Endoscopic closure of tracheoesophageal fistulas with the over-the-scope clip system.
Management of Tracheoesophageal Fistulas (TEFs) is associated with high morbidity and mortality and remains an interdisciplinary challenge. We describe the first two cases of successful endoscopic closure of TEFs due to tracheostomy tube and thoracic hydatid cysts surgery, using the Over-The-Scope Clip (OTSC) system. The OTSC system is composed of an application cap, which is mounted onto the distal tip of the endoscope and a connected releasing mechanism, installed on the handle of the scope. The rotation of the handle allows the release of the clip by a two tube sliding mechanism. Atraumatic version of OTSCs with medium sized caps, twin graspers and anchor were used in these cases. Both fistulae were successfully sealed with one clip. No complication was observed that could be ascribed to the clip itself or to the technique. One patient died because of pneumonia and septicemia after 1 week, but the symptoms of other patient were immediately improved. A thoracic radiography taken after 1 month showed that the clip is in place. Although prospective comparative clinical studies are needed to work out the drawbacks of the new OTSC device, it might be considered as a valid alternative to operation in TEFs.


Early diagnosis of pregnancy failure with transvaginal ultrasound.
Vaginal ultrasound was used to assess a consecutive series of 353 patients to determine the minimum mean gestation sac diameter at which a failed pregnancy could be diagnosed. Fetal heart movements could be demonstrated in all pregnancies with living fetuses when the mean sac diameter exceeded 1.2 cm. Vaginal ultrasound is superior to both static and transabdominal real-time ultrasound in the diagnosis of early pregnancy failure.


Cytomegalovirus Disease in Children With Acute Lymphoblastic Leukemia in the Nontransplant Setting: Case Series and Review of the Literature.
Cytomegalovirus (CMV) disease in pediatric acute lymphoblastic leukemia in the nontransplant setting is very rare. We report our experience with 4 such cases, and review the literature (n=12). The median age at diagnosis was 10 years and 50% of patients were males. Among the 11 cases with available information at the time of diagnosis, CMV disease occurred during maintenance therapy in 10 patients. Fever was present in 9 cases. CMV disease manifested as retinitis in 6, hepatosplenic disease in 3, pneumonitis in 1, and hemophagocytic lymphohistiocytosis in 1 patient. One patient had both CMV retinitis and CMV-related hemophagocytic lymphohistiocytosis. Four of the 7 patients with retinitis complained of visual disturbance at diagnosis. CMV viremia was present in 10 patients. Three patients had at least 1 relapse and developed permanent visual defects, and 1 patient developed recurrent retinal detachment. In conclusion, prolonged immunosuppression is the major etiology and retinitis is the most common manifestation of CMV disease. As a significant number of patients with retinitis are asymptomatic, early diagnosis and treatment is important to prevent permanent visual loss.


Vitamin E protects against retinopathy of prematurity through action on spindle cells.
In the premature infant, exposure of the incompletely vascularized retina to increased oxygen tension can result in the development of a blinding disease, retinopathy of prematurity (ROP). Despite the judicious curtailment of oxygen, the incidence of ROP is on the increase due to the technological advances that have improved the survival of the very young preterm infant. Six clinical trials have documented the efficacy of vitamin E supplementation in suppressing the development of severe ROP, but the mechanism of this protection has remained unknown. This report proposes that spindle cells, mesenchymal precursors of the inner retinal capillaries, are the primary inducers of the neovascularization associated with ROP. Exposure of spindle cells to elevated oxygen tension increases their gap junction area. This early morphologic event immediately halts the normal vasoformative process and eventually triggers the neovascularization that is observed clinically 8-12 weeks later. Vitamin E supplementation above the deficient plasma levels of these infants suppresses gap junction formation and clinically reduces the severity without altering the total incidence of ROP.


The effect of prenatal highly active antiretroviral therapy on the transmission of congenital and perinatal/early postnatal cytomegalovirus among HIV-infected and HIV-exposed infants.
Before highly active antiretroviral therapy (HAART), congenital cytomegalovirus (CMV) rates were higher among human immunodeficiency virus (HIV)-exposed infants than unexposed infants. This study examines congenital and perinatal/early postnatal (P/EP) CMV among HIV-exposed infants pre- and post- HAART. Infants born to HIV-infected women were evaluated for congenital CMV (CMV-positive culture in first 3 weeks of life) and P/EP CMV (positive culture in first 6 months of life). Prenatal maternal HAART was defined as triple antiretroviral therapy (ART) with at least 1 nonnucleoside reverse-transcriptase inhibitor or protease inhibitor. Among 414 infants evaluated, 1678 CMV assessment days were completed (mean = 3 assessment days per infant). Congenital CMV rates did not differ by time period, HAART use, or infant HIV infection status. P/EP CMV rates were greater for the 1988-1996 birth cohort (17.9%) compared with the 1997-2002 birth cohort (8.9%) (P < .01), HIV-infected versus uninfected infants (P < .01), and infants with no maternal ART versus those with ART (P < .01). Controlling for potential confounders, P/EP CMV was associated with no maternal ART (odds ratio = 4.7; P < .01), and among those with no maternal ART, P/EP CMV was associated with maternal CD4 count ≤200 cells/μL (P < .01). For HIV-uninfected infants with P/EP CMV, symptoms including splenomegaly, lymphadenopathy, and hepatomegaly were associated with no maternal HAART versus those with HAART (41% vs 6%; P < .05). Although congenital CMV rates did not change, the post-HAART era showed reduced P/EP CMV and occurrence of related clinical symptoms. These findings underscore the importance of prenatal HAART for all HIV-infected pregnant women.


Student perspectives on animal-welfare education in American veterinary medical curricula.
Animal welfare is a subject of increasing interest to society, and the veterinary medical profession has an opportunity--and a duty--to provide leadership and expertise. This commentary presents the view of two veterinary students at the Louisiana State University School of Veterinary Medicine and the University of Missouri College of Veterinary Medicine on the current state of animal-welfare education in American veterinary colleges. In our experience, animal welfare and its related disciplines are underemphasized in current American professional curricula. We present a case for why animal welfare must be a cardinal subject of instruction in veterinary colleges, detail the essential components of sufficient animal-welfare education, and discuss specific methods for integrating animal welfare into the current curricula. We strongly encourage veterinary colleges to identify animal-welfare education as a priority and to work toward increasing instruction and educational resources in this critical topic area.


A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth.
The family of tissue inhibitors of metalloproteinases (TIMPs) presently numbers four distinct gene products that are specific inhibitors of the matrix metalloproteinases (MMPs). The local balance between MMPs and TIMPs is believed to play a major role in extracellular matrix (ECM) remodeling during development and in diseases such as cancer and arthritis. Unlike the other TIMPs, which are soluble. TIMP-3 is unique in being a component of ECM. Mutations in the human TIMP-3 gene cause a dominantly inherited, adult-onset blindness (Sorsby's fundus dystrophy or SFD). In this article, we summarize what is currently known about TIMP-3, discuss possible mechanisms leading up to SFD, and investigate the effect of TIMP-3 on tumor growth. Breast carcinoma and malignant melanoma cell lines were transfected with TIMP-3 expression plasmids and injected subcutaneously into nude mice. Growth curves of the resulting tumors over a period of 6 to 8 weeks demonstrated that increased expression of TIMP-3 resulted in a statistically significant suppression of tumor growth. Deposition of TIMP-3 in the surrounding ECM by tumor cells may inhibit tumor growth by preventing local expansion of tumor, retarding the release of growth factors sequestered in ECM, or inhibiting angiogenesis. TIMP-3 over-expression had no effect on the growth of the two tumor cell lines in vitro. Because recombinant TIMP-3 inhibits endothelial cell migration and tube formation in response to angiogenic factors, we believe that the effect of TIMP-3 on tumor growth seen in this study may be a consequence of its angiostatic action.


Early compensation of vestibulo-oculomotor symptoms after unilateral vestibular loss in rats is related to GABA(B) receptor function.
The horizontal vestibulo-oculomotor reflex was studied in pigmented rats during the first 5 days after a unilateral chemical or surgical vestibular deafferentation. Spontaneous eye movements in darkness and slow phase velocity gain of compensatory eye movements during horizontal sinusoidal rotation were evaluated. The most evident vestibulo-oculomotor symptom immediately after a unilateral vestibular loss was a spontaneous nystagmus, which gradually abated during the following days. Further, an asymmetry between ipsi- and contra-lesional gains was evident during sinusoidal vestibular stimulation. Single systemic doses of the GABA(B) receptor antagonist [3-[1-(S)-[[3-(cyclohexylmethyl)-hydroxyphosphinoyl]-2-(S)-hydroxypropyl]amino]ethyl]-benzoic acid (CGP 56433A), the agonist baclofen, or the GABA(A) receptor agonist (4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol (THIP) were given at different intervals after unilateral vestibular deafferentation. CGP 56433A highly aggravated the vestibulo-oculomotor symptoms, observed as an increase in spontaneous nystagmus and slow phase velocity gain asymmetry. This effect was most pronounced during the first 2 days after unilateral vestibular loss, when CGP 56433A even decompensated the vestibular system to the extent that all vestibular responses were abolished. Baclofen caused no effect during the first days after unilateral vestibular loss, but in parallel with the abatement of spontaneous nystagmus, the drug equilibrated or even reversed the remaining spontaneous nystagmus with corresponding effects on the slow-phase velocity gain asymmetry. The effects of baclofen were very similar after both chemical and surgical deafferentation. THIP caused a slight depression of all vestibular responses. All single dose effects of the drugs were transient. Altogether these results reveal that endogenous stimulation of GABA(B) receptors in GABA-ergic vestibulo-oculomotor circuits are important for reducing the vestibular asymmetry during the early period after unilateral vestibular deafferentation. A possible role for GABA(B) receptors in the reciprocal inhibitory commissural pathways in the vestibular nuclei is suggested.


Efficacy of mesenchymal stem cells in the treatment of gastrointestinal malignancies.
Mesenchymal stem cells (MSCs), which are a kind of stem cell, possess an immune privileged nature, tumour homing features, and multi-lineage differentiation ability. MSCs have been studied in many fields, such as tissue engineering, nervous system diseases, and cancer treatment. In recent years, an increasing number of researchers have focused on the effects of MSCs on various kinds of tumours. However, the concrete anticancer efficacy of MSCs is still controversial. Gastrointestinal (GI) malignancies are the major causes of cancer-related death worldwide. The interactions of MSCs and GI cancer cells in specific conditions have attracted increasing attention. In this review, we introduce the characteristics of MSCs and analyse the effects of MSCs on GI malignancies, including gastric cancer, hepatoma, pancreatic cancer, and colorectal cancer. In addition, we also provide our perspectives on why MSCs may play different roles in GI malignancies and further research directions to increase the treatment efficacy of MSCs on GI malignancies.


Sleep well, think well: sleep-wake disturbance in mild cognitive impairment.
While literature suggests that sleep is important for cognition and mood, and that sleep disturbance is a prominent feature of neurodegenerative and neuropsychiatric disorders, these relationships have not yet been examined in older people ''at risk" of dementia. In this study, 15 older people with the nonamnestic subtype of mild cognitive impairment ([MCI] mean age = 66.7 years, SD = 8.7) underwent psychiatric and neuropsychological assessment. Participants completed sleep diaries, questionnaires, and 2 weeks of actigraphy. Key outcome data during the rest interval were time spent ''awake" or wake after sleep onset (WASO) and the number of arousals/wake bouts. Results showed that even after controlling for age, greater WASO was associated with reduced attention and executive functioning and increased arousals were related to poorer nonverbal learning and problem solving. This preliminary data suggests that sleep-wake disturbance in nonamnestic forms of MCI is related to cognitive functioning and may be indicative of shared neurobiological underpinnings.


Association of neutrophil gelatinase associated lipocalin, ischemia modified albumin with uric acid in the etiopathogenesis of preeclampsia.
Preeclampsia is a multisystem illness that manifests in the third trimester of pregnancy after 20 weeks of gestation and is marked by proteinuria and hypertension (PE). Changes in lifestyle, such as eating a high-calorie diet and delaying delivery, have raised the likelihood of developing PE. Eclampsia, abrupt renal failure, thromboembolic episodes leading to cardiac and brain problems, pulmonary embolism, and coagulopathy associated with HELLP syndrome are a few of the complications that might follow preeclampsia in pregnant moms. The objects of this study is to estimate and correlate the levels of NGAL (neutrophil gelatinase associated lipocalin), IMA (ischemia modified albumin) and Uric acid in prreclampsia. 40 diagnosed cases of preeclampsia and 40 healthy age and gestational age matched healthy controls were included in the study. Blood samples were collected from them and serum NGAL, IMA and Uric acid levels were estimated. Estimation of NGAL (neutrophil gelatinase associated lipocalin), IMA (ischemia modified albumin) was done by commercially available ELISA kits standard spectrophotometry methods in autoanalyzer Mind ray BS300 using commercially available kits. The parameters of NGAL and IMA were significantly increased in patients with PE (p<0.001) when compared with the healthy control subjects. γ-glutamyl transferases and OPN were found in patients with ALD (p<0.001) when compared with the control subjects. OPN showed significant positive correlations with AST (r=0.76, p<0.001), ALT (r=0.64 p<0.001), ALP (r=0.68, p<0.001), and GGT (r=0.61, p<0.001). The current study focuses on the roles of NGAL and IMA, two sensitive markers of kidney injury that are particularly useful in identifying widespread endothelial dysfunction. As a result, the pattern of elevated NGAL and IMA levels can be useful for diagnosis.


Arterial features of inner canthus region: confirming the safety for the flap design.
The medial canthus represents a fixed-point fulcrum that is necessary for eyelid function. The aim of the study was to investigate the arterial distribution of the inner canthus. The origin, calibration, and branches of the inner canthus arteries and their topographical relations were examined by dissecting 19 cadavers, injecting red latex to their corresponding 38 nasal sections before the dissection. The distance from the dorsal nasal artery to the inner canthus was found to be 7.2 +/- 0.3 mm. In this study, the average diameter of the dorsal nasal artery was 0.74 mm on the right side and 0.88 mm on the left. Concerning the course of dorsal nasal artery on the lateral side of the nose, 4 types were observed. In most of the examples (44.7%), dorsal nasal artery anastomosed with angular artery via thick branch and gave off supplying branches to the medial canthus and to the lateral side of the nose. Dorsal nasal artery is a vessel of satisfactory size and is potentially a good vascular source for a thin free flap. It may be an ideal flap to reconstruct the eyelid defect for texture and color similarity of the inner canthus skin. A better understanding of the inner canthus vascularity should allow modification of reconstructive techniques and reduce postoperative complications.


Eradication of cervical canal colonization associated with prophylactic cervical cerclage: the look further study.
The perioperative management of the cervical cerclage procedure is not unified. In general population controlling microbiome cervical status does not affect obstetric outcomes, but it might be beneficial in patients with cervical insufficiency. The aim of our study was to present the obstetric, neonatal and pediatric outcomes of patients undergoing the cervical cerclage placement procedure in our obstetric department using a regimen of care that includes control of the microbiological status of the cervix and elimination of the pathogens detected. Thirty-five patients undergoing cervical cerclage in the 2nd Department of Obstetrics and Gynecology, Medical University of Warsaw, were included in the study. The procedure was performed only after receiving a negative culture from the cervical canal. Thirty-one (88.6%) patients delivered after the 34th and twenty-eight (80.0%) after the 37th week of gestation. The colonization of the genital tract was present in 31% of patients prior to the procedure, in 42% of patients - during the subsequent pregnancy course and in 48% of patients - before delivery. A total of 85% of patients who had miscarriage or delivered prematurely had abnormal cervical cultures. In patients with normal cervical cultures, and 91.7% of women delivered at term. No abnormalities in children's development were found. Controlling microbiological status of the cervical canal results in better or similar outcomes to those reported by other authors in terms of obstetric and neonatal outcomes. Active eradication of the reproductive tract colonization potentially increases the effectiveness of the cervical cerclage placement.


[Clinical evaluation of gallbladder and common bile duct stones treated though cholecystostomy tube].
Objective: To investigate the efficacy, feasibility and safety of treatment of gallbladder and common bile duct stones treated through cholecystostomy tube. Methods: The clinical data of 17 patients with gallbladder and common bile duct stones treated through cholecystostomy tube from January 2012 to December 2016 was analyzed retrospectively. Results: Seventeen patients were successfully treated with percutaneous transhepatic gallbladder (PTGD), and 88.2% (15/17) patients had clinical symptom relief. There was no complication happened after PTGD and fistula expansion. All the stones were removed and there was 11.7% (2/17) of gallbladder bleeding, 5.9% (1/17) of pancreatitis, and 5.9% (1/17) of hyperamylasemia after stones extraction. The patients had gone through an average treatment period of 87.8±16.0 days, hospitalization of 5.5±0.6 times and 43.3±4.5 days, cost of 60.0±8.0 thousand, 6.9±0.9 operations, 1.4±0.6 stone extraction operations with the average time of 58.4±21.2 min. The duodenal papillary balloon dilatation rate was 82.4% (14/17). Conclusion: The treatment through cholecystostomy tube is an effective, safe and feasible technique for gallbladder and common bile duct stones. However, there are many shortcomings such as long treatment cycle, large number of hospitalization and operations, difficult operation and high cost.


Association between triglyceride levels and cardiovascular disease in patients with acute pancreatitis.
Conventional wisdom supports prescribing "fibrates before statins", that is, prioritizing treatment of hypertriglyceridemia (hTG) to prevent pancreatitis ahead of low-density lipoprotein cholesterol to prevent coronary heart disease. The relationship between hTG and acute pancreatitis, however, may not support this approach to clinical management. This study analyzed administrative data from the Veterans Health Administration for evidence of (1) temporal association between assessed triglycerides level and days to acute pancreatitis admission; (2) association between hTG and outcomes in the year after hospitalization for acute pancreatitis; (3) relative rates of prescription of fibrates vs statins in patients with acute pancreatitis; (4) association of prescription of fibrates alone versus fibrates with statins or statins alone with rates of adverse outcomes after hospitalization for acute pancreatitis. Only modest association was found between above-normal or extremely high triglycerides and time until acute pancreatitis. CHD/MI/stroke occurred in 23% in the year following AP, supporting cardiovascular risk management. Fibrates were prescribed less often than statins, defying conventional wisdom, but the high rates of cardiovascular events in the year following AP support a clinical focus on reducing cardiovascular risk factors.


Innovative dairy cow management to improve resistance to metabolic and infectious diseases during the transition period.
The incidence of metabolic and infectious diseases varies greatly during the lactation cycle. Most new cases of clinical mastitis appear at the beginning of lactation, and the incidence increases with the level of milk production. In addition to mastitis, many other infectious diseases become clinically apparent during the first 2weeks of lactation. During this time, cows are in a negative energy balance and must mobilize body reserves to balance the deficit between food energy intake and energy required for milk production. The relationships between energy deficit and metabolic diseases, such as ketosis and hepatic lipidosis, are well known. Furthermore, cows in energy deficit have a weakened immune system and are therefore more susceptible to infections. There is now good evidence that the increase in circulating non-esterified fatty acids impairs immune cell functions. Therefore, management approaches that reduce the negative energy balance and the increase in non-esterified fatty acids at the beginning of lactation are likely to improve resistance to infection. Improving the nutrient supply through periparturient nutritional management has been the subject of considerable research. However, another way to reduce the imbalance between nutrient supply and demand is to temporarily decrease the latter. In this review, we examine how management strategies such as conjugated linoleic acid feeding, prepartum milking, or limiting postpartum milk production could be used to reduce metabolic perturbations and immunosuppression during the transition period. At this stage, it appears that reducing the amount of milk harvested postpartum by means of partial milking in the first days after calving is the most promising approach to reduce metabolic stress and immunosuppression without compromising the productivity of high-yielding dairy cows.


Effect of scaling and root planing with and without adjunct use of an essential-oil-based mouthwash on whole salivary interleukin-1β levels in patients with periodontal disease: A short-term follow-up study.
The aim of the present short-term follow-up study was to assess the effect of scaling and root planing (SRP) with and without adjunct use of an essential-oil-based mouthwash (EOBM) on whole salivary interleukin (IL)-1beta (β) levels in patients with periodontal disease. Ninety individuals with periodontal disease were divided into two groups. Patients in group 1 underwent SRP and were instructed to rinse with 10 mL of an EOBM twice daily for 30 days. Patients in group 2 underwent SRP and were instructed to rinse with 10 mL of water twice daily for 30 days. Whole saliva samples were collected, and IL-1β levels were measured at baseline and after 60 days of treatment. P-values < 0.05 were considered statistically significant. At baseline, whole salivary IL-1β levels were comparable among patients in groups 1 (135.6 ± 13.5 μg/mL) and 2 (141.2 ± 5.4 μg/mL). After 60 days of follow-up, there is a significant decrease in whole salivary IL-1β levels among patients in group 1 (10.2 ± 6.4 μg/mL) as compared to those in group 2 (56.6 ± 10.2 μg/mL) (P < 0.01). SRP, when performed with adjunct use of an EOBM, is more effective in reducing whole salivary IL-1β levels as compared to when SRP is performed without the use of an EOBM.


Prophylaxis in gynaecological and obstetric surgery: a comparative randomised multicentre study of single-dose cefotetan versus two doses of cefazolin.
Antimicrobial prophylaxis is recommended in all clean-contaminated surgery where the critical threshold of number and virulence of the contaminating organisms with respect to host resistance is reached. Obstetric and gynaecological surgery is clean-contaminated and risk of infection due to aerobic and anaerobic bacteria without prophylaxis can be quantified at 30-40% for vaginal hysterectomy, 10-35% for abdominal hysterectomy and 10-34% for caesarean section. To assess the role of two different cephalosporins as short term prophylaxis, we carried out a multicentre randomised study involving a single 2 g i.v. dose of cefotetan in comparison with two doses of cefazolin (2 g i.v. before surgery and after 8 hours). Criteria for exclusion were: exposure to antibiotics within 7 days, preoperative infection, hypersensitivity to beta-lactams. Four hundred and sixty patients entered the study, of which 229 received cefotetan and 231 cefazolin. No significant differences in mean age, obesity, preoperative weight loss, diabetes, type of disease, type of surgery (vaginal or abdominal hysterectomies and caesarean sections) and number of pregnancies and abortions existed between the two groups of patients. The total rate of infected patients undergoing hysterectomy was 8.6% (13/151) in the cefotetan group and 17.4% (29/167) in the cefazolin group (p less than 0.05). This difference was due to cases of symptomatic bacteriuria and antibiotic retreatment, while wound infections were not significantly different (2.6% and 1.8% respectively). Among patients undergoing caesarean section, 9 of 78 (11.5%) and 7 of 64 (10.9%) were infected following cefotetan and cefazolin, respectively (not significant). Cefotetan mean tissue concentrations in gynaecological organs were higher than those of cefazolin (25.5-44.8 vs. 7.4-9.5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)


[Orofaciodigital syndrome].
The AA. behaving the orofaciodigital syndromes, describe the main peculiarity of the etiology, anatomo-pathology, clinical features, diagnosis to the light of the late acquisitions about these.


Epigenetic Manipulation Induced Production of Immunosuppressive Chromones and Cytochalasins from the Mangrove Endophytic Fungus Phomopsis asparagi DHS-48.
A mangrove endophytic fungus Phomopsis asparagi DHS-48 was found to be particularly productive with regard to the accumulation of substantial new compounds in our previous study. In order to explore its potential to produce more unobserved secondary metabolites, epigenetic manipulation was used on this fungus to activate cryptic or silent genes by using the histone deacetylase (HDAC) inhibitor sodium butyrate and the DNA methyltransferase (DNMT) inhibitor 5-azacytidine (5-Aza). Based on colony growth, dry biomass, HPLC, and 1H NMR analyses, the fungal chemical diversity profile was significantly changed compared with the control. Two new compounds, named phaseolorin J (1) and phomoparagin D (5), along with three known chromones (2-4) and six known cytochalasins (6-11), were isolated from the culture treated with sodium butyrate. Their structures, including their absolute configurations, were elucidated using a combination of detailed HRESIMS, NMR, and ECD and 13C NMR calculations. The immunosuppressive and cytotoxic activities of all isolated compounds were evaluated. Compounds 1 and 8 moderately inhibited the proliferation of ConA (concanavalin A)-induced T and LPS (lipopolysaccharide)-induced B murine spleen lymphocytes. Compound 5 exhibited significant in vitro cytotoxicity against the tested human cancer cell lines Hela and HepG2, which was comparative to the positive control adriamycin and fluorouracil. Our finding demonstrated that epigenetic manipulation should be an efficient strategy for the induction of new metabolites from mangrove endophytic fungi.


P2X7 antagonists for CNS indications: recent patent disclosures.
P2X7, a ligand-gated purinergic ion channel, has been at the center of intense efforts in the pharmaceutical industry in the last 15 years due to the growing appreciation of its role in inflammation. Since 2008-2009, increased focus on CNS available compounds has led to the publication of various patents on behalf of several pharmaceutical companies. This patent review aims at analyzing the recent patent literature (2008-2016) with a particular emphasis on those patents that are thought to deal with CNS penetrant compounds on the basis of their physicochemical features, the assays described in the patents and the uses these compounds are claimed for.


Physical activities: teaming up patients and programs.
Physical activities programs are suggested for the average deconditioned individual over 35 years of age. They involve noncontact, noncompetitive aerobic activities which require minimal expense. Their purpose is to delay to some degree the progression of the degenerative diseases associated with aging and inactivity. The best activities are walking, running, bicycling, or other exercise in which a sustained cardiac rate of 70% of the individual's work capacity is achieved.


Assessment of co-occurring depression and substance use in an ethnically diverse patient sample during behavioral health intake interviews.
Co-occurring disorders present a challenge for providers who often fail to diagnose them with accuracy. This study explores the assessment process of co-occurring depressive and substance use disorders in community health clinics serving ethnically diverse patients. The goals are to identify how symptoms discussed in intake, as well as patient and provider characteristics, are associated with receiving a diagnosis of co-occurring disorders or not. Participation in the study consisted of videotaping the intake, conducting a semi-structured interview, and completing demographic and clinical measures. Quantitative analyses were conducted based on information coded from videotapes of intakes with 119 patients who screened positive for symptoms of depressive disorders and substance use. A subset of cases (28) diagnosed with co-occurring disorders were qualitatively analyzed. Results suggest that being female and any discussion of "depression" as a general term increased the likelihood of receiving a diagnosis of depression. Discussing symptoms of drug and alcohol use increased the likelihood of receiving a substance use disorder diagnosis, and discussing symptoms of substance use only increased the likelihood of receiving a dual diagnosis. Qualitative analyses indicate that providers report conducting more systematic assessments for substance use than depressive disorders, which is not supported by the quantitative findings. Our results point to discrepancies in the ways providers and patients describe the assessment of dual diagnoses. Factors such as the role of nonverbal information and patient presentation were identified as contributing to complexity of the assessment.


Studying physician knowledge, attitudes, and practices regarding the herpes zoster vaccine to address perceived barriers to vaccination.
To increase usage of the herpes zoster (HZ) vaccine at an academic medical center by studying physicians' knowledge, attitudes, practices, and perceived barriers and analyze the findings by practice setting. A cross-sectional Internet-based survey administered to all 266 general internal medicine physicians in 4 clinical settings at an academic medical center between October 6 and December 12, 2011. Outcomes measures included knowledge questions regarding the disease and vaccine recommendations, Likert-type items about physician attitudes and practices, and questions about barriers and proposed interventions to improve utilization. Response rate was 33.5% (89 of 266). Responders did not answer all questions. Only 66% (42 of 64) responded that HZ vaccination was an important clinical priority, and 48% (38 of 79) reported that less than 10% of their patients received the HZ vaccine. 95% responded that the influenza (61 of 64) and 92% that the pneumococcal (59 of 64) vaccines were important. Approximately 53% (42 of 79) and 51% (40 of 78) reported that more than 75% of their patients received these vaccines, respectively. Top barrier to vaccination was cost to patients (51 of 66; 77%). Lack of awareness of national recommendations (46 of 65, 71%) varied by setting. Physicians' preferred interventions included nurse-initiated prompting about vaccination (36 of 75, 48%) and chart reminders (34 of 74, 46%). Not only increased knowledge but also a change in attitudes and practice are needed to enhance implementation of national recommendations. To improve use of this vaccine, physicians including ophthalmologists need to recommend it more strongly.


Pathogenesis of infective valvular endocarditis.
Infectious bacteria have been found within the spongiosa of the mitral valves of clinically healthy pigs. As a result, the theory on the pathogenesis of human infective valvular endocarditis may be questioned.


Left atrial appendage resection can be performed minimally invasively with good clinical and echocardiographic outcomes without any severe risk.
The adverse effects of left atrial appendage (LAA) closure have not yet been evaluated. This study aimed to prove the safety and low invasiveness of LAA resection through our thoracoscopic stand-alone left atrial appendectomy experience. Eighty-seven patients [mean age 68 ± 9 years, 68 men (78%), mean congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack to thromboembolism, vascular disease, age 65-74 years and sex category (CHA2DS2-VASc) score 2.9 ± 1.6 points] who had undergone thoracoscopic left atrial appendectomy were selected. The operative and clinical data (left atrial diameter, left ventricular diameter of systole/diastole, ejection fraction, brain natriuretic peptide and human atrial natriuretic peptide) were evaluated. All procedures were performed without cardiopulmonary bypass or cardiac arrest. The LAA was resected with an endoscopic linear cutter device. Except for 1 case with severe pleural adhesion, all operations were performed thoracoscopically. The preoperative and postoperative data are as follows: left atrial diameter 43 ± 5 mm and 43 ± 5 mm (P = 0.8); left ventricular diameter of systole/diastole 50 ± 5/35 ± 6 mm and 48 ± 5/34 ± 6 mm (P < 0.01); ejection fraction 57 ± 10% and 56 ± 10% (P = 0.11); brain natriuretic peptide 97 ± 77 pg/ml and 72 ± 65 pg/ml (P < 0.01) and human atrial natriuretic peptide 73 ± 64 pg/ml and 96 ± 67 pg/ml (P = 0.03), respectively. The mean volume of bleeding in the operation was very small (<10 ml). The mean length of postoperative in-hospital stay was 3.8 ± 1.8 days. All the patients were discharged while maintaining their preoperative activities of daily living without major complications. No thrombus or residual stumps were detected during the 3-month postoperative computed tomography follow-up. The perioperative heart function did not change significantly in this study. Bleeding with resection was minimal, and no rebleeding events occurred. LAA resection did not affect negatively on the cardiac function and did not increase the risk of bleeding risk.


An attempt to implement the nematode-trapping fungus Duddingtonia flagrans in biological control of trichostrongyle infections of first year grazing calves.
An attempt was made to control Ostertagia ostertagi by feeding the nematode-trapping fungus Duddingtonia flagrans (DSM 6703) to grazing calves. One group of calves (group E) was fed the fungal material in the first two months of the grazing season while another group was a non-treated control group (group C). Group E showed significantly lower faecal egg count in August and September. On four occasions in July and September, the herbage larval counts were significantly lower on the plot with the fungal-treated group than those recorded on the control plot. The average abomasal larval and adult worm counts were significantly reduced in August in group E and the average total worm count in the abomasum of group E was reduced by 87% in August compared to the non-treated group C. In October, the difference in average abomasal worm counts between group E and C was insignificant. Due to weight loss at the end of the grazing season, the control group showed a significantly lower average weight increase.


Heterologous expression and biochemical characterization of alpha-glucosidase from Aspergillus niger by Pichia pastroris.
The aglu of Aspergillus niger encodes the pro-protein of alpha-glucosidase, and the mature form of wild-type enzyme is a heterosubunit protein. In the present study, the cDNA of alpha-glucosidase was cloned and expressed in Pichia pastoris strain KM71. The activity of recombinant enzyme in a 3 L fermentor reached 2.07 U/mL after 96 h of induction. The recombinant alpha-glucosidase was able to produce oligoisomaltose. The molecular weight of the recombinant enzyme was estimated to be about 145 kDa by SDS-PAGE, and it reduced to 106 kDa after deglycosylation. The enzymatic activity of recombinant alpha-glucosidase was not significantly affected by a range of metal ions. The optimum temperature of the enzyme was 60 degrees C, and it was stable below 50 degrees C. The enzyme was active over the range of pH 3.0-7.0 with maximal activity at pH 4.5. Using pNPG as substrate, the K(m) and V(max) values were 0.446 mM and 43.48 U/mg, respectively. These studies provided the basis for the application of recombinant alpha-glucosidase in the industry of functional oligosaccharides.


Simultaneous extraction of endocardial and epicardial contours of the left ventricle by distance regularized level sets.
Segmentation of the cardiac left ventricle (LV) is still an open problem and is challenging due to the poor contrast between tissues around the epicardium and image artifacts. To extract the endocardium and epicardium of the cardiac left ventricle accurately, the authors propose a two-layer level set approach for segmentation of the LV from cardiac magnetic resonance short-axis images. In the proposed method, the endocardium and epicardium are represented by two specified level contours of a level set function. Segmentation of the LV is formulated as a problem of optimizing the level set function such that these two level contours best fit the epicardium and endocardium, subject to a distance regularization (DR) term to preserve a smoothly varying distance between them. The DR term introduces a desirable interaction between the two level contours of a single level set function, which contributes to preserve the anatomical geometry of the epicardium and endocardium of the LV. In addition, the proposed method has an intrinsic ability to deal with intensity inhomogeneity in MR images, which is a common image artifact in MRI. Their method is quantitatively validated by experiments on the datasets for the MICCAI 2009 grand challenge on left ventricular segmentation and the MICCAI 2013 challenge workshop on segmentation: algorithms, theory and applications (SATA). To overcome discontinuity of 2D segmentation results at some adjacent slices for a few cases, the authors extend distance regularized two-layer level set to 3D to refine the segmentation results. The corresponding metrics for their method are better than the methods in the MICCAI 2009 challenge. Their method was ranked at the first place in terms of Hausdorff distance and the second place in terms of Dice similarity coefficient in the MICCAI 2013 challenge. Experimental results demonstrate the advantages of their method in terms of segmentation accuracy and consistency with the heart anatomy.


cycloSal-2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (cycloSal-d4TMP): synthesis and antiviral evaluation of a new d4TMP delivery system.
The synthesis, hydrolysis, and antiviral evaluation of novel, lipophilic cycloSal-d4TMP derivatives 3a-h of the anti-HIV dideoxynucleoside 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, 1) are reported. This pro-nucleotide concept has been designed to deliver d4TMP (2) by selective chemical hydrolysis. All compounds 3a-h were synthesized using phosphorus(III) chemistry in good yields and in somewhat lower yields using phosphorus(V) chemistry starting from substituted salicyl alcohols 6a-h. The phosphotriesters 3 were obtained without stereochemical preference with respect to the configuration at the phosphorus center as 1:1 diastereomeric mixtures. However, a few of the triesters 3 could be separated into the diastereomers by means of semipreparative HPLC. In a 1-octanol/phosphate buffer mixture, all compounds 3 exhibited 9-100-fold higher lipophilicity as judged from their Pa values as compared to d4T (1). Furthermore, in hydrolysis studies 3 decomposed under mild aqueous basic conditions releasing solely d4TMP (2) and the diols 6 following the designed tandem reaction sequence. A correlation of the electronic properties introduced by the substituents and the half-lives of triesters 3 was observed. Thus, by varying the substituent, the half-lives of 3 could be adjusted over a wide range of compounds still delivering d4TMP (2) selectively. Phosphotriesters 3 exhibited considerable activity against HIV-1 and HIV-2 in wild-type human T-lymphocyte (CEM/O) cells as well as mutant thymidine kinase-deficient (CEM/TK-) cells. Surprisingly, we observed a 3-80-fold difference in antiviral activity between the two diastereomers. Our data clearly prove that the cycloSal-d4TMPs deliver exclusively the nucleotide d4TMP not only under simulated hydrolysis conditions but also under cellular conditions and thus fulfill the thymidine kinase-bypass premise. Therefore, the cycloSal-nucleotide concept is the first reported pro-nucleotide system that delivers the dideoxynucleotide by a pH-driven, chemically activated, tandem reaction without the requirement of an enzymatic contribution.


Nontuberculous Mycobacterial Infection Predisposing to Chronic Cavitary Pulmonary Aspergillosis.
Aspergillus is a large group of spore-forming fungi in the phylum Ascomycota. Aspergillus infections more frequently occur in individuals with pre-existing lung conditions such as cystic fibrosis and asthma and immunosuppressed individuals, and less frequently in the immunocompetent population. Pulmonary aspergillosis can be subdivided into three categories: allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, and invasive pulmonary aspergillosis. We present a rare case of a 57-year-old male with a previously known diagnosis of pancreatic adenocarcinoma on chemotherapy who was found to have a co-infection of the respiratory tract by Aspergillus flavus and Mycobacterium avium intracellulare.


Sexual harassment victimization and perpetration among high school students.
This large, population-based study is one of the few to examine prevalence rates of sexual harassment occurring during the past 12 months by victimization and perpetration among adolescents. In this large, cross-sectional survey of students attending 26 high schools, sexual harassment was defined using three questions from the Sexual Experiences Questionnaire. Among 18,090 students completing the survey, 30% disclosed sexual harassment victimization (37% of females, 21% of males) and 8.5% reported perpetration (5% of females, 12% of males). Sexual harassment perpetration was highly correlated with male sex, minority race/ethnicity, same-sex attraction, bullying, alcohol binge drinking, and intraparental partner violence.


Induction chemotherapy in Barrett cancer: influence on surgical risk and outcome.
To study the impact of induction chemotherapy on surgical risk and outcome in locally advanced Barrett cancer. Induction chemotherapy has become an accepted choice for the treatment of locally advanced adenocarcinoma of the esophagus and the esophagogastric junction. It has been shown that early assessment of metabolic response using positron emission tomography predicts response to chemotherapy. Metabolic response has also been revealed to be an independent prognostic factor. Surgical risk and outcome in metabolic responders were compared with those in nonresponders. The study design predefined a 12-week multicourse preoperative chemotherapy regimen in metabolic responders. In contrast, chemotherapy was stopped after a 2-week induction period in metabolic nonresponders. All patients were scheduled for surgical resection. Of 110 evaluable patients, 50 metabolic responders and 54 nonresponders underwent resection. Postoperative complications occurred in 34%. Two patients (1.8%) died. There were no significant differences between responders and nonresponders in terms of postoperative morbidity and mortality. Major histologic remissions were seen in 58% of metabolic responders. Metabolic responders had an increased chance of having an R0 resection (96% vs. 74%; P=0.002) and a decreased risk of developing hematogenous or distant lymphatic recurrence (32% vs. 54%, P=0.019). This translated into better recurrence-free and overall survival. Induction chemotherapy and early metabolic response assessment is a new concept in the treatment of locally advanced Barrett cancer. Metabolic responders undergoing multicourse preoperative chemotherapy have a good prognosis. The best treatment strategy for nonresponders remains to be defined.


Routes to Rural Readiness: Enhancing Clinical Training Experiences for Physician Assistants.
The purpose of this study was to describe practices and experiences of rurally oriented physician assistant (PA) training programs in providing rural clinical training to PA students. A survey of PA program directors (PDs) included questions about program characteristics, student and clinical preceptor (CP) recruitment in rural areas, and barriers to, and facilitators of, rural clinical training. Programs that considered rural training "very important" to their goals were identified. We interviewed PDs from rurally oriented programs about their rural clinical training and rural CPs about their experiences training PA students for rural practice. We identified key themes through content analysis. Of 178 programs surveyed, 113 (63.5%) responded, 61 (54.0%) of which were rurally oriented and more likely than other programs to recruit rural students or those with rural practice interests and to address rural issues in didactic curriculum. The 13 PDs interviewed linked successful rural training to finding and supporting rural preceptors who enjoy teaching and helping students understand rural communities. The 13 rural CPs identified enthusiastic and rurally interested students as key elements to successful rural training. Interviewees identified systemic barriers to rural training, including student housing, decreased productivity, competition for training slots, and administrative burden. Physician assistant students can be coached to capitalize on their rural clinical experiences. Knowing how to "jump in" to rotations and having genuine interest in the community are particularly important. Student housing, competition for training slots, and lack of financial incentives are major system-level challenges for sustaining and increasing the availability of PA rural clinical training.


[Daily number of births in Norway 1989-93. Variations across months, day of week, phase of the moon and changes in leave entitlements].
The variation in the daily numbers of births across month, day of week, phase of the moon and maternity leave entitlements have been studied for all births in Norway between 1989 and 1993, a total of 302,209 newborn children. The number of births was highest in the spring and lowest in November and December. A secondary birth maximum was observed in September, possibly related to activities during Christmas and New Year celebrations nine months before. Furthermore, births were least numerous at weekends and were concentrated in the middle of the week. This pattern probably reflects less active obstetric intervention at weekends. The number of births does not seem to vary with phase of the moon. At the time of the latest, and largest increase in national birth maternity leave entitlements, fewer births occurred in the days before and correspondingly more births in the days immediately after the date when the change came into force.


(Bi,Sb)2 Se3 Alloy Thin Film for Short-Wavelength Infrared Photodetector and TFT Monolithic-Integrated Matrix Imaging.
Short-wavelength infrared photodetectors play a significant role in various fields such as autonomous driving, military security, and biological medicine. However, state-of-the-art short-wavelength infrared photodetectors, such as InGaAs, require high-temperature fabrication and heterogenous integration with complementary metal-oxide-semiconductor (CMOS) readout circuits (ROIC), resulting in a high cost and low imaging resolution. Herein, for the first time, a low-cost, high-performance, high-stable, and thin-film transistor (TFT) ROIC monolithic-integrated (Bi,Sb)2 Se3 alloy thin-film short-wavelength infrared photodetector is reported. The (Bi,Sb)2 Se3 alloy thin-film short-wavelength infrared photodetectors demonstrate a high external quantum efficiency (EQE) of 21.1% (light intensity of 0.76 µW cm-2 ) and a fast response time (3.24 µs). The highest EQE is about two magnitudes than that of the extrinsic photoconduction of Sb2 Se3 (0.051%). In addition, the unpackaged devices demonstrate high electric and thermal stability (almost no attenuation at 120 °C for 312 h), showing potential for in-vehicle applications that may experient such a high temperature. Finally, both the (Bi,Sb)2 Se3 alloy thin film and n-type CdSe buffer layer are directly deposited on the TFT ROIC (with a 64 × 64-pixel array) with a low-temperature process and the material identification and imaging applications are presented. This work is a significant breakthrough in ROIC monolithic-integrated short-wavelength infrared imaging chips.


Emergency cricothyroidotomy: a randomised crossover study of four methods.
Emergency physicians and registrars performed emergency cricothyroidotomy on an artificial airway model using a standard surgical approach and three common commercial products, participants had received no refresher training. The order in which the methods were used was randomised to minimise any learning effect. Three methods (standard surgical, Minitrach II, and Quicktrach) were universally successful in obtaining ventilation within 150 s, whilst the Melker kit had a 26% failure rate and significantly longer median time to ventilation (126 s vs<or=48 s for other methods, p < 0.001). Despite success in using the surgical method, the Quicktrach and Minitrach II were rated as first or second preference by the majority of operators (78% and 70% respectively). Without refresher training emergency physicians and registrars successfully performed emergency cricothyroidotomy using the standard surgical method, Quicktrach and Minitrach II kits however the use of the Melker kit under these conditions resulted in significant delays or failure to establish an airway.


A descriptive analysis of the indications for caesarean section in mainland China.
In recent decades we have observed a remarkable increase in the rate of caesarean section (CS) in both developed and developing countries, especially in China. However, the real reasons for this phenomenon are uncertain. Notably, the number of women requesting elective CS without accepted valid medical indication has also increased, generating a nationwide debate because several studies have shown that this may be the underlying cause of the increase in CS rates observed recently. Therefore, we carried out a multicentre, large-sample, cross-sectional study to describe the CS rate and indications for CS in mainland China during 2011. This was a multicentre, large-sample, cross-sectional study of women who delivered infants in 39 hospitals in 14 provinces in China during 2011. We selected 111, 315 deliveries that occurred during 2011, excluding miscarriages or termination of pregnancy before 28 gestational weeks. The overall rate of CS in mainland China was 54.90%. The most common indication for CS was caesarean delivery on maternal request (CDMR; 28.43%), followed by cephalo-pelvic disproportion (14.08%), fetal distress (12.46%), previous CS (10.25%), malpresentation and breech presentation (6.56%), macrosomia (6.10%) and other indications (22.12%). CDMR accounted for 15.53% of all the deliveries and 28.43% of all CS deliveries in mainland China. CDMR appears to be a considerable driver behind the increasing CS rate in mainland China. The relaxation of China's "one-child policy" may translate into a greater number of CS because of previous CS delivery. To decrease the CS rate, we should first decrease the rate of CS on maternal request. Appropriate policies and guidelines should be considered to accomplish the goal.


Intracapsular aspiration.
Through a 2-mm. limbal incision, the aspiration of the lens is accomplished; this assures a strong eye immediately after operation. It frees the eye from the complications associated with the large incision required for linear extraction of the lens. Intracapsular aspiration of the entire lens cortex and nucleus is performed through a 2-mm. hole in the anterior capsule near the equator. Posterior synechiae are prevented by leaving the anterior capsule intact and in apposition with the posterior iris surface, assuring a round, mobile pupil. An axial 5-mm. hole placed through the collapsed anterior and posterior lens capsule usually remains free of secondary membrane formation, obviating the need for further surgery. The complication of vitreous presentation in the corneoscleral incision is managed by performing an anterior vitrectomy with an instrument that cuts and aspirates the vitreous.


Brazilian Berry Extract Differentially Induces Inflammatory and Immune Responses in Androgen Dependent and Independent Prostate Cancer Cells.
Jaboticaba is a Brazilian berry, which is rich in fibers and bioactive compounds and shows high antioxidant and antiproliferative activities. Prostate cancer (PCa) is the second most common type of cancer among men and its progression is influenced by androgens and inflammation. Previous studies reported the ability of the jaboticaba to modulate pathways involved in prostate diseases. The main objective of this study was to provide significant data about molecular targets of the jaboticaba peel extract (JPE) and its mechanisms of action in PCa cell lines with different androgenic status (LNCaP and PC-3). The results showed that JPE was able to decrease cell viability in both cell lines. LNCaP showed more sensitivity to JPE exposure, indicating the efficacy of the JPE treatment in terms of androgen responsiveness. JPE showed a distinct hormone dependent effect on the NF-κB signaling, with reduced NF-κB levels for LNCaP and increased NF-κB levels in PC-3 cells. Mechanisms related to cell death by apoptosis were stimulated after the JPE treatment, modulating B-cell lymphoma 2 and BAX for LNCaP and PC-3. Particularly for PC-3, the JPE treatment resulted in cytokine-cytokine receptor interaction activation mostly by up regulating pro-inflammatory, pro-angiogenic, immunostimulatory and immunosuppressive genes. Also, a set of genes related to angiogenesis and metastasis were down-regulated by JPE. In conclusion, JPE exerted an antitumor effect on PCa for both cell lines which can be enhanced if androgenic reliance is considered.


Elevated retrotransposon activity and genomic instability in primed pluripotent stem cells.
Naïve and primed pluripotent stem cells (PSCs) represent two different pluripotent states. Primed PSCs following in vitro culture exhibit lower developmental potency as evidenced by failure in germline chimera assays, unlike mouse naïve PSCs. However, the molecular mechanisms underlying the lower developmental competency of primed PSCs remain elusive. We examine the regulation of telomere maintenance, retrotransposon activity, and genomic stability of primed PSCs and compare them with naïve PSCs. Surprisingly, primed PSCs only minimally maintain telomeres and show fragile telomeres, associated with declined DNA recombination and repair activity, in contrast to naïve PSCs that robustly elongate telomeres. Also, we identify LINE1 family integrant L1Md_T as naïve-specific retrotransposon and ERVK family integrant IAPEz to define primed PSCs, and their transcription is differentially regulated by heterochromatic histones and Dnmt3b. Notably, genomic instability of primed PSCs is increased, in association with aberrant retrotransposon activity. Our data suggest that fragile telomere, retrotransposon-associated genomic instability, and declined DNA recombination repair, together with reduced function of cell cycle and mitochondria, increased apoptosis, and differentiation properties may link to compromised developmental potency of primed PSCs, noticeably distinguishable from naïve PSCs.


Brimonidine for glaucoma.
Brimonidine is a drug used in the management of glaucoma throughout the world and is the most modern alpha(2)-adrenoceptor agonist available. This review comprehensively discusses the use of brimonidine for glaucoma. A historical insight into the development of selective adrenergic glaucoma drugs is given, followed by a description of the mechanisms of action and a discussion of the main clinical trials investigating clinical applications. The safety of brimonidine is evaluated, and our expert opinion is provided on how brimonidine is used in our clinical practice. The most relevant literature on the role of brimonidine in glaucoma is discussed. A clear understanding of the role of brimonidine for glaucoma treatment, with an explanation of its efficacy, limitations and use in clinical practice. Brimonidine is an effective drug for lowering intraocular pressure. It has potentially serious systemic effects in children, in whom it is contraindicated. Its use in adults is limited by its ocular side effects such as allergy. Brimonidine is, however, an important part of the range of intraocular pressure lowering drugs available to prescribers.


Functional equivalence of spatial representations derived from vision and language: evidence from allocentric judgments.
Past research (e.g., J. M. Loomis, Y. Lippa, R. L. Klatzky, & R. G. Golledge, 2002) has indicated that spatial representations derived from spatial language can function equivalently to those derived from perception. The authors tested functional equivalence for reporting spatial relations that were not explicitly stated during learning. Participants learned a spatial layout by visual perception or spatial language and then made allocentric direction and distance judgments. Experiments 1 and 2 indicated allocentric relations could be accurately reported in all modalities, but visually perceived layouts, tested with or without vision, produced faster and less variable directional responses than language. In Experiment 3, when participants were forced to create a spatial image during learning (by spatially updating during a backward translation), functional equivalence of spatial language and visual perception was demonstrated by patterns of latency, systematic error, and variability.


Bending dynamics of acetylene: new modes born in bifurcations of normal modes.
Semiclassical techniques are used to analyze highly excited pure bending vibrational dynamics from spectra of C2H2. An analytic bifurcation approach is developed, based on critical points of a classical version of the quantum fitting Hamiltonian. At high energy four new types of anharmonic modes are born in bifurcations of the normal modes: local, orthogonal, precessional, and counter-rotator. Visual insight into their nature is obtained with the help of computer-generated three-dimensional animations. The connection between the local mode and the acetylene-vinylidene isomerization "reaction mode" is considered.


Maternal Sleep Quality and Diurnal Cortisol Regulation Over Pregnancy.
Poor sleep in pregnancy is related to adverse neonatal health. Elevated maternal cortisol has been proposed as a pathway, yet the association in pregnancy is not well understood. The goals of the current study were to examine associations between (a) sleep and cortisol, (b) sleep, cortisol, and neonatal outcomes, and (c) variables that could explain these associations. Two hundred pregnant women completed the Pittsburgh Sleep Quality Index (PSQI; Buysse, Reynolds, Monk, Berman, & Kupfer, 1989) and provided diurnal salivary cortisol samples at two times over pregnancy. Poor sleep quality was associated with greater evening cortisol concentrations at 36 weeks' gestation. This association was mediated by anxiety symptoms. Higher evening cortisol at 36 weeks' gestation was associated with shorter gestation.


Permeability of blood-ocular barriers of neonatal and adult cats to fluorescein-labeled dextrans of selected molecular sizes.
The permeability of the ocular blood vessels and neuroepithelial layers (the blood-ocular barriers) to fluorescein-labeled dextrans of selected molecular sizes was evaluated in neonatal and adult cats by fluorescence microscopy. The iris and ciliary process vessels were permeable to molecules as large as 85A effective diffusion radius (EDR). In the kitten, the choriocapillaris was permeable to molecules as large as 58A EDR, and in the adult to molecules only as large as 32A EDR. The retinal vessels and the retinal pigment epithelium were impermeable to all markers. The role of the cat's iris vessel in aqueous humor formation appears dissimilar to that of other species in that molecules larger than serum proteins traverse the walls of the iris capillaries.


Epidemiology of ankle fracture 1950 and 1980. Increasing incidence in elderly women.
During 1980-82, 739 ankle fractures occurred in Malmö. These were compared with 383 ankle fractures occurring in 1950-52. In men there was an increase in the age-specific incidence up to the age of 60, especially in fractures of the lateral malleolus. In women there was an increase in the age-specific incidence above the age of 50, both in lateral malleolar fractures and, even more pronounced, in bi- and tri- malleolar fractures.


[Neuromuscular blockade with vecuronium and its reversal with edrophonium during total intravenous anesthesia, neuroleptanalgesia and sevoflurane anesthesia].
The neuromuscular blocking effect of vecuronium and its reversibility ith edrophonium were studied under total intravenous anesthesia (TIVA) and compared with those under NLA or sevoflurane anesthesia (SA) in 30 surgical patients. The degree of neuromuscular blockade was evaluated by acceleration of thumb adduction in response to supramaximal stimulation of the ulnar nerve using Accelograph (Biometer). TIVA was induced with droperidol 0.25 mg.kg-1, fentanyl 2-4 micrograms.kg-1 and ketamine 2 mg.kg-1, and maintained with continuous infusion of ketamine 2 mg.kg-1.h-1 with 30-35% O2 in air. NLA was induced with droperidol 0.25 mg.kg-1 and fentanyl 5-10 micrograms.kg-1 and maintained with 66% nitrous oxide in oxygen. SA was induced with thiamylal 5 mg.kg-1 i.v. and maintained with 66% nitrous oxide in oxygen supplemented with sevoflurane (1 MAC). A single bolus intravenous injection of vecuronium 0.1 mg.kg-1 was used for paralysis and reversed with edrophonium 0.75 mg.kg-1 followed by atropine 0.015 mg.kg-1 when the TOF ratio returned to 25%. The times required from administration of vecuronium to completion of maximal block with TIVA, NLA and SA were 196.5 +/- 52.2 sec, 182.5 +/- 47.6 sec and 166.0 +/- 69.0 sec, respectively. There was no significant difference among them. The times from completion of maximal block to 25% recovery of the twitch height in TIVA and NLA were 39.5 +/- 11.0 min and 37.4 +/- 5.8 min without significant difference. Those values, however, were significantly shorter than 64.5 +/- 35.2 min of SA.(ABSTRACT TRUNCATED AT 250 WORDS)


Geodesic Video Stabilization in Transformation Space.
We present a novel formulation of video stabilization in the space of geometric transformations. With the setting of the Riemannian metric, the optimized smooth path is cast as the geodesics on the Lie group embedded in transformation space. While solving the geodesics has a closed-form expression in a certain space, path smoothing can be easily implemented by using geometric interpolation, rather than optimizing any space-time energy function. Specially, by using the geodesic solution in the space of rigid transformations, our approach even gains speedup 10× faster than state-of-the-art methods for path smoothing and motion compensation, and guarantees no extra distortion drawn into the stabilized frames. The experiments demonstrate the efficiency and effectiveness of our algorithm on stabilizing a variety of shaky videos.


Enhanced glomerular filtration and Na+-K+-ATPase with furosemide administration.
To evaluate the effect of furosemide on kidney function, glomerular filtration rate (GFR), urinary Na excretion (UNaV), Na reabsorption (NAR), and Na+-K+-ATPase in isolated nephron segments were measured in 1) rats treated with furosemide 10 mg X 100 g-1 X 24 h-1 ip for 7 days, and 2) rats receiving an oral Na load for 12 days. In furosemide-treated rats, GFR rose from 0.61 +/- 0.03 (mean +/- SD) to 0.83 +/- 0.06 ml/min (P less than 0.01), UNaV rose from 904 +/- 71 to 1,402 +/- 85 mueq/day (P less than 0.001), and net NAR rose from 87.5 +/- 3.7 to 116.7 +/- 9.0 mueq/min (P less than 0.01). Na+-K+-ATPase remained unchanged in the proximal convoluted tubule (PCT), proximal straight tubule (PST), cortical thick ascending limb of Henle's loop (cTALH), and medullary thick ascending limb of Henle's loop (mTALH), but was increased in the distal convoluted tubule (DCT) and in cortical collecting duct (CCD) from 48.5 +/- 1.2 to 75.3 +/- 0.7 (P less than 0.001) and from 18.6 +/- 0.7 to 27.1 +/- 2.7 (P less than 0.02) X 10(-11) mol X mm-1 X min-1, respectively. In Na-loaded rats GFR rose from 0.61 +/- 0.04 to 0.86 +/- 0.03 ml/min (P less than 0.001), UNaV rose from 1,064 +/- 118 to 18,532 +/- 2,045 mueq/day (P less than 0.001), net NAR from 88.1 +/- 3.0 to 107.8 +/- 3.9 mueq/min and Na-K-ATPase in the mTALH rose from 40.3 +/- 1.4 to 56.2 +/- 2.11 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Internal dosimetry of uranium isotopes using Bayesian inference methods.
A group of personnel at Los Alamos National Laboratory is routinely monitored for the presence of uranium isotopes by urine bioassay. Samples are analysed by alpha spectroscopy, and the results are examined for evidence of an intake of uranium. Because the measurement uncertainties are often comparable to the quantities of material we wish to detect, statistical considerations are crucial for the proper interpretation of the data. The problem is further complicated by the significant, but highly non-uniform, presence of uranium in local drinking water and, in some cases, food supply. Software originally developed for internal dosimetry of plutonium has been adapted to the problem of uranium dosimetry. The software uses an unfolding algorithm to calculate an approximate Bayesian solution to the problem of characterising any intakes which may have occurred, given the history of urine bioassay results for each individual in the monitored population. The program uses biokinetic models from ICRP Publications 68 and later, and a prior probability distribution derived empirically from the body of uranium bioassay data collected at Los Alamos over the operating history of the laboratory. For each individual, the software creates a posterior probability distribution of intake quantity and solubility type as a function of time. From this distribution, estimates are made of the cumulative committed dose (CEDE) to each individual. Results of the method are compared with those obtained using an earlier classical (non-Bayesian) algorithm for uranium dosimetry. We also discuss the problem of distinguishing occupational intakes from intake of environmental uranium, within a Bayesian framework.


Canadian guidelines for research on somatic cell gene therapy in humans (1)
The Medical Research Council of Canada (MRC) published Guidelines on Research on Somatic Cell Gene Therapy in Humans in 1990. The article discusses the context of these Guidelines within other work by the MRC and within the mechanisms for control of research in Canada, and identify the overall conclusions.


Modulation of propofol on the effects of blood pressure and firing activity of related neurons in the medulla.
Many studies have demonstrated that the ventrolateral medulla (VLM) plays an important role in the maintenance of systemic arterial pressure (SAP) and vascular tone. The VLM is divided into rostral (RVLM) and caudal (CVLM) portions which play opposing roles in regulating cardiovascular functions. The purposes of this study are to explore the relationship of fibers projecting between the RVLM and CVLM, and to investigate the effect of propofol (PPF, 2 mg/kg), an anesthetic agent, on modulating their neuronal firing rate (NFR). Forty-four adult cats were anaesthetized intraperitoneally with urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). The femoral artery was cannulated to allow monitoring of SAP and heart rate (HR). The femoral vein was cannulated for intravenous drug administration. Microinjection of glutamate (Glu, 3.0 nmol/30 nl), kynurenic acid (Kyn, 3.0 nmol/30 nl), gamma-aminobutyric acid (GABA, 4.0 nmol/30 nl), or bicuculline (Bicu, 4.0 nmol/30 nl) into the RVLM produced SAP increases or decreases, but did not significantly change the NFR in the CVLM. This occurred even after intravenous administration of PPF. This shows that there are few fiber projections from the RVLM to the CVLM. Conversely, microinjection of Glu, Kyn, GABA or Bicu into the CVLM produced SAP changes, and the NFR in the RVLM was significantly changed. These changes were more significant after intravenous administration of PPF. These results show that there are more fibers projecting from the CVLM to the RVLM and fewer fibers projecting from the RVLM to the CVLM to affect the SAP and its NFR.


Classroom contextual effects of race on children's peer nominations.
Black children generally receive poorer sociometric nominations compared with Whites. This effect is not fully understood because Black children rarely hold a classroom majority and teachers' race is rarely investigated. Research from a person-environment perspective suggests that the effects of children's race depend on the racial composition of the classroom and society's racial attitudes. Sociometric nominations were obtained from 1,268 5th graders, between 9 and 11 years old (53% Black), across 57 classrooms (3-95% Black students). Half of the teachers were Black. The results indicated that ratings of Black children were more influenced by the racial context of classrooms than were ratings of White children. The implications of this study are discussed in relation to group dynamics and racial discrimination.


A statistical analysis of natural images matches psychophysically derived orientation tuning curves.
A neural net method is used to extract principal components from real-world images. The initial components are a Gaussian followed by horizontal and vertical operators, starting with the first derivative and moving to successively higher orders. Two of the components are 'bar-detectors'. Their measured orientation selectivity is similar to that suggested by Foster & Ward (Proc. R. Soc. Lond. B 243, 75 (1991] to account for brief-exposure psychophysical data. In tests with noise images, the ratio of sensitivity between the two components is controlled by the degree of anisotropy in the image.


Real-time expert system for advising anesthesiologists in the cardiac operating room.
This paper describes the initial work towards building a distributed real-time expert system for advising anesthesiologists in the cardiac operating room. The goal of this project is to build a vigilant system that contains knowledge relevant to the practice of cardiac anesthesiology. The system is being designed to use this knowledge in conjunction with continuous automated patient data acquisition in order to provide clinically useful differential diagnoses and treatment recommendations in real time.


Prevalence of and risk factors for intraoperative gastroesophageal reflux and postanesthetic vomiting and diarrhea in dogs undergoing general anesthesia.
To determine the prevalence of intraoperative gastroesophageal reflux (GER) and postanesthetic vomiting and diarrhea, and to evaluate risk factors associated with these gastrointestinal disorders (GID) in dogs undergoing general anesthesia. Prospective observational study. University teaching hospital. Two hundred thirty-seven client-owned dogs undergoing general inhalant anesthesia for diagnostic or surgical purposes. None MEASUREMENTS AND MAIN RESULTS: Patient, surgical, and anesthetic variables, and postanesthetic treatments administered in the immediate postanesthesia period were evaluated in relation to GID using univariate and multivariate logistic regression analysis (P < 0.05). Seventy-nine of the 237 (33.4%) dogs developed GID during the perianesthetic period. The prevalences of GER, vomiting, and diarrhea were 17.3%, 5.5%, and 10.5%, respectively. Intraabdominal surgery (P = 0.016; odds ratio [OR] 2.82, 95% confidence interval [CI]: 1.21-6.62), changes in body position (P = 0.003; OR 3.17, 95% CI: 1.47-6.85), and length of anesthesia (P = 0.052; OR 1.006, 95% CI: 1.000-1.013) were associated with GER. Changes in the ventilation mode during surgery (P = 0.011; OR 6.54, 95% CI: 1.8-23.8), length of anesthesia (P = 0.024; OR 1.001, 95% CI: 1.001-1.020), and rescue synthetic colloid support due to hypotension (P = 0.005; OR 6.9, 95% CI: 1.82-26.3) were positively associated with postanesthetic vomiting. On the contrary, dogs that received acepromazine as premedication were significantly less likely (P < 0.019; OR 12.3, 95% CI: 1.52-100) to vomit. Finally, length of anesthesia, changes in body position, changes in ventilation mode, or hypoxemia during the procedure tended to increase the risk (univariate model) of diarrhea during the recovery phase. GID are common in dogs undergoing general anesthesia. Duration and characteristics of the procedure, anesthetic management, and changes in certain patient variables are significant risk factors for the presence of GID in the perioperative period.


A virulent parent with probiotic progeny: comparative genomics of Escherichia coli strains CFT073, Nissle 1917 and ABU 83972.
Escherichia coli is a highly versatile species encompassing a diverse spectrum of strains, i.e. from highly virulent isolates causing serious infectious diseases to commensals and probiotic strains. Although much is known about bacterial pathogenicity in E. coli, the understanding of which genetic determinants differentiates a virulent from an avirulent strain still remains limited. In this study we designed a new comparative genomic hybridization microarray based on 31 sequenced E. coli strains and used it to compare two E. coli strains used as prophylactic agents (i.e. Nissle 1917 and 83972) with the highly virulent uropathogen CFT073. Only relatively minor genetic variations were found between the isolates, suggesting that the three strains may have originated from the same virulent ancestral parent. Interestingly, Nissle 1917 (a gut commensal strain) was more similar to CFT073 with respect to genotype and phenotype than 83972 (an asymptomatic bacteriuria strain). The study indicates that genetic variations (e.g. mutations) and expression differences, rather than genomic content per se, contribute to the divergence in disease-causing ability between these strains. This has implications for the use of virulence factors in epidemiological research, and emphasizes the need for more comparative genomic studies of closely related strains to compare their virulence potential.


A survey on radiographic prescription practices in dental implant assessment among dentists in Kerala, India.
To conduct a survey of the current radiographic prescription practices among implant practitioners in the state of Kerala, India. 300 dentists were interviewed by employing a questionnaire which enquired about the radiographic evaluation methods prescribed by practitioners in implant site assessment in their implantology practice. Other reasons for choosing particular imaging modalities were also enquired. The data collected from the survey was analysed using Epi-Info 7.1.3 software. Around 87.33% of the dentists prescribed only OPG for the implant site assessment and only 4.66% ordered Orthopantomograph (OPG) in combination with an Intra Oral Periapical Radiograph (IOPAR) and 4.33% ordered OPG with Computed Tomography (CT). Only 0.02% of the practitioners ordered CT as a single examination and 1% ordered it in conjunction with other modalities. 0.066% individuals ordered IOPAR as the sole imaging modality and none of them ever prescribed conventional or Cone beam computed tomography. Our study has conclusively proven that most of the dentists prescribe OPG followed by a combination of OPG and Intraoral periapical radiographs in their implant practices. Many of them were not aware and did not follow the American Academy of Oral and Maxillofacial Radiology, European Academy of Dentomaxillofacial Radiology, European Association of Osseointegration and International Congress of Oral Implantology recommendations regarding cross-sectional imaging.


Use and nursing of the helmet in delivering non invasive ventilation.
Continuous positive end-expiratory pressure (CPAP) and Pressure Support Ventilation (PSV) are commonly used for the therapy of several forms of respiratory failure. CPAP and PSV can be delivered both during invasive respiratory treatment, by means of an endotracheal tube or tracheostomy, and during non invasive respiratory treatment. Non Invasive Ventilation (NIV) is commonly used for the therapy of several forms of respiratory failure (COPD, Weaning period from Invasive Mechanical Ventilation, Cardiogenic Edema,.) and the helmet could be a good new device to deliver it with a better compliance instead the common facial mask without increasing the nurses' workload.


3-Aryl-4-methyl-2-quinolones targeting multiresistant Staphylococcus aureus bacteria.
The NorA efflux pump lowers intracellular fluoroquinolone concentrations by expelling antibiotics through the membrane of Staphylococcus aureus. We identified 3-aryl-4-methyl-2-quinolin-2-ones as compounds able to restore the activity of the NorA substrate, ciprofloxacin, against resistant S. aureus strains, and acting as efflux pump inhibitors (EPI). In particular, 5-hydroxy-7-methoxy-4-methyl-3-phenylquinolin-2-one (6 c) presents both an EPI and an antimicrobial effect. Its efficacy and safety make it a potential candidate for further investigations.


Tracing kinetic intermediates during ligand binding.
Specific protein-ligand interactions are central to biological control. Although structure determination provides important insight into these interactions, it does not address dynamic events that occur during binding. While many biophysical techniques can provide a global view of these dynamics, NMR can be used to derive site-specific dynamics at atomic resolution. Here we show how NMR line shapes can be analyzed to identify long-lived kinetic intermediates for individual amino acids on the reaction pathway for a protein-ligand interaction. Different ligands cause different intermediate states. The lifetimes of these states determine the specificity of binding. This novel approach provides a direct, site-specific visualization of the kinetic mechanism of protein-ligand interactions.


Very early great saphenous vein graft aneurysm treated by percutaneous coronary intervention under ChromaFlo imaging guidance.
A 73-year-old man, who had undergone coronary artery bypass grafting (CABG) 10 days prior, presented with a great saphenous vein graft aneurysm (SVGA). CT revealed the increasing size of the aneurysm. Since the SVGA occurred immediately after CABG and there were no other complications, the aneurysm was treated percutaneously. While intravascular ultrasonography (IVUS) and optical coherence tomography failed to detect the entry point, an IVUS catheter with the addition of ChromaFlo imaging clearly revealed the entry point, size and length of the SVGA. To prevent migration and edge restenosis associated with covered stents, the covered stent (3.0×19 mm) was superimposed on a drug-eluting stent (3.0×28 mm) that covered the entry site. A follow-up study demonstrated the absence of flow into the aneurysm.


In vivo ultrasonic attenuation in cetacean soft tissues.
In vivo ultrasonic attenuation was estimated for extracranial soft tissues of two Tursiops truncatus and one Delphinapterus leucas. Backscatter data was non-invasively collected as part of routine health-based ultrasound examinations using a transducer operating in the 1.6-3.7 MHz frequency range. Data collected over the proximal mandible and temporal regions was processed to yield attenuation estimates using a reference tissue phantom whose properties had been independently determined. The estimated attenuations were at the low end of the range of literature-reported values for mammalian fatty and connective tissues. A companion model-based analysis quantified errors arising from tissue composition and sound speed uncertainties.


Noun verb dissociation in Parkinson's disease.
A noun/verb dissociation with a relative verb deficit was found in patients affected by Parkinson's disease, even in relatively early stages, when mental deterioration is not severe. This finding is compatible with earlier observations, according to which verbs are dealt with in more anterior regions with respect to nouns. It also supports the speculation that the co-ordination and the manipulation of information associated with a verb world rely on the frontostriatal system.


Prescribing physical activity for healthy aging: longitudinal follow-up and mixed method analysis of a primary care intervention.
There is a shortage of literature describing the experience of individuals who have participated in a physical activity and mobile health (mHealth) intervention. Many physical activity interventions are of short duration and do not report long-term changes in clinical measures or adoption of prescribed health behaviors. Previously, we have reported the clinical and behavioral outcomes from the first phase of a physical activity prescription and mHealth intervention delivered through the primary care setting. The purpose of this next phase is to perform a longitudinal follow-up 6-months postintervention. Mixed methods analysis including repeated measures ANOVA of functional aerobic capacity (VO2max) at preintervention, postintervention, and follow-up clinic visits, and whole text analysis of semistructured interviews discussing the participant experience in a health behavior intervention. Twenty participants, mean age 63 ± 5 years, participated. Gains made in VO2max were maintained at 6 months (P < 0.05). Participants reported engaging in sustained and routine physical activity, yet some identified a need for additional support to adopt the prescribed health behaviors. Emergent themes included the desire for short-term mHealth intervention to educate individuals about prescribed health behaviors without need for ongoing management by clinicians, leveraging mHealth to build social networks around prescribed health behaviors and to connect individuals to build a sense of community, and participant views of physical activity as medicine. The present study investigated both the long-term adoption of physical activity behaviors as well as the participant experience in a physical activity and mHealth intervention. Findings from the current study may be used to inform the development of user-centered lifestyle interventions.


Evaluation of the Effect of Probiotic Yogurt Consumption on Salivary pH, Buffering Capacity and Calcium Level in 6-12-year-old Children: An In Vivo Study.
Dental caries is a preventable disease that can be prevented by suppressing any one of the factors of the Keyes triad. To investigate the effect of probiotic yogurt on salivary pH, calcium level, and buffering capacity. A total of 60 children were randomly selected and were divided into 2 groups. The test group consumed 200 mL of probiotic yogurt and the control group consumed 200 mL of regular curd everyday for 30 days. A base-line nonstimulated salivary sample (2 mL) was collected. The salivary pH, buffering capacity, and calcium level was assessed at baseline, after 15 and 30 days. The data were statistically analyzed. The mean pH levels of the probiotic group were 7.03 and salivary buffering capacity was found to be 2.000. Salivary calcium levels increased with the use of probiotic yogurt at the end of 30 days (mean of 4.79) compared to the control group. Consumption of probiotic yogurt for a short period of time can prevent dental caries by increasing salivary calcium level. Malavalli PL, Shetty SB, Thimmaiah C, et al. Evaluation of the Effect of Probiotic Yogurt Consumption on Salivary pH, Buffering Capacity and Calcium Level in 6-12-year-old Children: An In Vivo Study. Int J Clin Pediatr Dent 2022;15(2):194-198.


Body mass index, neck circumference, and hypertension: a prospective cohort study.
This study aimed to investigate the association between BMI combined with neck circumference and the risk of hypertension. We selected participants from the Kailuan study in 2014 who were normotensive as our research subjects. We compared the risk of hypertension among individuals in group 1 (non-obese with low neck circumference), group 2 (non-obese with high neck circumference), group 3 (obese with low neck circumference), and group 4 (obese with high neck circumference). After a median observation period of 3.86 years, hypertension occurred in 13,383 participants. Subjects in Group 2, 3, and 4 had significantly higher risks of hypertension compared to Group 1, with hazard ratios (HRs) of 1.066 (95% CI: 1.025, 1.110), 1.322 (95% CI: 1.235, 1.415), and 1.422 (95% CI: 1.337, 1.512), respectively. Additionally, adding BMI to a conventional model had a greater incremental effect on predicting hypertension compared to adding neck circumference alone. However, considering both BMI and neck circumference together further improved the prediction of hypertension. Individuals with both high BMI and high neck circumference face a higher risk of hypertension. Moreover, BMI is a superior predictor of hypertension risk compared to neck circumference, but using both of these measures can further enhance the accuracy of hypertension risk prediction.


Polariton-Mediated Electron Transfer via Cavity Quantum Electrodynamics.
We investigate the polariton-mediated electron transfer reaction in a model system with analytic rate constant theory and direct quantum dynamical simulations. We demonstrate that the photoinduced charge transfer reaction between a bright donor state and dark acceptor state can be significantly enhanced or suppressed by coupling the molecular system to the quantized radiation field inside an optical cavity. This is because the quantum light-matter interaction can influence the effective driving force and electronic couplings between the donor state, which is the hybrid light-matter excitation, and the molecular acceptor state. Under the resonance condition between the photonic and electronic excitations, the effective driving force can be tuned by changing the light-matter coupling strength; for an off-resonant condition, the same effect can be accomplished by changing the molecule-cavity detuning. We further demonstrate that using both the electronic coupling and light-matter coupling helps to extend the effective couplings across the entire system, even for the dark state that carries a zero transition dipole. Theoretically, we find that both the counter-rotating terms and the dipole self-energy in the quantum electrodynamics Hamiltonian are important for obtaining an accurate polariton eigenspectrum as well as the polariton-mediated charge transfer rate constant, especially in the ultrastrong coupling regime.


Sarcoidosis-Lymphoma Syndrome Associated with Folliculotropic Peripheral T Cell Lymphoma Not Otherwise Specified.
Sarcoidosis is occasionally accompanied by hematologic malignancies, including cutaneous T-cell lymphoma, called sarcoidosis-lymphoma syndrome. Although the mechanism underlying the induction of lymphomas is still unknown, understanding the immunological background of sarcoidosis could help explain the possible mechanisms of the induction of lymphomas. In this report, we describe a case of sarcoidosis-lymphoma syndrome associated with folliculotropic peripheral T cell lymphoma not otherwise specified, which caused dense infiltration of CD30+ CD163+ tumor-associated macrophages (TAMs) only in the lesional skin. Our present case might suggest the significance of TAMs in developing sarcoid-lymphoma syndrome.


Ni(ii)-Catalyzed vinylic C-H functionalization of 2-acetamido-3-arylacrylates to access isotetronic acids.
A ligand-free Ni(ii)-catalyzed cascade annulation reaction for the synthesis of 4-aryl-substituted isotetronic acids from 2-acetamido-3-arylacrylates via vinylic C-H functionalization is reported. The reaction proceeds through heteroatom guided electrophilic insertion of nickel to the vinylic double bond followed by annulation with dibromomethane. This unconventional route features cascade steps, sole product formation, multiple functional group tolerance, low cost of catalysts and reagents, and readily available starting materials. Using this method, various aryl-substituted isotetronic acids have been synthesized which are biologically relevant. The annulation of 2-acetamido-3-arylacrylates has also been assessed with 1,2-dichloroethane, which resulted in the rearranged annulated products of 5-methyl substituted isotetronic acids.


Aminoglycoside toxicity - a review of clinical studies published between 1975 and 1982.
The present survey of aminoglycoside nephro- and ototoxicity covers approximately 10,000 patients reported on in clinical trials published between 1975 and 1982. Included in the survey were clinical trials with at least 15 patients evaluable for nephro and/or ototoxicity provided relevant data were given on methodology, patient material and aminoglycoside dosage. Each publication was evaluated by both investigators and relevant data entered into a chart. One hundred and forty-four published trials were surveyed; 139, 63 and 34 for renal, cochlear and vestibular side effects, respectively. Frequencies were calculated as number of patients with side effect of total number of evaluated patients. In the average overall figures toxicity labelled by respective authors as 'definitely', 'probably' and 'possibly' related to study drug is included. When available, frequencies of toxicity 'definitely' and 'probably' related to study drug were analysed separately. The average daily dosages of gentamicin, tobramycin, netilmicin and amikacin were 3.9, 3.8, 5.2 and 15.4 mg/kg, respectively. The average frequencies of nephrotoxicity for gentamicin and tobramycin were 14.0 and 12.9%, respectively, and of netilmicin and amikacin 8.7 and 9.4%, respectively. The average frequency of cochlear toxicity was 13.9% for amikacin, 8.3 and 6.1% for gentamicin and tobramycin, respectively, and 2.4% for netilmicin. The material available for evaluation of vestibular toxicity was considerably smaller. The average frequencies for gentamicin, tobramycin and amikacin were similar (3.2 to 3.7%) while netilmicin again exhibited a somewhat lower figure (1.4%). The overall figures and the clinical ranking that they imply were basically substantiated when prospective comparative trials were analysed separately. However, some inconsistencies go unexplained: for example the frequency of gentamicin nephrotoxicity was markedly higher in trials where it was compared to tobramycin (20 trials) than when it was compared to netilmicin (16 trials).


Inpatient management of hyperglycemia: the Northwestern experience.
To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner.


Recovery of an antiviral antibody response following attrition caused by unrelated infection.
The homeostatic mechanisms that regulate the maintenance of immunological memory to the multiple pathogen encounters over time are unknown. We found that a single malaria episode caused significant dysregulation of pre-established Influenza A virus-specific long-lived plasma cells (LLPCs) resulting in the loss of Influenza A virus-specific Abs and increased susceptibility to Influenza A virus re-infection. This loss of LLPCs involved an FcγRIIB-dependent mechanism, leading to their apoptosis. However, given enough time following malaria, the LLPC pool and humoral immunity to Influenza A virus were eventually restored. Supporting a role for continuous conversion of Influenza A virus-specific B into LLPCs in the restoration of Influenza A virus immunity, B cell depletion experiments also demonstrated a similar requirement for the long-term maintenance of serum Influenza A virus-specific Abs in an intact LLPC compartment. These findings show that, in addition to their established role in the anamnestic response to reinfection, the B cell pool continues to be a major contributor to the maintenance of long-term humoral immunity following primary Influenza A virus infection, and to the recovery from attrition following heterologous infection. These data have implications for understanding the longevity of protective efficacy of vaccinations in countries where continuous infections are endemic.


Addressable nanowell arrays formed using reversibly sealable hybrid elastomer-metal stencils.
There are two major array formats used in life science research and biomedical analysis. The first is the microwell plate format with millimeter-sized wells each with microliter capacity addressed individually and repeatedly during experiments. The second is the microarray format with micrometer-sized spots that are patterned initially but not addressable individually thereafter. Here, we present an addressable nanoliter-well plate with micrometer sized wells that combines the advantages of the two array formats. The nanowells are formed by reversibly sealing a steel stencil featuring an array of micrometer-scale openings to an optically transparent substrate. The nanowells have a capacity of approximately 1 nL, are approximately 140 microm in diameter, and are arrayed at a density of 1600 wells cm(-2). A soft polymer is patterned photolithographically around each opening so as to form a microgasket for pressure sensitive, liquid tight, and reversible sealing to any type of smooth substrate, either hydrophilic or hydrophobic. The rigidity of the steel prevents the distortion that occurs in soft, all-polymeric stencils and permits accurate registration across the entire array, which in turn allows for repeated, individual addressing of wells using an inkjet spotter. The stencils are used to pattern cells, make protein microarrays, and create nanowells on surfaces to study reverse transfection by first spotting plasmids encoding fluorescent proteins into the wells, seeding cells, and monitoring the transfection of the cells in real time using time-lapse imaging. The hybrid elastomer-metal stencils (HEMSs) are versatile and useful for multiplexed analysis of drugs, biomolecules, and cells with microarray density.