Comparison study of single and concurrent administrations of carbapenem, new quinolone, and macrolide against in vitro nontypeable Haemophilus influenzae mature biofilms.
Nontypeable Haemophilus influenzae (NTHi) is an opportunistic pathogen and a common cause of otitis media in children, chronic bronchitis, and pneumonia in patients with chronic obstructive pulmonary disease. Many studies have reported that NTHi is capable of producing biofilms, which may be one of the important factors involved in chronic diseases and accelerating antimicrobial resistance. Unfortunately, there is still no consensus about the elimination of biofilms. In this study, concurrent administrations of levofloxacin (LVFX)-imipenem (IPM) and clarithromycin (CAM)-IPM, as well as the single administration of IPM, LVFX, and CAM, were performed to treat the mature biofilms produced by NTHi, respectively. Biofilm inhibition was quantified using microtiter biofilm assay (MBA), and relative biomass was calculated as the ratio compared to that of untreated control biofilms. The relative biomasses of biofilms treated with IPM, LVFX-IPM, and CAM-IPM against a β-lactamase-negative ampicillin-resistant strain was 1.10, 0.08, and 0.13 at 1× minimum inhibitory concentration (MIC), 0.90, 0.05, and 0.07 at 10× MIC, and 0.80, 0.06, and 0.07 at 100× MIC, respectively. Biofilms were also visually observed by scanning electron microscopy, and a focused ion-beam system showed that high concentrations of combined administration strongly inhibited the biofilms, which was consistent with the results of MBA. Our data demonstrated the antibiofilm effect of concurrent administration against mature NTHi biofilms, which indicated a rationale for the potential use of concurrent administrations in diseases involving chronic NTHi biofilms.


Dual production of biopolymers from bacteria.
Rapid depletion of natural resources with continued demands of an increasing population and high consumption rates of today's world will cause serious problems in the future. This, along with environmental concerns, has directed research towards finding alternatives in variety of sectors including sustainable and environmentally friendly consumer goods. Biopolymers of bacterial origin, with their vast range of applications, biodegradability and eco-friendly manufacturing processes, are one of the alternatives for a more sustainable future. However, the cost of their production is a drawback. Simultaneous production processes have always been an option for researchers in order to reduce cost, but the variable requirements of microorganisms to produce both different and valuable products are a hindering factor. This review will look at some examples and identify ideas towards developing a successful strategy for simultaneous production of bio-products.


Endoplasmic reticulum stress in mouse decidua during early pregnancy.
Unfolded or misfolded protein accumulation in the endoplasmic reticulum lumen leads to endoplasmic reticulum stress (ER stress). Although it is known that ER stress is crucial for mammalian reproduction, little is known about its physiological significance and underlying mechanism during decidualization. Here we show that Ire-Xbp1 signal transduction pathway of unfolded protein response (UPR) is activated in decidual cells. The process of decidualization is compromised by ER stress inhibitor tauroursodeoxycholic acid sodium (TUDCA) and Ire specific inhibitor STF-083010 both in vivo and in vitro. A high concentration of ER stress inducer tunicamycin (TM) suppresses stromal cells proliferation and decidualization, while a lower concentration is beneficial. We further show that ER stress induces DNA damage and polyploidization in stromal cells. In conclusion, our data suggest that the GRP78/Ire1/Xbp1 signaling pathway of ER stress-UPR is activated and involved in mouse decidualization.


No relationship between risk of schizophrenia and prenatal exposure to stress during the Six-Day War or Yom Kippur War in Israel.
Maternal stress during pregnancy is a possible risk factor for schizophrenia in the offspring. Using data from the Israel Psychiatric Registry we examined the impact of wars in Israel. Retrospective birth cohort study. Relative risks for cohorts exposed to Six-Day War and Yom Kippur War were 0.98 (95% CI: 0.85-1.13) and 1.00 (0.86-1.16). The evidence for maternal stress as a risk factor for schizophrenia remains insufficient.


Dietary polyamines are essential luminal growth factors for small intestinal and colonic mucosal growth and development.
Polyamines are essential for cell growth. Dietary and probably gut bacterial derived polyamines contribute significantly to the polyamine body pool. To evaluate the influence of dietary, luminal polyamines on growth and development of different gastrointestinal organs in normally growing rats. Male suckling Wistar rats were randomly allocated to four treatment groups: polyamine deficient diet (PDD); PDD plus antibiotics (neomycin 2 g/kg and metronidazole 34 mg/kg); PDD plus polyamine supplementation at normal concentrations; or normal standard laboratory chow. After a six month feeding period 7-10 animals/group were sacrificed. No differences in body weight gain, food consumption, or general behaviour could be observed between the four groups of animals. Feeding of PDD alone or PDD plus antibiotics resulted in a highly significant decrease in organ weight, protein content, and DNA content in small intestinal and colonic mucosa whereas no alterations were found in the liver. Long term feeding of polyamine deficient diets resulted in a significant hypoplasia of small intestinal and colonic mucosa. Dietary, luminal polyamines are important local factors for growth and the development of small intestinal and colonic mucosa.


[Production of infectious units of Isaria fumosorosea (Hypocreales: Cordycipitaceae) from different indigenous isolates of northeastern Mexico using 3 propagation strategies].
The aim of this study was to evaluate the production of blastospores and conidia of different native isolates and a strain of Isaria fumosorosea using different propagation techniques. Two liquid culture media of casamino acids and peptone as nitrogen sources and glucose as carbon source for both media cultures were respectively used in the production of blastospores, while for the production of conidia, the fungi were grown in potato dextrose agar; from these cultures, solutions of conidia to a concentration of 1×106 per milliliter were prepared to inoculate flasks with Sabouraud dextrose broth for the liquid phase of the biphasic culture, also known as preculture. Subsequently, rice grain bags were inoculated with the preculture and the conidia solutions, which were incubated for 14 days for solid fermentation and biphasic culture, respectively. The HIB-23 isolate recorded a concentration of 4.90×108 blastospores/ml in the casamino acid medium, while a concentration of 2.15×108 blastospores/ml was obtained in the peptone collagen medium. For the Pfr-612 strain, the conidia production in solid-state fermentation was 1.58×109 conidia/g, and for HIB-30 in the biphasic culture of 9.00×106 conidia/g. Solid-state fermentation proved to be the most effective method with an average of 1.09×109 conidia/g, whereas the biphasic culture was the least effective method with 2.76×106 conidia/g; no significant difference was reported for the submerged production media.


GABA-like immunoreactivity in cholinergic amacrine cells of the rabbit retina.
In the ganglion cell layer of the rabbit retina, the inhibitory transmitter gamma-aminobutyric acid (GABA) and its analogues are accumulated by neurons that appear to match in size and number the population of displaced amacrine cells that synthesize the excitatory transmitter acetylcholine. In this double-label study, we have established directly that the cholinergic amacrine cells, selectively stained with diamidino-phenylindole, are strongly immunoreactive with GABA antisera. The coexistence of two classical transmitters, one excitatory and the other inhibitory, in this defined neuronal population, suggests that stimulation of the cholinergic amacrines may give rise to complex responses in their target neurons.


Infantile onset spinocerebellar ataxia with sensory neuropathy: a new inherited disease.
We report the clinical findings in 19 Finnish patients, including six pairs of siblings, with a new, early onset spinocerebellar ataxia. The slowly progressive clinical symptoms manifested between one and two years of age in previously healthy infants. The first manifestation of children at that age was clumsiness and loss of ability to walk. Ataxia, athetosis and muscle hypotonia with loss of deep tendon reflexes were discovered on clinical examination. By school age ophthalmoplegia and hearing loss were diagnosed, while sensory neuropathy developed by adolescence. In addition, an acute crisis with status epilepticus was a late manifestation. We found a marked decrease in sensory nerve condition velocities, a progressive loss of myelinated fibers in sural nerve specimen, and abnormal background activity in EEG with advancing age. The main finding in neuroradiological investigations was cerebellar atrophy. The occurrence of the disease in siblings and lack of manifestations in parents indicate recessive inheritance.


Angular changes in pelvic tilt and cup orientation at a minimum of eighteen years after primary total hip arthroplasty with an uncemented cup.
Changes in pelvic tilt angle (PTA) and cup orientation have been reported in patients after total hip arthroplasty, but the current literature generally has a brief follow-up period. This study will be the first to report PTA and cup orientation changes in the supine position for a minimum 18 years after total hip arthroplasty (THA) and investigate the factors associated with pelvic tilt and cup orientation changes. In this study, 101 patients (120 hips) who underwent THA were retrospectively analyzed. The aims of our study were to evaluate the PTA and cup orientation change over 18 years after THA to assess differential PTA, cup inclination, and anteversion. We also investigated whether factors such as gender, body mass index, and age have any influence on PTA and cup orientation after THA. Patients showed a significant incremental change in PTA pre-operatively, immediately post-operatively, and at final follow-up. Cup orientation increased significantly at the final follow-up compared to the immediate post-operative period. Gender subgroup analysis showed that PTA was significantly greater in females than in males at the final follow-up (p = 0.025). Age subgroup analysis showed that PTA was significantly greater in the over 60 years group than in the other groups. Our patients showed significant changes in PTA and cup orientation at a minimum 18 years after surgery, especially in females over 60 years. Female patients over 60 are a risk factor after THA.


Superficial keratectomy with mitomycin-C for the treatment of Salzmann's nodules.
To evaluate the success of treatment and prevention of recurrence of Salzmann's nodules by superficial keratectomy with intraoperative mitomycin-C (MMC). Price Vision Group, Indianapolis, Indiana, USA. This retrospective consecutive case series comprised 30 eyes of 25 patients who had superficial keratectomy with MMC between January 1997 and June 2000 at a large tertiary-care center. Twenty-four patients reported improvement in their symptoms. The remaining patient lost 1 line of visual acuity. Ninety-seven percent of eyes maintained or improved best corrected visual acuity. No patient had a recurrence of Salzmann's nodular degeneration over a mean follow-up of 28 months +/- 15 (SD) (range 4.0 days to 4.1 years). Superficial keratectomy with MMC appears to be a valid and safe method for treating and preventing the recurrence of Salzmann's nodular degeneration.


Assessing Protein Sequence Database Suitability Using De Novo Sequencing.
The analysis of samples from unsequenced and/or understudied species as well as samples where the proteome is derived from multiple organisms poses two key questions. The first is whether the proteomic data obtained from an unusual sample type even contains peptide tandem mass spectra. The second question is whether an appropriate protein sequence database is available for proteomic searches. We describe the use of automated de novo sequencing for evaluating both the quality of a collection of tandem mass spectra and the suitability of a given protein sequence database for searching that data. Applications of this method include the proteome analysis of closely related species, metaproteomics, and proteomics of extinct organisms.


Preventing vaginal stenosis after brachytherapy for gynaecological cancer: an overview of Australian practices.
Despite advances in brachytherapy techniques in recent years, patients still experience a variety of treatment-related complications. Vaginal stenosis is a recognised toxicity of brachytherapy for the treatment of gynaecological cancer. It can result in long-term sexual dysfunction and painful vaginal examinations; however, it is generally accepted that it may be prevented by regular sexual intercourse or the use of vaginal dilators. The incidence of vaginal stenosis is variably reported in the literature, while preventative strategies and compliance are infrequently described and rarely evaluated. A telephone survey of radiation oncology centres in Australia was undertaken as a quality improvement activity to determine best practice for the use of vaginal dilators for the prevention of vaginal stenosis, by way of identifying similarities of practice. The results revealed a lack of consistency for all variables, including which patients are advised to use vaginal dilators, the time to initiate use, frequency of use, insertion time and duration of use. These findings suggest that current methods for preventing radiation-induced vaginal stenosis warrant formal evaluation in order to establish an evidence base for practice.


The Ubangi misnomer.
Lip plates are a form of body modification practiced today by several tribes in Africa and Amazonia. In 1930, the American people were introduced to lip plates in a most spectacular fashion, when the Ringling Bros. and Barnum & Bailey Circus brought in 13 Congolese natives to star as the newest attraction in their sideshow. The Congolese women wore huge lip plates, a result of cultural lip piercing with progressive lip stretching by wooden pegs and plates. The Congolese exhibit was publicized throughout the country as the "Ubangi Savages," a made-up name selected from an African map, because it had an exotic ring to it. This contribution tells the story of the Ubangi Savages and explains their practice of lip piercing and stretching. It also discusses how tissue expansion has been adapted for use in reconstructive surgery which, along with lip plates, is a way people strive to maintain and enhance the beauty of their bodies, whether for medical or cultural reasons.


The epithelium overlying rabbit bronchus-associated lymphoid tissue does not express the secretory component of immunoglobulin A.
The epithelium associated with lymphoid aggregates in the bronchial tract (BALT) was studied in rabbits by immunohistochemistry using monoclonal antibodies against the secretory component (SC) of IgA. The normal bronchus epithelium was intensely labelled. In contrast, epithelium overlying the central parts of the follicles was negative. This specialized epithelium cannot participate in the SC-mediated transport of IgA, which might be a basis for the adherence and transport of microorganisms into the lymphoid tissue, thus initiating immune responses of the BALT.


Rare intracanalicular ophthalmic aneurysm: endovascular treatment and review of the literature.
This report outlines the diagnosis and endovascular management of a rare intracanalicular ophthalmic aneurysm in a patient presenting with progressive visual loss.


Comparison of two forms of albuterol for treatment of acute bronchospasm in pediatric patients.
The Circulaire nebulizer (C-Neb) is marketed as superior to low-dose albuterol for acute bronchospasm. This clinical trial design compared clinical and fiscal outcomes of patients treated with C-Neb and high-dose albuterol (HDA). Eligibility criteria included reactive airway disease, age >5 years, and asthma score (AS) of 2 to 10. Patients with odd medical record numbers received HDA, and those with even numbers received C-Neb. Treatment was concluded if AS was 0, peak flow was >70% predicted, or after three treatments. One hundred eight patients were enrolled: 48 received HDA, 52 received C-Neb, and 8 were excluded. The two groups were comparable by admission rates (G2 = 0.90, P = 0.34), return visit rates (G2 = 0.73, P = 0.39), and final AS (z = 0.59, P = 0.55). Side effects were similar: change in heart rate (t = 1.61, P = 0.11) and mean arterial pressure (t = 1.36, P = 0.17). Charges per treatment, per delivery, and total charges were greater for HDA. The C-Neb is equally effective, has similar side effects, and requires less time and charges than HDA.


Next generation biofuel engineering in prokaryotes.
Next-generation biofuels must be compatible with current transportation infrastructure and be derived from environmentally sustainable resources that do not compete with food crops. Many bacterial species have unique properties advantageous to the production of such next-generation fuels. However, no single species possesses all characteristics necessary to make high quantities of fuels from plant waste or CO2. Species containing a subset of the desired characteristics are used as starting points for engineering organisms with all desired attributes. Metabolic engineering of model organisms has yielded high titer production of advanced fuels, including alcohols, isoprenoids, and fatty acid derivatives. Technical developments now allow engineering of native fuel producers, as well as lignocellulolytic and autotrophic bacteria, for the production of biofuels. Continued research on multiple fronts is required to engineer organisms for truly sustainable and economical biofuel production.


Haem peptide/protein interaction. Part 6: The kinetic mechanisms of the interactions with, and inhibition of enzymic activity of the human erythrocyte glutathione S-transferase isoenzyme rho (p), by haem octa-, nona-, and undecapeptides MP-8/-9/-11.
The binding of the cytochrome-c derived haem peptides microperoxidase-8, -9, and -11 (MP-8, -9, and -11) to the human erythrocyte glutathione S-transferase rho (GST-p) enzyme is demonstrated. Inhibition by the haem peptides of the enzymic conjugation of glutathione (GSH) with the electrophilic cosubstrate 1-chloro-2, 4-dinitrobenzene (CDNB) is mixed-type with respect to CDNB, and Ki, the inhibition constant, increases with increasing length of the peptide chain. The results obtained here for the GST-p are compared to those published recently for the previously-supposed identical isoenzyme human placental GST-pi.


Interleukin-38 overexpression prevents bleomycin-induced mouse pulmonary fibrosis.
Pulmonary fibrosis is a kind of pulmonary disorder with chronic inflammation and excessive collagen deposition, and its etiology is not clear. Interleukin (IL)-38 is a new member of IL-1 family cytokines, but its role in pulmonary fibrosis has not been elucidated. In this study, a lentivirus expressing IL-38 was injected into the nasal cavity of mice with bleomycin-induced pulmonary fibrosis. We found that IL-38 overexpression reduced the body weight loss and improved the survival of mice induced by bleomycin. Furthermore, IL-38 expression attenuated the pulmonary inflammation and fibrosis damage induced by bleomycin, decreased the production of pro-inflammatory and pro-fibrotic cytokines such as IL-1β, IL-6, IL-17A, monocyte chemoattractant protein-1, and tumor necrosis factor-α, but increased the release of anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) in the lungs of bleomycin-challenged mice. Our data suggest that IL-38 may inhibit bleomycin-induced pulmonary inflammation and fibrosis through its anti-inflammatory effect and regulation of IL-1β/IL-1Ra balance, and IL-38 may be a new strategy for the treatment of pulmonary fibrosis.


Factors associated with poor mental health among Guatemalan refugees living in Mexico 20 years after civil conflict.
From 1981 to 2001, 46 000 refugees who fled the 36-year civil conflict in Guatemala for Chiapas, Mexico were under the protection of the United Nations High Commissioner for Refugees. To estimate the prevalence of mental illness and factors associated with poor mental health of underserved Guatemalan refugee communities located in Chiapas, Mexico, since 1981 and to assess need for mental health services. Cross-sectional survey of 183 households in 5 Mayan refugee camps in Chiapas representing an estimated 1546 residents (adults and children) conducted November-December 2000. Symptom criteria of Posttraumatic Stress Disorder (PTSD), anxiety, and depression as measured by the Harvard Trauma Questionnaire and Hopkins Symptom Checklist-25 (Hopkins-25). One adult (aged > or =16 years) per household (n = 170 respondents) who agreed to participate was included in the analysis, representing an estimated 93% of households. All respondents reported experiencing at least 1 traumatic event with a mean of 8.3 traumatic events per individual. Of the respondents, 20 (11.8%) had all symptom criteria for PTSD. Of the 160 who completed the Hopkins Symptom Checklist-25, 87 (54.4%) had anxiety symptoms and 62 (38.8%) had symptoms of depression. Witnessing the disappearance of family members (adjusted odds ratio [AOR], 4.58; 95% confidence interval [CI], 1.35-15.50), being close to death (AOR, 4.19, 95% CI, 1.03-17.00), or living with 9 to 15 persons in the same home (AOR, 3.69; 95% CI, 1.19-11.39) were associated with symptoms of PTSD. There was a protective factor found for lacking sufficient food (AOR, 0.08; 95% CI, 0.01-0.59). Elevated anxiety symptoms were associated with witnessing a massacre (AOR, 10.63; 95% CI, 4.31-26.22), being wounded (AOR, 3.22; 95% CI, 0.95-10.89), and experiencing 7 to 12 traumatic events (AOR, 2.67; 95% CI, 1.14-6.27) and 13 to 19 traumatic events (AOR, 2.26; 95% CI, 0.65-7.89). Elevated symptoms of depression were associated with being a woman (AOR, 3.64; 95% CI, 1.47-9.04), being widowed (AOR, 27.55; 95% CI, 2.54-299.27), being married (AOR, 1.93; 95% CI, 0.59-6.33), witnessing disappearances (AOR, 2.68; 95% CI, 1.16-6.19), experiencing 7 to 12 traumatic events (AOR, 1.57; 95% CI, 0.64-3.88), or experiencing 13 to 19 traumatic events (AOR, 7.44; 95% CI, 2.18-25.37). Psychiatric morbidity related to human rights violations, traumatic events, and refugee status was common among Guatemalan refugees surveyed 20 years after the Guatemalan civil conflict.


Flavonoid concentrations in three grass species and a sedge grown in the field and under controlled environment conditions in response to enhanced UV-B radiation.
An investigation was carried out to find whether enhanced levels of UV-B radiation induce increased concentrations of flavonoids in the leaves of the grass species Deschampsia antarctica, Deschampsia borealis and Calamagrostis epigeios and the sedge Carex arenaria. Whether the enhanced levels of UV-B influenced the proportions of the various flavonoids in the leaves was also studied. Increased flavonoid concentrations would improve the UV-B shielding of UV-B susceptible tissues. Using HPLC analysis the flavonoids orientin and luteolin were identified in D. antarctica, orientin in D. borealis and tricin in C. arenaria. Neither flavonoid concentrations nor the proportion of the various flavonoids in climate room grown D. antarctica and D. borealis plants differed between individuals grown under 0, ambient or elevated UV-B levels. After 12 weeks of growth biomass production and shoot-to-root ratios of D. antarctica were not affected by elevated UV-B radiation. Greenhouse grown C. epigeios plants contained higher concentrations and different proportions of flavonoids grown under elevated levels of UV-B than when grown under ambient or 0 UV-B. In C. epigeios plants grown in their natural habitat in the field under ambient or elevated levels of UV-B, flavonoid concentrations and proportions were the same in plants from both treatments. In the leaves of the sedge C. arenaria grown in a greenhouse flavonoid concentrations and proportions were not affected by UV-B radiation. Leaves were harvested four times during the growing season from C. arenaria plants grown in their natural habitat in the field under ambient or elevated levels of UV-B. Leaves harvested in January contained higher concentrations of flavonoids when grown under elevated UV-B than when grown under ambient UV-B radiation. In leaves harvested in May, September and December flavonoid concentrations were the same in plants grown under ambient or elevated UV-B. The proportion of the different flavonoids was the same for both treatments in all months. These results indicate that constitutive levels of flavonoids in these grass and sedge species are adequately high to protect them against ambient and elevated levels of solar UV-B radiation.


Zr- and Hf-based nanoscale metal-organic frameworks as contrast agents for computed tomography.
Nanoscale metal-organic frameworks (NMOFs) of the UiO-66 structure containing high Zr (37 wt%) and Hf (57 wt%) content were synthesized and characterized, and their potential as contrast agents for X-ray computed tomography (CT) imaging was evaluated. Hf-NMOFs of different sizes were coated with silica and poly(ethylene glycol) (PEG) to enhance biocompatibility, and were used for in vivo CT imaging of mice, showing increased attenuation in the liver and spleen.


The effect of vestibular rehabilitation in Meniere's disease: a systematic review and meta-analysis of clinical trials.
Meniere's disease (MD) is a complex disease that can severely affect the quality of life. In this systematic review and meta-analysis, we aimed to investigate the effect of vestibular rehabilitation (VR) versus control/other interventions on the quality of life in patients with MD. We searched six electronic databases (PubMed/MEDLINE, Web of Science, EMBASE, Scopus, ProQuest, CENTRAL) from inception to September 30, 2022 with no language restriction for publications comparing the effect of VR with control/ other interventions in patients with MD. The primary outcome was quality of life assessed by dizziness handicap inventory (DHI). Overall, three studies with a total of 465 patients were included in the meta-analysis. All the included studies reported immediate-term DHI scores. A medium effect (standardized mean difference [SMD] = - 0.58, 95% confidence interval [CI] - 1.12; - 0.05) was observed favoring the use of VR to improve DHI scores in patients with MD in the immediate term. Moreover, there was severe heterogeneity in immediate DHI scores among the included studies (χ2 = 22.33, P = 0.00, I2 = 82.1%). VR rehabilitation can improve the quality of life in patients with MD immediately after treatment. Since all the included studies had a high risk of bias and none had long-term follow-ups, further high-quality research is required to determine the short-, intermediate-, and long-term effects of VR compared to control/other interventions.


Interrelationships of glucose and insulin uptake by muscle of normal and diabetic man. Evidence of a difference in metabolism of endogenous and exogenous insulin.
A forearm perfusion technique was used to study glucose and insulin uptake by muscle. In normal subjects at glycaemic levels above 130 mg/100 ml, glucose uptake was independent of glucose concentration;it was directly related in insulin concentration but not to insulin uptake. In non-obese maturity-onset diabetic subjects, glucose uptake was dependent on glucose concentration and insulin uptake, but not on insulin concentration. In both groups there was a strong correlation between insulin concentration and insulin uptake; diabetics had a normal insulin uptake in relation to concentration. For a given change in insulin concentration the increase in glucose uptake was as great in diabetics as in controls, but the effect of insulin was mediated through a mechanism involving its uptake. Thus in the non-obese maturity-onset diabetic, forearm muscle is not insulin resistant. The apparent uptake of insulin measured by a radioimmunoassay in relation to its arterial concentration was lower and more variable for heterologous than for endogenous insulin. With a receptor assay the venous insulin concentrations were lower than with the immunoassay and differences in uptake between endogenous and exogenous insulin disappeared. It is concluded that in muscle exogenous insulin was less severely degraded than endogenous insulin.


The inhibition of Th17 immune response in vitro and in vivo by the carbosilane dendrimer 2G-NN16.
We evaluated the 2G-NN16-carbosilane dendrimer activities in Th17 response as a potential therapy for Th17 deregulated pathologies. IL17A, IL17F, IL22, IL23 and other interleukins secreted by Th17 cells CD4+ cells were down regulated when cells were cultured in the presence of this dendrimer. Furthermore, IL17F and IL17A protein levels in splenocytes from mice pretreated with 2G-NN16 dendrimer in a Th17 induction mouse model were lower than those corresponding to PBS treated mice. Treatment of mice with 2G-NN16 inhibited the Th17 response causing much more pathogenicity as indicated by the increase in the number of Candida albicans colonies in the kidneys as compared to PBS-treated mice. All these results suggest a potential pharmacological application for this dendrimer in the therapy of Th17-mediated diseases.


Meconium-stained amniotic fluid exposure is associated with a lower incidence of offspring long-term infectious morbidity.
Meconium-stained amniotic fluid (MSAF) is a well-established risk factor for immediate adverse neonatal outcomes and was recently suggested to be associated with microbial invasion of the amniotic cavity. We aimed to determine whether MSAF exposure during labor carries a longer lasting impact on pediatric infectious morbidity. A population-based cohort analysis was performed including all singleton deliveries occurring between 1991 and 2014 at a single tertiary medical center. Exposure was defined as the presence of MSAF during labor. Hospitalizations of the offspring up to the age of 18 years involving infectious diseases were evaluated. A Kaplan-Meier survival curve was used to compare cumulative morbidity and a Cox regression model to control for confounders. During the study period, 243 725 deliveries met the inclusion criteria. Of them, 35 897 (14.7%) involved MSAF. Rate of infectious-related hospitalizations of the offspring was significantly lower in children exposed to MSAF as compared with the unexposed group (10.8% vs 11.1%, P < 0.05). Specifically, hospitalizations involving respiratory infections were significantly less common among the MSAF group (5.1% vs 5.6%, P < 0.001). The survival curve demonstrated significantly lower cumulative total infectious morbidity rates in the MSAF-exposed group (log rank P < 0.001). In the Cox model, controlled for maternal age, diabetes, hypertension, mode of delivery, and gestational age, exposed children exhibited lower rates of long-term childhood infectious morbidity (adjusted HR 0.96, 95% CI 0.92-0.99, P < 0.001). Fetal exposure to MSAF during labor and delivery appears to be associated with lower rates of long-term infectious-related hospitalizations in the offspring.


[Synthesis and study of the antitumor properties of 13-hydrazone-substituted carminomycin].
13-Tret-butoxycarbonyl hydrazone (BOC hydrazone) of carminomycin was prepared by interaction of carminomycin with tret-butoxycarbonyl hydrazine. Interaction of carminomycin with N-amino-N'-methyl piperazine resulted in 13-(4-methyl piperazinyl) imine (MP imine) of carminomycin. BOC hydrazone and MP imine of carminomycin had a significant antiblastomic activity against lymphosarcoma LIO-1. Still, they had no advantages over carminomycin.


Abnormal cortical-striatal-thalamic-cortical circuit centered on the thalamus in MDD patients with somatic symptoms: Evidence from the REST-meta-MDD project.
Somatic symptoms are common comorbidities of major depressive disorder (MDD), and negatively impact the course and severity of the disease. In order to enrich the understanding of the pathological mechanism and clarify the neurobiological basis of somatic symptoms in depression, we attempted to explore the changes of brain structure and function in a large sample between depression with and without somatic symptoms. Structure magnetic resonance imaging (MRI) data were collected from 342 patients with somatic symptoms (SD), 208 patients without somatic symptoms (NSD), and 510 healthy controls (HCs) based on the REST-meta-MDD project. We analyzed the whole brain VBM maps of the three groups, and combined with weight degree centrality (DC) index, we investigated whether the brain regions with gray matter volume (GMV) and gray matter density (GMD) abnormalities in MDD patients with somatic symptoms had corresponding brain functional abnormalities. Between depression with and without somatic symptoms, we found that there are extensive GMV and GMD differences involving cortical regions such as the temporal lobe, occipital lobe, and insula, as well as subcortical brain regions such as thalamus and striatum. The comparison results of weight DC signals of GMV and GMD abnormal clusters between the SD and NSD groups were basically consistent with the GMV and GMD abnormal clusters. The results indicate that the structure and function of cortical-striatal-thalamic-cortical (CSTC) circuit centered on the thalamus were abnormal in MDD patients with somatic symptoms. This may be the neurobiological basis of somatic symptoms in MDD.


Ethyl 2-[4-(4-meth-oxy-benz-yl)-3-methyl-6-oxopyridazin-1-yl]acetate.
In the title mol-ecule, C17H20N2O4, the inner part of the ester substituent is nearly perpendicular to the di-hydro-pyridazine ring, forming a dihedral angle of 83.21 (7)°. In the crystal, inversion dimers are formed by pairwise C-H⋯O inter-actions with the dimers connected into chains extending along the b-axis direction by C-H⋯π(ring) inter-actions. The chains are connected by π-stacking inter-actions to give corrugated layers parallel to the ab plane. The terminal ethyl group is disordered over two two sets of sites with the major component having a site occupancy factor of 0.715 (10).


Enhanced oxidative stress in GH-transgenic rat and acromegaly in humans.
Excessive oxidative stress plays a causal role in various diseases such as diabetes, hypertension, atherosclerosis, and heart failure. Acromegaly is a pathological condition associated with excess growth hormone (GH) and insulin-like growth factor-I (IGF-I) and a high prevalence of diabetes, hypertension, atherosclerosis, and heart failure; resulting in premature death. We hypothesized that these conditions may be associated with increased oxidative stress. We explored the oxidative stress levels in the serum and tissues of GH-transgenic rats as an animal model for acromegaly. We also measured the oxidative stress levels in the serum of patients with acromegaly and age-, sex-, and BMI-matched control subjects. We examined the effects of GH and IGF-I on reactive oxygen species (ROS) production in C2C12 myocytes. The levels of an oxidative stress marker, serum thiobarbituric acid reactive substances (TBARS) were increased in the GH-transgenic rats. Further, tissue oxidative stress damage was enhanced in the cardiomyocytes and vascular smooth muscle cells in the aorta of the GH-transgenic rats. In addition, serum TBARS levels and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were increased in acromegaly in humans. IGF-I but not GH induced ROS production in C2C12 myocytes in vitro. These data indicate that the increased levels of IGF-I are associated with enhanced oxidative stress in rats and humans. In addition, increased ROS may play an important role in the complications and premature death in acromegaly.


Association of urine phthalate metabolites levels with kidney function in 1610 US adolescents.
Phthalates are widely used as plasticizer or fragrance ingredients in various consumer products worldwide. However, evidence for the overall effects of mixed exposure to phthalate on kidney function has not been widely investigated. The purpose of this article was to assess the association of urine phthalate metabolite levels and kidney injury parameters in adolescents. We used data from the combined 2007-2016 National Health and Nutrition Examination Survey (NHANES). We fitted weighted linear regressions and Bayesian kernel machine regressions (BKMR) models to explore the association of urinary phthalate metabolites with four parameters of kidney function after adjusting for covariates. Weighted linear regression models showed that MiBP (β = 8.057; PFDR = 0.016) was significantly positively associated with eGFR and MEP (β = -0.799; PFDR < 0.001) was significantly negatively correlated with BUN. BKMR analysis showed that the higher the concentration of phthalate metabolite mixture, the higher eGFR in adolescents. Based on the results of these two models, our findings revealed that mixed exposure to phthalates was associated with elevated eGFR in adolescents. However, as the study is cross-sectional, reverse causality is possible, and altered kidney function may impact the concentration of phthalate metabolites in urine.


Hydroxyurea for secondary stroke prevention in children with sickle cell anemia in Nigeria: a randomized controlled trial.
We tested the hypothesis that fixed oral moderate-dose hydroxyurea (20 mg/kg per day) for initial treatment of secondary stroke prevention results in an 80% relative risk reduction of stroke or death when compared with fixed oral low-dose hydroxyurea (10 mg/kg per day) in a phase 3 double-blind, parallel-group, randomized controlled trial in children with sickle cell anemia (SCA) living in Nigeria. A total of 101 participants were randomly allocated to low-dose (n = 49) and moderate-dose (n = 52) hydroxyurea treatment groups. The median participant follow-up was 1.6 years (interquartile range, 1.0-2.3), with a planned minimum follow-up of 3.0 years. A total of 6 recurrent strokes and 2 deaths vs 5 recurrent strokes and 3 deaths occurred in the low- and moderate-dose groups, respectively. The incidence rate ratio (IRR) of the primary outcome measure of stroke or death in the low- and moderate-dose hydroxyurea treatment groups was 0.98 (95% confidence interval [CI], 0.32-3.00; P = .97). The trial was stopped early owing to no clinical difference in the incidence rates of the primary outcome measure. The incidence rates of recurrent strokes were 7.1 and 6.0 per 100 person-years in the low- and moderate-dose groups, respectively, (IRR, 1.18; 95% CI, 0.30-4.88; P = .74). As a measure of adherence to the oral hydroxyurea therapy, the median percent of returned pills was 3.0% and 2.6% in the low- and moderate-dose groups, respectively. No participant had hydroxyurea therapy stopped for myelosuppression. For children with SCA in low-income settings without access to regular blood transfusion therapy, initial low-dose hydroxyurea is a minimum known efficacious dose for secondary stroke prevention.


The differences in early haemodynamic response between surgery and angioplasty after successful re-opening of the superficial femoral artery.
In 40 patients with superficial femoral artery disease we prospectively evaluated the effect of angioplasty (n = 20) or femoropopliteal bypass (n = 20) on the ankle-brachial pressure index (ABI) using the Doppler ultrasound probe. The ABI was measured as a baseline 1 day before the procedure, 1 day after the procedure and 30 days later. In the angioplasty group the baseline ABI was 0.57 (0.11), increasing to 0.74 (0.26) 1 day postangioplasty and increasing further to 0.88 (0.26) after 30 days. The increase in ABI over 30 days was significantly greater than the increase over 1 day. In the femoropopliteal bypass group the baseline ABI was lower at 0.46 (0.17). However 1 day postoperatively it had increased to 0.92 (0.2) with almost no further increase at 30 days [0.95 (0.17)]. We concluded that by contrast to a surgical bypass where there was a large improvement in the ABI over the first day, the ABI following angioplasty continued to improve significantly beyond the first day.


Evaluating the regional elastic modulus of a cylindrical shell with nonuniform wall thickness.
For noninvasive diagnosis of atherosclerosis, we attempted to evaluate the elasticity of the arterial wall by measuring small changes in thickness caused by the heartbeat. The elasticity of the arterial wall has been evaluated noninvasively by measuring the change in diameter of the artery or the pulse-wave velocity; however, there is no method for noninvasively evaluating the elasticity of the arterial wall from changes in its thickness. Employing the phased tracking method that we developed, changes in thickness of less than 100 µm were measured in each regional area, which corresponded to the diameter of the ultrasonic beam. The elasticity of the arterial wall could be evaluated with better spatial resolution from the change in thickness than from the change in diameter of the artery or pulse-wave velocity. We therefore propose a method for evaluating the elastic modulus of an arterial wall of nonuniform wall thickness. In basic experiments employing silicone rubber tubes with nonuniform wall thickness as arterial models, the elastic moduli of silicone rubber tubes were evaluated by measuring changes in wall thickness. These results confirm the value of the proposed method.


[Residual neuromuscular blockade].
Despite the availability of modern neuromuscular blocking agents with short or intermediate duration of action, incidence of residual neuromuscular blockade remains very high. Evidences have been recently provided that residual curarization must be defined as a train-of-four ratio below 0.9 at the thumb adductor during the recovery period after anaesthesia. Residual curarization may be associated with serious adverse events related to respiratory depression, pharyngeal dysfunction, hypoxemia and prolongation of the length of stay in the recovery room. Appropriate choice of drugs, perioperative monitoring of neuromuscular function and large indications of pharmacological reversal may reduce the incidence of residual curarization and improve the patient's safety in the postoperative setting.


APOC3 inhibition with volanesorsen reduces hepatic steatosis in patients with severe hypertriglyceridemia.
ApoC-III inhibits lipoprotein lipase and hepatic uptake of triglyceride-rich lipoproteins. It is unknown whether targeting apoC-III affects hepatic steatosis in patients with hypertriglyceridemia. We studied the effect of volanesorsen, a potent antisense oligonucleotide targeting APOC3 mRNA, on hepatic fat fraction (HFF) assessed by MRI in patients with severe hypertriglyceridemia (SHTG, triglycerides ≥500 mg/dL), familial partial lipodystrophy (FPL, triglycerides ≥200 mg/dL) and familial chylomicronemia syndrome (FCS, triglycerides ≥750 mg/dL). The data were evaluated individually in COMPASS (SHTG), APPROACH (FCS), and BROADEN (FPL) trials. The baseline absolute HFF were elevated in all three trials and ranged from 6.3-18.1%. In COMPASS, compared to placebo, volanesorsen significantly reduced the absolute HFF by -3.02% (95% CI, (-5.60, -0.60), p = 0.009) (placebo-adjusted % change from baseline -24.2%, p = 0.034) from baseline to 6 months. In APPROACH a non-significant absolute -1.0% (95% CI, -2.9, 0.0, p = 0.13) reduction in HFF was noted from baseline to 12 months (placebo-adjusted % change from baseline -37.1%, p = 0.20). In BROADEN volanesorsen significantly reduced the absolute HFF by -8.34% (95% CI, -13.01, -3.67, p = 0.001) from baseline to 12 months (placebo-adjusted % change from baseline -52.7%, p = 0.004). In all 3 trials individually, a strong inverse correlation was present between the baseline HFF and the change in HFF in the volanesorsen groups, but not in the placebo groups. In conclusion, apoC-III inhibition with volanesorsen has favorable effects in HFF in patients with different etiologies of hypertriglyceridemia.


The cargo-binding domain regulates structure and activity of myosin 5.
Myosin 5 is a two-headed motor protein that moves cargoes along actin filaments. Its tail ends in paired globular tail domains (GTDs) thought to bind cargo. At nanomolar calcium levels, actin-activated ATPase is low and the molecule is folded. Micromolar calcium concentrations activate ATPase and the molecule unfolds. Here we describe the structure of folded myosin and the GTD's role in regulating activity. Electron microscopy shows that the two heads lie either side of the tail, contacting the GTDs at a lobe of the motor domain (approximately Pro 117-Pro 137) that contains conserved acidic side chains, suggesting ionic interactions between motor domain and GTD. Myosin 5 heavy meromyosin, a constitutively active fragment lacking the GTDs, is inhibited and folded by a dimeric GST-GTD fusion protein. Motility assays reveal that at nanomolar calcium levels heavy meromyosin moves robustly on actin filaments whereas few myosins bind or move. These results combine to show that with no cargo, the GTDs bind in an intramolecular manner to the motor domains, producing an inhibited and compact structure that binds weakly to actin and allows the molecule to recycle towards new cargoes.


Proteomic Characterization of EVs in Non-pathogenic Yeast Cells.
Most research on extracellular vesicles (EVs) from non-pathogenic fungi has been conducted in S. cerevisiae, taking advantage of the tools available for this model organism; but a few studies on EVs from yeasts of biotechnological interest are also available. Proteomic analyses in EVs from different yeast species and under different culture conditions are consistent in the identification of proteins related to glycolysis and cell wall biogenesis. Consequently, cell wall metabolism and biosynthesis appear as major functions of EVs. Additional functions have been proposed attending to the known biological activities identified on EVs proteomes, including interspecific antagonism, protection against antimicrobial agents, or clearance of aggregates of misfolded proteins (e.g. prion-like proteins). However, caution should be taken since some of these proteins might play a different role in the intracellular space or EVs (including some well known moonlighting proteins). It is also possible that many proteins appear in EVs as an indirect consequence of cellular metabolism and protein traffic, not related to a specific role in the extracellular space. These considerations become especially relevant in the context of the increasing detection power of proteomic technologies, leading in some cases to the identification of thousands of different proteins in the EVs proteome. Mutations in different secretory pathways have been related to differences in protein cargo of EVs, but no mutation has been found completely abolishing the production of EVs. Further work on the composition and biogenesis of EVs is required to better understand their biological significance.


Brain Endothelial Cell-Derived Exosomes Induce Neuroplasticity in Rats with Ischemia/Reperfusion Injury.
Exosomes derived from the cerebral endothelial cells play essential roles in protecting neurons from hypoxia injury, but little is known regarding the biological effects and mechanisms of exosomes on brain plasticity. In this study, exosomes were isolated from rodent cerebral endothelial cells (bEnd.3 cells) by ultracentrifugation, either endothelial cell-derived exosomes (EC-Exo) or PBS was injected intraventricularly 2 h after the middle cerebral artery occlusion/reperfusion (MCAO/R) model surgery in the Exo group and control group, respectively. Sham group rats received the same surgical but not ischemic procedure. We evaluated the motor function of rats after MCAO/R, and the foot-fault rate of the Exo group was significantly lower than that of the control group within 23 days (p < 0.05); the Catwalk analysis also showed gait difference between two groups (p < 0.05). On day 28 after MCAO/R, we euthanized the rats, removed the motor cortex from the brain, and then sequenced the genes by using GO and KEGG to find transcriptome analysis of biological terms and functional annotations: The pathway enrichment revealed that the function of synaptic transmission, regulation of synaptic plasticity, and regulation of synaptic vesicle cycle was significantly enriched with the Exo group than control group. Furthermore, the upregulation of synapsin-I expression in the motor cortex (p < 0.05) as well as the increase of the length of the dendrites were found in the Exo group (p < 0.05) than the control group. We determined the content of exosome microRNA levels, and microRNA-126-3p was the highest (TPM) by transcriptome analysis. Moreover, the microRNA-126-3p protected PC12 cells from apoptosis and increased neurite outgrowth, illustrating the mechanism of how exosomes play a role in altering brain plasticity. This study demonstrated that EC-Exo promoted functional motor recovery in the MCAO/R model, exosomes were critical for the reconstruction of synaptic function in ischemic brain injury, and microRNA-126-3p from EC-Exo could serve as a treatment for nerve damage.


A correlation study between meteorological parameters and COVID-19 pandemic in Mumbai, India.
Meteorological parameters play a major role in the transmission of infectious diseases such as COVID-19. In this study, we aim to analyze the correlation between meteorological parameters and COVID-19 pandemic in the financial capital of India, Mumbai. In this research, we collected data from April 27 till July 25, 2020 (90 days). A Spearman rank correlation test along with two-tailed p test and an Artificial Neural Network (ANN) technique have been used to predict the associations of COVID-19 with meteorological parameters. A significant correlation of COVID-19 was found with temperature (Tmin), dew point (DPmax), relative humidity (RHmax, RHavg, RHmin) and surface pressure (Pmax, Pavg, Pmin). The parameters which showed significant correlation were then taken for the modeling and prediction of COVID-19 infections using Artificial Neural Network technique. It was found that the relative humidity and pressure parameters had the most influencing effect out of all other significant parameters (obtained from Spearman's method) on the active number of COVID-19 cases. The finding in this study might be useful for the public, local authorities, and the Ministry of Health, Govt. of India to combat COVID-19.


Trained Innate Immunity and Its Implications for Mucosal Immunity and Inflammation.
The long-standing dogma that immunological memory is the exclusive prerogative of the adaptive immune system has been challenged by emerging evidence that innate immunity can also maintain memory of past events. Such immunological imprinting takes two forms, trained innate immunity and tolerance. Trained immunity involves metabolic and epigenetic adaptations in innate immune cells and their progenitors in the bone marrow upon exposure to certain microbial and/or inflammatory stimuli so that the "trained" cells would be poised to respond much faster and stronger to a subsequent challenge (e.g., a new infection that is not necessarily the same as the earlier one). Conversely, tolerance leads to attenuated immune responses to secondary stimuli. This review focuses on trained immunity and discusses evidence for its existence from lower organisms to humans, its mechanistic underpinnings, and its translational ramifications. Although trained immunity can be considered as an evolutionarily conserved beneficial response against reinfections, in the setting of modern societies with high prevalence of chronic mucosal and systemic inflammatory diseases, trained immunity could also promote maladaptive immune responses that aggravate pathology. Thus, depending on context, innate immune memory could be therapeutically manipulated using defined agonists to either promote innate immune responses (particularly useful for the treatment of infections or chemotherapy-induced myelosuppression) or suppress excessive inflammation in inflammatory and autoimmune diseases.


Sunlight-directed fluorophore-switch in photosynthesis of cyanine subcellular organelle markers for bio-imaging.
The photoconvertible fluorophore synthesis enables the light controlled imaging channels switch for accurate tracking the quantity and localization of intracellular biomolecules in chemical biology. Herein, we repurposed the photochemistry of Fischer's base and developed a sunlight-directed fluorophore-switch strategy for high-efficiency trimethine cyanine (Cy3.5/Cy3) synthesis. The unexpected sunlight-directed photoconversion of Fischer's base proceeds in conventional solvents and accelerates in chloroform via photo-oxidation and hydrogen atom transfer without using extra additives, and the heterogenous dimerization mechanism was proposed and confirmed by isolation of the reactive intermediates. The reliable strategy is employed in the photosynthesis of commercially available cytomembrane marker (DiI) and other cyanine based organelle markers with appreciable yields. Sunlight-controlled fluorophore-switch of subcellular organelle markers in living cells validated the feasibility of our strategy with cell-tolerant character. Moreover, remote control synthesis of Cy3.5 in vivo directed via sunlight further demonstrated the extended application of our strategy. Therefore, this sunlight-directed strategy will facilitate exploitation of cyanine-based probes with switched fluorescence imaging channels and further enable precise description of the dynamic variations in living cells with minimal autofluorescence and cellular disturbance.


Endovascular thrombectomy with or without intravenous thrombolysis in acute basilar artery occlusion ischemic stroke: A meta-analysis.
It is poorly understood if endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) better facilitates clinical outcomes in patients with acute basilar artery occlusion (BAO) ischemic stroke. A systematic literature review and meta-analysis was completed to investigate the outcomes of EVT with IVT versus direct EVT alone in acute BAO. Data was collected from the literature and pooled with the authors' institutional experience. The primary outcome measure was 90-day modified Rankin sale (mRS) of 0-2. Secondary measures were successful post-thrombectomy recanalization defined as mTICI ≥2b, 90-day mortality, and rate of symptomatic ICH. Our institutional experience combined with three multicenter studies resulted in a total of 1,127 patients included in the meta-analysis. 756 patients underwent EVT alone, while 371 were treated with EVT+IVT. Patients receiving EVT+IVT had a higher odds of achieving a 90-day mRS of ≤ 2 compared to EVT alone (OR: 1.50, 95% CI 1.15 to 1.95, P =0.002, I2 =0%). EVT+IVT also had a lower odds of 90-day mortality (OR: 0.57, 95% CI 0.37 to 0.89, P=0.01, I2=24%). There was no difference in sICH between the two groups (OR: 1.0, 95% CI: 0.56 to 1.79, P=0.99, I2=0%). There was also no difference in post-thrombectomy recanalization rates defined as mTICI ≥2b (OR: 1.11, 95% CI 0.70 to 1.75, P = 0.65, I2=37%). On meta-analysis, EVT with bridging IVT results in superior 90-day functional outcomes and lower 90-day mortality without increase in symptomatic ICH. These findings likely deserve further validation in a randomized controlled setting.


Steady-state pharmacokinetics of atazanavir given alone or in combination with saquinavir hard-gel capsules or amprenavir in HIV-1-infected patients.
The aim of this pilot study was to examine the pharmacokinetics of atazanavir (ATV) when given in combination with amprenavir (APV) or saquinavir hard-gel capsules (SQV) to human immunodeficiency virus (HIV)-positive patients. Included in the study were 34 HIV-infected patients enrolled in the ATV Early Access Program, who were treated with unboosted ATV alone (group 1) or with the double protease inhibitor combinations, ATV plus APV (group 2) or ATV plus SQV (group 3). ATV was given at a daily dose of 400 mg q.d. with the morning meal with SQV 1200 mg per day or APV 1200 mg per day. Serial blood samples for steady-state ATV pharmacokinetics were collected before the morning dose and at 1, 2, 3, 6, 8 and 24 h post-dosing. ATV plasma concentrations were measured using a high-performance liquid chromatography method with ultraviolet detection. Of the patients, 12 received ATV as a single protease inhibitor; 12 received ATV in combination with APV; and 10 in combination with SQV. Geometric mean (coefficient of variation) ATV C(trough) was 110 ng/ml (2.38), 86 ng/ml (0.84) and 149 ng/ml (2.01) in groups 1, 2 and 3, respectively. ATV C(trough) in both double protease inhibitor combination regimens was not significantly different from that as a single protease inhibitor [geometric mean ratio (GMR): 0.77; 95% confidence interval (CI): 0.38-1.58, P=not significant for group 2 versus group 1 and 1.34, 0.40-4.49, P=not significant, for group 3 versus group 1). Patients treated with ATV plus APV had a 40.2% lower ATV C(max) and a 30.8% smaller ATV AUC than the reference group treated with unboosted ATV alone: both these differences were statistically significant (GMR, 95% CI: 0.59, 0.41-0.85, P=0.005 and 0.69, 0.48-0.99, P=0.056, respectively). No difference was observed for either C(max) or AUC between the group treated with ATV plus SQV and the reference group (GMR, 95% CI: 0.78, 0.47-1.30, P=not significant and 1.24, 0.73-2.10, P=not significant, respectively). ATV pharmacokinetics does not seem to be influenced by the concomitant administration of SQV, whereas APV significantly lowers plasma ATV levels.


Intrauterine growth restriction and placental location.
The purpose of this study was to determine whether an association exists between intrauterine growth restriction (IUGR) and second-trimester placental location. A case-control study was performed in well-dated singleton pregnancies with (n = 67) and without (n = 205) IUGR (defined as estimated fetal weight <10th percentile for gestational age at the last sonographic examination) to investigate the association between IUGR and placental location. Placental location was determined by sonography at 16 to 20 weeks' gestation. Maternal, perinatal, and delivery characteristics were abstracted from medical records. Group comparisons were made by the Student t test, chi(2) analysis, the Fisher exact test, the Wilcoxon test, and analysis of variance. Multivariable logistic regression analysis was used to determine the relationship between IUGR and placental location. In both groups, the most common placental locations in the second trimester were anterior and posterior. After adjusting for potential confounders (including race, chronic hypertension, and hypertensive disorders of pregnancy), IUGR pregnancies were nearly 4-fold more likely to have lateral placentation (odds ratio, 3.8; 95% confidence interval, 1.3-11.2) compared with anterior or posterior placentation. Pregnancies complicated by IUGR are significantly more likely than non-IUGR pregnancies to have lateral placentation in the second trimester.


Local stabilization of microtubule assembly improves recovery of facial nerve function after repair.
Within a recent study on the recovery of vibrissae motor performance after facial nerve repair in blind (strain SD/RCS) and sighted (strain SD) rats, we found that, despite persisting myotopic disorganization in the facial nucleus, the blind animals fully restored vibrissal whisking. Searching for the morphological substrates of this improved recovery, we compared the amount of cytoskeletal proteins in the leading edge of elongating axons between both strains. Since our results showed an enhanced expression of neuronal class III beta-tubulin in the blind rats, we wondered whether this was due to an increased synthesis or to a delayed turnover of microtubules. In the present report, we approached this question applying established pharmacological agents to the transected buccal branch of the facial nerve in sighted Wistar rats perturbing either microtubule assembly towards stabilization (enhanced polymerization with 10 microg/ml taxol) or towards increased synthesis (challenged by destabilization with 100 microg/ml nocodazole and 20 microg/ml vinblastine). Evaluation of the effect(s) 2 months later included estimation of (i) vibrissae motor performance by video-based motion analysis, (ii) the degree of collateral axonal branching by double retrograde neuronal labeling with crystals of Fluoro-Gold and DiI and (iii) the pattern of motor end-plate reinnervation (proportions of mono- and poly-reinnervated) in the largest extrinsic vibrissal muscle, the m. levator labii superioris. We found that only stabilization of microtubules with 10 microg/ml taxol reduced intramuscular axonal sprouting and polyinnervation of the motor end-plates, which was accompanied by improved restoration of function.


Prediction of mortality using quantification of renal function in acute heart failure.
Renal function, as quantified by the estimated glomerular filtration rate (eGFR), is a predictor of death in acute heart failure (AHF). It is unknown whether one of the clinically-available serum creatinine-based formulas to calculate eGFR is superior to the others for predicting mortality. We quantified renal function using five different formulas (Cockroft-Gault, MDRD-4, MDRD-6, CKD-EPI in patients<70 years, and BIS-1 in patients≥70 years) in 1104 unselected AHF patients presenting to the emergency department and enrolled in a multicenter study. Two independent cardiologists adjudicated the diagnosis of AHF. The primary endpoint was the accuracy of the five eGFR equations to predict death as quantified by the time-dependent area under the receiver-operating characteristics curve (AUC). The secondary endpoint was the accuracy to predict all-cause readmissions and readmissions due to AHF. In a median follow-up of 374 days (IQR: 221 to 687 days), 445 patients (40.3%) died. eGFR as calculated by all equations was an independent predictor of mortality. The Cockcroft-Gault formula showed the highest prognostic accuracy (AUC 0.70 versus 0.65 for MDRD-4, 0.55 for MDRD-6, and 0.67 for the combined formula CKD-EPI/BIS-1, p<0.05). These findings were confirmed in patients with varying degrees of renal function and in three vulnerable subgroups: women, patients with severe left ventricular dysfunction, and the elderly. The prognostic accuracy for readmission was poor for all equations, with an AUC around 0.5. Calculating eGFR using the Cockcroft-Gault formula assesses the risk of mortality in patients with AHF more accurately than other commonly used formulas.


Status of insecticide resistance and biochemical characterization of chlorpyrifos resistance in Sogatella furcifera (Hemiptera:Delphacidae) in Sichuan Province, China.
The white-backed planthopper, Sogatella furcifera (Horváth) (Hemiptera, Delphacidae), is an energetic rice insect pest in rice production or rice-growing areas. Due to excessive use of the chemical insecticide, S. furcifera has produced the high resistance to some frequently used insecticides. In this paper, the resistance levels of S. furcifera from the eight different areas of Sichuan Province against the five chemicals were monitored by using the rice seedling dipping during 2017-2018 to understand the resistance levels. The results showed that most of all populations have developed low or moderate level of resistance for chlorpyrifos (3.4 to 44.3-fold) and thiamethoxam (3.9- to 15.5-fold), the populations in the LS (1.7 to 5.4- fold)and WS (1.6 to 5.0- fold) regions were still sensitive or low resistance levels compared with other local populations. Almost all populations displayed the susceptible to imidacloprid (0.9- to 5.0-fold), buprofezin (0.9- to 4.3-fold) or low levels of resistance to pymetrozine (1.5- to 6.8-fold). The synergism experiment indicated that P450 enzymes may be important contributed to the metabolic detoxification of chlorpyrifos. The cross-resistance bioassay showed that there was no cross-resistance between chlorpyrifos and triflumezopyrim, but for sulfoxaflor, in the XY17 population. The relative expression level of twelve insecticide resistant-related P450 genes were analyzed by using qRT-PCR and found that CYP4C77, CYP418A1, CYP418A2, CYP408A3 and CYP6ER4 were significantly more expressed in the 3rd-instar nymph of the XY17 and XY18 field populations. To determine the main resistant-related P450 gene for chlorpyrifos, the relative expression level of five P450 genes were detected by using qRT-PCR from the G2 and G4 generation of XY17 under the pressure with LC50 of chlorpyrifos. The results showed that CYP6ER4 was significantly up-regulated expression in XY17 G2 and G4 generations population over 700-fold (P < 0.01). The full length and proteins tertiary structure were also cloned and predicted. Meanwhile, the function of CYP6ER4 was analyzed by RNA interference and the results indicated that the relative expression of CYP6ER4 in the XY17 (G4) population after injected dsRNA was lower than that in the dsGFP injected group. Moreover, the mortality rates of the S. furcifera treated with the LC50 concentration of chlorpyrifos after dsRNA microinjection was significantly higher than that of the dsGFP injected group 72 h after treatment (P < 0.01). Therefore, the overexpression of CYP6ER4 may be one of the primary factors in the development of chlorpyrifos resistance in S. furcifera.


The aggregate value of cancer screenings in the United States: full potential value and value considering adherence.
Although cancer mortality has been decreasing since 1991, many cancers are still not detected until later stages with poorer outcomes. Screening for early-stage cancer can save lives because treatments are generally more effective at earlier than later stages of disease. Evidence of the aggregate benefits of guideline-recommended single-site cancer screenings has been limited. This article assesses the benefits in terms of life-years gained and associated value from major cancer screening technologies in the United States. A mathematical model was built to estimate the aggregate benefits of screenings for breast, colorectal, cervical, and lung cancer over time since the start of US Preventive Services Task Force (USPSTF) recommendations. For each type, the full potential benefits under perfect adherence and the benefits considering reported adherence rates were estimated. The effectiveness of each screening technology was abstracted from published literature on the life-years gained per screened individual. The number of individuals eligible for screening per year was estimated using US Census data matched to the USPSTF recommendations, which changed over time. Adherence rates to screening protocols were based on the National Health Interview Survey results with extrapolation. Since initial USPSTF recommendations, up to 417 million people were eligible for cancer screening. Assuming perfect adherence to screening recommendations, the life-years gained from screenings are estimated to be 15.5-21.3 million (2.2-4.9, 1.4-3.6, 11.4-12.3, and 0.5 million for breast, colorectal, cervical, and lung cancer, respectively). At reported adherence rates, combined screening has saved 12.2-16.2 million life-years since the introduction of USPSTF recommendations, ~ 75% of potential with perfect adherence. These benefits translate into a value of $8.2-$11.3 trillion at full potential and $6.5-$8.6 trillion considering current adherence. Therefore, single-site screening could have saved an additional 3.2-5.1 million life-years, equating to $1.7-$2.7 trillion, with perfect adherence. Although gaps persist between the full potential benefit and benefits considering adherence, existing cancer screening technologies have offered significant value to the US population. Technologies and policy interventions that can improve adherence and/or expand the number of cancer types tested will provide significantly more value and save significantly more patient lives.


Production of nitric oxide (NO) in human hydatidosis: relationship between nitrite production and interferon-gamma levels.
Human hydatidosis is characterized by a prolonged coexistence of parasite (Echinococcus granulosus) and host without effective rejection. The basis of the immune response of the patient is poorly understood. Previously, we reported the presence of IFN, TNF-alpha and IL-6 activities in the serum of patients with liver and lung hydatidosis. In the present work, we have investigated the production of nitrite (NO2-) in the serum of hydatidic patients carrying hepatic and pulmonary cysts (range 36-300 microM). Our present data show a correlation between the production of nitrite + nitrate (NO2- + NO3-) and that of circulating cytokines IFN and IL-6. In relapsing patients who did not produce IFN and IL-6, the observed serum NO2- concentrations were low (range 10-37.2 microM), as compared to those detected in patients before surgery. Induction of NO synthase in leukocytes from hydatidic patients was induced by stimulating these cells with a specific parasitic antigen, Antigen-5, as assessed by the increased levels of NO3- + NO2- in the range of 60-85 microM for patients with liver hydatidosis, as compared to the 20-25 microM detected in healthy controls. Collectively, our data indicate that NO2- + NO3- levels correlate with IFN levels and immunoreactivity, and overall suggest that IFN-gamma and nitric oxide production together play a role in the host defense mechanisms in human hydatidosis.


Antiamnesic properties of analogs and mimetics of the tripeptide human urocortin 3.
Amnesia is a deficit in memory caused by brain damage, disease, or trauma. Until now, there are no successful medications on the drug market available to treat amnesia. Short analogs and mimetics of human urocortin 3 (Ucn 3) tripeptide were synthetized and tested for their action against amnesia induced by eletroconvulsion in mice. Among the 16 investigated derivatives of Ucn 3 tripeptide, eight compounds displayed antiamnesic effect. Our results proved that the configuration of chiral center of glutamine does not affect the antiamnesic properties. Alkyl amide or isoleucyl amide at the C-terminus may lead to antiamnesic compounds. As concerned the N-terminus, acetyl, Boc, and alkyl ureido moieties were found among the active analogs, but the free amino function at the N-terminus usually led to an inactive derivatives. These observations may lead to the design and synthesis of small peptidomimetics and amino acid derivatives as antiamnesic drug candidates, although the elucidation of the mechanism of the action requires further investigations.


Time course of motor excitability before and after a task-related movement.
The time course of motor excitability during a task-related unilateral right thumb movement was studied using sub-threshold transcranial magnetic stimulation (TMS) to the contralateral left motor cortex. The level of stimulation evoked a motor evoked potential (MEP) in the thumb when the subject was at rest in approximately 10% of the trials. Subjects made a brief right thumb movement to the predictable omission of regularly presented tone bursts allowing experimental definition of TMS relative to the cue to move. Motor cortical excitability was characterized by amplitude and/or probability of eliciting MEPs. There were four periods of altered motor excitability during task performance compared to a control resting state: a first period of weak facilitation before movement between -500 to -200 ms, a second period without increased excitability approximately 150 ms before movement onset when MEPs amplitude was below that seen in rest, a third period of strong facilitation between -100 ms before movement and +200 ms after facilitation and a fourth period of weak facilitation between +200 to +500 ms. These results show that during performance of a task requiring a motor response, motor cortical excitability is increased above resting for hundreds of millisecond before and after the response, except for a transient period between 75 and 150 ms prior to movement onset. The temporal pattern of these excitability changes is compatible with multiple excitatory and inhibitory inputs interacting on motor cortex.


The reliability of biomedical science: A case history of a maturing experimental field.
There is much discussion in the media and some of the scientific literature of how many of the conclusions from scientific research should be doubted. These critiques often focus on studies - typically in non-experimental spheres of biomedical and social sciences - that search large datasets for novel correlations, with a risk that inappropriate statistical evaluations might yield dubious conclusions. By contrast, results from experimental biological research can often be interpreted largely without statistical analysis. Typically: novel observation(s) are reported, and an explanatory hypothesis is offered; multiple labs undertake experiments to test the hypothesis; interpretation of the results may refute the hypothesis, support it or provoke its modification; the test/revise sequence is reiterated many times; and the field moves forward. I illustrate this experimental/non-experimental dichotomy by examining the contrasting recent histories of: (a) our remarkable and growing understanding of how several inositol-containing phospholipids contribute to the lives of eukaryote cells; and (b) the difficulty of achieving any agreed mechanistic understanding of why consuming dietary supplements of inositol is clinically beneficial in some metabolic diseases.


A subfamily of relatively large and basic cytokeratin polypeptides as defined by peptide mapping is represented by one or several polypeptides in epithelial cells.
Epithelial cells contain a class of intermediate-sized filaments formed by proteins related to epidermal alpha-keratins ('cytokeratins'). Different epithelia can express different combinations of cytokeratin polypeptides widely varying in apparent mol. wt. (40 000-68 000) and isoelectric pH (5.0-8.5). We have separated, by two-dimensional gel electrophoresis, cytokeratin polypeptides from various tissues and cultured cells of man, cow, and rodents and examined their relatedness by tryptic peptide mapping. By this method, a subfamily of closely related cytokeratin polypeptides has been identified which comprises the relatively large (greater than or equal to mol. wt. 52 500 in human cells) and basic (pH greater than or equal to 6.0) polypeptides but not the smaller and acidic cytokeratins. In all species examined, the smallest polypeptide of this subfamily is cytokeratin A, which is widespread in many simple epithelia and is the first cytokeratin expressed during embryogenesis. This cytokeratin polypeptide subfamily is represented by at least one member in all epithelial and carcinoma cells examined, indicating that polypeptides of this subfamily serve an important role as tonofilament constitutents . Diverse stratified epithelia and tumours derived therefrom contain two or more polypeptides of this subfamily, and the patterns of expression in different cell types suggest that some polypeptides of this subfamily are specific for certain routes of epithelial differentiation.


Supernatants from culture of type I collagen-stimulated PBMC from patients with cutaneous systemic sclerosis versus localized scleroderma demonstrate suppression of MMP-1 by fibroblasts.
Systemic sclerosis (SSc) is a chronic fibrosing disease characterized by vasculopathy, autoimmunity, and an accumulation of collagen in tissues. Numerous studies have shown that compared to healthy or diseased controls, the peripheral blood mononuclear cells (PBMC) from patients with SSc produce a variety of cytokines or proliferate when cultured with solubilized type I collagen (CI) or constituent α1(II) and α2(I) polypeptide chains. The purpose of this study was to determine whether PBMC isolated from patients with SSc and cultured in vitro with soluble CI elaborated soluble mediators that inhibit the production of collagenase (i.e., matrix metalloproteinase, MMP-1) by fibroblasts. Supernatants of CI-stimulated PBMC from juvenile and adult diffuse cutaneous (dc)SSc patients significantly reduced MMP-1 production by SSc dermal fibroblasts, while supernatants of CI-stimulated PBMC from patients with localized scleroderma (LS) did not. CI-stimulated PBMC culture supernatants from patients with dcSSc in contrast to patients with LS exhibited increased levels of platelet-derived growth factor (PDGF)-AA, PDGF-BB, TNF-α, IL-13, and EGF. Prolonged culture of SSc dermal fibroblasts with recombinant PDGF-BB or IL-13 inhibited the induction of MMP-1 in response to subsequent TNF-α stimulation. These data suggest that therapies aimed at reducing these cytokines may decrease collagen accumulation in SSc, preventing the development of chronic fibrosis.


Multiple comet tail artifacts in the liver: a case of congenital hepatic fibrosis showing unusual biliary appearance.
Congenital hepatic fibrosis (CHF) is a form of autosomal recessive polycystic kidney disease. Because of the common underlying pathophysiology of ductal plate malformation, CHF can be accompanied by an abnormal biliary appearance, which is characterized by a saccular or fusiform dilatation of the bile ducts. We encountered the case of a 35-year-old man suffering from CHF concomitant with esophageal varices, which were treated by endoscopic sclerotherapy. The patient had elevated serum concentrations of alkaline phosphatase and γ-glutamyl transpeptidase without apparent biliary disease, including hepatolithiasis or a history of cholangitis. Magnetic resonance cholangiography showed an abnormal biliary appearance, which was not saccular or fusiform but had multiple stenosis with unknown causes. B-mode sonogram showed multiple comet tail artifacts in the liver parenchyma, probably corresponding to the compact fibrosis bands and bile in the bile duct as well as peripheral bile duct dilatation, which was proven pathologically. We propose that multiple comet tail artifacts in the liver may suggest the presence of a bile duct abnormality in patients with CHF, suggesting the potential risk for developing biliary complications.


Synergistic antimicrobial system based on nisin and α-hydroxy organic acids.
Synergistic antimicrobial is a promising way to overcome microbial contamination in food and drugs. In the study, the synergistic effect between nisin and α-hydroxy organic acids on E. coli and S. aureus was investigated. The experimental results showed that the combined antibacterial ability of nisin-citric acid system was the most prominent. The FCI index also indicated that the combination of nisin and citric acid had synergistic effects on E. coli. When nisin was combined with citric acid, the inhibition rates of E. coli and S. aureus were increased to 4.43 and 1.49 times, respectively. Nisin-citric acid complex system could effectively slow down the proliferation of S. aureus and E. coli at lower concentrations, and can quickly destroy the cell membrane after 4 h of action. Therefore, the combination of nisin and citric acid is expected to be a potential solution for food and drug preservation.


Red-cell pyrimidine 5'-nucleotidase and lead poisoning.
In an effort to determine its value as a biological index of lead poisoning, we investigated the red-cell pyrimidine 5'-nucleotidase (Py5N) activity, along with the classical parameters, in 22 subjects with varying degrees of lead intoxication. In all cases, the red-cell Py5N activity was found to be decreased, even when most of the other biological tests of lead intoxication remained negative. Below the level of 150 microgram of lead per 100 ml of blood, the magnitude of the red-cell Py5N decrease was roughly proportional to the level of lead in peripheral blood. We conclude that red-cell Py5N is a convenient, reliable and sensitive index of lead exposure.


e6a2 BCR/ABL1 fusion with cryptic der(9)t(9;22) deletions in a patient with chronic myeloid leukemia.
This is the first report of e6a2 and e1a2 BCR/ABL1 positive chronic myeloid leukemia (CML) with cryptic deletions of the 5'ABL1 and 3'BCR in separate clones which differ in genomic regions of the deleted der(9). Both deletions were detected throughout monitoring. Imatinib mesylate stabilized this CML with rare genetic aberrations for a relatively long time.


Endoscopic internalization by cutting versus removal of the endoscopic transpapillary naso-gallbladder drainage tube in preoperative management of acute cholecystitis: A retrospective multicenter cohort study.
Endoscopic transpapillary naso-gallbladder drainage (ENGBD) has been reported to be an effective treatment option for acute cholecystitis. At our institution, ENGBD was first placed for external fistula management, and endoscopic internalization by cutting was performed, shifting to endoscopic transpapillary gallbladder stenting (EGBS) after improvement of cholecystitis. However, there has been no comparative study to define which preoperative management is better: converting ENGBD to EGBS or removing ENGBD. The study aimed to compare the incidence rate of the late adverse events (AEs) related to biliary system between shifting from ENGBD to EGBS and removal of ENGBD. We retrospectively studied 122 patients who underwent ENGBD for acute cholecystitis between January 2010 and October 2022. The patients were divided into two groups: the cutting group (converting ENGBD to EGBS) and the removal group (removal of ENGBD). The short and late clinical outcomes were compared between groups. Endoscopic transpapillary naso-gallbladder drainage was successfully placed in 78.6% (96/122), and elective cholecystectomy was performed in 31 and 36 patients in the cutting and removal groups, respectively. The cumulative late-AE rates were 6.4% and 33.3% (p = .007), with a median waiting period for elective cholecystectomy of 58 and 33 days (p = .390) in the cutting and removal groups, respectively. In the multivariate analysis, only endoscopic internalization by cutting was an independent factor affecting late AEs. Endoscopic internalization by cutting ENGBD after the resolution of acute cholecystitis was considered effective in reducing the risk of late AEs during the waiting period for an elective cholecystectomy.


Suppression and regression of a transplanted tumor in the guinea pig colon mediated by Mycobacterium bovis, strain BCG.
The growth in the colon wall of a diethylnitrosamine-induced hepatocarcinoma was suppressed by BCG. Injection of BCG into established colon-wall tumors caused tumor regression. Successful therapy required a limited tumor burden. Guinea pigs in which growth of the neoplasm was suppressed at the site of BCG infection developed systemic tumor transplantation immunity.


Mohs frozen tissue sections in comparison to similar paraffin-embedded tissue sections in identifying perineural tumor invasion in cutaneous squamous cell carcinoma.
Perineural invasion (PNInv) in cutaneous squamous cell carcinoma (cSCC) increases the risk of recurrence, possibly because of suboptimal identification on frozen or paraffin-embedded tissue sections. Perineural inflammation (PNInf) may portend PNInv. We sought to correlate identification of PNInv and PNInf in hematoxylin-eosin-stained Mohs frozen sections with PNInv and PNInf identified in similarly oriented paraffin-embedded sections obtained in cases of cSCC. We reviewed same patient Mohs frozen and paraffin-embedded tissue sections for all patients presenting within a 2-year period to our Mohs micrographic surgical unit for removal of cSCC with PNInv or PNInf identified on either type of tissue section. Of 537 patients undergoing surgical resection of cSCC, 21 (3.9%) had either PNInv (n = 11) or PNInf (n = 10) on frozen sections. PNInv on Mohs frozen sections was identified in 11 cases and confirmed on paraffin-embedded sections in 9 cases (82%). Paraffin-embedded sections failed to identify PNInv present in Mohs frozen sections in two (2/11), or 18% of cases. PNInf on Mohs frozen sections was confirmed on paraffin-embedded sections in 3 cases (30%), but PNInv was identified in 5 cases (50%). Our results are a retrospective case review from a specific time period by one institution. Furthermore, it is impossible to compare identical tissue specimens using two sequential tissue processing techniques. PNInv can be accurately identified with Mohs frozen sections. PNInf on Mohs frozen sections suggests the presence of PNInv and requires further histologic investigation.


Alarming and Threatening Signals from Health Centers About Multi Drug Resistance Staphylococcus haemolyticus.
Nowadays, due to the biofilm formation among coagulase-negative staphylococci (CoNS), acquisition of antibiotic resistance and virulence genes could be noted. These organisms resemble other staphylococcus that harbor mecA gene, which encode methicillin resistance but the diversity in CoNS is higher than other species. Based on increasing antibiotic resistance in Staphylococcus haemolyticus, analyzing of phenotypic and genotypic biofilm formation, antibiotic resistance and genes involved in this process, SCCmec and ACME typing were the aims of the current study. 256 clinical CoNS isolates were collected that 49 isolates were identified as S. haemolyticus. For evaluation the antibiotic resistance patterns, disk agar diffusion method was applied, and also biofilm assay carried out among methicillin resistant S. haemolyticus and SCCmec and ACME typing. The results of antibiotic susceptibility indicated that the highest resistance was found for cotrimoxazole and erythromycin (86.6%) and the frequency of blaA (96.5%) and msrA (79.3%) genes was much higher than others. Among MRSH isolates 58.6 % showed a weak biofilm phenotype and 41.4% demonstrated a moderate biofilm density. Also, among the biofilm correlated genes, IS 256 (79.31%) was the most frequent. The SCCmec typing of MRSH isolates indicated that the type V was dominant. Our findings indicated that the correlation between high rates of existence Is 256 gene and high prevalence of weak biofilm phenotype was among MRSH isolates. The current study revealed that multiple antibiotic resistance existed in S. haemolyticus isolates that is a warning for public health.


Adenylate and guanylate cyclase activities and cellular differentiation in rat small intestine.
Adenylate and guanylate cyclase activities were measured in rat small intestinal villus and crypt cells to determine possible correlations with cellular differentiation. Isolated intestinal cells were prepared by a method which effectively separates differentiated villus cells from undifferentiated crypt cells (J Biol Chem 248:2542, 1973). Crypt cells were found to have a significantly lower guanylate cyclase activity than villus cells. Adenylate cyclase activity was higher in crypt cells than villus cells, although the difference was less striking than the reverse gradient observed for guanylate cyclase. There was no gradient of activity for cyclic guanosine 3':5'-monophosphate phosphodiesterase. However, cyclic adenosine 3':5'-monophosphate phosphodiesterase activity was lower in villus cells. No villus to crypt gradient of cyclic adenosine 3':5'-monophosphate concentration was detected in mucosa frozen rapidly in liquid nitrogen. The properties and subcellular localization of the cyclases were also evaluated, and of particular interest was the localization of guanylate cyclase to the microvillus membrane and the confirmation of adenylate cyclase activity in the lateral-basal membrane. The villus to crypt gradient of guanylate cyclase suggests that this enzyme has a specialized role in the differentiated villus cell. The contrasting subcellular localization of the cyclases suggests that the cyclases may be interrelated, possibly reflecting the epithelial cell polarity for absorption and secretion.


Advanced treatment of urban wastewater by UV-C/free chlorine process: Micro-pollutants removal and effect of UV-C radiation on trihalomethanes formation.
The effect of the UV-C/free chlorine (FC) process on the removal of contaminants of emerging concern (CECs) from real urban wastewater as well as the effect of UV-C radiation on the formation of trihalomethanes (THMs) compared to FC process alone was investigated. Unlike of FC process, UV-C/FC was really effective in the degradation of the target CECs (carbamazepine (CBZ), diclofenac, sulfamethoxazole and imidacloprid) in real wastewater (87% degradation of total CECs within 60 min, QUVC = 1.33 kJ L-1), being CBZ the most refractory one (49.5%, after 60 min). The UV-C radiation significantly affected the formation of THMs. THMs concentration (mainly chloroform) was lower in UV-C/FC process after 30 min treatment (<1 μgL-1 = limit of quantification (LOQ)) than in FC process in dark (2.3 μgL-1). Noteworthy, while in FC treated wastewater chloroform concentration increased after treatment, UV-C/FC process resulted in a significant decrease (residual concentrations below the LOQ), even after 24 h and 48 h post-treatment incubation. The formation of radicals due to UV-C/FC process can reduce THMs compared to chlorination process, because part of FC reacts with UV-C radiation to form radicals and it is no longer available to form THMs. These results are encouraging in terms of possible use of UV-C/FC process as advanced treatment of urban wastewater even for possible effluent reuse.


Measurements of uridine diphosphate glucose and uridine diphosphate galactose--an appraisal.
The recent disproof of a major deficiency of uridine diphosphate galactose in galactosemia should not lead investigators to assume either that enzymatic methods are unreliable for uridine sugar assays or that a defect in galactosylation in galactosemia has been excluded.


An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line.
Humans are exposed to a cocktail of heavy metal toxicants in the environment. Though heavy metals are deleterious, there is a paucity of information on the toxicity of mixtures. In this study, four common neurotoxicity heavy metals lead (Pb) cadmium (Cd), arsenic (As), and methylmercury (MeHg) were exposed individually and as mixtures to HT-22 cell line for 8days. The study established that low dose exposures induced toxicity to the HT-22 cell line during 8days. The results indicates potency dependent response, the toxicity of single metals on the HT-22 cells; MeHg > As > Cd > Pb. The cytotoxicity data of single metals were used to determine the mixtures interaction profile by using the dose additivity and effect additivity method. Metal mixtures showed higher toxicities compared to individual metals. Synergistic, antagonistic or additive effects of the toxicity were observed in different mixtures in low dose exposure. The interactive responses of mixtures depend on the co-exposure metal and their respective concentration. We concluded that the combined effects should be considered in the risk assessment of heavy metal co-exposure and potency. In future, comprehensive mechanistic based investigations needed for understanding the real interactive mixtures effects at molecular level.


Body composition in mink (Mustela vison) kits during 21-42 days postpartum using estimates of hydrogen isotope dilution and direct carcass analysis.
We compared carcass analysis and hydrogen isotope dilution methods to measure total body water (TBW) and body composition in a small altricial carnivore, the mink. Dilution space (D) of mink at 21-42 days of age (n=20), was determined after subcutaneous administration of tritiated water. The same animals were then used to determine TBW and body composition by carcass analysis and to derive predictive empirical relationships between TBW and total body fat, protein and energy. A separate validation set of 27 kits was used to test the accuracy of predicting body composition from TBW. D overestimated TBW by a consistent and predictable 4.1% (R(2)=0.999, P<0.001). Our estimates of fat, protein and energy content, using equations derived from TBW, were not significantly different than those obtained from direct carcass analysis (P>0.980) in either the initial or validation set of mink. TBW was shown to decrease from 81 to 76% and total body protein to increase from 14 to 19% of LBM of the kits from 21 to 42 days of age. Although a rapidly changing hydration state was apparent in neonates, we conclude that when this is taken into account, accurate estimates of body composition can be obtained from hydrogen isotope dilution.


Variability in microbial inactivation: From deterministic Bigelow model to probability distribution of single cell inactivation times.
Phenotypic heterogeneity seems to be an important component leading to biological individuality and is of great importance in the case of microbial inactivation. Bacterial cells are characterized by their own resistance to stresses. This inherent stochasticity is reflected in microbial survival curve which, in this context, can be considered as cumulative probability distribution of lethal events. The objective of the present study was to present an overview on the assessment and quantification of variability in microbial inactivation originating from single cells and discuss this heterogeneity in the context of predicting microbial behavior and Risk assessment studies. The detailed knowledge of the distribution of the single cells' inactivation times can be the basis for stochastic inactivation models which, in turn, may be employed in a risk - based food safety approach.


[Not Available].
3970 feedsamples were analysed for the Fusariumtoxins deoxynivalenol and zearalenone. 979 (24.6 %) of the submitted feed samples came from farms with case history (swine herds: decreased feed intake and daily weight gain, vomiting, cannibalism, impaired fertility, small litter size, weakness of newborn piglets, prolonged oestrus of sows; cattle: persistence of the follicular ovarian cysts, enteritis, decreased slaughter weight, feed refuse), which correlated positively with the mycotoxicological results. 74 % of the samples contained cereal and corn components respectively or complete diet samples from swine herds. Based on economic losses the fusariumtoxin Desoxynivalenol is most important in Austrian husbandry and particularly found in maize, cornsilage, wheat and oat.


Type I diabetes mellitus: a chronic autoimmune disease?
Currently defined categories of diabetes mellitus reflect our growing knowledge of the biochemical and immunologic basis of several disorders resulting in hyperglycemia. The authors discuss the autoimmune phenomenon and autoimmune diseases associated with Type I diabetes mellitus. Special focus is placed on the impact of immunologic assays on the current and future clinical care of patients with Type I diabetes and their genetically susceptible relatives.


Trace-Level Determination of Triazole Fungicides Using Effervescence-Assisted Liquid-Liquid Microextraction Based on Ternary Deep Eutectic Solvent Prior to High-Performance Liquid Chromatography.
A simple and sensitive preconcentration method, namely, effervescence-assisted liquid-liquid microextraction based on the ternary deep eutectic solvent method, was developed for enrichment of triazole fungicide residues prior to their determination by high-performance liquid chromatography coupled with UV detection. In this method, a ternary deep eutectic solvent (as extractant) was prepared by combination of octanoic acid, decanoic acid, and dodecanoic acid. The solution was well dispersed with sodium bicarbonate (as effervescence powder) without using auxiliary devices. In order to obtain relatively high extraction efficiency, analytical parameters were investigated and optimized. Under optimum conditions, the proposed method showed good linearity within the range of 1-1000 μg L-1 with a coefficient for determination (R2) greater than 0.997. The low limits of detection (LODs) were in the range of 0.3-1.0 μg L-1. The precisions were assessed from the relative standard deviations (RSDs) of retention time and peak area obtained from intra- (n = 3) and inter-day (n = 5 × 5) experiments, which were greater than 1.21 and 4.79%, respectively. Moreover, the proposed method provided high enrichment factors ranging from 112 to 142 folds. A matrix-match calibration method was used for analysis of real samples. Finally, the developed method was successfully applied for determination of the triazole fungicide in environmental water (near agricultural area), honey, and bean samples, and it represents a promising alternative method for analysis of triazoles. The recoveries of the studied triazoles were obtained in the range of 82-106% with an RSD less than 4.89.


[Tension changes of the anterior cruciate ligament in the movement process of the knee joint].
Relative tension of the anteromedial part of the anterior cruciate ligament of five cadaver knees is measured. The ligament is taut at 80 degrees - 90 degrees flexion and loosened to a maximum at 30 degrees and 130 degrees flexion. On internal rotation it is taut at each stage of flexion, on external rotation, only at full extension and full flexion.


Treatment of missed Monteggia fracture with intact annular ligament after an interval of 9 years: a case report and literature review.
Missed Monteggia fractures are commonly observed among children. Both the interval from the injury to surgery and the patient's age at operation are thought to be correlated directly with the success of the surgery and prognosis. The aim of the present work was to report one interesting adult case of a missed Monteggia fracture with an intact annular ligament 9 years after injury and the outcomes at a 7-year follow-up. One missed lesion with a 9-year delay for surgery occurred in a skeletally mature individual, and it was treated by open reduction and ulnar angulation and elongation osteotomy. The annular ligament was interpositioned intact in the radiocapitellar joint, and therefore, instead of the annular ligament reconstruction (ALR), relocation was performed. After one revision surgery for the complication of nonunion, good radiographic and functional outcomes were eventually sustained at the 7-year follow up. Good radiographic and functional outcomes can be expected in adult patients in whom the annular ligament is intact and interpositioned, and this was treated by open reduction and ulnar osteotomy 9 years after the initial injury in our patient.