Differential sensitivities of plant and animal mitochondria to the herbicide paraquat.
Paraquat herbicide is toxic to animals, including humans, via putative toxicity mechanisms associated to microsomal and mitochondrial redox systems. It is also believed to act in plants by generating highly reactive oxygen free radicals from electrons of photosystem I on exposure to light. Paraquat also acts on non-chlorophyllous plant tissues, where mitochondria are candidate targets, as in animal tissues. Therefore, we compared the interaction of paraquat with the mitochondrial bioenergetics of potato tuber, using rat liver mitochondria as a reference. Paraquat depressed succinate-dependent mitochondrial Delta(psi), with simultaneous stimulation of state 4 O2 consumption. It also induced a slow time-dependent effect for respiration of succinate, exogenous NADH, and N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD)/ascorbate, which was more pronounced in rat than in potato mitochondria. However, with potato tuber mitochondria, the Delta(psi) promoted by complex-I-dependent respiration is insensitive to this effect, indicating a protection against paraquat radical afforded by complex I redox activity, which was just the reverse of to the findings for rat liver mitochondria. The experimental set up with the tetraphenyl phosphonium (TPP+)-electrode also indicated production of the paraquat radical in mitochondria, also suggesting its accessibility to the outside space. The different activities of protective antioxidant agents can contribute to explain the different sensitivities of both kinds of mitochondria. Values of SOD activity and alpha-tocopherol detected in potato mitochondria were significantly higher than in rat mitochondria, which, in turn, revealed higher values of lipid peroxidation induced by paraquat.


How I do it: Side-to-side isoperistaltic strictureplasty for extensive Crohn's disease.
Bowel-sparing surgical techniques, such as the Heineke-Mikulicz and the Finney strictureplasty, have been proposed as an alternative to lengthy intestinal resection in the treatment of small bowel strictures in Crohn's disease. However, these conventional strictureplasty techniques lend themselves poorly to cases of multiple short strictures closely clustered over a lengthy small bowel segment. In this article, we present the surgical technique of the side-to-side isoperistaltic strictureplasty, which is optimal in addressing these specific situations.


Automated platelet production during plasmapheresis.
Manual plasmapheresis is widely used to permit collection of fresh-frozen plasma with return of the red cells to the donor. However, this method is time-consuming and carries the inherent risk of returning the wrong cells to any individual donor. Automated plasmapheresis, using a specially designed discontinuous cell separator, permits the collection of 500 ml of plasma within 30 minutes without disconnecting the donor from the bag containing the donor's red cells. However, this plasma contains a small number of platelets which are not suitable for transfusion. We now report the modification of this machine to permit simultaneous collection of 3 units of platelet concentrate as well as 500 ml of plasma in less than 50 minutes. Reduction of the g force of the separator from 1200 to 650 g permits the simultaneous collection of plasma and a platelet concentrate with an average yield of 2.21 X 10(11) platelets. Platelet size distribution, in-vitro function. 51Cr survival, posttransfusion increment, and bleeding time correction are all normal. This modification has increased the flexibility of the separator and provides an instrument which can be used with a random volunteer blood donor population to generate both plasma and cells in less than 50 minutes and with increased cost-effectiveness over plasmapheresis alone.


RIPK3 Restricts Viral Pathogenesis via Cell Death-Independent Neuroinflammation.
Receptor-interacting protein kinase-3 (RIPK3) is an activator of necroptotic cell death, but recent work has implicated additional roles for RIPK3 in inflammatory signaling independent of cell death. However, while necroptosis has been shown to contribute to antiviral immunity, death-independent roles for RIPK3 in host defense have not been demonstrated. Using a mouse model of West Nile virus (WNV) encephalitis, we show that RIPK3 restricts WNV pathogenesis independently of cell death. Ripk3-/- mice exhibited enhanced mortality compared to wild-type (WT) controls, while mice lacking the necroptotic effector MLKL, or both MLKL and caspase-8, were unaffected. The enhanced susceptibility of Ripk3-/- mice arose from suppressed neuronal chemokine expression and decreased central nervous system (CNS) recruitment of T lymphocytes and inflammatory myeloid cells, while peripheral immunity remained intact. These data identify pleiotropic functions for RIPK3 in the restriction of viral pathogenesis and implicate RIPK3 as a key coordinator of immune responses within the CNS.


[Spontaneous rupture of the spleen caused by primary amyloidosis. Description of a clinical case].
Spontaneous rupture of the spleen in primary amyloidosis is an uncommon event. After a review of the pertinent literature (10 case-reports between 1948 and 1987) a case of spontaneous splenic rupture with hemoperitoneum is presented. The diagnosis depends on the demonstration of amyloid deposit in splenic and hepatic tissues.


[Effect of antibodies to glial glycolipid antigens on miniature end-plate potentials].
Less than 4% of miniature end-plate potentials (MEPPs) in frog cutaneous-pectoral muscles, normal or exposed to nonimmune rabbit serum were atypical. These MEPPs were of normal amplitude, but their time course was nearly twice as slow as that of normal MEPPs. The exposure of muscles to rabbit anti-galactocerebroside serum induced more than three-fold increase in the fraction of atypically slow MEPPs. Inhibition of acetylcholinesterase caused an appearance of giant MEPPs, the fraction of slow MEPPs being unchanged. Possible mechanisms of increase in fraction of atypical slow MEPPs based on modification of the synaptic Schwann cell functioning are discussed.


Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS)-pilot evaluation of a simple point-of-care ultrasound protocol and short training program for detecting urinary tract morbidity in highly endemic settings.
Urogenital schistosomiasis (UGS) causes inflammation and fibrosis of the urinary tract. In resource-limited settings, affordable tools for morbidity assessment in clinical care are needed. Point-of-care ultrasound has not yet been validated for UGS-related pathology. We developed a protocol for Focused Assessment with Sonography for Urinary Schistosomiasis (FASUS), assessing pathology of the bladder wall, ureters and kidneys. Following standardized training, two clinicians performed FASUS on children and adults with hematuria in Lambaréné, Gabon. Recorded ultrasound clips were remotely reviewed by two ultrasound experts as a diagnostic reference. In 2015 and 2016, scans were performed in 118 patients. The image quality was sufficient in 90% of bladder views and more than 97% of kidney views. UGS-compatible pathology was detected in 51/118 (43%) by the operator and in 46/107 (43%) by the experts among baseline scans of sufficient quality. Inter-rater agreement between operators and experts was very good (κ > 0.8) for hydronephrosis and good (κ > 0.6) for bladder wall thickening. FASUS is a promising clinical, point-of-care tool for detecting UGS-related urinary tract morbidity in symptomatic patients. Based on larger validation studies, appropriate diagnostic and therapeutic algorithms for the use of FASUS should be established.


Application of the hybrid BOPPPS teaching model in clinical internships in gynecology.
The traditional gynecological teaching model is not conducive to the cultivation of trainee doctors' clinical skills, thinking patterns and doctor‒patient communication ability. This study aims to explore the effect of the application of the hybrid BOPPPS (bridge-in, objective, preassessment, participant learning, postassessment, summary) teaching model in clinical internships in gynecology. This observational study was conducted among final-year undergraduate medical trainee doctors at Jiaxing Maternity and Child Health Care Hospital from September 2020 to June 2022. Members of the control group were introduced to the traditional teaching model, while members of the experimental group were introduced to the hybrid BOPPPS teaching model. Trainee doctors' final examination scores and teaching satisfaction were compared. The control group consisted of 114 students who entered the university to pursue undergraduate degrees in 2017, and the experimental group consisted of 121 students who entered the university to pursue undergraduate degrees in 2018. The final examination scores attained by trainee doctors in the experimental group were higher than those attained by trainee doctors in the control group (P < 0.05). The final theoretical exam scores attained by members of the control group were significantly higher than their preassessment scores (P < 0.01). The scores differed significantly between female and male subjects before the internship (p<0.05) but not after the internship (p>0.05). In total, 93.4% of trainee doctors in the experimental group thought that the hybrid BOPPPS teaching model helped them improve their case analysis ability, and the difference in this measure between the experimental and control groups was statistically significant (P < 0.05). A total of 89.3% of trainee doctors in the experimental group supported the promotion and application of the hybrid BOPPPS model in practice in other disciplines. The hybrid BOPPPS teaching model helps improve trainee doctors' learning environment, stimulate their interest and initiative in learning, enhance their clinical practice ability and increase their satisfaction; therefore, this model is worth promoting and applying in practice in other disciplines.


Design and synthesis of selective and blood-brain barrier-permeable hydroxamate-based gelatinase inhibitors.
Matrix metalloproteinases (MMPs), a family of zinc-containing endopeptidases involved in the degradation of the extracellular matrix, make a major contribution to the progression of a vast number of diseases, such cancer or epilepsy. Although several MMP inhibitors (MMPi) have been developed to date for the treatment of cancer, they have all failed in clinical trials due to lack of efficacy and, most importantly, the presence of severe side effects. The latter can be explained by their lack of selectivity of these inhibitors. In this regard, MMPs' family members have a high structural homology, which challenge the development of selective inhibitors for a specific MMP. Here, we have used in silico calculations and in vitro data to design MMPi that selectively target gelatinases (MMP-2 and MMP-9) and have the capacity to cross the blood-brain barrier. Following this approach, we obtained compound 40 that shows high proteolytic stability and low cytotoxicity. This compound may be of particular interest for the treatment of central nervous diseases such epilepsy or Alzheimer's disease, where gelatinase activity is increased. Our data show the specificity of compound 40 for recombinant MMP-9 and MMP-2 and endogenous MMP-9 from rat hippocampal cell cultures, and reveals its permeability across the blood-brain barrier in vivo.


The alarmones (p)ppGpp directly regulate translation initiation during entry into quiescence.
Many bacteria exist in a state of metabolic quiescence where energy consumption must be minimized so as to maximize available resources over a potentially extended period of time. As protein synthesis is the most energy intensive metabolic process in a bacterial cell, it would be an appropriate target for down-regulation during the transition from growth to quiescence. We observe that when Bacillus subtilis exits rapid growth, a subpopulation of cells emerges with very low protein synthetic activity. This phenotypic heterogeneity requires the production of the nucleotides (p)ppGpp, which we show are sufficient to inhibit protein synthesis in vivo. We then show that one of these molecules, ppGpp, inhibits protein synthesis by preventing the allosteric activation of the essential GTPase Initiation Factor 2 (IF2) during translation initiation. Finally, we demonstrate that the observed attenuation of protein synthesis during the entry into quiescence is a consequence of the direct interaction of (p)ppGpp and IF2.


Concentration distribution and potential health risk of heavy metals in Mactra veneriformis from Bohai Bay, China.
To investigate the pollution level and evaluate the potential health risks of heavy metals, the concentrations of chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), molybdenum (Mo), cadmium (Cd), antimony (Sb), and lead (Pb) were determined by inductively coupled plasma-mass spectrometry (ICP-MS) in 198 clams (Mactra veneriformis) collected from 11 sites of the Bohai Bay. The results showed that heavy metal concentrations in the clams were different at different sites (p<0.05). Mn was dominant with a percentage of 22.08-77.03% in heavy metals, followed by Zn with 12.66-57.11%, and the concentration of Pb was the lowest with 0.45-1.04%. The potential health risk to consumers was evaluated by the target hazard quotient (THQ) and the maximum daily consumption rate (CRmax). The results indicated that the THQs of Co were the highest with the values of 1.125, 1.665, and 1.144 at three sections; the values of other individual metals were <1, which indicated that consumption of clams from the study areas caused health risks due to Co. Moreover, the CRmax values also indicated the potential health risk caused by Co in clams consumed in this area. Pearson correlation analysis and principal component analysis (PCA) indicated that there were significantly positive or negative correlations between the heavy metals (p<0.05), and the studied metals were divided into four groups. The results indicated that the concentrations of heavy metals in clams were affected not only by pollution sources but also by the characteristics of clams that could absorb selectively and accumulate special metals. This study offers important information on the pollution levels of heavy metals in clams and warns consumers of the health risks associated with the consumption of clams in the area.


Clinical therapeutic trials.
The term clinical trial implies an investigation of a therapeutic intervention in the pursuit of evidence of benefit, short or sustained, and observations on the possibility of toxicity related to the therapeutic intervention. It is possible that the first clinical trial took place in the court of the Babylonian King Nebuchadnezzar circa 600 BC, as recorded in Chapter 1 of the Book of Daniel, verse 3-20. However, it is in the last 500 years that there has been good written documentation at attempts to interpret therapeutic benefit from the use of treatments. Lind's demonstration on the usefulness of oranges and lemons in the treatment of scurvy in 1747, and the unethical experiment by Edward Jenner (1749-1823) on the inoculation in 1796, of an 8-year-old boy, with cow pox obtained from a milk maid, followed by an attempt to give the young boy smallpox by direct inoculation 18 days later, are striking examples of clinical trials. Human ethics, strict clinical observations, statistics, the governed scientific purity of therapeutic agents, and safety testing of therapeutics, devices, and physical interventions, have created the basis for the modern clinical trial.


Nanosecond structural dynamics of intrinsically disordered β-casein micelles by neutron spectroscopy.
β-casein undergoes a reversible endothermic self-association, forming protein micelles of limited size. In its functional state, a single β-casein monomer is unfolded, which creates a high structural flexibility, which is supposed to play a major role in preventing the precipitation of calcium phosphate particles. We characterize the structural flexibility in terms of nanosecond molecular motions, depending on the temperature by quasielastic neutron scattering. Our major questions are: Does the self-association reduce the chain flexibility? How does the dynamic spectrum of disordered caseins differ from a compactly globular protein? How does the dynamic spectrum of β-casein in solution differ from that of a protein in hydrated powder states? We report on two relaxation processes on a nanosecond and a sub-nanosecond timescale for β-casein in solution. Both processes are analyzed by Brownian oscillator model, by which the spring constant can be defined in the isotropic parabolic potential. The slower process, which is analyzed by neutron spin echo, seems a characteristic feature of the unfolded structure. It requires bulk solvent and is not seen in hydrated protein powders. The faster process, which is analyzed by neutron backscattering, has a smaller amplitude and requires hydration water, which is also observed with folded proteins in the hydrated state. The self-association had no significant influence on internal relaxation, and thus, a β-casein protein monomer flexibility is preserved in the micelle. We derive spring constants of the faster and slower motions of β-caseins in solution and compared them with those of some proteins in various states (folded or hydrated powder).


Hypertensive emergency presenting as blurry vision in a patient with hypertensive chorioretinopathy.
A 42-year-old man presented with 3 weeks of blurry vision in the right eye. His exam was significant for decreased vision in the right eye, diffuse retinopathy in both eyes, and serous retinal detachment in the right eye. The patient was found to be hypertensive with blood pressure of 256/160 mmHg. He was diagnosed with hypertensive emergency with end-organ damage due to features of hypertensive chorioretinopathy. He was admitted with abnormal urinalysis, elevated troponin, and abnormal EKG. After appropriate control of his blood pressure, his vision and his labs normalized. Hypertensive emergencies can be manifested first in the eyes. When the choroid is associated, the hypertensive event is often more acute and associated with increased morbidity. It is imperative to obtain a fundus exam in any patient with elevated blood pressure and concomitant vision complaints.


Utilization review and quality assurance: staying in the black and working with the blues.
Utilization review (UR), Quality Assurance (QA), and Peer Review (PR) have become essential aspects in the practice of general hospital psychiatry. This article first defines and elaborates the basic elements of UR, QA, and PR and then outlines the development of a program for these professionally initiated and maintained methods of problem seeking and solving as it occurred on a short-term voluntary inpatient psychiatric unit. Finally, current trends and conflicts inherent to QA, UR, and PR are discussed, with a view towards the future.


Synchronous driver gene alterations (EGFR L858R, T790M, and ROS1) rearrangements in a patient with early-stage lung adenocarcinoma.
Concurrent EGFR mutation and ROS1 rearrangement is a rare event in early-stage non-small-cell lung cancer. In addition, a co-occurring de novo EGFR T790M mutation in such a case is extremely rare. We encountered a 72-year-old woman who developed 3 early-stage lung lesions synchronously, one each harboring EGFR L858R, ROS1 rearrangement, and EGFR L858R and de novo T790M. These three nodules were pathologically time-matched lepidic predominant adenocarcinoma with small invasive lesions, which may reflect the concept of field cancerization with driver mutations.


The Impact of Silymarin on Improvement of Hepatic Abnormalities in Patients with Severe Preeclampsia: A Randomized Clinical Trial.
Preeclampsia is a pregnancy-specific disorder, associated with increased blood pressure and proteinuria, and in extreme cases it can also cause liver and kidney problems. To determine the impact of silymarin on the improvement of severe preeclampsia. This randomized clinical trial was conducted at Hajar Hospital in Shahrekord, Iran, from April 2014 to September 2015. Sixty patients whose pregnancy had ended as a result of severe preeclampsia, were entered into the study. Patients were randomly divided into two groups of thirty study and control groups. In addition to current treatment for preeclampsia, case groups were administered 70 mg of silymarin, three and twenty four hours after the termination of pregnancy. The control group received placebo at the same time. The blood pressure and AST, ALT, ALP, LDH, uric acid, bilirubin and kidney tests were compared at the baseline and 12, 36 and 60 hours post-measurements in two groups by SPSS software, version 22, by the ANOVA test, and by the independent-samples t-test. AST and ALT liver enzyme levels decreased significantly 36 and 60 hours after the termination of pregnancy in the study group compared to the control group (p <0.01). Silymarin is used to treat liver disorders, and has beneficial results. It seems that this drug can be used for accelerating improvement of liver disorders in severe preeclampsia. However, adjusting the dose of the drug for the treatment of liver disorders in severe preeclampsia requires further studies. The trial was registered at the Iranian Registry of Clinical Trials (http://www.irct.ir) with the Irct ID: IRCT201509042388/N1. Shahrekord University of Medical Sciences supported this research (project no. 2006).


Waste to value: Global perspective on the impact of entomocomposting on environmental health, greenhouse gas mitigation and soil bioremediation.
The innovative use of insects to recycle low-value organic waste into value-added products such as food, feed and other products with a low ecological footprint has attracted rapid attention globally. The insect frass (a combination unconsumed substrate, faeces, and exuviae) contains substantial amounts of nutrients and beneficial microbes that could utilised as fertilizer. We analyse research trends and report on the production, nutrient quality, maturity and hygiene status of insect-composted organic fertilizer (ICOF) generated from different organic wastes, and their influence on soil fertility, pest and pathogen suppression, and crop productivity. Lastly, we discuss the impact of entomocomposting on greenhouse gas mitigation and provide critical analysis on the regulatory aspects of entomocomposting, and utilization and commercialisation ICOF products. This information should be critical to inform research and policy decisions aimed at developing and promoting appropriate standards and guidelines for quality production, sustainable utilization, and successful integration of entomocompost into existing fertilizer supply chains and cropping systems.


The cut-off effect of n-alcohols in lipid rafts: A lipid-dependent phenomenon☆.
n-Aliphatic alcohols act as anesthetics only up to a certain chain length, beyond which its biological activity disappears. This is known as the 'cut-off' phenomenon. Although the most accepted explanation is based on action sites in membrane proteins, it is not well understood why alcohols alter their functions. The structural dependence of these protein receptors to lipid domains known as 'lipid rafts', suggests a new approach to tackle the puzzling phenomenon. In this work, by performing molecular dynamic simulations (MDS) to explore the lipid role, we provide relevant molecular details about the membrane-alcohol interaction at the cut-off point regime. Since the high variability of the cut-off points found on protein receptors in neurons may be a consequence of differences in the lipid composition surrounding such proteins, our results could have a clear-cut importance.


Focal brachytherapy for selected low-risk prostate cancers: a pilot study.
To evaluate the feasibility and the early toxicity of focal brachytherapy in highly selected localized prostate cancer patients. Twenty-one patients underwent a focal brachytherapy between February 2010 and March 2012, representing 3.7% of the cases treated by our group during this period. Patient selection was based on (at least) two series of prostate biopsies and a high-resolution MRI. Only patients with very limited and localized tumors, according to strict criteria, were selected for the procedure. The technique used a real-time procedure with the implantation of free (125)I seeds and dynamic dose calculation. The prescribed dose for the focal volume was 145Gy. The treated volume corresponded to a mean value of 34% of the total prostatic volume (range, 20-48%). For the focal volume, the mean D90 and V100 was 183.2Gy (range, 176-188Gy) and 99.3% (range, 98.8-100%), respectively. The technique was performed in an hour and a half. When compared with a previous cohort treated by whole-prostate brachytherapy, urinary toxicity (International Prostate Symptom Score) was borderline reduced (p = 0.04) at 6 months only, whereas the recovery of the International Index of Erectile Function 5 was better (p = 0.014). The International Continence Score was nil in almost all cases as well as rectal toxicity. Focal treatment by brachytherapy is easily feasible with little acute toxicity. Further investigation is needed to assess the results in terms of tumor control and long-term toxicity.


Mechanism of retinal pigment epithelium tear formation following intravitreal anti-vascular endothelial growth factor therapy revealed by spectral-domain optical coherence tomography.
To demonstrate the mechanism by which retinal pigment epithelium (RPE) tears occur in eyes with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) agents using spectral-domain optical coherence tomography (OCT). Retrospective observational case series. OCT images of 8 eyes that developed RPE tears following the administration of intravitreal anti-VEGF agents for neovascular AMD were evaluated. Pretear and posttear images were compared in order to elucidate the mechanism by which RPE tears occur in this setting. In all eyes, pretear images revealed a vascularized pigment epithelial detachment (PED) containing hyperreflective material consistent with choroidal neovascularization (CNV). This CNV was adherent to the undersurface of the RPE and created contractile folds in the RPE contour. In 6 eyes, contractile neovascular tissue spanned the PED, causing outward bowing of the Bruch membrane and a peaked appearance to the overlying RPE monolayer. RPE tears occurred after the first anti-VEGF injection in 6 of 8 eyes. The posttear OCT images showed a discontinuity in the RPE with the CNV adherent to the retracted RPE. In all eyes, the RPE ruptured along a segment of bare RPE not in contact with the CNV or Bruch membrane. Eyes with vascularized PEDs secondary to AMD may show specific OCT findings that increase the risk for RPE tear following intravitreal anti-VEGF injection. Rapid involution and contraction of neovascular tissue adherent to the undersurface of the RPE may impart a substantial contractile force that tears this already-strained tissue layer.


Application of alkaline sucrose gradient sedimentation to the study of DNA damage and its repair in mammalian cells treated with methylmethanesulfonate and 4-nitroquinoline-1-oxide.
KB cells and L cells were treated with methylmethanesulfonate (MMS) or 4-nitroquinoline-1-oxide (4 NQO) and the resulting damage to DNA and its repair were examined by sedimentation in an alkaline sucrose gradient. The sedimentation profiles obtained were found to be the resultant of a complex interrelationship between drug dosage, duration of the lysis period and the repair capacity of the cells. A systematic study of these variables was made which led to a plausible and useful interpretation of the sedimentation profiles. Both drugs produce two kinds of DNA modifications which show up as a single-strand breaks but affect the sedimentation profile in characteristic ways. One of these modifications which is quite alkali-labile can be studied using a 30-min lysis period. The other modification is less alkali-labile and can be studied using a long lysis period. Both KB cells and L cells can repair the former type of damage but only KB cells can repair the latter type of damage.


Device-based percutaneous treatments to decompress the left atrium in heart failure with preserved ejection fraction.
Heart failure with preserved ejection fraction (HFpEF) accounts for more than half of heart failure hospital admissions in the last years and is burdened by high mortality and poor quality of life. Providing effective management for HFpEF patients is a major unmet clinical need. Increase in left atrial pressure is the key determinant of pulmonary congestion, with consequent dyspnoea and exercise limitation. Evidence on benefits of medical treatment in HFpEF patients is limited. Thus, alternative strategies, including devices able to reduce left atrial pressure, through an interatrial communication determining a left-right shunt, were developed. This review aims to summarize evidence regarding the use of percutaneous interatrial shunting devices. These devices are safe and effective in improving hemodynamic and clinical parameters, including pulmonary capillary wedge pressure, 6-min walking distance, and New York Heart Association functional class. Data on cardiovascular mortality and re-hospitalization for heart failure are still scarce.


The Effectiveness of E-Cigarettes for Smoking Cessation.
Our primary aim was to assess-in the German population-the effectiveness of e-cigarettes (ECs; with or without nicotine), nicotine replacement therapy (NRT), and no use of evidence-based aids in smoking cessation. Analysis of cross-sectional data from a representative survey of the population (age 14-96 years) conducted in 2016-2021. All current smokers and recent ex-smokers (< 12 months since quitting) who had made ≥ 1 attempt to quit in the past 12 months (n = 2740) were included. They were asked about use of cessation aids in their most recent quit attempt and their current smoking status. Two hundred thirty-nine respondents had used ECs, 168 NRT, and 2333 no aid. After adjustment for potential confounders, the odds of abstinence were 1.78 times higher for smokers who had used ECs in their quit attempt than in the group that had used no aids (95% confidence interval [1.09; 2.92]; p = 0.02) and 1.46 times higher than in the NRT group ([0.68; 3.13]; p = 0.34, Bayes factor = 1.26). Compared with the unaided group, the odds of abstinence were 2.34 times higher ([1.21; 4.53]; p = 0.01) in the subgroup using ECs with nicotine and 1.48 times higher ([0.68; 3.26]; p = 0.33) in the subgroup using ECs without nicotine. The unadjusted abstinence rates in people who had started their quit attempt > 6 months earlier were 15.6% [9.4; 23.8] in the ECs group and 13.8% [7.3; 22.9] in the NRT group. In Germany, use of ECs in an attempt to quit smoking is associated with a higher rate of abstinence than attempting to quit unaided.


Pancreatic tuberculosis mimicking a neoplastic mass in an immunosuppressed patient who also presented adenopathy syndrome: Case report.
Pancreatic tuberculosis is unusual, with an incidence reported to be less than 4,7 % worldwide. We report the case of a 32-year-old man recently diagnosed with HIV whose adenopathy syndrome was understudy. Lymph node cervical and bone marrow biopsies were performed without evidence of neoplastic infiltration, fungal infection, or tuberculosis. He arrived at the emergency room for acute band abdominal pain radiating to the back. Contrast-enhanced abdominal computed tomography revealed a mass in the head of the pancreas which generates intra- and extrahepatic bile duct dilation. Serial sputum, PPD, Genexpert, bronchoscopy and ultrasound fine needle aspiration biopsy were negative for tuberculosis, with no evidence of microorganisms or malignancy; cultures results pending. A second biopsy was requested using a No. 19 needle reporting a necrotizing process with acid-fast bacilli, compatible with tuberculosis, and the pending cultures results were positive for the mycobacterium tuberculosis complex, confirming the diagnosis. Clinical awareness of pancreatic tuberculosis in immunosuppressed patients in our country, may lead to faster and accurate diagnosis study and management, using minimally invasive techniques as diagnostic tools.


Local pelvic irradiation modulates Pharmacokinetics of 5-Fluorouracil in the plasma but not in the Lymphatic System.
5-fluorouracil (5-FU) is employed to enhance radiotherapy (RT) effect. Here, we evaluated the influence of whole-pelvic irradiation on the pharmacokinetics (PK) of 5-FU in plasma and lymphatic system of rats as the experimental model. RT with 2 Gy was delivered to the whole pelvis of Sprague-Dawley rats. 5-FU at 100 mg/kg was intravenously infused 24 hours after radiation. The pharmacokinetics of 5-FU in plasma and lymphatic system were calculated. RT at 2 Gy reduced the area under the plasma concentration vs. time curve and mean residence time of 5-FU by 21.5% and 31.5%, respectively compared with those of non-RT controls. By contrast, RT at 2 Gy increased drug clearances of 5-FU by 28.2% when compared with those of non-RT controls. There was no significant difference in T1/2, Cmax and Vss in plasma between both groups. Intriguingly, 5-Fu could be detected in the lymphatic system. In addition, the AUC in 5-FU without and with RT was 3.3-fold and 4.9-fold greater for lymph than for plasma, respectively. Compared with the non-RT group, the RT group showed increase in distribution of 5-FU in the lymphatic system (p = 0.001). The local whole pelvic RT at 2 Gy could modulate systemic PK of 5-FU in plasma of rats and intravenous 5-FU passing into the lymphatic system was proved. The metabolism of 5-FU might be modulated by RT but the distribution of 5-FU from blood circulation to the lymphatic system might not be changed. The RT-PK phenomena in plasma provide references for adjustment of drug administration. Chemotherapy drugs entering the lymphatic system is worthy of further investigation.


Effects of Omega-3 Fatty Acids on Flow-mediated Dilatation and Carotid Intima Media Thickness: A Meta-analysis.
To investigate the effects of omega-3 fatty acids on flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT) and explore the factors influencing these effects. FMD was significantly higher in the omega-3 fatty acid group compared to the control group (mean difference = 0.90%; p = 0.0003). In particular, the subgroup with CHD (both EPA + DHA < 1 g/day and ≥ 1 g/day) and the subgroup without CHD but with CHD risk factors (only EPA + DHA ≥ 1 g/day) showed significantly increased FMD after supplementation of omega-3 fatty acids. CIMT was not significantly different between the omega-3 fatty acid and control groups (standardized mean difference = -0.08; p = 0.26). Subgroup analysis of CHD patients was not conducted because of the limited number of studies. Intake of omega-3 fatty acids improved FMD in patients with CHD and patients with risk factors for CHD. Further research is needed on the effects of omega-3 fatty acids on CIMT.


Episodic memory for object location versus episodic memory for object identity: do they rely on distinct encoding processes?
Three experiments were conducted to determine whether encoding processes that support episodic memory for object location are distinct from those that support memory for object identity. Guided by transfer-appropriate processing notions, we examined with an incidental learning paradigm whether an attentional focus on object location at encoding promotes subsequent recovery of object location, whereas a focus on object identity promotes recovery of object identity. We found that judging spatial relationships at encoding selectively supports recovery of object location, provided the test assesses memory for these relationships (rather than absolute location); our results also showed that judging physical and semantic object attributes promotes recovery of object identity preferentially. Contrasting with these domain-specific effects was evidence that identification processes involved in object naming boost memory for object identity as well as for absolute object location. Object identification at encoding may support memory performance in both domains by triggering the binding of identity and location information through a mechanism of object-based attentional selection.


Aripiprazole blocks acute self-administration of cocaine and is not self-administered in mice.
The novel antipsychotic aripiprazole in use for treatment of schizophrenia is a partial agonist at dopamine D2 receptors with actions at a variety of other receptors as well. Cocaine is believed to exert an important part of its rewarding effect by increasing extracellular levels of dopamine that subsequently act at dopamine D2 receptors. As a partial agonist, aripiprazole may antagonize effects at D2 receptors and we accordingly tested whether aripiprazole could antagonize self-administration of cocaine. Because D2-like receptor agonists are self-administered, a D2 receptor partial agonist like aripiprazole might itself be reinforcing. Thus, we also assessed whether mice would acquire self-administration of aripiprazole. A single session, mouse self-administration procedure was used. Oral pretreatment with aripiprazole dose-dependently decreased cocaine self-administration under a fixed ratio 1 schedule at the peak cocaine dose (0.03 mg/kg/infusion), reaching significance at 0.2 and 0.4 mg/kg of aripiprazole. Using 0.4 mg/kg, aripiprazole decreased rates of cocaine self-administration without shifting the peak of the dose-response function. There was no effect of aripiprazole per se, suggesting that its inhibitory action was due to effects on cocaine self-administration rather than non-specific motor effects. Aripiprazole was not found to be self-administered in the tested dose range (0.0003-0.3 mg/kg/infusion). The three highest doses (0.03, 0.1, and 0.3 mg/kg/infusion) even caused significant decreases in nose-poking activity, possibly due to extrapyramidal side effects. These data are consistent with a potential role for aripiprazole in treatment of cocaine addiction without abuse potential per se.


Release of prostaglandins and thromboxanes by guinea pig isolated type II pneumocytes.
Lung cells have been isolated by enzymatic digestion of guinea pig lungs and mechanical dispersion to obtain a suspension of viable cells (approximately 500 X 10(6) cells). Type II pneumocytes have been purified to approximately 92% by centrifugal elutriation (2000 rpm, 15 ml/min) followed by a plating in plastic dishes coated with guinea pig IgG (500 micrograms/ml). We have investigated the arachidonic acid metabolism through the cyclooxygenase pathway in this freshly isolated type II cells (2 x 10(6) cells/ml). Purified type II pneumocytes produced thromboxane B2 (TxB2) predominantly and to a smaller extent the 6-keto prostaglandin PGF1 alpha (6-keto-PGF1 alpha) and prostaglandin E2 (PGE2) after incubation with 10 microM arachidonic acid. The stimulation of pneumocytes with 2 microM calcium ionophore A23187 released less eicosanoids than were produced when cells were incubated with 10 microM arachidonic acid. There was no additive effect when the cells were treated with both arachidonic acid and the ionophore A23187. Guinea pig type II pneumocytes failed to release significant amounts of TxB2, 6-keto-PGF1 alpha and PGE2 after stimulation with 10 nM leukotriene B4, 10 nM leukotriene D4, 10 nM platelet-activating factor, 5 microM formyl-methionyl-leucyl-phenylalanine, 0.2 microM bradykinin and 10 nM phorbol myristate acetate. Our findings indicate that guinea pig type II pneunomocytes possess the enzymatic machinery necessary to convert arachidonic acid to specific cyclooxygenase products, which may suggest a role for these cells in lung inflammatory processes.


Engineered osteoclasts as living treatment materials for heterotopic ossification therapy.
Osteoclasts (OCs), the only cells capable of remodeling bone, can demineralize calcium minerals biologically. Naive OCs have limitations for the removal of ectopic calcification, such as in heterotopic ossification (HO), due to their restricted activity, migration and poor adhesion to sites of ectopic calcification. HO is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these unexpected calcified plaques. In the present study, we develop a chemical approach to modify OCs with tetracycline (TC) to produce engineered OCs (TC-OCs) with an enhanced capacity for targeting and adhering to ectopic calcified tissue due to a broad affinity for calcium minerals. Unlike naive OCs, TC-OCs are able to effectively remove HO both in vitro and in vivo. This achievement indicates that HO can be reversed using modified OCs and holds promise for engineering cells as "living treatment agents" for cell therapy.


Single intrauterine death in twin pregnancy: Evidenced-based counselling and management.
Twins have a significantly higher risk of stillbirth, preterm delivery, perinatal morbidity and mortality. Single intrauterine fetal death is a relatively common and devastating occurrence for families and clinicians alike. Monochorionic twins are up to 13 times more likely to suffer an intrauterine death when compared to singletons. Additionally, longer term neurological sequelae affect monochorionic twins disproportionately. The timing of the death of the co-twin and the fetal order at the time of death have an impact on the outcome for the survivor. The risk in dichorionic pregnancies is lower with respect to neurological injury; however, the risk of prematurity remains high, particularly where the leading twin dies in utero. Recent published studies report lower rates of neurological injury in monochorionic twin pregnancies that incur an intrauterine fetal death after foetoscopic laser ablation for twin-to-twin transfusion syndrome - an important finding for patient counselling. TWEETABLE ABSTRACT: Single intrauterine fetal death in twins is a relatively common and devastating occurrence for families and clinicians alike. Adhering to collegiate guidelines will likely reduce but not eliminate the incidence of SIUD in twins.


Histidine residues in the region between transmembrane domains III and IV of hZip1 are required for zinc transport across the plasma membrane in PC-3 cells.
The proteins from the ZIP and the CDF families of zinc transporters contain a histidine-rich sequence in a loop domain located between transmembrane domains III and IV for the ZIP family and transmembrane domains IV and V for the CDF family. Topological predictions suggest that these loops are located in the cytoplasm. The loops contain a histidine-rich sequence with a variable number of histidine residues depending on the transporter. The histidine-rich sequence was postulated to serve as an extra-membrane metal binding site in these proteins. hZip1 is a human zinc transporter ubiquitously expressed. The histidine-rich motif located in the large loop of this transporter is composed of the following sequence, H(158)WHD(161). To determine if this motif is involved in the zinc transport activity of the protein, we performed site directed-mutagenesis to replace the loop histidines with alanines. Results suggest that both histidines are necessary for the zinc transport function and are not involved in the plasma membrane localization of the transporter as has been reported for the Zrt1 transporter in yeast. In addition, two histidine residues in transmembrane domains IV and V are also important in the zinc transport function. The results support an intermolecular exchange mechanism of zinc transport.


MicroRNA expression profiles in molecular subtypes of clear-cell renal cell carcinoma are associated with clinical outcome and repression of specific mRNA targets.
Clear-cell renal cell carcinomas (ccRCC) can be divided into four transcriptomic subtypes, two of which have a favorable and two an unfavorable prognosis. To assess mechanisms driving these subtypes, we investigated their miRNA expression patterns. miRNAs are master regulators of mRNAs, that are widely deregulated in cancer. Unsupervised clustering in our dataset (n = 128) and The Cancer Genome Atlas (TCGA) validation set identified two distinct miRNA clusters that overlapped with the transcriptomic subtypes, underscoring the validity of these subtypes on a multi-omics level and suggesting a driving role for miRNAs. Discriminatory miRNAs for the favorable subtypes repressed epithelial-to-mesenchymal transition, based on gene set enrichment analysis and target-mRNA expression levels. Strikingly, throughout the entire dataset, miRNAs associated with favorable subtypes were also associated with longer overall survival after diagnosis, and miRNAs associated with unfavorable subtypes with shorter overall survival (Pearson r = -0.54, p<0.0001). These findings indicate a general shift in miRNA expression between more and less aggressive tumors. This adds to current literature, which usually suggests only a small subset of miRNAs as markers of aggressive disease. In conclusion, this study reveals distinct mRNA expression patterns underlying transcriptomic ccRCC-subtypes, whereby miRNAs associated with favorable subtypes counteract epithelial-to-mesenchymal transition. There is a general shift in miRNA expression in ccRCC, between more and less aggressive tumors.


Effect of temperature on the rate of pupal-adult development of the noctuid moth,Mamestra configurata Wlk.: evidence for differential effects on the initiation of development and subsequent metamorphic development.
Moths eclosed earlier from pupae of the bertha armyworm,Mamestra configurata, that were exposed briefly (1 to 5 days) to a warm temperature (15 or 20°C) at the beginning of postdiapause pupal-adult metamorphosis and then incubated at 10 or 12.5°C than from pupae incubated at 10 or 12.5°C throughout metamorphosis. The differences were greater than could be explained by the additional thermal units received at the higher temperature. Analyses of the times of peak concentrations of ecdysteroids (insect growth and development hormones) in metamorphosing pupae and of moth eclosion after exposure to various combinations of temperatures indicated that the 'warm termperature effect' was not on the rate metamorphic development but on an earlier neuroendocrine process concerned with the initiation of development.The magnitude of the difference in eclosion time between pupac receiving a brief warm temperature "trigger" and the control suggests that the differential effect of temperature on the initiation of development and subsequent metamorphic development is of biological significance and should be considered in the construction of models of insect development under natural conditions.


The pedicle artery sign based on sonography with color Doppler imaging can replace second-stage tests in women with abnormal vaginal bleeding.
Unenhanced transvaginal sonography is not accurate in the detection of endometrial polyps. Currently, second-stage tests such as saline contrast sonohysterography and office hysteroscopy are used to diagnose endometrial lesions, but both have limitations and side effects. We proposed visualization of the pedicle artery on color Doppler imaging as a sign of polyps. This was a prospective observational study involving 3099 consecutive patients referred for assessment of the endometrium and myometrium. The uterus was assessed in sagittal and coronal planes using color Doppler sonography. Patients with suspected endometrial pathology on sonography were noted and the volume of the focal lesion was calculated. Patients with a clearly visible pedicle artery reaching the central part of the endometrium were regarded as test-positive. The gold standard was defined as the presence or absence of an endometrial polyp at hysterectomy, hysteroscopy and/or endometrial histology on dilatation and curettage within 1 year of sonography. Of the 3099 women, no gold standard was available in 2230. Only 28 of the 199 patients who were test-positive did not have a gold standard. In the 869 patients in whom a gold standard was available, 182 had one or more endometrial polyps. The pedicle artery test had an apparent sensitivity for detection of endometrial polyps of 76.4%, specificity of 95.3%, positive predictive value (PPV) of 81.3%, and negative predictive value of 93.8%. When extending the test to the prediction of any focal intracavitary pathology the PPV was 94.2%. The pedicle artery test has a very high PPV for intracavitary pathology. We expect that in the majority of patients with an endometrial polyp this test may replace more invasive established second-stage tests, such as saline contrast sonohysterography and office hysteroscopy.


Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease.
Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected "congenital Zika syndrome", while causing asymptomatic or mild exanthematous febrile infections which are dengue- or rubella-like in infected individuals. Despite having been discovered in Uganda for almost 60 years, <20 human cases were reported before 2007. The massive epidemics in the Pacific islands associated with the ZIKV Asian lineage in 2007 and 2013 were followed by explosive outbreaks in Latin America in 2015. Although increased mosquito breeding associated with the El Niño effect superimposed on global warming is suspected, genetic changes in its RNA virus genome may have led to better adaptation to mosquitoes, other animal reservoirs, and human. We reviewed the epidemiology, clinical manifestation, virology, pathogenesis, laboratory diagnosis, management, and prevention of this emerging infection. Laboratory diagnosis can be confounded by cross-reactivity with other circulating flaviviruses. Besides mosquito bite and transplacental transmission, the risk of other potential routes of transmission by transfusion, transplantation, sexual activity, breastfeeding, respiratory droplet, and animal bite is discussed. Epidemic control requires adequate clearance of mosquito breeding grounds, personal protection against mosquito bite, and hopefully a safe and effective vaccine.


Synthesis and induction of G0-G1 phase arrest with apoptosis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one.
The multistep synthesis of 3,5-dimethyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one 15 has been carried out. The compound showed antiproliferative and apoptotic effects against K562, K562-R (imatinib mesilate resistant), HL60 and multidrug resistant (MDR) HL60 cell lines. Compound 15 showed a pro-apoptotic activity against HL60 and K562 resistant cell lines markedly higher than etoposide and busulfan, respectively. Flow cytometry studies carried out on K562 cells allowed to establish that 15 induces G0-G1 phase arrest followed by apoptosis.


Discriminability and dimensionality effects in visual search for featural conjunctions: a functional pop-out.
Treisman and Gelade's (1980) feature-integration theory of attention states that a scene must be serially scanned before the objects in it can be accurately perceived. Is serial scanning compatible with the speed observed in the perception of real-world scenes? Most real scenes consist of many more dimensions (color, size, shape, depth, etc.) than those generally found in search paradigms. Furthermore, real objects differ from each other along many of these dimensions. The present experiment assessed the influence of the total number of dimensions and target/distractor discriminability (the number of dimensions that suffice to separate a target from distractors) on search times for a conjunction of features. Search was always found to be serial. However, for the most discriminable targets, search rate was so fast that search times were in the same range as pop-out detection times. Apparently, greater discriminability enables subjects to direct attention at a faster rate and at only a fraction of the items in a scene.


Interventions targeting hypertension and diabetes mellitus at community and primary healthcare level in low- and middle-income countries:a scoping review.
Hypertension (HTN) and diabetes mellitus (DM) are highly prevalent in low- and middle-income countries (LMIC) and a leading cause of morbidity and mortality. Recent evidence on effectiveness of primary care interventions has attracted renewed calls for their implementation. This review aims to synthesize evidence pertaining to primary care interventions on these two diseases, evaluated and tested in LMICs. Two reviewers conducted an electronic search of three databases (Pubmed, EMBASE and Web of Science) and screened for eligible articles. Interventions covering health promotion, prevention, treatment, or rehabilitation activities at the PHC or community level were included. Studies published in English, French, Portuguese and Spanish, from January 2007 to January 2017, were included. Key extraction variables included the 12 criteria identified by the Template for Intervention Description and Replication (TIDieR) checklist and guide. The Innovative Care for Chronic Conditions Framework (ICCCF) was used to guide analysis and reporting of results. 198 articles were analyzed. The strategies focused on healthcare service organization (76.5%), community level (9.7 %), creating a positive policy environment (3.6%) and strategies covering multiple domains (10.2%). Studies included related to the following topics: description or testing of interventions (n=81; 41.3%), implementation or evaluation projects (n=42; 21.4%), quality improvement initiatives (n=15; 7.7%), screening and prevention efforts (n=26; 13.2%), management of HTN or DM (n=13; 6.6%), integrated health services (n=10; 5.1%), knowledge and attitude surveys (n=5; 2.5%), cost-effective lab tests (n=2; 1%) and policy making efforts (n=2; 1%). Most studies reported interventions by non-specialists (n=86; 43.4%) and multidisciplinary teams (n=49; 25.5%). Only 198 articles were found over a 10 year period which demonstrates the limited published research on highly prevalent diseases in LMIC. This review shows the variety and complexity of approaches that have been tested to address HTN and DM in LMICs and highlights the elements of interventions needed to be addressed in order to strengthen delivery of care. Most studies reported little information regarding implementation processes to allow replication. Given the need for multi-component complex interventions, study designs and evaluation techniques will need to be adapted by including process evaluations versus simply effectiveness or outcome evaluations.


Hydrophobic scaffolds of pH-sensitive cationic lipids contribute to miscibility with phospholipids and improve the efficiency of delivering short interfering RNA by small-sized lipid nanoparticles.
Despite the fact that small-sized lipid nanoparticles (LNPs) are important for improved tissue penetration and efficient drug delivery, their poor stability and intracellular trafficking significantly hinders their use as potent small-sized LNPs. It has been reported that both the diffusion of lipid components from LNPs and the adsorption of proteins on the surface of LNPs are responsible for their decreased potency. To overcome this issue, we focused on the chemical structure of hydrophobic scaffolds of pH-sensitive cationic lipids with various lengths and shapes. LNPs composed of a pH-sensitive cationic lipid with long, linear scaffolds induced gene silencing in a dose-dependent manner, while LNPs with a classical scaffold length (C18) failed. Replacing the helper lipid from cholesterol to egg sphingomyelin (ESM) resulted in the formation of smaller LNPs with a diameter of ~22 nm and enhanced gene silencing activity. Most of the ESMs were located in the outer layer and functioned to stabilize the LNPs. Long, linear scaffolds contributed to immiscibility with phosphocholine-containing lipids including ESM. This contribution was dependent on the scaffold length of pH-sensitive cationic lipids. Although phosphocholine-containing lipids usually inhibit membrane fusion-mediated endosomal escape, long, linear scaffolds contributed to avoiding the inhibitory effect and to enhance the potency of the LNPs. These findings provide useful information needed for the rational design of pH-sensitive cationic lipid structures and the selection of appropriate helper lipids and will facilitate the development of highly potent small-sized LNPs. STATEMENT OF SIGNIFICANCE: Despite the fact that small-sized lipid nanoparticles (LNPs) are important for improved tissue penetration and efficient drug delivery, the size reduction-associated decrease in the stability and intracellular trafficking significantly hinders the development of potent small-sized LNPs. Our limited understanding of the mechanism underlying the reduced potency has also hindered the development of more potent small-sized LNPs. The findings of the present study indicate that long and linear hydrophobic scaffolds of pH-sensitive cationic lipids could overcome the loss of efficiency for nucleic acid delivery. In addition, the long hydrophobic scaffolds led to immiscibility with neutral phospholipids, resulting in efficient endosomal escape. These findings provide useful information needed for the rational design of pH-sensitive cationic lipid structures and will facilitate the development of highly potent small-sized LNPs.


Assembly of the eukaryotic PLP-synthase complex from Plasmodium and activation of the Pdx1 enzyme.
Biosynthesis of vitamins is fundamental to malaria parasites. Plasmodia synthesize the active form of vitamin B(6) (pyridoxal 5'-phosphate, PLP) using a PLP synthase complex. The EM analysis shown here reveals a random association pattern of up to 12 Pdx2 glutaminase subunits to the dodecameric Pdx1 core complex. Interestingly, Plasmodium falciparum PLP synthase organizes in fibers. The crystal structure shows differences in complex formation to bacterial orthologs as interface variations. Alternative positioning of an α helix distinguishes an open conformation from a closed state when the enzyme binds substrate. The pentose substrate is covalently attached through its C1 and forms a Schiff base with Lys84. Ammonia transfer between Pdx2 glutaminase and Pdx1 active sites is regulated by a transient tunnel. The mutagenesis analysis allows defining the requirement for conservation of critical methionines, whereas there is also plasticity in ammonia tunnel construction as seen from comparison across different species.


[Continuous monitoring of critical patients with a newly developed pulmonary arterial catheter. A cost analysis].
The introduction of flow-directed pulmonary artery (PA) catheters has helped to improve our knowledge of cardiovascular physiology. There have been several developments of this equipment in recent years, including continuous monitoring of mixed-venous O2 saturation (SvO2) and cardiac output (CO). The high purchase price, however, is an obstacle to its use in the critically ill. The aim of the present study was to analyse the actual costs of these devices in comparison to standardly used intermittent monitoring of SvO2 and CO. METHODS. Thirty critically ill patients in a surgical intensive care unit (ICU) were prospectively studied. PA catheter monitoring was indicated by physicians who were not involved in the study. The patients were randomly allocated to one of the following groups: 1. a standard PA catheter was used, and SvO2 and CO were intermittently measured 6 times a day on a routine basis and additionally when necessary from the clinical point of view; 2. SvO2 was continuously measured using a fiberoptic PA catheter; and 3. CO was continuously monitored using a newly developed PA catheter. Costs for the catheter equipment and laboratory analyses (SvO2) were calculated and the durations of intermittent monitoring techniques were measured. Costs for the 'hardware' (monitor, blood gas analyser) were not taken into account. SvO2 was measured by the ICU staff using an ICU-owned blood gas analyser (4.78 DM/analysis) and by a central laboratory unit, which had to be paid for its analyses (30.50 DM/analysis), respectively. RESULTS. The groups were comparable with regard to their demographic data. A total of 378 intermittent measurements of SvO2 and 449 mean CO measurements (1611 single bolus CO measurements) were carried out in the patients in whom a standard PA catheter was inserted. For daily calibration, a total of 50 single SvO2 measurements were done in the group in which SvO2 was continuously monitored. A total of 27.7 h were spent for intermittent SvO2 measurements (time range of one analysis using the ICU-based blood gas analyser: 4.0 to 7.9 min); intermittent CO monitoring took a total of 14.2 h (time range of one mean CO measurement: 1.6 to 3.0 min). When blood gases were analysed by a central laboratory unit, costs for intermittent SvO2 were tremendously higher than when monitored continuously. CONCLUSION. Monitoring devices that provide us with continuous information on the patient's state may have advantages in the management of the critically ill. Whether the patient's 'outcome' can be improved by monitoring SvO2 and CO continuously was not addressed by the present study. Instead, this study focused on the question of whether these devices are more cost-intensive than standard PA catheter monitoring systems. Costs for laboratory analyses can blunt the advantage of lower costs for the standard PA catheter. Intermittent (standard) monitoring of SvO2 and CO was significantly more time-consuming than the continuous methods. It can be summarised that although purchase costs for the more advanced PA catheters are higher than for standard PA catheters, the use of these continuous monitoring devices in the critically ill can be justified from a financial point of view.


Decreased chronic lymphocytic leukemia incidence in Asians in Los Angeles County.
Chronic lymphocytic leukemia (CLL) is rare in Asians living in Asia and possibly in US Asians. In contrast, CLL is the most common leukemia in whites. The basis for this ethnic and geographic variation is unknown. We compared average annual age-adjusted incidence rates (AAIR) of CLL diagnosed from 1972 to 1995 among Los Angeles County-resident Asians, non-Spanish-surnamed- and Spanish-surnamed whites (non-Hispanic and Hispanic-whites) and blacks using the University Southern California-Cancer Surveillance Program (USC-CSP), the population-based cancer registry for Los Angeles County. Asian groups studied included Chinese, Japanese, Filipinos and Koreans. Expected numbers of CLL cases were based on the age-adjusted incidence rates in non-Hispanic whites and compared to numbers of cases observed in Chinese, Japanese and Filipinos. Possible association of socioeconomic state (SES) was assessed using AAIRs with SES-specific denominators. In the absence of denominators by birthplace, the association of birthplace and CLL-incidence was evaluated using proportional odds ratios (POR). Los Angeles County Asian males and females had significantly lower AAIRs than non-Hispanic whites (males: AAIR=0.7 per 100000 population, 95% confidence interval (CI), 0.5-1.0 vs. 4.4, 95% CI, 4.3-4.6; and females: AAIR=0.5, 95% CI, 0.3-0.7 vs. 2.3, 95% CI, 2.2-2.4). Fewer Japanese Chinese and Filipinos were diagnosed with CLL than expected (P<0.01). There was no association of birthplace (POR=0.9, 95% CI, 0. 5-1.9) or SES on CLL-risk. CLL-risk was markedly lower in Los Angeles County Asians compared to non-Hispanic whites. Neither birthplace nor socioeconomic state accounted for this difference suggesting a role for genetic or other environmental factors in decreasing CLL-risk.


A laboratory study on temperature relations of egg production and development in two related species of carabid beetle.
Egg production and development of the carabid beetles Notiophilus biguttatus F. and Notiophilus rufipes Curtis were studied in relation to temperature. Adult beetles and larvae were fed springtails of the species Orchesella cincta (Linné). The rate of egg production, at the different temperatures did not differ between the species. As observed in N. biguttatus egg production at a daily fluctuating temperature regime is high compared to egg production at the constant temperatures. Food supply not only has a strong effect on egg production but also on the relation of egg production with temperature, as shown in N. biguttatus. Development times in N. rufipes are longer than in N. biguttatus particularly at low temperatures. The temperature during development has a distinct effect on adult body size. As observed in N. biguttatus body size and fecundity show a strong positive correlation.


Inflammatory "adiposopathy" in major amputation patients.
Much has been made of obesity's health impact, largely founded on data regarding patient weight and circulating adipose-derived mediator levels. Paradoxically, a "healthy obese" state exists, but substantial knowledge gaps also exist regarding human adipose-phenotype determinants. Surgical major amputation (AMP) patients are the "sickest-of-the-sick." Conversely, elective knee replacement (TKR) is reserved for patients who expect continued health and longevity. To delineate human adipose biology variability and clinical determinants, we studied fresh subcutaneous adipose from AMP patients, using TKR patients as controls. We hypothesized that AMP patients would display a pro-inflammatory adipokine signature, and that certain clinical conditions (diabetes, hypertension, hyperlipidemia, high BMI, uremia) would independently drive elevated adipose inflammation. AMP (n = 29) and TKR (n = 20) adipose tissue samples and clinical data were collected prospectively, and protein was isolated and analyzed for 8 adipose-related mediators. Statistical analyses included Wilcoxon's rank sum test, Fisher's exact test, and multiple linear regression modeling of clinical parameter predictors of mediator expression. Interleukin-(IL)-6, IL-8, leptin, resistin, and PAI-1 were differentially expressed (up to 200-fold) between AMP/TKR cohorts. Key clinical parameters that associated with protein levels of adipose phenotype included age, gender, hypertension, hyperlipidemia, congestive heart failure, cerebrovascular disease, renal disease, and warfarin, statin, and insulin use. BMI failed to be predictive. AMP patients display adiposopathy with a pro-inflammatory adipose phenotypic signature compared with TKR controls. BMI fails to predict phenotype, yet other clinical conditions, such as age, hyperlipidemia, and renal insufficiency, do drive adipokine expression. Understanding human adipose phenotypic determinants stands as a fundamental priority when future studies dissect the interplay between adipose biology and surgical diseases/outcomes.


Role of treatment configuration in simultaneous removal of priority phthalic acid esters and nitrogen in a post anoxic integrated biofilm activated sludge system.
To develop future wastewater treatment systems, focus is to improve/investigate existing biological wastewater treatment processes for the concurrent treatment of conventional pollution parameters (essentially nitrogen) and micro pollutants. Majority of the existing biological wastewater treatment systems were not designed for the removal of micro pollutants. This study focuses on understanding the role of treatment configuration for efficient removal of nitrogen and priority phthalic acid esters (PAEs) from real municipal wastewater in an integrated biofilm activated sludge (IBAS) system. The reactor was operated in two phases: Run I, without external carbon source in anoxic reactor and Run II, a nitrogen removal process, with partial diversion of untreated wastewater in anoxic reactor. Nitrogen removal was 70 ± 12% in both operational phases, however, during Run I, removal of PAEs fluctuated with an average removal of 60-78%. Comparatively, removal of PAEs in Run II varied over a smaller range with average removal increased to 89-95%. In both operational scenarios, secondary oxic tank contributed maximum to the overall removal of PAEs in treatment system. Mass balance calculations showed significant contribution of biodegradation towards overall removal of PAEs which was enhanced by the supply of external carbon source. Kinetics and model output supported the PAEs removal performance observed in different reaction environments of IBAS process. A correlation between food to microorganism (F/M) ratio and PAEs removal showed increase in PAEs removal with decrease in F/M ratio. The study showed that treatment configuration and F/M ratio may be one of the guiding parameters for efficient removal of PAEs in biological wastewater treatment.


Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission.
Synaptic vesicle glycoprotein 2A (SV2A) is a prototype synaptic vesicle protein regulating action potential-dependent neurotransmitters release. SV2A also serves as a specific binding site for certain antiepileptics and is implicated in the treatment of epilepsy. Here, to elucidate the role of SV2A in modulating epileptogenesis, we generated a novel rat model (Sv2a(L174Q) rat) carrying a Sv2a-targeted missense mutation (L174Q) and analyzed its susceptibilities to kindling development. Although animals homozygous for the Sv2a(L174Q) mutation exhibited normal appearance and development, they are susceptible to pentylenetetrazole (PTZ) seizures. In addition, development of kindling associated with repeated PTZ treatments or focal stimulation of the amygdala was markedly facilitated by the Sv2a(L174Q) mutation. Neurochemical studies revealed that the Sv2a(L174Q) mutation specifically reduced depolarization-induced GABA, but not glutamate, release in the hippocampus without affecting basal release or the SV2A expression level in GABAergic neurons. In addition, the Sv2a(L174Q) mutation selectively reduced the synaptotagmin1 (Syt1) level among the exocytosis-related proteins examined. The present results demonstrate that dysfunction of SV2A due to the Sv2a(L174Q) mutation impairs the synaptic GABA release by reducing the Syt1 level and facilitates the kindling development, illustrating the crucial role of SV2A-GABA system in modulating kindling epileptogenesis.


Community structure of denitrifying and total bacteria during nitrogen accumulation in an ammonia-loaded biofilter.
To obtain insight into the complex behaviour of denitrifying and total bacterial groups during the nitrogen accumulation process in an ammonia-loaded biofiltration system. Denitrifying and total bacterial communities in a laboratory-scale rockwool biofilter with intermittent water recirculation were analysed by using denaturing gradient gel electrophoresis targeting nosZ and metabarcoding sequencing of the 16S rRNA gene. Gene abundance was evaluated by quantitative PCR. The nosZ number increased from 6·59 × 106 to 3·33 × 108 copies per gram dry sample over the 436 days of operation, during which nitrogen mass balance errors increased to 39%. The nosZ sequences associated with the genera Castellaniella, Hyphomicrobium and Pseudomonas were detected. Metabarcoding sequencing analysis indicated that the proportions of the genera for which at least one denitrifying strain or species possessing nosZ had been characterized corresponded well to the nitrogen loss. In addition, the genus Nitrosococcus (γ-proteobacteria) increased its relative abundance at days 317 and 436. The increased proportion of denitrifying bacteria in this ammonia-loaded biofiltration system could be related to the nitrogen loss. These results will help to clarify the complex behaviour of nitrifiers and denitrifiers within ammonia-loaded biofiltration systems.


Spontaneous mutants of the bacteriophage fd and mutants resulting from fd-infected cultures of E. coli grown in the presence of 2.7-diaminofluoren and proflavin were isolated by means of free flow electrophoresis.The amino acid analyses of the mutant coat proteins (B-proteins) show significant differences in comparison with the amino acid analyses of wild type coat protein.


Capsaicin-sensitive and -insensitive vagal bronchopulmonary C-fibres in the mouse.
We developed an isolated tracheally perfused (35-37 degrees C) nerve-lung preparation for the study of bronchopulmonary afferent nerve activity in the mouse. Extracellular recordings were made from the vagal sensory neurons located in the jugular-nodose ganglia complex (JNC) with identified receptive fields in the lungs. Analysis of the vagal compound action potential revealed that the mouse vagal C-fibre conduction velocities range from 0.3 to 1.5 m s(-1). A total of 83 bronchopulmonary C-fibres were studied. The sensitivity of the bronchopulmonary C-fibres to the vanilloid receptor 1 (VR1) agonist capsaicin was dependent on conduction velocity. Thus C-fibres with conduction velocities between 0.3 and 0.7 m s(-1) responded to capsaicin (1 microM) while C-fibres with conduction velocities between 0.7 and 1.5 m s(-1) were capsaicin insensitive. Similarly, bradykinin (1 microM) excited only those C-fibres with conduction velocities < 0.7 m s(-1). The response to bradykinin was not mimicked by the B1 receptor agonist [des-Arg9]bradykinin (1 microM) and was abolished by the bradykinin B2 receptor antagonist HOE 140 (1 microM). Adenosine 5'-triphosphate (ATP, 30 microM) activated the C-fibres irrespective of the conduction velocities. This response was mimicked by the selective P2X agonist alpha,beta-methylene-adenosine 5'-triphosphate (30 microM). Consistent with the electrophysiology, morphological analysis revealed that only approximately 40% of the lung-specific small diameter (< 20 microm) JNC neurons consistent with the C-fibre cell bodies display VR1 immunoreactivity. This study describes a convenient in vitro method for the study of mouse bronchopulmonary C-fibres. The results indicate that C-fibres in the mouse lungs are not homogeneous, but can be subclassified into capsaicin-sensitive and capsaicin-insensitive phenotypes.


Low density lipoprotein S-homocysteinylation is increased in acute myocardial infarction patients.
We have investigated on the levels of homocysteine linked to LDL in acute myocardial infarction patients. We used capillary electrophoresis to measure LDL-bound thiols in 16 AMI individuals and 32 healthy volunteers. We found a significant increase of apo-B homocysteine and cysteine levels in LDL fraction of AMI subjects. Our findings suggest that also LDL S-homocysteinylation may be considered among the markers for the CVD risk evaluation.


Down-regulation of HAI-1 is associated with poor-differentiation status of colorectal cancer.
Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a Kunitz-type serine protease inhibitor which is widely expressed in epithelial cells. The purpose of this study is to investigate the relationship between HAI-1 expression and differentiation status of colorectal epithelia. The expression of HAI-1 in clinical samples of both cancerous and normal colorectal tissues was evaluated by immunohistochemical staining. An in vitro epithelial differentiation model of Caco-2 cell was established, and the characteristics of differentiation of Caco-2 cells were observed by transmission electron microscopy. The expression of HAI-1 in Caco-2 cells at different differentiation stages was examined by western blot. Immunohistochemical staining of 52 human colorectal cancer tissues showed a definite correlation between HAI-1 expression and differentiation status: IHC score (mean ± SE) of HAI-1 was higher for well- or moderately-differentiated colorectal cancer tissues than for poorly-differentiated colorectal cancer tissues, with significant differences in HAI-1 positive rate (P < 0.01 and P < 0.05 for well-differentiated vs. poorly-differentiated and moderately-differentiated vs. poorly-differentiated, respectively). Immunohistochemical staining of normal colorectal tissues showed positive HAI-1 expression in well-differentiated epithelial cells whereas the under-differentiated crypt cells showed very weak HAI-1 staining signals. The result of western blot also showed the gradual increasing of HAI-1 expression during the process of Caco-2 differentiation in vitro. HAI-1 expression correlates with the differentiation status of colorectal epithelia and could serve as a differentiation marker.


The optimal threshold for prompt clinical review: An external validation study of the national early warning score.
The aim of this study was to determine the optimal threshold for national early warning score in clinical practice. The national early warning score is an aggregate early warning score aiming to predict patient mortality. Studies validating national early warning score did not use standardised patient outcomes or did not always include clinical workload in their results. Since all patients with a positive national early warning score require a clinical workup, it is crucial to determine the optimal threshold to limit false-positive alerts. An external validation study using retrospectively collected data of patient admissions in six Belgian hospitals. We adhered to the STARD guideline for reporting. Two sample groups were selected: the cross-sectional sample (admitted patients, 1 day every 4 months) and the serious adverse event sample (all patients with unexpected death, cardiac arrest and unplanned admission to the intensive care unit). The maximum registered national early warning score value was collected in both groups. Predictive values were used as estimates for clinical workload. We collected 1,523 in the cross-sectional sample and 390 patients in the serious adverse event sample. A national early warning score ≥5 had a predictive value of 6.8% and a negative predictive value of 99.5% to predict unexpected death, cardiac arrest with cardiopulmonary resuscitation or unplanned admission to intensive care (AUROC 0.841). The performance of national early warning score differed between outcome measures. Considering the predictive value, the optimal threshold for national early warning score is ≥5. We validated national early warning score to be applied in general hospital wards and confirmed the optimal threshold (≥5). When a patient has a national early warning score <5, we may assume that in the next 24 hr this patient is less likely to die unexpectedly, receive cardiopulmonary resuscitation or be transferred to the ICU. Because of the significant number of false positives when national early warning score is ≥5, hospitals should create workable guidelines for clinical practice.


Bedsharing, roomsharing, and sudden infant death syndrome in Scotland: a case-control study.
To examine the hypothesis that bedsharing with an infant is associated with an increased risk of sudden infant death syndrome (SIDS). A 1:2, case:control study in Scotland UK, population 5.1 million, including 123 infants who died of SIDS between January 1, 1996 and May 31, 2000, and 263 controls. The main outcome measure was sharing a sleep surface during last sleep. Sharing a sleep surface was associated with SIDS (multivariate OR 2.89, 95% CI 1.40, 5.97). The largest risk was associated with couch sharing (OR 66.9, 95% CI 2.8, 1597). Of 46 SIDS infants who bedshared during their last sleep, 40 (87%) were found in the parents' bed. Sharing a bed when <11 weeks (OR 10.20, 95% CI 2.99, 34.8) was associated with a greater risk, P = .010, compared with sharing when older (OR 1.07, 95% CI 0.32, 3.56). The association remained if mother did not smoke (OR 8.01, 95% CI 1.20, 53.3) or the infant was breastfed (OR 13.10, 95% CI 1.29, 133). Bedsharing is associated with an increased risk of SIDS for infants <11 weeks of age. Sharing a couch for sleep should be strongly discouraged at any age.


Evolution of a focus of Lyme disease.
Epidemiological investigations were initiated in 1984 when significant Lyme disease activity was observed within a 5-km radius of an area previously used as a non-endemic control site for Lyme disease research in New Jersey. Through 1983, collections of Ixodes dammini from vegetation and feral rodents were infrequent and no human cases were identified within a 16-km radius of the control site. In 1984, 4 human cases and 3 serologically reactive canines (greater than or equal to 1:512) were recognized within the area and adult I. dammini populations were over 3-fold greater than those at our primary study location where Lyme disease has been endemic since 1981. Using darkfield microscopy, 53.4% of adult I. dammini were infected with Borrelia burgdorferi as compared to 50.0% of adults collected during the same period at the known endemic study site. These data indicate that a focus of Lyme disease has recently become established at the previously non-endemic control site and that the establishment of new foci may occur more rapidly than once thought.


Eu3+ detects two functionally distinct luminal Ca2+ binding sites in ryanodine receptors.
Ryanodine receptors (RyRs) are Ca2+ release channels, gated by Ca2+ in the cytosol and the sarcoplasmic reticulum lumen. Their regulation is impaired in certain cardiac and muscle diseases. Although a lot of data is available on the luminal Ca2+ regulation of RyR, its interpretation is complicated by the possibility that the divalent ions used to probe the luminal binding sites may contaminate the cytoplasmic sites by crossing the channel pore. In this study, we used Eu3+, an impermeable agonist of Ca2+ binding sites, as a probe to avoid this complication and to gain more specific information about the function of the luminal Ca2+ sensor. Single-channel currents were measured from skeletal muscle and cardiac RyRs (RyR1 and RyR2) using the lipid bilayer technique. We show that RyR2 is activated by the luminal addition of Ca2+, whereas RyR1 is inhibited. These results were qualitatively reproducible using Eu3+. The luminal regulation of RyR1 carrying a mutation associated with malignant hyperthermia was not different from that of the wild-type. RyR1 inhibition by Eu3+ was extremely voltage dependent, whereas RyR2 activation did not depend on the membrane potential. These results suggest that the RyR1 inhibition site is in the membrane's electric field (channel pore), whereas the RyR2 activation site is outside. Using in silico analysis and previous results, we predicted putative Ca2+ binding site sequences. We propose that RyR2 bears an activation site, which is missing in RyR1, but both isoforms share the same inhibitory Ca2+ binding site near the channel gate.


Protective effects of Radix Stellariae extract against Alzheimer's disease via autophagy activation in Caenorhabditis elegans and cellular models.
Enhancing the clearance of proteins associated with Alzheimer's disease (AD) emerges as a promising approach for AD therapeutics. This study explores the potential of Radix Stellariae, a traditional Chinese medicine, in treating AD. Utilizing transgenic C. elegans models of AD, we demonstrated that a 75% ethanol extract of Radix Stellariae (RSE) (at 50 µg/mL) effectively diminishes Aβ and Tau protein expression, and alleviates their induced impairments including paralysis, behavioral dysfunction, neurotoxicity, and ROS accumulation. Additionally, RSE enhances the stress resistance of C. elegans. Further investigations revealed that RSE promotes autophagy, a critical cellular process for protein degradation, in these models. We found that inhibiting autophagy-related genes negated the neuroprotective effects of RSE, suggesting a central role for autophagy in the actions of RSE. In PC-12 cells, we observed that RSE not only inhibited Aβ fibril formation but also promoted the degradation of AD-related proteins and reduced their cytotoxicity. Mechanistically, RSE was found to induce autophagy via modulating PI3K/AKT/mTOR and AMPK/mTOR signaling pathways. Importantly, inhibiting autophagy counteracted the beneficial effects of RSE on the clearance of AD-associated proteins. Moreover, we identified Dichotomine B, a β-carboline alkaloid, as a key active constituent of RSE in mitigating AD pathology in C. elegans at concentrations ranging from 50 to 1000 µM. Collectively, our study presents novel discoveries that RSE alleviates AD pathology and toxicity primarily by inducing autophagy, both in vivo and in vitro. These findings open up new avenues for exploring the therapeutic potential of RSE and its active component, Dichotomine B, in treating neurodegenerative diseases like AD.


Unaltered drug metabolizing enzyme systems in type II diabetes mellitus before and during glyburide therapy.
Diabetes mellitus is associated with alterations in hepatic drug metabolizing enzyme activities in experimental animals. To determine whether Type II diabetes or glyburide affect hepatic drug metabolism, the authors used 13C-labeled aminopyrine and caffeine breath tests as in vivo probes of the hepatic cytochrome P450 and P(1)450 enzyme activities respectively in six subjects with Type II diabetes (4 women, 2 men). These subjects had been treated previously with diet, had an age range of 41-63 years, had a body mass index range of 24.1-43.3 kg/m2 and had a mean fasting plasma glucose of 14.6 +/- 1.2 mM and a mean hemoglobin A1c of 12.2 +/- 0.7%. These subjects did not drink alcohol or take drugs known to affect hepatic drug metabolism. The caffeine and aminopyrine breath tests (CBT, ABT) were performed sequentially while fasting before the start of glyburide treatment (5 mg daily) and at weekly intervals for 4 weeks. ABT and CBT values are expressed as cumulative percentage of dose exhaled through 2 hours. Before beginning glyburide, the mean ABT and CBT results were 10.2 +/- 0.7% and 4.2 +/- 0.7% respectively, well within the normal ranges for these tests (ABT 6.5-15%; CBT 2.5-10%). The ABT and CBT values remained unaltered during 4 weeks of glyburide therapy. However, FBS decreased to 10.2 +/- 1.1 mM and HbA1C to 10.1 +/- 0.8% by the end of drug treatment. Type II diabetes that is poorly controlled by diet alone is not associated with alterations of the hepatic drug metabolizing enzymes as judged by the caffeine and aminopyrine breath tests. Furthermore, glyburide does not induce or inhibit the drug metabolizing enzyme systems in the liver, thereby precluding drug-drug interactions of this type.


An influenza B outbreak during the 2007/2008 winter among appropriately immunized elderly people living in a nursing home.
The study evaluated the immunogenicity and efficacy of a trivalent subunit MF59-adjuvanted influenza vaccine (A/Wisconsin/67/05 (H3N2), A/Solomon Islands/3/06 (H1N1) and B/Malaysia/2506/04) in preventing serologically diagnosed infections in a group of 67 institutionalized elderly volunteers during 2007/2008 winter, characterized by co-circulation of drifted A/H3N2, A/H1N1 and B influenza viruses. Influenza vaccination induced a significant increase in the amounts of hemagglutination inhibiting antibodies, both against the vaccine and the epidemic drifted strains. However, vaccination did not prevent the circulation of the new drifted influenza B virus (B/Florida/4/06-like), belonging to the B/Yamagata/16/88-lineage, antigenically and genetically distinct from B/Victoria/2/87-lineage viruses from which the vaccine B strain was derived.


[Weather and climatic factors at the resort of the Southern coast of Crimea in the medical rehabilitation of patients with hypertension].
To evaluate the effect of weather and climatic factors of the South Coast of Crimea (SCC) on the effectiveness of health resort medical rehabilitation (MR) of patients with arterial hypertension (AH). One hundred and thirty-four patients with AH were examined. The effect of weather and climatic factors of the SCC was assessed using the methods of Modified Clinical Weather Pathogenicity Index (CWPI-M, developed at the I.M. Sechenov Institute) and assessment of medical rehabilitation according to International Classification of Functioning, Disability and Health (ICF) criteria. The regression equations for the change of ICF domains b2401, b420, b4301, b4552, d240 and the change of mean values of all domains depending on air temperature and humidity, wind velocity, amount of clouds, variability of air temperature, and atmospheric pressure were developed. The equations permit the generation of reliable rehabilitation prognosis for patients with AH for all terms of health resort care at the SCC. The use of CWPI-M makes it possible to form a rehabilitation prognosis for patients with AH based on certain ICF domains. The best rehabilitation prognosis for the SCC resorts is for the warm period of the year.


Stress-associated poor health among adult immigrants with a language barrier in the United States.
The healthy migrant hypothesis supported by the 'Hispanic paradox' suggests that immigrants are healthier than non-immigrants. To test the generalizability of this hypothesis, we studied the stress-associated health status of adult immigrants with a language barrier in the USA. Three stress-related conditions (Unhappiness, Depression, and Anxiety) and self-reported health status were ascertained from participants of the Community Tracking Study Health Survey conducted in 2003. The associations between these conditions as well as the immigrants' length of time living in the USA and health were assessed. Our results demonstrated that the three stress-related conditions were significantly associated with a dramatically elevated poor health status (Unhappiness: OR = 5.22, 95% CI: 4.43-6.14; Depression: OR = 3.03, 95% CI: 2.31-3.98; Anxiety: OR = 5.12, 95% CI: 3.53-7.41). Compared to US citizens without a language barrier, immigrants with a language barrier were more likely to report poor health (OR = 2.15, 95% CI: 1.66-2.78). After adjustment for stressors, the likelihood of reporting poor health among immigrants with a language barrier decreased significantly (OR = 1.75, 95% CI: 1.05-2.91). In addition, these immigrants were more likely to report poor health within the first 10 years of their living in the USA (<or=5 years: OR = 2.79, 95% CI: 1.94-4.02; 6-10 years: OR = 2.68, 95% CI: 1.86-3.86). In summary, immigrants who have a language barrier were generally more stressed, especially at the beginning of their lives as immigrants. The combined effect of stress and a language barrier led to poorer health in these immigrants. Thus, the healthy migrant hypothesis may not be generalizable to this population.


Differentiation of intrahepatic mass-forming cholangiocarcinoma from hepatocellular carcinoma on gadoxetic acid-enhanced liver MR imaging.
To determine the different imaging features of intrahepatic mass-forming cholangiocarcinoma (IMCC) from hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced magnetic resonance imaging (MRI). This retrospective study was institutional review board approved and the requirement for informed consent was waived. Patients who underwent gadoxetic acid-enhanced MRI with histologically confirmed IMCCs (n = 46) or HCCs (n = 58) were included. Imaging features of IMCCs and HCCs on gadoxetic acid-enhanced MRI including T2- and T1-weighted, diffusion weighted images, dynamic study and hepatobiliary phase (HBP) images were analyzed. Univariate and multivariate logistic regression analyses were performed to identify relevant differentiating features between IMCCs and HCCs. Multivariate analysis revealed heterogeneous T2 signal intensity and a hypointense rim on the HBP as suggestive findings of IMCCs and the wash-in and "portal wash-out" enhancement pattern as well as focal T1 high signal intensity foci as indicative of HCCs (all, p < 0.05). When we combined any three of the above four imaging features, we were able to diagnose IMCCs with 94 % (43/46) sensitivity and 86 % (50/58) specificity. Combined interpretation of enhancement characteristics including HBP images, morphologic features, and strict application of the "portal wash-out" pattern helped more accurate discrimination of IMCCs from HCCs. • Analysis of enhancement characteristics helped accurate discrimination of IMCCs from HCCs. • Wash-out should be determined on the PVP of gadoxetic acid-enhanced MRI. • A hypointense rim on the HBP was a significant finding of IMCCs.


Histochemical study on lipid metabolism in acute myocardial infarction.
As a part of the series of studies on lipid metabolism in ischemic myocardium, the present study was attempted to analyse 29 infarcted hearts with acute or scar lesions by a routine histopathology and lipid histochemistry. The time after the onset of attack till death ranged from one day to years. Sixteen were of the acute form, less than 2 month-old, and 13 were of the chronic scarred form. Within the first day, fat deposition appeared in the survived muscle cells around the infarcts reaching the peak from 2 days to one week, but necrotized cells never contained fat droplets. Macrophages in granulation tissue in periphery of the infarcts tended to have significant fat droplets usually in 10 days to one month. Fat disappeared from the survived muscle cells and also from the scar later than 2 months. The survived cells around the infarcts might be degenerated with fat, probably triglyceride, which accumulated by a relative ischemia not severe enough to produce coagulation necrosis, and they bear some relationship with extension or limitation of size of infarcts.


Reproductive Concerns Among Women with Disability: A Host of Opportunities for Reproductive Health Care Professionals.
Maternal health in India is likely to move towards an obstetric transition, wherein there is sustained reduction of maternal mortality and focus shifts towards improving quality of care. In such a context, reproductive concerns of special populations gain prominence. One such population group is women with disability. This mini-review examines the incremental importance given to people with disabilities and the sparse data available on the topic of reproductive concerns among women with disability. The attitudes of the women with disability towards childbearing and the association between disability and obstetric problems are discussed. The limited available data on specific medical and obstetric problems among women with disability are reviewed. The article calls for all obstetricians to display increased sensitivity and heightened cognizance towards the reproductive concerns among women with disability.


Bioflora probiotic in immunomodulation and prophylaxis of intestinal bacterial translocation in rats.
The immunomodulator effect of Bioflora probiotic on T (CD4+) and B (CD20) lymphocytes in gastrointestinal mucosa and intestinal bacterial translocation was studied using Wistar rats (n = 10 per group). Two experiments were used: (I) stress with immobilization and water immersion at 22 degrees C for 7 h plus the application of indomethacin (Indo) 10 mg/kg SC every 24 h for 3 days (comparator group), and (II) stress experiment I with the addition of 1 mL of Bioflora applied through a orogastric tube every 12 h for 3 days. At the 4th day, in asepsis, a dissection laparotomy of liver, spleen, mesenteric lymphatic nodes, and cecum was performed for microbiological culture, and stomach, ileum, and colon were also dissected for immunohistochemical and quantification of CD4+ and CD20. Findings in experiment I revealed cecum bacterial overdevelopment of 6 x 10(10) +/- 2.3 x 10(9) colony-forming units (CFU) (P < 0.01) and positive cultures in liver, spleen, and all mesenteric lymphatic nodes. On the other hand, in the group treated with Probiotic Bioflora, cecum without overdevelopment (3 x 10(6) +/- 1.3 x 10(5) CFU), negative cultures in liver and spleen, and in lymphatic nodes two positive and eight negative cultures for E. coli and P. vulgaris (P < 0.01) were observed. Immunohistochemistry revealed a relevant increase of T lymphocytes (CD4+) in ileum and colon. Bioflora probiotic was shown to be an intestinal immunomodulator that induced increased T (CD4+) lymphocytes that also offer prophylaxis of intestinal bacterial translocation in a stressed rat model.


3D Mammometric Changes in the Treatment of Idiopathic Gynecomastia.
Three-dimensional surface imaging (3DSI) has shown promise for plastic surgeons to objectively assess changes in body contour and breast volume. To assess the surgical outcome after bilateral subcutaneous mastectomy (BSM) and water jet-assisted liposuction (WAL) as treatment for idiopathic gynecomastia, using 3DSI to document changes regarding nipple-areolar complex (NAC) and breast volume. Thirty male patients (Simon II A to B) receiving BSM and WAL were enrolled. Eight subjects received additional mastopexy and NAC reduction. Use of a Vectra 3D Imaging System® before and 6 months after surgery provided data regarding changes of NAC placement and NAC and breast dimensions. The sum volume of intraoperatively approximated lipoaspirate before and after centrifugation and mastectomy specimens quantified using water displacement were compared with 3D-assessed differences in volume. When compared to the NAC dimensions defined during surgery, patients receiving NAC reductions showed nonsignificant postoperative changes in NAC dimensions. Patients without additional mastopexy showed a significant (p < 0.001) vertical (15.7 ± 14.3%) and horizontal (17.1 ± 15.0%) reduction in NAC diameter. 3D volume changes (92.8 ± 26.4 mL) showed significant differences (p < 0.001) 6 months after surgery compared to the intraoperatively measured lipoaspirate before (182 ± 54.5 mL) and after (120 ± 34.6 mL) centrifugation. Although it is clear that patient satisfaction must remain the prime focus of surgical body contouring, 3DSI has proven valuable to objectively demonstrate both the anticipated outcome and further findings regarding treatment of idiopathic gynecomastia. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .