Response to radiation in renal medullary carcinoma

Renal medullary carcinoma (RMC) is a rare and highly aggressive malignancy arising from the renal medulla and found mostly in patients with sickle cell trait. RMC usually presents with widely metastatic disease. We describe a young man diagnosed with metastatic RMC who sustained a complete response to systemic chemotherapy but developed brain metastases with leptomeningeal involvement and subsequently had a partial response to brain irradiation. The use of radiation in the management of RMC is reviewed. Due to the apparent propensity for RMC to spread to the central nervous system, prophylactic treatment such as craniospinal irradiation should be considered along with chemotherapy in patients with metastatic RMC to potentially improve the progression-free interval

Partnering with Parteras: Multi-Collaborator International Service-Learning Project Impacts on Traditional Birth Attendants in Mexico

Medical students are increasingly seeking global health service-learning opportunities; however, the impact of these interventions is often not assessed. In this article, the authors describe a model for global health service-learning programs as well as a pilot tool for assessing program impacts on populations traditionally difficult to evaluate.  Specifically, a group of medical students from the United States, in collaboration with local health officials and a global NGO, successfully implemented a training program for parteras, or traditional birth attendants, in Mexico. The training included educational objectives from the Ministry of Health.  A pilot assessment tool was developed which included oral pretest and posttest self-reported knowledge and task-specific ability in 12 program-specific categories. The assessment was administered in an effort to determine educational impact: parteras, who were receptive to students as teachers, reported increased knowledge and skill in all topics except nutrition and postpartum care. The results of the assessment suggest that undergraduate medical students, when collaborating with a facilitating organization, community-based healthcare workers, and local ministries of health, can improve lay birth attendants’ confidence in basic obstetric knowledge and skills through global service-learning. Moreover, creative assessments are required to understand impacts on difficult to access populations.

Community health workers improve disease control and medication adherence among patients with diabetes and/or hypertension in Chiapas, Mexico: an observational stepped-wedge study

Background: Non-communicable diseases (NCDs) contribute greatly to morbidity and mortality in low-income and middle-income countries (LMICs). Community health workers (CHWs) may improve disease control and medication adherence among patients with NCDs in LMICs, but data are lacking. We assessed the impact of a CHW-led intervention on disease control and adherence among patients with diabetes and/or hypertension in Chiapas, Mexico. Methods: We conducted a prospective observational study among adult patients with diabetes and/or hypertension, in the context of a stepped-wedge roll-out of a CHW-led intervention. We measured self-reported adherence to medications, blood pressure and haemoglobin A1c at baseline and every 3 months, timed just prior to expansion of the intervention to a new community. We conducted individual-level mixed effects analyses of study data, adjusting for time and clustering by patient and community. Findings: We analysed 108 patients. The CHW-led intervention was associated with a twofold increase in the odds of disease control (OR 2.04, 95% CI 1.15 to 3.62). It was also associated with optimal adherence assessed by 30-day recall (OR 1.86; 95% CI 1.15 to 3.02) and a positive self-assessment of adherence behaviour (OR 2.29; 95% CI 1.26 to 4.15), but not by 5-day recall. Interpretation A CHW-led adherence intervention was associated with disease control and adherence among adults with diabetes and/or hypertension. This study supports a role of CHWs in supplementing comprehensive primary care for patients with NCDs in LMICs. Trial registration number NCT02549495

The Genomic and Immune Landscapes of Lethal Metastatic Breast Cancer.

The detailed molecular characterization of lethal cancers is a prerequisite to understanding resistance to therapy and escape from cancer immunoediting. We performed extensive multi-platform profiling of multi-regional metastases in autopsies from 10 patients with therapy-resistant breast cancer. The integrated genomic and immune landscapes show that metastases propagate and evolve as communities of clones, reveal their predicted neo-antigen landscapes, and show that they can accumulate HLA loss of heterozygosity (LOH). The data further identify variable tumor microenvironments and reveal, through analyses of T cell receptor repertoires, that adaptive immune responses appear to co-evolve with the metastatic genomes. These findings reveal in fine detail the landscapes of lethal metastatic breast cancer.CRUK

Dietary Acrylamide Intake and the Risk of Lymphatic Malignancies: The Netherlands Cohort Study on Diet and Cancer

BACKGROUND: Acrylamide, a probable human carcinogen, is present in many everyday foods. Since the finding of its presence in foods in 2002, epidemiological studies have found some suggestive associations between dietary acrylamide exposure and the risk of various cancers. The aim of this prospective study is to investigate for the first time the association between dietary acrylamide intake and the risk of several histological subtypes of lymphatic malignancies. METHODS: The Netherlands Cohort Study on diet and cancer includes 120,852 men and women followed-up since September 1986. The number of person years at risk was estimated by using a random sample of participants from the total cohort that was chosen at baseline (n =5,000). Acrylamide intake was estimated from a food frequency questionnaire combined with acrylamide data for Dutch foods. Hazard ratios (HRs) were calculated for acrylamide intake as a continuous variable as well as in categories (quintiles and tertiles), for men and women separately and for never-smokers, using multivariable-adjusted Cox proportional hazards models. RESULTS: After 16.3 years of follow-up, 1,233 microscopically confirmed cases of lymphatic malignancies were available for multivariable-adjusted analysis. For multiple myeloma and follicular lymphoma, HRs for men were 1.14 (95% CI: 1.01, 1.27) and 1.28 (95% CI: 1.03, 1.61) per 10 µg acrylamide/day increment, respectively. For never-smoking men, the HR for multiple myeloma was 1.98 (95% CI: 1.38, 2.85). No associations were observed for women. CONCLUSION: We found indications that acrylamide may increase the risk of multiple myeloma and follicular lymphoma in men. This is the first epidemiological study to investigate the association between dietary acrylamide intake and the risk of lymphatic malignancies, and more research into these observed associations is warranted

Two Coregulated Efflux Transporters Modulate Intracellular Heme and Protoporphyrin IX Availability in Streptococcus agalactiae

Streptococcus agalactiae is a major neonatal pathogen whose infectious route involves septicemia. This pathogen does not synthesize heme, but scavenges it from blood to activate a respiration metabolism, which increases bacterial cell density and is required for full virulence. Factors that regulate heme pools in S. agalactiae are unknown. Here we report that one main strategy of heme and protoporphyrin IX (PPIX) homeostasis in S. agalactiae is based on a regulated system of efflux using two newly characterized operons, gbs1753 gbs1752 (called pefA pefB), and gbs1402 gbs1401 gbs1400 (called pefR pefC pefD), where pef stands for ‘porphyrin-regulated efflux’. In vitro and in vivo data show that PefR, a MarR-superfamily protein, is a repressor of both operons. Heme or PPIX both alleviate PefR-mediated repression. We show that bacteria inactivated for both Pef efflux systems display accrued sensitivity to these porphyrins, and give evidence that they accumulate intracellularly. The ΔpefR mutant, in which both pef operons are up-regulated, is defective for heme-dependent respiration, and attenuated for virulence. We conclude that this new efflux regulon controls intracellular heme and PPIX availability in S. agalactiae, and is needed for its capacity to undergo respiration metabolism, and to infect the host

A communal catalogue reveals Earth's multiscale microbial diversity

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity.Peer reviewe