The effect of acute blood-flow-restricted resistance exercise on postexercise blood pressure.
Blood-flow-restricted (BFR) exercise is an emerging type of exercise that may be particularly beneficial to elderly or special populations. These populations may also benefit from reductions in blood pressure (BP). The effect of BFR exercise on postexercise BP has not been examined; this should first be examined in a young, healthy population as a preliminary investigation. The main purpose of this study was to determine whether postexercise hypotension (PEH) occurred following low-intensity [20% 1 repetition maximum (1-RM)] BFR resistance exercise. A secondary purpose was to compare this response to both a work-matched low-intensity (20% 1-RM) (LI) and a traditional high-intensity (70% 1-RM) resistance exercise bout (HI). In a randomized cross-over design, ten normotensive, young (18-35 years) men performed one of the three lower-body resistance exercise bouts (HI, LI or low-intensity BFR) during separate visits to the laboratory. Brachial BP, cardiac ultrasound and calf blood flow measurements were taken prior to and 30 and 60 min following exercise. Repeated measures analysis of variance (3 × 3; condition × time) was performed on all variables. A significant interaction (P<0·05) was found for brachial systolic blood pressure which decreased following HI only. Significant interactions (P<0·05) were also seen for heart rate, total peripheral resistance and calf vascular resistance. Postexercise hypotension occurred only following HI. Thus, if one is exercising with the intent of lowering BP, HI resistance exercise may be more useful than low-intensity BFR resistance exercise.


Review of the fundamentals of thin-film growth.
The properties of a thin film of a given material depend on the film's real structure. The real structure is defined as the link between a thin film's deposition parameters and its properties. To facilitate engineering the properties of a thin film by manipulating its real structure, thin-film formation is reviewed as a process starting with nucleation followed by coalescence and subsequent thickness growth, all stages of which can be influenced by deposition parameters. The focus in this review is on dielectric and metallic films and their optical properties. In contrast to optoelectronics all these film growth possibilities for the engineering of novel optical films with extraordinary properties are just beginning to be used.


Placental macrophages are impaired in chorioamnionitis, an infectious pathology of the placenta.
Pregnancy is dependent on maternal-fetal tolerance that may be compromised because of infections or inflammation of the placenta. In this study, we examined whether the context of placental immune tolerance affected the functions of resident macrophages and if their functions were altered during chorioamnionitis, an infectious pathology of the placenta. Macrophages from at-term placentas expressed CD14, exhibited macrophage microbicidal functions, but were less inflammatory than monocyte-derived macrophages. Moreover, placental macrophages spontaneously matured into multinucleated giant cells (MGCs), a property not exhibited by monocyte-derived macrophages, and we detected MGCs of myeloid origin in placental tissue. Compared with placental macrophages, MGCs exhibited a specific phenotype and gene expression signature, consisting of increased cytoskeleton-associated gene expression along with depressed expression of inflammatory response genes. Furthermore, placental macrophages from patients with chorioamnionitis were unable to form MGCs, but this defect was partially corrected by incubating these placental macrophages with control trophoblast supernatants. MGCs formation likely serves to regulate their inflammatory and cytocidal activities in a context that imposes semiallograft acceptance and defense against pathogens.


Cytokine Profiling in Chinese SLE Patients: Correlations with Renal Dysfunction.
Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease that commonly causes kidney damage. Therefore, we measured plasma levels of cytokines that may be related to renal dysfunction in SLE patients. To explore the differences between SLE patients with renal dysfunction and healthy volunteers, the levels of cytokines in plasma were screened using a human cytokine antibody array. Then, we chose fourteen of the elevated cytokines for verification with an expanded sample size by a human magnetic Luminex assay. Plasma samples were isolated from SLE patients (n = 72) and healthy volunteers (n = 8). Cytokine antibody array data showed elevated plasma cytokines in SLE patients with renal dysfunction compared with healthy volunteers. By using the human magnetic Luminex assay, we found that plasma levels of CHI3L1, GDF-15, IGFBP-2, MIF, ST2, TFF3, and uPAR were significantly higher in SLE patients than in healthy volunteers. Plasma levels of CXCL4 were significantly lower in the active group than in the inactive group, and plasma levels of CHI3L1, IGFBP-2, MIF, and MPO were significantly higher in the active group than in the inactive group. We also analyzed the correlation between plasma cytokine levels and the SLEDAI-2K, and our results showed that the plasma levels of the fourteen selected cytokines were weakly correlated or not correlated with the SLEDAI-2K. We further analyzed the correlation between cytokines and renal dysfunction. Plasma levels of GDF-15 and TFF3 were highly positively correlated with serum creatinine levels and 24-hour urine protein levels. Our data suggest that plasma levels of GDF-15 and TFF3 are potential renal dysfunction markers in SLE patients, but plasma levels of these cytokines are not correlated with the SLEDAI-2K. Further study is warranted to determine how these cytokines regulate inflammatory responses and renal dysfunction in SLE.


The sleep of older people in hospital and nursing homes.
Disturbed sleep can affect personal wellbeing and impede the rehabilitation and recovery of older people from illness. This paper reports the findings of a pilot study which included examination of sleep quality and sleep patterns of older people in community hospital and nursing home settings. A marked proportion of older people reported sleeping well in nursing care settings, and those in nursing homes slept better than those in the community hospital. The main causes of sleep disturbance in both settings were: needing to go to the toilet, noise, pain, and discomfort; a similar pattern was seen across the different settings. No discernible difference was found in quality of sleep and whether patients felt rested or not between those patients on hypnotic medication and those who were not. The implications of the findings for practice and future research are discussed.


[Role of human cytochrome P-450 enzymes in the metabolism of xenobiotics].
Cytochrome P450 enzymes play essential role in metabolism of exogenous compounds. They are found mainly in endoplasmic reticulum of hepatocytes. Purification of different P450 isoforms and determination of their structures and catalytic activities allowed to investigate their participation in metabolism of xenobiotics. Numerous factors cause variations in the expression of these P450: the effect of genetic and environmental factors results in the production of series of enzymes catalyzing biotransformation of xenobiotics. Several genetic polymorphisms have been described: CYP2D6, CYP2C and 'Ah locus' polymorphism. Some P450 (CYP1A, CYP3A, CYP2E1) are inducible by xenobiotics. Additionally, P450 expression and inducibility vary depending on tissues. It is now possible to determine which isoform(s) is (are) responsible for the production of a metabolite and to predict the fate of a compound in vivo.


Surgical Anatomy of the Knee A Review of Common Open Approaches.
Knee-related complaints are among the most commonly encountered conditions by orthopaedic surgeons. Knee pathology varies widely and includes arthritis, deformities, fractures, infections, neuromuscular disorders, oncologic diseases, and soft-tissue injury. While nonoperative treatment modalities (activity modification, medications, injections, and physical therapy) are typically used as primary interventions, surgical treatment may ultimately become necessary. The purpose of this review is to discuss the most common open approaches to the knee, with an emphasis on surgically relevant anatomy for each approach. Understanding of the anatomy of the knee joint and associated neurovascular structures is necessary in order to avoid intraoperative complications and optimize postoperative recovery.


Fertility Preservation in Women With Endometriosis.
Infertility affects 30% to 50% of women with endometriosis. Women with endometriosis are at risk of decreased ovarian reserve, both because of the pathophysiology of the disease and iatrogenic injury resulting from surgical intervention. Fertility preservation must occur at multiple levels, including careful selection of surgical candidates, avoidance of repeat procedures, and meticulous surgical technique. Fertility preservation with oocyte or ovarian tissue cryopreservation may be considered on an individual basis for women with endometriosis, particularly those at risk of bilateral ovarian injury, such as women with bilateral endometriomas.


Temperature-mediated absorption of phenylmercuric nitrate on polyethylene and polypropylene containers in chloramphenicol eye drops.
The aim of this work was to find the effect of temperature and manufacturing source of phenylmercuric nitrate (PMN) on PMN absorption on low-density polyethylene (LDPE) and polypropylene containers in chloramphenicol eye drops. Two factorial experiments were designed to study the effect of temperature on PMN assay in chloramphenicol eye drops stored in LDPE and prepared from two different PMN sources. PMN source had no effect on PMN assay at 2-8 °C, however at stress conditions (30 °C/75%RH) for 3 weeks, the effect of PMN source on PMN assay was found significant (p < 0.05) in formulations stored in LDPE bottles. Temperature was the major contributor to decreased PMN assay. In formulations stored in polypropylene containers, PMN source had significant effect on PMN assay at 2-8 °C and 30 °C/75%RH. Overall, new PMN and polypropylene bottles performed better. The eye drops complied with preservative efficacy test both initially and at the end of shelf life. The concentration exponent of PMN is very low and in spite of its high absorption by container/closure, PMN was still able to protect the eye drops at the end of shelf life. It can be inferred that preservative efficacy test is the better indicator of preservative activity.


Adenosine triphosphate bioluminescence for bacteriologic surveillance and reprocessing strategies for minimizing risk of infection transmission by duodenoscopes.
Recent outbreaks of duodenoscope-transmitted infections underscore the importance of adequate endoscope reprocessing. Adenosine triphosphate (ATP) bioluminescence testing allows rapid evaluation of endoscopes for bacteriologic/biologic residue. In this prospective study we evaluate the utility of ATP in bacteriologic surveillance and the effects of endoscopy staff education and dual cycles of cleaning and high-level disinfection (HLD) on endoscope reprocessing. ATP bioluminescence was measured after precleaning, manual cleaning, and HLD on rinsates from suction-biopsy channels of all endoscopes and elevator channels of duodenoscopes/linear echoendoscopes after use. ATP bioluminescence was remeasured in duodenoscopes (1) after re-education and competency testing of endoscopy staff and subsequently (2) after 2 cycles of precleaning and manual cleaning and single cycle of HLD or (3) after 2 cycles of precleaning, manual cleaning, and HLD. The ideal ATP bioluminescence benchmark of <200 relative light units (RLUs) after manual cleaning was achieved from suction-biopsy channel rinsates of all endoscopes, but 9 of 10 duodenoscope elevator channel rinsates failed to meet this benchmark. Re-education reduced RLUs in duodenoscope elevator channel rinsates after precleaning (23,218.0 vs 1340.5 RLUs, P < .01) and HLD (177.0 vs 12.0 RLUs, P < .01). After 2 cycles of manual cleaning/HLD, duodenoscope elevator channel RLUs achieved levels similar to sterile water, with corresponding negative cultures. ATP testing offers a rapid, inexpensive alternative for detection of endoscope microbial residue. Re-education of endoscopy staff and 2 cycles of cleaning and HLD decreased elevator channel RLUs to levels similar to sterile water and may therefore minimize the risk of transmission of infections by duodenoscopes.


Model based generalization analysis of common spatial pattern in brain computer interfaces.
In the motor imagery based Brain Computer Interface (BCI) research, Common Spatial Pattern (CSP) algorithm is used widely as a spatial filter on multi-channel electroencephalogram (EEG) recordings. Recently the overfitting effect of CSP has been gradually noticed, but what influence the overfitting is still unclear. In this work, the generalization of CSP is investigated by a simple linear mixing model. Several factors in this model are discussed, and the simulation results indicate that channel numbers and the correlation between signals influence the generalization of CSP significantly. A larger number of training trials and a longer time length of the trial would prevent overfitting. The experiments on real data also verify our conclusion.


In situ hybridization analysis for expression of myogenic regulatory factors in regenerating muscle of mdx mouse.
Precise temporal and spatial coordination of expression of the myogenic regulatory factors (MRF) plays a critical role in the development of skeletal muscle. Whether this pattern is recapitulated postnatally during regeneration of mature muscle after injury is not known. The aim of this study was to determine the cellular distribution of mRNA expression of the various myogenic regulatory factors (MyoD, Myogenin, Myf-5 and Myf-6) during regeneration in mature skeletal muscle. We used the mdx mouse, an animal model for Duchenne muscular dystrophy, which undergoes necrosis and vigorous regeneration of muscle fibers, as a natural model to study muscle fibers at various stages of maturity ranging from satellite cells to mature muscle fibers. In situ hybridization analysis revealed that MyoD expression was the most widespread and was expressed in satellite cells and small regenerating muscle fibers surrounding necrotic fibers. Myogenin, Myf5, and Myf6 were expressed weakly in some immature fibers and none of the MRF's could be detected in mature muscle. These findings, taken together with previous studies, suggests that the pattern of expression of the various MRF's in regenerating skeletal muscle differs from that in developing muscle in embryos and that MyoD may play a critical role in the initiation and progression of events which lead to regeneration in mature skeletal muscle.


Sirolimus-based therapy for kidney transplantation from expanded criteria donors.
The new class of immunosuppressants--inhibitors of the mammalian target of rapamycin--has no nephrotoxicity and the capacity to inhibit vascular smooth cell proliferation. These characteristics may afford considerable clinical advantages in the transplantation of kidneys from expanded criteria donors (ECD). Six clinical experiences of the use of sirolimus (SRL) in ECD kidneys recipients have been reported in the literature. Although the results varied somewhat, probably due to differences in the types of deceased donor and in the immunosuppressive regimens used, it seems that a calcineurin inhibitor free, SRL-based protocol can assure a good immunosuppressive effect with less nephrotoxicity and a low incidence of cytomegalovirus infection. For recipients of ECD kidneys at low immunological risk, we would recommend a regimen based on antithymocyte globulin induction and SRL, mycophenolate mofetil, and steroids for maintenance. For strongly responding recipients, we recommend SRL combined with a reduced, 76% to 87% dose of calcineurin inhibitor.


Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease.
Nocturnal sleep disruption develops in Alzheimer disease (AD) owing to the derangement of the sleep-wake cycle regulation pathways. Orexin contributes to the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness. To study cerebrospinal fluid levels of orexin in patients with AD, to evaluate the relationship of orexin cerebrospinal fluid levels with the degree of dementia and the cerebrospinal fluid AD biomarkers (tau proteins and β-amyloid 1-42), and to analyze potentially related sleep architecture changes measured by polysomnography. We conducted a case-control study from August 1, 2012, through May 31, 2013. We included 48 drug-naive AD patients referred to the Neurological Clinic of the University Hospital of Rome Tor Vergata. Based on the Mini-Mental State Examination score, 21 patients were included in mild AD group (score, ≥21), whereas 27 were included in the moderate to severe AD group (score, <21). The control group consisted of 29 nondemented participants of similar age and sex. Laboratory assessment of cerebrospinal fluid levels of orexin, tau proteins, and β-amyloid 1-42 and polysomnographic assessment of sleep variables. Levels of orexin, tau proteins, and β-amyloid 1-42; macrostructural variables of nocturnal sleep (total sleep time, sleep efficiency, sleep onset and rapid eye movement [REM] sleep latencies, non-REM and REM sleep stages, and wakefulness after sleep onset); and Mini-Mental State Examination scores. Patients with moderate to severe AD presented with higher mean (SD) orexin levels compared with controls (154.36 [28.16] vs 131.03 [26.55]; P < .01) and with more impaired nocturnal sleep with respect to controls and patients with mild AD. On the other hand, in the global AD group, orexin levels were positively correlated with total tau protein levels (r = 0.32; P = .03) and strictly related to sleep impairment. Finally, cognitive impairment, as measured by the Mini-Mental State Examination, was correlated with sleep structure deterioration. Our results demonstrate that, in AD, increased cerebrospinal fluid orexin levels are related to a parallel sleep deterioration, which appears to be associated with cognitive decline. Therefore, the orexinergic system seems to be dysregulated in AD, and its output and function appear to be overexpressed along the progression of the neurodegenerative process. This overexpression may result from an imbalance of the neurotransmitter networks regulating the wake-sleep cycle toward the orexinergic system promoting wakefulness.


Cognitive impairment and psychiatric morbidity in HIV+ Zambians with new-onset seizure.
A prospective cohort study of new-onset seizure in people with human immunodeficiency virus (HIV) in Zambia is ongoing to determine the incidence of subsequent epilepsy and risk factors for epileptogenesis in this population. At enrollment, we evaluated this cohort for cognitive impairment and psychiatric morbidity. Over 50% of participants had cognitive impairment and significant psychiatric morbidity. Most participants had advanced HIV disease based on CD4+ T-cell count and World Health Organization stage, but we found no association between cognitive impairment or psychiatric morbidity and HIV disease staging.


Perception of complex sounds in autism: abnormal auditory cortical processing in children.
The authors have previously described less activation of left speech-related temporal areas in adults with autism when listening to speech-like sounds than in normal adults. Here, they investigated whether this abnormal cortical processing was also present in children with primary autism. Regional cerebral blood flow was measured with positron emission tomography after premedication in 11 autistic children and six nonautistic mentally retarded children during rest and while they were listening to speech-like sounds. As with autistic adults, direct comparison between the two groups revealed significantly less activation in the autistic group localized in left speech-related areas. For the first time to their knowledge, an activation study was performed in children with autism and has confirmed previous results obtained in adults. The abnormal cortical auditory processing observed in both children and adults with autism could be involved in inadequate behavioral responses to sounds and in language impairments characteristic of autism.


The effect of inbreeding, body size and morphology on health in dog breeds.
Dog breeds are known for their distinctive body shape, size, coat color, head type and behaviors, features that are relatively similar across members of a breed. Unfortunately, dog breeds are also characterized by distinct predispositions to disease. We explored the relationships between inbreeding, morphology and health using genotype based inbreeding estimates, body weight and insurance data for morbidity. The average inbreeding based on genotype across 227 breeds was Fadj = 0.249 (95% CI 0.235-0.263). There were significant differences in morbidity between breeds with low and high inbreeding (H = 16.49, P = 0.0004). There was also a significant difference in morbidity between brachycephalic breeds and non-brachycephalic breeds (P = 0.0048) and between functionally distinct groups of breeds (H = 14.95 P < 0.0001). Morbidity was modeled using robust regression analysis and both body weight (P < 0.0001) and inbreeding (P = 0.013) were significant (r2 = 0.77). Smaller less inbred breeds were healthier than larger more inbred breeds. In this study, body size and inbreeding along with deleterious morphologies contributed to increases in necessary health care in dogs.


Acute Aortic Treatment Center.
Acute aortic syndromes are a life-threatening set of conditions that require rapid triage and intervention to obtain satisfactory outcomes. The Methodist Hospital is the first institution to establish an Acute Aortic Treatment Center (AATC) based on a clinical care pathway that expedites the care of acute aortic syndromes. This pathway has resulted in a 64% reduction in time to definitive therapy and a reduction in intensive care unit (ICU) length of stay. Establishment of a multidisciplinary pathway to treat acute aortic syndromes improves efficiency and enhances outcomes.


Integrating Nano-Cu₂O@ZrP into In Situ Polymerized Polyethylene Terephthalate (PET) Fibers with Enhanced Mechanical Properties and Antibacterial Activities.
The approach of in situ polymerization modification has proven to be an effective route for introducing functions for polyester materials. In this work, Cu₂O@ZrP nanosheets with excellent dispersity and high antibacterial activity were integrated into in situ polymerized polyethylene terephthalate (PET) fibers, revealing an enhanced mechanical performance in comparison with the PET fibers fabricated directly via a traditional melt blending method. Additionally, such an in situ polymerized PET/Cu₂O@ZrP fibers displayed highly enhanced mechanical properties; and great antibacterial activities against multi-types of bacterium, including S. aureus, E. coli and C. albicans. For the as-obtained two types of PET/Cu₂O@ZrP fibers, we have detailed their molecular weight (detailed molecular weight) and dispersibility of nano-Cu₂O@ZrP and fibers crystallinity was investigated by Gel chromatography (GPC), Scanning electron microscope (SEM), and X-ray diffractometer (XRD), respectively. The results showed that the aggregation of the nano-Cu₂O@ZrP in the resultant PET matrix could be effectively prevented during its in situ polymerization process, hence we attribute its highly enhanced mechanical properties to its superior dispersion of nano-Cu₂O@ZrP.


Evaluation of synergistic effect of tazobactam with meropenem and ciprofloxacin against multi-drug resistant Acinetobacter baumannii isolated from burn patients in Tehran.
Background: Acinetobacter baumannii is an increasingly important cause of nosocomial infections worldwide. In addition to the intrinsic resistance of Acinetobacter baumannii to many antibiotics, available treatment approaches with older antibiotics are significantly associated with an increase in multiresistant strains. The aim of this study was to evaluate the synergistic effect of tazobactam with meropenem and ciprofloxacin against carbapenems and drug resistant Acinetobacter baumannii isolated from burn patients in a tertiary burn center in Tehran. Materials and methods: In this study, a total of 47 clinical isolates of A. baumannii were included from burn patients admitted to the Shahid Motahari Burns Hospital, Tehran, from June 2018 to August 2018. The disk diffusion method was used to determine resistance patterns. The synergistic effect of tazobactam with meropenem and ciprofloxacin was evaluated by determining the MIC. A PCR assay was performed to determine bla OXA-40-like , bla OXA-58-like and bla OXA-24-like . Results: Antibiotic susceptibility testing revealed that all of the isolates were resistant to meropenem and ciprofloxacin. The MIC values decreased in the cases of combined use of ciprofloxacin and meropenem with tazobactam. The blaOXA-24-like gene was the predominant carbapenemase gene (93.6%), followed by bla OXA-40-like , which was detected in 48.9% of isolates. None of the A. baumannii isolates harbored the bla OXA-58-like gene. Conclusions: Based on in-vitro antimicrobial susceptibility in the current study, the MIC of tazobactam combined with meropenem or ciprofloxacin have been shown to be variable. Furthermore, the data acquired from such in vitro conditions should be confirmed by reliable results from sufficiently controlled clinical trials.


Simultaneous determination of chlortetracycline, ampicillin and sarafloxacin in milk using capillary electrophoresis with electrochemiluminescence detection.
A fast, inexpensive and sensitive approach for the simultaneous determination of chlortetracycline, ampicilline and sarafloxacin in milk was developed using capillary electrophoresis coupled with an electrochemiluminescence detector. Under the optimal detection conditions, the linear ranges for chlortetracyline, ampicilline and sarafloxacin were 0.030-5.0, 0.050-5.0 and 0.0040-2.0 μg ml-1, respectively. The correlation coefficients of chlortetracycline, ampicilline and sarafloxacin were determined as 0.9997, 0.9952 and 0.9978, respectively. Detection limits (S/N = 3) of chlortetracycline, ampicilline and sarafloxacin were found as 0.017, 0.018 and 0.0013 μg ml-1, respectively. This method was successfully applied for the determination of chlortetracycline, ampicilline and sarafloxacin in milk. The recoveries were between 95.3% and 100%. The relative standard deviations of the detection limit and recovery were less than 2.6% and 3.2%, respectively.


Effects of vitamin K(2) on bone of ovariectomized rats and on a rat osteoblastic cell line.
The effects of vitamin K(2) on bone mineral density (BMD) and bone metabolic markers of ovariectomized rats, and those on mRNA expression of osteocalcin and IL-6 on a rat osteoblastic cell line, were investigated. BMD and bone metabolic markers were examined in ovariectomized rats after 2 months' treatment with vitamin K(2), and mRNA expression of osteocalcin and IL-6 were measured in the cell line after 24-hour treatment with vitamin K(2). Vitamin K(2) attenuated the decline in BMD after ovariectomy in the rats, and suppressed serum deoxypyridinoline levels of the ovariectomized rats. No effect on osteocalcin and IL-6 mRNA expression on the cell line was observed. In conclusion, vitamin K(2) has a bone-protective effect on ovariectomized rats.


Measles outbreak among young adults in Victoria.
An outbreak of laboratory confirmed measles involving 30 young adults and an infant is reported. Of the young adult cases, 17 (57%) were hospitalised. After a trip to India, the primary case returned to Sydney early in January 2001 and then visited Melbourne infecting several individuals. Secondary spread appears to have occurred at a nightclub. On the basis of RNA typing the measles strain involved is of genotype 'D'.


Baofukang suppository promotes the repair of vaginal epithelial cells in response to Candida albicans.
Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection predominantly caused by Candida albicans affecting a significant number of women of reproductive age. The Chinese medicine, the Baofukang suppository is widely used in the clinic for its antimicrobial activity and is therefore of great interest as a potential antifungal drug for the prevention of VVC. We evaluated the cytotoxic activity of the Baofukang suppository using the VK2/E6E7 vaginal epithelial cell (VEC) line. When treated with the Baofukang suppository, all of the immunocompetent cytokines and chemokines (e.g., IL-2, IL-4, IL-6, IL-8, and IL-17) by infected VK2/E6E7 cells was statistically up-regulated (P < 0.05), except IL-4 (11.70 ± 1.82 vs. 14.88 ± 4.72, P = 0.343) compared to the infected control cells. The secretion of non-B IgG also exhibited the same trend. Our scanning electron microscopy results revealed that C. albicans can invade VECs by both induced endocytosis and active penetration. The Baofukang suppository could effectively inhibit the adhesion, hyphal formation, and proliferation, as well as notably restore the vaginal epithelial cell morphology, viability, and enhance the local immune function of the VECs. These preliminary results suggest promising antimicrobial properties of the Baofukang suppository, which may be efficacious as an antifungal therapy candidate via up-regulating Th1 cellular immunity, the Th17-axis of the innate immune response, and the secretion of vaginal epithelial-derived IgG. These combined effects collectively restore the immune function of the infected VECs against C. albicans in vitro.


Effects of different techniques during the second stage of labour on reducing perineal laceration: An overview of systematic reviews.
To summarize the evidence on the effects of different techniques during the second stage of labour on reducing perineal laceration depending on available systematic reviews to provide optimal evidence for decision-making. Preventing perineal laceration has been considered an important part of improving women's health. Various techniques have been used to prevent perineal laceration during the second stage of labour. However, systematic reviews evaluating the effects of different techniques on reducing perineal laceration show inconsistent results. Overview of systematic reviews. Five English and four Chinese databases were systematically searched for relevant systematic reviews and meta-analyses published between 1 January 2016 and 31 August 2021. The quality of the included reviews was assessed by the AMSTAR 2 tool. A narrative synthesis was conducted to report the results of moderate-to-high quality systematic reviews. The overview was reported according to the PRISMA statement. Eighteen reviews were included, of which four reviews had moderate-to-high methodological quality. Perineal massage and warm compresses significantly decreased the incidence of third- or fourth-degree perineal laceration (moderate-quality evidence). Hands-off technique had no impact on perineal laceration (low-to-moderate quality evidence). Ritgen's manoeuvre could reduce the incidence of first-degree perineal laceration but increase the incidence of second-degree perineal laceration (very low-quality evidence). Spontaneous pushing (low-quality evidence) and delayed pushing (moderate-quality evidence) had no impact on the incidence of third- or fourth-degree perineal laceration. Upright positions did not increase the risk of third- or fourth-degree perineal laceration (very low- to low-quality evidence) but increased the risk of second-degree perineal laceration for women without epidural analgesia (low-quality evidence). Perineal massage and warm compresses could be the better choice for preventing perineal laceration in the second stage of labour. Midwives and obstetricians could use perineal massage and warm compresses to prevent perineal laceration and should consider women's preferences and experience with perineal techniques.


Modulation of Gut Microbial Diversity through Non-Pharmaceutical Approaches to Treat Schizophrenia.
Schizophrenia (SCZ) is a psychotic syndrome with well-defined signs and symptoms but indecisive causes and effective treatment. Unknown underpinning reasons and no cure of the disease profoundly elevate the risk of illness. Gut microbial dysbiosis related metabolic dysfunction is providing a new angle to look at the potential causes and treatment options for schizophrenia. Because of the number of side effects, including gut dysbiosis, of traditional antipsychotic drugs, new alternative therapeutic options are under consideration. We propose that non-pharmacotherapy using biotherapeutic products could be a potent treatment to improve cognitive impairment and other symptoms of schizophrenia. Use of live microorganisms (probiotics), fibers (prebiotics), and polyphenols alone or in a mixture can maintain gut microbial diversity and improve the two-way relationship of the gut microbiota and the central nervous system. Fiber and polyphenol induced management of gut microbiota may positively influence the gut-brain axis by increasing the level of brain-derived neurotrophic factors involved in schizophrenia. Furthermore, we endorse the need for comprehensive clinical assessment and follow-up of psychobiotic (pro and prebiotics) treatment in mental illness to estimate the level of target recovery and disability reduction in schizophrenia.


Impact of cannabis and other drugs on age at onset of psychosis.
The aim of this study was to investigate the relationship between age and cannabis use in patients with a first psychotic episode, and to analyze the mediating effect of comorbid use of other drugs and sex on age at onset of psychosis. All consenting patients (aged 15 to 65 years) with a first psychotic episode needing inpatient psychiatric treatment during a 2-year period between February 1997 and January 1999 were considered, confirming a total of 131 patients. Subjects were interviewed using the Structured Clinical Interview for DSM-IV Axis I Disorders, and clinical and demographic data were collected. We used general linear models with age at onset as the response variable and survival Cox models to confirm the results. Both a multivariate linear model and the corresponding Cox model were fitted with a covariate that summarizes the most significant contributors that seemed to decrease age at onset. Regarding the effect of cannabis use, a significant gradual reduction on age at onset was found as dependence on cannabis increased, consisting in a decrement of 7, 8.5, and 12 years for users, abusers, and dependents, respectively, with respect to nonusers (p = .004, p < .001, and p < .001, respectively). Multivariate analysis showed a clear effect of cannabis use on age at onset, which was not explained by the use of other drugs or by gender. The finding was similar in the youngest patients, suggesting that this effect was not due to chance. The major contribution of this investigation is the independent and strong link between cannabis use and early age at onset of psychosis, and the slight or nonexistent effect of sex and comorbid substance abuse in this variable. These results point to cannabis as a dangerous drug in young people at risk of developing psychosis.


Therapist Perspectives: Wii Active Videogames Use in Inpatient Settings with People Who Have Had a Brain Injury.
Brain injuries (BIs) are a major public health issue. Clinical experience and literature have identified that it is often challenging to motivate people who have had a BI to engage in repetitive exercises commonly prescribed for rehabilitation. As a result, some therapists include commercial active videogames (AVGs) in their therapy sessions to help make repetitive actions fun and engaging. In this project, we explored how the therapists used commercial AVGs to better understand the major barriers and enablers of use. We interviewed 17 therapists from two rehabilitation hospitals who work with people who have had a BI. After the interviews were transcribed, we identified salient themes. At the time of the interviews, therapists were using only the Nintendo(®) (Kyoto, Japan) Wii™ console. Common therapeutic goals included balance and weight shifting. Several patient factors, such as cognitive and physical abilities, age, and previous gaming experience, were considered important considerations when deciding to use games. Therapists also indicated many desired changes to games, including better control/interface, better feedback, and the ability to adjust timing, challenge, and stimulation levels. When considering therapy-centered game design, the needs of both therapists and patients should be considered. There is a necessary balance to consider in game design: They need to (a) be perceived as fun, (b) meet therapy goals, and (c) address therapists' needs (e.g., adjustability to address a range of patient abilities). Additionally, there is a need for a wide variety of available games to address novelty and personal preferences.


Overexpression of the wip1 gene abrogates the p38 MAPK/p53/Wip1 pathway and silences p16 expression in human breast cancers.
Wild-type p53-induced phosphatase (Wip1 or PPM1D) is a serine/threonine protein phosphatase expressed under various stress conditions, which selectively inactivates p38 MAPK. The finding that this gene is amplified in association with frequent gain of 17q21-24 in breast cancers supports its role as a driver oncogene. However, the pathogenetic mechanism of the wip1 gene expression in breast carcinogenesis remains to be elucidated. In this study, we examine Wip1 mRNA and protein expression in 20 breast cancer tissues and six cell lines. We additionally investigate the relationship among Wip1, active p38 MAPK, p53, and p16 proteins. In our experiments, Wip1 mRNA was significantly upregulated in 7 of 20 (35%) invasive breast cancer samples. Overexpression of Wip1 was inversely correlated with that of active (phosphor-) p38 MAPK (P = 0.007). Furthermore, Wip1-overexpressing tumors exhibited no or low levels of p16, which normally accumulates upon p38 MAPK activation (P = 0.057). Loss of p16 expression was not associated with hypermethylation of its promoter or loss of heterozygosity on 9p21. Among the 135 primary breast carcinomas further examined, a significant association was found between the Wip1 overexpression and negative staining for p53 (P value = 0.057), indicating that the tumors are wild-type for p53. This is first report showing that Wip1 overexpression abrogates the homeostatic balance maintained through the p38-p53-Wip1 pathway, and contributes to malignant progression by inactivating wild-type p53 and p38 MAPK as well as decreasing p16 protein levels in human breast tissues.


t-Bu2SiF-derivatized D2-receptor ligands: the first SiFA-containing small molecule radiotracers for target-specific PET-imaging.
The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride acceptor (SiFA) derivatized D(2)-receptor ligands is reported. The SiFA-technology simplifies the introduction of fluorine-18 into target specific biomolecules for Positron-Emission-Tomography (PET). However, one of the remaining challenges, especially for small molecules such as receptor-ligands, is the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA-conjugates derivatized either directly at the benzoic acid ring system (SiFA-DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested their receptor affinities. We found D(2)-receptor affinities for all compounds in the nanomolar range (K(i(SiFA-DMFP)) = 13.6 nM, K(i(SiFA-FP)) = 33.0 nM, K(i(SiFA-DDMFP)) = 62.7 nM and K(i(SiFA-M-FP)) = 4.21 nM). The radiofluorination showed highest yields when 10 nmol of the precursors were reacted with [(18)F]fluoride/TBAHCO(3) in acetonitrile. After a reversed phased cartridge purification the desired products could be isolated as an injectable solution after only 10 min synthesis time with radiochemical yields (RCY) of more than 40% in the case of SiFA-DMFP resulting in specific activities >41 GBq/µmol (>1,100 Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the injectable solutions, as well as in human plasma, for at least 90 min.


Sequence requirement and subtype specificity in the high-affinity interaction between human frizzled and dishevelled proteins.
Members of the Wnt family of lipoglycoproteins initiate signaling by binding to Frizzled (Fz) receptors, and the signal is then relayed by Disheveled (Dvl). The Dvl PDZ domain is known to interact directly with a peptide derived from the KTXXXW motif of Fz7, which is conserved in all known Fz subtypes. We found that an extended region spanning the KTXXXW motif on both its N-terminal and C-terminal sides dramatically influences the affinity of peptides derived from Fz7 for Dvl PDZ. An alanine scanning study identified the specific residues external to the KTXXXW motif that are important for high-affinity binding. In a circular dichroism analysis, mutation of some of these critical residues resulted in peptide conformational changes, suggesting that the secondary structure of the peptides contributes to Fz-Dvl PDZ binding. Of the 10 known Fz subtypes, peptides derived from only Fz1, Fz2, Fz3, Fz4, and Fz7 directly bound to Dvl PDZ domain in our study. Other Fz subtypes, including some known to be involved in Wnt/beta-catenin signaling (Fz5, Fz9), did not bind to Dvl, suggesting that direct interaction with Dvl PDZ does not determine the subtype-specific functionality of Fz. Molecular modeling and circular dichroism studies indicated that the Fz peptides that bind to Dvl PDZ domain form specific conformations that are different from those of nonbinding peptides.


Green fluorescent protein as a marker for gene expression and subcellular localization in budding yeast.
The green fluorescent protein (GFP) from the jellyfish Aequorea victoria has attracted much attention as a tool to study a number of biological processes. This study describes the use of GFP as a vital reporter molecule for localization and expression studies in Saccharomyces cerevisiae. Construction of GFP expression vectors which allow N- or C-terminal fusion of the gfp gene to a gene of interest allowed the generation of fusion proteins whose subcellular localization was followed by fluorescence microscopy in living yeast cells. Analysis of three unknown open reading frames obtained from the budding yeast chromosome XIV resulted in distinct staining patterns, allowing prediction of the cellular localization of these unknown proteins. Furthermore, GFP was used to construct a gene replacement cassette which, after homologous integration into the genomic locus, placed the gfp gene behind a promoter of interest. The amount of GFP produced from this promoter was then quantified in living yeast cells by flow cytometry. With this novel replacement cassette a gene of interest can be deleted and at the same time its expression level studied under various growth conditions. The experiments presented here suggest that GFP represents a convenient fluorescent marker for localization studies as well as gene expression studies in budding yeast. Systematic studies of a large number of genes should benefit from such assays.


The drumbeat of renal failure: symbiosis of prevention and renal replacement therapy.
The global population of patients with end-stage renal disease is rising rapidly, especially in developing countries. The possibility and economic burden of renal replacement therapy will be greatly challenged in the next decade as the prevalence of diabetes and hypertension rises. The establishment of effective prevention and intervention measures creates a means by which the increasing burden of renal replacement therapy can be reduced.


Absolute Intensities of the nu(1) and nu(3) Bands of (16)O(3).
New experimental data on the nu(1) and nu(3) bands of (16)O(3) improving the value of absolute line intensities have been obtained. The intensities of 295 lines have been measured with an average accuracy between 2.5% and 3% and the rotational expansion of the transition moment operators for the nu(1) and nu(3) bands has been deduced. Finally, a complete listing of line intensities has been computed with an intensity cutoff of 1x10(-25) cm(-1)/molecule cm(-2). Copyright 2001 Academic Press.


Hemispheric specialisation, spatial activity experience, and sex differences on tests of mental rotation ability.
A sex difference in mental rotation ability is well established. Among the explanations offered for this difference are that males are more frequently right hemisphere specialised for spatial processing and that they receive more spatial processing experience because of the sex stereotyping of activities involving spatial ability that exists in Western societies. Several studies have shown that males do report more spatial activity experiences on the Spatial Activity Questionnaire of Newcombe, Bandura, and Taylor (1983) and that such experience does correlate with performances on tests of mental rotation. However, two prior lateralised tachistoscopic studies failed to show right hemisphere superiority for spatial task performance or that it was positively associated with better performances on the Vandenberg Mental Rotation Test. The tachistoscopic tasks used in these studies can be criticised on methodological grounds. The present study employed a new tachistoscopic task that showed that males were significantly more right hemisphere specialised (left visual-field superior) for the tachistoscopic task than females. Magnitudes of right hemisphere specialisation on the tachistoscopic task were positively and significantly related to mental rotation ability. Spatial activity experiences were also more common in males. Covariance and partial correlation analyses indicated that the sex difference in spatial ability was primarily due to sex differences in right hemisphere specialisation for mental rotation, while sex differences in spatial activity experiences were only secondarily involved.


[Myxedema coma].
Myxedema coma, an extreme expression of hypothyroidism, represents a medical emergency with high mortality. Hypothermia and cerebro-vascular accidents should be taken into account for correct differential diagnosis. The treatment of myxedema coma is based on prevention of the precipitating factors and on the administration of generous doses of L-thyroxine and/or triiodothyronine, associated with steroids and drugs for respiratory and cardio-vascular complications.


Prevalence, course and factors associated with delirium in elderly patients with advanced cancer: a longitudinal observational study.
The aim of this study was to investigate the prevalence of delirium on admission, the course of delirium during a 2-week period after admission and factors associated with delirium on admission, among elderly patients with advanced cancer. Patients aged ≥ 65 years with incurable lung or gastroenterological cancer and the Eastern Cooperative Oncology Group Performance Status 2 or greater were continuously sampled after admission to a university hospital. Participants were evaluated for DSM-IV-TR delirium by trained psychiatrists and the delirium subtype was assessed using the Delirium Motor Subtype Scale within 4 days after admission and again 2 weeks later. In addition, we assessed associated factors with delirium on admission. Among 73 eligible patients, complete data were available from 61 on admission and 49 after 2 weeks. Twenty-six patients (43%) met delirium criteria on admission (hypoactive: 58%, unspecified: 35%, hyperactive: 4%, mixed: 4%). Of these, 19 (73%) remained delirious 2 weeks later. Of 35 patients without delirium on admission, 21 (60%) remained delirium-free 2 weeks later and 7(20%) became delirious. Overall, 33/61 (54%) developed delirium at some point during the study. Patients receiving steroids at admission were more likely to have delirium (odds ratio = 5.0; 95% confidence interval = 1.5-16). Given the high prevalence of the delirium, all patients with advanced cancer should be screened for delirium both on admission and regularly thereafter. In addition, medical staff should be aware that steroid use on admission is an additional indicator of elevated risk for delirium.


Rapid kinetics of second messenger production in bitter taste.
The tasting of bitter compounds may have evolved as a protective mechanism against ingestion of potentially harmful substances. We have identified second messengers involved in bitter taste and show here for the first time that they are rapid and transient. Using a quench-flow system, we have studied bitter taste signal transduction in a pair of mouse strains that differ in their ability to taste the bitter stimulus sucrose octaacetate (SOA); however, both strains taste the bitter agent denatonium. In both strains of mice, denatonium (10 mM) induced a transient and rapid increase in levels of the second messenger inositol 1,4,5-trisphosphate (IP3) with a maximal production near 75-100 ms after stimulation. In contrast, SOA (100 microM) brought about a similar increase in IP3 only in SOA-taster mice. The response to SOA was potentiated in the presence of GTP (1 microM). The GTP-enhanced SOA-response supports a G protein-mediated response for this bitter compound. The rapid kinetics, transient nature, and specificity of the bitter taste stimulus-induced IP3 formation are consistent with the role of IP3 as a second messenger in the chemoelectrical transduction of bitter taste.


Distinct cerebral coherence in task-based fMRI hyperscanning: cooperation versus competition.
This study features an functional magnetic resonance imaging (fMRI) hyperscanning experiment from 2 sites, 305 km apart. The experiment contains 2 conditions: the dyad collaborated to win and then split the reward in the cooperation condition, whereas the winner took all the reward in the competition condition, thereby resulting in dynamic strategic interactions. To calculate the cerebral coherence in such jittered event-related fMRI tasks, we first iteratively estimated the feedback-related blood oxygenation level-dependent responses of each trial, using 8 finite impulse response functions (16 s) and then concatenated the beta volume series. With the right temporal-parietal junction (rTPJ) as the seed, the interpersonal connected brain areas were separately identified: the right superior temporal gyrus (rSTG) (cooperation) and the left precuneus (lPrecuneus) (competition), both peaking at the designated frequency bin (1/16 s = 0.0625 Hz), but not in permuted pairs. In addition, the extended coherence analyses on shorter and longer concatenated volumes verified that only in the optimal trial frequency did the rTPJ-rSTG and rTPJ-lPrecuneus couplings peak. In sum, our approach both showcases a flexible analysis method that widens the applicability of interpersonal coherence in the rapid event-related fMRI hyperscanning and reveals a context-based inter-brain coupling between interacting pairs during cooperation and during competition.


K11-linked ubiquitin chains as novel regulators of cell division.
Modification of proteins with ubiquitin chains is an essential regulatory event in cell cycle control. Differences in the connectivity of ubiquitin chains are believed to result in distinct functional consequences for the modified proteins. Among eight possible homogenous chain types, canonical Lys48-linked ubiquitin chains have long been recognized to drive the proteasomal degradation of cell cycle regulators, and Lys48 is the only essential lysine residue of ubiquitin in yeast. It thus came as a surprise that in higher eukaryotes atypical K11-linked ubiquitin chains regulate the substrates of the anaphase-promoting complex and control progression through mitosis. We discuss recent findings that shed light on the assembly and function of K11-linked chains during cell division.


Evaluating the biotic ligand model for toxicity and the alleviation of toxicity in terms of cell membrane surface potential.
The electrostatic nature of plant cell membrane (CM) plays significant roles in ionic interactions at the CM surface and hence in the biotic effects of metal ions. Increases in major cations (commonly Ca2+, Mg2+, H+, Na+, K+, etc.) in bulk-phase medium reduce the negativity of CM surface electrical potential (psi0), but these slightly increase the driving force of a metal ion crossing CMs (surface-to-surface transmembrane potential difference, Em,surf). Toxicologists commonly attributes the interactions between heavy metals and common cations (e.g., H+, Ca2+, and Mg2+) to competitions for binding sites at a hypothetical CM surface ligand. The psi0 effects are likely to be more important to metal toxicity and the alleviation of toxicity than site-specific competition. Models that do not consider psi0, such as the biotic ligand model (BLM) and the free ion activity model (FIAM), as usually employed are likely to lead to false conclusions about competition for binding at CM surface ligands. In the present study a model incorporating psi0 effects and site-specific competition effects was developed to evaluate metal (Cu2+, Co2+, and Ni2+) toxicities threshold (EA50, causing 50% inhibition) for higher plants. In addition, the mechanisms for the effects of common cations on toxicity of metals were also explored in terms of CM surface electrical potential.


Biomarkers of Irritable Bowel Syndrome.
Traditionally, irritable bowel syndrome (IBS) has not been regarded as an organic disease, and the pathophysiology of IBS is heterogeneous. Currently, the diagnosis of IBS is based upon the Rome diagnostic criteria. The performance of these criteria is only modest in predicting IBS, and moreover their validation is lacking. Additionally, as functional symptoms are common in the general population, healthy controls or volunteers are difficult to define and there is currently no definition of "normal" in the Rome criteria. Due to the weaknesses of the current diagnostic criteria, patients and doctors expect new gold standard diagnostic tools. Various etiologic mechanisms result in potential biomarkers. The focus of this research has been to find non-invasive biomarkers from serum, breath gas, and fecal materials. Though biomarkers should be based on biological and pathogenic processes, most biomarkers for IBS have been developed to identify organic diseases and therefore eliminate IBS. To date, these types of biomarkers for IBS have been disappointing. The purposes of developing biomarkers include improvement of diagnosis, differentiation from other organic diseases, and discrimination of IBS subtypes. A true mechanistic biomarker would make it possible to rule in IBS, rather than to rule out other organic diseases. New serologic biomarkers for diarrhea-predominant IBS have been introduced based on the pathophysiologic findings from a rat model and validation in a large-scale clinical trial. Further investigations of abnormal organic findings from each subtype of IBS would enable the development of new, simple subtype-specific biomarkers.


The relationship between posttraumatic stress disorder and self-reported health problems.
There is increasing awareness that posttraumatic stress disorder (PTSD) influences physical health. The current study used the National Comorbidity Survey (NCS) data to determine if the physical health risk imparted by PTSD was an artifact of a broad range of empirically identified confounding variables. Participants (n = 5877) were administered a modified version of the DSM-III-R PTSD module from the Diagnostic Interview Schedule (DIS). The prevalence of 14 classes of physical disorders was assessed along with six groups of variables predictive of negative health outcomes (demographics, perception of health, stress, health-related behaviors, insurance coverage, trauma/psychiatric history, and neuroticism). The PTSD group had a higher frequency of most disorders and scored higher on variables predictive of negative health outcomes. To determine if the health risk imparted by PTSD was an artifact of these confounding variables, a mixed direct-sequential binary logistic regression was computed. After controlling for sex, health perceptions, stress, health-related behaviors, insurance coverage, total trauma exposure, total number of psychiatric diagnoses, and neuroticism, persons with PTSD were more likely to report the presence of a disorder. Previous scholars have noted that PTSD could affect health outcomes. This study found that after controlling for a wide range of variables predictive of poor health, PTSD was predictive of poor health.


Possibilities of simulation of coronavirus SARS-CoV-2 by using light scattering approach.
Issues related to human coronavirus (SARS CoV-2) are a burning topic of research in present times. Due to its easily contagious nature, real experimentation under laboratory conditions requires a high level of biosafety. A powerful algorithm serves as a potential tool for the analysis of these particles. We attempted to simulate the light scattering from coronavirus (SARS CoV-2) model. Different images were modelled using a modified version of a Monte Carlo code. The results indicate that spikes on the viruses exhibit a significant scattering profile and that the presence of spikes during modelling contributes to the distinctiveness of the scattering profiles.


[Comparison of prognostic models for patients with early-stage diffuse large B-cell lymphoma].
To compare the prognostic value of different models in patients with early-stage diffuse large B-cell lymphoma (DLBCL). Early-stage DLBCL patients diagnosed from January 2000 to December 2012 were analyzed retrospectively. All patients received with at least 2 cycles of immunochemotherapy R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) with or without radiotherapy. The prognostic value of international prognostic index (IPI) , revised IPI (R-IPI) and enhanced IPI (NCCN-IPI) was compared. Ninety-seven cases of early-stage DLBCL were included in the study. The median age was 58 years (15-88 years) with a median follow-up of 34.7 months (range 7.3-77.4 months). The expected 5-year overall survival (OS) for entire group was 82%. There was no patient in the high risk group according to IPI or NCCN-IPI. According to IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 95%, 38% and 60%, respectively. According to R-IPI, the 5-year OS in the very good, good, and poor risk groups were 93%, 75% and 60%, respectively. According to NCCN-IPI, the 5-year OS in the low, low intermediate, high intermediate risk groups were 92%, 85% and 29%, respectively. NCCN-IPI would be of an ideal prognostic model for early-stage DLBCL patients.


Schistosomiasis control program in the state of Minas Gerais in Brazil.
The Schistosomiasis Control Program (PCE) was implemented in Minas Gerais (MG) in 1984. In 1999, the state started the investigation and control of schistosomiasis in 470 municipalities. The aim of the present paper is to report the evolution of this Program from 1984-2007. The program included a coproscopic survey carried out in the municipalities of known endemic areas using a quantitative method. Positives were treated with praziquantel and given a program of health education. The information for this study was obtained from data collected and stored by the Health State Department. From 2003-2007, 2,643,564 stool examinations resulted in 141,284 positive tests for Schistosoma mansoni (5.3%). In the first evaluation after treatment, a decrease in the number of municipalities with prevalence over 10% was documented. In one village, selected for a more detailed evaluation, the percentage of positive tests decreased from 14.9% in the baseline survey to 5.3% after treatment. A reference centre for patients with severe schistosomiasis was created in Belo Horizonte, MG. Based on our findings, we believe that the implementation of PCE in MG is on the right path and in due time these new initiatives will provide desirable results.


Independence day explosion on lovers key.
The display of fireworks is a popular holiday celebration in the United States. Because injuries due to recreational fireworks-related explosions among private consumers are relatively common, the sale of fireworks is regulated by the federal government and is also limited by state and local laws. In contrast, because fireworks display companies are under tight safety regulations, explosions in the professional pyrotechnics industry are uncommon occurrences, and the literature contains rare reports of injuries and fatalities resulting from such explosions. We report the 2003 Fourth of July commercial fireworks explosion on Lovers Key in southwest Florida that resulted in five fatalities. Events occurring during the investigation of the scene of this explosion illustrate the unique considerations and hazards for medicolegal death investigators, law enforcement and other investigative agencies. Additionally, this case demonstrates unusual aspects of the postmortem examinations performed on victims of fireworks-related incidents.


Effects of perinatal exposure to bisphenol A on play behavior of female and male juvenile rats.
In higher vertebrates, estrogen can exert an organizational effect on sexually dimorphic areas of the central nervous system (CNS) during the perinatal phase of development. The possibility that estrogenic pollutants may mimic estrogen action on the CNS during development and produce long-lasting or irreversible effects is an issue of great concern. Bisphenol A (BPA), a compound widely used in the food industry and in dentistry, has proven estrogenic actions. To study its potential developmental effects on behavior, we gave female Sprague-Dawley rats 40 microg/kg/day BPA from conception to weaning postnatal day 21 and 400 microg/kg/day BPA from gestation day 14 to postnatal day 6. After exposure, we studied social behavior in a play situation in juvenile male and female offspring. The attempt to use play behavior to study the effects of BPA yielded some interesting results. We observed an early action of BPA on several behavioral categories in both males and females. In particular we observed a masculinization of female behavior in two behavioral categories (play with females and sociosexual exploration), an effect probably mediated by the estrogenic activity of BPA in the CNS. These long-lasting effects of BPA could have important consequences at individual and population levels.


Cell Internalization in Fluidic Culture Conditions Is Improved When Microparticles Are Specifically Targeted to the Human Epidermal Growth Factor Receptor 2 (HER2).
To determine if the specific targeting of microparticles improves their internalization by cells under fluidic conditions. Two isogenic breast epithelial cell lines, one overexpressing the Human Epidermal Growth Factor Receptor 2 (HER2) oncogene (D492HER2) and highly tumorigenic and the other expressing HER2 at much lower levels and non-tumorigenic (D492), were cultured in the presence of polystyrene microparticles of 1 µm in diameter, biofunctionalized with either a specific anti-HER2 antibody or a non-specific secondary antibody. Mono- and cocultures of both cell lines in static and fluidic conditions were performed, and the cells with internalized microparticles were scored. Globally, the D492 cell line showed a higher endocytic capacity than the D492HER2 cell line. Microparticles that were functionalized with the anti-HER2 antibody were internalized by a higher percentage of cells than microparticles functionalized with the non-specific secondary antibody. Although internalization was reduced in fluidic culture conditions in comparison with static conditions, the increase in the internalization of microparticles biofunctionalized with the anti-HER2 antibody was higher for the cell line overexpressing HER2. The biofunctionalization of microparticles with a specific targeting molecule remarkably increases their internalization by cells in fluidic culture conditions (simulating the blood stream). This result emphasizes the importance of targeting for future in vivo delivery of drugs and bioactive molecules through microparticles.


Relationship Between Adipokines, Cognition, and Brain Structures in Old Age Depending on Obesity.
Adipokines such as leptin and adiponectin are associated with cognitive function. Although adiposity crucially affects adipokine levels, it remains unclear whether the relationship between adipokines and cognition is influenced by obesity. We enrolled 171 participants and divided them into participants with obesity and without obesity to explore the effect of obesity on the relationship between adipokines and cognition. In addition to plasma levels of leptin and adiponectin, multidomain cognitive functions and brain structures were assessed using neuropsychological testing and magnetic resonance imaging. Association between levels of these adipokines and Alzheimer's disease (AD) was then assessed by logistic regression. We found that cognitive function was negatively associated with leptin levels and leptin-to-adiponectin ratio (LAR). Such correlations between leptin and cognitive domains were prominent in participants with obesity but were not observed in those without obesity. Leptin levels were associated with lower hippocampal volumes in participants with obesity. A significant interaction of leptin and obesity was found mostly in the medial temporal lobe. Both leptin and LAR were positively associated with insulin resistance and inflammation markers in all participants. Of note, LAR was associated with a higher risk of AD after adjusting for demographic variables, Apolipoprotein E genotype, and body mass index. Obesity might be a factor that determines how adipokines affect brain structure and cognition. Leptin resistance might influence the relationship between adipokines and cognition. In addition, LAR rather than each adipokine levels alone may be a better indicator of AD risk in older adults with metabolic stress.


Endometrial factors similarly induced by IFNT2 and IFNTc1 through transcription factor FOXS1.
In ruminants, Interferon tau (IFNT) is the pregnancy recognition protein produced by the mononuclear trophectoderm of the conceptus, and is secreted into the uterine lumen during the peri-attachment period. In our previous study, the high-throughput RNA sequencing (RNA-seq) data obtained from bovine conceptuses during the peri-attachment period identified two IFNT mRNAs, IFNT2 and IFNTc1. However, how each of these IFNT variants regulates endometrial gene expression has not been characterized. Using RNA-seq analysis, we evaluated how IFNT2 and IFNTc1 affected transcript expression in primary bovine endometrial epithelial cells (EECs). IFNT treatment induced 348 differentially expressed genes (DEGs); however, there are few DEGs in IFNT2 or IFNTc1 treated EECs, indicating that IFNT2-induced DEGs were similar to those induced by IFNTc1 treatment. In in silico analysis, we identified four IFNT2- and IFNTc1-induced pathways: 1) type II interferon signaling, 2) proteasome degradation, 3) type III interferon signaling, and 4) DNA damage response. We further demonstrated that IFNT2 and IFNTc1 up-regulated several transcription factors, among which forkhead box S1 (FOXS1) was identified as the most highly expressed gene. Furthermore, the knockdown of FOXS1 in IFNT2- or IFNTc1-treated EECs similarly down-regulated 9 genes including IRF3 and IRF9, and up-regulated 9 genes including STAT1, STAT2, and IRF8. These represent the first demonstration that effects of each IFNT on EECs were studied, and suggest that endometrial response as well as signaling mechanisms were similar between two IFNT variants existed in utero.


Effects of atypical antidepressants on LSD potentiated apomorphine hypermotility in rats.
The model of LSD potentiated apomorphine hypermotility [5] was used to classify different atypical antidepressants (danitracen, mianserin, cyproheptadine) and pizotifen. All drugs have been shown to inhibit specifically the locomotor activity potentiating effect of LSD in a low dosage range (0.1-0.5 mg/kg i. p.) without influencing the apomorphine effect. Since there is some evidence that the effect of LSD is due to the inhibition of the activity of serotonergic raphe neurons, the marked antagonizing effects of danitracen, mainserin, cyproheptadine and pizotifen are regarded to be an expression of pronounced antiserotonin activity.


Parasites in surgically removed appendices as a neglected public health concern: a systematic review and meta-analysis.
The role of various parasitic infections in the occurrence of appendicitis is illustrated through cases recorded all over the world. The purpose of the current study was to estimate the global prevalence of parasite infestation (other than E. vermicularis) in appendectomy specimens.In the setting of the PRISMA guidelines, multiple databases (Science Direct, Scopus, Web of Science, PubMed, and Google Scholar) were explored in articles published until 28 September 2020. Totally, 62 studies (106 datasets) with 77, 619 participants were included in the analysis.The pooled prevalence of parasites in appendectomy samples was as follows; 0.012% (95% CI; 0.004-0.025) for Ascaris lumbricoides, 0.004% (95% CI; 0.001-0.009) for Trichuris trichiura, 0.025% (95% CI; 0.007-0.052) for Schistosoma mansoni, 0.002% (95% CI; 0.001-0.005) for Taenia spp., 0.061% (95% CI; 0.020-0.122) for Entamoeba histolytica and 0.034% (95% CI; 0.018-0.056) for Giardia lamblia.Our results demonstrated that the risk of appendicitis may increase in the presence of helminth and protozoan infections. As such, the most cases of parasites in appendectomy specimens were reported in developing countries. Regular screening plans for diagnosis, treatment and prevention are needed for prevention of parasitic infection as well as parasitic associated appendicitis, especially in endemic regions of the world.


Polyolefin matrixes with permanent antibacterial activity: preparation, antibacterial activity, and action mode of the active species.
Poly[2-(tert-butylamino)ethyl methacrylate] (PTBAEMA) belongs to a novel class of water-insoluble biocides. Dispersion of a poly(ethylene-co-butylene)-b-poly[2-(tert-butylamino)ethyl methacrylate] diblock copolymer (PEB-b-PTBAEMA) within low-density polyethylene (LDPE) imparts antimicrobial properties to the polyolefin as assessed by the viable cell counting method against Escherichia coli (E. coli). This diblock copolymer has been synthesized by atom transfer radical polymerization (ATRP) with a poly(ethylene-co-butylene) (PEB) oligomer end-capped by an activated bromide as a macroinitiator for the polymerization of 2-(tert-butylamino)ethyl methacrylate (TBAEMA). Morphological changes of E. coli bacteria in contact with modified LDPE have been observed by transmission and scanning electron microscopy and indicate that the diblock copolymer is bactericide rather than bacteriostatic. Finally, the action mode of the PEB-b-PTBAEMA copolymer more likely relies on the displacement of the Ca(2+) and/or Mg(2+) ions of the outer membrane of the bacteria, which is disorganized and finally disrupted.


[Glaucoma County Center].
Sunday 10 April it was opened in Braila Regional Centre of Glaucoma. It was located in the hospital in a new and modern space. The Braila Regional Glaucoma Centre will desire to monitoring and excellent diagnosis in Glaucoma.


Ultracytochemical and biochemical evidence for guanylate cyclase in guinea pig testis.
Guanylate cyclase activity has been studied biochemically and cytochemically in guinea pig testis. The results of the biochemical assays indicate an equal distribution of this enzyme between the soluble and particulate fractions, which have a different sensitivity to adenosine triphosphate. The cytochemical results demonstrate that the reaction product of guanylate cyclase is detectable in the interstitial capillary endothelial cells and, in the seminiferous epithelium, mainly at the level of the adjacent surfaces of Sertoli and germ cells of the intermediate and adluminal compartments. Guanylate cyclase activity appears at the level of pachytene spermatocytes and persists throughout subsequent stages of development. The distribution in the seminiferous epithelium seems to indicate that guanylate cyclase is involved in the interrelationships between Sertoli and germ cells during gamete differentiation.


Mental illness and accidental death. Case-control psychological autopsy study.
Few studies have systematically investigated the psychiatric antecedents of accidental death. To examine the patterns of psychiatric morbidities contributing to accidental death in three ethnic groups (Han, Ami and Atayal) in Taiwan. A case-control psychological autopsy was conducted among 90 accidental deaths (randomly selected from a total of 413) and 180 living controls matched for age, gender, ethnicity and area of residence in Taiwan. The risk of accidental death was significantly associated with alcohol use disorder and with other common mental disorders. When jointly considered, it was greatest when these two types of disorders co-existed, followed by common mental disorders alone. The risk of accidental death increased with the number of comorbid conditions. The prevention of accidental death should be incorporated into preventive psychiatry, not just for alcohol use disorder, but also for all other common mental disorders.


Increased liver tumor formation in neutral sphingomyelinase-2-deficient mice.
Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C16-ceramide, concurrent with upregulation of ceramide synthase 5. The fro/fro liver tumor, but not adjacent tissue, exhibited substantial accumulation of lipid droplets, suggesting that nSMase2 deficiency is associated with tumor growth and increased neutral lipid generation in the tumor. Tumor tissue expressed significantly increased levels of CD133 and EpCAM mRNA, two markers of liver cancer stem-like cells (CSCs) and higher levels of phosphorylated signal transducer and activator of transcription 3, an essential regulator of stemness. CD133(+) cells showed strong labeling for SM and ceramide. In conclusion, these results suggest that SMase-2 deficiency plays a role in the survival or proliferation of CSCs, leading to spontaneous tumors, which is associated with tumor-specific effects on lipid homeostasis.


Vasculitis confined to the peripheral nerve and skin: a variant of non-systemic vasculitic neuropathy.
We describe a patient presenting with vasculitic neuropathy associated with cutaneous vasculitis in the absence of other clinical or laboratory evidence of the underlying systemic vasculitis, and showing a favourable prognosis. Although the early proposed criteria for the diagnosis of non-systemic vasculitic neuropathy (NSVN) exclude the involvement of extraneural tissues, the condition observed in our patient might represent a variant of NSVN, with the vasculitis confined to the small vessels in both the peripheral nerve and the skin.


The effect of population shift on land cover change and illegal forest activities.
Interaction between humans and forests has always been strong. Wood has been at the core of all humankind's endeavors since the discovery of fire and learning how to fabricate it out of trees. The exploitation of forests has not been limited to the procurement of wood, but the concepts of sheltering, hunting, and protection have also been matured near or within the forests. This win-win situation intuitively attracted more and more people to this type of resource. As the human population has grown in forest villages, the pressure caused by the human on the forests has increased. Without active management of the forests, the situation has become so dire that uncontrolled and irregular utilization has started jeopardizing the existence of this resource. The objective of this study was to examine the changes in forest road, forestland cover, and forest crimes in the Daday Forest Enterprise (DFE) located in Kastamonu Regional Directorate of Forestry, Turkey. The results indicated that the population in 51 forest villages was decreased from 1975 to 1990. This decrease was also apparent in all villages across the region during the 1990-2000 period and continued decreasing in 45 villages during the 2000-2016 period. The forestland cover was 57% in 1975, 44% in 2000, and 57% in 2016 while the density in the forest road kept increasing. A noticeable decrease in the forest-related crimes was also determined, and the results showed that effective forest management, consciousness, and conservation policies stopped the deterioration.


Future population distribution in the past and present.
"There is at present much public interest in the future geography of the Netherlands. Plans for new infrastructure to accommodate rail, road and air traffic are hotly debated. The location of new residential areas and the disposition of economic activity are also frequently discussed. Supply and demand of employment and housing show diverging trends in various parts of the country. For planners this raises the question as to the likely or advisable future population distribution."


Microbiological impact of spray washing broiler carcasses using different chlorine concentrations and water temperatures.
A study was conducted to investigate the microbiological impact of spray washing broiler carcasses with chlorinated water (0 or 50 ppm) at different temperatures (21.1, 43.3, or 54.4 degrees C). A whole carcass rinse (WCR) was performed on each carcass before (control) and after spray washing (final). After the control WCR, carcasses were inoculated with 0.1 g of cecal material containing 2 x 10(5) cells per gram of Campylobacter and 2 x 10(5) cells per gram of nalidixic acid-resistant Salmonella. Carcasses were held at room temperature for 12 min before washing in an inside-outside bird washer (80 psi for 5 s). Chlorine level and water temperature had no effect on total aerobic bacteria, Escherichia coli, or Campylobacter numbers recovered from the final WCR. Levels of bacteria found on carcasses before and after washing were 4.6, 3.6, and 3.5 log10 cfu/mL rinse for total aerobic bacteria, E. coli, and Campylobacter, respectively. Average counts for nalidixic acid-resistant Salmonella after washing were 3.1 log10 cfu/ mL rinse irrespective of water temperature or chlorine level (P < 0.05). In addition, chlorine level and water temperature had no effect on the breast skin color, with average values of L* = 66.6; a* = -0.09; b* = -0.05 (P < 0.05). Under the conditions outlined in the present study, adding chlorine and/or elevating the water temperature during spray washing in an inside-outside bird washer did not enhance the removal of bacteria from broiler carcasses and had no effect on carcass skin color.


Gamete intrafallopian transfer. An overview.
Gamete intrafallopian transfer involves a direct transfer of both human gametes, sperm and oocytes, into the fallopian tube. Since the first report of a successful pregnancy following the use of this technique by Asch et al in 1984, its role in the treatment of infertile women with patent tubes has been established. Recent data demonstrate a 34.4% clinical pregnancy rate, with the highest pregnancy rate achieved in infertile women due to endometriosis or unexplained infertility.


Comparative study of two trehalases from Candida utilis.
Candida utilis ATCC 60459 contains two intracellular trehalase enzymes clearly distinguishable by molecular weight, behaviour in ion-exchange chromatography and kinetic properties. The high molecular weight trehalase (500 kDa trehalase) is specifically inhibited by acetate and accounts for less than 30% of the total trehalase activity found in cell extracts. The smaller trehalase (280 kDa trehalase) exists mostly as a cryptic enzyme whose activity can be postranslationally activated by cAMP-dependent phosphorylation. The enzyme activity of the 280 kDa trehalase is strongly inhibited by Zn2+ and markedly enhanced in the presence of Ca2+ and Mn2+. The activation by these cations, contrariwise to that induced by ATP and cAMP, does not imply a covalent modification of the 280 kDa enzyme. Several parameters have been determined for both enzymes. The 280 kDa enzyme has the properties shown by the so-called regulatory trehalases whereas the 500 kDa enzyme presents characteristics of a nonregulatory type of trehalase.


The Impact of Plastic Surgery Volume on Inpatient Burn Outcomes.
Acute burn care involves multiple types of physicians. Plastic surgery offers the full spectrum of acute burn care and reconstructive surgery. The authors hypothesize that access to plastic surgery will be associated with improved inpatient outcomes in the treatment of acute burns. Acute burn encounters with known percentage total body surface area were extracted from the National Inpatient Sample from 2012 to 2014 based on International Classification of Diseases, Ninth Edition, codes. Plastic surgery volume per facility was determined based on procedure codes for flaps, breast reconstruction, and complex hand reconstruction. Outcomes included odds of receiving a flap, patient safety indicators, and mortality. Regression models included the following variables: age, percentage total body surface area, gender, inhalation injury, comorbidities, hospital size, and urban/teaching status of hospital. The weighted sample included 99,510 burn admissions with a mean percentage total body surface area of 15.5 percent. The weighted median plastic surgery volume by facility was 245 cases per year. Compared with the lowest quartile, the upper three quartiles of plastic surgery volume were associated with increased likelihood of undergoing flap procedures (p < 0.03). The top quartile of plastic surgery volume was also associated with decreased odds of patient safety indicator events (p < 0.001). Plastic surgery facility volume was not significantly associated with a difference in the likelihood of inpatient death. Burn encounters treated at high-volume plastic surgery facilities were more likely to undergo flap operations. High-volume plastic surgery centers were also associated with a lower likelihood of inpatient complications. Therefore, where feasible, acute burn patients should be triaged to high-volume centers. Therapeutic, III.


Oxidative stress enhances cephalosporin resistance of Enterococcus faecalis through activation of a two-component signaling system.
Enterococcus faecalis is a low-GC Gram-positive bacterium, a normal resident of the gastrointestinal (GI) tract, and an important hospital-acquired pathogen. An important risk factor for hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporins, antibiotics that impair cell wall biosynthesis by inhibiting peptidoglycan cross-linking. Enterococci are intrinsically resistant to cephalosporins; however, environmental factors that modulate cephalosporin resistance have not been described. While searching for the genetic determinants of cephalosporin resistance in E. faecalis, we unexpectedly discovered that oxidative stress, whether from external sources or derived from endogenous metabolism, drives enhanced intrinsic resistance to cephalosporins. A particular source of oxidative stress, H2O2, activates signaling through the CroR-CroS two-component signaling system, a known determinant of cephalosporin resistance in E. faecalis. We find that CroR-CroS is required for adaptation to H2O2 stress and that H2O2 potentiates the activities of cephalosporins against E. faecalis when the CroR-CroS signaling system is nonfunctional. Rather than directly detecting H2O2, our data suggest that the CroR-CroS system responds to cell envelope damage caused by H2O2 exposure in order to promote cell envelope repair and enhanced cephalosporin resistance.


Community-adapted methicillin-resistant Staphylococcus aureus (MRSA): population dynamics of an expanding community reservoir of MRSA.
To define methicillin-resistant Staphylococcus aureus (MRSA) reservoirs in the community and their population dynamics, we studied the molecular epidemiology of a random sample (n=490) from a collection of 2154 inpatient and outpatient MRSA isolates during a 7-year period in San Francisco. We noted a progressive replacement of type II staphylococcal chromosomal cassette (SCC)mec-bearing isolates with type IV SCCmec-bearing isolates, which coincided with >4-fold increase in methicillin resistance between 1998 and 2002. Type IV SCCmec-bearing isolates involved in the increase in methicillin resistance belonged to 4 molecular genotypes. These 4 genotypes were associated predominantly with community-onset disease, rather than hospital- or long-term-care facility-onset disease (76.9% vs. 19.4% vs. 3.7%; P=.0005), suggesting that they are not feral descendants of hospital isolates. The longitudinal results linked the dramatic increase in MRSA infections to an expanding community reservoir of MRSA genotypes with intrinsic community survival advantage.


[A case report of a solid and cystic tumor of the pancreas in a 33-year-old woman].
An unusual case of a solid and cystic tumor of the pancreas is presented. A 33-year-old woman with a 15-year history of an abdominal tumor underwent a pancreatectomy. The tumor was encapsulated by a thick connective tissue and exhibited two main patterns: solid sheets of relatively uniform small cells; and, a papillary proliferation with a central fibrovascular talk. The tumor cells had PAS and d-PAS reactive granules in the cytoplasm. Immunohistochemically, a positive reaction for alpha l-antitrypsin and a carcinoembryonic antigen, as well as a weekly positive reaction for a vasoactive intestinal polypeptide also were found in the cytoplasm. Our results lead us to suggest that an S-C tumor is likely to be a tumor of a acinar cell origin.


Two conserved essential motifs of the murine immunoglobulin lambda enhancers bind B-cell-specific factors.
Two highly homologous enhancers associated with the two murine immunoglobulin lambda constant-region clusters were recently identified. In order to better understand the molecular basis for the developmental stage- and cell-type-restricted expression of lambda genes, we have undertaken an analysis of the putative regulatory domains of these enhancers. By using a combination of DNase I footprinting, electrophoretic mobility shift assay, and site-specific mutations, four candidate protein binding sites have been identified at analogous positions in both enhancers. A mutation of any of these sites decreases enhancer activity. Two of the sites, lambda A and lambda B, are essential for enhancer function, and both of these sites appear to bind both B-cell-specific and general factors. Nevertheless, isolated lambda A and lambda B sites show no evidence of inherent transactivating potential, alone or together, even when present in up to three copies. We suggest that the generation of transactivating signals from these enhancers may require the complex interaction of multiple B-cell-specific and nonspecific DNA-binding factors.


Structure of the 5'-flanking regulatory region of the mouse gene encoding the clearance receptor for atrial natriuretic peptide.
A full-length cDNA, encoding the mouse atrial natriuretic peptide clearance receptor (ANP-CR), was isolated from a mouse lung cDNA library. The deduced amino acid sequence of the mouse ANP-CR, showing a typical tripartite organization which lacks a guanylyl cyclase domain, was extremely well conserved compared with the ANP-CR homologs. To understand the molecular mechanisms underlying the regulation of mouse ANP-CR gene expression and to define the essential DNA sequences for the transcriptional activity, a genomic clone containing over 9 kb of the 5'-flanking region of the mouse ANP-CR gene has been isolated from a mouse genomic library. Sequence analysis revealed that the 2.3-kb region upstream from an ATG codon of the mouse ANP-CR gene contained a number of putative regulatory elements; TATA box, CAAT box, cAMP response element, AP-1 and two shear stress responsive elements. Additionally, an unusual feature was the presence of the tandem-repeated AP-2-like elements, which were closely overlapped with SP-1 element. Promoter analysis using deletion plasmids in mouse Balb/3T3 cells, highly producing ANP-CR mRNA, demonstrated that deletion of the sequence from -144 to +46 relative to the transcription start point caused a dramatic decrease of the transcriptional activity and that the TATA box at -269 was not essential for the basal transcriptional activity. Primer extension analysis indicated that transcription of the mouse ANP-CR gene starts from at least two major sites, suggesting that the sequence from -144 to +46, which was shown to involve a novel sequence composed of tandem-repeated TATA-box-like elements, contained promoter sequences. Furthermore, cis-acting negative elements were shown to be situated in three regions (from -1178 to -708, from -707 to -625 and from -248 to -145) of the mouse ANP-CR gene promoter.


Adenine nucleotide regulation of malate oxidation in isolated mung bean hypocotyl mitochondria.
We have studied the effects of ATP and ADP on the oxidation of malate by coupled and uncoupled mitochondria prepared from etiolated hypocotyls of mung bean (Vigna radiata L.).In coupled mitochondria, ATP (1 millimolar) increased pyruvate production and decreased oxaloacetate formation without altering the rate of oxygen consumption. ATP also significantly decreased oxaloacetate production and increased pyruvate production in mitochondria that were uncoupled by carbonyl cyanide p-trifluoromethoxyphenyl hydrazone plus oligomycin.In coupled mitochondria, ADP (1 millimolar) increased the production of both pyruvate and oxaloacetate concomitantly with the acceleration of oxygen uptake to the state 3 rate. The effects of ADP were largely eliminated in uncoupled mitochondria. These results indicate that, whereas the ADP stimulation of oxaloacetate and pyruvate production in the coupled mitochondria is brought about primarily as the result of the accelerated rates of electron transport and NADH oxidation by the respiratory chain in state 3, ATP has significant regulatory effects independent of those that might be exerted by control of electron transport.


[The combined radiation and hormonal therapy of prostatic carcinoma: a conceptual analysis].
The concept of a combination of radiotherapy and hormonal therapy for the treatment of locally advanced carcinoma of the prostate was evaluated in view of an improved success rate compared to radiotherapy alone. At present, however, radiotherapy still remains the central mode of therapy in the treatment of the local tumor. The time sequence in a combination with hormonal therapy is of importance. Antecedent hormonal treatment can reduce tumor size, thus improving local conditions for percutaneous--and especially interstitial--radiotherapy; it is indicated in patients with voiding problems. An improvement in survival rates has so far not been achieved, however, local tumor remission rates are better. With concomitant hormonal therapy, compared to radiotherapy alone, tumor progression rates are lower. It remains to be seen, whether these results can be improved by using newer pharmacological ways of androgen blockade. The application of androgen withdrawal as a secondary measure with local tumor persistence or progression after radiotherapy remains a palliative treatment of limited efficacy. Due to the heterogeneity of the available study reports and the concurrent lack of controlled, randomized trials, a conclusive evaluation of the concept of combined radio- and hormonal therapy of prostatic cancer is as yet not possible.


Differential Induction of Cytoplasmic Vacuolization and Methuosis by Novel 2-Indolyl-Substituted Pyridinylpropenones.
Because many cancers harbor mutations that confer resistance to apoptosis, there is a need for therapeutic agents that can trigger alternative forms of cell death. Methuosis is a novel form of non-apoptotic cell death characterized by accumulation of vacuoles derived from macropinosomes and endosomes. Previous studies identified an indole-based chalcone, 3-(5-methoxy-2-methylindol-3-yl)-1-(4-pyridinyl)-2-propen-1-one (MOMIPP), that induces methuosis in human cancer cells. Herein, we describe the synthesis of related 2-indolyl substituted pyridinylpropenones and their effects on U251 glioblastoma cells. Increasing the size of the 2-indolyl substituent substantially reduces growth inhibitory activity and cytotoxicity, but does not prevent cell vacuolization. Computational models suggest that the results are not due to steric-driven conformational effects. The unexpected uncoupling of vacuolization and cell death implies that the relationship between endosomal perturbations and methuotic cell death is more complex than previously realized. The new series of compounds will be useful in further defining the molecular and cellular mechanisms underlying methuosis.


Knockdown of lncRNA LEF1-AS1 inhibited the progression of oral squamous cell carcinoma (OSCC) via Hippo signaling pathway.
It is verified that long non-coding RNAs (lncRNAs) play crucial roles in various cancers. LncRNA LEF1-AS1 is a reported oncogene in colorectal cancer and glioblastoma. In this study, we unveiled that LEF1-AS1 markedly increased in oral squamous cell carcinoma (OSCC) tissues and cell lines. Besides, OSCC patients with high levels of LEF1-AS1 were apt to poor prognosis. Functionally, LEF1-AS1 knockdown inhibited cell survival, proliferation and migration, whereas enhanced cell apoptosis and induced G0/G1 cell cycle arrest in vitro. Consistently, LEF1-AS1 silence hindered tumor growth in vivo. Moreover, LEF1-AS1 inhibition stimulated the activation of Hippo signaling pathway through directly interacting with LATS1. Furtherly, we disclosed that LEF1-AS1 silence abolished the interaction of LEF1-AS1 with LATS1 while enhanced the binding of LATS1 to MOB, therefore promoting YAP phosphorylation but impairing YAP1 nuclear translocation. Additionally, we demonstrated that LEF1-AS1 regulated YAP1 translocation via a LATS1-dependent manner. Furthermore, we also uncovered that YAP1 overexpression abolished the suppressive impact of LEF1-AS1 repression on the biological processes of OSCC cells. In a word, we concluded that LEF1-AS1 served an oncogenic part in OSCC through suppressing Hippo signaling pathway by interacting with LATS1, suggesting the therapeutic and prognostic potential of LEF1-AS1 in OSCC.


Trimetazidine reduces endogenous free fatty acid oxidation and improves myocardial efficiency in obese humans.
The metabolic modulator trimetazidine (TMZ) has been suggested to induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose utilization, but this mechanism remains unproven in humans. The oxidation of plasma derived FA is commonly measured in humans, whereas the contribution of FA from triglycerides stored in the myocardium has been poorly characterized. To verify the hypothesis that TMZ induces a metabolic shift, we combined positron emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to measure myocardial FAO from plasma and intracellular lipids, and myocardial glucose metabolism. Nine obese subjects were studied before and after 1 month of TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure myocardial lipids, the latter being integrated into the PET data analysis to quantify myocardial triglyceride turnover. Myocardial FAO derived from intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and cardiac work were positively associated with the oxidation of plasma derived FA (P ≤ 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 ± 8.0 to 19.6 ± 4.0 μmol/min and 23.7 ± 7.5 to 10.3 ± 2.7 μmol/min, respectively; P ≤ 0.05). These changes were accompanied by increased cardiac efficiency since unchanged LV work (1.6 ± 0.2 to 1.6 ± 0.1 Watt/g × 10(2), NS) was associated with decreased work energy from the intramyocardial triglyceride oxidation (1.6 ± 0.5 to 0.4 ± 0.1 Watt/g × 10(2), P = 0.036). In obese subjects, we demonstrate that myocardial intracellular triglyceride oxidation significantly provides FA-derived energy for mechanical work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving myocardial efficiency.