[Acute and long-term psychological problems following hypoglycemias].
1. Detection of hypoglycaemic episodes is of psychiatric importance with respect to acute therapy, long-term treatment, which includes consideration of changes in specific behaviour patterns, and also forensic questions. 2. All possible therapeutic efforts must be focussed on the avoidance of repeated hypoglycaemic episodes to ensure the prevention of organic psychosyndromes (dementia). 3. The therapeutic proceedings should consider methods of behavioural medicine and behavioural modification too. Such techniques may amplify the traditional medical aspects, especially stressing the significance of compliance, illness-related information, family variables, diet, and bodily exercise (according to Epstein). Methods of behavioural medicine have shown that specific techniques should be applied with care and take individual variability and conditions into account according to single subject methodology. Uncritical application of such techniques is useless.


Modern technologies for improving cleaning and disinfection of environmental surfaces in hospitals.
Experts agree that careful cleaning and disinfection of environmental surfaces are essential elements of effective infection prevention programs. However, traditional manual cleaning and disinfection practices in hospitals are often suboptimal. This is often due in part to a variety of personnel issues that many Environmental Services departments encounter. Failure to follow manufacturer's recommendations for disinfectant use and lack of antimicrobial activity of some disinfectants against healthcare-associated pathogens may also affect the efficacy of disinfection practices. Improved hydrogen peroxide-based liquid surface disinfectants and a combination product containing peracetic acid and hydrogen peroxide are effective alternatives to disinfectants currently in widespread use, and electrolyzed water (hypochlorous acid) and cold atmospheric pressure plasma show potential for use in hospitals. Creating "self-disinfecting" surfaces by coating medical equipment with metals such as copper or silver, or applying liquid compounds that have persistent antimicrobial activity surfaces are additional strategies that require further investigation. Newer "no-touch" (automated) decontamination technologies include aerosol and vaporized hydrogen peroxide, mobile devices that emit continuous ultraviolet (UV-C) light, a pulsed-xenon UV light system, and use of high-intensity narrow-spectrum (405 nm) light. These "no-touch" technologies have been shown to reduce bacterial contamination of surfaces. A micro-condensation hydrogen peroxide system has been associated in multiple studies with reductions in healthcare-associated colonization or infection, while there is more limited evidence of infection reduction by the pulsed-xenon system. A recently completed prospective, randomized controlled trial of continuous UV-C light should help determine the extent to which this technology can reduce healthcare-associated colonization and infections. In conclusion, continued efforts to improve traditional manual disinfection of surfaces are needed. In addition, Environmental Services departments should consider the use of newer disinfectants and no-touch decontamination technologies to improve disinfection of surfaces in healthcare.


Modeling the impact of early interventions on the transmission dynamics of coronavirus infection.
A deterministic model is proposed to describe the transmission dynamics of coronavirus infection with early interventions. Epidemiological studies have employed modeling to unravel knowledge that transformed the lives of families, communities, nations and the entire globe. The study established the stability of both disease free and endemic equilibria. Stability occurs when the reproduction number, R0, is less than unity for both disease free and endemic equilibrium points. The global stability of the disease-free equilibrium point of the model is established whenever the basic reproduction number R0 is less than or equal to unity. The reproduction number is also shown to be directly related to the transmission probability (β), rate at which latently infected individuals join the infected class (δ) and rate of recruitment (Λ). It is inversely related to natural death rate (μ), rate of early treatment (τ 1), rate of hospitalization of infected individuals (θ) and Covid-induced death rate (σ). The analytical results established are confirmed by numerical simulation of the model.


[Determination of micro-elements in six condiments by AAS].
In this paper, through atomic absorption detector, we determined the content of micro-elements, such as Sr, Ba, Fe, Al, Cu, Cr, Zn, Mo, Ni, Co, Mn, Cd, Mg, in six condiments. From the result, we found there is a differing content of micro-element in different condiments. At the same time, we also made a reclaiming experiment for these micro-elements in ginger, the rate of reclamation is about 90%-108%.


Raised levels of immunoglobulin G, A and M are associated with an increased risk of total and cause-specific mortality: the Vietnam Experience Study.
Immunoglobulins (Ig) are essential for combating infectious disease. However, high levels are associated with a range of diseases and/or poor health behaviours, such as autoimmune diseases, chronic infection, HIV and excessive alcohol consumption. In the present analyses, we extend this body of work by examining whether higher levels of serum Ig G, A and M are associated with increased mortality risk. Participants were 4255 Vietnam-era, former US army personnel (the Vietnam Experience Study). From military service files, telephone interviews in 1983 and a medical examination in 1986, sociodemographic, and health data were collected. Contemporary morning fasted blood samples were taken from which IgG, IgA and IgM concentrations were determined. Mortality surveillance over 15 years gave rise to deaths ascribed to all-causes, cardiovascular disease mortality, all cancers combined mortality, external cause and 'other' causes (predominantly comprising deaths due to infectious disease). Cox proportional hazard models were utilised to compute HRs per SD increase in Ig which were first adjusted for age and then additionally adjusting for a range of candidate confounders. In multiply adjusted analyses, in general, the higher the immunoglobulin concentration, the greater the risk of death. Thus, IgA (HR=2.0 95% CI 1.47 to 2.73), IgM (HR=1.5 95% CI 1.11 to 1.91) and IgG (HR=5.8 95% CI 3.38 to 9.95) were positively related to all-cause mortality. Corresponding results for 'other' causes of mortality were 4.7 (2.64 to 8.19), 3.5 (2.29 to 5.45) and 33.4 (15.13 to 73.64). In the present study, high levels of Ig are associated with an elevated risk of death from total and 'other' causes, mainly infectious disease. High levels of Ig, particularly IgG, may signal subclinical disease.


Influences on gene expression in vivo by a Shine-Dalgarno sequence.
The Shine-Dalgarno (SD+: 5'-AAGGAGG-3') sequence anchors the mRNA by base pairing to the 16S rRNA in the small ribosomal subunit during translation initiation. We have here compared how an SD+ sequence influences gene expression, if located upstream or downstream of an initiation codon. The positive effect of an upstream SD+ is confirmed. A downstream SD+ gives decreased gene expression. This effect is also valid for appropriately modified natural Escherichia coli genes. If an SD+ is placed between two potential initiation codons, initiation takes place predominantly at the second start site. The first start site is activated if the distance between this site and the downstream SD+ is enlarged and/or if the second start site is weakened. Upstream initiation is eliminated if a stable stem-loop structure is placed between this SD+ and the upstream start site. The results suggest that the two start sites compete for ribosomes that bind to an SD+ located between them. A minor positive contribution to upstream initiation resulting from 3' to 5' ribosomal diffusion along the mRNA is suggested. Analysis of the E. coli K12 genome suggests that the SD+ or SD-like sequences are systematically avoided in the early coding region suggesting an evolutionary significance.


Use of ratings of perceived exertion for predicting maximal work rate and prescribing exercise intensity in patients taking atenolol.
The purpose of this study was to assess the efficacy of Borg's rating of perceived exertion (RPE) scale to predict maximal exercise levels to control exercise intensity in patients taking atenolol for the treatment of essential hypertension. Normally, a standard formula (220-age) is used for calculating a percentage of exercise intensity, but beta blockade can cause reductions in maximal heart rate of between 20 and 30%. Patients were split into a control group-10 men and 10 women, aged 50 (SD 12) and 46 (9) respectively, who had risk factors for cardiovascular disease but were not taking any drugs, and a treatment group-11 men and 11 women, aged 53 (13) and 55 (13) respectively, who were established on 25-100 mg of atenolol. All patients performed two submaximal tests on a cycle ergometer. Test 1 was an estimation test, during which the RPE was reported for each increment in work rate. Test 2 was an RPE production test, during which the patient regulated the work rate according to his/her perception of effort at four predetermined points on the RPE scale (RPE 9, 13, 15, 17). In both tests the individual correlations (r) between RPE, heart rate, and work rate ranged from 0.96 to 0.99. Analysis of variance showed no significant difference in maximal heart rate and maximal power output for the control group when predicted from the regression lines of RPE versus heart rate and RPE versus power output in the estimation test. However, the prediction of maximal power output was lower in the women in the control group and patients in the treatment group when this was predicted from the effort production protocol (P < 0.01). When exercise intensity at each RPE was expressed relative to maximal power output there were no differences between treatment and control groups. The findings from this study confirmed the strong positive relation between RPE, heart rate, and work rate in these patients in both passive effort estimation and active effort production protocols. However, caution in applying these procedures is required because the prediction of maximal exercise levels may be lower when effort production procedures are used.


Modified beamformers for coherent source region suppression.
Many tomographic source localization algorithms used in biomagnetic imaging assume, explicitly or sometimes implicitly, that the source activity at different brain locations are either independent or that the correlation structure between sources is known. Among these algorithms is a class of adaptive spatial filters known as beamformers, which have superior spatiotemporal resolution abilities. The performance of beamformers is robust to weakly coherent sources. However, these algorithms are extremely sensitive to the presence of strongly coherent sources. A frequent mode of failure in beamformers occurs with reconstruction of auditory evoked fields (AEFs), in which bilateral auditory cortices are highly coherent in their activation. Here, we present a novel beamformer that suppresses activation from regions with interfering coherent sources. First, a volume containing the interfering sources is defined. The lead field matrix for this volume is computed and reduced into a few significant columns using singular value decomposition (SVD). A vector beamformer is then constructed by rejecting the contribution of sources in the suppression region while allowing for source reconstruction at other specified regions. Performance of this algorithm was first validated with simulated data. Subsequent tests of this modified beamformer were performed on bilateral AEF data. An unmodified vector beamformer using whole head coverage misplaces the source medially. After defining a suppression region containing the temporal cortex on one side, the described method consistently results in clear focal activations at expected regions of the contralateral superior temporal plane.


Alterations of hand sensorimotor function and cortical motor representations over the adult lifespan.
Using a cross sectional design, we aimed to identify the effect of aging on sensorimotor function and cortical motor representations of two intrinsic hand muscles, as well as the course and timing of those changes. Furthermore, the link between cortical motor representations, sensorimotor function, and intracortical inhibition and facilitation was investigated. Seventy-seven participants over the full adult lifespan were enrolled. For the first dorsal interosseus (FDI) and abductor digiti minimi (ADM) muscle, cortical motor representations, GABAA-mediated short-interval intracortical inhibition (SICI), and glutamate-mediated intracortical facilitation (ICF) were assessed using transcranial magnetic stimulation over the dominant primary motor cortex. Additionally, participants' dexterity and force were measured. Linear, polynomial, and piecewise linear regression analyses were conducted to identify the course and timing of age-related differences. Our results demonstrated variation in sensorimotor function over the lifespan, with a marked decline starting around the mid-thirties. Furthermore, an age-related reduction in cortical motor representation volume and maximal MEP of the FDI, but not for ADM, was observed, occurring mainly until the mid-forties. Area of the cortical motor representation did not change with advancing age. Furthermore, cortical motor representations, sensorimotor function, and measures of intracortical inhibition and facilitation were not interrelated.


[Chemotherapy in combination with whole-body hyperthermia in advanced malignant pleural mesothelioma].
A 57-year-old man presented with dyspnoea, cough, fatigue and weight loss. He had been exposed to asbestos 30 years ago. Physical examination was unremarkable apart from a suspected pleural effusion. Computed tomography (CT) of the thorax showed multiple pleural masses with pleural effusion on the left side. CT of the abdomen and bronchoscopy were normal. The patient underwent explorative thoracoscopy; biopsies were taken, and diffuse malignant pleural mesothelioma was demonstrated. The patient was evaluated at the University Hospital Lübeck for Phase II experimental therapy with whole-body hyperthermia (WBH). The pretreatment evaluation revealed normal cardiorespiratory function and a normal contrast-enhanced CT of the brain. The patient's haematologic profile and electrolytes were normal. The WBH-radiant heat device (RHD) used for therapy was Aquatherm provided by the Cancer Research Institute (CRI, New York, USA). The patient received ifosfamide (5 g/m2, day 1), carboplatin (300 mg/m2, day 1), etoposide (150 mg/m2, days 2-3) combined with WBH at 41.8 degrees C (for 60 minutes). Two cycles were applied without complications and a partial remission of the disease was observed. Radiant heat whole body hyperthermia, in conjunction with a defined anticancer treatment and pharmacological approach to sedation, was a safe and effective palliative treatment in this patient.


Imaging of the ovary.
Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian cancer. Detection before the disease has spread beyond the ovary would significantly improve the survival from ovarian cancer, which is currently only 30% over 5 years, despite extensive efforts to improve the survival. This study describes initial investigation of the use of optical technologies to improve the outcome for this disease by detecting cancers at an earlier and more treatable stage. Women undergoing oophorectomy were recruited for this study. Ovaries were harvested for fluorescence spectroscopy, confocal microscopy, and optical coherence tomography. Fluorescence spectroscopy showed large diagnostic differences between normal and abnormal tissue at 270 and 340 nm excitation. Optical coherence tomography was able to image up to 2mm deep into the ovary with particular patterns of backscattered intensity observed in normal versus abnormal tissue. Fluorescence confocal microscopy was able to visualize sub-cellular structures of the surface epithelium and underlying cell layers. Optical imaging and/or spectroscopy has the potential to improve the diagnostic capability in the ovary, but extended systematic investigations are needed to identify the unique signatures of disease. The combination of optical technologies supported by modern molecular biology may lead to an instrument that can accurately detect early carcinogenesis.


Reduction of Chromate via Biotic and Abiotic Pathways in the Presence of Three Co-contaminating Electron Acceptors.
Bioreduction of Cr(VI) to Cr(III) is a promising technology for removing Cr(VI), but Cr(VI) reduction alone cannot support microbial growth. This study investigated the reduction of Cr(VI) in the presence of three electron acceptors that typically coexist with Cr(VI): NO3-, SO42-, and Fe(III). All three systems could reduce Cr(VI) to Cr(III), but the fate of Cr, its impacts on reduction of the other acceptors, and its impact on the microbial community differed. Although Cr(VI) was continuously removed in the NO3--reduction systems, batch tests showed that denitrification was inhibited primarily through impeding nitrite reduction. The SO42- and Fe(III) reduction systems reduced Cr(VI) using a combination of biotic and abiotic processes. Across all three systems, the abundance of genera capable of reducing Cr(VI) increased following the introduction of Cr(VI). Conversely, the abundance of genera that cannot reduce or resist Cr(VI) decreased, leading to restructuring of the microbial community. Furthermore, the abundance of sulfide oxidizers and Fe(II) oxidizers substantially increased after the introduction of chromate. This study provides fundamental knowledge about how Cr(VI) bioreduction interacts with bioreductions of three other co-contaminating electron acceptors.


Beta-arrestins and cell signaling.
Upon their discovery, beta-arrestins 1 and 2 were named for their capacity to sterically hinder the G protein coupling of agonist-activated seven-transmembrane receptors, ultimately resulting in receptor desensitization. Surprisingly, recent evidence shows that beta-arrestins can also function to activate signaling cascades independently of G protein activation. By serving as multiprotein scaffolds, the beta-arrestins bring elements of specific signaling pathways into close proximity. beta-Arrestin regulation has been demonstrated for an ever-increasing number of signaling molecules, including the mitogen-activated protein kinases ERK, JNK, and p38 as well as Akt, PI3 kinase, and RhoA. In addition, investigators are discovering new roles for beta-arrestins in nuclear functions. Here, we review the signaling capacities of these versatile adapter molecules and discuss the possible implications for cellular processes such as chemotaxis and apoptosis.


Intraoperative near-infrared imaging can distinguish cancer from normal tissue but not inflammation.
Defining tumor from non-tumor tissue is one of the major challenges of cancer surgery. Surgeons depend on visual and tactile clues to select which tissues should be removed from a patient. Recently, we and others have hypothesized near-infrared (NIR) imaging can be used during surgery to differentiate tumors from normal tissue. We enrolled 8 canines and 5 humans undergoing cancer surgery for NIR imaging. The patients were injected with indocyanine green (ICG), an FDA approved non-receptor specific NIR dye that accumulates in hyperpermeable tissues, 16-24 hours prior to surgery. During surgery, NIR imaging was used to discriminate the tumor from non-tumor tissue. NIR imaging identified all tumors with a mean signal-to-background ratio of 6.7. Optical images were useful during surgery in discriminating normal tissue from cancer. In 3 canine cases and 1 human case, the tissue surrounding the tumor was inflamed due to obstruction of the vascular supply due to mass effect. In these instances, NIR imaging could not distinguish tumor tissue from tissue that was congested, edematous and did not contain cancer. This study shows that NIR imaging can identify tumors from normal tissues, provides excellent tissue contrast, and it facilitates the resection of tumors. However, in situations where there is significant peritumoral inflammation, NIR imaging with ICG is not helpful. This suggests that non-targeted NIR dyes that accumulate in hyperpermeable tissues will have significant limitations in the future, and receptor-specific NIR dyes may be necessary to overcome this problem.


Asymptomatic peripheral arterial disease in HIV patients in Ghana: A case-control study.
Peripheral arterial disease (PAD) is common in HIV patients and can be diagnosed noninvasively using the ankle-brachial index (ABI). The burden of PAD has not been investigated in Ghanaian HIV patients. We investigated the prevalence and risk factors associated with PAD in HIV patients at a periurban hospital in Ghana. In a case-control design, ABI was measured in 158 cART-treated HIV patients, 150 cART-naïve HIV patients and 156 non-HIV controls with no clinical symptoms of CVDs. PAD was defined as ABI ≤ 0.9. A structured questionnaire was used to collect socio-demographic and clinical data. Fasting venous blood samples were collected to measure plasma levels of glucose, lipid profile, and CD4+ lymphocytes. The prevalence of PAD was 13.9% among cART-treated HIV patients, 21.3% among cART-naïve HIV patients, and 15.4% among non-HIV controls. Patients with PAD had increased odds of having low CD4+ cell counts [OR (95% CI) = 3.68 (1.41-12.85)]. In cART-treated HIV patients, those on TDF-based [5.76 (1.1-30.01), p = 0.038] and EFV-based [9.28 (1.51-57.12), p = 0.016] regimens had increased odds of having PAD. In our study population, there was no difference in the prevalence of PAD between cART-treated HIV patients compared to cART-naïve HIV patients or non-HIV controls. Having a low CD4 cell count and being on TDF- or EFV-based regimens were associated with an increased likelihood of having PAD.


A Potential Tension in DSM-5: The General Definition of Mental Disorder versus Some Specific Diagnostic Criteria.
The general concept of mental disorder specified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders is definitional in character: a mental disorder might be identified with a harmful dysfunction. The manual also contains the explicit claim that each individual mental disorder should meet the requirements posed by the definition. The aim of this article is two-fold. First, we shall analyze the definition of the superordinate concept of mental disorder to better understand what necessary (and sufficient) criteria actually characterize such a concept. Second, we shall consider the concepts of some individual mental disorders and show that they are in tension with the definition of the superordinate concept, taking pyromania and narcissistic personality disorder as case studies. Our main point is that an unexplained and not-operationalized dysfunction requirement that is included in the general definition, while being systematically violated by the diagnostic criteria of specific mental disorders, is a logical error. Then, either we unpack and operationalize the dysfunction requirement, and include explicit diagnostic criteria that can actually meet it, or we simply drop it.


Forensic applications of infrared imaging for the detection and recording of latent evidence.
We report on a simple method to record infrared (IR) reflected images in a forensic science context. Light sources using ultraviolet light have been used previously in the detection of latent prints, but the use of infrared light has been subjected to less investigation. IR light sources were used to search for latent evidence and the images were captured by either video or using a digital camera with a CCD array sensitive to IR wavelength. Bloodstains invisible to the eye, inks, tire prints, gunshot residue, and charred document on dark background are selected as typical matters that may be identified during a forensic investigation. All the evidence types could be detected and identified using a range of photographic techniques. In this study, a one in eight times dilution of blood could be detected on 10 different samples of black cloth. When using 81 black writing inks, the observation rates were 95%, 88% and 42% for permanent markers, fountain pens and ball-point pens, respectively, on the three kinds of dark cloth. The black particles of gunshot residue scattering around the entrance hole under IR light were still observed at a distance of 60 cm from three different shooting ranges. A requirement of IR reflectivity is that there is a contrast between the latent evidence and the background. In the absence of this contrast no latent image will be detected, which is similar to all light sources. The use of a video camera allows the recording of images either at a scene or in the laboratory. This report highlights and demonstrates the robustness of IR to detect and record the presence of latent evidence.


Atorvastatin induces autophagic cell death in prostate cancer cells in vitro.
Athough it is well known that apoptosis contributes to cancer cell death, the role of autophagy in cancer cell death has remained in dispute. Atorvastatin has been suggested to exhibit anti-cancer effects. The present study aimed to examine atorvastatin-induced autophagy-associated cell death and the autophagy‑associated gene expression profile in the PC3 prostate carcinoma cell line. The atorvastatin‑induced process of autophagy in PC3 cells was determined via evaluation of the cellular expression levels of autophagosomal marker light-chain-3 (LC3)‑II, using immunoblotting and counting of green fluorescent protein (GFP)‑LC3-transfected autophagic cells. Apoptosis was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling assay and an MTT assay was used to evaluate cell viability. Total RNA of PC3 cells was isolated for characterization of the gene expression profile following atorvastatin treatment. Atorvastatin treatment of PC3 cells for 24 h increased the expression of green fluorescent protein‑LC3‑II by >25%, and expression continued for >72 h, while apoptosis was not significantly induced within this time period. Four genes associated with the autophagy machinery were also significantly upregulated. In the presence of atorvastatin, autophagy may be unable to abrogate cell damage and may therefore contribute to cellular dysfunction, leading to autophagic/type II programmed cell death. In response to atorvastatin treatment, the expression of genes involved in autophagic mediating pathways may have a role in tumor suppression.


Peritalar Kinematics With Combined Deltoid-Spring Ligament Reconstruction in Simulated Advanced Adult Acquired Flatfoot Deformity.
Adult acquired flatfoot deformity (AAFD) is a complex and progressive deformity involving the ligamentous structures of the medial peritalar joints. Recent anatomic studies demonstrated that the spring and deltoid ligaments form a greater medial ligament complex, the tibiocalcaneonavicular ligament (TCNL), which provides medial stability to the talonavicular, subtalar, and tibiotalar joints. The aim of this study was to assess the biomechanical effect of a spring ligament tear on the peritalar stability. The secondary aim was to assess the effect of TCNL reconstruction in restoration of peritalar stability in comparison with other medial stabilization procedures, anatomic spring or deltoid ligament reconstructions, in a cadaveric flatfoot model. Ten fresh-frozen cadaveric foot specimens were used. Reflective markers were mounted on the tibia, talus, navicular, calcaneus, and first metatarsal. Peritalar joint kinematics were captured by a multiple-camera motion capture system. Mild, moderate, and severe flatfoot models were created by sequential sectioning of medial capsuloligament complex followed by cyclic axial loading. Spring only, deltoid only, and combined deltoid-spring ligament (TCNL) reconstructions were performed. The relative kinematic changes were compared using 2-way analysis of variance (ANOVA). Compared with the initial condition, we noted significantly increased valgus alignment of the subtalar joint of 5.1 ± 2.3 degrees (P = .031) and 5.8 ± 2.7 degrees (P < .01) with increased size of the spring ligament tear to create moderate to severe flatfoot, respectively. We noted an increased tibiotalar valgus angle of 5.1 ± 2.0 degrees (P = .03) in the severe model. Although all medial ligament reconstruction methods were able to correct forefoot abduction, the TCNL reconstruction was able to correct both the subtalar and tibiotalar valgus deformity (P = .04 and P = .02, respectively). The TCNL complex provided stability to the talonavicular, subtalar, and tibiotalar joints. The combined deltoid-spring ligament (TCNL) reconstructions restored peritalar kinematics better than isolated spring or deltoid ligament reconstruction in the severe AAFD model. The combined deltoid-spring ligament (TCNL) reconstruction maybe considered in advanced AAFD with medial peritalar instability: stage IIB with a large spring ligament tear or stage IV.


Early Postmenopausal Phase Is Associated With Reduced Prostacyclin-Induced Vasodilation That Is Reversed by Exercise Training: The Copenhagen Women Study.
The postmenopausal phase is associated with an accelerated rate of rise in the prevalence of vascular dysfunction and hypertension; however, the mechanisms underlying these adverse vascular changes and whether exercise training can reverse the decline in vascular function remains unclear. We examined the function of the vascular prostanoid system in matched pre- and postmenopausal women before and after 12 weeks of exercise training. Twenty premenopausal and 16 early postmenopausal (3.1±0.5 [mean±SE] years after final menstrual period) women only separated by 4 (50±0 versus 54±1) years of age were included. Before the training period, the vasodilator response to intra-arterial infusion of either the prostacyclin analog epoprostenol or acetylcholine was lower (≈13%-41%; P<0.05) in the postmenopausal compared with the premenopausal women. Acetylcholine infusion induced a similar release of prostacyclin (6-keto prostaglandin F1a). To elucidate the role of vasoconstrictor prostanoids, acetylcholine infusion was combined with the cyclooxygenase inhibitor ketorolac and here the vascular response to acetylcholine was reduced to a similar extent in pre- and postmenopausal women. Exercise training increased (P<0.05) the vasodilator response to epoprostenol (≈100%-150%) and acetylcholine (≈100%-120%) infusion in the postmenopausal group. These findings demonstrate that the early postmenopausal phase is associated with a marked reduction in vascular function. Despite of a reduced sensitivity to prostacyclin, the overall balance between vasodilator and vasoconstrictor prostanoids does not seem to be altered. Exercise training can reverse the decline in vascular sensitivity to epoprostenol and acetylcholine, suggesting that beneficial vascular adaptations with exercise training are preserved in recent postmenopausal women.


Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice.
The production of B lymphocytes is regulated in part by physiologic levels of androgens and estrogens. While these sex hormones down-regulate B lymphopoiesis, augmentation of B lymphopoiesis occurs under conditions where androgen or estrogen levels are decreased. In this study we examine the effect of androgen ablation of male mice on B lymphopoiesis and on the phenotypic composition of peripheral B lymphocyte populations. Spleen and thymic weights are significantly increased following castration, as is the total number of peripheral blood lymphocytes. However, the absolute numbers of B cells in the periphery are selectively increased following castration; the numbers of T cells, NK cells and granulocytes remain unchanged. The increase in circulating B cells is due largely to increases in the numbers of recent bone marrow emigrants expressing a B220(lo+)CD24(hi+) phenotype and these cells remain significantly elevated in castrated mice for up to 54 days post-castration. Similar increases in the percentages of newly emigrated B cells are observed in mice that lack a functional androgen receptor (TFM:). Finally, assessments of B cell progenitors in the bone marrow revealed significant increases in the relative numbers of IL-7-responsive B cell progenitors, including cells in Hardy fractions B (early pro-B cells), C (late pro-B cells), D (pre-B cells) and E (immature B cells). These findings demonstrate that androgen ablation following castration significantly and selectively alters the composition of peripheral B cells in mice. Further, these alterations result from the potentiating effects of androgen ablation on IL-7-responsive pro-B cell progenitors.


[Plasmacytoma of the parotid gland].
Extramedullary plasmocytomas of the salivary glands are extremely rare. Not more than four cases have been described in the literature. A further case of an extended extramedullary plasmocytoma of the parotid gland is presented. Radiotherapy of 40 Gy was sufficient for a complete remission of this tumour. Only three months later, however, the patient developed multiple medullary plasmocytoma, which could not be influenced by cytostatic drug treatment. Twelve months after diagnosis, the patient died from medullary plasmocytoma, but without any signs of local recurrence in the parotid gland. The prognosis of extramedullary plasmocytomas of the salivary glands seems to be poor, as about half of the presented cases developed multiple medullary plasmocytoma. Local recurrence at the primary site, however, was not seen in any case. Surgical treatment of extramedullary plasmocytomas of the salivary of extramedullary plasmocytomas of the salivary glands is recommended for those cases where complete removal of the tumour masses seems possible without greater functional damage. Extended plasmocytomas, especially of the parotid gland, should be treated by radiotherapy. They have an excellent radiosensitivity, and the high risk of multiple medullary plasmocytoma in these cases does not seem to justify a mutilating surgery including hemimandibulectomy or sacrifice of the facial nerve.


Whole-body Electromyostimulation plus Caloric Restriction in Metabolic Syndrome.
We investigated early effects of Whole-Body Electromyostimulation added to hypocaloric diet on metabolic syndrome features in sedentary middle-aged individuals. We randomly assigned 25 patients to Whole-Body Electromyostimulation plus caloric restriction or caloric restriction alone for 26 weeks. Anthropometrics, blood pressure, fasting glucose and insulin, HOMA-IR, glycated hemoglobin, lipids, uric acid, creatinphosphokynase, C-reactive protein were assessed. Body composition was evaluated with direct-segmental, multi-frequency Bioelectrical Impedance Analysis. Both groups lost approximately 10% of weight, with similar effects on waist circumference and fat mass. Change in free-fat mass was significantly different between groups (caloric restriction -1.5±0.2 vs. Whole-Body Electromyostimulation plus caloric restriction +1.1±0.4 kg, p=0.03). Whole-Body Electromyostimulation plus caloric restriction group experienced greater percent reductions in insulin (-45.5±4.4 vs. -28.2±3.6%, p=0.002), HOMA-IR (-51.3±3.2 vs. -25.1±1.8%, p=0.001), triglycerides (-22.5±2.9 vs. -4.1±1.6%, p=0.004) and triglycerides/HDL (p=0.028). Subjects trained with Whole-Body Electromyostimulation had also significant improvement in systolic pressure (138±4 vs. 126±7 mmHg, p=0.038). No discontinuations for adverse events occurred. In middle-aged sedentary subjects with the metabolic syndrome, Whole-Body Electromyostimulation with caloric restriction for 26 weeks can improve insulin-resistance and lipid profile compared to diet alone. Further studies are needed to ascertain long-term efficacy and feasibility of this approach in individuals with the metabolic syndrome.


Bacteroides cellulosilyticus sp. nov., a cellulolytic bacterium from the human gut microbial community.
A strictly anaerobic cellulolytic bacterium, strain CRE21(T), was isolated from a human faecal sample. Cells were Gram-negative non-motile rods that were about 1.7 microm in length and 0.9 microm in width. Strain CRE21(T) degraded different types of cellulose and was able to grow on a variety of carbohydrates. Cellulose and sugars were mainly converted to acetate, propionate and succinate. The G+C content of the DNA was 41.1 mol%. 16S rRNA gene sequence analysis revealed that the isolate belonged to the genus Bacteroides with highest sequence similarity to the type strain of Bacteroides intestinalis (98 %). DNA-DNA hybridization results revealed that strain CRE21(T) was distinct from B. intestinalis (40 % DNA-DNA relatedness). Strain CRE21(T) also showed several characteristics distinct from B. intestinalis. In particular, it exhibited different capacity to degrade polysaccharides such as cellulose. On the basis of phylogenetic analysis and the morphological, physiological and biochemical data presented in this study, strain CRE21(T) can be readily differentiated from recognized species of the genus Bacteroides. The name Bacteroides cellulosilyticus sp. nov. is proposed to accommodate this organism. The type strain is CRE21(T) (=DSM 14838(T)=CCUG 44979(T)).


[Brachial plexus block by infraclavicular approach in children. Value of a nerve stimulator? Apropos of 20 cases].
This study included 20 children (average 8.5 years) undergoing surgery of the upper limb under brachial plexus block. A method of blocking the brachial plexus using an infraclavicular approach is described. Eighteen brachial plexus block were performed under general anesthesia. No complication was observed. Post-operative analgesia was satisfactory in all cases. In 10 cases a nerve stimulator was used. It is not necessary for the realization of a brachial plexus block, but the punction is easier under general anesthesia with this instrument.


Options for regulating new genomic techniques for plants in the European Union.
Which option for regulating plants derived from new genomic techniques in European Union law is feasible and justifiable scientifically? The European Commission has proposed a new regulation on plants obtained by specific new genomic techniques, which is now subject to discussion in the legislative process. From the perspective of the European Commission's envisaged legal reforms of European Union law towards the integration of greater sustainability, we conclude that the option focusing on plant traits delivering sustainability benefits should be chosen, which is most fitting to facilitate a contribution to climate action, the transition towards climate neutrality, and promptly integrate sustainability into all food-related policies. To assist the decision-making in the legislative process, we outline six regulatory options resulting from regulatory research involving interdisciplinary teams.


Plasmin induces degradation and dysfunction of laminin 332 (laminin 5) and impaired assembly of basement membrane at the dermal-epidermal junction.
The epidermal basement membrane (BM), located at the dermal-epidermal junction (DEJ), plays important roles not only in adhesion between epidermis and dermis, but also in controlling skin functions. In sun-exposed skin, the BM becomes disrupted and multilayered. In order to explore the impairment of BM assembly, we have used a skin-equivalent (SE) as a model of BM damage and previously clarified the involvement of matrix metalloproteinases (MMPs) in impairment of BM assembly. In this work, we examined the role of urokinase-type plasminogen activator (uPA) and plasmin in impairment of BM assembly at the DEJ by using the SE, as ultraviolet irradiation to the skin increases uPA as well as MMPs. SEs were used as a model of formation and damage of BM. Human uPA was detected by enzyme-linked immunosorbent assay and zymography, and gelatinases such as MMP-2 and MMP-9 were detected by zymography. Human plasminogen was added at 0.06 micromol L(-1) (about 3% of plasma level) to increase plasmin to a pathological level. N-terminal peptide sequence analysis of plasmin-treated laminin 332 was carried out to identify alpha3, beta3 and gamma2 chains of laminin 332 and their cleavage sites of each chain. Plasmin-treated laminin 332 was analysed in keratinocyte adhesion activity and binding to type VII collagen. Human uPA was detected in addition to MMP-2 and MMP-9, in conditioned medium of SE. Although the BM was well organized in the presence of an MMP inhibitor alone, the activated plasmin disorganized the BM even in the presence of the inhibitor. The impairment of BM assembly made the epidermis thinner as compared with that of a control cultured in the presence of MMP inhibitor, indicating that the BM affects the polarity and differentiation of the epidermis. The addition of aprotinin, a serine proteinase inhibitor, and tranexamic acid, a uPA-plasmin inhibitor, inhibited the plasmin-induced impairment of BM assembly and facilitated BM reorganization, thereby improving the epidermal structure. N-terminal peptide sequence analysis of plasmin-treated laminin 332 revealed the removal of a 5- or 10-kDa fragment, including the cell adhesion region, from the G3 domain of the alpha3 chain, and the LN domain, which binds to the noncollagenous 1 domain in type VII collagen, from the beta3 chain. Plasmin-treated laminin 332 showed lower keratinocyte adhesion activity and reduced binding to type VII collagen. These results suggest that uPA and plasmin are involved in the impairment of BM assembly and epidermal differentiation, and that these effects arise at least partly through direct degradation of laminin 332.


Paranoia in patients with gender dysphoria: A clinical exploration.
Gender identity disorder (GID) is a distressing disorder characterized by a persistent unhappiness with one's own gender and a desire to be of the opposite gender as well as seeking sex reassignment surgery for the same. The aim of the study was to assess the Minnesota Multiphasic Personality Inventory (MMPI) profiles in patients with GID and compare with healthy normal population and also examine differences in the profiles based on original gender of the patients. A total of 56 patients with GID that fulfilled the Diagnostic and Statistical Manual of Mental Disorders 5 criteria for the same were participants of the study, and there were 54 control participants. They were administered the MMPI, and the scores across various scales were statistically analyzed. It was seen that apart from masculinity feminity (Mf) scale, other scales such as Paranoia (Pa, P < 0.01), Schizophrenia (Sc, P = 0.01), and Psychopathic deviate (Pd, P < 0.01) were also elevated in many patients. Male patients seeking surgery to become female showed higher scores on Pa and Sc scales than female patients. On detailed inquiry, it was found that there was no evidence of psychosis clinically, and in fact, their paranoia was reality based. MMPI profiles in patients with GID needs to interpreted with caution and clinicians must keep in mind that elevated Pa and Sc scales on the MMPI in these patients need not indicate a psychotic profile.


Quantitative cell array screening to identify regulators of gene expression.
In the last decade or so, advances in genome-scale technologies have allowed systematic and detailed analysis of gene function. The experimental accessibility of budding yeast makes it a test-bed for technology development and application of new functional genomic tools and resources that pave the way for comparable efforts in higher eukaryotes. In this article, we review advances in reporter screening technology to discover trans-acting regulators of promoters (or cis-elements) of interest in the context of a novel functional genomics approach called Reporter Synthetic Genetic Array (R-SGA) analysis. We anticipate that this methodology will enable researchers to collect quantitative data on hundreds of gene expression pathways in an effort to better understand transcriptional regulatory networks.


[Characterization of ESBL-producing Escherichia coli and Klebsiella pneumoniae strains isolated from urine of nonhospitalized patients in the Zagreb region].
To determine the prevalence of ESBL-producing Escherichia coli and Klebsiella pneumoniae strains isolated from urine of nonhospitalized patients during a three-year period, to determine their antibiotic susceptibility, investigate the transfer of ESBL genes with cotransfer of resistance and to characterize isolated beta-lactamases. Antimicrobial susceptibility was determined by disk diffusion and broth microdilution methods. The double-disk test was used for ESBL detection. Transfer of resistance was performed by broth mating method and characterization of isolated beta-lactamases by polymerase chain reaction. The prevalence of ESBL-producing E. coli was 1.5% and of K. pneumoniae 4.1% with its different distribution according to patients' age and gender. ESBL-producing K. pneumoniae showed high resistance rates to aminoglycosides, cotrimoxazole, nitrofurantoin and quinolones while ESBL-producing E. coli isolates, with exception of high aminoglycoside resistance, showed low resistance rates to other antibiotics. Successful conjugation of ESBL genes was obtained with 25% E. coli and 76.2% K. pneumoniae strains. Comparing to E. coli, K. pneumoniae strains showed higher rates of aminoglycoside and cotrimoxazole resistance cotransfer. Beta-lactamases of investigated strains belonged to TEM, SHV and CTX-M families. The existence of multiple-resistant ESBL-producing E. coli and K. pneumoniae strains was confirmed in observed outpatient population. ESBL-producing K. pneumoniae isolates, in contrast to ESBL-producing E. coli, showed higher resistance rates to non-beta-lactam antibiotics, probably caused by cotransfer of resistance genes located on the same plasmid as ESBL genes. It is important to monitor the prevalence of such strains and their possible spreading in the outpatient population of the Zagreb region.


[Anemia during inflammatory processes: pathogenesis and clinical and morphological manifestations].
The review sums up the results of the current stage of studying the so-called anemia of inflammation (AI). The key mediator of AI is the polypeptide hepatic hormone hepcidin, the hepatocytic secretion of which is initiated by proinflammatory macrophageal cytokines (IL-6, IL-lalpha, and tumor necrosis factor-alpha) and T-lymphocyte gamma-interferon. Hepcidin has bactericidal properties and promotes iron retention in the enterocytes, macrophages, and hepatocytes through the internalization and degradation of ferroportin (a cell iron exporter into the plasma). The limited iron availability to microorganisms in AI is aimed at enhancing the body's natural resistance to infection. Therefore, AI serves as an example of fundamental reactions of innate immunity. The latent and manifest phases of AI can be identified. The major clinical and morphological manifestations of AI are a decreased functional iron stores and hepatic and splenic hemosiderosis.


The synthesis of primitive 'living' forms: definitions, goals, strategies and evolution synthesizers.
The arbitrariness of the definition of life is discussed in relation to both the archaic biological entities that preceded cells during the Molecular Evolution era, and the hypothetical, primitive, 'living' entities that presumably can be synthesized in the laboratory. Several experimental approaches to the synthesis, detection, and characterization of 'living' entities are discussed. The experimental approaches considered for the synthesis are the constructionist strategy, the whole-environment strategy, and the modular strategy, which is a combination of the first two. The whole-environment strategy is discussed in more detail and the establishment of an Evolution Synthesizer, based on this strategy, is proposed and rationalized. The guidelines for the detection and characterization of populations and processes of 'living' entities include chemical and physical analyses, but are based mainly on the reproductive characterization of these entities. It is expected that the higher the evolutionary level of the 'living' entities, the longer and more difficult it will be to synthesize them, but the easier it will be to detect them.


Teaching ethics in dentistry.
This paper describes a curriculum project designed to help dental students identify, reason about, and adequately resolve ethical problems in their chosen profession. The project involved application of a theoretical approach to the study of ethical development that had not been applied previously in professional education. Tests were designed to measure the abilities defined by the theory and used to evaluate the program and to monitor student progress. To date, studies of student abilities and attitudes clearly indicate that the curriculum is needed. Learning activities, created to promote the abilities, are based on studies of the real-life ethical problems confronting dentists and dental students. A program of research and development has been established to study the influence of this curriculum on the abilities defined, and to link them to clinical performance. Half of the dental schools in the United States have requested these materials. Suggestions are made to professional schools considering expanding the teaching of ethics.


Detection and identification of platelet antibodies and antigens in the clinical laboratory.
As a result of the unique functional properties of platelets, more-robust methods were required for detection of antibodies raised against them. Immunofluorescence detection by flow cytometry, solid-phase red cell adherence, and antigen capture ELISAs are some of the current tests that have been developed to meet the challenges of platelet antibody detection and identification and antigen phenotyping. Recently developed protein liquid bead arrays are becoming the next-generation platelet antibody tests. Fueled by development of PCR and determination of the molecular basis of the PlA1 human platelet antigen (HPA), serologic platelet typing has now been replaced by genotyping of DNA. Allele-specific PCR, melting curve analysis, and 5'-nuclease assays are now evolving into more high-throughput molecular tests. Laboratory testing for the diagnosis of immune platelet disorders has advanced considerably from its humble beginnings.


Harnessing 2D Ruddlesden-Popper Perovskite with Polar Organic Cation for Ultrasensitive Multibit Nonvolatile Transistor-Type Photomemristors.
Photomemristors have been regarded as one of the most promising candidates for next-generation hardware-based neuromorphic computing due to their potentials of fast data transmission and low power consumption. However, intriguingly, so far, photomemristors seldom display truly nonvolatile memory characteristics with high light sensitivity. Herein, we demonstrate ultrasensitive photomemristors utilizing two-dimensional (2D) Ruddlesden-Popper (RP) perovskites with a highly polar donor-acceptor-type push-pull organic cation, 4-(5-(2-aminoethyl)thiophen-2-yl)benzonitrile+ (EATPCN+), as charge-trapping layers. High linearity and almost zero-decay retention are observed in (EATPCN)2PbI4 devices, which are very distinct from that of the traditional 2D RP perovskite devices consisting of nonpolar organic cations, such as phenethylamine+ (PEA+) and octylamine+ (OA+), and traditional 3D perovskite devices consisting of methylamine+ (MA+). The 2-fold advantages, including desirable spatial crystal arrangement and engineered energetic band alignment, clarify the mechanism of superior performance in (EATPCN)2PbI4 devices. The optimized (EATPCN)2PbI4 photomemristor also shows a memory window of 87.9 V and an on/off ratio of 106 with a retention time of at least 2.4 × 105 s and remains unchanged after >105 writing-reading-erasing-reading endurance cycles. Very low energy consumptions of 1.12 and 6 fJ for both light stimulation and the reading process of each status update are also demonstrated. The extremely low power consumption and high photoresponsivity were simultaneously achieved. The high photosensitivity surpasses that of a state-of-the-art commercial pulse energy meter by several orders of magnitude. With their outstanding linearity and retention, rabbit images have been rebuilt by (EATPCN)2PbI4 photomemristors, which truthfully render the image without fading over time. Finally, by utilizing the powerful ∼8 bits of nonvolatile potentiation and depression levels of (EATPCN)2PbI4 photomemristors, the accuracies of the recognition tasks of CIFAR-10 image classification and MNIST handwritten digit classification have reached 89% and 94.8%, respectively. This study represents the first report of utilizing a functional donor-acceptor type of organic cation in 2D RP perovskites for high-performance photomemristors with characteristics that are not found in current halide perovskites.


Kidney pseudotumour diagnosed by emission computed tomography.
Emission computed tomography is a new, useful imaging technique; when a rotating gamma camera capable of such imaging is used multiple adjacent transverse sections may be obtained simultaneously, from which coronal and sagittal sections may be computed. The technique was used in a man undergoing urological investigation in whom excretion urography indicated a space-occupying lesion in the left kidney. Ultrasonography and radionuclide imaging showed nothing abnormal, but emission computed tomography using a rotating gamma camera showed that functioning cortical tissue extended across the middle of the left kidney. Radiographs were therefore reviewed and ultrasonography repeated, and it was concluded that the abnormality was a hypertrophied column of Bertin. Emission tomographic imaging of the kidney is a useful adjunct to other non-invasive studies.


Serosurvey of West Nile virus and other flaviviruses of the Japanese encephalitis antigenic complex in birds from Andalusia, southern Spain.
Flaviviruses of the Japanese encephalitis virus (JEV) antigenic complex, including West Nile virus (WNV), are recognized as emerging and reemerging pathogens. Circulation of flaviviruses has been recently detected in different mosquito and vertebrate species in several European countries. A serosurvey study was carried out to evaluate the circulation of WNV and other flaviviruses of the JEV antigenic complex in different wild bird species in Spain between 2006 and 2009. Seropositiviy against JEV using a competitive enzyme-linked immunosorbent assay was found in common coot, Montagu's Harrier, black kite, black vulture, Bonelli's eagle, Spanish imperial eagle, Egyptian vulture, and Eurasian spoonbill. Seropositivity to JEV antigenic complex viruses was significantly higher in samples collected during autumn compared with animals sampled during summer. Significantly higher seroprevalence was also observed in 2007 compared with 2009, whereas there were no significant differences in seropositivity among taxonomic levels, migratory versus resident behavior, body size (large vs. medium), or habitats (free-ranging vs. captivity). Neutralizing antibodies against WNV were detected in common coot and Spanish imperial eagle using a virus-neutralization test. Oral shedding of WNV was not detected in any of the Spanish imperial eagles, Egyptian vultures, Eurasian Spoonbills, Lammergeiers, and the Black vultures analyzed by means of real-time reverse transcription-polymerase chain reaction. The results indicate that WNV and others flaviviruses of the JEV antigenic group circulated in migratory and resident wild bird species in Spain between 2007 and 2008. Further studies are necessary to determine the precise role that each of these wild bird species, some of them cataloged as "near threatened," "vulnerable," or "endangered," play in the epidemiology of those viruses.


Higher incidence of embryonic defects in mouse offspring conceived with assisted reproduction from fathers with sperm Epimutations.
Assisted reproductive technologies (ART) account for 1-6% of births in developed countries. While most children conceived are healthy, increases in birth and genomic imprinting defects have been reported; such abnormal outcomes have been attributed to underlying parental infertility and/or the ART used. Here, we assessed whether paternal genetic and lifestyle factors that are associated with male infertility and affect the sperm epigenome, can influence ART outcomes. We examined how paternal factors, haploinsufficiency for Dnmt3L, an important co-factor for DNA methylation reactions, and/or diet-induced obesity, in combination with ART (superovulation, in vitro fertilization, embryo culture and embryo transfer), could adversely influence embryo development and DNA methylation patterning in mice. While male mice fed high-fat diets (HFD) gained weight and showed perturbed metabolic health, their sperm DNA methylation was minimally affected by the diet. In contrast, Dnmt3L haploinsufficiency induced a marked loss of DNA methylation in sperm; notably, regions affected were associated with neurodevelopmental pathways and enriched in young retrotransposons, sequences that can have functional consequences in the next generation. Following ART, placental imprinted gene methylation and growth parameters were impacted by one or both paternal factors. For embryos conceived by natural conception, abnormality rates were similar for WT and Dnmt3L+/- fathers. In contrast, paternal Dnmt3L+/- genotype, as compared to WT fathers, resulted in a 3-fold increase in the incidence of morphological abnormalities in embryos generated by ART. Together, the results indicate that embryonic morphological and epigenetic defects associated with ART may be exacerbated in offspring conceived by fathers with sperm epimutations.


Evidence for reflex and perceptual vestibular contributions to postural control.
Vestibular signals are known to have an important role in stance under specific conditions. Potentially these effects could be modulated by vestibular reflexes or by voluntary responses to perceived vestibular signals. Our preliminary aim was to confirm that vestibulospinal reflexes change in parallel with sway under different postural conditions, and then to determine whether any relationship was present between these reflexes and body sway within fixed postural conditions. Sixteen subjects (eight male, eight female) were tested in conditions assessing the effects of vision (eyes open or closed), support surface (firm or compliant), external support (with or without) and stance width (feet apart or together). Sway (centre of pressure) in the anteroposterior (AP) and mediolateral planes was measured using a force platform. A subgroup of 11 subjects (five male, six female) underwent testing to measure short (SL) and medium latency (ML) reflexes from soleus. Bipolar, transmastoid galvanic stimulation (1 mA, 200 ms) was administered while subjects stood in the most unstable of our conditions (eyes closed, compliant surface and feet together). In the final part, to assess possible perceptual contributions to body sway, short duration AP sway levels were measured and expressed in angular terms (sway in mrad, velocity in mrad s(-1)) in the 11 subjects for both our baseline (eyes open, firm surface and feet apart) and most unstable conditions. Average sway levels increased more than seven-fold between conditions and had significant, positive correlations with reported changes in mean vestibulospinal reflexes under similar conditions (overall r = 0.75, P < 0.001). However, the SL reflex for the subgroup of 11 subjects had a significant negative correlation (r = -0.71; P = 0.014) with the degree of AP sway in the condition with maximum reliance on vestibular inputs (eyes closed, compliant surface, and feet together). Under baseline conditions, 5/125 (4%) of the short-term AP sway displacements were above the threshold previously reported for the detection of imposed sway. In the unstable condition, when sway was increased, 43/138 (31%) of the short-term AP sway movements were above the threshold for perception of imposed body sway based on vestibular signals. Our results confirm that vestibulospinal reflexes appear to be acutely facilitated as body sway increases. For the most unstable condition, when non-vestibular information was absent or attenuated, subjects with larger SL reflexes had less AP sway, suggesting that the SL reflex acted to attenuate sway. Under the same condition, short duration sway levels increased such that 31% were above the previously published threshold for detection using vestibular afferents. We conclude that both vestibular reflexes and perceptual signals appear to have a specific role in the maintenance of upright stance, under conditions in which other sources of postural information are attenuated or absent.


Glutathione-independent isomerization of maleylpyruvate by Bacillus megaterium and other gram-positive bacteria.
Maleylpyruvate, the ring fission product of gentisic acid, was found to be isomerized to fumarylpyruvate without a requirement for glutathione by an enzyme activity found in cell extracts of m-hydroxybenzoate-grown Bacillus megaterium 410. The isomerization reaction was detected as a shift in the absorbance maximum from 330 nm, the maximum for maleylpyruvate, to 345 nm, the maximum for fumarylpyruvate, when assayed at pH 8.0. Ammonium sulfate precipitation and dialysis of B. megaterium cell extracts resolved the isomerase activity from low-molecular-weight compounds such as glutathione but did not eliminate the isomerase activity. Iodoacetate and p-chloromercuribenzoate were potent inhibitors of the isomerase from B. megaterium. However, N-ethylmaleimide and iodoacetamide did not significantly inhibit this activity. In addition, fumaric acid was demonstrated as a product of gentisate oxidation by dialyzed cell extracts of B. megaterium. Glutathione-independent maleylpyruvate isomerases with properties similar to the isomerase found in B. megaterium were also found in other genera of gram-positive organisms. Eleven different organisms representing the genera Bacillus, Arthrobacter, Corynebacterium, Nocardia, and Rhodococcus were all found to possess this novel type of glutathione-independent maleylpyruvate isomerase.


Mastocytosis in children: a protocol for management.
Mastocytosis is characterized by an increased number of mast cells with an abnormal growth and accumulation in one or more organs. In most children mastocytosis is limited to the skin (cutaneous mastocytosis) and often transient as compared with that in adults in whom mastocytosis is usually progressive and systemic. Generally, we recognize three more common forms of cutaneous mastocytosis: maculopapulous mastocytosis (formerly urticaria pigmentosa), mastocytoma of skin, and diffuse cutaneous mastocytosis. Childhood mastocytosis can further be divided into cutaneous mastocytosis (nonpersisting and persisting) and systemic mastocytosis (extremely rare). An approach to management using a set protocol is described in table form. In most cases of mastocytosis, only yearly checkups are necessary and no treatment is required; preventive recommendations are warranted in those individuals with systemic disease and constitutional symptoms. Symptomatic therapy is advised in only a minority of cases. This article is meant as a guideline for physicians involved in the care of children with mastocytosis and their parents.


Relationships between Flexural and Bonding Properties, Marginal Adaptation, and Polymerization Shrinkage in Flowable Composite Restorations for Dental Application.
To evaluate the flexural and bonding properties, marginal adaptation, and polymerization shrinkage in flowable composite restorations and their relationships, four new generation flowable composites, one conventional, and one bulk-fill flowable composite were used in this study. Flexural properties of the composites and shear bond strength to enamel and dentin for flowable restorations were measured immediately and 24 h after polymerization. Marginal adaptation, polymerization shrinkage, and stress were also investigated immediately after polymerization. The flexural properties, and bond strength of the flowable composites to enamel and dentin were much lower immediately after polymerization than at 24 h, regardless of the type of the composite. Polymerization shrinkage and stress varied depending on the material, and bulk-fill flowable composite showed much lower values than the others. The marginal adaptation and polymerization shrinkage of the composites appeared to have a much stronger correlation with a shear bond strength to dentin than to enamel. The weak mechanical properties and bond strengths of flowable composites in the early stage after polymerization must be taken into account when using them in the clinic. In addition, clinicians should be aware that polymerization shrinkage of flowable composites can still lead to the formation of gaps and failure of adaptation to the cavity regardless of the type of composite.


HCV RNA in serum of asymptomatic blood donors involved in post-transfusion hepatitis (PTH).
A group of blood donors involved in post-transfusion hepatitis was investigated for the presence of the anti-HCV antibody and of HCV RNA as a more direct infection marker. RNA was extracted from serum, reverse transcribed and amplified using primers which belonged to the non structural region. The amplified product of the PCR reaction was 582 base pairs. Seven (25.9%) of the 27 blood donors examined were found anti-HCV-positive by ELISA; five (71.4%) of these were HCV RNA positive. Among the 20 anti-HCV-negative blood donors, four (20.0%) were HCV RNA positive. ALT levels were below 45 UI/l in 18 donors, while the other nine had ALTs over the limit accepted for transfusion. The anti-HCV-negative HCV RNA-positive blood donors had normal ALTs. Our study offers a direct explanation for the substantial proportion of residual cases of anti-HCV-positive post-transfusion hepatitis and suggests the necessity of creating a register of blood donors who have at some time presented blood enzyme abnormalities and for whom second level investigations such as HCV RNA should be used.


A novel 268 kb deletion combined with a splicing variant in IL7R causes of severe combined immunodeficiency in a Chinese family: a case report.
Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population. Here, we retrospectively analyzed a case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient's genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother. To our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients.


The Differential Metabolic Signature of Breast Cancer Cellular Response to Olaparib Treatment.
Metabolic reprogramming and genomic instability are key hallmarks of cancer, the combined analysis of which has gained recent popularity. Given the emerging evidence indicating the role of oncometabolites in DNA damage repair and its routine use in breast cancer treatment, it is timely to fingerprint the impact of olaparib treatment in cellular metabolism. Here, we report the biomolecular response of breast cancer cell lines with DNA damage repair defects to olaparib exposure. Following evaluation of olaparib sensitivity in breast cancer cell lines, we immunoprobed DNA double strand break foci and evaluated changes in cellular metabolism at various olaparib treatment doses using untargeted mass spectrometry-based metabolomics analysis. Following identification of altered features, we performed pathway enrichment analysis to measure key metabolic changes occurring in response to olaparib treatment. We show a cell-line-dependent response to olaparib exposure, and an increased susceptibility to DNA damage foci accumulation in triple-negative breast cancer cell lines. Metabolic changes in response to olaparib treatment were cell-line and dose-dependent, where we predominantly observed metabolic reprogramming of glutamine-derived amino acids and lipids metabolism. Our work demonstrates the effectiveness of combining molecular biology and metabolomics studies for the comprehensive characterisation of cell lines with different genetic profiles. Follow-on studies are needed to map the baseline metabolism of breast cancer cells and their unique response to drug treatment. Fused with genomic and transcriptomics data, such readout can be used to identify key oncometabolites and inform the rationale for the design of novel drugs or chemotherapy combinations.


Development of the outflow tract and closure of the interventricular septum in the normal human heart.
The majority of congenital heart malformations in humans involve defects in the atrioventricular valves, the crest of the interventricular septum, and/or the outflow tract, but the position and timing of these structures during cardiac development is controversial. We examined all 622 staged, serially sectioned normal human embryos and fetuses in the Carnegie Embryological Collection, and obtained a statistical tabulation of the appearance of the endocardial cushion components and surrounding structures for 382 embryos in good condition between stages 9 and 23 inclusive, when the heart normally develops. Accurately scaled drawings of ventral and lateral views of the hearts of seven embryos from stage 13 through 22 were prepared from graphic reconstructions in order to visualize the relationships of the structures under consideration. We found that development of the outflow tract septum follows the apparent functional separation of both the left and right ventricles and the blood streams leaving them. Elevations of the endocardial cushion material are continuous throughout the outflow tract and develop as a consequence of the elliptical configuration imposed on the circular cross section of the outflow tract. The membranous interventricular septum is formed of cushion material in the space bounded by the outflow tract septum, interventricular septum, and the fused AV cushion and right outflow tract cushion. The results of this study are consistent with the assertion that functional separation of the aortic and pulmonary outflow tracts precedes anatomic septation, and that anatomic septation is brought about by mechanical modeling of developing myocardium and endocardial cushion material.


[Moderate financial incentives for organ donation].
Despite many efforts to increase the number of organs for transplantations, there is still a worrying shortage of transplantable organs - in Germany as well as in almost every developed country. One possibility to increase the amount of organs is the introduction of financial incentives for cadaveric organ donation. In this article, several forms of moderate financial incentives for organ donation are described. Ethical arguments for and against an implementation of financial incentives are weighed against each other. Finally, an argument is developed in favour of moderate financial incentives which supports careful research into possible modes of implementation.


Detergent-type membrane fragmentation by MSI-78, MSI-367, MSI-594, and MSI-843 antimicrobial peptides and inhibition by cholesterol: a solid-state nuclear magnetic resonance study.
Multidrug resistance against the existing antibiotics is becoming a global threat, and any potential drug that can be designed using cationic antimicrobial peptides (AMP) could be an alternate solution to alleviate this existing problem. The mechanism of action of killing bacteria by an AMP differs drastically in comparison to that of small molecule antibiotics. The main target of AMPs is to interact with the lipid bilayer of the cell membrane and disrupt it to kill bacteria. Consequently, the modes of membrane interaction that lead to the selectivity of an AMP are very important to understand. Here, we have used different membrane compositions, such as negatively charged, zwitterionic, or mixed large unilamellar vesicles (LUVs), to study the interaction of four different synthetically designed cationic, linear antimicrobial peptides: MSI-78 (commercially known as pexiganan), MSI-367, MSI-594, and MSI-843. Our solid-state nuclear magnetic resonance (NMR) experiments confirmed that the MSI peptides fragmented LUVs through a detergent-like carpet mechanism depending on the amino acid sequence of the MSI peptide and/or the membrane composition of LUVs. Interestingly, the fragmented lipid aggregates such as SUVs or micelles are sufficiently small to produce an isotropic peak in the (31)P NMR spectrum. These fragmented lipid aggregates contain only MSI peptides bestowed with lipid molecules as confirmed by NMR in conjunction with circular dichroism spectroscopy. Our results also demonstrate that cholesterol, which is present only in the eukaryotic cell membrane, inhibits the MSI-induced fragmentation of LUVs, suggesting that the MSI peptides can discriminate the bacteria and the eukaryotic cell membranes, and this selectivity could be used for further development of novel antibiotics.


Occupational exposure to antineoplastic agents induces a high level of chromosome damage. Lack of an effect of GST polymorphisms.
The aim of our study was to investigate whether occupational exposure to antineoplastic drugs (AND) resulted in genetic damage, possibly indicative of adverse health effects in the long term. We performed a chromosomal aberrations (CA) analysis in peripheral blood lymphocytes (PBL) of a group of 76 trained nurses occupationally exposed to AND. Furthermore, we analysed whether genetic polymorphisms in four metabolic genes of the glutathione S-transferase (GST) family involved in antineoplastic drugs detoxification (GSTM1, GSTT1, GSTP1, GSTA1) had any effect on the yield of chromosomal aberrations in nurses exposed to antineoplastic agents. The exposed group showed a very significant increase of genetic damage (p<0.0001) potentially indicative of an increased risk of cancer. Unexpectedly, besides the elevated level of chromatid-type aberrations usually related to exposure to chemical agents, we found also severe chromosome damages such as chromosome deletions and dicentric chromosomes, usually related to radiation exposure. No significant association was detected between all GSTs genotypes and chromosome damage. In conclusion, our data show how the occupational exposure to AND is associated to a potential cancer risk, suggesting that current prevention methods do not completely eliminate opportunities for exposure and supporting the need to improve the actual safety practices.


Rates of ICD-10 Code U09.9 Documentation and Clinical Characteristics of VA Patients With Post-COVID-19 Condition.
A significant proportion of SARS-CoV-2 infected individuals experience post-COVID-19 condition months after initial infection. To determine the rates, clinical setting, risk factors, and symptoms associated with the documentation of International Statistical Classification of Diseases Tenth Revision (ICD-10), code U09.9 for post-COVID-19 condition after acute infection. This retrospective cohort study was performed within the US Department of Veterans Affairs (VA) health care system. Veterans with a positive SARS-CoV-2 test result between October 1, 2021, the date ICD-10 code U09.9 was introduced, and January 31, 2023 (n = 388 980), and a randomly selected subsample of patients with the U09.9 code (n = 350) whose symptom prevalence was assessed by systematic medical record review, were included in the analysis. Positive SARS-CoV-2 test result. Rates, clinical setting, risk factors, and symptoms associated with ICD-10 code U09.9 in the medical record. Among the 388 980 persons with a positive SARS-CoV-2 test, the mean (SD) age was 61.4 (16.1) years; 87.3% were men. In terms of race and ethnicity, 0.8% were American Indian or Alaska Native, 1.4% were Asian, 20.7% were Black, 9.3% were Hispanic or Latino, 1.0% were Native Hawaiian or Other Pacific Islander; and 67.8% were White. Cumulative incidence of U09.9 documentation was 4.79% (95% CI, 4.73%-4.87%) at 6 months and 5.28% (95% CI, 5.21%-5.36%) at 12 months after infection. Factors independently associated with U09.9 documentation included older age, female sex, Hispanic or Latino ethnicity, comorbidity burden, and severe acute infection manifesting by symptoms, hospitalization, or ventilation. Primary vaccination (adjusted hazard ratio [AHR], 0.80 [95% CI, 0.78-0.83]) and booster vaccination (AHR, 0.66 [95% CI, 0.64-0.69]) were associated with a lower likelihood of U09.9 documentation. Marked differences by geographic region and facility in U09.9 code documentation may reflect local screening and care practices. Among the 350 patients undergoing systematic medical record review, the most common symptoms documented in the medical records among patients with the U09.9 code were shortness of breath (130 [37.1%]), fatigue or exhaustion (78 [22.3%]), cough (63 [18.0%]), reduced cognitive function or brain fog (22 [6.3%]), and change in smell and/or taste (20 [5.7%]). In this cohort study of 388 980 veterans, documentation of ICD-10 code U09.9 had marked regional and facility-level variability. Strong risk factors for U09.9 documentation were identified, while vaccination appeared to be protective. Accurate and consistent documentation of U09.9 is needed to maximize its utility in tracking patients for clinical care and research. Future studies should examine the long-term trajectory of individuals with U09.9 documentation.


Psychogenic paralysis and recovery after motor cortex transcranial magnetic stimulation.
Psychogenic paralysis presents a real treatment challenge. Despite psychotherapy, physiotherapy, antidepressants, acupuncture, or hypnosis, the outcome is not always satisfactory with persistent symptoms after long-term follow-up. We conducted a retrospective study to assess clinical features and to propose an alternative treatment based on repetitive transcranial magnetic stimulation (rTMS). Seventy patients (44 F/26 M, mean age: 24.7 +/- 16.6 years) experienced paraparesis (57%), monoparesis (37%), tetraparesis (3%), or hemiparesis (3%). A precipitating event was observed in 42 patients, primarily as a psychosocial event or a physical injury. An average of 30 stimuli over the motor cortex contralateral to the corresponding paralysis was delivered at low frequency with a circular coil. The rTMS was effective in 89% of cases, with a significantly better outcome for acute rather than chronic symptoms. In conclusion, motor cortex rTMS seem to be very effective in patients with psychogenic paralysis and could be considered a useful therapeutic option.


Characterisation of TcFUT1, a mitochondrial fucosyltransferase from Trypanosoma cruzi.
Previous work has shown that the TbFUT1 and LmjFUT1 genes encode essential fucosyltransferases located inside the single mitochondria of the protozoan parasites Trypanosoma brucei and Leishmania major, respectively. However, nothing was known about the orthologous gene TcFUT1 or its gene product in Trypanosoma cruzi, aetiological agent of Chagas disease. In this study, we describe the overexpression of TcFUT1 with a C-terminal 6xMyc epitope tag in T. cruzi epimastigote cells. Overexpressed and immunoprecipitated TcFUT1-6xMyc was used to demonstrate enzymatic activity and to explore substrate specificity. This defined TcFUT1 as a GDP-Fuc : βGal α1-2 fucosyltransferase with a strict requirement for acceptor glycans with non-reducing terminal Galβ1-3GlcNAc structures. This differs from the specificity of the T. brucei orthologue TbFUT1, which can also tolerate non-reducing terminal Galβ1-4GlcNAc and Galβ1-4Glc acceptor sites. Immunofluorescence microscopy using α-Myc tag antibodies also showed a mitochondrial location for TcFUT1 in T. cruzi epimastigote cells. Collectively, these results are like those described for TbFUT1 and LmjFUT1 from T. brucei and L. major, suggesting that FUT1 gene products have conserved function for across the trypanosomatids and may share therapeutic target potential.


Surgical Management of Normocalcemic Primary Hyperparathyroidism and the Impact of Intraoperative Parathyroid Hormone Testing on Outcome.
Objective To review our surgical experience and the impact of intraoperative parathyroid hormone (IOPTH) testing among patients with normocalcemic primary hyperparathyroidism. Study Design Case series with chart review. Setting Academic referral hospital. Subject and Methods Normocalcemic hyperparathyroidism (NCHPT) patients were identified with normal-range blood ionized calcium and serum elevated parathyroid hormone. Patient demographics, intraoperative findings, IOPTH dynamics, and biochemical outcomes were compared with those of classic primary hyperparathyroidism (PHPT) patients. Results Of the 2120 patients who underwent parathyroidectomy, 616 patients met the inclusion criteria: 119 (19.5%) patients had NCHPT, and 497 (80.5%) had classic PHPT. NCHPT patients had higher rates of multigland hyperplasia as compared with classic PHPT (12% vs 4%, P = .002) and smaller gland size ( P < .001). Of 119 NCHPT patients, 114 (97%) achieved >50% drop in IOPTH intraoperatively, as opposed to 492 (99%) among 497 classic PHPT patients ( P = .014). IOPTH drop >50% had an equivalent positive predictive value for long-term cure in both groups. Conclusions Surgeons treating NCHPT patients should suspect the presence of multigland disease and have a low threshold for converting to bilateral exploration depending on IOPTH decay dynamics.


IgA anti-tissue transglutaminase as a diagnostic marker of gluten sensitive enteropathy.
To compare and contrast the sensitivity, specificity, and positive predictive values of IgA antibodies to guinea pig tissue transglutaminase (ELISA), endomysium, and reticulin (immunofluorescence), and gliadin (ELISA), and IgG antibodies to gliadin and tissue transglutaminase. Sera from 27 newly diagnosed patients with coeliac disease, 65 biopsied gastrointestinal disease controls, and 50 consecutive blood donors were tested. All cases were adults. IgA anti-tissue transglutaminase showed a sensitivity of 85% (23/27 coeliac disease cases seropositive), specificity 97% (2/65 controls and one blood donor showing low titre positivity), and a positive predictive value of 92%. High titre anti-tissue transglutaminase was only seen in coeliac disease. Disease controls with mucosal damage unrelated to gluten enteropathy were IgA anti-tissue transglutaminase negative. Sensitivity, specificity, and positive predictive values for IgA anti-endomysial antibody (monkey oesophagus) were 100%, 100%, and 100%, respectively, and for IgA anti-gliadin, 93%, 95%, and 89%, respectively. Tissue transglutaminase is a major autoantigen in coeliac disease. IgA (but not IgG) anti-tissue transglutaminase, especially when in high titre, is closely associated with coeliac disease, but low titres may not be disease specific. In this small pilot study, the established IgA anti-endomysial assay was the superior test.


A new approach to the determination of tubular membrane capacitance: passive membrane electrical properties under reduced electrical conductivity of the extracellular solution.
The transverse-axial tubular system (tubular system) of cardiomyocytes plays a key role in excitation-contraction coupling. To determine the area of the tubular membrane in relation to the area of the surface membrane, indirect measurements through the determination of membrane capacitances are currently used in addition to microscopic methods. Unlike existing electrophysiological methods based on an irreversible procedure (osmotic shock), the proposed new approach uses a reversible short-term intermittent increase in the electrical resistance of the extracellular medium. The resulting increase in the lumen resistance of the tubular system makes it possible to determine separate capacitances of the tubular and surface membranes. Based on the analysis of the time course of the capacitive current, computational relations were derived to quantify the elements of the electrical equivalent circuit of the measured cardiomyocyte including both capacitances. The exposition to isotonic low-conductivity sucrose solution is reversible which is the main advantage of the proposed approach allowing repetitive measurements on the same cell under control and sucrose solutions. Experiments on rat ventricular cardiomyocytes (n = 20) resulted in the surface and tubular capacitance values implying the fraction of tubular capacitance/area of 0.327 ± 0.018. We conclude that the newly proposed method provides results comparable to the data obtained by the currently used detubulation method and, in addition, by being reversible, allows repeated evaluation of surface and tubular membrane parameters on the same cell.


Ex Vivo Human Skin: An Alternative Test System for Skin Irritation and Corrosion Assays.
Native human skin has been reported in the literature as being an important experimental model for studying skin biology. Studies performed by our group have shown that ex vivo skin, from elective plastic surgery, maintains the biological characteristics of native skin under specific culture conditions. As such, it might be a feasible model for the safety and efficacy testing of topical substances. While Brazil is at the forefront of global regulation implementation, Brazilian researchers are not always able to transfer certain widely used protocols to their laboratories, particularly protocols that involve the use of reconstructed tissues with limited viability, such as those for skin corrosion (OECD TG 431) and irritation testing (OECD TG 439). In this study, we investigated the applicability of the ex vivo skin model to the evaluation of irritation and corrosion potential of a number of proficiency substances described in TG 431 and TG 439. The skin fragments were standardised in size and diameter, and placed into cell culture inserts. The experimental protocol was conducted according to TG 431 and TG 439. The results obtained show that ex vivo skin could represent a promising tool for the evaluation of irritation and corrosion potential of substances (subject to inclusion and exclusion criteria), as recommended by OECD guidelines. While this is a proof-of-concept study, the use of ex vivo skin should be considered for such testing.


Stress mitigation to promote development of prosocial values and school engagement of inner-city urban African American and Latino youth.
Studies of predictors of development of young men of color have been primarily focused on factors that impede positive development rather than factors that promote it. There are also few examples of longitudinal studies of positive development of this population and few that consider multiple protective factors simultaneously. Little is also known about how such positive outcomes might relate to prediction of problematic functioning. This study tests a developmental-ecological framework of positive and risky development among a sample of young men of color growing up in high-risk urban environments. African American and Latino adolescent males (148 African American, 193 Latino) were followed from early to late adolescence. Stress in early adolescence was related to school engagement and prosocial values as well as depressive symptoms and problems assessed 2 years later. The role of family and individual protective factors as direct effects and as mitigating the stress-outcome relation were also tested. Stress predicted problem outcomes but not positive functioning. Early engagement in prosocial activities and coping skills did predict positive outcomes. In contrast, problem outcomes were predicted directly by stress, with some indication of interaction with some protective factors for both such outcomes. Overall results suggest value in focusing on positive outcomes along with negative outcomes, as they are not the antithesis and have some shared but some different predictors. Implications for supporting positive development are presented.


Addressing Challenges in Fabricating Reflection-Based Fiber Optic Interferometers.
Fabrication of multimode fiber optic interferometers requires accurate control of certain parameters to obtain reproducible results. This paper evaluates the consequences of practical challenges in fabricating reflection-based, fiber optic interferometers by the use of theory and experiments. A guided-mode propagation approach is used to investigate the effect of the end-face cleave angle and the accuracy of the splice in core-mismatched fiber optic sensors. Cleave angles from high-end fiber cleavers give differences in optical path lengths approaching the wavelength close to the circumference of the fiber, and the core-mismatched splice decides the ensemble of cladding modes excited. This investigation shows that the cleave angle may significantly alter the spectrum, whereas the splice is more robust. It is found that the interferometric visibility can be decreased by up to 70% for cleave angles typically obtained. An offset splice may reduce the visibility, but for offsets experienced experimentally the effect is negligible. An angled splice is found not to affect the visibility but causes a lower overall intensity in the spectrum. The sensitivity to the interferometer length is estimated to 60 nm/mm, which means that a 17 µm difference in length will shift the spectrum 1 nm. Comparisons to experimental results indicate that the spliced region also plays a significant role in the resulting spectrum.


Photoelectrochemistry as a novel strategy for DNA hybridization detection.
The special properties of ssDNA and dsDNA molecules in structure and electric behavior, may offer us some new ideas for the fabrication of genosensors and DNA-chips. In this work, the photoelectrochemical method was firstly employed to characterize the photoelectric behavior of a ssDNA probe electrode, which was prepared with the self-assembly technique, and its resulting dsDNA electrode. The obvious decrease in the photocurrent of the dsDNA modified electrode at open potential or a bias voltage indicated that photoelectrochemistry was another useful method for DNA hybridization detection. Using the special design of ssDNA probes, we attempt to discuss further the relationship between the properties of DNA molecules and their photoelectric behaviors. In addition, the electrochemical impedance method was employed to verify the occurrence of some modifications over the electrode interface before and after the hybridization event.


Endovascular maneuvers for contralateral stent graft limb misplacement in endovascular aortic repair.
Cannulation and placement of the contralateral stent graft limb during endovascular aortic repair (EVAR) procedure are crucial steps as mispositioning may lead to conversion to open aortic repair. Endovascular bail-out strategies for stent graft relocation in EVAR are underreported though detailed knowledge may facilitate application and prevent conversion. We present three endovascular bail-out strategies for repositioning of a mispositioned contralateral stent graft limb. (1) Retraction of the mispositioned component with an inflated reliant balloon and placement of an interposition stent graft after successful cannulation; (2) Push-maneuver of the mispositioned stent graft into the infrarenal aortic aneurysm with an inflated reliant balloon supported by a large lumen introducer sheath and (3) Parallel placement of a second contralateral stent graft limb displacing the mispositioned one against the atrial wall in cases with adequate vessel diameter. Prevention of stent graft mispositioning by applying recognized tests to ensure correct placement are essential, following the slogan: check twice, deploy once.


4-Methylthioamphetamine increases dopamine in the rat striatum and has rewarding effects in vivo.
4-Methylthioamphetamine (MTA) is a phenylisopropylamine derivative whose use has been associated with severe intoxications. MTA is usually regarded as a selective serotonin-releasing agent. Nevertheless, previous data have suggested that its mechanism of action probably involves a catecholaminergic component. As little is known about dopaminergic effects of this drug, in this work the actions of MTA upon the dopamine (DA) transporter (DAT) were studied in vitro, in vivo and in silico. Also, the possible abuse liability of MTA was behaviourally assessed. MTA exhibited an in vitro affinity for the rat DAT in the low micromolar range (6.01 μM) and induced a significant, dose-dependent increase in striatal DA. MTA significantly increased c-Fos-positive cells in striatum and nucleus accumbens, induced conditioned place preference and increased locomotor activity. Docking experiments were performed in a homology model of the DAT. In conclusion, our results show that MTA is able to increase extracellular striatal DA levels and that its administration has rewarding properties. These effects were observed at concentrations or doses that can be relevant to its use in human beings.


Genetic alterations in RAS-regulated pathway in acral lentiginous melanoma.
Studies integrating clinicopathological and genetic features have revealed distinct patterns of genomic aberrations in Melanoma. Distributions of BRAF or NRAS mutations and gains of several oncogenes differ among melanoma subgroups, while 9p21 deletions are found in all melanoma subtypes. In the study, status of genes involved in cell cycle progression and apoptosis was evaluated in a panel of 17 frozen primary acral melanomas. NRAS mutations were found in 17% of the tumors. In contrast, BRAF mutations were not found. Gains of AURKA gene (20q13.3) were detected in 37.5% of samples, gains of CCND1 gene (11q13) or TERT gene (5p15.33) in 31.2% and gains of NRAS gene (1p13.2) in 25%. Alterations in 9p21 were identified in 69% of tumors. Gains of 11q13 and 20q13 were mutually exclusive, and 1p13.2 gain was associated with 5p15.33. Our findings showed that alterations in RAS-related pathways are present in 87.5% of acral lentiginous melanomas.


The cost of assuming the life history of a host: acoustic startle in the parasitoid fly Ormia ochracea.
In the obligatory reproductive dependence of a parasite on its host, the parasite must trade the benefit of 'outsourcing' functions like reproduction for the risk of assuming hazards associated with the host. In the present study, we report behavioral adaptations of a parasitic fly, Ormia ochracea, that resemble those of its cricket hosts. Ormia females home in on the male cricket's songs and deposit larvae, which burrow into the cricket, feed and emerge to pupate. Because male crickets call at night, gravid female Ormia in search of hosts are subject to bat predation, in much the same way as female crickets are when responding to male song. We show that Ormia has evolved the same evasive behavior as have crickets: an acoustic startle response to bat-like ultrasound that manifests clearly only during flight. Furthermore, like crickets, Ormia has a sharp response boundary between the frequencies of song and bat cries, resembling categorical perception first described in the context of human speech.


Efficacy of a minimally guided internet treatment for alcohol misuse and emotional problems in young adults: Results of a randomized controlled trial.
Many young adults struggle with comorbid alcohol misuse and emotional problems (i.e., depression and anxiety). However, there is currently a paucity of evidence-based, integrated, accessible treatment options for individuals with these comorbidities. The main goal of this study was to examine efficacy of a novel online, minimally guided, integrated program for comorbid alcohol misuse and emotional problems in young adults. Method: The study was an open-label two-arm RCT. Participants (N = 222, M age = 24.6, 67.6% female) were randomized to one of two conditions: the Take Care of Me program (an 8-week, online integrated treatment condition consisting of 12 modules), or an online psychoeducational control condition. Intervention modules incorporated content based on principles of cognitive behavioral therapy and motivational interviewing. Participants completed assessment data at baseline, at the end of treatment (i.e., 8 weeks), and at follow-up (i.e., 24 weeks). Data were analyzed using generalized linear mixed models. Results: We observed that participants in the treatment condition showed larger reductions in depression, hazardous drinking, as well as increases in psychological quality of life and confidence at the end of treatment. We did not find group differences on total alcohol use at follow-up, but participants in the treatment group reduced their hazardous drinking and improved their quality of life at 24-week follow-up. Conclusions: Our study provides promising initial evidence for the first iteration of the comorbid alcohol misuse and emotional problems online program.