Ethanol potentiates gamma-aminobutyric acid-mediated inhibition in the inferior colliculus: evidence for local ethanol/gamma-aminobutyric acid interactions.
The effect of ethanol on gamma-aminobutyric acid (GABA)-mediated inhibition of neurons of the inferior collicular cortex (IC) was investigated. Systemic administration of 0.5 g/kg ethanol, but not 0.25 g/kg ethanol, potentiated the inhibitory effect of GABA on IC neuronal activity. As with systemic administration of ethanol, local application of two concentrations of ethanol potentiated, in a dose-dependent and concentration-dependent manner, GABA-mediated inhibition of IC activity. When utilizing the lower ethanol concentration (270 mM), increasing ethanol ejection currents produced a correspondingly greater amount of augmentation of GABA inhibition without concomitant changes in spontaneous neural activity. At the highest ejection current tested (90 nA), ethanol doubled the inhibitory effects of GABA on IC neuronal activity. Local application of a higher concentration of ethanol (2.7 M) also potentiated GABA-mediated inhibition, with greater ejection currents producing greater potentiation of GABA-inhibition. Compared to the lower ethanol concentration, the higher ethanol concentration required lower ejection currents to produce comparable amounts of potentiation of GABA inhibition. These findings demonstrate that ethanol potentiates GABA inhibition of IC activity via a local action. In contrast to the effects of ethanol on GABA inhibition, locally applied ethanol failed to potentiate the inhibition by glycine of IC activity, indicating that ethanol does not indiscriminately potentiate all types of inhibition of IC neural activity. Additionally, locally applied ethanol failed to potentiate inhibition by GABA in the lateral septum, indicating that ethanol/GABA interactions are site specific. These findings indicate that ethanol specifically potentiates GABA-mediated inhibition of neural activity, and that this action occurs via a local action at specific sites in brain.


[Possibilities for the polyclinic cardiologist in treating hyperlipoproteinemias in men with risk factors for ischemic heart disease].
A total of 158 males with coronary risk factors and excessive (4 to 55% above normal) body weight were treated by diet and exercise for hyperlipoproteinemia in an out-patient clinic for 18 months. Blood cholesterol decreased significantly, by 14.4% (p less than 0.001), in 10% of the males who had lost at least 10% of excessive weight. Blood triglycerides decreased by 23% in 22% of the patients, who had lost 5.5% and more of excessive body weight (p less than 0.01). A two-month course of treatment with essential forte in combination with diet and regular exercise reduced blood cholesterol by 15.1% in 62%, and blood triglycerides, by 44.5% in 61.9% (p less than 0.001).


[Amebic colitis and liver abscess complicated by high serum procalcitonin in acute myeloid leukemia].
We present a case of amebic colitis and liver abscess complicated by acute myeloid leukemia (AML) with high serum procalcitonin (PCT). A 61-year-old Japanese man seen at our hospital for severe diarrhea and high fever was found to have multiple ulcers in the transverse and sigmoid colon and rectum by colonoscopy and biopsies were conducted. Immature leukocytes with mild anemia and thrombocytopenia were seen in peripheral blood, necessitating bone marrow aspiration and biopsy that yielded a diagnosis of AML (FAB M4Eo). Serum C-reactive protein and PCT were extremely elevated. Blood cultures for bacteria and fungi were negative. Multiple low-density areas in the liver were found in abdominal computed tomography. Histological colon biopsy findings revealed amebic colitis, strongly suggesting amebic liver abscess. Metronidazole treatment was initiated for amebiasis and subsequent standard chemotherapy for AML was followed after fever was lowered. Hematological and cytogenetic CR was maintained with good clinical condition. Few case reports have been published in Japan to date on amebic colitis and liver abscess complicated by AML and no reports have been made on PCT elevation caused by amebiasis. In conclusion, differential diagnosis of amebiasis is necessary in addition to that of bacterial or fungal infection in serum PCT elevation.


[Epidemiology of diabetes type 1 in children aged 0-14 in Podlasie Province in years 2005-2012].
Epidemiological studies performed during last decades in many European countries and in the world proved increasing incidence rate of diabetes, especially diabetes type 1 in children (DMT1). In Europe there is one of the highest diabetes incidence rate. The aim of the study was to estimate the incidence rate of diabetes type 1 in children aged 0-14 years in North-East Poland during 2005-2012 years and to analyse this rates in relation to age, gender and season of the diabetes onset. The study was performed among patients staying under care of outpatient diabetes clinic of the Department of Pediatric, Endocrinologym Diabetology with Cardilogy Division, medical University of Białystok, Poland. The DMT1 incidence rate was calculated as the number of all newly diagnosed cases per 100 000 persons 0-14 aged matched. During the studied 8-years- period DMT1 was diagnosed in 306 children aged 0-14 years, 159 boys and 147 girls, in Podlasie Province. The highest number of new cases was found in 2011: 49, and 2012: 47, with the lowest number in 2005 and 2009: 32 each year. The average incidence rate in the studied period was 20,84/100 000 population, aged matched. The lowest incidence rate was found in 0-4 yrs old group: 14,59 /100 000, in 5-9 years old group was: 22,04/100 000, and was highest in 10-14 years old group: 24,94/100 000. The highest increase in incidence rate was noted in the youngest group: from 9,14/100 000 in 2005, to 23,45/100 000 in 2012. The greatest number of new recognisions was found in from November to March, and the lowest number from June to August. 1. The DMT1 incidence rate among children aged 0-14 years, in Podlasie Province, during 2005-2012 years was 20,84/100 000. 2. Increase in incidence rate was observed in the studied period from 15,23/100 000 in 2005 to 26,71/100 000 in 2012. The highest increase in incidence rate, 2,5 times, was fund in the youngest group, aged 0-4 years. 3. The seasonal incidence of New onset was observed with the greater number in autumn-winter months.


Preliminary Study on Artificial versus Animal-Based Feeding Systems for Amblyomma Ticks (Acari: Ixodidae).
Hard ticks pose a threat to animal and human health. Active life stages need to feed on a vertebrate host in order to complete their life cycle. To study processes such as tick-pathogen interactions or drug efficacy and pharmacokinetics, it is necessary to maintain tick colonies under defined laboratory conditions, typically using laboratory animals. The aim of this study was to test a membrane-based artificial feeding system (AFS) applicable for Amblyomma ticks using Amblyomma tonelliae as a biological model. Adult ticks from a laboratory colony were fed in a membrane-based AFS. For comparison, other A. tonelliae adults were fed on calf and rabbit. The proportions of attached (AFS: 76%; calf/rabbit: 100%) and engorged females (AFS: 47.4%; calf/rabbit: 100%) in the AFS were significantly lower compared to animal-based feeding (p = 0.0265). The engorgement weight of in vitro fed ticks (x¯ = 658 mg; SD ± 259.80) did not significantly differ from that of ticks fed on animals (p = 0.3272, respectively 0.0947). The proportion of females that oviposited was 100% for all three feeding methods. However, the incubation period of eggs (x¯ = 54 days; SD ± 7) was longer in the AFS compared to conventional animal-based feeding (p = 0.0014); x¯ = 45 days; SD ± 2 in the rabbit and (p = 0.0144). x¯ = 48 days; SD ± 2 in the calf). Egg cluster hatching (x¯ = 41%; SD ± 44.82) was lower in the AFS than in the other feeding methods (rabbit: x¯ = 74%; SD ± 20; p = 0.0529; calf: x¯ = 81%; SD ± 22; p = 0.0256). Although the attachment, development, and the hatching of AFS ticks were below those from animal-based feeding, the method may be useful in future experiments. Nevertheless, further experiments with a higher number of tick specimens (including immature life stages) and different attractant stimuli are required to confirm the preliminary results of this study and to evaluate the applicability of AFS for Amblyomma ticks as an alternative to animal-based feeding methods.


Linkage mapping with paralogs exposes regions of residual tetrasomic inheritance in chum salmon (Oncorhynchus keta).
Gene sequence similarity due to shared ancestry after a duplication event, that is paralogy, complicates the assessment of genetic variation, as sequences originating from paralogs can be difficult to distinguish. These confounded sequences are often removed prior to further analyses, leaving the underlying loci uncharacterized. Salmonids have only partially rediploidized subsequent to a whole-genome duplication; residual tetrasomic inheritance has been observed in males. We present a maximum-likelihood-based method to resolve confounded paralogous loci by observing the segregation of alleles in gynogenetic haploid offspring and demonstrate its effectiveness by constructing two linkage maps for chum salmon (Oncorhynchus keta), with and without these newly resolved loci. We find that the resolved paralogous loci are not randomly distributed across the genome. A majority are clustered in expanded subtelomeric regions of 14 linkage groups, suggesting a significant fraction of the chum salmon genome may be missed by the exclusion of paralogous loci. Transposable elements have been proposed as drivers of genome evolution and, in salmonids, may have an important role in the rediploidization process by driving differentiation between homeologous chromosomes. Consistent with that hypothesis, we find a reduced fraction of transposable element annotations among paralogous loci, and these loci predominately occur in the genomic regions that lag in the rediploidization process.


Evaluation of stress and pain during rapid maxillary expansion treatments.
The purpose of this study was to use salivary cortisol levels, pressure pain threshold (PPT) and Spielberger's State-Trait Anxiety Inventory for Children (STAIC) to assess stress, anxiety and pain during the expansion and retention phase of rapid maxillary expansion (RME) in children and investigate to whether this parameters are associated with gender or skeletal maturity stages. STAIC was used to assess the anxiety levels of the children. Salivary samples were collected for stress hormone determination. Visual Analog Scale was used for pain determination. Pressure pain threshold (PPT) was measured by using algometer. Data collection was performed a week before RME treatment (T0), at the day of the expansion appliance was bonded (T1), at the days of 1st, 4th, 7th, 14th, 25th, 36th activations of expansion screw (T2, T3, T4, T5, T6, T7) and after the retention period of 3 months (T8). The results of this study showed that the differences were statistically significant within-day (P < 0·001) and within-hours (P < 0·001) in cortisol levels during treatment. PPT levels were statistically significant within sex differences and skeletal maturity stages (P < 0·05). State-trait anxiety scale scores were similar with respect to gender (P > 0·05). There were statistically significant differences of state-trait anxiety levels between pre and post-treatment stages (P < 0·05). The maximum number of patients reporting pain were days at T3 and T4. From day T5 the percentage of patients reporting pain then gradually reduced. Based on the findings of this study, it has been shown that RME leads to changes in patients' state-trait anxiety and cortisol levels.


Initial development of a measure of expectancies for combinations of alcohol and caffeine: the Caffeine + Alcohol Combined Effects Questionnaire (CACEQ).
Caffeinated alcoholic beverage (CAB) consumption is widespread among young adults in the United States and is associated with increased negative consequences from alcohol. In addition to the direct pharmacological effects of adding caffeine to alcohol, another possible risk mechanism is via socially learned expectancies, which has received very little consideration. The current study conducted an initial psychometric validation of a measure of CAB expectancies to facilitate research in this area. Participants were 409 undergraduate regular drinkers (71% female) who were assessed for alcohol and CAB use, alcohol use/misuse, and expectancies about CABs. The majority (62%) of participants reported CAB experience and 48% reported CAB use in the past month. Participants primarily consumed spontaneously-prepared as opposed to premixed-CABs. More frequent CAB use was significantly positively correlated with levels of alcohol use and misuse. For the expectancy items, exploratory factor analysis revealed two factors that were labeled "Intoxication Enhancement" and "Avoid Negative Consequences." The patterns of expectancies reflected beliefs that CABs enhanced intoxication, but did not protect against negative consequences. The measure was titled the Caffeine + Alcohol Combined Effects Questionnaire (CACEQ). Intoxication enhancement scores were significantly associated with frequency of CAB use, even after adjusting for the role of weekly drinking and alcohol misuse, supporting the convergent validity of the CACEQ. These data provide initial support for the CACEQ and suggest it may be useful for clarifying the role of expectancies in CAB use. Applications for studying the risks associated with CAB use and methodological considerations are discussed.


[Schwannomas of the neck. About 3 cases, and literature review].
Schwannomas of the neck are rare. Their diagnosis remains difficult despite the evolution of imaging techniques. The goals of our study were to review the diagnostic and therapeutic approach for these tumors. Retrospective study (1998-2005) concerning 3 cases of schwannoma in rare localizations: superior laryngeal nerve, ansa cervicalis and deep cervical plexus. These 3 patients were operated on in our ENT head and neck department. We made a review of the literature using the Medline database. The mean delay between symptomatology and treatment was 5 years. In all cases, the schwannoma presented with a slowly-growing cervical mass. In only one case, the diagnosis of schwannoma was maded preoperatively. All 3 patients were treated surgically and the involved nerve was sacrificied. There were no postoperative complications. The mean follow-up duration was 3.5 years, with no recurrence. To establish a diagnosis of neck schwannoma, ultrasound is the least sensitive imaging tool. Fine needle aspiration is especially useful to rule out other conditions. The most relevant diagnostic tools are CT-scan and especially MRI. Treatment is surgical; it should include sacrifice of the involved nerve. Surgical exploration of the neck and tumor resection could be performed at the same operation in the informed patient aware of the sequelae of nerve sacrifice, or otherwise be performed in two steps in the uninformed patient.


Results and potential of somatostatin receptor imaging in gastroenteropancreatic tract tumours.
Somatostatin receptor imaging with 111In-pentetreotide is widely accepted as an essential step in the management of patients affected by neuroendocrine tumours of the gastro-entero-pancreatic tract. Many data are already available on the high sensitivity of this technique. We present a review of the published data together with the results of a study involving 253 patients submitted to somatostatin receptor imaging in three Italian hospitals. The patients were divided into two groups treated with different acquisition and processing protocols. The overall sensitivity was as high as (169/176) 96% in both groups, while the specificity was higher in the group in which semi-quantitative evaluation of somatostatin receptor density was performed: (23/26) 88% vs (39/51) 76%. The use of this method is recommended to increase the specificity of 111In-pentetreotide imaging. Our results with somatostatin receptor imaging in neuroendocrine tumours of the gastro-entero-pancreatic tract demonstrate that all figures of merit are excellent when imaging is accurately performed and analysed by experienced operators.


Theoretical investigation of compact couplers between dielectric slab waveguides and two-dimensional metal-dielectric-metal plasmonic waveguides.
We theoretically investigate the properties of compact couplers between high-index contrast dielectric slab waveguides and two-dimensional metal-dielectric-metal subwavelength plasmonic waveguides. We show that a coupler created by simply placing a dielectric waveguide terminated flat at the exit end of a plasmonic waveguide can be designed to have a transmission efficiency of ~70% at the optical communication wavelength. We also show that the transmission efficiency of the couplers can be further increased by using optimized multisection tapers. In both cases the transmission response is broadband. In addition, we investigate the properties of a Fabry-Perot structure in which light is coupled in and out of a plasmonic waveguide sandwiched between dielectric waveguides. Finally, we discuss potential fabrication processes for structures that demonstrate the predicted effects.


[The HLA system antigens in delayed sexual development].
Frequency distribution of HLA antigens of A and B loci was examined in 138 adolescent boys aged 14-18 with delayed sexual development (DSD) of stages I-III, residing in the north-eastern region of Ukraine. Increase of A28- and B40-antigens and haplotypes A1-B40, A28-B40, A10-B40 determination frequencies was established. There were revealed positive and negative correlation between some of HLA antigens and DSD. Relative and attributive risks of DSD formation were calculated.


The medical aspects of soccer injury epidemiology.
In this article, the six major studies of soccer injury epidemiology are reviewed. Strengths and weaknesses of each epidemiologic design are critiqued and the crucial importance of the definition of injury is emphasized. The effect of age, sex, and intensity of play on injury rates is discussed. Our present knowledge of injury rate by anatomical site, player position, and the type of playing surface are reviewed. We examined the importance of player factors such as flexibility, joint laxity, weakness, and incomplete rehabilitation from other injuries. In addition, we reviewed the role played by inadequate equipment, field conditions, and rule violations. A successful program for soccer injury prevention is described, and guidelines for future soccer injury epidemiology research are proposed.


Burden of Predominant Psychological Reactions Among the Healthcare Workers and General Population During COVID-19 Pandemic Phase: A Systematic Review and Meta-Analysis.
Present systematic review and meta-analysis examined the burden of psychological reactions predominantly anxiety, depression, stress, and insomnia during the novel COVID-19 pandemic phase among the frontline healthcare, nonfrontline healthcare, and general population. PubMed, EMBASE, and SCOPUS were searched for studies between January 1, 2020, and May 25, 2020. Brief protocol of the systematic review was registered with the PROSPERO database, (CRD42020186229). Any study that reported the burden of at least one of psychological reactions including anxiety or depression or stress or insomnia was eligible. Heterogeneity was assessed using I2 statistic and results were synthesized using random-effect meta-analysis. Out of 49 eligible studies, 41 databases from 37 studies reported anxiety, 39 databases (35 studies) reported depression, 20 studies reported stress and 12 databases from 11 studies reported insomnia. The overall prevalence for anxiety, depression, stress, and insomnia was 26.3%, 25.9%, 26.2%, and 31.3%, respectively. Prevalence of anxiety, depression, stress, and insomnia were found highest among the frontline healthcare as compared to general healthcare workers and the general population. Anxiety, depression, stress, and insomnia were more prevalent among frontline health-care workers compared to general. Such increased prevalence is prompting toward the global mental health emergency. Therefore, a call of urgent attention and pan-region effective mental-health intervention are required to mitigate these psychological reactions.


Comments on the Pteranodontidae (Pterosauria, Pterodactyloidea) with the description of two new species.
Considered one of the best known flying reptiles, Pteranodon has been subject to several reviews in the last century. Found exclusively in the Upper Cretaceous Niobrara Formation and Pierre Shale Group 11 species have been attributed to this genus (excluding the ones presently regarded as representing Nyctosaurus). While reviewers agree that this number is inflated, there is disagreement on how many species can be identified. The last review recognized only two species (Pteranodon longiceps and Pteranodon sternbergi) both being sexually dimorphic. Based on several cranial features, some specimens previously referred to the genus Pteranodon are re-evaluated leading to the recognition of the following species, two of which new that are described here: Pteranodon longiceps, Geosternbergia sternbergi, Geosternbergia maiseyi sp. nov., and Dawndraco kanzai gen. et sp. nov. They differ mainly by features such as the direction and extension of the frontal crest, the angle and extension of the posterior process of the premaxillae, the shape and extension of the lower temporal fenestra and the length and proportion of the rostrum. The procedures to recognize a pterosaur species are also discussed here, and must take into account primarily morphology, in conjunction with stratigraphic and geographic data. Although well aware that changes in morphology not always reflect taxonomy, the lack of stratigraphic data and the limited number of specimens that can be confidently assigned to one species hampers our understanding on the morphological variations as a function of ontogeny, individual variation and sexual dimorphism. Although the present study has not eliminated the possibility to recognize such differences, caution is needed before models are generalized for pterosaurs.


Illness representations are associated with fluid nonadherence among hemodialysis patients.
Patients with end-stage renal disease are required to limit fluid and salt intake. We examined illness representations [common-sense model (CSM)] among a sample of hemodialysis (HD) patients, investigating whether fluid-adherent patients held illness representations different from those of nonadherent patients. We also explored the utility of illness perceptions in predicting fluid nonadherence after controlling for clinical parameters, including residual renal function (KRU). Illness perceptions were assessed [Revised Illness Perception Questionnaire (IPQ-R)] in 99 HD patients. Clinical parameters were collected and averaged over a 3-month period prior to and including the month of IPQ-R assessment. Depression scores, functional status, and comorbidity were also collected. Fluid nonadherence was defined using interdialytic weight gain (IDWG) and dry weight (ideal weight). Patients in the upper quartile of percent weight gain were defined as nonadherent (IDWG> or =3.21% dry weight). Nonadherent patients had timeline perceptions significantly lower than those of adherent patients. Logistic regression models were computed in order to identify predictors of fluid nonadherence. After several demographic and clinical variables, including age, gender, and KRU, had been controlled for, lower consequence perceptions predicted nonadherence. Illness representations appear to predict fluid nonadherence among HD patients. Extending the CSM to investigate specific perceptions surrounding treatment behaviors may be useful and merits attention in this setting.


Steatosis and bile duct damage in chronic hepatitis C: distribution and relationships in a group of Northern Italian patients.
Hepatitis C virus (HCV) related disease follows a long, benign course and most affected patients have mild disease. Liver biopsy is mandatory to grade and stage the disease. Characteristic, though non-specific, HCV histological lesions such as bile duct damage and steatosis have been singled out but their association with non-histological parameters has not been completely defined. Our aim was to study the relationships among these histological lesions and clinical, biochemical, functional and virological characteristics in a group of Northern Italian patients with chronic hepatitis. We studied 172 patients with HCV-related chronic hepatitis. Patients were divided into groups on the basis of histology including bile duct damage and steatosis. Clinical, biochemical, functional and virological profiles were related to histological findings. Histological grading and staging of disease increased as the age of patients increased. Steatosis was present in 70% of our patients and was related to a higher degree of fibrosis and to decreased functional activity. The prevalence of bile duct damage was 20%. This lesion was present in older patients with higher staging and impaired liver function. Biochemically it was associated with an increase in aspartate aminotransferase, gammaglutamyltranspeptidase, alkaline phosphatase, and total bilirubin. In the population we studied, HCV chronic hepatitis was predominantly a mild disease. Moreover both steatosis and bile duct damage were also mild. Steatosis was associated with fibrosis and this might influence liver metabolic function. Bile duct lesions were found in older patients with advanced disease showing biochemical evidence ofcholestasis. The molecular role HCV might play in the pathogenesis of these histological features should be addressed in further studies.


[Immunotropic properties of anaferon and anaferon pediatric].
Anaferon and pediatric anaferon based on release-active antibodies to interferon-gamma (R-A antibodies to INF-gamma) proved to be efficient in the treatment of many viral infections. Immunomodulating (immunotropic) properties of the drugs were revealed in the preclinical studies at many Russian and foreign research medical institutions and are reviewed herein. Anaferon and pediatric anaferon stimulated the humoral and cellular immune responses and increased the neutrophil and macrophage activity. The crucial mechanism of the immunotropic action of R-A antibodies to INF-gamma was the effect on the system of interferons and in particular on INF-gamma and functionally conjugated cytokines, resulting in normalization of the functional activity of the innate factors of the immune defense and increasing of the antiviral action. The broad spectrum of the immunotropic activity provided the success of anaferon and anaferon pediatric for more than 10 years in the treatment and prophylaxis of the diseases associated with disorders in the immune system functional state.


Endoscopic follow-up of gastric ulcer in a population at intermediate risk for gastric cancer.
Primary: to assess the necessity of a second endoscopy with a pathology study to confirm the healing of all gastric ulcers previously diagnosed through endoscopy in a population at intermediate risk for gastric cancer. Secondary: to assess correlation between endoscopic findings and pathology diagnosis. a prospective analysis of patients diagnosed with gastric ulcer through endoscopy at Hospital General de Ciudad Real (Spain) over three years. We collected demographic, clinical, endoscopic, and pathological data for the first and subsequent endoscopies. We collected at least six biopsies obtained from ulcer margins, and assessed H. pylori infection. Three hundred and two patients were included in this study. H. pylori infection was diagnosed in 173 (57%), and 113 (37%) patients had used NSAIDs. The positive and negative predictive value for malignancy of endoscopic diagnosis regarding ulcer fold, base, and margins were 34 and 97%, respectively. Only one patient was diagnosed with a tumor during the second endoscopy. At the end of follow-up, the etiology of the ulcer was considered as peptic in 276 patients; Crohn s disease-related in one, and neoplastic in 25 patients (21 adenocarcinomas, 4 lymphomas). in an intermediate-risk population for gastric cancer a second endoscopy is not justified for gastric ulcer patients when endoscopy and biopsy results do not suggest malignancy.


Baseline oxygen delivery is associated with an increased risk of severe postoperative complications after elective open repair of abdominal aortic aneurysm.
Oxyhemodynamic parameters have been shown to have a relevant impact on the immediate postoperative outcome after major surgery, but it is not known their specific impact on the outcome after elective repair of abdominal aortic aneurysm (AAA). One-hundred and forty-one patients underwent elective open repair of infrarenal AAA and hemodynamic parameters were monitored perioperatively. One patient (0.7%) died postoperatively, 23 (16.3%) experienced a myocardial ischemic event and 9 of them (6.4%) had a myocardial infarction. Baseline oxygen delivery was not predictive of such myocardial ischemic events. Thirty-three patients (23.4%) suffered severe postoperative complications. The median baseline oxygen delivery was 429.5 mL/min/m2 among patients who had severe postoperative complications, whereas it was 505.5 mL/min/m2 among those who did not have severe complications (p=0.03). However, this parameter did not retain its significance at multivariate analysis. When only the preoperative variables were included in the logistic regression model, the Glasgow Aneurysm Score (P=0.004, Oddsratio 1.94, 95% C.I. 1.24-3.05) was the only predictor of severe postoperative complications. The Glasgow Aneurysm Score was significantly correlated with baseline oxygen delivery (P=-0.256, P=0.003). Baseline oxygen delivery is associated with an increased risk of severe postoperative complications after elective open repair of AAA. The value of preoperative optimization of oxygen delivery should be evaluated in this patient population.


Molecular Characterization of Multidrug Resistant Strains of Acinetobacter baumannii Isolated from Intensive Care Units in West of Iran.
According to the results of various studies using phenotypic methods, the prevalence of Multidrug Resistant (MDR) Acinetobacter baumannii (A. baumannii) isolates has been increasing worldwide. Pulsed-Field Gel Electrophoresis (PFGE) technique is known as the gold standard method to determine clonal characterization of bacterial species, especially A. baumannii. To determine the clonal relatedness and investigate the prevalence of integron classes 1 and 2 and genes encoding OXA-23 and 24 in A.baumanii isolates. A cross-sectional study was conducted from November 2011 to January 2013. A total of 140 A.baumannii isolates collected from three hospitals of Kermanshah were considered out of which 75 ICU isolates were included in this study. Antibiotics susceptibility test was done by disk diffusion method. Polymerase Chain Reaction (PCR) was performed in order to detect class 1 and 2 integrons and blaOXA-23-like, blaOXA-24-like genes. Isolates identified as MDR from a total of 75 Intensive Care Units (ICU) strains were subjected to genotyping for clonal relatedness. A total of 37 isolates among 75 ICU isolates were identified as MDR. The maximum drug resistance was observed against ceftriaxone, mezlocycline, cefotaxime, piperacilin, ciprofloxacin and imipenem. Frequency of Class 1 and Class 2 Integrons, blaOXA-23-like and blaOXA-24-like genes were 33(44%), 27(36%), 60(80%) and 14(18.6%) respectively. Four clusters with high level of similarity were obtained showing homogeneity among MDR isolates. Significant correlation between presence of integrons and resistance to different classes of antibiotic was observed in this study. Monitoring of drug resistance using gene integrase PCR and blaOXA gene by cluster analysis is very important to plan specific infection control measures due to MDR A. baumannii.


Short-Term Outcomes Following Laparoscopic vs Open Pancreaticoduodenectomy in Patients With Pancreatic Ductal Adenocarcinoma: A Randomized Clinical Trial.
The safety and efficacy of laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma remain controversial. To compare laparoscopic and open pancreaticoduodenectomy performed by experienced surgeons in patients with pancreatic ductal adenocarcinoma. This was a noninferiority, open-label randomized clinical trial between September 20, 2019 and March 20, 2022, at 10 hospitals in China. A total of 412 adult patients were assessed for eligibility; 200 patients with histologically confirmed or clinically diagnosed pancreatic ductal adenocarcinoma who were eligible to undergo pancreaticoduodenectomy were enrolled. Study recruitment is complete, and follow-up is ongoing. This article reports prespecified early safety results from the trial. Participants were randomized in a 1:1 ratio to undergo either laparoscopic or open pancreaticoduodenectomy, to be performed by experienced surgeons who had already performed at least 104 laparoscopic pancreaticoduodenectomy operations. The primary end point is 5-year overall survival, but the data for this end point are not yet mature; thus, secondary short-term outcomes, including operative findings, complications, mortality, and oncological results are reported here. The outcomes were analyzed according to a modified intention-to-treat and per-protocol principle. Among 412 patients for eligibility, 200 patients were enrolled and randomly assigned 1:1 to have laparoscopic pancreaticoduodenectomy or open pancreaticoduodenectomy. The mean (SD) age was 61.3 (9.3) years, and 78 participants (39%) were female. Laparoscopic procedures had longer operative times (median [IQR], 330.0 [287.5-405.0] minutes vs 297.0 [245.0-340.0] minutes; P < .001). Patients in the laparoscopic group lost less blood than those in the open group (median [IQR], 145.0 [100.0-200.0] mL vs 200.0 [100.0-425.0] mL; P = .02). Ninety-day mortality occurred in 2 of 100 patients in the laparoscopic group and 0 of 100 patients in the open group. There was no difference in the rates of complications of the Clavien-Dindo grades III-IV (n = 17 [17.0%] vs n = 23 [23.0%]; P = .29), comprehensive complication index (median [IQR], 0.0 [0.0-22.6] vs 8.7 [0.0-26.2]; P = .79) or median (IQR) postoperative length of stay (14.0 [11.0-17.0] days vs 14.0 [12.0-18.5] days; P = .37) between the 2 groups. Laparoscopic pancreaticoduodenectomy performed by experienced surgeons in high-volume specialized institutions resulted in similar short-term outcomes compared with open pancreaticoduodenectomy among patients with pancreatic ductal adenocarcinoma. ClinicalTrials.gov Identifier: NCT03785743.


A 6 μW per channel analog biomimetic cochlear implant processor filterbank architecture with across channels AGC.
A new analog cochlear implant processor filterbank architecture of increased biofidelity, enhanced across-channel contrast and very low power consumption has been designed and prototyped. Each channel implements a biomimetic, asymmetric bandpass-like One-Zero-Gammatone-Filter (OZGF) transfer function, using class-AB log-domain techniques. Each channel's quality factor and suppression are controlled by means of a new low power Automatic Gain Control (AGC) scheme which is coupled across the neighboring channels and emulates lateral inhibition (LI) phenomena in the auditory system. Detailed measurements from a five-channel silicon IC prototype fabricated in a 0.35 μm AMS technology confirm the operation of the coupled AGC scheme and its ability to enhance contrast among channel outputs. The prototype is characterized by an input dynamic range of 92 dB while consuming only 28 μW of power in total ( ∼ 6 μW per channel) under a 1.8 V power supply. The architecture is well-suited for fully-implantable cochlear implants.


A calmodulin-related protein that suppresses posttranscriptional gene silencing in plants.
Posttranscriptional gene silencing (PTGS) is an ancient eukaryotic regulatory mechanism in which a particular RNA sequence is targeted and destroyed. The helper component-proteinase (HC-Pro) of plant potyviruses suppresses PTGS in plants. Using a yeast two-hybrid system, we identified a calmodulin-related protein (termed rgs-CaM) that interacts with HC-Pro. Here we report that rgs-CaM, like HC-Pro itself, suppresses gene silencing. Our work is the first report identifying a cellular suppressor of PTGS.


Serial computed tomography and lung function testing in pulmonary Langerhans' cell histiocytosis.
Little is known about longitudinal lung function variation in patients with pulmonary Langerhans' cell histiocytosis (LCH). The contribution of serial lung computed tomography (CT) to managing these patients has not been evaluated. This long-term retrospective study included 49 patients who were serially evaluated by lung CT and pulmonary function tests. The lung function variation was categorised as improvement or deterioration. The extent of the CT lesions was correlated with lung function. Lung function deteriorated in ∼60% of the patients. Forced expiratory volume in 1 s (FEV(1)) and diffusing capacity of the lung for carbon monoxide (D(L,CO)) were the parameters that most frequently deteriorated. A subgroup of patients experienced a dramatic decline in FEV(1) within 2 yrs of diagnosis. Airway obstruction was the major functional pattern observed. In a multivariate analysis, % predicted FEV(1)at diagnosis was the only factor associated with the incidence of airway obstruction. The increase in cystic lesions on the lung CTs was associated with impaired lung function but did not anticipate the decline in FEV(1) or D(L,CO). Serial lung function tests are essential for following patients with pulmonary LCH, who frequently develop airway obstruction. A lung CT at diagnosis is informative, but routine sequential CTs seem less useful. A prospective study is needed to characterise those patients with early progressive disease.


Association of hyperopia with incident clinically significant depression: epidemiological and genetic evidence in the middle-aged and older population.
To investigate the association between hyperopia and clinically significant depression (CSD) in middle-aged and older individuals. The effect of genetic determinants of hyperopia on incident CSD was also explored. We included participants who had available data on mean spherical equivalent (MSE) and were free of depression at baseline from the UK Biobank. For the phenotypic association, hyperopia was defined as MSE of+2.00 dioptres (D) or greater, and was divided into mild, moderate and high groups. Diagnosis of CSD across follow-up was determined based on electronic hospital inpatients records. For the genetic association analysis, the association between hyperopia Polygenic Risk Score and incident CSD was assessed. Mendelian randomisation was assessed for causality association. Over a median follow-up of 11.11 years (IQR: 10.92-11.38), hyperopia was significantly associated with incident CSD independent of genetic risk (HR 1.29, 95% CI 1.05 to 1.59) compared with emmetropia participants, especially in those hyperopic patients without optical correction (HR 1.38, 95% CI 1.07 to 1.76). In addition, participants in the high degree of hyperopia were more likely to have incident CSD than participants in the mild degree of hyperopia (P for trend=0.009). Genetic analyses did not show any significant associations between hyperopia and incident CSD (p≥0.1). Hyperopia was significantly associated with an increased risk of incident CSD. This was independent of genetic predisposition to hyperopia, emphasising the importance of regular vision screening and correction of hyperopia to reduce the risk of CSD regardless of genetic risk.


The chick chorioallantoic membrane as an in vivo xenograft model for Burkitt lymphoma.
Burkitt lymphoma (BL) is an aggressive malignancy that arises from B-cells and belongs to the group of Non-Hodgkin lymphomas (NHL). Due to the lack of appropriate in vivo models NHL research is mainly performed in vitro. Here, we studied the use of the chick chorioallantoic membrane (CAM) for the generation of human BL xenograft tumors, which we compared with known characteristics of the human disease. In order to generate experimental BL tumors, we inoculated human BL2B95 and BL2-GFP cells on the CAM. BL2B95 xenograft-tumors were grown for seven days and subsequently analyzed with transmission electron and immunofluorescence microscopy, as well as histological staining approaches. BL2-GFP cells were studied at regular intervals up to seven days, and their metastatic behavior was visualized with intravital immunofluorescence techniques. Xenografted BL2B95 cells formed solid tumors in the CAM model with a Ki67-index greater than 90%, preservation of typical tumor markers (CD10, CD19, CD20), a 'starry sky' morphology, production of agyrophilic fibers in the stroma, formation of blood and lymphatic vessels and lymphogenic dissemination of BL2B95 to distant sites. We identified macrophages, lymphocytes and heterophilic granulocytes (chick homolog of neutrophils) as the most abundant immune cells in the experimental tumors. BL2-GFP cells could be traced in real-time during their distribution in the CAM, and the first signs for their dissemination were visible after 2-3 days. We show that xenografted BL2B95 cells generate tumors in the CAM with a high degree of cellular, molecular and proliferative concord with the human disease, supporting the application of the CAM model for NHL research with a focus on tumor-stroma interactions. Additionally we report that BL2-GFP cells, grafted on the CAM of ex ovo cultured chick embryos, provide a powerful tool to study lymphogenic dissemination in real-time.


Two types of leptin-responsive gastric vagal afferent terminals: an in vitro single-unit study in rats.
In vitro gastric vagal afferents' (GVAs) unit activities were recorded from the ventral GVA nerve strands in rats. The responsiveness of 16 GVA terminals to close intra-arterial injection of vehicle (0.1 ml), leptin (350 pmol), and cholecystokinin (CCK)-8 (10 pmol) was analyzed to generate a spike count-versus-time histogram. Data of 5-min spike counts before and after each treatment were normalized by dividing the latter by the former. A quotient (Q) > 1 indicates an excitatory effect, Q < 1 indicates an inhibitory effect, and Q close to 1 indicates no effect. Two types of GVA terminals were identified. Type 1 (n = 8) responded to leptin with Q > 1; CCK-8 pretreatment did not consistently alter leptin sensitivity. In contrast, Type 2 (n = 8) responded to leptin with Q < 1 or close to 1, and CCK-8 pretreatment increased the leptin sensitivity so that the terminals responded to subsequent leptin with Q > 1. These data suggest that Type 1 and Type 2 GVA terminals may provide afferent neural signals, which, in turn, will be involved in body weight and food intake control systems, respectively.


Towards an AIDS vaccine: challenges and prospects.
Since the human immunodeficiency virus (HIV) started its spread through the human population, the AIDS epidemic has steadily increased on all continents unchecked by any therapeutic or preventive intervention, except for education. The search for an AIDS cure is facing great difficulties as HIV, a human retrovirus, is able to integrate and remain latent in the human genome for years. An effective vaccine thus remains the only foreseeable way to control and eventually eradicate AIDS. The unique pathogenicity and variability of HIV have raised new challenges in vaccine design, testing and evaluation. The status of the intense research efforts undertaken to solve these problems were assessed at a recent workshop on the AIDS vaccines.


Incidence of high erythrocyte count in infants and young children with iron deficiency anemia: re-evaluation of an old parameter.
To investigate the frequency of high erythrocyte count (red blood cell count >or=5.0 x 106/microL) in infants and young children with iron deficiency anemia and to document the differences in hematologic parameters at diagnosis and during iron therapy in IDA patients with and without a high erythrocyte count. A total of 140 infants and young children aged 6 to 48 months with nutritional IDA without a history of any bleeding disorder were the subjects of this study. The patients were divided into three groups according to the severity of anemia. Group A1 children had Hb values 8.0 g/dL or less (severe anemia); group A2, 8.1 to 10.0 g/dL (moderate anemia); and group A3, 10.1-11.0 g/dL (mild anemia). All children received oral iron (3-5 mg/kg per day) for 12 weeks. Complete blood counts were done weekly during treatment. A total of 36 of the 140 patients (26%) had a high erythrocyte count. Of the 140 patients, 37 were in group A1, 80 in A2, and 23 in A3. The frequency of high erythrocyte count was 11%, 23%, and 61% in groups A1, A2, and A3, respectively. The patients with a high erythrocyte count had significantly higher Hb and Hct but significantly lower mean corpuscular volume and mean corpuscular hemoglobin (MCH) values than those with a low erythrocyte count (n = 104). A continuous elevation in the erythrocyte count has been observed in patients with a high red cell count, as in those with a low red cell count, after the institution of iron therapy. A high erythrocyte count is a common feature of iron deficiency anemia in infants and young children, with an increasing frequency from severe to moderate to mild anemia. High erythrocyte count cannot be regarded as a reliable preliminary parameter in differentiating iron deficiency from thalassemias in infants and children aged up to 48 months.


Cleavage of colicin Ia by the Escherichia coli K-12 outer membrane is not mediated by the colicin Ia receptor.
Colicin Ia can be cleaved by isolated outer membranes prepared from sensitive and resistant (lacking the colicin Ia receptor) strains of Escherichia coli. Both active and heat-denatured colicin Ia are extensively fragmented. Such proteolysis does not occur when colicin Ia is added to whole sensitive or resistant cells. These results demonstrate that cleavage of colicin Ia is not mediated by its outer membrane receptor.


Critical analysis of the evidence for current technologies in bone-healing and repair.
Substances that enhance fracture-healing and bone regeneration have valuable clinical application and merit future research. Advances in these technologies will enhance our ability to heal fractures in a more effective and expedient manner. This review provides a brief description of the different techniques and technologies and their respective clinical utility. This paper also reviews the available literature on gene therapy, tissue engineering, growth factors, osteoconductive agents, and physical forces and assesses the evidence regarding the current status of these techniques of healing and regenerating bone. Only twenty-seven articles met our guidelines for studies containing Level-I evidence. We were able to determine that atrophic nonunions and pseudarthrosis led to poorer outcomes, and the results were uniformly poor irrespective of the technique used. Although the literature contains a large number of studies on the effects of different agents and modalities on bone repair and healing, it still is not clear how these agents work or in what circumstances they should be used. Many of the treatment modalities of interest are still at an experimental stage, so good evidence to support clinical practice is lacking. Additional multicenter, prospective randomized studies are needed to define the indications, specifications, dosage, limitations, and contraindications in the treatment of nonunions. Studies are also needed to address the full clinical feasibility of the role of each modality in fracture-healing and repair.


Structures of domains I and IV from YbbR are representative of a widely distributed protein family.
YbbR domains are widespread throughout Eubacteria and are expressed as monomeric units, linked in tandem repeats or cotranslated with other domains. Although the precise role of these domains remains undefined, the location of the multiple YbbR domain-encoding ybbR gene in the Bacillus subtilis glmM operon and its previous identification as a substrate for a surfactin-type phosphopantetheinyl transferase suggests a role in cell growth, division, and virulence. To further characterize the YbbR domains, structures of two of the four domains (I and IV) from the YbbR-like protein of Desulfitobacterium hafniense Y51 were solved by solution nuclear magnetic resonance and X-ray crystallography. The structures show the domains to have nearly identical topologies despite a low amino acid identity (23%). The topology is dominated by β-strands, roughly following a "figure 8" pattern with some strands coiling around the domain perimeter and others crossing the center. A similar topology is found in the C-terminal domain of two stress-responsive bacterial ribosomal proteins, TL5 and L25. Based on these models, a structurally guided amino acid alignment identifies features of the YbbR domains that are not evident from naïve amino acid sequence alignments. A structurally conserved cis-proline (cis-Pro) residue was identified in both domains, though the local structure in the immediate vicinities surrounding this residue differed between the two models. The conservation and location of this cis-Pro, plus anchoring Val residues, suggest this motif may be significant to protein function.


Tailoring Design of Nanomaterials and Systems to Individualize Patient Treatments.
Nanomedicine encompasses usage of materials smaller than 100 nm for diagnosis, monitoring and treatment of disease. A frequent application of these materials is in reformulation of active drugs, which were previously approved for clinical use. As illustrated with chemotherapeutics, delivery of a drug within a nanocarrier can represent a clear clinical benefit as it can increase its targeted uptake and reduce the off-target toxicity. Matching nanomedicine treatments with patient-specific biomarkers provides an exciting prospect for moving the filed towards precision medicine. In parallel, a strong potential for personalized treatments comes from employing nanomaterials for the delivery of patient-tailored biologically active molecules. Recent research and clinical data have highlighted mRNA and siRNA molecules, as well as short peptides, as powerful new drug classes that can be designed according to patient profiles and effectively delivered within nanoparticles. Particles used for therapeutic delivery are based on biodegradable and safe materials, frequently lipids and polymers, which can be further functionalized into more complex forms. Currently, there is a strong interest in developing specific nanocarrier formulations which can achieve optimal delivery of active molecules to targeted cells while reducing unwanted side-effects. Here, we discuss recent developments and future perspectives in the nanomedicine field and specifically highlight innovative approaches for the personalized patient treatments.


Neural decoding reveals impaired face configural processing in the right fusiform face area of individuals with developmental prosopagnosia.
Most of human daily social interactions rely on the ability to successfully recognize faces. Yet ∼2% of the human population suffers from face blindness without any acquired brain damage [this is also known as developmental prosopagnosia (DP) or congenital prosopagnosia]). Despite the presence of severe behavioral face recognition deficits, surprisingly, a majority of DP individuals exhibit normal face selectivity in the right fusiform face area (FFA), a key brain region involved in face configural processing. This finding, together with evidence showing impairments downstream from the right FFA in DP individuals, has led some to argue that perhaps the right FFA is largely intact in DP individuals. Using fMRI multivoxel pattern analysis, here we report the discovery of a neural impairment in the right FFA of DP individuals that may play a critical role in mediating their face-processing deficits. In seven individuals with DP, we discovered that, despite the right FFA's preference for faces and it showing decoding for the different face parts, it exhibited impaired face configural decoding and did not contain distinct neural response patterns for the intact and the scrambled face configurations. This abnormality was not present throughout the ventral visual cortex, as normal neural decoding was found in an adjacent object-processing region. To our knowledge, this is the first direct neural evidence showing impaired face configural processing in the right FFA in individuals with DP. The discovery of this neural impairment provides a new clue to our understanding of the neural basis of DP.


The SMC5/6 Complex Subunit NSE4A Is Involved in DNA Damage Repair and Seed Development.
The maintenance of genome integrity over cell divisions is critical for plant development and the correct transmission of genetic information to the progeny. A key factor involved in this process is the STRUCTURAL MAINTENANCE OF CHROMOSOME5 (SMC5) and SMC6 (SMC5/6) complex, related to the cohesin and condensin complexes that control sister chromatid alignment and chromosome condensation, respectively. Here, we characterize NON-SMC ELEMENT4 (NSE4) paralogs of the SMC5/6 complex in Arabidopsis (Arabidopsis thaliana). NSE4A is expressed in meristems and accumulates during DNA damage repair. Partial loss-of-function nse4a mutants are viable but hypersensitive to DNA damage induced by zebularine. In addition, nse4a mutants produce abnormal seeds, with noncellularized endosperm and embryos that maximally develop to the heart or torpedo stage. This phenotype resembles the defects in cohesin and condensin mutants and suggests a role for all three SMC complexes in differentiation during seed development. By contrast, NSE4B is expressed in only a few cell types, and loss-of-function mutants do not have any obvious abnormal phenotype. In summary, our study shows that the NSE4A subunit of the SMC5-SMC6 complex is essential for DNA damage repair in somatic tissues and plays a role in plant reproduction.


Synaptic vesicle protein 2A tumoral expression predicts levetiracetam adverse events.
The efficacy of levetiracetam (LEV) in controlling seizures in patients with brain tumor-related epilepsy (BTRE) depends on tumoral expression of synaptic vesicle protein 2A (SV2A). Although LEV is generally well tolerated, neuropsychiatric adverse events (NPAEs) might occur, limiting compliance and seizure control. We aimed to assess the influence of tumoral SV2A expression on the occurrence of LEV-related NPAEs in patients with glioma. Specimens from patients enrolled in the multicenter COMPO study, with glioma and BTRE treated with LEV, undergoing neurosurgery were retrieved. Immunohistochemistry-based expression of SV2A in tumoral and peritumoral tissue was scored in a four-point scale from absent (score = 0) to strong (score = 3). Low immunoreactivity (IR) corresponded to scores < 2. Staining ratios (tumoral SV2A IR/peritumoral SV2A IR) were grouped into low (≤ 0.5) and high (> 0.5). NPAEs were assessed longitudinally with the Neuropsychiatry Inventory 12 test (NPI-12). Overall, 18 patients were eligible for analysis. All received LEV monotherapy, with 67% developing NPAEs. Patients with NPAEs had significantly lower median SV2A intensity score compared to patients without NPAEs (score 1 vs 0, p = 0.025). Low staining ratio (≤ 0.5) associated with higher NPAE occurrence compared to SR > 0.5 (85.7% vs 0%, p < 0.01). A SR ≤ 0.5 predicted a consistent increase in risk of NPAEs (OR 45.0; 95% CI 1.8-1128; p = 0.02). Our results suggest that SV2A expression in tumoral and peritumoral tissue correlates with the occurrence of LEV-related NPAEs. Thus, considering that SV2A expression also influences LEV effectiveness, SV2A staining might help in tailoring treatment to patients.


Variation in stem mortality rates determines patterns of above-ground biomass in Amazonian forests: implications for dynamic global vegetation models.
Understanding the processes that determine above-ground biomass (AGB) in Amazonian forests is important for predicting the sensitivity of these ecosystems to environmental change and for designing and evaluating dynamic global vegetation models (DGVMs). AGB is determined by inputs from woody productivity [woody net primary productivity (NPP)] and the rate at which carbon is lost through tree mortality. Here, we test whether two direct metrics of tree mortality (the absolute rate of woody biomass loss and the rate of stem mortality) and/or woody NPP, control variation in AGB among 167 plots in intact forest across Amazonia. We then compare these relationships and the observed variation in AGB and woody NPP with the predictions of four DGVMs. The observations show that stem mortality rates, rather than absolute rates of woody biomass loss, are the most important predictor of AGB, which is consistent with the importance of stand size structure for determining spatial variation in AGB. The relationship between stem mortality rates and AGB varies among different regions of Amazonia, indicating that variation in wood density and height/diameter relationships also influences AGB. In contrast to previous findings, we find that woody NPP is not correlated with stem mortality rates and is weakly positively correlated with AGB. Across the four models, basin-wide average AGB is similar to the mean of the observations. However, the models consistently overestimate woody NPP and poorly represent the spatial patterns of both AGB and woody NPP estimated using plot data. In marked contrast to the observations, DGVMs typically show strong positive relationships between woody NPP and AGB. Resolving these differences will require incorporating forest size structure, mechanistic models of stem mortality and variation in functional composition in DGVMs.


Collimator optimization in myocardial perfusion SPECT using the ideal observer and realistic background variability for lesion detection and joint detection and localization tasks.
In SPECT imaging, collimators are a major factor limiting image quality and largely determine the noise and resolution of SPECT images. In this paper, we seek the collimator with the optimal tradeoff between image noise and resolution with respect to performance on two tasks related to myocardial perfusion SPECT: perfusion defect detection and joint detection and localization. We used the Ideal Observer (IO) operating on realistic background-known-statistically (BKS) and signal-known-exactly (SKE) data. The areas under the receiver operating characteristic (ROC) and localization ROC (LROC) curves (AUCd, AUCd+l), respectively, were used as the figures of merit for both tasks. We used a previously developed population of 54 phantoms based on the eXtended Cardiac Torso Phantom (XCAT) that included variations in gender, body size, heart size and subcutaneous adipose tissue level. For each phantom, organ uptakes were varied randomly based on distributions observed in patient data. We simulated perfusion defects at six different locations with extents and severities of 10% and 25%, respectively, which represented challenging but clinically relevant defects. The extent and severity are, respectively, the perfusion defect's fraction of the myocardial volume and reduction of uptake relative to the normal myocardium. Projection data were generated using an analytical projector that modeled attenuation, scatter, and collimator-detector response effects, a 9% energy resolution at 140 keV, and a 4 mm full-width at half maximum (FWHM) intrinsic spatial resolution. We investigated a family of eight parallel-hole collimators that spanned a large range of sensitivity-resolution tradeoffs. For each collimator and defect location, the IO test statistics were computed using a Markov Chain Monte Carlo (MCMC) method for an ensemble of 540 pairs of defect-present and -absent images that included the aforementioned anatomical and uptake variability. Sets of test statistics were computed for both tasks and analyzed using ROC and LROC analysis methodologies. The results of this study suggest that collimators with somewhat poorer resolution and higher sensitivity than those of a typical low-energy high-resolution (LEHR) collimator were optimal for both defect detection and joint detection and localization tasks in myocardial perfusion SPECT for the range of defect sizes investigated. This study also indicates that optimizing instrumentation for a detection task may provide near-optimal performance on the more challenging detection-localization task.


Urban-rural linkages: effective solutions for achieving sustainable development in Ghana from an SDG interlinkage perspective.
Urbanization and concomitant challenges pose a great threat to sustainable development. Urban and rural development interacts through the flows of people, materials, energy, goods, capital, and information. Without building sound urban-rural linkages, achieving development in one area could compromise it in another area. Achieving sustainable development needs customized policy prioritization and implementation in both urban and rural areas. Much literature exists in the research field of urban-rural linkages, but little has been done via a comprehensive analysis from an interlinkage perspective in the context of the Sustainable Development Goals (SDGs). Sustainable Development Goal 11 on sustainable cities and several targets embedded under other Goals provides a good framework for analyzing the urban-rural linkages. This paper contributes to this novel research perspective using Ghana as a case. The study applied an integrated approach by combining the results from a solution-scanning exercise with an SDG interlinkage analysis to identify the challenges and priority solutions and assess the synergies and trade-offs of the identified solutions. It extends the conventional solution-scanning approach by further assessing the synergies and trade-offs of the solutions from an SDG interlinkage perspective. It also enables a more practical SDG interlinkage analysis through the contributions from the multi-stakeholder consultations conducted in Ghana. The analyses show that prioritizing gender inclusion (Goal 5) will positively affect many social and well-being outcomes, including poverty elimination (Goal 1), hunger reduction (Goal 2), health improvement (Goal 3) and access to quality education (Goal 4) and basic services, such as water (Goal 6). However, gender inclusion could have potential trade-offs in the agricultural sector (Goal 2) in the case that women who dominate agricultural value chains could move to work in other sectors. Lack of proper infrastructure (Goal 9), such as transport, will hinder wide gender inclusion. An integrated approach that considers both the synergies and trade-offs of relevant solutions is critical for effective policymaking, specifically in developing countries.


Induction of cytoskeleton-associated proteins during differentiation of human myeloid leukemic cell lines.
Alterations in the expression of proteins associated with the cytoskeletal framework during differentiation of two human myeloid leukemia cell lines were analyzed by two-dimensional gel electrophoresis of Triton-insoluble cellular framework fractions. During in vitro differentiation of HL60 (human promyelocytic leukemia line) and U937 (human monocytoid leukemia line), several new cytoskeleton-associated (CSK) proteins are induced. All of these CSK proteins are also present in freshly isolated normal granulocytes and macrophages. One of these differentiation-induced proteins comigrates with vimentin. There are several differentiation-sensitive proteins, i.e., those that are no longer synthesized upon differentiation. The changes in CSK protein synthesis during differentiation of HL60 and U937 cells do not seem to be related to drug treatment per se since exposure to conditioned medium from phytohemagglutinin-stimulated lymphocytes as well as to dimethyl sulfoxide and 12-O-tetradecanoylphorbol-13-acetate results in the production of many similar proteins. In vitro conditions that do not result in differentiation of HL60 and U937, such as cultivation in serum-free medium, do not induce the CSK proteins that we describe. A notable finding in this study is that all of the qualitative changes in the proteins synthesized during differentiation are detected in the cytoskeletal (Triton-insoluble) fraction, whereas only minor quantitative alterations are observed in the Triton-insoluble extract. The changes in CSK protein components occur in an orderly fashion. Vimentin, an intermediate-filament protein, is synthesized in large amounts prior to changes in cellular morphology and the induction or loss of other CSK proteins. Vimentin may play an important role in the reorganization of the cytoskeleton to support the process of differentiation. The other CSK proteins are synthesized sequentially along with the morphological and functional changes during differentiation. These model systems, therefore, present an opportunity to investigate the role of specific cytoskeletal components in cellular differentiation.


Work activity in pregnancy, preventive measures, and the risk of delivering a small-for-gestational-age infant.
We undertook a case-control study to evaluate whether some occupational conditions during pregnancy increase the risk of delivering a small-for-gestational-age (SGA) infant and whether taking measures to eliminate these conditions decreases that risk. The 1536 cases and 4441 controls were selected from 43898 women who had single live births between January 1997 and March 1999 in Québec, Canada. The women were interviewed by telephone after delivery. The risk of having an SGA infant increased with an irregular or shift-work schedule alone and with a cumulative index of the following occupational conditions: night hours, irregular or shift-work schedule, standing, lifting loads, noise, and high psychological demand combined with low social support. When the conditions were not eliminated, the risk increased with the number of conditions (P(trend) =.004; odds ratios=1.00, 1.08, 1.28, 1.43, and 2.29 for 0, 1, 2, 3, and 4-6 conditions, respectively). Elimination of the conditions before 24 weeks of pregnancy brought the risks close to those of unexposed women. Certain occupational conditions experienced by pregnant women can increase their risk of having an SGA infant, but preventive measures can reduce the risk.


Matrix formalism to describe functional states of transcriptional regulatory systems.
Complex regulatory networks control the transcription state of a genome. These transcriptional regulatory networks (TRNs) have been mathematically described using a Boolean formalism, in which the state of a gene is represented as either transcribed or not transcribed in response to regulatory signals. The Boolean formalism results in a series of regulatory rules for the individual genes of a TRN that in turn can be used to link environmental cues to the transcription state of a genome, thereby forming a complete transcriptional regulatory system (TRS). Herein, we develop a formalism that represents such a set of regulatory rules in a matrix form. Matrix formalism allows for the systemic characterization of the properties of a TRS and facilitates the computation of the transcriptional state of the genome under any given set of environmental conditions. Additionally, it provides a means to incorporate mechanistic detail of a TRS as it becomes available. In this study, the regulatory network matrix, R, for a prototypic TRS is characterized and the fundamental subspaces of this matrix are described. We illustrate how the matrix representation of a TRS coupled with its environment (R*) allows for a sampling of all possible expression states of a given network, and furthermore, how the fundamental subspaces of the matrix provide a way to study key TRS features and may assist in experimental design.


Disruption of tetR type regulator adeN by mobile genetic element confers elevated virulence in Acinetobacter baumannii.
Acinetobacter baumannii is an important human pathogen and considered as a major threat due to its extreme drug resistance. In this study, the genome of a hyper-virulent MDR strain PKAB07 of A. baumannii isolated from an Indian patient was sequenced and analyzed to understand its mechanisms of virulence, resistance and evolution. Comparative genome analysis of PKAB07 revealed virulence and resistance related genes scattered throughout the genome, instead of being organized as an island, indicating the highly mosaic nature of the genome. Many intermittent horizontal gene transfer events, insertion sequence (IS) element insertions identified were augmenting resistance machinery and elevating the SNP densities in A. baumannii eventually aiding in their swift evolution. ISAba1, the most widely distributed insertion sequence in A. baumannii was found in multiple sites in PKAB07. Out of many ISAba1 insertions, we identified novel insertions in 9 different genes wherein insertional inactivation of adeN (tetR type regulator) was significant. To assess the significance of this disruption in A. baumannii, adeN mutant and complement strains were constructed in A. baumannii ATCC 17978 strain and studied. Biofilm levels were abrogated in the adeN knockout when compared with the wild type and complemented strain of adeN knockout. Virulence of the adeN knockout mutant strain was observed to be high, which was validated by in vitro experiments and Galleria mellonella infection model. The overexpression of adeJ, a major component of AdeIJK efflux pump observed in adeN knockout strain could be the possible reason for the elevated virulence in adeN mutant and PKB07 strain. Knocking out of adeN in ATCC strain led to increased resistance and virulence at par with the PKAB07. Disruption of tetR type regulator adeN by ISAba1 consequently has led to elevated virulence in this pathogen.


Placental restriction reduces insulin sensitivity and expression of insulin signaling and glucose transporter genes in skeletal muscle, but not liver, in young sheep.
Poor growth before birth is associated with impaired insulin sensitivity later in life, increasing the risk of type 2 diabetes. The tissue sites at which insulin resistance first develops after intrauterine growth restriction (IUGR), and its molecular basis, are unclear. We have therefore characterized the effects of placental restriction (PR), a major cause of IUGR, on whole-body insulin sensitivity and expression of molecular determinants of insulin signaling and glucose uptake in skeletal muscle and liver of young lambs. Whole-body insulin sensitivity was measured at 30 d by hyperinsulinaemic euglycaemic clamp and expression of insulin signaling genes (receptors, pathways, and targets) at 43 d in muscle and liver of control (n = 15) and PR (n = 13) lambs. PR reduced size at birth and increased postnatal growth, fasting plasma glucose (+15%, P = 0.004), and insulin (+115%, P = 0.009). PR reduced whole-body insulin sensitivity (-43%, P < 0.001) and skeletal muscle expression of INSR (-36%), IRS1 (-28%), AKT2 (-44%), GLUT4 (-88%), GSK3α (-35%), and GYS1 (-31%) overall (each P < 0.05) and decreased AMPKγ3 expression in females (P = 0.030). PR did not alter hepatic expression of insulin signaling and related genes but increased GLUT2 expression (P = 0.047) in males. Whole-body insulin sensitivity correlated positively with skeletal muscle expression of IRS1, AKT2, HK, AMPKγ2, and AMPKγ3 in PR lambs only (each P < 0.05) but not with hepatic gene expression in control or PR lambs. Onset of insulin resistance after PR and IUGR is accompanied by, and can be accounted for by, reduced expression of insulin signaling and metabolic genes in skeletal muscle but not liver.


[Antioxidative response of Phytolacca americana and Nicotiana tabacum to manganese stresses].
Plant species capable of accumulating heavy metals are of considerable interest for phytoremediation and phytomining. The mechanism of Mn tolerance/hyperaccumulate in Phytolacca americana L. is less known. To elucidate the role of antioxidative enzyme in response to Mn, the 6-week-old seedling of Mn hyperaccumulator P. americana and non-accumulator-tobacco (Nicotiana tabacum) were exposed to half strength Hoagland solution with 1 mmol x L(-1) or 3 mmol x L(-1) MnCl2 for 4 days. The photosynthetic rate in P. americana decreased more slowly than that in tobacco, while the MDA content and electrolyte leakage in tobacco increased more rapidly than that in P. americana. For example, after exposure to 1 mmol x L(-1) Mn for 4 days, the photosynthetic rates of P. americana and tobacco in comparison to the control reduced by 13.3% and 75.5%, respectively. The MDA content and electrolyte leakage in tobacco increased by 347.3% and 120.1%, respectively, whereas Mn had no marked effect on both of it in P. americana, indicated that the oxidative damage in tobacco was more serious than that in P. americana. The activities of SOD and POD of both species increased rapidly with elevated Mn concentration and exposure time in both species, the increase of SOD activity in P. americana was higher than that in tobacco. CAT activity in tobacco declined rapidly, while the activity of CAT in P. americana was increased. The activities of SOD, POD and CAT in P. americana upon 1 mmol x L(-1) Mn exposure increased by 161.1%, 111.3% and 17.5%, respectively. The activities of SOD and POD in tobacco increased by 55.5% and 206.0%, respectively, while CAT activity decreased by 15.6%, indicating that the antioxidative enzymes in P. americana, particularly in CAT,could fully scavenge the reactive oxygen species generated by Mn toxicity. These results collectively indicate that the enzymatic antioxidation capacity is one of the important mechanisms responsible for Mn tolerance in hyperaccumulator plant species.


The effect of social context on the use of visual information.
Social context modulates action kinematics. Less is known about whether social context also affects the use of task relevant visual information. We tested this hypothesis by examining whether the instruction to play table tennis competitively or cooperatively affected the kind of visual cues necessary for successful table tennis performance. In two experiments, participants played table tennis in a dark room with only the ball, net, and table visible. Visual information about both players' actions was manipulated by means of self-glowing markers. We recorded the number of successful passes for each player individually. The results showed that participants' performance increased when their own body was rendered visible in both the cooperative and the competitive condition. However, social context modulated the importance of different sources of visual information about the other player. In the cooperative condition, seeing the other player's racket had the largest effects on performance increase, whereas in the competitive condition, seeing the other player's body resulted in the largest performance increase. These results suggest that social context selectively modulates the use of visual information about others' actions in social interactions.


Management of bilateral locked facets of the cervical spine.
The management of 15 cases of bilateral locked facets of the cervical spine is reviewed. The C-6, C-7 interspace was the most common interspace involved. There were 4 females and 11 males who were 16 to 63 years old (average, 26 years). Thirteen patients had a complete spinal cord lesion with loss of function below the level of the locked facets. Two had intact dorsal column function. One patient had an ascending spinal cord deficit, which did not change after open reduction. The remainder had no change in spinal cord function after reduction. However, after reduction, 1 patient had a transient root deficit and 2 patients improved in the function of the involved roots. Closed reduction was accomplished by (a) skeletal traction and weight application, (b) manual reduction under sedatives, or (c) manual reduction under general anesthesia. Five patients required open reduction. The failure of closed reduction was attributed to accompanying fractures of one of the facets in 2 cases, increasing neurological deficits during traction in 2 cases, and associated higher cervical fractures in 1 case. Internal stabilization with wire and bone or external stabilization with a halo vest or a brace was used. Twelve patients were followed for 1 1/2 to 7 years (average, 2.7 years). Stabilization after reduction was successful irrespective of the methods used. The various methods of reduction and stabilization are reviewed and discussed.


The neurosteroid pregnenolone promotes degradation of key proteins in the innate immune signaling to suppress inflammation.
Pregnenolone is a steroid hormone precursor that is synthesized in various steroidogenic tissues, in the brain, and in lymphocytes. In addition to serving as the precursor for other steroid hormones, pregnenolone exerts its own effect as an anti-inflammatory molecule to maintain immune homeostasis in various inflammatory conditions. Pregnenolone and its metabolic derivatives have been shown to have beneficial effects in the brain, including enhancing memory and learning, reversing depressive disorders, and modulating cognitive functions. A decreased level of pregnenolone has been observed in neuroinflammatory diseases, which emphasizes its role in neuroprotection and neuroregeneration. Although the anti-inflammatory property of pregnenolone was recognized several decades ago, its mechanism of action remains unknown. Here we report that pregnenolone promotes ubiquitination and degradation of the TLR2/4 adaptor protein TIRAP and TLR2 in macrophages and microglial cells. Pregnenolone and its metabolites suppressed the secretion of tumor necrosis factor α and interleukin-6 mediated through TLR2 and TLR4 signaling. Pregnenolone has been reported to induce activation of cytoplasmic linker protein 170, and this protein has recently been shown to promote targeted degradation of TIRAP. We observed enhanced degradation of TIRAP and TLR4 suppression by cytoplasmic linker protein 170 in the presence of pregnenolone. Our experimental data reveal novel nongenomic targets of pregnenolone and provide important leads to understand its role in restoring immune homeostasis in various inflammatory conditions.


Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry.
Peptide sequence analysis using a combination of gas-phase ion/ion chemistry and tandem mass spectrometry (MS/MS) is demonstrated. Singly charged anthracene anions transfer an electron to multiply protonated peptides in a radio frequency quadrupole linear ion trap (QLT) and induce fragmentation of the peptide backbone along pathways that are analogous to those observed in electron capture dissociation. Modifications to the QLT that enable this ion/ion chemistry are presented, and automated acquisition of high-quality, single-scan electron transfer dissociation MS/MS spectra of phosphopeptides separated by nanoflow HPLC is described.


Impacts of climate change on reservoir water availability, quality and irrigation needs in a water scarce Mediterranean region (southern Portugal).
Future climate for the Mediterranean climatic region is expected to bring an increase in temperatures, decrease in the precipitation quantity and shifts in the seasonal precipitation pattern. Although the impacts of climate change on water resources have been relatively well explored for the Mediterranean climatic region, the specific consequences for reservoirs and, in particular, water availability and irrigation issues have been less studied. The objective of this work is two-fold: (i) to assess the impacts of future climate changes on water resources availability, quality (focusing on phosphorus loads as this is the limiting nutrient for eutrophication) and irrigation needs for two multipurpose reservoirs in southern Portugal; (ii) to suggest climate change adaptation strategies, especially for the agricultural sector. To this end, the SWAT model was first calibrated against existing data on reservoir inflows as well as phosphorus loads. Then, SWAT was run with climate derived EURO-CORDEX models (RCA4/RACMO22E) for four periods (1970-2000, 2010-2040, 2040-2070 and 2070-2100). Water availability was analysed using the Water Exploitation Index (WEI) that was calculated for both reservoirs combining changes of inflows and irrigation requirements. The results indicated that climate change will negatively impact water availability in both reservoirs, especially under RCP8.5. In the case of the Monte Novo reservoir, future domestic water supply could be constrained by water quality problems related with phosphorus loads. For Vigia reservoir, the high water exploitation will lead to water scarcity problems, mainly as this reservoir on present-day conditions is restrictive on irrigation requirements. Adaptation strategies such as the implementation of high end technology (e.g. soil moisture and plant water stress probes, satellite imagery and drones to evaluate water stress - NDVI) as well as the renewal of the irrigation network and adequate crop selection can help attenuating the effects of climate change on the water resources in this region.


Effects of manganese superoxide dismutase silencing on androgen receptor function and gene regulation: implications for castration-resistant prostate cancer.
Advanced prostate cancer is first treated with androgen deprivation therapy. However, tumors become resistant to and grow despite castrate levels of testosterone. Growth and proliferation of CRPC is mediated by gain-of-function changes in the AR and AR reactivation. Expression of manganese superoxide dismutase (SOD2), which regulates cellular ROS, is markedly down-regulated in CRPC when compared with hormone-responsive tumors. Here, we knocked down SOD2 expression in AR-expressing LNCaP prostate cancer cells and determined gene expression changes, transcription factor binding, and AR transcription activity in SOD2 knockdown cells. SOD2 knockdown results in an increase in ROS. Gene expression changes induced by SOD2 knockdown results in the up-regulation of genes that are also androgen responsive and 46% of genes up-regulated 2-fold by the androgen ligand R1881 are also up-regulated to the same extent with SOD2 knockdown. The induction of many of these genes with SOD2 knockdown, such as VEGFA and FKBP5, is reversible with the antioxidant N-acetylcysteine, suggesting that this mechanism is directly linked to ROS. Furthermore, an array for transcription factor DNA-binding activity shows that SOD2 knockdown induces DNA binding by several transcription factors, including AR. SOD2 knockdown-induced AR activation was confirmed by electrophoretic mobility shift assay and luciferase activity, and both were readily reversible with N-acetylcysteine. These findings show that down-regulation of SOD2 induces AR activity in a ROS-dependent manner, and suggest that there may be a role for antioxidant therapy in CRPC.


Antimicrobial efficacy of aloe-emodin mediated photodynamic therapy against antibiotic-resistant Pseudomonas aeruginosa in vitro.
Multidrug-resistant Pseudomonas aeruginosa is a common pathogen that causes topical infections following burn injuries. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising approach for treating antibiotic-resistant bacterial infections. The objective of this study was to evaluate the aPDT efficacy of aloe-emodin (AE), which is a photosensitizer extracted from traditional Chinese herbs, on antibiotic-sensitive and antibiotic-resistant P. aeruginosa in vitro. In this study, we confirmed the effectiveness of AE-mediated aPDT against both standard and MDR P. aeruginosa, explored the effects of irradiation time and AE concentration on bacterial survival in AE-mediated aPDT, and observed the structural damage of P. aeruginosa by using transmission electron microscope. Our results showed that neither AE nor light irradiation alone caused cytotoxic effects on P. aeruginosa. However, AE-mediated aPDT effectively inactivated both antibiotic-sensitive and antibiotic-resistant P. aeruginosa. The transmission electron microscope investigation showed that aPDT mediated by AE primarily caused damage to the cytoplasm and cell membrane. Our findings suggest that AE is a photosensitizer in the aPDT of MDR P. aeruginosa-caused topical infections following burn injuries. Future investigations will concentrate on the safety and efficacy of AE-mediated aPDT in animal models and clinical trials.


[Introduction of next-generation sequencing in health care: what are the implications for physicians and patients?].
Next-generation sequencing (NGS) involves the laying down of the sequence of the entire genome or exome at one time. This technique is expected to become one of the approaches in diagnostic testing. The genetically determined vulnerability of individuals to disorder and their response to treatment can be determined at one go. However, this gives rise to ethical and legal questions, particularly in the area of the protection of patient privacy. These questions include provision of information to the patient about the DNA investigation and the chance of incidental findings, feedback to the patient concerning incidental findings and the storage and reuse of the genetic information. It is important to begin discussion of the legal and ethical consequences of NGS investigations at an early stage. This article may be the stimulus for this discussion.


Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate Egress.
Ebola virus (EBOV) is a member of the Filoviridae family and the cause of hemorrhagic fever outbreaks. The EBOV VP40 (eVP40) matrix protein is the main driving force for virion assembly and budding. Indeed, expression of eVP40 alone in mammalian cells results in the formation and budding of virus-like particles (VLPs) which mimic the budding process and morphology of authentic, infectious EBOV. To complete the budding process, eVP40 utilizes its PPXY L-domain motif to recruit a specific subset of host proteins containing one or more modular WW domains that then function to facilitate efficient production and release of eVP40 VLPs. In this report, we identified additional host WW-domain interactors by screening for potential interactions between mammalian proteins possessing one or more WW domains and WT or PPXY mutant peptides of eVP40. We identified the HECT family E3 ubiquitin ligase WWP1 and all four of its WW domains as strong interactors with the PPXY motif of eVP40. The eVP40-WWP1 interaction was confirmed by both peptide pulldown and coimmunoprecipitation assays, which also demonstrated that modular WW domain 1 of WWP1 was most critical for binding to eVP40. Importantly, the eVP40-WWP1 interaction was found to be biologically relevant for VLP budding since (i) small interfering RNA (siRNA) knockdown of endogenous WWP1 resulted in inhibition of eVP40 VLP egress, (ii) coexpression of WWP1 and eVP40 resulted in ubiquitination of eVP40 and a subsequent increase in eVP40 VLP egress, and (iii) an enzymatically inactive mutant of WWP1 (C890A) did not ubiquitinate eVP40 or enhance eVP40 VLP egress. Last, our data show that ubiquitination of eVP40 by WWP1 enhances egress of VLPs and concomitantly decreases cellular levels of higher-molecular-weight oligomers of eVP40. In sum, these findings contribute to our fundamental understanding of the functional interplay between host E3 ligases, ubiquitination, and regulation of EBOV VP40-mediated egress.IMPORTANCE Ebola virus (EBOV) is a high-priority, emerging human pathogen that can cause severe outbreaks of hemorrhagic fever with high mortality rates. As there are currently no approved vaccines or treatments for EBOV, a better understanding of the biology and functions of EBOV-host interactions that promote or inhibit viral budding is warranted. Here, we describe a physical and functional interaction between EBOV VP40 (eVP40) and WWP1, a host E3 ubiquitin ligase that ubiquitinates VP40 and regulates VLP egress. This viral PPXY-host WW domain-mediated interaction represents a potential new target for host-oriented inhibitors of EBOV egress.


Evaluating the Positive Drinking Consequences Questionnaire: Support for a Four-Factor Structure and Measurement Invariance.
The 14-item Positive Drinking Consequences Questionnaire (PDCQ) was developed to assess experienced positive drinking consequences. The present study sought to advance the psychometric evaluation of the PDCQ via exploratory and confirmatory factor analyses, measurement invariance, criterion-related validity, and internal consistency. Participants were 1,088 traditional-age college students (81% female) who reported drinking in the past month. Exploratory factor analysis supported a four-factor model (i.e. Sociability, Tension Reduction, Liquid Courage, and Sexual Enhancement), and the confirmatory factor analysis indicated the four factors loaded on a higher-order factor ("PDCQ"). Invariance testing supported invariance for the PDCQ across gender. The PDCQ was positively associated with alcohol use and alcohol-related negative consequences, and negatively associated with protective behavioral strategies. Finally, the four factors of the PDCQ were discriminant from positive expectancies. Collectively, positive drinking consequences appear to be more nuanced than originally conceptualized. Evaluation of specific types of positive drinking consequences may assist in more precise prevention and intervention efforts in the future.


Evaluation of Postoperative Sensory and Motor Deficit Following Craniomaxillofacial Reconstruction Using Bicoronal Flap: An Evaluative Study.
The ideal surgical approach to treat craniomaxillofacial skeleton should provide maximum exposure of the facial skeleton, ensure less potential for injury to facial structures and allow for good cosmetic result. Several designs have been described such as hemicoronal, preauricular, lateral eyebrow, and bicoronal approach. Although the bicoronal flap gives superior long-term cosmetic results, it has a few disadvantages. We conducted this study to assess neurosensory disturbances and motor deficit following craniomaxillofacial reconstruction using bicoronal flap. A prospective study was carried out in the Department of Oral and Maxillofacial Surgery, North Karnataka, India. Forty patients with craniomaxillofacial trauma requiring fixation of fracture or reconstruction were included in the study. Postoperative neurosensory evaluation is carried out at intervals of 1 week, 1 month, 3 months, and 6 months clinically using mechanoreceptive and nociceptive testing. Among 40 cases, 11 (27.5%) had postoperative paraesthesia affecting the supraorbital region; 9 (22.5%) of them had return of normal sensation within 6 months and 2 (5%) patients became normal after one year. Four patients had unilateral frontalis weakness on the right side for a period of 6 months. The bicoronal flap is a preferred approach for access to the craniofacial skeleton and orbit with minimal sensory and motor complications. However, before choosing the same, the advantage of raising such a wide flap should be weighted comparing the benefits and complications.


Retinoid-induced limb malformations.
The developing limb has been studied extensively and is a useful model to study morphogenesis. During embryogenesis, limb formation is initiated as a budding off from the embryonic lateral body wall. Limb pattern is specified by a series of epithelial-mesenchymal interactions, directing proximodistal, dorsoventral and anteroposterior axes. Vitamin A metabolites, especially retinoic acid, are known to play an important role in limb development, and the effects of retinoic acid may be mediated through the retinoid receptor signaling pathways. Accumulated evidence has shown that inadequate levels (excess or deficiency) of retinoic acid cause a wide range of limb malformations. Some species have the capacity to regenerate amputated limbs, and retinoids certainly affect this process, but there is debate regarding the extent that regeneration recapitulates development. In this review, phenotypic features, pathogenesis and the molecular basis of retinoid-induced limb malformations are discussed with a description of normal limb development and endogenous retinoid pathways.


Eleven years of alloimmunization in 6496 transfused patients with sickle cell disease in France.
Red blood cell (RBC) transfusion is a major therapy for sickle cell disease (SCD). Patients are at risk of forming antibodies to RBC antigens which can result in the impossibility to find compatible units and cause hemolytic transfusion reactions. This retrospective study investigates the evolution of RBC consumption, the frequencies, specificities and chronology of appearance of antibodies in a population of patients consistently receiving RH-K matched RBC units (RBCu) from a predominantly European donor population. Over the 11 year period in the Paris area, 6496 patients were transfused at least once for a total of 239944 units. Antibodies were made by 1742 patients. The first antibodies of a patient were predictive of subsequent immunization. By the 17th RBC unit transfused (by the 20th, excluding warm autoantibodies), 75% of patients who would make antibodies had made their first. By the 16th, 90% who would make antibodie(s) to a high frequency antigen had made their first antibody to these antigens. Females made their first antibodies slightly earlier than males. Multitransfused patients (>50 units) had a higher immunization prevalence than rarely transfused patients (<12 units) but fewer clinically significant antibodies. Patients with SCD and prophylactic RH-K matching not immunized by the 20th RBCu are likely to have a low alloimmunization risk (to antigens other than RH-K), i.e. be low responders, especially relative to the most clinically significant antibodies. This number of 20 units is a point before which close monitoring of patients is most important, but remains open to future adjustment.


Lymphoproliferative responses to mouse mammary tumor virus in lymphocyte subsets of breast cancer patients.
Altered immunologic reactions were observed in breast cancer patients as compared to those in normal subjects. Lymphoproliferative responses to murine mammary tumor virus (MuMTV) were significantly enhanced in peripheral blood mononuclear cells from patients with metastatic disease. These reactivities occurred with mammary tumor virus purified from either mouse milk or infected feline kidney cells but not with Rauscher murine leukemia virus. For the assessment of the role of peripheral blood mononuclear leukocyte subpopulations in the responsiveness to MuMTV, the cell preparations were fractionated according to their ability to form spontaneous rosettes with sheep red blood cells (E-rosettes). The effectiveness of the separation was ascertained by means of cell surface markers, i.e., presence of surface immunoglobulins or a T-cell marker. Leu-1 antigen, and mitogen-induced blastogenesis. The responsiveness to the MuMTV antigen(s) was associated with the T-cell subset, identified as the E-rosetting. Leu-1-positive, and surface immunoglobulin-negative population. Although some subjects with the normal population gave positive reactions, the results reveal an apparent association between high levels of responsiveness to MuMTV within the T-lymphocyte subset and breast cancer disease.


Exploring dermatologists' perspectives on vaccines in dermatology: a qualitative study.
Vaccination rates among adults in the United States, including dermatology patients, remain suboptimal. Previous research has concluded that outpatient specialty offices often have administrative and patient-related barriers to administering vaccines in their clinics, however, this has never been examined specifically in dermatology. This study aims to examine dermatologists' perspectives on vaccine education in dermatology clinics, identify facilitators and barriers to vaccine administration in dermatology clinics, and explore strategies to improve vaccination rates in dermatology patients. Virtual, semi-structured interviews were conducted with board-certified dermatologists to explore their perspectives on vaccines in dermatology clinic. The Consolidated Framework for Implementation Research was used to analyze the data. Participating dermatologists were 60% female (n = 9) and 40% male (n = 6) and had a median of 7 years of clinic experience (min-max: 3-39 years). Vaccine education emerged as one of the prominent themes during the interview with dermatologists, who emphasized the importance of comprehensive vaccine education for both healthcare providers and patients. Barriers identified encompassed patient hesitancy, lack of provider knowledge, resource limitations, and logistical challenges. Dermatologists proposed solutions such as standardized protocols, improved patient communication, enhanced coordination with other healthcare providers, and increased clinic resources. These results emphasize that dermatologists can play a crucial role in advocating for and addressing preventative care through vaccine implementation and provide a high-level framework to think about implementation. Additionally, this study highlights the need for comprehensive vaccine education, systematic implementation strategies, and organizational support within dermatology clinics to improve vaccine administration for patients.