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Immunoglobulin G (IgG) mediates its immune functions through complement and cellular IgG-Fc receptors (FcγR). IgG contains an evolutionary conserved N-linked glycan at position Asn297 in the Fc-domain. This glycan consists of variable levels of fucose, galactose, sialic acid, and bisecting N-acetylglucosamine (bisection). Of these variations, the lack of fucose strongly enhances binding to the human FcγRIII, a finding which is currently used to improve the efficacy of therapeutic monoclonal antibodies. The influence of the other glycan traits is largely unknown, mostly due to lack of glyco-engineering tools. We describe general methods to produce recombinant proteins of any desired glycoform in eukaryotic cells. Decoy substrates were used to decrease the level of fucosylation or galactosylation, glycosyltransferases were transiently overexpressed to enhance bisection, galactosylation and sialylation and in vitro sialylation was applied for enhanced sialylation. Combination of these techniques enable to systematically explore the biological effect of these glycosylation traits for IgG and other glycoproteins.

As well-known to the scientific community, Alzheimer's disease (AD) is an irreversible neurodegenerative disease that ends up with impairment of memory and cognition. Patient quality of life can be enhanced by targeting neurogenesis as a therapeutic paradigm. Preserving functional activity of SDF-1α and GLP-1 by DPPIV inhibition will enhance the homing of stem cells and modulate cell signalling pathways. The non-invasive approach presented in this article is a major advantage for managing AD, as regular/conventional stem-cell therapy necessarily relies on the application of regenerative stem cells exogenously. Using DPP-4 inhibitors to achieve the SDF-1α/CXCR4 axis stabilisation and augmenting GLP-1 levels, will enhance the homing/recruitment of brain resident and non-resident circulating stem cells/progenitor cells towards the sites of lesion to increase synaptic plasticity, a promising approach and also a novel one as well.

The restructuring of production resulting from the Port Modernization Law (Law 8.630/90) caused significant changes in work organization of Brazilian Ports. In the case of Mucuripe (Fortaleza, Ceará), in particular, the changes were very intense as Mucuripe is an old port that, before the Law, had labor regulation being governed by Trade Unions. This paper aims to present the perceptions of Union Representatives on the changes brought about by the Law on work organization in the port of Fortaleza, its influence in the organization and in the way the Unions deal with this new reality. Open and exploratory interviews were conducted with representatives of occasional labor workers registered in the Port of Fortaleza OGMO (Orgão Gestor de Mão de Obra, Labor Regulation Management). The analysis of the collected material in the interviews was based on the technique of content analysis proposed by Bardin (1979). Trade Unions have undergone a great loss of power and it has reflected in a relative inability to perform its function and to fight for the rights of the workers. The obvious Trade Unions weakness - a reduction of strikes and less unionized workers - reflects the dominating ideology of capital.

Knowledge of the precise molecular mechanisms during the discharge and recharge processes in the lithium-air battery is critical for achieving desired improvements in specific capacity, current density, and cyclability. The initial oxygen reduction product formed in the presence of Li(+) ions is lithium superoxide LiO(2). In this study, we report the computed structures and thermodynamic parameters of LiO(2) dimerization in the gas phase, which enables us to provide a baseline for the reaction free energy profile of the subsequent disproportionation of (LiO(2))(2) to lithium peroxide Li(2)O(2) and O(2). Our calculations identified several low-lying (LiO(2))(2) dimers, with the singlet bipyramidal structure giving IR bands that are consistent with the characteristic IR vibration frequencies of (LiO(2))(2) in the oxygen matrix at T = 15-40 K. The activation barrier for (LiO(2))(2) = Li(2)O(2)+O(2) is 10.9 kcal/mol at the UCCSD(T)/CBS level (T = 298 K), suggesting that in the gas phase LiO(2) and its aggregates could only be observed at low temperatures.

In mid-trimester amniocentesis (MTA), 12-15 ml of amniotic fluid is aspirated for cytogenetic analysis. When a similar volume of amniotic fluid is removed by early amniocentesis (EA), it represents a significant proportion of the total amniotic fluid volume in the first trimester. The fluid depletion, which may persist for 7 to 10 days, is considered to impair development of fetal lungs and extremities and, possibly, contribute towards procedure-related congenital abnormalities and miscarriages. By only removing 7 ml of amniotic fluid, we have demonstrated a total miscarriage rate (3.8 per cent) comparable with previous large studies (Table V), a low incidence of respiratory difficulties at birth (2.7 per cent) and a low incidence of fixed flexion deformities (1.6 per cent), at the expense of a small increase in the incidence of culture failure (2.2 per cent).

Axon guidance by commissural neurons has been well documented, providing us with a molecular logic of how midline crossing is achieved during development. Despite these advances, knowledge of the intrinsic genetic programs is still limited and it remains obscure whether the expression of a single transcription factor is sufficient to activate transcriptional programs that ultimately enable midline crossing. Here, we show in the mouse that the homeodomain transcription factor Dbx1 is expressed by a subset of progenitor cells that give rise to commissural neurons in the dorsal midbrain. Gain- and loss-of-function analyses indicate that the expression of Dbx1 alone is sufficient and necessary to trigger midline crossing in vivo. We also show that Robo3 controls midline crossing as a crucial downstream effector of the Dbx1-activated molecular programs. Furthermore, Dbx1 suppresses the expression of the transcriptional program for ipsilateral neuron differentiation in parallel. These results suggest that a single transcription factor, Dbx1, has an essential function in assigning midline-crossing identity, thereby contributing crucially to the establishment of the wiring laterality in the developing nervous system.

This study investigated the ability of four hypnotically induced mood states (euphoria, depression, anxiety, and anger) to trigger craving and other drug-related conditioned responses in detoxified opiate abuse patients. Hypnotically induced depression produced significant increases in drug craving for opiates. Depression also tended to increase global self-ratings of opiate withdrawal. Other trends included increases in self-rated craving by induced anxiety and increases in withdrawal symptoms by induced anger. These results suggest that negative mood states, perhaps in the context of repeated attempts at self-medication, may become conditioned stimuli capable of triggering craving and other drug-related conditioned responses. The ability of depression to produce reliable effects in this particular patient group may reflect the high lifetime prevalence of depression diagnoses for this sample. The implications of these findings for therapeutic strategies are discussed.

In its book " The great secrecy", Dr. Gübler revealed that President of French Republic, Franpois Mitterrand, had lied on his cancer as of his accession with the capacity. 1981 to 1994, Dr. Gübler was the personal doctor of the President of French Republic, deceased on January 8, 1996. The great secrecy was diffused on January 17, 1996. French Justice ordered the interruption of its diffusion on January 18, 1996. The recourse led to a compensation for family of President. However, the European Court of the Humans Right (CEDH), May 18, 2004, condemned France retaining that the general and absolute character medical secrecy could not attack the freedom of expression and to the right to knowledge by the Nation of the truth on health of its former President of Republic. The CEDH however approves initial prohibition but not the maintenance of this prohibition, 9 months later. The great secrecy remained interdict in France until 2004 and was republished at the beginning of 2005. Dr Gübler was condemned for violation of medical secrecy and was erased Order of the doctors, decision confirmed by the Council of State. This story started again the medical, legal and political debate around the medical secrecy concerning politicians. In September 2005, President of French Republic, Jacques Chirac, was hospitalized after a cerebral vascular accident. Communicate were regularly published on its health, but questions were asked concerning medical activity under these conditions.

Although health disparities research has already contributed to decreased mortality and morbidity in underserved communities, more work is needed. The NYC Epi Scholars program of the New York City Department of Health and Mental Hygiene (NYC DOHMH) aims to address gaps in critical public health needs and to train future public health leaders in epidemiology. The program is designed to increase racial/ethnic and socioeconomic diversity in the public health workforce, to provide fieldwork and practica opportunities, and to cultivate future leaders in epidemiology and public health.

Stories may provide a useful way of communicating about health and promoting engagement for health promotion campaigns. In this study, we examined the effectiveness of a particular type of narrative, restorative narratives (stories that highlight hope and resilience), relative to negative narratives (stories that focus on suffering or challenges). We also tested the effect of labeling the story as fact or fiction. The results suggested that restorative narratives may foster greater prosocial behavior than negative narratives and effectiveness does not differ depending on whether a story is labeled as "factual" or "fictional." Our findings offer encouraging implications for future promotional efforts by health organizations.

The hemodynamic and clinical response to oral and intravenous piroximone was examined in 25 patients with chronic cardiac failure secondary to ischemic or myopathic heart disease: 14 with severe failure, who were clinically unstable (group I), and 11 with stable failure of mild to moderate severity (group II) in whom maximal O2 uptake (VO2 max) to treadmill exercise could be monitored serially. Intravenous (0.5 to 1.0 mg/kg) and oral (0.7 to 4.9 mg/kg) piroximone significantly (p less than 0.05) improved right and left ventricular pump function in both groups while causing an insignificant rise in heart rate and reduction in arterial pressure. Myocardial O2 uptake was not altered acutely or subacutely after piroximone, and myocardial lactate production was not observed. The salutary hemodynamic response to oral piroximone was sustained for 5 hours and there was no evidence of tolerance to the third and fourth doses. In group II, VO2 max was increased (p less than 0.05) at 4, 8, 12, 24, and 48 weeks of oral piroximone therapy. Adverse gastrointestinal effects were observed in two patients and a supraventricular tachycardia in another. Thus, piroximone may prove useful in the long-term management of chronic cardiac failure. Controlled clinical trials should be undertaken to determine the ultimate efficacy and safety of piroximone in these patients.

Recent years have seen a growing awareness of the role the immune system plays in successful cancer treatment, especially in novel therapies like immunotherapy. The characterization of the immunological composition of tumors and their micro-environment is thus becoming a necessity. In this paper we introduce a deep learning-based immune cell detection and quantification method, which is based on supervised learning, i.e., the input data for training comprises labeled images. Our approach objectively deals with staining variation and staining artifacts in immunohistochemically stained lung cancer tissue and is as precise as humans. This is evidenced by the low cell count difference to humans of 0.033 cells on average. This method, which is based on convolutional neural networks, has the potential to provide a new quantitative basis for research on immunotherapy.

Diabetic dyslipidemia is characterized by hepatic very low density lipoprotein (VLDL) and intestinal chylomicron overproduction, reduced high density lipoprotein cholesterol (HDL-C) level, increased propensity of small dense LDL (sdLDL) and increased postprandial lipemia. This dyslipidemic profile is also strongly linked to other features of the metabolic syndrome. Diabetic dyslipidemia is a well-recognized risk factor for atherosclerotic cardiovascular diseases. Currently, statins remain the first line therapy primarily through reducing the atherogenic LDL. Clinical trials on other lipid modifying agents were met with variable success in selective patient populations. Emerging new insights into the pathophysiology of lipid metabolism, in general, and diabetic dyslipidemia, in particular, have opened up potentially novel therapeutic strategies to further reduce the risk associated with diabetic dyslipidemia and insulin resistant state.

The ovarian follicle represents the basic functional unit of the ovary and consists of an oocyte, which is surrounded by granulosa cells (GCs). GCs play an important role in the growth and development of the follicle. They are subject to increased attention since it has recently been shown that the subpopulation of GCs within the growing follicle possesses exceptionally plasticity showing stem cell characteristics. In assisted reproduction programs, oocytes are retrieved from patients together with GCs, which are currently discarded daily, but could be an interesting subject to be researched and potentially used in regenerative medicine in the future. Isolated GCs expressed stem cell markers such as OCT-4, NANOG and SOX-2, showed high telomerase activity, and were in vitro differentiated into other cell types, otherwise not present within ovarian follicles. Recently another phenomenon demonstrated in GCs is transdifferentiation, which could explain many ovarian pathological conditions. Possible applications in regenerative medicine are also given.

The aim of this study was to investigate thiotepa (TT) and fludarabine (Fluda) as a preparative regimen for allogeneic peripheral stem cell transplant in patients not eligible for a standard myeloablative regimen due to comorbidities and/or poor performance status. TT was given at a dose of 10 mg/kg over 2 days and Fluda at 125 mg/m(2) over 5 days. In all, 21 patients (14 male, seven female; 10 acute leukaemia, eight myelodysplastic syndrome, two non-Hodgkin's lymphoma, one Hodgkin's disease) were treated. The median age was 51 years (range 30-55 years). All patients achieved full donor-type chimaerism. Adverse events included mild nausea and vomiting in two patients and a slight increase of serum amylase in three. A total of 13 patients received RBC transfusions (median 6 U, range 1-23), and all received platelets (median 4 U, range 1-27). Four patients died of nonrelapse causes and five of relapse. The 1-year probabilities of transplant-related mortality and relapse were 19 and 29%, respectively. In total, 12 patients remain in complete remission (median follow-up: 786 days). The 3-year overall survival probability was 58%. We conclude that this regimen is feasible and well tolerated.

230 adults estimated the ages at which children and adolescents ages 1 to 16 years could perform certain tasks like, "Say the months of the year backwards" and "Ride a bicycle". Nearly two-thirds of the participants consistently underestimated the age at which young people could perform. A total "correct" score, computed for each participant, formed a normal distribution. This score was used as a criterion measure for a series of multiple regressions. The strongest predictor was the extent to which people had regular contact with children, indicating the role of experience.

Microorganisms are employed to mine economically important elements from rocks, including the rare earth elements (REEs), used in electronic industries and alloy production. We carried out a mining experiment on the International Space Station to test hypotheses on the bioleaching of REEs from basaltic rock in microgravity and simulated Mars and Earth gravities using three microorganisms and a purposely designed biomining reactor. Sphingomonas desiccabilis enhanced mean leached concentrations of REEs compared to non-biological controls in all gravity conditions. No significant difference in final yields was observed between gravity conditions, showing the efficacy of the process under different gravity regimens. Bacillus subtilis exhibited a reduction in bioleaching efficacy and Cupriavidus metallidurans showed no difference compared to non-biological controls, showing the microbial specificity of the process, as on Earth. These data demonstrate the potential for space biomining and the principles of a reactor to advance human industry and mining beyond Earth.

This paper presents the analysis of trends in a number of cases and an average age of patients for whom determination of tricyclic antidepressants (TCA) showed positive results. The studied data were gathered in toxicological laboratory of Dept. of Analytical Toxicology and Therapeutic Drug, CM UJ in Kraków. The data were collected in period December 2001 August 2004. The main findings of this study are: The number of cases is exponentially increasing at the rate of 0.068% per day (p = 0.0165). No statistically significant correlation between the number of cases and: (a) day-length (p = 0.9819), (b) day-length change (p = 0.2312), (c) direction of change of day-length (p = 0.4640), d) day of the week (p = 0.7588) has been found, so periodicity of this phenomenon is questionable. It has been observed that the average age of patients is decreasing and the estimated rate of this decrease equals 0.0092-years per day (p = 0.0555). TCA positive patients treated in the Clinic on different days of the week differ in average age (p = 0.0016). From Tuesday till Friday the average age of patients is increasing. In the middle of the studied period the increase started from 30-year-olds on Mondays and ended with 48-year-old patients on Friday. At weekends the average dropped to 38 and stayed constant. On Mondays the average was about 46.

As a result of concerns regarding possible health hazards of synthetic antioxidants, gallic acid and methyl gallate may be introduced as natural antioxidants to improve oxidative stability of marine oil. Since conventional modelling could not predict the oxidative parameters precisely, artificial neural network (ANN) and neuro-fuzzy inference system (ANFIS) modelling with three inputs, including type of antioxidant (gallic acid and methyl gallate), temperature (35, 45 and 55 °C) and concentration (0, 200, 400, 800 and 1600 mg L(-1) ) and four outputs containing induction period (IP), slope of initial stage of oxidation curve (k1 ) and slope of propagation stage of oxidation curve (k2 ) and peroxide value at the IP (PVIP ) were performed to predict the oxidation parameters of Kilka oil triacylglycerols and were compared to multiple linear regression (MLR).

The TRPV ion channels mediate responses to many sensory stimuli including heat, low pH, neuropeptides, and chemical ligands. All TRPV subfamily members contain an intracellular N-terminal ankyrin repeat domain (ARD), a prevalent protein interaction motif. The 1.6-A crystal structure of the TRPV2-ARD, with six ankyrin repeats, reveals several atypical structural features. Repeats one through three display unusually long and flexible fingers with a large number of exposed aromatic residues, whereas repeats five and six have unusually long outer helices. Furthermore, a large counterclockwise twist observed in the stacking of repeats four and five breaks the regularity of the domain, altering the shape of surfaces available for interactions with proteins or other cellular ligands. Both solution studies and crystal packing interactions indicate that the TRPV2-ARD does not form homo-oligomers, suggesting that the ARD of TRPV ion channels may be used for interactions with regulatory factors rather than in promoting tetrameric assembly of the ion channels.

The genomic RNA of vitiviruses contains 5 open reading frames (ORF). ORF3 encodes a protein to which the function of a movement protein (MP) was assigned, based on sequence homology with other viral proteins. The aim of the research described in this paper was to gain further insight in distribution profile of the ORF3 product encoded by the vitiviruses Grapevine virus A (GVA) and Grapevine virus B (GVB). Expression of the GVA MP-GFP fusion protein via the virus genome in Nicotiana benthamiana leaves resulted in the formation of irregular spots and fibrous network structures on the outermost periphery of epidermal cells. Expression of GVA MP-GFP and GVB MP-GFP was involved in the formation of the tubule-like and punctate structures on the periphery of N. benthamiana and Vitis vinifera protoplasts. Co-expression of the GVA MP-GFP and GVA MP-RFP in protoplasts resulted in co-localization of these proteins into the same punctate structures, indicating that the MP is not accumulated randomly onto the cell surface, but targeted to particular sites at the cell periphery, where punctate and tubule-like structures are likely formed. With the use of cytoskeleton and secretory pathway inhibitors, we showed that the cytoskeletal elements are not likely to be involved in targeting of the MP-GFP to the punctate cellular structures. In addition to MP, a functional coat protein was found to be essential for virus spread within inoculated leaves.

Small cell neuroendocrine carcinoma of the ampulla of Vater is extremely rare and different from the common ampullary adenocarcinoma. The ampullary adenoma is also a rare neoplasm and has the potential to develop an adenocarcinoma. Their coexistence has been rarely reported in the literature. We herein describe an unusual case of a small cell neuroendocrine carcinoma associated with a villous adenoma in the ampulla of Vater with emphasis on computed tomography (CT) and histopathological findings. We also discuss their clinical, histopathological and radiological features as well as possible histogenesis.

Popliteal fossa and distal thigh swellings have many causes in young active adult. Cysts are the main cause, but they may also evolve from fatty tissue, lymph nodes or the popliteal artery. Semimembranosus muscle hypertrophy, found in athletes and young active adults, is only rarely the main or only cause of swelling, and only four such cases are reported in the literature. The present article reports our experience in the management of a case of semimembranosus hypertrophy as the only cause of a swelling above the popliteal fossa, and its favorable evolution.

Kümmell disease (KD) causes serious vertebral body collapse in patients. However, only a few case reports have been conducted and the number of patients with KD investigated was limited. Additionally, the frequently used poly(methyl methacrylate) (PMMA) bone cement for KD is limited by excessive modulus and poor biocompatibility. Herein, we aimed to modify PMMA bone cement with mineralized collagen (MC), and compare the clinical effects, image performance and finite element analysis between the modified bone cement and PMMA bone cement for the treatment of phase I and II KD. Thirty-nine KD patients treated with PMMA bone cement and 40 KD patients treated with MC-modified PMMA bone cement from June 2015 to March 2017 were retrospectively analyzed. The surgical procedure, intraoperative blood loss, hospital stay and complications were compared between different groups. Visual analog scale, Oswestry disability index, anterior vertebral height, posterior vertebral height, computed tomography value, adjacent vertebral re-fracture, Cobb angle and wedge-shaped correction angle were evaluated. Additionally, the representative sample was selected for finite element analysis. We found that the MC-modified PMMA bone cement could achieve the same effect as that of PMMA bone cement and was associated with better vertebral height restoration in the long term.

Several fields of research such as medicine, robotics, sports, informatics, etc., require the analysis of human movement. Traditional systems for acquisition and analysis of human movement data are based on video cameras or active sensors. However, those systems are limited to high-resource settings. Wearable devices allow monitoring subjects outside typical clinical or research environments. Here, we present an open source low-cost wireless sensor system for acquisition of human movement data. Our system consists of two main parts: a server that stores data and, one or more wearable sensor modules that collect movement data through Inertial Measurement Units (IMUs) and transmit them wirelessly to the server. As a proof of concept, we measured human gait activity. Our results show that our system with IMUs can acquire quantifiable movement data. Characteristics such as open source code and its low-cost, make our system a viable alternative for clinical or research.

A considerable amount of employees incur injuries in professions with mandatory on-duty fitness training. The training is necessary for maintaining a good health status, physical condition and strength in professions requiring such qualities. Injuries in Swedish firemen from on-duty fitness training between 1992 and 1998 were selected retrospectively from the Information System of Occupational Injuries (ISA) at the National Board of Occupational Safety and Health and, if having caused a sick-leave exceeding 2 weeks, to the Labour Market Insurance (AMF Insurance). The latter comprised injuries from 1995 only. During the seven-year period 1,468 injuries from fitness training occurred in male firemen. With an estimated 147 h per man and year the injury incidence was 2.6 per 10,000 h of exposure. The mean number of days of absence from work was 24.1 days (SD 39.8). In 1995, the mean cost per injury for medical treatment was close to 7,000 Euro and for production loss almost 4,500 Euro. By far the major part of the injuries, 75 %, occurred during team and contact sports (primarily floorball and soccer) and this sport category also accounted for 83% of the medical costs and 78% of the costs for production loss. It is suggested that a restriction of team and contact sports as mandatory on-duty fitness training for firemen should be tested and evaluated concerning the injury incidence.

Using three typical pi-conjugated molecules (1,3,5-hexatriene, 1-formyl-6-hydroxyhexa-1,3,5- triene, and 1,1-diamino-6,6-dinitrohexa-1,3,5-triene) we investigate the level of ab initio theory necessary to produce reliable values for linear and nonlinear optical properties, with emphasis on the vibrational contributions that are known to be important or potentially important. These calculations are made feasible by employing field-induced coordinates in combination with a finite field procedure. For many, but not all, purposes the MP2/6-31+G(d) level is adequate. Based on our results the convergence of the usual perturbation treatment for vibrational anharmonicity was examined. Although this treatment is initially convergent in most circumstances, a problematic situation has been identified.

We performed two case-control studies on brain tumours diagnosed during 1 January 1997 to 30 June 2000 and 1 July 2000 to 31 December 2003, respectively. Living cases and controls aged 20-80 years were included. An additional study was performed on deceased cases with a malignant brain tumour using deceased controls. Pooled results for glioma yielded for ipsilateral use of mobile phone odds ratio (OR)=2.9, 95% confidence interval (CI)=1.8-4.7 in the >10 years latency group. The corresponding result for cordless phone was OR=3.8, 95% CI=1.8-8.1. OR increased statistically significant for cumulative use of wireless phones per 100h and per year of latency. For high-grade glioma ipsilateral use of mobile phone gave OR=3.9, 95% CI=2.3-6.6 and cordless phone OR=5.5, 95% CI=2.3-13 in the >10 years latency group. Heredity for brain tumour gave OR=3.4, 95% CI=2.1-5.5 for glioma. There was no interaction with use of wireless phones. X-ray investigation of the head gave overall OR=1.3, 95% CI=1.1-1.7 for glioma without interaction with use of wireless phones or heredity. In conclusion use of mobile and cordless phone increased the risk for glioma with highest OR for ipsilateral use, latency >10 years and third tertile of cumulative use in hours. In total, the risk was highest in the age group <20 years for first use of a wireless phone.

When initially isotropic three-dimensional (3D) turbulence is compressed along two dimensions, the compression supplies energy directly to the flow components in the compressed directions, while the flow component in the noncompressed direction experiences the effects of compression only indirectly through the nonlinearity of the hydrodynamic equations. Here we study such 2D compressions using numerical simulations. For initially isotropic turbulence, we find that the nonlinearity can be insufficient to maintain isotropy, with the energy components parallel to the compression coming to dominate the turbulent energy, with a number of consequences. Among these are the possibilities for stronger and more easily sustained growth of turbulent energy than in 3D compressions and for an increasing turbulent Mach number even in a compression without thermal losses.

Androgens are critical for normal prostate development and function, as well as prostate cancer initiation and progression. Androgens function mainly by regulating target gene expression through the androgen receptor (AR). Many studies have shown that androgen-AR signaling exerts actions on key events during prostate carcinogenesis. In this review, androgen action in distinct aspects of prostate carcinogenesis, including (i) cell proliferation, (ii) cell apoptosis, and (iii) prostate cancer metastasis will be discussed.

Knowledge about drug interactions with plastic materials used in medical and surgical practice is at an elementary stage. Information that has appeared so far on the sorption of drugs to intravenous fluid containers, delivery sets, syringes, or other plastic apparatus has highlighted that polyvinyl chloride (PVC) is the major offender in this respect. Fortunately, in only a few cases is this sorption phenomenon and loss of drug from fluid likely to present a clinical hazard; in most instances, methods are available to prevent or overcome the problem, providing it is recognized. Current information suggests that the following drugs may exhibit clinically significant sorption to plastic materials: insulin, glyceryl trinitrate (nitroglycerin), diazepam, chlormethiazole, vitamin A acetate, isosorbide dinitrate, and a miscellaneous group of drugs including some phenothiazines, warfarin sodium, hydralazine hydrochloride, and thiopentone sodium. In addition, chloroquine binds strongly to glass and to cellulose acetate, but seemingly not to plastics. Brief details of these interactions and their management are given, together with some preliminary information and warnings on drug interactions (e.g., epinephrine, rifampicin) with hydrophilic contact lenses. The latter interactions may cause irreversible coloration of the lenses.

Camptothecin (CPT), a broad-spectrum anticancer drug, has been extensively used clinically. However, its hydrophobic properties seriously hinder its antitumor therapeutic effect. Herein, we synthesized acid-degradable Fe₃O₄@poly(vinylpyrrolidone) (Fe₃O₄@PVP)/gold nanoclusters@zeolitic imidazolate framework-8 composite nanoparticles (ZIF-8CNPs) via a facile method and utilized them as carriers to efficiently load CPT. The excellent fluorescence properties of gold nanoclusters (AuNCs) and the photothermal properties of Fe₃O₄@poly(vinylpyrrolidone) (Fe₃O₄@PVP) endowed the nanocomposites with excellent cell imaging and photothermal functions. In addition, the surface modification of the composite nanoparticles with folic acid-grafted bovine serum albumin (FA-BSA) enables them to efficiently target tumor cells. Once FA-BSA/ZIF-8CNPs-CPT are taken up by tumor cells and irradiated with a near-infrared laser, the nanoparticles show a highly effective inhibitory effect against various tumor cells through a chemo-photothermal synergistic effect. Hence, it is conceivable that this acid-responsive multifunctional ZIF-8 nanocomposite has promising bioapplication prospects in cancer treatment.

Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver-α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and α-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that GcgrV369M+/+ mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of α-cell proliferation and hyperglucagonemia.

Aneurysms are a rare cause of hemobilia, and usually involved are branches of the hepatic and gastro-duodenal arteries. A case of a patient with hemobilia secondary to a pseudoaneurysm of the cystic artery is presented. Fewer than 10 cases have been reported in the literature, and in all of them the condition was associated with inflammation of the gall bladder, as in our case. Selective hepatic angiography is the procedure of choice for diagnosis. Upper gastrointestinal endoscopy with side-viewing scopy can demonstrate bleeding from papilla. Color-Doppler ultrasonography also may prove to be useful in equivocal cases. Cholecystectomy and ligation of cystic artery with proximal control of the hepatic artery was done at laparotomy after diagnosis was made.

Comparative cognition is an approach that seeks to describe cognitive processes in general computational terms so that the appropriate behavioral testing procedures can be established for any animal, including humans. Some examples of this approach are discussed in the context of memory and attention, emphasizing the ways in which historically disparate research traditions can be integrated together to provide new approaches for behavioral testing in animals. This comparative approach helps to integrate animal models using different species, and to develop tasks that have more direct connection to the assessment of cognitive processes in people.

Integrating soft sensors with wearable platforms is critical for sensor-based human augmentation, yet the fabrication of wearable sensors integrated into ready-to-wear platforms remains underdeveloped. Disposable gloves are an ideal substrate for wearable sensors that map hand-specific gestures. Here, we use solution-based metallization to prepare resistive sensing arrays directly on off-the-shelf nitrile butadiene rubber (NBR) gloves. The NBR glove acts as the wearable platform while its surface roughness enhances the sensitivity of the overlying sensing array. The NBR sensors have a sheet resistance of 3.1 ± 0.6 Ω/sq and a large linear working range (two linear regions ≤70%). When stretched, the rough NBR substrate facilitates microcrack formation in the overlying metal, enabling high gauge factors (62 up to 40% strain, 246 from 45 - 70% strain) that are unprecedented for metal film sensors. We apply the sensing array to dynamically monitor gestures for gesture differentiation and robotic control.

A technique for isolation of adult Schwann cells (ScC) from dorsal root ganglia (DRG) is described. Decapsulated DRG explants embedded into type I collagen gels were cultured for 3 days in serum-free medium during which ScC migrated from the explant. These explants were then grown in serum-supplemented medium to allow ScC proliferation. On day 10 the number of ScC isolated from DRG explants per mouse was about 2.5 x 10(5), and the purity was greater than 95%. This culture system provided sufficient numbers of highly purified adult ScC in a shorter culture period (2-3 times) than other methods. We used ScC from this method to determine the age-related changes in attachment, growth, and survival of ScC cultured in serum-free medium. The attachment capacity of adult ScC on type I collagen or polylysine was similar to that of newborn ScC. However, the collagen promoted growth and survival of adult ScC but not that of neonatal ScC, indicating age-related differences of ScC properties in vitro.

An application of neural networks to the classification of photon-limited images is reported. A three-level feedforward network architecture is employed in which the input units of the network correspond to the pixels of a two-dimensional image. The network is trained in a minicomputer by the use of the backpropagation technique. The statistics of the network components are analyzed, resulting in a method by which the probability of correct classification of a given input image can be calculated. Photon-limited images of printed characters are obtained with a photon-counting camera and are classified. The experimental results are in excellent agreement with theoretical predictions.

In this paper we examine changes in the time American children spent with their parents between 1981 and 1997, and the contribution to these changes made by shifting patterns of female labor force participation, family structure, and parental education. We decompose changes into the parts attributable to changes in demographic characteristics and the parts probably due to changes in behavior. In general, children's time with parents did not decrease over the period; in two-parent families it increased substantially. Population-level changes in demographic characteristics exerted only small direct effects on the time children spent with parents.

Stimulation of lignin peroxidase production by exogenous phospholipids depends on the composition of the phospholipid fraction prepared by using the Nattermann process. The fraction composed mainly of negatively charged phospholipids (NAT 89) was the most efficient source for exoprotein secretion by Phanerochaete chrysosporium INA-12. The results of biochemical marker assays and ultrastructural morphology determination by electron microscopy were correlated. Activities of succinate dehydrogenase, a mitochondrial marker, and cytochrome c oxidoreductase, an endoplasmic reticulum (ER) marker, were increased 1.3- and 2.2-fold, respectively, in the presence of NAT 89. Electron microscopy observations suggested that the amount of mitochondria and ER in culture containing phospholipids was increased at the optimum day of lignin peroxidase production. Therefore, phospholipids enhanced energetic metabolism of strain INA-12 and markedly modified fungus physiology. Since ER is involved in enzyme synthesis, we suggest that its increased amount in mycelium cultured with NAT 89 is directly associated with the higher production of lignin peroxidase.

A cohort of 4,400 persons treated for various cancers of childhood in France and the UK was followed up over an extended period to assess risks of subsequent brain tumour in relation to the radiotherapy and chemotherapy that the children received for their first cancer. Elevated risks of subsequent brain tumours were associated with first central nervous system (CNS) tumour (two-sided p = 0.0002) and neurofibromatosis (two-sided p = 0.001). There was also elevated brain tumour risk (two-sided p = 0.003) associated with ionising radiation exposure, the risk being concentrated among benign and unspecified brain tumours. The radiation-related risk of benign and unspecified brain tumours was significantly higher than that of malignant brain tumours (two-sided p< or =0.05); there was no significant change of malignant brain tumour risk with ionising radiation dose (two-sided p > 0.2). In general, there were no strong associations between alkylating agent dose and brain tumour risk. The only significant association between brain tumour risk and alkylating agent dose was in relation to compounds used (bleomycin, chloraminophen) that are thought not to deliver substantial doses to the brain; the statistical significance of the trend with dose depended on a single case, and thus must be considered a weak result.

The DNA mismatch repair (MMR) pathway removes errors that appear during genome replication. MutS is the primary mismatch sensor and forms an asymmetric dimer that encircles DNA to bend it to scan for mismatches. The mechanism utilized to load DNA into the central tunnel was unknown and the origin of the force required to bend DNA was unclear. We show that, in absence of DNA, MutS forms a symmetric dimer wherein a gap exists between the monomers through which DNA can enter the central tunnel. The comparison with structures of MutS-DNA complexes suggests that the mismatch scanning monomer (Bm) will move by nearly 50 Å to associate with the other monomer (Am). Consequently, the N-terminal domains of both monomers will press onto DNA to bend it. The proposed mechanism of toroid formation evinces that the force required to bend DNA arises primarily due to the movement of Bm and hence, the MutS dimer acts like a pair of pliers to bend DNA. We also shed light on the allosteric mechanism that influences the expulsion of adenosine triphosphate from Am on DNA binding. Overall, this study provides mechanistic insight regarding the primary event in MMR i.e. the assembly of the MutS-DNA complex.

Immediately following the formation of the Solar System, small planetary bodies accreted, some of which melted to produce igneous rocks. Over a longer timescale (15-33 Myr), the inner planets grew by incorporation of these smaller objects through collisions. Processes operating on such asteroids strongly influenced the final composition of these planets, including Earth. Currently there is little agreement about the nature of asteroidal igneous activity: proposals range from small-scale melting, to near total fusion and the formation of deep magma oceans. Here we report a study of oxygen isotopes in two basaltic meteorite suites, the HEDs (howardites, eucrites and diogenites, which are thought to sample the asteroid 4 Vesta) and the angrites (from an unidentified asteroidal source). Our results demonstrate that these meteorite suites formed during early, global-scale melting (> or = 50 per cent) events. We show that magma oceans were present on all the differentiated Solar System bodies so far sampled. Magma oceans produced compositionally layered planetesimals; the modification of such bodies before incorporation into larger objects can explain some anomalous planetary features, such as Earth's high Mg/Si ratio.

When PTSD entered the DSM, advocacy for the diagnosis was a critical part of advocacy for Vietnam veterans. Over the next two decades, the range of contexts in which this clinical concept was applied increased dramatically. In a recent article in Culture, Medicine and Psychiatry, Breslau (2004) describes PTSD as a "prominent cultural model" to account for suffering as well as the synergy between human rights or political advocacy and traumatic stress advocacy. In this article I question the sequence of steps that Breslau took to critique the internationalization of the PTSD construct. I also question Breslau's critique on our work in Nepal. Finally, I will formulate some future challenges for psychiatry and anthropology to bridge their universalistic and relativistic points of view.

The purpose of this article is to evaluate the role of community and interpersonal functioning in the developmental course and outcome of schizophrenic disorders. Based on a review of the research literature, it appears that certain patterns of poor functioning may be characteristic of at least a subgroup of schizophrenic individuals, predate the onset of the disorder, and predict the outcome of the disorder. Thus, some patterns of poor community and interpersonal functioning may be seen as potential indicators of vulnerability to the development of schizophrenic episodes rather than solely as consequences of schizophrenic psychotic symptoms.

UV light and photocatalysts such as titanium dioxide (TiO(2)) and silver (Ag) are useful for disinfection of water and surfaces. However, the effect of UV wavelength on photocatalytic disinfection of spores is not well understood. Inactivation of Bacillus spores has been examined using different UV wavelengths and TiO(2) or TiO(2)/Ag composite materials. The level of UVA disinfection of Bacillus anthracis and Bacillus brevis vegetative cells increased with the presence of the TiO(2) and Ag photocatalysts, but had little effect on their spores. B. brevis spores were slightly more sensitive to UVB and UVC than the spores of B. atrophaeus. Photocatalytic sterilization against spores was strongest in UVC and UVB and weakest in UVA. The rate of inactivation of Bacillus spores was significantly increased by the presence of TiO(2), but was not markedly different from that induced by the presence of Ag. Therefore, TiO(2)/Ag plus UVA can be used for the sterilization of vegetative cells, while TiO(2) and UVC are effective against spores.

The long QT syndrome (LQTS) and the Brugada syndrome (BrS) are the most common genetic causes of malignant ventricular arrhythmias and sudden cardiac death in young patients with normal cardiac morphology. To date, more than 250 different mutations in seven genes have been identified as causing LQTS, whereas the only gene identified to be linked to BrS is SCN5A. In both syndromes, gene-specific mutations have been shown to be associated with specific phenotypic expressions. Risk stratification in LQTS and BrS is based mainly upon a constellation of electrocardiographic findings and a history of prior symptoms. In patients identified as high risk for arrhythmic mortality, the implantable cardioverter defibrillator is the most effective treatment and has been shown to provide near-complete protection during long-term follow-up.

A simple procedure for the measurement of cortisol and 11-deoxycortisol in plasma or serum is described. One-half ml. of plasma is extracted with methylene chloride. Separation of cortisol and deoxycortisol is achieved by a Sephadex LH-20 mini-column. The assay itself is achieved by the use of a commercially available cortisol kit employing rabbit anti-cortisol coated tubes. This antibody exhibits a 20% crossreactivity with 11-deoxycortisol. This procedure is extremely useful in the assessment of a pituitary-adrenal reserve in the Metyrapone test.

Echocardiography (Echo), a widely available, noninvasive, and portable bedside imaging tool, is the most frequently used imaging modality in assessing cardiac anatomy and function in clinical practice. On the other hand, its operator dependability introduces variability in image acquisition, measurements, and interpretation. To reduce these variabilities, there is an increasing demand for an operator- and interpreter-independent Echo system empowered with artificial intelligence (AI), which has been incorporated into diverse areas of clinical medicine. Recent advances in AI applications in computer vision have enabled us to identify conceptual and complex imaging features with the self-learning ability of AI models and efficient parallel computing power. This has resulted in vast opportunities such as providing AI models that are robust to variations with generalizability for instantaneous image quality control, aiding in the acquisition of optimal images and diagnosis of complex diseases, and improving the clinical workflow of cardiac ultrasound. In this review, we provide a state-of-the art overview of AI-empowered Echo applications in cardiology and future trends for AI-powered Echo technology that standardize measurements, aid physicians in diagnosing cardiac diseases, optimize Echo workflow in clinics, and ultimately, reduce healthcare costs.

Pedigree segregation analysis was used to examine several one- and two-locus models of the inheritance of phenylthiocarbamide (PTC) taste deficiency that extend the traditional one-locus recessive model by the addition of either another allele or another locus, and in some cases predict two types of nontasters. These models allow nontaster by nontaster matings to produce taster offspring, consistent with our data and several previous studies which use the Harris and Kalmus [Annals of Eugenics 15:24-32, 1949] dilution method. The models fit our data set of 1,152 individuals from 120 families significantly better than the one-locus recessive model. The best fit was obtained with a two-locus model in which one locus controls PTC tasting and the other locus controls a more general taste ability. This model is consistent with research on the physiology of PTC tasting and with results from genetic linkage studies. Further study is suggested to evaluate better the accuracy of the proposed model.

Electroosmotic flow (EOF) has been widely used in various biochemical microfluidic applications, many of which use viscoelastic non-Newtonian fluid. This study numerically investigates the EOF of viscoelastic fluid through a 10:1 constriction microfluidic channel connecting two reservoirs on either side. The flow is modelled by the Oldroyd-B (OB) model coupled with the Poisson-Boltzmann model. EOF of polyacrylamide (PAA) solution is studied as a function of the PAA concentration and the applied electric field. In contrast to steady EOF of Newtonian fluid, the EOF of PAA solution becomes unstable when the applied electric field (PAA concentration) exceeds a critical value for a fixed PAA concentration (electric field), and vortices form at the upstream of the constriction. EOF velocity of viscoelastic fluid becomes spatially and temporally dependent, and the velocity at the exit of the constriction microchannel is much higher than that at its entrance, which is in qualitative agreement with experimental observation from the literature. Under the same apparent viscosity, the time-averaged velocity of the viscoelastic fluid is lower than that of the Newtonian fluid.

The fluoroquinolones ciprofloxacin (Ciproxin) and ofloxacin (Tarivid) have recently been marketed in Norway. Fluoroquinolones are active against most Gram-negative aerobic pathogens, but have a relatively poor impact on Gram-positive organisms. Mutation in the gyrase-A-gene of a bacteria may lead to resistance to all quinolones. There is little cross-resistance towards other antibiotics. A strong tendency to resistance has been observed among Pseudomonas, Staphylococci and Enterococci. Ciprofloxacin and ofloxacin are administered orally, and are distributed well in the body. The dose should be reduced in elderly patients. Approximately 10% experience adverse effects, mostly in the gastrointestinal and central nervous systems. Ciprofloxacin and ofloxacin are used mainly in the treatment of recurrent and/or complicated urinary tract infections. Other indications include gonorrhea, serious gastrointestinal infections and chronic Salmonella carrier states.

Histone deacetylases (HDAC) family is vital for tumorigenesis and tumor progression. However, the exact role of the HDAC family in clear cell renal cell carcinoma (ccRCC) remains unclear. Based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and The Human Protein Atlas (HPA) database, we investigated and validated the expression profile, clinical significance and prognostic value of HDAC family members in ccRCC. Moreover, we further explored the correlation between HDACs and tumor microenvironment, tumor stemness, drug activity and immune subtype. The HDAC8, HDAC10, and HDAC11 manifested potential clinical value for prognosis, and the correlation analyses reveals underlying molecular mechanisms, which deserve further investigation for ccRCC. This Integrated bioinformatics analysis, based on transcriptomics and proteomics, implied that HDAC8, HDAC10, and HDAC11 may serve as potential molecular biomarkers and therapeutic targets for ccRCC, but some underlying molecular mechanisms still need to be elucidated.

The photocycloaddition reaction between a 4',5'-dihydropsoralen derivative and thymine was studied in solution using a synthetic bichromophoric model 8 in which the two rings are associated by a tetramethylene chain. In water this model molecule exhibits intramolecular ring-ring stacking interactions as evidenced by UV and NMR spectroscopies. Irradiation at 365 nm at usual concentrations (greater than or equal to 5.10(-4) M) leads exclusively to a regio- and stereo-selective dimerization reaction involving the 3,4 double bonds of the psoralen moities. Extreme dilutions (ca less than or equal to 2.10(-5) M) were necessary to observe the intramolecular reaction which results in the exclusive formation of a 3,4 cis-anti adduct. This reaction is completely reversed by irradiation at 254 nm. These results are discussed with regard to the behavior of the homologous models in which the furan part of the psoralen ring is not hydrogenated. These latter compounds also lead exclusively to a 3,4 cis-anti adduct. It appears that saturation of the furan ring increases strongly the quantum yield of the photoaddition at 365 nm (0.01----0.18) and that the triplet excited state of the 4',5'-dihydropsoralen is involved in the photoaddition.

Borderline coronary lesions are responsible for about 80% of acute coronary syndromes (ACS). Statins have been found to improve long-term prognosis in patients with coronary artery disease due to plaque stabilization. There are no reports on the frequency of new events caused by progression of borderline lesions in patients with (ACS). Percutaneous coronary intervention (PCI) as a method of mechanical stabilization of borderline coronary lesions could be an alternative to pharmacological approach.

Letitia Fairfield - doctor, lawyer, public health worker, feminist and war worker - was a woman of surprising contradictions. She displayed some eccentric tendencies that sometimes did not sit comfortably with her role as a medical professional; she was, for example, a believer in witchcraft and a convert to Roman Catholicism. However, she made great contributions to medicine throughout her active career and did so during a period in which female access to medical education was limited. Few of her female or male peers received such respect or oversaw such change. Despite pushing contemporary professional boundaries and reaching a level of seniority unusual for female doctors of her era, however, Letitia was, whether through choice or through convention, channelled into traditionally female areas of medicine. Thus, her medical success arguably was due not only to her motivation and capability but also because she represented no real competition to men.

Human B lymphocytes have been shown to have at least five polymorphic specificities defined by 32 antisera. The antisera were produced by absorption with pooled platelets to remove HLA activity and were selected out of over 400 tested sera. The sera that defined the five specificities had high correlation coefficients within a group (generally in the range of 0.6-0.9). As shown by the fit in the Hardy-Weinberg equilibrium, the five specificities appear to be determined by alleles at one genetic locus. No association between these specificities and HLA was noted.

Adenosine triphosphate (ATP) induces the release of catecholamines, endogenous ATP, and soluble protein from chromaffin granules isolated from the adrenal medulla. When ATP exerts this action, it is hydrolyzed by enzymes present in the granule membrane, and part of the Pi liberated from ATP is transferred to the protein and lipid of the granule membrane. The phosphorylated lipid component, which was identified by thin-layer and ion-exchange chromatography as diphosphatidylinositol, was formed from ATP and monophosphatidylinositol. This latter phospholipid was the substrate for the enzyme phosphatidylinositol kinase. Both substrate and enzyme are components of the granule membranes, because they have a similar subcellular distribution as dopamine beta-hydroxylase (a granule membrane marker). The formation of diphosphatidylinositol was Mg(2 plus)-dependent, it was further stimulated by Mn(2 plus), it was inhibited by N-ethylmaleimide and the reaction had an optimal pH of 5. The synthesis of diphosphatidylinositol was also shown to occur in chromaffin granules "in situ". during the stimulation of the adrenal medulla by acetylcholine.

Neurofibromatosis type 1 (NF1) is increased about 150-fold in autistic patients. The aim of this study was to test for an association between the NF1 locus and autistic disorder. The allele distributions of three markers of the NF1 gene were studied in 85 autistic patients and 90 controls. No differences in allele distributions were observed. However, we found a new allele (allele 5) of the GXAlu marker in four autistic patients. Allele 5 was absent in a larger control population (213 individuals). The patients with allele 5 had a more severe clinical picture, mainly in the fields of motility and tonus. Our preliminary results suggest that the NF1 region is not a major susceptibility locus for autism. However, the GXAlu marker of the NF1 gene appears as a possible candidate for a susceptibility locus in a small subgroup of severely affected autistic patients. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:729-732, 1999.

Extraskeletal chondrosarcomas are rare and there is only one reported case of primary pancreatic chondrosarcoma. We report the case of a 34-year-old woman with a 6-month history of abdominal pain and distention. Radiological studies indicated a mass in the pancreas, and exploratory laparotomy revealed a tumour of the pancreas extending to the hepatic vessels and hepatoduodenal ligament. The mass was completely excised, and the histopathological diagnosis was primary mesenchymal pancreatic chondrosarcoma. Tumour recurred at follow-up 52 months postoperatively.

In 261 girls year-to-year morphofunctional transformations of spatial composition of the skin microcirculatory bed have been studied at rest and after a dynamic local load. By means of biomicroscopy main regularities in development of the skin capillary network have been revealed in the nail torus in the postnatal ontogenesis. Formation of the microvessels reactivity during various age periods and maturation of mechanisms of the compensatory-adaptive reactions are connected with formation of the definitive composition of the microcirculatory bed, that in girls corresponds to 11-12 years. Qualitative transformations in the skin capillary network bring certain quantitative changes in the structural microcirculatory parameters--increasing diameter of microvessels and increasing density of functioning capillaries.

Eye movement research during the last year is discussed. The review covers the fields of: memory-guided saccades in supplementary motor area lesions, and the vertical saccadic system; cerebral hemispheric localization of smooth pursuit asymmetry; oculomotor disturbances in Wallenberg's syndrome; locomotory gaze instability in vestibular dysfunction; smooth pursuit disorders in vermal infarct; physiologic end-point and rebound nystagmus and the results of surgical and optical treatment of manifest latent nystagmus; clinical/magnetic resonance imaging correlations in abnormalities of horizontal gaze; mesencephalic cholinergic nuclei in progressive supranuclear palsy; as well as mesencephalic damage in diabetic third nerve palsy, divisional oculomotor nerve paresis; and new hypotheses on eye muscle susceptibility in myasthenia gravis.

The tensor fasciae latae flap is a well known musculocutaneous flap used for many indications in the field of plastic surgery. The flap has some modifications to fit different reconstructive requirements of the defects. Osseous-muscle flap, osseous musculocutaneous flap, muscle flap, muscle-fascial flap and musculocutaneous-fasciocutaneous flap are some known alternatives. We used a modification of this well-known flap as musculocutaneous and fascia flap for a composite reconstruction of groin and urogenital defect. We reconstructed the groin defect with musculocutaneous part of the flap, and the defect over neourethra with the fascial extension and grafting. The aim of this modification was to reconstruct a genital defect with a thin and more pliable tissue to overcome the problem of distortion, kinking and thickness of the flap.

Idiopathic pneumoperitoneum has an unknown etiology despite exploratory laparotomy. However, it may occur without definite abdominal symptoms; thus, adequate management could be in clinical dilemma. We experienced three cases of idiopathic nonsurgical pneumoperitoneum in healthy individuals during a health check-up. Their cases were not accompanied by any relevant etiology or definite abdominal symptoms. All of the three cases exhibited a benign clinical course. The three patients underwent an abdominal computed tomography (CT) scan as part of a health check-up program, which incidentally revealed free air in the right paracolic gutter without evidence of visceral perforation or inflammation. Among the three cases, two patients underwent colonoscopy before abdominal CT, whereas one patient did not. Two cases were completely asymptomatic and were observed without any treatment in the outpatient clinic. Only the third case with minimal symptoms was treated conservatively for a short time. If a small amount of free air typically located in the right paracolic gutter is detected in the absence of perforation during colonoscopy, close observation without unnecessary treatment would be sufficient.

Immune checkpoint inhibitors (ICIs) are antibodies that target certain immune checkpoints (ICs), such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) or its ligand (PD-L1), and have emerged as a powerful new tool for oncologists. As these immune checkpoints are crucial for immunological self-tolerance, such therapies can trigger autoimmune adverse effects. Endocrine complications are among the most common, including hypophysitis, thyroid dysfunction, diabetes mellitus and primary adrenal insufficiency, while autoimmune polyendocrine syndrome type 2 (APS-2) may also present. The aim of this article is to critically appraise the literature and present (i) the biological role and function of the main ICs, (ii) the use of ICIs in the treatment of various cancer types, (iii) the endocrine complications of cancer immunotherapy with ICIs and (iv) practical recommendations for screening and management of patients with such endocrinopathies in everyday clinical practice.

The occurrence of "secondary crashes" is one of the critical yet understudied highway safety issues. Induced by the primary crashes, the occurrence of secondary crashes does not only increase traffic delays but also the risk of inducing additional incidents. Many highway agencies are highly interested in the implementation of safety countermeasures to reduce this type of crashes. However, due to the limited understanding of the key contributing factors, they face a great challenge for determining the most appropriate countermeasures.

Psychoactive substances are ubiquitous in the environment at low concentrations, and tobacco, cannabis, etc. are all widely-existing examples. Given their potent biological activity, psychoactive substances are suspected to be harmful to the environment, and reports of their ecological risks are gradually increasing. Since the 1990s, the investigations into psychoactive substances have made remarkable progress, yet some research fields still need to be modernised. For example, the unification of standardised analytical methods as well as the supplementation of occurrence literature. In addition, a relatively lagging risk evaluation system caused by a lack of toxicity data is particularly in need of improvement. The purpose of this article is to develop a review of current research on psychoactive substances, including analytical methods, distribution in environmental compartments, and ecological risk assessment, as well as to point out deficiencies and development prospects and to offer motivation for enhancing the research level in this field.

Mg-ATP particles from bovine heart mitochondria have more than 95% of their F1 in complex with the inhibitor protein (IF1). The F1-IF1 complex was solubilized and purified. The question addressed was if this naturally occurring complex existed as monomers or dimers. Size exclusion chromatography and electron microscopy showed that most of the purified F1-IF1 complex was a dimer of two F1-IF1. As determined by the former method, the relative concentrations of dimeric and monomeric F1-IF1 depended on the concentration of protein that was applied to the column. Apparently, there is an equilibrium between the two forms of F1-IF1.

COVID-19 was officially declared a pandemic in March 2020. Since then, our understanding of its effects on pregnancy have evolved rapidly. Emerging surveillance data and large cohort studies suggest that pregnancy is associated with an increased risk of intensive care unit hospitalization, invasive ventilation, and death. Pregnancies complicated by SARS-CoV-2 infection are associated with increased likelihood of cesarean delivery and preterm birth. Intrauterine transmission occurs, but seems to be rare. Critical gaps remain, and rigorous high-quality data are needed to better ascertain pregnancy risks and to inform antenatal and obstetrical management.

There is an increasing body of evidence to suggest that benign rolandic epilepsy and benign occipital epilepsy of childhood are frequently associated with migraine. This however has not been universally recognized. Clearly further investigation of this association is required. The purpose of this report is to examine the varied diagnostic criteria for common migraine utilized by epileptologists and other neurologists, to review clinical migraine epilepsy relationships, EEG abnormalities in migraine and epilepsy, and the association of seizures with vascular headache in patients with various forms of epilepsy. Hopefully, this will stimulate further research into this intriguing association of two conditions which though they have different pathophysiology frequently coexist.

The analysis of oscillatory EEG phenomena such as interregional coherence (task-related coherence [TRCoh] or event-related coherence) has advanced our knowledge of neurophysiological processes underlying the performance and learning of skilled finger movements. It has become clear that various types of higher task demands are reflected by changes in the functional coupling of different cortical areas and not only by changes in regional activation. Neuroscientists are merely starting to understand how coherent oscillations might encode information in the human motor system ("sensorimotor binding") and how well this can be measured from the surface EEG. However, interregional coherence is a potentially independent mechanism that can, up to now, only be investigated with electrophysiological techniques such as EEG and MEG. The studies reviewed below focus on coherence of finger movements and motor learning: increasing complexity of a movement sequence, internal rhythm generation, visuomotor integration, deficits in interhemispheric coupling, and bimanual coordination. Evidence is presented for a special functional significance of TRCoh in the beta frequency range (13 to 21 Hz) for information processing in large-scale sensorimotor networks during motor tasks.

We report on emission and detection of pulsed terahertz radiation of radial and azimuthal polarization by microstructured photoconductive antennas. To this end the electrode geometry of the emitter is inverse to the desired THz field pattern and a second periodic structure prevents destructive interference effects. Beam profiles of freely propagating THz waves are studied for divergent and refocused beams. They can be well described as the lowest order Bessel-Gauss modes with a divergence comparable to linearly polarized Gaussian beams. Additionally, mode sensitive detection is demonstrated for radially polarized radiation.

Bile acids (BAs) regulate the absorption of fat-soluble vitamins, cholesterol and lipids but have also a key role as signaling molecules and in the modulation of epithelial cell proliferation, gene expression and metabolism. These homeostatic pathways, when disrupted, are able to promote local inflammation, systemic metabolic disorders and, ultimately, cancer. The effect of hydrophobic BAs, in particular, can be linked with cancer in several digestive (mainly oesophagus, stomach, liver, pancreas, biliary tract, colon) and extra-digestive organs (i.e. prostate, breast) through a complex series of mechanisms including direct oxidative stress with DNA damage, apoptosis, epigenetic factors regulating gene expression, reduced/increased expression of nuclear receptors (mainly farnesoid X receptor, FXR) and altered composition of gut microbiota, also acting as a common interface between environmental factors (including diet, lifestyle, exposure to toxics) and the molecular events promoting cancerogenesis. Primary prevention strategies (i.e. changes in dietary habits and lifestyle, reduced exposure to environmental toxics) mainly able to modulate gut microbiota and the epigenome, and the therapeutic use of hydrophilic BAs to counterbalance the negative effects of the more hydrophobic BAs might be, in the near future, part of useful tools for cancer prevention and management.

Incidence and clinical manifestations of main morphological variants of primary glomerulonephritis (2142 biopsies) were studied retrospectively. Correlative changes in the clinical and morphological structure of primary glomerulonephritis with the increase in the incidence of nephrotic forms (minimal alterations, focal segmental glomerulohyalinosis, membranous nephropathy) and a trend to reduce the mesangiocapillary glomerulonephritis in patients with nephrotic and nephrotic-hypertensive syndrome were noted. A bimodal distribution of patients with membranous nephropathy with increasing age probably indicate the change of etiologic factors in the age groups.

Bladder cancer (BC) is the 10th most frequent cancer in the world. The initial diagnosis and surveillance of BC require a combination of invasive and non-invasive methods, which are costly and suffer from several limitations. Cystoscopy with urine cytology and histological examination presents the standard diagnostic approach. Various biomarkers (e.g., proteins, genes, and RNAs) have been extensively studied in relation to BC. However, the new trend of liquid biopsy slowly proves to be almost equally effective. Cell-free DNA, non-coding RNA, and other subcellular structures are now being tested for the best predictive and diagnostic value. In this review, we focused on published gene mutations, especially in DNA fragments, but also epigenetic modifications, and non-coding RNA (ncRNA) molecules acquired by liquid biopsy. We performed an online search in PubMed/Medline, Scopus, and Web of Science databases using the terms "bladder cancer", in combination with "markers" or "biomarkers" published until August 2022. If applicable, we set the sensitivity and specificity threshold to 80%. In the era of precision medicine, the development of complex laboratory techniques fuels the search and development of more sensitive and specific biomarkers for diagnosis, follow-up, and screening of BC. Future efforts will be focused on the validation of their sensitivity, specificity, predictive value, and their utility in everyday clinical practice.

Scabies was adopted by the World Health Organization (WHO) as a Neglected Tropical Disease in 2017. There is currently no formal global scabies control programmes or existing WHO guidelines on scabies control although at least two countries, Fiji and Ethiopia, have adopted national approaches to scabies control. In February 2019 WHO held a first Informal Consultation on a Framework for Scabies Control, in part as a response to multiple national requests for guidance on public health management in high disease burden areas. Below we outline control strategies proposed at this meeting and summarise the role that modelling can play in supporting the development of evidence to translate these proposals into formal WHO recommendations and national and global control programmes. Provisional proposals discussed at the WHO Informal Consultation for a scabies control programme include the use of mass drug administration when the community prevalence of scabies is ≥ 10% (generally considered to reflect a childhood prevalence of at least 20%) and the use of intensified case management when the prevalence is below 10%.

Bidirectional changes in synaptic transmission have the potential to optimize the control of movement. However, it can be difficult to establish a causal relationship between the bidirectionality of synaptic plasticity and bidirectional changes in the speed of actual movements. We asked whether metabotropic glutamate receptor 1 (mGluR1) receptors, which participate in cerebellar long-term depression (LTD), are necessary for bidirectional motor learning in the vestibulo-ocular reflex (VOR). Cerebellar LTD and long-term potentiation (LTP) are thought to cause increases and decreases, respectively, in the gain of the VOR; the direction of learning depends on the behavioral protocol. We injected either the mGluR1 agonist (S)-DHPG or the antagonist YM 298198 bilaterally into the flocculus of alert cats, and then induced motor learning. In the presence of YM 298198, the VOR gain decreased in gain-up, as well as in gain-down protocols. (S)-DHPG augmented gain-up learning. Gain-down learning was not significantly affected by either drug. These results supported the hypothesis that gain-up learning relies on cerebellar LTD, but gain-down learning relies on a different mechanism. In the absence of mGluR1 activity, cerebellar LTD may be replaced with LTP, permitting learning in only one direction.

This study investigated the effects of perinatal genistein (GEN) exposure on the central nervous system of rat offspring. Pregnant dams orally received GEN (1 or 10 mg/kg/day) or vehicle (1 ml/kg/day) from gestation day 10 to postnatal day 14. In order to assess the effects of GEN on rat offspring, we used a battery of behavioral tests, including the open-field, elevated plus-maze, MAZE and step-through passive avoidance tests. MAZE test is an appetite-motivation test, and we used this mainly for assessing spatial learning and memory. In the MAZE test, GEN groups exhibited shorter latency from start to goal than the vehicle-treated group in both sexes. On the other hand, performances in the step-through passive avoidance test were non-monotonically inhibited by GEN in both sexes, and a significant difference was observed in low dose of the GEN-treated group compared to the vehicle-treated group in female rats. Furthermore, we found that perinatal exposure to GEN did not significantly alter locomotor activity or emotionality as assessed by the open-field and elevated-plus maze tests. These results suggest that perinatal exposure to GEN improved spatial learning and memory of rat offspring, but impaired their passive avoidance learning and memory.

Genome-wide association studies have identified twenty loci associated with late-onset Alzheimer disease (LOAD). We examined each of the twenty loci, specifically the ±50kb region surrounding the most strongly associated variant, for changes in gene(s) transcription specific to LOAD. Post-mortem human brain samples were examined for expression, methylation, and splicing differences. LOAD specific differences were detected by comparing LOAD to normal and "disease" controls. Eight loci, prominently ABCA7, contain LOAD specific differences. Significant changes in the CELF1 and ZCWPW1 loci occurred in genes not located nearest the associated variant, suggesting that these genes should be investigated further as LOAD candidates.

Structural distributions of each amino acid were compared between 20 pairs of thermophilic and mesophilic proteins to obtain thermostable factors. Five kinds of residual structure states such as fully-exposed, exposed, partially exposed (or partially buried), buried, well-buried states were considered for analyzing the structural patterns of amino acids. The statistical tests revealed that lower frequency in partially exposed state of SER, lower frequency in exposed state and higher frequency in well-buried state of ALA, higher frequency in buried state of GLU, higher frequency in exposed state of ARG, etc. could be critical factors related with protein thermostability.

Segregated-network carbon nanotube (CNT)-polymer composites were prepared, and their thermoelectric properties were measured as a function of CNT concentration at room temperature. This study shows that electrical conductivity can be dramatically increased by creating a network of CNTs in the composite, while the thermal conductivity and thermopower remain relatively insensitive to the filler concentration. This behavior results from thermally disconnected, but electrically connected, junctions in the nanotube network, which makes it feasible to tune the properties in favor of a higher thermoelectric figure of merit. With a CNT concentration of 20 wt %, these composites exhibit an electrical conductivity of 4800 S/m, thermal conductivity of 0.34 W/m x K and a thermoelectric figure of merit (ZT) greater than 0.006 at room temperature. This study suggests that polymeric thermoelectrics are possible and provides the basis for further development of lightweight, low-cost, and nontoxic polymer composites for thermoelectric applications in the future.

A total of 128 bovine and 134 human group B streptococci were serotyped by conventional methods. Among the bovine cultures, 60 (47%) had type antigen X, and among the human cultures, 53 (39%) had type antigen R. The occurrence of type antigens X and R was significantly related to the growth pattern of the bacteria in fluid media. Type X- and R-positive cultures and most of the nontypeable cultures predominantly formed long chains and grew as granular sediment with clear supernatant. In addition, group B streptococci with surface antigen X or R showed compact colony formation in soft agar and reacted positively in the salt aggregation test. These properties, possibly caused by the surface charges of the X- and R-positive cultures, might be related to bacterial pathogenicity.

Five women with multiple sclerosis (MS) and simple urinary stress incontinence were informally evaluated and taught a program of pubococcygeal exercises to determine if inadvertent loss of urine during activities which increase intraabdominal pressure could be improved or eliminated. A correlation seemed to exist between the client's ability to experience vaginal contraction during sexual climax and elimination or improvement of simple urinary stress incontinence using a pubococcygeal exercise program. The purpose of this article is to encourage nurses to consider a pubococcygeal teaching program for treatment of simple urinary stress incontinence in female clients with MS who do experience vaginal contraction during sexual climax.

A shared enthusiasm towards the highly promising utility of stem cell research brought together clinicians and scientists from academic institutions, government, and industry at the Second Annual International Stem Cells and Regenerative Medicine meeting presented by GeneExpression Systems, Inc. earlier this year. A common theme was echoed by presenters that a deeper understanding of natural development of the whole organism and individual organ systems is needed. Armed with this greater knowledge, a more efficient and conscientious translation of stem cell research may be achieved. Guest lectures included presentations by Dr. Elizabeth H. Blackburn, Dr. Irving L. Weissman, and Dr. Erin Lavik. Attendees were updated and encouraged by these and several other speakers on such topics as stem cell biology, epigenetics, biotechnology, regenerative medicine, tissue engineering, and bioethics. Biomedical engineers and scientists are making steady strides in designing specific three dimensional scaffolds, tracking and controlling stem cells. The future of stem cell research continues to be promising with applications for treating cardiac and neurodegenerative diseases, hearing loss, diabetes, and so on.

The memory resistor with the moniker memristor was a harmless postulate in 1971. Since 2008 a device that claims to be the memristor is on the prowl, seeking recognition as a fundamental circuit element, sometimes wanting electronics textbooks to be rewritten, always promising remarkable digital, analog and neuromorphic computing possibilities. A systematic discussion about the fundamental nature of the device is almost absent within the memristor community. Advocates use incomplete constitutive relationships, ignore concepts of activity/passivity and aver that nonlinearity is central to their case. Few researchers have examined these claims. Our report investigates the assertion that the memristor is a fundamental passive circuit element, from the fresh perspective that electrical engineering is the science of charge management. We demonstrate with a periodic table of fundamental elements that the 2008 memristor is not the 1971 postulate and neither of them is fundamental. The ideal memristor is an unphysical active device and any physically realizable memristor is a nonlinear composition of resistors with active hysteresis. We also show that there exists only three fundamental passive circuit elements.

Hand hygiene is the primary measure to prevent healthcare-associated infections and the spread of antimicrobial resistance. Low staff compliance remains a major problem. Successful promotion requires a multimodal strategy. The World Health Organization (WHO) proposes an approach including at least five components: system change, in particular the recourse to alcohol-based hand rubbing as the new standard of care, staff education using newly developed tools, monitoring and feedback of staff performance, reminders in the workplace, and promotion of an institutional safety climate. Patient participation in hand hygiene promotion is under testing. Early results of the strategy tested in a large number of healthcare settings in both limited- and high-resource countries are extremely encouraging.

Label="BACKGROUND" NlmCategory="BACKGROUND">Diabetes mellitus (DM) is a prime risk factor for cardiovascular disease. The convincing experimental and clinical evidence indicated that the onset of DM is closely associated with oxidative stress and that the generation of reactive oxygen species increases in both the types of diabetes. The aim of the present study was to evaluate the effect of <i>Teucrium polium</i> (TP) hydroalcoholic extract on the blood glucose, cholesterol, triglyceride, and oxidative stress markers of the heart and aorta in streptozotocin (STZ)-induced diabetic rats.

SARS-CoV-2 infection poses a global health crisis. In parallel with the ongoing world effort to identify therapeutic solutions, there is a critical need for improvement in the prognosis of COVID-19. Here, we report plasma proteome fingerprinting that predict high (hospitalized) and low-risk (outpatients) cases of COVID-19 identified by a platform that combines machine learning with matrix-assisted laser desorption ionization mass spectrometry analysis. Sample preparation, MS, and data analysis parameters were optimized to achieve an overall accuracy of 92%, sensitivity of 93%, and specificity of 92% in dataset without feature selection. We identified two distinct regions in the MALDI-TOF profile belonging to the same proteoforms. A combination of SDS-PAGE and quantitative bottom-up proteomic analysis allowed the identification of intact and truncated forms of serum amyloid A-1 and A-2 proteins, both already described as biomarkers for viral infections in the acute phase. Unbiased discrimination of high- and low-risk COVID-19 patients using a technology that is currently in clinical use may have a prompt application in the noninvasive prognosis of COVID-19. Further validation will consolidate its clinical utility.

Using a novel natural cryoprotectant to maintain better quality of frozen aquatic products is attracting increasing interests in recent years. This study investigated the cryoprotective effects of bamboo shoot nanocrystalline cellulose (NCC) on <i>Nemipterus virgatus</i> surimi during 60&#160;days of frozen storage. Compared with surimi without any cryoprotectant, NCC addition significantly retard the quick decrease of salt soluble protein content, Ca²⁺-ATPase activity and sulfhydryl content of myofibrillar protein. SDS-PAGE results suggested that NCC could protect the structural integrity of myofibrillar protein, which was confirmed by the enhanced stability of &#945;-helix content of protein. It was also observed that surimi gel incorporated with NCC showed improved gel strength and a more compact microstructure with dense surfaces. This study demonstrated that NCC could potentially serve as a novel natural cryoprotectant for the surimi.

We previously showed that mRNAs synthesized from three genes that naturally lack introns contain a portion of their coding sequence, known as a cytoplasmic accumulation region (CAR), which is essential for stable accumulation of the intronless mRNAs in the cytoplasm. The CAR in each mRNA is unexpectedly large, ranging in size from ∼160 to 285 nt. Here, we identified one or more copies of a 10-nt consensus sequence in each CAR. To determine whether this element (designated CAR-E) functions in cytoplasmic accumulation of intronless mRNA, we multimerized the most conserved CAR-E and inserted it upstream of β-globin cDNA, which is normally retained/degraded in the nucleus. Significantly, the tandem CAR-E, but not its antisense counterpart, rescued cytoplasmic accumulation of β-globin cDNA transcripts. Moreover, dinucleotide mutations in the CAR-E abolished this rescue. We show that the CAR-E, but not the mutant CAR-E, associates with components of the TREX mRNA export machinery, the Prp19 complex and U2AF2. Moreover, knockdown of these factors results in nuclear retention of the intronless mRNAs. Together, these data suggest that the CAR-E promotes export of intronless mRNA by sequence-dependent recruitment of the mRNA export machinery.

G protein-coupled receptors (GPCRs) play a central role in eukaryotic signal transduction. However, the GPCR component of this signalling system, at the early origins of metazoans is not fully understood. Here we aim to identify and classify GPCRs in Amphimedon queenslandica (sponge), a member of an earliest diverging metazoan lineage (Porifera). Furthermore, phylogenetic comparisons of sponge GPCRs with eumetazoan and bilaterian GPCRs will be essential to our understanding of the GPCR system at the roots of metazoan evolution.

Migraine is an important health problem that negatively affects individuals' activities of daily living. The decrease in the quality of life because of migraine increases the need for the development of new pharmacological and nonpharmacological treatment methods for pain management. Limited studies have reported the application of a traditional therapy, such as Su Jok seed therapy, to prevent or minimize migraine. This study aimed to examine the effect of Su Jok seed therapy on the severity, duration, and frequency of headaches in patients with migraine.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nt that are involved in cardiovascular diseases (CVDs). To determine whether lncRNAs are involved in stable angina pectoris (SAP), we analysed the expression profile of lncRNAs and mRNAs on a genome-wide scale in SAP of Uyghur population. Five pairs of SAP patients and healthy controls were screened by an Agilent microarray (human lncRNA + mRNA Array V4.0). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the lncRNA expression levels in 50 SAP and 50 controls. Data analyses were performed using R and Bioconductor. A total of 1871 up- and 231 down-regulated lncRNAs were identified to be differentially expressed in the peripheral blood mononuclear cells (PBMCs). Microarray analysis results identified the lncRNAs NR_037652.1, ENST00000607654.1, ENST00000589524.1 and uc004bhb.3, which were confirmed by qRT-PCR. Among screened lncRNAs, the annotation result of their co-expressed mRNAs showed that the most significantly related pathways were the NF-κB signalling pathway, apoptosis and the p53 signalling pathway, while the main significantly related diseases were the cholesterol, calcium and coronary disease. Our study indicated that clusters of lncRNAs were significantly differentially expressed between SAP patients and matched controls. These lncRNAs may play a significant role in SAP development and could serve as biomarkers and potential targets for the future treatment of SAP.

Canine atopic dermatitis is a genetically predisposed inflammatory and pruritic allergic skin disease that is often complicated by (secondary) bacterial and fungal (yeast) infections. High-throughput DNA sequencing was used to characterize the composition of the microbiome (bacteria and fungi) inhabiting specific sites of skin in healthy dogs and dogs with atopic dermatitis (AD) before and after topical antimicrobial treatment. Skin microbiome samples were collected from six healthy control dogs and three dogs spontaneously affected by AD by swabbing at (non-) predilection sites before, during and after treatment. Bacteria and fungi were profiled by Illumina sequencing of the 16S ribosomal RNA gene of bacteria (16S) and the internally transcribed spacer of the ribosomal gene cassette in fungi (ITS). The total cohort of dogs showed a high diversity of microbes on skin with a strong individual variability of both 16S and ITS profiles. The genera of Staphylococcus and Porphyromonas were dominantly present both on atopic and healthy skin and across all skin sites studied. In addition, bacterial and fungal alpha diversity were similar at the different skin sites. The topical antimicrobial treatment increased the diversity of bacterial and fungal compositions in course of time on both AD and healthy skin.

Oxidative stress plays a crucial role in traumatic brain injury (TBI) pathogenesis. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) formed in excess after TBI synergistically contribute to secondary brain damage together with lipid peroxidation products (reactive aldehydes) and inflammatory mediators. Furthermore, oxidative stress, endoplasmic reticulum stress and inflammation potentiate each other. Following TBI, excessive oxidative stress overloads the endogenous cellular antioxidant system leading to cell death. To combat oxidative stress, several antioxidant therapies were tested in preclinical animal models of TBI. These include free radical scavengers, activators of antioxidant systems, Inhibitors of free radical generating enzymes and antioxidant enzymes. Many of these therapies showed promising outcomes including reduced edema, blood-brain barrier (BBB) protection, smaller contusion volume, and less inflammation. In addition, many antioxidant therapies also promoted better sensory, motor, and cognitive functional recovery after TBI. Overall, preventing oxidative stress is a viable therapeutic option to minimize the secondary damage and to improve the quality of life after TBI.

We describe a 32 year old male with a distal 6p24.3-->pter deletion. He has specific developmental anomalies of the anterior chamber of the eye and a cleft uvula which is consistent with the recent localisation of genes for iris development and orofacial clefting to distal 6p. In addition he has progressive sensorineural deafness and this may localise a gene for deafness to this region. We conclude that a refined distal 6p deletion syndrome exists and includes a characteristic facial appearance with hypertelorism, downward slanting palpebral fissures, tented mouth, smooth philtrum, palatal malformation, ear anomalies, anterior chamber eye defects, progressive sensorineural deafness, cardiac defects, abdominal herniae, small external genitalia, and motor and speech delay.

Extrapulmonary Pneumocystis infection has been increasingly reported in patients with acquired immune deficiency syndrome (AIDS), in particular, recently in association with the increasing use of aerosolized pentamidine. This report describes the unusual presentation of extrapulmonary Pneumocystis infection as a thyroid neck mass and clinical hypothyroidism in a 37-year-old man with hemophilia and AIDS. This case differs from the previously reported single case of isolated thyroid pneumocystosis in the presence of a rapidly enlarging neck mass, lack of previous Pneumocystis, and prior prophylaxis with aerosolized pentamidine. The pathologic and electron microscopic description of the peculiar flocculent necrotic thyroid material is contrasted with typical pulmonary alveolar findings in Pneumocystis pneumonia (PCP), the differential diagnoses of a rapidly expanding neck mass, and diagnostic difficulties of hypothyroidism in patients with AIDS are discussed. Finally, it is emphasized that use of aerosolized pentamidine, although successful for prevention of pulmonary PCP, may be insufficient to prevent extrapulmonary infection.

Of all known arrhythmia's, atrial fibrillation (AF) is the most often met in the clinical setting and it is associated with an increase in mortality risk. Several risk factors for AF have been described and several mechanisms of induction and maintenance have been proposed. Studies in patients with AF have shown that structural changes occur in the atria, but the relationship between the structural remodelling and the chronicity of the arrhythmia are not well understood. The changes mainly concern adaptive (dedifferentiation of cardiomyocytes) and maladaptive (degeneration of cells with replacement fibrosis) features. In order to characterise the time course of the structural remodelling the need for animal models which adequately mimic chronic atrial fibrillation in humans is felt essential. In this review, the structural changes that are observed during prolonged sustained AF in patients and animal models, are described. Furthermore, the time course and potential mechanisms of structural remodelling are discussed and methods for elucidation of the underlying molecular mechanisms are presented.

Anterior segment surgery via the pars plana was done on 114 eyes with the Klöti vitreous stripper between January, 1977 and December 31, 1982. In every case the posterior capsule was removed when present and anterior or total vitrectomy was performed. None of the 114 eyes had a history of retinal detachment prior to nor at the time of anterior segment surgery. There were 37 cases of trauma in this series. Follow-up varied from 1 to 66 months with 58% of cases having a follow-up of greater than one year. There was a 10.50% post-operative retinal detachment rate (12/114 eyes). Seven detachments occurred in the 37 traumatized eyes (19.10%) versus 5 detachments in 77 non-traumatized eyes (6.49%). Of the 12 detachments, 7 presented signs of severe proliferative vitreoretinopathy (PVR) while the remaining 5 detachments appeared to be uncomplicated. No detachment was related to an iatrogenic tear and no case of PVR seemed to be related to the sclerotomy site. Successful reattachment was achieved in 3 out of 4 uncomplicated cases and 3 out of 5 cases with PVR. Vitrectomy and posterior capsulectomy are often mandatory in anterior segment problems: pupillary membranes, secondary cataracts, lens ectopiae and dislocations, vitreous wick and vitreocorneal touch. In our opinion other indications for vitrectomy and posterior capsulectomy are congenital, juvenile and post-uveitis cataracts.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of transforming growth factor beta1 (TGF beta1) in airway remodeling in asthma and chronic obstructive pulmonary disease (COPD) has not been fully described. To evaluate the possible pathogenetic role of TGF beta1 in asthma and COPD, immunohistochemical expression of TGF beta1 was described in bronchial biopsies from patients with asthma and COPD compared with healthy individuals. Twelve subjects with asthma, 13 subjects with COPD, and 10 healthy individuals enrolled in the study. Bronchial biopsies were stained with hematoxylin and eosin and anti-TGF beta1 antibody. As a result, immunoreactive TGF beta1 was mainly localized in association with connective tissue in all groups. The staining intensity was not statistically different among the groups in bronchial epithelium, whereas it was significantly higher in the group of asthma in the submucosa. Because there is evidence showing a significant increase of staining intensity in the submucosa from asthmatics but not from subjects with COPD, we may conclude that TGF beta1 may play a significant role in pathogenesis of asthma but not in COPD.