The effect of sequel symptoms and signs of Complex Regional Pain Syndrome type 1 on upper extremity disability and quality of life.
Although properly treated, patients with Complex Regional Pain Syndrome type 1 (CRPS type 1) of upper limb may continue to have sequel signs and symptoms of the disease in long-term. The aim of this study is to analyse the effect of the sequel findings of CRPS type 1 on upper limb disability and quality of life. Thirty patients with CRPS type 1 of the upper extremity were re-evaluated for the sequel sign and symptoms of CRPS type 1 after 18 months (8-60 months). Pain, range of motion, strength, manual dexterity and touch perception thresholds of the hands, upper extremity disability [Disability of arm, shoulder and hand (DASH) questionnaire] and health-related quality of life [Short Form-36 (SF-36)] were measured and compared to 38 healthy controls. Of the 30 patients, only 3 patients (10%) were symptom free. Pain after use was the most frequently found symptom. Strength and range of motion of the involved hand was reduced in CRPS type 1 patients. Manual dexterity was impaired and touch perception threshold was elevated in CRPS type 1 patients. The involved upper extremities were more disabled in CRPS type 1 patients than controls. The severity of the pain, and numbness of the hands were the factors causing disability. Pain caused reduced quality of life in physical functioning. In conclusion, prolonged follow-up period and efforts to improve sensory disturbances (especially pain) may reduce the upper extremity disability and reduced quality of life in CRPS type 1 patients.


High current pulser for transmural and field stimulation.
The determination of the requirements and the design of a constant current pulse generator with low internal resistance capable of providing the high currents required for transmural and field stimulation of biologic tissues are described. It is concluded that direct measurement of current flowing and voltage applied to electrodes is the best way of monitoring stimulus parameters.


Prognostic impact of carcinoembryonic antigen (CEA) on patients with metastatic pancreatic cancer: A retrospective cohort study.
Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its level is increased in 30-60% of patients with pancreatic cancer (PC). However, little is known about the implications of CEA as a prognostic marker in metastatic PC. The purpose of this study was to examine the usefulness of CEA levels as a prognostic marker in patients with metastatic PC. We conducted a retrospective cohort study using data from a computerized database. A total of 433 patients with metastatic disease were analyzed. Median overall survival (OS) was significantly shorter for patients with high CEA (>5 ng/ml) than with normal CEA (≤5 ng/ml) (6.8 vs. 10.3 months, respectively; p < 0.001). After adjustment, CEA level was an independent predictive factor for OS (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.45-2.26). In the high CEA group, OS in patients treated with combination chemotherapy was similar to that with single-agent chemotherapy (median, 7.1 vs. 6.8 months; HR for OS, 0.99; 95% CI, 0.71-1.40). The present results show that CEA level is an independent prognostic factor in patients with metastatic PC. A combination chemotherapy regimen may offer modest survival benefit in patients with high CEA.


Acupuncture as an alternative or in addition to conventional treatment for chronic non-specific low back pain: A systematic review and meta-analysis.
Conventional therapies (CTs), pharmacological (PH) and non-pharmacological (NPH), do not always achieve benefits in the treatment of chronic low back pain (CLBP). We assessed efficacy and safety of acupuncture for CLBP as alternative or addition to CT. We included randomised controlled trials (RCTs) comparing acupuncture alone or in combination with CT to CT. We searched Medline, Cochrane Library, Embase up to May 2022. We assessed risk of bias with the original Cochrane tool and GRADE certainty of evidence. Results were pooled through meta-analysis. Ten RCTs (2122 participants) were included comparing acupuncture versus CT and 4 RCTs (374 participants) were comparing acupuncture plus CT to CT alone. In terms of comparing acupuncture with NPH or PH, no differences were found for pain and disability. Comparing acupuncture with PH and NPH combined, pain and disability were reduced (SMD=-0.50, 95% CI -0.62 to -0.37; SMD=-0.71, 95% CI -1.17 to -0.24). Comparing acupuncture plus NPH with NPH alone, pain and disability were reduced (SMD=-0.70, 95% CI -0.94 to -0.46; SMD=-0.95, 95% CI -1.36 to -0.54). Comparing acupuncture plus PH with PH alone, pain and disability were reduced (MD=-0.21, 95% CI -433.28 to -10.42; MD=-3.1, 95% CI -4.87 to -1.83). Comparing acupuncture plus combined treatment versus combined treatment alone, no differences were found in pain, while disability was reduced (MD=-3.40 95% CI -5.17 to -1.63). No studies assessed adverse event. Certainty of evidence ranged from moderate to very low. We are uncertain whether acupuncture is more effective and safer than CT. In the comparisons without estimates' imprecision, acupuncture showed promising results. Acupuncture could be an option based on patients' preferences.


Fatty acid acylation of proteins in Physarum polycephalum.
We have investigated the occurrence of protein-fatty acid acylation by metabolic incorporation of [3H]myristic and [3H]palmitic acids in Physarum polycephalum. We show that this organism contains fatty acylated proteins with mainly myristic acid covalently attached in alkali-stable linkages, probably amides. We find no evidence for ester-linked fatty acids, in contrast to the situation in vertebrate cells.


Effects of prolonged social isolation on responses of neurons in the bed nucleus of the stria terminalis, preoptic area, and hypothalamic paraventricular nucleus to stimulation of the medial amygdala.
The studies presented demonstrate changes in hypothalamo-pituitary-adrenocortical secretion, and in electrical activity and synaptic responses of neurons in the bed nucleus of the stria terminalis, preoptic area, and hypothalamic paraventricular nucleus of rats exposed to early, long-term social isolation. Rats isolated from all social contact from an early preweaning time showed reduced basal plasma corticosterone concentrations, compared with littermate controls raised under social conditions. Isolated animals also exhibited a selective decrease in the spontaneous electrical activity of neurons within the hypothalamic paraventricular nucleus and lateral preoptic area, but not in adjacent structures. Moreover, isolation also altered the response of neurons in certain nuclei to electrical stimulation of the medial amygdala. Thus, a reduction in excitatory responses, and an increase in inhibition and nonresponsiveness, of preoptic area and paraventricular nucleus neurons was recorded, compared with control rats. Neurons in the bed nucleus of the stria terminalis were less affected, but showed an increase in the duration of excitatory responses following medial amygdala stimulation. These results, obtained from urethane-anesthetized rats, together with the reduced basal plasma corticosterone concentrations, suggest a reduction in limbic-hypothalamo-pituitary-adrenocortical (LHPA) activity following maternal deprivation and prolonged social isolation. This may result from altered limbic activity, specifically in the amygdala and its pathways to the paraventricular nucleus (PVN). Such alterations may include the stria terminalis, in so much as increased efficacy of inhibitory components and reduced efficacy of excitatory components was observed. The neural mechanisms underlying these alterations could involve an altered synaptology of the regions examined and/or a disruption of glucocorticoid feedback events.


Biofloc technology (BFT): An alternative aquaculture system for prevention of Cyprinid herpesvirus 2 infection in gibel carp (Carassius auratus gibelio).
Gibel carp (Carassius auratus gibelio), a major aquaculture species in China, has emerged in a seriously epizootic disease caused by Cyprinid herpesvirus 2 (CyHV-2). There are no effective methods to prevent or control this serious disease. Biofloc technology (BFT) can improve water quality, reduce pathogens introduction, enhance cultured species immunity and disease resistance. In this study, a 30-day experiment was conducted to investigate the effect of BFT on innate immune response and disease resistance of gibel carp against CyHV-2 infection. Gibel carp was cultured at different total suspended solid (TSS) concentrations of 10, 300, 600, 800 and 1000 mg L-1, which were named as groups BF0, BF300, BF600, BF800 and BF1000. Results showed that fish in groups BF600/800 had significantly higher weight gain (WG) and specific growth rate (SGR) than them in control group (BF0). The transcriptional levels of seven immune-related genes in BF300/600/800 groups, including myeloid-specific- peroxidase (MPO), keratin 8 (KRT 8), dual specificity phosphatase 1 (DUSP 1), interleukin-11 (IL-11), intelectin (ITLN), purine nucleoside phosphorylase 5α (PNP 5α) and c-type lysozyme (c-lys), were up-regulated significantly compared to BF0 group. Furthermore, cumulative mortality of gibel carp in BF600 group after being challenged with CyHV-2 reduced significantly. In vivo viral replication in kidney demonstrated that CyHV-2 load at 168 h post injection in BF600 group was significantly higher than that in BF0 group. In conclusion, BFT could improve growth, immune response and disease resistance of gibel carp, and the effect was related with TSS concentration. The optimal TSS concentration of 600-800 mg L-1 was recommended in the present study.


The utriculo-endolymphatic valve in pediatric temporal bones.
The utriculo-endolymphatic valve (UEV) is located in the posterior wall of the utricle at its junction with the utricular duct and was first described in a human fetus by Bast in 1928. Although different theories about its normal position and function have been postulated, the function of the UEV remains unclear. In the present investigation we studied 118 temporal bones from 70 children to determine whether there were differences in the position of the valve and by inference, its function between children and adults. Premortem ages ranged from newborn to 10 years (mean age, 11.6 months). All temporal bones were fixed in 10% formalin, decalcified and processed by the celloidin technique. Specimens were sectioned in a horizontal plane at a thickness of 20 microns. Every tenth section was stained with hematoxylin-eosin and studied by light microscopy. The position of the UEV was then classified as closed or open. Valves damaged by preparation or having an uncertain position were classified as artifact. The chi-square test was used to determine a correlation between the position of the valve and the status of the rest of the endolymphatic system and whether or not endolymphatic hydrops was present in the cochlear and vestibular systems. The UEV was closed in 39 temporal bones (33.1%) and open in 13 (11.0%). Artifacts were found in 66 bones (55.9%). In the group of patients with a collapsed ductus reuniens the UEV was closed in 38% of the specimens, suggesting that the UEV prevented loss of endolymph from the pars superior, but these findings were not statistically significant.


Effect of pterygium on corneal astigmatism, irregularity and higher-order aberrations: a comparative study with normal fellow eyes.
Pterygium is an abnormal growth of fibrous conjunctival tissue that invades the cornea, resulting in corneal distortion, astigmatism, and increased higher-order aberrations (HOAs). However, few studies have compared eyes with pterygium to normal fellow eyes when interpreting HOAs and there is no study that revealed the effect of the thickness or grading of the pterygium on the change of HOAs. Therefore, we evaluated the effects of nasal pterygium by comparing the normal fellow eye of 59 patients. The pterygium significantly increased with-the-rule corneal astigmatism and corneal irregularity. Trefoils, horizontal coma, and quatrefoils were significantly induced by the pterygium. The grading of the pterygium was not correlated with its characteristics except for the thickness. In multiple linear regression analysis, pterygium-induced corneal astigmatic/irregularity values and horizontal trefoil/quatrefoil were associated with the area of the pterygium. The length of the pterygium was an independent inducer of oblique trefoil/quatrefoil, while horizontal coma was independently associated with both its length and width. The thickness was not correlated with any optical parameters. Together, the results demonstrate that nasal pterygium significantly induces corneal astigmatism, irregularity and some HOAs. These pterygium-associated changes in optical parameters could be predicted by the length, width and area of the pterygium.


An automated HPLC method to determine intracellular vincristine concentrations in mononuclear cells of children with acute lymphoblastic leukemia.
A method to determine intracellular vincristine concentrations in vivo in leukemic cells of patients is useful to investigate mechanisms of vincristine resistance. We developed a high-performance liquid chromatographic (HPLC) method to measure vincristine concentrations in human mononuclear cells (MNC). This method, with on-line column solid-phase extraction and electrochemical detection, previously developed for determination of vincristine concentrations in human plasma, was validated for determination of intracellular vincristine concentrations over a range of 1.17 to 50.8 micro g/L with a lower limit of quantitation (LOQ) of 1.17 micro g/L. Linearity of the relationship between concentration and response was characterized by a slope (sd) of 0.0683 (0.0008), an intercept (sd) of 0.0004 micro g/L (0.0085), and a regression coefficient of 0.997 (P = 0.05). Maximum bias and within-day and between-day coefficients of variation (CV) were 14.2%, 4.8%, and 5.7%, respectively. The HPLC detector response did not interfere with the vincristine peaks of five independent MNC sources. The method was used successfully to measure intracellular vincristine concentrations in 8 of 35 bone marrow MNC samples of children newly diagnosed with acute lymphoblastic leukemia (ALL), 3 days after the first injection of 1.5 mg/m2 vincristine. Vincristine concentrations were in the range of 4.0 to 26.4 micro g/L, which was 5 to 20 times the bone marrow plasma concentration. The described HPLC method is accurate and precise and is suitable for detection of intracellular vincristine concentrations in MNC of children with ALL. The results confirm that in vivo vincristine accumulates in bone marrow MNC of patients.


Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection in 2015.
Overall prevalence of HCV infection in India has been estimated to be approximately 1.3% in the general population. Recent introduction of sofosbuvir in India at a relatively affordable price has led to great optimism about prospects of cure for these patients. This drug is likely to form the backbone of current and future treatment regimes for HCV infection, displacing pegylated interferon. Availability of directly acting antiviral drugs (DAAs) has necessitated revision of INASL guidelines for the treatment of HCV published in 2014, as has happened across the world. Current considerations for the treatment of HCV in India include the poorer response of genotype 3, nonavailability of many of the DAAs recommended by other guidelines and the cost of therapy. Since only one DAA, sofosbuvir, is available in India, only two sofosbuvir-based regimes are possible: either dual drug therapy in combination with ribavirin alone for 6 months or triple drug therapy in combination with ribavirin and pegylated interferon for 3 months. The utility of these regimes in various situations has been discussed. Availability of a few other newer DAAs, expected in 2016, is expected to lead to more widespread use of these agents. Current guidance will be updated once newer DAAs, newer evidence with DAAs and 'real-life experience' with use of DAAs accumulate in India.


Identification of cardiac rejection with magnetic resonance imaging in heterotopic heart transplantation model.
It is important to evaluate the severity and extent of cardiac rejection in heart transplantations. Eight heterotopic heart transplantations using mongrel dogs were performed, and grated magnetic resonance imaging (MRI) of the donor hearts was carried out. High signal intensity was obtained in the rejected myocardium at the time of cardiac rejection, especially from the right ventricular wall to the intraventricular septal wall compared with the left ventricular posterolateral wall. In addition, MRI was performed in the excised heart. High signal intensity was also observed in the same region of the excised donor hearts. The histopathological rejection scores were well in agreement with prolonged T1 and T2 relaxation times; severe and mild rejection of the myocardium were distinguished by the T1 and T2 relaxation times. Our results suggest that MRI is able to visualize the transplanted myocardium undergoing rejection and that the right ventricular wall is more sensitive to cardiac rejection than the left. MRI may allow noninvasive evaluation of the severity and extent of cardiac rejection.


Harvesting microalgal biomass using a magnetically induced membrane vibration (MMV) system: filtration performance and energy consumption.
This study was performed to investigate the effectiveness of submerged microfiltration to harvest both a marine diatom Phaeodactylum tricornutum and a Chlorella vulgaris in a recently developed magnetically induced membrane vibrating (MMV) system. We assess the filtration performance by conducting the improved flux step method (IFM), fed-batch concentration filtrations and membrane fouling autopsy using two lab-made membranes with different porosity. The full-scale energy consumption was also estimated. Overall results suggest that the MMV offers a good fouling control and the process was proven to be economically attractive. By combining the membrane filtration (15× concentration) with centrifugation to reach a final concentration of 25% w/v, the energy consumption to harvest P. tricornutum and C. vulgaris was, respectively, as low as 0.84 and 0.77kWh/m(3), corresponding to 1.46 and 1.39 kWh/kg of the harvested biomass.


Presynaptic D1 heteroreceptors and mGlu autoreceptors act at individual cortical release sites to modify glutamate release.
The aim of this work was to study release of glutamic acid (GLU) from one-axon terminal or bouton at-a-time using cortical neurons grown in vitro to study the effect of presynaptic auto- and heteroreceptor stimulation. Neurons were infected with release reporters SypHx2 or iGluSnFR at 7 or 3 days-in-vitro (DIV) respectively. At 13-15 DIV single synaptic boutons were identified from images obtained from a confocal scanning microscope before and after field electrical stimulation. We further stimulated release by raising intracellular levels of cAMP with forskolin (10µM). Forskolin-mediated effects were dependent on protein kinase A (PKA) and did not result from an increase in endocytosis, but rather from an increase in the size of the vesicle readily releasable pool. Once iGluSnFR was confirmed as more sensitive than SypHx2, it was used to study the participation of presynaptic auto- and heteroreceptors on GLU release. Although most receptor agonizts (carbamylcholine, nicotine, dopamine D2, BDNF) did not affect electrically stimulated GLU release, a significant increase was observed in the presence of metabotropic D1/D5 heteroreceptor agonist (SKF38393 10µM) that was reversed by PKA inhibitors. Interestingly, stimulation of group II metabotropic mGLU2/3 autoreceptors (LY379268 50nM) induced a decrease in GLU release that was reversed by the specific mGLU2/3 receptor antagonist (LY341495 1µM) and also by PKA inhibitors (KT5720 200nM and PKI14-22 400nM). These changes in release probability at individual release sites suggest another level of control of the distribution of transmitter substances in cortical tissue.


Vulnerability, ageism, and health: is it helpful to label older adults as a vulnerable group in health care?
Despite the diversity of ageing, society and academics often describe and label older persons as a vulnerable group. As the term vulnerability is frequently interchangeably used with frailty, dependence, or loss of autonomy, a connection between older age and deficits is promoted. Concerning this, the question arises to what extent it may be helpful to refer to older persons as vulnerable specifically in the context of health care. After analyzing different notions of vulnerability, I argue that it is illegitimate to conclude that older age is related to increased vulnerability. Much more, identifying older adults as a vulnerable group is closely related to ageism and can be associated with paternalistic benevolence and a tendency to overprotection, especially within health care. Additionally, even though older adults are more often in situations of increased vulnerability due to their potentially higher need for health care, I argue further that older adults mainly become a vulnerable group due to ageism. In this way, it can be concluded that the vulnerability of older adults does not originate in certain attributes of the group, but arises from a characteristic of society and, in turn, health personnel, namely ageism. Labeling older adults as vulnerable therefore is only helpful, when it is used to raise awareness of the widespread ageism in society, in this context, especially in the setting of health care, and the negative consequences thereof for older adults.


Perspective: Tyrosine phosphatases as novel targets for antiplatelet therapy.
Arterial thrombosis is the primary cause of most cases of myocardial infarction and stroke, the leading causes of death in the developed world. Platelets, highly specialized cells of the circulatory system, are key contributors to thrombotic events. Antiplatelet drugs, which prevent platelets from aggregating, have been very effective in reducing the mortality and morbidity of these conditions. However, approved antiplatelet therapies have adverse side effects, most notably the increased risk of bleeding. Moreover, there remains a considerable incidence of arterial thrombosis in a subset of patients receiving currently available drugs. Thus, there is a pressing medical need for novel antiplatelet agents with a more favorable safety profile and less patient resistance. The discovery of novel antiplatelet targets is the matter of intense ongoing research. Recent findings demonstrate the potential of targeting key signaling molecules, including kinases and phosphatases, to prevent platelet activation and aggregation. Here, we offer perspectives to targeting members of the protein tyrosine phosphatase (PTP) superfamily, a major class of enzymes in signal transduction. We give an overview of previously identified PTPs in platelet signaling, and discuss their potential as antiplatelet drug targets. We also introduce VHR (DUSP3), a PTP that we recently identified as a major player in platelet biology and thrombosis. We review our data on genetic deletion as well as pharmacological inhibition of VHR, providing proof-of-principle for a novel and potentially safer VHR-based antiplatelet therapy.


Comparative expression of major histocompatibility complex (MHC) antigens on CD5+ and CD5- B cells in patients with chronic lymphocytic leukaemia (CLL)
The aim of this study was to investigate the expression of major histocompatibility complex (MHC) antigens on CD5+ and CD5- B cells of 13 patients with chronic lymphocytic leukaemia (CLL). This was carried out using a series of monoclonal antibodies (MAbs) against polymorphic and monomorphic class I and class II antigens, as well as to the transferrin receptor and assessed by flow cytometry and direct and indirect immunofluorescence. The expression of these molecules was assessed as mean fluorescent intensity (MFI). The results showed that cells from all 13 individuals expressed monomorphic class I antigens. The number of cases expressing polymorphic HLA-Bw6, -Bw4, -B7, -B27 and -A2 class I antigens on CD5- B cells was 11 (85%), 6(46%), 2(15%), 1(8%), 3 (23%), respectively, which was consistent with the expected population frequency distributions of these antigens. For each of the class I antigens on CD5+ and CD5- B cells, the ratio of the MFI was greater than 1 in 12 of 13 cases. For the transferrin receptor (CD71), this ratio was also almost always greater than 1. These results indicate that, unlike solid tumours where the loss or abnormal expression of class I and II antigens is a frequent event, the expression of class I antigens in CLL patients seems to be normal. This indicates that the loss of these antigens cannot provide the leukaemic cells with a selective advantage to escape immunological detection.


A Paradigm Shift in Primary Liver Cancer Therapy Utilizing Genomics, Molecular Biomarkers, and Artificial Intelligence.
Primary liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related death. Conventional therapies offer limited survival benefit despite improvements in locoregional liver-directed therapies, which highlights the underlying complexity of liver cancers. This review explores the latest research in primary liver cancer therapies, focusing on developments in genomics, molecular biomarkers, and artificial intelligence. Attention is also given to ongoing research and future directions of immunotherapy and locoregional therapies of primary liver cancers.


Acetylcholinesterase neurons in the lateral hypothalamus project to the spinal cord.
The possibility that cholinergic neurons of the basal forebrain project to the spinal cord was investigated utilizing the retrograde transport of bisbenzimide and [3H]choline as well as acetylcholinesterase histochemistry. A striking similarity was observed in the distributions of lateral hypothalamic neurons labeled with bisbenzimide and acetylcholinesterase. Only a small number of these neurons contained both markers, suggesting the possibility of a small cholinergic projection from the lateral hypothalamus to the spinal cord. The use of [3H]choline to test this hypothesis yielded negative results. Thus the present observations indicating that lateral hypothalamic neurons are cholinoceptive, are consistent with choline acetylcholinesterase immunohistochemical studies. The potential for basal forebrain cholinergic neurons to influence spinal autonomic activity via the lateral hypothalamus is discussed.


Prey susceptibilities, prey utilization and variable attack efficiencies of Ural owls.
To investigate the factors that influence prey utilization among predators with active prey, three series of experiments were performed in which Ural owls (Strix uralensis) searched for and attacked three prey species of wild mice, Microtus montebelli, Apodemus speciosus, and A. argenteus, in a large flight cage. Over the whole study, owls attacked mice about ten times a night. The number of attacks on each prey species did not differ from that predicted by a random attack model. M. montebelli was taken more than either Apodemus species. Prey utilization appears to be influenced by prey susceptibilities only and it is unlikely that prey selection by the owls affected prey utilization patterns. Under the experimental conditions, random attack is predicted by optimal foraging theory. However, random attack may be explained just as well by the inability of the owl to discriminate prey type. The owls, energy gain was adjusted not by alteration in the number of attacks on a prey species but rather by alteration in the capture success between experiments. Capture success increased in poor food conditions for the same prey species. This flexibility in capture success has not been considered in the assumptions of optimal foraging theory. In conventional optimal foraging theory, the probability of capture success is implicitly assumed as constant and unity. We suggest that this assumption is inadequate to understand the foraging behavior of owls.


Calreticulin expression in infiltrating ductal breast carcinomas: relationships with disease progression and humoral immune responses.
The aim of this study was to evaluate calreticulin expression in infiltrating ductal breast carcinomas (IDCAs), as well as its relationships with clinicopathological parameters of the disease. Using a two-dimensional gel electrophoresis/matrix-assisted laser desorption ionization time of flight mass spectrometry investigation coupled to an immunohistochemical approach, we have assessed the expression of calreticulin in IDCAs, as well as in other types of breast tumors. The humoral immune response against calreticulin was estimated using a serological proteomics-based strategy. Proteomic analyses revealed an increased expression of calreticulin in IDCA tumors. Using immunohistochemistry, overexpression of calreticulin was confirmed in 51 additional tumor specimens. Statistical analyses revealed, however, no significant correlations between calreticulin expression and clinicopathological parameters of the disease including tumor stage, patient age, SBR grade, and lymph node metastasis occurrence. A significant association was found, however, with estrogen receptor status. This study demonstrates the upregulation of calreticulin in IDCA tissues which may highlight its involvement in breast cancer development. Our findings also support a link between calreticulin expression and estrogen transduction pathways. Our results do not, however, support the involvement of calreticulin in the development of a humoral immune response in IDCAs.


The effect of flash vacuum cooling on the flavor of ultrapasteurized milk.
Ultrapasteurization (UP) extends the shelf life of milk. Direct steam injection (DSI) is commonly used for UP because milk is quickly heated and cooled. During this process, steam is directly injected into milk and removed by a vacuum cooler. Consumers do not prefer the flavor of DSI-UP milk compared with traditional high temperature short time (HTST) milk due to the higher cooked and eggy flavors of DSI-UP milk. The objective of this research was to characterize the effect of the vacuum cooler on the flavor of DSI-UP milk. Raw skim milk was pasteurized at 140°C for 2.3 s by DSI and homogenized at 20.7 MPa. By using a liquid sample port, steam-infused pasteurized milk was sampled after heating but before reaching the vacuum chamber. A septum was installed in the vacuum chamber to allow sampling of the removed volatiles by solid-phase microextraction (SPME) fiber followed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) combined with a sulfur-selective flame photometric detector. Steam-infused milk and vacuum-cooled milk diluted to the same solids contents were evaluated by descriptive sensory analysis and volatile compound analysis. The entire experiment was replicated 3 times. Milks cooled by the vacuum cooler were lower in sweet aromatic, sulfur/eggy, and cooked flavors than milk sampled before the vacuum cooler. Volatile compounds removed by the vacuum cooler included the sweet aromatic flavor contributors furaneol, maltol, furfural, sotolon, 2-heptanone, γ-dodecalactone, γ-decalactone, and δ-decalactone, as well as the cooked and sulfur/eggy contributors hydrogen sulfide and dimethyl sulfide. The vacuum cooler applied during DSI-UP of milk is effective at removing steam and cooling UP milk, but this process may also remove important flavor compounds from fluid milk.


Loss of heat shock protein 70 from apical region of buffalo (Bubalus bubalis) sperm head after freezing and thawing.
The post-thaw fertility of frozen-thawed mammalian spermatozoa is substantially low as compared with that of fresh sperm. Furthermore, the post-thaw fertility of the cryopreserved buffalo sperm has been reported to be poor as compared with that of cattle sperm. Recently, heat shock protein 70 (HSP70) has been found to play a critical role in mammalian fertilization and early embryonic development in boar and cattle. However, the presence of such fertility-related HSP70 in buffalo sperm and its status after cryopreservation has not been reported so far. Thus, a study was conducted to determine the effect of cryopreservation on the level and distribution pattern of HSP70 molecule in buffalo sperm after cryopreservation. Buffalo semen samples, after dilution in semen extender, were aliquoted in straws and divided into two groups. One group was not cryopreserved, and the other group was cryopreserved for 60 days. Sperm proteins were extracted from both non-cryopreserved (NC) and cryopreserved (C) sperm and subjected to Western blot analysis for detection of HSP70 using a monoclonal anti-HSP70 antibody. The distribution pattern of these proteins in buffalo sperm was also monitored before and after cryopreservation using indirect immunofluorescence technique. A prominent 70-kDa protein band of HSP70 protein was detected in protein extracts of both NC and C buffalo sperm. Densitometry analysis revealed that the intensity of 70-kDa HSP70 protein band of cryopreserved sperm decreased significantly (P < 0.05) compared with that of NC sperm. However, the level of HSP70 in cryopreserved extended seminal plasma (ESP) did not change as compared with that of NC samples indicating a possible degradation of HSP70 in the spermatozoa itself rather than leakage of the protein into the ESP. Furthermore, Western blot also confirmed that several HSP70 immunoreactive protein bands detected in the ESP were contributed by the egg yolk that was added to the extender. Immunocytochemistry revealed that HSP70 proteins were distributed over the apical region of sperm head and/or acrosome, post-acrosomal, and middle piece regions of NC buffalo spermatozoa. However, the fluorescence signal of apical region of sperm head was lost significantly (P < 0.05) after a cycle of freezing and thawing. Thus, the present study confirmed that there was loss of HSP70 from buffalo sperm head after freezing and thawing of buffalo spermatozoa, and this may be one of the causes of the reduced post-thaw fertility of sperm in this species.


Stimulation of cardiac sympathetic afferents activates glutamatergic neurons in the parabrachial nucleus: relation to neurons containing nNOS.
Our previous studies have demonstrated that stimulation of cardiac sympathetic afferents activates neurons in the parabrachial nucleus (PBN), a region known to play a role in central integration of cardiovascular autonomic reflexes. However, phenotypes of these activated neurons have not been well identified. Glutamate, an important excitatory neurotransmitter in the brain, is involved in PBN-mediated cardiovascular responses. Recent identification of vesicular glutamate transporter 3 (VGLUT3) has provided a novel and unique marker to locate distinctive perikarya of neurons that use glutamate as a neurotransmitter. The action of glutamate in the brain is influenced by nitric oxide. Thus, using triple immunofluorescent labeling, the present study examined expression of c-Fos, an immediate early gene, in the neurons containing VGLUT3 and neuronal nitric oxide synthase (nNOS) in the PBN following stimulation of cardiac sympathetic afferents. In anesthetized cats with bilateral barodenervation and cervical vagotomy, topical application of bradykinin (BK, 1-10 microg/ml, 50 microl, n = 6) on the left ventricle was performed six times, every 20 min. Repeated administration of BK elicited consistent increases in blood pressure over a 100 min period while no changes were noted in the animals treated with the vehicle for BK (0.9% saline, n=5). Compared to control cats, c-Fos expression was increased significantly in the cell bodies containing VGLUT3 as well as both VGLUT3 and nNOS in the external lateral PBN (elPBN) in BK-treated animals (all P < 0.01). In addition, using similar triple-staining method, we noted that fibers of activated neurons containing nNOS in the elPBN co-localized with vesicular glutamate transporter 2 following BK stimulation. These data suggest that glutamatergic neurons represent a cell type in the PBN that is activated by stimulation of cardiac sympathetic afferents. Nitric oxide has the potential to influence the action of glutamatergic neurons in regulation of excitatory cardiovascular responses induced by activation of cardiac sympathetic afferents.


The rapid evolution of reproductive proteins.
Many genes that mediate sexual reproduction, such as those involved in gamete recognition, diverge rapidly, often as a result of adaptive evolution. This widespread phenomenon might have important consequences, such as the establishment of barriers to fertilization that might lead to speciation. Sequence comparisons and functional studies are beginning to show the extent to which the rapid divergence of reproductive proteins is involved in the speciation process.


Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees.
Abnormal serum immunoglobulin (Ig) free light chains (FLC) are established biomarkers of early disease in multiple B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL). Heavy chains have also been shown to be biomarkers in plasma cell disorders. An unanswered question is whether these Ig biomarkers are heritable, i.e., influenced by germline factors. CLL is heritable but highly heterogeneous. Heritable biomarkers could elucidate steps of disease pathogenesis that are affected by germline factors, and may help partition heterogeneity and identify genetic pleiotropies across malignancies. Relatives in CLL pedigrees present an opportunity to identify heritable biomarkers. We compared FLCs and heavy chains between relatives in 23 high-risk CLL pedigrees and population controls. Elevated IgM (eIgM) and abnormal FLC (aFLC) ratio was significantly increased in relatives, suggesting that these Ig biomarkers are heritable and could offer risk stratification in pedigree relatives. Within high-risk CLL pedigrees, B-cell lymphoid malignancies were five times more prevalent in close relatives of individuals with eIgM, prostate cancer was three times more prevalent in relatives of individuals with aFLC, and monoclonal B-cell lymphocytosis increased surrounding individuals with normal Ig levels. These different clustering patterns suggest Ig biomarkers have the potential to partition genetic heterogeneity in CLL and provide insight into distinct heritable pleiotropies associated with CLL.


A child psychiatry consultation service to paediatricians.
A review of referrals to the University department of child psychiatry in Newcastle upon Tyne demonstrated active consultation and collaboration between the department and paediatric departments. Important differences in sex, distribution of psychiatric disorders and presence of associated physical and social handicap were found between patients referred from different sources. The presence of some psychological disturbance in those children referred from hospital wards was evident to most paediatricians, and constituted the most frequent reason for referral. Recommendation for psychiatric treatment was made for the majority of patients, but subsequent parental co-operation was often poor. In the authors' view the greatest value of this research is that it highlights atrange of disorders of common concern to paediatricians and children's psychiatrists, using not only the terminology traditional in child psychiatry but also employing a descriptive terminology. They believe it is essential that trainees of both disciplines should have adequate experience in this wide range of disorders.


Individual variation in pathogen attack and differential reproductive success in the annual legume, Amphicarpaea bracteata.
Demographic analyses in two natural populations of the annual legume Amphicarpaea bracteate examined whether variation in attack by the host-specific fungal pathogen Synchytrium decipiens was associated with variation in the reproductive success of individual plants. In both populations, fungal infection early in life was significantly associated with reduced seedling growth rates. Laboratory inoculation experiments confirmed that S. decipiens infection had a negative impact on plant growth. The laboratory experiments further indicated that there was significant variation among the progenies of different plant genotypes in the degree of growth reduction caused by pathogen attack. Prereproductive mortality rates in natural environments were significantly higher for plants with infection intensities above the median; for the two populations studied, heavily infected plants had 3.8 and 12 gimes higher death rates compared with low infection plants. Among surviving plants, fungal infection intensity was significantly negatively correlated with total seed biomass in both populations. As a result of these associations between plant survivorship, fecundity, and fungal infection, lifetime relative fitness within both plant populations was strongly negatively correlated with the intensity of S. decipiens infection. These results demonstrate the existence of consistent natural selection for increased resistance to pathogen attack in this plant species.


Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma.
Peritoneal carcinomatosis (PC) is associated with a dismal prognosis. Small bowel adenocarcinoma is a rare etiology for PC. Due to the rarity, poor prognosis, and lack of standard treatment, we chose to review our experience with this disease process treated with cytoreductive surgery (CS) and intraperitoneal hyperthermic chemotherapy (IPHC). From a prospective database of IPHC patients, six patients diagnosed with PC from adenocarcinoma of the small bowel were identified. Between 1995 and 2004 these patients underwent CS and IPHC with Mitomycin C. A retrospective review was performed on these patients with mortality as the primary outcome measure. Three of the six patients in this series are still alive, with a mean follow-up of 19.7 months after treatment with CS and IPHC. Three patients died of disease progression 29, 30, and 45 months after IPHC. Median survival after diagnosis of small bowel adenocarcinoma was 54 months, while median survival after CS and IPHC for PC was 30.1 months. Small bowel adenocarcinoma with PC remains an unusual therapeutic challenge. Treatment with CS and IPHC is an attractive option for patients in this setting.


Reduced frequency of baseline sister chromatid exchanges in lymphocytes grown in antibiotics and serum-excluded culture medium.
Peripheral venous blood from man, muntjac, and cattle were grown in medium (1) containing different serum (human AB+/FCS/autologous), (2) without serum or antibiotics (penicillin and streptomycin), or (3) without both serum and antibiotics to investigate to what extent certain essential culture components used in in vitro mammalian cell cultures affect the incidence of spontaneous sister chromatid exchanges (SCEs). The observation that exclusion of only serum from culture medium enhanced the frequency of SCEs whereas exclusion of both serum and antibiotics, which influence the cell cycle kinetics to a great extent, exhibited the lowest frequency of SCEs reported so far for lymphocyte cultures, indicates that the frequency of so-called spontaneous SCEs usually observed in normal lymphocyte cultures grown in medium supplemented with serum and antibiotics is in fact an elevated frequency.


Network pharmacology exploration reveals a common mechanism in the treatment of cardio-cerebrovascular disease with Salvia miltiorrhiza Burge. and Carthamus tinctorius L.
This study aimed to identify the key genes and KEGG pathways in Carthamus tinctorius L. (Safflower) and Salvia miltiorrhiza Burge. (Salvia) for the treatment of cardio-cerebrovascular disease, and to explore their potential molecular mechanisms. Compounds and targets in Safflower and Salvia were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). We obtained targets of myocardial infarction (MI) and cerebral infarction (CI) data from Therapeutic Target Database (TTD), Drugbank and DisGeNET datasets. The network of Safflower, Salvia, CI and MI was established and then executing, and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses of the functional characteristics were performed. The Chinese herbal prescription and target for CI and MI were obtained by searching in the database. Finally, the main pathways of Salvia and Safflower in Chinese patent medicines were analyzed. The MCAO model was established in rats, and compatibility of salvia with safflower was experimentally verified. We obtained a total of 247 genes targeted by 52 compounds from Safflower and 119 genes targeted by 48 compounds from Salvia. In total, we identified 299 known therapeutic targets for the treatment of CI and 960 targets for the treatment MI. There are 23 common targets for Salvia, Safflower, MI, and CI. A total of 85 KEGG pathways were also enriched and intersected with the pathway of proprietary Chinese medicine to yield 25 main pathways. Safflower and Salvia have the best therapeutic effect in MCAO. We identified gene lists for Safflower and Salvia in CI and MI. Bioinformatics and interaction analyses may provide new insight into the treatment of cardio-cerebrovascular diseases with Safflower and Salvia.


Discounting the duration of bolus exposure in impedance testing underestimates acid reflux.
Combined impedance-pH testing (MII) allows for detection of reflux episodes regardless of pH. However impedance-based diagnosis of reflux may not routinely account for duration of the reflux episode. We hypothesize that impedance testing may be less sensitive than pH-testing in detecting acid reflux off therapy as a result of discounting duration of exposure. Baseline characteristics and reflux parameters of MII studies performed off-anti-secretory medications were analyzed. Studies on acid suppressive medication and those with recording times less than 20 h or low baseline impedance were excluded. A total of 73 consecutive MII studies were analyzed of which 31 MII studies had elevated acid exposure while 16 were abnormal by impedance criteria. MII testing off-therapy was more likely to be abnormal by pH criteria (percent time pH < 4) than impedance criteria (total reflux):[42 vs 22 % (p =0.02)]. Acid exposure (percent time pH < 4) identified more studies as abnormal than MII-detected acid reflux episodes [42 vs 34 % (p < 0.01)]. Mean acid clearance time (pH-detected) was significantly longer than median bolus clearance time (impedance-detected) in the total [98.7 s vs 12.6 s (p < 0.01)], upright [58.6 s vs 13.1 s (p < 0.01)], and recumbent positions [136.7 s vs 14.2 s (p < 0.01)] with the greatest difference seen in the recumbent position. The mean ratio of mean acid clearance time (pH-detected) and the median bolus clearance time (impedance-detected) was significantly higher in the recumbent position compared to the upright position [11. vs 5.3 (p = 0.01)]. Ambulatory impedance testing underestimates acid reflux compared to esophageal acid exposure by discounting the prolonged period of mucosal contact with each acid reflux episode, particularly in the recumbent position.


Effect of interprofessional and intraprofessional clinical collaboration on patient related outcomes in multimorbid older patients - a retrospective cohort study on the Intensive Collaboration Ward.
The management and care of older patients with multiple health problems is demanding and complex. Interprofessional and intraprofessional collaboration has the potential to improve both the efficiency and the quality of care for these patients. However, it has proven difficult to demonstrate the efficacy of this approach in terms of objective patient-related outcomes. Recently, a care model with interprofessional and intraprofessional care was started, the Intensive Collaboration Ward (ICW). This ward combines interprofessional care and intraprofessional care for older patients with multiple health problems. The aim of this study was to evaluate the effects of ICW care in older patients with multiple health problems. This retrospective cohort study evaluated the effects on patients outcomes. This was done by comparing patients of the new model, the ICW (ICW group), to a historical cohort of comparable patients who would have been eligible for the ICW (control group). Outcomes were medical consultations, allied health professional consultations, radiological procedures, waiting time for radiological procedures, change in primary treating specialty, length of hospital stay, readmission rate, and mortality rate. Linear and logistic regression analyses were performed, adjusted for baseline differences. The ICW group required significantly fewer medical consultations than the control group. Calls to specialists from the emergency room decreased significantly, but there was no change in in-person consultations on the ER. 51% of control patients had ≥ 1 in-hospital consultation compared to 21% of ICW patients (p < 0.05). Patients in the ICW group received significantly more consultations with allied health professionals and more often had a change in primary treating specialty. Interprofessional and intraprofessional clinical collaboration on the ICW reduced in-hospital consultations and increased allied health professionals' consultations. This approach may decrease fragmentation of care and provide more integrated, efficient and patient centered care. This may improve the overall care of older patients with multiple health problems.


Distress and its correlates in Korean cancer patients: pilot use of the distress thermometer and the problem list.
The distress thermometer (DT), a one-item measure for distress, provides a means for rapidly and effectively screening psychological distress in cancer patients. In this pilot study, a screening efficacy of the DT was investigated in a mixed cohort of 108 Korean cancer patients. Participants completed the DT, the problem list (PL), and the Hospital Anxiety and Depression Scale (HADS), and answered questions regarding supportive needs and their degree of satisfaction with several aspects of care. Receiver operating characteristic (ROC) curve analyses indicated that a DT cutoff score of 4 yielded an area under the ROC curve of 0.75 with a sensitivity of 0.83 and a specificity of 0.59 for HADS-total score defined cases (> or =15). HADS--Anxiety and Depression subscale scores explained 27% of the variability in the DT scores, implying that 'distress' is a broader concept that includes anxiety and depressive symptoms but has a more comprehensive meaning that encompasses multiple contributory factors. Regarding the PL, distressed patients (DT> or =4) reported significantly more problems (23 of 35) in all categories, suggesting, although degrees differ, that a wide variety of problems contribute to distress in cancer patients. Distress as defined by DT and HADS subscale scores was also significantly associated with higher supportive needs, a poor ECOG performance status (both physician and patient-rated), and a reduced level of satisfaction with treatment, staff, and communications. In conclusion, the DT and the PL were found to be simple yet effective screening instruments for detecting psychosocial distress in Korean cancer patients, and for identifying problems that warrant intervention.


The unfolding enthalpy of the pH 4 molten globule of apomyoglobin measured by isothermal titration calorimetry.
The unfolding enthalpy of the pH 4 molten globule from sperm whale apomyoglobin has been measured by isothermal titration calorimetry, using titration to acid pH. The unfolding enthalpy is close to zero at 20 degrees C, in contrast both to the positive values expected for peptide helices and the negative values reported for holomyoglobin and native apomyoglobin. At 20 degrees C, the hydrophobic interaction should make only a small contribution to the unfolding enthalpy according to the liquid hydrocarbon model. Our result indicates that some factor present in the unfolding enthalpies of native proteins makes the unfolding enthalpy of the pH 4 molten globule less positive than expected from data for peptide helices.


Analyzing the chance of developing dementia among geriatric people: a cross-sectional pilot study in Bangladesh.
Alzheimer's disease is the most common form of dementia, representing 60-80% of cases, and ageing is the primary risk factor for the development of Alzheimer's disease. The objective of this study was to examine the chance of developing dementia (i.e. mild cognitive impairment (MCI), Alzheimer's disease) among geriatric people in Bangladesh. This study included 390 adult citizens of Bangladesh (age range: 60-70 years). The Takeda Three Colors Combination (TTCC) test was used to detect the prevalence of MCI and mild dementia among the subjects, and then the Clinical Dementia Rating was used to determine the level of dementia. The subjects who were aged 60-65 years included 154 with MCI, 76 with mild dementia, 1 with moderate dementia, 4 with severe dementia, and 29 without dementia. The subjects who were aged 66-70 years included 75 with MCI, 36 with mild dementia, 0 with moderate dementia, 2 with severe dementia, and 13 without dementia. The sensitivity of the TTCC was 75% and 58% for the mild dementia and MCI groups, respectively, and the specificity was 52%. The odds ratio of incorrect responses to the TTCC was 3.42 (95% confidence interval: 1.63-7.21) for subjects with mild dementia compared those without dementia. However, the TTCC outcomes revealed no significant differences between the MCI and non-dementia groups. The results showed no significant associations between cognitive decline/developing dementia and social status/occupation. The outcomes of this study indicated that most of the subjects had MCI or mild dementia and were farmers aged 60-65 years.


Prostate cancer risk among men with diabetes mellitus (Spain).
Observational studies have associated diabetes with a decreased risk of prostate cancer. We aimed to evaluate this association using the General Practitioner Research Database in the UK. Population based case-control study nested in a cohort. We identified 2,183 incident cases of prostate cancer between January 1995 and December 2001. We found that diabetic patients had a decreased risk of prostate cancer (OR = 0.72; 95% CI: 0.59-0.87). This association was observed among treated diabetics (OR = 0.63; 95% CI: 0.50-0.80) but not among untreated diabetics (OR = 1.01; 95% CI: 0.73-1.40). Our results suggest that the observed reduced risk could be restricted to users of insulin or sulphonylureas. Patients with diabetes have a decreased risk of prostate cancer. The role of antidiabetic treatment in this association warrants further research.


Gender imbalance in infant mortality: a cross-national study of social structure and female infanticide.
Sex differentials in infant mortality vary widely across nations. Because newborn girls are biologically advantaged in surviving to their first birthday, sex differentials in infant mortality typically arise from genetic factors that result in higher male infant mortality rates. Nonetheless, there are cases where mortality differentials arise from social or behavioral factors reflecting deliberate discrimination by adults in favor of boys over girls, resulting in atypical male to female infant mortality ratios. This cross-national study of 93 developed and developing countries uses such macro-social theories as modernization theory, gender perspectives, human ecology, and sociobiology/evolutionary psychology to predict gender differentials in infant mortality. We find strong evidence for modernization theory, human ecology, and the evolutionary psychology of group process, but mixed evidence for gender perspectives.


Identification and characterization of two enhancers of the human albumin gene.
A 12.5-kilobase pair (kb) segment upstream of the human albumin gene was analyzed for transcription enhancing activity using transient transfection analysis, gel mobility shift assays, DNase I footprinting, and site-specific mutagenesis. Two enhancer regions were identified, one 1.7 kb upstream of the transcription initiation site (E1.7) and the other 6 kb upstream (E6). In E1.7, a nuclear protein from HuH-7 hepatoma cells binds to an AT-rich sequence, GTTACTAATTGAC. Competition gel mobility shift assays suggested that this protein is HNF-1, which regulates the promoter of the albumin gene and several other liver-specific genes. A 60-base pair E1.7 fragment carrying the AT-rich sequence stimulates a heterologous (alpha-fetoprotein) promoter in a dose-dependent manner. In E6, a HuH-7 nuclear protein binds to a GT-rich sequence, TGTTTGGC.A 27-base pair E6 fragment carrying this sequence is able to stimulate the SV40 promoter in an orientation-independent manner. An alteration of this sequence by site-specific mutagenesis resulted in the loss of transcriptional activity as well as binding to the HuH-7 nuclear protein. Competition gel mobility shift assays showed that homologous elements exist in the albumin promoter. These results show that the promoter and enhancer of the human albumin gene are regulated by two common transcription factors through two shared cis-acting elements, one AT-rich and the other GT-rich.


When is it considered reasonable to start a risky and uncomfortable treatment in critically ill patients? A random sample online questionnaire study.
Health care professionals have to judge the appropriateness of treatment in critical care on a daily basis. There is general consensus that critical care interventions should not be performed when they are inappropriate. It is not yet clear which chances of survival are considered necessary or which risk for serious disabilities is acceptable in quantitative terms for different stakeholders to start intensive care treatment. We performed an anonymous online survey in a random sample of 1,052 participants recruited via email invitation and social media. Age, sex, nationality, education, professional involvement in health care, critical care medicine and treatment decisions in critical care medicine as well as personal experience with critical illness were assessed as potential influencing variables. Participants provided their opinion on the necessary chances of survival and the acceptable risk for serious disabilities to start a high-risk or uncomfortable therapy for themselves, relatives or for their patients on a scale of 0-100%. Answers ranged from 0 to 100% for all questions. A three-peak pattern with different distributions of the peaks was observed. Sex, education, being a health care professional, being involved in treatment decisions and religiosity influence these opinions. Male respondents and those with a university education would agree that a risky and uncomfortable treatment should be started even with a low chance of survival for themselves, relatives and patients. More respondents would choose a lower necessary chance of survival (0-33% survival) when deciding for patients compared to themselves or relatives to start a risky and uncomfortable treatment. On the other hand, the majority of respondents would accept only a low risk of severe disability for both themselves and their patients. No cut-off can be identified for the necessary chances of survival or the acceptable risk of disability to help quantify the "inappropriateness" of critical care treatment. Sex and education are the strongest influencing factors on this opinion. The large variation in personal opinions, depending on demographic and personality variables and education needs to be considered in the communication between health care professionals and patients or surrogates.


Lack of altered cyclic nucleotide phosphodiesterase activity in the aorta and heart of the spontaneously hypertensive rat.
DEAE-cellulose chromatography demonstrated that the levels of the individual cyclic nucleotide phosphodiesterases were unchanged in the aorta and heart of the spontaneously hypertensive rat as compared with the normotensive control rat. Three peaks of cyclic nucleotide phosphodiesterases activity were observed in both heart and aorta. Peak I enzyme hybrolyzed predominantly cyclic GMP while peak III enzyme hydrolyzed predominantly cyclic AMP. Peak II enzyme was less specific but hydrolyzed more cyclic GMP than cyclic AMP. The levels of phosphodiesterase activator in aorta and the responsiveness of peaks I and II from aorta and heart to activator were unchanged in the hypertensive rat. Therefore the decrease in cyclic AMP levels observed by others in aorta and heart of the spontaneously hypertensive rat were probably not due to altered phosphodiesterase activity.


DNA extraction of ancient animal hard tissue samples via adsorption to silica particles.
A large number of subfossil and more recent skeletal remains, many of which are stored in museums and private collections, are potentially accessible for DNA sequence analysis. In order to extract the small amount of DNA preserved in these specimens, an efficient DNA release and purification method is required. In this chapter, I describe an efficient and straightforward purification and concentration method that uses DNA adsorption to a solid surface of silica particles. Comparative analysis of extraction methods has shown that this method works reliably for ancient as well as younger, museum-preserved specimens.


Review: Morphology, behaviour and interactions of organelles.
High quality transmission electron micrographs have played a major role in shaping our views on organelles in plant cells. However, these snapshots of dead, fixed and sectioned tissue do not automatically convey an appreciation of the dynamic nature of organelles in living cells. Advances in the imaging of subcellular structures in living cells using multicoloured, targeted fluorescent proteins reveal considerable changes in organelle pleomorphy that might be limited to small regions of the cell. The fresh data and insights also challenge several existing ideas on organelle behaviour and interactivity. Here, using succinct examples from plastids, mitochondria, peroxisomes, and the endoplasmic reticulum I present an evolving view of subcellular dynamics in the plant cell.


Synthesis, cytotoxicity, and DNA-topoisomerase inhibitory activity of new asymmetric ureas and thioureas.
A new series of N-3,3-diphenylpropyl-N-(p-X-benzyl)-N'-phenylureas (5a-g) and thioureas (6a-g) were synthesized by the reaction of secondary amines and phenyl isocyanate or isothiocyanate. The cytotoxic effects of the urea and thiourea derivatives were evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay against Ehrlich carcinoma and K562 human leukemia cells. Moreover, the activity of compounds in the inhibition of DNA topoisomerases I and II-alpha was tested. The results indicated that the compounds presented important and promising antiproliferative action.


The patch test--who should and should not use it and why.
Since its introduction into medicine by Joseph Jadassohn in 1895, the patch test has proven its supreme value in tens of thousands of cases and in research. But emphasis must be placed on the grave errors which can occur when the test is used improperly. Errors are common in the direction of both false positives and false negatives. Common causes of errors are described in detail. The conclusion is drawn that this valuable test had best be used only by those who have been adequately trained and who can apply it regularly on a sufficiently large number of selected patients.


Uptake of galactose and lactose by Kluyveromyces lactis: biochemical characteristics and attempted genetical analysis.
Study of the lactose and galactose transport systems in Kluyveromyces lactis has shown that lactose uptake is by active transport. The transport system is under monogenic control and is inducible. Galactose uptake is also by active transport but the system is controlled by two genes which, in the four strains we studied, are present only in K. lactis CBS 2359. Galactose uptake in the other K. lactis strains is by a simple diffusion process.


What we have learned regarding antibiotic therapy for the reduction of infant morbidity after preterm premature rupture of the membranes.
Preterm premature rupture of the membranes (pPROM) is responsible for approximately one third of the over 450,000 preterm births occurring in the United States annually. In this manuscript, we summarize the outcomes and analyses related to the National Institute of Child Health and Human Development Maternal Fetal Medicine Units Network (NICHD-MFMU) network multicenter trial of antibiotics to reduce infant morbidity after pPROM. Based on evident reduction in gestational age dependent and infectious infant morbidity, we provide the rationale for aggressive intravenous and oral, broad spectrum Ampicillin/Amoxicillin, and Erythromycin therapy during conservative management of pPROM before 32 weeks' gestation. We further review the histopathologic correlates to pPROM, to antibiotic treatment, and to perinatal outcome, and discuss the relationships between maternal and neonatal cytokine levels intercellular adhesion molecule, and other clinical and plasma markers regarding perinatal morbidity. The use and limitations of ultrasound and vaginally collected amniotic fluid pulmonary maturity assessment are discussed.


The incidence of neoplasms in Syrian hamsters with particular emphasis on intestinal neoplasia.
The incidence of neoplasms is presented for 600 Syrian hamsters (Mesocricetus auratus) used as controls in the evaluation of carcinogenicity of various experimental viral vaccines administered as a single subcutaneous injection at birth. Approximately 30% of the animals had neoplasms with no appreciable sex difference in the overall tumor incidence. The most frequent tumor types were those of the adrenal cortex (13.5%), the lymphoreticular system (3%), and the endometrium (3%). Small intestinal adenocarcinomas occurred in 0.8% of the animals. In this laboratory, the incidence of intestinal tumors is greater and more variable than that in the mouse or the rat. Furthermore, several unusual morphologic and biologic features of this tumor type were identified. These findings raise questions about the suitability of the Syrian hamster in carcinogenic bioassays.


Killer-cell lines derived from mouse thymus, resembling large granular lymphocytes and expressing natural killer-like cytotoxicity.
Murine thymus cells were maintained in vitro with supernatant-factors derived from Concanavalin-A-stimulated spleen cells. After an initial phase of vigorous proliferation, large granular cells (GC), which were not observed in fresh thymus cell preparations, appeared in these cultures. GC, derived from C3Hf/Tif-, BALB/c-, and C57BL/10-thymus cultures, could be slowly expanded and have been maintained as increasingly homogeneous (oligoclonal) lines for up to six months. During this time, other types of thymus cells died or were diluted out. Thymic GC differ functionally and histochemically from macrophages and mast cells. They do not phagocytize zymosan particles, bind opsonized SRBC, express nonspecific esterases or contain detectable amounts of histamine. GC share many features with natural killer (NK) cells and large granular lymphocytes (LGL). One morphologically representative line (C3Hf/Tif) had the following surface phenotype: Thy-1+, Lyt-1-, Lyt-2-, H-2K+, I-A-, asialo Gm1+. GC bind peanut agglutinin (PNA) on their surface and contain azurophilic granules. These cytoplasmic granules are considerably larger than those in LGL. Cells of a GC line derived from mouse strain C3Hf/Tif (H-2k) lysed the NK-sensitive YAC-1 (H-2a) and EL-4 (H-2b), but not the NK-insensitive P815 cells.


Dispersal syndromes can link intraspecific trait variability and meta-ecosystem functioning.
Dispersal mediates the flow of organisms in meta-communities and subsequently energy and material flows in meta-ecosystems. Individuals within species often vary in dispersal tendency depending on their phenotypic traits (i.e., dispersal syndromes), but the implications of dispersal syndromes for meta-ecosystems have been rarely studied. Using empirical examples on vertebrates, arthropods, and microbes, we highlight that key functional traits can be linked to dispersal. We argue that this coupling between dispersal and functional traits can have consequences for meta-ecosystem functioning, mediating flows of functional traits and thus the spatial heterogeneity of ecosystem functions. As dispersal syndromes may be genetically determined, the spatial heterogeneity of functional traits may be further carried over across generations and link meta-ecosystem functioning to evolutionary dynamics.


Antidepressants induce regeneration of catecholaminergic axon terminals in the rat cerebral cortex.
Although repeated but not single administration of antidepressants exerts therapeutic effect on clinical depression, the mechanism of the clinical efficacy of antidepressants remains unknown. This report shows a novel action of antidepressants which can explain the delayed onset of clinical action of the drugs. Continuous infusion of the antidepressants maprotiline or desipramine into the rat cerebral cortex pretreated with the catecholamine neurotoxin 6-hydroxydopamine induced regeneration of noradrenergic axon terminals. This finding provides evidence that antidepressants possess the ability to cause axonal sprouting of central noradrenergic (and possibly dopaminergic) neurons in the mature brain.


Pancreatic duct organoid swelling is chloride-dependent.
Pancreatic secretions become viscous and acidic in Cystic fibrosis (CF), highlighting the role of CFTR in pancreatic fluid and bicarbonate secretion. Forskolin-induced swelling (FIS) assay developed in intestinal organoids measures residual CFTR function. It is not known whether FIS reflects bicarbonate secretion in pancreas, an organ that secretes near-isotonic NaHCO3 levels. To investigate this, we generated pancreatic duct organoids from CF and non-CF pigs. Epithelial and ductal origin was confirmed with epithelial markers, ion transporters and lack of acinar, islet cell markers. CF organoids were small with no identifiable lumen; CFTR was expressed only in non-CF organoids. Utilizing FIS, organoid size increased only in response to chloride, not bicarbonate. This report highlights pancreatic duct organoids isolated for the first time from CF pigs and evidence for chloride and not bicarbonate driving pancreatic organoid swelling. These organoids would be useful to test chloride permeability of CFTR mutations that cause CF pancreatic disease.


Isolation and characterization of proteins cross-linked to DNA by the antitumor agent methylene dimethanesulfonate and its hydrolytic product formaldehyde.
This study attempted to characterize proteins cross-linked to DNA of Yoshida lymphosarcoma cells treated with methylene dimethanesulfonate (MDMS) and its hydrolytic products formaldehyde (HCHO) and methanesulfonic acid (MSA). MDMS and HCHO treatments produced a similar extent and type of DNA-protein cross-linking in Yoshida lymphosarcoma cells. All five major histones (H1, H2a, H2b, H3, and H4) were among the nuclear proteins cross-linked to DNA. Certain discrete differences were also apparent in these studies. MDMS cross-linked proteins of 29 and 48 kDa to DNA that were not observed following HCHO treatment alone, and HCHO cross-linked a 26-kDa protein to DNA that was not observed following MDMS treatment. Because semicarbazide prevented all MDMS-induced DNA-protein cross-linking, HCHO must be the component responsible for this lesion. The 26-kDa protein has been identified as an H4-H2b dimer. The formation of this dimer is particularly sensitive to MSA release on hydrolysis of MDMS because, in the presence of MSA, HCHO preferentially cross-linked an H2a-H2b dimer and a 48-kDa non-histone protein to DNA. Differences in DNA-protein cross-linking between these two agents are therefore proposed to arise from discrete changes in chromatin structure induced directly by MSA release.


IRAS Modulates Opioid Tolerance and Dependence by Regulating μ Opioid Receptor Trafficking.
Imidazoline receptor antisera-selected (IRAS) protein, the mouse homologue named Nischarin, was found to target to early endosomes with properties of sorting nexins in vitro. Recently, we generated IRAS knockout mice and found IRAS deficiency exacerbated the analgesic tolerance and physical dependence caused by opioids, suggesting that IRAS plays a role in regulating μ opioid receptor (MOR) functions. In the present study, we found that IRAS interacts with MOR and regulates MOR trafficking in vitro. In the CHO or HEK293 cells co-expressing MOR and IRAS, IRAS, through its PX domain, interacted with MOR. The interaction facilitated the recycling of internalized MOR and prevented MOR downregulation induced by DAMGO, the MOR agonist. Functionally, IRAS accelerated MOR resensitization and attenuated DAMGO-induced MOR desensitization, which is believed as one of mechanisms mediating opioid tolerance and dependence. Taken together, we propose that IRAS is a new MOR interacting protein and regulates agonist-induced trafficking of MOR via sorting internalized MOR to the recycling pathway, which may be a molecular mechanism underlying IRAS modulating opioid tolerance and dependence.


Ocular immune reactants in patients dying with systemic lupus erythematosus.
Immunopathologic studies were performed on ocular tissue obtained at autopsy in five patients with systemic lupus erythematosus (SLE). The immunopathologic findings were correlated with histopathologic and clinical features of SLE. Immune reactants were demonstrated by direct immunofluorescence in all patients in a granular pattern suggesting immune complex aggregates; control ocular tissues from four patients without SLE were negative. Ultrastructural studies demonstrated corresponding electron-dense aggregates in a majority of samples. Histologic and gross anatomic evidence of inflammation were generally more focal and less frequent than the distribution of immune reactants. Most of the immune deposits were localized in the walls of blood vessels of the conjunctiva, ciliary body, retina, choroid, and sclera. Diffuse deposits were also found in association with basement membranes in ciliary body (two of five patients) and along the epithelial basement membrane in the cornea (two of five). Immune deposits in peripheral nerves of the ciliary body and conjunctiva in one patient with visual symptoms contained immunoglobulins A and E. The most intense and widespread ocular immune deposits were observed in patients with persistently increased serologic and clinical activity of their systemic disease. These results suggest a role for immune complex localization in the pathogenesis of the ocular lesions of SLE.


Sex differences in the locus coeruleus-norepinephrine system and its regulation by stress.
Women are more likely than men to suffer from post-traumatic stress disorder (PTSD) and major depression. In addition to their sex bias, these disorders share stress as an etiological factor and hyperarousal as a symptom. Thus, sex differences in brain arousal systems and their regulation by stress could help explain increased vulnerability to these disorders in women. Here we review preclinical studies that have identified sex differences in the locus coeruleus (LC)-norepinephrine (NE) arousal system. First, we detail how structural sex differences in the LC can bias females towards increased arousal in response to emotional events. Second, we highlight studies demonstrating that estrogen can increase NE in LC target regions by enhancing the capacity for NE synthesis, while reducing NE degradation, potentially increasing arousal in females. Third, we review data revealing how sex differences in the stress receptor, corticotropin releasing factor 1 (CRF1), can increase LC neuronal sensitivity to CRF in females compared to males. This effect could translate into hyperarousal in women under conditions of CRF hypersecretion that occur in PTSD and depression. The implications of these sex differences for the treatment of stress-related psychiatric disorders are discussed. Moreover, the value of using information regarding biological sex differences to aid in the development of novel pharmacotherapies to better treat men and women with PTSD and depression is also highlighted. This article is part of a Special Issue entitled SI: Noradrenergic System.


Neurotoxicity of chemotherapeutic and biologic agents in children with cancer.
The sequelae of treatment modalities used to treat childhood cancer are of increasing clinical importance. In children with pediatric malignancies, the full impact of such sequelae may not be apparent until years after treatment. The earlier recognition of these neurotoxicities could possibly alter the course of a treatment or facilitate interventions to improve quality of life.


Weight-Bearing Computed Tomography of the Foot and Ankle-What to Measure?
Weight-bearing computed tomography (WBCT) was introduced in 2012 for foot and ankle applications as a breakthrough technology that enables full weight-bearing, three-dimensional imaging unaffected by x-ray beam projections or foot orientation. The literature describing the use of WBCT in the treatment of foot and ankle disorders is growing, and this article provides an overview of what can be measured with WBCT.


The Minimum Data Set Agitated and Reactive Behavior Scale: Measuring Behaviors in Nursing Home Residents With Dementia.
Interventions aimed at managing agitated and aggressive behaviors in dementia without the use of antipsychotics are currently being tested in nursing homes (NHs). Researchers and clinicians require a measure that can capture the severity of residents' behaviors. We test the internal consistency and construct validity of the Agitated and Reactive Behavior Scale (ARBS), a measure created using data from mandatory NH assessments. Cross-sectional. The 2016 national sample of 15,326 Centers for Medicare and Medicaid Services-certified NHs. The analytic sample included 489,854 new admissions and 765,367 long-stay residents (at least 90 days in NH). All participants have a dementia diagnosis. Minimum Data Set (MDS), version 3.0. The ARBS is a composite measure of (1) physical behavioral symptoms directed at other people; (2) verbal behavioral symptoms directed at other people; (3) other behavioral symptoms not directed at other people; and (4) rejection of care. Variables used to establish construct validity included degree of cognitive impairment, use of medications for managing agitation and aggression, and co-occurring conditions associated with agitated and aggressive behaviors (eg, schizophrenia, depression, or delirium). This report has 3 important findings: (1) the ARBS score has borderline-adequate internal consistency (α = .64-.71) in the national population NH residents with dementia; (2) only 18% of new admissions and 21% of long-stay residents with dementia evidence any agitated or aggressive behaviors in the last week, as rated in the MDS assessment; and (3) the ARBS demonstrates good construct validity; it increases with cognitive impairment, treatment with relevant medications, and co-occurring psychiatric conditions and symptoms. Nationally available MDS data may significantly underestimate the prevalence of agitated and aggressive behaviors among NH residents with dementia. Researchers conducting pragmatic trials of non-pharmaceutical interventions to manage behaviors in NH residents with dementia should consider the likely underdetection of these behaviors in the available MDS data.


Correction of Bileaflet Mitral Valve Prolapse Through Reduction of Posterior Leaflet Height.
Mitral regurgitation due to bileaflet prolapse can be corrected with height reduction of the posterior leaflet through detachment at its base, division of accompanying secondary chordae, and leaflet-annular reapproximation. This technique lowers the posterior leaflet height to approximately 1.5 cm, thereby displacing the line of coaptation posteriorly to achieve symmetry without the need for additional artificial chordae. Of 37 patients who underwent this type of repair at our institution, no patient had recurrent mitral regurgitation ≥ 2 at an average follow-up of 1.9 years (range, 0.2-4.5).


Construction of the physical map of the gpa7 locus reveals that a large segment was deleted during rice domestication.
To facilitate cloning gene(s) underlying gpa7, a deep-coverage BAC library was constructed for an isolate of common wild rice (Oryza rufipogon Griff.) collected from Dongxiang, Jiangxi Province, China (DXCWR). gpa7, a quantitative trait locus corresponding to grain number per panicle, is positioned in the short arm of chromosome 7. The BAC library containing 96,768 clones represents approximate 18 haploid genome equivalents. The contig spanning DXCWR gpa7 was constructed with a series of ordered markers. The putative physical map near the gpa7 locus of another accession of O. rufipogon (Accession: IRGC 105491) was also isolated in silico. Analysis of the physical maps of gpa7 indicated that a segment of about 150 kb was deleted during domestication of common wild rice.


Correction to: Services according to mental health needs for youth in foster care? - a multi-informant study.
Following publication of the original article [1], the authors reported a misaligning of data in Table 3 (weekly results have been put in the column for monthly results).


Expression of enzymatically active enkephalinase (neutral endopeptidase) in mammalian cells.
A cDNA encoding the rat enkephalinase protein (neutral endopeptidase; EC 22.214.171.124) has been constructed from overlapping lambda gt10 cDNA clones. This cDNA was inserted into an expression plasmid containing the cytomegalovirus enhancer and promoter. When transfected with this plasmid, Cos 7 cells transiently expressed the enkephalinase protein in a membrane-bound state. Recombinant enkephalinase recovered in solubilized extracts from transfected Cos 7 cells was enzymatically active and displayed properties similar to those of the native enzyme with respect to sensitivity to classical enkephalinase inhibitors.


The mechanism of anaesthesia: a new hypothesis based on the effects on electrical properties of a model membrane: preliminary studies.
Changes induced by inhalational anaesthetic agents were investigated in a simple membrane model. All the agents tested increased the membrane's electrical capacitance and conductance linearly, proportional to concentration and potency, and decreased its dialectric strength independently of concentration. When protein was substituted for lipid, the same agents had no significant effect on capacitance, conductance, or dielectric strength. Based on these findings, the following hypothesis is presented. Anaesthetic agents exert their influence on the lipid portion of nerve membranes. They enhance excitability by reducing the dielectric strength of the membrane and depress excitability by increasing the membrane's dielectric constant and passive conductance. The degree of excitability or narcosis at any instant depends upon the relative magnitude of these opposing effects.


[Effects of erythropoietin pretreatment on pro-and anti-inflammatory balance in rats with severe acute pancreatitis].
To evaluate the effect of pretreatment with erythropoietin (EPO) on disordered pro- and anti- inflammatory balance in rats with severe acute pancreatitis (SAP) and explore the underlying mechanisms. Ninety healthy male SD rats were randomized equally into sham-operated group, SAP group and EPO pretreatment group. SAP model was induced in the latter two groups by retrograde injection of 1 ml/kg 3.5% sodium traurocholate into the biliopancreatic duct. In EPO group, 3000 U/kg EPO (1000 U/ml) was administered intravenously 1 h before SAP, and normal saline was administered in the other two groups. Serum amylase activity, interleukin-10 (IL-10)and IL-18 levels were measured at different time points after the operation. The translocation and activation of nuclear factor-κB (NF-κB) in the pancreatic tissue was detected using immunofluorescence staining, and pancreatic pathologies were evaluated. Compared with SAP group, EPO group showed a markedly decreased activation rate of NF-κB after SAP except for 12 h (P<0.05), significantly decreased serum amylase activity at 3, 6, and 12 h (P<0.05) and decreased serum IL-18 levels at 3, 6, 24 h (P<0.05), whereas serum IL-10 underwent no significant changes. The rats in EPO group showed an obviously milder pancreatic pathology than those in SAP group at 6, 12, and 24 h (P<0.05). EPO can effectively inhibit NF-κB activation by regulating the inflammatory mediators and restoring the pro-and anti-inflammatory balance to alleviate SAP in rats.


Prenatal nonylphenol exposure, oxidative and nitrative stress, and birth outcomes: A cohort study in Taiwan.
Data concerning the effects of prenatal exposures to nonylphenol (NP) and oxidative stress on neonatal birth outcomes from human studies are limited. A total of 146 pregnant women were studied (1) to investigate the association between prenatal NP exposure and maternal oxidative/nitrative stress biomarkers of DNA damage (8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-nitroguanine (8-NO2Gua)) and lipid peroxidation (8-iso-prostaglandin F2α (8-isoPF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)) and (2) to explore the associations among oxidative stress biomarkers, NP exposure, and neonatal birth outcomes, including gestational age, birth weight, length, Ponderal index, and head and chest circumferences. NP significantly increased the 8-OHdG and 8-NO2Gua levels. All infants born to mothers with urinary 8-OHdG levels above the median exhibited a significantly shorter gestational duration (Badjusted = -4.72 days; 95% CI: -8.08 to -1.36 days). No clear association was found between NP levels and birth outcomes. Prenatal 8-OHdG levels might be a novel biomarker for monitoring fetal health related to NP exposure.


Involvement of Galectin-3 in neurocognitive impairment in obstructive sleep apnea via regulating inflammation and oxidative stress through NLRP3.
Accumulated studies have revealed that oxidative stress and inflammation play important roles in the development of OSA related cognitive dysfunction. Galectin-3, a member of the galectin family, has been reported to be involved in the neuroinflammatory diseases. However, the relationship between Galectin-3 and cognitive impairment in OSA remains ambiguous. 47 new diagnosed OSA patients and 18 age-, gender-, education- and body mass index-matched healthy control subjects were enrolled in the present study. All subjects underwent whole-night in-laboratory polysomnography (PSG). Montreal Cognitive Assessment (MoCA) was used to evaluated the cognitive function of OSA patients. Serum Galectin-3, interleukin (IL)-1β and IL-8 were examined by enzyme-linked immunosorbent assay (ELISA). The levels of malonaldehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) were measured to evaluate oxidative stress. Protein level of Galectin-3 and NLRP3 in peripheral blood mononuclear cells (PBMCs) and human microglial clone 3 (HMC3) cells were measured by Western Blot. Serum Galectin-3 level in severe OSA patients (2.31 ± 0.43 ng/m) was higher than those in mild-moderate OSA patients (1.87 ± 0.32 ng/m, p < 0.001) and those in the healthy controls (1.56 ± 0.22 ng/ml, p < 0.001). Similarly, Galectin-3 level in PBMCs was increased with disease severity (p < 0.01). In addition, OSA patients also showed higher levels of inflammation and oxidative stress (p < 0.01). Patients with OSA scored significantly lower than healthy controls on the MoCA test after controlling for age, gender, education, and BMI. CPAP treatment for 12 weeks effectively reduced the levels of Galectin-3, inflammation and oxidative stress, as well as improved cognitive function of severe OSA patients. Closed correlations were observed between Galectin-3 with sleep respiratory parameters and cognitive dysfunction. In addition, we explored the underlying mechanism of Galectin-3 in neuroinflammation and oxidative stress. We treated HMC3 cells with LPS to mimic neuroinflammatory response in vitro. The results showed that LPS treatment led to a dose-dependent increase in Galectin-3 expression, meanwhile induced inflammation and oxidative stress. Inhibiting Galectin-3 with a specific Galectin-3 inhibitor, TD139, significantly ameliorated LPS-induced neuroinflammation and oxidative stress via suppressing NLRP3. Current findings suggest that increased Galectin-3 might be involved in the cognitive impairment of OSA patients by promoting neuroinflammation and oxidative stress via regulating NLRP3. These results suggested that Galectin-3 inhibition may exert a protective role against the neurocognitive dysfunction associated with OSA.


Imaging findings of cerebral fat embolism syndrome: a case report.
Cerebral fat embolism (CFE) syndrome is relatively rare in clinical practice. Currently, there is no uniform standard of magnetic resonance imaging for the diagnosis of the disease. In this report, we present head computed tomography and magnetic resonance images (T2-weighted images, fluid-attenuated inversion recovery images, diffusion-weighted images, and susceptibility-weighted images) in a case of CFE. This report explains the imaging characteristics of CFE and improves the clinician's understanding of this disease and its etiology.


Uts2b is a microbiota-regulated gene expressed in vagal afferent neurons connected to enteroendocrine cells producing cholecystokinin.
Enteroendocrine cells (EECs) are the primary sensory cells that sense the gut luminal environment and secret hormones to regulate organ function. Recent studies revealed that vagal afferent neurons are connected to EECs and relay sensory information from EECs to the brain stem. To date, however, the identity of vagal afferent neurons connected to a given EEC subtype and the mode of their gene responses to its intestinal hormone have remained unknown. Hypothesizing that EEC-associated vagal afferent neurons change their gene expression in response to the microbiota-related extracellular stimuli, we conducted comparative gene expression analyses of the nodose-petrosal ganglion complex (NPG) using specific pathogen-free (SPF) and germ-free (GF) mice. We report here that the Uts2b gene, which encodes a functionally unknown neuropeptide, urotensin 2B (UTS2B), is expressed in a microbiota-dependent manner in NPG neurons. In cultured NPG neurons, expression of Uts2b was induced by AR420626, the selective agonist for FFAR3. Moreover, distinct gastrointestinal hormones exerted differential effects on Uts2b expression in NPG neurons, where cholecystokinin (CCK) significantly increased its expression. The majority of Uts2b-expressing NPG neurons expressed CCK-A, the receptor for CCK, which comprised approximately 25% of all CCK-A-expressing NPG neurons. Selective fluorescent labeling of Uts2b-expressing NPG neurons revealed a direct contact of their nerve fibers to CCK-expressing EECs. This study identifies the Uts2b as a microbiota-regulated gene, demonstrates that Uts2b-expressing vagal afferent neurons transduce sensory information from CCK-expressing EECs to the brain, and suggests potential involvement of UTS2B in a modality of CCK actions.


DNA content of mycosis fungoides cells.
DNA content of mycosis infiltrate cells was measured in 5 patients with the Feulgen cytophotometric method in the plaque and tumor stages. In addition, the infiltrate cells were differentiated cytochemically into histiocytes and atypical lymphoid cells with NaF-sensitive naphthol-AS-D-acetate esterase. In no case was an aneuploid stem line demonstrated. However, increasing duration of the tumor stage was associated with a larger proportion of tetraploid and octoploid cells. The DNA histograms also exhibited a local proliferation of atypical lymphoid cells. This proliferation was arrested by cytostatic therapy. Comparison with semi-thin-sections of tumor tissue showed that the mycosis fungoides cells are atypical lymphoid cells. These DNA measurements do not contradict the concept of limited aneuploidy, as reported in cytogenic studies. Thus mycosis fungoides fits in with the DNA distribution pattern in the group of lymphomas.


Computed tomographic findings of the skeletal musculature in sporadic distal myopathy with early adult onset.
This report describes the clinical, laboratory, electromyographic, histopathological and computed tomographic studies of three patients suffering from sporadic distal myopathy. The most conspicuous features were: early onset in adulthood, weakness first affecting the distal leg muscles, marked elevation of serum creatine kinase (CK) activity, and electromyographic and histopathological findings predominantly consistent with myopathy. Computed tomographic examination of the skeletal musculature revealed that the most extensive changes were in the distal muscles of the legs. However, some proximal muscles also appeared to be involved, both clinically and radiologically. One conspicuous finding in all patients was the presence of marked low density abnormalities in the gluteus minimus muscles.


Real-time reverse transcriptase polymerase chain reaction assays for Middle East Respiratory Syndrome.
Here we designed and tested two highly specific quantitative TaqMan(®)-MGB-based reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assays for Middle East Respiratory Syndrome (MERS). The primers and probes for these assays were evaluated and found to have a limit of detection (LOD) of 0.005 plaque-forming units/PCR (pfu/PCR).


Effect of Water Compressibility, Sea-floor Elasticity, and Field Gravitational Potential on Tsunami Phase Speed.
Tsunamis can propagate thousands of kilometres across the ocean. Precise calculations of arrival times are essential for reliable early warning systems, determination of source and earth properties using the inverse problem, and time series modulation due to frequency dependency of phase speed. Far field observatories show a systematic discrepancy between observed and calculated arrival times. Models in present use and based on incompressible hydrodynamics and interaction with a rigid ocean floor overestimate the phase speed of tsunamis, leading to arrival time differences exceeding tens of minutes. These models neglect the simultaneous effects of the slight compressibility of water, sea-bed elasticity, and static compression of the ocean under gravity, hereinafter gravity. Here, we show that taking these effects into account results in more accurate phase speeds and travel times that agree with observations. Moreover, the semi-analytical model that we propose can be employed near real-time, which is essential for early warning inverse models and mitigation systems that rely on accurate phase speed calculations.


Therapeutic efficacy of pyronaridine-artesunate (Pyramax®) against uncomplicated Plasmodium falciparum infection at Hamusit Health Centre, Northwest Ethiopia.
Early case detection and prompt treatment are important malaria control and elimination strategies. However, the emergence and rapid spread of drug-resistant strains present a major challenge. This study reports the first therapeutic efficacy profile of pyronaridine-artesunate against uncomplicated Plasmodium falciparum in Northwest Ethiopia. This single-arm prospective study with 42-day follow-up period was conducted from March to May 2021 at Hamusit Health Centre using the World Health Organization (WHO) therapeutic efficacy study protocol. A total of 90 adults ages 18 and older with uncomplicated falciparum malaria consented and were enrolled in the study. A standard single-dose regimen of pyronaridine-artesunate was administered daily for 3 days, and clinical and parasitological outcomes were assessed over 42 days of follow-up. Thick and thin blood films were prepared from capillary blood and examined using light microscopy. Haemoglobin was measured and dried blood spots were collected on day 0 and on the day of failure. Out of 90 patients, 86/90 (95.6%) completed the 42-day follow-up study period. The overall PCR-corrected cure rate (adequate clinical and parasitological response) was very high at 86/87 (98.9%) (95% CI: 92.2-99.8%) with no serious adverse events. The parasite clearance rate was high with fast resolution of clinical symptoms; 86/90 (95.6%) and 100% of the study participants cleared parasitaemia and fever on day 3, respectively. Pyronaridine-artesunate was highly efficacious and safe against uncomplicated P. falciparum in this study population.