Prediabetes as a risk factor for all-cause and cause-specific mortality: a prospective analysis of 115,919 adults without diabetes in Mexico City.

BACKGROUND: Prediabetes has been associated with increased all-cause and cardiovascular mortality. However, no large-scale studies have been conducted in Mexico or Latin America examining these associations. METHODS: We analyzed data from 115,919 adults without diabetes (diagnosed or undiagnosed) aged 35-84 years who participated in the Mexico City Prospective Study between 1998 and 2004. Participants were followed until January 1st, 2021 for cause-specific mortality. We defined prediabetes according to the American Diabetes Association (ADA, HbA1c 5.7% to 6.4%) and the International Expert Committee (IEC, HbA1c 6.0-6.4%) definitions. Cox regression adjusted for confounders was used to estimate all-cause and cause-specific mortality rate ratios (RR) at ages 35-74 years associated with prediabetes. FINDINGS: During 2,085,392 person-years of follow-up (median in survivors 19 years), there were 6,810 deaths at ages 35-74, including 1,742 from cardiovascular disease, 892 from renal disease and 108 from acute diabetic crises. Of 110,405 participants aged 35-74 years at recruitment, 28,852 (26%) had ADA-defined prediabetes and 7,203 (7%) had IEC-defined prediabetes. Compared with those without prediabetes, individuals with prediabetes had higher risk of all-cause mortality at ages 35-74 years (RR 1.13, 95% CI 1.07-1.19 for ADA-defined prediabetes and RR 1.28, 1.18-1.39 for IEC-defined prediabetes), as well as increased risk of cardiovascular mortality (RR 1.22 [1.10-1.35] and 1.42 [1.22-1.65], respectively), renal mortality (RR 1.35 [1.08-1.68] and 1.69 [1.24-2.31], respectively), and death from an acute diabetic crisis (RR 2.63 [1.76-3.94] and 3.43 [2.09-5.62], respectively). RRs were larger at younger than at older ages, and similar for men compared to women. The absolute excess risk associated with ADA and IEC-defined prediabetes at ages 35-74 accounted for6% and 3% of cardiovascular deaths respectively, 10% and 5% of renal deaths respectively, and 31% and 14% of acute diabetic deaths respectively. INTERPRETATION: Prediabetes is a significant risk factor for all-cause, cardiovascular, renal, and acute diabetic deaths in Mexican adults. Identification and timely management of individuals with prediabetes for targeted risk reduction could contribute to reducing premature mortality from cardiometabolic causes in this population. FUNDING: Wellcome Trust, the Mexican Health Ministry, the National Council of Science and Technology for Mexico, Cancer Research UK, British Heart Foundation, UK Medical Research Council. Instituto Nacional de Geriatría (Mexico City).

Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease.

Obesity is a major risk factor for many common diseases and has a substantial heritable component. To identify new genetic determinants, we performed exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare loss-of-function variants in two genes (BSN and APBA1) with effects substantially larger than those of well-established obesity genes such as MC4R. In contrast to most other obesity-related genes, rare variants in BSN and APBA1 were not associated with normal variation in childhood adiposity. Furthermore, BSN protein-truncating variants (PTVs) magnified the influence of common genetic variants associated with BMI, with a common variant polygenic score exhibiting an effect twice as large in BSN PTV carriers than in noncarriers. Finally, we explored the plasma proteomic signatures of BSN PTV carriers as well as the functional consequences of BSN deletion in human induced pluripotent stem cell-derived hypothalamic neurons. Collectively, our findings implicate degenerative processes in synaptic function in the etiology of adult-onset obesity.

A Difficult-To-Diagnose Case of American Tegumentary Leishmaniasis.

This case report presents a difficult-to-diagnose case of American tegumentary leishmaniasis (ATL) caused by Leishmania (Viannia) guyanensis in a 24-year-old Hispanic male with a travel history to the Panama jungle, an endemic region for tropical infectious diseases. The patient initially presented with persistent skin lesions that progressed to abscesses with ulceration. Despite negative initial diagnostic tests, including microbiological investigations and histopathological examination, a comprehensive diagnostic workup and subsequent polymerase chain reaction (PCR) confirmed the presence of Leishmania parasites. This case underscores the need to consider tropical infectious diseases despite initial negative tests. Accurate species identification is vital for proper drug treatment, with miltefosine as an emerging option. Early, precise diagnosis and tailored management are essential for successful treatment. This report emphasizes the significance of conducting a comprehensive diagnostic workup, including PCR, in individuals with a history of travel to endemic regions, to accurately diagnose and effectively manage complex infectious diseases.

Emphysematous Pyelonephritis, Emphysematous Cystitis, and Emphysematous Ureteritis: A Case Report.

Emphysematous urinary tract infections (EUTIs) are rare, severe, and suppurative infections affecting various parts of the urinary tract. We report a case of a 75-year-old male presenting with hematuria and generalized weakness with uncontrolled diabetes mellitus (DM) and hypertension. He tested positive for COVID-19 on the second day of hospital admission. A non-contrast-enhanced CT of the abdomen and pelvis revealed gas within the left renal parenchyma, walls of the left ureter, and urinary bladder, establishing the diagnosis of EUTIs. The patient was treated using intravenous antibiotics without any surgical intervention, and four weeks later was stable and transported to long-term acute care (LTAC) facility. DM is the most common risk factor for the development of EUTIs and Escherichia coli is the most common causative pathogen.

Did a 3800-year-old Mw ~9.5 earthquake trigger major social disruption in the Atacama Desert?

Early inhabitants along the hyperarid coastal Atacama Desert in northern Chile developed resilience strategies over 12,000 years, allowing these communities to effectively adapt to this extreme environment, including the impact of giant earthquakes and tsunamis. Here, we provide geoarchaeological evidence revealing a major tsunamigenic earthquake that severely affected prehistoric hunter-gatherer-fisher communities ~3800 years ago, causing an exceptional social disruption reflected in contemporary changes in archaeological sites and triggering resilient strategies along these coasts. Together with tsunami modeling results, we suggest that this event resulted from a ~1000-km-long megathrust rupture along the subduction contact of the Nazca and South American plates, highlighting the possibility of Mw ~9.5 tsunamigenic earthquakes in northern Chile, one of the major seismic gaps of the planet. This emphasizes the necessity to account for long temporal scales to better understand the variability, social effects, and human responses favoring resilience to socionatural disasters.

Sequencing of 640,000 exomes identifies GPR75 variants associated with protection from obesity.

Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors (CALCR, MC4R, GIPR, GPR151, and GPR75). Protein-truncating variants in GPR75 were observed in ~4/10,000 sequenced individuals and were associated with 1.8 kilograms per square meter lower BMI and 54% lower odds of obesity in the heterozygous state. Knock out of Gpr75 in mice resulted in resistance to weight gain and improved glycemic control in a high-fat diet model. Inhibition of GPR75 may provide a therapeutic strategy for obesity.

Seismic rate variations prior to the 2010 Maule, Chile MW 8.8 giant megathrust earthquake.

The MW 8.8 Maule earthquake is the largest well-recorded megathrust earthquake reported in South America. It is known to have had very few foreshocks due to its locking degree, and a strong aftershock activity. We analyze seismic activity in the area of the 27 February 2010, MW 8.8 Maule earthquake at different time scales from 2000 to 2019. We differentiate the seismicity located inside the coseismic rupture zone of the main shock from that located in the areas surrounding the rupture zone. Using an original spatial and temporal method of seismic comparison, we find that after a period of seismic activity, the rupture zone at the plate interface experienced a long-term seismic quiescence before the main shock. Furthermore, a few days before the main shock, a set of seismic bursts of foreshocks located within the highest coseismic displacement area is observed. We show that after the main shock, the seismic rate decelerates during a period of 3 years, until reaching its initial interseismic value. We conclude that this megathrust earthquake is the consequence of various preparation stages increasing the locking degree at the plate interface and following an irregular pattern of seismic activity at large and short time scales.

Diversity analysis of 80,000 wheat accessions reveals consequences and opportunities of selection footprints.

Undomesticated wild species, crop wild relatives, and landraces represent sources of variation for wheat improvement to address challenges from climate change and the growing human population. Here, we study 56,342 domesticated hexaploid, 18,946 domesticated tetraploid and 3,903 crop wild relatives in a massive-scale genotyping and diversity analysis. Using DArTseqTM technology, we identify more than 300,000 high-quality SNPs and SilicoDArT markers and align them to three reference maps: the IWGSC RefSeq v1.0 genome assembly, the durum wheat genome assembly (cv. Svevo), and the DArT genetic map. On average, 72% of the markers are uniquely placed on these maps and 50% are linked to genes. The analysis reveals landraces with unexplored diversity and genetic footprints defined by regions under selection. This provides fertile ground to develop wheat varieties of the future by exploring specific gene or chromosome regions and identifying germplasm conserving allelic diversity missing in current breeding programs.

Familial mesial temporal lobe epilepsy in Mexico: Inheritance pattern and clinical features.

PURPOSE: The objectives of this study were to determine the inheritance pattern by which familial mesial temporal lobe epilepsy (FMTLE) is segregated in Mexican families, and to identify if there was an association between the clinical characteristics and the inheritance pattern. METHOD: We included a total of 25 families with two or more members affected with MTLE during two years and elaborated a family pedigree for each family. The inheritance pattern was classified as autosomal dominant (AD) or autosomal recessive (AR), considering the affected members. We used statistical analysis association and differences between clinical characteristics and inheritance patterns. RESULTS: The affected families with the AD pattern were 15.7 fold times more likely to start seizures at 5 years of age or earlier than families with AR pattern, OR = 15.7 (IC 95% = 1.9-128.9). We observed a predominance and greater déjà vu association (64.4% vs 31.3%; p = 0.021), OR = 3.9 (CI 95% = 1.1-13.5) in patients with AD versus AR pattern. Finally, we identified that patients with AD pattern had a likelihood of presenting emotional alterations 5.6 times higher than AR (OR = 5.6, IC = 1.1-27.5). CONCLUSION: FMTLE is a heterogeneous syndrome, both phenotypically and genotypically; thus, our findings may be helpful for clinical use to perform an early diagnosis, to provide timely treatment, and to prevent comorbidities associated to this disease. However, in order to identify the possible genetic causes underlying these inheritance patterns, the use of molecular studies is necessary.

Let-7c overexpression inhibits dengue virus replication in human hepatoma Huh-7 cells.

MicroRNAs (miRNAs) constitute an important class of non-coding RNA implicated in gene expression regulation. More than 1900 miRNA molecules have been identified in humans and their modulation during viral infection and it is recognized to play a role in latency regulation or in establishing an antiviral state. The liver cells are targets during DENV infection, and alteration of liver functions contributes to severe disease. In this work the miRNAs expression profile of the human hepatoma cell line, Huh-7, infected with DENV-2 was determined using microarray and real-time PCR. Let-7c is one of the miRNAs up-regulated during DENV infection in the hepatic Huh-7 as well as in the macrophage-monocytic cell line U937-DC-SIGN. Let-7c overexpression down-regulates both DENV-2 and DENV-4 infection. Additionally, we found that the transcription factor BACH1, a let-7c target, is also down-regulated during DENV infection. In accordance with this finding, HO-1, the main responsive factor of BACH1 was found up-regulated. The up-regulation of HO-1 may contribute to the stress oxidative response in infected cells.

Parasitic wasp responses to symbiont-based defense in aphids.

BACKGROUND: Recent findings indicate that several insect lineages receive protection against particular natural enemies through infection with heritable symbionts, but little is yet known about whether enemies are able to discriminate and respond to symbiont-based defense. The pea aphid, Acyrthosiphon pisum, receives protection against the parasitic wasp, Aphidius ervi, when infected with the bacterial symbiont Hamiltonella defensa and its associated bacteriophage APSE (Acyrthosiphon pisum secondary endosymbiont). Internally developing parasitoid wasps, such as A. ervi, use maternal and embryonic factors to create an environment suitable for developing wasps. If more than one parasitoid egg is deposited into a single aphid host (superparasitism), then additional complements of these factors may contribute to the successful development of the single parasitoid that emerges. RESULTS: We performed experiments to determine if superparasitism is a tactic allowing wasps to overcome symbiont-mediated defense. We found that the deposition of two eggs into symbiont-protected aphids significantly increased rates of successful parasitism relative to singly parasitized aphids. We then conducted behavioral assays to determine whether A. ervi selectively superparasitizes H. defensa-infected aphids. In choice tests, we found that A. ervi tends to deposit a single egg in uninfected aphids, but two or more eggs in H. defensa-infected aphids, indicating that oviposition choices may be largely determined by infection status. Finally, we identified differences in the quantity of the trans-ß-farnesene, the major component of aphid alarm pheromone, between H. defensa-infected and uninfected aphids, which may form the basis for discrimination. CONCLUSIONS: Here we show that the parasitic wasp A. ervi discriminates among symbiont-infected and uninfected aphids, and changes its oviposition behavior in a way that increases the likelihood of overcoming symbiont-based defense. More generally, our results indicate that natural enemies are not passive victims of defensive symbionts, and that an evolutionary arms race between A. pisum and the parasitoid A. ervi may be mediated by a bacterial symbiosis.

HPV-16 and HLA-DRB1 alleles are associated with cervical carcinoma in Mexican Mestizo women.

The aim of this report was to investigate the contribution of HLA-DRB1/DQB1 alleles to the expression of cervical cancer (CC) and squamous intraepithelial lesion (SIL) in Mexican patients. A total of 257 women were included in the study: 61with low-grade squamous intraepithelial lesions (LSIL), 30 with high-grade (HSIL), 73 with CC and 93 healthy females. All were Mexican Mestizos. For HLA class II typing, PCR-SSOP methodology was used. HPV-16 viral DNA was detected by PCR with specific primers for E6-E7 region. HPV-16 was found in 52% of the patients with CC as well as in 19% of women with HSIL and in 12.5% of females with LSIL. HLA-DRB1∗04:03 (OR = 5.88) was found increased in patients with HSIL as compared with controls, although significance (p = 0.04) was lost after correction (pc =NS). HLA-DRB1∗04:03 seems to influence the risk for developing HSIL, disregarding the presence of HPV-16. HLA-DRB1∗01:01 (OR = 0.12; p = 0.01) may confer protection to the development of CC. An analysis performed stratifying by the presence of HPV-16 infection showed that the frequency of HLA-DRB1∗04:07 (OR = 2.71) was increased in CC patients infected with HPV-16, confirming that the HLA association is HPV dependent. These results shed light on the influence that this virus may have in the expression of CC in the susceptible host. Genetic background is, therefore, a crucial factor in understanding the etiopathogenesis of CC in HPV-positive patients.

Population dynamics of defensive symbionts in aphids.

Vertically transmitted micro-organisms can increase in frequency in host populations by providing net benefits to hosts. While laboratory studies have identified diverse beneficial effects conferred by inherited symbionts of insects, they have not explicitly examined the population dynamics of mutualist symbiont infection within populations. In the pea aphid, Acyrthosiphon pisum, the inherited facultative symbiont, Hamiltonella defensa, provides protection against parasitism by the wasp, Aphidius ervi. Despite a high fidelity of vertical transmission and direct benefits of infection accruing to parasitized aphids, Hamiltonella remains only at intermediate frequencies in natural populations. Here, we conducted population cage experiments to monitor the dynamics of Hamiltonella and of another common A. pisum symbiont, Serratia symbiotica, in the presence and absence of parasitism. We also conducted fitness assays of Hamiltonella-infected aphids to search for costs to infection in the absence of parasitism. In the population cages, we found that the frequency of A. pisum infected with Hamiltonella increased dramatically after repeated exposure to parasitism by A. ervi, indicating that selection pressures from natural enemies can lead to the increase of particular inherited symbionts in insect populations. In our laboratory fitness assays, we did not detect a cost to infection with Hamiltonella, but in the population cages not exposed to parasitism, we found a significant decline in the frequency of both Hamiltonella and Serratia. The declining frequencies of Hamiltonella-infected aphids in population cages in the absence of parasitism indicate a probable cost to infection and may explain why Hamiltonella remains at intermediate frequencies in natural populations.

How can the University of Hawai'i meet needs for public health education? Results of a students' needs assessment.

INTRODUCTION: A strong public health workforce is necessary to maintain the health and well-being of any community. Currently, the ability of the public health workforce to meet demand is being challenged in Hawai'i and the Pacific. This is due, in part, to the downsizing of the public health program at the University of Hawai'i (UH) in the year 2000. Knowing the current perceptions of the community in regards to public health and identifying ways to attract more students to public health are essential in reversing this trend. MATERIALS AND METHODS: Students from a class on needs assessment and program planning at the UH Department of Public Health Sciences assessed public health education needs. The class first conducted a literature review, focus groups, and interviews to inform the development of an on-line survey. The survey was sent to 200 individuals, including current public health students, faculty, workers, employers, and alumni. RESULTS: Of the 200 individuals invited to participate in the on-line survey, 128 (64%) responded. Almost half of the respondents were >50 years of age, and another 19% were between ages 41 and 50. Of the 118 who responded to this question, 85 had degrees in public health (80%from UH), and 62% had worked in public health for at least 10 years. However, only 50% of the total respondents knew that UH Masters of Public Health (MPH) and the Masters of Science (MS) programs were accredited. Forty percent or more of public health workers noted continuing education needs in 1) policy development and program planning skills, 2) analytical skills, 3) leadership and systems thinking skills, and 4) financial planning and management skills. Fully 43 of the respondents would consider applying to a DrPH program at UH, and 27 public health workers without an MPH would consider pursuing one. However potential students noted lack of time and timing of classes as barriers to attending school. Specific ideas for attracting students to public health were provided. Respondents also called for a greater commitment to public health from top leadership at UH and in Hawai'i. DISCUSSION: Findings confirm a need for a strong public health education program in Hawai'i and a lack of awareness about the MPH and MS programs at UH. Expanding options and opportunities for public health education will require better marketing and a cohesive commitment to public health education at UH.

[Human papilloma virus and cervical cancer]. / Virus del papiloma humano y cáncer del cuello uterino.

Cervical cancer (CC) is the second most common cause of death from cancer among women worldwide and about 80% of the half of million new cases detected every year, occurs in less-developed countries. Human papillomavirus is an obligate factor for the development of CC, since some HPVtype are detected in 100% of CC. HPV16 and HPV18 are the most common viral types, accounting for about 50% and 15% of CC, respectively. HPV infection is the most common sexual transmitted infection, with an estimated prevalence of about 2-44% among sexually active young women. However, only a very small fraction of these infections evolve to CC (1-2 out of 1000), indicating that some other factors should be important in the evolution of the disease. Preventive vaccines against HPVs 16 and 18 have been developed, and in phase III clinical trials they have demonstrated 100% efficacy for prevention of persistent infection and high risk cervical squamous intraepithelial neoplasias positive for these HPV types, suggesting that these vaccines, if made widely available, will dramatically reduce the burden of CC.

Topiramate in the prophylactic treatment of migraine in children.

We present a prospective case series of 24 children diagnosed with migraine refractory to prophylactics and treated for 4 months with topiramate as the only prophylactic drug. At the final visit, the mean topiramate dose was 3.5 +/- 1.7 mg/kg/day. Nearly all patients (87.5%) reported a shorter duration of attacks, and the average pain intensity was rated as mild by 14 patients (58.3%). Eight (33.3%) patients had adverse events, none of which were serious. In our sample of pediatric patients, topiramate was effective for the prophylactic treatment of migraine in children. It was well tolerated at the doses used for titration and maintenance. Controlled trials are needed to verify the efficacy of topiramate for migraine in children.