English language proficiency and academic performance: A study of a medical preparatory year program in Saudi Arabia.
All medical schools in Saudi Arabia have English as the primary official medium of instruction. Most of the high school education, however, is delivered in Arabic and hence the transition to an English based learning environment tends to be difficult for some students. Our study aims to correlate English language proficiency with academic performance among medical students in their preparatory year. A cross-sectional study design was used. Test scores of 103 preparatory year students (54 female and 49 male) were analyzed after the students completed an English language course and medical introductory course in their preparatory year. The total score obtained in the English course assessment was compared to each component of the medical content assessment. A significantly positive correlation (Spearman's Rho, at 0.01 levels) was seen between the scores of the English exam and the written exam (P <0.001) and the oral exam (P = -0.003) parts respectively of the medical examination. Significant correlation with the English exam score was not obtained for the other components of the medical assessment, namely; student assignments, presentations and portfolios. English language proficiency is an important factor in determining academic proficiency of medical students in our college at the preparatory year level.


Women Using Mobile Phones for Health Communication Are More Likely to Use Prenatal and Postnatal Services in Bangladesh: Cross-Sectional Study.
The public health system in Bangladesh has been struggling to provide coverage and utilization of basic maternal health care services in pursuit of achieving maternal and child mortality-related goals. Interestingly, the rapid popularization of mobile technology in the country is transforming the landscape of health care access and delivery. However, little is known regarding the use of mobile phones from the perspective of maternal health care service utilization. In this study, we aimed to investigate the prevalence and sociodemographic pattern of mobile phone use for health services among women and relationship between the use of mobile phone use and the uptake of essential maternal health services (MHSs). Cross-sectional data from the Bangladesh Demographic and Health Survey on 4494 mothers aged between 15 and 39 years were used in the analysis. Using mobile phones to get health services or advice was hypothesized to have a positive association with the uptake of basic MHSs (antenatal care, ANC, facility delivery services, postnatal care) and postnatal care for the newborn. Data were analyzed using bivariate and multivariable techniques. More than a quarter (1276/4494, 28.4%; 95% CI 26.8-30.3) of the women aged 15-39 years reported using mobile phones to get health services with significant sociodemographic variations in the use of mobile phones. Analysis of the specific purposes revealed that, in most cases, mobile phones were used to contact service providers and consult with the same about what to do, whereas a smaller proportion reported using mobile phone for the purposes of arranging money and transportation. Multivariable analysis showed that compared with respondents who reported not using mobile phones for health care services, those who used them had higher odds of making 3+ ANC visits and delivering at a health facility. The odds were slightly higher for rural residents than for those in the urban areas. The findings of this study conclude that women who use mobile phones are more likely to use ANC and professional delivery services than those who do not. More in-depth studies are necessary to understand the mechanism through which mobile phone-based services enhance the uptake of maternal health care.


Platelet-leukocyte crosstalk in COVID-19: How might the reciprocal links between thrombotic events and inflammatory state affect treatment strategies and disease prognosis?
Platelet-leukocyte crosstalk is commonly manifested by reciprocal links between thrombosis and inflammation. Platelet thrombus acts as a reactive matrix that recruits leukocytes to the injury site where their massive accumulation, activation and migration promote thrombotic events while triggering inflammatory responses. As a life-threatening condition with the associations between inflammation and thrombosis, COVID-19 presents diffuse alveolar damage due to exaggerated macrophage activity and cytokine storms. These events, together with direct intracellular virus invasion lead to pulmonary vascular endothelialitis, cell membranes disruption, severe endothelial injury, and thrombosis. The developing pre-alveolar thrombus provides a hyper-reactive milieu that recruits circulating leukocytes to the injury site where their activation contributes to thrombus stabilization and thrombosis propagation, primarily through the formation of Neutrophil extracellular trap (NET). NET fragments can also circulate and deposit in further distance where they may disseminate intravascular thrombosis in severe cases of disease. Thrombi may also facilitate leukocytes migration into alveoli where their accumulation and activation exacerbate cytokine storms and tissue damage, further complicating the disease. Based on these mechanisms, whether an effective anti-inflammatory protocol can prevent thrombotic events, or on the other hand; efficient antiplatelet or anticoagulant regimens may be associated with reduced cytokine storms and tissue damage, is now of interests for several ongoing researches. Thus shedding more light on platelet-leukocyte crosstalk, the review presented here discusses the detailed mechanisms by which platelets may contribute to the pathogenesis of COVID-19, especially in severe cases where their interaction with leukocytes can intensify both inflammatory state and thrombosis in a reciprocal manner.


Influence of gender on the association of alcohol drinking with blood pressure.
The purpose of this study was to determine whether gender influences the association of alcohol drinking with blood pressure. The subjects (43,810 healthy men and women at ages of 35-54 years) were divided into five groups by average daily ethanol intake (non-, very light (<10 g per day), light (> or =10 g and <20 g per day), moderate (> or =20 g and <30 g per day), and heavy (> or =30 g per day) drinkers). The means of each variable after adjustment for age, body weight, and history of smoking were compared among the groups. Systolic blood pressure of men was significantly higher in moderate and heavy drinkers than in nondrinkers, and systolic blood pressure of women was significantly higher in heavy drinkers but not in moderate drinkers than in nondrinkers. Diastolic blood pressure of men and women was significantly higher in light, moderate and heavy drinkers than in nondrinkers. The differences in systolic and diastolic blood pressure between drinkers and nondrinkers were greater in men than in women. Both in men and women, serum HDL cholesterol was significantly higher in all four drinker groups than in the nondrinker group, and the difference between drinkers and nondrinkers was greater in women than in men. The above findings were not altered when age- and alcohol intake-matched groups of subjects were used. The results suggest that blood pressure is more prone to be elevated by alcohol drinking in men than in women.


Implementation of a primary screen for developmental neurotoxicity.
A battery of tests to evaluate physical growth/development and neurobehavioral function was conducted with 78 litters of control Sprague-Dawley rats given purified water by intubation. The objectives of this study were to optimize test methods and to document the range and variability of the experimental endpoints. Data are presented for maternal evaluations (body weight gain, food consumption), gestation length, litter size, and postnatal survival. Pup body weight was used to assess postnatal somatic growth rate from birth to 85 days of age, while whole and regional brain weight measurements at 7, 28, and 85 days provided a more specific measure of physical growth relevant to a neurobehavioral study. Physical landmarks of development evaluated were pinna unfolding, incisor eruption, and eye opening while reflex landmarks of development evaluated were the negative geotaxis and pupillary reflexes. The mean percentage of litters acquiring a physical trait or reflex increased sigmoidally with age, and the data suggest that the potential to detect developmental delays would be optimal when ca. 90% of control litters reach the test landmark. Functional evaluations were arranged according to four testing subsets so that each litter was evaluated in each test (1 pup/sex/litter), but repeated testing on pups was minimized. Auditory and tactile startle reflexes, as well as prepulse inhibition, were measured at ages 22 days and 60-64 days and found to increase with age. A passive avoidance paradigm (age 40-43 days) was used to assess exploratory behavior (approach) and memory (avoidance). Swimming performance in a water maze was used to evaluate learning. In this test, escape times and error rates improved to their highest level by five or six trials and showed acceptable degrees of variability. Spontaneous motor activity was monitored for 23 hr at age 54-61 days to evaluate exploratory activity, photoperiod entrainment, and catecholamine-induced locomotion (amphetamine challenge). Finally, landmarks of sexual maturation (balanopreputial separation evident at 45 days of age, vaginal perforation evident at 33 days) and estrous cyclicity (4.8 cycles per 21 days) were evaluated as measures of reproductive neuroendocrine function. In sum, the test battery provided an efficient yet comprehensive screen for evaluating effects on physical growth/development and neurobehavioral function which meets practical criteria for preclinical testing of pharmaceutical agents.


RNA synthesis in primary cultures of adult rat hepatocytes.
The ability of hepatocyte monolayers to synthesize RNA was investigated by measuring [3H]orotic acid incorporation into RNA and the total nuclear RNA polymerase activity as a function of the time in culture. The results demonstrate that primary cultures of hepatocytes maintained in a chemically defined serum- and hormone-free medium are able to synthesize RNA actively. This ability increases within the first 2 d of culture, despite the concomitant decrease in [3H]orotic acid uptake, and decreases only after 3 d. Factors such as serum, insulin, and dexamethasone, known to improve maintenance of functional hepatocytes, markedly stimulate the uptake of labeled precursor without apparently affecting the rate of RNA synthesis by cultured cells. It is suggested that the culture of adult rat hepatocytes provides a useful experimental model for the studies of hormonal regulation of transcription in liver.


Long-term hemodynamic performance of bileaflet prostheses versus tilting-disc prostheses in the aortic position.
The aim of this study was to compare the long-term hemodynamic performances of Medtronic-Hall (MH) and ATS medical bileaflet (ATS) valves in the aortic position. We reviewed 249 patients that underwent AVR using MH or ATS valves between October 1994 and February 2004. MH valves were implanted in 117 patients (the MH group) and ATS valves in 132 patients (the ATS group). Serial changes in echocardiographic findings and clinical outcomes were analyzed. No early mortality occurred, and the late valve-related mortality was 11.2% (28/249). The transaortic mean pressure gradient (TMPG) in the MH group increased more rapidly than that in the ATS group during follow-up. Concomitant mitral valve replacement (double valve replacement, DVR) and placement of small aortic prostheses (indexed effective orifice area less than 0.85 cm(2)/m(2)) were found to contribute to a postoperative increase in TMPG. No inter-group difference in cumulative survival was observed at 10 years (88.2 ± 3.1% vs. 84.7 ± 3.1%, p=0.847). Cox regression analysis revealed that old age and DVR were predictors of late death, and that female gender, inclusion in the MH group and DVR were predictive of major adverse valve-related events (MAVREs). The MH group showed higher MAVREs than the ATS group and a relatively rapid increase in TMPG. Furthermore, DVR and placement of small prostheses were related to a late increase in TMPG irrespective of valve type.


Molecular diagnosis of a case of Hb Phnom Penh [alpha117(GH5)Phe-I1e-alpha118(H1)Thr (alpha1)].
We report the first case of Hb Phnom Penh where a molecular study was done on the patient's sample. The result confirmed the predicted DNA sequence change involved in the mutation, which was delineated by another group in 1998 using amino acid analysis.


In vitro self-propagation of recombinant PrPSc-like conformation generated in the yeast cytoplasm.
Self-propagation is characteristic property for a prion conformation. Previous studies revealed that prion protein expressed in the cytoplasm gained a PrP(Sc)-like conformation. However, it remains unclear whether the PrP(Sc)-like conformation has the self-propagating property. We found that PrP partially purified from yeast cytoplasm formed amyloid fiber like structures, and we found that the PrP(Sc)-like conformation is able to convert normal PrP(C) in the brain homogenate to a proteinase K-resistant conformation. These results suggest that yeast cytoplasm expressed recombinant PrP(Sc)-like conformation has the characteristic self-propagating property of a prion, which may have implications in the pathogenesis of sporadic and inherited prion diseases.


Fractional exhaled nitric oxide exchange parameters among 9-year-old inner-city children.
To determine the feasibility of using a multiple flow offline fractional exhaled nitric oxide (FeNO) collection method in an inner-city cohort and determine this population's alveolar and conducting airway contributions of NO. We hypothesized that the flow independent NO parameters would be associated differentially with wheeze and seroatopy. As part of a birth cohort study, 9-year-old children (n=102) of African-American and Dominican mothers living in low-income NYC neighborhoods had FeNO samples collected offline at constant flow rates of 50, 83, and 100 ml/sec. Seroatopy was defined as having measurable (≥ 0.35 IU/ml) specific IgE to any of the five inhalant indoor allergens tested. Current wheeze (last 12 months) was assessed by ISAAC questionnaire. Bronchial NO flux (J(NO) ) and alveolar NO concentration (C(alv)) were estimated by the Pietropaoli and Hogman methods. Valid exhalation flow rates were achieved in 96% of the children. Children with seroatopy (53%) had significantly higher median J(NO) (522 pl/sec vs. 161 pl/sec, P<0.001) when compared to non-seroatopic children; however, median C(alv) was not significantly different between these two groups (5.5 vs. 5.8, P=0.644). Children with wheeze in the past year (21.6%) had significantly higher median C(alv) (8.4 ppb vs. 4.9 ppb, P<0.001), but not J(NO) (295 pl/sec vs. 165 pl/sec, P=0.241) when compared with children without wheeze. These associations remained stable after adjustment for known confounders/covariates. The multiple flow method was easily implemented in this pediatric inner-city cohort. In this study population, alveolar concentration of NO may be a better indicator of current wheeze than single flow FeNO.


Radiosynthesis of [11C]BBAC and [11C]BBPC as potential PET tracers for orexin2 receptors.
Radiosynthesis of [N-methyl-(11)C](S)-N-([1,1'-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide ([(11)C]BBAC or [(11)C]3) and [N-methyl-(11)C] (S)-N-([1,1'-biphenyl]-2-yl)-1-(3-(1-methyl-1H-benzo[d]imidazol-2-yl)propanoyl)pyrrolidine-2-carboxamide ([(11)C]BBPC or [(11)C]-4), two potential PET tracers for orexin2 receptors are described. Syntheses of non-radioactive standards 3, 4 and corresponding desmethyl precursors 1, 2 were achieved from common intermediate (S)-2-([1,1'-biphenyl]-2-yl)-1-(pyrrolidin-2-yl)ethanone. Methylation using [(11)C]CH(3)OTf in the presence of base in acetone afforded [(11)C]3 and [(11)C]4 in 30±5% yield (EOS) with >99 % radiochemical purities with a specific activity ranged from 2.5±0.5 Ci/μmol (EOB). The logP of [(11)C]3 and [(11)C]4 were determined as 3.4 and 2.8, respectively. The total synthesis time was 30 min from EOB. However, PET scans performed in a rhesus monkey did not show tracer retention or appropriate brain uptake. Hence [(11)C]3 and [(11)C]4 cannot be used as PET tracers for imaging orexin2 receptors.


Shared office space and the risk of the common cold.
The common cold persists as a major economic and public health problem worldwide. Despite its long-established ubiquity, little is yet certain about the determinants of indoor environment in spreading of the infection, and even less about the role of indoor air quality as a mediator. The effect of sharing an office with one or more colleagues on the risk of the common cold was studied in a modern, mechanically ventilated, 8 story office building in central Helsinki. Data on respiratory infections and the relevant personal and environmental determinants were collected in a self-administered questionnaire (response rate 71.0%). The study population, one person from each office on floors 3 to 8, consisted of 893 workers, 493 males (49.2%) and 454 females (50.8%). In logistic regression analysis the adjusted odds ratio (OR) for more than two episodes of common cold during the past 12 months in subjects with one or more office colleagues vs those working alone was 1.35 (95% CI 1.00-1.82). Among all workers higher risk also emerged for those with young children (OR 1.46, 1.05-2.04) or a history of hay fever (OR 2.07, 1.47-2.92). Females (OR 1.25, 0.95-1.66) and all under 40 years of age (OR 1.15, 0.86-1.55) had non-significantly increased risk, while smokers did not differ essentially from non-smokers (OR 1.05, 0.76-1.42). The results suggest that sharing office space increases the risk of the common cold, although the primary mode of transmission-airborne, direct or indirect contact-remains controversial.


Inferior survival outcomes of pancreas transplant alone in uremic patients.
Theoretically, pancreas transplant alone in uremic (PTAU) patients could also be one of the options for those waiting for both pancreas and kidney grafts, but it has never been reported. There were 160 cases of pancreas transplant in this study, including 16% PTAU. The 5-year patient survival was 66.2% after PTAU, 94.5% after SPK, 95.8% after PAK, and 95.4% after PTA. Rejection of pancreas graft was significantly lower in PTAU group (3.8%), followed by 16.7% in pancreas after kidney transplant (PAK), 29.8% in simultaneous pancreas and kidney transplant (SPK) and 37.0% in pancreas transplant alone (PTA). Fasting blood sugar and serum HbA1c levels after PTAU were not significantly different from those by other subgroups. The 5-year death-censored pancreas graft survival was 100% after PTAU and PAK, and 97.0% after SPK and 77.9% after PTA. However, the 5-year death-uncensored pancreas graft survival was 67.0% after PTAU, 100% after PAK, 91.3% after SPK, and 74.0% after PTA. The superior graft survival in the PTAU group was achieved only if deaths with a functioning graft were censored. In conclusion, given the inferior patient survival outcome, PTAU is still not recommended unless SPK and PAK is not available. Although PTAU could be a treatment option for patients with diabetes complicated by end-stage renal disease (ESRD) in terms of surgical risks, endocrine function, and immunological and graft survival outcomes, modification of the organ allocation policies to prioritize SPK transplant in eligible patients should be the prime goal.


[Urethro-cystometry: a comparison between open-end catheters with flow and microtransducer catheters (author's transl)].
In 40 women a comparative urethrocystometric study between microtransducer catheters and open-end catheters was performed. Analysis of resting and cough urethrapressure profile concerned clinical and practical value as well as reproducibility. All of these aspects can better be achieved by microtransducer catheters compared to the open-end catheter system. Best results were obtained when measuring with microtransducers in standing position.


A Call for Improved Screening of Preoperative Prescription Drug Abuse: A Scalar Assessment Not Limited to Opioids.
Prescription-drug abuse has strained US healthcare. While several investigations highlight an association between opioid use and adverse postoperative outcomes, similar associations with nonopioid prescription-drugs remain under-studied. Furthermore, patients' underlying prescription drug use patterns remain poorly characterized. This perspective details such obstacles which hinder translating literature-reported findings into practice.


Comparative analyses of effective population size within and among species: ranid frogs as a case study.
It has recently become practicable to estimate the effective sizes (N(e) ) of multiple populations within species. Such efforts are valuable for estimating N(e) in evolutionary modeling and conservation planning. We used microsatellite loci to estimate N(e) of 90 populations of four ranid frog species (20-26 populations per species, mean n per population = 29). Our objectives were to determine typical values of N(e) for populations of each species, compare N(e) estimates among the species, and test for correlations between several geographic variables and N(e) within species. We used single-sample linkage disequilibrium (LD), approximate Bayesian computation (ABC), and sibship assignment (SA) methods to estimate contemporary N(e) for each population. Three of the species-Rana pretiosa, R. luteiventris, and R. cascadae- have consistently small effective population sizes (<50). N(e) in Lithobates pipiens spans a wider range, with some values in the hundreds or thousands. There is a strong east-to-west trend of decreasing N(e) in L. pipiens. The smaller effective sizes of western populations of this species may be related to habitat fragmentation and population bottlenecking.


Graphene-driving strain engineering to enable strain-free epitaxy of AlN film for deep ultraviolet light-emitting diode.
The energy-efficient deep ultraviolet (DUV) optoelectronic devices suffer from critical issues associated with the poor quality and large strain of nitride material system caused by the inherent mismatch of heteroepitaxy. In this work, we have prepared the strain-free AlN film with low dislocation density (DD) by graphene (Gr)-driving strain-pre-store engineering and a unique mechanism of strain-relaxation in quasi-van der Waals (QvdW) epitaxy is presented. The DD in AlN epilayer with Gr exhibits an anomalous sawtooth-like evolution during the whole epitaxy process. Gr can help to enable the annihilation of the dislocations originated from the interface between AlN and Gr/sapphire by impelling a lateral two-dimensional growth mode. Remarkably, it can induce AlN epilayer to pre-store sufficient tensile strain during the early growth stage and thus compensate the compressive strain caused by hetero-mismatch. Therefore, the low-strain state of the DUV light-emitting diode (DUV-LED) epitaxial structure is realized on the strain-free AlN template with Gr. Furthermore, the DUV-LED with Gr demonstrate 2.1 times enhancement of light output power and a better stability of luminous wavelength compared to that on bare sapphire. An in-depth understanding of this work reveals diverse beneficial impacts of Gr on nitride growth and provides a novel strategy of relaxing the vital requirements of hetero-mismatch in conventional heteroepitaxy.


Long non-coding RNA SOX21-AS1: A potential tumor oncogene in human cancers.
Emerging data have proposed that the aberrant level of long noncoding RNAs (lncRNA) is related to the onset and progression of cancer. Among them, lncRNA SOX21-AS1 was shown to upregulate and seem to be a novel oncogene in various cancer, including ovarian cancer, lung cancer, breast cancer, pancreatic cancer, osteosarcoma, and melanoma. Available data indicated that SRY-box transcription factor 21 antisense divergent transcript 1 (SOX21-AS1) mostly acts as a competing endogenous RNA (ceRNA) to inhibit the level of its target microRNAs (miRNAs), leading to upregulation of their targets. In addition, SOX21-AS1 is engaged in various signaling pathways like transforming growth factor-β (TGF-β) signaling, Wnt signaling, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling. Moreover, this lncRNA was revealed to be correlated with the clinicopathological features of affected patients. SOX21-AS1 was also proved to enhance the resistance of ovarian cancer cells to cisplatin chemotherapy. SOX21-AS1 is markedly associated with poor prognosis and low survival of patients, proposing that it may be a prognostic and diagnostic biomarker in cancer. Overexpression of SOX21-AS1 is related to various cancer-related pathways, like epithelial mesenchymal transition (EMT), invasion, migration, apoptosis, and cell cycle arrest. In this work, we aimed to discuss the biogenesis, function, and underlying molecular mechanism of SOX21-AS1 in cancer progression as well as its potential as a prognostic and diagnostic biomarker in human cancers.


Adenosine diphosphate-induced platelet aggregation is associated with P2Y12 gene sequence variations in healthy subjects.
The adenosine diphosphate (ADP) receptor P2Y12 plays a pivotal role in platelet aggregation, as demonstrated by the benefit conferred by its blockade in patients with cardiovascular disease. Some studies have shown interindividual differences in ADP-induced platelet aggregation responses ex vivo, but the mechanisms underlying this variability are unknown. We examined ADP-induced platelet aggregation responses in 98 healthy volunteers, and we identified 2 phenotypic groups of subjects with high and low responsiveness to 2 micromol/L ADP. This prompted us to screen the recently identified Gi-coupled ADP receptor gene P2Y12 for sequence variations. Among the 5 frequent polymorphisms thus identified, 4 were in total linkage disequilibrium, determining haplotypes H1 and H2, with respective allelic frequencies of 0.86 and 0.14. The number of H2 alleles was associated with the maximal aggregation response to ADP in the overall study population (P=0.007). Downregulation of the platelet cAMP concentration by ADP was more marked in 10 selected H2 carriers than in 10 noncarriers. In healthy subjects, ADP-induced platelet aggregation is associated with a haplotype of the P2Y12 receptor gene. Given the crucial role of the P2Y12 receptor in platelet functions, carriers of the H2 haplotype may have an increased risk of atherothrombosis and/or a lesser clinical response to drugs inhibiting platelet function.


Silage for upcycling oil from saithe (Pollachius virens) viscera - Effect of raw material freshness on the oil quality.
The main objective of this study was to investigate how the freshness of saithe (Pollachius virens) viscera affected the quality, composition and yield of oil obtained by silaging. Minced viscera with and without liver were stored separately for up to 3 days at 4 °C before silaging at pH 3.8 for 6 days at 10 °C. An antioxidant mixture was added to evaluate the effect on the lipid oxidation. Oil was extracted thermally from untreated raw material during storage (day 0-3) and after silaging. For oil obtained after silaging of viscera with liver, the oil yields increased significantly when the raw material was stored for more than one day prior to the treatment. Use of fresh raw material (collected at day 0) led to significantly lower oxidation compared to longer raw material storage. After one day of storage, the oxidation was less dependent on the freshness. Silaging with antioxidants resulted in significantly lower formation of oxidation products compared to acid without antioxidants and the most significant differences were observed after one day of storage. Contents of docosahexaenoic acid (DHA) and total omega-3 fatty acids decreased significantly when the raw material was stored for 1-3 days prior to silaging compared to fresh raw material. Results obtained by high resolution nuclear magnetic resonance (NMR) spectroscopy indicated that oxidation of esterified DHA might explain the DHA decrease. The free fatty acid content was highest when fresh raw material was used and was most likely affected by the formation of cholesteryl esters observed in NMR spectra after longer storage. The study shows that although the oil quality is reduced during silaging, processing shortly after catch and use of antioxidants can optimize the quality resulting in less oxidized oil richer in omega-3 fatty acids.


Postpartum electroconvulsive therapy: a systematic review and case report.
Postpartum depression can have devastating consequences on the mother and child. Prompt treatment is challenging. Whereas electroconvulsive therapy (ECT) is considered to be an effective treatment modality in severe depression and brings about rapid clinical improvement, little is known about ECT during the postpartum period. We systematically reviewed the literature on the use of ECT during the postpartum period using PubMed, Institute for Scientific Information Web of Knowledge and PsycINFO databases until September 2014, using the search terms "electroconvulsive therapy" or "ECT" and "postpartum". Then, we described the successful treatment with ECT and the joint mother-baby hospitalization of a woman with severe depression. Eight case reports and 8 studies were identified. All of the studies reported that ECT is effective in the postpartum period. It is well tolerated, provides a fast response and allows for breastfeeding. In addition, our case report showed the benefits of the hospitalization of the mother-baby unit. Combined ECT and joint mother-baby hospitalization could be a valuable treatment by targeting both the mother-infant relationship and the maternal depressive symptoms.


Neutral and ionic per- and polyfluoroalkyl substances (PFASs) in atmospheric and dry deposition samples over a source region (Tianjin, China).
Per- and polyfluoroalkyl substances (PFASs) were detected in the atmosphere of a source region in Tianjin, China. Fluorotelomer alcohols (FTOHs) were the dominant neutral PFASs in the atmosphere with total concentrations of 93.6-131 pg/m(3) and 8:2 FTOH contributing the most, whereas perfluorooctane sulfonamide derivatives (PFOSAs) were two magnitudes lower or undetected. In comparison, ionic PFASs (perfluoroalkyl carboxyl acids (PFCAs)) in the atmosphere were detected at similar or even higher levels. At wastewater treatment plants (WWTPs), the air over influent was found with higher levels of FTOHs than over aeration tank and effluent; whereas in the air over the aeration tank, the concentrations of PFOSAs and nonvolatile ionic PFASs substantially increased, suggesting a possible direct release of ionic PFASs to the atmosphere besides the atmospheric conversion from volatile precursors. In the air phase, a low proportion (1-5%) of PFCAs was subjected to dry deposition in the source region. Interestingly, the dry-deposition-to-bulk-air ratios of PFCA analogues were the lowest at medium chain lengths (C8 and C9) and increased with either shorter or longer chain length. The extraordinary affinity of shorter-chain PFCAs (C6-C7) to particles was presumed to be due to their smaller molecular size favoring the interactions between the carboxyl head groups and specific sorption sites on particulate matter.


Monitoring the effects and side-effects on wine colour and flavonoid composition of the combined post-fermentative additions of seeds and mannoproteins.
One of the main consequences of the advancement of harvest date associated to global climate change is that the phenolic maturity of grapes can be delayed in relation to their technological maturity. As a consequence, wines made from these grapes can be poor in phenolic compounds or possess an unbalanced phenolic composition, affecting their global quality. The combined post-fermentative addition of seeds and an astringency-modulator mannoprotein (MP) might be a potential strategy to solve this problem, since seeds might supply flavanols and improve wine chemical stability and the mannoprotein might modulate the changes induced in astringency by the addition of seeds and improve wine colloidal stability. The present study aimed at monitoring at different moments of winemaking and ageing the effects and side-effects of this combined strategy on the detailed flavanol, flavonol and anthocyanin compositions and on colour of wines made from Syrah grapes. Seeds were obtained from Pedro Ximénez overripe grapes. Flavanol composition and flavonol and anthocyanin compositions were determined by HPLC-MSn-MRM and HPLC-DAD-MSn analyses, respectively. Colour changes caused by these additions were studied from CIELAB parameters as well as the ability of these techniques to protect colour from bleaching agents, such as SO2. In general, the addition of seeds initially increased the levels of flavanols and anthocyanins. However, during bottle ageing a reduction in the levels of flavanols, flavonols and anthocyanins could be observed in seed treated wines, which might be related to the greater formation of flavanol aggregates associated with greater levels of flavanols. This effect was partially solved for most of the flavonoids studied with the additional MP treatment. Treated and control wines showed colour differences that were visible to human eye, although they were reduced over time. At the end of the study, treated wines showed colour parameters corresponding to younger wines than those observed in control wines. A greater resistance against SO2 bleaching was also observed in treated wines, which can be mainly associated to the greater percentages of polymeric pigments caused by seed treatment and to the improvement of the colloidal stability of SO2-resistant pigments caused by the addition of the MP.


Metoptic canal, duplication of the optic canal and Warwick's foramen in human orbits.
The region of the optic strut is sometimes traversed by some minor canals whose incidence and general characteristics have never been studied. As such canals could be the route for vessels that could interfere in the surgery of the orbital apex, we undertook a detailed anatomical study on a vast collection of dry skulls. The examination of 943 dry adult skulls and 360 foetal skulls was carried out to precise the anatomy of canals in the optic strut area, their development and relationships with the optic canal. A canal traversing the optic strut was present in 8.54 % of the orbits. Based on diameter, position within the optic strut, and thickness of the bony plate separating it from the optic canal or from the superior orbital fissure, the canals piercing the optic strut were classified into four types, which include the well-known duplication of the optic canal, different aspects of the metoptic canal and a type of canal that to our knowledge has never been reported. Warwick's foramen was found in 0.74 % of orbits. The area of the optic strut is the frequent site of canals joining the orbit with the middle cranial fossa. Some of them can host the ophthalmic artery; others could be run by minor vessels which, however, could be the source of annoying bleedings in surgical procedures.


Hypoxia prevents seizures and neuronal damages of the hippocampus induced by kainic acid in rats.
The effects of hypoxia on the epileptic seizures and neuronal damages induced by kainic acid were studied in rats using hypoxic chamber equipment. Rats treated with kainic acid and placed in atmospheric pressure showed typical limbic seizures and regressive neuronal changes in CA3 and CA4 of the hippocampus, while those kept in a hypoxic chamber with 8.5% O2 and 91.5% N2 showed moderate hypoxia and a slight decline of mean arterial blood pressure. In these hypoxic rats, seizures were completely prevented and there was remarkably less regressive neuronal injury of the hippocampus. Thus hypoxia has a rather ameliorative effect on the occurrence of seizures and excitotoxic neuronal injuries induced by kainic acid. The contribution of oxygen radicals and endogenous adenosine to preventing excitotoxic neuronal damages by kainic acid was discussed.


Emoqol-100: Development and validation of a single question for low mood in primary care. A retrospective audit.
Patients with depression need to be diagnosed and managed effectively in primary care. However, current inventories for case-finding low mood are time-consuming when considering the limited time available during appointments. To validate the diagnostic accuracy of a single question on the emotional quality of life (Emoqol-100) as a measure of depression in symptomatic patients. A retrospective clinical audit, validating the Emoqol-100 compared with the 9-item Patient Health Questionnaire (PHQ-9) and Burns Depression Scale Today (BDST) in South Auckland, New Zealand. Consecutive patients with suspected low mood, seen over 22 months in a single primary care clinic by one of the authors, were eligible for this retrospective audit (n = 160). The index test was the verbally asked Emoqol-100: 'How is your emotional quality of life now, with 100 being perfect and 0 being the worst imaginable?' The reference standard was the PHQ-9 (n = 426 visits) with a cut-off point of ≥10 or BDST (n = 513 visits) with a cut-off point of ≥6. The Emoqol-100 range 0-20 had a likelihood ratio (LR) of 25.2 for low mood compared with the BDST as the reference standard; and for Emoqol-100 scores of 21-40, 41-60, 61-80, and 81-100 the LRs were 3.6, 1.7, 0.35, and 0.09, respectively. For the PHQ-9, these were 10.1, 2.9, 1.3, 0.40, and 0.2, respectively. Any score ≤60 was associated with a low mood. The Emoqol-100 appears to have high validity, so when it is low (≤60), it is suggestive of a high PHQ-9 or BDST score, and a mood issue probably exists. Emoqol-100 could be helpful for busy primary care professionals and other clinicians.


Irradiation effects on embryotoxicity and oxidative properties of gossypol dissolved in methanol.
Gossypol dissolved in methanol (0.25 and 0.5 mg/ml) was gamma-irradiated at 0, 5, 10, and 20 kGy. The gossypol content was significantly reduced by irradiation in a dose-dependent manner. Ames test performed with nonirradiated and irradiated gossypol solutions was negative at the level of 0.1, 0.5, 1, 10, 50, and 100 microg gossypol/plate. At the gossypol concentration of 2.5 microg/ml, the blastocysts formation rate of mice embryo were decreased by a factor of two as compared with the control, but irradiation at 20 kGy increased the blastocysts formation, resulting in no difference from the control. Addition of gossypol to oil emulsion system or oil showed a prooxidative effect of lipids at the beginning stage by increasing 2-thiobarbituric acid reactive substances (TBARS) and peroxide value but irradiation of the gossypol solution decreased the oxidative changes significantly as compared with the nonirradiated one. Results indicated that irradiation decreased the gossypol concentration dissolved in methanol, resulting in a reduction of embryotoxicity in mice.


Stalking in the United States: recent national prevalence estimates.
Stalking is a major public health concern, primarily for women, and is associated with many adverse health outcomes, including death. However, the prevalence of stalking among adults in the United States has not been assessed since 1995-1996. The objective of this analysis is to provide more recent national estimates on lifetime stalking and demographic characteristics of stalking victims. A sample of adults aged 18 years and older living in the United States (n = 9684) participated in the second Injury Control and Risk Survey (ICARIS-2), a cross-sectional, random-digit-dial telephone survey conducted from 2001 to 2003. Analyses conducted in 2005 focused on the respondents' reports of having ever been stalked in a way that was somewhat dangerous or life-threatening. In the United States, 4.5% of adults reported having ever been stalked. Women had significantly higher prevalence (7%) of stalking victimization than did men (2%) (odds ratio [OR] = 3.68, 95% confidence interval [CI] = 2.77-4.90). People who were never married (OR = 1.43, 95%CI = 1.03-1.99) or who were separated, widowed, or divorced (OR = 1.68, 95% CI = 1.28-2.21) had significantly higher odds of being stalked than those who were married or had a partner. People aged 55 years or older and those who were retired were least likely to report stalking victimization. Comparable to previous national estimates, this study shows that stalking affects many adults. Nearly 1 in 22 adults (almost 10 million, approximately 80% of whom were women) in the United States were stalked at some time in their lives.


Recent advances in direct C-H arylation: Methodology, selectivity and mechanism in oxazole series.
Catalytic direct (hetero)arylation of (hetero)arenes is an attractive alternative to traditional Kumada, Stille, Negishi and Suzuki-Miyaura cross-coupling reactions, notably as it avoids the prior preparation and isolation of (hetero)arylmetals. Developments of this methodology in the oxazole series are reviewed in this article. Methodologies, selectivity, mechanism and future aspects are presented.


Tuning orbital-selective phase transitions in a two-dimensional Hund's correlated system.
Hund's rule coupling (J) has attracted much attention recently for its role in the description of the novel quantum phases of multi-orbital materials. Depending on the orbital occupancy, J can lead to various intriguing phases. However, experimental confirmation of the orbital occupancy dependency has been difficult as controlling the orbital degrees of freedom normally accompanies chemical inhomogeneities. Here, we demonstrate a method to investigate the role of orbital occupancy in J related phenomena without inducing inhomogeneities. By growing SrRuO3 monolayers on various substrates with symmetry-preserving interlayers, we gradually tune the crystal field splitting and thus the orbital degeneracy of the Ru t2g orbitals. It effectively varies the orbital occupancies of two-dimensional (2D) ruthenates. Via in-situ angle-resolved photoemission spectroscopy, we observe a progressive metal-insulator transition (MIT). It is found that the MIT occurs with orbital differentiation: concurrent opening of a band insulating gap in the dxy band and a Mott gap in the dxz/yz bands. Our study provides an effective experimental method for investigation of orbital-selective phenomena in multi-orbital materials.


An electrochemical method for functionalization of a 316L stainless steel surface being used as a stent in coronary surgery: irreversible immobilization of fibronectin for the enhancement of endothelial cell attachment.
An electrochemistry-based method for the formation of functionalized alkanethiol layers on a 316L stainless steel surface was developed. The method was efficient in forming a very stable, irreversibly-attached COOH-terminated (mercaptoundecanoic acid) surface layer. This layer was used as a 'linker' to immobilize the extracellular matrix protein fibronectin to the 316L stainless steel surface. Fibronectin was irreversibly attached to the surface and, unlike physisorbed fibronectin, resisted detachment more in aggressive 0.1 M NaOH under sonication. The fibronectin-modified 316L stainless steel surface was more biocompatible towards attachment of endothelial cells than a bare (unmodified) 316L stainless steel surface, yielding a 25% improvement in cell density.


Impact of hypoxic and acidic extracellular conditions on cytotoxicity of chemotherapeutic drugs.
In the microenvironment of solid growing tumors, pronounced hypoxia or extracellular acidosis is commonly found. The aim of this study was the analysis of the cytotoxic effect of different chemotherapeutic agents (cisplatin, daunorubicin, docetaxel) under these conditions in vitro. Prostate carcinoma cells (R3327-AT1) were exposed to hypoxia (pO2 < 0.5 mmHg) or extracellular acidosis (pH = 6.6) for 6h. After 3h, cytotoxic drugs were added. The cytotoxic effect was assessed by measuring caspase 3-activity (apoptosis), LDH release (necrosis) and repopulation of the cells after chemotherapy (cell death). Compared to aerobic control conditions, severe hypoxia over 6 h per se led to a slight increase in apoptosis, necrosis and cell death. With all three chemotherapeutic agents, hypoxia led to a reduced (by approx. 25%) caspase 3-activity and a marked increase in necrosis. However, the overall cytotoxicity of the drug was not affected by O2-deficiency. By contrast, during extracellular acidosis, the cytotoxic effect of daunorubicin was reduced by 40%, preferentially due to a marked reduction in apoptosis. With cisplatin and docetaxel no change in overall cell death was detected. However, for daunorubicin the tumor-pH seems to have a strong impact on cytotoxicity. With this chemotherapeutic drug the therapeutic efficacy is markedly reduced in an acidotic environment.


Phylogenetic relationships among tribes of the green lacewing subfamily Chrysopinae recovered based on mitochondrial phylogenomics.
Chrysopidae (green lacewings) is the second largest family in Neuroptera, and it includes medium-size lacewings largely recognized by the presence of golden-colored eyes, bright green bodies and delicate wings with dense venation patterns. The subfamily Chrysopinae includes 97% of the species diversity in the family and it is currently divided into four tribes: Ankylopterygini, Belonopterygini, Chrysopini and Leucochrysini. Here we sequenced and annotated the nearly complete mitochondrial genomes of four species of each these tribes: Abachrysa eureka, Italochrysa insignis, Leucochrysa pretiosa, Parankyloteryx sp. We then reconstructed the phylogenetic relationships with estimated divergence times among tribes of Chrysopinae based on the mt genomic data. Our results suggest that Chrysopinae sans Nothancyla verreauxi evolved as two reciprocally monophyletic lineages formed by stem members of the tribes Leucochrysini plus Belonopterygini on one hand, and the stem members of Ankylopterygini plus Chrysopini on the other. Our estimations of divergence times place the diversification of stem Chrysopinae into the extant tribes during the Middle Jurassic to Late Cretaceous. The relatively young ages previously estimated for the green lacewing divergences were probably underestimated due to false inferences of homology between non-sister taxa that are later correctly identified as homoplasy after more taxa are added.


TEACHING BASIC COLONOSCOPY SKILLS: QUALITY AND SAFETY STANDARDS CAN BE FULFILLED IN AN OUTPATIENT UNIVERSITY CENTER.
Recent studies have shown that endoscopy fellows can perform colonoscopy effectively and safely. However, little is known about the performance of surgical residents without prior knowledge of endoscopic techniques. To assess whether quality indicators were met at an outpatient endoscopy center and whether surgical residents, without prior upper or lower endoscopy skills, could perform colonoscopy adequately. A prospective non-randomized cohort study was undertaken. All exams were performed either by assistant physicians or by residents. Quality measures were compared between those groups. A total of 2720 colonoscopies were analyzed. In the resident group, we observed older patients (57.7±12.7 years vs 51.5±14.5 years, P<0.001), a higher prevalence of screening colonoscopies (52% vs 39.4%, P<0.001) and a higher prevalence of colorectal cancer (6.4% vs 1.8%, P<0.001). The cecal intubation rate was higher in the attending group (99.9% vs 89.3%; P<0.001). The polyp detection rate was 40.8%, and no differences were observed between the studied groups. The residents had a higher rate of perforation in all exams (0.4% vs 0%; P=0.02). Postpolypectomy bleeding and 7-day readmission rates were the same (0.2%). All readmissions in 7 days occurred due to low digestive bleeding, and none required intervention. Quality indicators were met at a university outpatient endoscopy center; however, medical residents achieved lower rates of cecal intubation and higher rates of perforation than the attending physicians.


Acute and sub-acute toxicity profile of ultra-hypofractionated low-dose total skin electron beam with two 4 Gy fractions for cutaneous T cell lymphoma.
Low-dose total skin electron beam therapy (TSEBT) over 3 weeks has proved to be a safe and effective treatment for cutaneous T cell lymphomas (CTCL). In this prospective trial, we examined the feasibility of ultra-hypofractionated low-dose TSEBT regimen in two fractions with 4 Gy combined with systemic therapy to minimize the number of visits to radiation centers. Six patients with mycosis fungoides (MF) or Sézary syndrome (SS) received TSEBT with a total radiation dose of 8 Gy in two fractions between April 2020 and June 2020. Patient and treatment characteristics, tumor burden, the impact on the quality of life using Skindex-29 questionnaires, and acute toxicities were analyzed. During TSEBT, all patients developed grade 1 toxicities while two patients developed grade 2 toxicities. One patient experienced sepsis. The most common adverse effects were erythema and edema. All grade 2 toxicities regressed after 4 weeks following TSEBT. Based on the reported symptoms measured by Skindex-29, we detected a significant reduction in total Skindex-29 score after 8 weeks of radiation (P = 0.03), particularly in the symptoms (P = 0.01) and emotional domains (P = 0.04). Ultra-hypofractionated low-dose TSEBT followed by systemic therapy seems to be a safe and feasible alternative to conventional fractionated TSEBT for patients with MF/SS. The skin tumor burden and the health-related quality of life have been significantly improved within 8 weeks following radiotherapy.


Ectopic pregnancy: current clinical trends.
During the 16 year period ending in November, 1978, 191 cases of ectopic pregnancy were managed at the University of Virginia Hospital. The overall incidence was 1/126 deliveries but during the last 3 years of the study the incidence was 1/60 deliveries. Only 56 patients have had a subsequent conception. Thirteen have had a recurrent ectopic implantation. Only 36 women (23.7% of those available for follow-up) have had subsequent term pregnancies. Ectopic pregnancy continues to be a major gynecologic problem and the potential for subsequent fertility is poor.


Intracorporeal versus extracorporeal urinary diversion following robot-assisted radical cystectomy: a meta-analysis, cumulative analysis, and systematic review.
Over the last decade, the increased utilization of robot-assisted radical cystectomy (RARC) in the surgical treatment of muscle-invasive bladder cancer has led to an uptrend in intracorporeal urinary diversions (ICUD). However, the operative results comparing ICUD to extracorporeal urinary diversion (ECUD) have varied widely. We performed a meta-analysis to analyze perioperative outcomes and complications of ICUD compared to ECUD following RARC. This study is registered at International Prospective Register of Systematic Reviews (PROSPERO) CRD42020164074. A systematic literature review was conducted using PubMed, EMBASE, and Cochrane databases in August 2019. A total of six studies comparing ICUD vs ECUD were identified and meta-analysis was conducted on these studies. In addition, a cumulative analysis was also performed on 83 studies that reported perioperative outcomes after RARC and ICUD or ECUD. The Weighed Mean Difference of operative time and blood loss between ICUD and ECUD group was (16; 95% confidence interval - 34 to 66) and (- 86; 95% confidence interval - 124 to - 48), respectively. ICUD and ECUD had comparable early (30-day) and mid-term (30-90-day) complication rate (RR 1.19; 95% confidence interval 0.71-2.0; p = 0.5) and (RR 0.91; 95% confidence interval 0.71-1.15 p = 0.4) respectively. In the 83 studies that were included in the cumulative analysis, the mean operative time for ileal conduit and neobladders by ICUD were 307 and 428 min, respectively, compared to ECUD 428 and 426 min, respectively. ICUD and ECUD have comparable short- and mid-term complication rate. The ICUD group has lower blood loss and lower rate of blood transfusion compared to ECUD.


Hydrocarbon signatures of egg maternity, caste membership and reproductive status in the common wasp.
In most ants, bees, and wasps, the workers are capable of challenging the reproductive monopoly of the queen by laying unfertilized, male eggs. An important mechanism that can resolve this conflict is policing, whereby the queen or workers prevent successful worker reproduction by selectively eating worker-laid eggs or by attacking egg-laying workers. Egg policing by workers has been shown to occur in several social wasp species, but the information used by worker wasps to discriminate between queen-laid and worker-laid eggs has never been investigated. Our aim, therefore, was to investigate if hydrocarbons might be used in egg policing by workers in the common wasp, Vespula vulgaris, where worker policing previously has been shown to be effective. Our results show that 51 different hydrocarbons are present on the surface of newly-laid eggs, and that there are pronounced quantitative differences in the hydrocarbon profiles of queen-laid and worker-laid eggs, with longer-chained alkenes and methylated alkanes (C(28)-C(31)) in particular being more abundant on the surface of queen-laid eggs. We further show that the hydrocarbon profiles on the surface of queen-laid and worker-laid eggs resemble those found on the mother queen's and workers' cuticles. Interestingly, longer-chained methylated alkanes also were more abundant on the cuticle of both mother queens and reproductive workers, suggesting that these compounds are linked to fertility, as has also been found to be the case in several ant species.


Spontaneous intracranial haemorrhage in children: aetiology, presentation and outcome.
We are aware of only few reports addressing spontaneous intracranial haemorrhage (SICH) in non-selected series of children. This is a retrospective analysis of clinical presentation and outcome in 34 children with SICH seen in the period 1990-2000 in our hospital. Traumatic, neonatal and subdural haemorrhages were excluded. The majority (47%, 16/34) of SICH was caused by an arteriovenous malformation (AVM). SICH was presented as an acute event in 53% (17/32) of patients. Forty-seven percent (15/32) of the cases had protracted courses, which made the diagnosis difficult. In our series, younger children had less specific symptoms. Mortality (25%, 8/32) and morbidity were considerable, particularly in infratentorial haemorrhages, in aneurysms, in children younger than 3 years and in those with underlying haematological disorders.


Radial, carotid and aortic distensibility in congestive heart failure: effects of high-dose angiotensin-converting enzyme inhibitor or low-dose association with angiotensin type 1 receptor blockade.
objectives; The aim of this study was to determine whether in patients with congestive heart failure (CHF) a distensibility (Dist) reduction: 1) similarly occurs in different arteries; 2) is related to CHF severity; and 3) is reversible with treatment. background: Several studies suggest that CHF is accompanied by a reduced arterial Dist. We measured diameter in radial artery, carotid artery (CA) and abdominal aorta (AO) by echotracking. Distensibility was obtained by relating it to blood pressure. Data were collected in 30 patients with CHF (New York Heart Association functional class I to III) under standard treatment with diuretic, digitalis and angiotensin-converting enzyme (ACE) inhibitor in whom CHF severity was assessed by maximum oxygen consumption (VO(2)max) percentage and in 30 age- and gender-matched controls. Patients with CHF were then randomized to maintain standard treatment (n = 10), double the ACE inhibitor dose (n = 10) or add an angiotensin II antagonist (n = 10) and restudied after two months. Distensibility was markedly reduced in the CHF group in all three vessels (p < 0.01), CA and AO Dist being related to CHF severity (p < 0.05). After two months, Dist did not change in the group maintained under standard treatment, but it increased significantly (p < 0.05) and similarly when the ACE inhibitor dose was doubled or an angiotensin II antagonist was added. Congestive heart failure is characterized by a reduction of Dist of large-elastic and middle-sized muscular arteries. The reduction of large-elastic artery Dist is related to the CHF severity. These alterations can be reversed by drugs, effectively interfering with the renin-angiotensin system either at the ACE or at the angiotensin receptor level.


BF3·OEt2-Catalyzed Vinyl Azide Addition to in Situ Generated N-Acyl Iminium Salts: Synthesis of 3-Oxoisoindoline-1-acetamides.
BF3·OEt2-catalyzed nucleophilic addition of vinyl azides to in situ generated N-acyl iminium salts obtained from 3-hydroxyisoindolinones is described in this article. The procedure is operationally simple, mild, additive, and metal-free. The reaction proceeds smoothly at ambient temperature with a wide range of 3-hydroxyisoindol-1-ones and vinyl azides to afford 3-oxoisoindoline-1-acetamides (32 examples) in high yields (up to 97%). Furthermore, the synthetic utility of this methodology is depicted by exploiting the reactivity of an amide functionality in the products.


Enzyme thermistor determination of glucose in serum using immobilized glucose oxidase.
An enzyme thermistor assay for serum glucose is described. The glucose present in the sample is reacted in a small column containing glucose oxidase immobilized to controlled pore glass (single thermistor device). The heat produced in the primary reaction is measured directly in the column without any need for coupling reactions. The useful linear range is 0.01-0.45 mM glucose, permitting 50-fold dilution of serum samples. Advantages are low enzyme cost, due to the immobilization, insensitivity for the color or any turbidity of the sample, and no requirement for coenzyme or any ancillary reaction. Improved sensitivity and extended linear range (0.01--0.9 mM) can be attained through a secondary reaction using catalase. The application to glucose analysis of a split-flow enzyme thermistor equipped with a reference column to eliminate unspecific heat effects is also described. The enzyme thermistor determinations were also compared with a spectrophotometric continuous flow technique using a small column with immobilized glucose oxidase and 4-aminoantipyrine and phenol as color reagents.


Dilated intracranial translucency and Blake's pouch cyst: first-trimester ultrasound markers of occipital cephalocele diagnosed using novel three-dimensional reslicing technique.
Abnormal intracranial translucency (IT) (fourth ventricle) and a Blake's pouch cyst with normal brain stem cavity may be valuable first-trimester call signs of defects in the skull base. Here, we report a case of presumptive two-dimensional sonographic diagnosis of occipital cephalocele that was posed at the time of 11-13 weeks aneuploidy scan. The two-dimensional sonographic finding elicited a detailed fetal neuroscan that was performed using either multiplanar mode or a novel three-dimensional reslicing and lightening technique. The use of three-dimensional sonographic software and offline "navigation" within the volume of interest enabled operators to capture a diagnostic snapshot of the condition, enhancing quality imaging and early detection of the encephalic lesion.


Syntheses and biological evaluation of 1-heteroaryl-2-aryl-1H-benzimidazole derivatives as c-Jun N-terminal kinase inhibitors with neuroprotective effects.
1-Heteroaryl-2-aryl-1H-benzimidazole derivatives were synthesized as inhibitors of c-Jun N-terminal kinases, JNK3. Their activities were evaluated through measurement of Kd using SPR, JNK3 kinase assay, and cell-viability of human neuroblastoma cells. Most tested compounds showed high affinity (10 μM-46 nM) to JNK3. Among them, compound 16f exhibited potent activities (Kd=46 nM). Especially, 16f was also found to present a potent cell protective effect (IC50=1.09 μM) against toxicity induced by anisomycin, showing a possibility as protective therapeutics in neuronal cell apoptosis.


Attention to detail: A photo-elicitation study of salience and packaging design for portion control and healthy eating.
Evidence demonstrates that food packaging attracts consumers to purchase and has the potential to nudge consumers towards healthy choices, including reducing portion size. However, food purchasing decisions are often automatic and packaging features may go unnoticed. Therefore, it is important to understand what consumers identify as most salient about packaging: what they notice and why, and which elements might nudge consumers towards healthy options and smaller portions of high-energy-density foods. This study explored consumer perception of food packaging, investigated specific features associated with portion control and elicited design ideas to improve packaging for healthy eating and downsizing. A qualitative approach was adopted applying a participant-driven photo-elicitation (PDPE) task with in-depth interviews. Participants were 25 adults living in the UK (aged 20-32 years; 17 females, 8 males, x ¯ BMI = 23 kg/m2 ). Participants took photographs of 10 food packages according to salience (n = 5) and portion control (n = 5). These were uploaded to a secure site and then discussed at the interview, which was transcribed and analysed. The salience of packaging was described in terms of trust building, stimulating appetite and relating to self-identity, whereas for portion control, themes included structural reminders, healthy prompts and portion awareness. Packaging can be designed to make health value or serving size more salient by prompting portion control and increasing the attractiveness of packaging. While food purchase decisions happen with little deliberation, when probed, consumers provide useful insights for packaging design to assist portion control.


Microcatheter use for difficult percutaneous biliary procedures.
Percutaneous biliary drainage procedures in patients with nondilated ducts are demanding, resulting in lower success rates than in patients with bile duct dilatation. Pertinent clinical settings include patients with iatrogenic bile leaks, diffuse cholangiocarcinomas, and sclerosing cholangitis. We describe a method to facilitate these procedures with the combined use of a 2.7-Fr microcatheter and a 0.018-in. hydrophilic wire.


Beta-adrenergic receptors in catfish liver membranes: characterization and coupling to adenylate cyclase.
beta-Adrenergic binding sites in catfish liver membranes have been characterized by centrifugal assay, using a beta-adrenergic receptor antagonist, (-)-[3H]dihydroalprenolol ([3H]DHA). Binding of the radioligand was saturable and reversible. At 22 degrees equilibrium conditions were established in 15 min and the half-time for dissociation of bound [3H]DHA was approximately 4 min. Analysis of binding data was compatible with the existence of two classes of binding sites: a low-affinity site had a Kd of 62.3 nM and a Bmax of 452.0 fmol/mg protein, while the high-affinity site had a Kd of 2.04 nM and a Bmax of 46.7 fmol/mg protein. The dissociation constant of (-)-alprenolol for the beta-adrenergic receptors was about 2 nM as determined independently by direct kinetic studies and by inhibition of isoproterenol-stimulated adenylate cyclase activity. Phenylephrine was as potent as other catecholamines in inhibiting [3H]DHA binding, indicating that fish adrenoceptor subtyping is different from that of mammals.


Interferon-γ differentially modulates the impact of tumor necrosis factor-α on human endometrial stromal cells.
The pro-inflammatory T helper (Th)-1 cytokines, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), are immunological factors relevant at the feto-maternal interface and involved in the pathophysiology of implantation disorders. The synergistic action of the two cytokines has been described with regard to apoptotic cell death and inflammatory responses in different cell types, but little is known regarding the human endometrium. Therefore, we examined the interaction of TNF-α and IFN-γ in human endometrial stromal cells (ESCs). ESCs were isolated from specimens obtained during hysterectomy and decidualized in vitro. Cells were incubated with TNF-α, IFN-γ or signaling-inhibitor. Insulin-like growth factor binding protein (IGFBP)-1, prolactin (PRL), leukemia inhibitory factor (LIF), interleukin (IL)-6, IL-8, regulated on activation normal T-cell expressed and secreted protein (RANTES) and monocyte chemotactic protein (MCP)-1 were measured using ELISA and real-time RT-PCR. Nuclear factor of transcription (NF)-κB and its inhibitor (IκBα) were analyzed by in-cell western assay and transcription factor assay. TNF-α inhibited and IFN-γ did not affect the decidualization of ESCs. In contrast, IFN-gamma differentially modulated the stimulating effect of TNF-alpha on cytokines by enhancing IL-6, RANTES and MCP-1 and attenuating LIF mRNA expression. These effects were time- and dose-dependent. IFN-γ had no impact on the initial activation of NF-κB signaling. Histone-deacetylase activity was involved in the modulating effect of IFN-γ on RANTES secretion. These observations showed a distinct pattern of interaction of the Th-1 cytokines, TNF-α and IFN-γ in the human endometrium, which could play an important role in the pathophysiology of implantation disorders.


Management of hypo- and hyperthyroidism during pregnancy.
Pregnancy has profound effects on the regulation of thyroid function, and on thyroidal functional disorders, that need to be recognized, carefully assessed and correctly managed. Relative hypothyroxinemia and goitrogenesis may occur in healthy women who reside in areas with restricted iodine intake, strongly suggesting that pregnancy constitutes a stimulatory challenge for the thyroid. Overt thyroid dysfunction occurs in 1-2% of pregnant women, but mild forms of dysfunction (both hyper- and hypothyroidism) are probably more prevalent and frequently remain unrecognized. Alterations of maternal thyroid function have important implications for fetal and neonatal development. In recent years, particular attention has been drawn to the potential risks for the developing fetus due to maternal hypothyroxinemia during early gestation. Concerning hyperthyroidism, the two main causes of thyrotoxicosis in the pregnant state are Graves' disease and gestational transient thyrotoxicosis (GTT). The natural history of Graves' disease is altered during pregnancy, with a tendency for exacerbation during the first trimester, and amelioration during the second and third trimesters. The natural history of the disorder must be considered when treating patients, since antithyroid drugs cross the placenta and can directly affect fetal thyroid function. Algorithms to routinely screen pregnant women for thyroid dysfunction have been proposed in recent years, but these have not yet been implemented systematically, nor have they been the subject of cost-effectiveness analyses.


The effect of habitat geology on calcium intake and calcium status of wild rodents.
Calcium is essential for normal physiological function, reproduction and growth in mammals but its distribution in the natural environment is heterogeneous. Spatial variation in calcium soil content is especially marked in the Peak District, United Kingdom, where both calcium-rich limestone and calcium-poor gritstone rock types occur. Wood mice Apodemus sylvaticus (L) and bank voles Clethrionomys glareolus (Schreber 1780) from limestone areas had significantly higher calcium concentrations in stomach contents and in faeces compared with their counterparts from gritstone areas. Calcium status was assessed from serum calcium concentration, femur weight, ash content of the body, calcium concentration in the femur and body ash. There was no significant difference in serum calcium concentration, femur calcium concentration and body ash calcium concentration between animals from the limestone and the gritstone. However, on the limestone, bank voles, but not wood mice, had significantly heavier femora and a greater proportion of ash in the body compared with their gritstone counterparts.


Gene expression profiling and multiplex immunofluorescence analysis of bullous pemphigoid immune-related adverse event reveal upregulation of toll-like receptor 4/complement-induced innate immune response and increased density of TH 1 T-cells.
Immune checkpoint inhibitor (ICI)-based cancer therapies cause a variety of cutaneous immune-related adverse events (irAEs) including immunobullous skin eruptions like bullous pemphigoid (BP). However, little is known about the underlying immunopathogenic drivers of these reactions, and understanding the unique gene expression profile and immune composition of BP-irAE remains a critical knowledge gap in the field of oncodermatology/oncodermatopathology. BP-irAE (n = 8) and de novo BP control (n = 8) biopsy samples were subjected to gene expression profiling using the NanoString® Technologies nCounter PanCancer Immune Profiling Panel. Multiplex immunofluorescence (mIF) studies using markers for T-cells (CD3 and CD8), T helper 1 (TH 1) cells (Tbet), TH 2 cells (Gata3), TH 17 cells (RORγT), and regulatory T-cells (Tregs; FoxP3) were further evaluated using InForm® image analysis. Compared with de novo BP controls, BP-irAE samples exhibited upregulation of 30 mRNA transcripts (p < 0.025), including toll-like receptor 4 (TLR4) and genes associated with complement activation, and downregulation of 89 mRNA transcripts (p < 0.025), including genes associated with TH 2, TH 17, and B-cell immune response. BP-irAE demonstrated a greater density of Tbet+ (TH 1) cells in the dermis (p = 0.004) and fewer Tregs in the blister floor (p = 0.028) when compared with that of de novo control BP samples. BP-irAE exhibited activation of the TLR4/complement-driven classical innate immune response pathway, with dermal TH 1 immune cell polarization and decreased Tregs in the blister floor. TLR/complement signaling may underlie the immunopathogenesis of BP-irAE.


Correction to: Epigenetic tuning of brain signal entropy in emergent human social behavior.
An amendment to this paper has been published and can be accessed via the original article.


Techno-economic assessment of implementing photovoltaic water villas in Maldives.
Solar energy is considered to be an effective measure to alleviate the shortage of power supply in the Maldives. In this paper, a roof photovoltaic (PV) system integrated into water villas in the Maldives was investigated. Three islands-Ayada Maldives, Angaga Island Resort, and JA Manafaru, located in the southern, central, and northern parts of Maldives-were selected for a case study. The potential of PV installations in Ayada Maldives, Angaga Island Resort, and JA Manafaru reaches 1,410, 445, and 742 kW, with corresponding annual power generation of 2.04, 0.64, and 1.12 GWh, respectively. The profits over the life cycle of 25 years of the above three studied islands are 4.86, 1.52, and 2.90 million USD, respectively, with payback periods in the range of 6-7 years.


Morphology and ultrastructure of the spermatozoa of Lonchoptera lutea Panzer, 1809 (Diptera: Lonchopteridae).
Lonchoptera lutea males produce giant spermatozoa that are more than 2000 μm long and 1.4 μm wide. Unlike the typical brachyceran spermatozoon, they have a highly asymmetrical cross-section with only a single, albeit very large, mitochondrial derivative and a pair of massive accessory bodies, one of which extends throughout the entire length of the sperm tail. The accessory bodies consist of an electron-dense matrix in which numerous peculiar electron-lucid substructures are embedded. In the mated female, the giant spermatozoa are found inside two tubular spermathecae which are also extremely long, measuring 4000 μm or more.


DEVELOPMENT AND VALIDATION OF AN EXPLAINABLE ARTIFICIAL INTELLIGENCE FRAMEWORK FOR MACULAR DISEASE DIAGNOSIS BASED ON OPTICAL COHERENCE TOMOGRAPHY IMAGES.
To develop and validate an artificial intelligence framework for identifying multiple retinal lesions at image level and performing an explainable macular disease diagnosis at eye level in optical coherence tomography images. A total of 26,815 optical coherence tomography images were collected from 865 eyes, and 9 retinal lesions and 3 macular diseases were labeled by ophthalmologists, including diabetic macular edema and dry/wet age-related macular degeneration. We applied deep learning to classify retinal lesions at image level and random forests to achieve an explainable disease diagnosis at eye level. The performance of the integrated two-stage framework was evaluated and compared with human experts. On testing data set of 2,480 optical coherence tomography images from 80 eyes, the deep learning model achieved an average area under curve of 0.978 (95% confidence interval, 0.971-0.983) for lesion classification. In addition, random forests performed accurate disease diagnosis with a 0% error rate, which achieved the same accuracy as one of the human experts and was better than the other three experts. It also revealed that the detection of specific lesions in the center of macular region had more contribution to macular disease diagnosis. The integrated method achieved high accuracy and interpretability in retinal lesion classification and macular disease diagnosis in optical coherence tomography images and could have the potential to facilitate the clinical diagnosis.


Adenovirus-mediated gene transfer in olfactory epithelium and olfactory bulb: a long-term study.
We sought to study the spatiotemporal gene expression mediated by adenoviral vector in the olfactory pathways. The replication-defective adenoviral vector AxCALacZ, which encodes the enzyme Escherichia coli beta-galactosidase, was applied to mouse olfactory epithelium by intranasal instillation. The LacZ gene product, beta-galactosidase, was expressed not only in the olfactory receptor neurons and their axons, but also in the olfactory bulbs. The first evidence of anterograde labeling was observed at postinfection day (PID) 2. At PID 3, beta-galactosidase was strongly expressed in olfactory nerve axons, as well as their terminal glomeruli, in the olfactory bulbs. beta-Galactosidase expression persisted up to PID 90, and there was a significant decrease in the number of labeled neurons at PID 30. These results suggest possible long-term effects of adenovirus-mediated gene transfer on the olfactory neurons, as well as the olfactory bulbs.


[Effectiveness of occupational therapy and other non-pharmacological therapies in cognitive impairment and Alzheimer's disease].
A review is presented on the existing knowledge about the usefulness of the occupational therapy in the non-pharmacological treatment of Alzheimer's disease. After conducting a literature search of the period 2010-2015, 25 articles that met the inclusion criteria were selected. The evidence obtained showed the efficiency and effectiveness of OT in delaying the progression of various disorders, especially when structured home OT programs are used. These programs should include aerobic and strengthening, sensory stimulation, and cognitive and memory training exercises based on learning without mistakes. These have shown benefits in the performance of activities of daily living, cognitive and emotional functioning. The importance is stressed of the combined and individual household level intervention and caregiver education. Finally, the need for more studies on the effectiveness of long-term sensory stimulation is highlighted.


Stress, order and survival.
Much of the sophisticated chemistry of life is accomplished by multicomponent complexes, which act as molecular machines. Intrinsic to their accuracy and efficiency is the energy that is supplied by hydrolysis of nucleoside triphosphates. Conditions that deplete energy sources should therefore cause decay and death. But studies on organisms that are exposed to prolonged stress indicate that this fate could be circumvented through the formation of highly ordered intracellular assemblies. In these thermodynamically stable structures, vital components are protected by a physical sequestration that is independent of energy consumption.


An analysis of the SFSTP guide on validation of chromatographic bioanalytical methods: progress and limitations.
The Société Française des Sciences et Techniques Pharmaceutiques (SFSTP) published in 1997 a guide on the validation of chromatographic bio-analytical methods, which introduces new concepts in three different areas: stages of the validation, test of acceptability of a method and design of experiments to perform. In 'stages of validation', the SFSTP guide requires two phases to validate a method. The first phase, called 'prevalidation', is intended to (1) identify the model to use for the calibration curve; (2) evaluate the limits of quantitation; and (3) provide good estimates of the precision and bias of the method before designing the 'validation' phase per se. In the 'test of acceptability', the use of the interval hypotheses is envisaged by the SFSTP guide, not on the parameters of bias and precision, but on individual results by mixing mean bias and intermediate precision in a single test. The SFSTP guide also avoids the use of Satterthwaite's df for testing the acceptability. The reasons for those choices are discussed extensively. In 'design of experiments', much effort has been devoted to improving the quality of results by optimally designing and sizing the experiments to perform in validation. The rationale for using near D-optimal designs for the calibration curve is demonstrated and sample sizes are proposed to correctly size the validation experiments.


Co-expression of Epstein-Barr virus latent membrane protein and vimentin in "aggressive" histological subtypes of Hodgkin's disease.
The presence of Epstein-Barr virus (EBV) genome in Hodgkin's and Reed-Sternberg (HRS) cells, as detected using in situ hybridization (ISH) with biotinylated BamHI "V" probes, along with the expression of EBV-encoded latent membrane protein (LMP) and vimentin was examined in paraffin-embedded sections of 39 immunomorphologically characterized cases of Hodgkin's disease (HD). ISH demonstrated EBV in HRS cells in 15 of 39 cases, whereas LMP expression was detected in 11 of 39 cases, only in the presence of EBV genome detection. With the exception of 1 case, in which HRS cells expressed B-cell-associated antigens, the LMP-positive cases included specimens in which HRS cells were of non-B, non-T phenotype. LMP expression showed a stronger association with lymphocyte depletion (LD) (3/3) and mixed cellularity (MC) (6/11) than with lymphocyte predominance (0/5) or nodular sclerosis (2/20) subtypes. Vimentin expression on HRS cells was found in all the LMP-expressing cases and only in a fraction (13/28) of LMP-negative cases. This study supports the view that HD represents a heterogeneous group of diseases also in terms of EBV association, LMP expression being strongly related to the "aggressive" LD and MC histological subtypes. In light of the supposed interactions between vimentin and LMP, their co-expression on HRS cells, as detected in this study, provides further evidence for a significant role of EBV in the development of a proportion of HD cases.


Prevention of trocar-wound hernia in laparoscopic bariatric operations.
Morbid obesity is a risk for fascial wound dehiscence and incisional hernia after abdominal surgery. The development of minimally invasive surgical techniques has led to a dramatic decrease in these complications. However, laparoscopic surgery may still be followed by trocar-wound herniation. Various methods have been advocated for its prevention. The records of 752 patients who underwent laparoscopic bariatric operations (610 mini-gastric bypass and 142 gastric banding) as treatment for morbid obesity between October 2001 and June 2005, with regular follow-up, were retrospectively reviewed. In all patients, the fascial layer of trocar wounds was not closed. Instead, a Surgicel plug was inserted into the muscle layer of trocar wounds of 10- and 12-mm diameter. 2 male patients in the mini-gastric bypass group developed a trocar wound hernia, for an overall prevalence of 0.33% (2/610). The intervals between surgery and diagnosis were 3 and 5 months respectively. In these 2 patients, the hernia occurred at the 12-mm trocar wound of the left midclavicular line, 2-3 cm below the costal margin, outside the left rectus muscle. These 2 patients have not developed intestinal obstruction as a consequence of the hernia, and have not undergone hernia repair. No patient in the gastric banding group has been found to develop a hernia. With our technique, the prevalence of trocar-wound hernia after laparoscopic bariatric surgery has been very rare.


Narrative review: screening for colorectal cancer in patients with a first-degree relative with colonic neoplasia.
Many patients and providers are aware that colorectal cancer (CRC) "runs in families." A patient with 1 first-degree relative with CRC has approximately twice the personal risk for CRC as a similar person without this family history. Colorectal cancer is the third most common type of cancer in the United States. When providers neglect to collect information on family history, they may fail to appropriately tailor recommendations for screening for CRC for many patients. This review considers the existing data and summarizes an evidence-based approach to the common clinical problem of how and when to implement screening for CRC in a patient with a family history of colonic neoplasia. The authors discuss the varying risks for CRC given the patient's age, health habits, and personal and family histories. In the context of a clinical case that focuses on the effect of a single affected first-degree relative, the authors weigh the risks and benefits of various screening alternatives and briefly address chemoprevention, genetic testing, and future directions in screening for CRC.


Primary and secondary adenocarcinomas associated with anal fistulae.
The purpose of this study was to evaluate the clinical features, pathology, and etiology of adenocarcinoma in patients with anal fistulae. We identified seven patients diagnosed with adenocarcinoma associated with anal fistulae from a retrospective chart review. Five patients were diagnosed with primary adenocarcinoma associated with anal fistulae. Two patients were diagnosed with secondary adenocarcinoma associated with anal fistulae originating from rectal cancer on the proximal side. The primary adenocarcinomas included cancers arising from long-standing anal fistulae fulfilling established diagnostic criteria in two patients, and cancer arising from short-duration anal fistulae in three patients. Excision of the fistula was performed based on the initial diagnosis of the anal fistula for all five patients. Increased suspicion of cancer was due to the existence of gelatinous material in the anal fistula in three patients and induration in the resected specimens in two patients. The etiologies of the secondary adenocarcinomas associated with anal fistulae included implantation in the anal fistula from rectal cancer and fistula formation originating due to the progression of rectal cancer. Anal fistulae are commonly seen in the coloproctology clinic, but special attention to similar conditions associated with malignant disease is needed.


Co-doping of Ag into Mn:ZnSe Quantum Dots: Giving Optical Filtering effect with Improved Monochromaticity.
In optics, when polychromatic light is filtered by an optical filter, the monochromaticity of the light can be improved. In this work, we reported that Ag dopant atoms could be used as an optical filter for nanosized Mn:ZnSe quantum dots (QDs). If no Ag doping, aqueous Mn:ZnSe QDs have low monochromaticity due to coexisting of strong ZnSe band gap emission, ZnSe trap emission, and Mn dopant emission. After doping of Ag into QDs, ZnSe band gap and ZnSe trap emissions can be filtered, leaving only Mn dopant emission with improved monochromaticity. The mechanism for the optical filtering effect of Ag was investigated. The results indicate that the doping of Ag will introduce a new faster deactivation process from ZnSe conduction band to Ag energy level, leading to less electrons deactived via ZnSe band gap emission and ZnSe trap emission. As a result, only Mn dopant emission is left.


Reporting of core items in hierarchical Bayesian analysis for aggregating N-of-1 trials to estimate population treatment effects is suboptimal.
N-of-1 trials can be aggregated to estimate population treatment effects using hierarchical Bayesian models. It is very important to report core items in hierarchical Bayesian analysis. In this study, we assessed reporting of items in hierarchical Bayesian analysis for aggregating N-of-1 trials to estimate population treatment effects. This was a systematic literature review of aggregating N-of-1 trials by hierarchical Bayesian models to estimate population treatment effects. A comprehensive search was performed to collect eligible articles. Pilot studies, formal N-of-1 trials and reports in which the data were reanalyzed using hierarchical Bayesian methods, were included. The information of reported items related with hierarchical Bayesian analysis was extracted by two independent reviewers. The guideline "ROBUST," developed for reporting Bayesian analysis of clinical studies, was published in Journal of Clinical Epidemiology in 2005. We assessed the included reports using ROBUST criteria and 18 other important items. After careful screening, 11 studies were identified to be eligible for inclusion. There were three pilot studies, four formal trials, and four reports in which the data were reanalyzed using hierarchical Bayesian methods. The number of reported items in ROBUST criteria ranged from six to seven, with a median number of six. Five of eleven included articles reported all items of the ROBUST criteria. But for justification and sensitivity analysis in prior distribution items, other items were reported in all of the included articles. Software and analysis data set items were reported the most frequently in additional items excluded from the ROBUST criteria. Less than half of the studies reported the other additional items. Reporting of core items in hierarchical Bayesian analysis for aggregating N-of-1 trials to estimate population treatment effects is suboptimal. A PRISMA-like guidance on reviews of Bayesian N-of-1 trials may be required in the future.


Neuropeptides in sensory neurons.
Substance P, somatostatin, VIP, CCK, angiotensin II, and bombesin have all been localized by immunohistochemical or radioimmunological means in neurons of sensory ganglia or in the dorsal horn of the spinal cord. Most of these neuropeptides have electrophysiological effects on spinal neurons and for substance P and somatostatin, these effects have been associated with particular sensory modalities. Newer investigations using the compound capsaicin are consistent with the hypothesis that substance P is an important neurochemical mediator of certain kinds of noxious peripheral stimuli. The newly described substance P antagonists promise to be important pharmacological tools for investigation of the long-neglected neurochemical bases of sensory neuron function. Elaboration of the roles of these sensory neuropeptides will no doubt shed light on many disease states in which there seems to be sensory neuron involvement.


Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity.
Although timely surgical treatment of liver disease can interrupt inflammation and reduce fibrosis, the mechanisms of repair are unknown. We questioned whether these mechanisms of repair include changes in the inflammatory infiltrate and associated biological activity of matrix metalloproteinases (MMPs) 8 and 2. Rats (n >or= 3) underwent biliary ductal suspension for 7 days followed by decompression. Livers were collected after 7 days of obstruction (d0) and after 2, 5, and 7 days of repair (d2, d5, d7, respectively), and assessed morphometrically for collagen, polymorphonuclear cells (PMNs), Kupffer cells (KCs), and inflammatory mononuclear phagocytes (MNPs). In situ zymography was performed by using fluorogenic substrates for MMP-8 and MMP-2 to spatially localize enzymatic activity. Cholestatic injury resulted in significantly elevated (P <or= .001) collagen deposition (3-fold), and elevated numbers of MNPs (10-fold), KCs (5-fold), and PMNs (4-fold), compared with shams. PMNs remained elevated through d7, while collagen deposition, KCs, and MNPs returned to sham levels by d2. In situ zymography showed no significant changes in MMP-2 activity after cholestatic injury and repair. MMP-8 activity was significantly (P <or= .05) elevated only during repair. Activity was localized to fibrotic portal triads containing PMNs. Cholestatic injury results in increased fibrosis, MNPs, KCs, and PMNs but no MMP-2 or MMP-8 activity. Biliary decompression results in increased MMP-8 activity co-localized to areas of portal fibrosis and PMN accumulation. We conclude that secretion of MMP-8 by neutrophils may play a critical role in resolving the fibrotic scar generated during cholestasis.


Role of jasmonate signaling in rice resistance to the leaf folder Cnaphalocrocis medinalis.
Jasmonate-induced accumulation of anti-herbivore compounds mediates rice resistance to the leaf folder Cnaphalocrocis medinalis. The rice leaf folder (LF), Cnaphalocrocis medinalis, is one of the most destructive insect pests in the paddy field. LF larvae induces leaf folding and scrapes the upper epidermis and mesophyll tissues reducing photosynthesis and yield in rice. Identifying plant defense pathways and genes involved in LF resistance is essential to understand better this plant-insect interaction and develop new control strategies for this pest. Jasmonate (JA) signaling controls a plethora of plant defenses against herbivores. Using RNA-seq time series analysis, we characterized changes in the transcriptome of wild-type (WT) leaves in response to LF damage and measured the dynamics of accumulation of JA phytohormone pools in time-course experiments. Genes related to JA signaling and responses, known to mediate resistance responses to herbivores, were induced by LF and were accompanied by an increment in the levels of JA pools in damaged leaves. The accumulation of defense compounds such as phenolamides and trypsin proteinase inhibitor (TPI) also increased after LF infestation in WT but not in JA mutant plants impaired in JA biosynthesis (aoc-2) and signaling (myc2-5). Consistent with all these responses, we found that LF larvae performed better in the JA mutant backgrounds than in the WT plants. Our results show that JA signaling regulates LF-induced accumulation of TPI and phenolamides and that these compounds are likely an essential part of the defense arsenal of rice plants against this insect pest.


Rational administration sequencing of immunochemotherapy elicits powerful anti-tumor effect.
As a research hotspot, immune checkpoint inhibitors (ICIs) is often combined with other therapeutics in order to exert better clinical efficacy. To date, extensive laboratory and clinical investigations into the combination of ICIs and chemotherapy have been carried out, demonstrating augmented effectiveness and broad application prospects in anti-tumor therapy. However, the administration of these two treatment modalities is usually randomized or fixed to a given chronological order. Nevertheless, the pharmacological effect of drug is closely related to its exposure behavior in vivo, which may consequently affect the synergistic outcomes of a combined therapy. In this study, we prepared a lipid nanoparticle encapsulating docetaxel (DTX-VNS), and associated it with the immune checkpoint inhibitor anti-PD-1 antibody (αPD-1) for the treatment of malignant tumors. To identify the optimum timing and sequencing for chemotherapy and immunotherapy, we designed three administration regimes, including the simultaneous delivery of DTX-VNS and αPD-1(DTX-VNS@αPD-1), DTX-VNS delivery before (DTX-VNS plus αPD-1) or post (αPD-1 plus DTX-VNS) PD-1 blockade with an interval of two days. Analysis from mass spectrometry, multi-factor detection and other techniques indicated that DTX-VNS plus αPD-1 initiated a powerful anti-tumor response in multiple tumor models, contributing to a remarkably reshaped tumor microenvironment landscape, which may attribute to the maximum therapeutic additive effects arise from a concomitant exposure of DTX-VNS and αPD-1 at the tumor site. By profiling the exposure kinetics of nanoparticles and αPD-1 in vivo, we defined the administration schedule with utmost therapeutic benefits, which may provide a valuable clinical reference for the rational administration of immunochemotherapy.


Effect of Rubus Occidentalis Extract on Metabolic Parameters in Subjects with Prediabetes: A Proof-of-concept, Randomized, Double-blind, Placebo-controlled Clinical Trial.
Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p < 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p < 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p < 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John Wiley & Sons, Ltd.


Cloning and sequencing of cDNA that encodes goat growth hormone.
The cDNA that encodes goat growth hormone (gGH) was isolated from a goat pituitary cDNA library. The cDNA, about 880 base pairs long, had a coding sequence, 5'- and 3'-untranslated regions and a poly(A) chain. The cDNA could encode a polypeptide of 217 amino acids. The amino acid sequence homology between gGH and the sequences of bovine GH, rat GH and human GH was 99, 83 and 66%, respectively. By Northern blot hybridization, we found that the possible gGH gene is transcribed in the goat pituitary.


The preterm infant: breast or bottle?
The long term survival of preterm infants has greatly improved in the last decade. Clinicians have consequently been able to concentrate more on their optimal nutrition and this has led to a controversy regarding the best milk for these infants. Current theory and practice suggests that the fastest growth and the best energy retention is obtained if a highly modified preterm formula milk is used. Banked mature human breast milk appears nutritionally inadequate and has no proven advantages. The use of fresh mothers' own milk merits further investigation, although its widespread use will usually be impractical.


Oral antihistamine therapy influences plasma tryptase levels in adult atopic dermatitis.
Atopic dermatitis (AD) is an allergic skin disease that follows a clinical course of 'flare-up' and remission. Histamine and tryptase are inducers of pruritus and non-sedating second-generation antihistamines, including fexofenadine, are widely used for treatment of allergic skin disorders. We assessed the efficacy of a second-generation antihistamine in AD patients and examined its pharmacological effects on chemical mediators. The scoring atopic dermatitis (SCORAD) instrument and visual analogue scale (VAS) for pruritus were used to assess disease severity in 349 AD patients. Twenty patients with moderate AD symptoms, who had not received any treatment for 2 weeks, were randomly assigned into two groups. Ten patients underwent fexofenadine and emollient treatment (Group 1) and 10 received fexofenadine and steroid treatment (Group 2) for 1 week. SCORAD and VAS for pruritus, and blood histamine and tryptase levels were evaluated before and after treatment. SCORAD and VAS improved in both Group 1 (p=0.01 and p=0.006, respectively) and Group 2 (p<0.001 and p=0.001, respectively). The improvement in Group 1 showed a significant correlation with the diminution rate of blood tryptase levels (SCORAD: r=0.83 and p=0.013, respectively; VAS: r=0.81, p=0.015, respectively). End-point plasma tryptase levels were significantly lower than baseline levels in Group 2 (p=0.046). Histamine levels did not show any significant changes in either group. These results suggest that second-generation antihistamine therapy reduces AD pruritus, resulting in the effective clinical treatment for AD. In addition, monitoring tryptase levels during antihistamine therapy in moderate AD treatment may prove to be useful in establishing treatment effects.


The Role of Centers of Excellence With Multidisciplinary Teams in the Management of Abnormal Invasive Placenta.
Abnormal invasive placenta (AIP) causes significant maternal and perinatal morbidity and mortality. With the increasing incidence of cesarean delivery, this condition is dramatically more common in the last 20 years. Advances in grayscale and Doppler ultrasound have facilitated prenatal diagnosis of abnormal placentation to allow the development of multidisciplinary management plans. Outcomes are improved when delivery is accomplished in centers with multidisciplinary expertise and experience in the care of AIP. This article highlights the desired features for developing and managing a multidisciplinary team dedicated to the treatment of AIP in center of excellence.