The role of antimicrobials in Crohn's disease.
This review summarizes literature regarding the role of antimicrobials for induction and maintenance of Crohn's disease (CD) remission. PubMed was searched (1966 to October 2012) for controlled trials involving adults and written in English. Five of the 13 identified studies showed benefit with the use of ciprofloxacin, metronidazole and rifaximin for induction of remission. Eight studies showed no benefit using ciprofloxacin, metronidazole, combination of metronidazole and ciprofloxacin or clarithromycin and rifaximin. Four of the five studies showed benefit based on colonic location. Perianal CD with draining fistulas responded in one of two studies. Two studies in postileocolonic resection demonstrated benefit of metronidazole or ornidazole in reducing CD recurrence. Antimicrobials, especially metronidazole, are promising for inducing remission in patients with colonic CD and preventing recurrence in postileocolonic resection.


Risk of Disabling Response Fluctuations and Dyskinesias for Dopamine Agonists Versus Levodopa in Parkinson's Disease.
Response fluctuations and dyskinesias develop during the use of both levodopa (LD) and dopamine agonists (DA), but may not be equally disabling. To compare the risk and time of onset of disabling response fluctuations and dyskinesias (DRFD) among patients with Parkinson's disease (PD) who were initially treated with either LD or DA. Open cohort study of all consecutive de-novo PD patients in routine clinical practice, included over a period of 15 years (median follow-up: 8.1 years, range 1.1-17.7), since embarking on LD or DA. Older patients and patients with more severe PD were started on LD (n = 77), younger patients on a DA (n = 50). Therapy was adjusted according to generally accepted guidelines. The primary endpoints were: the onset of response fluctuations, dyskinesias, and the moment when these complications became disabling (DRFD). LD-starters developed response fluctuations 0.8 years earlier than DA-starters (p = 0.07), while dyskinesias appeared around 2.5 years earlier (p = 0.003). However, the risk and time of onset of DRFD did not differ statistically between the groups (LD-starters: 60% , median interval 7.3 years, DA-starters: 52% , 6.1 years, p = 0.63). DA-starters displayed a 0.19 points lower adjusted mean improvement in motor scores than LD-starters (p = 0.002). Adjustments for age and severity of PD at start of dopaminergic therapy did not change these results. In routine clinical practice, the risk and time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor functioning is worse in DA-starters. These results support the use of LD as initial therapy for PD.


Nano-level instrumentation for analyzing the dynamic accuracy of a rolling element bearing.
The rotational performance of high-precision rolling bearings is fundamental to the overall accuracy of complex mechanical systems. A nano-level instrument to analyze rotational accuracy of high-precision bearings of machine tools under working conditions was developed. In this instrument, a high-precision (error motion < 0.15 μm) and high-stiffness (2600 N axial loading capacity) aerostatic spindle was applied to spin the test bearing. Operating conditions could be simulated effectively because of the large axial loading capacity. An air-cylinder, controlled by a proportional pressure regulator, was applied to drive an air-bearing subjected to non-contact and precise loaded axial forces. The measurement results on axial loading and rotation constraint with five remaining degrees of freedom were completely unconstrained and uninfluenced by the instrument's structure. Dual capacity displacement sensors with 10 nm resolution were applied to measure the error motion of the spindle using a double-probe error separation method. This enabled the separation of the spindle's error motion from the measurement results of the test bearing which were measured using two orthogonal laser displacement sensors with 5 nm resolution. Finally, a Lissajous figure was used to evaluate the non-repetitive run-out (NRRO) of the bearing at different axial forces and speeds. The measurement results at various axial loadings and speeds showed the standard deviations of the measurements' repeatability and accuracy were less than 1% and 2%. Future studies will analyze the relationship between geometrical errors and NRRO, such as the ball diameter differences of and the geometrical errors in the grooves of rings.


Histological Subtype Remains a Significant Prognostic Factor for Survival Outcomes in Patients With Appendiceal Mucinous Neoplasm With Peritoneal Dissemination.
It has been increasingly recognized that appendiceal mucinous neoplasm with peritoneal dissemination is not a homogenous disease. This study aimed to examine the impact of different histological subtypes on survival of a large cohort of patients with appendiceal mucinous neoplasms uniformly treated by cytoreductive surgery and intraperitoneal chemotherapy. This was a retrospective study of prospectively collected data of patients with peritoneal dissemination of appendiceal neoplasm who underwent cytoreductive surgery and intraperitoneal chemotherapy. The study was conducted by 1 surgical team at St. George Hospital. A total of 444 patients formed the cohort of this study. Histological diagnoses were categorized based on Carr criteria to include acellular mucin, disseminated peritoneal adenomucinosis, peritoneal mucinous neoplasms without signet ring cells, and peritoneal mucinous carcinomatosis with signet cells. Patients with low-grade appendiceal mucinous neoplasms with neoplastic epithelium absent tended to have lower CEA, CA19-9, and CA125 levels preoperatively (p = 0.109, 0.008, and 0.034). Factor analysis showed that histological diagnosis was an independent prognostic factor for survival outcomes (HR = 3.13 (95% CI, 2.34-4.39); p < 0.001), adjusted for peritoneal cancer index >20, completeness of cytoreductive score ≥2, use of early postoperative intraperitoneal chemotherapy, transfusion units, CEA >7.0 mg/L, CA19-9 >24.0 U/mL, and CA125 >24 U/mL. This study was limited by its retrospective nature, lack of uniform classifications of appendiceal mucinous neoplasms in early years, and the heterogeneity of this study cohort given the long study period. Histological subtype remains a significant prognostic factor for survival outcomes in patients with appendiceal mucinous neoplasms. It should be taken into account when selecting patients for cytoreductive surgery, tailoring appropriate adjuvant therapies and follow-up surveillance plan.


Modeling Variables With a Spike at Zero: Examples and Practical Recommendations.
In most epidemiologic studies and in clinical research generally, there are variables with a spike at zero, namely variables for which a proportion of individuals have zero exposure (e.g., never smokers) and among those exposed the variable has a continuous distribution. Different options exist for modeling such variables, such as categorization where the nonexposed form the reference group, or ignoring the spike by including the variable in the regression model with or without some transformation or modeling procedures. It has been shown that such situations can be analyzed by adding a binary indicator (exposed/nonexposed) to the regression model, and a method based on fractional polynomials with which to estimate a suitable functional form for the positive portion of the spike-at-zero variable distribution has been developed. In this paper, we compare different approaches using data from 3 case-control studies carried out in Germany: the Mammary Carcinoma Risk Factor Investigation (MARIE), a breast cancer study conducted in 2002-2005 (Flesch-Janys et al., Int J Cancer. 2008;123(4):933-941); the Rhein-Neckar Larynx Study, a study of laryngeal cancer conducted in 1998-2000 (Dietz et al., Int J Cancer. 2004;108(6):907-911); and a lung cancer study conducted in 1988-1993 (Jöckel et al., Int J Epidemiol. 1998;27(4):549-560). Strengths and limitations of different procedures are demonstrated, and some recommendations for practical use are given.


Hyperekplexia: report of a nonfamilial adult onset case associated with obstructive sleep apnea and abnormal brain nuclear tomography.
We report the unique occurrence of hyperekplexia and obstructive sleep apnea (OSA) in a 48-year-old male. Polysomnography and multiple sleep latency testing excluded cataplexy, which can be confused with startle attacks. A new imaging finding was a nuclear tomography abnormality in the left frontal lobe. We postulate that this finding may represent a functional cortical lesion of a descending pathway that normally inhibits the startle reflex. Serious complications of pharmacotherapy with clonazepam, the drug of choice for hyperekplexia, can be avoided by first evaluating for OSA.


Education, Income, and Employment and Prevalence of Chronic Disease Among American Indian/Alaska Native Elders.
Chronic disease studies have omitted analyses of the American Indian/Alaska Native (AI/AN) population, relied on small samples of AI/ANs, or focused on a single disease among AI/ANs. We measured the influence of income, employment status, and education level on the prevalence of chronic disease among 14,632 AI/AN elders from 2011 through 2014. We conducted a national survey of AI/AN elders (≥55 y) to identify health and social needs. Using these data, we computed cross-tabulations for each independent variable (annual personal income, employment status, education level), 2 covariates (age, sex), and presence of any chronic disease. We also compared differences in values and used a binary logistic regression model to control for age and sex. Most AI/AN elders (89.7%) had been diagnosed with at least one chronic disease. AI/AN elders were also more than twice as likely to have diabetes and more likely to have arthritis. AI/AN elders with middle-to-low income levels and who were unemployed were more likely to have a chronic disease than were high-income and employed AI/AN elders. Addressing disparities in chronic disease prevalence requires focus on more than access to and cost of health care. Economic development and job creation for all age cohorts in tribal communities may decrease the prevalence of long-term chronic diseases and may improve the financial status of the tribe. An opportunity exists to address health disparities through social and economic equity among tribal populations.


Soda lime temperatures during low-flow sevoflurane anaesthesia and differences in dead-space.
Sevoflurane degrades during low-flow anaesthesia to compound A, and high carbon dioxide absorbent temperatures cause increased degradation. The purpose of this investigation was to determine if larger tidal volumes, without increasing alveolar ventilation, decrease the temperature in the carbon dioxide absorber during low- and minimal-flow sevoflurane anaesthesia. Prospective, randomized study, including 45 patients (ASA 1-2), scheduled for elective general or urology surgery. The patients were randomly assigned to one of three treatments. Patients in group 1 (NDS) received fresh gas flow of 1 litre/min without using additional dead-space volumes. In group 2 (DS + 1.0), the patients received fresh gas flow of 1 litre/min using additional dead-space volumes, placed between the Y-piece and the HME, and patients in group 3 (DS + 0.5) received the same technique with a fresh gas flow of 0.5 litre/min. The soda lime temperatures, dead-space volumes, end-tidal carbon dioxide, sevoflurane concentrations, ventilation volumes and pressures, absorbent weight and ear temperatures were measured. The maximum temperature of the soda lime was 44.1 +/- 1.1 degrees C in the NDS group, 37.8 +/- 0.8 degrees C in the DS + 1.0 group and 38.5 +/- 2.7 degrees C in the DS + 0.5 group (P<0.0001). The dead-space volume between the Y-piece the tracheal tube was 164 +/- 69 ml in the DS + 1.0 group and 196 +/- 15 ml in the DS + 0.5 group (P<0.05). The ventilator pressure were higher in the DS groups compared with the NDS group (P<0.001). Soda lime weight increased in all groups. End-tidal carbon dioxide, sevoflurane concentrations and ear temperatures were similar between the groups. Increasing dead-space volumes can reduce carbon dioxide absorber temperature during low- and minimal-flow sevoflurane anaesthesia.


Early Life Stress: Effects on the Regulation of Anxiety Expression in Children and Adolescents.
This study examined children's (N = 79; 9-10 years) and adolescents' (N = 82; 15-16 years) ability to regulate their emotion expressions of anxiety as they completed a modified version of the Trier Social Stress Test for Children (TSST-C). Approximately half in each age group were internationally adopted from institutional care (N = 79) and half were non-adopted, age-matched peers (N = 82). Institutional care was viewed as a form of early life stress. Coders who were reliable and blind to group status watched videos of the session to assess anxiety expressions using the Child and Adolescent Stress and Emotion Scale developed for this study. Children exhibited more expressions of anxiety than adolescents, and youth adopted from institutions showed more expressions of anxiety than their non-adopted counterparts. The role of early life stress on observed anxiety expressions remained significant after controlling for differences in age, physiological stress responses measured through salivary cortisol reactivity, and self-reports of stress during the TSST-C. This suggests possible deficits in the regulation of expressive behavior for youth with early life stress histories, which cannot be explained by experiencing the task as more stressful.


Negative regulation of vascular smooth muscle cell migration by blood shear stress.
Vortex blood flow with reduced blood shear stress in a vein graft has been hypothesized to promote smooth muscle cell (SMC) migration and intimal hyperplasia, pathological events leading to vein graft restenosis. To demonstrate that blood shear stress regulates these processes, we developed a modified vein graft model where the SMC response to reduced vortex blood flow was compared with that of control vein grafts. Vortex blood flow induced SMC migration and neointimal hyperplasia in control vein grafts, whereas reduction of vortex blood flow in the modified vein graft strongly suppressed these effects. A venous polymer implant with known fluid shear stress was employed to clarify the molecular mechanism of shear-dependent SMC migration in vivo. In the polymer implant, the phosphorylation of extracellular signal-regulated kinase (ERK1/2) and myosin light chain kinase (MLCK), found primarily in SMCs, increased from day 3 to day 5 and returned toward the control level from day 5 to day 10, with the peak phosphorylation associated with the maximal speed of SMC migration. Treatment with PD-98059 (an inhibitor specific to the ERK1/2 activator MEK1/2) significantly suppressed the phosphorylation of MLCK, suggesting a role for ERK1/2 in regulating the activity of MLCK. Treatment with PD-98059 or ML-7 (an inhibitor specific to MLCK) reduced shear stress-dependent SMC migration, resulting in an SMC distribution independent of fluid shear stress. These results suggest that fluid shear stress regulates SMC migration via the mediation of ERK1/2 and MLCK.


Morphological and morphometrical characteristics of the esophageal intrinsic nervous system in the golden hamster.
Very little is known about esophageal innervation in the hamster. In the present study, we used protein gene product 9.5 (PGP 9.5) to determine immunohistochemically the architectural features of the enteric nervous system in the hamster esophagus. The myenteric plexus consisted of a loose and irregular network of ganglia and interganglionic nerve bundles. The density of the neurons in the myenteric plexus was relatively low (479 +/- 75/cm(2), n = 5), with a preferentially higher density in the upper cervical portion than other parts of the esophagus. Regional differences in the number of PGP 9.5-positive neurons and ganglia were observed. PGP 9.5-immunoreactive fibers in the ganglia often branched, giving rise to expanding nerve endings of laminar morphology resembling intraganglionic laminar endings described in rats and cats. Fine varicose fibers originating from the secondary plexus were occasionally observed near the motor endplates, suggested a dual innervation of the striated muscle. The submucosal plexus was free from ganglionated plexus. A regional difference in the submucosal nervous network was observed. The number of motor endplates in the inner muscle layer was higher than that in the outer muscle layer.


Recent advancements in erythrocytes, platelets, and albumin as delivery systems.
In the past few years, nanomaterial-based drug delivery systems have been applied to enhance the efficacy of therapeutics and to alleviate negative effects through the controlled delivery of targeting and releasing agents. However, few drug carriers can achieve high targeting efficacy, even when targeting modalities and surface markers are introduced. Immunological problems have also limited their wide applications. Biological drug delivery systems, such as erythrocytes, platelets, and albumin, have been extensively investigated because of their unique properties. In this review, erythrocytes, platelets, and albumin are described as efficient drug delivery systems. Their properties, applications, advantages, and limitations in disease treatment are explained. This review confirms that these systems can be used to facilitate a specific, biocompatible, and smart drug delivery.


Uptake and Short-term Outcomes of High-risk Screening Colonoscopy Billing Codes: A Population-based Study Among Young Adults.
Persons suspected or confirmed with familial colorectal cancer syndrome are recommended to have biennial colonoscopy from late adolescence or early adulthood. Persons without a syndrome but with one or more affected first-degree relatives are recommended to begin colonoscopy 10 years before the age at diagnosis of the youngest affected relative, and every 5 to 10 years. Ontario introduced colonoscopy billing codes for these two indications in 2011. We identified persons in Ontario under 50 years of age, without a prior history of colorectal cancer or inflammatory bowel disease, with one or more of these billing claims between 2013 and 2017. We described the index colonoscopy, and subsequent colonoscopy up-to-date status. We computed average annual rates of colorectal and other cancer diagnoses, and displayed mean cumulative function plots, stratified by billing code, age and sex. Billing claims for 'familial syndrome' high-risk screening colonoscopy were identified among 14,846 persons; the average annual rate of CRC diagnoses was 38.6 per 100,000 among males and 22.2 among females. Colonoscopy up-to-date status fell to 50% within 7 years. Billing claims for 'first-degree relative' screening colonoscopy was identified among 49,505 persons; average annual rates of CRC diagnoses were 16.3 among males and 13.5 per 100,000 among females, respectively. Colorectal cancer was more frequent following billing claims for high-risk screening colonoscopy for familial syndromes, as were noncolorectal malignancies potentially associated with these syndromes. This billing claim for familial colorectal cancer syndrome colonoscopy appears to identify a group at elevated short-term risk for cancer.


The Alapahoochee watershed microgeographic structure and its potential influence on metal concentrations and genetic structure in the Florida cottonmouth, Agkistrodon piscivorus conanti, within the watershed.
This study examines the microgeographic structure of the Alapahoochee watershed, part of the Suwannee River basin, south-central GA, USA, and relates it to variations in liver metal concentrations and genetic structure of the Florida cottonmouth, Agkistrodon piscivorus conanti. One objective was to determine if liver metal concentrations in A. piscivorus differ between Grand Bay and Mud creeks, which form the watershed's upper portion. Grand Bay Creek is relatively pristine, whereas Mud Creek is polluted with various metals. Genetic analyses were used to assess possible migration patterns between the creeks indicating whether the basin possesses a single population or two populations. Collections occurred in 2008 and 2009. Specimens were captured, euthanized, or collected as road kills, and liver metal concentrations were analyzed and DNA extracted. No differences in metal concentrations were detected between the creeks, except for nickel in females. Metal concentrations in A. piscivorus were not significantly different between males and females nor show a relationship to body size. Genetic analyses were limited to three primer sets, which amplified informative loci. Locus, CH4B, was highly divergent between the putative populations and particularly informative. Genetic structure indicates potential population isolation within the two creeks. Results suggest that two distinct A. piscivorus populations were present and those populations did not differ in their liver metal concentrations (exception being nickel), despite the differences in environmental metal concentrations in the areas. These findings provide new insight into metal accumulation and detoxification in these animals.


Morphological and functional changes in skeletal muscle in type 2 diabetes mellitus: A systematic review and meta-analysis.
Changes in the skeletal muscle are common in patients with type 2 diabetes mellitus (T2DM). These changes impair your motor skills. This systematic review aimed to investigate changes in skeletal muscle in patients with T2DM. The search was carried out in the PubMed, Scopus, and Web of Science databases until December 1, 2021. Observational studies that evaluated musculoskeletal changes in people with T2DM were included. The review was based on PRISMA recommendations. The primary parameters analyzed were muscle strength, muscle mass, muscle power, and muscle endurance. Forty-eight studies were included, with a total of 26,042 participants. The results revealed that T2DM is associated with a reduction in handgrip [-2.64 (CI 95% = -3.33 to -1.95, Z = -7.50, p < .0001], and knee extension muscle strength [-0.56 (CI 95% = -0.76 to -0.36, Z = -5.64, p < .0001)], a higher percentage of type II fibers [11.74 (CI 95% = 6.24 to 17.25, Z = 4.18, p < .0001)], and a lower percentage of type I fibers [-15.69 (CI 95% = -18.22 to -13.16, Z = -12.16, p < .0001], in addition to a greater thickness of the calcaneus tendon (p < .0001). Individuals with T2DM present skeletal muscle impairments, mainly reduced muscle strength, mass, and endurance; increase in the thickness of the calcaneus tendon, and alteration in the proportion of type I and II fibers, even in the initial stage of the disease.


Molecular guided therapy for advanced pancreatic cancer patients with PI3K activated mutation: vision or illusion?
Despite a modern validated regimen of chemotherapy, advanced pancreatic adenocarcinoma remains the fourth most common cause of cancer-related death worldwide. The phosphoinositide 3-kinase pathway (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a major signaling pathway that may be activated in advanced pancreatic cancer. To highlight the potential interest of this targetable pathway in selected advanced pancreatic cancer patients, we report herein a patient with an activated PI3K mutation who was treated in a phase I trial evaluating a treatment combination including an mTOR inhibitor.


Urinary iodine concentration and radioactive iodine therapeutic response in patients with differentiated thyroid cancer.
Aim: Urinary iodine concentration (UIC) may assess radioactive iodine ablation. Materials & methods: According the 2015 American Thyroid Association guidelines, patients were categorized into low- to intermediate-risk or high-risk groups. The iodine concentration in the morning urine specimens was measured by the ceric ion-arsenious acid method. Results: In the low- to intermediate-risk group (113 cases), nonexcellent response (non-ER) was associated with higher UIC, higher UIC subgroups (p < 0.05), higher pre-ablative stimulated thyroglobulin levels (p < 0.01). In the high-risk group (68 cases), the non-ER rate was higher in the higher pre-ablative stimulated thyroglobulin group (p < 0.01), but not significantly different between the UIC and UIC subgroups (p > 0.05). Conclusion: The non-ER rate was related to UIC in the low- to intermediate-risk group; however, UIC did not affect the non-ER rate in the high-risk group.


Modeling the effects of varicella vaccination programs on the incidence of chickenpox and shingles.
Two possible dangers of an extensive varicella vaccination program are more varicella (chickenpox) cases in adults, when the complication rates are higher, and an increase in cases of zoster (shingles). Here an age-structured epidemiologic-demographic model with vaccination is developed for varicella and zoster. Parameters are estimated from epidemiological data. This mathematical and computer simulation model is used to evaluate the effects of varicella vaccination programs. Although the age distribution of varicella cases does shift in the simulations, this does not seem to be a danger because many of the adult cases occur after vaccine-induced immunity wanes, so they are mild varicella cases with fewer complications. In the simulations, zoster incidence increases in the first three decades after initiation of a vaccination program, because people who had varicella in childhood age without boosting, but then it decreases. Thus the simulations validate the second danger of more zoster cases.


Microinjection of ANG II into paraventricular nucleus enhances cardiac sympathetic afferent reflex in rats.
The aims of present study were to determine whether angiotensin II (ANG II) in the paraventricular nucleus (PVN) is involved in the central integration of the cardiac sympathetic afferent reflex and whether this effect is mediated by the ANG type 1 (AT(1)) receptor. While the animals were under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate, and renal sympathetic nerve activity (RSNA) were recorded in sinoaortic-denervated and cervical-vagotomized rats. A cannula was inserted into the left PVN for microinjection of ANG II. The cardiac sympathetic afferent reflex was tested by electrical stimulation (5, 10, 20, and 30 Hz in 10 V and 1 ms) of the afferent cardiac sympathetic nerves or epicardial application of bradykinin (BK) (0.04 and 0.4 microg in 2 microl). Microinjection of ANG II (0.03, 0.3, and 3 nmol) into the PVN resulted in dose-related increases in the RSNA responses to electrical stimulation. The percent change of RSNA response to 20- and 30-Hz stimulation increased significantly at the highest dose of ANG II (3 nmol). The effects of ANG II were prevented by pretreatment with losartan (50 nmol) into the PVN. Microinjection of ANG II (0.3 nmol) into the PVN significantly enhanced the RSNA responses to epicardial application of BK, which was abolished by pretreatment with losartan (50 nmol) into the PVN. These results suggest that exogenous ANG II in the PVN augments the cardiac sympathetic afferent reflex evoked by both electrical stimulation of cardiac sympathetic afferent nerves and epicardial application of BK. These central effects of ANG II are mediated by AT(1) receptors.


Impact of COVID-19 lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 and type 2 diabetes mellitus.
Malaysia implemented nationwide lockdown from 18th March till 3rd May 2020 to mitigate the spread of coronavirus disease (COVID-19). This study aimed to examine the impact of the lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 (T1DM) and 2 diabetes mellitus (T2DM) aged less than 18 years old. In this cross-sectional study, interviews and a standardised questionnaire comparing lifestyle changes before and during the lockdown were performed in follow-up clinic visits after the lockdown. Anthropometry measurements and glycated haemoglobin (HbA1c) values were compared 3 months prior and after the lockdown. Participants were 93 patients with T1DM (11.08 ± 3.47 years) and 30 patients with T2DM (13.81 ± 2.03 years). Male gender, T2DM and pubertal adolescents were found to have a significant deterioration in glycaemic control. A significant increment of HbA1c was observed in patients with T2DM (8.5 ± 0.40 vs 9.9 ± 0.46%), but not in patients with T1DM (8.6 ± 0.28 vs 8.7 ± 0.33%). Contrarily, there was an improved glycaemic control in pre-pubertal T1DM children likely due to parental supervision during home confinement. Weight and BMI SDS increased in T1DM patients but surprisingly reduced in T2DM patients possibly due to worsening diabetes control. Reduced meal frequency mainly due to skipping breakfast, reduced physical activity level scores, increased screen time and sleep duration were observed in both groups. Adverse impact on glycaemic control and lifestyle were seen mostly in patients with T2DM and pubertal adolescent boys.


[Combined form of chronic aggressive hepatitis primary biliary cirrhosis].
15 patients with primary biliary cirrhosis (PBC) and 109 patients with chronic aggressive hepatitis (CAH) have been followed. Features of PBC, namely the generalized pruritus, massive rise in alkaline phosphatase, antimitochondrial antibodies and high levels of IgM-globulins, were present in 7 patients with CAH. This group was treated with immunosuppressive drugs for 1-2 years. Clinical, biochemical, immunological and histological parameters were used to assess the therapeutic effect. The pruritus improved and there was a statistically significant reduction in the IgG-hyperglobulinemia. Some resolution of the piecemeal necroses was seen. However, in judging these changes the sampling error must be taken into account. The unknown agent attacks both the hepatocytes and the epithelial cells of the bile ducts. The immunosuppressive treatment protects the liver cells from further damage while the progressive destruction of the bile ducts remains uninfluenced. The results suggest that the smallest possible dose sufficient to suppress the activity of CAH must be selected.


A possible link between exercise-training adaptation and dehydroepiandrosterone sulfate- an oldest-old female study.
The purpose of this study was to determine the association between the level of salivary dehydroepiandrosterone sulfate (DHEA-S) and the magnitude of adaptation to exercise training in insulin sensitivity for aged females. A group of 16 females, aged 80-93 years old, was divided into 2 groups according to their baseline DHEA-S levels: Lower Halves (N = 8) and Upper Halves (N = 8), and participated in a 4-month exercise intervention trial. Insulin response with an oral glucose tolerance test (OGTT), cholesterol, blood pressure (BP), motor performance, and DHEA-S were determined at baseline and 4 months after the training program. Glucose tolerance and body mass index (BMI) remained unchanged with training for both groups. Insulin, fasted cholesterol, diastolic blood pressure, reaction time, and locomotive function were significantly lowered by training only in the Upper Halves group. Changes in the area under curve of insulin (IAUC) were negatively correlated with the baseline DHEA-S level (R= - 0.60, P < 0.05). The current study provides the first evidence that oldest-old subjects with low DHEA-S level appear to be poor responders to exercise-training adaptations.


Central hypoventilation with PHOX2B expansion mutation presenting in adulthood.
Congenital central hypoventilation syndrome most commonly presents in neonates with sleep related hypoventilation; late onset cases have occurred up to the age of 10 years. It is associated with mutations in the PHOX2B gene, encoding a transcription factor involved in autonomic nervous system development. The case history is described of an adult who presented with chronic respiratory failure due to PHOX2B mutation-associated central hypoventilation and an impaired response to hypercapnia.


Effectiveness of iterative algorithms in recovering phase in the presence of noise.
Inversion of coherent X-ray diffraction patterns allows the imaging of three-dimensional density distributions. The recovery of such shapes often requires application of iterative algorithms, such as Fienup's error reduction or hybrid input/output. Since the measurement of such a pattern records the intensity in reciprocal space, any errors due to noise will probably not have a straightforward impact on the final real-space result. In this paper, the effect of the types of noise common in coherent X-ray diffraction (CXD) experiments, counting statistics, scatter from alien particles and detector noise, on the recovered real-space density projection is explored by simulating a two-dimensional CXD pattern and adding noise. It is found that an R factor measuring the reproducibility between the best and second-best real-space result is a leading indicator of performance.


Detection of Cryptosporidium spp. and Giardia duodenalis in small wild mammals in northeastern Brazil.
This study investigated the occurrence of Giardia duodenalis and Cryptosporidium spp. in rodents and marsupials from the Atlantic Forest in southern Bahia, northeastern Brazil. Two hundred and four fecal samples were collected from different forest areas in the municipalities of Ilhéus, Una, Belmonte, and Mascote. Identifications were performed using PCR and nested PCR followed by sequencing of the gdh and tpi genes for G. duodenalis, and the gp60 and Hsp-70 genes for Cryptosporidium. The total frequency of positive PCR samples for both G. duodenalis and Cryptosporidium spp. was 5.4% (11/204). Giardia duodenalis occurred in 2.94% (4/136) of rodents and 2.94% (2/68) of marsupials. The prevalence of Cryptosporidium in rodents and marsupials was 1.47% (2/136) and 4.41% (3/68), respectively. In the areas sampled, the frequency of parasitism was 50% (7/14), while the Mascote region alone had no parasitized animals. The G. duodenalis subgenotype AI was identified in the rodent species Hylaeamys laticeps, Oecomys catherinae, Oligoryzomys nigripes and Akodon cursor, and in the marsupials Gracilinanus agilis and Monodelphis americana. In the rodents Rhipidomys mastacalis, H. laticeps and in the marsupial Marmosa murina the protozoa Cryptosporidium fayeri, Cryptosporidium parvum and Cryptosporidium ubiquitum with subtypes IIa and IVg by the gp60 gene were found. In conclusion, this study provides the genetic characterization of Giardia and Cryptosporidium species and genotypes in rodents and marsupials. And, these findings reinforce that the rodent and marsupial species mentioned above play a role as new hosts for Giardia and Cryptosporidium.


A randomised controlled pilot study to compare filtration factor of a novel non-fit-tested high-efficiency particulate air (HEPA) filtering facemask with a fit-tested N95 mask.
Use of a fit-tested N95 or FFP2 mask is recommended to protect against transmission of airborne pathogens. This poses considerable logistic problems when preparing for, or dealing with, an epidemic. Some of these problems might be overcome by use of a compact reusable high-efficiency particulate air filtering mask that can be cut to size. We carried out a randomised controlled cross-over study to compare the efficacy of such a mask (Totobobo, Dream Lab One Pte Ltd, Singapore) with fit-tested N95 masks (1860 or 1860s or 1862; 3M, St Paul, MN, USA) in 22 healthy volunteers. The median (interquartile range) reduction in airborne particle counts was significantly higher [193-fold (145-200)] for N95 masks than for Totobobo masks [135-fold (83-184)] (P<0.05). There was no statistically significant difference between the proportion of subjects achieving a reduction of > or =100-fold between N95 (19/22) and Totobobo (16/22) masks. We conclude that use of the Totobobo mask without fit testing cannot be recommended, but its performance is sufficiently promising to warrant further investigation.


Modulation of differentiation and proliferation in human colon carcinoma cells by transforming growth factor beta 1 and beta 2.
We have previously characterized the diversity of cellular responses to transforming growth factor (TGF)-beta 1 from human colon carcinoma cells. We now show that morphological alteration and part of the growth-inhibitory responses elicited by growth factor (GF) are associated with the secondary effect of the induction of synthesis of extracellular matrix (ECM) glycoproteins. Specifically, morphological alteration is associated with the ECM glycoprotein laminin, and growth inhibition is associated with both laminin and fibronectin. Both TGF-beta 1 and TGF-beta 2 down-modulate the expression of nucleolar protein B23 (also known as numatrin or nucleophosmin, a positive regulator of cell proliferation). With one exception, the biological effects of both TGF-beta 1 and TGF-beta 2 on these human colon carcinoma cell lines are identical. Both GFs up-modulate the expression of carcinoembryonic antigen (CEA) and CEA-related gene products. However, some of these products are differentially regulated by TGF-beta 1 and TGF-beta 2. The differences in the profile of the induction of these CEA and CEA-related gene products, in the responsive cells, functionally distinguish TGF-beta 1 from TGF-beta 2. Finally, we identified and characterized some of the cellular proteins, the expression of which is up-modulated by GF. These proteins are epithelium-associated, differentiation-related cytokeratins. Both TGF-beta 1 and TGF-beta 2 up-modulate expression of the acidic and basic subtypes of human keratins in the responsive human colon carcinoma cells. Both the responsive and unresponsive cells, however, possess receptors for GFs.


Discovery of Novel Apigenin-Piperazine Hybrids as Potent and Selective Poly (ADP-Ribose) Polymerase-1 (PARP-1) Inhibitors for the Treatment of Cancer.
Poly (ADP-ribose) polymerase-1 (PARP-1) is a potential target for the discovery of chemosensitizers and anticancer drugs. Amentoflavone (AMF) is reported to be a selective PARP-1 inhibitor. Here, structural modifications and trimming of AMF have led to a series of AMF derivatives (9a-h) and apigenin-piperazine/piperidine hybrids (14a-p, 15a-p, 17a-h, and 19a-f), respectively. Among these compounds, 15l exhibited a potent PARP-1 inhibitory effect (IC50 = 14.7 nM) and possessed high selectivity to PARP-1 over PARP-2 (61.2-fold). Molecular dynamics simulation and the cellular thermal shift assay revealed that 15l directly bound to the PARP-1 structure. In in vitro and in vivo studies, 15l showed a potent chemotherapy sensitizing effect against A549 cells and a selective cytotoxic effect toward SK-OV-3 cells through PARP-1 inhibition. 15l·2HCl also displayed good ADME characteristics, pharmacokinetic parameters, and a desirable safety margin. These findings demonstrated that 15l·2HCl may serve as a lead compound for chemosensitizers and the (BRCA-1)-deficient cancer therapy.


Conservative aortic valve surgery and supra-coronary tube: a case report.
Conservative aortic valve surgery is becoming an effective alternative to aortic valve replacement for patients with aortic insufficiency (AI) and ascending aortic aneurysms. It has become a crucial component of the therapeutic arsenal recommended by the learned societies. This paper reports the case of a patient with severe AI following dilatation of the supra-coronary aorta that underwent aortic plasty associated with a supra-coronary tube in the Cardiovascular Surgery Department 'A' of the Ibn Sina Hospital, Rabat, Morocco.


Living with and without an intestinal stoma: Factors that promote psychological well-being and self-care: A cross-sectional study.
This study compared those living with and without an intestinal stoma in relation to physical and psychological health, stress and coping, quality of life and resilience. Also, identifying factors that could be used to promote better self-care in stoma patients in the future. A cross-sectional and comparative study design was employed. Participants were recruited via email and social media (Facebook and Twitter) between August 2018 and March 2019, to complete an online survey. The data were analysed using analysis of variance to examine group difference and a series of hierarchical linear regression analyses determining predictors of psychological well-being. Of 278 participants aged 18-68 years who completed the survey, 129 (46%) had a stoma and reported significantly poorer physical health. Approximately one-fifth experienced problems with stoma management. Psychological well-being was mediated by the duration of living with a stoma (under 3 years) and frequency of leaks (weekly and monthly).


Changing Nonstuttering Preschool Children's Stuttering Attitudes.
Negative or uninformed stuttering attitudes proliferate among the general public, and bourgeoning research has shown that such attitudes might emerge as early as the preschool years. Much remains unknown about young children's stuttering attitudes, and conclusive recommendations to improve attitudes toward stuttering have yet to be advanced. This study sought to determine the effect of a new educational program on improving stuttering attitudes among preschool children using objective measures. Thirty-seven preschool children learned about stuttering and sensitive peer interactions by participating in the newly developed Attitude Change and Tolerance program. The program teaches children about human differences with an emphasis on stuttering and how to interact with people who stutter. Children's stuttering attitudes were measured using the Public Opinion Survey of Human Attributes-Stuttering/Child (Weidner & St. Louis, 2014) before and after the program. Pre-post comparisons showed statistically significant improvements in children's overall stuttering attitudes. In particular, children demonstrated gains relative to their perceptions of and reactions toward people who stutter. This study provides empirical evidence that young children's stuttering attitudes can be improved using the Attitude Change and Tolerance program. In addition, it supports previous research that negative stuttering attitudes emerge as early as preschool.


The role of hepatokines in metabolism.
The liver is known to be involved in the natural history of the ongoing epidemics of type 2 diabetes mellitus and cardiovascular disease. In particular, the liver has a role in increased glucose production and dysregulated lipoprotein metabolism, conditions that are often found in patients with nonalcoholic fatty liver disease. Additionally, several proteins that are exclusively or predominantly secreted from the liver are now known to directly affect glucose and lipid metabolism. In analogy to the functional proteins released from adipose tissue and skeletal muscle-adipokines and myokines-these liver-derived proteins are known as hepatokines. The first hepatokine that has been proven to have a major pathogenetic role in metabolic diseases is α2-HS-glycoprotein (fetuin-A). Production of this glycoprotein is increased in steatotic and inflamed liver, but not in expanded and dysregulated adipose tissue. Thus, research into this molecule and other hepatokines is expected to aid in differentiating between the contribution of liver and those of skeletal muscle and adipose tissue, to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease.


Porcine blood used as ingredient in meat productions may serve as a vehicle for hepatitis E virus transmission.
The aim of the present study was to investigate whether the use of porcine blood(products) in food could be a risk for a hepatitis E virus (HEV) infection. HEV RNA was detected in 33/36 batches of (non-heated) liquid products and in 7/24 spray dried powder products. Contamination levels varied among the products, but were highest in liquid whole blood, plasma and fibrinogen reaching levels of 2.2×102 to 2.8×102 HEV genome copies per 0.2g. Sequence analyses revealed genotype 3 strains, of which two were 100% (493nt) identical to recently diagnosed HEV cases, although no direct epidemiological link was established. The industry provided information on processing of blood products in (ready-to-eat)-meat. From this, it was concluded that blood products as an ingredient of processed meat may not be sufficiently heated prior to consumption, and therefore could be a vehicle for transmission.


The Biopsychosocial Impact of COVID-19 on Older Adults.
COVID-19 has spread rapidly around the world and taken over 2.6 million lives. Older adults experience disproportionate morbidity and mortality from the disease because increasing age and the presence of comorbidities are important predictors of negative outcomes. Lasting effects of COVID-19 have been described after recovery from the acute illness despite eradication of the virus from the body. The impact of COVID-19 on a person's biological health post-infection is observed in multiple systems including respiratory, cardiac, renal, haematological, and neurological. Psychological dysfunction following recovery is also prevalent. Social factors such as distancing and stay at home measures leave older adults isolated and food insecure; they also face intertwined financial and health risks due to the resulting economic shutdown. This study examines the effects of COVID-19 on older adults using the biopsychosocial model framework.


Numerical Model Study of In Vivo Magnetic Nanoparticle Tumor Heating.
Iron oxide nanoparticles are currently under investigation as heating agents for hyperthermic treatment of tumors. Major determinants of effective heating include the biodistribution and minimum iron oxide loading required to achieve adequate heating at practically achievable magnetic field strengths. These inter-related criteria ultimately determine the practicality of this approach to tumor treatment. Further, in our experience the currently used treatment assessment criterion for hyperthermia treatment-cumulative equivalent minutes at 43 °C, CEM43 -provides an inadequate description of the expected treatment effectiveness. Couple numerical models to experimental measurements to study the relative heating effectiveness described by cell death predictions. FEM numerical models were applied to increase the understanding of a carefully calibrated series of experiments in mouse mammary adenocarcinoma. The numerical model results indicate that minimum tumor loadings between approximately 1.3 to 1.8 mg of Fe per cm3 of tumor tissue are required to achieve the experimentally observed temperatures in magnetic field strengths of 32 kA/m (rms) at 162 kHz. We show that including multiple cell death processes operating in parallel within the numerical models provides valuable perspective on the likelihood of successful treatment. We show and believe that these assessment methods are more accurate than a single assessment figure of merit based only on the comparison of thermal histories, such as the CEM method.


Determination of contents and antioxidant activity of free and bound phenolics compounds and in vitro digestibility of commercial black and red rice (Oryza sativa L.) varieties.
Black and red rices (Oryza sativa L.) were analysed for total flavonoids and phenolics and the HPLC profile including both free and bound phenolic fractions. Moreover, antioxidant activity and in vitro digestibility was determined. Content of flavonoids and polyphenols as well as antioxidant activity was higher in free phenolic fractions. Bound flavonoids in black rices were not significant contributors to antioxidant activity. The main free phenolics in black rices were ferulic, protocatechuic and trans-p-coumaric acids, while the major free phenolics in red rices were catechin, protocatechuic and caffeic acids. The main bound phenolics in black rices were ferulic and vanillic acids and quercetin, in red rice types, they were ferulic, syringic, trans-p-coumaric acids and quercetin. Newly, the presence of m-coumaric acid in red rices was detected. Steam cooked rices showed very high levels of organic matter digestibility, whereas red rices were significantly more digestible than black rices (p<0.05).


Cocaine abuse in methadone maintenance programs: integrating pharmacotherapy with psychosocial interventions.
Cocaine abuse by methadone-maintained patients threatens to undermine the success of methadone programs by sustaining a drug-abusing lifestyle as well as contributing to the spread of HIV. The search for a pharmacotherapeutic agent for the treatment of cocaine has met with limited success. The most promising results emerge when specific agents, such as desipramine, are matched appropriately to specific patient characteristics, such as depression or antisocial personality disorder. For some patients, abstinence from cocaine may also require the addition of intensive psychosocial treatments that target the considerable problems faced by inner-city opioid-addicted individuals. This article discusses ways in which future research could be directed toward investigating the interaction between psychosocial services and pharmacologic treatments, while at the same time developing and testing hypotheses concerning appropriate patient-treatment matching variables.


Induction and Stabilization of Columnar Mesophases in Fluorinated Polycyclic Aromatic Hydrocarbons by Arene-Perfluoroarene Interactions.
The straightforward synthesis of several Fluorinated Polycyclic Aromatic Hydrocarbons by the efficient, transition-metal-free, arene fluorine nucleophilic substitution reaction is described, and the full investigation of their liquid crystalline and optical properties reported. The key precursors for this study, i. e. 2,2'-dilithio-4,4',5,5'-tetraalkoxy-1,1'-biphenyl derivatives, were obtained in two steps from the highly selective Scholl oxidative homo-coupling of 3,4-dialkoxy-1-bromobenzene, followed by quantitative double-lithiation. In situ room temperature nucleophilic annulation with either perfluorobenzene or perfluoronaphthalene leads to 1,2,3,4-tetrafluoro-6,7,10,11-tetraalkxoytriphenylenes and 9,10,11,12,13,14-hexafluoro-2,3,6,7-tetraalkoxybenzo[f]tetraphenes, respectively, in good yields. Exploiting the same strategy, subsequent double annulations resulted in the formation of 9,18-difluoro-2,3,6,7,11,12,15,16-octa(alkoxy)tribenzo[f,k,m]tetraphenes and 9,10,19,20-tetrafluoro-2,3,6,7,12,13,16,17-octakis(hexyloxy)tetrabenzo[a,c,j,l]tetracenes, respectively. Despite the presence of only four alkoxy chains, the polar "Janus" mesogens display a columnar hexagonal mesophase over broad temperature ranges, with higher mesophase stability than the archetypical 2,3,6,7,10,11-hexa(alkoxy)triphenylenes and their hydrogenated counterparts. The improvement or induction of mesomorphism is attributed to efficient antiparallel face-to-face π-stacking driven by the establishment of non-covalent perfluoroarene-arene intermolecular interactions. The larger lipophilic discotic π-extended compounds also exhibit columnar mesomorphism, over similar temperature ranges and stability than their hydrogenated homologs. Finally, these fluorinated molecules form stringy gels in various solvents, and show interesting solvatochromic emission properties in solution as well as strong emission in thin films and gels.


The nitroblue tetrazolium test in Crohn's disease and ulcerative colitis.
In subjects with Crohn's disease and ulcerative colitis, an increased percentage of peripheral blood neutrophils reduces the dye nitroblue tetrazolium. This is probably a non-specific index of inflammatory activity. There is no evidence that defective neutrophil function, as measured by this test, contributes to granuloma formation in Crohn's disease.


A High Fiber Cookie Made with Resistant Starch Type 4 Reduces Post-Prandial Glucose and Insulin Responses in Healthy Adults.
Distarch phosphate is a resistant starch type 4 (RS4) containing phosphodiester cross-links within and between starch molecules. This study examined the glycemic effects of VERSAFIBE 1490™ resistant starch, a distarch phosphate derived from potato, containing 90% total dietary fiber (TDF, AOAC 991.43 method). In this double-blind, randomized, placebo-controlled, cross-over study, 28 healthy adults consumed a cookie containing 24 g fiber from distarch phosphate (fiber cookie) or a control cookie containing 0.5 g fiber that was matched for fat, protein, and total carbohydrate content. Intravenous blood glucose, intravenous blood insulin, and capillary glucose were measured for two hours after cookie consumption. The fiber cookie reduced the post-prandial blood glucose incremental area under the curve from 0 to 120 minutes (iAUC0-120min) by 44% (p = 0.004) and reduced the maximum glucose concentration (Cmax0-120min) by 8% (p = 0.001) versus the control cookie. Consumption of the fiber cookie resulted in a significant 46% reduction of the post-prandial serum insulin iAUC0-120min (p < 0.001) and a 23% reduction in Cmax0-120min (p = 0.007) versus the control cookie. This study shows that distarch phosphate RS4 can be incorporated into a cookie and significantly reduce post-prandial glucose and insulin responses in healthy adults.


Dante's 'Two Suns': Reflections on the psychological sources of the Divine Comedy.
The power of Dante's Divine Comedy is unmistakable, but surprising in view of its theological structure and assumptions that are no longer current among most modern readers. This paper suggests that its power derives from the deep psychological truthfulness with which Dante deals with the painful personal crisis that underlies the poem and is his starting point. It attempts to clarify what may have constituted that crisis, and why the structure of the Comedy, and in particular its use of two guides, Virgil and Beatrice, who might be thought a somewhat incompatible pairing, point significantly to the nature of the solution Dante arrived at. In particular it suggests that the puzzling fictions to do with Statius in the Purgatorio are a clue to Dante's own difficulties in bridging the classical and Christian traditions, and that his highly original solution to these difficulties, by no means conforming to conventional Christian orthodoxy in the 13th/14th century, was needed with special urgency in a time of pervasive civil conflict.


Growth rate and physiology of Yersinia enterocolitica; influence of temperature and presence of the virulence plasmid.
The effect of temperature on the growth rate, protein pattern and fatty acid composition of Yersinia enterocolitica strain W22703 pYV+, its plasmidless isogeneic derivative W22703 pYV- and four recent field isolates was examined. The growth rate was clearly influenced by presence or absence of the virulence plasmid: pYV- strains grew consistently faster than pYV+ strains. This difference in growth rate was high at 30-35 degrees C, moderate at 1-10 degrees C and 25 degrees C, but hardly significant at 15-20 degrees C. Increasing the growth temperature above 25 degrees C resulted in the induction of the 220 kDa virulence plasmid-encoded Yop1 protein. In the 1-20 degrees C range no obvious temperature- or plasmid-related differences in protein patterns could be detected. The fatty acid composition showed a clear temperature-dependent change: with all strains the degree of saturation was low at 1 degrees C and gradually increased with raising temperatures. All strains had similar fatty acid patterns, except one of the field isolates which showed aberrant C16: 1 and cyclic fatty acid contents in the 5-25 degrees C and < or = 15 degrees C ranges respectively. With strain W22703, the presence or absence of the virulence plasmid did not significantly alter the fatty acid pattern.


Fetal pathology produced by ethylene oxide treatment of the murine zygote.
Exposure of female mice to ethylene oxide by inhalation 1 or 6 h after mating produced not only multitemporal death of conceptuses but also high rates of abnormalities among surviving fetuses. In contrast, only marginal effects were observed when females were exposed 9 or 25 h after mating. The abnormalities found among 17 day gestation live fetuses were predominated by hydrops and eye defects, which, together, constitute 54% of all anomalies. Most of the remaining anomalies were distributed among 5 other types: small size, cleft palate, and cardiac, abdominal wall, or extremity and/or tail defects. In a follow-up study, the fetuses of females treated 6 h postmating were examined at 11-15 days gestation and the progression of fetal death and of malformations was studied. Results indicate that the expression of most fetal anomalies does not become apparent until late in gestation. Several of these induced anomalies are similar to common human sporadic birth defects. This new class of experimentally induced fetal anomalies provides a new avenue for investigating zygotic biology and a system for studying the progression of aberrant development.


Full-length cDNA cloning utilizing the polymerase chain reaction, a degenerate oligonucleotide sequence and a universal mRNA primer.
A full-length cDNA was selectively amplified by the polymerase chain reaction (PCR) utilizing a primer pair consisting of a "universal" 21-base synthetic deoxyoligonucleotide (oligo dT 17GGCC) and a specific degenerate deoxyoligonucleotide sequence (DOS) derived from the N-terminal amino acid sequence. This double-stranded amplified cDNA was uni-directionally cloned into M13mp19 utilizing two restriction sites that had been previously incorporated into the termini of the universal and specific DOS primers. Cloning of the specific cDNA via this PCR amplification with the universal/specific DOS primer pair approach was confirmed by screening with a second DOS contiguous with the DOS employed to prime second (sense)-strand cDNA synthesis. This technique allows for the selective full-length cDNA cloning of low-abundance mRNAs from a single-protein sequence determination.


A comparative study on knowledge towards COVID-19 prevention among undergraduate students in Macao and Zhuhai, China.
In order to develop the strategy more suitable campus-based coronavirus disease 2019 (COVID-19) prevention programs for undergraduate students, it is critical to identify discrepancies in knowledge of COVID-19 prevention among students from different campuses in China. The present study examined the difference in preventive knowledge about COVID-19 pandemic in undergraduate students from two cities of Guangdong-Hong Kong-Macao Greater Bay Area (GBA), Macao Special Administrative Region (SAR), which had very few cases of COVID-19 patients, and Zhuhai, which is borders Macao SAR. In August 2020, two cohorts of undergraduate students from universities in Macao (n = 977) and Zhuhai (n = 2,818) were recruited for online. The self-rating questionnaire was used to gain information about their knowledge in COVID-19 prevention. Macao and Zhuhai students had similar correct rates in terms of heat inactivation conditions of SARS-CoV-2, (76.8% vs. 76.9%, P = 0.950), etiquette when coughing and sneezing (75.9% vs. 75.0%, P = 0.562), and use of disposable masks (92.2% vs. 90.6%, P = 0.126). However, students from Macao had significantly higher rates in correct use of disinfectants against SARS-CoV-2 (24.6% vs. 17.5%, P < 0.001) and in the route of transmission of SARS-CoV-2 (84.5% vs. 79.6%, P < 0.001) than those from Zhuhai. In conclusion, the knowledge level of COVID-19 prevention differs among undergraduate students from Macao and Zhuhai, which warrants an appropriate region-specific health education strategie for COVID-19 prevention.


Conjunctival impression cytology in patients with glaucoma using long-term topical medication.
Increasing evidence indicates that long-term use of topically administered medications can induce changes in the conjunctiva and ocular surface. We used the technique of conjunctival impression cytology to evaluate the conjunctival changes that develop with long-term use of topically administered antiglaucoma medications. Patients with glaucoma who were on a stable regimen of one, two, or three topically administered medications were recruited for study; glaucoma suspects who were not using topically administered medications served as controls. Eyes with clinical or historical evidence of external eye disease or conjunctival surgery were excluded. Impression cytology specimens, collected from the bulbar and palpebral conjunctiva, were coded and subsequently graded by a masked observer. We examined specimens from 72 eyes by using this technique. Aggregate scores for the bulbar conjunctiva were compiled, using a previously described grading system with a range of 0 (normal) to 3 (diffuse, severe metaplasia). The results show statistically significant degrees of conjunctival metaplasia associated with the number of glaucoma medications used. These results suggest that the long-term use of antiglaucoma medications induces changes in the conjunctival surface. These changes may be related to the medications themselves, the preservatives in the commercial preparations, or the duration of topical treatment. The clinical relevance of these changes remains unknown.


Ablation of the N-type calcium channel ameliorates diabetic nephropathy with improved glycemic control and reduced blood pressure.
Pharmacological blockade of the N- and L-type calcium channel lessens renal injury in kidney disease patients. The significance of specific blockade of α1 subunit of N-type calcium channel, Cav2.2, in diabetic nephropathy, however, remains to be clarified. To examine functional roles, we mated Cav2.2(-/-) mice with db/db (diabetic) mice on the C57BLKS background. Cav2.2 was localized in glomeruli including podocytes and in distal tubular cells. Diabetic Cav2.2(-/-) mice significantly reduced urinary albumin excretion, glomerular hyperfiltration, blood glucose levels, histological deterioration and systolic blood pressure (SBP) with decreased urinary catecholamine compared to diabetic Cav2.2(+/+) mice. Interestingly, diabetic heterozygous Cav2.2(+/-) mice also decreased albuminuria, although they exhibited comparable systolic blood pressure, sympathetic nerve activity and creatinine clearance to diabetic Cav2.2(+/+) mice. Consistently, diabetic mice with cilnidipine, an N-/L-type calcium channel blocker, showed a reduction in albuminuria and improvement of glomerular changes compared to diabetic mice with nitrendipine. In cultured podocytes, depolarization-dependent calcium responses were decreased by ω-conotoxin, a Cav2.2-specific inhibitor. Furthermore, reduction of nephrin by transforming growth factor-β (TGF-β) in podocytes was abolished with ω-conotoxin, cilnidipine or mitogen-activated protein kinase kinase inhibitor. In conclusion, Cav2.2 inhibition exerts renoprotective effects against the progression of diabetic nephropathy, partly by protecting podocytes.


Law & psychiatry: Genetic discrimination in mental disorders: the impact of the genetic information nondiscrimination act.
Genetics is one of the most active areas of research on mental disorders. As genetic tests related to psychiatric disorders and their treatments proliferate in research and clinical settings, the possibility becomes more troubling that such information will be used for purposes other than those for which it was collected. Because of this, the federal Genetic Information Nondiscrimination Act of 2008 is of substantial importance to persons with mental disorders, persons at risk for the conditions, and family members of both groups. This column discusses the process of passing the legislation, along with the implications of the act.


Nonmedical prescription drug use (NMPDU) in the Swedish general population--correlates of analgesic and sedative use.
Nonmedical prescription drug use (NMPDU) is a growing problem in many countries. The aim of the present study was to report correlates of and compare different subtypes of NMPDU in the Swedish general population. Data were drawn from a Swedish national household survey conducted in 2008-2009. A stratified sample of 58,000 individuals aged 15 to 64 was randomly selected, with a response rate of 38.3%. Hierarchical logistic regression analysis was used to compare sociodemographic, substance use, and health correlates of nonmedical analgesic use, nonmedical sedative use, and combined nonmedical use of these two types of prescription drugs. In the final logistic regression model, all three patterns of NMPDU were equally associated with female gender, hazardous alcohol use, habitual smoking and cannabis use, but there were several significant differences in other demographic, health, and drug use correlates between the groups. CONCLUSIONS/IMPORTANCE: Nonmedical use of prescription analgesics, prescription sedatives and combined nonmedical use of these drugs might constitute clinically distinct subgroups of NMPDU. This study is one of few to report correlates of NMPDU from a large, national household survey in a country other than the United States.


Noncovalent control for bottom-up assembly of functional supramolecular wires.
Noncovalent bonds have been used to assemble stacks of pi-electron-rich moieties at a surface, generating a pathway for charge transport. The system is comprised of a tetrathiafulvalene (TTF) derivative incorporating two amide groups which fasten the relative orientations of the electroactive moieties in the supramolecular polymer that is formed at the surface of graphite in octanoic acid. Scanning tunneling microscopy (STM) combined with molecular mechanics calculations has been used to prove the structure of the wires, and theory, corroborated with STS experiments, predicts that they are promising superstructures for charge transport.


Dicarbonyl-dichloridobis(trimethyl-phosphane)iron(II)-carbonyl-dichlorido-tris(trimethyl-phosphane)iron(II)-tetra-hydro-furan (1/1/2).
The asymmetric unit of the title crystal, [FeCl(2)(C(3)H(9)P)(3)(CO)]·[FeCl(2)(C(3)H(9)P)(2)(CO)(2)]·2C(4)H(8)O, contains half mol-ecules of the two closely related Fe(II) complexes lying on mirror planes and a tetra-hydro-furan solvent mol-ecule, one C atom of which is disordered over two sets of sites with site occupancy factors 0.633 (9) and 0.367 (9). In both Fe(II) complex mol-ecules, a distorted octa-hedral coordination geometry has been observed around the Fe atoms. Weak intermolecular C-H⋯O inter-actions are observed in the crystal structure.


The Free and Cued Selective Reminding Test in Parkinson's Disease Mild Cognitive Impairment: Discriminative Accuracy and Neural Correlates.
Introduction: Memory alterations are common in Parkinson's disease (PD) patients but the mechanisms involved in these deficits remain poorly understood. The study aims to explore the profile of episodic memory deficits in non-demented early PD patients. Methods: We obtained neurological, cognitive and behavioral data from 114 PD patients and 41 healthy controls (HC). PD participants were grouped as normal cognition (PD-NC) and mild cognitive impairment (PD-MCI) according to the Level II criteria of the Movement Disorders Society Task Force (MDS-TF). We evaluate the performance amongst groups on an episodic memory task using the Free and Cued Selective Reminding Test (FCSRT). Additionally, gray matter volume (GMV) voxel based morphometry, and mean diffusivity (MD) analyses were conducted in a subset of patients to explore the structural brain correlates of FCSRT performance. Results: Performance on all subscores of the FCSRT was significantly worse in PD-MCI than in PD-NC and HC. Delayed total recall (DTR) subscore was the best at differentiating PD-NC from PD-MCI. Using crosstabulation, DTR allowed identification of PD-MCI patients with an accuracy of 80%. Delayed free and cued recall was associated with decreased GMV and increased MD in multiple fronto-temporal and parietal areas. Conclusion: Encoding and retrieval deficits are a main characteristic of PD-MCI and are associated with structural damage in temporal, parietal and prefrontal areas.


Accurate indel prediction using paired-end short reads.
One of the major open challenges in next generation sequencing (NGS) is the accurate identification of structural variants such as insertions and deletions (indels). Current methods for indel calling assign scores to different types of evidence or counter-evidence for the presence of an indel, such as the number of split read alignments spanning the boundaries of a deletion candidate or reads that map within a putative deletion. Candidates with a score above a manually defined threshold are then predicted to be true indels. As a consequence, structural variants detected in this manner contain many false positives. Here, we present a machine learning based method which is able to discover and distinguish true from false indel candidates in order to reduce the false positive rate. Our method identifies indel candidates using a discriminative classifier based on features of split read alignment profiles and trained on true and false indel candidates that were validated by Sanger sequencing. We demonstrate the usefulness of our method with paired-end Illumina reads from 80 genomes of the first phase of the 1001 Genomes Project ( http://www.1001genomes.org) in Arabidopsis thaliana. In this work we show that indel classification is a necessary step to reduce the number of false positive candidates. We demonstrate that missing classification may lead to spurious biological interpretations. The software is available at: http://agkb.is.tuebingen.mpg.de/Forschung/SV-M/.


Pregnancy's effects on the skin. Common and uncommon changes.
The skin almost always shows changes during pregnancy. Some of these alterations are so predictable as to be considered normal. Not nearly so common are a host of pruritic dermatoses, including pruritus gravidarum, herpes gestationis, pruritic urticarial papules and plaques of pregnancy, Spangler 's papular dermatitis of pregnancy, and impetigo herpetiformis. Some of these conditions can cause maternal and/or fetal complications and even death; others, although benign and transient, add to the stress of pregnancy. Physician adeptness at diagnosing and treating skin diseases specific to or affected by pregnancy is thus of vital importance in caring for pregnant women.


Beef flavor vegetable hamburger patties with high moisture meat analogs (HMMA) with pulse proteins-peas, lentils, and faba beans.
Pulses have been an excellence source of foods due to their nutritional profile including high protein content. In addition, they have less concerns about allergens, gluten, and genetically modified organisms. In this study, high moisture meat analogs (HMMA) that contained commercial pea protein (55.4% protein), lentil protein (55.4% protein), or faba bean protein (61.5% protein) mixed with other constant ingredients (pea isolates, and wheat gluten and canola oil) were produced using a twin-screw extruder (TX-52) with an attached cooling chamber. For consumer sensory tests and texture profile analysis, vegetable hamburger patties with HMMA were produced with the addition of spices, binders, and so on. Trained panelists reported that HMMA with pulses had higher scores on bean-like, sweet, and cohesiveness of mass compared to HMMA with soy that had higher soy, cardboardy, hardness, and springiness scores. Compared to the control, consumer panelists indicated that samples containing pulse proteins had no differences in consumers' liking for the cooked appearance and overall flavor, but had a lower overall texture liking score, and samples with faba bean proteins (FP) had a lower overall liking score. Cooked patties containing pulse proteins were redder and had more cooking yield. Patties with FP required less cooking time. Therefore, vegetable patties with pulse proteins are competitive with soy-based samples.


Activity of lung neutrophils and matrix metalloproteinases in cyclophosphamide-treated mice with experimental sepsis.
Sepsis in patients receiving chemotherapy may result in acute respiratory distress syndrome, despite decreased number of blood neutrophils [polymorphonuclear neutrophils (PMNs)]. In the present study, we investigated the correlation of cyclophosphamide (CY)-induced neutropenia with the destructive potential of lung PMN in respect to formation of septic acute lung injury (ALI). Mice were treated with 250 mg/kg of CY or saline (control) and subjected to cecal ligation and puncture (CLP) or sham operation. ALI was verified by histological examination. Lung PMNs and matrix metalloproteinases (MMPs) were assessed by flow cytometry and gelatin zymography. CLP in CY-treated mice induced a typical lung injury. Despite profound neutropenia, CY treatment did not attenuate CLP-induced ALI. This might relate to only a partial suppression of PMN: CY has significantly reduced PMN influx into the lungs (P = 0.008) and suppressed their oxidative metabolism, but had no suppressive effect on degranulation (P = 0.227) and even induced MMP-9 activity (P = 0.0003). In CY-untreated animals, peak of CLP-induced ALI coincided with massive PMN influx (P = 0.013), their maximal degranulation (P = 0.014) and activation of lung MMP-9 (P = 0.002). These findings may indicate an important role of the residual lung PMN and activation of MMP-9 in septic lung injury during CY chemotherapy.


Three Musketeers for Lowering Cholesterol: Statins, Ezetimibe and Evolocumab.
Coronary heart disease (CHD) is closely related to hypercholesterolemia, and lowering serum cholesterol is currently the most important strategy in reducing CHD. In humans, the serum cholesterol level is determined mainly by three metabolic pathways, namely, dietary cholesterol intake, cholesterol synthesis, and cholesterol degradation in vivo. An intervention that targets the key molecules in the three pathways is an important strategy in lowering serum lipids. Statins inhibit 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) to reduce low-density lipoprotein (LDL) by about 20% to 45%. However, up to 15% of patients cannot tolerate the potential side effects of high statin dosages, and several patients also still do not reach their optimal LDL goals after being treated with statins. Ezetimibe inhibits cholesterol absorption by targeting the Niemann-Pick C1-like 1 protein (NPC1L1), which is related to cholesterol absorption in the intestines. Ezetimibe lowers LDL by about 18% when used alone and by an additional 25% when combined with statin therapy. The proprotein convertase subtilisin/kexin type 9 (PCSK9) increases hepatic LDLR degradation, thereby reducing the liver's ability to remove LDL, which can lead to hypercholesterolemia. Evolocumab, which is a PCSK9 monoclonal antibody, can reduce LDL from baseline by 53% to 56%. The three drugs exert lipid-lowering effects by regulating the three key pathways in lipid metabolism. Combining any with the two other drugs on the basis of statin treatment has improved the lipid-lowering effect. Whether the combination of the three musketeers will reduce the side effects of monotherapy and achieve the lipid-lowering effect should be studied further in the future.


Statistical analysis of structural characteristics of protein Ca2+-binding sites.
To better understand the biological significance of Ca(2+), we report a comprehensive statistical analysis of calcium-binding proteins from the Protein Data Bank to identify structural parameters associated with EF-hand and non-EF-hand Ca(2+)-binding sites. Comparatively, non-EF-hand sites utilize lower coordination numbers (6 +/- 2 vs. 7 +/- 1), fewer protein ligands (4 +/- 2 vs. 6 +/- 1), and more water ligands (2 +/- 2 vs. 1 +/- 0) than EF-hand sites. The orders of ligand preference for non-EF-hand and EF-hand sites, respectively, were H(2)O (33.1%) > side-chain Asp (24.5%) > main-chain carbonyl (23.9%) > side-chain Glu (10.4%), and side-chain Asp (29.7%) > side-chain Glu (26.6%) > main-chain carbonyl (21.4%) > H(2)O (13.3%). Less formal negative charge was observed in the non-EF-hand than in the EF-hand binding sites (1 +/- 1 vs. 3 +/- 1). Additionally, over 20% of non-EF-hand sites had formal charge values of zero due to increased utilization of water and carbonyl oxygen ligands. Moreover, the EF-hand sites presented a narrower range of ligand distances and bond angles than non-EF-hand sites, possibly owing to the highly conserved helix-loop-helix motif. Significant differences between ligand types (carbonyl, side chain, bidentate) demonstrated that angles associated with each type must be classified separately, and the EF-hand side-chain Ca-O-C angles exhibited an unusual bimodal quality consistent with an Asp distribution that differed from the Gaussian model observed for non-EF-hand proteins. The results of this survey more accurately describe differences between EF-hand and non-EF-hand proteins and provide new parameters for the prediction and design of different classes of Ca(2+)-binding proteins.


Functional neuromuscular stimulation neuroprostheses for the tetraplegic hand.
Functional neuromuscular stimulation (FNS) of the C5 and C6 tetraplegic upper extremity has been shown to be a valid clinical tool for restoring controlled movement in the paralyzed hand. The current clinical system consists of a shoulder position transducer controlling an external microprocessor-based stimulator, which excites paralyzed muscle via the peripheral nerve using percutaneous leads or a multichannel, implantable stimulator. Tendon transfer surgery of paralyzed but innervated muscle may augment the neurologically deficient upper extremity by allowing the substitution of stronger motors or the addition of new motors where flaccid paralysis (dennervation) eliminates the usual muscle from a grasp pattern. Sensory feedback in the form of machine state and cognitive information can be provided to the normally innervated C5 dermatome skin by subcutaneous electrodes. C5- and C6-level tetraplegics using FNS can independently perform single-hand manipulative tasks at a level similar to that of subjects with intact C7 roots, although they lack the elbow control.


Coarctate and Pseudocoarctate Reactions: Stereochemical Rules.
Coarctate reactions are a distinct class of concerted reactions. They differ from other concerted reactions, such as S(N)2, E2, or pericyclic reactions, in such a way that atoms are involved in the transition state at which two bonds are made and two bonds are broken simultaneously. Similar to pericyclic reactions, an electron count can be used to predict reactivity and stereochemistry. The "coarctate rules" are derived from a topological variant of the aromaticity of the transition state principle. Pseudocoarctate transition states exhibit disconnections in the topology of orbital overlap and do not necessarily follow the coarctate rules.


Anatomic and Clinical Pathology Characterization of Drug-Induced Sinusoidal Obstruction Syndrome (Veno-Occlusive Disease) in Cynomolgus Macaques.
Sinusoidal obstruction syndrome (SOS) is a unique form of liver injury that occurs after exposure to chemotherapeutic drugs and toxins. The diagnosis of SOS in humans remains a challenge as the clinical criteria have low specificity and there are no reliable noninvasive biomarkers. The mechanism of injury is believed to be damage to liver endothelial cells, primarily sinusoidal endothelial cells (SECs), which leads to sinusoidal dilation, central venous fibrosis, and/or nodular regeneration. Nonclinical data suggest that this uncommon liver toxicity can be recapitulated in cynomolgus monkeys, and it is critical that pathologists are familiar with its characteristic clinicopathologic features. Elevations in liver enzymes, in particular aspartate aminotransferase, associated with isolated thrombocytopenia, should raise the suspicion of SEC injury for specific drug classes. Characterization of liver microscopic findings in monkeys benefits from the use of appropriate stains, such as reticulin stain, and VEGFR2 and CD34 immunohistochemical (IHC) stains. CD41 IHC demonstrates platelet accumulation in injured sinusoids, the likely cause of thrombocytopenia commonly reported in SOS. In conclusion, this report provides a comprehensive characterization of the pathology findings of drug-induced SOS in monkeys with the objectives of ensuring appropriate nonclinical recognition of the liability and informing clinical development strategy and monitoring.


Sutured Intrascleral Posterior Chamber Intraocular Lens Fixation with Ciliary Sulcus Location Guided by Ultrasonic Biological Microscopy: A Retrospective Analysis of Anatomical and Refractive Outcome.
To report the outcome of sutured intrascleral posterior chamber intraocular lens (PC IOL) fixation with ciliary sulcus location guided by ultrasonic biological microscopy (UBM). Patients who underwent a sutured intrascleral PC IOL fixation were reviewed and divided into four groups. In group 1, the traditional sulcus fixation (2 mm from limbus) of IOL was performed. In groups 2, 3, and 4, UBM was performed before surgery to locate the position of the ciliary sulcus as the haptics insertion position. IOL power was selected by decreasing the calculated value of the IOL power by 1.0 D, 1.0 D, 0.5 D, and 0.0 D, respectively. Sixty-one patients (63 eyes) were included in the four groups. After 4.1 ± 3.0 months' follow-up, the postsurgery spherical equivalent (SE) was 0.73 ± 1.86, 0.71 ± 0.84, 1.14 ± 0.45, and 0.07 ± 0.89 diopters (D), respectively. Statistical significance was reached for the postsurgery SE with target refraction between group 1 (p = 0.027, <0.05), group 2 (p = 0.003, <0.01), and group 3 (p = 0.017, <0.05). No significant difference existed for the postsurgery SE with target refraction in group 4 (p = 0.779, >0.05), and the postsurgery SE in group 4 was the nearest to target refraction. Intrascleral PC IOL fixation guided by UBM is helpful for locating the ciliary sulcus and satisfactory visual outcomes with a predictable IOL power calculation.


Characterization of the ligand binding activities of vitronectin: interaction of vitronectin with lipids and identification of the binding domains for various ligands using recombinant domains.
Vitronectin is a multifunctional plasma glycoprotein which may regulate the systems related to protease cascades such as the coagulation, fibrinolysis, and complement systems as well as cell adhesion. Solid-phase assays and affinity chromatography on immobilized glycolipids indicated that vitronectin purified under denaturing conditions bound to sulfatide (Gal(3-SO4)beta1-1ceramide), cholesterol 3-sulfate, and various phospholipids, but not gangliosides. Only the unfolded or multimeric form of vitronectin bound to sulfatide, suggesting a conformational dependency of the binding activity, while vitronectin bound to cholesterol 3-sulfate regardless of its conformational state. The recombinant domains of human vitronectin and mutants with certain domains deleted were separately expressed in E. coli as fusion proteins. Using the recombinants, sulfatide-, phosphatidylserine-, cholesterol 3-sulfate-, Type I collagen-, heparin-, and beta-endorphin-binding activities were found to be attributable to hemopexin domain 2 and hemopexin domain 1. The possibility was suggested that the presence of a somatomedin domain and/or connecting region flanking hemopexin domain 1 inactivated its heparin binding. De-N-glycosylation of plasma vitronectin significantly affected the cholesterol sulfate- and collagen-binding activities, although its effects were opposite. These findings suggest that diverse ligand-binding activities could be attributed to pexin family motifs but that the interdomain interactions and glycosylations modulate the ligand binding activities of vitronectin.


Apoptosis mediated chemosensitization of tumor cells to 5-fluorouracil on supplementation of fish oil in experimental colon carcinoma.
5-Fluorouracil has been considered as a cornerstone therapy for colorectal cancer; however, it suffers from low therapeutic response rate and severe side effects. Therefore, there is an urgent need to increase the clinical efficacy of 5-fluorouracil. Recently, fish oil rich in n-3 polyunsaturated fatty acids has been reported to chemosensitize tumor cells to anti-cancer drugs. This study is designed to understand the underlying mechanisms of synergistic effect of fish oil and 5-fluorouracil by evaluation of tumor cell-associated markers such as apoptosis and DNA damage. The colon cancer was developed by administration of N,N-dimethylhydrazine dihydrochloride and dextran sulfate sodium salt. Further these animals were treated with 5-fluorouracil, fish oil, or a combination of both. In carcinogen-treated animals, a decrease in DNA damage and apoptotic index was observed. There was also a decrease in the expression of Fas, FasL, caspase 8, and Bax, and an increase in Bcl-2. In contrast, administration of 5-fluorouracil and fish oil as an adjuvant increased both DNA damage and apoptotic index by activation of both extrinsic and intrinsic apoptotic pathways as compared to the other groups. The increased pro-apoptotic effect by synergism of 5-fluorouracil and fish oil may be attributed to the incorporation of n-3 polyunsaturated fatty acids in membrane, which alters membrane fluidity in cancer cells. In conclusion, this study highlights that the induction of apoptotic pathway by fish oil may increase the susceptibility of tumors to chemotherapeutic regimens.


Adolescents and young adults differ in their neural response to and recognition of adolescent and adult emotional faces.
Peer relationships become increasingly important during adolescence. The success of these relationships may rely on the ability to attend to and decode subtle or ambiguous emotional expressions that are common in social interactions. However, most studies examining youths' processing and labeling of facial emotion have employed adult faces and faces that depict emotional extremes as stimuli. In this study, 40 adolescents and 40 young adults viewed blends of angry-neutral, fearful-neutral, and happy-neutral faces (e.g., 100% angry, 66% angry, 33% angry, neutral) portrayed by adolescent and adult actors as electroencephalogram (EEG) was recorded. Participants also labeled these faces according to the emotion expressed (i.e., angry, fearful, happy, or neutral). The Late Positive Potential (LPP), an event-related potential (ERP) component that reflects sustained attention to motivationally salient information, was scored from the EEG following face presentation. Among adolescents, as peer-age faces moved from ambiguous (33%) to unambiguous (100%) emotional expression, the LPP similarly increased. These effects were not found when adolescents viewed emotional face blends portrayed by adult actors. Additionally, while both adolescents and young adults showed greater emotion labeling accuracy as faces increased in emotional intensity from ambiguous to unambiguous emotional expression, adolescent participants did not show greater accuracy when labeling peer-compared to adult-age faces. Together, these data suggest that adolescents attend more to subtle differences in peer-age emotional faces, but they do not label these emotional expressions more accurately than adults.


Contribution of Group Therapeutic Factors to the Outcome of Cognitive-Behavioral Therapy for Patients with Panic Disorder.
Investigating the contribution of therapeutic factors arising from the collective nature or group therapy to treat mental disorders may help therapists maximize the outcome of therapy. Studies about the role of therapeutic factors in cognitive-behavioral group therapy (CBGT) for panic disorder (PD) patients are still scarce. To identify the therapeutic factors rated as the most useful by patients during CBGT. Also, we aimed to investigate the relationship between patient rating of therapeutic factors and specific stages of CBGT. Non-controlled clinical trial. A 12-session CBGT protocol was set up, covering psychoeducation, techniques for anxiety coping, cognitive restructuring, interoceptive and naturalistic exposure, and live exposure to avoidant behavior. PD symptom severity was assessed before and after the CBGT protocol. Yalom's Curative Factors Questionnaire was self-administered at the end of each session to evaluate the 12 therapeutic factors. The sample consisted of 16 patients, who produced 192 assessments of therapeutic factors. Severity of symptoms improved at the end of CBGT, with a large effect size (>1.0). Different ratings were attributed to therapeutic factors at different phases of CBGT. Seven factors were rated as significantly helpful: altruism, interpersonal learning/input, guidance, identification, family reenactment, self-understanding, and existential factors. Therapeutic factors are dynamic and interdependent. Therefore, recognizing the impact of these factors during CBGT may potentially contribute to a better understanding of the therapeutic process.


[Influence of the anatomy of the pedicle on the survival of venous vascularized flaps. Experimental study on the rat].
The aim of this work was to compare the survival of an arteriovenous island flap with the survival of an island flap with a venous supply. The anatomy of the pedicule was modified to assess the conditions of survival. Our experimental studies were performed on 125 Wistar rats randomised into eight groups. Group 1: control group of epigastric flaps deprived of vascularisation. Group 2: control group of abdominal transverse flaps with arteriovenous supply. Group 3: control group of epigastric flaps with arteriovenous supply. Groupe 4: through-flow abdominal transverse venous flaps. Group 5: epigastric through-flow venous flaps with a main venous trunck. Group 6: epigastric flaps with nervous and perivenous pedicule. Group 7: epigastric flaps with nervous and venous pedicule. Group 8: epigastric flaps with through-flow nervous and venous pedicule. Twenty-four additional rats were histologically assessed. The survival of flaps was monitored by direct examination and histological examination. Two out of the 20 flaps of group 4 survived as well as two out of the 30 flaps of group 5. Four of the 15 flaps of group 8 partially survived around the pedicule area. The venous vascularisation does not explain the survival of so-called venous flaps. The survival is increased by through-flow venous supply, and preservation of perivenous tissues.


Natural Products from Mediterranean Diet: From Anti-hyperlipidemic Agents to Dietary Epigenetic Modulators.
Cardiovascular Diseases (CVD) are, currently, the major contributor to global mortality and will continue to dominate mortality rates in the future. Hyperlipidemia refers to the elevated levels of lipids and cholesterol in the blood, and is also identified as dyslipidemia, manifesting in the form of different disorders of lipoprotein metabolism. These abnormalities may lead to the development of atherosclerosis, which can lead to coronary artery disease and stroke. In recent years, there is a growing interest in the quest for alternative therapeutic treatments based on natural products, offering better recovery and the avoidance of side effects. Recent technological advances have further improved our understanding of the role of epigenetic mechanisms in hyperlipidemic disorders and dietary prevention strategies. This is a comprehensive overview of the anti-hyperlipidemic effects of plant extracts, vegetables, fruits and isolated compounds thereof, with a focus on natural products from the Mediterranean region as well as the possible epigenetic changes in gene expression or cardiometabolic signaling pathways. For the purpose of this study, we searched the PubMed, Scopus and Google Scholar databases for eligible articles and publications over the last five years. The keywords included: "hyperlipidemia", "plant extract", "herbs", "natural products", "vegetables", "cholesterol" and others. We initially included all relevant articles referring to in vitro studies, animal studies, Randomized Controlled Trials (RCTs) and previous reviews. Many natural products found in the Mediterranean diet have been studied for the treatment of hyperlipidemia. The antihyperlipidemic effect seems to be dose and/or consumption frequency related, which highlights the fact that a healthy diet can only be effective in reversing disease markers if it is consistent and within the framework of a healthy lifestyle. Finally, epigenetic biomarkers are increasingly recognized as new lifestyle management tools to monitor a healthy dietary lifestyle for the prevention of hyperlipidaemic disorders and comorbidities to promote a healthy life.


["I want to die" – dealing with suicidal wishes in primary palliative care].
Different attitudes towards, and ideas about the end of life, represent an often experienced challenge in palliative care provided by family doctors. If values diverge too strongly, considerable strain can originate from it for the health care professionals, in particular if it is about assisted suicide. How do family doctors experience the incompatibility between patients' wishes and personal values? How do they succeed to bridge value divergences? Based on group discussions with family doctors in Switzerland the contribution focusses on these questions and identifies different strategies of family doctors. The results indicate that in particular 'convergence of perspectives' with patients can reduce the strain for family doctors and can at the same time guarantee high quality of care.


Prediction of Response to Targeted Treatment in Rheumatoid Arthritis.
Rheumatoid arthritis is an autoimmune syndrome presenting with chronic inflammation of the joints. Patients with the same diagnosis can present with different phenotypes. In some patients severe joint inflammation and early joint destruction are observed, whereas a milder phenotype can be seen in others. Conversely, patients with the same signs and symptoms may exhibit different immunological and molecular abnormalities. Since the introduction of early treatment in clinical practice, the treat to target principle, and new medicines such as biologic disease-modifying antirheumatic drugs, clinical remission can be achieved early in the disease course, albeit not in all patients. The clinical response and efficacy of biologic disease-modifying antirheumatic drugs vary among different individuals. Therefore, there is a need to develop a more personalized approach toward treatment to achieve rapid remission in every patient to prevent disability and restore and maintain quality of life, without unnecessary adverse effects, in a cost-effective manner. The latest data from explorative studies of predictive markers of response are discussed here, together with a preliminary treatment algorithm based on currently available knowledge.


Infertility and endometriosis: a need for global management that optimizes the indications for surgery and ART.
Endometriosis causes pelvic pain and infertility. Infertility results from effects of endometriosis exerted in the pelvic cavity, in the ovaries and/or on the uterus. Medical treatment effective on pain and at preventing disease recurrence following surgery is of no use for improving the chances of conceiving naturally. Surgery however improves the chances of conceiving in the 12-18 months afterward. Endometriosis through extension of the disease to the ovaries may harm ovarian response to COS needed in ART. Surgery for endometrioma(s) may further reduce ovarian responses to COS in case of endometriosis. Remarkably however, reduced ovarian responses due to endometriosis are not necessarily associated with reduced oocyte quality and ART outcome. Pre-ART treatment with oral contraceptives (OC) improves ART outcome in case of ovarian endometriosis particularly, if endometriomas are present at the time of oocyte retrieval. This measure requires however that a proper OC-FSH/hMG interval is respected and that "LH" effects are provided during the ovarian stimulation, using either hMG or small doses of hCG. These latter precautions prevent the adverse outcome reported in case of pre-ART use of OC when ovarian stimulation is conducted using r-FSH exclusively.


Hyperadrenalism in childhood and adolescence.
Hyperadrenalism in childhood and adolescence has unique features that influence diagnosis and management. We reviewed our experience with 18 patients, ranging in age from 18 months to 18 years. Nine had bilateral adrenal hyperplasia, eight had adrenal neoplasms, and one had micronodular hyperplasia. Patients with congenital adrenal hyperplasia and hyperaldosteronism were excluded. Six patients with Cushing's disease diagnosed in earlier years were treated by total adrenalectomy and recently two patients underwent transsphenoidal removal of pituitary tumors. Bilateral adrenalectomy was carried out in one patient with micronodular hyperplasia and in a second because of elevated adrenocorticotrophic hormone (ACTH) levels from an undefined source. Eight patients had adrenal neoplasms, including five adenomas and three carcinomas. We found no reliable criteria to differentiate before surgery between adrenal adenomas and adrenal carcinomas. The most recognizable characteristic of malignancy was tumor size, specifically weight greater than 75 gms. Of the three patients with adrenal carcinoma, one expired 20 months after adrenalectomy and 8 months after receiving palliative partial hepatectomy for liver metastasis. Two patients are well with normal growth and development at 11 and 20 years following adrenalectomy. With the exception of one patient who died 6 years after surgery from a glioblastoma multiforme, all patients with adrenal adenomas are well. Eight patients underwent bilateral adrenalectomy for hypercortisolism. Five of the six who have reached their adult stature are significantly stunted. Four of six patients with Cushing's disease, treated by total adrenalectomy, have developed Nelson's syndrome at 2, 6, 10, and 12 years after surgery. Of the two patients undergoing transsphenoidal surgery, one had recurrent disease at 2 years and was treated by pituitary irradiation with recovery. The patients undergoing adrenalectomy for micronodular hyperplasia and ectopic ACTH are well at 2 and 4 years, respectively. Cushing's disease in children and adolescents is best treated by transsphenoidal removal of the pituitary adenoma. Adrenalectomy, once the most accepted approach, plays a secondary role and is indicated primarily in micronodular adrenal hyperplasia, in patients with ectopic ACTH production of an undefined source, and in recurrent Cushing's disease following prior pituitary irradiation. The high incidence of Nelson's syndrome in children treated by adrenalectomy mandates that patients at risk be monitored lifelong for the progression of a pituitary tumor.(ABSTRACT TRUNCATED AT 400 WORDS)