Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme ...uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin. The hemO locus includes a gene coding for a heme scavenger (HphA), which is secreted by a Slam protein. Furthermore, heme uptake is dependent on a TonB-dependent receptor (HphR), which is important for survival and/or dissemination into the vasculature in a mouse model of pulmonary infection. Our results indicate that A. baumannii uses a two-component receptor system for the acquisition of heme from host heme reservoirs.
This study introduces a flexible, adhesive-integrated electrode array that was developed to enable non-invasive monitoring of cervical nerve activity. The device uses silver-silver chloride as the ...electrode material of choice and combines it with an electrode array consisting of a customized biopotential data acquisition unit and integrated graphical user interface (GUI) for visualization of real-time monitoring. Preliminary testing demonstrated this electrode design can achieve a high signal to noise ratio during cervical neural recordings. To demonstrate the capability of the surface electrodes to detect changes in cervical neuronal activity, the cold-pressor test (CPT) and a timed respiratory challenge were employed as stressors to the autonomic nervous system. This sensor system recording, a new technique, was termed Cervical Electroneurography (CEN). By applying a custom spike sorting algorithm to the electrode measurements, neural activity was classified in two ways: (1) pre-to-post CPT, and (2) during a timed respiratory challenge. Unique to this work: (1) rostral to caudal channel position-specific (cephalad to caudal) firing patterns and (2) cross challenge biotype-specific change in average CEN firing, were observed with both CPT and the timed respiratory challenge. Future work is planned to develop an ambulatory CEN recording device that could provide immediate notification of autonomic nervous system activity changes that might indicate autonomic dysregulation in healthy subjects and clinical disease states.
This report investigates the mechanism of photochemical Povarov-type reactions of N,N-dialkylanilines and maleimides in polar solvents (DMF or dioxane) in the presence of light. Fundamental aspects ...of the electron donor–acceptor (EDA) photoactivation pathway proposed to underpin this chemistry are examined through integrated experimental and computational studies. This approach provided evidence supporting the involvement of an EDA complex in facilitating this chemistry via a reaction mechanism that does not involve a triplet manifold. Most notably, our findings indicate that relying solely on UV–vis absorption spectroscopic data to either account for or predict reactivity in synthetic experiments may not always provide the complete picture. More specifically, this relates to considering UV–vis absorption spectroscopic data, calculated values for association constants (K EDA) and molar extinction coefficients (ε), with the reactivity observed in associated synthetic reactions in practice.
Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find ...thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 - 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913T in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10
, β = -0.090) and confers risk of hip fracture (P = 1.0 × 10
, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density.
The Vietnamese Mekong Delta (VMD) is an example of a complex dynamic socio-hydrological system in which societies and hydrology interact and co-evolve. The dominant engineering approach in the VMD ...has enhanced the dynamics of society and hydrology. This study looks at the implications of socio-hydrological dynamics in the coastal VMD where saline water is controlled by various infrastructures. In the first phase, key informant interviews and focus group discussions were used to explore socio-hydrological dynamics in the study area. The results show divergence in livelihood strategies inside the freshwater-projected area, shaping a heterogeneous agricultural landscape of fresh- and brackish-water livelihoods manifested by four socio-hydrological groups. Next, the Motivation and Ability (MOTA) framework and household surveys were used to assess the adaptability in the agricultural development pathway advocated by the freshwater policy. The result revealed differentiations among these socio-hydrological groups. The findings suggest other practices may be required to help the area navigate towards future adaptations to socio-hydrological changes.
Generalized pustular psoriasis is a relatively rare variant of psoriasis characterized by diffuse eruption of sterile pustules on an erythematous background. Untreated flares can result in ...life-threatening complications including sepsis and organ failure. Generalized pustular psoriasis has historically proven challenging to treat with an unpredictable clinical course and paucity of reliably efficacious treatment options. Until recently, there have been no FDA-approved therapies for generalized pustular psoriasis in the United States. In September 2022, the IL-36 receptor antagonist spesolimab became the first FDA-approved treatment for generalized pustular psoriasis in adults. We present a case of generalized pustular psoriasis with complete and rapid response to spesolimab.
ObjectivesTranscatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian ...patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.MethodsPatients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.ResultsEight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p<0.01); however, 30-day stroke and mortality (women vs men: 1.5% vs 1.6%, p=0.95% and 4.3% vs 3.4%, p=0.48) were similar. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements (11.2% vs 9.0%, p=0.52) were also similar as was 1-year survival (women vs men: 85.6% vs 88.2%, p=0.25). The only predictors of 30-day mortality were major vascular injury in women and age in men.ConclusionsAsian women had significantly smaller stature and anatomy with some differences in clinical profiles. Despite more frequent major vascular complications, women had similar 30-day stroke or mortality rates. Functional status improvement was significant and comparable between the sexes. Conduction disturbance and permanent pacemaker requirements were similar as was 1-year survival.
The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read 'School of Medicine Sydney, ...University of Notre Dame Australia, Sydney, WA, 6160, Australia' and 'St Vincent's Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.' This has now been corrected in both the PDF and HTML versions of the Article.
Patients with severe COVID-19 disease require monitoring with pulse oximetry as a minimal requirement. In many low- and middle- income countries, this has been challenging due to lack of staff and ...equipment. Wearable pulse oximeters potentially offer an attractive means to address this need, due to their low cost, battery operability and capacity for remote monitoring. Between July and October 2021, Ho Chi Minh City experienced its first major wave of SARS-CoV-2 infection, leading to an unprecedented demand for monitoring in hospitalized patients. We assess the feasibility of a continuous remote monitoring system for patients with COVID-19 under these circumstances as we implemented 2 different systems using wearable pulse oximeter devices in a stepwise manner across 4 departments.
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