Health inequalities in early adulthood: a comparison of young men and women in Britain and Finland.
Several studies have recently reported that social class differences in ill-health during adolescence are almost non-existent or invisible. The aims of this comparative study of two different welfare states are first, to compare whether the relationship between social class and health is similar among young men and women at different age groups in these two welfare states; second, to examine at what age social class differences in self-reported health and illness among young adults emerge in these two countries; and third, to find out whether class of origin (i.e. parental social class) or class of destination (i.e. individual's achieved social class) have greater explanatory power in studies of health among young adults. We used comparable nationally representative interview surveys from Britain and Finland. The British data is derived from the General Household Survey for 1988 and 1989, and the Finnish data from the 1986 Level of Living Survey. We analysed five year age groups between 16 and 39 years in Britain (N = 16,626) and 15 and 39 years in Finland (N = 5950). Two health indicators (limiting long-standing illness and self-assessed health), and several indicators for social class were compared. The best discriminator of differences in ill-health among young adults both in Finland and Britain was education. Social class differences by own occupation (achieved class) emerged soon after the age of 20 among men and women in both countries and strengthened with increasing age. There was a weaker but consistent association with class of origin in both countries. Housing tenure is strongly associated with young adults' health in Britain but not Finland.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunolocalization and distribution patterns of type IV collagen alpha chains in oral mucosal melanoma.
The basement membrane (BM) is mainly composed of type IV collagen, which is composed of triple combinations of six distinct alpha (alpha) chains in a tissue-specific manner. The six collagen chain-specific antibodies (alpha1-alpha6) were used to examine the BMs of the oral epithelium (OE) and tumor clusters in oral mucosal melanoma (OMM). Eight OMM cases were examined. Results showed that the alpha1 and alpha2 chains were constantly detected at the BM of the normal OE as well as at the OE with atypical melanocytic proliferation and in invasive melanoma with nodular nests. The alpha1 and alpha2 chains were intermittently detected in in situ OMM, early invasive OMM and advanced invasive OMM with sheet-like nests. Gradual loss of alpha5 and alpha6 from the OE with atypical melanocyte through in situ OMM and early invasive OMM was observed. These findings suggest that changes in the immunolocalization and distribution patterns of type IV collagen alpha chains are associated with the progression of OMM. The distribution pattern of type IV collagen alpha chain varies depending on the architecture of the nest.


Anorexia nervosa and "reverse anorexia" among 108 male bodybuilders.
Two disorders of body image encountered in a study of 108 bodybuilders are described. In a study of the psychiatric effects of anabolic steroids, structured interviews were administered to 55 bodybuilders who had used anabolic steroids and 53 non-user controls. Three (2.8%) of the subjects reported a history of anorexia nervosa--a rate far higher than the 0.02% rate typically reported among American men (P < .001). Nine (8.3%) of the subjects, two of whom were former anorexics, described a "reverse anorexia" syndrome, where they believed that they appeared small and weak even though they were actually large and muscular. Reverse anorexic subjects reported that they declined social invitations, refused to be seen at the beach, or wore heavy clothes even in the heat of summer because they feared that they looked too small. All nine reverse anorexia cases occurred among steroid users; none occurred among non-users (P < .003). Four subjects reported that their reverse anorexic symptoms contributed to their decision to start using steroids. Disorders of body image, including both anorexia nervosa and its reverse form, may occur frequently in men who lift weights regularly. Reverse anorexia may precipitate or perpetuate the use of anabolic steroids in some individuals.


Author Correction: Mechanosensing through immunoreceptors.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Does the radiographic transition zone correlate with the level of aganglionosis on the specimen in Hirschsprung's disease?
The correlation between radiographic transition zone on contrast enema in Hirschsprung's disease and the total length of aganglionosis is known to be inaccurate. The aim of our study was to analyse this correlation more precisely to improve preoperative planning of the corrective surgery. From 1998 to 2009, 79 patients were operated on for Hirschsprung's disease. All available preoperative contrast enemas (n = 61) had been single blind reviewed by the same radiologist who defined the radiographic transition zone when present in vertebral level. Four groups were determined (rectal, rectosigmoid, long segment, and absence of transition zone) and by Kappa coefficient of agreement correlated to the length of aganglionosis in the pathological report. Radiological findings were concordant with the specimen in pathology in 8 cases of 19 in rectal form (42 %), in 20 cases of 35 in rectosigmoid form (57 %), in all 6 cases of long-segment form (100 %), in the 2 cases of total colonic form (100 %) with a global agreement of 58.1 %, κ = 0.39 CI [0.24; 0.57]. Correlation between level of radiographic transition zone on contrast enema and length of aganglionosis remains low. Systematic preoperative biopsy by coelioscopy or ombilical incision is mandatory.


Antiviral properties of trans-δ-viniferin derivatives against enveloped viruses.
Over the last century, the number of epidemics caused by RNA viruses has increased and the current SARS-CoV-2 pandemic has taught us about the compelling need for ready-to-use broad-spectrum antivirals. In this scenario, natural products stand out as a major historical source of drugs. We analyzed the antiviral effect of 4 stilbene dimers [1 (trans-δ-viniferin); 2 (11',13'-di-O-methyl-trans-δ-viniferin), 3 (11,13-di-O-methyl-trans-δ-viniferin); and 4 (11,13,11',13'-tetra-O-methyl-trans-δ-viniferin)] obtained from plant substrates using chemoenzymatic synthesis against a panel of enveloped viruses. We report that compounds 2 and 3 display a broad-spectrum antiviral activity, being able to effectively inhibit several strains of Influenza Viruses (IV), SARS-CoV-2 Delta and, to some extent, Herpes Simplex Virus 2 (HSV-2). Interestingly, the mechanism of action differs for each virus. We observed both a direct virucidal and a cell-mediated effect against IV, with a high barrier to antiviral resistance; a restricted cell-mediated mechanism of action against SARS-CoV-2 Delta and a direct virustatic activity against HSV-2. Of note, while the effect was lost against IV in tissue culture models of human airway epithelia, the antiviral activity was confirmed in this relevant model for SARS-CoV-2 Delta. Our results suggest that stilbene dimer derivatives are good candidate models for the treatment of enveloped virus infections.


"Everyone is Living in the Same Storm, but our Boats are all Different": Safety and Safety Planning for Survivors of Intimate Partner and Sexual Violence During the COVID-19 Pandemic.
Survivors of intimate partner violence (IPV) and sexual assault (SA) faced increased violence, new safety risks, and reduced services access in the face of the COVID-19 pandemic. IPV and SA service providers have a critical role in safety planning and advocacy with survivors; however their patterns of working were dramatically impacted by changes brought on by the pandemic. Little is known about safety planning strategies and service adaptations employed in this context. Through semi-structured interviews with 33 service providers from across the United States, this study explores the experiences and perspectives of victim service agency staff with IPV and SA survivor safety and safety planning from March to December 2020. Qualitative data were analyzed using conventional content analysis. Four overarching themes related to survivor safety and safety planning emerged, including (1) "The violence is more severe, it's more escalated," describing an increase in the severity and frequency of violence; (2) "Perpetrating the violence through [technology]," describing a specific surge in technology based abuse (TBA) as the world shifted to virtual communication to facilitate social distancing; (3) "COVID-19 is now a tool in their toolbox," describing the emergence of the COVID-19 pandemic and health guidance as a life generated risk that abusive partners used to further control and isolate their partner; and (4) "You just get real crafty," highlighting the wide range of "work-arounds" and safety planning adaptations employed by victim service professionals trying to maintain services in a disrupted environment and in the face of evolving safety risks and increasing violence severity. These findings highlight the safety and safety planning challenges encountered as the COVID-19 pandemic unfolded and the many creative strategies employed by service providers to adapt in the moment.


Simulating maize water productivity at deficit irrigated field in north west Ethiopia.
Irrigation agriculture in Ethiopia can be improved by applying appropriate irrigation levels. Since water scarcity is the major problem in Ethiopia, and farmers apply water without knowledge of the amount of water to be applied, appropriate irrigation levels for maize crops should be investigated in the central Gondar zone, Ethiopia. This paper aims to investigate the effect of deficit levels of irrigation on crop parameters and evaluate the AquaCrop model for its predictability potential of water productivity. The experiment has four levels of water application (Full Irrigation (100%), 75%, 50%, and 25% of crop evapotranspiration) at 10 days of irrigation interval using Randomized Complete Block Design with three replications. Data collected in two experiments in the different seasons were soil moisture, canopy cover, biomass, and final yield. As high R 2 (0.93) and Nash-Sutcliffe Efficiency (NSE) (0.91) values indicated, the model performed well in simulating canopy cover, above-ground biomass, and yield in all treatments except 25% full irrigation (FI) with prolonged water deficit. Grain yield measured from experiment 2 was within the range of 4.6 t/ha to 7.4 t/ha. Even though a high yield was found from FI, the measured water use efficiency was better in 75% FI treatment, indicating a potential for water-saving by this treatment than FI. Higher grain yield was observed for maize sown in January at experiment 1. This was attributed to the rainfall impact on the experiment since it was spring season in Ethiopia at which some rainfall in the region is pronounced. In addition, AquaCrop thoroughly underestimated the seasonal evapotranspiration values and the deviations were commonly bigger as stress levels increased. Therefore, AquaCrop can be used in the simulation of crop parameters, prediction of irrigated outputs, and assessing the impact of irrigation scheduling.


Mechanical stretch-induced hypertrophy of neonatal rat ventricular myocytes is mediated by beta(1)-integrin-microtubule signaling pathways.
Mechanical stress plays a crucial role in tissue morphogenesis and remodeling. These processes depend in part on force transmission mediated through integrins and the cytoskeleton. Ventricular myocytes isolated from neonatal Sprague-Dawley rats (NRVMs) were exposed to persistent centrifugal force stretch for 12 or 24 h. The NRVMs were exposed to colchicine (4 micromol/ml) and anti-integrin beta1 specific antibody (10 microg/ml). Cell viability was assessed by MTT assay and lactate dehydrogenase (LDH) activity. Incorporation of 3H-leucine, and atrial natriuretic peptide (ANP) and angiotensin II (Ang II) levels were assessed. Pixel intensity and distribution of the microtubule were estimated from laser scanning confocal images. Changes in LDH release and the MTT assay showed that 180 rpm. centrifugal force had minimal effect on the viability and number of NRVMs. Mechanical stretch significantly increased 3H-leucine incorporation into cardiomyocytes. Anti-integrin beta1 blocking antibody effectively inhibited the increase in 3H-leucine incorporation and release of ANP (p < 0.05). Following anti-integrin-beta1-blocking antibody, the pixel intensity of the microtubule image was decreased after both12 and 24 h stretch, this was similar to the effect of colchicine. Both treatments also inhibited the secretion of Ang II induced by stretch (p < 0.05). Anti-integrin-beta1-blocking antibody and colchicine had similar effects, partly inhibiting the stretch-induced increase in microtubule polymerization and the secretion of Ang II in hypertrophic cardiac myocytes.


Medical therapy in spinal muscular atrophy: a realistic expectation?
The hereditary spinal muscular atrophies (SMA) type I-III belong to those diseases for which even the thought of medical therapy seems forbidden. Two neurotrophic factors are, however, now known to exert a markedly stimulating effect on survival of motor neurons in vivo! In principle such factors may become available by recombinant DNA techniques for experiments in animal models of SMA and if these experiments are successful for clinical trials in man. Medical therapy in SMA should aim primarily at patients early in the rapidly progressive phase of their disease, before massive loss of motoneuron has taken place.


Rolipram impairs NF-kappaB activity and MMP-9 expression in experimental autoimmune encephalomyelitis.
Rolipram suppresses experimental autoimmune encephalomyelitis (EAE) and diminishes cell infiltration of the central nervous system (CNS). In Lewis rats with EAE, rolipram reduced matrix metalloproteinase-9 (MMP-9) gene expression in lymph node cells (LNCs) and spinal cord, decreased basal levels of nuclear (p50/p65) NF-kappaB in LNCs from treated rats, and impaired CD3 mediated NF-kappaB translocation. Rolipram reduced the luciferase activity directed by the NF-kappaB binding site of the MMP-9 gene in lymphocytes. It also diminished NF-kappaB activity and the ability of a myelin basic protein (MBP) specific cell line to migrate across artificial basement membranes. IL-2 induced MMP-9 proteolytic activity was only slightly reduced indicating that additional factors contribute to inhibit cell migration mediated by rolipram.


Plasma apolipoprotein E levels and risk of dementia: A Mendelian randomization study of 106,562 individuals.
In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. In observational analyses risk of Alzheimer's disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10-17 and 9 × 10-21). APOE-weighted allele scores were associated with stepwise decreases in apoE (P for trend, <1 × 10-300). In instrumental variable analysis, the causal risk ratios for a 1 mg/dL genetically determined lower apoE were 1.41 (1.27-1.57) for Alzheimer's disease and 1.33 (1.25-1.43) for all dementia (F-statistics = 3821). Genetic and hence lifelong low apoE is associated with high risk of dementia in the general population. The concordance between observational and genetic estimates suggests a potential causal relationship.


[Lower urinary tract dysfunction following radical hysterectomy].
Radical hysterectomy is associated with a significant amount of urinary functional complications and a negative impact on quality of life. The aim of this review is to provide a comprehensive overview of the neurological etiology of lower urinary tract dysfunction following radical hysterectomy and to establish an optimal postoperative management strategy. We performed a comprehensive overview using the following terms: "radical hysterectomy" and "urologic diseases etiology" or "urologic disease prevention and control". The reported incidence of lower urinary tract dysfunction after radical hysterectomy varies from 12 to 85%. Several animal and clinical urodynamic studies corroborate the neurologic etiology of the dysfunction. Lower urinary tract dysfunction is a common postoperative finding (70-85%) but spontaneous recovery is to be expected within 6-12 months after surgery. The most frequent long term sequela is stress urinary incontinence (40% of cases) and its management is complex and challenging. Postoperative refractory overactive bladder and bladder underactivity can be treated by neuromodulation of sacral roots and superior hypogastric plexus, respectively. In the absence of good clinical predictors, preoperative urodynamic examinations could have a role in understanding the pathophysiology of the dysfunction before such interventions. The pathophysiology of lower urinary tract dysfunction following radical hysterectomy is multifactorial. Its management is complex and should be multidisciplinary.


A Year of Pandemic-Comparison of Depression Among Neurosurgeons After the Advent of the COVID-19 Vaccine.
To determine factors associated with anxiety and depression among neurosurgeons after vaccination during the coronavirus disease 2019 (COVID-19) pandemic. An online survey was completed by neurosurgeons worldwide over 4 weeks. Depression in neurosurgeons was assessed by the 20-item self-reporting questionnaire. A total of 534 responses were received and analyzed. Almost half of the respondents were from Asia (50.9%), followed by Europe (38.8%). The majority of the respondents were <40 years old (88%), and almost two thirds were trainees (62.2%). Half of the respondents worked in departments with <40 beds (50.7%), and the majority were practicing in the private sector (72.5%). Most of the respondents (85.8%) had COVID-19-positive colleagues in their department, and 64% had exposure to a COVID-19-positive colleague, family member, and/or patient. More than half of the respondents were exposed to infected patients and/or colleagues, and almost half (43.1%) underwent COVID-19 testing when exposed. Nearly half of the respondents underwent COVID-19 testing more than twice (52.4%). Of respondents, 83% had received at least the first dose of the vaccine. The odds of depression among vaccinated respondents were found to be significantly less than among unvaccinated respondents in the univariable model. Among health care workers, neurosurgeons are one of the groups indirectly affected by the pandemic. Adaptation to the new normal and advent of vaccines is speculated to control psychological distress among all groups of health care workers, including neurosurgeons. We found that odds of depression among vaccinated people were lower than among people who were not vaccinated.


A tension spline fitted numerical scheme for singularly perturbed reaction-diffusion problem with negative shift.
The paper is focused on developing and analyzing a uniformly convergent numerical scheme for a singularly perturbed reaction-diffusion problem with a negative shift. The solution of such problem exhibits strong boundary layers at the two ends of the domain due to the influence of the perturbation parameter, and the term with negative shift causes interior layer. The rapidly changing behavior of the solution in the layers brings significant difficulties in solving the problem analytically. We have treated the problem by proposing a numerical scheme using the implicit Euler method in the temporal direction and a fitted tension spline method in the spatial direction with uniform meshes. Stability and uniform error estimates are investigated for the developed numerical scheme. The theoretical finding is demonstrated by numerical examples. It is obtained that the developed numerical scheme is uniformly convergent of order one in time and order two in space.


Generation of cationic indenyl silylamide gadolinium and scandium complexes [(Ind)Ln{N(SiMe3)2}]+[B(C6F5)4]- and their reactivity for 1,3-butadiene polymerization.
Highly efficient cis-polymerization of butadiene was achieved by using new bis(indenyl) silylamide rare earth complexes with the cooperation of both a borate salt and i-Bu3Al; treatment of these complexes with organoboron compounds unexpectedly yielded new cationic mono(indenyl) amido species relevant to polymerization.


Regional glucose uptake and protein synthesis in isolated perfused rat hearts immediately after training and later.
The effect of 10 weeks of running training and termination of training on the regional distribution of cardiac glucose uptake and protein synthesis were studied in isolated perfused hearts in male rats. The left ventricular glucose uptake in hearts from sedentary rats was 1.87 +/- 0.14 mumol/min per g protein (mean +/- SE), being about 30% higher in the subendocardial than in the subepicardial layer (p less than 0.05). The gradient of left ventricular glucose uptake was similar to the controls in the rats retired from training, but was absent in the trained animals. The altered transmural glucose uptake probably reflects differences in the adaptive response of various myocardial muscle layers to a long-term intermittent increase in cardiac work load. Phenylalanine incorporation was evenly distributed through the left ventricle in all the groups, but was lowered in the left and right ventricles of the trained rats. Phenylalanine incorporation returned to the control level 5 weeks after the cessation of training.


The causes of heroin addiction-- a review of the literature. Part II.
Theories on the causes of heroin addiction are reviewed in this two part article. Part II reviews the literature that considers the family of the addict and the stepping stone theory.


The novel gluconeogenesis inhibitor FR225654 that originates from Phoma sp. no. 00144. I. Taxonomy, fermentation, isolation and physico-chemical properties.
FR225654, a novel gluconeogenesis inhibitor, was isolated from the culture broth of Phoma sp. No. 00144 and purified by adsorptive resin and reverse-phase column chromatography. This compound is a potent inhibitor of gluconeogenesis and is a promising candidate of anti-diabetic agent.


Metabolism of naturally occurring propenylbenzene derivatives. III. Allylbenzene, propenyl benzene, and related metabolic products.
The acidic and neutral urinary metabolites of allylbenzene, propenylbenzene, 1'-hydroxyallylbenzene, and cynnamyl alcohol were identified and related through a common metabolic scheme. The rat metabolizes allylbenzene to 1'-hydroxyallylbenzene which can rearrange to yield cinnamyl alcohol whick is further metabolized. This mechanism is proposed to account for the appearance of "propenyl type" metabolites from allylbenzene compounds. Propenylbenzene is oxidized to cynnamyl alcohol. Both 1'-hydroxyallylbenzene and cunnamyl alcohol are excreted unchanged in the neutral extract when given to rats. Allylbenzene and 1'-hydroxyallylbenzene yield basic ninhydrin-positive metabolites. Allylbenzene is first oxidized on the benzylic carbon to form 1'-hydroxyallylbenzene, which is further oxidized to form phenyl vinyl ketone, which condenses with the secondary amines piperidine and dimethylamine to form tertiary aminopropiophenones (Mannich bases). Analogous compounds, cinnamyl alcohol and propenylbenzene, do not yield Mannich base metabolites. This proposed metabolic scheme is consistent with the chemical mechanism operative in the synthesis of Mannich base from allylbenzene via chromic acid oxidation followed by amine addition.


Interventions to Improve Self-Efficacy in Colorectal Cancer Patients and/or Caregivers: A Systematic Review and Meta-Analysis.
High levels of self-efficacy (SE) in colorectal cancer (CRC) patients and/or caregivers enable patients to cope with cancer, reduce caregiver burden, and promote quality of life (QOL) in patients and caregivers alike. This review aims to (a) identify the SE theory sources covered by SE interventions or interventions, including targeting improved SE for CRC patients and/or caregivers, to guide future development of SE interventions; and (b) explore intervention effects based on SE theory through meta-analysis. Using five electronic databases-CINAHL, Cochrane Library, Embase, PsycINFO, and PubMed-a systematic search was performed in April 2021 to identify English or Chinese literature that studied improving SE interventions for CRC patients and/or caregivers. Manual screening of the articles' references list was also performed. A total of 18 studies were found to be suitable and included in this review. Of the 18 studies that were included, 10 randomized controlled trials (RCTs) studies with 917 participants were eligible for meta-analysis. Interventions provide support for SE drawing on different sources of information. Performance accomplishment (PA) is the key source, with vicarious experience (VE) and verbal persuasion (VP) assisting in improving PA. Reducing negative emotional arousal (NEA) and improving positive emotional arousal (PEA) are also indispensable factors in improving SE. The meta-analysis results show that interventions based on the SE theory can bring about positive effects for CRC patients and/or caregivers. Different sources of information aimed at improving SE, covered by the interventions, including PA, VE, VP, NEA, and PEA, have been explored. Positive intervention outcomes that focused on improving SE for CRC patients and/or caregivers were identified and highlighted. For future SE interventions, we advocate choosing combination sources of SE information to design interventions. It is recommended that future SE improvement interventions should focus on improving PA, supplemented by increasing VE, while reducing NEA and providing useful VP.


Multi-resolution convolutional networks for chest X-ray radiograph based lung nodule detection.
Lung cancer is the leading cause of cancer death worldwide. Early detection of lung cancer is helpful to provide the best possible clinical treatment for patients. Due to the limited number of radiologist and the huge number of chest x-ray radiographs (CXR) available for observation, a computer-aided detection scheme should be developed to assist radiologists in decision-making. While deep learning showed state-of-the-art performance in several computer vision applications, it has not been used for lung nodule detection on CXR. In this paper, a deep learning-based lung nodule detection method was proposed. We employed patch-based multi-resolution convolutional networks to extract the features and employed four different fusion methods for classification. The proposed method shows much better performance and is much more robust than those previously reported researches. For publicly available Japanese Society of Radiological Technology (JSRT) database, more than 99% of lung nodules can be detected when the false positives per image (FPs/image) was 0.2. The FAUC and R-CPM of the proposed method were 0.982 and 0.987, respectively. The proposed approach has the potential of applications in clinical practice.


Art therapy in pediatric burn care: A conceptual framework for clinical practice.
Burn injuries are an unexpected traumatic event and can be physically and emotionally devastating for a child and their families. This article presents a conceptual framework for art therapy practice with pediatric burns, founded on the three stages of burn treatment- critical, acute, and rehabilitation. The framework is based on narrative synthesis of research on the psychosocial needs of children with burn injuries, art therapy literature on pediatric burn patients, as well as in medical settings. Based on the stages of burn recovery, and the role of other relevant stakeholders, the framework provides recommendations for clinical practice of art therapy with children sustaining burn injuries, their caregivers and siblings, and healthcare providers. Robust studies including art therapy as interventions are recommended to determine their effectiveness in addressing the specific psychosocial needs in different stages of pediatric burn care.


Cardiac rhythm in atrial isomerism.
Standard electrocardiograms from 126 consecutive patients with atrial isomerism were reviewed. Of 67 patients with left isomerism, 49 had sinus rhythm, 8 nodal rhythm and 10 atrioventricular (AV) block. Fifty-eight of 59 patients with right isomerism had sinus rhythm. Complete AV block was significantly more frequent in association with AV septal defect in left isomerism (5 of 45 patients) than in right isomerism (0 of 47 patients, p = 0.049). The P-wave axis was superior in 49% of patients with left isomerism but did not correlate with abnormalities of systemic or pulmonary venous connection. A significant shift of P-wave axis (more than 90 degrees) was seen on a subsequent electrocardiogram in 14 of 44 patients (32%) with left isomerism and 2 of 16 (13%) with right isomerism. Ambulatory electrocardiographic monitoring in 17 patients (14 with left isomerism) showed that only 4 had sinus rhythm throughout 24 hours. Only 1 patient with complete AV block received a permanent pacemaker. Despite the high incidence of electrocardiographic abnormalities, significant arrhythmias appear to be rare. The arrhythmias apparently do not influence the natural history of this condition or affect the outcome of palliative or corrective surgery. The prognosis is determined mainly or solely by the associated anatomic abnormalities.


Analysis of the genetic contribution to thoracic aortic aneurysm or dissection in a prospective cohort of patients with familial and sporadic cases in East China.
Thoracic aortic aneurysm or dissections (TAADs) represent a group of life-threatening diseases. Genetic aetiology can affect the age of onset, clinical phenotype, and timing of intervention. We conducted a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harbouring the pathogenic variants. One hundred and one unrelated TAAD patients underwent genetic sequencing and analysis for 23 TAAD-associated genes using a targeted PCR and next-generation sequencing-based panel. A total of 47 variants were identified in 52 TAAD patients (51.5%), including 5 pathogenic, 1 likely pathogenic and 41 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 patient with familial and 5 patients with sporadic TAAD (5.9%). In addition to harbouring one variant causing familial TAAD, the FBN1 gene harboured half of the P/LP variants causing sporadic TAAD. Individuals with an age of onset less than 50 years or normotension had a significantly increased genetic risk. TAAD patients with a younger age at diagnosis or normotension were more likely to carry a P/LP variant; thus, routine genetic testing will be beneficial to a better prognosis through genetically personalized care prior to acute rupture or dissection.


Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells.
Lung alveoli, which are unique to air-breathing organisms, have been challenging to generate from pluripotent stem cells (PSCs) in part because there are limited model systems available to provide the necessary developmental roadmaps for in vitro differentiation. Here we report the generation of alveolar epithelial type 2 cells (AEC2s), the facultative progenitors of lung alveoli, from human PSCs. Using multicolored fluorescent reporter lines, we track and purify human SFTPC+ alveolar progenitors as they emerge from endodermal precursors in response to stimulation of Wnt and FGF signaling. Purified PSC-derived SFTPC+ cells form monolayered epithelial "alveolospheres" in 3D cultures without the need for mesenchymal support, exhibit self-renewal capacity, and display additional AEC2 functional capacities. Footprint-free CRISPR-based gene correction of PSCs derived from patients carrying a homozygous surfactant mutation (SFTPB121ins2) restores surfactant processing in AEC2s. Thus, PSC-derived AEC2s provide a platform for disease modeling and future functional regeneration of the distal lung.


The Egydio geometrical procedure for managing penile curvature using a single relaxing incision: A single-centre experience with 330 patients.
To present our 3-year experience with the Egydio's geometrical procedure for managing penile curvature with some modifications. In all, 330 patients (mean age 51 years) that underwent the Egydio's procedure as day cases were included in this study. The mean penile curvature was 45° and 27.3% of the patients reported mild erectile dysfunction (ED) preoperatively. Partial excision of the calcified plaque was performed in 12.1% of the patients. Partial glans necrosis was recorded in one patient, while haematoma was recorded in 9%, and delayed wound healing in 3%. There was residual curvature (mean 20°) requiring reoperation in 8.2% of the patients. In all, 10% of the patients were dissatisfied with their results, while of the remainder, 75.2% were totally satisfied and 14.8% partially satisfied. ED was reported in 31.8% of the patients (moderate: 17.3% and significant: 2.7%). The Egydio geometrical technique for the treatment of penile curvature seems to be a simple, reproducible, safe, and efficient operation.


Prolonged exposure versus dynamic therapy for adolescent PTSD: a pilot randomized controlled trial.
To examine the efficacy and maintenance of developmentally adapted prolonged exposure therapy for adolescents (PE-A) compared with active control time-limited dynamic therapy (TLDP-A) for decreasing posttraumatic and depressive symptoms in adolescent victims of single-event traumas. Thirty-eight adolescents (12 to 18 years old) were randomly assigned to receive PE-A or TLDP-A. Both treatments resulted in decreased posttraumatic stress disorder and depression and increased functioning. PE-A exhibited a greater decrease of posttraumatic stress disorder and depression symptom severity and a greater increase in global functioning than did TDLP-A. After treatment, 68.4% of adolescents beginning treatment with PE-A and 36.8% of those beginning treatment with TLDP-A no longer met diagnostic criteria for posttraumatic stress disorder. Treatment gains were maintained at 6- and 17-month follow-ups. Brief individual therapy is effective in decreasing posttraumatic distress and behavioral trauma-focused components enhance efficacy. CLINICAL TRIAL REGISTRY INFORMATION: Prolonged Exposure Therapy Versus Active Psychotherapy in Treating Post-Traumatic Stress Disorder in Adolescents, URL: http://clinicaltrials.gov, unique identifier: NCT00183690.


Driving in Parkinson Disease.
Driving is impaired in most patients with Parkinson disease because of motor, cognitive, and visual dysfunction. Driving impairments in Parkinson disease may increase the risk of crashes and result in early driving cessation with loss of independence. Drivers with Parkinson disease should undergo comprehensive evaluations to determine fitness to drive with periodic follow-up evaluations as needed. Research in rehabilitation of driving and automation to maintain independence of patients with Parkinson disease is in progress.


Pd(0)-catalyzed reaction of alkynes with trifurylgermane and CO providing acylgermanes: the example of hydrometalcarbonylation of alkynes.
A direct synthesis of acylmetals from alkynes with group 14 metal hydride and CO is reported. The Pd(0)-catalyzed reaction of alkynes with tri(2-furyl)germane under ambient pressure of CO provides alpha,beta-unsaturated acylgermanes in good yields. Conversion of acylgermanes to the corresponding amides is achieved.


Pathological tremors as diffusional processes.
Two types of pathological tremors, essential and Parkinsonian, are studied using dynamical systems theory. It is shown that pathological tremors can be characterized as diffusional processes. The time-scale range for the diffusional scaling law to be valid starts from about one to several tens of the mean oscillation period. This time-scale range contrasts sharply with the predictable time scale for deterministic chaos, which is usually only a small fraction of the mean oscillation period. The diffusions in pathological tremors are usually anomalous. A number of quantities are designed to characterize the diffusions in the tremor. Their relevance to potential clinical applications is discussed. It is argued that in order to discriminate between Parkinsonian and essential tremors, quantities not of purely dynamical origin may be more useful, since purely dynamical quantities emphasize more the dynamical similarities between the two types of tremors.


External skeletal fixation as treatment for total puerperal rupture of the pubic symphysis.
A case of total puerperal rupture of the pubic symphysis during non-operative delivery is reported and the literature reviewed. The patient in our case was successfully treated by external skeletal fixation. In agreement with the literature the authors recommend external skeletal fixation when lesions are unstable, when inadequate reduction is achieved, or when the diastasis is more than 40 mm.


Application of biophysical methods for improved protein production and characterization: A case study on an high-temperature requirement A-family bacterial protease.
The high-temperature requirement A (HtrA) serine protease family presents an attractive target class for antibacterial therapeutics development. These proteins possess dual protease and chaperone functions and contain numerous binding sites and regulatory loops, displaying diverse oligomerization patterns dependent on substrate type and occupancy. HtrA proteins that are natively purified coelute with contaminating peptides and activating species, shifting oligomerization and protein structure to differently activated populations. Here, a redesigned HtrA production results in cleaner preparations with high yields by overexpressing and purifying target protein from inclusion bodies under denaturing conditions, followed by a high-throughput screen for optimal refolding buffer composition using function-agnostic biophysical techniques that do not rely on target-specific measurements. We use Borrelia burgdorferi HtrA to demonstrate the effectiveness of our function-agnostic approach, while characterization with both new and established biophysical methods shows the retention of proteolytic and chaperone activity of the refolded protein. This systematic workflow and toolset will translate to the production of HtrA-family proteins in higher quantities of pure and monodisperse composition than the current literature standard, with applicability to a broad array of protein purification strategies.


Single-walled carbon nanotube based coating modified with reduced graphene oxide for the design of amperometric biosensors.
In this study a polycarbonate filter membrane (PcFM) with 400 nm diameter holes was covered/protruded by single walled carbon nanotubes (SWCNT) and then formed PcFM/SWCNT structure was covered by thin layer of graphene oxide (GO) or reduced graphene oxide (rGO) in order to get the multilayered PcFM/SWCNT/GO and PcFM/SWCNT/rGO coatings, respectively. It was determined that the SWCNTs filaments were able to form a layer on the polycarbonate membrane having a number of carbon nanotube arranged in different orientations. A fraction of SWCNT filaments protruded through the holes of polycarbonate membrane and in such way significantly enhanced the adhesion of SWCNT-based layer and provided electrical conductivity across the PcFM. Atomic force microscopy (AFM), scanning electron microscopy (SEM) images and Raman spectroscopy-based evaluation revealed the characteristic morphology features: wide distribution of height profile, separate GO/rGO flakes on the top of PcFM/SWCNT/GO structure and close attachment of rGO flakes on the top of multilayered PcFM/SWCNT/rGO coating. Performed contact angle measurement (CAM) enabled to determine the surface energy components and wettability data of prepared coatings. Both PcFM/SWCNT/GO and PcFM/SWCNT/rGO coatings were modified with glucose oxidase (GOx). Amperometric measurements revealed that multilayered PcFM/SWCNT/rGO/GOx coating is the most suitable structure for glucose biosensor design.


Assessment of quality in screening colonoscopy for colorectal cancer.
The effectiveness of screening colonoscopy in decreasing the incidence of colorectal cancer (CRC) is largely dependent on the detection of polyps and the quality of the procedure. Several key quality measures have been proposed to improve the effectiveness of screening colonoscopies. To evaluate quality indicators of screening colonoscopy in a tertiary hospital. All CRC screening colonoscopies performed between 2005 and 2009 in a single tertiary center were reviewed for internationally accepted quality measures. Of the 1545 individuals who underwent first-time screening colonoscopy 38% were male and 62% were female. The mean age of the patients was 60.4 years and the mean difference in ages was ± 10.3 years. Cecal intubation rate was 91% (1336), however ileocecal valve photo documentation was performed in only 81% (1248) colonoscopies. The quality of bowel preparation was classified as: good 76% (1171), reasonable 11% (174), and poor 13% (200). Polyp detection rate (PDR) was 33% (503). The prevalence of polyps ≥1 cm in size was 5% (82). PDR was significantly higher in men than in women (44% [260] vs 25% [243], P = 0.0001). Other factors significantly influencing PDR were quality of bowel preparation (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 0.9-1.6) and age over 50 (OR: 1.9, 95% CI: 1.3-2.9). Left colonic polyps were associated with a risk ratio of 2.3 (95% CI: 1.8-2.9) of lesions in the other colonic segments compared to no polyps in the left colon. None of the colonoscopists reported withdrawal time. Cecal intubation rate and quality of bowel preparation were suboptimal. The polyp detection rate compares favorably to accepted standards and its main determinants are male sex, age >50 years, quality of bowel preparation, and the presence of left colonic polyps.


Inflammation in the lungs of infants dying suddenly. A comparative study from two countries.
An investigation of lung tissue samples from sudden unexpected infant deaths from the German Democratic Republic (G.D.R.) (n = 106) and Finland (n = 94) shows the German material to contain 54 cases (51%) with advanced inflammatory changes allowing a definite pathologico-anatomical diagnosis and explanation for the death, whereas there were only 19 such cases (20%) in the Finnish material. Slight changes indicating an inflammatory process but not allowing a definite diagnosis ("borderline cases") were seen in one fifth of the cases in both countries. Thus a greater proportion of the child deaths below the age of 1 year in Finland are real cot deaths than in the G.D.R. where signs of respiratory infection can be found more often.


The effect of cold on adrenergic neurotransmission in canine saphenous arteries and veins.
The effect of severe cold (5 to 10 degrees C) on adrenergic neurotransmission was compared in the isolated cutaneous (saphenous) artery and vein of the dog. The vein contracted to sympathetic nerve stimulation at temperatures as low as 10 degrees C; higher temperatures were needed for the artery to contract. Both blood vessels contracted to exogenous norepinephrine at temperatures as low as 5 degrees C. However, the contractile response to exogenous norepinephrine was less in the saphenous artery, and contractions to high K+ solution were depressed by cooling more in the artery than in the vein. During electrical stimulation of the sympathetic nerves in saphenous arteries and veins previously incubated with labeled norepinephrine, progressive cooling from 37 to 5 degrees C caused a sharp decline in overflow of [3H]norepinephrine and its metabolites. However, overflow of labeled norepinephrine in both blood vessels continued at very cold temperatures. Thus the inability of the saphenous artery to contract to sympathetic nerve stimulation at 10 degrees C can be explained by a greater sensitivity of the arterial smooth muscle to the direct depressant effect of cold, rather than to a differential release or metabolism or norepinephrine in the arterial wall or a loss of responsiveness to norepinephrine at very cold temperatures.


A novel approach to ventricular rupture: clinical needs and surgical technique.
Cardiac rupture is a life-threatening event that often occurs after myocardial infarction and is often associated with significant death. Pericardiocentesis provides hemodynamic short-term improvement; however, patients with cardiac rupture require an emergency operation. This report describes a new procedure used to repair left ventricle free wall rupture after myocardial infarction. The technique described repairs the rupture off-pump and without the need for suturing. Midterm results demonstrate the feasibility and durability of this procedure.


Synthesis of a versatile 1H-indene-3-carboxylate scaffold enabled by visible-light promoted Wolff rearrangement of 1-diazonaphthalen-2(1H)-ones.
Herein, we have developed a sequential visible-light-promoted Wolff rearrangement of 1-diazonaphthalen-2(1H)-ones, followed by capturing the in situ generated ketene intermediates with various alcohols, producing diverse 1H-indene-3-carboxylates in moderate to good yields under mild reaction conditions. The broad substrate scope, high functional group tolerance, and robust conditions make the resulting derivative a versatile platform for the synthesis of plenty of bioactive molecules.


Changing pattern of hepatocellular carcinoma (HCC) and its risk factors in Egypt: possibilities for prevention.
The burden of hepatocellular carcinoma (HCC) has been increasing in Egypt with a doubling in the incidence rate in the past 10 years. This has been attributed to several biological (e.g. hepatitis B and C virus infection) and environmental factors (e.g. aflatoxin, AF). Other factors such as cigarette smoking, occupational exposure to chemicals such as pesticides, and endemic infections in the community, such as schistosomiasis, may have additional roles in the etiology or progression of the disease. Estimates of the burden of cancer caused by these factors provide an opportunity for prevention. Previously, there was strong evidence that hepatitis B virus (HBV) was the major cause of HCC in Egypt, but more recently HCV has become the predominant factor associated with the more recent epidemic of HCC. It has been well documented that Egypt has one of the highest prevalence rates of HCV infection in the world. The natural history of HCV infection and disease progression, however, are influenced by additional factors such as duration of infection, age at infection, sex, co-infection with HBV, the level of HCV viraemia and its genotype. The role of exposure to aflatoxins and development of HCC in Egypt was historically less clear. Nevertheless, recent food sampling surveys and population-based studies indicated that exposure to aflatoxins in Egypt may have been underestimated in the past. Recent results indicated that both local and imported samples were positive for aflatoxin B1 (AFB1, 17.5% and 20%, respectively), with concentrations ranging from 3 to 25 microg/kg. The level of AFB1 was dependent on the area of collection as well as the season of the year. In a population-based study, the level and frequency of aflatoxin M1 (AFM1, a major metabolite of aflatoxin B1 excreted in breast milk) was assessed as a biomarker of maternal exposure. The samples were collected from a selected group of 388 Egyptian lactating mothers during May-September 2003. Non-working status, obesity, high corn oil consumption, and the number of offspring contributed to the variability in occurrence of AFM1 in breast milk. Prevention and intervention approaches directed to risk factors of HCC can play a critical role in its prevention. In the case of HCV infection a prevention programme can be achieved by changing personal behaviors and/or cultural habits which are risk factors for HCV transmission, such as injection with contaminated syringes, blood transfusion, surgical operations, venous catheterization, use of common syringes, dental treatment and circumcision at home. Prevention of exposure to aflatoxins can be achieved either at community (via good agriculture practices) or individual levels (treatment or dietary interventions). In conclusion, due to the alarming increase in the incidence of HCC in Egypt, there is a need to further investigate the contribution of these emerging risk factors to the development of HCC in Egypt. This may enable us to determine the susceptibility to HCC among high-risk groups and to provide these individuals with effective measures for early prevention or intervention.


Synthesis and anti-cancer activities of new sulfonamides 4-substituted-triazolyl nucleosides.
Nucleoside analogues are among the most known drugs commonly used in antiviral and anticancer chemotherapies. Among them, those featuring a five-membered ring nucleobase are of utmost interest such as the anti-cancer agent AICAR or the anti-viral drug ribavirin. Despite its low activity in vitro in different cell lines, AICAR is under clinical development for several pathologies, thanks to its original mode of action. Indeed, AICAR induced autophagy cell death and is able, following this mechanism, to circumvent resistance to apoptotic drugs including kinase inhibitors currently on the market. To improve the activity of AICAR, we report herein an efficient synthesis of new series of sulfonamide-4-substituted-1,2,3-triazolyl nucleosides using a Cu-catalyzed 1,3-dipolar cycloaddition. All these molecules have been fully characterized and evaluated against two aggressive tumor cell lines, RCC4 and MDA-MB-231. Among them, nucleoside analogue 5i belonging to the ribose series was found to be 19 to 66-fold more active than AICAR. Western blot analyses on RCC4 cells showed that 5i displayed an interesting mode of action by inducing both apoptosis and autophagy cell death, making therefore this class of molecules highly promising for further hit-to-lead optimization.


[Genetic and peristatic aspects of research on twins].
The incidence of multiplets according to Hellin is no more valid in the last years. The reasons have been discussed. Different comprehensions about the valence of the different methodic variants of twin research have been explained.


Potential of engineering methodologies for the application to pharmaceutical research.
Current engineering methods and their potential for use in cell-based research are reviewed. The basis of the suggested engineering methods is that real cellular responses can be assessed when the cells are under the same conditions as in vivo. Providing various conditions for this various engineering methodologies can be adopted. Three major factors should be considered when we apply bio-mimetic conditions to cells under in vitro culture conditions. They are the surface pattern and stiffness of the substrate, physical stimuli and neighboring cells. Various outcomes affected by those factors are introduced and reviewed. In particular, those outcomes from stem cell research have been reported. Even though some limitations of adopting those factors alone or combined still exist, the potential is now widely being recognized. The readers are kindly asked to consider those methodologies in relation to pharmaceutical research.


Evolution of renal pathology in Fabry disease.
Fabry disease is a rare lysosomal storage disorder which results from deficient activity of the enzyme alpha-galactosidase A. The resultant deposition and progressive accumulation of glycosphingolipids in all types of body tissue leads to severe clinical manifestations involving the heart, CNS and kidney. Renal manifestations are observed relatively early in the course of the disease, and progression to end-stage renal failure is common in hemizygous males in the third to fifth decades of life. Renal biopsy specimens reveal evidence of diffuse intracytoplasmic glycosphingolipid accumulation, mainly affecting podocytes and epithelial cells of distal tubules, which are strikingly enlarged and vacuolated. On electron microscopy the deposits appear as typical osmiophilic inclusion bodies in the cytoplasm of all kinds of renal cells, and show a characteristic 'onion skin' or 'zebra' appearance. These pathological features are also evident in heterozygous females. Deposits occur before the development of renal impairment. As patients age, the disease progresses in cells throughout the kidney, and is associated with increasing glycosphingolipid accumulation. The age-related evolution of renal pathology in Fabry disease is closely correlated with progressive intracellular deposition of glycosphingolipid and ultimately leads to end-stage renal failure.


Effect of Moringa oleifera Leaf Powder on Hematological Profile of Male Wistar Rats.
Indonesia is a country with high biodiversity of more than 20,000 plant species, and 35% of them are identified as having health benefits. Moringa oleifera is one plant that almost all of its parts have been used as nutritional supplements and traditional medicines. Moringa leaves contain nutrients, antioxidants, and bioactive substances that have anti-inflammatory, wound healing, and anti-anemia properties. This study aimed to investigate the hematological effect of Moringa leaf powder in male Wistar rats under normal conditions. Twenty-four male Wistar rats strain (Rattus norvegicus) 9-10 weeks old and 250-275 grams were divided into four groups (n=6), normal as a control group and three other groups were given Moringa leaf powder at doses 200, 400, and 800 mg/kgBW during 12 weeks. Blood samples at week 12 were administered to determine blood count. The results of this study showed differences between the various doses of Moringa leaf powder for each hematological profile. These differences were more significant for MCH parameters that indicated a decrease in the D800 group compared with the control group. In conclusion, this study revealed that the consumption of Moringa leaf powder for 12 weeks did not have a significant change in the hematological profile, except for the MCH value that revealed a modification.


Selective arylation at the vinylic site of cyclic olefins.
Cyclic olefins usually give Heck products having an aryl ring residing at the allylic or homoallylic position. We describe herein a new method that allows arylation at the vinylic position of various cyclic olefins.


Effects of Ultraviolet Radiation (UV-A+UV-B) on the Antioxidant Metabolism of the Red Macroalga Species Acanthophora spicifera (Rhodophyta, Ceramiales) From Different Salinity and Nutrient Conditions.
Acanthophora spicifera (M.Vahl) Børgesen is a macroalga of great economic importance. This study evaluated the antioxidant responses of two algal populations of A. spicifera adapted to different abiotic conditions when exposed to ultraviolet-A+ultraviolet-B radiation (UV-A+UV-B). Experiments were performed using the water at two collection points for 7 days of acclimatization and 7 days of exposure to UVR (3 h per day), followed by metabolic analyses. At point 1, water of 30 ± 1 practical salinity unit (psu) had concentrations of 1.06 ± 0.27 mm NH 4 + , 8.47 ± 0.01 mm NO 3 - , 0.17 ± 0.01 mm PO 4 - 3 and pH 7.88. At point 2, water of 35 ± 1 psu had concentrations of 1.13 ± 0.05 mm NH 4 + , 3.73 ± 0.01 mm NO 3 - , 0.52 ± 0.01 mm PO 4 - 3 and pH 8.55. Chlorophyll a, phycobiliproteins, carotenoids, mycosporins, polyphenolics and antioxidant enzymes (catalase, superoxide dismutase and guaiacol peroxidase) were evaluated. The present study demonstrates that ultraviolet radiation triggers antioxidant activity in the A. spicifera. However, such activation resulted in greater responses in samples of the point 1, with lower salinity and highest concentration of nutrients.


Profile of human leukocyte antigen class I alleles in patients with dengue infection from Western India.
Human leukocyte antigen (HLA) class I alleles are known to affect the cytotoxic T lymphocyte responses and influence susceptibility to viral infections. The objective of the present study was to find out whether HLA class I alleles are associated with clinical manifestations of dengue virus infection. The profile of HLA class I alleles were investigated in 224 human subjects [85 dengue fever (DF) cases, 29 dengue hemorrhagic fever (DHF) cases and 110 healthy controls (HCs)] from Western India using PCR based methods. Results revealed significantly higher frequency of HLA-A(∗)33 in DF cases compared to HCs [P = 0.032, Odds ratio (OR) 2.12]. The frequency of HLA-A(∗)02:11 was higher in DHF cases compared to DF cases. The frequency of HLA-B(∗)18 was significantly higher in dengue (DEN) cases [P = 0.047 Pc = 0.846, OR 3.53]. The frequency of HLA-Cw(∗)07 allele was significantly higher in DEN cases [DEN vs. HCs: P = 0.0120, Pc = 0.168, OR 2.00]. Significance was observed even when the cases were categorized in to DF and DHF [DF vs. HCs: P = 0.0349, Pc = 0.49, OR 1.87; DHF vs. HCs: P = 0.0399, Pc = 0.56, OR 2.4]. The combined frequency of HLA-Cw(∗)07 with HLA-DRB1(∗)07/(∗)15 genotype was significantly higher in DHF cases as compared to DF and HCs [DHF vs. HCs: P = 0.022, OR 5.31; DHF vs. DF: P = 0.027, OR 5.49]. On the other hand, the frequency of combination of HLA-Cw(∗)07 without HLA-DRB1(∗)07 was significantly higher in DF cases compared to HCs [DF vs. HCs: P = 0.002, OR 2.42 (1.28-4.55)]. The results suggest that HLA-A(∗∗)33 may be associated with DF while HLA-B(∗)18 and HLA-Cw(∗)07 alleles may be associated with symptomatic dengue requiring hospitalization. In the presence of HLA-DRB1(∗)07/(∗)15 genotype, HLA-Cw(∗)07 is associated with increased risk of developing DHF while in the presence of other HLA-DRB1 alleles, HLA-Cw(∗)07 is associated with DF.


Determination of six Alternaria toxins with UPLC-MS/MS and their occurrence in tomatoes and tomato products from the Swiss market.
An ultra performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method was developed for the determination of the Alternaria toxins tenuazonic acid, alternariol, alternariol monomethyl ether, altenuene, altertoxin I and tentoxin. Owing to its instability, altenusin could not be determined. The sample preparation includes an acidic acetonitrile/water/methanol extraction, followed by SPE clean-up step, before injection into the UPLC-MS/MS system. The separation was made on an Acquity UPLC column using a water/acetonitrile gradient with ammonium hydrogen carbonate as a modifier. Matrix compounds of real samples led to enhancement as well as suppression of the target compounds, depending on analyte and matrix. The recoveries were between 58 and 109% at a level of 10 μg/kg. Eighty-five tomato products, consisting of peeled and minced tomatoes, soup and sauces, tomato purées and concentrates, ketchup as well as dried and fresh tomatoes, were taken from the Swiss market in 2010. Tenuazonic acid was found most frequently (81 out of 85 samples) and in the highest levels of up to 790 μg/kg. Alternariol and alternariol monomethyl ether were found in lower concentrations, ranging from <1 to 33 μg/kg for alternariol and <5 to 9 μg/kg for alternariol monomethyl ether. Only a few samples were positive for altenuene and tentoxin. Altertoxin I was never detected.


Influence of vibratory signals on the phonotaxis of the gryllid Gryllus bimaculatus DeGeer (Ensifera: Gryllidae).
Biophysical measurements exhibit that males of the ground-living gryllid Gryllus bimaculatus DeGeer (Ensifera: Gryllidae) produce vibratory signals while stridulating. Transmitted via the ground, these signals are perceiveable for conspecifics at a distance of a few dm. Experiments on the phonotactic behaviour of females of this species reveal that vibratory signals do influence this phonotactic behaviour pattern when no other directional cue is available. The significance of vibratory signals for the orientation of the gryllid in the biotope is discussed.


Aortoenteric fistula.
A fistula between the aorta and the gastrointestinal (GI) tract is a relatively uncommon and often lethal cause of GI bleeding. This report describes a patient with massive upper GI bleeding due to an aortoduodenal fistula. Such fistulae arise because of a combination of mechanical factors and local infection; the varied clinical presentations can be explained by the pathogenesis of the disease entity. These clinical presentations are reviewed, and a suggested approach to the diagnosis and management is presented.


GLI2 cell-specific activity is controlled at the level of transcription and RNA processing: Consequences to cancer metastasis.
High activity of GLI family zinc finger protein 2 (GLI2) promotes tumor progression. Removal of the repressor domain at the N terminus (GLI2∆N) by recombinant methods converts GLI2 into a powerful transcriptional activator. However, molecular mechanisms leading to the formation of GLI2∆N activator proteins have not been established. Herein we report for the first time that the functional activities of GLI2 are parted into different protein isoforms by alternative promoter usage, selection of alternative splicing, transcription initiation and termination sites. Functional studies using melanoma cells revealed that transcriptional regulation of GLI2 is TGFbeta-dependent and supports the predominant production of GLI2∆N and C-terminally truncated GLI2 (GLI2∆C) isoforms in cells with high migratory and invasive phenotype. Taken together, these results highlight the role of transcription and RNA processing as major processes in the regulation of GLI2 activity with severe impacts in cancer development.


Iris metastasis of gastric adenocarcinoma.
Iris metastasis in patients with gastric cancer is extremely rare. Herein, it is aimed to report on a patient with gastric adenocarcinoma and iris metastasis. A 65-year-old patient with the history of gastric cancer was admitted for eye pain and eye redness on his left eye. There was ciliary injection, severe +4 cells with hypopyon in the anterior chamber and a solitary, friable, yellow-white, fleshy-creamy vascularized 2 mm × 4 mm mass on the upper nasal part of the iris within the left eye. The presented patient's mass lesion in the iris fulfilled the criteria of the metastatic iris lesion's appearance. The ocular metastasis occurred during chemotherapy. Iris metastasis can masquerade as iridocyclitis with pseudohypopyon or glaucoma. In patients with a history of gastric cancer that present with an iris mass, uveitis, and high intraocular pressure, ocular metastasis of gastric cancer should be a consideration.


Amorphous Solid Dispersions of Felodipine and Nifedipine with Soluplus®: Drug-Polymer Miscibility and Intermolecular Interactions.
The objective of this study was to investigate thermodynamic and kinetic miscibility for two structurally similar model compounds nifedipine (NIF) and felodipine (FEL) when formulated as amorphous solid dispersions (ASDs) with an amphiphilic polymer Soluplus®. Thermodynamic miscibility was studied via melting point depression approach for the two systems. The Flory Huggins theory was used to calculate the interaction parameter and generate the phase diagrams. It was shown that NIF was more miscible in Soluplus® than FEL. The nature of drug polymer interactions was studied by fourier transform infra-red spectroscopy (FTIR) and solid-state nuclear magnetic resonance spectroscopy (ssNMR). The data from spectroscopic analyses showed that both the drugs interacted with Soluplus® through hydrogen bonding interactions. Furthermore, 13C ssNMR data was used to get quantitative estimate of the extent of hydrogen bonding for ASDs samples. Proton relaxation measurements were carried out on ASDs in order to evaluate phase heterogeneity on two different length scales of mixing. The data suggested that better phase homogeneity in NIF:SOL systems especially for lower Soluplus® content ASDs on smaller domains. This could be explained by understanding the extent of hydrogen bonding interactions for these two systems. This study highlights the need to consider thermodynamic and kinetic mixing, when formulating ASDs with the goal of understanding phase mixing between drug and polymer.


Differential Diagnosis of Arterial Phase Enhanced Hepatic Inflammatory Lesions and Hepatocellular Carcinomas with Contrast-enhanced Ultrasound.
We aimed to investigate the enhancement patterns of contrast-enhanced ultrasound (CEUS) with SonoVue and determine the utility of this method for differential diagnosis between hepatic inflammatory lesions with arterial phase enhancement and hepatocellular carcinomas (HCC). Twenty-three patients with arterial-enhanced inflammatory liver lesions and 46 HCC patients were included. These lesions had been subjected to CEUS examination and confirmed by pathologic results or imaging follow-up for at least 1 y. In the arterial phase of CEUS, 65.2% of the inflammatory lesions showed patchy (slight enhancement with poorly defined margins) or centripetal enhancement, whereas 89.1% of the HCC lesions showed homogeneous or heterogeneous enhancement (p < 0.001). Moreover, 82.6% of the inflammatory lesions had poorly defined margins, and 78.3% were irregular in shape at the peak, whereas 87.0% of the HCC lesions had well-defined margins and 76.1% were regular (both p < 0.001). Feeding vessels were more frequently visualized in HCCs (71.7%) than in inflammatory lesions (26.1%, p < 0.001). Additionally, 88.2% of the internal non-perfused areas in inflammatory lesions were regular in shape, while 68.0% of these areas in HCCs had an irregular shape (p < 0.001). CEUS pattern analysis provides important information for differentiating inflammatory liver lesions and HCCs and is helpful for improving diagnostic accuracy.


Differential influence of Clinical Disease Activity Index components based on disease state in rheumatoid arthritis patients: real-world results from the Ontario Best Practices Research Initiative.
The Clinical Disease Activity Index (CDAI) is routinely used in clinical care when treating-to-target RA patients. Previous validation studies have looked at CDAI's overall performance; this analysis aimed at evaluating its properties by disease state and identifying drivers of variance. RA patients enrolled in the OBRI registry, with available follow-up of ≥6 months were included. Construct validity of CDAI was assessed with principal component analysis; internal consistency with Cronbach's alpha (α); correlational validity with Spearman's rho (ρ); agreement in disease state classification with the kappa statistic. Stratification by disease states was performed. CDAI correlation with DAS28 was strong when CDAI>10 (ρ=0.79), moderate when CDAI≤10 (ρ=0.56) or 2.8<CDAI≤10 (ρ=0.44), and very weak when CDAI≤2.8 (ρ=0.02). Classification agreement of low disease activity (LDA)/remission between CDAI (≤10) and DAS28 (≤3.2) or HAQ-DI (≤2) was fair-to-moderate, while poor-to-fair for remission. For CDAI>10, CDAI was able to be reduced to a single component with patient global assessment (PtGA) having the lowest loading. When CDAI≤10, two distinct components were identified: (1) PtGA and physician global assessment; (2) SJC28 and TJC28. Moderate levels (α=0.71) of internal consistency were observed when CDAI>10 but low when CDAI≤10 (α=0.23), 2.8<CDAI≤10 (α=-0.42) or CDAI≤2.8 (α=-0.35). PtGA showed lowest correlation with remaining CDAI components. CDAI and DAS28 correlated well in moderate/high disease activity and poorly in LDA/remission. PtGA correlated weakly with other CDAI components and had a stronger influence on CDAI in LDA/remission. Thus, careful interpretation of PtGA is necessary when making treatment decisions, particularly in patients in CDAI LDA who are non-remitters.


The Impact of Polyphenolics in the Management of Breast Cancer: Mechanistic Aspects and Recent Patents.
Breast cancer is the most frequently diagnosed type of cancer in women, accounting for 2.1 million cases, and stands as the fifth leading cause of death. Several treatment strategies are available, such as surgical resection, radiation, hormonal therapy, and conventional chemotherapy; however, these are associated with severe adverse effects in the patients. This review aims to summarize the different studies (in vitro, in vivo, and new patents) concerning the therapeutic potential of plant polyphenolics in the management of breast cancer, published in the period from January 2016 to January 2021. Moreover, this review will focus on the underlying mechanisms of action and molecular characteristics of these compounds. The data of this review were collected from different scientific databases, such as Pub- Med, Science Direct, Google Scholarship, SciFinder, and Egyptian Knowledge Bank (EKB). During the period 2016-2021, in the in vitro studies, investigation on 52 compounds of polyphenolic nature with promising anti-breast cancer activity has been conducted, while 14 compounds have been reported via in vivo studies. Besides, about 15 compounds have been registered as patent drugs. Different mechanisms of action and molecular targets have been reported, providing a clarified basis and precise reflection of the anticancer properties of these compounds against breast cancer. Polyphenolics represent a comprehensive source of anticancer lead compounds against the progression of breast cancer invasion and metastasis.


Reconsideration of echocardiographic standards for mitral valve prolapse: lack of association between leaflet displacement isolated to the apical four chamber view and independent echocardiographic evidence of abnormality.
Mitral valve prolapse by current echocardiographic criteria can be diagnosed with surprising frequency in the general population, even when preselected normal subjects are examined. In most of these individuals, however, prolapse is present in the apical four chamber view and absent in roughly perpendicular long-axis views. Previous studies have shown that systolic annular nonplanarity can cause apparent prolapse in the four chamber view without actual leaflet displacement above the most superior points of the anulus, and there is evidence for such nonplanarity in vivo. It is then reasonable to ask whether superior leaflet displacement limited to the four chamber view has any pathologic significance or complications. The purpose of this study, therefore, was to address the following hypothesis: that patients with superior leaflet displacement confined to the four chamber view have no higher frequency of associated echocardiographic abnormalities than do patients without displacement in any view. Such abnormalities, which would provide independent evidence of mitral valve pathology or dysfunction, include leaflet thickening, left atrial enlargement and mitral regurgitation. Leaflet displacement was measured in the parasternal long-axis and apical four chamber views in 312 patients who were studied retrospectively and selected for the absence of forms of heart disease other than mitral valve prolapse. Leaflet thickness and left atrial size were measured and mitral regurgitation was graded. Patients with leaflet displacement limited to the four chamber view were no more likely to have associated abnormalities than were patients without displacement in any view (0 to 2% prevalence, p greater than 0.5). In contrast, patients with leaflet displacement in the long-axis view were significantly more likely to have associated abnormalities (12 to 24%, p less than 0.005), the frequency of which increased with the extent of leaflet displacement in that view (p less than 0.0001). These results suggest that displacement limited to the apical four chamber view is, in general, a normal geometric finding unassociated with echocardiographic evidence of pathologic significance.


Effect of ultralow doses of antibodies to S-100 antigen (Proproten-100) on spatial learning in rats.
In experiments on rats we studied the effect of potentiated antibodies against S-100 antigen on training a step-down passive avoidance task and choice between drinking bowls with sucrose solution. Peroral treatment with antibodies accelerated inhibition of ineffective and punished locomotor reactions in animals.


Aberrant protamine 1/protamine 2 ratios in sperm of infertile human males.
Protamines were extracted from the sperm of fertile and infertile human males and the relative proportion of protamines 1, 2, and 3 were determined by scanning microdensitometry following electrophoresis of total protamine in polyacrylamide gels. The proportion of the three protamines was found to be similar in sperm obtained from different normal males. The distribution of protamines in sperm obtained from a select group of infertile males producing an elevated level of large sperm heads, in contrast, was different from that of the fertile males.


Implementing Sensitivity and Contingency in Medical Contexts: The Case of Prematurity.
In the context of relational situations, sensitivity and contingency are identified as pivotal variables that contribute to the enhancement of patients' overall wellbeing [...].


Anal Intraepithelial Neoplasia and Anal Squamous Cell Carcinoma: Updates From the Last 3 Years.
In the last 3 years, new and relevant information has been published on anal cancer and anal precancerous lesions epidemiology, screening, treatment, and vaccination. This information will likely change prevention and treatment strategies for these patients in the upcoming years.


New m-calpain substrate-based azapeptide inhibitors.
Calpains are intracellular cysteine proteases with several important physiological functions. Calpain inhibitors may be promising tools in the analysis of the function of the enzyme in diseases caused by overexpression/activation. Here, we report on the synthesis, solution conformation, and characterization of novel group of azapeptides whose sequences originate from an efficient m-calpain substrate, TPLKSPPPSPR, described by us earlier and possess varying levels of calpain inhibition. The Lys residue at P1 position was replaced with azaglycine (NH2 -NH-COOH) and further changes were made as follows: the N-terminal or/and C-terminal were truncated, amino acids were also changed at P3, P2, P'1, or P'2 positions. Our results indicate that the identity of amino acid moieties between P4 and P'5 positions is essential for the inhibitory activity. Only changes at position P3 (Pro) are tolerated. Azapeptide analogs, described in this communication could be considered as useful set of compounds for elucidation of the enzyme interaction at P and P' sites.


Impact of opening an acute palliative care unit on administrative outcomes for a general oncology ward.
Acute palliative care units (APCUs) are gaining popularity in tertiary care centers. In this study, the authors examined the impact of opening an APCU on administrative outcomes for a general oncology ward (GOW) at a comprehensive cancer center. The GOW database was reviewed for 3 periods: June 2000 through May 2002 (before the APCU opened), June 2002 through May 2004 (transitional period, including APCU opening in a temporary location), and June 2004 through May 2006 (after opening of the APCU). Data were extracted on demographics, reasons for admission, admission type, waiting time for admission, length of stay (LOS), overstay (>2 days over expected LOS), death rate, and discharge destination. Linear regression analysis and the Cochran-Armitage test were used for data analysis. There were 5340 admissions: The median patient age was 60 years, and 55% of patients were women. The most common primary cancers were head and neck (22%), gynecologic (21%), gastrointestinal (13%), and lung (12%). There were significant trends on the GOW in decreased admissions for palliative care (12.2%, 9.6%, and 7.9%, respectively, for the 3 periods; P < .0001), fewer inpatient deaths (11.4%, 8.6%, and 6.1%, respectively; P < .0001), and fewer patients with prolonged waits for a bed on a palliative care unit (3.4%, 3%, and 1.7%, respectively; P = .002). Admissions increased for interventions (10.4%, 17.3%, and 22.5%, respectively, for the 3 periods; P < .0001) and for chemotherapy (6.8%, 6.6%, and 9.7%, respectively; P = .001). After the opening of an APCU at the authors' cancer center, the GOW experienced a decrease in administrative endpoints related to palliative and end-of-life care and an increase in endpoints related to cancer-directed interventions. Prospective studies with clinical endpoints will be required to determine whether this specialization of inpatient care improves quality of life, quality of death, and psychosocial well being.


Sequence analysis of three tRNA(Phe) nuclear genes and a mutated gene, and one gene for tRNA(Ala) from Arabidopsis thaliana.
Three genes and one mutant gene for tRNA(Phe) (GAA) and one gene for tRNA(Ala) (UGC) were isolated from a whole-cell DNA library of Arabidopsis thaliana. All three tRNA(Phe) genes are identical in their nucleotide sequence, but differ in their 5' and 3' flanking regions. The mutant tRNA(Phe) (GAA) gene differs from the other three genes by one nucleotide change from highly conserved G to C at the 57th nucleotide position. The primary structure of the first tRNA(Ala) gene was also determined in this experiment.


The role of peroxiredoxin 6 in biosynthesis of FAHFAs.
Peroxiredoxin 6 (Prdx6) is a multifunctional enzyme, a unique member of the peroxiredoxin family, with an important role in antioxidant defense. Moreover, it has also been linked with the biosynthesis of anti-inflammatory and anti-diabetic lipids called fatty acid esters of hydroxy fatty acids (FAHFAs) and many diseases, including cancer, inflammation, and metabolic disorders. Here, we performed metabolomic and lipidomic profiling of subcutaneous adipose tissue from mouse models with genetically modified Prdx6. Deletion of Prdx6 resulted in reduced levels of FAHFAs containing 13-hydroxylinoleic acid (13-HLA). Mutation of Prdx6 C47S impaired the glutathione peroxidase activity and reduced FAHFA levels, while D140A mutation, responsible for phospholipase A2 activity, showed only minor effects. Targeted analysis of oxidized phospholipids and triacylglycerols in adipocytes highlighted a correlation between FAHFA and hydroxy fatty acid production by Prdx6 or glutathione peroxidase 4. FAHFA regioisomer abundance was negatively affected by the Prdx6 deletion, and this effect was more pronounced in longer and more unsaturated FAHFAs. The predicted protein model of Prdx6 suggested that the monomer-dimer transition mechanism might be involved in the repair of longer-chain peroxidized phospholipids bound over two monomers and that the role of Prdx6 in FAHFA synthesis might be restricted to branching positions further from carbon 9. In conclusion, our work linked the peroxidase activity of Prdx6 with the levels of FAHFAs in adipose tissue.


Detection of endotracheal tube obstruction by analysis of the expiratory flow signal.
Acute obstruction of endotracheal tubes (ETT) increases airway pressure, decreases tidal volume, increases the risk of dynamic hyperinflation by prolonging the duration of passive expiration, and prevents reliable calculation of tracheal pressure. We propose a computer-assisted method for detecting ETT obstruction during controlled mechanical ventilation. The method only requires measurement of the expiratory flow. Computer simulation; prospective study in two cases; retrospective study in one case and in seven patients with the adult respiratory distress syndrome (ARDS). Laboratory of the Section of Experimental Anaesthesiology (University of Freiburg); surgical adult intensive care units in a university hospital (University of Basel) and in a university affiliated hospital (Zentralklinikum Augsburg). 3 patients with partial ETT or bronchial obstructions and 7 ARDS patients. Expiratory flow was measured using a pneumotachograph and integrated to obtain expiratory volume. The time-constant of passive expiration (tauE) as a function of expired volume [tauE(V(E)) function] was calculated from the expiratory volume/flow curve. We investigated the tauE(V(E)) function of data obtained from: (1) computer simulation of mechanically ventilated homogeneous and inhomogeneous lungs intubated with ETTs of different sizes; (2) one patient with an artificial ETT obstruction of 7.5 and 25% of the cross-sectional area of the ETT (case 1); (3) one patient with ETT obstruction due to secretions (case 2); (4) one patient with acute bronchial constriction (case 3); (5) seven ARDS patients who showed an increase in airway resistance of more than 2 cm H2O x s/l. It was found that an ETT obstruction caused an increase in tauE in early expiration (at high flow), whereas tauE in late expiration was virtually unchanged. The reason for this is the flow dependency of the increase in ETT resistance produced by ETT obstruction. Unlike ETT obstruction, an increase in pure airway resistance produced an increase in tauE throughout expiration. An ETT obstruction can be reliably distinguished from an increase in pure airway resistance by a characteristic pattern change in the tauE(V(E)) function, which can be detected easily even by an automated pattern recognition system.


A one step real-time RT-PCR assay for the quantitation of Wheat yellow mosaic virus (WYMV).
Wheat yellow mosaic virus (WYMV) is an important pathogen in China and other countries. It is the member of the genus Bymovirus and transmitted primarily by Polymyxa graminis. The incidence of wheat infections in endemic areas has risen in recent years. Prompt and dependable identification of WYMV is a critical component of response to suspect cases. In this study, a one step real-time RT-PCR, followed by standard curve analysis for the detection and identification of WYMV, was developed. Two reference genes, 18s RNA and β-actin were selected in order to adjust the veracity of the real-time RT-PCR assay. We developed a one-step Taqman-based real-time quantitative RT-PCR (RT-qPCR) assay targeting the conserved region of the 879 bp long full-length WYMV coat protein gene. The accuracy of normalized data was analyzed along with appropriate internal control genes: β-actin and 18s rRNA which were included in detecting of WYMV-infected wheat leaf tissues. The detectable end point sensitivity in RT-qPCR assay was reaching the minimum limit of the quantitative assay and the measurable copy numbers were about 30 at 10⁶-fold dilution of total RNA. This value was close to 10⁴-fold more sensitive than that of indirect enzyme-linked immunosorbent assay. More positive samples were detected by RT-qPCR assay than gel-based RT-PCR when detecting the suspected samples collected from 8 regions of China. Based on presented results, RT-qPCR will provide a valuable method for the quantitative detection of WYMV. The Taqman-based RT-qPCR assay is a faster, simpler, more sensitive and less expensive procedure for detection and quantification of WYMV than other currently used methods.


Selective detection of rat and mouse specific albumin and alpha-fetoprotein mRNA molecules under highly stringent hybridization conditions.
The molecular analysis of some important interactions observed between the parental genomes in interspecific cell hybrids requires the availability of highly specific hybridization assays to selectively quantitate mRNA sequences coding for the same protein but transcribed from the two different genomes. Specific hybridization techniques which should permit the selective detection of rat and mouse albumin and alpha-fetoprotein (AFP) mRNA molecules in a mixture of the two types of mRNAs are presented here. The high degree of homology existing between the AFP mRNA sequences coding for mouse and rat AFP, and, presumably, albumin, results in extensive cross-hybridization with the cDNA probes under standard hybridization conditions. No size differences could be detected between the two types of mRNA molecules from the two species. A Tm difference of 7 degrees C between the intra- and interspecific mRNA:rat cDNA hybrids allowed the establishment of highly stringent solution hybridization conditions necessary to measure separately the contents of rat albumin and AFP mRNAs. Mouse albumin and AFP cDNA clones were then isolated from mouse liver and yolk sac cDNA libraries, and used to show the usefulness of highly stringent washing conditions to discriminate between rat and mouse albumin and AFP mRNA molecules in conventional "Northern blotting" techniques. In combination with the solution hybridization assay, these filter hybridization techniques can be used to specifically quantitate the content of rat and mouse albumin and AFP mRNA molecules in interspecific cell hybrids.


Supercritical carbon dioxide extraction of Usnea longissima (L.) Ach.: Optimization by Box-Behnken design (BBD).
Usnic acid (UA) was extracted from Usnea longissima (L.) Ach. in supercritical carbon dioxide (SC-CO2) medium. The selected process parameters were extraction temperature (35-45 °C), amount of co-solvent (0%-5%) and extraction time (5-9 h). These parameters were applied to Box-Behnken design (BBD) belonging to response surface methodology (RSM) to determine optimum process parameters for the highest amount of UA in the extract. g UA/100g lichen, extraction yield % and UA content values were calculated in the range of 0.045-0.317, 2.77-5.4 and 71%-82% in different experimental conditions, respectively. The optimum conditions were predicted as 42 °C, 4.3% (ethanol) and 7.48 h. It was determined that the predicted and experimental values of g UA/100g lichen were compatible, and the suggested model was valid.


Targeting cell plasticity for regeneration: From in vitro to in vivo reprogramming.
The discovery of induced pluripotent stem cells (iPSCs), reprogrammed to pluripotency from somatic cells, has transformed the landscape of regenerative medicine, disease modelling and drug discovery pipelines. Since the first generation of iPSCs in 2006, there has been enormous effort to develop new methods that increase reprogramming efficiency, and obviate the need for viral vectors. In parallel to this, the promise of in vivo reprogramming to convert cells into a desired cell type to repair damage in the body, constitutes a new paradigm in approaches for tissue regeneration. This review article explores the current state of reprogramming techniques for iPSC generation with a specific focus on alternative methods that use biophysical and biochemical stimuli to reduce or eliminate exogenous factors, thereby overcoming the epigenetic barrier towards vector-free approaches with improved clinical viability. We then focus on application of iPSC for therapeutic approaches, by giving an overview of ongoing clinical trials using iPSCs for a variety of health conditions and discuss future scope for using materials and reagents to reprogram cells in the body.


Evaluation of indicated preventive intervention (secondary prevention) mental health programs for children and adolescents.
Evaluated the outcomes of 130 indicated preventive interventions (secondary prevention) mental health programs for children and adolescents that seek to identify early signs of maladjustment and to intervene before full-blown disorders develop. Results indicate such programs significantly reduce problems and significantly increase competencies. In particular, behavioral and cognitive-behavior programs for children with subclinical disorders (mean ESs in the 0.50s) appear as effective as psychotherapy for children with established problems and more effective than attempts to prevent adolescent smoking alcohol use, and delinquency. In practical terms, the average participant receiving behavioral or cognitive-behavior intervention surpasses the performance of approximately 70% of those in a control group. Of particular interest was the high mean effect (0.72) achieved by programs targeting incipient externalizing problems which are customarily the least amenable to change via traditional psychotherapeutic efforts when they reach clinical levels. Priorities for future research include greater specification of intervention procedures, assessment of treatment implementation, more follow-up studies, and identifying how different participants respond to early intervention.


Immunohistochemical evidence for the coexistence of calcitonin gene-related peptide- and choline acetyltransferase-like immunoreactivity in neurons of the rat hypoglossal, facial and ambiguus nuclei.
The present immunocytochemical study demonstrates that calcitonin gene-related peptide-like immunoreactivity (CGRPI) coexists with acetylcholine in single cells of hypoglossal, facial and ambiguus nuclei. The experiments were done using alternate frozen sections from relevant regions of the rat brain. We further show that CGRPI is localized in the nerve terminals that form neuromuscular junctions in the tongue muscles.


Factors Associated with Access to Maternal and Reproductive Health Care among Somali Refugee Women Resettled in Ohio, United States: A Cross-Sectional Survey.
This study examined maternal and reproductive health (MRH) access of Somali refugees in the U.S. across four access dimensions (willingness to seek care, gaining entry to the health system, seeing a primary provider and seeing a specialist). We conducted a cross-sectional survey of 427 Somali refugee reproductive-age women in Franklin County, Ohio. Following descriptive statistics of demographics, we conducted multivariate analyses to test associations between demographics and the four access dimensions. Most Somali refugee women were married (68%), attained primary education (92%), employed (64%) and were circumcised (82%). Young (OR 2.61, 95% CI 1.25-5.60), single (OR 1.78, 95% CI 1.15-2.78), and minors upon arrival (OR 2.36, 95% CI 1.44-3.90) were more willing to seek care. Lack of insurance, limited language fluency and being circumcised limited access to care across all dimensions. Barriers to access need to be systematically addressed. Deconstructing beliefs regarding health systems may improve access, especially among older Somali women.


Land use/cover changes, the environment and water resources in northeast China.
Land use/cover in Northeast China went through extensive changes during the 1990s. This report explores the interaction between these changes and the environment, and the implication of these changes for rational allocation of water resources. Two maps of land use/cover produced from 1990 and 2000 Landsat TM satellite images were overlaid in Arc Info to reveal changes in land cover. Results indicate that farmland and grassland decreased by 386,195 and 140,075 ha, respectively, while water, built-up areas, and woodland increased by 238,596, 194,231, and 192,682 ha, respectively. These changes bore a mutual relationship with the environmental change. On the one hand, climate warming made some of these changes (e.g., conversion of woodland and grassland to farmland) possible. On the other hand, the changed surface cover modified the local climate. These changes, in turn, caused severe environmental degradation and increased flooding. The change between dry field and rice paddy, in particular, raised severe implications for the proper allocation of limited water resources in the Northeast. Efforts are needed to coordinate their rational allocation to reap maximum and sustainable return over the entire area, not just in some localities. Results obtained in this study should be of interest to the international audience of Environmental Management in that they highlight the interactive nature of human activities and the environment and the off-site impact of these activities on the environment.


Using an algorithm to assess the rate and trend over time of inappropriate proton pump inhibitors prescription upon hospital discharge.
There is an increasing interest in inappropriate proton pump inhibitors prescription (InPPIp), as defined by the National Institute for Clinical Excellence (NICE) guidelines. To evaluate the rate, trend over time and factors associated with InPPIp upon discharge from internal medicine departments. We evaluated patients discharged from internal medicine departments with a PPI prescription in 2014 and 2017 at an academic referral center according to a developed algorithm. A total of 3,982 patients were included (50.8% women, 74% ≥ 65 years). The rate of InPPIp was 44.3% (95% CI 42.8-45.9) for the entire cohort; 68.1% for subjects aged < 65 years and 36.0% for those aged ≥ 65 years (p<0.001); 43.2% in 2014 and 45.6% in 2017 (p = 0.130). In a decision-tree analysis, after the exclusion of 448 patients with gastrointestinal indications, 89.4% (1,580/1,766) of all InPPIp cases were of patients without dual antiplatelet treatment (DAPT) and 8.6% (151/1,766) were of patients younger than 65 years, who were taking aspirin. The rate of InPPIp is high, especially among patients not receiving DAPT and young patients taking aspirin. Time trend analysis showed no improvement over time. Our algorithm may serve as an automated quality measuring tool to reduce InPPIp.


Cooexpression of FTDP-17 tau and GSK-3beta in transgenic mice induce tau polymerization and neurodegeneration.
Here we have tested whether tau modification either by point mutation or by hyperphosphorylation can exert maximal pathogenic effects or if, on the contrary, both types of tau modifications can act synergistically to induce neuropathology. For this, we have combined transgenic mice overexpressing the enzyme GSK-3beta (Tet/GSK-3beta mice), with transgenic mice expressing Tau with a triple FTDP-17 mutation which develop prefibrillar tau-aggregates (VLW mice). Tet/GSK-3beta/VLW transgenic mice show tau hyperphosphorylation in hippocampal neurons. This is accompanied by thioflavin-S staining, and formation of filaments similar in width to those found in tauophaties. Finally, the atrophy of the hippocampal dentate gyrus observed in Tet/GSK-3beta mice develops much faster in Tet/GSK-3beta/VLW mice. All these morphological and biochemical data demonstrate that there is a synergistic contribution of both types of tau modifications and that the potential of GSK-3 inhibitors for AD therapeutics also extends to tauopathies caused by point mutations in tau gene.


Helicase-independent function of RIG-I against murine gammaherpesvirus 68 via blocking the nuclear translocation of viral proteins.
Innate immunity is the first line of defense against viral pathogens. Retinoic Acid-Inducible Gene 1 (RIG-I) is a pattern recognition receptor that recognizes virus-associated double-stranded RNA and initiates the interferon responses. Besides signal transduction, RIG-I exerts direct antiviral functions to displace viral proteins on dsRNA via its Helicase activity. Nevertheless, this effector-like activity of RIG-I against herpesviruses remains largely unexplored. It has been previously reported that herpesviruses deamidate RIG-I, resulting in the abolishment of its Helicase activity and signal transduction. In this study, we discovered that RIG-I possessed signaling-independent antiviral activities against murine gamma herpesviruses 68 (γHV68, murid herpesvirus 4). Importantly, a Helicase-dead mutant of RIG-I (K270A) demonstrated comparable inhibition on herpesviruses lytic replication, indicating that this antiviral activity is Helicase-independent. Mechanistically, RIG-I bound the Replication and Transcription Activator (RTA) and diminished its nuclear localization to repress viral transcription. We further demonstrated that RIG-I blocked the nuclear translocation of ORF21 (Thymidine Kinase), ORF75c (vGAT), both of which form a nuclear complex with RTA and RNA polymerase II (Pol II) to facilitate viral transcription. Moreover, RIG-I retained ORF59 (DNA processivity factor) in the cytoplasm to repress viral DNA replication. Altogether, we illuminated a previously unidentified, Helicase-independent effector-like function of RIG-I against γHV68, representing an exquisite host strategy to counteract viral manipulations on innate immune signaling. IMPORTANCE: Retinoic acid-inducible gene I (RIG-I), a member of DExD/H box RNA helicase family, functions as a key pattern recognition receptor (PRR) responsible for the detection of intracellular double-stranded RNA (dsRNA) from virus-infected cells and induction of type I interferon (IFN) responses. Nevertheless, our understanding of the helicase-independent effector-like activity of RIG-I against virus infection, especially herpesvirus infection, remains largely unknown. Herein, by deploying murine gamma herpesviruses 68 (γHV68) as a model system, we demonstrated that RIG-I possessed an interferon and helicase-independent antiviral activity against γHV68 via blocking the nuclear trafficking of viral proteins, which concomitantly repressed the viral early transcription and genome replication thereof. Our work illuminates a previously unidentified antiviral strategy of RIG-I against herpesvirus infection.