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In 2012, we witnessed a resurgence of West Nile virus (WNV) in the United States, with the largest outbreak of human cases reported since 2003. WNV is now endemic and will continue to produce epidemics over time, therefore defining the long-term consequences of WNV infection is critical. Over a period of eight years, we prospectively followed a cohort of 157 WNV-infected subjects in the Houston metropolitan area to observe recovery over time and define the long-term clinical outcomes. We used survival analysis techniques to determine percentage of recovery over time and the effects of demographic and co-morbid conditions on recovery. We found that 40% of study participants continued to experience symptoms related to their WNV infection up to 8 years later. Having a clinical presentation of encephalitis and being over age 50 were significantly associated with prolonged or poor recovery over time. Since the health and economic impact as a result of prolonged recovery, continued morbidity, and related disability is likely substantial in those infected with WNV, future research should be aimed at developing effective vaccines to prevent illness and novel therapeutics to minimize morbidity, mortality, and long-term complications from infection.

Background. Although the biological basis for the increased susceptibility of diabetic patients to tuberculosis remains unclear, the world is undergoing a type 2 diabetes pandemic. We hypothesize that chronic hyperglycemia leads to immunocompromise that facilitates progression to active tuberculosis. To assess this possibility, we determined whether patients with tuberculosis and diabetes (particularly those with chronic hyperglycemia), compared with patients with tuberculosis who did not have diabetes, presented altered cytokine responses to a mycobacterial antigen. Methods. Samples of whole blood from patients with tuberculosis and diabetes and from patients with tuberculosis who did not have diabetes was stimulated in vitro with purified protein derivative from Mycobacterium tuberculosis. We then determined whether there was an association between the levels of innate and adaptive cytokines secreted in response to the antigen and diabetes status, or diabetes with chronic hyperglycemia (measured by glycosylated hemoglobin level), after controlling for possible confounders. Results. Innate and type 1 cytokine responses were significantly higher in patients with tuberculosis who had diabetes than in nondiabetic control subjects. The effect was consistently and significantly more marked in diabetic patients with chronic hyperglycemia. Conclusions. These data provide preliminary evidence that type 2 diabetes, especially type 2 diabetes involving chronic hyperglycemia, is associated with an altered immune response to M. tuberculosis. More-detailed knowledge of the underlying mechanisms should focus on the effect of chronic hyperglycemia on the immune response to help in understanding the enhanced susceptibility of diabetic patients to tuberculosis.

There are few carefully-designed studies investigating the safety of individual probiotics approved under Investigational New Drug policies. The primary aim of this prospective, double-blind placebo-controlled trial was to investigate if daily treatment of adults with Lactobacillus reuteri DSM 17938 (LR) for 2 months is safe and well-tolerated. Our secondary aim was to determine if LR treatment has immune effects as determined by regulatory T cell percentages, expression of toll-like receptors (TLR)-2 and -4 on circulating peripheral blood mononuclear cells (PMBCs), cytokine expression by stimulated PBMC, and intestinal inflammation as measured by fecal calprotectin. Forty healthy adults were randomized to a daily dose of 5 × 10(8) CFUs of LR (n = 30) or placebo (n = 10) for 2 months. Participants completed a daily diary card and had 7 clinic visits during treatment and observation. There were no severe adverse events (SAEs) and no significant differences in adverse events (AEs). There were no differences in PBMC subclasses, TLRs, or cytokine expression after treatment. The probiotic-treated group had a significantly higher fecal calprotectin level than the placebo group after 2 months of treatment: 50 µg/g (IQR 24-127 µg/g) vs. 17 µg/g (IQR 11-26 µg/g), p = 0.03, although values remained in the normal clinical range (0-162.9 µg/g). LR vials retained >10(8) CFUs viable organisms/ml. LR is safe and well tolerated in adults, without significant changes in immunologic markers. There was a small but significant increase in fecal calprotectin, perhaps indicating some element of immune recognition at the intestinal level. Clinical Trials.gov NCT00922727.

Type 2 diabetes patients (DM2) have a higher risk of tuberculosis (TB) that may be attributed to functional defects in their mononuclear phagocytes given the critical role of these cells in Mycobacterium tuberculosis containment. Our previous findings suggest that monocytes from DM2 have reduced association with serum-opsonized M. tuberculosis. To determine if this alteration is due to defects in phagocytosis via complement or Fc-gamma receptors (FcγRs), in this study we evaluated the uptake of sheep red blood cells coated with IgG or complement, respectively, by monocytes from individuals with and without DM2. We found that chronic hyperglycemia was significantly associated with reduced phagocytosis via either receptor by univariable and multivariable analyses. This defect was independent of host serum opsonins and flow cytometry data indicated this was not attributed to reduced expression of these phagocytic receptors on DM2 monocytes. The positive correlation between both pathways (R = 0.64; p = 0.003) indicate that monocytes from individuals with chronic hyperglycemia have a defect in the two predominant phagocytic pathways of these cells. Given that phagocytosis is linked to activation of effector mechanisms for bacterial killing, it is likely that this defect is one factor contributing to the higher susceptibility of DM2 patients to pathogens like M. tuberculosis.

Global and regional cortical thicknesses based on T1-weighted magnetic resonance images acquired at 1.5 T and 3 T were measured on a relatively large cohort of 295 subjects using FreeSurfer software. Multivariate regression analysis was performed using Pillai's trace test to determine significant differences in cortical thicknesses measured at these two field strengths. Our results indicate that global cortical thickness is not affected by the field strength or gender. In contrast, the regional cortical thickness was observed to be field dependent. Specifically, the cortical thickness in regions such as parahippocampal, superior temporal, precentral and posterior cingulate is thicker at 3 T than at 1.5 T. In contrast regions such as cuneus and pericalcarine showed higher cortical thickness at 1.5 T than at 3 T. These differences appear to be age-dependent. The differences in regional cortical thickness between field strengths were similar in both genders. Further, male vs. female differences in regional cortical thickness were observed only at 1.5 T and not at 3 T. Our results indicate that magnetic field strength has a significant effect on the estimation of regional, but not global, cortical thickness. In addition, the pulse sequence, scanner type, and spatial resolution do not appear to have significant effect on the measured cortical thickness.

Globally half of all diabetes mellitus is undiagnosed. We sought to determine the extent and characteristics of undiagnosed type 2 diabetes mellitus and pre-diabetes in Mexican Americans residing in the United States. This disadvantaged population with 50% lifetime risk of diabetes is a microcosm of the current pandemic. We accessed baseline data between 2004 and 2014 from 2,838 adults recruited to our Cameron County Hispanic Cohort (CCHC); a two-stage randomly selected 'Framingham-like' cohort of Mexican Americans on the US Mexico border with severe health disparities. We examined prevalence, risk factors and metabolic health in diagnosed and undiagnosed diabetes and pre-diabetes. Two thirds of this Mexican American population has diabetes or pre-diabetes. Diabetes prevalence was 28.0%, nearly half undiagnosed, and pre-diabetes 31.6%. Mean BMI among those with diabetes was 33.5 kg/m2 compared with 29.0 kg/m2 for those without diabetes. Significant risk factors were low income and educational levels. Most with diabetes had increased waist/hip ratio. Lack of insurance and access to health services played a decisive role in failure to have diabetes diagnosed. Participants with undiagnosed diabetes and pre-diabetes had similar measures of poor metabolic health similar but generally not as severe as those with diagnosed diabetes. More than 50% of a minority Mexican American population in South Texas has diabetes or pre-diabetes and is metabolically unhealthy. Only a third of diabetes cases were diagnosed. Sustained efforts are imperative to identify, diagnose and treat individuals in underserved communities.

Soon after commencement of the SARS-CoV-2 disease outbreak of 2019 (COVID-19), it became evident that the receptor-binding domain of the viral spike protein is the target of neutralizing antibodies that comprise a critical element of protective immunity to the virus. This study addresses the relative lack of information regarding actual antibody concentrations and binding affinities in convalescent plasma (CP) samples from COVID-19 patients and extends these analyses to post-vaccination (PV) samples to estimate protective IgG antibody (Ab) levels. A direct enzyme-linked immunosorbent assay (ELISA) was used to measure IgG anti-spike protein (SP) antibodies (Abs) relative to human chimeric spike S1 Ab standards. Microplate wells were coated with recombinant SP. Affinities of Ab binding to SP were determined by previously described methods. Binding affinities were also determined in an RBD-specific sandwich ELISA. Two indices of protective immunity were determined as permutations of Ab molar concentration divided by affinity as dissociation constant (K D ). The range and geometric means of Ab concentrations in 21 CP and 21 PV samples were similar and a protective Ab level of 7.5 μg/ml was determined for the latter population, based on 95% of the normal distribution of the PV population. A population (n = 21) of plasma samples from individuals receiving only one vaccination with the BNT162b2 or mRNA-1273 vaccines (PtV) exhibited a geometric mean Ab concentration significantly (p < 0.03) lower than the PV population. The results of this study have implications for future vaccine development, projection of protective efficacy duration, and understanding of the immune response to SARS-CoV-2 infection.

Background Jamaican soil is abundant in heavy metals including mercury (Hg). Due to availability and ease of access, fish is a traditional dietary component in Jamaica and a significant source of Hg exposure. Mercury is a xenobiotic and known neuro-toxicant that affects children's neurodevelopment. Human glutathione S-transferase (GST) genes, including GSTT1, GSTM1 , and GSTP1 , affect Hg conjugation and elimination mechanisms. Methods In this exposure assessment study we used data from 375 typically developing (TD) 2–8-year-old Jamaican children to explore the association between environmental Hg exposure, GST genes, and their interaction effects on blood Hg concentrations (BHgCs). We used multivariable general linear models (GLMs). Results We identified the child’s age, consumption of saltwater fish, canned fish (sardine, mackerel), string beans, grain, and starches (pasta, macaroni, noodles) as the environmental factors significantly associated with BHgCs (all P  < 0.05). A significant interaction between consumption of canned fish (sardine, mackerel) and GSTP1 in relation to BHgC using either a co-dominant or recessive genetic model (overall interaction P  = 0.01 and P  < 0.01, respectively) indicated that consumption of canned fish (sardine, mackerel) was significantly associated with higher mean BHgC only among children with the GSTP1 Ile105Val, Ile/Ile [Ratio of mean Hg (95% CI) = 1.59 (1.09, 2.32), P  = 0.02] and Ile/Val [Ratio of mean Hg (95% CI) = 1.46 (1.12, 1.91), P  = 0.01] genotypes. Conclusions Since this is the first study from Jamaica to report these findings, replication in other populations is recommended.

Stroke is the second leading cause of mortality globally with higher burden and younger age in low‐middle income countries (LMICs) than high‐income countries (HICs). However, it is unclear to what extent differences in healthcare access and quality (HAQ) and prevalence of risk factors between LMICs and HICs contribute to younger age of stroke in LMICs. In this systematic review, we conducted meta‐analysis of 67 articles and compared the mean age of stroke between LMICs and HICs, before and after adjusting for HAQ index. We also compared the prevalence of main stroke risk factors between HICs and LMICs. The unadjusted mean age of stroke in LMICs was significantly lower than HICs (63.1 vs. 68.6), regardless of gender (63.9 vs. 66.6 among men, and 65.6 vs. 70.7 among women) and whether data were collected in population‐ (64.7 vs. 69.5) or hospital‐based (62.6 vs. 65.9) studies (all p < 0.01). However, after adjusting for HAQ index, the difference in the mean age of stroke between LMICs and HICs was not significant (p ≥ 0.10), except among women (p = 0.048). In addition, while the median prevalence of hypertension in LMICs was 23.4% higher than HICs, the prevalence of all other risk factors was lower in LMICs than HICs. Our findings suggest a much larger contribution of HAQ to the younger mean age of stroke in LMICs, as compared with other potential factors. Additional studies on stroke care quality and accessibility are needed in LMICs.

To estimate the contribution of clinically-confirmed diabetes mellitus to tuberculosis (TB) rates in communities where both diseases are prevalent as a way to identify opportunities for TB prevention among diabetic patients. This is a prospective study in which TB patients ≥ 20 years old at TB clinics in the Texas-Mexico border were tested for diabetes. The risk of tuberculosis attributable to diabetes was estimated from statistics for the corresponding adult population. The prevalence of diabetes among TB patients was 39% in Texas and 36% in Mexico. Diabetes contributed 25% of the TB cases studied, whereas human immunodeficiency virus (HIV) infection contributed 5% or fewer. Among TB patients, fewer Mexicans than Texans were aware that they had diabetes before this study (4% and 19%, respectively). Men were also less frequently aware than women that they had diabetes (P = 0.03). Patients who knew that they had diabetes before the study had an 8-year history of the disease, on average, before being diagnosed with TB. Patients with diabetes are at higher risk of contracting TB than non-diabetic patients. Integrating TB and diabetes control programmes worldwide would facilitate TB prevention among diabetes patients and increase the number of diabetics who learn of their condition, particularly among males. Such a strategy would lead to earlier case detection and improve the management of both TB and diabetes.