Management of esophagorespiratory fistula due to carcinoma esophagus with palliative intubation, gastric decompression and transgastric feeding jejunostomy.
Carcinoma esophagus with esophagorespiratory fistula has a poor prognosis. Water and food intake suffers and pulmonary contamination leads to lung infection. Treatment is essentially palliative. Thirty-five patients with esophagorespiratory fistula secondary to esophageal carcinoma were treated with palliative esophageal intubation, gastrostomy and transgastric feeding jejunostomy. Esophageal prosthesis could be implanted in 34 patients. One patient died in the postoperative period. Twenty-nine patients were able to swallow saliva without leakage into the lungs. Only four patients were able to take full diet orally for any significant length of time. An 18-G needle inserted in the gastrostomy Malecot's catheter provided outlet for air in the stomach and prevented rise in intragastric pressure and gastroesophageal reflux. Transgastric feeding jejunostomy functioned satisfactory. Twenty patients were followed up; the average survival was 58 days (range 9-337 days). Esophageal intubation, gastrostomy and transgastric feeding jejunostomy provide satisfactory palliation for patients with esophagorespiratory fistula secondary to carcinoma esophagus.


Microjoule-level all-polarization-maintaining femtosecond fiber source.
We report on a high-power, high-energy femtosecond fiber source based on direct amplification of parabolic pulses from an environmentally stable passively mode-locked fiber oscillator in an Yb-doped single-polarization photonic crystal fiber. The special pulse shape allows for the generation of high-quality femtosecond pulses beyond nonlinearity limits. The system delivers a pulse energy of 1.2 microJ (21 W average power) at a repetition rate of 17 MHz and a pulse duration of 240 fs in a linearly polarized beam with diffraction-limited quality.


Evaluation of 2'-deoxy-2'-flouro-5-methyl-1-beta-D-arabinofuranosyluracil as a potential gene imaging agent for HSV-tk expression in vivo.
2'-Deoxy-2'-flouro-5-methyl-1-beta-D-arabinofuranosyluracil (FMAU) has been evaluated in HT-29 cells as a potential positron emission tomography (PET) radiotracer for imaging HSV-tk gene expression in vivo. In vitro experiments demonstrate that the accumulation of [14C]-FMAU in HSV-tk-expressing cells is 2.4-fold (p < .02), 4.0-fold (p < .001), and 5.3-fold (p < .001) higher than the wild-type cells at 1, 3, and 5 hr, respectively. In vivo studies revealed that the tumor uptake in HSV-tk-expressing cells was 2.3-fold (p < .001), 3.0-fold (p < .001), and 5.5-fold (p < .001) higher than the control cells at 1, 2, and 5 hr, respectively. FMAU was found to be more sensitive compared to our earlier studies using 9-[(3-18F-fluoro-1-hydroxy-2-propoxy)methyl]-guanine ([18F]-FHPG) and 9-(4-[18F]-fluoro-3-hydroxy-methylbutyl)guanine ([18F]-FHBG) in the same cell lines, although, the specificity was less than FHBG. These results suggest that while FMAU labeled with PET isotopes may be useful for imaging HSV-tk-expressing tumors in vivo, multitracer studies across additional tumor models are necessary in order to identify an optimal PET radiotracer.


A rare cause of ileus: invagination due to ectopic pancreas.
Invagination is seen rarely as a cause of ileus in adults. The cause of invagination in children differs from that in adults. In adults it is mostly due to organic lesions (tumour). In a 49 years old patient, with 3 months of intermittant abdominal pain, radiologic investigations suspected a of small bowel tumour. The patient was operated on. At exploration, there was an ileo-ileal invagination on the terminal ileum over 40 cm distance A totally necrosed ileum segment was resected and an end-to-end anastomosis was performed. Inside the excised ileal loop their was a polyp-like lesion originating from submucosa, bordered by the wall but not protruding to the lumen. The pathological examination of the lesion revealed ectopic pancreatic tissue between the muscular layers of the bowel wall. Intestinal invagination must be got in mind as a rare cause of ileus in adults. During it's clinical course their is enough time to reach the diagnosis. So unnecessory resections and postoperative complications can be prevented.


Modifications of biochemical parameters related to protein metabolism and renal function in male soccer players after a match.
The impact of a soccer match on parameters related to protein catabolism and renal function was evaluated in male players. Blood was collected before and immediately after a 90 minutes soccer match from 19 athletes of two first division teams in Brazil. Red blood cells (RBC), hemoglobin (Hb), hematocrit (Ht), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC), ammonia, uric acid, urea and creatinine were analyzed. The modification of plasma volume was calculated, and biochemical values were corrected for this change. Urea/creatinine ratio and equations to estimate the glomerular filtration rate (eGFR) were used to assess kidney function. Plasma volume decreased from pre- to post-match. Post-match values higher than the pre-match ones were observed for RBC, Hb and Ht, as a consequence of plasma volume decrease. An increase in ammonia and creatinine concentrations post-match in comparison with pre-match values was registered, without changes in uric acid and urea levels. A reduction in urea/creatinine ratio and in eGFR was observed post-match, suggesting a decrease of renal function. A soccer match induced alterations in parameters linked to renal function and protein metabolism in male athletes. Particular attention should be paid in the monitoring of the ammonia concentration as an indicator of metabolic activity and energy requirement during prolonged exercise.


Comparative Efficacy of Once-Daily Umeclidinium/Vilanterol and Tiotropium/Olodaterol Therapy in Symptomatic Chronic Obstructive Pulmonary Disease: A Randomized Study.
We report the results of the first direct comparison of the once-daily fixed-dose long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA) combinations umeclidinium/vilanterol (UMEC/VI) and tiotropium/olodaterol (TIO/OLO) in patients with COPD. This was a randomized, two-period crossover open-label study in symptomatic patients with COPD [age 40 years or older, postbronchodilator forced expiratory volume in 1 s (FEV1) of 70% or less and 50% or more of predicted normal values, and modified Medical Research Council Dyspnoea Scale score of 2 or greater] not receiving inhaled corticosteroid therapy. Patients were randomized to receive UMEC/VI (62.5/25 µg once daily) via a multidose dry powder inhaler (ELLIPTA) followed by TIO/OLO (5/5 µg once daily) via a soft mist inhaler (Respimat), each for 8 weeks with an interim 3-week washout or vice versa. The primary end point was the change from baseline in trough FEV1 at week 8 with a noninferiority margin of - 50 mL in the per-protocol (PP) population. The incidence of adverse events was also assessed. In total, 236 patients (mean age 64.4 years, 60% male) were included in the intent-to-treat population and 227 were included in the PP population. UMEC/VI treatment was noninferior in the PP population and superior in the intent-to-treat population to TIO/OLO treatment with regard to trough FEV1 at week 8 [FEV1 change from baseline 180 mL vs 128 mL; difference 52 mL (95% confidence interval 28-77 mL); p < 0.001]. Patients receiving UMEC/VI had twofold increased odds of experiencing a clinically meaningful increase (100 mL or more) from baseline in trough FEV1 at week 8 compared with patients receiving TIO/OLO (odds ratio 2.05; 95% confidence interval 1.34-3.14). Adverse events occurred in 25% of patients in the UMEC/VI group and in 31% of patients in the TIO/OLO group. In this first direct comparison of two once-daily fixed-dose LAMA/LABA combinations, superiority was observed for the primary end point of trough FEV1 at week 8 with UMEC/VI compared with TIO/OLO in patients with symptomatic COPD. Both treatments had similar safety profiles. These findings confirm the results of previous indirect LAMA/LABA comparisons, and show that an efficacy gradient exists within the LAMA/LABA class. ClinicalTrials.gov identifier NCT02799784. GlaxoSmithKline.


Interband π plasmon of graphene: strong small-size and field-enhancement effects.
The interband π plasmon of graphene has energy corresponding to the ultraviolet (UV) wave band, and hence is promising for UV nanophotonics and nanooptoelectronics. However, its special size effect and electric field-enhancement effect have not been well understood. Here, we have investigated the far-field optical extinction and near-field enhancement features of the interband π plasmon in a graphene nanodisk using discrete dipole approximation and finite-difference time-domain methods. Very interestingly, it has been found that the in-plane (transverse mode) optical extinction peak of monolayer graphene firstly significantly red shifts with increasing diameter, but then tends to a saturation value when the diameter is above 20 nm, showing a strong small-size-sensitive effect. Furthermore, the transverse mode optical extinction peak obviously blue shifts with increasing thickness when the thickness is relatively small. Significantly, the corresponding local electric field enhancement factor produced by the plasmon, which can be found to be as large as several tens, firstly increases with the increase of the size and then reaches a maximum value at only several nanometers in size. Such an ultrasmall-size-sensitive plasmon in the UV region endows graphene dots with new promising potential uses in ultrasmall photo-electric devices and nanoantennas, and in UV enhancers.


How Is Physician Work Valued?
Strategies to value physician work continue to evolve. The Society of Thoracic Surgeons and The Society of Thoracic Surgeons National Database have an increasingly important role in this evolution. An understanding of the Current Procedural Terminology (CPT) system (American Medical Association [AMA], Chicago, IL) and the Relative Value Scale Update Committee (RUC) is necessary to comprehend how physician work is valued. In 1965, with the dawn of increasingly complex medical care, immense innovation, and the rollout of Medicare, the need for a common language describing medical services and procedures was recognized as being of critical importance. In 1966, the AMA, in cooperation with multiple major medical specialty societies, developed the CPT system, which is a coding system for the description of medical procedures and medical services. The RUC was created by the AMA in response to the passage of the Omnibus Budget Reconciliation Act of 1989, legislation of the United States of America Federal government that mandated that the Centers for Medicare & Medicaid Services adopt a relative value methodology for Medicare physician payment. The role of the RUC is to develop relative value recommendations for the Centers for Medicare & Medicaid Services. These recommendations include relative value recommendations for new procedures or services and also updates to relative value recommendations for previously valued procedures or services. These recommendations pertain to all physician work delivered to Medicare beneficiaries and propose relative values for all physician services, including updates to those based on the original resource-based relative value scale developed by Hsaio and colleagues. In so doing, widely differing work and services provided can be reviewed and comparisons of their relative value (to each other) can be established. The resource-based relative value scale assigns value to physician services using relative value units (RVUs), which consist of three components: work RVU, practice expense RVU, and malpractice RVU, also known as professional liability insurance RVU. The Centers for Medicare & Medicaid Services retains the final decision-making authority on the RVUs associated with each procedure or service. The purpose of this article is to discuss the role that the CPT codes and the RUC play in the valuation of physician work and to provide an example of how the methodology for valuation of physician work continues to evolve.


Bright insights into palladium-triggered local chemotherapy.
The incorporation of transition metal catalysts to the bioorthogonal toolbox has opened the possibility of producing supra-stoichiometric amounts of xenobiotics in living systems in a non-enzymatic fashion. For medical use, such metals could be embedded in implantable devices (i.e. heterogeneous catalyst) to "synthesize" drugs in desired locations (e.g. in a tumour) with high specificity and for extended periods of time, overcoming the useful life limitations of current local therapy modalities directed to specific organ sites (e.g. brachytherapy, controlled release systems). To translate this approach into a bona fide therapeutic option, it is essential to develop clinically-accessible implantation procedures and to understand and validate the activation process in relevant preclinical models. Herein we report the development of a novel Pd-activatable precursor of the red-fluorescent drug doxorubicin and Pd devices of optimized size and activity. Screening in state-of-the-art cancer models provided fundamental insights into the insertion protocols, safety and stability of the devices and into the prodrug distribution profile before and after activation.


The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?
From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage microbiome knowledge and tools. The rationale for our working group has been structured around four domains of innovation that could derive from ongoing efforts in deciphering the interactions between human cells and intestinal microbiome as a central component of human health, namely: (1) development of stratification and monitoring tools; (2) identification of new target and drug discovery, as a part of our supra-genome; (4) exploitation of microbiota as a therapeutic target that can be modulated; (4) and finally as a source of live biotherapeutics and adjuvants. These four streams will exemplify how microbiota has changed the way we consider a wide range of chronic and incurable diseases and the consequences of long-lasting dysbiosis. In-depth microbiota analysis is opening one of the broadest fields of investigation for improving human and animal health and will be a source of major therapeutic innovations for tackling today's medical unmet needs. We thus propose a range of recommendations for basic researchers, care givers as well as for health authorities to gain reliability in microbiome analysis and accelerate discovery processes and their translation into applications for the benefits of the people. Finally, les Ateliers de Giens round table on microbiota benefited from the richness of the French ecosystem. France represents a center of excellence in the microbiota research field, with French institutions as Institut national de la recherche agronomique (INRA [Metagenopolis, Micalis]), Centre national de la recherché scientifique (CNRS), Unité de recherche sur les maladies infectieuses et tropicales émergentes (URMITE), Institut of Cardiometabolism and Nutrition (ICAN), Institut des maladies métaboliques et cardiovasculaires (I2MC), Institut national de la santé et de la recherche médicale (Inserm), Pasteur Institute and Gustave-Roussy being top-players for the number of publications.


Sensitivity of 2DEG-based Hall-effect sensors at high temperatures.
The magnetic sensitivity of Hall-effect sensors made of InAlN/GaN and AlGaN/GaN heterostructures was measured between room temperature and 576 °C. Both devices showed decreasing voltage-scaled magnetic sensitivity at high temperatures, declining from 53 mV/V/T to 8.3 mV/V/T for the InAlN/GaN sample and from 89 mV/V/T to 8.5 mV/V/T for the AlGaN/GaN sample, corresponding to the decreasing electron mobility due to scattering effects at elevated temperatures. Alternatively, current-scaled sensitivities remained stable over the temperature range, only varying by 13.1% from the mean of 26.3 V/A/T and 10.5% from the mean of 60.2 V/A/T for the InAlN/GaN and AlGaN/GaN samples, respectively. This is due to the minimal temperature dependence of the electron sheet density on the 2-dimensional electron gas (2DEG). Both devices showed consistency in their voltage- and current-scaled sensitivity over multiple temperature cycles as well as nearly full recovery when returned to room temperature after thermal cycling. Additionally, an AlGaN/GaN sample held at 576 °C for 12 h also showed nearly full recovery at room temperature, further suggesting that GaN-based Hall-effect sensors are a good candidate for use in high temperature applications.


Liver iron sensing and body iron homeostasis.
The liver orchestrates systemic iron balance by producing and secreting hepcidin. Known as the iron hormone, hepcidin induces degradation of the iron exporter ferroportin to control iron entry into the bloodstream from dietary sources, iron recycling macrophages, and body stores. Under physiologic conditions, hepcidin production is reduced by iron deficiency and erythropoietic drive to increase the iron supply when needed to support red blood cell production and other essential functions. Conversely, hepcidin production is induced by iron loading and inflammation to prevent the toxicity of iron excess and limit its availability to pathogens. The inability to appropriately regulate hepcidin production in response to these physiologic cues underlies genetic disorders of iron overload and deficiency, including hereditary hemochromatosis and iron-refractory iron deficiency anemia. Moreover, excess hepcidin suppression in the setting of ineffective erythropoiesis contributes to iron-loading anemias such as β-thalassemia, whereas excess hepcidin induction contributes to iron-restricted erythropoiesis and anemia in chronic inflammatory diseases. These diseases have provided key insights into understanding the mechanisms by which the liver senses plasma and tissue iron levels, the iron demand of erythrocyte precursors, and the presence of potential pathogens and, importantly, how these various signals are integrated to appropriately regulate hepcidin production. This review will focus on recent insights into how the liver senses body iron levels and coordinates this with other signals to regulate hepcidin production and systemic iron homeostasis.


Neural Substrates of the Drift-Diffusion Model in Brain Disorders.
Many studies on the drift-diffusion model (DDM) explain decision-making based on a unified analysis of both accuracy and response times. This review provides an in-depth account of the recent advances in DDM research which ground different DDM parameters on several brain areas, including the cortex and basal ganglia. Furthermore, we discuss the changes in DDM parameters due to structural and functional impairments in several clinical disorders, including Parkinson's disease, Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorders, Obsessive-Compulsive Disorder (OCD), and schizophrenia. This review thus uses DDM to provide a theoretical understanding of different brain disorders.


[Medical service of the Red Army during the Great Patriotic War].
The article presents an analyze of contribution of military medicine in victory in the Great Patriotic War 1941-1945. Nevertheless big difficulties the medical service has effectuated deployment of network of medical units and institutes, organization of effective work of delivery of medical care on frontline and in rear of country. For the first time in the history of official military-medical service, it transformed from service of regard for ill and wounded persons in service of securing by men resources of active army. Experience of medical securing is as well actual nowday, as years ago. In a big quantity of questions the service saves it's practical value in complex solving of questions of modern military medicine.


Design and implementation of high-content imaging platforms: lessons learned from end user-developer collaboration.
Automated high-content screening and analysis (HCS/HCA) technology solutions have become indispensable in expediting the pace of drug discovery. Because of the complexity involved in designing, building, and validating HCS/HCA platforms, it is important to design, build, and validate a HCS/HCA platform before it is actually needed. Managed properly, collaboration between technology providers and end users in research is essential in accelerating development of the hardware and software of new HCS/HCA platforms before they become commercially available. Such a collaboration results in the cost effective creation of new technologies that meet specific and customized industrial requirements. This review outlines the history of, and considerations relevant to, the development of the Cytometrix Profiling System by Cytokinetics, Inc. and the "Complete Imaging Solution" for high-content screening, developed by Molecular Devices Corporation (MDC) (now MDS Analytical Technologies), from original conception and testing of various components, to multiple development cycles from 1998 to the present, and finally to market consolidation.


Research Priorities in Sudden Unexpected Infant Death: An International Consensus.
Despite the success of safe sleep campaigns and the progress in understanding risk factors, the rate of reduction in the cases of sudden infant death syndrome has now slowed and it remains a leading cause of postneonatal mortality in many developed countries. Strategic action is needed to tackle this problem and it is now vital to identify how the sudden infant death research community may best target its efforts. The Global Action and Prioritization of Sudden Infant Death Project was an international consensus process that aimed to define and direct future research by investigating the priorities of expert and lay members of the sudden unexpected infant death (SUID) community across countries. The aim was to identify which areas of research should be prioritized to reduce the number of SUID deaths globally. Scientific researchers, clinicians, counselors, educators, and SUID parents from 25 countries took part across 2 online surveys to identify potential research priorities. Workshops subsequently took place in the United Kingdom, United States, and Australia to reach consensus and 10 priority areas for research were established. Three main themes among the priorities emerged: (1) a better understanding of mechanisms underlying SUID, (2) ensuring best practice in data collection, management and sharing, and (3) a better understanding of target populations and more effective communication of risk. SUID is a global problem and this project provides the international SUID community with a list of shared research priorities to more effectively work toward explaining and reducing the number of sudden infant deaths.


Combined impact of lifestyle factors on prospective change in body weight and waist circumference in participants of the EPIC-PANACEA study.
The evidence that individual dietary and lifestyle factors influence a person's weight and waist circumference is well established; however their combined impact is less well documented. Therefore, we investigated the combined effect of physical activity, nutrition and smoking status on prospective gain in body weight and waist circumference. We used data of the prospective EPIC-PANACEA study. Between 1992 and 2000, 325,537 participants (94,445 men and 231,092 women, aged between 25-70) were recruited from nine European countries. Participants were categorised into two groups (positive or negative health behaviours) for each of the following being physically active, adherent to a healthy (Mediterranean not including alcohol) diet, and never-smoking for a total score ranging from zero to three. Anthropometric measures were taken at baseline and were mainly self-reported after a medium follow-up time of 5 years. Mixed-effects linear regression models adjusted for age, educational level, alcohol consumption, baseline body mass index and follow-up time showed that men and women who reported to be physically active, never-smoking and adherent to the Mediterranean diet gained over a 5-year period 537 (95% CI -706, -368) and 200 (-478, -87) gram less weight and 0.95 (-1.27, -0.639) and 0.99 (-1.29, -0.69) cm less waist circumference, respectively, compared to participants with zero healthy behaviours. The combination of positive health behaviours was associated with significantly lower weight and waist circumference gain.


Antitumor protection from the murine T-cell leukemia/lymphoma EL4 by the continuous subcutaneous coadministration of recombinant macrophage-colony stimulating factor and interleukin-2.
Combined continuous s.c. coadministration of macrophage-colony stimulating factor (M-CSF) plus interleukin-2 (IL-2) by osmotic pump protected mice given i.v. injections of a lethal dose of EL4 T-cell leukemia/lymphoma. Antitumor protection was significantly greater than that afforded by treatment with either cytokine alone. Since neither IL-2 receptors nor M-CSF receptors were expressed on EL4, the antitumor effect was likely attributed to murine effector cells. To determine how M-CSF+IL-2 provided this effect, we performed immunophenotypic and functional analyses as well as in vivo depletion studies of putative antitumor effector cells. Splenic phenotyping experiments revealed that the highest levels of macrophages and natural killer cells were observed in mice given the cytokine combination rather than either M-CSF or IL-2 alone. In vivo depletion of natural killer cells ablated the antitumor protective effect of M-CSF and IL-2. T-cells were also important for M-CSF+IL-2 efficacy, since adult thymectomy/T-cell depletion significantly inhibited the ability of cytokine coadministration to protect against EL4. Coadministration of the 2 cytokines significantly elevated in vivo levels of CD3+CD4+, CD3+CD8+, CD3+NK1.1+ T-cells, and CD3+CD25+ (activated) T-cells, and elevated anti-EL4 cytotoxic T-cell activity measured in vitro. Although WBC counts and fluorescence-activated cell sorter studies showed that M-CSF+IL-2 treatment significantly elevated neutrophils, s.c. delivery of granulocyte-colony stimulating factor at doses sufficient to induce neutrophilia was unable to confer anti-EL4 protection. These studies indicate that macrophages, T-cells, and natural killer cells are all important in the M-CSF+IL-2 anti-EL4 response. The superior antitumor effect of this cytokine combination along with the ability of M-CSF to diminish the toxicity of IL-2 in this model suggests that further investigations into the clinical potential of this combination treatment are warranted.


Detection of cervical cancer based on photoacoustic imaging-the in-vitro results.
In current clinical practice, the diagnosis of cervical cancer (CC) is mainly through the cervical screening followed by a necessary biopsy, but this method is labor consuming and expensive, and can only detect superficial lesions around the external cervical orifice. In contrast, photoacoustic imaging (PAI) is sensitive to the abnormal angiogenesis deep in the biological tissue, and may be capable for the intact scanning both around the external orifice and in cervical canal. In this paper, we for the first time put forward the photoacoustic diagnosis of CC. A total of 30 in-vitro experiments were carried out in this study, and the obtained depth maximum amplitude projection (DMAP) images were analyzed to evaluate the extent of the angiogenesis for different clinical stages of CC. Stronger absorption from the cervical lesions is observed relative to that of normal tissue. Paired t-test indicates that the difference in mean optical absorption (MOA) between normal tissue and cervical lesion has statistical significance with a confidential coefficient of 0.05. Statistical results also show that the MOAs of the cervical lesions are closely related to the severity of CC. These results imply that PAI may have great utility in the clinical diagnosis of CC.


Extraction of beta-carotene from orange peels.
Extraction of beta-carotene from orange peels and its nutritional evaluation through feeding study were carried out to compare the bioavailability of the extractable beta-carotene with that of synthetic beta-carotene. The highest yield of extractable beta-carotene was recovered using a mixture of acetone and hexane (1:1 v/v) as a solvent in a ratio of 15:1 (solvent/sample) and an extraction time of 15 minutes. Growth of rats fed a diet containing beta-carotene extracted from orange peels was normal and their weight gain during feeding period was real. In addition, bioavailability of the extractable beta-carotene was higher than that of synthetic beta-carotene, as a result of the presence of extra oils in the diet that contained beta-carotene extracted from orange peels. Finally, the economical advantage can be reached by extracting beta-carotene from orange peels. The bioavailability of this extractable beta-carotene was high enough to compete with that of commercial synthetic beta-carotene. So, it can be strongly recommended to produce such product in a large scale.


Gait change in tongue movement.
During locomotion, humans switch gaits from walking to running, and horses from walking to trotting to cantering to galloping, as they increase their movement rate. It is unknown whether gait change leading to a wider movement rate range is limited to locomotive-type behaviours, or instead is a general property of any rate-varying motor system. The tongue during speech provides a motor system that can address this gap. In controlled speech experiments, using phrases containing complex tongue-movement sequences, we demonstrate distinct gaits in tongue movement at different speech rates. As speakers widen their tongue-front displacement range, they gain access to wider speech-rate ranges. At the widest displacement ranges, speakers also produce categorically different patterns for their slowest and fastest speech. Speakers with the narrowest tongue-front displacement ranges show one stable speech-gait pattern, and speakers with widest ranges show two. Critical fluctuation analysis of tongue motion over the time-course of speech revealed these speakers used greater effort at the beginning of phrases-such end-state-comfort effects indicate speech planning. Based on these findings, we expect that categorical motion solutions may emerge in any motor system, providing that system with access to wider movement-rate ranges.


TransFuser: Imitation With Transformer-Based Sensor Fusion for Autonomous Driving.
How should we integrate representations from complementary sensors for autonomous driving? Geometry-based fusion has shown promise for perception (e.g., object detection, motion forecasting). However, in the context of end-to-end driving, we find that imitation learning based on existing sensor fusion methods underperforms in complex driving scenarios with a high density of dynamic agents. Therefore, we propose TransFuser, a mechanism to integrate image and LiDAR representations using self-attention. Our approach uses transformer modules at multiple resolutions to fuse perspective view and bird's eye view feature maps. We experimentally validate its efficacy on a challenging new benchmark with long routes and dense traffic, as well as the official leaderboard of the CARLA urban driving simulator. At the time of submission, TransFuser outperforms all prior work on the CARLA leaderboard in terms of driving score by a large margin. Compared to geometry-based fusion, TransFuser reduces the average collisions per kilometer by 48%.


The effects of anthropogenic particulate emissions on roadway dust and Nerium oleander leaves in Messina (Sicily, Italy).
Complementary studies on the inorganic chemical composition of Nerium oleander leaves collected in the town of Messina (Sicily, Italy) and seven grain-size fractions of local roadway dust have been carried out. Data and maps are presented to show that the particulate matter present in the air of Messina contains trace elements significantly in excess with respect to the average continental earth crust. The anomalies follow the outline of the urban area, the highest concentrations of trace elements being observed where traffic density is highest. Chemical and isotopic analyses of both road dust and Nerium oleander leaves indicate that Pb contamination still characterizes roads with heavy traffic. In addition to Pb, other metals such as Pt, Pd, Sb, Au, Br, Zn, Cu, Mo, and Cd are significantly enriched in roadway dust, indicating their common anthropogenic origin, especially from traffic. SEM/EDS study of some roadway dust particles has shown the presence of gypsum probably of secondary origin, mixed particles formed by coagulation or gas-to-particle conversion, and porous spherical particles apparently emanating from combustion processes.


Association Between Social Vulnerability Index and Mortality Following Acute Myocardial Infarction in the US Counties.
Social determinants of health (SDOH) play a major role in cardiovascular outcomes. The social vulnerability index (SVI) is a tool designed by the Center for Disease Control (CDC) to measure a community's vulnerability to respond and recover from disasters. The parameters of SVI can be used to gauge social disparities amongst different US counties and its association with acute myocardial infarction (AMI) related to age- adjusted mortality rate (AAMR) by using the multiple causes of death database from CDC, Prevention's Wide-Ranging Online Data for Epidemiological Research (WONDER 2016-2020) and Agency for Toxic Substances and Disease Registry (ATSDR). We used segmented regression models to evaluate the association between quintiles of SVI scores and AAMR using STATA. A total of 2908 of 3289 US counties were used in the analysis. The mean AAMR was 89.3 per 100,000 (95% CI: 87.1-91.5) from 2016 to 2020. US counties with higher SVI were associated with higher AMI-related age-adjusted mortality when compared to counties with lower SVI. Counties with the highest SVI and AAMR were in the mid-western and southern states The findings of our study can guide focused care for a uniform upliftment of CV health across the nation by identifying the distribution of socio-economically disadvantaged counties.


Pathogenicty and immune prophylaxis of cag pathogenicity island gene knockout homogenic mutants.
To clarify the role of cag pathogenicity island (cagPAI) of Helicobacter pylori (H pylori ) in the pathogenicity and immune prophylaxis of H pylori infection. Three pairs of H pylori including 3 strains of cagPAI positive wildtype bacteria and their cagPAI knockout homogenic mutants were utilized. H pylori binding to the gastric epithelial cells was analyzed by flow cytometry assays. Apoptosis of gastric epithelial cells induced by H pylori was determined by ELISA assay. Prophylaxis effect of the wildtype and mutant strains was compared by immunization with the sonicate of the bacteria into mice model. No difference was found in the apoptasis between cagPAI positive and knockout H pylori strains in respective of the ability in the binding to gastric epithelial cells as well as the induction of apoptosis. Both types of the bacteria were able to protect the mice from the infection of H pylori after immunization, with no difference between them regarding to the protection rate as well as the stimulation of the proliferation of splenocytes of the mice. The role of cagPAI in the pathogenicity and prophylaxis of H pylori infection remains to be cleared.


Control and Transferability of Magnetic Interactions in Supramolecular Structures: Trimers of {Cr7 Ni} Antiferromagnetic Rings.
A synthetic strategy is demonstrated to prepare two distinct trimers of antiferromagnetically coupled {Cr7 Ni} rings, substantially varying the magnetic interactions between the spin centres. The interactions were studied using multi-frequency cw EPR: in a trimer linked via non-covalent H-bonding interactions no measurable interaction between rings was seen, while in a trimer linked via iso-nicotinate groups isotropic and anisotropic exchange interactions of +0.42 and -0.8 GHz, respectively, were observed. The latter are the same as those for a simpler hetero-dimer system, showing how the spin-spin interactions can be built in a predictable and modular manner in these systems.


[Chromatographic and spectral characteristics of liposoluble fluorescent compounds accumulated during damaging and aging of plants].
The chromatographic properties (e. g. thin layer mobility, separation by molecular adsorption and gel chromatography) and the fluorescence parameters of liposoluble fluorescent compounds (LFC) accumulated in the tissues during aging of detached leaves, in autumn leaves of deciduous plants and in the leaves treated with diquat, 2,4-dichloro- and 2,4,5-trichlorophenoxyacetic acids were studied. The peculiarities of detection and analysis of LFC in plant tissues are discussed. Fractionation of individual components of LFC was carried out and their properties were compared. The properties of LFC were compared to those of lipofuscine-like animal pigments and fluorescent products formed by NADPH-dependent lipid peroxidation system in rat liver microsomes stimulated by reduced pyridine nucleotides in pea leaf microsomes and by lipid photoperoxidation in isolated chloroplasts. The data obtained suggest that accumulation of "heavy" LFC fractions can reflect the enhancement of the peroxidative degradation processes involving unsaturated lipids in damaged and aging plant cells.


Future trends in parenteral nutrition.
With our present knowledge of total, intravenous nutrition it is now possible to eliminate, or greatly reduce, the incidence of malnutrition, as a complication of various medical and surgical conditions in modern hospitals. There is a tendency to include supplementary or total intravenous nutrition in the feeding program of the hospital, to ensure that the patients get an adequate daily amount of nutrients. The trend in the development of intravenous nutrition is, to supply all nutrients in the same proportions as those in which they enter the general circulation following a well-balanced oral food intake. Various mixtures of amino acids have been used as part of a complete intravenous nutrition. All studies in this field indicate a trend to use those amino acids mixtures which contain the essential and the nonessential L-amino acids in the same proportions as are found in the aminogram of proteins with high biological value. There is a trend to include fat, as fat emulsion (soybean oil-egg yolk-phospholipid emulsion), for intravenous nutrition, in an amount corresponding to about 40 energy percent as both the source of energy and of essential fatty acids for the body. To make an intravenous nutrition as complete as possible, all essential minerals should be included. Phosphorus is of special interest here as it aids in the prevention of hypophatemia and tissue anoxia caused by deficiency of diphosphateglycerate in the erythrocytes. Zinc may also be mentioned because of its importance for wound healing. There is also a tendency to include all the 13 necessary vitamins in an intravenous feeding program. In this connection vitamin K1 is of special importance. If patients on intravenous nutrition are treated with antibiotics, this may result in a change in the intestinal flora and a loss of intestinal vitamin K production, causing vitamin K deficiency, with severe or fatal bleeding. Consequently, vitamin K1 should be given daily to every patient on intravenous alimentation. The future trend in parenteral nutrition will also be to use this method for exact nutrition balances. In this way it will be possible to determine the endogenous loss via feces, as well as to study the requirements of nutrients in different conditions.


Lethal and sublethal effects of essential oils from Eucalyptus camaldulensis and Heracleum persicum against the adults of Callosobruchus maculatus.
The cowpea weevil, Callosobruchus maculatus F. (Coleoptera: Bruchidae), is an important pest of stored cowpea, Vigna ungiculata (L.) Walpers (Fabales: Fabaceae), with ample distribution in tropical and subtropical regions. Many plant essential oils have a broad-spectrum activity against pest insects, and these oils traditionally have been used in the protection of stored products. In this study, the lethal and sublethal effects of essential oils from Eucalyptus camaldulensis Dehnh. (Myrtales: Myrtaceae) and Heracleum persicum Desf. (Apiales: Apiaceae) were evaluated on the adults of C. maculatus at 26 ± 1° C, 70 ± 5% RH, and a photoperiod of 16:8 L:D. The LC50 values of E. camaldulensis and H. persicum were 56.7 and 219.4 µL/L air after 12 hr and 26.1 and 136.4 µL/L air after 24 hr of exposure, respectively. The LT50 values of E. camaldulensis and H.persicum were 6.3 and 10.9 hr, respectively. The results showed that low lethal concentration (LC20) of essential oils negatively affected the longevity, fecundity, and fertility of female adults. The sex ratio of C. maculatus offspring was not significantly affected by essential oils. Therefore, these essential oils can be suggested for controlling C. maculatus in storage systems. The introduction of essential oils into storage systems could potentially decrease seed losses.


[Initial clinical results of tissue characterization by T1, T2 and proton density in nuclear magnetic resonance tomography].
The NMR parameters (proton density, relaxation times T1 and T2) have been assessed by Carr-Purcell-Meiboom-Gill (CPMG) spin echo sequences. A computer assisted analysis of the data of 21 patients with cerebral tumours allowed a classification of tumour tissue in different tumours. The use of quantitative procedures for tissue characterisation allows the differentiation of benign and malignant brain tissue by characteristic colour coding demonstrating morphological details like tumour, edema and necrosis as well as indicating the histological types of the tumours of the central nervous system.


The polar night shift: seasonal dynamics and drivers of Arctic Ocean microbiomes revealed by autonomous sampling.
The Arctic Ocean features extreme seasonal differences in daylight, temperature, ice cover, and mixed layer depth. However, the diversity and ecology of microbes across these contrasting environmental conditions remain enigmatic. Here, using autonomous samplers and sensors deployed at two mooring sites, we portray an annual cycle of microbial diversity, nutrient concentrations and physical oceanography in the major hydrographic regimes of the Fram Strait. The ice-free West Spitsbergen Current displayed a marked separation into a productive summer (dominated by diatoms and carbohydrate-degrading bacteria) and regenerative winter state (dominated by heterotrophic Syndiniales, radiolarians, chemoautotrophic bacteria, and archaea). The autumn post-bloom with maximal nutrient depletion featured Coscinodiscophyceae, Rhodobacteraceae (e.g. Amylibacter) and the SAR116 clade. Winter replenishment of nitrate, silicate and phosphate, linked to vertical mixing and a unique microbiome that included Magnetospiraceae and Dadabacteriales, fueled the following phytoplankton bloom. The spring-summer succession of Phaeocystis, Grammonema and Thalassiosira coincided with ephemeral peaks of Aurantivirga, Formosa, Polaribacter and NS lineages, indicating metabolic relationships. In the East Greenland Current, deeper sampling depth, ice cover and polar water masses concurred with weaker seasonality and a stronger heterotrophic signature. The ice-related winter microbiome comprised Bacillaria, Naviculales, Polarella, Chrysophyceae and Flavobacterium ASVs. Low ice cover and advection of Atlantic Water coincided with diminished abundances of chemoautotrophic bacteria while others such as Phaeocystis increased, suggesting that Atlantification alters microbiome structure and eventually the biological carbon pump. These insights promote the understanding of microbial seasonality and polar night ecology in the Arctic Ocean, a region severely affected by climate change.


Down syndrome fibroblasts and mouse Prep1-overexpressing cells display increased sensitivity to genotoxic stress.
PREP1 (PKNOX1) maps in the Down syndrome (DS) critical region of chromosome 21, is overexpressed in some DS tissues and might be involved in the DS phenotype. By using fibroblasts from DS patients and by overexpressing Prep1 in F9 teratocarcinoma and Prep1(i/i) MEF to single out the role of the protein, we report that excess Prep1 increases the sensitivity of cells to genotoxic stress and the extent of the apoptosis directly correlates with the level of Prep1. The apoptotic response of Prep1-overexpressing cells is mediated by the pro-apoptotic p53 protein that we show is a direct target of Prep1, as its depletion reverts the apoptotic phenotype. The induction of p53 overcomes the anti-apoptotic role of Bcl-X(L), previously shown to be also a Prep1 target, the levels of which are increased in Prep1-overexpressing cells as well. Our results provide a rationale for the involvement of PREP1 in the apoptotic phenotype of DS tissues and indicate that differences in Prep1 level can have drastic effects.


Impact of bariatric surgery on serum urate targets in people with morbid obesity and diabetes: a prospective longitudinal study.
Weight loss leads to reduced serum urate (SU) in people with obesity. However, the clinical relevance of such reductions in SU is unknown. This study examined the impact of non-surgical weight loss and bariatric surgery on SU targets in people with morbid obesity and diabetes. The study was a single-centre, prospective study of 60 people with type 2 diabetes and body mass index ≥35 kg/m(2). Following 6 months of non-surgical weight loss, all participants had laparoscopic sleeve gastrectomy, with a further 1 year of follow-up. Serial SUs were measured throughout the study. Participants experienced mean (SD) weight loss of 5.5 (4.1) kg prior to surgery and 34.3 (11.1) kg following surgery. SU did not change following non-surgical weight loss (0.38 (0.09) mmol/L at baseline and 0.38 (0.10) mmol/L at follow-up), but increased to 0.44 (0.15) mmol/L in the immediate postoperative period and reduced to 0.30 (0.08) mmol/L 1 year after surgery (p<0.05 for both compared with baseline). Baseline SU, cessation of diuretics, female sex and change in creatinine independently predicted change in SU at the final visit. In participants without gout, SU above saturation levels (≥0.41 mmol/L) were present in 19/48 (40%) at baseline and 1/48 (2%) 1 year after surgery (p<0.0001). In participants with gout, SU above therapeutic target levels (≥0.36 mmol/L) were present in 10/12 (83%) at baseline and 4/12 (33%) 1 year after surgery (p=0.031). Clinically relevant reductions in SU occur following bariatric surgery in people with diabetes and WHO class II or higher obesity.


What are the sleep characteristics of elite female athletes? A systematic review with meta-analysis.
With the recent growth in female sport, practitioners need to be able to provide specific support to female athletes to ensure their sleep, health and athletic performance are optimised. Examine the patterns, duration and quality of sleep among elite female athletes, and consider the impact of situational challenges and their effects on the sleep of elite female athletes. Data was located through a search of SPORTDiscus, MEDLINE and Scopus from inception up to May 2021. Studies needed to be peer-reviewed research reporting quantitative sleep outcomes for female athletes ≥ 18 years of age and competing at a predefined elite level. A meta-analysis was performed on habitual sleep outcomes (e.g. total sleep time [TST] and sleep efficiency [SE]) measured with actigraphy. A total of 38 studies were included. Meta-analysis showed habitual TST (n = 14) was 7.8 h [7.4, 8.2] (mean [95% CI]), and SE was 86.7% [84.7, 88.6], with high variability among studies (I2 = 97.8-98.2%). Subjective sleep complaints are common before a competition, as do post-training sleep disturbances (63% studies report TST decrease), and post-competition sleep disturbances (75% studies report TST decrease). Female athletes achieve satisfactory objective sleep quantity and quality during habitual periods, but experience sleep disturbances pre- and post-situational challenges. There is high variability of objective sleep outcomes, demonstrating the individual nature of habitual female athlete sleep. Overall, future research must focus on optimising the sleep appraisal methods and creating high-quality study designs in a broader number of sports.


Loss and recovery of excitability by normal and by degenerating nerves deprived of sodium.
A study has been made of the loss of excitability in a sodium-free medium and of the recovery of excitability in Ringer's solution by A fibers of normal frog nerves and of nerves in advanced stages of Wallerian degeneration. With normal nerves that are being kept in a sodium-free medium the number of conducting fibers does not undergo a readily detectable decrease in less than 1 to 2 hours; inexcitability of all the A fibers does not develop in less than 7 to 8 hours. During the development of inexcitability the speed of conduction of the still conducting fibers undergoes a progressive decrease; in advanced stages the speed of conduction is not more than one-fifth of the normal speed. The nerve fibers lose the ability to conduct rhythmic trains of impulses earlier than the ability to conduct single impulses. The recovery of excitability in Ringer's solution duplicates in a reverse order the sequence of changes that have been previously observed during the development of inexcitability. The rate of the recovery of excitability in Ringer's solution is higher than the rate of the loss of excitability in the sodium-free medium. With degenerating nerves the effect of the lack of sodium develops qualitatively in the same manner in which it develops with normal nerves. Degenerating nerve fibers, however, become inexcitable in a sodium-free medium earlier than normal fibers. The recovery of the excitability in Ringer's solution takes place in much the same manner in normal and in degenerating nerve fibers. The loss of excitability during Wallerian degeneration is a process that develops simultaneously, or practically so, throughout the entire length of the fibers. The nerve fibers retain a great deal of functional ability throughout the several days which precede the onset of inexcitability and then suddenly become inexcitable.


Pepper asparagine synthetase 1 (CaAS1) is required for plant nitrogen assimilation and defense responses to microbial pathogens.
Asparagine synthetase is a key enzyme in the production of the nitrogen-rich amino acid asparagine, which is crucial to primary nitrogen metabolism. Despite its importance physiologically, the roles that asparagine synthetase plays during plant defense responses remain unknown. Here, we determined that pepper (Capsicum annuum) asparagine synthetase 1 (CaAS1) is essential for plant defense to microbial pathogens. Infection with Xanthomonas campestris pv. vesicatoria (Xcv) induced early and strong CaAS1 expression in pepper leaves and silencing of this gene resulted in enhanced susceptibility to Xcv infection. Transgenic Arabidopsis (Arabidopsis thaliana) plants that overexpressed CaAS1 exhibited enhanced resistance to Pseudomonas syringae pv. tomato DC3000 and Hyaloperonospora arabidopsidis. Increased CaAS1 expression influenced early defense responses in diseased leaves, including increased electrolyte leakage, reactive oxygen species and nitric oxide bursts. In plants, increased conversion of aspartate to asparagine appears to be associated with enhanced resistance to bacterial and oomycete pathogens. In CaAS1-silenced pepper and/or CaAS1-overexpressing Arabidopsis, CaAS1-dependent changes in asparagine levels correlated with increased susceptibility or defense responses to microbial pathogens, respectively. Linking transcriptional and targeted metabolite studies, our results suggest that CaAS1 is required for asparagine synthesis and disease resistance in plants.


X chromosome monosomy restricted to the left ventricle is not a major cause of isolated hypoplastic left heart.
Hypoplastic left heart sequence (HLHS) encompasses obstructive lesions of the left side of the heart accompanied by varying degrees of underdevelopment of the mitral valve, either atresia or stenosis, left ventricle, aortic valve, and ascending aorta. HLHS has an incidence of 0.016-0.036% live births and can occur as an isolated defect or several different chromosome abnormalities. In particular, about 20% of patients with monosomy X, have HLHS, suggesting a relationship between this form of aneuploidy and this congenital heart defect (CHD). Somatic mutations restricted to the cardiac affected structure have been considered a mechanism of CHD. The aim of this study was to evaluate if monosomy X restricted to the left ventricle causes isolated HLHS. Formalin-fixed, paraffin-embedded cardiac tissue obtained from 19 patients with HLHS (10 males and 9 females) without extra cardiac anomalies and with a normal constitutional karyotype, were investigated by FISH analysis, using X/Y/18 centromeric probes. The results of this analysis were compared with those obtained by examining the heart specimens of 15 chromosomally normal pediatric patients affected by either restrictive or dilated cardiomyopathy, which were used as negative controls. Mosaic monosomy X was detected in the cardiac tissue nuclei of both groups, with similar frequencies (6-16% and 12-16%, respectively), suggesting that chromosome X monosomy is not rare in this tissue, but is not a major cause of isolated HLHS.


Continuous control of flagellar gene expression by the σ28-FlgM regulatory circuit in Salmonella enterica.
The flagellar genes in Salmonella enterica are expressed in a temporal hierarchy that mirrors the assembly process itself. The σ(28)-FlgM regulatory circuit plays a key role in controlling this temporal hierarchy. This circuit ensures that the class 3 genes are expressed only when the hook-basal body (HBB), a key intermediate in flagellar assembly, is complete. In this work, we investigated the role of the σ(28)-FlgM regulatory circuit in controlling the timing and magnitude of class 3 gene expression using a combination of mathematical modelling and experimental analysis. Analysis of the model predicted that this circuit continuously controls class 3 gene expression in response to HBB abundance. We experimentally validated these predictions by eliminating different components of the σ(28)-FlgM regulatory system and also by rewiring the transcriptional hierarchy. Based on these results, we conclude that the σ(28)-FlgM regulatory circuit continuously senses the HBB assembly process and regulates class 3 gene expression and possibly flagellar numbers in response.


Breast cancer after use of estrogen plus progestin in postmenopausal women.
Following the release of the 2002 report of the Women's Health Initiative (WHI) trial of estrogen plus progestin, the use of menopausal hormone therapy in the United States decreased substantially. Subsequently, the incidence of breast cancer also dropped, suggesting a cause-and-effect relation between hormone treatment and breast cancer. However, the cause of this decrease remains controversial. We analyzed the results of the WHI randomized clinical trial--in which one study group received 0.625 mg of conjugated equine estrogens plus 2.5 mg of medroxyprogesterone acetate daily and another group received placebo--and examined temporal trends in breast-cancer diagnoses in the WHI observational-study cohort. Risk factors for breast cancer, frequency of mammography, and time-specific incidence of breast cancer were assessed in relation to combined hormone use. In the clinical trial, there were fewer breast-cancer diagnoses in the group receiving estrogen plus progestin than in the placebo group in the initial 2 years of the study, but the number of diagnoses increased over the course of the 5.6-year intervention period. The elevated risk decreased rapidly after both groups stopped taking the study pills, despite a similar frequency of mammography. In the observational study, the incidence of breast cancer was initially about two times as high in the group receiving menopausal hormones as in the placebo group, but this difference in incidence decreased rapidly in about 2 years, coinciding with year-to-year reductions in combined hormone use. During this period, differences in the frequency of mammography between the two groups were unchanged. The increased risk of breast cancer associated with the use of estrogen plus progestin declined markedly soon after discontinuation of combined hormone therapy and was unrelated to changes in frequency of mammography.


FMNL2 regulates dynamics of fascin in filopodia.
Filopodia are peripheral F-actin-rich structures that enable cell sensing of the microenvironment. Fascin is an F-actin-bundling protein that plays a key role in stabilizing filopodia to support efficient adhesion and migration. Fascin is also highly up-regulated in human cancers, where it increases invasive cell behavior and correlates with poor patient prognosis. Previous studies have shown that fascin phosphorylation can regulate F-actin bundling, and that this modification can contribute to subcellular fascin localization and function. However, the factors that regulate fascin dynamics within filopodia remain poorly understood. In the current study, we used advanced live-cell imaging techniques and a fascin biosensor to demonstrate that fascin phosphorylation, localization, and binding to F-actin are highly dynamic and dependent on local cytoskeletal architecture in cells in both 2D and 3D environments. Fascin dynamics within filopodia are under the control of formins, and in particular FMNL2, that binds directly to dephosphorylated fascin. Our data provide new insight into control of fascin dynamics at the nanoscale and into the mechanisms governing rapid cytoskeletal adaptation to environmental changes. This filopodia-driven exploration stage may represent an essential regulatory step in the transition from static to migrating cancer cells.


Capsazepine is a novel activator of the delta subunit of the human epithelial Na+ channel.
The amiloride-sensitive epithelial Na+ channel (ENaC) regulates Na+ homeostasis into cells and across epithelia. So far, four homologous subunits of mammalian ENaC have been isolated and are denoted as alpha, beta, gamma, and delta. The chemical agents acting on ENaC are, however, largely unknown, except for amiloride and benzamil as ENaC inhibitors. In particular, there are no agonists currently known that are selective for ENaCdelta, which is mainly expressed in the brain. Here we demonstrate that capsazepine, a competitive antagonist for transient receptor potential vanilloid subfamily 1, potentiates the activity of human ENaCdeltabetagamma (hENaCdeltabetagamma) heteromultimer expressed in Xenopus oocytes. The inward currents at a holding potential of -60 mV in hENaCdeltabetagamma-expressing oocytes were markedly enhanced by the application of capsazepine (> or =1 microM), and the capsazepine-induced current was mostly abolished by the addition of 100 microM amiloride. The stimulatory effects of capsazepine on the inward current were concentration-dependent with an EC50 value of 8 microM. Neither the application of other vanilloid compounds (capsaicin, resiniferatoxin, and olvanil) nor a structurally related compound (dopamine) modulated the inward current. Although hENaCdelta homomer was also significantly activated by capsazepine, unexpectedly, capsazepine had no effect on hENaCalpha and caused a slight decrease on the hENaCalphabetagamma current. In conclusion, capsazepine acts on ENaCdelta and acts together with protons. Other vanilloids tested do not have any effect. These findings identify capsazepine as the first known chemical activator of ENaCdelta.


Cause of death in patients with poststroke epilepsy: Results from a nationwide cohort study.
The risk of death is increased for persons with epilepsy. The literature on causes of death in epilepsy is based mainly on cohorts with epilepsy of mixed aetiologies. For clinical purposes and improved understanding of mortality in different epilepsies, more information is needed on mortality in epilepsies of specific causes. In poststroke epilepsy (PSE), seizures occur in a setting of vascular disease and high mortality rates. The extent to which epilepsy contributes to mortality in this patient group is poorly understood. We therefore aimed to describe causes of death (COD) in PSE on a national scale. A previously identified cohort of 7740 patients with epilepsy or seizures after a stroke in 2005-2010 was investigated. A total of 4167 deaths occurred before the end of 2014. The standardized mortality ratio for the study cohort was 3.56 (95% CI: 3.45-3.67). The main underlying causes of death were disorders of the circulatory system (60%) followed by neoplasms (12%). Diseases of the nervous system were the sixth leading underlying COD (3%), and epilepsy or status epilepticus was considered the underlying COD in approximately a similar proportion of cases as neurodegenerative disorders (0.9% and 1.1%, respectively). Epilepsy was considered a contributing COD in 14% of cases. Our findings highlight the importance of optimal management of vascular morbidity in patients with PSE. The large proportion of patients with epilepsy as a contributing COD indicate the need of high ambitions also regarding the management of seizures in patients with PSE.


Ossifying fibroma of bone. Report of two cases.
Two cases are reported of a hitherto undescribed type of lesion for which the term "ossifying fibroma of bone" is suggested. The lesions occurred in children aged 12 and 13 years, and involved the tibia and the humerus. Histologically they consisted of fibrous tissue containing small, partly calcified spherules: in this respect they differ from the usual types of fibro-osseous lesion such as fibrous dysplasia and osteofibrous dysplasia. The term "ossifying fibroma" is proposed for this condition, although in the past it has been applied to other types of bone lesion.


Variability in triactinomyxon production from Tubifex tubifex populations from the same mitochondrial DNA lineage infected with Myxobolus cerebralis, the causative agent of whirling disease in salmonids.
Myxobolus cerebralis, the causative agent of whirling disease, infects both salmonid fish and an aquatic oligochaete, Tubifex tubifex. Although M. cerebralis has been detected in river drainages throughout the United States, disease severity among wild fish populations has been highly variable. Tubifex tubifex populations have been genetically characterized using sequences from the 16S mitochondrial DNA (mtDNA) gene, the 18S ribosomal RNA gene, the internal transcribed spacer region 1 (ITS1), and randomly amplified polymorphic DNA (RAPD). Our earlier work indicated that large differences in compatibility between the parasite and populations of T. tubifex may play a substantial role in the distribution of whirling disease and resulting mortality in different watersheds. In the present study, we examined 4 laboratory populations of T. tubifex belonging to 16S mtDNA lineage III and 1 population belonging to 16S mtDNA lineage I for triactinomyxon (TAM) production after infection with M. cerebralis myxospores. All 4 16S mtDNA lineage III populations produced TAMs, but statistically significant differences in TAM production were observed. Most individuals in the 16S mtDNA lineage III-infected populations produced TAMs. The 16S mtDNA lineage I population produced few TAMs. Further genetic characterization of the 16S mtDNA lineage III populations with RAPD markers indicated that populations producing similar levels of TAMs had more genetic similarity.


Serum levels of mannose-binding lectin and the risk of future coronary artery disease in apparently healthy men and women.
To determine the association between serum levels of mannose-binding lectin (MBL) and the risk of future coronary artery disease (CAD) in apparently healthy men and women. We performed a prospective case-control study among apparently healthy men and women nested in the EPIC-Norfolk cohort. Baseline concentrations of MBL were measured in serum samples of 946 patients who experienced a myocardial infarction or died of CAD during follow-up, and 1799 matched controls who remained free of CAD. Among men, median MBL levels were 1.63 ng/mL (interquartile range [IQR]: 0.59 to 3.80) in cases and 1.20 ng/mL (IQR: 0.48 to 3.37) in controls. Among women, median MBL levels were 1.02 ng/mL (IQR: 0.43 to 2.95) in cases and 1.01 ng/mL (IQR: 0.43 to 2.94) in controls. After adjustment, the odds ratio in men for future CAD was 1.59 (95% confidence interval [CI]: 1.09 to 2.32; P for linearity=0.01) for those in the highest quartile compared with those in the lowest quartile. In women no such relation was observed. Elevated levels of MBL are associated with an increased risk of future CAD in apparently healthy men but not in women. The sex difference merits further exploration.


Variation in acclimation of photosynthesis in Trifolium repens after eight years of exposure to Free Air CO2 Enrichment (FACE).
The initial stimulation of photosynthesis observed on elevation of [CO2] in grasslands has been predicted to be a transient phenomenon constrained by the loss of photosynthetic capacity due to other limitations, notably nutrients and sinks for carbohydrates. Legumes might be expected partially to escape these feedbacks through symbiotic N2 fixation. The Free-Air Carbon dioxide Enrichment (FACE) experiment at Eschikon, Switzerland, has been the longest running investigation of the effects of open-air elevation of [CO2] on vegetation. The prediction of a long-term loss of photosynthetic capacity was tested by analysing photosynthesis in Trifolium repens L. (cv. Milkanova) in the spring and autumn of the eighth, ninth and tenth years of treatment. A high and low N treatment also allowed a test of the significance of exogenous N-supply in maintaining a stimulation of photosynthetic capacity in the long-term. Prior work in this Free Air CO2 Enrichment (FACE) experiment has revealed that elevated [CO2] increased both vegetative and reproductive growth of T. repens independent of N treatment. It is shown here that the photosynthetic response of T. repens was also independent of N fertilization under both current ambient and elevated (600 micro mol mol-1) [CO2]. There was a strong effect of season on photosynthesis, with light-saturated rates (Asat) 37% higher in spring than in autumn. Higher Asat in the spring was supported by higher maximum Rubisco carboxylation rates (Vc,max) and maximum rates of electron transport (Jmax) contributing to RuBP regeneration. Elevated [CO2] increased Asat by 37% when averaged across all measurement periods and both N fertilization levels, and decreased stomatal conductance by 25%. In spring, there was no effect of elevated [CO2] on photosynthetic capacity of leaves, but in autumn both Vc,max and Jmax were reduced by approximately 20% in elevated [CO2]. The results show that acclimation of photosynthetic capacity can occur in a nitrogen-fixing species, in the field where there are no artificial restrictions on sink capacity. However, even with acclimation there was a highly significant increase in photosynthesis at elevated [CO2].


Estriol strongly inhibits DNCB-induced contact dermatitis: role of antigen-specific antibodies in pathogenesis.
The endogenous estrogens are important modulators of the immune system and its functions. However, their effects are rather complex and many aspects have not been studied. In this study, we used the 1-chloro-2,4-dinitrobenzene (DNCB)-induced contact dermatitis as a disease model and investigated the effect of estriol (E3), along with two other estrogens, 17β-estradiol and estrone, on the pathogenesis of contact hypersensitivity. A series of parameters, such as ear swelling, skin inflammation, antigen-specific immunoglobulins, and lymphocyte compositions in peripheral lymphoid organs, were evaluated in mice following development of contact dermatitis. We found that administration of all three estrogens elicited strong inhibition of DNCB-induced dermatitis, while E3 exerted the strongest suppressive effect. Administration of E3 alleviated dermatitis, and this effect was accompanied by decreases in serum DNCB-specific immunoglobulins, such as IgA, IgG1, IgG2a, and IgG2b. Besides, treatment with E3 reduced B cell population, especially IgG-producing cells in the peripheral lymphoid organs following the induction of dermatitis. These observations consistently suggest that the antibody (Ab)-mediated humoral immune reactions play a critical role in the pathogenesis of DNCB-induced contact dermatitis. The results from this study demonstrate, for the first time, that estrogen administration has a strong suppressive effect on the pathogenesis of contact dermatitis. These findings offer important insights concerning the pathogenic role of antigen-specific Abs in contact dermatitis and the treatment of chemical-induced, Ab-mediated skin hypersensitivity reactions in humans.


Human papillomavirus infection and risk determinants for squamous intraepithelial lesion and cervical cancer in Japan.
A case control design was used to investigate human papillomavirus (HPV) prevalence and risk factors associated with development of cervical squamous intraepithelial lesion (SIL) and cervical cancer (CC) in Japan. One hundred and twenty-three women with histologically confirmed SIL or CC were compared to a control group of 778 cytologically normal women. With the use of a polymerase chain reaction (PCR)-based method for detection of low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33, 35, 52 and 58) HPVs, a high prevalence of HPV infection was observed in smokers among the controls. Logistic regression analysis demonstrated that high-risk HPV infection was the most significant risk determinant for LSIL (OR=9.4, 95% CI=4.5-19), HSIL (OR=77, 95% CI=28-217) and CC (OR=97, 95% CI=35-269). It also showed that unmarried women, women married for 5 to 19 years and smokers represented high risk groups for SIL, while smokers and women with a history of many pregnancies/parities had increased risk for CC. Smoking was the only HPV infection-independent factor for CC, suggesting that smoking may have a carcinogenic effect on the cervix. Since neither history of other cancer nor family cancer history was associated with SIL or CC, genetic factors appear to play little role in cervical carcinogenesis. The risk for cervical neoplasia due to HPV infection increased after marriage in Japan, suggesting a role for husbands as carriers of HPV transmission. Protection from high-risk HPV infection may be of greatest importance for prevention of cervical cancer.


Evolution of thermotolerance in hot spring cyanobacteria of the genus Synechococcus.
The extension of ecological tolerance limits may be an important mechanism by which microorganisms adapt to novel environments, but it may come at the evolutionary cost of reduced performance under ancestral conditions. We combined a comparative physiological approach with phylogenetic analyses to study the evolution of thermotolerance in hot spring cyanobacteria of the genus Synechococcus. Among the 20 laboratory clones of Synechococcus isolated from collections made along an Oregon hot spring thermal gradient, four different 16S rRNA gene sequences were identified. Phylogenies constructed by using the sequence data indicated that the clones were polyphyletic but that three of the four sequence groups formed a clade. Differences in thermotolerance were observed for clones with different 16S rRNA gene sequences, and comparison of these physiological differences within a phylogenetic framework provided evidence that more thermotolerant lineages of Synechococcus evolved from less thermotolerant ancestors. The extension of the thermal limit in these bacteria was correlated with a reduction in the breadth of the temperature range for growth, which provides evidence that enhanced thermotolerance has come at the evolutionary cost of increased thermal specialization. This study illustrates the utility of using phylogenetic comparative methods to investigate how evolutionary processes have shaped historical patterns of ecological diversification in microorganisms.


Rimantadine therapy of influenza A infection in mice.
Eighty per cent of mice infected with a mouse-adapted strain of influenza virus died within 3 to 8 days after infection. Rimantadine given at maximum protective doses reduced mortality to 10%. This protection is dose related and can be demonstrated with doses from 4.5 to 24 mg per kg per day. Significant survival rates are shown by delaying treatment as long as 48 hr after infection. Lungs of treated mice have significantly less virus than those of controls at 24, 48, and 72 hr after infection. Antibody production as measured by hemagglutination inhibition is not different in treated and controlled mice. These results indicate that rimantadine is an effective prophylactic and therapeutic agent and that its activity is associated with decreased viral titers.


The effects of oxytocin on eating behaviour and metabolism in humans.
Oxytocin, a hypothalamic hormone that is secreted directly into the brain and enters the peripheral circulation through the posterior pituitary gland, regulates a range of physiologic processes, including eating behaviour and metabolism. In rodents and nonhuman primates, chronic oxytocin administration leads to sustained weight reduction by reducing food intake, increasing energy expenditure and inducing lipolysis. Oxytocin might improve glucose homeostasis, independently of its effects on weight. Clinical studies are beginning to translate these important preclinical findings to humans. This Review describes key data linking oxytocin to eating behaviour and metabolism in humans. For example, a single intranasal dose of oxytocin can reduce caloric intake, increase fat oxidation and improve insulin sensitivity in men. Furthermore, a pilot study of 8 weeks of oxytocin treatment in adults with obesity or overweight led to substantial weight loss. Together, these data support further investigation of interventions that target pathways involving oxytocin as potential therapeutics in metabolic disorders, including obesity and diabetes mellitus. Therapeutic considerations and areas for further research are also discussed.


Migratory ichthyosiform dermatosis with type 2 diabetes mellitus and insulin resistance.
In addition to the well-defined hereditary primary ichthyoses, many sporadic or less well-defined keratinization disorders with or without systemic manifestations have been reported. Herein we describe ichthyosiform dermatosis associated with type 2 diabetes mellitus. The patients were members of a large Arab family with heavy consanguinity. Eighteen members were affected with a variously severe scaly disorder. They showed migratory polycyclic keratotic scaly plaques evolving into diffuse generalized scaling or complete remission. Acanthosis nigricans-like lesions were also noted, and there was an association with type 2 diabetes mellitus. A scarcity of intercorneocyte lamellae and reduction in lamellar body contents were observed. We could not find a report of a similar dermatosis. Furthermore, an association between ichthyosis and diabetes has not been documented. Therefore, we believe that this may constitute a new entity.


An evidence-based and practical approach to using Bydureon™ in patients with type 2 diabetes.
Glucagon-like peptide (GLP)-1 agonists are one of the newer classes of medications for use in type 2 diabetes. There are currently three GLP-1 agonists on the market: exenatide twice daily, liraglutide, and exenatide extended release (ER). Exenatide ER is a new weekly formulation of exenatide. Exenatide ER reduces glycosylated hemoglobin by 1.6%, with fewer gastrointestinal side effects compared with twice-daily exenatide. Like other GLP-1 agonists, exenatide ER can be used in combination with metformin, sulfonylureas, or thiazolidinediones. Patients should be assessed for risk of pancreatitis and renal impairment. Education about proper administration technique is vital with the novel delivery system. Prescribers may also consider the use of exenatide ER to improve medication adherence in patients who have successfully tolerated exenatide twice daily or use in patients who have gastrointestinal side effects with exenatide twice daily. Exenatide is a reasonable option that can be added to the regimen of a patient with type 2 diabetes.


Cryptic protein priming sites in two different domains of duck hepatitis B virus reverse transcriptase for initiating DNA synthesis in vitro.
Initiation of reverse transcription in hepadnaviruses is accomplished by a unique protein-priming mechanism whereby a specific Y residue in the terminal protein (TP) domain of the viral reverse transcriptase (RT) acts as a primer to initiate DNA synthesis, which is carried out by the RT domain of the same protein. When separate TP and RT domains from the duck hepatitis B virus (DHBV) RT protein were tested in a trans-complementation assay in vitro, the RT domain could also serve, unexpectedly, as a protein primer for DNA synthesis, as could a TP mutant lacking the authentic primer Y (Y96) residue. Priming at these other, so-called cryptic, priming sites in both the RT and TP domains shared the same requirements as those at Y96. A mini RT protein with both the TP and RT domains linked in cis, as well as the full-length RT protein, could also initiate DNA synthesis using cryptic priming sites. The cryptic priming site(s) in TP was found to be S/T, while those in the RT domain were Y and S/T. As with the authentic TP Y96 priming site, the cryptic priming sites in the TP and RT domains could support DNA polymerization subsequent to the initial covalent linkage of the first nucleotide to the priming amino acid residue. These results provide new insights into the complex mechanisms of protein priming in hepadnaviruses, including the selection of the primer residue and the interactions between the TP and RT domains that is essential for protein priming.


Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects.
1. In this study an acute anti-hypertensive effect of three anti-oxidant agents (vitamin C, thiopronine and glutathione) in hypertensive subjects and in both hypertensive and non-hypertensive diabetic patients is reported. 2. The anti-oxidants had no effect on blood pressure in healthy normal subjects at a dose of 6 mmol, but thiopronine and glutathione produced a significant hypotensive effect at a dose of 12 mmol. 3. These data suggest that anti-oxidants might have a dilatatory effect and that an imbalance of the nitric oxide-free radical interaction might facilitate the development of hypertension in humans.


Histone chaperone NAP1 mediates sister chromatid resolution by counteracting protein phosphatase 2A.
Chromosome duplication and transmission into daughter cells requires the precisely orchestrated binding and release of cohesin. We found that the Drosophila histone chaperone NAP1 is required for cohesin release and sister chromatid resolution during mitosis. Genome-wide surveys revealed that NAP1 and cohesin co-localize at multiple genomic loci. Proteomic and biochemical analysis established that NAP1 associates with the full cohesin complex, but it also forms a separate complex with the cohesin subunit stromalin (SA). NAP1 binding to cohesin is cell-cycle regulated and increases during G2/M phase. This causes the dissociation of protein phosphatase 2A (PP2A) from cohesin, increased phosphorylation of SA and cohesin removal in early mitosis. PP2A depletion led to a loss of centromeric cohesion. The distinct mitotic phenotypes caused by the loss of either PP2A or NAP1, were both rescued by their concomitant depletion. We conclude that the balanced antagonism between NAP1 and PP2A controls cohesin dissociation during mitosis.


The Orphan G-Protein Coupled Receptor 182 Is a Negative Regulator of Definitive Hematopoiesis through Leukotriene B4 Signaling.
The G protein-coupled receptor 182 (GPR182) is an orphan GPCR, the expression of which is enriched in embryonic endothelial cells (ECs). However, the physiological role and molecular mechanism of action of GPR182 are unknown. Here, we show that GPR182 negatively regulates definitive hematopoiesis in zebrafish and mice. In zebrafish, gpr182 expression is enriched in the hemogenic endothelium (HE), and gpr182 -/- display an increased expression of HE and hematopoietic stem cell (HSC) marker genes. Notably, we find an increased number of myeloid cells in gpr182 -/- compared to wild-type. Further, by time-lapse imaging of zebrafish embryos during the endothelial-to-hematopoietic transition, we find that HE/HSC cell numbers are increased in gpr182 -/- compared to wild-type. GPR182 -/- mice also exhibit an increased number of myeloid cells compared to wild-type, indicating a conserved role for GPR182 in myelopoiesis. Using cell-based small molecule screening and transcriptomic analyses, we further find that GPR182 regulates the leukotriene B4 (LTB4) biosynthesis pathway. Taken together, these data indicate that GPR182 is a negative regulator of definitive hematopoiesis in zebrafish and mice, and provide further evidence for LTB4 signaling in HSC biology.


Nickel-Catalyzed Highly Regioselective Hydrocyanation of Terminal Alkynes with Zn(CN)2 Using Water as the Hydrogen Source.
The first efficient and general nickel-catalyzed hydrocyanation of terminal alkynes with Zn(CN)2 in the presence of water has been developed. The reaction provides a regioselective protocol for the synthesis of functionalized vinyl nitriles with a range of structural diversity under mild reaction conditions while obviating use of the volatile and hazardous reagent of HCN. Deuterium-labeling experiments confirmed the role of water as the hydrogen source in this hydrocyanation reaction.


State-of-the-art review of secondary pulmonary infections in patients with COVID-19 pneumonia.
The incidence of secondary pulmonary infections is not well described in hospitalized COVID-19 patients. Understanding the incidence of secondary pulmonary infections and the associated bacterial and fungal microorganisms identified can improve patient outcomes. This narrative review aims to determine the incidence of secondary bacterial and fungal pulmonary infections in hospitalized COVID-19 patients, and describe the bacterial and fungal microorganisms identified. We perform a literature search and select articles with confirmed diagnoses of secondary bacterial and fungal pulmonary infections that occur 48 h after admission, using respiratory tract cultures in hospitalized adult COVID-19 patients. We exclude articles involving co-infections defined as infections diagnosed at the time of admission by non-SARS-CoV-2 viruses, bacteria, and fungal microorganisms. The incidence of secondary pulmonary infections is low at 16% (4.8-42.8%) for bacterial infections and lower for fungal infections at 6.3% (0.9-33.3%) in hospitalized COVID-19 patients. Secondary pulmonary infections are predominantly seen in critically ill hospitalized COVID-19 patients. The most common bacterial microorganisms identified in the respiratory tract cultures are Pseudomonas aeruginosa, Klebsiella species, Staphylococcus aureus, Escherichia coli, and Stenotrophomonas maltophilia. Aspergillus fumigatus is the most common microorganism identified to cause secondary fungal pulmonary infections. Other rare opportunistic infection reported such as PJP is mostly confined to small case series and case reports. The overall time to diagnose secondary bacterial and fungal pulmonary infections is 10 days (2-21 days) from initial hospitalization and 9 days (4-18 days) after ICU admission. The use of antibiotics is high at 60-100% involving the studies included in our review. The widespread use of empirical antibiotics during the current pandemic may contribute to the development of multidrug-resistant microorganisms, and antimicrobial stewardship programs are required for minimizing and de-escalating antibiotics. Due to the variation in definition across most studies, a large, well-designed study is required to determine the incidence, risk factors, and outcomes of secondary pulmonary infections in hospitalized COVID-19 patients.


Myogenic properties of cerebral blood vessels from normotensive and hypertensive rats.
Myogenic properties of posterior cerebral arteries from normotensive and hypertensive rats were analyzed in vitro and quantified in terms of both pressure range limits and degree of myogenic activity. Spontaneously hypertensive rat (SHR) vessels were significantly narrower in a fully relaxed state, and both wall thickness and wall-to-radius ratios were increased. After equilibration in 1.6 mM calcium physiological saline solution a substantial tone developed which resulted in average diameter decreases of 34 and 37% in Wistar-Kyoto (WKY) and SHR, respectively; average lumen diameters were approximately 125 micron. Rapid changes in transmural pressure (delta P 10-25 mmHg/s) were applied and diameter responses measured continuously. Myogenic responses began 1-3 s after a change in transmural pressure, and arteries regained their initial diameters after a pressure step in about 2 min; a final, steady-state diameter was achieved in 4-5 min. Myogenic pressure ranges were 49-145 mmHg in WKY and 64-181 in SHR; when responses were segregated according to positive and negative pressure steps, more myogenic responses were observed at lower pressures for pressure step decreases when compared with pressure step increases. Thus myogenic ranges for increasing pressure steps were 71-151 (WKY) and 72-188 mmHg (SHR) and for decreasing steps 45-117 (WKY) and 57-148 mmHg (SHR). Myogenic responses in SHR were weaker than in WKY rats: the former maintained essentially a constant diameter over a wide range of pressures, whereas arteries from the latter decreased diameter with increasing pressures.(ABSTRACT TRUNCATED AT 250 WORDS)


Dietary cysteine is used more efficiently by children with severe acute malnutrition with edema compared with those without edema.
Children with edematous severe acute malnutrition (SAM) produce less cysteine than do their nonedematous counterparts. They also have marked glutathione (GSH) depletion, hair loss, skin erosion, gut mucosal atrophy, and depletion of mucins. Because GSH, skin, hair, mucosal, and mucin proteins are rich in cysteine, we hypothesized that splanchnic extraction and the efficiency of cysteine utilization would be greater in edematous than in nonedematous SAM. We aimed to measure cysteine kinetics in childhood edematous and nonedematous SAM. Cysteine flux, oxidation, balance, and splanchnic uptake (SPU) were measured in 2 groups of children with edematous (n = 9) and nonedematous (n = 10) SAM at 4.4 ± 1.1 d after admission (stage 1) and at 20.5 ± 1.6 d after admission (stage 2) when they had replenished 50% of their weight deficit. In comparison with the nonedematous group, the edematous group had slower cysteine flux at stage 1 but not at stage 2; furthermore, they oxidized less cysteine at both stages, resulting in better cysteine balance and therefore better efficiency of utilization of dietary cysteine. Cysteine SPU was not different between groups but was ∼45% in both groups at the 2 stages. These findings suggest that children with edematous SAM may have a greater requirement for cysteine during early and mid-nutritional rehabilitation because they used dietary cysteine more efficiently than did their nonedematous counterparts and because the splanchnic tissues of all children with SAM have a relatively high requirement for cysteine. This trial was registered at clinicaltrials.gov as NCT00069134.


Metagenomics survey unravels diversity of biogas microbiomes with potential to enhance productivity in Kenya.
The obstacle to optimal utilization of biogas technology is poor understanding of biogas microbiomes diversities over a wide geographical coverage. We performed random shotgun sequencing on twelve environmental samples. Randomized complete block design was utilized to assign the twelve treatments to four blocks, within eastern and central regions of Kenya. We obtained 42 million paired-end reads that were annotated against sixteen reference databases using two ENVO ontologies, prior to β-diversity studies. We identified 37 phyla, 65 classes and 132 orders. Bacteria dominated and comprised 28 phyla, 42 classes and 92 orders, conveying substrate's versatility in the treatments. Though, Fungi and Archaea comprised 5 phyla, the Fungi were richer; suggesting the importance of hydrolysis and fermentation in biogas production. High β-diversity within the taxa was largely linked to communities' metabolic capabilities. Clostridiales and Bacteroidales, the most prevalent guilds, metabolize organic macromolecules. The identified Cytophagales, Alteromonadales, Flavobacteriales, Fusobacteriales, Deferribacterales, Elusimicrobiales, Chlamydiales, Synergistales to mention but few, also catabolize macromolecules into smaller substrates to conserve energy. Furthermore, δ-Proteobacteria, Gloeobacteria and Clostridia affiliates syntrophically regulate PH2 and reduce metal to provide reducing equivalents. Methanomicrobiales and other Methanomicrobia species were the most prevalence Archaea, converting formate, CO2(g), acetate and methylated substrates into CH4(g). Thermococci, Thermoplasmata and Thermoprotei were among the sulfur and other metal reducing Archaea that contributed to redox balancing and other metabolism within treatments. Eukaryotes, mainly fungi were the least abundant guild, comprising largely Ascomycota and Basidiomycota species. Chytridiomycetes, Blastocladiomycetes and Mortierellomycetes were among the rare species, suggesting their metabolic and substrates limitations. Generally, we observed that environmental and treatment perturbations influenced communities' abundance, β-diversity and reactor performance largely through stochastic effect. Understanding diversity of biogas microbiomes over wide environmental variables and its' productivity provided insights into better management strategies that ameliorate biochemical limitations to effective biogas production.


Analysis on the Association Among Stunting, Wasting and Underweight in Malawi: An Application of a Log-Linear Model for the Three-Way Table.
Childhood undernutrition is an important public health problem. Many studies have investigated the factors of childhood undernutrition, but not the association between the undernutrition indicators. This study aimed at investigating the association between the childhood undernutrition indicators. A loglinear model of cell counts of a three way table of stunting, wasting, and underweight was fitted based on the 2010 Malawi demographic health survey data. Interaction terms in the model depicted deviations from independence. A multiple correspondence analysis of undernutrition indicators was also plotted to have a visual impression of association of the undernutrition variables. A loglinear model showed that underweight was associated with both stunting (P<0.001), and wasting (P<0.001). There was no association between stunting and wasting (P=1). Furthermore there was no three way association of stunting, wasting and underweight (P=1). Lack of three way interaction of stunting, wasting and underweight means that childhood undernutrition multidimensional nature is still valid, and no each indicator can represent the other.


The long-term effect of acupuncture for patients with chronic tension-type headache: study protocol for a randomized controlled trial.
The effectiveness of acupuncture for patients with chronic tension-type headache (CTTH) is controversial. In this article, we report the protocol for a randomized controlled trial aiming to evaluate the long-term effect of acupuncture for CTTH, in comparison with superficial acupuncture. A two-armed, parallel-design, patient-assessor blind, randomized controlled trial is underway in China. A total of 218 participants with CTTH will be randomly assigned to the treatment group or the control group in a 1:1 ratio. Participants in the treatment group and control group will receive acupuncture or superficial acupuncture treatments in a fixed prescription of acupoints respectively, for a total of 20 sessions over 8 weeks. The posttreatment follow-up period will be 24 weeks. The primary outcome will be the proportion of responders assessed at week 16 after randomization. The secondary outcomes will include the number of headache days, the mean intensity of headache, the reduction of medication intake, results from the 36-item short form health survey, the Hamilton Depression Scale and the Hamilton Anxiety Scale, the number of participants with adverse events, the expectation value of acupuncture treatment, and the intensity of deqi sensation. The first five secondary outcomes will be assessed or calculated at baseline, and at 4, 8, 12, 16, 20, 24, 28, and 32 weeks after randomization. Moreover, the expectation value will be collected at baseline and at week 8 after randomization, the intensity of deqi sensation will be assessed at 5 minutes after each treatment and adverse events will be summarized at the end of the follow-up period. Results from this trial will provide evidence for the long-term effect of acupuncture for CTTH with a long follow-up period. ClinicalTrial.gov NCT03133884 . Registered on 25 April 2017.


Ribosome Dimerization Protects the Small Subunit.
When nutrients become scarce, bacteria can enter an extended state of quiescence. A major challenge of this state is how to preserve ribosomes for the return to favorable conditions. Here, we show that the ribosome dimerization protein hibernation-promoting factor (HPF) functions to protect essential ribosomal proteins. Ribosomes isolated from strains lacking HPF (Δhpf) or encoding a mutant allele of HPF that binds the ribosome but does not mediate dimerization were substantially depleted of the small subunit proteins S2 and S3. Strikingly, these proteins are located directly at the ribosome dimer interface. We used single-particle cryo-electron microscopy (cryo-EM) to further characterize these ribosomes and observed that a high percentage of ribosomes were missing S2, S3, or both. These data support a model in which the ribosome dimerization activity of HPF evolved to protect labile proteins that are essential for ribosome function. HPF is almost universally conserved in bacteria, and HPF deletions in diverse species exhibit decreased viability during starvation. Our data provide mechanistic insight into this phenotype and establish a mechanism for how HPF protects ribosomes during quiescence.IMPORTANCE The formation of ribosome dimers during periods of dormancy is widespread among bacteria. Dimerization is typically mediated by a single protein, hibernation-promoting factor (HPF). Bacteria lacking HPF exhibit strong defects in viability and pathogenesis and, in some species, extreme loss of rRNA. The mechanistic basis of these phenotypes has not been determined. Here, we report that HPF from the Gram-positive bacterium Bacillus subtilis preserves ribosomes by preventing the loss of essential ribosomal proteins at the dimer interface. This protection may explain phenotypes associated with the loss of HPF, since ribosome protection would aid survival during nutrient limitation and impart a strong selective advantage when the bacterial cell rapidly reinitiates growth in the presence of sufficient nutrients.