Burkholderia thailandensis Isolated from the Environment,United States

Burkholderia thailandensis, an opportunistic pathogen found in the environment, is a bacterium closely related to B. pseudomallei, the cause of melioidosis. Human B. thailandensis infections are uncommon. We isolated B. thailandensis from water in Texas and Puerto Rico and soil in Mississippi in the United States, demonstrating a potential public health risk.     

A histomorphometric analysis of heavily loaded and non-loaded implants

PURPOSE: To investigate the bone tissue response at the interface of loaded and non-loaded implants used in an orthopedic anchorage system after a continuous, non-axial force application of 5 N over 2 months. MATERIALS AND METHODS: Twenty-nine Br?nemark System implants were placed in the zygomatic arches of 5 dogs. After a healing period of 8 weeks, 20 implants (4 in each dog) were loaded during 8 weeks with a large non-axial orthopedic force application of 5 N. This force was directed between the implants and a maxillary splint to move the maxilla forward. Nine implants were not loaded during this period. At the termination of the experiment, all 29 implants were retrieved for radiographic as well as for histologic analysis. Computer-based histomorphometric quantifications were performed via light microscopy and computer software. Bone-metal contact (BMC), bone surface area (BSA) inside the threads, and the bone mirror area (BMA) of the implants were measured. Statistical comparisons between the loaded and non-loaded implants were carried out. In the group of loaded implants a 2-factor analysis of variance was used. RESULTS: There were no statistically significant differences found in BMC, BSA, and BMA between the loaded and non-loaded implants, both for all the threads and for only the cervical region of the implants. Nor were there statistically significant differences between the non-pressure and pressure sides or for different lengths of the loaded implants. DISCUSSION: The loaded implants maintained the osseointegration achieved during the 8-week healing period. CONCLUSIONS: The results of this study indicate that titanium implants can be used as anchorage for orthopedic force application systems.     

Under-five mortality in the Democratic Republic of the Congo: secondary analyses of survey and conflict data by province

ObjectiveTo compare coverage of key child health policy indicators across provinces and to explore their association with under-five mortality and level of conflict in the Democratic Republic of the Congo.MethodsWe made a secondary analysis of nationally representative data from 1380 health facilities and 20 792 households in 2017–2018. We analysed provincial-level data on coverage of 23 different indicators for improving common causes of childhood mortality, combined into mean scores for: newborn health, pneumonia, diarrhoea, malaria and safe environment. Using negative binomial regression we compared the scores with provincial-level under-five mortality. With binary logistic regression at the individual level we compared indicators (outcome) with living in a conflict-affected province (exposure).FindingsAll grouped coverage scores demonstrated large ranges across the 26 provinces: newborn health: 20% to 61%; pneumonia: 26% to 86%; diarrhoea: 25% to 63%; malaria: 22% to 53%; and safe environment: 4% to 53%. The diarrhoea score demonstrated the strongest association with under-five mortality (adjusted coefficient: −0.026; 95% confidence interval: −0.045 to −0.007). Conflict-affected provinces had both the highest as well as the lowest mortality rates and indicator coverages. The odds of coverage were higher in conflict-affected provinces for 13 out of 23 indicators, whereas in provinces unaffected by conflict only one indicator had higher odds of coverage.ConclusionConflict alone is a poor predictor for child health. Ensuring that children in unaffected provinces are not neglected while addressing the needs of the most vulnerable in conflict settings is important. Prevent, protect and treat strategies for diarrhoeal disease could help improve equity in child survival.     

Inhibitors of Activin Receptor-like Kinase 5 Interfere with SARS-CoV-2 S-Protein Processing and Spike-Mediated Cell Fusion via Attenuation of Furin Expression

Screening of a protein kinase inhibitor library identified SB431542, targeting activin receptor-like kinase 5 (ALK5), as a compound interfering with SARS-CoV-2 replication. Since ALK5 is implicated in transforming growth factor β (TGF-β) signaling and regulation of the cellular endoprotease furin, we pursued this research to clarify the role of this protein kinase for SARS-CoV-2 infection. We show that TGF-β1 induces the expression of furin in a broad spectrum of cells including Huh-7 and Calu-3 that are permissive for SARS-CoV-2. The inhibition of ALK5 by incubation with SB431542 revealed a dose-dependent downregulation of both basal and TGF-β1 induced furin expression. Furthermore, we demonstrate that the ALK5 inhibitors SB431542 and Vactosertib negatively affect the proteolytic processing of the SARS-CoV-2 Spike protein and significantly reduce spike-mediated cell–cell fusion. This correlated with an inhibitory effect of ALK5 inhibition on the production of infectious SARS-CoV-2. Altogether, our study shows that interference with ALK5 signaling attenuates SARS-CoV-2 infectivity and cell–cell spread via downregulation of furin which is most pronounced upon TGF-β stimulation. Since a TGF-β dominated cytokine storm is a hallmark of severe COVID-19, ALK5 inhibitors undergoing clinical trials might represent a potential therapy option for COVID-19.     

Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers: A Randomized,Single-Blind,Placebo-Controlled,Crossover Study

Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. This bioactive signalling molecule is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate–nitrite–NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in age-matched healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL, 400 mg nitrate) and placebo BJ (70 mL, 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity.     

Blaming Machismo: How the Social Imaginary is Failing Men with HIV in Santa Cruz,Bolivia

Drawing from an ethnography of HIV care in Santa Cruz, Bolivia, in this article I explore how the social imaginary surrounding gender relations shapes men’s experiences of seeking care for and living with HIV. Popular understandings of gender relations, which draw heavily on the machismo concept, intersect with a global health master narrative that frames women as victims in the AIDS epidemic in a way that generates a strong sentiment of blaming machismo within local HIV/AIDS-related services. Statements such as, “it’s because of machismo” are used to explain away epidemiological trends. Participant observation in the context of HIV care, coupled with illness narrative interviews, illuminate how blaming machismo shapes men’s experiences of care and the ways that they feel excluded from various forms of support. Thus, the illness experiences of men with HIV problematize the machismo concept and how it is drawn upon in the context of care.     

GETTING NO RESPECT: BARRIERS TO MAMMOGRAPHY FOR A GROUP OF SWEDISH WOMEN

Mammography screening is a highly sensitive and specific method to detect breast cancer at an early stage. If screening campaigns are to be cost effective, compliance is valuable. However, many women do not attend when called for mammography screening. Our aim in this study is to understand and explain why women become nonattenders. A sample of 16 nonattending women, aged between 43 and 73 years, participated in this qualitative study, by interviews or written comments. The core category discovered in the data was ``getting no respect.'' The informants did not feel respected from either the society or the health care system. Below this core category, two categories were identified: the mammography examination and affecting circumstances. The performance and its effects comprised the content of the category of mammography examination. The category affecting circumstances included knowledge about risk factors, prevention, and practical or emotional arguments.     

Lithium Chloride Therapy Fails to Improve Motor Function in a Transgenic Mouse Model of Machado-Joseph Disease

The accumulation of misfolded proteins in neurons, leading to the formation of cytoplasmic and nuclear aggregates, is a common theme in age-related neurodegenerative diseases, possibly due to disturbances of the proteostasis and insufficient activity of cellular protein clearance pathways. Lithium is a well-known autophagy inducer that exerts neuroprotective effects in different conditions and has been proposed as a promising therapeutic agent for several neurodegenerative diseases. We tested the efficacy of chronic lithium (10.4 mg/kg) treatment in a transgenic mouse model of Machado-Joseph disease, an inherited neurodegenerative disease, caused by an expansion of a polyglutamine tract within the protein ataxin-3. A battery of behavioral tests was used to assess disease progression. In spite of activating autophagy, as suggested by the increased levels of Beclin-1, Atg7, and LC3-II, and a reduction in the p62 protein levels, lithium administration showed no overall beneficial effects in this model concerning motor performance, showing a positive impact only in the reduction of tremors at 24 weeks of age. Our results do not support lithium chronic treatment as a promising strategy for the treatment of Machado-Joseph disease (MJD).