA was identified as the cause. Commonly abused drugs are undergoing a period of proliferation and diversification, with a corresponding increase in the challenges faced by emergency and critical care physicians, substance abuse professionals, psychiatrists, and toxicologists. New psychoactive substances provide users with alternatives to older and better-characterized drugs of abuse, such as amphetamines, heroin, cocaine, and cannabis. Of the more than 540 new psychoactive substances that have been reported to the United Nations Office on Drugs and Crime, 1 synthetic cannabinoids are the fastest growing class, with more than 177 identified by the agency in 2014 and 24 new synthetic cannabinoids reported by Europol in 2015. . . .

The aquatic environment and the associated fish assemblages are being exposed to an increasing amount of microplastics. Despite the high number of publications on the presence of microplastics in fish, little is known about their uptake, translocation and accumulation within fish organs. Experimental studies on the detection and effects of pristine microplastics in fish have shown controversial and ambiguous results, respectively. Here, we conducted two experiments to detect and assess the impacts of dietary exposure of Danio rerio to different types of pristine microplastics. Our results show that D. rerio recognizes plastic particles as inedible materials but ingests them when mixed with food or fish oil. Accidental ingestion occurs in fish exposed to relatively small (1–5 µm) microplastic particles without associated food or fish oil. Additionally, D. rerio effectively eliminated pristine microplastics 24 h after ingestion; however, retention time was associated with increasing particle size and the intake of additional meals. Clinical signs, such as anorexia and lethargy, are present in fish fed relatively large microplastics (120–220 µm). The ingestion of microplastics does not induce any histopathological changes. To the best of our knowledge, we are able, for the first time, to fully demonstrate the uptake and translocation of plastic microbeads using confocal microscopy. Our results question the findings of previous studies on the detection and effects of pristine microplastics in fish and state that inaccurate interpretations of the histological findings regarding microplastics in fish organs is a prevalent flaw in the current scientific literature.

Historically, human monkeypox virus cases in the UK have been limited to imported infections from west Africa. Currently, the UK and several other countries are reporting a rapid increase in monkeypox cases among individuals attending sexual health clinics, with no apparent epidemiological links to endemic areas. We describe demographic and clinical characteristics of patients diagnosed with human monkeypox virus attending a sexual health centre. In this observational analysis, we considered patients with confirmed monkeypox virus infection via PCR detection attending open-access sexual health clinics in London, UK, between May 14 and May 25, 2022. We report hospital admissions and concurrent sexually transmitted infection (STI) proportions, and describe our local response within the first 2 weeks of the outbreak. Monkeypox virus infection was confirmed in 54 individuals, all identifying as men who have sex with men (MSM), with a median age of 41 years (IQR 34–45). 38 (70%) of 54 individuals were White, 26 (48%) were born in the UK, and 13 (24%) were living with HIV. 36 (67%) of 54 individuals reported fatigue or lethargy, 31 (57%) reported fever, and ten (18%) had no prodromal symptoms. All patients presented with skin lesions, of which 51 (94%) were anogenital. 37 (89%) of 54 individuals had skin lesions affecting more than one anatomical site and four (7%) had oropharyngeal lesions. 30 (55%) of 54 individuals had lymphadenopathy. One in four patients had a concurrent STI. Five (9%) of 54 individuals required admission to hospital, mainly due to pain or localised bacterial cellulitis requiring antibiotic intervention or analgesia. We recorded no fatal outcomes. Autochthonous community monkeypox virus transmission is currently observed among MSM in the UK. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact, during sexual activity. Additional resources are required to support sexual health and other specialist services in managing this condition. A review of the case definition and better understanding of viral transmission routes are needed to shape infection control policies, education and prevention strategies, and contact tracing. None.

Hypothyroidism is a common condition of thyroid hormone deficiency, which is readily diagnosed and managed but potentially fatal in severe cases if untreated. The definition of hypothyroidism is based on statistical reference ranges of the relevant biochemical parameters and is increasingly a matter of debate. Clinical manifestations of hypothyroidism range from life threatening to no signs or symptoms. The most common symptoms in adults are fatigue, lethargy, cold intolerance, weight gain, constipation, change in voice, and dry skin, but clinical presentation can differ with age and sex, among other factors. The standard treatment is thyroid hormone replacement therapy with levothyroxine. However, a substantial proportion of patients who reach biochemical treatment targets have persistent complaints. In this Seminar, we discuss the epidemiology, causes, and symptoms of hypothyroidism; summarise evidence on diagnosis, long-term risk, treatment, and management; and highlight future directions for research.

BACKGROUND: Protein intake has been inversely associated with frailty. However, no study has examined the effect of the difference of protein sources (animal or plant) or the amino acid composing the protein on frailty. Therefore, we examined the association of protein and amino acid intakes with frailty among elderly Japanese women. METHODS: A total of 2108 grandmothers or acquaintances of dietetic students aged 65 years and older participated in this cross-sectional multicenter study, which was conducted in 85 dietetic schools in 35 prefectures of Japan. Intakes of total, animal, and plant protein and eight selected amino acids were estimated from a validated brief-type self-administered diet history questionnaire and amino acid composition database. Frailty was defined as the presence of three or more of the following four components: slowness and weakness (two points), exhaustion, low physical activity, and unintentional weight loss. RESULTS: The number of subjects with frailty was 481 (23%). Adjusted ORs (95% CI) for frailty in the first, second, third, fourth, and fifth quintiles of total protein intake were 1.00 (reference), 1.02 (0.72, 1.45), 0.64 (0.45, 0.93), 0.62 (0.43, 0.90), and 0.66 (0.46, 0.96), respectively (P for trend = 0.001). Subjects categorized to the third, fourth, and fifth quintiles of total protein intake (>69.8 g/d) showed significantly lower ORs than those to the first quintile (all P <0.03). The intakes of animal and plant protein and all selected amino acids were also inversely associated with frailty (P for trend <0.04), with the multivariate adjusted OR in the highest compared to the lowest quintile of 0.73 for animal protein and 0.66 for plant protein, and 0.67-0.74 for amino acids, albeit that the ORs for these dietary variables were less marked than those for total protein. CONCLUSIONS: Total protein intake was significantly inversely associated with frailty in elderly Japanese women. The association of total protein with frailty may be observed regardless of the source of protein and the amino acid composing the protein.

Acalabrutinib (ACP-196) is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK) with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL). First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR) was 25% (5/20) with a median progression free survival (PFS) of 22.5 days. Clinical benefit was observed in 30% (6/20) of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL).

This study evaluated whether dietary spray-dried plasma (SDP) can ameliorate inflammation, lethargic behaviors, and impairment of reproduction caused by lipopolysaccharide (LPS) challenge during late pregnancy. Two experiments were conducted with 125 mated female mice (C57BL/6 strain) in each experiment. All mice were shipped from a vendor on the gestation day (GD) 1 and arrived at the laboratory on GD 3. Mice were randomly assigned to dietary treatments with or without 8% SDP in the diet. On GD 17, mice determined pregnant by BW and abdomen shape were randomly assigned to intraperitoneal injections with or without 2 μg LPS. In experiment 1, 17 mice (26.7 ± 1.7 g BW) were identified pregnant and euthanized 6 h after the LPS challenge to measure inflammatory responses in uterus and placenta. In experiment 2, 44 mice (26.0 ± 1.6 g BW) were identified pregnant and euthanized 24 h after the LPS challenge to assess behavior and late-term pregnancy loss. Growth performance and reproductive responses, such as loss of pregnancy, percentage of fetal death, and etc., were measured in all pregnant mice. The LPS challenge increased (P < 0.05) uterine and placental tumor necrosis factor-α and interferon-γ, late-term pregnancy loss, and lethargy score, and decreased (P < 0.05) uterine transforming growth factor-β1, moving time and number of rearing, and growth and feed intake. The SDP decreased (P < 0.05) concentrations of both pro-inflammatory and anti-inflammatory cytokines in one or both tissues, and the lethargy score, and increased (P < 0.05) moving time and number of rearing, growth of pregnant mice, and fetal weight. However, the SDP did not affect late-term pregnancy loss caused by the LPS challenge. Consequently, dietary SDP attenuated acute inflammation and lethargic behaviors of pregnant mice caused by the LPS challenge, but did not affect late-term pregnancy loss after the acute inflammation.

As the 'third brain' the placenta links the developing fetal brain and the maternal brain enabling study of epigenetic process in placental genes that affect infant neurodevelopment. We described the characteristics and findings of the 17 studies on epigenetic processes in placental genes and human infant neurobehavior. Studies showed consistent findings in the same cohort of term healthy infants across epigenetic processes (DNA methylation, genome wide, gene and miRNA expression) genomic region (single and multiple genes, imprinted genes and miRNAs) using candidate gene and genome wide approaches and across biobehavioral systems (neurobehavior, cry acoustics and neuroendocrine). Despite limitations, studies support future work on molecular processes in placental genes related to neurodevelopmental trajectories including implications for intervention.

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m2, or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries.

Improved knowledge of glacial-to-interglacial global temperature change yields Charney (fast-feedback) equilibrium climate sensitivity 1.2 ± 0.3°C (2σ) per W/m2, which is 4.8°C ± 1.2°C for doubled CO2. Consistent analysis of temperature over the full Cenozoic era—including ‘slow’ feedbacks by ice sheets and trace gases—supports this sensitivity and implies that CO2 was 300–350 ppm in the Pliocene and about 450 ppm at transition to a nearly ice-free planet, exposing unrealistic lethargy of ice sheet models. Equilibrium global warming for today’s GHG amount is 10°C, which is reduced to 8°C by today’s human-made aerosols. Equilibrium warming is not ‘committed’ warming; rapid phaseout of GHG emissions would prevent most equilibrium warming from occurring. However, decline of aerosol emissions since 2010 should increase the 1970–2010 global warming rate of 0.18°C per decade to a post-2010 rate of at least 0.27°C per decade. Thus, under the present geopolitical approach to GHG emissions, global warming will exceed 1.5°C in the 2020s and 2°C before 2050. Impacts on people and nature will accelerate as global warming increases hydrologic (weather) extremes. The enormity of consequences demands a return to Holocene-level global temperature. Required actions include: (1) a global increasing price on GHG emissions accompanied by development of abundant, affordable, dispatchable clean energy, (2) East-West cooperation in a way that accommodates developing world needs, and (3) intervention with Earth’s radiation imbalance to phase down today’s massive human-made ‘geo-transformation’ of Earth’s climate. Current political crises present an opportunity for reset, especially if young people can grasp their situation.