Dyke-Davidoff-Masson Syndrome: Main clinical and radiological findings- systematic literature review.
Dyke-Davidoff-Masson syndrome (DDMS), or cerebral hemiatrophy, was first described in 1933. It is characterised by cerebral injury that causes hypoplasia in one of the cerebral hemispheres. The disease has different clinical degrees and two aetiologies: congenital and acquired. Radiological findings depend on the degree of injury and the patient's age at the time. To provide information on the main clinical and radiological characteristics of this disease. A systematic review of the PubMed, MEDLINE, and LILACS databases was conducted using only one keyword. Dyke-Davidoff-Masson syndrome. A total of 223 studies were identified, and the results are presented in tables and graphics. The mean age of the patients was 19.44 (0-83 years), and the majority were male (55.32%). The most common types of epileptic seizures were generalised tonic-clonic seizures (31 cases), focal impaired awareness seizures (20 cases), focal motor seizures (13 cases), focal to bilateral tonic-clonic seizures (nine cases), and focal myoclonic seizures (one case). The main features of the disease were rapid deep tendon reflexes and extensor cutaneous-plantar tendon reflexes (30 cases - 16%), contralateral hemiparesis or hemiplegia (132 cases - 70%), gait alterations (16 cases - 9%), facial paralysis (nine cases - 5%), facial asymmetry (58 cases - 31%), limb asymmetry (20 cases - 11%), delayed developmental milestones (39 cases - 21%), intellectual disability (87 cases - 46%), and language/speech disorders (29 cases - 15%). Left hemisphere atrophy was the most prevalent. DDMS is a rare syndrome, and several questions regarding this disease remain unanswered. This systematic review aims to elucidate the most common clinical and radiological aspects of the disease and emphasises the need for further investigation.


Cytotoxicity of the rare earth metals cerium, lanthanum, and neodymium in vitro: comparisons with cadmium in a pulmonary macrophage primary culture system.
The rare earth metals cerium, lanthanum, and neodymium each were evaluated in an in vitro cytotoxicity assay system using adult, male Sprague-Dawley rat pulmonary alveolar macrophages. Both the soluble chloride form of these metals and their insoluble metal oxides were studied. For comparison purposes, the cytotoxicities of cadmium chloride and cadmium oxide were also quantified in this test system. In general, regardless of the cytotoxicity parameter measured, i.e., cell viability, lysosomal enzyme leakage, or changes in cell surface morphology, cadmium was more toxic to these cells than were the rare earth metals. Of the rare earth metals studied, only lanthanum chloride (LC50 = 52 microM), cerium chloride (LC50 = 29 microM), and neodymium oxide (LC50 = 101 microM) displayed significant cytotoxicity in this test system. Cadmium chloride exhibited an LC50 value of 28 microM, whereas the LC50 value for cadmium oxide was found to be 15 microM. These findings suggest that rare earth metal fumes should be considered as cytotoxic to lung tissue and therefore potentially fibrogenic.


Position-controlled marker formation by helium ion microscope for aligning a TEM tomographic tilt series.
We formed nano-dots using a helium ion microscope (HIM) equipped with a gas injection system. Because of position controllability, the nano-dot markers could be placed efficiently on a specimen using the HIM. The sizes of the dots were controlled by changing the beam radiation time. We tried for the first time to form dots on a rod-shaped specimen to use them as markers for aligning a transmission electron microscope tomographic tilt series before reconstructing 3D images.


Incidence of dye coupling among magnocellular paraventricular nucleus neurons in male rats is testosterone dependent.
Recently published work in the rat has shown that: the incidence of electrical coupling, as measured by dye coupling, is decreased from control levels by 8 days of drinking hypertonic saline; an index of circulating testosterone, seminal vesicle weight, is also decreased by 8 days of saline drinking; and both plasma and urinary vasopressin levels are reduced in castrated males, but can be returned to normal with testosterone replacement. These findings have led to the hypothesis that dye coupling, particularly that involving vasopressinergic cells, may be affected by gonadal steroids. We have investigated the effects of castration and testosterone replacement on the incidence of dye coupling among the neurons of the predominantly vasopressinergic magnocellular lateral paraventricular nucleus in slices of male rat hypothalamus. Incidence of dye coupling in this nucleus of castrated rats was found to be decreased by 67% from sham castrated control levels. Testosterone-filled Silastic capsules (but not empty capsules) implanted subcutaneously at the time of castration abolished the effect of castration on dye coupling. We conclude that testosterone has a powerful influence upon coupling among PVN vasopressinergic neurons and may participate in the control of vasopressin release in intact animals.


Impact of neoadjuvant therapy in downstaging of lower rectal adenocarcinoma and the role of pelvic magnetic resonance in staging.
to evaluate the effect of neoadjuvant therapy on the stage (TNM) of patients with rectal adenocarcinoma and validate the use of MRI as a method of determining locoregional stage. we conducted a retrospective study of 157 patients with lower rectum adenocarcinoma, whom we divided into two groups: Group 1, 81 patients (52%) who had undergone surgical treatment initially, with the purpose to analyze the accuracy of locoregional staging by pelvic magnetic resonance imaging throug the comparison of radiological findings with pathological ones; Group 2, 76 patients (48%), who had been submitted to neoadjuvant therapy (chemotherapy and radiation) prior to definitive surgical treatment, so as to evaluate its effects on the stage by comparing clinical and radiological findings with pathology. In group 1, the accuracy of determining tumor depth (T) and lymph node involvement (N) was 91.4% and 82.7%, respectively. In group 2, neoadjuvant therapy decreased the T stage, N stage and TNM stage in 51.3%, 21% and 48.4% of cases, respectively. neoadjuvant therapy in patients with rectal adenocarcinoma is effective in decreasing disease stage, and pelvic magnetic resonance imaging is effective for locoregional staging. avaliar o efeito da terapia neoadjuvante, nos pacientes portadores de adenocarcinoma de reto, sobre o estádio (TNM) e validar o emprego da ressonância magnética como método de determinação do estádio locorregional. estudo retrospectivo de 157 pacientes com diagnóstico de adenocarcinoma de reto baixo, que foram divididos em dois grupos: Grupo 1, 81 pacientes (52%), submetidos ao tratamento cirúrgico de princípio, cuja finalidade foi analisar a acurácia da determinação do estádio locorregional pela ressonância magnética da pelve, através da comparação entre os achados radiológicos e os achados anatomopatológicos; Grupo 2, 76 pacientes (48%), encaminhados à terapia neoadjuvante (quimioterapia e radioterapia), antes do tratamento cirúrgico definitivo, com o intuito de avaliar seus efeitos sobre o estádio, através da comparação dos achados clínico-radiológicos com os anatomopatológicos. no grupo 1, a acurácia da determinação da profundidade da lesão (T) e do comprometimento linfonodal (N), foram de 91,4% e 82,7%, respectivamente. No grupo 2, a terapia neoadjuvante diminuiu o estádio T, estádio N e o estádio TNM em 51,3%, 21% e 48,4% dos casos, respectivamente. a terapia neoadjuvante nos pacientes com adenocarcinoma de reto é efetiva na diminuição do estádio e a ressonância magnética da pelve é eficaz na determinação do estádio locorregional.


Effects of ciprofibrate on LDL metabolism in man.
This study examined the effects of ciprofibrate therapy (100 mg/day) on plasma lipids, lipoproteins and low density lipoprotein (LDL) kinetic heterogeneity in moderately hypercholesterolaemic subjects. The drug lowered plasma triglyceride and cholesterol by 41% and 17%, respectively. Very low density lipoprotein (VLDL) cholesterol fell by 38%, LDL cholesterol fell by 22%, while the content of the lipid in high density lipoprotein (HDL) increased by 11%. LDL structural and metabolic heterogeneity were assessed before and during therapy in eight subjects. Density gradient centrifugation was used to fractionate LDL into three species. LDL-I, the least dense, was not affected by therapy whereas LDL-II and LDL-III were decreased by 28% (P < 0.01) and 31% (N.S.). Baseline turnover studies revealed that LDL catabolism was subnormal and this was the cause of the raised cholesterol in these subjects. Ciprofibrate therapy increased the apoLDL fractional catabolic rate (FCR) by 19%, principally by inducing a 38% enhancement (P < 0.03) in apoLDL removal by the receptor pathway. ApoLDL kinetics exhibited metabolic heterogeneity both before and during drug therapy. Analysis of plasma decay curves for the LDL tracer and urinary excretion data indicated that the lipoprotein comprised two metabolically distinct species, one with an FCR of about 0.50 pools/day (Pool A), the other with an FCR of about 0.18 pools/day (Pool B). Drug therapy decreased synthesis of and hence reduced the plasma mass of apoLDL in the slow metabolised pool B. This perturbation in synthesis was linked to the change in plasma triglyceride concentration. The resultant reduced proportion of pool B vs. pool A material accounted for the observed promotion of LDL receptor-mediated clearance. Ciprofibrate, therefore, produced beneficial changes in the plasma levels of VLDL, LDL and HDL and in the metabolism of LDL.


Where have our patients gone? The impact of COVID-19 on stroke imaging and intervention at an Australian stroke center.
Australia has fortunately had a low prevalence coronavirus disease 2019 (COVID-19), and our healthcare system has not been overwhelmed. We aimed to determine whether, despite this, a decline in acute stroke presentations, imaging and intervention occurred during the pandemic at a busy stroke centre. The number of 'code stroke' activations, multimodal CTs and endovascular clot retrievals (ECRs) performed during the pandemic period (3/1/2020-5/10/2020) at a large comprehensive stroke centre was compared against the pre-pandemic period (3/1/2019-1/31/2019) using Z-statistics. Year-on-year comparison of the number of patients with large vessel occlusions (LVOs) and ECRs performed per month was also made. The number of 'code stroke' activations and patients undergoing multimodal CT per month decreased significantly (P < 0.0025) following lockdown on 29th March. The number of ECRs also decreased (P = 0.165). The nadir in the weekly number of CTs coincided with lockdown and the peak of new COVID-19 cases. The number of patients with LVOs and ECRs increased by 15% and 14%, respectively, in March but decreased by 55% and 48%, respectively, in April. The significant decrease in volume of 'code stroke' activations and acute stroke imaging following lockdown was accompanied by a concomitant decrease in patients with LVOs and ECRs. The decrease in imaging was therefore not driven purely by patients with mild strokes and stroke mimics, but also included those with severe strokes. Since Australia had a low prevalence of COVID-19, this observed decrease cannot be attributed to hospital congestion and is instead likely driven by patient fear.


Placental villous expression of TNFα and IL-10 and effect of oxygen tension in euploid early pregnancy failure.
The objective was to investigate placental inflammation in chromosomally normal miscarriages in vivo and in vitro. Chorionic villous tissue was collected from missed miscarriages and normal gestation-matched controls and cultured at 6 and 20% O(2) concentrations. Tissue was karyotyped. Flowcytometric bead arrays and real-time PCR were carried out for protein and gene expression studies. The levels of TNFα and IL-10 were significantly (P < 0.005 and P < 0.05) higher, and the levels of TNF-R1 and TNF-R2 were significantly (P < 0.01 and P < 0.05) lower in culture conditioned medium of villous explants of miscarriages compared to control group. Villous tissue homogenates from miscarriages contained significantly (P < 0.005) lower levels of TNF-R1. There was a significant O(2) -dependent increase in the secretion of IL-10 (P < 0.01) and decrease in TNFα/IL-10 ratio (P < 0.005) in the culture medium in both groups. Increased levels of TNFα and decreased levels of receptors in miscarriage villous tissue confirm an excessive placental inflammation in miscarriage patients.


Selective cloning of B cell hybridoma-specific rearranged immunoglobulin gene loci using the polymerase chain reaction.
The use of conventional DNA cloning procedures to obtain productively rearranged Ig genes from B cell hybridomas for structure/function analysis of immunoglobulins is tedious and time-consuming. Here we describe a procedure based on PCR which permits rapid, selective isolation of DNA segments containing individual hybridoma-specific Ig gene rearrangements. The method, an adaptation of the so-called 'inverted PCR' technique (IPCR), can be applied most efficiently to specific genes where a preliminary restriction map is available from Southern blot analysis of the hybridoma genomic DNA. To achieve amplification of a given rearranged Ig locus, small amounts of total hybridoma DNA are digested to completion with a chosen restriction endonuclease and the fragments circularised by DNA ligase. Cleavage of the DNA circles using a second restriction enzyme, chosen specifically to cut 3' to a rearranged V-(D)-J exon, leads to linear DNA segments where the rearranged gene is now flanked by segments of known nucleotide sequence derived originally from the 3' region of the Ig H or L chain gene locus. This permits the selection of oligonucleotides that provide convergent primers for specific amplification of DNA segments containing the required gene rearrangement. Amplified DNA fragments can be cloned and rapidly characterised by sequence analysis.


Comparison of clinical results between heparin surface modified hydrophilic acrylic and hydrophobic acrylic intraocular lens.
To compare the clinical results of heparin surface modified (HSM) hydrophilic acrylic intraocular lens (IOL) with those of hydrophobic acrylic IOL. One hundred patients with cataract were randomized to receive one of acrylic foldable IOLs after phacoemulsification: HSM hydrophilic acrylic IOL (n=50) BioVue3 (BioVue, OII, Ontario, CA, USA) and hydrophobic acrylic IOL (n=50) Sensar (AR40e, AMO, Santa Ana, CA, USA). Bestcorrected visual acuity and refractive error were measured at 1 week, 2 months, 6 months and 12 months after surgery in both IOL groups. To assess posterior capsular opacification (PCO), digital retroillumination image of posterior capsule was analyzed at 12 months using POCOman software. Best-corrected visual acuity (log MAR) was 0.032+/-0.082 in BioVue3 group and 0.034+/-0.077 in Sensar group at 12 months. There was no statistically significant difference between the two groups (p=0.554). Refractive error was -0.247+/-0.821 diopter in BioVue3 group and -0.264+/-0.808 diopter in Sensar group at 12 months. There was no statistically significant difference of refractive error between the two groups (p=0.909). At 12 months, BioVue3 IOL group had a lower percentage area and severity of PCO than Sensar group. However, it was not statistically significant (p=0.349, p=0.288). No Nd:YAG capsulotomy was performed in BioVue3 group while it was required in two eyes (4.0%) in Sensar group. There was no statistically significant difference of postoperative visual acuity, refractive error and degree of PCO between HSM hydrophilic acrylic IOL and hydrophobic acrylic IOL.


The dermatologist as expert witness.
Expert witnesses are practitioners who provide varying opinions for use in a variety of legal forums. There are many technical requirements to be satisfied before a tribunal recognizes such opinions. Regulation, rules, restrictions and potential liability must be considered. Increasingly, state licensing boards, societies and accreditation groups are regulating doctors in the medico-legal arena and sanctions and penalties are being meted out. Legal immunities and privileges may not be always available as protection. The American Academy of Dermatology and AMA have promulgated principles that must be followed to insure accuracy and integrity. The challenge of being an expert is rewarding but must be treated as seriously as clinical practice as the concomitant risks are now the same.


Impact of the evolution of the Fontan operation on early and late mortality: a single-center experience of 405 patients over 3 decades.
Postoperative mortality has decreased in patients undergoing the Fontan operation, and the determinants of such mortality may also have changed significantly. We conducted a study intended to focus on clarifying the determinants of mortality in 405 consecutive patients who had undergone a Fontan operation (62 patients after an atriopulmonary connection, 105 after an intra-atrial rerouting, and 238 patients after an extracardiac rerouting) between 1979 and 2010. The overall 1-year, 5-year, 10-year, and 15-year rates of survival were 87.1%, 84.6%, 83.4%, and 81.6%, respectively, and the type of procedure as well as heterotaxy syndrome, ventricular ejection fraction, and atrioventricular valve repair at the time of the Fontan operation were independent predictors of overall mortality (p < 0.05 for all). Heterotaxy syndrome and atrioventricular (AV) valve repair were independent predictors of early (less than 6 months postoperative) mortality and the type of procedure was an independent predictor of late (6 or more months postoperative) mortality (p < 0.05 to 0.01). In the era of intra-atrial rerouting, heterotaxy syndrome was the only independent predictor of total, early, and late mortality (p < 0.05 for all), whereas a low ejection fraction, AV valve repair, and repair of a total anomalous pulmonary vein connection, rather than heterotaxy syndrome, were independent predictors of total or early mortality or both (p < 0.05 for all) in the era of extracardiac rerouting. Even in the modern era of extracardiac rerouting in the Fontan operation, a low ventricular ejection fraction, AV valve dysfunction, or a total anomalous pulmonary vein connection remain significant risk factors for mortality in patients with a single-ventricle physiology.


Medical dissolution therapy for the treatment of uric acid nephrolithiasis.
Uric acid (UA) nephrolithiasis represents 10% of kidney stones in the US with low urine pH and high saturation of UA as the main risk factors for stone development. Dissolution therapy for UA kidney stones via urinary alkalization has been described as a treatment option. We present our experience in treating UA nephrolithiasis with medical dissolution therapy. A retrospective review was performed of UA stone patients referred for surgery but treated with dissolution therapy between July 2007 and July 2016. Patients were identified using ICD-9 codes. Patients were treated with potassium citrate alone or in combination with allopurinol. Serial imaging and urine pH were obtained at follow-up. Demographics, aggregate stone size, time to stone clearance, urine pH (office dip), and complications were recorded. Twenty-four patients (14 men and 10 women) were identified that started medical dissolution therapy for UA nephrolithiasis after initial referral for surgical management. Three patients (13%) did not tolerate the initiation of dissolution therapy and discontinued this treatment. Of the 21 patients that were maintained on dissolution therapy, 14 patients (67%) showed complete resolution of nephrolithiasis and 7 patients (33%) showed partial reduction. Patients with partial response had a mean reduction in stone burden of 68%. There were 3 recorded complications (UTI, GI upset with therapy, and throat irritation) and 4 recorded stone recurrences among these 21 patients. Based on our study population, medical dissolution therapy is a well-tolerated, non-invasive option for UA nephrolithiasis.


Assessment of marginal gaps and image quality of crowns made of two different restorative materials: An in vitro study using CBCT images.
The present study assessed the quality of images and the presence of marginal gaps on cone-beam computed tomography (CBCT) images of teeth restored with all-ceramic and metal-ceramic crowns and compared the gap sizes observed on CBCT images with those obtained on micro-CT images. Thirty teeth restored with metal-ceramic and all-ceramic crowns, properly adapted and with gaps of 0.30 and 0.50 mm, were submitted to micro-CT and CBCT scans. Linear measurements corresponding to the marginal gap (MG) and the absolute marginal discrepancy (AMD) were obtained. The objective assessment of the quality of CBCT images was performed using the contrast-to-noise ratio (CNR), and the subjective assessment was defined by the diagnoses made by five examiners regarding the presence or absence of gaps. The measurements were always higher for CBCT, with a significant difference regarding AMD. No significant difference in image quality was observed using CNR between the crowns tested. Low accuracy and sensitivity values could be observed for both crowns. Marginal mismatch measures were overestimated in CBCT images. No difference in image quality was observed between the crowns. The correct diagnosis of gaps was considered low, irrespective of crown type and gap size.


Insights into the diagnosis and pathogenesis of the antiphospholipid syndrome.
The Antiphospholipid syndrome (APS), formerly known as Anticardiolipin or Hughes syndrome, is a systemic autoimmune disorder characterized by obstetrical complications and thrombotic events affecting almost every organ-system in patients persistently testing positive for antiphospholipid antibodies (aPL). The contribution of the extra-criteria aPL to the pathogenesis of APS have exceeded the expectations of a simple, direct pathologic 'hit' leading to thrombogenesis or obstetrical complications, and more pathologic pathways are being linked directly or indirectly to aPL. The value of extra-criteria aPL is on the rise, and these antibodies are nowadays evaluated as markers for risk assessment in the diagnostic approach to APS. A diagnosis of APS should be considered in pediatric patients with suggestive clinical and laboratory picture. Management of APS remains mostly based on anticoagulation, while other drugs are being tested for efficacy and side effects. Low-dose aspirin may have a role in the management of thrombotic and obstetric APS. Due to the high variability in disease severity and complication recurrence outcomes, new tools are being developed and validated to assess the damage index and quality of life of APS patients.


Inhibition of herpes simplex-1 virus replication by 25-hydroxycholesterol and 27-hydroxycholesterol.
Oxysterols are known pleiotropic molecules whose antiviral action has been recently discovered. Here reported is the activity of a panel of oxysterols against HSV-1 with the identification of a new mechanism of action. A marked antiviral activity not only of 25HC but also of 27HC against HSV-1 was observed either if the oxysterols were added before or after infection, suggesting an activity unrelated to the viral entry inhibition as proposed by previous literature. Therefore, the relation between the pro-inflammatory activity of oxysterols and the activation of NF-kB and IL-6 induced by HSV-1 in the host cell was investigated. Indeed, cell pre-incubation with oxysterols further potentiated IL-6 production as induced by HSV-1 infection with a consequent boost of the interleukin's total cell secretion. Further, a direct antiviral effect of IL-6 administration to HSV-1 infected cells was demonstrated, disclosing an additional mechanism of antiviral action by both 25HC and 27HC.


A controlled intervention study to improve antibiotic use in a Russian paediatric hospital.
A controlled intervention study was performed in a paediatric hospital in Russia to improve antibiotic use and to see whether improvements persisted. During October-December 2002, clinical and microbiological data, antibiotic use, costs and outcome were recorded at two wards for gastrointestinal infections (GIIs) and two wards for respiratory tract infections (RTIs). Guidelines for diagnosis and treatment of infections were developed and implemented at one ward for GIIs and one ward for RTIs in 2003. The other two wards served as controls. The same data were recorded during the same 3-month periods in 2003 and 2004. At the intervention ward, the percentage of patients with GII who received antibiotics decreased from 94% in 2002 to 41% in 2003, but increased to 73% in 2004. In RTI patients these percentages were 90% in 2002, 53% in 2003 and 83% in 2004. The proportions of patients who received antibiotics in 2004 were still lower than in 2002: risk difference (RD)=0.217 (P</=0.001) in GIIs and RD=0.073 (P=0.013) in RTIs. From 2002 to 2004 there was a decrease in cephalosporin use (P=0.021) and an increase in penicillin use (P=0.032) in pneumonia. There was no difference in mortality, duration of fever or duration of hospital stay between the intervention and control wards. Antibiotic use could be halved without compromising the quality of patient care, but 1 year after the intervention the use of antibiotics approached pre-intervention levels. Strategies to sustain the effect of interventions are needed.


Fast separation of large biomolecules using short monolithic columns.
Chromatographic monoliths have already penetrated in many different areas of separation sciences. This is due to their properties, especially advantageous for fast separation and purification of large biologic macromolecules, even at low pressure drop. Probably the most outstanding features are flow unaffected binding capacity and resolution, later resulting in very short analysis times. Furthermore, since large biomolecules interact with the matrix via many binding sites, efficient separation can be achieved with the monolithic columns of a very short length, further reducing pressure drop over matrix. In this review brief introduction to the monoliths is given with the emphasize on the theory of separation of large molecules, particularly on a linear gradient elution and estimation of peak broadening. As an outcome of this analysis the most efficient separation is expected when short monolithic column with accordingly adjusted gradient is implemented, especially for macromolecules interacting with the monolith functionalities via over 10 binding sites. This is experimentally demonstrated by several recent examples of short monolithic column applications for analysis of antibodies, viruses, virus like particles (VLPs) and polynucleotides like plasmid DNA (pDNA) and RNA, indicating their potential for process monitoring, control and optimization but also for product final formulation and quality control.


A statistical mechanical model of the lipid bilayer above its phase transition.
A statistical mechanical model of a bilayer of dipalmitoyl-3-sn-phosphatidylcholine molecules above their phase transition is presented. A molecular field approximation developed in previous work by Marcelja is extended by setting the molecular field at each depth in the bilayer in proportion to the average chain order at that depth. The free energy of the hydrocarbon/water interface and that due to the interaction of the polar headgroups is included in the evaluation of the statistical weights of the chain conformations. The model gives good agreement with several independent experimental results. It resolves the dilemma posed by the experimental evidence that there is (i) a considerable variation in order parameter along the lipid chain, but (ii) no collective tilt in the more ordered region of the chain. The model gives an explanation of how the lipid chains pack under these two constraints. The order parameter profile down the chain does not correspond to the profile across the bilayer.


Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.
Major depressive disorder (MDD) is a chronic, generally episodic and debilitating disease that affects an estimated 300 million people worldwide, but its pathogenesis is poorly understood. The heritability estimate of MDD is 30-40%, suggesting that genetics alone do not account for most of the risk of major depression. Another factor known to associate with MDD involves environmental stressors such as childhood adversity and recent life stress. Recent studies have emerged to show that the biological impact of environmental factors in MDD and other stress-related disorders is mediated by a variety of epigenetic modifications. These epigenetic modification alterations contribute to abnormal neuroendocrine responses, neuroplasticity impairment, neurotransmission and neuroglia dysfunction, which are involved in the pathophysiology of MDD. Furthermore, epigenetic marks have been associated with the diagnosis and treatment of MDD. The evaluation of epigenetic modifications holds promise for further understanding of the heterogeneous etiology and complex phenotypes of MDD, and may identify new therapeutic targets. Here, we review preclinical and clinical epigenetic findings, including DNA methylation, histone modification, noncoding RNA, RNA modification, and chromatin remodeling factor in MDD. In addition, we elaborate on the contribution of these epigenetic mechanisms to the pathological trait variability in depression and discuss how such mechanisms can be exploited for therapeutic purposes.


FSPBO-DQN: SeGAN based segmentation and Fractional Student Psychology Optimization enabled Deep Q Network for skin cancer detection in IoT applications.
Skin cancer is one of the dangerous types of cancer and the rate of death is increasing due to the lack of knowledge in prevention and the symptoms. It is a common cancer type around the world and it occurs when the skin cells are damaged. Hence, the detection of skin cancer near the beginning is important to prevent the spread of cancer and to increase the survival rate. Recently, image processing and machine learning techniques gained more interest in medical applications. However, early analysis of skin cancer images is very challenging due to factors, like variations in the color illumination, light reflections from the skin surface, and different sizes and shapes of lesions. To detect skin cancer at an early stage and to increase the survival rate, an effective skin cancer detection method is introduced in this study using the proposed Fractional Student Psychology Based Optimization-based Deep Q Network (FSPBO-based DQN) in the wireless network scenario. At first, the nodes simulated in the network area are allowed to capture the healthcare information to make the detection strategy using the proposed method. Then, the routing is performed by the proposed Fractional Student Psychology Based Optimization (FSPBO) algorithm by considering the fitness parameters, like distance, energy, trust, and delay. After the images (healthcare information) are reached the Base Station (BS), the pre-processing, segmentation, and cancer detection processes are carried out to detect the skin lesions. Initially, the image is fed to pre-processing phase, where a Type II Fuzzy System and cuckoo search optimization algorithm (T2FCS) filter is employed to remove the noise of images. Then, the pre-processed images are fed to the segmentation phase, where speech enhancement Generative Adversarial Network (SeGAN) is used to generate the segmented results. Afterward, the Deep Q Network (DQN) detects the skin cancer based on the segmented results, and the training of DQN is made using the proposed FSPBO algorithm, which is designed by integrating the Student Psychology Based Optimization (SPBO) and Fractional Calculus (FC). The proposed method is more robust and reduces computation time and complexity. Moreover, the proposed method achieved higher performance by considering the measures, namely accuracy, sensitivity, and specificity with the values of 92.364%, 93.20%, and 92.63%.


Association of cadherin 23 with polygenic inheritance and genetic modification of sensorineural hearing loss.
Age-related hearing loss (AHL) in common inbred mouse strains is a genetically complex quantitative trait. We found a synonymous single-nucleotide polymorphism in exon 7 of Cdh23 that shows significant association with AHL and the deafness modifier mdfw (modifer of deafwaddler). The hypomorphic Cdh23(753A) allele causes in-frame skipping of exon 7. Altered adhesion or reduced stability of CDH23 may confer susceptibility to AHL. Homozygosity at Cdh23(753A) or in combination with heterogeneous secondary factors is a primary determinant of AHL in mice.


Increased presence of common systemic lupus erythematosus (SLE) anti-DNA idiotypes (16/6 Id, 32/15 Id) is induced by procainamide.
Sixty-seven patients on treatment with procainamide were examined for the presence of two common idiotypes of anti-DNA antibodies (16/6 Id and 32/15 Id). These idiotypes have been shown previously to have clinical relevance in patients with systemic lupus erythematosus (SLE). An enzyme-linked immunosorbent assay (ELISA) with rabbit anti-Id antibodies revealed increased concentrations of the 16/6 Id and 32/15 Id in 25 (37%) and 16 (24%) patients, respectively. Five of eight patients with drug-induced lupus had elevated titers of both idiotypes. A high correlation (R = 0.56, P less than 0.001 for 16/6 Id) was found between Id levels and anti-single-stranded DNA (ssDNA) antibody titers and between 16/6 Id titers and antihistone antibodies (IgG, R = 0.43; IgM, R = 0.25). It seems that procainamide, a component known to be associated with drug-induced lupus, may induce an increased production of common anti-DNA idiotypes in apparently normal subjects.


Multiple biomarkers for the prediction of ischemic stroke: the PRIME study.
To simultaneously evaluate 14 biomarkers from distinct biological pathways for risk prediction of ischemic stroke, including biomarkers of hemostasis, inflammation, and endothelial activation as well as chemokines and adipocytokines. The Prospective Epidemiological Study on Myocardial Infarction (PRIME) is a cohort of 9771 healthy men 50 to 59 years of age who were followed up over 10 years. In a nested case-control study, 95 ischemic stroke cases were matched with 190 controls. After multivariable adjustment for traditional risk factors, fibrinogen (odds ratio [OR], 1.53; 95% confidence interval [CI], 1.03-2.28), E-selectin (OR, 1.76; 95% CI, 1.06-2.93), interferon-γ-inducible-protein-10 (OR, 1.72; 95% CI, 1.06-2.78), resistin (OR, 2.86; 95% CI, 1.30-6.27), and total adiponectin (OR, 1.82; 95% CI, 1.04-3.19) were significantly associated with ischemic stroke. Adding E-selectin and resistin to a traditional risk factor model significantly increased the area under the receiver-operating characteristic curve from 0.679 (95% CI, 0.612-0.745) to 0.785 and 0.788, respectively, and yielded a categorical net reclassification improvement of 29.9% (P=0.001) and 28.4% (P=0.002), respectively. Their simultaneous inclusion in the traditional risk factor model increased the area under the receiver-operating characteristic curve to 0.824 (95% CI, 0.770-0.877) and resulted in an net reclassification improvement of 41.4% (P<0.001). Results were confirmed when using continuous net reclassification improvement. Among multiple biomarkers from distinct biological pathways, E-selectin and resistin provided incremental and additive value to traditional risk factors in predicting ischemic stroke.


Review article: a pharmacoeconomic analysis of thrombocytopenia in chronic liver disease.
Patients with chronic liver disease commonly experience thrombocytopenia resulting from disease or treatment. Such patients often require multiple platelet transfusions, and consequently can experience associated complications including systemic infection, iron overload, and platelet refractoriness. To discuss the limited data available on the impact of thrombocytopenia on the medical procedures and their associated costs. Thrombocytopenia and its treatment can have a negative impact on outcomes and cost of therapy; costs associated with platelet transfusion can constitute a significant portion of the hospital budget. Inability to initiate or complete antiviral therapy for chronic hepatitis C infection due to low platelet counts can lead to dose reduction or discontinuation, lower efficacy, increased risks, and increased overall costs. Routine medical procedures can be complicated, prolonged, or precluded as a result of severe thrombocytopenia. Novel therapies can safely and effectively prevent or treat thrombocytopenia in this patient population with chronic liver disease resulting in improved quality of care and significant cost savings in addition to improving treatment outcomes and quality of life (QOL) measures.


Reusable sensors in intrapartum foetal reflection pulse oximetry.
To evaluate the accuracy of intrapartum foetal pulse oximetry (SO(2POX)) using reusable sensors and the effect of a sensor performance test on data quality. Furthermore, to assess the sensor-related costs by using reusable sensors and sensor performance test. 36 reusable sensors were used for SO(2POX) during labour of 289 term foetuses. A sensor performance test device assessing the emitter and receiver capability and the firmness of attachment of the sensors had been developed and used in the last 134 measurements before each resterilisation. Oxygen saturation (SaO(2)) at birth was measured spectrophotometrically after cord blood sampling. The accuracy of SO(2POX) was evaluated by analysing its relationship to SaO(2). The valid SO(2POX) data, as confirmed by subsequent sensor test in the second group, was considered comparable with those with single sensor use. Sensor-related average cost (sensors, test device and sterilisation) of such measurements was compared with that of single sensor use. Eight sensors failed performance test despite valid pulse oximetry signal output during their last measurements. There were significant overall linear correlations between SO(2POX) and SaO(2) (r=0.45, P<0.0001). Separate analyses of regression in the group without sensor performance testing showed an r(2) of 0.41, whereas in the group with subsequent sensor performance testing, the r(2) was 0.52 (P<0.05). By reusing the sensors, the sensor-related cost per valid measurement was $18.9 and 71% lower compared to single use of sensors ($65). Pulse oximetry may reflect fetal oxygen saturation. Data quality may be compromised by insufficient sensor performance, even though the reflection signal quality is acceptable. If sensor performance is tested before each measurement, reusable sensors may reduce the costs of fetal pulse oximetry.


Treatment of relapsing Clostridium difficile diarrhoea by administration of a non-toxigenic strain.
Two patients with relapsing Clostridium difficile diarrhoea following metronidazole and vancomycin therapy were colonised with a non-toxigenic avirulent Clostridium difficile strain given orally in three doses. Both patients appeared to respond without side-effects. Oral bacteriotherapy with a defined nontoxigenic strain of Clostridium difficile would appear to represent an acceptable, alternative and novel way to treat hospitalised patients who relapse with Clostridium difficile diarrhoea after specific antibiotic therapy.


Clinical and functional comparison of bicondylar sledge prostheses retaining all ligaments and constrained total knee replacement.
Comparison of different total knee replacements regarding clinical and functional differences with respect to gait and electromyographic analyses. Retrospective, comparative, clinical and functional study. Three groups (control group of 11 healthy subjects, 15 patients with bicondylar sledge prostheses retaining all ligaments (cemented unicondylar prostheses in both the medial and lateral compartment), 15 patients with constrained total knee replacement sacrificing all cruciate and collateral ligaments (cemented total knee prosthesis with intramedullary stems and a large intercondylar tibial post) were compared by clinical evaluation using a number of clinical evaluation scores, a pain scale, surface electromyographic examinations of the lower limb, and gait analysis. Clinical scores revealed significantly worse results for patients with constrained prostheses. Both patient groups had significantly lower clinical scores compared to the control group. Gait analysis and electromyographic parameters revealed no significant differences between both patient groups. Compared to the control group, patients revealed significantly impaired parameters. Electromyography also demonstrated significant differences between patients and controls: mean electromyographic activities were reduced in vastus medialis and lateralis, semitendinosus, tibialis anterior and gastrocnemius. Peak activities were reduced in all muscles but rectus femoris. Clinical scores demonstrated significantly better results in bicondylar sledge than in constrained prostheses. Nevertheless, gait and electromyographic analyses did not reveal significant differences. Retaining of ligaments in bicondylar sledge prostheses apparently improved the activities of daily living but is not reflected in gait and electromyographic parameters.


RhoC induces differential expression of genes involved in invasion and metastasis in MCF10A breast cells.
Inflammatory breast cancer (IBC) is the most deadly form of breast cancer in humans presumably due to its ability to metastasize from its inception. In our laboratory, overexpression of RhoC GTPase was observed to be specific for IBC tumors, but not for stage-matched, non-IBC tumors. RhoC is known to contribute to an IBC-like phenotype in HPV-E6E7 immortalized breast cells. To further study the effect of RhoC overexpression on IBC metastasis, we generated stable transfectants of spontaneous immortalized mammary epithelial cells (MCF10A) overexpressing wild-type RhoC or a constitutively active RhoC mutant (G14V). Both the RhoC wild type and the G14V transfectants were highly invasive and proliferated more rapidly compared to vector-only control clones. Overexpression of RhoC led to an increase in actin stress fiber and focal adhesion contact formation. Comparative microarray analysis of these clones further revealed that RhoC overexpression upregulated 108 genes whereas seven genes were down-regulated. We have further verified by quantitative RT-PCR that genes involved in cell proliferation, invasion/adhesion, and angiogenesis were modulated by RhoC. This work suggests strong candidates for the downstream oncogenic functions of RhoC.


Potentiation of histamine-induced itch and flare responses in human skin by the enkephalin analogue FK-33-824, beta-endorphin and morphine.
The effect of various opioid or putative neurotransmitter peptides on histamine-induced itch and flare responses was studied in humans after intradermal injection. Significant enhancement of the histamine responses was induced by the stable methionine-enkephalin analogue FK 33-824, beta-endorphin and morphine. The putative neurotransmitters substance P and vasoactive intestinal polypeptide (VIP)--which moreover are potent histamine liberators--had no enhancing effect. The potentiation induced by FK 33-824 was induced neither by local pretreatment with Compound 48/80 to deplete the local stores of mast-cell-bound histamine, nor by oral pretreatment with indomethacin to inhibit prostaglandin formation in the skin. Thus, the enhancement did not seem to be due to histamine release or to prostaglandin formation and the mechanism of the effect remains to be shown. The specific morphine antagonist naloxone did not inhibit the potentiation by FK 33-824, which might indicate that ordinary opiate receptors were not involved. The results support the idea that pain and itch are qualitatively separate processes and suggest possible mechanisms of morphine-induced pruritus. The findings are of particular interest in view of recent reports on the presence of methionine-enkephalin in Merkel cells.


Chemical interference competition by Monomorium minimum (Hymenoptera: Formicidae).
Workers of Monomorium minimum forage above-ground for dead arthropods. Small particles (<1 mg) are retrieved individually, but larger particles stimulate recruitment and are dissected by groups of workers. The recruitment pheromone originates in the Dufour's gland and the number of ants responding to a trail varies with pheromone concentration. When ants of other species are encountered at food resources, workers of M. minimum gaster-flag and extrude an irritating poison gland secretion from the sting. This chemical interference delays invasion by competitors and prolongs the period during which the colony can dissect and retrieve pieces of the food resource. M. minimum recruits at higher temperatures than sympatric ant species. The probability of interference at food baits rises from 5% to 100% when they become too large for a single worker to carry. The probability of food resource loss is higher for baits of intermediate weight (x=18.1 mg) than for those of low weight (x=0.1 mg) or high weight (x=403.1 mg).


Integrating microbial metagenomics and physicochemical parameters and a new perspective on starter culture for fine cocoa fermentation.
Cocoa beans used for chocolate production are fermented seeds of Theobroma cacao obtained by a natural fermentation process. The flavors and chemical compounds produced during the fermentation process make this step one of the most important in fine chocolate production. Herein, an integrative analysis of the variation of microbial community structure, using a shotgun metagenomics approach and associated physicochemical features, was performed during fermentation of fine cocoa beans. Samples of Forastero variety (FOR) and a mixture of two hybrids (PS1319 and CCN51) (MIX) from Bahia, Brazil, were analyzed at 7 different times. In the beginning (0 h), the structures of microbial communities were very different between FOR and MIX, reflecting the original plant-associated microbiomes. The highest change in microbial community structures occurred at the first 24 h of fermentation, with a marked increase in temperature and acetic acid concentration, and pH decrease. At 24-48 h both microbial community structures were quite homogenous regarding temperature, acetic acid, succinic acid, pH, soluble proteins and total phenols. During 72-96 h, the community structure resembles an acidic and warmer environment, prevailing few acetic acid bacteria. Taxonomic richness and abundance at 72-144 h exhibited significant correlation with temperature, reducing sugars, succinic, and acetic acids. Finally, we recommend that dominant microbial species of spontaneous fine cocoa fermentations should be considered as inoculum in accordance with the farm/region and GMP to maintain a differential organoleptic feature for production of fine chocolate. In our study, a starter inoculum composed of Acetobacter pausterianus and Hanseniaspora opuntiae strains is indicated.


Comparison of the effect of various irrigants on apically extruded debris after root canal preparation.
Several factors can influence the amount of apically extruded debris. The aim was to quantitatively compare the amount of debris extruded apically from root canals when 3 different irrigants were used during canal preparation with rotary instruments. Ninety-one extracted single-rooted human mandibular premolar teeth with straight root canals were used. The teeth were randomly divided into 1 control group (group 1, n = 4) and 3 experimental groups of 29 teeth each. Hero 642 instruments were used for root canal preparation in all teeth, and 3 different irrigants were used (group 2, 2% chlorhexidine; group 3, 5.25% sodium hypochlorite; group 4, 2.5% sodium hypochlorite). Seven Eppendorf tubes served as a second control group. Debris extruded from the apical foramen during root canal preparation was collected into preweighed Eppendorf tubes. The weight of the dry extruded debris was established by subtracting the preinstrumentation and postinstrumentation weight of the Eppendorf tubes for each group. The data obtained were analyzed by using one-way analysis of variance and Tukey honestly significant difference. Group 3 (sodium hypochlorite 5.25%) had the highest amount of extruded debris, which was significantly different from the other groups (P < .05). The type of irrigant used can affect the amount of apically extruded debris. The 5.25% solution of sodium hypochlorite had the greatest amount of debris.


Positive selection on HIV accessory proteins and the analysis of molecular adaptation after interspecies transmission.
Studies examining positive selection on accessory proteins of HIV are rare, although these proteins play an important role in pathogenesis in vivo. Moreover, despite the biological relevance of analyses of molecular adaptation after viral transmission between species, the issue is still poorly studied. Here we present evidence that accessory proteins are subjected to positive selective forces exclusively in HIV. This scenario suggests that accessory protein genes are under adaptive evolution in HIV clades, while in SIVcpz such a phenomenon could not be detected. As a result, we show that comparative studies are critical to carry out functional investigation of positively selected protein sites, as they might help to achieve a better comprehension of the biology of HIV pathogenesis.


A study of variable decelerations in association with other heart rate patterns during monitored labor.
A review of 1,011 consecutive intrapartum heart rate tracings yielded 37.3% with some degree of variable deceleration pattern. No differences in Apgar score distribution were observed in the presence of uncomplicated variable deceleration pattern when compared to those tracings marked normal. However, the presence of variable decelerations in association with other heart rate patterns resulted in lower mean Apgar scores at 1 and 5 minutes, which were significantly different from those of the fetal heart rate (FHR) normal group. Mean Apgar scores at 1 and 5 minutes were significantly different from normal when variable decelerations were noted in the presence of tachycardia and loss of variability. Mean Apgar scores were lower when bradycardia (prolonged episodes of heart rate less than 120 bpm) was present in the record when compared to normal, but the presence of variable decelerations with bradycardia did not result in different mean scores. The presence of baseline changes with loss of variability and variable decelerations appeared to result in the lowest mean scores. When bradycardia or tachycardia occurred in exclusive association with variable decelerations, the percentage of depressed newborn infants was relatively high.


Exon 1 donor splice site mutations in the porphobilinogen deaminase gene in the non-erythroid variant form of acute intermittent porphyria.
Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial defect of the heme biosynthesis enzyme, porphobilinogen deaminase (PBGD). PBGD is encoded by two distinct mRNA species expressed in a tissue-specific manner from a single gene. One transcript is expressed in erythroid tissues, while the housekeeping transcript is expressed in all tissues. In classical AIP (95% of cases) the housekeeping and the erythroid-specific enzymes both have half-normal activity in erythroid and non-erythroid tissues, whereas in the variant non-erythroid form of the disease the enzymatic defect is present only in non-erythroid cells. A large allelic heterogeneity of mutations (n>135) has been demonstrated in classical AIP, but to date only three different mutations have been characterized in the non-erythroid variant form of AIP. We describe the molecular abnormalities responsible for the non-erythroid variant form of AIP in two French and two German unrelated AIP patients with normal PBGD activity in the erythrocytes. Three different splicing defects located in the intron 1 donor splice site were identified: a 33+1 g-->a mutation, previously described in a Dutch family, was found in two patients; two novel mutations (33+2 t-->a, 33+5 c-->g) affected the two remaining patients. All the mutations resulted in the activation of a cryptic splice site 67 bp downstream in intron 1, leading to a frameshift and a premature stop codon in exon 4. Mutations in the exon 1 donor splice site are involved in eight of the nine non-erythroid variant AIP families reported in the literature. These data show that most mutations causing the non-erythroid variant AIP are exon 1 splice defects, in contrast with classical AIP, where missense mutations are chiefly involved. Moreover, the allelic heterogeneity of PBGD gene defects causing the non-erythroid variant AIP is demonstrated, with five different mutations identified. These mutations could be easily detected by a single denaturing gradient gel electrophoresis which also allows the presymptomatic detection of gene carriers in the affected families.


Intracerebral hemorrhage from a metastatic brain tumor. Importance of differential diagnosis preceding stereotaxic hematoma aspiration.
Three cases of sudden intracerebral hemorrhage, which were diagnosed as hemorrhage from metastatic brain tumors following stereotaxic aspiration of a hematoma, are reported. Two cases had subcortical hemorrhage and one had cerebellar hemorrhage. Neither contrast-enhanced computed tomography scans nor angiograms revealed any findings other than those indicating the hematoma in all three cases. However, retrospective study of the anamnesis showed very mild symptoms due to metastasis to the brain or spinal cord in one case each. In cases of intracerebral hematoma located at atypical sites, extreme care is required for the differential diagnosis.


Clinical course of patients with insufficient viral suppression during entecavir therapy in genotype C chronic hepatitis B.
The clinical course of patients with insufficient virologic suppression diagnosed with chronic hepatitis B undergoing entecavir therapy is unclear. We retrospectively investigated the long-term clinical outcomes of entecavir treatment for more than 12 months in 355 nucleos(t)ide-naïve chronic hepatitis B patients, particularly those with primary non-response or partial virologic response. The median duration of entecavir therapy was 40 months (range, 12-64 months). Virologic response was achieved in 315 patients (88.7%). One hundred forty-four (96.6%) of 149 HBeAg-negative patients achieved virologic response. Among 206 HBeAg-positive patients, 52 (25.2%) achieved HBeAg seroconversion. Virologic breakthrough was observed in 7 patients (2.0%). Of these 7 patients, 5 (1.4%) had genotypic resistance to entecavir. Primary non-response and partial virologic response were evident in 6 (1.7%) and 63 (17.7%) patients, respectively. During continuous prolonged entecavir therapy, virologic response of patients with primary non-response and partial virologic response was achieved in 6 (100%) and 28 (44.4%) patients, respectively. The vast majority of chronic hepatitis B patients in this study achieved virologic response through prolonged entecavir therapy, with only 1.4% chance of viral resistance. Furthermore, all patients with primary non-response were able to achieve virologic response without adjustment of antiviral therapy.


Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations.
Oncogenic mutations in PIK3CA, which encodes the phosphoinositide-3-kinase (PI3K) catalytic subunit p110α, occur in ∼25% of human breast cancers. In this study, we report the development of a knock-in mouse model for breast cancer where the endogenous Pik3ca allele was modified to allow tissue-specific conditional expression of a frequently found Pik3ca(H1047R) (Pik3ca(e20H1047R)) mutant allele. We found that activation of the latent Pik3ca(H1047R) allele resulted in breast tumors with multiple histological types. Whole-exome analysis of the Pik3ca(H1047R)-driven mammary tumors identified multiple mutations, including Trp53 mutations that appeared spontaneously during the development of adenocarinoma and spindle cell tumors. Further, we used this model to test the efficacy of GDC-0941, a PI3K inhibitor, in clinical development, and showed that the tumors respond to PI3K inhibition.


Genome-wide cfDNA Mutation Profiles Allow for Noninvasive Cancer Detection.
Low-coverage sequencing of genome-wide somatic mutations in cfDNA can noninvasively detect cancer.


Box-Behnken supported validation of stability-indicating high performance thin-layer chromatography (HPTLC) method: An application in degradation kinetic profiling of ropinirole.
Stability-indicating high-performance thin-layer chromatographic (HPTLC) method for the analysis of ropinirole HCl was developed and validated as per the ICH guidelines. The method employed the mobile phase and toluene-ethyl acetate-6 M ammonia solution (5:6:0.5, v/v/v) was optimized with the help of a design expert. Densitometric analysis of ropinirole HCl was carried out in the absorbance mode at 250 and 254 nm. Compact spots for ropinirole HCl were found at R f value of 0.58 ± 0.02. The linear regression analysis data for the calibration plots showed R (2) = 0.9989 ± 0.0053 with a concentration range of 100-3000 ng spot(-1). The method was validated for precision, accuracy, ruggedness, robustness, specificity, recovery, limit of detection (LOD) and limit of quantitation (LOQ). The LOD and LOQ were 12.95 and 39.25 ng spot(-1) respectively. Drug was subjected to acidic, alkaline, oxidative, dry heat, wet heat and photo degradation stress. All the peaks of degradation products were well resolved from the standard drug peak with significant difference of R f. The acidic and alkaline stress degradation kinetics of ropinirole, were found to be in first order, showing high stability (t 1/2, 146.37 h(-1); t 0.9, 39.11 h(-1)) in the acidic medium and low stability (t 1/2, 97.67 h(-1); t 0.9, 14.87 h(-1)) in the alkaline environment.


Recovery Migration to the City of New Orleans after Hurricane Katrina: A Migration Systems Approach.
Hurricane Katrina's effect on the population of the City of New Orleans provides a model of how severe weather events, which are likely to increase in frequency and strength as the climate warms, might affect other large coastal cities. Our research focuses on changes in the migration system - defined as the system of ties between Orleans Parish and all other U.S. counties - between the pre-disaster (1999-2004) and recovery (2007-2009) periods. Using Internal Revenue Service county-to-county migration flow data, we find that in the recovery period Orleans Parish increased the number of migration ties with and received larger migration flows from nearby counties in the Gulf of Mexico coastal region, thereby spatially concentrating and intensifying the in-migration dimension of this predominantly urban system, while the out-migration dimension contracted and had smaller flows. We interpret these changes as the migration system relying on its strongest ties to nearby and less damaged counties to generate recovery in-migration.


Neural plasticity of basal forebrain cholinergic neurons: effects of gangliosides.
Nucleus basalis magnocellularis (NBM) cholinergic neurons, furnishing the major portion of the extrinsic cholinergic innervation of the rat cortex, undergo specific retrograde changes in cell somata and choline acetyltransferase (ChAT) activity after cortical lesions. These are prevented in young and mature animals, but not in aged rats, by the chronic administration of exogenous ganglioside GM1 after lesioning. However, a delay of 10 days (in young animals) in the commencement of treatment averted the responses to GM1 in lesioned animals. It is suggested that the effects of exogenous gangliosides on retrograde biochemical and morphological alteration of cholinergic neurons may vary with circumstances permissive of plastic changes of central nervous system neurons at the time of administration.


Azithromycin Use and Increased Cancer Risk among Patients with Bronchiolitis Obliterans after Hematopoietic Cell Transplantation.
Azithromycin exposure during the early phase of allogeneic hematopoietic cell transplantation (HCT) has been associated with an increased incidence of hematologic relapse. We assessed the impact of azithromycin exposure on the occurrence of relapse or new subsequent neoplasm (SN) in patients with bronchiolitis obliterans syndrome (BOS) after HCT who are commonly treated with azithromycin alone or in combination with other agents. In a retrospective study of patients with BOS from 2 large allograft centers, the effect of azithromycin exposure on the risk of relapse or SN was estimated from a Cox model with a time-dependent variable for treatment initiation. The Cox model was adjusted on time-fixed covariates measured at cohort entry, selected for their potential prognostic value. Similar models were used to assess the exposure effect on the cause-specific hazard of relapse, SN, and death free of those events. Sensitivity analyses were performed using propensity score matching. Among 316 patients, 227 (71.8%) were exposed to azithromycin after BOS diagnosis. The corresponding adjusted hazard ratio (HR) in patients exposed to azithromycin versus unexposed was 1.51 (95% confidence interval [CI], 0.90 to 2.55) for relapse or SN, 0.82 (95% CI, 0.37 to 1.83) for relapse, and 2.00 (95% CI, 1.01 to 3.99) for SN. Patients exposed to azithromycin had a significantly lower cause-specific hazard of death free of neoplasm and relapse (adjusted HR, 0.54; 95% CI, 0.34 to 0.89). In conclusion, exposure to azithromycin after BOS after HCT was associated with an increased risk of SN but not relapse.


Fundraising in Education: Road Map to Involving Medical Educators in Fundraising.
Traditional funding models must change as governments decrease funding and often freeze tuition at a domestic level. As a result, universities face an increasing need to diversify their business models, including revenue streams. Therefore, interest in raising significant funds from other sources is stronger than ever, leading to the need for a fundraising approach that is more sophisticated. Medical educators and health professionals are some of the most trusted members of society, and with this paper, the authors aim to raise awareness of the critical role they play in helping universities with their global impact and fundraising efforts.


A dynamical-systems model for Parkinson's disease.
The juxtaposition of hypokinetic and hyperkinetic symptoms in Parkinson's disease (PD) presents a challenge in modeling the basal ganglia. We propose a model of the striatum that can account for the mixture of symptoms seen in PD. In the model, the problem of motor planning is cast in terms of a particle in a potential, where potentials are generated internally in striatal modules, subject to afferent control. Planned movement is governed by Hamilton's equations, where potential energy is supplied by potentials expressed in the striatum. To test the model in realistic situations, a dynamic simulation of a two-link robot arm was used. Normal movement is modeled and shown to exhibit observed experimental properties. Symptoms of PD are reproduced by modeling hypothetical consequences of PD pathology.


Are group identity and sense of belonging relevant for group pain management programmes? An exploratory pilot study.
Cognitive Behaviour Therapy (CBT)-based programmes for chronic pain are often conducted in groups, most likely for time and cost efficiencies. However, there has been very little investigation of the role that the group itself, and particularly the processes occurring within the group, may play in individual outcomes. The objective of this study was to explore whether social group processes were relevant to key treatment outcomes of group CBT for chronic pain. Data were collected from 15 groups (N = 118) undertaking a pain management programme in a tertiary setting. Intraclass correlations were computed to determine any clustering of outcomes in groups, and linear mixed modelling analysis explored pre-registered hypotheses of associations between treatment outcomes and the social group processes of Group Identification and Sense of Belonging. A weak association between early identification with the group and changes in pain-related disability was shown. In addition, an enhanced global Sense of Belonging was associated with increased pain self-efficacy. These associations, in a programme that had not been designed to address group processes, suggest that their relevance is worth further investigation, particularly in group programmes that do focus on the social consequences of chronic pain. Future studies should investigate whether manipulation of social group processes within a CBT-based pain programme enhances pain-related outcomes and improves the overall well-being of people with chronic pain.


A better landmark for positioning a central venous catheter.
Improper positioning of central venous catheters (CVCs) can lead to erosion through the superior vena cava (SVC) or right atrium (RA) and pericardial tamponade. It is widely recommended that the tip of CVCs be placed above the heart or the pericardial reflection. The purpose of this study was to identify an easily recognized landmark to allow identification of the proximal extent of the pericardial reflection on a routine chest radiograph (CXR). We analyzed the computerized tomograms of the chest from 97 adults to evaluate the relationship between the pericardial reflection, SVC, carina, and right mainstem bronchus. Correlations between demographic data and length of SVC or pericardial reflection were sought. The mean length of the SVC was 6.5 cm. The pericardial reflection covered an average of 3.6 cm of the distal SVC. The carina was a mean of 1.3 cm below the mid-point of the SVC and 0.7 cm below the pericardial reflection. There was no significant correlation between SVC or pericardial length and either age, height, or weight. The distal half of the SVC lies within the pericardial reflection, and the upper limit of the pericardial reflection is slightly above the level of the carina. These landmarks are useful for determining proper position of the tip of a CVC on CXR.


[Stenosis of the popliteal artery due to adventitial cysts].
The authors report a case of popliteal artery adventitial cystic disease. They discuss diagnosis and treatment.


Scalable Signature-Based Molecular Diagnostics Through On-chip Biomarker Profiling Coupled with Machine Learning.
Molecular diagnostics have traditionally relied on discrete biological substances as diagnostic markers. In recent years however, advances in on-chip biomarker screening technologies and data analytics have enabled signature-based diagnostics. Such diagnostics aim to utilize unique combinations of multiple biomarkers or diagnostic 'fingerprints' rather than discrete analyte measurements. This approach has shown to improve both diagnostic accuracy and diagnostic specificity. In this review, signature-based diagnostics enabled by microfluidic and micro-/nano- technologies will be reviewed with a focus on device design and data analysis pipelines and methodologies. With increasing amounts of data available from microfluidic biomarker screening, isolation, and detection platforms, advanced data handling and analytics approaches can be employed. Thus, current data analysis approaches including machine learning and recent advances with image processing, along with potential future directions will be explored. Lastly, the needs and gaps in current literature will be elucidated to inform future efforts towards development of molecular diagnostics and biomarker screening technologies.


Growth reduction in Plantago lanceolata in relation to biotic factors in the soil environment.
To investigate the influence of soil-borne pathogens on the population biology of a grassland species in natural vegetation, soil samples were collected, partly disinfected or sterilized and then planted with Plantago lanceolata. Those on some of the untreated soils showed growth reduction due to a biotic factor in the soil. This growth reduction was not associated with the density of P. lanceolata plants at the sampling sites. It was only visible when differences in abiotic factors - especially nutrient levels -were eliminated. In the natural situation the nutritional status of the soil has a far greater impact than biotic soil factors. Micro-organisms harmful to Plantago roots are considered to be of minor importance in the distribution of the individuals in the P. lanceolata population studied.


Motivational interviewing for adolescent substance use: a pilot study.
We developed and pilot tested a 2-session motivational interviewing intervention for substance use among 14- to 18-year-old medical patients. Recruitment and retention were more challenging than anticipated. A substantial number of completers reduced their use of substances and risk of driving after drinking during the 3-month follow-up period.


Longitudinal Plasma Protein Profiling Using Targeted Proteomics and Recombinant Protein Standards.
Spike-in of standards of known concentrations used in proteomics-based workflows is an attractive approach for both accurate and precise multiplexed protein quantification. Here, a quantitative method based on targeted proteomics analysis of plasma proteins using isotope-labeled recombinant standards originating from the Human Protein Atlas project has been established. The standards were individually quantified prior to being employed in the final multiplex assay. The assays are mainly directed toward actively secreted proteins produced in the liver, but may also originate from other parts of the human body. This study included 21 proteins classified by the FDA as either drug targets or approved clinical protein biomarkers. We describe the use of this multiplex assay for profiling a well-defined human cohort with sample collection spanning over a one-year period. Samples were collected at four different time points, which allowed for a longitudinal analysis to assess the variable plasma proteome within individuals. Two assays toward APOA1 and APOB had available clinical data, and the two assays were benchmarked against each other. The clinical assay is based on antibodies and shows high correlation between the two orthogonal methods, suggesting that targeted proteomics with highly parallel, multiplex analysis is an attractive alternative to antibody-based protein assays.


Chaotic alternation of waves in ring lasers.
We intend to give an analytic description of the mechanisms involved in the periodic and chaotic wave alternation frequently observed in ring lasers. A set of amplitude equations is derived from the Maxwell-Bloch equations. These equations are studied analytically and numerically.


An on-line detection system for screening small molecule inhibitors of α-Amylase and α-Glucosidase in Prunus mume.
High-throughput screening of inhibitors from natural products is an efficient approach to target key enzymes in diabetes progression. In this study, an on-line detection system was established for the first time to rapidly screen inhibitors of α-amylase and α-glucosidase from Prunus mume. Among 28 identified compounds, 26 and 21 compounds showed strong inhibitory effect against α-amylase and α-glucosidase, respectively. Their inhibitory effects were validated by in vitro enzyme assay and fluorescence quenching which demonstrated that these inhibitors effectively interfered enzyme active sites. The inhibition kinetics suggested that chemical structures are of great importance for interfering the enzyme structures and their microenvironment polarity. Among evaluated compounds, isorhamnetin-3-O-glucoside (19) showed the strongest binding activities to α-amylase and α-glucosidase (6.34×106·nmol-1 and 6.28×106·nmol-1, respectively) by the on-line detection system. Its IC50 values were 0.16 ± 0.06 and 0.09 ± 0.01 µM against α-amylase and α-glucosidase, respectively. 19 gave a much higher Ki for α-amylase (0.1307 mM) than α-glucosidase (0.0063 mM), indicating its selectivity towards α-glucosidase. This reported method was rapid and reliable to identify prototype inhibitors against key enzymes in diabetes, and thus might serve as a general platform to screen enzyme inhibitors from natural products.


Exogenous GM1 ganglioside caused G1-arrest of human diploid fibroblasts. Flow cytometric studies.
Exogenous GM1 ganglioside (II3 NeuAc-Gg0se4-Cer) inhibited growth and DNA synthesis of human diploid fibroblasts, TIG-1 cells. We examined the effect of exogenous GM1 on their cell cycle traverse by flow cytometry. When the cells were partially synchronized by serum deprivation, addition of GM1 at the time of refeeding caused about 70% reduction of their reentry into S phase from the level observed in the control culture untreated with the ganglioside. However, the addition of GM1 6 h later caused only about 30% reduction of the reentry from the control level. These results suggest that the exogenous ganglioside blocks the cell cycle traverse in an early G1 period. This is consistent with the fact that GM1-treated cells showed a high level of histone H1(0) similar to that observed in G1-arrested cells in confluent culture.


Determination of bupivacaine and three of its metabolites in rat urine by capillary electrophoresis.
A capillary electrophoretic (CE) method for the analysis of urinary extracts of the local anesthetic, bupivacaine, and its three main metabolites, desbutylbupivacaine, 3'-hydroxybupivacaine, and 4'-hydroxybupivacaine, in rat urine has been developed. The limits of detection were 0.22 microM for desbutylbupivacaine and bupivacaine, 0.15 microM for 3'-hydroxybupivacaine, and 0.16 microM for 4'-hydroxybupivacaine. The linear range was from 0.7 microM to 16.8 microM for all four compounds. Migration time and peak height reproducibilities, and extraction efficiencies were determined for all four compounds. Peak height reproducibilities (n = 5) for the overall method were improved through the use of prilocaine as an internal standard. Peak height reproducibilities were 5.6% RSD for desbutylbupivacaine and bupivacaine, and 9.9% RSD for 3'-hydroxybupivacaine and 4'-hydroxybupivacaine. Migration time reproducibilities (n = 5) were 2.4% for all compounds. Urine samples were collected from rats administered therapeutic doses of bupivacaine and extracted using a solid-phase extraction method (SPE). Separation of bupivacaine and its metabolites was achieved in 15 min.


Nanoparticles in photodynamic therapy: an emerging paradigm.
Photodynamic therapy (PDT) has emerged as one of the important therapeutic options in management of cancer and other diseases [M. Triesscheijn, P. Baas, J.H. Schellens, F.A. Stewart, Photodynamic therapy in oncology, Oncologist 11 (2006) 1034-1044]. Most photosensitizers are highly hydrophobic and require delivery systems. Previous classification of delivery systems was based on presence or absence of a targeting molecule on the surface [Y.N. Konan, R. Gurny, E. Allemann, State of the art in the delivery of photosensitizers for photodynamic therapy, J. Photochem. Photobiol., B 66 (2002) 89-106]. Recent reports have described carrier nanoparticles with additional active complementary and supplementary roles in PDT. We introduce a functional classification for nanoparticles in PDT to divide them into passive carriers and active participants in photosensitizer excitation. Active nanoparticles are distinguished from non-biodegradable carriers with extraneous functions, and sub-classified mechanistically into photosensitizer nanoparticles, [A.C. Samia, X. Chen, C. Burda, Semiconductor quantum dots for photodynamic therapy, J. Am. Chem. Soc. 125 (2003) 15736-15737, R. Bakalova, H. Ohba, Z. Zhelev, M. Ishikawa, Y. Baba, Quantum dots as photosensitizers? Nat. Biotechnol. 22 (2004) 1360-1361] self-illuminating nanoparticles [W. Chen, J. Zhang, Using nanoparticles to enable simultaneous radiation and photodynamic therapies for cancer treatment, J. Nanosci. Nanotechnology 6 (2006) 1159-1166] and upconverting nanoparticles [P. Zhang, W. Steelant, M. Kumar, M. Scholfield, Versatile photosensitizers for photodynamic therapy at infrared excitation, J. Am. Chem. Soc. 129 (2007) 4526-4527]. Although several challenges remain before they can be adopted for clinical use, these active or second-generation PDT nanoparticles probably offer the best hope for extending the reach of PDT to regions deep in the body.


Direct and indirect methods for the quantification of leg volume: comparison between water displacement volumetry, the disk model method and the frustum sign model method, using the correlation coefficient and the limits of agreement.
Volume changes can be measured either directly by water-displacement volumetry or by various indirect methods in which calculation of the volume is based on circumference measurements. The aim of the present study was to determine the most appropriate indirect method for lower leg volume calculation using water displacement volumetry as a 'golden standard'. For 20 male volunteers, age range: 20-35 years, the volume of both lower legs was determined directly by water-displacement volumetry, and indirectly by the frustum sign model method and the disc model method. Calculation of the correlation coefficient and the limits of agreement showed that water-displacement volumetry and the disc model method are interchangeable (r = +0.99, mean +/- 2s = -45 +/- 78 ml), whereas this does not hold for the frustum sign model (r = +0.93, mean +/- 2s = 521 +/- 238 ml). In the clinical situation volume measurement can be valuable for monitoring of the severity of oedema or haematoma occurrence after surgery or severe trauma. This non-invasive diagnostic aid may be a valuable adjuvant means of diagnosis for several volume dependent disorders of the extremities.


Intracellular acidic mucins and their identification in diagnostic cytology.
Exfoliative, abrasive and aspiration cytology were increasingly relied upon for tissue diagnosis of tumours. The established histological stains for the differentiation of mucin and non-mucin-secreting tumours are not ideal for alcohol-fixed cytology smears and a more reliable cytological technique for the preservation and staining of intra-cellular acidic mucins using Alcohol Alcian Blue 8GX is presented.


On-board safety monitoring systems for driving: review, knowledge gaps, and framework.
Fatal highway incidents remain the leading type of fatal work-related event, carrying tremendous personal, social, and economic costs. While employers with a fixed worksite can observe and interact directly with workers in an effort to promote safety and reduce risk, employers with workers who operate a motor vehicle as part of their job have fewer options. New technologies such as on-board safety monitoring systems offer the potential to further improve safety. These technologies allow vehicle owners to collect safety-specific information related to a driver's on-the-road behavior and performance. While many such devices are being developed and implemented in both commercial fleets and private vehicles, the scientific examination of these devices has lagged by comparison. In the current paper, we: (a) describe the general features and functionality of current generations of on-board monitoring devices and how they might impact various driver behaviors; (b) review the current state of scientific knowledge specific to on-board devices; (c) discuss knowledge gaps and potential areas for future research, borrowing from the related domain of computer-based electronic performance monitoring (EPM); and (d) propose a framework that can be used to explore some of the human-system interactions pertaining to monitoring systems. Motor vehicle crashes can carry tremendous costs for employers, in terms of injury, disability, and loss of potentially productive work years. New technologies can offer tremendous benefits in terms of promoting safer on-the-road behaviors.


Retroperitoneal bronchogenic cyst presenting as adrenal tumor in adult successfully treated with retroperitoneal laparoscopic surgery.
A bronchogenic cyst in the retroperitoneum is rare in adults. A 41-year-old woman presented with an incidental left retroperitoneal mass that was suspicious for an adrenal tumor. Retroperitoneal laparoscopic excision and complete resection were performed. The pathologic examination confirmed a bronchogenic cyst in the retroperitoneum. We present the case with review of the relevant published data.


Dental students' knowledge of human immunodeficiency virus.
This study evaluated final year dental students' knowledge of human immunodeficiency virus (HIV), lesions associated with HIV, potential transmission routes of HIV, and their perception of the teaching received on cross-infection precautions, virology, sterilization practice and procedure, barrier dentistry and recognition of blood-borne virus risk group. Structured questionnaires on knowledge of human immunodeficiency virus were filled by final year dental students of University of Lagos, Nigeria. A total of 35 out of 37 questionnaires were returned filled giving a response rate of 94.6%. Most of the students rated the teaching they received on cross-infection precautions, sterilization practice and procedure, as adequate. More than a quarter (28.5%) of the students rated the teaching they received on virology and recognition of blood-borne virus risk group to be less than adequate. Most of the students were able to recognize the association of oral Kaposi sarcoma, oral candidiasis, oral hairy leukoplakia, and salivary gland enlargement with HIV infection. There was a much lower level of knowledge of oral melanotic hyperpigmentation and idiopathic thrombocytopaenic pupura. Their knowledge of HIV and its potential transmission routes were adequate. This study revealed that final year dental students of the University of Lagos in southwestern region of Nigeria had adequate knowledge of routes of transmission of HIV in clinical practice. However, there is need for improvement in teaching of the students on virology and recognition of blood-borne virus risk group.


4-Formyl-2-nitro-phenyl 4-bromo-benzoate.
In the title compound, C14H8BrNO5, the benzene rings form a dihedral angle of 62.90 (7)°. The central ester group is twisted away from the nitro-substituted and bromo-substituted rings by 71.67 (7) and 8.78 (15)°, respectively. The nitro group forms a dihedral angle of 7.77 (16)° with the benzene ring to which it is attached. In the crystal, mol-ecules are linked by weak C-H⋯O inter-actions, forming C(12) chains which run along [001]. Halogen-halogen inter-actions [Br⋯Br = 3.523 (3) Å] within the chains stabilized by C-H⋯O inter-actions are observed.


The relationship between activities of daily living and psychological distress among Chinese older adults: A serial multiple mediation model.
Few studies have shed light on the mechanisms underlying the link between activities of daily living (ADL) and psychological distress. This study aimed to explore the multiple mediating roles of loneliness and sleep quality in this relationship among Chinese older adults. A total of 3250 older adults completed the Barthel Index, UCLA 20-item Loneliness Scale, Pittsburgh Sleep Quality Index, and Depression, Anxiety, and Stress Scale Questionnaire. Serial multiple mediation analysis was conducted using Hayes' PROCESS macro. ADL was found to directly impact psychological distress through three significant mediation pathways: (1) loneliness (B=-0.124, 95% CI=-0.140, -0.109), which accounted for 23.98% of the total effect, (2) sleep quality (B=-0.050, 95% CI=-0.063, -0.039), which accounted for 9.67% of the total effect, and (3) loneliness and sleep quality (B=-0.015, 95% CI=-0.020, -0.012), accounting for 2.91% of the total effect. The total mediating effect was 36.56%. The cross-sectional design we used limited causal interpretations. Future studies could examine longitudinal changes in outcome measures. These findings highlight the role of loneliness and sleep quality as serial mediators of the relationship between ADL and psychological distress. Thus, for the early detection and prevention of psychological distress, it is necessary to conduct loneliness and sleep quality interventions for older adults with ADL limitations.


Plasma cell and memory B cell differentiation from the germinal center.
Germinal centers (GCs) form in secondary lymphoid tissues in response to antigenic challenge and are the site of somatic hypermutation, generating GC B cells with increasing affinity for the inciting agent that are positively selected over time. However, it is not until GC B cells differentiate into memory B cells and plasma cells and egress from the GC back into the circulation that effective long-lived humoral immunity is conferred upon the host. Here we review what is known about the signals that initiate the transition from a GC B cell into the memory B cell and plasma cell compartments and the downstream transcriptional regulation of these processes.


Investigation and analysis of antibody levels of hepatitis A among children before and after implementing the Expanded National Immunization Program in China.
To analyze changes of hepatitis A antibody levels and immunization coverage of HAV vaccine among children before and after implementing the Expanded National Immunization Program in five counties of China, and to provide evidence for developing hepatitis A vaccine immunization strategies. 449 children born in 2001, 2005 and 2009 were selected from five counties for an immunization coverage and a sero-prevalence survey of hepatitis A. The chemiluminescence microparticle immunoassays (CMIA) were used to detect hepatitis A IgG antibody and analyzed the factors which influenced the immunization coverage and positive rates. Among 449 subjects of children born in 2001, 2005 and 2009, the immunization coverage were 53.02%, 78.52% and 99.34% (χ2 = 91.285, P < 0.001). The positivity rates of hepatitis A IgG antibody were 61.07%, 81.21%, 95.36% (χ2 = 54.198, P < 0.001), respectively. The immunization coverage and positivity rate significantly increased with the delay of birth year. Children accepting different doses of HA vaccines are significantly different in positive rates of HA antibody, while there are no significant differences of different genders, years of birth, residence types, or types of registered permanent residence in different regions. The positivity rate increased significantly with administration of hepatitis A vaccine and shorter intervals between sample collection and HAV immunization. After the Expanded National Immunization Program was implemented, hepatitis A antibody levels were significantly increased in five counties, which indicates a successful result of EPI.


Correction to: Comparison of three different methods of internal sinus lifting for elevation heights of 7 mm: an ex vivo study.
An amendment to this paper has been published and can be accessed via the original article.


Assessment of the accuracy and reproducibility of RV volume measurements by CMR in congenital heart disease.
The purpose of this study was to determine whether right ventricular (RV) volumes are more accurately and reproducibly measured by cardiac magnetic resonance (CMR) in an axial orientation or in a short-axis orientation in patients with congenital heart disease (CHD). There is little agreement on the most suitable imaging plane for RV volumetric analysis in the setting of abnormal RV physiology. Measurements of RV volumes from datasets acquired in axial and short-axis orientations were made in 50 patients with CHD. RV stroke volumes (SV) calculated using these 2 methods were compared with forward flow measured in the pulmonary trunk by phase contrast (PC) imaging. Repeated volume measurements were made to assess intraobserver and interobserver reliability. Bland-Altman plots and Lin's concordance correlation coefficient (CCC) were used for all analyses of agreement. Analysis of all subjects revealed a statistically significant difference in interobserver reliability of RV end-systolic volume (ESV) measurements that favored the axial method (p = 0.047). The magnitude of measurement differences between observers in this case was small (-2.8 ml/m(2); 95% confidence interval: -5.6 to 0.0). There was no difference between the 2 contouring methods in terms of intraobserver reliability in measurements of RV end-diastolic volume (EDV), ESV, ejection fraction, or SV (p > 0.05 in all cases). In subjects with RV EDV ≥ 150 ml/m(2), RV SV measured using axial contours yielded better agreement with forward flow measured in the pulmonary trunk (CCC = 0.63) than did measurements made using short-axis contours (CCC = 0.56; p = 0.007). Trends favoring the axial orientation in terms of reproducibility were not clinically significant. In subjects with RV EDV ≥ 150 ml/m(2), the axial orientation yields RV volume measurements that agree more closely with flow measured in the pulmonary trunk than does the short-axis orientation.


Influence of portal hemodynamics on long-term survival of alcoholic cirrhotic patients after small-diameter portacaval H grafts.
Estimating postoperative survival rates after portasystemic shunt procedures has concerned surgeons during the last 40 years. The relationship between survival and Child's classification has clearly demonstrated the importance of preoperative hepatic functional reserve. Maintaining hepatic portal perfusion has been proposed as an additional protective factor but has never been proved clinically. Our analysis of survival after partial shunting with small-diameter portacaval H grafts has shown that both hepatic functional reserve and postoperative portal perfusion correlate with postoperative survival in alcoholic patients, but the latter was a stronger correlate of long-term survival. A predictive model based on both factors has been described for estimating the overall survival rate of alcoholics after partial shunting with small-diameter portacaval H grafts.


Testicular and spermatogenic characteristics of Lagria villosa (Tenebrionidae: Lagriinae) with taxonomic inferences.
In the present study testicular and spermatogenetic aspects were described for Lagria villosa using light and scanning electron microscopy. In this species, spermiogenesis results in the formation of sperm bundles with spermatozoa arranged in an antiparallel manner, a characteristic observed only in Tenebrionidae. L. villosa, however, has about 60 follicles per testis and up to 1200 spermatozoa per cyst, in contrast to other tenebrionids that exhibit only six follicles in each testis and up to 512 spermatozoa per cyst. Therefore, the antiparallel arrangement of the spermatozoa in the bundle give support to previous works classifying the lagriids in a subfamily (Lagriinae) of Tenebrionidae. Just as the number of spermatozoa per cyst and follicles per testis suggest that they constitute, in fact, a distinct branch of this family.


Deep learning approach for accurate prostate cancer identification and stratification using combined immunostaining of cytokeratin, p63, and racemase.
Prostate cancer (PCa) is the most frequently diagnosed cancer in men worldwide, affecting around 1.4 million individuals. Current PCa diagnosis relies on histological analysis of prostate biopsy samples, an activity that is both time-consuming and prone to observer bias. Previous studies have demonstrated that immunostaining of cytokeratin, p63, and racemase can significantly improve the sensitivity and the specificity of PCa detection compared to traditional H&E staining. This study introduces a novel approach that combines diagnosis-specific immunohistochemical (IHC) staining and deep learning techniques to provide reliable stratification of prostate glands. Our approach leverages a customized segmentation network, called K-PPM, that incorporates adaptive kernels and multiscale feature integration to enhance the functional information of IHC. To address the high class-imbalance problem in the dataset, we propose a weighted adaptive patch-extraction and specific-class kernel update. Our system achieved noteworthy results, with a mean Dice Score Coefficient of 90.36% and a mean absolute error of 1.64 % in specific-class gland quantification on whole slides. These findings demonstrate the potential of our system as a valuable support tool for pathologists, reducing workload and decreasing diagnostic inter-observer variability. Our study presents innovative approaches that have broad applicability to other digital pathology areas beyond PCa diagnosis. As a fully automated system, this model can serve as a framework for improving the histological and IHC diagnosis of other types of cancer.


Persistent increases in Ca(2+) influx through Cav1.2 shortens action potential and causes Ca(2+) overload-induced afterdepolarizations and arrhythmias.
Persistent elevation of Ca(2+) influx due to prolongation of the action potential (AP), chronic activation of the β-adrenergic system and molecular remodeling occurs in stressed and diseased hearts. Increases in Ca(2+) influx are usually linked to prolonged myocyte action potentials and arrhythmias. However, the contribution of chronic enhancement of Cav1.2 activity on cardiac electrical remodeling and arrhythmogenicity has not been completely defined and is the subject of this study. Chronically increased Cav1.2 activity was produced with a cardiac specific, inducible double transgenic (DTG) mouse system overexpressing the β2a subunit of Cav (Cavβ2a). DTG myocytes had increased L-type Ca(2+) current (ICa-L), myocyte shortening, and Ca(2+) transients. DTG mice had enhanced cardiac performance, but died suddenly and prematurely. Telemetric electrocardiograms revealed shortened QT intervals in DTG mice. The action potential duration (APD) was shortened in DTG myocytes due to significant increases of potassium currents and channel abundance. However, shortened AP in DTG myocytes did not fully limit excess Ca(2+) influx and increased the peak and tail ICa-L. Enhanced ICa promoted sarcoplasmic reticulum (SR) Ca(2+) overload, diastolic Ca(2+) sparks and waves, and increased NCX activity, causing increased occurrence of early and delayed afterdepolarizations (EADs and DADs) that may contribute to premature ventricular beats and ventricular tachycardia. AV blocks that could be related to fibrosis of the AV node were also observed. Our study suggests that increasing ICa-L does not necessarily result in AP prolongation but causes SR Ca(2+) overload and fibrosis of AV node and myocardium to induce cellular arrhythmogenicity, arrhythmias, and conduction abnormalities.


The effectiveness of a novel treatment of TIM-3(-) NK cells infusion in murine models of immune-mediated bone marrow failure.
T-cell immunoglobulin and mucin-containing domain (TIM)-3 exerts its inhibitory effect on NK cells and participates in the immune pathogenesis of SAA. In this study, we aimed to explore a novel treatment method of TIM-3(+) NK or TIM-3(-) NK cell infusion in combination with immunosuppressive therapy for bone marrow failure (BMF)/aplastic anemia (AA) mice. BMF/AA mouse model was constructed. The TIM-3 expression and functional molecules on TIM-3(+) and TIM-3(-) NK cells of the BMF group, total body irradiation (TBI) group, and normal control (NC) group mice were detected by flow cytometry. After treatment, the general condition, whole blood cell and bone marrow cell (BMC) count, and immune condition of mice from each group were compared. TIM-3 expression in the peripheral blood NK cells of BMF mice was significantly lower than that of the TBI and NC group mice. TIM-3(-) NK cells expressed more NKG2D receptors than TIM-3(+) NK cells. The levels of P-Akt and PI3K in TIM-3(-) NK cells were higher than those in TIM-3(+) NK cells. On the 17th day after BMF induction, the weight, peripheral whole blood cell count, and BMC count of BMF mice decreased significantly compared with that of the NC group mice. The therapeutic effect in the TIM-3(-) NK cell treatment group was better than that in the TIM-3(+) NK cell treatment and CsA treatment groups. Concurrently, the ratio of CD4+ T and CD8+ T cells of BMF mice was significantly lower than that of the NC group mice. The therapeutic effect in CsA + TIM-3(-) NK group was more significant than that of the CsA treatment and the CsA + TIM-3(+) NK groups. In this study, we found that the general condition, peripheral whole blood cell and BMC count, and immune status of BMF mice improved significantly after CsA + TIM-3(-) NK cell treatment. These results may provide further insights into the immune pathogenesis of SAA and novel therapeutic ideas for improving SAA treatment.


[Special medical outpatient care-3.5 years of outpatient specialist care in rheumatology : An inventory].
In 2012 the outpatient specialist medical care (ASV) was introduced as an intersectoral, interdisciplinary, outpatient care concept. As from 19 April 2018 there is the possibility to form teams for the ASV for rheumatic diseases in adults as well as in children and adolescents.. Analysis of previously unpublished data of the National Confederation of Statutory Health Insurance (GKV-SV) and of data of the ASV service department and a comparison with data of standard healthcare services and with the previous care concept of outpatient care in hospitals (ABK). After its introduction for 3.5 years, the ASV in rheumatology for adult care has developed into a significant healthcare model for rheumatologists in private practices and hospitals. There were 57 teams consisting of 458 rheumatologists in ASV rheumatism for adults, which represent 44% of all rheumatologists involved in adult care. For children and adolescents, there were 7 teams with 19 pediatric rheumatologists, i.e. 8% of pediatric rheumatologists in health care. The number of patients treated was still significantly lower than the potential, but showed a strong increase. Almost 64,000 adults and 811 children and adolescents were treated in the ASV in the second quarter of 2021. Whether the facilitation of outpatient care and the introduction of hybrid diagnosis-related groups planned in the coalition agreement will spur the ASV development remains to be seen.