Hierarchical glycolytic pathways control the carbohydrate utilization regulator in human gut .

Human dietary choices control the gut microbiome. Industrialized populations consume abundant glucose and fructose, resulting in microbe-dependent intestinal disorders. Simple sugars inhibit the carbohydrate utilization regulator (Cur), a transcription factor in the prominent gut bacterial phylum, .

Dietary sugars silence the master regulator of carbohydrate utilization in human gut Bacteroides species.

The mammalian gut microbiota is a critical human health determinant with therapeutic potential for remediation of many diseases. The host diet is a key factor governing the gut microbiota composition by altering nutrient availability and supporting the expansion of distinct microbial populations. Diets rich in simple sugars modify the abundance of microbial subsets, enriching for microbiotas that elicit pathogenic outcomes.

Harnessing gut microbes for glycan detection and quantification.

Glycans facilitate critical biological functions and control the mammalian gut microbiota composition by supplying differentially accessible nutrients to distinct microbial subsets. Therefore, identifying unique glycan substrates that support defined microbial populations could inform therapeutic avenues to treat diseases via modulation of the gut microbiota composition and metabolism. However, examining heterogeneous glycan mixtures for individual microbial substrates is hindered by glycan structural complexity and diversity, which presents substantial challenges to glycomics approaches.

The Angiopoietin-Tie2 axis contributes to placental vascular disruption and adverse birth outcomes in malaria in pregnancy.

Background: Malaria during pregnancy is a major contributor to the global burden of adverse birth outcomes including fetal growth restriction, preterm birth, and fetal loss. Recent evidence supports a role for angiogenic dysregulation and perturbations to placental vascular development in the pathobiology of malaria in pregnancy. The Angiopoietin-Tie2 axis is critical for placental vascularization and remodeling.

Innate and adaptive immune dysregulation in critically ill ICU patients.

This study aimed to evaluate whether ICU patients who developed persistent critical illness displayed an immune profile similar to an aged immune phenotype and any associations with patient outcomes. Twenty two critically ill ICU patients (27-76 years, 15 males), at day 5 of mechanical ventilation, and 22 healthy age-matched controls (27-77 years, 13 males) were recruited. Frequency and phenotype of innate and adaptive immune cells and telomere length in peripheral blood mononuclear cells (PBMCs) were measured.

PI3Kδ Regulates the Magnitude of CD8+ T Cell Responses after Challenge with Listeria monocytogenes.

PI3Ks regulate diverse immune cell functions by transmitting intracellular signals from Ag, costimulatory receptors, and cytokine receptors to control cell division, differentiation, survival, and migration. In this study, we report the effect of inhibiting the p110δ subunit of PI3Kδ on CD8(+) T cell responses to infection with the intracellular bacteria Listeria monocytogenes. A strong dependency on PI3Kδ for IFN-γ production by CD8(+) T cells in vitro was not recapitulated after Listeria infection in vivo.

Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model.

Peptide immunotherapy (PIT) is a targeted therapeutic approach, involving administration of disease-associated peptides, with the aim of restoring antigen-specific immunological tolerance without generalized immunosuppression. In type 1 diabetes, proinsulin is a primary antigen targeted by the autoimmune response, and is therefore a strong candidate for exploitation via PIT in this setting. To elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms of action, we developed a preclinical model of proinsulin autoimmunity in a humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse.

Mapping patient pathways and estimating resource use for point of care versus standard testing and treatment of chlamydia and gonorrhoea in genitourinary medicine clinics in the UK.

Objectives: We aimed to explore patient pathways using a chlamydia/gonorrhoea point-of-care (POC) nucleic acid amplification test (NAAT), and estimate and compare the costs of the proposed POC pathways with the current pathways using standard laboratory-based NAAT testing.

Design/participants: Workshops were conducted with healthcare professionals at four sexual health clinics representing diverse models of care in the UK. They mapped out current pathways that used chlamydia/gonorrhoea tests, and constructed new pathways using a POC NAAT.

An osteoporotic fracture mimicking cervical dystonia in idiopathic Parkinson's disease.

We report on a case of a 65-year-old (CD) woman who sustained an atraumatic neck fracture. A combination of Parkinson's disease with motor fluctuations, chronic cervical dystonia and osteoporosis provided the basis for this interesting diagnosis. Mrs CD had progressed to complex phase idiopathic Parkinson's disease within 13 years of diagnosis.

'Do it yourself' sexual health care: the user experience.

Objectives: To describe client experience of self-management within a busy walk-in, sexual health service. Self-management in this context is self-registration and take-home pregnancy tests, chlamydia (Chlamydia trachomatis) and gonorrhoea (Neisseria gonorrhoeae) tests, or condoms dispensed from a free vending machine.

Methods: Twenty-four in-depth, semi-structured interviews with users; 19 structured written reports from mystery shoppers paid to visit the service and report their experience; demographic details of those using the self-management option from the clinic database and 40 h of recorded observation in the clinic waiting room.

Stem cells and neuroprotection: understanding the players.

The use of neuroprotective therapies begs the question of how such therapies could affect preexisting stem cell populations within the host, as well as those introduced through cell-replacement therapy. Multiple mechanisms may mediate stem cell responses to neuroprotectants such as host/donor age and gender, cellular lineage/differentiation status, and mitochondrial dynamics. Current therapeutic sources for stem cells are embryonic, somatic, or induced pluripotent, with very little known about the effects of gender, age, cell type, and mitochondrial dynamics.

Role of lipid peroxidation in cellular responses to D,L-sulforaphane, a promising cancer chemopreventive agent.

D,L-sulforaphane (SFN), a synthetic analogue of the broccoli-derived l-isomer, is a highly promising cancer chemopreventive agent substantiated by inhibition of chemically induced cancer in rodents and prevention of cancer development and distant site metastasis in transgenic mouse models of cancer. SFN is also known to inhibit growth of human cancer cells in association with cell cycle arrest and reactive oxygen species-dependent apoptosis, but the mechanism of these cellular responses to SFN exposure is not fully understood. Because 4-hydroxynonenal (4-HNE), a product of lipid peroxidation (LPO), the formation of which is regulated by hGSTA1-1, assumes a pivotal role in oxidative stress-induced signal transduction, we investigated its contribution in growth arrest and apoptosis induction by SFN using HL60 and K562 human leukemic cell lines as a model.

Hand dermatitis and lymphoedema.

Hand dermatitis is common, with lymphoedema of the hand and forearm a rare complication. The mechanism of lymphoedema in such cases is poorly understood, hence management can be challenging. To investigate the underlying mechanism of lymphoedema associated with hand dermatitis and outline recommendations for management, we identified all patients with lymphoedema associated with hand dermatitis referred to our lymphoedema service, a tertiary referral centre.

4-Hydroxynonenal induces p53-mediated apoptosis in retinal pigment epithelial cells.

4-Hydroxynonenal (4-HNE) has been suggested to be involved in stress-induced signaling for apoptosis. In present studies, we have examined the effects of 4-HNE on the intrinsic apoptotic pathway associated with p53 in human retinal pigment epithelial (RPE and ARPE-19) cells. Our results show that 4-HNE causes induction, phosphorylation, and nuclear accumulation of p53 which is accompanied with down regulation of MDM2, activation of the pro-apoptotic p53 target genes viz.

Leprosy: recognizing red flags.

A 28-year-old man from the Philippines presented with multiple papules and plaques symmetrically distributed on the arms and legs. This was associated with worsening paraesthesia of the hands and feet. A right common peroneal nerve decompression had been performed 2 years earlier.

Estrogen actions on mitochondria--physiological and pathological implications.

Estrogens are potent neuroprotective hormones and mitochondria are the site of cellular life-death decisions. As such, it is not surprising that we and others have shown that estrogens have remarkable effects on mitochondrial function. Herein we provide evidence for a primary effect of estrogens on mitochondrial function, achieved in part by the import of estrogen receptor beta (ERbeta) into the mitochondria where it mediates a number of estrogen actions on this vital organelle.

Methamphetamine dependence and human immunodeficiency virus risk behavior.

We examined human immunodeficiency virus (HIV)-related risk behaviors among methamphetamine (MA)-dependent users. Secondary data analysis was performed on data from a large clinical trial: The Methamphetamine Treatment Project (N = 784). All MA-dependent participants were enrolled in an outpatient treatment program, receiving either a standardized psychosocial protocol (Matrix model) or treatment-as-usual.

Look who's taking notes in your clinic: mystery shoppers as evaluators in sexual health services.

Objectives: To test the feasibility of professional patients as a tool for sexual health service evaluation. Professional patients are paid to use services specifically for audit or evaluation purposes without disclosing their identity as evaluators.

Methods: Professional patients visited five large sexual health departments used by 3000 clients per week in two inner London Boroughs with very high rates of sexual ill health.

Immortalization of epithelial progenitor cells mediated by resveratrol.

Within the hierarchy of epithelial stem cells, normal progenitor cells may express regulated telomerase during renewal cycles of proliferation and differentiation. Discontinuous telomerase activity may promote increased renewal capacity of progenitor cells, while deregulated/continuous telomerase activity may promote immortalization when differentiation and/or senescent pathways are compromised. In the present work, we show that resveratrol activates, while progesterone inactivates, continuous telomerase activity within 24 h in subpopulations of human Li-Fraumeni syndrome-derived breast epithelial cells.

Chlamydia testing in community pharmacies: evaluation of a feasibility pilot in south east London.

Background And Objective: Chlamydia trachomatis infection is a common sexually transmitted infection with serious sequelae. Excellent access to testing, treatment and contact tracing are an essential part of strategies to control it. With traditional sexual health services over-stretched, community pharmacies are well placed to provide this service.

Bupropion for the treatment of methamphetamine dependence.

Bupropion was tested for efficacy in increasing weeks of abstinence in methamphetamine-dependent patients, compared to placebo. This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 30-day follow-up. Five outpatient substance abuse treatment clinics located west of the Mississippi participated in the study.

The NIDA Methamphetamine Clinical Trials Group: a strategy to increase clinical trials research capacity.

Aims: In order to increase the number of investigative teams and sites conducting research on pharmacological treatments for methamphetamine use disorders, the National Institute on Drug Abuse (NIDA) established an infrastructure of clinical sites in areas where methamphetamine addiction is prevalent. This multi-site infrastructure would serve to run multiple Phases II and III protocols effectively and expeditiously.

Methods: NIDA collaborated with investigators from the University of California at Los Angeles (UCLA) to set up the Methamphetamine Clinical Trials Group (MCTG).

Involving service users in sexual health service development.

Objectives: The study objectives were to document users' experience of family planning and genitourinary medicine clinics and young people's services working within the time constraints of rapid service development and maximising the utility of this data for service improvement.

Methods: A total of 93 users of family planning and genitourinary medicine services participated in one of 13 facilitated discussion groups. Some 61% of the sample were women, 64% were aged over 25 years and 47% were Black Caribbean or Black African.