Self-management strategies and multicomponent training to mitigate the effects of the interruption of physical exercise programmes in the pandemic context on functionality, sedentary behaviour, physical capacity, mental health, body composition and quality of life in older adults: a blinded randomized controlled study protocol.
Considering the confinement recommended by the World Health Organization due to the pandemic caused by COVID-19, many community physical exercise programmes for older adults have had their activities cancelled. In this context, proposing strategies to recover the possible adverse effects of the confinement period is pertinent. The use of self-management strategies associated with regular physical activity reduces sedentary behaviour and improves physical capacity in older adults. Thus, the purpose of this study was to describe a multicomponent training programme combined with a self-management strategy protocol to mitigate the effects of interruptions in physical exercise programmes on functionality, physical capacity, mental health, body composition and quality of life in older adults. This will be a blinded, randomized and controlled clinical trial performed in São Carlos, SP, Brazil. Eighty older adults will be divided into two groups: multicomponent training (Multi) and multicomponent training + self-management strategies (Multi+SM). The intervention will be performed over 16 weeks on three alternate days of every week, with 50-min sessions. The assessment of physical capacity will be performed before the interruption of physical exercise programmes (T0: initial assessment, March 2020), preintervention (T1: immediately after the return of the exercise programme) and postintervention (T2). The assessments of physical activity level, quality of life, mental health, functionality and body composition will be performed at T1 and T2. The results from this MC+SM protocol will allow us to contribute clinical support to evaluate the variables analysed and to guide future public health policies with the aim of minimizing the possible deleterious effects arising from the physical exercise interruption periods caused by epidemics and pandemics. RBR-10zs97gk . Prospectively registered in Brazilian Registry of Clinical Trials (ReBEC) on 17 June 2021. Registry name: Use of self-management strategies combined with multicomponent training to mitigate the effects of social distancing due to COVID-19 on capacity, physical capacity, mental health and quality of life in older adults - A blind, randomized and controlled clinical trial.


Does metabolic radiolabeling stimulate the stress response? Gene expression profiling reveals differential cellular responses to internal beta vs. external gamma radiation.
DNA microarray analyses were used to investigate the effect of cell-incorporated 35S-methionine on human colorectal carcinoma cells. This beta-radiation-induced gene expression profile was compared with that induced by external gamma-radiation. The extent of DNA fragmentation was used as a biomarker to determine the external gamma dose that was bioequivalent to that received by cells incubated in medium containing 35S-methionine. Studies showed that 35S-methionine at 100 microCi/mL induced a much more robust transcriptional response than gamma-radiation (2000 cGy) when evaluated 2 h after the labeling or irradiation period. The cellular response to internal beta-radiation was greater not only with respect to the number of genes induced, but also with respect to the level of gene induction. Not surprisingly, the induced genes overlapped with the set of gamma-responsive genes. However, a distinct beta-gene induction profile that included a large number of cell adhesion proteins was also observed. Taken together, these studies demonstrate that metabolic incorporation of a low energy beta-emitter, such as 35S-methionine, can globally influence a diverse set of cellular activities that can, in turn, affect the outcome of many experiments by altering the cell cycle, metabolic, signaling, or redox status (set point) of the cell. Additional studies of the mechanism of beta-induced proliferation arrest and cell death and of the significance of its differential gene induction/repression profile in comparison to pulsed gamma-irradiation may lead to new insights into the ways in which ionizing radiation can interact with cells.


Pathogenesis of porcine circovirus; experimental infections of colostrum deprived piglets and examination of pig foetal material.
The results of virus and antigen distribution following experimental infection of colostrum deprived pigs with pig circovirus (PCV) by oral/nasal and intravenous routes are reported. PCV and antigen were detected using virus isolation and indirect immunofluorescence on cryostat sections respectively. PCV antigen was detected in tissues throughout the body but primarily in spleen thymus, and lung. No PCV antigen or virus was detected in tissue samples from the central nervous system. Examination of pig foetal material from field cases of abortion/stillbirth resulted in 3 PCV isolates from 2 sera and a spleen sample from 2 groups of stillborn piglets from the same farm. No antibody to PCV alone was detected in 160 foetal sera tested. These results suggest that transplacental infection with PCV does occur, possibly prior to foetal immunocompetance. However, it is probably not a significant cause of reproductive disorders in pigs in Northern Ireland.


Respiratory bronchiolitis and lung carcinoma.
Cigarette smoking is the primary causative factor for lung carcinoma and respiratory bronchiolitis (RB), particularly RB-associated interstitial lung disease (RB-ILD). However, the link between lung cancer and RB/RB-ILD remains undefined. We examined whether pathological fibrosis lesions exist simultaneously in patients with lung carcinoma because the fibrous lesions could be precancerous. Clinical, radiological, and pathological features were consecutively evaluated in 67 current smokers, 22 ex-smokers, and 35 nonsmokers who underwent surgical resection for lung carcinoma. The presence of interstitial changes was evaluated by high-resolution computed tomography (HRCT). The pathological examination focused on RB, RB with fibrosis, and coexistent interstitial changes. RB with fibrosis was observed in 13/67 current smokers with centrilobular nodular and/or patchy ground-glass opacities patterns or emphysema on HRCT. RB without fibrosis was observed in 12/67 current smokers with a centrilobular pattern, emphysema, or a normal pattern on HRCT. The Brinkman smoking index was significantly higher in the RB with fibrosis group (1278±133) than in the RB without fibrosis group (791±131). No RB with/without fibrosis features were noted in nonsmokers or ex-smokers. Squamous cell carcinoma was observed in 11/13 patients with RB with fibrosis, whereas adenocarcinoma was observed in 7/12 patients with RB without fibrosis. Squamous cell carcinoma located in peripheral areas was primarily observed in patients with RB with fibrosis, whereas adenocarcinoma was primarily observed in patients with RB without fibrosis. Interstitial fibrosis with RB caused by continuous heavy cigarette smoking may increase the risk of developing squamous cell carcinoma.


[Pharyngolplasty by transposition of the posterior tonsillar pillar (author's transl)].
13 children suffering from velo-pharyngeal insufficiency were operated. A transposition of the posterior pillar was carried out. After exposing the principle of the method, the anatomical bases of the operation and the operation technique used are described. The pharyngeal sphincter thus reconstituted has nearly always resulted in an improvement in the phonation in these subjects.


Slip prevention: validation of duplicates reproducing industrial floor surface state microgeometry.
The present study falls within the scope of work on the prevention of slips occurring on industrial workplace floor surfaces. Floor microgeometry is a determining factor in anti-slip flooring. Industrial environment-based quantification of floor microgeometrical properties is more restricting than laboratory quantification. The aim of the present study was to develop a duplication technique allowing reproduction of in situ floor microgeometry so as to be able to quantify this microgeometry in the laboratory. Duplicates were produced from a sample of five industrial floors. Surface microgeometry was characterized for both industrial floors and associated duplicates in order to study their microgeometrical changes following the duplicating operation. The purpose of this process was to reach a conclusion on the "reliability" of the duplication technique, on which the use of such duplicates depends. Parameters established from digitalized surfaces reveal differences of less than 5% between duplicates and original floor and this enables us to conclude that these duplicates offer a high degree of reliability with respect to results dispersion.


Superficial femoral pseudoaneurysm and arterial thromboembolism caused by an osteochondroma.
A 13-year-old boy with a symptomatic distal femoral osteochondroma was found to have a pseudoaneurysm of the superficial femoral artery caused by the tumor and occlusion of the anterior tibial artery due to arterial thromboembolism. Excision of the exostosis followed by saphenous vein grafting resulted in an excellent clinical recovery.


Free and conjugated estrogens detections in drainage tiles and wells beneath fields receiving swine manure slurry.
Although livestock manure, such as from swine (Sus scrofa domestica), have high capacity to introduce endocrine-disrupting free estrogens into the environment, the frequency of estrogen detections from reconnaissance studies suggest that these compounds are ubiquitous in the environment, perhaps resulting from historic manure inputs (e.g. cattle grazing residues, undocumented historic manure applications) or uncontrolled natural sources. Compared to free estrogens, conjugates of estrogens are innocuous but have greater mobility in the environment. Estrogen conjugates can also hydrolyze to re-form the potent free estrogens. The objective of this study was to identify the transport of free and conjugated estrogens to subsurface tile drains and groundwater beneath fields treated with swine manure slurry. Three field treatments were established, two receiving swine lagoon manure slurry and one with none. Manure slurry was injected into soils at a shallow depth (∼8 cm) and water samples from tile drains and shallow wells were sampled periodically for three years. Glucuronide and sulfate conjugates of 17β-estradiol (E2) and estrone (E1) were the only estrogen compounds detected in the tile drains (total detects = 31; 5% detection frequency; conc. range = 3.9-23.1 ng L-1), indicating the important role conjugates played in the mobility of estrogens. Free estrogens and estrogen conjugates were more frequently detected in the wells compared to the tile drains (total detects = 70; 11% detection frequency; conc. range = 4.0-1.6 × 103 ng L-1). No correlations were found between estrogen compound detections and dissolved or colloidal organic carbon (OC) fractions or other water quality parameters. Estrogenic compounds were detected beneath both manure treated and non-treated plots; furthermore, the total potential estrogenic equivalents (i.e. estrogenicity of hydrolyzed conjugates + free estrogens) were similar between treated and non-treated plots.


Quadrifurcation Variants of the Celiac Trunk.
The celiac trunk (CT) commonly trifurcates into the left gastric artery, common hepatic artery (CHA), and splenic artery (SA). The CHA then sends off the proper hepatic artery and gastroduodenal artery (GDA). The arcades of the head of the pancreas are celiacomesenteric anastomoses between branches of the GDA and the superior mesenteric artery. A quadrifurcation of the CT commonly occurs when a different branch is added to the 3 normal ones. An uncommon quadrifurcation of the CT occurs when only one or 2 of the normal branches of the CT participate. The CT quadrifurcations were documented on 112 computed tomography angiograms. Five different types of CT quadrifurcation-3 uncommon (types 1-3) and 2 common (types 4-5)-were found in 15/112 cases (13.39%). A marginal significant association was found between the presence of quadrifurcations and male gender (P = 0.05; Fisher's exact test). Type 1 showed a hepatogastric trunk+SA + right hepatic artery+GDA pattern, type 2 had an HGT + right inferior phrenic artery + CHA + SA pattern, type 3 had a gastrophrenic trunk + left inferior phrenic artery+CHA + SA pattern, type 4 showed an left gastric artery + CHA + SA + left inferior phrenic artery combination, and type 5 had an additional common inferior phrenic trunk. One of the type 4 cases showed a buildup of a mesentericomesenteric anastomotic pancreatic arcade between the inferior pancreaticoduodenal arteries, rather than a celiacomesenteric one. Anatomic variation of the celiacomesenteric axis is important during hepatobiliary and duodenopancreatic approaches. Therefore, preoperative evaluation is essential because theoretical anatomic possibilities could be real arterial variants.


Haematospermia: diagnosis and treatment.
Men perceive a bloody ejaculate as an alarming physical symptom and often seek the help of urologists for explanation and treatment. After a complete urological step-by-step examination including imaging studies and flexible cystoscopy, malignancy or another significant disease can be ruled out in the majority of cases. However, many of these cases of haematospermia may still remain idiopathic and thus unsatisfactory for both the patient and his physician. The following paper reviews the aetiology, the diagnostic work-up escalation and the treatment options of haematospermia.


Imaging Pitfall in the Pediatric Knee: Irregular Epiphyseal Ossification at the Femoral Condyle.
Teaching point: Age-related variability in endochondral ossification of the femoral condyles in children is a normal variant of skeletal maturation and should not be misdiagnosed as osteochondritis dissecans or any other epiphyseal abnormality.


The incidence and consequences of cytomegalovirus transmission via blood transfusion to low birth weight, premature infants in north east Scotland.
In a 2-year study involving 133 premature low birth weight (less than 1,500 g) infants, the impact of CMV infection via blood transfusion was assessed. 8.4% (7 out of 83) of transfused infants and 10% (7 out of 70) of those exposed to seropositive blood acquired CMV. In those less than 1,250 g the infection rate rose to 13.2% (7 out of 46). Seropositive infants were at a higher risk of acquiring CMV infection than seronegative ones. CMV infection did not give rise to specific immediate morbidity, and no deaths were attributed to CMV. The only source of nosocomial CMV infection was the transfused seropositive blood. Based on these findings, it was possible to formulate a CMV transfusion policy to premature infants in our region.


Viscoelasticity assessment of tumoral skin with the use of a novel contact-free palpation methodology based upon surface waves.
The ensuing pilot investigation sheds new light on characterizing tumoral and non-tumoral human skin mechanical properties that will not only assist the dermatologist's diagnosis but also could constitute the creation of an Artificial Intelligence database for upcoming research. A modern, non-invasive, and contact-free methodology-UNDERSKIN-was developed, and hinges upon Fourier transform computations that permit the analysis of surface wave dispersion with a specific skin inversion model and viscoelastic model. It yields a detailed look at how particle movements of the medium propagate throughout its near sub-surface, hence a novel knowledge of the mechanical responses of skin tumors. The research results display the tumors' viscoelastic responses alongside their respective healthy skin outcomes for each skin layer as well as the dermatologist's touch analysis. Although dermatologists are capable of sensing and having a fair overall assessment of what they are palpating, they are unable heretofore to quantify it and inform where the firmness or softness derives from, which it is necessary to be acquainted with so as to perform an accurate diagnosis, prognosis, treatment, future surgery, and teledermatology.


Impacts of educational debt on physical therapist employment trends.
Newly graduated physical therapists have high amounts of educational debt. Educational debt may negatively affect job satisfaction, aspirations for professional development, and choice of workplace setting. Research has not shown this association directly, yet it is conceptually supported by the Labor-Search Model. The purpose of this study was to understand the role that educational debt has on additional factors related to job choice in the Labor-Search Model. Retrospective data were captured through the Virginia Longitudinal Data System (VLDS) for 12,594 licensed physical therapists within the Commonwealth of Virginia from 2014 to 2020. A fixed effects panel analysis, with inflation-adjusted educational debt as the variable of interest, was conducted to assess whether patterns of professional certifications, volume of work, workplace setting, and job satisfaction were related to educational debt. Educational debt was positively correlated with higher professional degrees (p = 0.009), the number of hours worked per week (p = 0.049), and expected number of years until retirement (p = 0.013). Job satisfaction was statistically significant (p = 0.042) and negatively correlated with educational debt. Those with higher educational debt appear to have the habit of working more hours per week and have a longer time horizon until retirement. Newly licensed physical therapists with higher amounts of educational debt are more likely to experience this trend. Income and job satisfaction demonstrated an interaction effect on educational debt, such that those with lower levels of income had a stronger, negative relationship between their debt and job satisfaction, as compared to those with higher income.


Highly enantioselective total synthesis of (+)-isonitramine.
A new efficient enantioselective synthetic method of (+)-isonitramine is reported. (+)-Isonitramine was obtained in 12 steps (98% ee and 43% overall yield) from δ-valerolactam via enantioselective phase-transfer catalytic alkylation, Dieckman condensation, and diastereoselective reduction as key steps.


Central serotonin 1A receptor binding in temporal lobe epilepsy: a [carbonyl-(11)C]WAY-100635 PET study.
We performed positron emission tomography using [carbonyl-(11)C]WAY-100635, a serotonin 1A (5-HT(1A)) receptor antagonist, in 13 patients with temporal lobe epilepsy (TLE) and in 13 controls. 5-HT(1A) receptor distribution mapping allowed correct lateralization of the epileptogenic temporal lobe in all patients. 5-HT(1A) receptor binding potential (BP(ND)) was significantly reduced in almost all temporal regions of the epileptogenic lobe. Compared with controls, the patients had significantly decreased BP(ND) values in the hippocampus, parahippocampal gyrus, and amygdala. The asymmetry index (AI), which characterizes the interhemispheric asymmetry in BP(ND), was significantly higher in patients than in controls in most regions. Depression scores were not significantly correlated with BP(ND) or AI values. Our data provide further evidence of functional changes in the serotonergic system in TLE. Molecular imaging of the 5-HT(1A) receptor may help to define the in vivo neurochemistry of TLE, and may provide a valuable tool in the noninvasive presurgical assessment of patients with medically refractory TLE.


Crystallization and preliminary X-ray analysis of human carbonic anhydrase III.
Carbonic anhydrases catalyze the interconversion of carbon dioxide to bicarbonate. Human carbonic anhydrase isozyme III with a C-terminal hexahistidine tag was overexpressed in Eschericha coli, purified and crystallized. Diffraction data (93.4% completeness) were collected to 2.2 A resolution on an in-house R-AXIS IV++ image-plate system with Osmic mirrors and a Rigaku HU-H3R CU rotating-anode generator operating at 50 kV and 100 mA. A 60 degrees sweep of data were collected from a single crystal with a crystal-to-detector distance of 150 mm and a 0.5 degrees oscillation angle per frame using an exposure of 60 s per frame at 293 K. The crystals were shown to conform to the Laue hexagonal crystal system P6, with unit-cell parameters a = 44.7, c = 222.5 A and a scaling R(sym) of 0.087 for 11 962 unique reflections. Using the known crystal structure of the rat form of carbonic anhydrase isozyme III, a molecular-replacement model was built. This model was used for rotation and translation searches and uniquely defined the space group as P6(5). Rigid-body refinement of the model was used to generate an initial phased electron-density map with an R(work) of 31.17%.


Regulation of amylase messenger RNA concentration in rat pancreas by food content.
Regulation of the expression of pancreatic amylase genes was studied by comparing groups of rats fed diets with high (75%), intermediate (20%) and low (11%) carbohydrate content. Animals on the high carbohydrate diet had nine times as much amylase mRNA as those on low carbohydrate diet, and twice as much as the intermediate group, as determined by filter hybridization of equal amounts of total pancreatic RNA to an excess of a cloned rat amylase cDNA probe. Parallel results were obtained when levels of translatable amylase RNA were compared by means of an RNA-dependent rabbit reticulocyte cell-free system. Amylase mRNA-directed synthesis represented 35% of the total in the high carbohydrate group, 4% in the low group and 14% in the intermediate group. Relative rates of amylase synthesis, determined 30 min after [3H]phenylalanine injection, followed the same pattern. While 37% of total was incorporated into amylase in the high carbohydrate group, only 8% was incorporated in the low carbohydrate group, as compared with 22% in the intermediate group. These data indicate that modifications of diet composition alter the expression of pancreatic amylase genes as a consequence of changing the level of their transcript, and that pancreatic amylase production is mostly regulated at the pre-translational level.


"CUIDARAS " : A Nominal and Personalized Health Care Model. Effectiveness of a Massive Screening for Colorectal Cancer Detection at Community level.
Health systems provides care only to those people who spontaneous demand for attention; excluding those who dont perceive illness or are not aware enough to consult. Alternative healthcare models based on the nominal-personalized care like "University Center for Integrated Care of Referred Health Care" (CUIDARAS) may have better results. In order to demonstrate benefits of this model, it was performed an experience based in colorectal cancer (CRC) detection and care that focused the entire population of the town. It is an intervention study for early detection of CRC. A survey and a physical examination were performed in each adult from "CH" town. Two visits were made. Blood in stool test (BIST) was self-collected, analyzed and results delivered with appointment for a programmed video-colonoscopy (VCC) when test was positive. people enrolled (n546) had 59.9+/-6.4 yrs. Adherence was 93.8% of the target population; 99.2% performed BIST; while 95.3% a positive BIST had access to VCC and treatment. Overall cost of the experience (stool test, VCC, biopsy, local treatment) was 7685 USD, while costs associated to an advanced CRC classic treatment was USD 9577/patient (USD 26098 if treatment included bevacizumab). The present study based on preventive actions like blood in stool test, applied as a screening to all inhabitants in town, had 93.8% of adherence and high level of CRC early detection. A health model based on personalized care (CUIDARAS), achieved more effective results in terms health care and disease prevention, with a favorable benefit/cost ratio compared with classical health care provide by current system. Key words: Model of care; colorectal cancer; CUIDARAS; personalized care.


H7-resistant protein kinase C substrates in two-dimensional gels of proestrous rat anterior pituitary gland.
The presence of Ca(2+)-dependent and -independent protein kinase C (PKC) activities which were stimulated by phorbol-12,13-dibutyrate (PDBu) and sensitive to the kinase inhibitor staurosporine (IC50 values approx. 100 nM) was demonstrated in proestrous rat anterior pituitary gland. These PDBu-induced activities were completely abolished by the PKC-specific inhibitors Ro31-8220 and GF109203X (3 microM). The Ca(2+)-independent activity was more resistant (IC50 = 61 microM) to the kinase inhibitor H7 than the Ca(2+)-dependent activity (IC50 approx. 20 microM), however, this (unusual) resistance to H7 was not observed in the brain regions, hypothalamus and hippocampus. Possible substrates for the Ca(2+)-independent PKC in anterior pituitary were identified by two-dimensional gel electrophoresis and autoradiography following incubation in vitro with [32P]phosphate and 300 nM PDBu +/- 300 nM staurosporine or 30 microM H7. The phosphorylation of six proteins (16, 16, 25, 36, 65 and 69 kDa) was found to be stimulated by PDBu and inhibited by staurosporine, but not H7, in whole tissue, and another two such phosphorylated proteins (each 76 kDa) were observed in microsomal subcellular fractions. These phosphoproteins may be substrates for an H7-resistant PKC isoform previously shown to mediate a number of cellular responses in rat anterior pituitary gland.


Effect of growth factors on hepatic drug metabolism in diabetic-hypophysectomized rats.
In vivo administration to diabetic-hypothysectomized rats of either the growth factor produced by the plerocercoid larvae of the tapeworm, Spirometra mansonoides, or mammalian growth hormone caused inhibition of hepatic drug metabolism measured in vitro.


Enrichment of hyperforin from St. John's wort (Hypericum perforatum) by pilot-scale supercritical carbon dioxide extraction.
St. John's Wort (Hypericum perforatum L.) was extracted with supercritical carbon dioxide using a pilot batch extraction plant. The effects of pressure, temperature, flow rate and extraction time were examined with respect to extraction yield and hyperforin content. Supercritical carbon dioxide showed a high selectivity for phloroglucinols. Extracts were analyzed using an isocratic HPLC method with a mixture of hyperforin/adhyperforin as an external standard. Within the studied range of extraction pressure (90-150 bar) and extraction time (1-5 h), extraction at 90 bar for 3 h and 120 bar for 1 h provided higher hyperforin content (up to 35%) in the resulting extracts. An increase in extraction temperature showed a negative effect, leading to increased degradation of hyperforin into orthoforin. When the total mass of carbon dioxide passing the extraction vessel was kept constant, changes in mass flow rate did not affect the extraction result.


Recent advances in the management of venous thromboembolism.
Deep venous thrombosis and pulmonary embolism are frequently diagnosed in patients encountered in a primary-care practice. In the past 10 years, many important advances have been made regarding the management of these disorders. Risk factors have been better defined than in the past. Several new prophylactic measures--such as external pneumatic compression of the lower extremities, dihydroergotamine in combination with heparin, adjusted-dose heparin, and two-step warfarin therapy--can be used to help prevent deep venous thrombosis in surgical patients. The use of serial impedance plethysmography has expanded options for noninvasive diagnosis of deep venous thrombosis. Correlations between pulmonary embolism and ventilation-perfusion lung scan patterns have been clarified. Although much has been learned about heparin and warfarin that affect common management decisions, the indications for thrombolytic therapy for venous thromboembolism remain controversial. Finally, studies have shown that calf vein thrombi that are not detectable by impedance plethysmography and that show no evidence of proximal propagation by serial impedance plethysmography do not require treatment.


Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells.
TαT1 cells are mouse thyrotroph cell line frequently used for studies on thyroid-stimulating hormone beta subunit gene expression and other cellular functions. Here we have characterized calcium-signaling pathways in TαT1 cells, an issue not previously addressed in these cells and incompletely described in native thyrotrophs. TαT1 cells are excitable and fire action potentials spontaneously and in response to application of thyrotropin-releasing hormone (TRH), the native hypothalamic agonist for thyrotrophs. Spontaneous electrical activity is coupled to small amplitude fluctuations in intracellular calcium, whereas TRH stimulates both calcium mobilization from intracellular pools and calcium influx. Non-receptor-mediated depletion of intracellular pool also leads to a prominent facilitation of calcium influx. Both receptor and non-receptor stimulated calcium influx is substantially attenuated but not completely abolished by inhibition of voltage-gated calcium channels, suggesting that depletion of intracellular calcium pool in these cells provides a signal for both voltage-independent and -dependent calcium influx, the latter by facilitating the pacemaking activity. These cells also express purinergic P2Y1 receptors and their activation by extracellular ATP mimics TRH action on calcium mobilization and influx. The thyroid hormone triiodothyronine prolongs duration of TRH-induced calcium spikes during 30-min exposure. These data indicate that TαT1 cells are capable of responding to natively feed-forward TRH signaling and intrapituitary ATP signaling with acute calcium mobilization and sustained calcium influx. Amplification of TRH-induced calcium signaling by triiodothyronine further suggests the existence of a pathway for positive feedback effects of thyroid hormones probably in a non-genomic manner.


Deep Learning Radiomics Nomogram Based on Magnetic Resonance Imaging for Differentiating Type I/II Epithelial Ovarian Cancer.
To develop and validate a T2-weighted magnetic resonance imaging (MRI)-based deep learning radiomics nomogram (DLRN) to differentiate between type I and type II epithelial ovarian cancer (EOC). This multicenter study incorporated 437 patients from five centers, divided into training (n = 271), internal validation (n = 68), and external validation (n = 98) sets. The deep learning (DL) model was constructed using the largest orthogonal slices of the tumor area. The extracted radiomics features were employed in building the radiomics model. The clinical model was developed based on clinical characteristics. A DLRN was built by integrating the DL signature, radiomics signature, and independent clinical predictors. Model performances were evaluated through receiver operating characteristic (ROC) analysis, Brier score, calibration curve, and decision curve analysis (DCA). The areas under the ROC curve (AUCs) were compared using the DeLong test. A two-tailed P < 0.05 was considered significantly different. The DLRN exhibited satisfactory discrimination between type I and type II EOC with the AUC of 0.888 (95% confidence interval [CI] 0.810, 0.966) and 0.866 (95% CI 0.786, 0.946) in the internal and external validation sets, respectively. These AUCs significantly exceeded those of the clinical model (P = 0.013 and 0.043, in the internal and external validation sets, respectively). The DLRN demonstrated optimal classification accuracy and clinical application value, according to Brier scores, calibration curves, and DCA. A T2-weighted MRI-based DLRN showed promising potential in differentiating between type I and type II EOC, which could offer assistance in clinical decision-making.


Dimensions of problem behavior in deaf children.
The Behavior Problem Checklist was completed by the teachers of 192 deaf students who attended a special day school for the deaf. Three separate factor analyses were performed. Four factors that correspond to the dimensions found in earlier research and previously labeled conduct disorder, personality problems, immaturity-inadequacy, and socialized delinquency were found. An additional factor labeled passive inferiority was also extracted.


A guide to wire myography.
Wire myography is an in vitro technique that allows us to examine functional responses and vascular reactivity of isolated small resistance arteries. Vessels from various species, including transgenic models, and vascular beds can be examined in a variety of pathological disease states. Vessels are dissected, cleaned, and then mounted onto a four-channel myograph under isometric techniques. Each vessel is then normalized to determine maximum active tension development. This allows the standardization of initial experimental conditions, an important consideration when examining pharmacological differences between vessels.


Gap junctions: The missing piece of the connectome.
The central pattern generator that controls flying power in Drosophila requires desynchronized firing to drive a steady wingbeat frequency. A new study reveals how gap junctions are the key to desynchronizing the motor neurons.


[Recent developments in animal welfare legislation (pig husbandry)].
Council Directive 91/630/EEC of 19 November 1991 laying down minimum standards for the protection of pigs has been amended in 2001. The following text provides a survey of the progress of the discussion at European level and of the options for transposing into national law.


Primary Care Intervention Provides Modest Gains in Prevention, Not Treatment, of Alcohol Use Disorder.
According to this study: An implementation trial in primary care practices resulted in modest increases in screening, diagnosis, and initiation of treatment for alcohol use disorder but not in patient engagement with treatment.


Capacity to Consent to Research Among Adolescent-Parent Dyads in Rakai, Uganda.
To assess the cognitive capacity of early, middle, and late adolescents and their parents or guardians to provide informed consent to a population-based cohort study. Adolescent-parent/guardian dyads including 40 early (n = 80; 10-14 years), 20 middle (15-17 years), and 20 late (18-19 years) adolescents were recruited from the Rakai Community Cohort Study, an open demographic cohort in Uganda. Participants were administered the MacArthur Competence Assessment Tool for Clinical Research, a structured open-ended assessment; interviews were recorded and transcribed. Twenty transcripts were scored independently by two coders; the intraclass correlation coefficient was 0.89. The remaining interviews were scored individually. We compared mean scores for early and middle/late adolescents using a one-sided t test and score differences between parent/guardian and adolescent dyads using two-sided paired t tests. Early adolescents (mean score, 28.8; 95% CI, 27.1-30.5) scored significantly lower (P < .01) than middle/late adolescents (32.4; 31.6-33.1). In paired dyad comparisons, we observed no statistically significant difference in scores between parents/guardians and middle/late adolescents (difference, -0.2; 95% CI, -1.0-0.6). We found a statistically significant difference in scores between parents/guardians and early adolescents (difference, 3.0; 95% CI, 1.2-4.8). The capacity of adolescents-of different ages and in diverse settings-to comprehend risks, benefits, and other elements of informed consent is a critical but understudied area in research ethics. Our findings support the practice of having middle and late adolescents provide independent informed consent for sexual and reproductive health studies. Early adolescents may benefit from supported decision-making approaches.


Key principles and operational practices for improved nanotechnology environmental exposure assessment.
Nanotechnology is identified as a key enabling technology due to its potential to contribute to economic growth and societal well-being across industrial sectors. Sustainable nanotechnology requires a scientifically based and proportionate risk governance structure to support innovation, including a robust framework for environmental risk assessment (ERA) that ideally builds on methods established for conventional chemicals to ensure alignment and avoid duplication. Exposure assessment developed as a tiered approach is equally beneficial to nano-specific ERA as for other classes of chemicals. Here we present the developing knowledge, practical considerations and key principles need to support exposure assessment for engineered nanomaterials for regulatory and research applications.


The periodic law of the chemical elements: 'The new system of atomic weights which renders evident the analogies which exist between bodies' [1].
The historical roots, the discovery and the modern relevance of Dmitri Mendeleev's remarkable advance have been the subject of numerous scholarly works. Here, with a brief overview, we hope to provide a link into the contents of this special issue honouring the great scientist. Mendeleev's advance, announced in March 1869, as he put it in 1889, to the '…then youthful Russian Chemical Society…', first set out the very basis of the periodic law of the chemical elements, the natural relation between the properties of the elements and their atomic weights. This was, and still is, the centrepiece of a historical journey for chemistry to today's position as a pre-eminent science. This article is part of the theme issue 'Mendeleev and the periodic table'.


Elongation and surface extension of individual cells of Escherichia coli B/r: comparison of theoretical and experimental size distributions.
The way individual cells grow and divide uniquely determines the (time-invariant) cell size distribution of populations in steady-state exponential growth. In the preceding article, theoretical distributions were derived for two exponential and six linear models containing a small number of adjustable parameters but no assumptions other than that all cells obey the same growth law. The linear models differ from each other with respect to the timing of the presumptive doubling in their growth rate, the exponential models--according to whether there is or is not a part of the cell that does not contribute to the growth rate. Here we compared the size distributions predicted by each of these models with those of cell length and surface area measured by electron microscopy; the quality of the fit, as determined by the mean-square successive-differences test and the chi 2 goodness-of-fit test, was taken as a measure of the adequacy of the model. The actual data came from two slow-growing E. coli B/r cultures, an A strain (pi = 125 min) and a K strain (pi = 106 min), and a correction was introduced in each to account for the distortion caused by the finite size of the picture frame. The parameter estimates produced by the various models are quite reliable (cv less than 0.1%); we discuss them briefly and compare their values in the two strains. All the length extension models were rejected outright whereas most of the surface growth versions were not. When the same models were tested on A-strain data from a faster growing culture (tau = 21 min), those models that provided an adequate fit to the cell surface area data proved equally satisfactory in the case of cell length. These findings are evaluated and shown to be consistent with cell surface area rather than cell length being the dimension under active control. Three surface area models, all linear, are rejected--those in which doubling of the growth rate occurs with a constant probability from cell birth, at a particular cell age, and precisely at cell division. The evidence in the literature that appears to contradict this last result, rejection of the simple linear surface growth model, is shown to be faulty. The 16 original models are here reduced to five, two involving exponential surface growth and three linear, and possible reasons are presented for our inability to discriminate further at this stage.


Sequelae of Anticoagulant Therapy in a Patient with History of Pulmonary Malignancy: A Case Report.
In patients with known malignancy and possible intracranial metastatic disease who are receiving treatment with therapeutic anticoagulation, limited data exist regarding risk of intracranial bleeding. We present a case of a 64-year-old female with known lung malignancy, evidence of possible metastatic disease, and bilateral deep vein thrombosis, who suffered severe intracranial hemorrhage following initiation of therapeutic anticoagulation. Current guidelines, available risk- stratification tools, and treatment options with their risks are discussed. In patients with known or suspected intracranial metastatic disease, clinical decision tools can assist both the clinician and the patient in weighing risks and benefits of anticoagulation.


Association of HLA DQB1 0602 in sarcoidosis patients with small fiber neuropathy.
Sarcoidosis has been reported to be associated with the HLA genes, in particular DQB1. High resolution DQB 1 of 103 sarcoidosis patients was obtained by sequence-based typing; low resolution HLA-A/B/DRB 1 typing was performed by serological and molecular methods. Small fiber neuropathy (SFN) was established by thermal threshold testing. Sixty-seven patients suffered from SFN (SFN+), in 36 patients SFN was absent (SFN-). Comparing HLA DQB 1 typings of SFN+ patients, SFN- patients and control individuals revealed a significant increase of the allele DQB 1 0602 in SFN+ patients compared to controls. This association might be correlated with a severe course of the disease.


Update from the 5th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumours of the Ear.
In the recently published 5th Edition of the World Health Organisation Classification of Head and Neck Tumours, there are relatively few changes to report in terms of nomenclature in lesions of ear and temporal bone and fewer developments in molecular pathogenesis in comparison to other sites, particularly in sinonasal tract. Ear and temporal bone tumours are rare and biopsy material is limited. As a result, resources in the literature are scarce with few large series, no controlled clinical trials and the approaches to staging and management are not standardised. New entities are difficult to characterise. The number of entries has, however, increased for tumours of the ear and temporal bone (thirteen) compared to the 4th Edition (eleven). Some lesions previously included in the 4th Edition considered to have no site-specific features have been excluded to be discussed elsewhere and other benign lesions that are specific to this site have been included. The tumours and tumour-like entities of ear and temporal bone are discussed here mindful that the chapter in the 5th edition better correlates disease processes with clinical information and imaging and as far as possible standardises nomenclature.


Comparison of intravenous ferrous sucrose and oral ferrous sulphate in treatment of postpartum iron deficiency anemia.
The objective of the study was to evaluate the efficacy, safety and tolerability of intravenous ferrous sucrose, compared to oral ferrous sulphate in women with postpartum iron deficiency anemia (IDA). In a single center, randomized, controlled study, 352 patients with hemoglobin 9 gm/dl or less and serum ferritin of <15 μg/l two days after delivery were equally randomized to receive intravenous ferrous sucrose (up to three calculated replacement doses) or oral ferrous sulphate (150 mg twice daily for six weeks). Primary measures were to assess the rise in hemoglobin (Hb) and serum ferritin. By day 5, the Hb level in women treated with intravenous ferrous sucrose had rised from 8.48 ± 0.47 to 9.4 ± 0.56 gm/dl. Women treated with intravenous ferrous sucrose had significantly higher Hb levels on day 5, day 14 and day 40 (p < 0.01) than those treated with oral ferrous sulphate. Throughout the study, ferritin level rose rapidly in those treated with intravenous iron and remained significantly higher than in those treated with oral iron (p < 0.001). Intravenous ferrous sucrose increases Hb level more rapidly than ferrous sulphate in women with postpartum IDA. It also replenishes iron stores more rapidly with better tolerability.


Cobalt and chromium exposure affects osteoblast function and impairs the mineralization of prosthesis surfaces in vitro.
Cobalt (Co) and chromium (Cr) ions and nanoparticles equivalent to those released through tribo-corrosion of prosthetic metal-on-metal (MOM) bearings and taper junctions are detrimental to osteoblast activity and function in vitro when examined as individual species. Here we examined the effects of Co(2+):Cr(3+) and Co(2+):Cr(6+) combinations on osteoblast-like SaOS-2 cellular activity, alkaline phosphatase (ALP) activity and mineralization to better reflect clinical exposure conditions in vivo. We also assessed the effect of Co(2+):Cr(3+) combinations and Co:Cr nanoparticles on SaOS-2 cell osteogenic responses on grit-blasted, plasma-sprayed titanium-coated, and hydroxyapatite-coated prosthesis surfaces. Cellular activity and ALP activity were reduced to a greater extent with combination treatments compared to individual ions. Co(2+) and Cr(3+) interacted additively and synergistically to reduce cellular activity and ALP activity, respectively, while the Co(2+) with Cr(6+) combination was dominated by the effect of Cr(6+) alone. Mineralization by osteoblasts was greater on hydroxyapatite-coated surfaces compared to grit-blasted and plasma-sprayed titanium-coated surfaces. Treatments with Co(2+):Cr(3+) ions and Co:Cr nanoparticles reduced the percentage mineralization on all surfaces, with hydroxyapatite-coated surfaces having the least reduction. In conclusion, our data suggests that previous studies investigating individual metal ions underestimate their potential clinical effects on osteoblast activity. Furthermore, the data suggests that hydroxyapatite-coated surfaces may modulate osteoblast responses to metal debris.


Correction to: Rapid and reliable detection of α-globin copy number variations by quantitative real-time PCR.
[This corrects the article DOI: 10.1186/2052-1839-14-4.].


Multidisciplinary Rheuma-Derma Clinics: 5 Years of Experience at the San Marco Hospital in Catania.
Early psoriatic arthritis (PsA) diagnosis is critical to prescribe timely treatment to prevent the irreversible joint damage and the many other problems that patients with PsA experience. This retrospective study aimed to highlight the benefits of a Rheuma-Derma Clinic focused on the early diagnosis and prompt treatment of PsA with a shared approach among Italian psoriasis patients. Diagnosing PsA early is the main goal to reduce joint damage and disability in the patients affected. Studies describing the results of rheuma-derma clinics aimed to reach this goal emerged in the last decade. This study presents limitations and advantages typical of retrospective designs. A Rheuma-Derma Clinic was created in 2017 at the Rheumatology Department of the Hospital Policlinico Gaspare Rodolico of the University of Catania in San Marco, Italy. This study compared the number of patients under disease-modifying antirheumatic treatment 5 years before and after the joint clinic was created. A rheumatologist and dermatologist simultaneously assessed patients with psoriasis and/or PsA to obtain a rapid multidisciplinary diagnostic approach and a shared therapeutic strategy. In addition, demographic, clinical, and clinimetrics data were collected. The number of patients with PsA receiving biological disease-modifying antirheumatic drugs increased 47% (from 255 to 374 patients) before and after the joint clinic was implemented. Likewise, those receiving conventional synthetic disease-modifying antirheumatic drugs increased by 47% (from 367 to 539) as well. Additionally, for all the clinimetrics evaluated (DAS28, HAQ, BASDAI, DAPSA, PASI, PGA), there was an improvement over the 12 months under the Rheuma-Derma Clinic care. The measures that improved the most were DAPSA, PGA, PASI, and BASDAI. The implementation of the Rheuma-Derma Clinic was associated with an increase in the number of patients diagnosed, the number of patients with PsA receiving DMARD treatments, and improvements in clinimetrics among the study participants.


Invasive intracardiac aspergillosis with widespread embolization.
Intracardiac extension of pulmonary aspergillosis is uncommon. We report a case of a patient with chronic necrotizing pulmonary aspergillosis without clinical evidence of cardiac disease in whom transthoracic echocardiography revealed an intracardiac mass. A subsequent transesophageal examination clearly defined a large and complex mass in the left atrium and pulmonary artery. Autopsy performed after cardiopulmonary arrest confirmed the presence of direct cardiac invasion of pulmonary aspergillosis with widespread embolization. This case illustrates the possibility of direct intracardiac extension of pulmonary aspergillosis and the value of transesophageal echocardiography in establishing the diagnosis.


Interleukin 1 activation of the AP-1 transcription complex in murine T cells is regulated at the level of Jun B protein accumulation.
We have examined the regulation of the AP-1 DNA transcription complex during T cell activation in response to interleukin 1 (IL-1) and phorbol ester (TPA) treatment of the IL-1 responsive murine thymoma T cell line, EL4 6.1 C 10. IL-1 synergistically enhances the stimulatory effect of TPA on AP-1-mediated gene expression in this cell line. To elucidate the mechanism(s) by which IL-1 enhances AP-1-mediated gene expression, we examined the effect of IL-1 on the synthesis and turnover of Jun B, the member of the jun gene family that is present in AP-1 complexes in EL4 cells. We found that IL-1 + TPA-treated cells contain significantly higher Jun B protein levels than cells treated with TPA alone. IL-1 promotes the prolonged accumulation of Jun B, whereas the cellular content of Jun B decreases dramatically after 6 hr in cells treated with only TPA. IL-1 enhancement of Jun B protein levels is not the result of a change in the turnover rate of the Jun B protein, but rather results from the maintenance of sufficient jun B mRNA to support continued accumulation of newly synthesized protein. In addition to Jun B, we found that the T cell AP-1 complex contains the Fra-1 protein, a member of the fos gene family. Although IL-1 dramatically increases Jun B accumulation, it does not enhance TPA-induced Fra-1 protein levels in EL4 cells. Thus, the stimulation of AP-1-mediated gene expression by IL-1 in EL4 cells is due to the promotion of Jun B protein accumulation that, in turn, facilitates Jun B heterodimerization with TPA-induced Fra-1 protein, thereby forming an active AP-1 complex.


Sudden cardiac death after aortic valve surgery: incidence and concomitant factors.
A retrospective analysis of 599 consecutive patients after aortic valve surgery aged 7-82 years (mean 56) was performed. During a follow-up of 1-14 years (mean 4.7 years) a 4-week perioperative mortality of 6.9% and a late annual mortality of 3.6% were observed. Sudden cardiac death was the most frequent single cause of death, accounting for 24% of all deaths. Patients dying suddenly were younger than patients dying from other causes (51 +/- 17 vs. 59 +/- 14 years, p less than 0.05) and showed more left ventricular hypertrophy by electrocardiographic criteria when compared with matched survivors (mean Estes score 5.2 +/- 2.4 vs. 2.8 +/- 1.9; p less than 0.01) and with patients dying nonsuddenly (mean Estes score 5.2 +/- 2.4 vs. 1.8 +/- 1.8; p less than 0.01). Ventricular premature beats in the resting electrocardiogram were more prevalent in patients dying suddenly than in matched survivors (55 vs. 20%; p less than 0.025) as well as in patients dying from other causes (55 vs. 25%; p less than 0.05). In addition, there were more intracardiac conduction disturbances and more ungrafted coronary vessels with insignificant stenoses at the time of surgery in sudden death patients. Our findings suggest that after aortic valve replacement patients with left ventricular hypertrophy, bundle-branch block, and ventricular premature beats in the resting electrocardiogram are at increased risk for sudden cardiac death. A possible etiological role of concomitant coronary artery disease must be considered.


Vaccination of young lambs by means of a protein fraction extracted from adult Haemonchus contortus.
Lambs aged 48-150 days which had been injected with extracts enriched in a functional antigen (contortin) obtained from adult Haemonchus contortus developed specific circulating antibodies and were less susceptible to haemonchosis when challenged 1 month later with a single dose of 20,000-25,000 infective 3rd-stage larvae. Sera from 18 out of a total of 19 lambs injected with the extract contained precipitating antibodies to 2-5 components of the extract. None of these lambs died. The one extract-injected lamb which did not develop antibodies and 9 of the 13 lambs used as controls died of haemonchosis. The average weight of worms recovered was 1.45 g from the immune lambs and 5.72 g from the non-immune lambs.


Evidence for novel 30,000-50,000Mr cofactor in the activation of muscle.
A new approach is described for reconstituting a fully desensitized skeletal muscle fiber to restore its contractility. These studies revealed a novel regulatory cofactor, 30-50,000Mr by filtration (26-55kDa by SDS PAGE). It was shown to be critical for the Ca2+-activation in the physiological milieu. The cofactor was present in skeletal and cardiac muscles as well as in brain, but not in kidney and liver. The cofactor may be a second Ca2+ switch in a dual-regulation scheme for vertebrate muscle, or could provide an essential link in the cross-bridge cycle beyond activation.


Effect of placental hypoxia on the plasma membrane Ca-ATPase (PMCA) activity and the level of lipid peroxidation of syncytiotrophoblast and red blood cell ghosts.
Term placental villous fragments from normotensive pregnant women were incubated under hypoxia in order to induce lipid peroxidation of the placental plasma membranes and, consequently, to increase their release of lipid peroxide products into the incubation medium. The homogenates of the villous fragments were assayed for plasma membrane Ca-ATPase (PMCA) activity and TBARS. The incubation medium, after placental hypoxia, was used to incubate intact red blood cells (RBCs) from normotensive pregnant women. Similarly, intact RBCs from normotensive pregnant women were incubated with deproteinized blood plasma from normotensive pregnant women and women with preeclampsia. In all the cases, red cell ghosts were prepared from the incubated cells and assayed for PMCA and TBARS. The incubation of placental villous fragments under hypoxia led to an increase in the TBARS and a significant reduction in the PMCA activity of their homogenates, as compared to those of villous fragments incubated under normoxia. The exposure of intact RBCs from normotensive pregnant women either to the incubation medium of placental hypoxia or to deproteinized blood plasma from women with preeclampsia, caused a rise of the TBARS and a diminution of PMCA activity of the red cell ghosts. Inside-out vesicles were also prepared from intact RBCs incubated with the medium where the placental hypoxia was carried out. These vesicles were assayed for active calcium transport. Pretreatment of RBCs with the incubation medium of placental hypoxia led to a lower active calcium transport as compared to that of inside-out vesicles from RBCs without any preincubation. These results are in agreement with the idea that the RBCs can be peroxidized when passing through a highly oxidized medium, such as the placental intervillous space from women with preeclampsia. The peroxidized RBCs would contribute then to the propagation of lipid peroxidation from the placenta to nearby and far away tissues.


Structural Aspects of Bacterial Outer Membrane Protein Assembly.
The outer membrane of Gram-negative bacteria is predominantly populated by β-Barrel proteins and lipid anchored proteins that serve a variety of biological functions. The proper folding and assembly of these proteins is essential for bacterial viability and often plays a critical role in virulence and pathogenesis. The β-barrel assembly machinery (Bam) complex is responsible for the proper assembly of β-barrels into the outer membrane of Gram-negative bacteria, whereas the localization of lipoproteins (Lol) system is required for proper targeting of lipoproteins to the outer membrane.


ProCoCoA: A quantitative approach for analyzing protein core composition.
Defining the amino acid composition of protein cores is fundamental for understanding protein folding, as different architectures might achieve structural stability only in the presence of specific amino acid networks. Quantitative characterization of protein cores in relation to the corresponding structures and dynamics is needed to increase the reliability of protein engineering procedures. Unambiguous criteria based on atom depth considerations were established to assign amino acid residues to protein cores and, hence, for classifying inner and outer molecular moieties. These criteria were summarized in a new tool named ProCoCoA, Protein Core Composition Analyzer. An user-friendly web interface was developed, available at the URL: http://www.sbl.unisi.it/prococoa. An accurate estimate of protein core composition for six protein architectures selected from the CATH database of solved structures has been carried out, and the obtained results indicate the presence of specific patterns of amino acid core composition in different protein folds.


The species of acyl-CoA in subcellular fractions of type II cells isolated from adult rat lung and their incorporation into phosphatidic acid.
Microsomes and cytosol were prepared from type II cells isolated from adult rat lung. Upon determination of the acyl-CoA composition in the microsomes, we found 49% palmitoyl-CoA, 2% myristoyl-CoA, 21% stearoyl-CoA, 5% palmitoleoyl-CoA, 16% oleoyl-CoA, 5% linoleoyl-CoA and 2% arachidonoyl-CoA. The acyl-CoA composition of the cytosol was very similar. Upon incubation of type II cell microsomes with [U-14C]glycerol 3-phosphate and with acyl-CoA species mixed in the proportions in which they were found in this cell fraction, approx. 40% of the synthesized phosphatidic acid was disaturated. Of the two quantitatively most important acyl-CoA species, the palmitoyl species was incorporated 4-times faster into total and disaturated phosphatidic acid than the stearoyl species. These two species were distributed very similarly among the phosphatidic acid species synthesized de novo. In newly formed disaturated phosphatidic acid, the palmitoyl groups were distributed approximately equally between the 1- and the 2-position. From these data, it can be estimated that of the phosphatidic acid molecules synthesized by type II cell microsomes, approx. 26% contain two palmitoyl moieties. Assuming that both phosphatidic acid phosphatase and cholinephosphotransferase are non-selective with regard to the substrate species that they convert, this would mean that 26% of the phosphatidylcholine molecules synthesized de novo would be dipalmitoylphosphatidylcholine. As in surfactant, approx. 60% of the phosphatidylcholine is constituted by the dipalmitoyl species, this would mean that approx. 45% of the surfactant dipalmitoylphosphatidylcholine would be made via de novo synthesis.


Visual outcome in Japanese patients with Acanthamoeba keratitis.
To identify prognostic factors affecting visual outcome in Acanthamoeba keratitis (AK) treated with topical chlorhexidine gluconate (CHG). A total of 35 eyes in 34 patients with AK were treated with 0.02% topical CHG. Patients were divided into two groups according to the final visual outcome: Group 1, final visual acuity (VA) of 20/25 or greater (22 eyes); Group 2, less than 20/25 (13 eyes). We compared these groups and evaluated the effectiveness of topical CHG compared with outcomes in previous reports. Ring infiltrate was observed more often in Group 2 (4.5% vs 61.5%, OR 33.6, 95% confidence interval (CI) 3.4-333.9, P<0.01). The duration between onset and diagnosis of AK was significantly longer (24.9 days vs 48.4 days, OR 1.03, 95% CI 1.00-1.06, P = 0.04) and VA at initial examination (log MAR) significantly lower (0.47 vs 1.59, OR 25.5, 95% CI 3.4-186.7, P<0.01) in Group 2 (visual outcome <20/25). Multivariate analysis revealed that only VA at initial examination was independently associated with worse visual outcome (adjusted OR 24.5, 95% CI 1.9-312.6, P=0.01). Seventeen (85.0%) of the 20 eyes diagnosed within 1 month and 24 (82.8%) of 29 eyes diagnosed within 2 months achieved a VA of 20/40 or greater. VA at initial examination was the most predictive factors for final visual outcome in AK. Topical CHG was comparably effective to other treatments, including polyhexamethyl biguanide and propamidine isethionate.


Oxidative degradation pathways of cellular DNA: product formation and mechanistic insights.
More than 100 oxidized purine and pyrimidine nucleosides including hydroperoxides and diastereomers have been characterized so far in extensive model studies. However, much less information is currently available on the oxidatively generated base damage to cellular DNA at the exception however of the overwhelming modifications produced by singlet oxygen ((1)O2). This is mostly due to analytical difficulties that are now, at least, partly overcome with the advent of the accurate and sensitive high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). Hydroxyl radical ((•)OH) and one-electron oxidants that may be either endogenously formed through oxidative metabolism, phagocytosis, inflammation and other pathological conditions are predominantly at the origin of oxidatively generated damage to cellular DNA. It is worth mentioning that exposure of cells to exogenous physical agents (UVA light, high intensity UV laser, ionizing radiation) and chemicals such as bromate may also induce oxidatively generated damage to DNA. Emphasis is placed in this presentation on the critical survey of the main recently available information concerning the formation of (1)O2, (•)OH and one-electron oxidant-mediated single and more complex DNA damage (tandem lesions, intra- and interstrand cross-links, DNA-protein cross-links) arising from one radical hit. Evidence was provided that (•)OH and one-electron oxidants, through the generation of neutral radicals and radical cations respectively from nucleobases, are able to induce partly common degradation pathways. In addition selective oxidative reactions giving rise to specific degradation products of (•)OH and one-electron oxidation reactions that can be used as representative biomarkers of these oxidants have been identified. Emphasis was recently placed on the detection of oxidatively generated damage to cytosine and 5-methylcytosine in human cells.


Development of a new method for the determination of nitrosamines by micellar electrokinetic capillary chromatography.
A new method was developed for separation and quantification of nitrosamines by micellar electrokinetic capillary chromatography (MEKC). The effects of composition of the buffer, concentration of sodium dodecyl sulfate (SDS), gamma-cyclodextrin (CD) and pH on the separation and migration times of the nitrosamines were investigated. The different instrumental variables affecting sensitivity and resolution, such as power supply, injection mode and wavelength for measurement, were carefully optimized. The direct application of this method to aqueous synthetic samples allowed the separation and determination of nitrosamine mixtures at the mg x L(-1) level. The calibration curves revealed a linear range between 0.25 and 10 mg x L(-1), with detection limit (DL) varying from 0.16 to 0.27 mg x L(-1), quantification limit (QL) varying from 0.52 to 0.90 mg x L(-1), and RSD relative standard deviation (RSD) from 4.5% to 8.5%. The proposed method was successfully applied to the determination of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), N-nitrosopyrrolidine (NPYR), N-nitrosomorpholine (NMOR) and N-nitrosopiperidine (NPIP).


In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds.
Adenosine deaminase acting on RNA 2 (ADAR2) is an important enzyme involved in RNA editing processes, particularly in the conversion of adenosine to inosine in RNA molecules. Dysregulation of ADAR2 activity has been implicated in various diseases, including neurological disorders (including schizophrenia), inflammatory disorders, viral infections, and cancers. Therefore, targeting ADAR2 with small molecules presents a promising therapeutic strategy for modulating RNA editing and potentially treating associated pathologies. However, there are limited compounds that effectively inhibit ADAR2 reactions. This study therefore employed computational approaches to virtually screen natural compounds from the traditional Chinese medicine (TCM) library. The shortlisted compounds demonstrated a stronger binding affinity to the ADAR2 (<-9.5 kcal/mol) than the known inhibitor, 8-azanebularine (-6.8 kcal/mol). The topmost compounds were also observed to possess high binding affinity towards 5-HT2CR with binding energies ranging from -7.8 to -12.9 kcal/mol. Further subjecting the top ADAR2-ligand complexes to molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations revealed that five potential hit compounds comprising ZINC000014637370, ZINC000085593577, ZINC000042890265, ZINC000039183320, and ZINC000101100339 had favorable binding free energies of -174.911, -137.369, -117.236, -67.023, and -64.913 kJ/mol, respectively, with the human ADAR2 protein. Residues Lys350, Cys377, Glu396, Cys451, Arg455, Ser486, Gln488, and Arg510 were also predicted to be crucial in ligand recognition and binding. This finding will provide valuable insights into the molecular interactions between ADAR2 and small molecules, aiding in the design of future ADAR2 inhibitors with potential therapeutic applications. The potential lead compounds were also profiled to have insignificant toxicities. A structural similarity search via DrugBank revealed that ZINC000039183320 and ZINC000014637370 were similar to naringin and naringenin, which are known adenosine deaminase (ADA) inhibitors. These potential novel ADAR2 inhibitors identified herein may be beneficial in treating several neurological disorders, cancers, viral infections, and inflammatory disorders caused by ADAR2 after experimental validation.


Implicit awareness of ambiguity: a role in the development of obsessive-compulsive disorder.
The cognitive-behavioral model of obsessive-compulsive disorder proposes that obsessional symptoms are the consequence of the manner in which intrusive cognitions are interpreted [e.g., Salkovskis, P. M. (1998). Cognitive-behavioral approach to understanding obsessional thinking. British Journal of Psychiatry, 173(35S), 53-63]. The present study suggests that this may be attributable to maladaptive implicit cognitive processing, a deficit that results in the explicit awareness of ambiguity in idiographic obsessive-compulsive disorder (OCD) stimuli. The present study examines decision-making responses of low and high OCD scorers in a non-clinical undergraduate sample. Via a computer console, participants were shown sentence statements for three levels of ambiguity. They were then presented with a propositional statement for which they had to indicate agreement or disagreement for sentences of varying ambiguity. After this, the participants indicated whether they were completely confident or unconfident as regards their previous agree-disagree decisions. Results indicate that the high compared to the low OCD scoring group had less agreement and subsequent less confidence in decisions made for sentences of varying ambiguity. Response latencies partially fitted the predicted hypotheses. Consequently, an addition to Salkovskis, Forester, and Richards' [1998. Cognitive-behavioral approach to understanding obsessional thinking. The British Journal of Psychiatry, 173(35S), 53-63] model of OCD is suggested: namely that an implicit ambiguity deficit mediates the likelihood of normally occurring intrusions developing into abnormal obsessions. Methodological limitations and future research are considered.


Nanotechnological breakthroughs in the development of topical phytocompounds-based formulations.
Cosmeceuticals are a type of cosmetic products distinguished by the presence of active ingredients that, in addition to their cosmetic effects, also hold therapeutic outcomes. This review is focused on phytocompounds (PHYTOCs)-based cosmeceuticals, an established segment of cosmetic industry, due to the great demand for vitamins and plant-derived products. PHYTOCs beauty and health-related applications are due to their anti-oxidant, anti-bacterial, wound-healing, anti-aging, sun protection, cytoprotective, anticarcinogenic and anti-inflammatory activities. However, PHYTOCs present disadvantages, precisely the poor solubility, instability, reduced skin permeation and low skin retention time, which strongly restrict their topical application. Therefore, and since the cosmetic industry constantly pursues groundbreaking technological products, nanotechnology emerges as an innovative strategy to tackle the PHYTOCs recognized limitations. Nanotechnology manipulates and reduces materials size to 1 and 100 nm, creating structures able to encapsulate active ingredients, such as PHYTOCs, with the purpose of overcoming their limitations and delivering them in a controlled manner to the skin. This review highlights the potential properties of PHYTOCs loaded in several types of nanocarriers (liposomes, niosomes, ethosomes, transferosomes, cubosomes, phytosomes, nanoemulsions, nanocrystals, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, carbon nanotubes, fullerenes, and dendrimers) used to overcome PHYTOCs free form limitations and potentiate their cosmeceutical properties. An approach to the "green" chemical synthesis of metallic nanoparticles taking advantage of PHYTOCS as natural reducing agents is exposed as well. Nanocosmeceuticals toxicity concerns and regulatory aspects are also addressed.


Bacterial translocation and barrier dysfunction enhance colonic tumorigenesis.
In the development of colon cancer, the intestinal dysbiosis and disruption of barrier function are common manifestations. In the current study, we hypothesized that host factors, e.g., vitamin D receptor deficiency or adenomatous polyposis coli (APC) mutation, contribute to the enhanced dysbiosis and disrupted barrier in the pathogenesis of colorectal cancer (CRC). Using the human CRC database, we found enhanced tumor-invading bacteria and reduced colonic VDR expression, which was correlated with a reduction of Claudin-10 mRNA and protein. In the colon of VDRΔIEC mice, deletion of intestinal epithelial VDR led to lower protein of tight junction protein Claudin-10. Lacking VDR and a reduction of Claudin-10 are associated with an increased number of tumors in the mice without myeloid VDR. Intestinal permeability was significantly increased in the mice with myeloid VDR conditional deletion. Further, mice with conditional colonic APC mutation showed reduced mucus layer, enhanced bacteria in tumors, and loss of Claudin-10. Our data from human samples and colon cancer models provided solid evidence- on the host factor regulation of bacterial translocation and dysfunction on barriers in colonic tumorigenesis. Studies on the host factor regulation of microbiome and barriers could be potentially applied to risk assessment, early detection, and prevention of colon cancer.


Compression anastomosis (AKA-2) in colorectal surgery: results in 442 consecutive patients.
The morbidity and mortality associated with colorectal surgery results partly from anastomotic leakage. Animal experiments have shown some advantages of sutureless anastomosis over conventional colorectal anastomosis. Compression anastomosis follows the same biological principles as sutureless anastomosis. The compression anastomosis AKA-2 was evaluated in a prospective consecutive audit of 442 patients between September 1989 and August 1998. Anastomoses were performed in 372 elective and 70 emergency situations. The indication for operation was colorectal cancer (56.3 per cent) and diverticulitis (23.5 per cent). A defunctioning colostomy was performed in 110 patients (24.9 per cent). Fourteen patients died (3.2 per cent). Death was related to anastomotic complications in three patients (0.7 per cent). Twenty-four patients (5.4 per cent) developed intra-abdominal complications. There were 11 symptomatic (2.5 per cent) and six asymptomatic (1.4 per cent) leakages. Anastomoses that were more than 10 cm from the anal verge leaked in seven (2.4 per cent) of 291 cases, while anastomoses between 5 and 10 cm leaked in three (2.6 per cent) of 116 cases and those less than 5 cm from the anal verge leaked in one (3 per cent) of 35 cases. The low incidence of anastomotic complications demonstrates good biological healing of compression anastomoses. The compression anastomosis AKA-2 is safe in both high and low anterior resection and can therefore be recommended for use in colorectal surgery.


Association of kidney function with cancer incidence and its influence on cancer risk of smoking: The Japan Multi-Institutional Collaborative Cohort Study.
The association between kidney function and cancer incidence is inconsistent among previous reports, and data on the Japanese population are lacking. It is unknown whether kidney function modifies the cancer risk of other factors. We aimed to evaluate the association of estimated glomerular filtration rate (eGFR) with cancer incidence and mortality in 55 242 participants (median age, 57 years; 55% women) from the Japan Multi-Institutional Collaborative Cohort Study. We also investigated differences in cancer risk factors between individuals with and without kidney dysfunction. During a median 9.3-year follow-up period, 4278 (7.7%) subjects developed cancer. Moderately low and high eGFRs were associated with higher cancer incidence; compared with eGFR of 60-74 ml/min/1.73 m2 , the adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) for eGFRs of ≥90, 75-89, 45-59, 30-44 and 10-29 ml/min/1.73 m2 were 1.18 (1.07-1.29), 1.09 (1.01-1.17), 0.93 (0.83-1.04), 1.36 (1.00-1.84) and 1.12 (0.55-2.26), respectively. High eGFR was associated with higher cancer mortality, while low eGFR was not; the adjusted subdistribution HRs (95% CIs) for eGFRs of ≥90 and 75-89 ml/min/1.73 m2 were 1.58 (1.29-1.94) and 1.27 (1.08-1.50), respectively. Subgroup analyses of participants with eGFRs ≥60 and <60 ml/min/1.73 m2 revealed elevated cancer risks of smoking and family history of cancer in those with eGFR <60 ml/min/1.73 m2 , with significant interactions. Our findings suggest that the relationship between eGFR and cancer incidence was U-shaped. Only high eGFR was associated with cancer mortality. Kidney dysfunction enhanced cancer risk from smoking.


Inhibiting alternative pathway complement activation by targeting the factor D exosite.
By virtue of its amplifying property, the alternative complement pathway has been implicated in a number of inflammatory diseases and constitutes an attractive therapeutic target. An anti-factor D Fab fragment (AFD) was generated to inhibit the alternative complement pathway in advanced dry age-related macular degeneration. AFD potently prevented factor D (FD)-mediated proteolytic activation of its macromolecular substrate C3bB, but not proteolysis of a small synthetic substrate, indicating that AFD did not block access of the substrate to the catalytic site. The crystal structures of AFD in complex with human and cynomolgus FD (at 2.4 and 2.3 Å, respectively) revealed the molecular details of the inhibitory mechanism. The structures show that the AFD-binding site includes surface loops of FD that form part of the FD exosite. Thus, AFD inhibits FD proteolytic function by interfering with macromolecular substrate access rather than by inhibiting FD catalysis, providing the molecular basis of AFD-mediated inhibition of a rate-limiting step in the alternative complement pathway.


Resection of primary tumor site is associated with prolonged survival in metastatic nonfunctioning pancreatic neuroendocrine tumors.
Nonfunctioning pancreatic neuroendocrine tumors (NFpNET) present with distant metastases in up to 50% of patients. It is unknown whether removal of the primary tumor in patients with NFpNET and metastases is beneficial. We used the Surveillance, Epidemiology, and End Results database to identify patients with NFpNET and distant metastases. The primary outcome measure in this study was overall survival. We identified 882 patients with metastatic NFpNET who had survival data; 303 (34%) patients had operative removal of their primary tumor of which 243 (80%) were grade I or II. Median survival of patients undergoing resection of the primary site was 65 (95% confidence interval 60-86) versus 10 (8-12) months for those without resection (P < .0001). Patients diagnosed after 2003 (n = 625, 71%) were more likely to undergo an operation than those diagnosed earlier (P = .001). Multivariable analysis showed that a lesser tumor grade (P < .0001), younger age (P < .0001), diagnosis during or after 2003 (P = .0003), tumor site in the body/tail (P = .009), and operative resection of the primary tumor site (P < .0001) were associated with prolonged survival of patients with NFpNET and distant metastases. This study suggests that resection of the site of the primary NFpNET is associated with greater survival in patients with distant metastases and could therefore be considered as a additional treatment option in this patient population.


Use of a wrist-mounted device for continuous outpatient physiologic monitoring after transsphenoidal surgery: a pilot study.
Patients who undergo transsphenoidal surgery can experience hormonal, electrolyte, and fluid disturbances in the postoperative period leading to outpatient readmissions for medical management. Our goal was to determine whether use of a wrist-mounted physiologic tracking device is feasible in this setting and whether changes or trends in these parameters after discharge can help predict aberrant physiology in these patients. Wrist-mounted physiologic tracking devices that transmit data via Bluetooth to a mobile device were used to monitor patients. Preoperative baseline data and postoperative data were aggregated daily to compare within-patient and between-patient trends. Of 11 patients enrolled in the study, 1 was readmitted for symptomatic hyponatremia. Device data completeness ranged from 78 to 93% with the exception of oxygen saturation (25% completeness). The patient with hyponatremia had a significantly lower baseline level of activity compared with other patients. Nonreadmitted patient activity variables (steps, calories, and distance) decreased by 48-52% after the operation (P < 0.001). The activity variables for the patient with hyponatremia were statistically unchanged after the operation; however, the patient did experience a significant decrease in heart rate compared with baseline. Deployment of a wrist-based physiologic tracking device is feasible for surgical patients in elective clinical practice. Overall, the device was associated with good patient adherence and high patient satisfaction. Patient activity significantly decreased after surgery. A significant decrease in heart rate was detected in a patient with hyponatremia who required readmission, which reflects the known intravascular volume expansion in this state.


Radiologists' leading position in image-guided therapy.
Image-guided diagnostic and therapeutic procedures are related to, or performed under, some kind of imaging. Such imaging may be direct inspection (as in open surgery) or indirect inspection as in endoscopy or laparoscopy. Common to all these techniques is the transformation of optical and visible information to a monitor or the eye of the operator. Image-guided therapy (IGT) differs by using processed imaging data acquired before, during and after a wide range of different imaging techniques. This means that the planning, performing and monitoring, as well as the control of the therapeutic procedure, are based and dependent on the "virtual reality" provided by imaging investigations. Since most of such imaging involves radiology in the broadest sense, there is a need to characterise IGT in more detail. In this paper, the technical, medico-legal and medico-political issues will be discussed. The focus will be put on state-of-the-art imaging, technical developments, methodological and legal requisites concerning radiation protection and licensing, speciality-specific limitations and crossing specialty borders, definition of technical and quality standards, and finally to the issue of awareness of IGT within the medical and public community. The specialty-specific knowledge should confer radiologists with a significant role in the overall responsibility for the imaging-related processes in various non-radiological specialties. These processes may encompass purchase, servicing, quality management, radiation protection and documentation, also taking responsibility for the definition and compliance with the legal requirements regarding all radiological imaging performed by non-radiologists.


Antiphospholipid antibody binding to bilayer-coated glass microspheres.
Thrombosis, recurrent fetal loss, and thrombocytopenia are clinical manifestations associated with circulating antibodies that recognize cardiolipin (CL)- or phosphatidylserine (PS)-dependent antigens. Enzyme-linked immunosorbent assays (ELISAs) are generally used to determine the presence and specificity of antiphospholipid antibodies (aPLs). However, the presentation of the phospholipid antigen in the ELISA assay is unknown. In this study, we determined the specificity of three mouse monoclonal aPLs for phospholipid bilayer membranes. These monoclonal aPLs had been characterized by ELISA to have different specificities for CL and PS and were designated BA3B5C4 (CL+/PS+), 3SB9b (CL-/PS+), and D11A4 (CL+/PS-). Bilayers composed of 0-100% PS or CL in phosphatidylcholine (PC) were formed on the surface of 1.6 microns diameter glass microspheres to permit analysis by flow cytometry. BA3B5C4 and 3SB9b bound specifically to both PS- and CL-containing bilayers, and binding increased with increasing percentage of anionic phospholipid. The threshold for PS-dependent binding was 20 mol% PS for both BA3B5C4 and 3SB9b. For CL-dependent binding, the threshold was below 25 mol% CL for both of these antibodies. Binding to PS-containing bilayers was tested as a function of ionic strength for BA3B5C4 and 3SB9b. The ionic strength dependence of the binding suggested that the intermolecular attractive forces between anti-PS antibodies and PS-containing bilayers are predominantly multiple weak electrostatic bonds. D11A4 bound only to bilayers composed of 100% PS and 100% PC, and this antibody did not bind to CL-containing bilayers. The binding specificities of these aPLs to bilayer membranes suggest that, in this system, the conformation of the epitope involving CL, and perhaps PS, is different from that expressed in the routine clinical ELISA. Two of the monoclonal antibodies reacted in this model system at the low levels of PS typically externalized in the plasma membranes of activated platelets, apoptopic lymphocytes, and senescent red blood cells: thus, these surfaces are plausible candidates for the site of pathologically relevant antibody interactions.


Moving forward-the 2019 ASCCP Risk-Based Management Consensus Guidelines for Abnormal Cervical Cancer Screening Tests and Cancer Precursors and beyond: implications and suggestions for laboratories.
The 2019 ASCCP Risk Based Management Consensus Guidelines for prevention of cervical cancer promote clinical management recommendations aligned with our increased understanding of HPV biology and cervical carcinogenesis. They employ HPV-based testing as the basis for risk estimation, allow for personalized risk-based management by incorporating knowledge of current results with prior results, and streamline incorporation of new test methods as they are validated. They continue to support the principles of "equal management for equal risk" and "balancing harms and benefits" adopted in the 2012 version of the guidelines. These updated guidelines will be able to adjust for decreasing CIN3+ risks as more patients who received HPV vaccination reach screening age. Pathology organizations were closely involved in the development of these guidelines. Herein the pathologists who served as representatives to the 2019 ASCCP guidelines steering committee and workgroups, summarize the changes that are relevant to laboratories, pathologists, and cytotechnologists. Prior relevant screening and reporting recommendations that have not been widely and/or inconsistently adopted by laboratories are also discussed and considerations for modification of laboratory practices offered.


Myotonia congenita (Thomsen's disease) excluded from the region of the myotonic dystrophy locus on chromosome 19.
Linkage analysis has been carried out in six German families with autosomal dominantly inherited myotonia congenita (Thomsen's disease) using five chromosome 19 markers known to be linked to the gene for myotonic dystrophy (DM). Two of the markers, APOC1 and APOC2, are tightly linked to DM. Close linkage between these markers and myotonia congenita (MC) has been excluded to a distance of 9 cM (z = -2.158). These data support the clinical suggestion that MC and DM are non-allelic disorders.


Combined Effect of Race/Ethnicity and Type of Insurance on Reuse of Urgent Hospital-Based Services in Children Discharged with Asthma.
Asthma is a leading cause of health disparity in children. This study explores the joint effect of race/ethnicity and insurance type on risk for reuse of urgent services within a year of hospitalization. Data were collected from 604 children hospitalized with asthma between 2012 and 2015 and stratified with respect to combination of patients' insurance status (public vs. private) and race/ethnicity (white vs. nonwhite). Highest rates for at least one emergency department (ED) revisit (49.5%, 95% CI 42.5, 56.5) and for average revisits (1.03, 95% CI 0.83, 1.22) were recorded in nonwhite children with public insurance. Adjusted models revealed higher chance for ED reuse in white as well as nonwhite children covered by public insurance. Hospitalization rate was not dependent on the combination of social determinants, but on the number of post-discharge ED revisits. The combined effect of race/ethnicity and health insurance are associated with post-discharge utilization of ED services, but not with hospital readmission.


"METAPAD" (METAbolic PAthways Decoded) - a gaming innovation to ease the complexity of metabolic pathways by promoting self-directed, active, participatory learning in small groups.
In medical education, the conventional didactic lectures make the learning process tedious and cause disinterest among students. To overcome this, an effective experiential learning integrated with game-based approach that intends to make the learning process fun filled, interesting and enhance the active participation of students to understand complex topics in a simple and optimum manner should be adopted. The purpose of this study is to assess the efficiency of a puzzle-based innovation, METAPAD (METAbolic PAthways Decoded) in understanding the complexity of biochemical pathways by enhancing the self-directed learning of students through active engagement in small groups METHODS: In this mixed-method study, 103 first professional year medical students in small groups were enrolled for the METAPAD gaming puzzle-based learning activity. The puzzles were integrated with a relevant clinical case study. Decoding the puzzle after identification of the metabolic pathway involved in the case was conducted in level 1,2 and 3 with increasing complexity of puzzles at every level. Following the puzzle activity, A 21-item questionnaire was administered to evaluate the usefulness of the innovation and students' perceptions towards different learning styles. Also, students' feedback was obtained through personal interviews for qualitative analysis and thematic analysis was performed. One hundred and three first year undergraduate medical students participated in the study. Most of the students perceived the METAPAD gaming puzzle to be an effective and innovative style of learning. There was not any significant association between age, gender and acceptance towards the METAPAD gaming puzzle. The predominant type of learning style among the students was multimodal (49.5%). Also, there was no great influence of the learning styles on the overall perception towards the METAPAD gaming puzzle. However, learners emphasized the need to focus more while solving the puzzles. Students perceive the METAPAD gaming puzzle as an actively engaging teaching-learning method that enhances their creativity, critical thinking and problem-solving abilities. It promotes self-directed learning of complex pathways in biochemistry which helps in remembering and recalling information and improves their learning skills.


Hypocalcemia in experimental pancreatitis occurs independently of changes in serum nonesterified fatty acid levels.
Hypocalcemia and lipid abnormalities commonly occur in acute pancreatitis. Experimentally, increased plasma concentrations of free fatty acids (NEFA) can lower the serum calcium (Ca). We hypothesized that changes in blood-ionized calcium might parallel changes in NEFA concentration in pancreatitis. This hypothesis was tested in a model of severe necrotizing pancreatitis and a model of mild edematous pancreatitis. Adult male Sprague-Dawley rats (300-400 g) were randomized to receive: 100 microL sodium glycodeoxycholic acid (GDOC 34 mmol/L) infused into the pancreatic duct to produce severe necrotizing pancreatitis (Group 1); 100 microL 0.9% NaCl (NS) infused into the pancreatic duct (Group 2); Sham laparotomy (Group 3); A 6 h IV infusion of cerulein (5 mucg/kg/h) to produce mild edematous pancreatitis (Group 4); and a 6 h IV infusion of NS (Group 5). A significant time dependent decrease in blood-ionized Ca concentration, compared to normal rats, was observed in both GDOC-pancreatitis (0.836 +/- .057 vs 1.069 +/- .038 mmol/L p less than 0.001) and cerulein pancreatitis (0.988 +/- .028 vs 1.069 +/- .038 p less than 0.05), which was maximal 24 h after induction of pancreatitis. The degree of hypocalcemia correlated with the severity of pancreatitis (GDOC 0.836 +/- .057 vs cerulein 0.988 +/- .028 p less than .001). Hypocalcemia was not observed in any of the control groups. All experimental and control groups had significantly increased baseline NEFA concentrations compared with normal rats (p less than 0.001); however, no further increase in NEFA concentration occurred in conjunction with the observed time-dependent decline in ionized calcium concentrations. Although the NEFA concentrations observed in these experiments were comparable to those measured in human acute pancreatitis (exclusive of hyperlipemic pancreatitis), the time course of the changes suggests that increases in serum NEFA concentrations in experimental pancreatitis are not the primary factor mediating hypocalcemia.


Production of cyclic AMP from extracellular ATP by intact LM cells.
Intact LM cells, a line of cultured mouse fibroblasts, exhibited an adenylate cyclase (ATP pyrophosphate-lyase (cyclizing), EC 188.8.131.52) activity in the presence of exogenous [alpha-32P]ATP which was 20--30% of that observed with comparable preparations of lysed cells. The extent of NaF and prostaglandin E1 stimulation was comparable in intact cells and lysed cells. 96% of the added ATP and 92% of the cyclic AMP produced by intact cells could be isolated extracellularly in the incubation medium. Cellular integrity under assay conditions was monitored by trypan blue exclusion. These data suggest that LM cells contain an adenylate cyclase activity which is accessible to extracellular ATP.


Multiplexed surface plasmon resonance imaging for protein biomarker analysis.
The reliable detection of ligand and analyte binding is of significant importance for the field of medical diagnostics. Recent advances in proteomics and the rapid expansion in the number of identified protein biomarkers enhance the need for reliable techniques for their identification in complex samples. Surface plasmon resonance imaging (SPRi) provides label-free detection of this binding process in real-time. This chapter details the fabrication of an SPR imaging instrument and its use in analyzing molecular binding interactions with the use of a high-density microfluidic SPRi chip, capable of multiplexed analysis as well as various immobilization chemistries. Controlled recovery of bound biomarkers is demonstrated to enable their identification using mass spectrometry. Finally, activated leukocyte cell adhesion molecule (ALCAM), a protein biomarker associated with a variety of cancers, is identified from human crude cell lysates using the microfluidic surface plasmon resonance imaging (SPRi) instrument.


Higher buccal mitochondrial DNA and mitochondrial common deletion number are associated with markers of neurodegeneration and inflammation in cerebrospinal fluid.
Human immunodeficiency virus (HIV) infection is potentially associated with premature aging, but demonstrating this is difficult due to a lack of reliable biomarkers. The mitochondrial (mt) DNA "common deletion" mutation (mtCDM) is a 4977-bp deletion associated with aging and neurodegenerative diseases. We examined how mtDNA and mtCDM correlate with markers of neurodegeneration and inflammation in people with and without HIV (PWH and PWOH). Data from 149 adults were combined from two projects involving PWH (n = 124) and PWOH (n = 25). We measured buccal mtDNA and mtCDM by digital droplet PCR and compared them to disease and demographic characteristics and soluble biomarkers in cerebrospinal fluid (CSF) and blood measured by immunoassay. Participants had a median age of 52 years, with 53% white and 81% men. Median mtDNA level was 1,332 copies/cell (IQR 1,201-1,493) and median mtCDM level was 0.36 copies × 102/cell (IQR 0.31-0.42); both were higher in PWH. In the best model adjusting for HIV status and demographics, higher mtDNA levels were associated with higher CSF amyloid-β 1-42 and 8-hydroxy-2'-deoxyguanosine and higher mtCDM levels were associated with higher plasma soluble tumor necrosis factor receptor II. The differences in mtDNA markers between PWH and PWOH support potential premature aging in PWH. Our findings suggest mtDNA changes in oral tissues may reflect CNS processes, allowing the use of inexpensive and easily accessible buccal biospecimens as a screening tool for CSF inflammation and neurodegeneration. Confirmatory and mechanistic studies on mt genome alterations by HIV and ART may identify interventions to prevent or treat neurodegenerative complications.


Ward Rounds With or Without an Attending Physician: How Interns Learn Most Successfully.
To explore pediatric interns' perspectives on the educational value of general pediatric ward rounds, in particular their rounding experiences with and without an attending physician. Qualitative study using individual interviews of pediatric interns (2013-2014) rotating on 2 general pediatric inpatient services at different institutions with different rounding team structures. In accordance with grounded theory methodology, data were analyzed using the constant comparative method. Codes were built using an iterative approach and organized into themes. Twenty pediatric interns participated in 25 interviews. Data analysis yielded 4 themes: what is being learned; learning environment on rounds; learning and work; and ways of learning. Senior residents generally taught practical aspects of patient care and attending physicians taught broader concepts with references to the medical literature. Rounds without an attending physician were perceived as less formal and promoted collaborative discussions with senior residents. Interns were more uncomfortable during rounds with an attending physician but appreciated how that facilitated their learning. Although patient care tasks provided opportunities for experiential learning, interns frequently perceived them to impede learning during rounds. Intern learning during ward rounds occurred via self-directed learning, interactive learning, and through caring for patients. Brief, clinically relevant teaching pearls and questioning clinical reasoning in a respectful manner were helpful. Interns learn different content and learn in different ways depending on the presence or absence of an attending physician at rounds. There might be educational value from rounding with teams that include and do not include an attending physician.