Phosphomannosyl receptors may participate in the adhesive interaction between lymphocytes and high endothelial venules.

Normal and malignant lymphocytes can migrate from the bloodstream into lymph nodes and Peyer's patches. This process helps distribute normal lymphocytes throughout the lymphoid system and may provide a portal of entry for circulating malignant cells. An adhesive interaction between lymphocytes and the endothelium of postcapillary venules is the first step in the migratory process. We have recently shown that the simple sugars L-fucose and D-mannose, and an L-fucose-rich polysaccharide (fucoidin), can inhibit this adhesive interaction in vitro. We now report that mannose-6-phosphate, the structurally related sugar fructose-1-phosphate, and a phosphomannan, core polysaccharide from the yeast Hansenula holstii (PPME) are also potent inhibitors. Inhibitory activity was assessed by incubating freshly prepared suspensions of lymphocytes, containing the various additives, over air-dried, frozen sections of syngeneic lymph nodes at 7-10 degrees C. Sections were then evaluated in the light microscope for the binding of lymphocytes to postcapillary venules. Mannose-6-phosphate and fructose-1-phosphate were potent inhibitors of lymphocyte attachment (one-half maximal inhibition at 2-3 mM). Mannose-1-phosphate and fructose-6-phosphate had slight inhibitory activity, while glucose-1-phosphate, glucose-6-phosphate, galactose-1-phosphate, and galactose-6-phosphate had no significant activity (at 10 mM). In addition, the phosphomannan core polysaccharide was a potent inhibitor (one-half maximal inhibition at 10-20 micrograms/ml); dephosphorylation with alkaline phosphatase resulted in loss of its inhibitory activity. Preincubation of the lymphocytes, but not the lymph node frozen sections, with PPME resulted in persistent inhibition of binding. Neither the monosaccharides nor the polysaccharide suppressed protein synthesis nor decreased the viability of the lymphocytes. Furthermore, inhibitory activity did not correlate with an increase in negative charge on the lymphocyte surface (as measured by cellular electrophoresis). These data suggest that a carbohydrate-binding molecule on the lymphocyte surface, with specificity for mannose-phosphates and structurally related carbohydrates, may be involved in the adhesive interaction mediating lymphocyte recirculation

Radiological Risks of Neutron Interrogation of Food

In recent years there has been growing interest in the use of neutron scanning techniques for security. Neutron techniques with a range of energy spectra including thermal, white and fast neutrons have been shown to work in different scenarios. As international interest in neutron scanning increases the risk of activating cargo, especially foodstuffs must be considered. There has been a limited amount of research into the activation of foods by neutron beams and we have sought to improve the amount of information available. In this paper we show that for three important metrics; Activity, Ingestion Dose and Time to Background there is a strong dependence on the food being irradiated and a weak dependence on the energy of irradiation. Previous studies into activation used results based on irradiation of pharmaceuticals as the basis for research into activation of food. The earlier work reports that 24Na production is the dominant threat which motivated the search for 23(n;\gamma)24Na in highly salted foods. We show that 42K can be more significant than 24Na in low salt foods such as Bananas and Potatoes

Vaccine effectiveness against influenza A(H3N2)-associated hospitalized illness: United States, 2022

BACKGROUND: The COVID-19 pandemic was associated with historically low influenza circulation during the 2020-2021 season, followed by an increase in influenza circulation during the 2021-2022 US season. The 2a.2 subgroup of the influenza A(H3N2) 3C.2a1b subclade that predominated was antigenically different from the vaccine strain. METHODS: To understand the effectiveness of the 2021-2022 vaccine against hospitalized influenza illness, a multistate sentinel surveillance network enrolled adults aged ≥18 years hospitalized with acute respiratory illness and tested for influenza by a molecular assay. Using the test-negative design, vaccine effectiveness (VE) was measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative controls, adjusting for confounders. A separate analysis was performed to illustrate bias introduced by including SARS-CoV-2-positive controls. RESULTS: A total of 2334 patients, including 295 influenza cases (47% vaccinated), 1175 influenza- and SARS-CoV-2-negative controls (53% vaccinated), and 864 influenza-negative and SARS-CoV-2-positive controls (49% vaccinated), were analyzed. Influenza VE was 26% (95% CI: -14% to 52%) among adults aged 18-64 years, -3% (-54% to 31%) among adults aged ≥65 years, and 50% (15-71%) among adults aged 18-64 years without immunocompromising conditions. Estimated VE decreased with inclusion of SARS-CoV-2-positive controls. CONCLUSIONS: During a season where influenza A(H3N2) was antigenically different from the vaccine virus, vaccination was associated with a reduced risk of influenza hospitalization in younger immunocompetent adults. However, vaccination did not provide protection in adults ≥65 years of age. Improvements in vaccines, antivirals, and prevention strategies are warranted

HIV-Associated Cryptococcal Meningitis: Bridging the Gap Between Developed and Resource-Limited Settings.

Cryptococcal meningitis is a major cause of HIV-associated morbidity and mortality worldwide. Most cases occur in low-income countries, where over half of patients die within 10 weeks of diagnosis compared to as few as 10 % of patients from developed countries. A host of factors, spanning the HIV care continuum, are responsible for this gap in treatment outcomes between developed and resource-limited settings. We explore factors responsible for this outcomes gap and describe low-cost, highly effective measures that can be implemented immediately to improve outcomes in resource-limited settings. We also explore health-system challenges that must be addressed to reduce mortality further, recent research in disease prevention, and novel short-course treatment regimens that, if efficacious, could be implemented in resource-limited settings where the cost of standard treatment regimens is currently prohibitive

Protection of messenger RNA vaccines against hospitalized coronavirus disease 2019 in adults over the first year following authorization in the United States

BACKGROUND: Coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization. METHODS: Case-control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states 11 March-15 December 2021, including COVID-19 case patients and reverse transcriptase-polymerase chain reaction-negative controls. We included adults who were unvaccinated or vaccinated with 2 doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (\u3c180 vs ≥180 days since dose 2) and continuous time modeled using restricted cubic splines. RESULTS: A total of 10 078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (interquartile range, 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE \u3c180 days was 90% (95% confidence interval [CI], 88-91) versus 82% (95% CI, 79-85) at ≥180 days (P \u3c .001). VE declined for Pfizer-BioNTech (88% to 79%, P \u3c .001) and Moderna (93% to 87%, P \u3c .001) products, for younger adults (18-64 years) (91% to 87%, P = .005), and for adults ≥65 years of age (87% to 78%, P \u3c .001). In models using restricted cubic splines, similar changes were observed. CONCLUSIONS: In a period largely predating Omicron variant circulation, effectiveness of 2 mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months

RANK/RANKL/OPG pathway: genetic associations with stress fracture period prevalence in elite athletes

Context: The RANK/RANKL/OPG signalling pathway is important in the regulation of bone turnover, with single nucleotide polymorphisms (SNPs) in genes within this pathway associated with bone phenotypic adaptations. Objective: To determine whether four SNPs associated with genes in the RANK/RANKL/OPG signalling pathway were associated with stress fracture injury in elite athletes. Design, Participants, and Methods: Radiologically confirmed stress fracture history was reported in 518 elite athletes, forming the Stress Fracture Elite Athlete (SFEA) cohort. Data were analysed for the whole group, and were sub-stratified into male and cases of multiple stress fracture group. Genotypes were determined using proprietary fluorescence-based competitive allele-specific PCR assays. Results: SNPs rs3018362 (RANK) and rs1021188 (RANKL) were associated with stress fracture injury (p<0.05). 8.1% of stress fracture group and 2.8% of the non-stress fracture group were homozygote for the rare allele of rs1021188. Allele frequency, heterozygotes and homozygotes for the rare allele of rs3018362 were associated with stress fracture period prevalence (p<0.05). Analysis of the male only group showed 8.2% of rs1021188 rare allele homozygotes to have suffered a stress fracture while 2.5% of the non-stress fracture group were homozygous. In cases of multiple stress fractures, homozygotes for the rare allele of rs1021188, and individuals possessing at least one copy of the rare allele of rs4355801 (OPG) were shown to be associated with stress fracture injury (p<0.05). Conclusions: The data support an association between SNPs in the RANK/RANKL/OPG signalling pathway and the development of stress fracture injury. The association of rs3018362 (RANK) and rs1021188 (RANKL) with stress fracture injury susceptibility supports their role in the maintenance of bone health, and offers potential targets for therapeutic interventions

Relationship of Foot Strike Pattern and Landing Impacts during a Marathon

Purpose: Foot strike patterns influence landing mechanics, with rearfoot strike (RFS) runners exhibiting higher impact loading than forefoot strike (FFS) runners. The few studies that included midfoot strike (MFS) runners have typically grouped them together with FFS. Additionally, most running studies have been conducted in laboratories. Advances in wearable technology now allow the measurement of runners' mechanics in their natural environment. The purpose of this study was to examine the relationship between foot strike pattern and impacts across a marathon race. Methods: 222 healthy runners (119 M, 103 F; 44.1±10.8 years) running a marathon race were included. A treadmill assessment was undertaken to determine foot strike pattern (FSP). An ankle mounted accelerometer recorded tibial shock (TS) over the course of the marathon. TS was compared between RFS, MFS and FFS. Correlations between speed and impacts were examined between FSPs. TS was also compared at the 10km and 40km race points. Results: RFS and MFS runners exhibited similar TS (12.24±3.59g vs. 11.82±2.68g, p=0.46) that was significantly higher (p<0.001 and p<0.01, respectively) than FFS runners (9.88±2.51g). Additionally, TS increased with speed for both RFS (r=0.54, p=0.01) and MFS (r=0.42, p=0.02) runners, but not FFS (r=0.05, p=0.83). Finally, both speed (p<0.001) and TS (p<0.001) were reduced between the 10km and 40km race points. However, when normalized for speed, TS was not different (p= 0.84). Conclusions: RFS and MFS exhibit higher TS than FFS. Additionally, RFS and MFS increase TS with speed, while FFS do not. These results suggest that the impact loading of MFS is more like RFS than FFS. Finally, TS, when normalized for speed, is similar between the beginning and end of the race

Neurological Sequelae of Adult Meningitis in Africa: A Systematic Literature Review.

The high human immunodeficiency virus (HIV) prevalence in sub-Saharan Africa has markedly changed the epidemiology and presentation of adult meningitis. We conducted a systematic review using PubMed, Embase, Ovid, CENTRAL, and African Index Medicus to identify studies in Africa with data on neurological outcomes in adults after meningitis. We found 22 articles meeting inclusion criteria. From 4 studies with predominately pneumococcal meningitis, a median of 19% of survivors experienced hearing loss up to 40 days. Two studies of cryptococcal meningitis evaluated 6- to 12-month outcomes; in one, 41% of survivors had global neurocognitive impairment and 20% severe impairment at 1 year, and in a second 30% of survivors had intermediate disability and 10% severe disability at 6 months. A single small study of patients with tuberculosis/HIV found marked disability in 20% (6 of 30) at 9 months. Despite the high burden of meningitis in sub-Saharan Africa, little is known about neurological outcomes of patients with HIV-associated meningitides

Prática de artes marciais e densidade mineral óssea em adolescentes de ambos os sexos

The purpose of this study was to analyze the relationship between martial arts practice (judo, karate and kung-fu) and bone mineral density in adolescents.METHODS: The study was composed of 138 (48 martial arts practitioners and 90 non-practitioners) adolescents of both sexes, with an average age of 12.6 years. Bone mineral density was measured using Dual-Energy X-ray Absorptiometry in arms, legs, spine, trunk, pelvis and total. Weekly training load and previous time of engagement in the sport modality were reported by the coach. Partial correlation tested the association between weekly training load and bone mineral density, controlled by sex, chronological age, previous practice and somatic maturation. Analysis of covariance was used to compare bone mineral density values according to control and martial arts groups, controlled by sex, chronological age, previous practice and somatic maturation. Significant relationships between bone mineral density and muscle mass were inserted into a multivariate model and the slopes of the models were compared using the Student t test (control versus martial art).RESULTS: Adolescents engaged in judo practice presented higher values of bone mineral density than the control individuals (p-value=0.042; Medium Effect size [Eta-squared=0.063]), while the relationship between quantity of weekly training and bone mineral density was significant among adolescents engaged in judo (arms [r=0.308] and legs [r=0.223]) and kung-fu (arms [r=0.248] and spine [r=0.228]).CONCLUSIONS: Different modalities of martial arts are related to higher bone mineral density in different body regions among adolescents.O objetivo desse estudo foi analisar a relac¸ão entre a prática de artes marciais (judô, karatê e kung-fu) e a densidade mineral óssea em adolescentes. Métodos: O estudo foi composto por 138 adolescentes (48 praticantes de artes marciais e 90 não praticantes) de ambos os sexos, com idade média de 12,6 anos. A densidade mineral óssea foi medida usando absortometria radiológica de dupla energia em brac¸os, pernas, coluna, tronco, pelve e total. A carga de treinamento semanal e o tempo anterior de envolvimento na modalidade esportiva foram relatados pelo treinador. A correlac¸ão parcial testou a associac¸ão entre a carga semanal de treinamento e a densidade mineral óssea, controlada para sexo, idade cronológica, prática anterior e maturac¸ão somática. A análise de covariância foi utilizada para comparar os valores de densidade mineral óssea de acordo com os grupos controle e de artes marciais, controlados para sexo, idade cronológica, prática anterior e maturac¸ão somática. Associac¸ões significativas entre a densidade mineral óssea e a massa muscular foram inseridas em um modelo multivariado e as inclinac¸ões dos modelos foram comparadas usando o teste t de Student (controle versus arte marcial). Resultados: Os adolescentes envolvidos na prática de judô apresentaram valores maiores de densidade mineral óssea do que os indivíduos do grupo controle (p=0,042; tamanho de efeito médio [eta-quadrado=0,063]), enquanto a relac¸ão entre a quantidade de treinos semanais e a densidade mineral óssea foi significativa entre os adolescentes praticantes de judô (brac¸os [r=0,308] e pernas [r=0,223]) e kung-fu (brac¸os [r=0,248] e coluna [r=0,228]). Conclusões: Diferentes modalidades de artes marciais estão relacionadas com maior densidade mineral óssea em diferentes regiões do corpo em adolescentes