Effect of perioperative fluid therapy on early phase prognosis after liver transplantation.
Although liver transplantation (LT) has made rapid progress, early pulmonary complications still occur. More attention should be paid to fluid therapy that may be an important factor leading to these complications. It is necessary to investigate the correlation between intraoperative and postoperative fluid therapy and early pulmonary complications after LT, then attempt to provide a reasonable fluid therapy in the perioperative period. Sixty-two patients who had undergone LT were enrolled and analyzed retrospectively. Based on early phase prognosis after LT, the 62 patients were divided into a non-pulmonary complication group and a pulmonary complication group. Twenty perioperative variables were analyzed in both groups to screen out several factors causing early pulmonary complications, then the parameters reflecting postoperative recovery were analyzed. The pulmonary complication group had 29 patients (46.77%), 3 (4.84%) of whom died during the perioperative period. Using monofactorial analysis for each variable, the two groups differed in the following variables: preoperative lung function, volume of intraoperative transfusion, volume of intraoperative bleeding, and volume of intraoperative net fluid retention and fluid balance (< or =-500 ml) in > or =2 of the first 3 days after operation. Analysis of the relationship between multivariate factors and pulmonary complications after LT by logistic multivariate regression analysis showed that preoperative lung function, volume of intraoperative bleeding, and fluid balance (< or =-500 ml) in > or =2 of the first 3 days after operation were influential factors. It is important to maintain fluid balance during the perioperative period of LT. If the hemodynamics are stable, appropriate negative fluid balance in the first 3 days after operation apparently decreases the incidence of early pulmonary complications after LT. These measures are associated with better postoperative recovery.


Dosimetric impact of respiratory motion, interfraction baseline shifts, and anatomical changes in radiotherapy of non-small cell lung cancer.
The survival rates for patients with non-small cell lung cancer (NSCLC) may be improved by dose escalation; however, margin reduction may be required in order to keep the toxicity at an acceptable level. In this study we have investigated the dosimetric impact of tumor motion and anatomical changes during intensity-modulated radiotherapy (IMRT) of patients with NSCLC. Sixteen NSCLC patients received IMRT with concomitant chemotherapy. The tumor and lymph node targets were delineated in the mid-ventilation phase of a planning 4DCT scan (CT1). Typically 66 Gy was delivered in 33 fractions using daily CBCT with bony anatomy match for patient setup. The daily baseline shifts of the mean tumor position relative to the spine were extracted from the CBCT scans. A second 4DCT scan (CT2) was acquired halfway through the treatment course and the respiratory tumor motion was extracted. The plan was recalculated on CT2 with and without inclusion of the respiratory tumor motion and baseline shifts in order to investigate the impact of tumor motion and anatomical changes on the tumor dose. Respiratory tumor motion was largest in the cranio-caudal (CC) direction (range 0-13.1 mm). Tumor baseline shifts up to 18 mm (CC direction) and 24 mm (left-right and anterior-posterior) were observed. The average absolute difference in CTV mean dose to the primary tumor (CTV-t) between CT1 and CT2 was 1.28% (range 0.1-4.0%) without motion. Respiratory motion and baseline shifts lead to average absolute CTV-t mean dose changes of 0.46% (0-1.9%) and 0.65% (0.0-2.1%), respectively. For most patients, the changes in the CTV-t dose were caused by anatomical changes rather than internal target motion. Anatomical changes had larger impact on the target dose distribution than internal target motion. Adaptive radiotherapy could be used to achieve better target coverage throughout the treatment course.


Clinical Presentation, Investigation and Control of an Outbreak of Adenoviral Conjunctivitis in a Neonatal Unit at a Tertiary Hospital.
Nosocomial spread of adenovirus infection has been reported in neonatal, pediatric and adult medical units. This nonenveloped and hardy virus is resistant to numerous disinfectants thus posing a challenge for control and prevention of adenovirus infections in health care settings. An epidemiologic outbreak investigation revealed an adenoviral outbreak in the neonatal nursery as well as in the neonatal screening outpatient department for Retinopathy of Prematurity (ROP). All suspected cases (94 neonates) underwent adenoviral conventional polymerase chain reaction (PCR) and representative samples underwent sequencing by Sanger's method. The clinical features and disease course were studied. Infected babies were started on tobramycin eye drops. Topical steroid eye drops were added for those who developed pseudomembranes. We found 58 cases of laboratory-confirmed neonatal adenovirus conjunctivitis (between July 10 and October 24, 2019). Redness (96%) was the most common presentation followed by discharge (68.9%) and lid edema (51.7%). Pseudomembrane were seen in 77.5% of the infected neonates. Prior ROP examination was carried out in 38 (65.5%) neonates. Respiratory symptoms were present in 7 (12.06%) neonates. Sequencing revealed serotype 8 as the cause of the outbreak. Control measures were strictly implemented. Standard Operating Procedures (SOPs) for ROP screening were revisited, revised and reinforced to prevent future outbreaks. We observed ROP screening as a risk factor for the development of adenoviral conjunctivitis in neonatal care units. Neonates present with different clinical manifestations as compared with adults. Prompt control measures were implemented to control the adenoviral outbreak.


Doppler imaging of the ophthalmic vasculature of the normal dog: blood velocity measurements and reproducibility.
The purpose of this study was to assess the feasibility and reproducibility of color Doppler imaging (CDI) of the vasculature of the normal canine orbit and eye. Eight normal Beagles were evaluated by Doppler imaging. The goals of the study were to determine the location, spectral waveform morphology, specific blood velocity parameters, and reproducibility for the ophthalmic and orbital vessels most frequently identified in the normal dog. Vessels identified a majority of the time (> 50%) included: external ophthalmic artery, dorsal external ophthalmic vein, ventral external ophthalmic vein, internal ophthalmic artery, anterior ciliary artery and vein, short and long posterior ciliary arteries, primary retinal arteries, and vortex veins. Other vessels imaged less frequently included: external ethmoidal artery (50%), and primary retinal veins (25%). For each blood vessel the time averaged velocity, peak systolic velocity, minimum diastolic velocity, pulsatility index, and resistive index were determined. The ophthalmic and orbital vessels have unique spectral waveforms and velocities which serve as a basis for identification. Reproducibility of the most commonly imaged vessels of the canine eye and orbit with Doppler imaging was high (< 10% variation). Doppler imaging has the potential for determining noninvasively and consecutively the blood velocity parameters found in orbital and ocular diseases, including orbital inflammations and neoplasms; intraocular inflammations and neoplasms; vascular diseases including systemic vascular disease (hypertension), vasculopathies, and anemia; the glaucomas; and documentable follow-up after medical and/or surgical treatment of these diseases.


Implementing a multi-sectoral response to HIV: a case study of AIDS councils in the Mpumalanga Province, South Africa.
A multi-sectoral response is advocated by international organisations as a good strategy to address the multiple drivers and impact of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), and was historically mandated as a condition of funding. In March 2017, the South African National AIDS Council (SANAC) launched the latest 5 year National Strategic Plan (NSP) to address HIV, sexually transmitted infections and tuberculosis. As with previous iterations, the NSP calls for multi-sectoral action (MSA) and mandates AIDS councils (ACs) at different levels to coordinate its implementation. Efforts have been made to advocate for the adoption of MSA in South Africa, yet evaluation of these efforts is currently limited. This paper assesses the implementation of a multi-sectoral response to HIV in South Africa, through a case study of the Mpumalanga Province. We identified and reviewed key policy documents, conducted 12 interviews and held six focus group discussions. We also drew on our involvement, through participant observation, in the development of NSPs and in AC meetings. SANAC is struggling to provide much-needed support to provincial, district and local ACs. Therefore, most ACs are generally weak and failing to implement MSA. Membership is voluntary, there is a lack of sustained commitment and they do not include representatives from all sectors. There is little capacity to undertake the activities necessary for coordinating the implementation of MSA, and unclear roles and responsibilities within ACs result in divisions and tension between sectors. There is inadequate senior political leadership and funding to facilitate effective implementation of MSA. We identified three interventions that we argue are required to support the effective implementation of MSA: strengthening and stabilising the SANAC structure; building capacity of ACs; and creating an enabling environment for effective implementation of MSA through political leadership, support and resourcing of the HIV response.


Obligatory role of cyclic adenosine monophosphate response element in cyclooxygenase-2 promoter induction and feedback regulation by inflammatory mediators.
Cyclooxygenase-2 (COX-2) plays a key role in human inflammatory disorders such as vascular inflammation. COX-2 promoter activity is induced by proinflammatory mediators, but the role of cyclic adenosine monophosphate response element (CRE) in promoter stimulation remains unclear. Transient transfection of a 0.9-kb COX-2 promoter fragment bearing CRE mutation abrogated COX-2 promoter activity induced by proinflammatory mediators in human endothelial cells and fibroblasts. Dual mutations of CRE and an upstream CCAAT/enhancer binding protein (C/EBP) site did not have an additional effect. Binding of CREB-2, ATF-2, USF-2, and c-Jun transactivators to a wild-type and CRE-mutated oligonucleotide was analyzed by a novel DNA-binding assay. CREB-2 and ATF-2 in nuclear extracts of unstimulated endothelial cells bound to CRE, whereas USF-2 and c-Jun or c-Fos bound to non-CRE sites. CREB-2 and c-Fos binding was increased by phorbol 12-myristate 13-acetate but not tumor necrosis factor-alpha. The binding assay and chromatin immunoprecipitation revealed binding of P300 coactivator to the COX-2 promoter region. CRE plays an obligatory role in COX-2 promoter activation by diverse stimuli. CREB-2 and ATF-2 bound to CRE serve as an anchor for P300 interaction with upstream transactivators and downstream transcription machinery.


The New Kid on the Block: HLA-C, a Key Regulator of Natural Killer Cells in Viral Immunity.
The human leukocyte antigen system (HLA) is a cluster of highly polymorphic genes essential for the proper function of the immune system, and it has been associated with a wide range of diseases. HLA class I molecules present intracellular host- and pathogen-derived peptides to effector cells of the immune system, inducing immune tolerance in healthy conditions or triggering effective immune responses in pathological situations. HLA-C is the most recently evolved HLA class I molecule, only present in humans and great apes. Differentiating from its older siblings, HLA-A and HLA-B, HLA-C exhibits distinctive features in its expression and interaction partners. HLA-C serves as a natural ligand for multiple members of the killer-cell immunoglobulin-like receptor (KIR) family, which are predominately expressed by natural killer (NK) cells. NK cells are crucial for the early control of viral infections and accumulating evidence indicates that interactions between HLA-C and its respective KIR receptors determine the outcome and progression of viral infections. In this review, we focus on the unique role of HLA-C in regulating NK cell functions and its consequences in the setting of viral infections.


An in vitro assessment of titanium functionalized with polysaccharides conjugated with vascular endothelial growth factor for enhanced osseointegration and inhibition of bacterial adhesion.
The long-term success of orthopedic implants may be compromised by defective osseointegration and bacterial infection. An effective approach to minimize implant failure would be to modify the surface of the implant to make it habitable for bone-forming cells and anti-infective at the same time. In this in vitro study, the surfaces of titanium (Ti) substrates were functionalized by first covalently grafting either dopamine followed by carboxymethyl chitosan (CMCS) or hyaluronic acid-catechol (HAC). Vascular endothelial growth factor (VEGF) was then conjugated to the polysaccharide-grafted surface. Antibacterial assay with Staphylococcus aureus (S. aureus) showed that the polysaccharide-modified substrates significantly decrease bacterial adhesion. The CMCS-functionalized Ti demonstrated better antibacterial property than the HAC-functionalized Ti since CMCS is bactericidal while HA only inhibits the adhesion of bacteria without killing them. Osteoblast attachment, as well as alkaline phosphatase (ALP) activity and calcium deposition were enhanced by the immobilized VEGF on the polysaccharide-grafted Ti. Thus, Ti substrates modified with polysaccharides conjugated with VEGF can promote osteoblast functions and concurrently reduce bacterial adhesion. Since VEGF is also known to enhance angiogenesis, the VEGF-polysaccharide functionalized substrates will have promising applications in the orthopedic field.


The Harris-Galante cementless femoral component: poor results in 57 hips followed for 3 years.
Between 1986 and 1991, 68 Harris-Galante femoral prostheses were implanted in 63 patients. 53 patients (57 hips) attended for follow-up after a mean of 3.4 (2-6) years. The average Harris Hip Score (HHS) was 39 preoperatively and 81 postoperatively. Only 34 hips were excellent (27) or good (7). Mid-thigh pain occurred in 30 cases. 10 femoral components were radiographically loose because of osteolysis. Although 7 cups seemed to be radiographically loose, they probably played only a minor role in the poor overall early clinical results.


Fructose-2,6-bisphosphate is lower in copper deficient rat cerebellum despite higher content of phosphorylated AMP-activated protein kinase.
Limitation in copper (Cu) leads to pathophysiology in developing brain. Cu deficiency impairs brain mitochondria and results in high brain lactate suggesting augmented anaerobic glycolysis. AMP activated protein kinase (AMPK) is a cellular energy "master-switch" that is thought to augment glycolysis through phosphorylation and activation phosphofructokinase 2 (PFK2) resulting in increases of the glycolytic stimulator fructose-2,6-bisphosphate (F2,6BP). Previously, Cu deficiency has been shown to augment cerebellar AMPK activation. Cerebella of Cu-adequate (Cu+) and Cu-deficient (Cu-) rat pups were assessed to evaluate if AMPK activation in Cu- cerebella functioned to enhance PFK2 activation and increase F2,BP concentration. Higher levels of pAMPK were detected in Cu- cerebella. However, PFK2 activity, mRNA, and protein abundance were not affected by Cu deficiency. Surprisingly, F2,6BP levels were markedly lower in Cu- cerebella. Lower F2,6BP may be due to inhibition of PFK2 by citrate, as citrate concentration was significantly higher in Cu- cerebella. Data suggest AMPK activation in Cu- cerebellum does not augment glycolysis through a PFK2 mechanism. Furthermore, other metabolite data suggest that glycolysis may actually be blunted, since levels of glucose and glucose-6-phosphate were higher in Cu- cerebella than controls.


Work-related factors associated with visiting a doctor for a medical diagnosis after a worksite screening for diabetes mellitus in Japanese male employees.
This paper aims to investigate the work-related factors that affect whether Japanese male employees will seek a medical diagnosis after being screened for diabetes mellitus. Participants in this study received a questionnaire two months after receiving the results of their physical checkup. The analysis focused on 213 regular employees of small and medium-sized companies who were aged 35-64 and who had tested positive for diabetes in a screening. Only 42% of the subjects visited a doctor for medical diagnosis during an average follow-up period of 47.5 d. Cox's proportional hazard regression was used to analyze the length of time between the employees' receipt of the results and their first visit to a doctor's office. The employees who could comfortably take a day off, compared to those who found it difficult to do so, were more likely to visit a doctor (hazard ratio (HR) 1.94; 95% confidence interval (CI) 0.85, 4.42; p for trend 0.05). In addition, employees with a high level of psychological job control, compared to those with low level of job control, were more likely to visit a doctor (HR 1.80; 95%CI 0.94, 3.45; p for trend 0.08). Employees who worked the longest (61 h per week or more) were less likely to visit a doctor than those working from 41 to 60 h weekly (HR 0.41; 95%CI 0.17, 0.98). The findings suggest that a flexible work schedule, autonomy at work, and no excessive working hours tend to improve the chance of visiting a doctor after screening for diabetes mellitus.


Prostaglandin E2 receptor EP1 transactivates EGFR/MET receptor tyrosine kinases and enhances invasiveness in human hepatocellular carcinoma cells.
Recent evidence indicates that cyclooxygenase-2 (COX-2) and epidermal growth factor receptor (EGFR) are involved in hepatocarcinogenesis. This study was designed to evaluate the possible interaction between the COX-2 and EGFR signaling pathways in human hepatocellular carcinoma (HCC) cells. Immunohistochemical analysis using serial sections of human HCC tissues revealed positive correlation between COX-2 and EGFR in HCC cells (P < 0.01). Overexpression of COX-2 in cultured HCC cells (Hep3B) or treatment with PGE(2) or the selective EP(1) receptor agonist, ONO-DI-004, increased EGFR phosphorylation and tumor cell invasion. The PGE(2)-induced EGFR phosphorylation and cell invasiveness were blocked by the EP(1) receptor siRNA or antagonist ONO-8711 and by two EGFR tyrosine kinase inhibitors, AG1478 and PD153035. The EP(1)-induced EGFR transactivation and cell invasion involves c-Src, in light of the presence of native binding complex of EP(1)/Src/EGFR and the inhibition of PGE(2)-induced EGFR phosphorylation and cell invasion by the Src siRNA and the Src inhibitor, PP2. Further, overexpression of COX-2 or treatment with PGE(2) also induced phosphorylation of c-Met, another receptor tyrosine kinase critical for HCC cell invasion. Moreover, activation of EGFR by EGF increased COX-2 promoter activity and protein expression in Hep3B and Huh-7 cells, whereas blocking PGE(2) synthesis or EP(1) attenuated EGFR phosphorylation induced by EGF, suggesting that the COX-2/PGE(2)/EP(1) pathway also modulate the activation of EGFR by its cognate ligand. These findings disclose a cross-talk between the COX-2/PGE(2)/EP(1) and EGFR/c-Met signaling pathways that coordinately regulate human HCC cell invasion.


Incidence and radiographic findings of primary central nervous system lymphoma in immunocompetent patients in southern Thailand.
In the last two decades there have been conflicting reports concerning a rising incidence of primary central nervous system lymphoma (PCNSL) in immunocompetent patients. This study is being conducted to review the incidence and radiographic findings of PCNSL in a large tertiary care institution in southern Thailand. A review was carried out in Songklanagarind University Hospital of the clinical records, CT and MRI images of immunocompetent patients who had histologically proven PCNSL diagnosed between January 1993 and December 2004. A total of 25 PCNSL patients were diagnosed over a 12-year period. The incidence trend was rising but not to a statistically significant extent. The median age at diagnosis was 57.4 years. Based on the Working Formulation classification, diffuse large cell was the most common subtype. All of the 20 patients with available immunohistochemical results had B-cell lymphomas. The radiographic findings in our series show that the majority of patients had a single lesion (60%) at a supratentorial location (50%). Most of the lesions were well circumscribed. Based on the density of the lesions before administration of a contrast medium, 56% of the lesions on CT images appeared hyperdense. On T1-weighted MRI images, the lesions of our patients were most frequently hypointense (67%) while the T2-weighted images were more commonly hyperintense (60%) and contrast enhancement was found in all lesions. There were 21 patients who received whole brain radiotherapy with doses ranging between 4.2 and 6.0 Gy. The median survival time was 14.4 months. This study indicates that there has been no significant increase in PCNSL cases over the last 12 years. The recognition of characteristic imaging features of PCNSL may facilitate a stereotactic procedure before steroid administration. In addition, we provide evidence that radiotherapy alone is insufficient in PCNSL.


Surgical and clinical management of a patient with Glanzmann thrombasthenia: a case report.
A 6-year-old girl with Glanzmann thrombasthenia presented with caries and periapical lesions in the primary mandibular second molars and moderate gingivitis of the maxillary and mandibular anterior teeth. Dental extraction was recommended, and before every surgical intervention, the patient underwent platelet-concentrate transfusion to prevent hemorrhage. Epsilon aminocaproic acid was administered 6 hours before, and 48 hours after every dental procedure to prevent bleeding. In this case, treatment was effective in the prevention of hemorrhagic complications, during the required dental procedures.


Healthy food outside: farmers' markets, taco trucks, and sidewalk fruit vendors.
This paper explores the many dimensions of street vending and public markets, the multiple intersections vending and markets have with food regulation, and the historical connection markets have with other policy problems. We develop the article in four parts, following the introduction found in section one the article touches on three elements of law and public policy. The second section considers markets and merchants in public goods with their associated dilemmas. Our approach is to reconfigure the emphasis on public space as transportation by justifying the use of the street and sidewalk for street vending. The importance of public space for commerce and other creative activities bridges the second and third sections of the article. The third section chronicles the history of law and regulation around street and public markets. Here we emphasize how cities historically used public markets as public policy tools to address food security, employment, and to help those growing cities accommodate new immigrants. The fourth section focuses on public health by examining the law of outdoor food sold on the street. Through our analysis we set forth numerous suggestions for advocacy, policy, and legal reform.


Therapeutic targets to reduce cardiovascular disease in type 2 diabetes.
The potential cardiovascular risks that are associated with drugs for type 2 diabetes have recently raised considerable clinical and regulatory concerns. As some risk factors for cardiovascular disease and type 2 diabetes are related, identifying agents that target shared underlying pathways and processes is an attractive therapeutic strategy. In this article, we review the background to and the implications of recent regulatory guidance on the development of new drugs for diabetes, and discuss the potential cardiovascular effects of selected classes of diabetes drugs that are currently being investigated.


Pregnancy following laparoscopic myomectomy: preliminary results.
The objective of this study was to assess the outcome of pregnancy in a series of women who underwent laparoscopic myomectomy. A total of 115 women underwent laparoscopic myomectomy for pressure and pain (76.5%), abnormal bleeding (52.2%) and/or infertility (29.6%). Follow up data were obtained either by reviewing the patient's chart or returned questionnaire. Of the 115 women, there were 42 pregnancies in 31 patients. Two women were lost to follow-up. Of the remaining 40 pregnancies, six ended with vaginal delivery at term. Caesareans were performed in 22 cases, including 21 at term and one at 26 weeks gestation. Two pregnancies were associated with a normal delivery, but the mode of delivery is unknown. Eight resulted in first trimester pregnancy loss, one was an ectopic pregnancy, and one patient underwent elective termination. Spontaneous uterine rupture was not noted during pregnancy or at term in any of the cases. Average length of follow-up from the date of surgery was 43 months, with a range of 9-99 months. Our series did not confirm the hypothesis that laparoscopic myomectomy is associated with an increased risk for uterine dehiscence during pregnancy. However, a larger series is needed to make a conclusive judgement.


Cardiovascular effects of antipsychotics used in bipolar illness.
Many antipsychotics are used to treat disorders other than schizophrenia, such as bipolar disorder. However, some of these agents are associated with cardiovascular side effects that can have serious or fatal implications for the patient. One dangerous side effect is QT prolongation, which can lead to torsades de pointes and ventricular arrhythmia. The group of drugs labeled as antipsychotics is diverse, making it challenging for the clinician to keep track of which agents cause which effects and important for the clinician to learn to identify signs of cardiovascular side effects and manage those events when they occur.


Association Between Minimum Inhibitory Concentration, Beta-lactamase Genes and Mortality for Patients Treated With Piperacillin/Tazobactam or Meropenem From the MERINO Study.
This study aims to assess the association of piperacillin/tazobactam and meropenem minimum inhibitory concentration (MIC) and beta-lactam resistance genes with mortality in the MERINO trial. Blood culture isolates from enrolled patients were tested by broth microdilution and whole genome sequencing at a central laboratory. Multivariate logistic regression was performed to account for confounders. Absolute risk increase for 30-day mortality between treatment groups was calculated for the primary analysis (PA) and the microbiologic assessable (MA) populations. In total, 320 isolates from 379 enrolled patients were available with susceptibility to piperacillin/tazobactam 94% and meropenem 100%. The piperacillin/tazobactam nonsusceptible breakpoint (MIC >16 mg/L) best predicted 30-day mortality after accounting for confounders (odds ratio 14.9, 95% confidence interval [CI] 2.8-87.2). The absolute risk increase for 30-day mortality for patients treated with piperacillin/tazobactam compared with meropenem was 9% (95% CI 3%-15%) and 8% (95% CI 2%-15%) for the original PA population and the post hoc MA populations, which reduced to 5% (95% CI -1% to 10%) after excluding strains with piperacillin/tazobactam MIC values >16 mg/L. Isolates coharboring extended spectrum β-lactamase (ESBL) and OXA-1 genes were associated with elevated piperacillin/tazobactam MICs and the highest risk increase in 30-day mortality of 14% (95% CI 2%-28%). After excluding nonsusceptible strains, the 30-day mortality difference from the MERINO trial was less pronounced for piperacillin/tazobactam. Poor reliability in susceptibility testing performance for piperacillin/tazobactam and the high prevalence of OXA coharboring ESBLs suggests that meropenem remains the preferred choice for definitive treatment of ceftriaxone nonsusceptible Escherichia coli and Klebsiella.


Discrepancies in adolescent-mother dyads' reports of core depression symptoms: Association with adolescents' help-seeking in school and their somatic complaints.
Parents of adolescents with mental problems do not always recognize the symptoms in their children, particularly regarding depression, and therefore do not seek professional help. Adolescents themselves tend to seek help from school personnel for their emotional or social difficulties. In contrast, adolescents do report somatic complaints and parents are likely to seek help for these problems. The current study explored whether the divergence between maternal and child reports of depression symptoms is associated with child's help-seeking in school and patterns of somatic complaints. A sample of 9th grade students (N = 693; 56% girls; mean age = 15.1) and their mothers representing the Muslim and Druze populations in northern Israel were interviewed simultaneously and independently. Maternal reports were classified either as underestimating, matching, or overestimating their own child self-report of three core symptoms of depression (depressed mood, anhedonia, and irritability). Adolescents reported whether they had consulted school staff and were classified into clusters based on self-reported somatic complaints. Maternal misidentification of their child's depression symptoms was associated with increased help-seeking in school, particularly by boys if depressed mood or irritability were misidentified and particularly by girls if anhedonia was misidentified. Hierarchical cluster analysis indicated that the number and severity of somatic complaints was higher among adolescents whose depression symptoms were not identified, regardless of gender. Mental health professionals, educators and parents should be aware that adolescents may attempt to communicate their emotional difficulties through somatic complaints and by seeking help in school.


Thulium-doped fiber chirped-pulse amplification system with 2 GW of peak power.
Thulium-doped fibers with ultra large mode-field areas offer new opportunities for the power scaling of mid-IR ultrashort-pulse laser sources. Here, we present a laser system delivering a pulse-peak power of 2 GW and a nearly transform-limited pulse duration of 200 fs in combination with 28.7 W of average power. This performance level has been achieved by optimizing the pulse shape, reducing the overlap with atmospheric absorption lines, and incorporating a climate chamber to reduce the humidity of the atmospheric environment.


[Cerebral oximeter INVOS-3100].
A new device is described: cerebral oximeter intended for monitoring cerebral oxygenation and early diagnosis of cerebral ischemia and hypoxia. The advantages and shortcomings of the proposed method are analyzed in comparison with other current methods for the early diagnosis of cerebral ischemia.


The revised Trypanosoma cruzi subspecific nomenclature: rationale, epidemiological relevance and research applications.
The protozoan Trypanosoma cruzi, its mammalian reservoirs, and vectors have existed in nature for millions of years. The human infection, named Chagas disease, is a major public health problem for Latin America. T. cruzi is genetically highly diverse and the understanding of the population structure of this parasite is critical because of the links to transmission cycles and disease. At present, T. cruzi is partitioned into six discrete typing units (DTUs), TcI-TcVI. Here we focus on the current status of taxonomy-related areas such as population structure, phylogeographical and eco-epidemiological features, and the correlation of DTU with natural and experimental infection. We also summarize methods for DTU genotyping, available for widespread use in endemic areas. For the immediate future multilocus sequence typing is likely to be the gold standard for population studies. We conclude that greater advances in our knowledge on pathogenic and epidemiological features of these parasites are expected in the coming decade through the comparative analysis of the genomes from isolates of various DTUs.


Adipose tissue monomethyl branched-chain fatty acids and insulin sensitivity: Effects of obesity and weight loss.
An increase in circulating branched-chain amino acids (BCAA) is associated with insulin resistance. Adipose tissue is a potentially important site for BCAA metabolism. It was evaluated whether monomethyl branched-chain fatty acids (mmBCFA) in adipose tissue, which are likely derived from BCAA catabolism, are associated with insulin sensitivity. Insulin-stimulated glucose disposal was determined by using the hyperinsulinemic-euglycemic clamp procedure with stable isotope glucose tracer infusion in nine lean and nine obese subjects, and in a separate group of nine obese subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery (38% weight loss). Adipose tissue mmBCFA content was measured in tissue biopsies taken in the basal state. Total adipose tissue mmBCFA content was ∼30% lower in obese than lean subjects (P=0.02) and increased by ∼65% after weight loss in the RYGB group (P=0.01). Adipose tissue mmBCFA content correlated positively with skeletal muscle insulin sensitivity (R(2) =35%, P=0.01, n=18). These results demonstrate a novel association between adipose tissue mmBCFA content and obesity-related insulin resistance. Additional studies are needed to determine whether the association between adipose tissue mmBCFA and muscle insulin sensitivity is causal or a simple association.


Investigation of film thickness uniformity on substrates located close to the source axis.
The thickness uniformity that can be obtained near the source axis in evaporation systems having long source-to-substrate distances (~50 cm) and small area sources has been investigated using multiplebeam interferometry. Silver films were evaporated from resistance-heated dimple boats in standard vacuum and ultrahigh vacuum onto stationary and rotating substrates 3.86 cm in diameter symmetrically placed about the source axis. Thickness variations in the films were measured across substrate diameters, and the average film thicknesses were compared. Similar data were also obtained for aluminum, aluminum oxide, and germanium films. Random thickness variations have been found on all the films, which are much larger than the uniform thickness gradations predicted by the geometric theory. These variations can be minimized but not eliminated by planetary rotation of the substrates.


Pharmacological inhibition of Rho-kinase signaling with Y-27632 blocks melanoma tumor growth.
Primarily through in vitro studies, the Rho-family of small GTPases and their effector proteins have been implicated in mediating oncogenic properties of cancer cells. We sought to determine if pharmacological inhibition of the RhoA effector proteins known as Rho-kinases (ROCK) with the small molecule inhibitor Y-27632 could inhibit melanoma in vitro and in vivo. We demonstrate that Y-27632 treatment of a panel of melanoma cells alters cellular morphology leading to spindly cells with decreased lamellipodia and increased filopodia formation. Y-27632 treatment decreases invasion and alters cell survival of cultured melanoma cells. IP injection of Y-27632 in tumor-bearing mice resulted in a reduction in melanoma tumor volume compared to control treated mice. These findings suggest that ROCK inhibition can reduce melanoma tumorigenicity.


Egg breakfast enhances weight loss.
To test the hypotheses that an egg breakfast, in contrast to a bagel breakfast matched for energy density and total energy, would enhance weight loss in overweight and obese participants while on a reduced-calorie weight loss diet. Men and women (n=152), age 25-60 years, body mass index (BMI) >or=25 and <or=50 kg m(-2). Otherwise healthy overweight or obese participants were assigned to Egg (E), Egg Diet (ED), Bagel (B) or Bagel Diet (BD) groups, based on the prescription of either an egg breakfast containing two eggs (340 kcal) or a breakfast containing bagels matched for energy density and total energy, for at least 5 days per week, respectively. The ED and BD groups were suggested a 1000 kcal energy-deficit low-fat diet, whereas the B and E groups were asked not to change their energy intake. After 8 weeks, in comparison to the BD group, the ED group showed a 61% greater reduction in BMI (-0.95+/-0.82 vs -0.59+/-0.85, P<0.05), a 65% greater weight loss (-2.63+/-2.33 vs -1.59+/-2.38 kg, P<0.05), a 34% greater reduction in waist circumference (P<0.06) and a 16% greater reduction in percent body fat (P=not significant). No significant differences between the E and B groups on the aforementioned variables were obtained. Further, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides, did not differ between the groups. The egg breakfast enhances weight loss, when combined with an energy-deficit diet, but does not induce weight loss in a free-living condition. The inclusion of eggs in a weight management program may offer a nutritious supplement to enhance weight loss.


Neonatal isolation enhances hippocampal dentate response to tetanization in freely moving juvenile male rats.
The impact of early neonatal isolation on measures of hippocampal neuronal plasticity was examined in freely moving male rats at 30 days of age. Beginning on Postnatal (PN) Day 2, one-half of pups from each experimental litter were individually isolated from the nest, dam, and siblings for a period of 1 h per day over PN Days 2-9, while their siblings remained in the nest. In addition, randomly selected litters served as unhandled controls. On PN Day 26 all pups were weaned and chronically implanted for recording of evoked field potentials and induction of hippocampal longterm potentiation. At 30 days of age, pups from the three treatment groups (isolated, nonisolated siblings, and unhandled controls) were tested for their ability to establish and maintain long-term potentiation across the perforant path/hippocampal dentate granule cell synapse. Changes in population EPSP slope and population spike amplitude (PSA) recorded following tetanization were used to assess the effects of neonatal isolation of hippocampal response measures. No significant between-group differences were obtained for input/output response curves constructed prior to tetanization. All three groups showed immediate and significant enhancement of the PSA measure at 15 min posttetanization. The level of PSA enhancement obtained from previously isolated pups was significantly greater than that obtained from both the nonisolated sibling and unhandled control groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiation therapy for rectal cancer: current status and future directions.
Treatment for rectal cancer has evolved over the past 70 years from surgery alone to the selective use of trimodality therapy for high-risk patients. Radiotherapy (RT) has improved the potential for tumor downstaging, thus enhancing sphincter preservation and local control. This article reviews the evolution of strategies that incorporate pelvic RT, intraoperative RT, and high-dose-rate endorectal brachytherapy (HDRBT). By tracing the arc of the pendulum that has swung from postoperative RT to preoperative RT, we address the current standard of care and explore the potential of novel radiation techniques and radiosensitizing agents to improve outcomes. With randomized trial data confirming that preoperative RT in addition to chemotherapy improves local control and decreases acute and late morbidity, neoadjuvant programs have now demonstrated the prognostic significance of downstaging as well. Patients with tumors that have a good response to preoperative treatment have superior survival. Future studies will determine the optimal regimen to enhance the pathologic complete or near complete response rates for locally advanced disease. Advances in radiation technology are being investigated to determine whether efficacy can be increased and toxicity decreased so that more aggressive chemotherapeutic agents can be combined. With the growing improvements in combined modality therapy, a future of better rectal cancer outcomes looms brighter than ever before.


Profile of Mental and Behavioral Disorders Among Preschoolers in a Tertiary Care Hospital in Oman: A Retrospective Study.
Early diagnosis and prompt treatment of mental and behavioral disorders in preschoolers is critical for a better prognosis, ultimately leading to improved quality of life for both the child and the family. Our study investigated the clinical profile of mental and behavioral disorders in children < 7 years of age, seeking consultation at Sultan Qaboos University Hospital, Muscat, Oman, between 1 June 2006 and 31 December 2010. The objective was to explore demographic variables, intervention types, and annual trends. This retrospective, descriptive study was conducted by reviewing the electronic records of preschoolers seeking consultation on mental and behavioral disorders at the Department of Behavioral Medicine. The diagnosis was based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. The total number of cases was 466, the majority (77.9%) being boys. The cumulative frequencies and annual hospital-based prevalence rates were estimated for each category of mental and behavioral disorders. Our findings showed increased service utilization among preschoolers, as reflected in the annual trend and case-specific prevalence rates. While comorbidity was common, the most frequent disorders encountered were attention deficit hyperactivity disorder (70.8%), developmental language disorder (23.6%), autism spectrum disorders (20.2%), and disruptive behavior disorders (11.6%). The most commonly prescribed drugs/supplementation were risperidone (18.7%), atomoxetine (9.7%), omega-3 (8.8%), and methylphenidate (6.2%). Consultations for mental and behavioral disorders are being sought for Omani preschoolers. Beside pharmacotherapy, other interventions, which are an integral part of a much desired multidisciplinary approach should be introduced. Readdressing the missing needs is essential for a comprehensive approach to managing mental and behavioral disorders.


[Congenital Heart Surgery in Patients with Coexisting Congenital Anomalies of Respiratory or Digestive System].
Congenital anomaly of respiratory or digestive system have a significant impact on the perioperative management of congenital heart disease. Therefore, it is important to make a long-term treatment strategy. It has been reported that 1-stage surgery is effective for pulmonary artery sling. Simultaneous repair is also useful if significant airway stenosis is present prior to cardiac surgery. In the case of congenital heart disease associated with gastrointestinal anomaly, gastrointestinal surgery precedes in more than 80% of cases. In recent years, though treatments of gastrointestinal atresia have a good outcome, the results of esophageal atresia are still bad. If we choice multi-stage surgery, there is a possibility that we cannot perform cardiac surgery at appropriate time due to postoperative mediastinitis. Therefore, we must consider the timing and method of operation individually. The important thing is to keep a good relationships with related departments and to provide close informed consent to the patient's parents.


Clinical studies of the cholinergic deficit in Alzheimer's disease. II. Psychopharmacologic studies.
Two studies investigated the ability of physostigmine, given both intravenously and orally, to reduce symptoms of Alzheimer's disease. Intravenous physostigmine significantly and reliably enhanced memory in 13 of 16 patients tested, but the dose producing the improvement varied among patients. Oral physostigmine decreased overall symptom severity in a reliable way in seven of 12 patients tested. The extent of improvement was correlated with the increase in mean cortisol secretion produced by physostigmine, suggesting that the drug improved behavior and cognition only to the extent that it had a specific central cholinomimetic effect. There was no significant association between response to physostigmine and results of a dexamethasone suppression test and physostigmine had no effect on growth hormone secretion.


Correlates of depressed mood in ambulatory head and neck cancer patients.
High levels of psychological distress, especially depressed mood, has been discussed in relation to head and neck cancer. Patients with head and neck cancer face functional impairment and disfigurement caused by cancer and/or its treatment. Psychosocial factors that predict depressed mood in this population have not been well elucidated. The aim of this study is to examine the psychosocial and medical risk factors for depressed mood in ambulatory head and neck cancer patients. Depressed mood and coping style were assessed with the Profile of Mood States (POMS) and the Mental Adjustment to Cancer (MAC) scales, respectively, in 99 ambulatory head and neck cancer patients. Simultaneously, patients' social support and satisfaction with it, and sociodemographic and medical data were obtained. Multiple regression analysis revealed that advanced disease, being unmarried, and helpless/hopeless coping were significantly associated with depressed mood. The results suggest that we should identify these factors and target psychosocial intervention for those patients most at risk.


Growth of Suspension-cultured Acer pseudoplatanus L. Cells in Automatic Culture Units of Large Volume.
A phytostat to mass culture higher plant cells in liquid medium is described. This apparatus allowed the culture in batch, turbidostat and chemostat of 20 liters of cells. Automatic control of cell suspension growth was based on culture turbidity. Changes with time of certain cell characteristics, particularly cell respiration and phospholipid content, indicated that the test time to harvest large amounts of sycamore cells (Acer pseudoplatanus L.) in good physiological state was about 2 days before the end of the exponential phase of growth, when the cell density reached one million cells per milliliter of culture.


Mast Cells and Serotonin Synthesis Modulate Chagas Disease in the Colon: Clinical and Experimental Evidence.
Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon. Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-KitW-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3). In both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p < 0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p > 0.05), rescuing its synthesis promoted trypanosomiasis (p < 0.01). T. cruzi-related 5-HT release (p < 0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p < 0.01). Knocking out mast cells reduced trypanosomiasis (p < 0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p > 0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p < 0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-KitW-sh mice (p > 0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic trypanosomiasis (p < 0.01). We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.


State 1-State 2 Transitions in a Unicellular Green Algae : Analysis of In Vivo Chlorophyll Fluorescence Induction Curves in the Presence of 3-(3,4-Dichlorophenyl)-1, 1-dimethylurea (DCMU).
A study has been made on the State 1-State 2 transitions exhibited by the unicellular green algae Chlorella pyrenoidosa. Chlorophyll fluorescence induction curves from algae adapted to State 1 or State 2 have been analyzed and a comparison made with similar curves produced by decreasing the intensity of light going to the photosystem II reaction centers. In both cases, quenching of the maximum fluorescence yield (F(m)) and the initial fluorescence yield (F(o)) were observed so that the F(v)/F(m) ratio and the area above the induction curve (A(max)) remained constant. The State 1-State 2 transition also produced changes in the beta(max) component indicative of some alteration within photosystem II organization. The implications of these experiments on the in vivo mechanism for energy redistribution between the two photosystems are discussed in terms of changes in absorption cross-section rather than being due to spillover from photosystem II to photosystem I. These changes may reflect the phosphorylation of the light-harvesting chlorophyll a/b protein complex and its subsequent migration away from the photosystem II core leading to its closer association with photosystem I.


Clinical and molecular studies of patients with characteristics of Opitz G/BBB syndrome shows a novel MID1 mutation.
Opitz G/BBB syndrome is characterized by midline abnormalities such as hypertelorism, cleft palate, and hypospadias. This syndrome is heterogeneous with an X-linked recessive form caused by mutations in the MID1 gene at band Xp22.3. However, mutations in MID1 have only been identified in 47% of familial cases of X-linked Opitz G/BBB syndrome, and 13% of sporadic cases. We performed a phenotype-genotype analysis of a group of nine new patients with clinical characteristics commonly seen in Opitz G/BBB syndrome, and of previously reported patients. We identified a novel mutation in exon 9 of the MID1 gene, c.1941insTGAGTCATCATCC, leading to a premature termination codon at amino acid 514 in a patient with hypertelorism, apparently low-set ears, a short philtrum, bilateral cleft of lip and palate and hypospadias. This mutation affects the PRY domain of the C-terminus of the MID1 protein.


Recent veterinary graduates over the last five decades: recollections and perceptions.
To describe the attitudes of veterinary graduates over the last 50 years to their experiences as recent graduates A questionnaire, sent by mail. A questionnaire seeking information on experiences as a recent graduate was sent to about 100 veterinarians who graduated in or about 1950, 1960, 1970, 1980, 1990 and 2000, and 68% responded. Data were entered onto an Excel spreadsheet, and analysed with the SAS System 8 for Windows. Most veterinarians who graduated in 1970 and earlier were generally satisfied with their conditions, even though these were often taxing. In the 1970s the cattle industry faltered and rural practice suffered a downturn. Veterinary positions became scarce, and there were few opportunities for graduates to move on from an unsatisfactory workplace--as many were at that time. By 1980 many recent graduates were questioning their decision to study veterinary science. Many of them, working long hours under often stressful conditions, felt that that they were not receiving adequate help or support--or remuneration--from their employers, or respect from their clients. This also afflicted many who graduated in 1990, but by 2000 graduates were reporting an improvement. Their hours of work and the expectations placed on them were more manageable, and the level of help and support, and remuneration, were more acceptable. As a result they found their first year much more enjoyable than had those who had graduated since about 1970. Many of the factors contributing to this improvement resulted from changes in society generally. Specifically, both graduates and employers have become more conscious of what might reasonably be expected, an Award specified minimum levels, the AVA started accrediting New Graduate Friendly Practices, publishing a most informative New Graduate Guide, and helping in other ways. Remuneration, especially when compared with comparable professions, continues to be a source of discontent. Furthermore, despite improved conditions on average, many graduates still suffer under substandard conditions, and these can have an adverse effect on their health and their attitude to their career in veterinary science. Average conditions of employment of recent veterinary graduates have improved somewhat after a nadir in the 1970s and 1980s, but they are still substandard for some. Remuneration remains the greatest source of dissatisfaction for recent graduates.


Design for a coherent-scatter imaging system compatible with screening mammography.
A system using a wide-slot beam and simple antiscatter grids or slots has been designed to provide a localized map of tissue type that could be overlaid on the simultaneous conventional transmission image to provide an inexpensive, low dose adjunct to conventional screening mammography. Depth information is obtainable from the stereoscopic viewing angles. The system was demonstrated to produce observable contrast between adipose tissue and a phantom chosen to mimic carcinoma at an exposure comparable with screening mammography. Imaging data was collected over a range of system parameters to optimize contrast and to allow verification of simulation modeling.


Extractive electrospray ionization mass spectrometry-enhanced sensitivity using an ion funnel.
Electrodynamic ion funnel interfaces for electrospray ionization (ESI) have shown to enhance the sensitivity of measurements by more than 2 orders of magnitude in the intermediate pressure region of the instrument (1-30 Torr). In this study, we use an ion funnel at ambient pressure to enhance the sensitivity of extractive electrospray ionization (EESI) by spraying directly into the ion funnel. EESI is a powerful ionization technique that is capable of handling complex matrixes that may contain dozens of compounds. Our results using atenolol, salbutamol, and cocaine as test compounds show that we can improve the limit of detection for these compounds by more than 3 orders of magnitude compared to standard EESI experiments.


Evidence for an incomplete mitral isthmus block after failed ablation of a left postero-inferior concealed accessory pathway.
We report the case of a young woman in whom previous ablation of a concealed left-sided accessory pathway (AP) created an iatrogenic mitral block. The mitral block was responsible for a split retrograde atrial activation pattern during orthodromic atrioventricular re-entrant tachycardia (AVRT). The differential diagnoses are discussed. The AP was ablated at the site with the shortest interval between the ventricular signal and the earliest component of the retrograde atrial activation. Meticulous mapping is paramount during AVRT with an unusual retrograde atrial activation pattern.


[Backache in women from a gynecologic and orthopedic viewpoint].
In differential diagnosis of low back pain in women defects of the skeletal system as well as affections of the female genital organs must be considered. In these diseases low back pain may be caused directly by mechanic or indirectly by nervous factors. It is referred to the possibility of differentiation of low back pain by clinical symptoms. Based on new findings particularly osteoporosis makes close cooperation of the two medical specialties-orthopedics and gynecology-necessary, because the question of oestrogen application for prophylaxis and therapy of osteoporosis arises.


The neuroectodermal tumor of bone.
Four small round cell malignant tumors of bone occurring in children are described. There was no catecholamine secretion and the clinical, radiologic, and biopsy diagnosis in each was Ewing's sarcoma. Glycogen was sparse both on imprints and in tissue sections. The tumors, when extensively sampled, had areas of a lobular growth pattern and Homer Wright rosettes. The rosettes were always focal and varied in complexity from case to case; they were rudimentary in one instance and markedly fibrillar in the most obvious instance. Neuron-specific enolase was demonstrated in tissue sections and in longterm cell cultures from three of the tumors. The cultured cells put out moderately long beaded processes in serum-free medium but had no catecholamine fluorescence. Electron microscopy of the tumor rosettes and the cultured cells showed processes containing aggregates of microtubules and only one case had rare neurosecretory granules. This study suggests that some small round cell tumors of bone and soft tissue in children, which present as Ewing's sarcoma, are neuroectodermal in nature.


Neurosurgical pathology of limited dorsal myeloschisis.
The term limited dorsal myeloschisis (LDM) was used by Pang et al. (2010) to describe a distinct clinicopathological entity. LDMs are characterized by two invariable features: a focal-closed neural tube defect and a fibroneural stalk that links the skin lesion to the underlying spinal cord. We retrospectively analyzed the neurosurgical pathologic findings of four LDM patients. Case 1 had a saccular skin lesion with nonterminal abortive myelocystocele at T11-12. Cases 2, 3, and 4 had a non-saccular (flat) skin lesion in the lumbosacral region. The morphologic features of the lesion in case 2 were those of meningocele manque. Cases 3 and 4 had accompanying non-LDM anomalies, caudal-type lipoma and type II split-cord malformation with neurenteric cyst, respectively. At preoperative diagnosis of the LDM stalk, magnetic resonance imaging, including 3D heavily T2-weighted image was useful; however, minute findings were often missed in the complicated cases 3 and 4. All patients had a favorable outcome following untethering of the stalk from the cord. The central histopathological feature of the LDM stalk is neuroglial tissue in the fibrocollagenous band; however, the stalk in cases 2 and 4 did not have glial fibrillary acidic protein-immunopositive neuroglial tissues. Therefore, the diagnosis of LDM should be made based on comprehensive evaluation of histologic and clinical findings.


Stimulation of Ca2+ influx by endothelin-1 is subject to negative feedback by elevated intracellular Ca2+.
Endothelin-1 (ET-1) has been shown to require Ca2+ influx for activation of vascular smooth muscle in vivo, but in vitro models show that ET-1 mobilizes intracellular Ca2+ and is independent of extracellular Ca2+. We present data that suggest ET-1 modulates cellular responses through a dual mechanism involving both phosphatidylinositol turnover and Ca2+ channel activation. Addition of low concentrations of ET-1 (less than 10(-9) M) to serum-deprived quiescent Rat-1 cells stimulated Ca2+ influx while having little effect on diacylglycerol (DG) release or intracellular Ca2+ levels. In contrast, higher concentrations of ET-1 (greater than 10(-9) M) stimulated intracellular Ca2+ transients and release of inositol trisphosphate (IP3) and DG but did not activate Ca2+ uptake. Stimulation of Ca2+ influx at low [ET-1] could not be accounted for by depletion of intracellular IP3-sensitive pools. Neither the stimulation of Ca2+ influx at low [ET-1] nor the inhibitory actions of high [ET-1] could be mimicked by the activation of protein kinase C. We tested the hypothesis that elevated intracellular Ca2+ was inhibitory for Ca2+ influx. When intracellular Ca2+ transients were maintained below approximately 165 nM by chelation with BAPTA or BAPTA derivatives with altered affinity for Ca2+, Ca2+ influx was stimulated over the entire range of ET-1 concentrations. In addition, experimentally elevating intracellular Ca2+ levels with the tumor promoter thapsigargin abolished ET-1-stimulated Ca2+ influx. These data suggest that the biological consequences of ET-1 release may be determined by local concentration differences. Thus in vascular smooth muscle cells ET-1 may act either to mobilize intracellular Ca2+ or to promote Ca2+ influx, depending on the distance from the endothelial cell source in the vascular wall. The activation of different processes by low and high ET-1 concentrations may determine the physiological response to ET-1 stimulation in vivo.


Fructokinases from developing maize kernels differ in their specificity for nucleoside triphosphates.
A new form of fructokinase has been identified from developing maize (Zea mays L.) kernels that utilizes CTP, UTP, and GTP from four to eight times more effectively than ATP at nonlimiting concentrations. Ten millimolar dithiothreitol was necessary to stabilize activity. A second form of fructokinase was nonspecific for nucleoside triphosphate whereas a third form was fairly specific for ATP.


Effects of galanin on electrical activity of pancreatic islet cells.
Intracellular microelectrode technique was used to investigate the effect of galanin on the electrical activity of beta cells of Langerhans islets of mice. Galanin 0.15 and 0.3 mumol/L in the perfusion medium inhibited the basic electrical activity induced by glucose 5.5, 11.1 and 20 mmol/L in decreasing the frequency and amplitude of the spikes. In some cells, during galanin inhibition there was a hyperpolarization after the spike. Verapamil (30, 60 and 90 mumol/L), a blocker of voltage-dependent Ca channels, blocked dose-dependently the electrical activity induced by glucose and attenuated the depolarization induced by KCl 50 mmol/L. Galanin 0.3 mumol/L also attenuated the depolarization induced by KCl 50 mmol/L, similar to the effect of verapamil. The results suggest that the effect of galanin on inhibition of the electrical activity of beta cell might be due to blocking of voltage-dependent Ca2+ channels.


Multifunctionalities of Graphene for Exploiting a Facile Conversion Reaction Route of Perovskite CoSnO3 for Highly Reversible Na Ion Storage.
Transition-metal oxides are promising anode materials for sodium ion batteries (SIBs) and have attracted a great deal of attention because of their natural abundance and high theoretical capacities. However, they suffer from low conductivity and large volumetric/structural variation during sodiation/desodiation processes, leading to unsatisfactory cycling stability and poor rate capability. This study proposes a novel conversion reaction using CoSnO3 (CSO) nanocubes uniformly wrapped in graphene nanosheets, which are fabricated using a wet-chemical strategy followed by low-temperature heat treatment. This optimized composite exhibits durable cyclability and high rate capability, which can be attributed to the strong interaction between reduced graphene oxide and CSO through its surface oxygen moieties. It develops a facile conversion reaction route, thereby leading to SnO2 formation during charging. This interactive phenomenon further contributes to improving the reaction kinetics and restraining the volume expansion during cycling. This study may provide a facile approach for addressing irreversible conversion of high-capacity oxide materials toward advanced SIBs.


Ureteritis and cholecystitis: two unusual manifestations of cytomegalovirus disease in renal transplant recipients.
Common clinical manifestations of cytomegalovirus (CMV) infection include flu-like symptoms with fever, diarrhea, leukopenia, and elevated liver enzymes. Diagnosis is made by detection of the virus by buffy-coat blood culture or by polymerase chain reaction (PCR) analysis. Here we describe two renal transplant recipients who presented with unusual manifestations of CMV disease (cholecystitis and ureteritis). In both patients, no symptoms or signs of systemic CMV infection were present, and they were thought to have other common causes for cholecystitis and ureteral obstruction. Retrospective analysis of peripheral blood by PCR analysis was positive for CMV DNA. Histologic examination of the resected gall bladder and stenotic ureteric segment showed CMV inclusions, confirmed subsequently by in situ hybridization. Thus, we report that CMV infection may present with acute cholecystitis or ureteral obstruction without its classical clinical symptoms. Because CMV infection is common in transplant patients, the atypical manifestations of CMV should be considered in the differential diagnosis of posttransplant complications. Detection of CMV DNA in the peripheral blood by PCR analysis may help identify these patients.


Correlation between craniofacial structures, anthropometric measurements, and nasopharyngeal dimensions in black adolescents.
To evaluate the correlation between craniofacial structures, anthropometric measurements, and bony and soft tissue nasopharyngeal dimensions in African Black adolescents. This retrospective cross-sectional study was conducted on 483 healthy adolescents (250 females and 233 males), randomly selected from one dental clinic. The inclusion criteria were skeletal and dental Class I, Black ethnicity, pubertal growth period as determined by the Greulich and Pyle atlas criteria, and no history of orthodontic treatment. Anthropometric measurements (stature, upper body height, lower body height, and BMI) and radiographic records (hand-wrist radiographs, and lateral cephalograms) were obtained. One investigator traced and analysed all cephalograms to determine three skeletal craniofacial parameters (maxillary length [Ar- ANS], mandibular length [Ar-Gn], and lower anterior facial height [ANS-Me]), and 14 (8 skeletal and 6 soft tissue) nasopharyngeal parameters. Pearson correlation coefficients and stepwise multiple linear regression analyses were conducted. The mean skeletal ages of females and males were 11.31±2.31y and 12.66±1.85y, respectively. Multiple linear regression analyses showed that stature, posterior height of nasal cavity (S-PNS), length of nasal floor (AA-PNS), and mean area of bony nasopharynx (Area 1) were significantly correlated with maxillary length, P<.001. Stature, BMI, S-PNS, vertical angle of nasopharynx (Ba-S-PNS), Area 1, adenoid height (AD), and linear hyoid bone measurements (H-AA, H-RGN, H-Ax) were all correlated with mandibular length, P<.05. Lower facial height showed sexual dimorphism and was significantly associated with vertical nasopharyngeal measurements, BMI and upper body height. Craniofacial structures were significantly associated with stature and upper body height. Maxillary growth was associated with bony nasopharyngeal variables. Mandibular growth and lower facial height were associated with bony and soft tissue nasopharyngeal variables. The sexual dimorphism in lower facial height warrants future studies to fully understand and manage the craniofacial complex and nasopharyngeal airway in African Black adolescents.


Rotavirus surveillance--United States, 1989-1990.
Rotavirus infection is the most common cause of dehydrating diarrhea in children in the United States. In January 1989, CDC established a National Rotavirus Surveillance System (NRSS) to monitor national patterns in the epidemiology of rotavirus. This report summarizes findings from the NRSS from January 1989 through November 1990.


[Pulmonary function in patients with rheumatic mitral valve disease. Preoperative evaluation].
The aim of the study was to observe the mechanism of cardiac-airway interaction in patients with rheumatic mitral valve disease. 61 pts with combined mitral disease and 9 with isolated mitral stenosis (42 females, 28 males; mean age 47 y) were studied. They were in NYHA functional class II-IV (36 pts in II, 22 in III, 12 in IV class). Each patient was assessed by clinical, noninvasive cardiological investigation (estimation of left atrium dimension, mitral gradient, mitral area and right ventricular systolic pressure on echocardiographic examination and relative heart volume on fluoroscopy) and lung function studies i.e. spirography, plethysmography, flow-volume curve and histamine provocation test. The bronchial hyperreactivity was found in 20 pts (75% undergoing test-mean PC40 = 0.1474 mg/ml). In 7 pts histamine test was negative. The reversible airway obstruction (after 200 micrograms FNT) was observed in 43 (61%) pts. In pts with mitral valve disease we observed significant bronchial hyperresponsiveness to histamine and reversible airway obstruction with no correlation between pulmonary function parameters and cardiological status.


State-dependent representations of mixtures by the olfactory bulb.
Sensory systems are often tasked to analyse complex signals from the environment, separating relevant from irrelevant parts. This process of decomposing signals is challenging when a mixture of signals does not equal the sum of its parts, leading to an unpredictable corruption of signal patterns. In olfaction, nonlinear summation is prevalent at various stages of sensory processing. Here, we investigate how the olfactory system deals with binary mixtures of odours under different brain states by two-photon imaging of olfactory bulb (OB) output neurons. Unlike previous studies using anaesthetised animals, we found that mixture summation is more linear in the early phase of evoked responses in awake, head-fixed mice performing an odour detection task, due to dampened responses. Despite smaller and more variable responses, decoding analyses indicated that the data from behaving mice was well discriminable. Curiously, the time course of decoding accuracy did not correlate strictly with the linearity of summation. Further, a comparison with naïve mice indicated that learning to accurately perform the mixture detection task is not accompanied by more linear mixture summation. Finally, using a simulation, we demonstrate that, while saturating sublinearity tends to degrade the discriminability, the extent of the impairment may depend on other factors, including pattern decorrelation. Altogether, our results demonstrate that the mixture representation in the primary olfactory area is state-dependent, but the analytical perception may not strictly correlate with linearity in summation.


[Inflammation and rejection].
The inflammation represents an important cause of allograft tissue lesions during ongoing rejection episodes. Such inflammation is mediated, at least in part, via the release of different soluble mediators. Some of these endogenous inflammation mediators are well known and include prostaglandins, leukotriens, histamine or histaminergic compounds and factors induced by the activation of the complement cascade (C3a, C5a). More recently, different molecules have been characterized, namely cytokines that are potent mediators of both immune and inflammatory reactions. Cytokines are produced by a wide variety of cells types (i.e., inducing immune and non immune cells) and expressing pleiotropic effects. The synergism between these various inflammation mediators finally provoke the anatomopathological lesions characteristic of a rejection process that are vascular lesions, edema formation and white blood cell chemotaxis leading to massive cellular infiltration. The aim of this brief review is to analyze the more recent data of the literature concerning cytokines that, applied to the field of organ transplantation, may provide further insights onto the relationships existing between inflammation and allograft rejection.


In Situ Observation of Dark Current Emission in a High Gradient rf Photocathode Gun.
Undesirable electron field emission (also known as dark current) in high gradient rf photocathode guns deteriorates the quality of the photoemission current and limits the operational gradient. To improve the understanding of dark current emission, a high-resolution (∼100 μm) dark current imaging experiment has been performed in an L-band photocathode gun operating at ∼100 MV/m of surface gradient. Scattered strong emission areas with high current have been observed on the cathode. The field enhancement factor β of selected regions on the cathode has been measured. The postexaminations with scanning electron microscopy and white light interferometry reveal the origins of ∼75% strong emission areas overlap with the spots where rf breakdown has occurred.


Impact of genetic polymorphism in relation to other factors on expression and function of human drug-metabolizing p450s.
A major cause for unpredictable drug response is the enormous variability of drug-metabolizing cytochrome P450s (CYPs) in human liver in which genetic polymorphisms, regulation of gene expression, and physiological factors, including sex, may play a role. To dissect these different factors, we established a large human liver bank with extensive clinical documentation. Recent work concentrated on CYPs 2D6, 2B6, and the 3A family. CYP2D6 expression is highly polymorphic with over 70 alleles. Using liver samples and DNA from phenotyped patients, we further elucidated the genetic basis of phenotypic differences and demonstrated a novel role of alternative splicing, leading to decreased enzyme activity. These studies further emphasize the intricacy of genetic regulation at the CYP2D6 locus. In contrast, CYP2B6, the human orthologue of the rodent phenobarbital-inducible P450 2B, is known to be inducible by a range of substances, but our recent studies also show a high degree of genetic polymorphism. However, the role of polymorphism in determining CYP2B6 expression and function is less decisive as compared with CYP2D6. Thus, with respect to the balance between genetic and nongenetic factors controlling expression, CYP2B6 appears to take an intermediate position. CYP3A4 is the major P450 of human liver and contributes critically to the metabolism of at least half of all drugs. CYP3A4 expression variability is not influenced much by genetic polymorphism. Studies in our liver bank confirm that both induction and down-regulation occur as a consequence of drug treatment. As a further major determinant of hepatic CYP3A4 expression, we found sexual dimorphism, with women expressing at least twice the amount of CYP3A4 protein than men. This surprising result explains the many pharmacokinetic findings of faster metabolism of CYP3A4 drug substrates in women. In conclusion, these data illustrate how various factors contribute to the individual CYP profile in human liver.


Conformational selection and induced fit as a useful framework for molecular motor mechanisms.
The linkage between macromolecular binding and conformational change that is ubiquitous in biological molecules can be understood in the context of the mechanisms of conformational selection and induced fit. Here, we explore mappings between these mechanisms of ligand binding and those underlying the translocation of molecular motors and the nucleic acid unwinding of helicases. The mechanism of biased motion exhibited by molecular motors is typically described as either a thermal ratchet or a power-stroke and nucleic acid helicases are characterized by either active or passive unwinding mechanisms. We posit that both Brownian ratchet translocation and passive unwinding are examples of conformational selection and that both power-stroke translocation and active unwinding are examples of induced fit. Furthermore, in ligand-binding reactions, both conformational selection and induced fit may exist in parallel leading to a ligand-dependent flux through the different mechanistic pathways. Given the mappings we describe, we propose that motors may be able to function via parallel ratchet and stroke mechanisms and that helicases may be able to function via parallel active and passive mechanisms.


Medical practice revenue and salaries of physician assistants.
Significant salary differences between male and female PAs have been noted. Several variables--hours worked per week, weeks worked per year, number of patients seen per week, and average fee per patient--were examined to assess their contribution to the differences in salary for PAs practicing in family medicine, internal medicine, and pediatrics. Although female PAs were found to earn significantly less than their male colleagues, the discrepancy could largely be explained when salary was examined as a proportion of revenue generated for the practice. The survey findings are compared with research findings on male and female physicians' salaries.


Lasers and Energy-Based Devices in Men.
The demand for cosmetic treatments with lasers and energy-based devices has increased among men, but there is a dearth of literature that addresses the approach and treatment of cosmetic male patients. To summarize common cosmetic concerns for which male patients seek cosmetic treatments and to provide sex-specific recommendations for the lasers and energy-based devices that can be used for treatment. The authors conducted a literature search using the PubMed/MEDLINE and Google Scholar databases using the search terms male, men, gender, and cosmetic dermatology. The authors review sex-specific treatment recommendations regarding the use of lasers and energy-based devices for the conditions for which men most commonly seek cosmetic treatment, which include photo-/actinic damage, acne scarring, rhinophyma, hair removal, axillary hyperhidrosis, and loose neck/submental skin. Cosmetic issues the authors will touch on, but whose approaches or considerations vary less in men compared with women, are hyperpigmentation, vascular lesions, and facial rejuvenation. Sex-specific treatment approaches with lasers and energy-based devices should be used to best serve male cosmetic patients.


Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial.
To investigate the safety and efficacy of MRA, a recombinant human anti-interleukin-6 (anti-IL-6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL-6, in patients with established rheumatoid arthritis (RA). A randomized, double-blind, placebo-controlled, dose-escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment. Demographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1- and 1-mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C-reactive protein values fell significantly in the 5- and 10-mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1-, 1-, 5-, and 10-mg/kg MRA cohorts, respectively) required corticosteroid or disease-modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1-, 1-, and 10-mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug. This is the first randomized controlled trial showing that inhibition of IL-6 significantly improved the signs and symptoms of RA and normalized the acute-phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.


Malignant melanoma of the vulva.
Malignant melanoma of the vulva is reviewed and four cases are presented. Fewer than 400 cases have been reported, from 0.05 to 0.5% of female genital cancers. Radical vulvectomy with inguinal lymph node dissection is of uncertain value and the prognosis usually is poor. Wide local excision alone is suggested for level II melanomas, and in such instances the prognosis may be favorable.


Flavonoids and steroid hormone-dependent cancers.
Steroid-hormone dependent cancers, including those of the breast, prostate and colon, are leading causes of morbidity and mortality in western countries. In rural Asian areas, these diseases are relatively uncommon. Dietary factors, including low consumption of fruit, vegetables and soy in the west have been shown in various epidemiologic studies as reasons for these differences. This review discusses flavonoids, one component of these plant foods that is being investigated for their role in chemoprevention. Epidemiological, in vitro, animal and human studies shall be explored to look at mechanisms involved, including steroid hormone activity, effects on cell growth, antioxidant activities, inhibition of chemical carcinogenesis and influences on modulators of cancer risk. Although the in vitro and animal models point to several pathways by which flavonoids may reduce incidence of these cancers, the clinical data are still relatively lacking. More research is needed to determine how best to use foods containing these compounds to reduce steroid hormone-dependent cancer risk.


Societal perspectives on disease and treatment attributes characterizing rare diseases: a qualitative study from the United States.
Under a societal perspective, disease and treatment attributes that the general public deem important should be considered within value frameworks. The objective was to investigate how members of the general public value attributes beyond health gains and healthcare system expenditures; and better understand their perspectives regarding the importance of attributes typically characterizing rare genetic diseases like Duchenne muscular dystrophy (DMD). Qualitative interviews were conducted to elicit feedback on the importance of disease and treatment attributes from general public participants from three US cities. Participants ranked attributes (scale, 1-10) in terms of importance for future research, reported their rationale for ranking, and provided feedback specific to rare diseases. Interview transcripts were coded using NVivo for thematic analysis. The 33 participants (median age, 51 years; 48.5% male) ranked disease severity (mean [median] ranking, 8.7 [9.0]), treatment availability (8.7 [9.0]), and impact on life expectancy (8.4 [9.0]), as most important. The impact on the family, need for equity, and intrinsic value of life were frequently provided rationales. While rare disease as an attribute received a relatively low ranking (6.1 [7.0]), 88% of participants prioritized disease profiles including attributes of severity, health related quality of life (HRQoL) impact, limited lifespan and young age at onset. Attributes including disease severity, impact on life expectancy and HRQoL, and treatment availability were all highly important to members of the general public. These findings support the growing evidence regarding the importance of expanding value assessments to include attributes considered important from a societal perspective.


Poor control increases the economic cost of asthma. A multicentre population-based study.
Up to now, few cost-of-illness (COI) studies have estimated the cost of adult asthma at an individual level on general population samples. We sought to evaluate the cost of current asthma from the societal perspective in young Italian adults and the determinants of cost variation. In 2000, a COI study was carried out in the frame of the Italian Study on Asthma in Young Adults on 527 current asthmatics (20-44 years) screened out of 15,591 subjects from the general population in seven centres. Detailed information about direct medical expenditures (DMEs) and indirect costs due to asthma was collected at an individual level over the past 12 months. The mean annual cost per patient was EUR 741 (95% CI: 599-884). DMEs represented 42.8% of the total cost, whereas the remaining 57.2% was indirect costs. The largest component of DMEs was medication costs (47.3%; 23.0% was due to hospitalization). The mean annual cost per patient ranged from EUR 379 (95% CI: 216-541)for well-controlled asthmatics to EUR 1,341 (95% CI: 978-1,706) for poorly controlled cases that accounted for 46.2% of the total cost. Poor control, coexisting chronic cough and phlegm, and low socio-economic status were significantly associated with high DMEs and indirect costs. In Italy, asthma-related costs were substantial even in unselected patients and were largely driven by indirect costs. Since about half of the total cost was due to a limited proportion of poorly controlled asthmatics, interventions aimed at these high-cost patients could reduce the economic burden of the disease.


Therapeutic hypothermia attenuates brain edema in a pig model of cardiac arrest: Possible role of the angiopoietin-Tie-2 system.
This study aimed to clarify whether therapeutic hypothermia protects against cerebral edema following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a porcine model via regulating the angiopoietin-Tie-2 ligand-receptor system. Male pigs were randomized into the therapeutic hypothermia group, the normothermia group or the sham control group. CA was induced in pigs by untreated ventricular fibrillation for 8min. Brain edema was determined by measuring the cerebral cortical water content at 24h after the return of spontaneous circulation (ROSC). The serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2 (Tie-2), and S100B were measured using enzyme immunoassay kits at 0.5, 6, 12 and 24h after ROSC. The levels of the Ang-1, Ang-2, phosphorylated Tie-2 and Tie-2 proteins in the cerebral cortex at 24h after ROSC were determined by Western blotting. Therapeutic hypothermia lessened brain cortex edema, alleviated histopathology injury, and improved neurologic outcomes at 24h after ROSC. Therapeutic hypothermia inhibited the CA- and CPR-induced increases in serum Ang-2 protein expression and the Ang-2/Ang-1 ratio and attenuated the decrease in serum Ang-1 expression. Therapeutic hypothermia also increased the protein expression of Ang-1 and the phosphorylated Tie-2/Tie-2 ratio and inhibited the expression of Ang-2 in the cerebral cortex at 24h after ROSC. Based on our experiment, therapeutic hypothermia decreased cerebral edema after CA, which may be, at least in part, related to its ability to modulate the expression of components of the Ang-Tie-2 system.


Siderophores provoke extracellular superoxide production by Arthrobacter strains during carbon sources-level fluctuation.
Superoxide and other reactive oxygen species (ROS) shape microbial communities and drive the transformation of metals and inorganic/organic matter. Taxonomically diverse bacteria and phytoplankton produce extracellular superoxide during laboratory cultivation. Understanding the physiological reasons for extracellular superoxide production by aerobes in the environment is a crucial question yet not fully solved. Here, we showed that iron-starving Arthrobacter sp. QXT-31 (A. QXT-31) secreted a type of siderophore [deferoxamine (DFO)], which provoked extracellular superoxide production by A. QXT-31 during carbon sources-level fluctuation. Several other siderophores also demonstrated similar effects to A. QXT-31. RNA-Seq data hinted that DFO stripped iron from iron-bearing proteins in electron transfer chain (ETC) of metabolically active A. QXT-31, resulting in electron leakage from the electron-rich (resulting from carbon sources metabolism by A. QXT-31) ETC and superoxide production. Considering that most aerobes secrete siderophore(s) and undergo carbon sources-level fluctuation, the superoxide-generation pathway is likely a common pathway by which aerobes produce extracellular superoxide in the environment, thus influencing the microbial community and cycling of elements. Our results pointed that the ubiquitous siderophore might be the potential driving force for the microbial generation of superoxide and other ROS and revealed the important role of iron physiology in microbial ROS generation.


[Screening in onco-gynecology : beneficial for all patients ?]
Every day, 5 women are diagnosed with gynecological cancer in Switzerland. Prognosis of ovarian, endometrial and cervical cancer is dependent on early diagnosis. Cervical cancer mortality has decreased since the introduction of screening. Unfortunately, screening in ovarian and endometrial cancer has not shown the same results. On the contrary, patients screened for these cancers have an increased morbidity without any additional benefit of survival. This article presents a review of the clinical benefits and harms of gynecological cancer screening.


Cell engineering: spearheading the next generation in healthcare.
Manipulating living mammalian cells present fascinating possibilities for a plethora of applications within our healthcare. These imply several possibilities in tissue engineering and regenerative medicine, to those of a therapeutic nature. The physical sciences are increasingly playing a pivotal role in this endeavour by both advancing existing cell engineering technology and pioneering new protocols for the creation of biologically viable structures. In this paper, the author introduces several direct needle/channel/orifice-based cell engineering protocols, currently undergoing intense investigation for a whole host of bio-applications. Hence, each protocol's advantages and disadvantages are clearly identified, whilst recognizing their future biological and engineering challenges. In conclusion, a few selected biotechnological applications present possibilities where these protocols could undergo focused exploration. Successful development of these bio-protocols sees the emergence of unique future strategies within a clinical environment having far-reaching consequences for our healthcare.


Ultra-Early Cranioplasty versus Conventional Cranioplasty: A Retrospective Cohort Study at an Academic Level 1 Trauma Center.
The goal of this study was to ascertain the efficacy, safety, and comparability of ultra-early cranioplasty (CP; defined here as <30 days from the original craniectomy) to conventional cranioplasty (defined here as >30 days from the original craniectomy). A retrospective review of CPs performed at our institution between January 2016 and July 2020 was performed. Craniectomies initially performed at other institutions were excluded. Seventy-seven CPs were included in our study. Ultra-early CP was defined as CP performed within 30 days of craniectomy whereas conventional CP occurred after 30 days. Post-operative wound infection rates, rate of return to the operating room (OR) with or without bone flap removal, operative length, and rate of post-CP hydrocephalus were compared between the two groups. Thirty-nine and 38 patients were included in the ultra-early and conventional CP groups, respectively. The average number of days to CP in the ultra-early group was 17.70 ± 7.75 days compared to 95.70 ± 65.60 days in the conventional group. The mean Glasgow Coma Scale upon arrival to the emergency room was 7.28 ± 3.90 and 6.92 ± 4.14 for the ultra-early and conventional groups, respectively. The operative time was shorter in the ultra-early cohort than that in the conventional cohort (ultra-early, 2.40 ± 0.71 h; conventional, 3.00 ± 1.63 h; p = 0.0336). The incidence of post-CP hydrocephalus was also lower in the ultra-early cohort (ultra-early, 10.3%; conventional, 31.6%; p = 0.026). No statistically significant differences were observed regarding post-operative infection, return to the OR, or bone flap removal. Our study shows that ultra-early CP can significantly reduce the rate of post-CP hydrocephalus, as well as operative time in comparison to conventional CP. However, the timing of CP post-DC should remain a patient-centered consideration.


Determination of the amino acid sequence of the plant cytolysin enterolobin.
The cytolytic seed protein enterolobin from seeds of Enterolobium contortisiliquum was purified by using FPLC on a Mono Q column giving a single peak in capillary electrophoresis. The complete amino acid sequence of the plant cytolysin was determined by an automated method, yielding a molecular mass of 54,806 Da. Databank searches and sequence alignment demonstrated a high degree of sequence identity and similarity between enterolobin and bacterial aerolysins from Aeromonas hydrophila and A. sobria. Several key residues involved in oligomerization of A. hydrophila aerolysin are conserved in enterolobin. Circular dichroism measurements and structural predictions revealed that enterolobin is very rich in beta sheet, like aerolysin. Light-scattering studies revealed that enterolobin oligomerizes as a hexamer at pH levels below 7.0. NaCl concentrations above 50 mM caused dimerization of enterolobin. Dithiothreitol did not cause oligomerization.


Isolation and characterisation of nocardia from clinical specimens.
Sixteen isolations of nocardia of which 12 were from pulmonary infections, one from wound infection, one from mycetoma and 2 from eye infections were studied from June, 1989 to May, 1990. The importance of Gram's stain findings of primary smear is being highlighted. The nocardia species were identified utilising the morphological characters including acid fastness and cultural and biochemical characters. Notable among the isolates were Nocardia brasiliensis, one each from mycetoma and pulmonary infection, which are rare in South India and Nocardia asteroides from a case of endophthalmitis probably of endogenous origin.


From Acute Pancreatitis to Stage IV Pancreatic Cancer in 12 Weeks.
Pancreatic cancer is well known to be an aggressive and highly malignant condition with varied ways of presentation. Pancreatic cystic neoplasms are very uncommon causes of pancreatic malignancy and can often be ignored or missed, especially in the early stages. We present the case of a 49-year-old Caucasian male with no past medical history presenting to an outside facility with sudden epigastric pain that was eventually diagnosed as acute pancreatitis. On transfer to our facility, he was eventually found to have metastatic malignant mucinous cystic pancreatic neoplasm. Barely 12 weeks after his initial presentation and following an aggressive hospital course, he passed away.


Assessing the reporting of Dengue, Chikungunya and Zika to the National Surveillance System in Colombia from 2014-2017: A Capture-recapture analysis accounting for misclassification of arboviral diagnostics.
Chikungunya, dengue, and Zika are three different arboviruses which have similar symptoms and are a major public health issue in Colombia. Despite the mandatory reporting of these arboviruses to the National Surveillance System in Colombia (SIVIGILA), it has been reported that the system captures less than 10% of diagnosed cases in some cities. To assess the scope and degree of arboviruses reporting in Colombia between 2014-2017, we conducted an observational study of surveillance data using the capture-recapture approach in three Colombian cities. Using healthcare facility registries (capture data) and surveillance-notified cases (recapture data), we estimated the degree of reporting by clinical diagnosis. We fit robust Poisson regressions to identify predictors of reporting and estimated the predicted probability of reporting by disease and year. To account for the potential misclassification of the clinical diagnosis, we used the simulation extrapolation for misclassification (MC-SIMEX) method. A total of 266,549 registries were examined. Overall arboviruses' reporting ranged from 5.3% to 14.7% and varied in magnitude according to age and year of diagnosis. Dengue was the most notified disease (21-70%) followed by Zika (6-45%). The highest reporting rate was seen in 2016, an epidemic year. The MC-SIMEX corrected rates indicated underestimation of the reporting due to the potential misclassification bias. These findings reflect challenges on arboviruses' reporting, and therefore, potential challenges on the estimation of arboviral burden in Colombia and other endemic settings with similar surveillance systems.


Bioinformatics analysis identifying FBXO45 gene as a potential oncogene in esophageal cancer.
F-box protein 45 (FBXO45) is a member of the F-box protein family, and is reportedly involved in the progression of many diseases. However, its role in esophageal cancer (ESCA) remains unclear. The expression, clinical characteristics, gene function, pathway, and correlation between the infiltration of different immune cells were analyzed using public data. The pan-cancer expression of FBXO45 was assessed using the TIMER2 database. The expression of FBXO45 in different tumor stages and histology subtypes were evaluated using the UALCAN database. The protein-protein interaction (PPI) network was constructed using the STRING database. Immune cell infiltration data were downloaded from the ImmuCellAI database. The top 300 genes most positively correlated with FBXO45 were screened into the enrichment analysis. The functional enrichment results showed that FBXO45 was mainly associated with proteasomal protein catabolic process and the regulation of DNA metabolic processing in the biological process (BP) category; spindle, chromosomal region, and focal adhesion in the cellular component category; and ATPase activity and ubiquitin-protein transferase activity terms in the molecular function category. FBXO45 was overexpressed in ESCA and other cancer types. FBXO45 expression was positively associated with the infiltration levels of immunosuppressive cells, such as CD8+ (cluster of differentiation 8+) T cells and NK (natural killer cell) cells, in ESCA. MYCBP2 and SKP1 were most associated with FBXO45. Our results suggested that FBXO45 is a potential oncogene in ESCA. Elevated FBXO45 expression indicates a relatively immunosuppressive microenvironment.