Roles of gibberellins and abscisic acid in dormancy and germination of red bayberry (Myrica rubra) seeds.
Intact seeds from freshly harvested fruits of Myrica rubra (Sieb et Zucc.) were dormant and required 8 weeks of warm stratification followed by 12 weeks of cold stratification for germination. Exogenous application of gibberellic acid (GA(3)) to intact fresh seeds was effective in breaking dormancy, with > 70% of seeds germinating when treated with 5.2 mM GA(3) and incubated at a day/night temperature of 30/20 degrees C for 20 weeks. Removing the hard endocarp or endocarp plus seed coat of fresh seeds promoted germination, and addition of GA(3) to the embryo accelerated germination. The gibberellins GA(1) and GA(4) were more effective than GA(3) in promoting germination of seeds with the endocarp removed. Endogenous contents of GA(1), GA(3), GA(4), GA(7) and GA(20) were quantified by gas chromatography-mass spectrometry-selected ion monitoring in the endocarps, seed coats and embryos of fresh seeds treated with 5.2 mM GA(3). The content of GA(3) decreased in the endocarp during incubation, whereas GA(1) contents increased in the endocarp and seed coat. A high GA(1) content was detected in the endocarps and embryos of newly germinated seeds. We speculate that GA(3) was converted to GA(1) during incubation and that GA(1) is involved in seed germination. Endogenous abscisic acid (ABA) contents were measured in fresh seeds and in warm and cold stratified seeds. The ABA content in fresh seeds was distributed in the order endocarp > seed coat > embryo, with the content in the endocarp being about 132-fold higher than in the seed coat and embryo. Total ABA content of seeds subjected to warm or cold stratification, or both, was 8.7- to 14.0-fold lower than that of fresh seeds. Low contents of endogenous GA(1), GA(3), GA(7) and GA(20), but elevated contents of GA(4), were found in the seed coats and endocarps of warm plus cold stratified seeds and in the seed coats and embryos of newly germinated seeds. These observations, coupled with the finding that GA stimulated germination of dormant Myrica seeds, provide evidence that endogenous ABA inhibited release of dormancy and that endogenous gibberellins, especially GA(4) or GA(1), or both, are involved in germination.


[State of homeostasis under administration of bear fat in rats with exogenous and endogenous thrombinemia].
In experimental studies on 448 rats treated with bear fat diet (0.08 ml/100 g body weight), the nature and mechanisms of influence of this additive on the process of blood coagulation in experimental thromboplastinemia of different origin has been studied. As a result of intravenous injection in the jugular vein of a suspension of thrombin (exogenous thrombinemia) all clothingsee tests lengthened in the control animals (p<0.05): prothrombin time by 11.1%, activated partial thromboplastin time - by 13.4%, thrombin time by 16.8%. Fibrinogen fell by 1.9 fold, that was accompanied by increase of the level of soluble fibrin monomer complexes and reduce of activity of antithrombin III by 20.2%. At the same time severe thrombocytopenia developed with a relative increase in the number of activated forms (by 73.1%). Consumption coagulopathy was also observed in rats treated with bear fat, but the potential of hemostatic cascade and anticoagulation system remained high (judging by the tests PTV, thrombin time and content of antithrombin III). Under endogenous thromboplastinemia caused by combined stress (hypothermia + physical activity) in animals of the control group on the background of the shortening of the APTT (by 24.9%) and PTV (16.8%), RCMP concentration increased by 52% and activity of antithrombin III increased compensatory. There was an increase of platelet count, due to the activated forms. To 3 h signs of hypocoagulation aggravated even more. In animals treated with bear fat, the results of clothing tests did not differ from the original figures, and by 3 h, the majority of the indicators have reached their original values. The increase in platelet count has not been observed.


Absolute configuration of sporotricale and structure of 6-hydroxysporotricale.
The absolute configuration of the two stereocenters of (+)-sporotricale (2a), a bioactive phthalide secondary metabolite, was determined through circular dichroism and by applying Mosher's method. The structure of 6-hydroxysporotricale (2c), isolated from cultures in vitro of Sporotrichum laxum, was also elucidated.


Epidemiological study on feline gastric Helicobacter spp. in Japan.
Epidemiological and pathological studies on Helicobacter spp. in feline stomachs in Japan were conducted using genus- and species-specific (H. felis, H. bizzozeronii, H. heilmannii sensu stricto [s.s.] and H. pylori) polymerase chain reactions (PCRs), ureAB gene sequencing and histopathology. PCR results showed that 28 of 56 cats were infected with Helicobacter spp., and H. heilmannii s.s. was the most prevalent species by both PCR (28/28) and ureAB gene sequencing (26/28). Some of the sequences showed high similarities with those from human patients with gastric diseases (99%). There were no significant differences between Helicobacter spp.-positive and -negative cats in the severity of chronic gastritis (P=0.69). This is the first extensive epidemiological study on feline gastric Helicobacter spp. in Japan.


Serum concentrations of type II collagen biomarkers (C2C, C1, 2C and CPII) suggest different pathophysiologies in patients with hip osteoarthritis.
Cartilage destruction in osteoarthritis (OA) involves excessive degradation and increased synthesis of cartilage matrix macromolecules including type II collagen and proteoglycans. Cartilage biomarkers exist for the measurement of cartilage matrix turnover and may reveal differences in patients with OA. To determine whether there are detectable differences in and relationships between biomarkers of type II collagen (CII) degradation (C2C, C1, 2C) and synthesis (CP II) in patients with only hip OA (OHOA) and those suffering from multiple sites OA (MSOA). Fifty-six patients classified as MSOA or OHOA. Minimum hip joint space width (Min JSW) measured by computer from standard radiographs. Serum measurement of CII synthesis C-propeptide (CPII) and cleavage of type II (C2C) and types I and II (C1, 2C) collagens. Aggrecan metabolism was assessed by serum CS 846 assay. Step to step logistic regression to determine the effect of the quantitative data on the assignment to each subgroup. Twenty-four subjects were classified with MSOA. Among the 32 OHAO patients, 15 had bilateral hip OA and 17 had unilateral hip OA. The latter were classified with "Isolated hip OA" (IHOA). CPII levels were significantly lower in patients with MSOA than in those with OHOA (99.9+/-50.3ng/mL versus 141.9+/-81.2ng/mL, p=0.04. OR= 0.18 for CPII >120 ng/mL, p<0.005). C2C levels were also lower in MSOA (9.7+/-2.3ng/mL) versus OHOA (11.4+/-3.2ng/mL, p=0.03. OR= 0.26 for C2C >10 ng/mL, p=0.02). There was an inverse correlation between min JSW and C2C only in patients with IHOA (r=0.50, p= 0.02). Hip OA, in patients with MSOA, might be related to alteration in CII metabolism which may result in a deficient type II collagen repair process. The significant relationship between C2C and JSW in IHOA suggests that this marker is of value in assessing cartilage degradation patients with involvement of a single joint.


Comparison of wear of ultra-high molecular weight polyethylene acetabular cups against surface-engineered femoral heads.
Alumina ceramic heads have been previously shown to reduce polyethylene wear in comparison to cobalt chrome (CoCr) heads in artificial hip joints. However, there are concerns about the brittle nature of ceramics. It is therefore of interest to investigate ceramic-like coatings on metallic heads. The aim of this study was to compare the friction and wear of ultra-high molecular weight polyethylene (UHMWPE) against alumina ceramic, CoCr, and surface-engineered ceramic-like coatings in a friction simulator and a hip joint simulator. All femoral heads tested were 28 mm diameter and included: Biolox Forte alumina, CoCr, arc evaporative physical vapour deposition (AEPVD) chromium nitride (CrN) coated CoCr, plasma-assisted chemical vapour deposition (PACVD) amorphous diamond-like carbon (aDLC) coated CoCr, sputter CrN coated CoCr, reactive gas controlled arc (RGCA) AEPVD titanium nitride (TiN) coated CoCr, and Graphit-iC coated CoCr. These were articulated against UHMWPE acetabular cups in a friction simulator and a hip joint simulator. Alumina and CoCr gave the lowest wear volumes whereas the sputter coated CrN gave the highest. Alumina also had the lowest friction factor. There was an association between surface parameters and wear. This study indicates that surface topography of surface-engineered femoral heads is more important than friction and wettability in controlling UHMWPE wear.


The retirement adjustment process: changes in the well-being of male retirees across time.
The purpose of this prospective study was to (1) evaluate the impact of retirement, (2) monitor the change in adjustment across time, and (3) identify the resources predictive of short- and long-term adjustment in retirement. A sample of 117 male retirees was assessed on indices of physical and psychological health, perceived control, retirement satisfaction, and life satisfaction at 2-4 months preretirement, 1 year post-, and 6-7 years postretirement. The results provided support for a positive impact of retirement, as retirees evidenced increases in well-being during the first year. There was also evidence of a retirement adjustment process, in that aspects of well-being (i.e., psychological health) changed from short- to long-term retirement. Finally, physical health, income, and voluntary retirement status predicted short-term adjustment, while internal locus of control was an additional resource for long-term adjustment. Changes in resources over time also differentially predicted short- and long-term adjustment (e.g., an increase in internal locus of control predicted an increase in activity satisfaction at 1 year but not at 6-7 years postretirement).


Time-restricted feeding regulates lipid metabolism under metabolic challenges.
Dysregulation of lipid metabolism is a commonly observed feature associated with metabolic syndrome and leads to the development of negative health outcomes such as obesity, diabetes mellitus, non-alcoholic fatty liver disease, or atherosclerosis. Time-restricted feeding/eating (TRF/TRE), an emerging dietary intervention, has been shown to promote pleiotropic health benefits including the alteration of diurnal expression of genes associated with lipid metabolism, as well as levels of lipid species. Although TRF likely induces a response in multiple organs leading to the modulation of lipid metabolism, a majority of the studies related to TRF effects on lipids have focused only on individual tissues, and furthermore there is a lack of insight into potential underlying mechanisms. In this review, we summarize the current insights regarding TRF effects on lipid metabolism and the potential mechanisms in adipose tissue, liver, skeletal muscle, and heart, and conclude by outlining possible avenues for future exploration.


Role of biomarkers in risk stratification of acute coronary syndrome.
Diagnosis of acute coronary syndrome (ACS) encompasses a wide spectrum of myocardial ischaemia varying from assuredly benign to potentially fatal. Cardiac biomarkers have had a major impact on the management of this disease and are now the cornerstone in its diagnosis and prognosis. In this review we discuss both the established and the newer emerging biomarkers in ACS and their role in highlighting not only myocardial necrosis but also different facets of the pathophysiology of ACS. The future of cardiac biomarker testing may be in multimarker testing to better characterize each patient of ACS and thus tailor both short-term and long-term therapy accordingly. This novel concept, however, needs to be tested in clinical trials for its incremental value and cost-effectiveness.


Revisiting blood transfusion and predictors of outcome in cardiac surgery patients: a concise perspective.
In the United States, cardiac surgery-related blood transfusion rates reached new highs in 2010, with 34% of patients receiving blood products. Patients undergoing both complex (coronary artery bypass grafting [CABG] plus valve repair or replacement) and non-complex (isolated CABG) cardiac surgeries are likely to have comorbidities such as anemia. Furthermore, the majority of patients undergoing isolated CABG have a history of myocardial infarction. These characteristics may increase the risk of complications and blood transfusion requirement. It becomes difficult to demonstrate the association between transfusions and mortality because of the fact that most patients undergoing cardiac surgery are also critically ill. Transfusion rates remain high despite the advances in perioperative blood conservation, such as the intraoperative use of cell saver in cardiac surgery. Some recent prospective studies have suggested that the use of blood products, even in low-risk patients, may adversely affect clinical outcomes. In light of this information, we reviewed the literature to assess the clinical outcomes in terms of 30-day and 1-year morbidity and mortality in transfused patients who underwent uncomplicated CABG surgery.


Diagnosis of human visceral leishmaniasis by PCR using blood samples spotted on filter paper.
The polymerase chain reaction (PCR) is a simple, rapid procedure that has been adapted for the diagnosis of leishmaniasis. In the present study, 85 blood samples and seven bone marrow aspirates from 85 patients with clinical symptoms suggestive of visceral leishmaniasis from the metropolitan region of Belo Horizonte in the Brazilian State of Minas Gerais were screened using molecular and serological techniques. Samples that were negative (N = 12) and positive (N = 19) in parasitological and serological tests were used as controls. Of the 85 samples analyzed by PCR, 61 (71.7%) showed the expected amplification products in agarose gels. However, when the technique was combined with molecular hybridization, 72 samples (83.5%) gave a positive signal on film. Nineteen patients with Leishmania parasites in bone marrow cultures (positive controls) showed PCR hybridization in whole-blood samples, as did the seven bone marrow aspirates positive for Leishmania. None of the negative controls reacted in PCR or in an indirect immunofluorescent assay. These results indicate that PCR could replace the conventional parasitological examination in the diagnosis of leishmaniasis since it provides very satisfactory results with blood samples spotted on filter paper.


A Unique Case of JOAG With Lamellar Ichthyosis With Rickets: A Case Report and Review of the Literature.
Ichthyosis is known to have ocular associations such as blepharitis, hypertrophic conjunctivitis, corneal vascularization, ectropion, lagophthalmos, etc. However, no reports of its association with glaucoma are there, to the best of our knowledge. We report a unique case of juvenile open-angle glaucoma (JOAG) with lamellar ichthyosis. A 16-year-old male child presented with a gradual, painless progressive diminution of vision in both eyes over a period of 3 years. Systemic examination revealed stunted body growth with knock-knees, suggestive of late-onset rickets. Generalized dry scaly lesions with erythema, along with hyperkeratosis of the palms and the soles, suggestive of lamellar ichthyosis were present. On ocular examination, the intraocular pressure was 36 mm Hg; optic nerve head examination revealed a horizontally oval disc with near total cupping in the right eye and total cupping in the left eye, with extensive neuroretinal rim thinning and pallor. Gonioscopy showed wide open angles with prominent iris processes. Screening of JOAG-associated genes (MYOC, NTF4, WDR36, and CYP1B1) and ichthyosis-associated gene (TGM1) was performed by the direct PCR-sequencing method. A diagnosis of JOAG with advanced glaucomatous optic neuropathy with lamellar ichthyosis and rickets was made. The patient underwent right followed by left eye trabeculectomy with 0.2 mg/dL MMC (for 1 min). Postoperatively, the intraocular pressure was 8 mm Hg at 1 week, and 12 to 14 mm Hg at the 6-week, the 3-month, and the 6-month follow-up, and the visual acuity was maintained in the right eye. No mutations in MYOC, NTF4, WDR36, CYP1B1, and TGM1 were observed in the patient and his family. An association of glaucoma with ichthyosis should be kept in mind. Therefore, a detailed baseline ocular examination in children with ichthyosis is required, as early detection of glaucoma could prevent irreversible blindness.


Adjuvant radiotherapy for primary breast cancer in BRCA1 and BRCA2 mutation carriers and risk of contralateral breast cancer with special attention to patients irradiated at younger age.
The purpose of this study was to estimate the influence of adjuvant radiotherapy for primary breast cancer (BC) on the risk of contralateral BC (CBC) in BRCA1 or BRCA2 (BRCA1/2) mutation carriers, with special attention to patients irradiated at age younger than 40 years. Additionally, tendencies in locoregional treatments and rates of contralateral risk-reducing mastectomy over time were explored. In this retrospective cohort study, 691 BRCA1/2-associated BC patients treated between 1980 and 2013 were followed from diagnosis until CBC or censoring event including ipsilateral BC recurrence, distant metastasis, contralateral risk-reducing mastectomy, other invasive cancer diagnosis, death, or loss to follow up. Hazard ratios (HR) for CBC associated with radiotherapy were estimated using Cox regression. Median follow-up time was 8.6 years [range 0.3–34.3 years]. No association between radiotherapy for primary BC and risk of CBC was found, neither in the total population (HR 0.82, 95 % CI 0.45–1.49) nor in the subgroup of patients younger than 40 years at primary diagnosis (HR 1.36, 95 % CI 0.60–3.09). During follow-up, the number of patients at risk decreased substantially since a large proportion of patients were censored after contralateral risk-reducing mastectomy or BC recurrence. Over the years, increasing preference for mastectomy without radiotherapy compared to breast-conserving surgery with radiotherapy was found ranging from less than 30 % in 1995 to almost 50 % after 2010. The rate of contralateral risk-reducing mastectomy increased over the years from less than 40 % in 1995 to more than 60 % after 2010. In this cohort of BRCA1/2-associated BC patients, no association between radiotherapy for primary BC and risk of CBC was observed in the total group, nor in the patients irradiated before the age of 40 years. The number of patients at risk after 10 and 15 years of follow-up, however, was too small to definitively exclude harmful effects of adjuvant radiotherapy.


A Retrospective Cohort Study Comparing the Outcomes of Conservative Versus Operative Fixation of Distal Radius Fractures in Children.
Objectives Distal radius fractures are common pediatric orthopedic injuries accounting for 25% of all fractures with a significant incidence in the age group 10-14 years. This study aims to evaluate the operative and non-operative methods of treating distal radius fractures in children. Methods This is a retrospective cohort study conducted on 176 children with distal radius fracture. We studied the operative and non-operative treatments of all children presented with distal radius fracture to the emergency department of the Bahrain Defense Force (BDF) Hospital from January 1, 2015, to February 1, 2022. The inclusion criteria were as follows: age of 17 years or younger, distal radius fracture with or without complete displacement and skeletal immaturity managed as of non-operative or operative groups. Patients who did not have follow-up data after the date of surgery were excluded. The statistical analysis was performed using the software SPSS version 23.0 (IBM Corp., Armonk, NY). Continuous data expressed as mean, standard deviation and discrete variables were expressed as frequency and percentages. One-way Analysis of Variance (ANOVA) was used to compare the continuous variables between groups. The Student's t-test was used for the two-group comparison. For the comparison of discrete variables, a Chi-Square test or Fisher's exact test was used. Results Seventy-seven patients were conservatively managed with cast immobilization ("non-operative" group) in comparison to 99 patients who were surgically managed ("operative" group) with either percutaneous pinning (n=56) or flexinail (n=43). Fewer patients underwent physiotherapy in the operative group with 14 (25.0%) patients for percutaneous pinning and seven (16.3%) patients for flexinail versus 31 (40.3%) patients in the non-operative group (p<0.015). There were statistically significant differences in radial inclination (p<0.001) between conservative and percutaneous pinning (22.22±2.86 vs 18.76±3.33 degrees) and percutaneous pinning and flexinail (18.76±3.33 vs 22.37±3.44 degrees). Likewise, there was a significant difference found in ulnar variance between conservative and percutaneous pinning (-0.45±2.14 mm vs -1.47±1.93 mm, p=0.012) and conservative and flexinail (-0.45±2.14 mm vs -1.59±1.90 mm, p=0.009). There were a total of 25 documented complications. Nineteen (19.8%) complications occurred in the non-operative group versus five (7.2%) and one (2.3%) complications in percutaneous pinning and flexinail groups, respectively (p=0.003). The most common complication in the non-operative group was loss of reduction while in cast and subsequent need for surgical intervention. Ten of these patients underwent percutaneous pinning whereas nine were fixed by flexinail. Conclusion This study illustrated an overall similar success between the surgical and the conservative treatments of distal radius fractures in children. Due to the higher complication rate reported in the conservative group, the conservative treatment cannot be considered safer than the surgical treatment.


Robust Filtering for Nonlinear Nonhomogeneous Markov Jump Systems by Fuzzy Approximation Approach.
This paper addresses the problem of robust fuzzy L2-L∞ filtering for a class of uncertain nonlinear discrete-time Markov jump systems (MJSs) with nonhomogeneous jump processes. The Takagi-Sugeno fuzzy model is employed to represent such nonlinear nonhomogeneous MJS with norm-bounded parameter uncertainties. In order to decrease conservation, a polytope Lyapunov function which evolves as a convex function is employed, and then, under the designed mode-dependent and variation-dependent fuzzy filter which includes the membership functions, a sufficient condition is presented to ensure that the filtering error dynamic system is stochastically stable and that it has a prescribed L2-L∞ performance index. Two simulated examples are given to demonstrate the effectiveness and advantages of the proposed techniques.


Dietary restriction of rodents decreases aging rate without affecting initial mortality rate -- a meta-analysis.
Dietary restriction (DR) extends lifespan in multiple species from various taxa. This effect can arise via two distinct but not mutually exclusive ways: a change in aging rate and/or vulnerability to the aging process (i.e. initial mortality rate). When DR affects vulnerability, this lowers mortality instantly, whereas a change in aging rate will gradually lower mortality risk over time. Unraveling how DR extends lifespan is of interest because it may guide toward understanding the mechanism(s) mediating lifespan extension and also has practical implications for the application of DR. We reanalyzed published survival data from 82 pairs of survival curves from DR experiments in rats and mice by fitting Gompertz and also Gompertz-Makeham models. The addition of the Makeham parameter has been reported to improve the estimation of Gompertz parameters. Both models separate initial mortality rate (vulnerability) from an age-dependent increase in mortality (aging rate). We subjected the obtained Gompertz parameters to a meta-analysis. We find that DR reduced aging rate without affecting vulnerability. The latter contrasts with the conclusion of a recent analysis of a largely overlapping data set, and we show how the earlier finding is due to a statistical artifact. Our analysis indicates that the biology underlying the life-extending effect of DR in rodents likely involves attenuated accumulation of damage, which contrasts with the acute effect of DR on mortality reported for Drosophila. Moreover, our findings show that the often-reported correlation between aging rate and vulnerability does not constrain changing aging rate without affecting vulnerability simultaneously.


Investigating an alternative ring design of transducer arrays for tumor treating fields (TTFields).
Tumor treating fields (TTFields) is a therapy that inhibits cell proliferation and has been approved by the U.S Food and Drug Administration (FDA) for the treatment of Glioblastoma Multiforme. This anti-mitotic technique works non-invasively and regionally, and is associated with less toxicity and a better quality of life. Currently a device called Optune™ is clinically used which works with two perpendicular and alternating array pairs each consisting of 3×3 transducers. The aim of this study is to investigate a theoretical alternative array design which consists of two rings of 16 transducers and thus permits various field directions. A realistic human head model with isotropic tissues was used to simulate the electric field distribution induced by the two types of array layouts. One virtual tumour was modelled as a sphere in the white matter close to one lateral ventricle. Four alternative ring design directions were evaluated by activating arrays of 2×2 transducers on opposite sides of the head. The same amount of current was passed through active transducer arrays of the Optune system and the ring design. The electric field distribution in the brain differs for the various array configurations, with higher fields between activated transducer pairs and lower values in distant areas. Nonetheless, the average electric field strength values in the tumour are comparable for the various configurations. Values between 1.00 and 1.91 V/cm were recorded, which are above the threshold for effective treatment. Increasing the amount of field directions could possibly also increase treatment efficacy, because TTFields' effect on cancer cells is highest when the randomly distributed cell division axis is aligned with the field. The results further predict that slightly changing transducer positions only has a minor effect on the electric field. Thus patients might have some freedom to adjust array positions without major concern for treatment efficacy.


Population heterogeneity of the Hpa I restriction site associated with the beta globin gene: implications for prenatal diagnosis.
The Hpa I restriction endonuclease site polymorphism that results in some human beta globin genes being contained in a 13-kilobase (kb) DNA restriction fragment rather than in the usual 7.6-kb fragment has been reported to be in linkage disequilibrium with the beta S mutation. The frequency of the 13-kb fragment among Baltimore black sickle cell (SS) disease patients (58%) is lower than that reported for San Francisco black SS disease patients (87%) and similar to that reported for such New York patients (59%). There is, then, considerable heterogeneity among American black populations. Therefore, for the purposes of prenatal diagnosis, the frequency in the particular population at risk should be established. When the frequency of association of the 13-kb fragment and the beta S mutation is low, the linkage phase must also be established. When the linkage phase is known, the Hpa I pattern alone can exclude SS disease 54% of the time for Baltimore AS X AS couples.


Associations between Parental and Friend Social Support and Children's Physical Activity and Time Spent outside Playing.
The purpose of this study was to examine the structural validity of a parent and a child questionnaire that assessed parental and friends' influences on children's physical activity and investigate the associations between the derived factors, physical activity, and time spent outside. Children (N = 154, mean age = 11.7) and 144 of their parents completed questionnaires assessing parental and friends' influences on children's physical activity. Children wore a pedometer for six days. Exploratory factor analyses revealed four factors for the parental and five for the child's questionnaire that explained 66.71% and 63.85% of the variance, respectively. Five factors were significantly associated with physical activity and five significantly associated with time spent outside. Higher correlations were revealed between "general friend support," "friends' activity norms," and physical activity (r = 0.343 and 0.333 resp., p < 0.001) and between "general friend support" and time spent outside (r = 0.460, p < 0.001). Obtaining information relating to parental and friends' influences on physical activity from both parents and children may provide a more complete picture of influences. Parents and friends seem to influence children's physical activity behavior and time spent outside, but friends' influences may have a stronger impact on children's behaviors.


Enhanced susceptibility of S-100B transgenic mice to neuroinflammation and neuronal dysfunction induced by intracerebroventricular infusion of human beta-amyloid.
S-100B is an astrocyte-derived protein that is increased in focal areas of the brain most severely affected by neuropathological changes in Alzheimer's disease (AD). Cell-based and clinical studies have implicated S-100B in progression of a pathologic, glial-mediated pro-inflammatory state in the CNS. However, the relationship between S-100B levels and susceptibility to AD-relevant neuroinflammation and neuronal dysfunction in vivo has not been determined. To test the hypothesis that overexpression of S-100B increases vulnerability to beta-amyloid (Abeta)-induced damage, we used S-100B-overexpressing transgenic (Tg) and S-100B knockout (KO) mice in a mouse model that involves intracerebroventricular infusion of human oligomeric Abeta1-42. This model mimics many features of AD, including robust neuroinflammation, Abeta plaques, synaptic damage and neuronal loss in the hippocampus. S-100B Tg, KO, and wild-type (WT) mice were infused with Abeta for 28 days, sacrificed at 60 days, and hippocampal endpoints analyzed. We found that Tg mice showed increased vulnerability to Abeta-induced neuropathology relative to either WT or KO mice. Specifically, Tg mice exhibited enhanced glial activation and neuroinflammation, increased nitrotyrosine staining (a marker of glial-induced neuronal damage), and more pronounced loss of synaptic markers. Interestingly, Tg mice showed no significant differences in Abeta plaque burden compared with WT or KO mice, suggesting that, as in the human situation, the severity of neuronal dysfunction did not correlate with amyloid deposition. Our data are consistent with a model in which S-100B overexpression in AD enhances glial activation and leads to an augmented neuroinflammatory process that increases the severity of neuropathologic sequelae.


Practicalities of a global poliomyelitis control program.
Much progress has been achieved in making the world free of poliomyelitis. The countries that have achieved control should be giving practical help to those where the disease is still endemic, while developing their own competence in surveillance, laboratory support, and effective immunization policies. The polio vaccines have been proved effective. The need is now to implement programs by solving their practical difficulties in order to make use of the presently available vaccines.


Investigation of the chemico-physical characteristics of the active components in the Chinese herb Gastrodia elata Bl. by capillary zone electrophoresis.
A CE method for investigating the chemico-physical characteristics of the active components of low molecular weight in Gastrodia elata Bl. is described. First, the dissociation constants of five active components were determined based on the relation between the effective mobility of the solutes and the buffer pH value. Second, an equation that describes the relation of the migration time and the molecular weight was developed and used to predict the migration order and to calculate the electroosmotic velocity. The results predicted by theory agreed well with that from experiments.


Crystallographic insights into the structural aspects of thioctic acid based halogen-bond donor for the functionalization of gold nanoparticles.
The synthesis and self-assembly capabilities of a new halogen-bond donor ligand, 2,3,5,6-tetrafluoro-4-iodophenyl 5-(1,2-dithiolan-3-yl)pentanoate (1), are reported. The crystal structure of ligand (1) and the formation of a cocrystal with 1,2-di(4-pyridyl)ethylene, (1)·(2), both show halogen bonds involving the 4-iodotetrafluorobenzene moiety. Ligand (1), being a self-complementary unit, forms an infinite halogen-bonded chain driven by the S...I synthon, while the cocrystal (1)·(2) self-assembles into a discrete trimeric entity driven by the N...I synthon. Ligand (1) was also successfully used to functionalize the surface of gold nanoparticles, AuNP-(1). Experiments on the dispersibility profile of AuNP-(1) demonstrated the potential of halogen bonding in facilitating the dispersion of modified NPs with halogen-bond donors in pyridine.


Professionalism, Ethics, and Realism of Television Medical Dramas as Perceived by Saudi Medical Students.
Since their debut, medical dramas have been popular, particularly among medical students. This study examined how much time medical students spend watching medical TV shows and their impressions of the shows' professionalism, ethics, and realism. A survey on medical students' medical drama viewing behavior and perceptions with regard to bioethics was given to 341 first- to fifth-year undergraduate medical students at a university in Al Majmaah, Saudi Arabia. The poll gathered demographic information, TV medical drama watching habits, bioethical and professional concerns in medical dramas, and the sources of bioethical knowledge. The most popular medical dramas were The Good Doctor, Grey's Anatomy, and House M.D. Compared with English-language television medical dramas, Arabic ones were less popular. Ninety-one percent of students watched television alone. There was no statistically significant difference in respondents' perceptions of ethics accuracy based on year of study, gender, or whether they discussed it with friends. In comparison to students who had not seen any medical dramas, those who had were more inclined to view them as a credible source of ethical advice (P-value .04). There is a high interest in medical programs among medical students, and these programs can be used to teach them about the ethical aspects of practicing medicine.


Intimate partner violence and HIV sexual risk behavior among Latino gay and bisexual men: the role of situational factors.
Using a probability sample of 912 Latino gay and bisexual men at bars in 3 U.S. cities (Los Angeles, Miami, New York), this study examines how participation in difficult sexual situations with interpersonal (e.g., wanting to please partner) and circumstantial constraints (e.g., sex in partner's home) may explain associations between dimensions of intimate partner violence (IPV) and HIV sexual risk behavior (unprotected anal intercourse with nonmonogamous partner). Findings suggest that all IPV types contribute to greater participation in sexual situations with circumstantial constraints, and that psychological and sexual IPV are also associated with higher likelihood of unprotected receptive anal intercourse with a nonmonogamous partner. Circumstantial constraints fully mediate the difference attributable to psychological IPV and partially mediate the difference attributable to sexual IPV. Intimacy concerns were unrelated to either IPV or HIV risk behavior. Results suggest HIV prevention and research should investigate immediate circumstances of the sexual encounter that may make engaging in HIV sexual risk behavior more likely.


[Delayed endolymphatic hydrops].
Delayed Endolymphatic Hydrops (DEH) is a disease entity that must be distinguished from idiopathic endolymphatic hydrops (Ménière's disease). Idiopathic hydrops is characterized by the following symptoms: 1) vertigo often accompanied by nausea and vomiting; 2) tinnitus; 3) hearing loss, usually fluctuating; and 4) sensation of pressure or fullness in the affected ear. Idiopathic hydrops most commonly occurs in middle-aged patients, usually between 30 and 50 years. It may involve one or both ears and usually exibits fluctuating hearing loss and episodic vertigo, although one symptom may precede the other by months or years. It is rare for Ménière's disease to present with a severe sensorineural hearing loss. Delayed Endolymphatic Hydrops was first described, under the name of "unilateral deafness with subsequent vertigo", by Wolfson and Lieberman and Nadol et al.; this was later confirmed by other authors. The disease is characterized by a profound sensorineural hearing loss in one ear, found to have been present in most cases from early childhood, due to an unknown cause, trauma or viral infections. After a prolonged period (usually many years) patients with DEH experience the onset of episodic vertigo from the deaf ear (Ipsilateral Delayed Endolymphatic Hydrops) or develop a fluctuating hearing loss and/or episodic vertigo in the opposite ear, previously with normal hearing (Controlateral Delayed Endolymphatic Hydrops). Vestibular symptoms are identical to those of Ménière's disease: in fact there is evidence that endolymphatic hydrops in the previously damaged ear or in the previously normal ear represents at least part of the labyrinthine pathology. Histopathology studies recently conducted on temporal bones of subjects affected with controlateral DEH show pathologic changes in the deaf ears similar to those found in viral labyrinthitis, whereas pathologic changes in the hearing ears resemble those known to occur in Ménière's disease. Medical treatment has not been found to be effective in patients with DEH, but it must be the first choice of treatment especially in controlateral forms of the disease. So far, surgical intervention has been demonstrated to give the best results; either conservative or more radical, depending on the type of DEH. Pharmacological labyrinthectomy with ototoxic drugs could be the therapy of choice in the future. In this paper we review the literature in order to summarize the clinical features and criteria for diagnosing DEH, we also report histopathologic findings and pathogenetic hypotheses formulated for this syndrome. Moreover, we discuss the best therapeutic approach for the ipsilateral and controlateral variants of DEH.


A labour-saving manoeuvre.
Slow progress in the first stage of labour was treated in 792 mothers by digital dilatation. This manoeuvre is described. Partial dilatation was converted to complete dilatation in 94.4 per cent of all cases, the incidence of success being 90.0 per cent in primiparae and 96.0 per cent in multiparae. Difficulties are described, but serious complications were conspicuously absent.The manoeuvre was helpful with mothers unable to resist premature bearing down, and especially valuable for reducing delay before applying forceps for fetal distress. The early perinatal loss of 20 (in the first 200 cases) was reduced to 3.3 (in the last 599 births) after a change of technique.


Deficiency of MFSD7c results in microcephaly-associated vasculopathy in Fowler syndrome.
Several missense mutations in the orphan transporter FLVCR2 have been reported in Fowler syndrome. Affected subjects exhibit signs of severe neurological defects. We identified the mouse ortholog Mfsd7c as a gene expressed in the blood-brain barrier. Here, we report the characterizations of Mfsd7c-KO mice and compare these characterizations to phenotypic findings in humans with biallelic FLVCR2 mutations. Global KO of Mfsd7c in mice resulted in late-gestation lethality, likely due to CNS phenotypes. We found that the angiogenic growth of CNS blood vessels in the brain of Mfsd7c-KO embryos was inhibited in cortical ventricular zones and ganglionic eminences. Vascular tips were dilated and fused, resulting in glomeruloid vessels. Nonetheless, CNS blood vessels were intact, without hemorrhage. Both embryos and humans with biallelic FLVCR2 mutations exhibited reduced cerebral cortical layers, enlargement of the cerebral ventricles, and microcephaly. Transcriptomic analysis of Mfsd7cK-KO embryonic brains revealed upregulation of genes involved in glycolysis and angiogenesis. The Mfsd7c-KO brain exhibited hypoxia and neuronal cell death. Our results indicate that MFSD7c is required for the normal growth of CNS blood vessels and that ablation of this gene results in microcephaly-associated vasculopathy in mice and humans.


An expanding family of archaeal transcriptional activators.
Transcriptional regulation in the archaea involves a mosaic of DNA-binding proteins frequently (although not exclusively) of bacterial type, modulating a eukaryal-type core transcription apparatus. Methanocaldococcus jannaschii (Mja) Ptr2, a homologue of the Lrp/AsnC family of bacterial transcription regulators that are among the most widely disseminated archaeal DNA-binding proteins, has been shown to activate transcription by its conjugate hyperthermophilic RNA polymerase. Here, two in vitro systems have been exploited to show that Ptr2 and a Lrp homologue from the thermophile Methanothermococcus thermolithotrophicus (Mth) activate transcription over a approximately 40 degrees C range, in conjunction with their cognate TATA-binding proteins (TBPs) and with heterologous TBPs. A closely related homologue from the mesophile Methanococcus maripaludis (Mma) is nearly inert as a transcriptional activator, but a cluster of mutations that converts a surface patch of Mma Lrp to identity with Ptr2 confers transcriptional activity. Mja, Mth, and Mma TBPs are interchangeable for basal transcription, but their ability to support Lrp-mediated transcriptional activation varies widely, with Mja TBP the most active and Mth TBP the least active partner. The implications of this finding for understanding the roles of TBP paralogues in supporting the gene-regulatory repertoires of archaeal genomes are briefly noted.


Functional and Highly Cross-Linkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation.
Binding to the receptor, CD4, drives the pretriggered, "closed" (state-1) conformation of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) trimer into more "open" conformations (states 2 and 3). Broadly neutralizing antibodies, which are elicited inefficiently, mostly recognize the state-1 Env conformation, whereas the more commonly elicited poorly neutralizing antibodies recognize states 2/3. HIV-1 Env metastability has created challenges for defining the state-1 structure and developing immunogens mimicking this labile conformation. The availability of functional state-1 Envs that can be efficiently cross-linked at lysine and/or acidic amino acid residues might assist these endeavors. To that end, we modified HIV-1AD8 Env, which exhibits an intermediate level of triggerability by CD4. We introduced lysine/acidic residues at positions that exhibit such polymorphisms in natural HIV-1 strains. Env changes that were tolerated with respect to gp120-gp41 processing, subunit association, and virus entry were further combined. Two common polymorphisms, Q114E and Q567K, as well as a known variant, A582T, additively rendered pseudoviruses resistant to cold, soluble CD4, and a CD4-mimetic compound, phenotypes indicative of stabilization of the pretriggered state-1 Env conformation. Combining these changes resulted in two lysine-rich HIV-1AD8 Env variants (E.2 and AE.2) with neutralization- and cold-resistant phenotypes comparable to those of natural, less triggerable tier 2/3 HIV-1 isolates. Compared with these and the parental Envs, the E.2 and AE.2 Envs were cleaved more efficiently and exhibited stronger gp120-trimer association in detergent lysates. These highly cross-linkable Envs enriched in a pretriggered conformation should assist characterization of the structure and immunogenicity of this labile state. IMPORTANCE The development of an efficient vaccine is critical for combating HIV-1 infection worldwide. However, the instability of the pretriggered shape (state 1) of the viral envelope glycoprotein (Env) makes it difficult to raise neutralizing antibodies against HIV-1. Here, by introducing multiple changes in Env, we derived two HIV-1 Env variants that are enriched in state 1 and can be efficiently cross-linked to maintain this shape. These Env complexes are more stable in detergent, assisting their purification. Thus, our study provides a path to a better characterization of the native pretriggered Env, which should assist vaccine development.


Effect of short-term exposure to ambient air pollutants on non-accidental mortality in emergency department visits: a time-series study.
Exposure to air pollution has been linked to an increased risk of premature mortality. However, the acute effects of air pollution on the risk of non-accidental mortality have not been extensively researched in developing countries, and the findings thus far have been inconsistent. Therefore, this study aimed to examine the association between short-term exposure to six pollutants (PM2.5, PM10, SO2, NO2, O3, and CO) and non-accidental mortality in Beijing, China. Daily data on non-accidental deaths were gathered from 1 January 2017 to 31 December 2018. Air pollution data for the same period were collected from 35 fixed-site air quality monitoring stations in Beijing. Generalized additive models (GAM) based on Poisson regression were used to investigate the association between non-accidental mortality in emergency department visits and the daily average levels of air pollutants. There were 8,676 non-accidental deaths recorded during 2017-2018. After sensitivity analysis, short-term exposure to air pollutants, particularly gaseous pollutants, was linked to non-accidental mortality. Specifically, for every 10 μg/m3 increase (5 μg/m3 in SO2, 0.5 mg/m3 in CO) of SO2 (lag 04), NO2 (lag 04), O3 (lag 05), and CO (lag 04), the relative risk (RR) values were 1.054 (95% CI: 1.009, 1.100), 1.038 (95% CI: 1.013, 1.063), 1.032 (95% CI: 1.011, 1.054), and 1.034 (95% CI: 1.004, 1.066), respectively. In terms of causes of death, short-term exposure to NO2, SO2, and O3 increased the risk of circulatory mortality. Further stratified analysis revealed that the stronger associations were presented in females for O3 while in males for CO. People aged 65 and over were strongly associated with ambient air pollution. Our study showed that ambient air pollutants were associated with non-accidental mortality. Our findings suggested that efforts to control gaseous pollution should be stepped up, and vulnerable groups should be the focus of health protection education.


Defect corrections for coherent optical information processing of grayscale images in a DMD-based 4f-system using a collimated light source.
Digital micromirror device (DMD)-based 4f-systems, a type of coherent optical information processing system, have become a powerful tool for optical convolutional neural networks taking advantage of their fast modulation speed and high-resolution capability. However, proper high bit-depth image information processing remains challenging due to the optical diffractions that arise from the binary nature of DMD operation. In this paper, we first characterize the diffraction phenomena that cause irradiance defects, namely the nonlinear grayscale and unintended dark lines. Then to resolve the issues, we propose a DMD operation method and a modified structure of the 4f-system based on blazed diffraction grating theory and numerical calculation of the Rayleigh-Sommerfeld propagation model. As a demonstration, we implement high bit-depth image information processing with an optimized optical 4f-system using DMDs and a collimated coherent light source.


Quantifying how location and dose of botulinum toxin injections affect muscle paralysis.
Despite the widespread use of botulinum toxin to treat muscle dystonias, no method exists to quantify muscle paralysis in either human or nonhuman models. In this study we examined how the location, dose, and volume of botulinum injection affects paralysis in the rat tibialis anterior muscle. Paralysis was quantified by electrically stimulating the nerve to the tibialis anterior and then staining sections of the muscle for glycogen. The areas of glycogen-containing fibers represented regions of botulinum action. The results showed that the most important injection technique is to inject botulinum directly into the motor endplate region of a muscle. Injections only 0.5 cm from the motor endplate resulted in a 50% decrease in paralysis. Increases in dose increased paralysis, however, some of that increase was simply due to the increased volume of injection. Thus, delivering toxin in small volumes near the MEP band of a muscle should produce the most effective paralysis.


[Oral manifestations of Crohn's disease].
Gastrointestinal symptoms are predominant in Crohn's disease. Oral manifestations may also occur. The prevalence of oral manifestations varies between 0.5% and 37%. The manifestations may coincide with or precede gastrointestinal symptoms, and can be subdivided into specific and non-specific lesions. In most patients, lesions are asymptomatic but some patients experience serious discomfort. Oral manifestations can be classified as specific lesions, such as diffuse lip and buccal swelling and cobblestones, and non-specific lesions, such as aphthous ulcers, pyostomatitis vegetans, caries, gingivitis and periodontitis. In many patients, these oral symptoms do not cause pain or discomfort and do not require treatment. For patients who do experience discomfort, pain caused by aphthous ulcers, for example, can be relieved with a lidocaine solution or a 0.1% dexamethasone gel, and corticosteroids can be used to treat pain caused by ulceration or cobblestoning. It is advisable in complex cases to consult the patient's gastroenterologist.


An analytical approach to network motif detection in samples of networks with pairwise different vertex labels.
Network motifs, overrepresented small local connection patterns, are assumed to act as functional meaningful building blocks of a network and, therefore, received considerable attention for being useful for understanding design principles and functioning of networks. We present an extension of the original approach to network motif detection in single, directed networks without vertex labeling to the case of a sample of directed networks with pairwise different vertex labels. A characteristic feature of this approach to network motif detection is that subnetwork counts are derived from the whole sample and the statistical tests are adjusted accordingly to assign significance to the counts. The associated computations are efficient since no simulations of random networks are involved. The motifs obtained by this approach also comprise the vertex labeling and its associated information and are characteristic of the sample. Finally, we apply this approach to describe the intricate topology of a sample of vertex-labeled networks which originate from a previous EEG study, where the processing of painful intracutaneous electrical stimuli and directed interactions within the neuromatrix of pain in patients with major depression and healthy controls was investigated. We demonstrate that the presented approach yields characteristic patterns of directed interactions while preserving their important topological information and omitting less relevant interactions.


Native valve Aspergillus endocarditis in two patients with aplastic anaemia.
Native valve fungal endocarditis is an uncommon disease with a high mortality rate. We present the clinical features, histological findings and outcome of 2 patients with native valve Aspergillus endocarditis. Both patients had aplastic anaemia as a predisposing disease. The diagnosis was made by Duke's criteria in 1 case and by histology in the other. Surgery was precluded owing to profound thrombocytopenia. Both patients had fatal outcome despite administration of liposomal amphotericin beta.


Entropic multirelaxation-time lattice Boltzmann method for moving and deforming geometries in three dimensions.
Entropic lattice Boltzmann methods have been developed to alleviate intrinsic stability issues of lattice Boltzmann models for under-resolved simulations. Its reliability in combination with moving objects was established for various laminar benchmark flows in two dimensions in our previous work [B. Dorschner, S. Chikatamarla, F. Bösch, and I. Karlin, J. Comput. Phys. 295, 340 (2015)JCTPAH0021-999110.1016/j.jcp.2015.04.017] as well as for three-dimensional one-way coupled simulations of engine-type geometries in B. Dorschner, F. Bösch, S. Chikatamarla, K. Boulouchos, and I. Karlin [J. Fluid Mech. 801, 623 (2016)JFLSA70022-112010.1017/jfm.2016.448] for flat moving walls. The present contribution aims to fully exploit the advantages of entropic lattice Boltzmann models in terms of stability and accuracy and extends the methodology to three-dimensional cases, including two-way coupling between fluid and structure and then turbulence and deforming geometries. To cover this wide range of applications, the classical benchmark of a sedimenting sphere is chosen first to validate the general two-way coupling algorithm. Increasing the complexity, we subsequently consider the simulation of a plunging SD7003 airfoil in the transitional regime at a Reynolds number of Re=40000 and, finally, to access the model's performance for deforming geometries, we conduct a two-way coupled simulation of a self-propelled anguilliform swimmer. These simulations confirm the viability of the new fluid-structure interaction lattice Boltzmann algorithm to simulate flows of engineering relevance.


From the battlefields to the states: the road to recovery. The role of Landstuhl Regional Medical Center in US military casualty care.
The transformation of the modern battlefield with respect to weaponry, modes of transportation, enemy capabilities and location, as well as technological advances, has greatly altered the tactical approach to the mission. Combat casualty care must continually evolve in response to the differences in types of injury, the number and triage of casualties, timing of treatment, and location of care. These battlefield changes have been demonstrated on a large scale in the global war on terrorism, which includes the military operations in Afghanistan and Iraq. The medical response has kept pace with this 21st-century conflict. Even in the new environment of armed conflict and with the advent of new technologies, the principles of managing orthopaedic combat casualties remain clear: preservation of life and limb, skeletal stabilization, and aggressive wound débridement. For United States service members wounded in the current conflicts, Landstuhl Regional Medical Center is a crucial stop along the road to recovery.


Motion sickness in quail: body-rotation-induced conditioned fluid aversions in C. coturnix japonica.
The presence of motion sickness in Japanese quail (C. coturnix japonica) was examined by using a conditioned fluid aversion as an index. Twenty-three birds were divided into three groups. One group received a novel fluid (yellow-sour water) followed by 30 min of body rotation at 70 rpm (on a schedule of 15 s on and 5 s off). Another group received the novel fluid followed by exposure to a sham rotation procedure. The third group experienced the rotation procedure following access to water. The group receiving the rotation procedure contingent on presentation of the novel fluid exhibited a conditioned aversion to this fluid (relative to the control groups) over days of acquisition (p less than .025) which subsequently dissipated when rotation was no longer contingent on the presentation of the yellow-sour water (extinction). These data thus demonstrate the presence of motion sickness in a gallinaceous species as indexed by a conditioned fluid aversion procedure.


Untapped research opportunities in China: promising future avenues and potential concerns for aging companion animals.
Companion animals have recently been proposed as ideal translational models of human aging due to their shared susceptibility for certain diseases, similar environments, and sophisticated veterinary medicine diagnostics, all of which are not possible in rodent laboratory models. Here, we introduce and propose the study of companion animals in China as a largely untapped resource in academic and veterinary aging research. Pet ownership rates along with economic gains in the pet industry have skyrocketed over the last decade in China. Yet, the majority of research institutions still focus on agricultural animal research, not companion animals. In this perspective, we compare available pet ownership rates between the USA, the European Union, and China before focusing on the potential of companion animal aging research in China. In addition, we highlight some ethical considerations that must be addressed before large-scale companion animal aging research can be completed.


Gene mapping and chromosome 19.
Chromosome 19 is currently the most fully mapped of the smaller chromosomes, with about 40 loci assigned to it (HGM8). Major inherited disorders on this chromosome include myotonic dystrophy and familial hypercholesterolaemia. Other loci include five blood groups, a cluster of apolipoprotein genes, and the receptors for insulin and polio virus. A number of cloned genes and random DNA sequences identify polymorphisms which, together with blood group and other protein polymorphisms, have been used to establish a framework for ordering the loci and estimating genetic distances. Hybrid cell lines allow loci to be assigned to one of eight different regions and a detailed genetic map of the chromosome will be possible in the near future.


Personalized discovery of altered pathways in clear cell renal cell carcinoma using accumulated normal sample data.
To identify altered pathways in an individual with clear cell renal cell carcinoma (ccRCC) using accumulated normal sample data. Gene expression data of E-GEOD-40435 was downloaded from the ArrayExpress database. Gene-level statistics of genes in tumor and normal samples were computed. Then, the Average Z method was applied to calculate the individual pathway aberrance score (iPAS). Subsequently, the significantly altered pathways in a ccRCC sample were identified using T-test based on the pathway statistics values of normal and ccRCC samples. Moreover, the identified altered pathways were verified through two methods: one was assessing classification capability for microarray data samples, and the other was computing the changed percentage of each pathway in ccRCC samples. Based on the threshold, 886 altered pathways were identified in all samples. The most significant pathways were potassium transport channels, proton-coupled monocarboxylate transport, beta oxidation of octanoyl-CoA to hexanoyl-CoA, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. Additionally, iPAS separated ccRCC from normal controls with an accuracy of 0.980. Moreover, a total of 5 significant pathways with change in 100% ccRCC samples were extracted including proton-coupled monocarboxylate transport, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. iPAS is useful to predict marker pathways for ccRCC with a high accuracy. Pathways of proton-coupled monocarboxylate transport, and antigen presentation: folding, assembly and peptide loading of class I MHC might play crucial roles in ccRCC progression.


Steroid profiling reveals widespread local regulation of glucocorticoid levels during mouse development.
Glucocorticoids (GCs) are produced by the adrenal glands and circulate in the blood to coordinate organismal physiology. In addition, different tissues may independently regulate their local GC levels via local GC synthesis. Here, we find that in the mouse, endogenous GCs show tissue-specific developmental patterns, rather than mirroring GCs in the blood. Using solid-phase extraction, HPLC, and specific immunoassays, we quantified endogenous steroids and found that in tissues of female and male mice, (1) local GC levels can be much higher than systemic GC levels, (2) local GCs follow age-related patterns different from those of systemic GCs, and (3) local GCs have identities different from those of systemic GCs. For example, whereas corticosterone is the predominant circulating adrenal GC in mice, high concentrations of cortisol were measured in neonatal thymus, bone marrow, and heart. The presence of cortisol was confirmed with liquid chromatography-tandem mass spectrometry. In addition, gene expression of steroidogenic enzymes was detected across multiple tissues, consistent with local GC production. Our results demonstrate that local GCs can differ from GCs in circulating blood. This finding suggests that steroids are widely used as local (paracrine or autocrine) signals, in addition to their classic role as systemic (endocrine) signals. Local GC regulation may even be the norm, rather than the exception, especially during development.


Are most published research findings false? Trends in statistical power, publication selection bias, and the false discovery rate in psychology (1975-2017).
The validity of scientific findings may be challenged by the replicability crisis (or cases of fraud), which may result not only in a loss of trust within society but may also lead to wrong or even harmful policy or medical decisions. The question is: how reliable are scientific results that are reported as statistically significant, and how does this reliability develop over time? Based on 35,515 papers in psychology published between 1975 and 2017 containing 487,996 test values, this article empirically examines the statistical power, publication bias, and p-hacking, as well as the false discovery rate. Assuming constant true effects, the statistical power was found to be lower than the suggested 80% except for large underlying true effects (d = 0.8) and increased only slightly over time. Also, publication bias and p-hacking were found to be substantial. The share of false discoveries among all significant results was estimated at 17.7%, assuming a proportion θ = 50% of all hypotheses being true and assuming that p-hacking is the only mechanism generating a higher proportion of just significant results compared to just nonsignificant results. As the analyses rely on multiple assumptions that cannot be tested, alternative scenarios were laid out, again resulting in the rather optimistic result that although research results may suffer from low statistical power and publication selection bias, most of the results reported as statistically significant may contain substantial results, rather than statistical artifacts.


Organ manifestations of COVID-19: what have we learned so far (not only) from autopsies?
The use of autopsies in medicine has been declining. The COVID-19 pandemic has documented and rejuvenated the importance of autopsies as a tool of modern medicine. In this review, we discuss the various autopsy techniques, the applicability of modern analytical methods to understand the pathophysiology of COVID-19, the major pathological organ findings, limitations or current studies, and open questions. This article summarizes published literature and the consented experience of the nationwide network of clinical, neuro-, and forensic pathologists from 27 German autopsy centers with more than 1200 COVID-19 autopsies. The autopsy tissues revealed that SARS-CoV-2 can be found in virtually all human organs and tissues, and the majority of cells. Autopsies have revealed the organ and tissue tropism of SARS-CoV-2, and the morphological features of COVID-19. This is characterized by diffuse alveolar damage, combined with angiocentric disease, which in turn is characterized by endothelial dysfunction, vascular inflammation, (micro-) thrombosis, vasoconstriction, and intussusceptive angiogenesis. These findings explained the increased pulmonary resistance in COVID-19 and supported the recommendations for antithrombotic treatment in COVID-19. In contrast, in extra-respiratory organs, pathological changes are often nonspecific and unclear to which extent these changes are due to direct infection vs. indirect/secondary mechanisms of organ injury, or a combination thereof. Ongoing research using autopsies aims at answering questions on disease mechanisms, e.g., focusing on variants of concern, and future challenges, such as post-COVID conditions. Autopsies are an invaluable tool in medicine and national and international interdisciplinary collaborative autopsy-based research initiatives are essential.


Investigation of dose reduction in cardiac perfusion SPECT via optimization and choice of the image reconstruction strategy.
We investigated the extent to which the administered dose (activity) level can be reduced without sacrificing diagnostic accuracy for three reconstruction strategies for SPECT-myocardial perfusion imaging (MPI). We optimized the parameters of the three reconstruction strategies for perfusion-defect detection over a range of simulated administered dose levels using a set of hybrid studies (derived from 190 subjects) consisting of clinical SPECT-MPI data modified to contain realistic simulated lesions. The optimized strategies we considered are filtered backprojection (FBP) with no correction for degradations, ordered-subsets expectation-maximization (OS-EM) with attenuation correction (AC), scatter correction (SC), and resolution correction (RC), and OS-EM with scatter and resolution correction only. Each study was evaluated using a total perfusion deficit (TPD) score computed by the Quantitative Perfusion SPECT (QPS) software package. We conducted a receiver operating characteristics (ROC) study based on the TPD scores for each dose level and reconstruction strategy. For FBP, the achieved optimum values of the area under the ROC curve (AUC) at 100%, 50%, 25%, and 12.5% of standard dose were 0.75, 0.74, 0.72, and 0.70, respectively, compared to 0.81, 0.79, 0.76, and 0.74 for OS-EM with AC-SC-RC and 0.78, 0.77, 0.74, 0.72 for OS-EM with SC-RC. Our results suggest that studies reconstructed by OS-EM with AC-SC-RC could possibly be reduced, on average, to 25% of the originally administered dose without causing diagnostic accuracy (AUC) to decrease below that of FBP.


[Antibodies to glial fibrillary antigen as potential carriers of drugs for glial tumors].
Polyclonal monospecific antibodies to the glial fibrillar antigen of the brain (GFA) and, as controls, antibodies not possessing specific tendency were injected intravenously separately into two groups of rats with glioblastomas transplanted into the brain. The immunoenzymatic method was used to study the content of the injected antibodies in tissue extracts collected from the zone of the glioblastoma, brain matter and other organs 2, 20, and 48 hours after the injection. It was established that polyclonal monospecific antibodies to GFA accumulate selectively in the zone of the glioblastoma. The use of antibodies to GFA for selective transport of medicinal agents to malignant glial tumors must be evaluated in further studies.


A proposed methodology for detecting the malignant potential of pulmonary nodules in sarcoma using computed tomographic imaging and artificial intelligence-based models.
The presence of lung metastases in patients with primary malignancies is an important criterion for treatment management and prognostication. Computed tomography (CT) of the chest is the preferred method to detect lung metastasis. However, CT has limited efficacy in differentiating metastatic nodules from benign nodules (e.g., granulomas due to tuberculosis) especially at early stages (<5 mm). There is also a significant subjectivity associated in making this distinction, leading to frequent CT follow-ups and additional radiation exposure along with financial and emotional burden to the patients and family. Even 18F-fluoro-deoxyglucose positron emission technology-computed tomography (18F-FDG PET-CT) is not always confirmatory for this clinical problem. While pathological biopsy is the gold standard to demonstrate malignancy, invasive sampling of small lung nodules is often not clinically feasible. Currently, there is no non-invasive imaging technique that can reliably characterize lung metastases. The lung is one of the favored sites of metastasis in sarcomas. Hence, patients with sarcomas, especially from tuberculosis prevalent developing countries, can provide an ideal platform to develop a model to differentiate lung metastases from benign nodules. To overcome the lack of optimal specificity of CT scan in detecting pulmonary metastasis, a novel artificial intelligence (AI)-based protocol is proposed utilizing a combination of radiological and clinical biomarkers to identify lung nodules and characterize it as benign or metastasis. This protocol includes a retrospective cohort of nearly 2,000-2,250 sample nodules (from at least 450 patients) for training and testing and an ambispective cohort of nearly 500 nodules (from 100 patients; 50 patients each from the retrospective and prospective cohort) for validation. Ground-truth annotation of lung nodules will be performed using an in-house-built segmentation tool. Ground-truth labeling of lung nodules (metastatic/benign) will be performed based on histopathological results or baseline and/or follow-up radiological findings along with clinical outcome of the patient. Optimal methods for data handling and statistical analysis are included to develop a robust protocol for early detection and classification of pulmonary metastasis at baseline and at follow-up and identification of associated potential clinical and radiological markers.


Half-lives of albumin and cholinesterase in critically ill patients.
Albumin and plasma cholinesterase are markedly reduced in critical illness. However, the plasma half-lives of these two proteins have only been determined in very limited numbers of patients mostly outside intensive care. Therefore, we determined the kinetics of decrease of albumin and cholinesterase in a large population of critically ill patients. Medical records of all patients of two university-affiliated surgical intensive care units during a time period of 8 years were retrospectively evaluated. To calculate the rate of fall, the first value in every episode of decreasing albumin or cholinesterase was arbitrarily set at 100% and the ensuing lower values were expressed as the respective fractions. Records of 3591 patients were evaluated. Regression analysis exhibited an exponential evolution of albumin and cholinesterase over time with corresponding mean apparent plasma half-lives of 11.8 days [95% confidence interval (CI): 10.8-12.9] for albumin and 7.8 days (95% CI: 7.4-8.3) for cholinesterase. These findings suggest that the apparent plasma half-lives of albumin and cholinesterase in critically ill surgical patients are considerably shorter than previously determined.


Morphological State Transition Dynamics in EGF-Induced Epithelial to Mesenchymal Transition.
Epithelial to Mesenchymal Transition (EMT) is a multi-state process. Here, we investigated phenotypic state transition dynamics of Epidermal Growth Factor (EGF)-induced EMT in a breast cancer cell line MDA-MB-468. We have defined phenotypic states of these cells in terms of their morphologies and have shown that these cells have three distinct morphological states-cobble, spindle, and circular. The spindle and circular states are the migratory phenotypes. Using quantitative image analysis and mathematical modeling, we have deciphered state transition trajectories in different experimental conditions. This analysis shows that the phenotypic state transition during EGF-induced EMT in these cells is reversible, and depends upon the dose of EGF and level of phosphorylation of the EGF receptor (EGFR). The dominant reversible state transition trajectory in this system was cobble to circular to spindle to cobble. We have observed that there exists an ultrasensitive on/off switch involving phospho-EGFR that decides the transition of cells in and out of the circular state. In general, our observations can be explained by the conventional quasi-potential landscape model for phenotypic state transition. As an alternative to this model, we have proposed a simpler discretized energy-level model to explain the observed state transition dynamics.


Effects of dietary supplementation with betaine on a nonalcoholic steatohepatitis (NASH) mouse model.
The effects of betaine supplementation on non-alcoholic steatohepatitis (NASH) model mice were examined by measuring the accumulation of fat in the livers of NASH model mice compared to a control. Betaine from sugar beets was provided to the model mice as a dietary supplement. After 3 wk of dietary supplementation, there were no significant differences in body weight or liver weight between the groups. However, the liver to body weight ratio in the high-fat diet with betaine (HFB) group was significantly (p<0.05) higher than that in the high-fat diet (HF) group. There were no differences in serum triglyceride (TG) concentrations, AST and ALT activities, or hepatic glutathione concentrations between the groups. Hepatic TG level in the HFB group was significantly (p<0.05) lower than that in the HF group. Hepatic cells obtained from the HF group showed increased occurrence of explosive puff and necrosis as compared with those in the HFB group. Betaine supplementation had an inhibitory effect on fat accumulation in the liver: the Oil red-positive area in the HFB group (0.82 ± 0.85%) was significantly (p<0.001) smaller than that in the HF group (9.06 ± 2.24%). These results indicate the potential of betaine to serve as an agent for amelioration of hepatic steatosis in NASH model mice.


Sentinel lymph node biopsy in cutaneous head and neck melanoma.
Sentinel lymph node biopsy (SLNB) is now a standard of care for cutaneous melanoma, but it is still controversial for cutaneous head and neck melanoma (CHNM). This study aims to confirm the feasibility, accuracy and low morbidity of SLNB in CHNM and evaluate its prognostic value. A monocentric and retrospective study on patients with CHNM treated in our tertiary care center (Gustave Roussy) between January 2008 and December 2012 was performed. The feasibility, morbidity and prognostic value of this technique were analysed. One hundred and twenty-four consecutive patients were included. SLNB was realized in 97.6% of the cases. No significant post-operative morbidity was observed. Nineteen percents of patients had a positive SN while only 14.3% of complete lymph node dissections (CLND) had additional nodal metastasis. The risk of recurrence after positive SN was significantly higher (69.2 vs 30.8%, p = 0.043). The false omission rate was low with 7.1%. Overall survival and disease-free survival were better in the negative SN group (82 vs 49%, p < 0.001 and 69.3 vs 41.8%, p = 0.0131). The risk of recurrence was significantly higher in the positive SN group (p = 0.043) and when primary tumour was ulcerated (p = 0.031). Only the mitotic rate of the primary tumour was associated with SN positivity (p = 0.049). As in other sites, SLNB status is a strong prognostic factor with comparable false omission rate and no superior morbidity.


[Comparison of ISE, ASV and FQ for complexation characterization of river water DOC with copper].
Condition stabilization constants of complexation between naturally occurring organic ligand in river water and copper were measured lgk and compared by using ISE, ASV and FQ methods. The measured lgk results were 2.29-6.47 by ISE, 2.61-6.91 by ASV, and 3.52-4.71 by FQ, respectively. The constants went up with the raise of pH, the decrease of copper content, and the increase of ligand concentration.


Cultured human uterine smooth muscle cells are retinoid responsive.
Primary cultures of human uterine smooth muscle cells have been widely used as a model system to evaluate agents that may play a role in the regulation of both normal and abnormal proliferative responses. We have used this in vitro system to determine if human uterine smooth muscle cells are responsive to treatment with a potent natural derivative of vitamin A, all-trans retinoic acid (ATRA). These studies were also designed to determine if there is a difference in retinoid responsiveness between normal smooth muscle and adjacent leiomyoma (a benign tumor of uterine smooth muscle). When cells were cultured in the presence of ATRA, a dose-dependent inhibition in proliferation was observed. This inhibition in proliferation was accompanied by an alteration in smooth muscle cell morphology. Both the inhibition in proliferation and the altered morphology were reversible when ATRA treatment was discontinued. Responsiveness to retinoids is determined, in part, by the expression of ligand-specific receptors belonging to the steroid/thyroid superfamily (RARs and RXRs); we have therefore identified the pattern of retinoid receptor transcript expression in human uterine smooth muscle cells. The data indicate that human uterine smooth muscle cells express retinoic acid receptors RAR alpha, beta, and gamma, and retinoid X receptors RXR alpha and beta. No difference in retinoid responsiveness or in the pattern of retinoid receptor expression was observed between normal smooth muscle and adjacent leiomyoma. This is the first observation of an antiproliferative effect of ATRA in uterine smooth muscle cells and the first report of retinoid receptor expression patterns in this cell type. Since retinoids are common pharmacologic tools in the treatment of a wide variety of hyperproliferative disorders, these observations may have both therapeutic and toxicologic implications.


Factors Associated with Emotional Distress in Children and Adolescents during Early Treatment for Cancer.
Children and adolescents diagnosed with cancer experience emotional distress, such as sadness, worrying, and irritability. However, there is little information about the psychological well-being of parents at the time of their child's diagnosis. We sought to identify factors that were associated with emotional distress in cancer patients as a basis for developing innovative psychological interventions. A retrospective chart review was performed on patients newly diagnosed with cancer at a single center in Korea from 2014 to 2016. Eighty-five patients and their mothers completed psychological inventories. To determine factors associated with emotional distress in patients, we assessed the psychological inventory results using multiple linear regression after performing correlation analysis. The maternal Beck Depression Inventory-II (BDI-II) score was positively correlated with total problem scores and externalizing scores in patients aged less than 7 years. In patients aged 7-12 years, there was no significant association between the patient's emotional distress and other variables. In contrast, the maternal BDI-II score was the strongest factor associated with patient depression in adolescents. We suggest that the most important factor affecting emotional distress in children and adolescents with cancer is maternal depression, especially in patients aged 1-6 years and aged 13-17 years. Understanding the factors associated with emotional distress of cancer patients allows us to develop early psychiatric interventions for patients and their parents at the initial psychological crisis.


Decontamination efficiency of high power ultrasound in the fruit and vegetable industry, a review.
Decontamination of fresh fruits and vegetables is an important unsolved technological problem. The main focus of this review is to summarize and synthesize the results of studies and articles about ultrasonic processing which can be adapted to the wash water decontamination process for fruits and vegetables. This review will also provide an overview about the importance of an effective wash water decontamination process in fruits and vegetables, the increase of foodborne outbreaks caused by fresh fruits and vegetables, microbial inactivation using ultrasound, and an interpretation of the high power ultrasound results in the fruits and vegetable industry. In addition, the limitations of ultrasonic processing in commercial applications have also been introduced.


Etiological Beliefs, Treatments, Stigmatizing Attitudes toward Schizophrenia. What Do Italians and Israelis Think?
Background: Although scientific research on the etiology of mental disorders has improved the knowledge of biogenetic and psychosocial aspects related to the onset of mental illness, stigmatizing attitudes and behaviors are still very prevalent and pose a significant social problem. Aim: The aim of this study was to deepen the knowledge of how attitudes toward people with mental illness are affected by specific personal beliefs and characteristics, such as culture and religion of the perceiver. More precisely, the main purpose is the definition of a structure of variables, namely perceived dangerousness, social closeness, and avoidance of the ill person, together with the beliefs about the best treatment to be undertaken and the sick person' gender, capable of describing the complexity of the stigma construct in particular as far as schizophrenia is concerned. Method: The study involved 305 university students, 183 from the University of Padua, Italy, and 122 from the University of Haifa, Israel. For the analyses, a latent class analysis (LCA) approach was chosen to identify a latent categorical structure accounting for the covariance between the observed variables. Such a latent structure was expected to be moderated by cultural background (Italy versus Israel) and religious beliefs, whereas causal beliefs, recommended treatment, dangerousness, social closeness, and public avoidance were the manifest variables, namely the observed indicators of the latent variable. Results: Two sets of results were obtained. First, the relevance of the manifest variables as indicators of the hypothesized latent variable was highlighted. Second, a two-latent-class categorical dimension represented by prejudicial attitudes, causal beliefs, and treatments concerning schizophrenia was found. Specifically, the differential effects of the two cultures and the religious beliefs on the latent structure and their relations highlighted the relevance of the observed variables as indicators of the expected latent variable. Conclusion: The present study contributes to the improvement of the understanding of how attitudes toward people with mental illness are affected by specific personal beliefs and characteristics of the perceiver. The definition of a structure of variables capable of describing the complexity of the stigma construct in particular as far as schizophrenia is concerned was achieved from a cross-cultural perspective.


On counting cranial nerves.
The enumeration of the cranial nerves is traced briefly from Galen's seven to Willis' ten and to von Sömmerring's twelve. The system of von Sömmerring, which has been followed for some 200 years, is a useful convention, although it is merely one of several possibilities. The naming of the cranial nerves was standardized nearly 100 years ago.


Filtering surgery in childhood glaucoma.
A review of 38 eyes of 24 patients receiving filtration surgery for childhood glaucoma is presented. A total of 54 procedures were performed, including both thermal sclerostomies and trabeculectomies. Successful control of intraocular pressure was obtained in 20 eyes (52%). Average follow-up time was four years, two months. Filtration surgery is seen as a useful technique in the treatment of childhood glaucoma when goniotomy fails. It also is useful in those conditions where the success rate of goniotomy is expected to be low.


Noradrenergic hyperactivity in primary hypertension; central and peripheral markers of both behavioral pathogenesis and efficacy of sympatholytic and relaxation therapy.
The effects of clonidine or relaxation therapy were determined in two separate groups of patients with primary hypertension. Ten patients were treated with clonidine monotherapy for 3 months. There were concurrent reductions of blood pressure, plasma and CSF norepinephrine, all p less than 0.01. The changes of blood pressure and norepinephrine were correlated, p less than 0.05 and 0.01, respectively. Thirty patients received hygienic instructions, and 17 of them had relaxation training in addition. Relaxation lowered blood pressures, p less than 0.01, the reduction of blood pressure was related to baseline plasma norepinephrine, p less than 0.05, and greater in patients with "raised" plasma norepinephrine, p less than 0.02. Plasma norepinephrine was lowered after hygienic therapy, p less than 0.05, the change was not significant after relaxation training. Arterial pressure elevation appears to be related to raised plasma norepinephrine. This noradrenergic hyperactivity is a marker for blood pressure responsiveness to sympatholytic therapy with clonidine or relaxation techniques.


Primary solitary cervical amyloidosis: case report and review of the literature.
A case report and literature review are presented. To describe and review the clinical presentations, characteristic findings from imaging studies, types, differential diagnosis, prognosis, and treatment of amyloidoma arising within the vertebrae. Amyloidoma can occur in the bone, skin, larynx, lymph nodes, urinary bladder, eye, tongue, and gastrointestinal system. However, amyloidomas affecting the vertebral bones are very rare. To our knowledge, only 3 cases of amyloidoma involving cervical spine have been reported previously. In this report, we present a case of solitary amyloidosis of the cervical spine. The differential diagnosis of primary solitary spinal amyloidoma includes metastasis, infection, primary bone tumors, plasmocytoma, and Potts abscess. The correct diagnosis can be achieved only after the specific staining of tissue. The prognosis of amyloidosis is related to the specific form of amyloidosis. However, primary solitary amyloidosis has the best prognosis, although a limited number of patients without long-term follow-up studies have been reported. Primary solitary amyloidosis is a rare form of the amyloidosis, which is different from the other forms of amyloidosis because of excellent prognosis with surgical excision. Combined surgical excision and spinal stabilization is the best treatment.


Magnetic and Electrical Properties of CoRE2W2O10 Ceramic Materials.
Microcrystalline samples of CoRE2W2O10 tungstates (RE = Y, Dy, Ho, Er) were prepared by a high-temperature solid-state reaction and then sintered into a ceramic form for unique properties and potential applications. For this purpose, structural, microscopic, ultraviolet-visible (UV-vis), magnetic, electrical, and thermoelectric measurements were performed. These studies showed a monoclinic structure, paramagnetism, short-range antiferromagnetic interactions in all samples, long-range ferrimagnetic interactions only in CoY2W2O10, poor n-type conductivity of 6.7 × 10-7 S/m at room temperature, strong thermal activation (Ea1 = 0.7 eV) in the intrinsic region, a strong increase in the power factor (S2σ) above 300 K, a Fermi energy (EF) of 0.16 eV, and a Fermi temperature (TF) of 1800 K. The above studies suggest that anion vacancy levels, which act as doubly charged donors, and to a lesser extent, the mixed valence band of cobalt ions (Co2+, Co3+), which are located below the bottom of the conduction band and below the Fermi level, are responsible for electron transport.


Efficacy and Safety of Adalimumab in Conjunction With Surgery in Moderate to Severe Hidradenitis Suppurativa: The SHARPS Randomized Clinical Trial.
Surgery is a mainstay in the management of hidradenitis suppurativa (HS). Adalimumab is the first drug approved for HS. To investigate the efficacy and safety of adalimumab in combination with wide-excision surgery followed by secondary intention healing. The Safety and Efficacy of Adalimumab for Hidradenitis Suppurativa Peri-Surgically (SHARPS) trial was a phase 4, randomized, double-blind, placebo-controlled study of adalimumab in conjunction with surgery. Patients were enrolled in 45 sites across 20 countries from July 18, 2016, to February 2, 2019, with the last patient visit on October 16, 2019. Eligible patients (aged 18-65 years) had moderate to severe HS that required radical surgery in an axillary or inguinal region and had 2 other anatomical regions affected, with 1 or more regions at Hurley stage II or III. Analysis was conducted in November 2019. Patients were randomized 1:1 to receive continuous adalimumab, 40 mg, or placebo during presurgery (12 weeks), perioperative (2 weeks), and postoperative (10 weeks) periods. The primary end point was the proportion of patients achieving HS clinical response across all body regions at week 12. Overall, 103 patients were randomized to adalimumab and 103 to matching placebo. Among all patients, 51% (n = 106) were women, 94% (n = 193) were White, and the mean (SD) age was 37.6 (11.3) years. At week 12, significantly more patients receiving adalimumab (49 of 103 [48%]) vs placebo (35 of 103 [34%]; P = .049) achieved HS clinical response across all body regions (treatment difference, 14% [95% CI, 0%-27%]). Treatment-emergent adverse events were reported in 74 of 103 patients (72%) and 69 of 103 patients (67%) in the adalimumab and placebo groups, respectively. No increased risk of postoperative wound infection, complication, or hemorrhage was observed with adalimumab vs placebo. Two deaths occurred in the adalimumab group; neither was considered as having a reasonable possibility of relationship to study drug. Adalimumab was efficacious in conjunction with wide-excision surgery followed by secondary intention healing, with no need to interrupt treatment prior to surgery. These data support further investigation of adalimumab as an adjuvant therapy to surgery in patients with moderate to severe HS. ClinicalTrials.gov Identifier: NCT02808975.


Early Postnatal and Preschool-Age Infection by Fasciola spp.: Report of Five Cases from Vietnam and Worldwide Review.
Fascioliasis is reported in five Vietnamese children aged 4 years or younger. A 10-month-old girl child and a 12-month-old boy child are the youngest patients ever diagnosed. Eggs in stools suggested an infection occurred at 5-6 months and 7-8 months of age, respectively. DNA sequencing and egg size indicated this to be the first report of a verified Fasciola gigantica infection in so small children. No specific diagnosis could be obtained in two 3-year-old children detected in the acute phase. A big and gravid ectopic F. gigantica-like worm was surgically found in a 4-year-old boy presenting with peritonitis. A worldwide review showed only 38 past cases in preschool children. They included 3, 7, 12, and 16 cases of 1, 2, 3, and 4 years, respectively, with a faster infection increase in males from 2 years onward. Reports were from all continents, except Oceania, including severe complications and death. The causal agent, when specifically diagnosed, was always Fasciola hepatica. Analyses include detection in hospital, surveys, and family outbreaks; infection sources; disease phases; parasite burden; ectopic cases; symptom onset; eosinophilia; biochemical markers; and clinical complications. C-reactive protein, creatinine, and γ-glutamyl transferase are the most useful biomarkers. A serological test and a coprological analysis are recommended for so small children, in which typical symptoms may be overlooked. Treatment problems were described with many drugs, except triclabendazole. Triclabendazole should be considered the drug of choice for such small children. The possibility of a very early infection by Fasciola spp. should be henceforth considered.


Minimizing dose variation from the interplay effect in stereotactic radiation therapy using volumetric modulated arc therapy for lung cancer.
It is important to improve the magnitude of dose variation that is caused by the interplay effect. The aim of this study was to investigate the impact of the number of breaths (NBs) to the dose variation for VMAT-SBRT to lung cancer. Data on respiratory motion and multileaf collimator (MLC) sequence were collected from the cases of 30 patients who underwent radiotherapy with VMAT-SBRT for lung cancer. The NBs in the total irradiation time with VMAT and the maximum craniocaudal amplitude of the target were calculated. The MLC sequence complexity was evaluated using the modulation complexity score for VMAT (MCSv). Static and dynamic measurements were performed using a cylindrical respiratory motion phantom and a micro ionization chamber. The 1 standard deviation which were obtained from 10 dynamic measurements for each patient were defined as dose variation caused by the interplay effect. The dose distributions were also verified with radiochromic film to detect undesired hot and cold dose spot. Dose measurements were also performed with different NBs in the same plan for 16 patients in 30 patients. The correlations between dose variations and parameters assessed for each treatment plan including NBs, MCSv, the MCSv/amplitude quotient (TMMCSv), and the MCSv/amplitude quotient × NBs product (IVS) were evaluated. Dose variation was decreased with increasing NBs, and NBs of >40 times maintained the dose variation within 3% in 15 cases. The correlation between dose variation and IVS which were considered NBs was shown stronger (R2 = 0.43, P < 0.05) than TMMCSv (R2 = 0.32, P < 0.05). The NBs is an important factor to reduce the dose variation. The patient who breathes >40 times during irradiation of two partial arcs VMAT (i.e., NBs = 16 breaths per minute) may be suitable for VMAT-SBRT for lung cancer.


Acrolein health effects.
Acrolein is a chemical used as an intermediate reactive aldehyde in chemical industry. It is used for synthesis of many organic substances, methionine production, and methyl chloride refrigerant. The general population is exposed to acrolein via smoking, second-hand smoke, exposure to wood and plastic smoke. Firefighters and population living or working in areas with heavy automotive traffic may expose to higher level of acrolein via inhalation of smoke or automotive exhaust. Degradation of acrolein in all environmental media occurs rapidly, therefore, environmental accumulation is not expected. Acrolein degrade in 6A days when applied to surface water, and it has not been found as a contaminant in municipal drinking water. Acrolein vapor may cause eye, nasal and respiratory tract irritations in low level exposure. A decrease in breathing rate was reported by volunteers acutely exposed to 0.3A ppm of acrolein. At similar level, mild nasal epithelial dysplasia, necrosis, and focal basal cell metaplasia have been observed in rats. The acrolein effects on gastrointestinal mucosa in the animals include epithelial hyperplasia, ulceration, and hemorrhage. The severity of the effects is dose dependent. Acrolein induces the respiratory, ocular, and gastrointestinal irritations by inducing the release of peptides in nerve terminals innervating these systems. Levels of acrolein between 22 and 249 ppm for 10 min induced a dose-related decrease in substance P (a short-chain polypeptide that functions as a neurotransmitter or neuromodulator).


Usual source of care and experiences with primary care among community health service centre patients in Changchun, China: A cross-sectional survey.
Under China's healthcare reforms, community health service centres (CHCs) have been established as the preferred primary care providers. Even with this change, there is still little attention paid to patients' usual source of care (USC) from CHCs in Northeastern China. The main purposes of this study were to explore the determinants of usual source of community health service and to examine the association between usual source of community health service and patients' experiences with primary care. A cross-sectional survey with 515 adult patients at CHCs in Jilin Province, China, was conducted between July 2016 and November 2016. The patients' experiences with primary care were assessed with the Primary Care Assessment Tool (PCAT). Patients with self-perceived poor health status (odds ratio = 1.984, 95% confidence interval = 1.145-3.437) and chronic disease (odds ratio = 2.207, 95% confidence interval = 1.203-4.051) were more likely to have a usual source of community health service than patients with self-perceived good health status or without chronic disease. Patients scored the highest on comprehensiveness of services available (Mean = 2.87) and the lowest on community orientation (Mean = 1.83) in all domains of the PCAT, with values ranging from 1 to 4. A multiple linear regression analysis revealed that patients with a usual source of community health service had significantly higher overall scores than those without (B = 0.205, p < .001). This study demonstrated the important role of CHCs in providing affordable health services for patients with chronic disease or poor health status. Moreover, patients who chose a CHC as a USC had better experiences with primary care compared with patients who did not choose a CHC as a USC. However, community-oriented services need to be improved, and efforts to improve patients' experiences should include policies that incentivise patients to adopt a CHC as their USC.