Has contemporary climate change played a role in population declines of the lizard Ctenophorus decresii from semi-arid Australia?
Whilst contemporary climatic changes are small in magnitude compared to those predicted for the coming decades, they have already been linked to species range shifts and local extinctions. Elucidating the drivers behind species' responses to contemporary climate change will better inform management strategies for vulnerable and pest species alike. A recent proposal to explain worldwide local extinctions in lizards is that increasing maximum temperatures have constrained lizard activity time in the breeding season beyond extinction thresholds. Here we document a significant population decline and potential local extinction at the warm (northern) range margin of the tawny dragon, Ctenophorus decresii, a rock-dwelling lizard from the Flinders Ranges in semi-arid Australia. We developed and tested a biophysical model of tawny dragon thermoregulatory behaviour and drove the model with daily weather data for the period 1990-2009 across the Flinders Ranges. Our results indicate that potential annual activity time has likely increased over this period throughout the historic range, with within-season declines only in the summer months at the northern range limit. However, populations that have declined since 2000 have also likely experienced higher active body temperatures and more stringent retreat-site requirements (deeper crevices) than have regions where the species remains common, during a period of declining rainfall. Our laboratory estimates of thermal preference in this species were insensitive to altered nutritional and hydric state. Thus it is possible that recent population declines are linked to desiccation stress driven by higher body temperatures and declining rainfall. Our study illustrates that simple indices of the impact of climate warming on animals, such as activity restriction, may in fact reflect a variety of potential mechanisms whose ultimate outcome will be contingent on other factors such as water and shelter availability.


Development of strain-specific real-time PCR and RT-PCR assays for quantitation of chicken anemia virus.
Chicken anemia virus (CAV) is a ubiquitous pathogen of poultry. A CAV specific TaqMan-based PCR and RT-PCR assay for real-time quantitation of viral load and relative quantitation of virus-specific transcript levels was developed. Detection of viral DNA copy number from infected MDCC-CU147 cells was determined by extrapolation from a CAV plasmid-based standard curve. Viral load increased proportionally with increasing cell number harvested, increasing from 4x10(2) copies in 250 cells with 38% virus positive cells in an indirect immunofluorescence assay to 8x10(5) copies in 250,000 cells with 64% infected cells. The estimated average viral copy number per infected cell ranged from 5 to 14. Strain-specific primers were developed to distinguish between the Cux-1 and CIA-1 strains of CAV. These primers exhibited a 3 to 4 log differential in amplification comparing homologous versus heterologous virus-primer combinations. The sensitivity of the real-time assay was found to be comparable to a nested PCR assay using DNA samples from a SPF poultry flock exposed to the SH-1 strain of CAV. The real-time PCR detected from 1.7 to 4.2 target molecules in three out of four samples that were positive by nested PCR using 50% of the DNA used in the nested PCR. Relative viral transcript levels for Cux-1 and CIA-1 infected cell cultures increased proportionally with increasing cell numbers harvested for RNA extraction. This assay will be important for both diagnosis and in understanding the complex pathogenesis of CAV infection.


Monoclonal gammopathy and glomerulonephritis with organized microtubular deposits.
We report a case with IgG-kappa monoclonal gammopathy of unidentified significance (MGUS) and glomerulonephritis (GN) with organized microtubular deposits on electron microscopy (EM). Light microscopy (LM) examination showed exudative features and moderate extracapillary proliferation. An acute nephritic syndrome with a rapidly progressive renal failure was clinically manifest at the onset and during each relapse. The patient was treated with methylprednisolone pulses followed by oral prednisone, cyclophosphamide, plasmapheresis, and maintenance courses of chemotherapy. The response to treatment was good, with a temporary improvement of renal function and control of the downhill course over a 3-year follow-up.


Lead-loaded ion-exchange resin bead as a calcergen.
Several heavy metals have direct calcifying effects in connective tissues; most notable among them is lead (Pb), whether administered topically (1) or systemically with local injury (2). The mechanisms of metal-induced soft tissue calcification have been studied by injecting salts of known in vitro calcifying potential into subcutaneous connective tissue (3); of the metals used, only lead and holmium produced an early accumulation of minerals on collagen in vivo. Lead is also claimed to accelerate bone healing in the rabbit leg with no toxic effects (4). Lead-loaded ion-exchange resin beads, implanted into surgically prepared subcutaneous pouches in rats, rapidly induced subcutaneous calcification which has been studied by microradiography and electron-probe microanalysis.


Treatment of tophaceous gout: When medication is not enough.
To review the literature concerning surgical intervention of tophaeceous gout and propose clinical circumstances for when it may be considered. Tophi develop in approximately 12-35% of patients with gout. Tophaceous disease is usually preventable given the availability of effective urate lowering therapies (ULT) including allopurinol, febuxostat, probenecid, lesinurad, and pegloticase. Despite medical therapy, there remains a subset of patients who develop significant complications of tophi including infection, ulceration, and entrapment neuropathy. Tophi in close proximity to joints can cause joint instability, severely limited range of motion, and significant functional impairment. For the rare circumstance when a tophus is causing an urgent complication or if a patient has a contraindication to all available ULTs, surgery may be an appropriate option. This review summarizes the published experience with surgical interventions for tophaceous gout and offers recommendations for its consideration. Using Medline and Google Scholar, all available series of surgery for tophaceous gout were reviewed. Overall, 7 published surgical series were identified. In all, 6 of these 7 series were published between 2002 and 2014. The reported outcomes of surgical interventions for tophaceous gout were generally positive without major post-surgical complications. Although medical therapy with ULTs should be the first-line approach to tophaceous gout, surgery should be considered for the rare patient with impending or severe, debilitating complications including infections, entrapment neuropathy or those at risk for permanent joint destruction. In these selected clinical circumstances, surgical intervention for tophaceous gout may be appropriate.


Inhibition by angiotensin converting enzyme inhibitors of endothelin secretion from cultured human endothelial cells.
We conducted a study to determine whether angiotensin converting enzyme inhibitors (ACEIs) inhibit endothelin secretion from cultured human endothelial cells. Confluent umbilical vein endothelial cells were incubated in multi-well plates with culture medium containing either captopril (10(-6), 10(-5), 10(-4) M) or enalaprilat (10(-7), 10(-6), 10(-5) M) for 6 hours. Immunoreactive endothelin in the medium was measured by radioimmunoassay. Calf serum (CS) stimulated endothelin release in a concentration-dependent manner, and both ACEIs inhibited 5% CS-stimulated endothelin release in a concentration-dependent manner. To explore the mechanisms of ACEI-induced suppression of endothelin release, the effects of angiotensin II (10(-8), 10(-7), 10(-6) M), angiotensin converting enzyme (0.1, 1, 10 mU/ml), bradykinin (10(-8), 10(-7), 10(-6) M), and sodium nitroprusside (10(-6), 10(-5), 10(-4) M) on endothelin release were also examined. Although angiotensin II and angiotensin converting enzyme had no significant effect on endothelin release, concentration-dependent suppression occurred with bradykinin and sodium nitroprusside. These results indicate that ACEIs inhibit the stimulated release of endothelin from human endothelial cells, and provide indirect evidence that ACEI-induced ET suppression may be mediated via potentiation of autacoid formation from the cells.


The cerebello-thalamo-cortical pathway. Topographical investigation at the unitary level in the cat.
1. The spatial organization of the cerebello-thalamo-cortical relations has been studied in semi-chronic cats. VL neurons were recorded during stimulation of two cerebellar nuclei, the nucleus interpositus posterior (NIP) and the dentate nucleus (ND). 2. Latency histograms of thalamic responses induced from the stimulation of each of two cerebellar nuclei are comparable and suggest that the cerebello-thalamic fibres have similar calibers whether they originate in the NIP or ND. 3. The anatomical localisation of recording sites indicates that the short latency (less than 1.5 msec) thalamic responses (transmitted by a monosynaptic pathway) are confined to a restricted VL region while the long latency responses are dispersed throughout the nucleus. The monosynaptic responses induced by NIP stimulation are localized in the ventrolateral part of the VL. This VL region is connected to the motor cortical area controlling the forelimb. The ND sends projections into a more medial and dorsal region which is principally connected to the motor area controlling the axial musculature and the shoulder. 4. In some cases it has been observed that the same thalamic cell cen be excited from both cerebellar nuclei. The fact that thalamic neurones are not tied specifically to a given afferent pathway is discussed. 5. The cerebellothalamic well as the thalamocortical relations have a divergent pattern. The efferents from each cerebellar site can excite a large number of VL neurons which can be sometimes several millimeters apart. 6. Cerebellar projections on small cortical foci have also been found. The functional interpretation of these two characteristics of the pathway is discussed.


Cerebral lateralisation at different stages of facial processing.
Two experiments are reported which explore the cerebral lateralisation of different stages of facial processing. In Experiment 1 subjects were briefly presented with either upright or inverted Mooney faces to either the left or right visual field. The subjects' task was to decide whether or not the stimulus had the configuration of a face. The data showed a left visual field superiority in performing this task. In Experiment 2 subjects were briefly presented with line drawings of faces to either the left or right visual field. On half the trials all the facial features were intact whilst in the remainder one feature had been replaced by an anomalous feature in the same position. The subjects were required to detect whether an anomalous feature was present or not and this task produced a right visual field superiority. These data argue against a global right hemisphere superiority in facial processing and suggest, instead, that hemispheric superiority will vary depending on the stage of facial analysis investigated. On the basis of these and other recent findings it would appear that the right hemisphere is advantaged for the holistic stages of facial processing whilst the left-hemisphere has superiority for analysis at the level of individual features. However, the data are ambiguous as to whether the hemispheric differences detected reflect face-specific or general processing characteristics of the cerebral hemispheres.


Crassifoside H improve the depressive-like behavior of rats under chronic unpredictable mild stress: Possible involved mechanisms.
Crassifoside (CH) is a novel chlorine-containing compound isolated from rhizomes of Curculigo glabrescens. This study aimed to explore the antidepressant-like effect of CH and involved mechanisms. A rat depression model was established using chronic unpredictable mild stress (CUMS) paradigm. Behavioral tests including sucrose preference test (SPT), open field test (OFT) and forced swimming test (FST) were used to evaluate the antidepressant-like effect of CH. The levels of plasma corticosterone (CORT) and corticotrophin-releasing factor (CRF) in hypothalamus were measured to determine the activity of hypothalamic pituitary-adrenal (HPA) axis. Protein expression of 5-hydroxytryptamine 1A (5-HT1A) receptor, brain-derived neurotrophic factor (BDNF), as well as the total and phosphorylated extracellular signal-regulated kinase (ERK)1/2 in hippocampus were also analyzed by Western blotting. The CH administration effectively ameliorated the depressive-like behaviors of CUMS rats, as indicated by the increased sucrose intake in SPT, reduced immobility time in FST, and the increased rearing and grooming numbers, spent more time in inner zone and less time in outer zone in OFT. CH improved CUMS-induced HPA axis hyperactivity by reduced plasma CORT and CRH expression in hypothalamus. Moreover, CH reversed CUMS-induced decrease of 5-HT1A receptor expression, and up-regulated BDNF and phosphorylated-ERK1/2 levels in hippocampus. These findings suggest that CH improved depressive behaviors of CUMS rats by modulating of HPA axis dysfunction, increasing 5-HT1A receptor expression, and activating BDNF-ERK signaling pathway.


Characterization of FMN-dependent NADH-quinone reductase induced by menadione in Escherichia coli.
It was found that when Escherichia coli is grown in the presence of 0.2-0.3 mM menadione (2-methyl-1,4-naphthoquinone), an FMN-dependent NADH-quinone reductase increases more than 20-fold in the cytoplasmic fraction. The menadione-induced quinone reductase was isolated from the cytoplasmic fraction of induced cells. The purified enzyme had an Mr of 24 kDa on SDS-polyacrylamide gel electrophoresis. The enzyme required flavin as a cofactor and a half-maximum activity was obtained with 0.54 microM FMN or 16.5 microM FAD. The enzyme had a broad pH optimum at pH 7.0-8.0 and reacted with NADH, but not with NADPH. The reaction followed a ping-pong mechanism and the intrinsic Km values for NADH and menadione were estimated to be 132 microM and 2.0 microM, respectively. Dicoumarol was a simple competitive inhibitor with respect to NADH with a Ki value of 0.22 microM. The electron acceptor specificity of this enzyme was very similar to that of NAD(P)H: (quinone acceptor) oxidoreductase (EC 18.104.22.168, DT-diaphorase) from rat liver. Since menadione is reduced by the two-electron reduction pathway to menadiol, the induction of this enzyme is likely to be an adaptive response of E. coli to partially alleviate the toxicity of menadione.


Adsorptive decolorization of methylene blue by crosslinked porous starch.
Crosslinked porous starch (CPS) was prepared by two steps. Native starch was crosslinked with epichlorohydrin and then CPS was prepared by hydrolyzing the crosslinked starch with α-amylase. As a biodegradable and safe adsorbent, CPS was used to remove methylene blue (MB) from the aqueous solution based on its characterizations, including surface area, pore volume and scanning electron microscopy (SEM). The results indicate that the adsorption capacity of CPS is much higher than native starch and relatively higher than porous starch. The effects of the initial concentration of MB, the time and temperature on the adsorption capacity were investigated. The pseudo-first-order kinetic model provides a better correlation of the experimental data in comparison with the pseudo-second-order model. The equilibrium adsorption data are well described by the Langmuir isotherm model with a maximum adsorption capacity of 9.46mg g(-1). The adsorption of MB on CPS is endothermic and spontaneous in nature. The thermodynamics data are in good agreement with physical adsorption mechanism.


Enteral nutrition reduces delayed gastric emptying after standard pancreaticoduodenectomy with child reconstruction.
Delayed gastric emptying (DGE) is a common complication following pancreaticoduodenectomy (PD). Our retrospective study aimed to evaluate the influence of enteral nutrition (EN) on DGE incidence after standard PD with antrectomy and Child reconstruction. We retrospectively analyzed 275 consecutive patients who underwent standard PD between January 2000 and September 2009. Patients operated on after January 2005 received EN (EN group, n = 152) until total oral alimentation. Patients operated on prior to 2005 did not receive EN (control group, n = 123) and were orally fed after removing the nasogastric tube. Primary endpoint was the incidence of DGE according to the International Study Group of Pancreatic Surgery criteria. Secondary endpoints were the incidence of any other complications. The incidence of DGE was 26% vs. 38% (p = 0.04) in the EN and control groups, respectively, with 17% vs. 19% for grade B DGE (NS) and 9% vs. 19% for grade C DGE (p = 0.02). The differences in DGE did not significantly decrease the duration of stay (18 ± 11 vs. 19 ± 13 days; NS). Postpancreatectomy hemorrhage was significantly reduced in the EN group (8% vs. 20%, p = 0.008), with the incidence of postoperative pancreatic fistula being similar in both groups (15% vs. 12%; NS). Using multivariate analysis, EN (p = 0.047, OR = 0.559 [0.315; 0.994]), operative time (p < 0.001, OR = 1.007 [1.003; 1.010]), and patient age (p = 0.014, OR = 1.031 [1.006; 1.057]) were independent factors affecting the incidence of DGE. EN reduces DGE and postpancreatectomy hemorrhage after PD.


Knockdown of mechanosensitive adaptor Hic-5 ameliorates post-traumatic osteoarthritis in rats through repression of MMP-13.
Osteoarthritis (OA) is the most common joint disease associated with articular cartilage destruction. Matrix metalloproteinase-13 (MMP-13) has an essential role in OA pathogenesis by degradation of collagen II, a major component of articular cartilage. Hydrogen peroxide-inducible clone-5 (Hic-5; TGFB1I1), a transforming growth factor-β-inducible mechanosensor, has previously been reported to promote OA pathogenesis by upregulating MMP-13 expression in mouse osteoarthritic lesions. In our current study, immunohistochemical analysis showed that Hic-5 protein expression was increased in human OA cartilage compared with normal cartilage. Functional experiments demonstrated that Hic-5 and MMP-13 expression was increased by mechanical stress, and mechanical stress-induced MMP-13 expression was suppressed by Hic-5 siRNA in human chondrocytes. Moreover, intracellular localization of Hic-5 shifted to the nucleus from focal adhesions in human chondrocytes subjected to mechanical stress, and nuclear Hic-5 increased MMP-13 gene expression. In vivo, intra-articular injection of Hic-5 siRNA decreased the Osteoarthritis Research Society International score and MMP-13 protein expression in articular cartilage of OA rats. Our findings suggest that Hic-5 regulates transcription of MMP-13 in human chondrocytes, and Hic-5 may be a novel therapeutic target for OA because OA progression was suppressed by intra-articular injection of Hic-5 siRNA in rats.


Budget Impact Analysis of Gemtuzumab Ozogamicin for the Treatment of CD33-Positive Acute Myeloid Leukemia.
Gemtuzumab ozogamicin (GO) was approved in 2017 in the US for the treatment of adults with newly diagnosed CD33-positive (CD33+) acute myeloid leukemia (AML), and adults and pediatric patients with CD33+ relapsed/refractory (R/R) AML. The aim of this study was to estimate the budgetary impact of introducing GO to a 1-million-member US health plan over a 5-year period. We developed models to estimate the impact of introducing GO in combination with conventional induction chemotherapy or as monotherapy for newly diagnosed AML, and as monotherapy for R/R AML. Models were built using data on drug costs and treatment-related outcomes obtained from published clinical trials and other publicly available sources. Results were reported on a per member/per year and per member/per month (PMPM) basis. Base-case results of the newly diagnosed model indicated that the addition of GO in the combination setting reduced the overall budget of a 1-million-member health plan. The estimated net cost (US$) savings ranged from $72,969 ($0.006 PMPM) in year 1 to $745,426 ($0.062 PMPM) in year 5. In the monotherapy setting, GO was associated with increased net costs ranging from $4118 (0.0003 PMPM) in year 1 to $31,885 ($0.003 PMPM) in year 5. Base-case results of the R/R AML model demonstrated increased net costs that ranged from $17,326 ($0.001 PMPM) in year 1 to $46,163 ($0.004 PMPM) in year 5. Scenario analyses in all settings indicated the budget impact was not overly sensitive to the selected input assumptions, with the exception of the scenario considering only the pharmacy budget impact in the combination setting. The introduction of GO for newly diagnosed and R/R AML would have a minimal impact on the budget of a US health plan and could result in cost savings in the combination therapy setting for newly diagnosed AML.


Compartment-specific phosphorylation of rat thyroid hormone receptor alpha1 regulates nuclear localization and retention.
The thyroid hormone receptor alpha1 (TRalpha1) is a transcription factor, which can activate or repress gene expression in response to thyroid hormone. In addition, some of its actions, including DNA binding and transcriptional activation, are thought to be regulated by phosphorylation. Results presented here, using Xenopus oocyte microinjection assays, demonstrate that a phosphorylated form of rat TRalpha1 is present in the nucleus, whereas unphosphorylated TRalpha1 remains cytoplasmic. Changes in the phosphorylation state of TRalpha1 occur rapidly and point to the possibility that phosphorylation occurs in the nucleus. Furthermore, increasing the overall phosphorylation state of the cell leads to enhanced nuclear retention of TRalpha1, suggesting that compartment-specific phosphorylation regulates nuclear localization of TRalpha1. Enhanced nuclear retention of TRalpha1 is not dependent on phosphorylation of serine 12, a well-characterized casein kinase II site, nor is phosphorylation of this site necessary for import of TRalpha1 into the Xenopus oocyte nucleus. Similarly, mutational analysis in mammalian cells shows that nuclear localization and partitioning of TRalpha1 to the nuclear matrix are independent of serine 12 phosphorylation. Taken together, these studies suggest that phosphorylation of one or more sites in TRalpha1, excluding serine 12, enhances nuclear retention and/or inhibits nuclear export but is not directly involved in nuclear import.


Mutational analysis of the RPGRIP1L gene in patients with Joubert syndrome and nephronophthisis.
Joubert syndrome (JS) is an autosomal recessive disorder, consisting of mental retardation, cerebellar vermis aplasia, an irregular breathing pattern, and retinal degeneration. Nephronophthisis (NPHP) is found in 17-27% of these patients, which was designated JS type B. Mutations in four separate genes (AHI1, NPHP1, CEP290/NPHP6, and MKS3) are linked to JS. However, missense mutations in a new ciliary gene (RPGRIP1L) were found in type B patients. We analyzed a cohort of 56 patients with JS type B who were negative for mutations in three (AHI1, NPHP1, and CEP290/NPHP6) of the four genes previously linked to the syndrome. The 26 exons encoding RPGRIP1L were analyzed by means of PCR amplification, CEL I endonuclease digestion, and subsequent sequencing. Using this approach, four different mutations in the RPGRIP1L gene in five different families were identified and three were found to be novel mutations. Additionally, we verified that missense mutations are responsible for JS type B and cluster in exon 15 of the RPGRIP1L gene. Our studies confirm that a T615P mutation represents the most common mutation in the RPGRIP1L gene causing disease in about 8-10% of JS type B patients negative for NPHP1, NPHP6, or AHI1 mutations.


Therapeutic genes for cancer gene therapy.
Cancer still represents a disease of high incidence and is therefore one major target for gene therapy approaches. Gene therapy for cancer implies that ideally selective tumor cell killing or inhibition of tumor cell growth can be achieved using nucleic acids (DNA and RNA) as the therapeutic agent. Therefore, the majority of cancer gene therapy strategies introduce foreign genes into tumor cells which aim at the immunological recognition and destruction, the direct killing of the target cells or the interference with tumor growth. To achieve this goal for gene therapy of cancer, a broad variety of therapeutic genes are currently under investigation in preclinical and in clinical studies. These genes are of very different origin and of different mechanisms of action, such as human cytokine genes, genes coding for immunostimulatory molecules/antigens, genes encoding bacterial or viral prodrug-activating enzymes (suicide genes), tumor suppressor genes, or multidrug resistance genes.


Chemical surface modifications for the development of silicon-based label-free integrated optical (IO) biosensors: a review.
Increasing interest has been paid to label-free biosensors in recent years. Among them, refractive index (RI) optical biosensors enable high density and the chip-scale integration of optical components. This makes them more appealing to help develop lab-on-a-chip devices. Today, many RI integrated optical (IO) devices are made using silicon-based materials. A key issue in their development is the biofunctionalization of sensing surfaces because they provide a specific, sensitive response to the analyte of interest. This review critically discusses the biofunctionalization procedures, assay formats and characterization techniques employed in setting up IO biosensors. In addition, it provides the most relevant results obtained from using these devices for real sample biosensing. Finally, an overview of the most promising future developments in the fields of chemical surface modification and capture agent attachment for IO biosensors follows.


Revision surgery for treatment of weight regain after Roux-en-Y gastric bypass.
This study aims to evaluate results on revision surgery for weight regain after gastric bypass, based on surgical technique and follow-up. This study is a retrospective analysis of 29 patients who presented weight regain on follow-up after more than 5 years, divided into four groups according to revision surgery type: group 1 (n = 9) includes patients who underwent an increase in the length of the alimentary limb to 200 cm; group 2 (n = 13) are patients who underwent an increase in the length of the alimentary limb and placing of a silicon ring; group 3 (n = 2) are patients who underwent an increase in the length of the alimentary limb and gastric plication, and group 4 (n = 5) are patients who underwent gastric plication and placing of a silicon ring. The average preoperative weight before revision surgery was 117.8 kg, and the average postoperative follow-up for revision surgery was 13.7 months. Weight loss after revision surgery was observed in all groups but was greater in patients with longer revisional postoperative follow-up. Patients who underwent placing of a silicon ring presented greater weight loss than those who had had such a band since the original gastric bypass operation. Data suggest that revision surgery may be a useful tool in achieving weight loss in patients presenting weight regain following gastric bypass, obesity, bariatric surgery, gastric bypass, weight regain, and revision surgery.


KIOM-79 inhibits aldose reductase activity and cataractogenesis in Zucker diabetic fatty rats.
KIOM-79, a combination of four plant extracts, has a preventive effect on diabetic nephropathy and retinopathy in diabetic animal models. In this study, we have investigated the inhibitory effects of KIOM-79 on diabetic cataractogenesis. We evaluated aldose reductase activity during cataractogenesis using Zucker diabetic fatty (ZDF) rat, an animal model of type 2 diabetes. ZDF rats were treated orally with KIOM-79 (50 mg/kg body weight) once a day for 13 weeks. In vehicle-treated ZDF rats, lens opacity was increased, and lens fibre swelling and membrane rupture were observed. In addition, aldose reductase activity and aldose reductase protein expression in diabetic lens were markedly enhanced. However, the administration of KIOM-79 inhibited the development of diabetic cataract through the inhibition of aldose reductase activity and protein expression in diabetic lenses. These observations suggested that KIOM-79 was useful against the treatment of diabetic cataractogenesis.


Vaginal infection of mice with HSV type 2 variant ER-: a new animal model for human primary genital HSV type 2 infections.
Studying the pathogenesis of vaginal infections in mice with two variants of Herpes simplex virus type 2 (HSV-2) strain ER we observed that both variants ER+ and ER- caused severe vaginitis but only ER+ invaded the CNS leading to lethal neurological disease. In contrast, mice infected with ER- cleared the virus from the vagina and recovered from infection. ER+ and ER- expressed equal levels of thymidine kinase (TK) indicating a TK-independent difference in neurovirulence. Using the non-neurovirulent variant ER-, we were able to investigate humoral immune responses later after infection. Vaginal infection with ER- suppressed serum antibody formation after a secondary systemic HSV-1 infection. Fresh isolates of HSV-1 and HSV-2 caused uniformly a lethal neurological disease after vaginal inoculation of mice. However, some animals survived an intraperitoneal infection with these isolates. Infection with HSV-1 isolates stimulated a strong antibody production, whereas infection with HSV-2 isolates suppressed antibody formation, thus supporting earlier results from our group obtained with laboratory strains. Since suppression of antibody formation could be demonstrated with clinical HSV-2 isolates and likewise after vaginal infection with HSV-2 variant ER- we consider this phenomenon to be of relevance in human genital HSV-2 infections. Vaginal infection of mice with variant ER- represents a new model for primary genital HSV-2 infections; this model could be useful for histopathological, virological, immunological and drug testing studies.


Developmental Psychopathology: Risk and Resilience in the Transition to Young Adulthood.
The transition from adolescence to young adulthood is a challenging time for many young people, given the multiple simultaneous demands placed by biological, psychological, and social forces that affect an individual's development. There are additional challenges when one is coping with ongoing or evolving mental health disorders. This article focuses on the demographics of transitional age youth, ages 16 to 26 years, in the United States, the unique characteristics of this developmental period, and how risk and resilience factors may affect the course of development and an individual's pathway to adulthood.


Weight gain and pregnancy outcome in underweight and normal weight women.
The relationship of antenatal weight gain to pregnancy outcome was studied in 362 pairs of underweight women (less than 90% Metropolitan Relative Weight) and normal weight (90% to 110%) women who were matched for age, occupation, height, parity, race, and smoking habits. The mothers, selected from a study of pregnancy outcome in 1,080 middle-class women, had early and regular prenatal care. Regression analyses within each initial weight category revealed that there was no relationship between initial weight of mothers and birth weight of their infants, but birth weight increased significantly with antenatal weight gain (p less than .0001). A 1-kg maternal increase in weight was associated with a 12.85-gm increase in birth weight in offspring of underweight women and an 8.59-gm increase in offspring of normal weight women. Underweight women had significantly larger prenatal weight gains (9.3 vs. 8.5 kg), but there were no statistically significant differences in mean birth weight, gestational age, or Apgar scores between infants of women in the two weight groups. Very underweight women (less than 80% MRW) had lower-birth-weight infants, more preterm infants, and more infants with medical complications. Antenatal weight gain accounted for the greatest variation in birth weight among infants of underweight and normal weight women. When underweight mothers gained less than 9 kg, their infants had mean birth weights 361 gm less than the mean birth weights of infants of underweight women who gained more weight.


Pre-anesthetic maternal separation increases pups' locomotor behavior during emergence from anesthesia in rats.
Problematic behavior at emergence from anesthesia in children, partly linked with maternal separation, is a major problem in pediatric anesthesia. In humans, as well as in many other mammalian species, such separation causes psychological and behavioral changes. This study was to investigate whether or not pre-anesthetic maternal separation has a similar effect on rat pups. This study was conducted on 66 3-week-old Sprague-Dawley male rats. The rats were divided into two groups; pups housed with a dam (n = 33) and those housed without (n = 33). Pups were anesthetized with 1.2% halothane for 30 min. Afterwards we recorded their locomotor behavior at emergence from general anesthesia using a video tracking system. Pre-anesthetic maternal separation significantly increased the maximum velocity and the distance traveled by pups at the emergence. Pre-anesthetic maternal separation influenced pups' locomotive behavior at emergence.


Perinatal Exposure to Neuregulin-1 Results in Disinhibition of Adult Midbrain Dopaminergic Neurons: Implication in Schizophrenia Modeling.
Aberrant neuregulin-1 (NRG1) signals are suggested to associate with the neuropathophysiology of schizophrenia. Employing a mouse schizophrenia model established by neonatal neuregulin-1 challenge, we analysed postpubertal consequence of the NRG1 pretreatment for the electrophysiological property of nigral dopamine neurons. In vivo single unit recordings from anaesthetized NRG1-pretreated mice revealed increased spike bursting of nigral dopamine neurons. In slice preparations from NRG1-pretreated mice, spontaneous firing was elevated relative to controls. The relative increase in firing rates was abolished by a GABAA receptor antagonist. Whole-cell recording showed that perinatal NRG1 pretreatment diminished inhibitory miniature synaptic currents as well as GABAA receptor sensitivity. These results collectively suggest that perinatal exposure to neuregulin-1 results in the disinhibition of nigral dopamine neurons to influence their firing properties at the adult stage when the behavioral deficits are evident.


Extensibility of the actin and myosin filaments in various states of skeletal muscle as studied by X-ray diffraction.
The effects of length changes applied to resting, contracting and rigor muscles on the reflection spacings of the X-ray diffraction patterns were summarized. The spacing changes of the actin- and myosin-based meridional reflections as a function of tension relative to an isometric tension of active muscle (P0) were linear and almost identical in the active and rigor states, showing that the extension of both filaments is Hookenian and does not depend upon the states of muscle. In addition to their length changes caused by tension generation, there are small but significant length changes of both filaments due purely to activation of muscle. The actin and myosin filaments are elongated by approximately 0.36% and approximately 0.43%, respectively under the maximum active tension. The results indicate that a large part of the sarcomere compliance of an active muscle is caused by the extensibility of the myofilaments. Inspection of the behavior of the meridional and layer-line reflection spacings reveals that there is a close relationship between the extensibility and helical twisting of the actin filaments under active and passive forces. The extension caused by tension is associated with an unwinding of right-handed helices following the actin monomers in the filament. At the pointed end of the filament could rotate anticlockwise through one fifth the complete turn during contraction.


Clinical and Economic Value of Routine Pathological Examination of Hernia Sacs and Scheduled Clinic Follow-Ups After Inguinal Hernia and Hydrocele Repair in a Canadian Tertiary Care Children's Hospital.
The clinical and economical value of routine submission of hernia sacs for pathological examination and scheduled clinic follow-ups after inguinal hernia and hydrocele repair has been questioned. Herein, we assessed the institutional variability in these routine practices. We retrospectively reviewed patients who underwent unilateral or bilateral inguinal hernia and/or hydrocele repair, open or laparoscopically, at our institution from 2015 to 2018. 1181 patients were included (1074 inguinal hernias and 157 hydroceles). Of 531 specimens obtained from 446 (38%) patients, 515 (97%) were normal. 16 (3%) abnormal pathological findings included 7 with mesothelial hyperplasia, 5 with nonfunctional genital ductal remnants, 3 with ectopic adrenal cortical tissues, and 1 epidydimal structure which was not recognized at the time of surgery. 418 (35%) patients had scheduled clinic follow-ups 65 (IQR 46-94) days postoperatively. 44 (4%) patients with unexpected postoperative Emergency Department visits within 30 days of surgery were identified. Only one patient required inpatient treatment, and the rest did not require intervention or admission. The total direct cost of analyzing specimens during the study period was $30,798 CAD ($10,266/year). The average cost to detect a potentially significant finding was $1924.88/specimen and $2053.20/patient. Routine pathological examination of hernia sacs and scheduled clinic follow-ups were associated with significant costs and predominantly nonsignificant findings. They should therefore be reserved for patients with a high clinical suspicion of injuries/abnormalities or risk factors for potential complications. This is a level III evidence study.


Clinical monitoring of smooth surface enamel lesions using CP-OCT during nonsurgical intervention.
Studies have shown that cross-polarization optical coherence tomography (CP-OCT) can be used to image the internal structure of carious lesions in vivo. The objective of this study was to show that CP-OCT can be used to monitor changes in the internal structure of early active carious lesions on smooth surfaces during non-surgical intervention with fluoride. Lesions on the smooth surfaces of teeth were imaged using CP-OCT on 17 test subjects. Lesion structural changes were monitored during fluoride varnish application at 6-week intervals for 30 weeks. The lesion depth (Ld ), integrated reflectivity (ΔR), and surface zone thickness (Sz ) were monitored. A distinct transparent surface zone that may be indicative of lesion arrestment was visible in CP-OCT images on 62/63 lesions before application of fluoride varnish. The lesion depth and internal structure were resolved for all the lesions. The overall change in the mean values for Ld , ΔR, and Sz for all the lesions was minimal and was not significant during the study (P > 0.05). Only 5/63 lesions manifested a significant increase in Sz during intervention. Even though it appears that most of the lesions manifested little change with fluoride varnish application in the 30 weeks of the study, CP-OCT was able to measure the depth and internal structure of all the lesions including the thickness of the important transparent surface zone located at the surface of the lesions, indicating that CP-OCT is ideally suited for monitoring lesion severity in vivo. Lasers Surg. Med. 48:915-923, 2016. © 2016 Wiley Periodicals, Inc.


Dosimetry in molecular nuclear therapy.
Advanced personalized dosimetry for molecular nuclear therapy has been shown to be feasible in clinical practice. At the same time instrumentation and dosimetric software are still evolving at a high pace. Procedures developed so far differ in approach and sophistication, and standard operating procedures necessary for accurate patient specific dosimetry do not yet exist. For this reason we restricted ourselves to reviewing the literature and highlighting relevant developments.


Comparative Investigation on the Phytochemicals and Biological Activities of Jackfruit (Artocarpus heterophyllus Lam.) pulp from Five Cultivars.
Jackfruit is one of the major tropical fruits, but information on the phytochemicals and biological benefits of its pulp is limited. In this study, the phytochemicals and biological activities including antioxidant, antitumor and anti-inflammatory activities of five jackfruit pulp cultivars (M1, M2, M3, M7 and T5) were comparatively investigated. A total of 11 compounds were identified in all cultivars of jackfruit pulp, among which 4-hydroxybenzoic acid, caffeic acid, ferulic acid and tryptophan N-glucoside were reported for the first time in jackfruit. T5 exhibited the highest total phenolic content (7.69 ± 0.73 mg GAE/g DW), antioxidant capacity (109.8, 96.7 and 207 mg VCE/g DW for DPPH, ABTS and FRAP, respectively), antitumor activity (80.31%) and anti-inflammatory activity (78.44%) among five cultivars. These results can provide a reference for growers to choose jackfruit cultivar and offer an insight into the industrial application of jackfruit pulp derived-products.


[Effect of batrachotoxin on the selectivity of sodium channels in the membrane of a myelinated nerve fiber].
Ionic currents under voltage clamp conditions were studied in the Ranvier node treated with batrachotoxin (5-10(-6)--10(-5) M). Ionic permeability ratios were measured from zero-current potential. The permeability sequence for modified (noninactivating) Na channels was: Tl greater than NH4 greater than Na approximately Li greater than K greater than guanidinum greater than Rb greater than Ca greater than Cs greater than methylamine. Deviation from the "independence relation" in modified channels for It1 was decreased.


A metaanalysis of studies of the effects of cancer chemotherapy on various domains of cognitive function.
Little is known about the effects of chemotherapy on cognitive function. The purposes of this metaanalysis were to estimate the effect sizes for the effect of chemotherapy on each domain of cognitive function and to differentiate effect sizes by each method of comparison of effects (i.e., normative data, control group, or baseline data). Sixteen studies that evaluated cognitive function in chemotherapy patients were included in the study. DSTAT metaanalysis software was used to calculate an effect size and confidence intervals for each neuropsychologic test. Tests were assigned to a specific cognitive domain, and an average effect size was determined for each domain. Only one domain of cognitive function (i.e., visual memory) had significant chemotherapy-induced impairment across all comparison types. However, when the neuropsychologic test scores of chemotherapy patients were compared with normative data, significant effect sizes were found for four domains of cognitive function (i.e., executive function, information processing speed, verbal memory, visual memory). In addition, significant, albeit small, effect sizes were found for language and verbal memory when chemotherapy patients' test scores were compared with test scores of healthy matched controls. All significant averaged effect sizes were in the negative direction, indicating that mean scores on neuropsychologic tests for patients who had received chemotherapy were on average lower than comparison scores. Data from this metaanalysis supported the hypothesis that chemotherapy can have a negative impact on cognitive function. However, most deficits in this study ranged from small to moderate and were nonsignificant.


Hypoxaemia and septic shock were independent risk factors for mechanical ventilation in Bangladeshi children hospitalised for diarrhoea.
In Bangladesh, approximately 6% of children under five years of age die due to diarrhoea. We evaluated the admission and hospitalisation risk factors for mechanical ventilation and outcomes in children with diarrhoea. This retrospective case-control chart analysis was conducted in the intensive care unit of Dhaka Hospital of International Centre for Diarrhoeal Disease Research, Bangladesh. We enrolled 219 children with diarrhoea aged 0-59 months between August 2009 and July 2013. The 73 cases were children who were initially identified as requiring mechanical ventilation during the study period, and the 146 controls were randomly selected from those who did not require mechanical ventilation. We compared the groups to determine the risk factors for mechanical ventilation. Mortality was significantly higher among the cases than the controls (p < 0.001). In the logistic regression analysis carried out for two separate time points, the independent risk factors for mechanical ventilation on admission were hypoxaemia (p < 0.001) and septic shock (p = 0.004) and during hospitalisation, they were intake of intravenous fluid (p = 0.015), hypokalaemia (p = 0.018), hyperkalaemia (p = 0.005) and septic shock (p = 0.001). Children under five with diarrhoea who required mechanical ventilation frequently had hypoxaemia and septic shock and were more likely to die than unventilated controls.


Volatile constituents from the leaves, fruits (berries), stems and roots of Solanum xanthocarpum from Nepal.
The essential oils from the leaves, fruits, roots, and stems of Solanum xanthocarpum, growing wild in Nepal, have been obtained and analyzed by gas chromatography-mass spectrometry. The fruit volatiles were dominated by benzyl benzoate (21.7%) and (E,E)-geranyl linalool (12.6%); heptacosane (20.0%) was the major component of the leaf oil; the stem oil was dominated by palmitic acid (28.9%), heptacosane (12.8%) and linoleic acid (10.1%); while solavetivone (22.9%), palmitic acid (21.0%), and linoleic acid (8.2%) were the major components of the root essential oil. There do not seem to be any common phytochemical taxonomic markers in the essential oils of Solanum spp; the chemical diversity observed in this genus mirrors the taxonomic diversity.


The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma-a pooled trials analysis.
Mantle cell lymphoma (MCL) is a distinct subtype of B-cell lymphoma and commonly used induction immunochemotherapies include the anti-CD20 antibody rituximab. However, efficacy data for rituximab regarding overall survival (OS) in first line MCL therapy remain conflicting.We report long-term outcomes of a pooled trials analysis comparing Cyclophosphamide, Doxorubicine, Vincristine, Prednisone (CHOP) to R-CHOP in MCL to confirm efficacy on failure free survival (FFS) and OS in relevant subgroups. Untreated, adult MCL patients of two prospective trials assigned to CHOP or R-CHOP were included. Primary endpoints were FFS and OS, secondary endpoints included duration of response (DOR), secondary malignancies and OS after relapse. Between 1996 and 2003, 385 MCL patients were assigned to CHOP (201) or R-CHOP (184). After a median follow-up of 13.4 years, the addition of Rituximab significantly improved FFS (1.36 vs. 2.07 years, HR 0.62 (0.50-0.77)), OS (4.84 vs. 5.81 years, HR 0.78 (0.61-0.99)) and DOR (1.48 vs. 2.08 years, HR 0.67 (0.53-0.86)). Furthermore, Rituximab improved survival across different MCL risk groups. In a post-hoc analysis of OS after relapse comparing patients receiving chemotherapy with / without rituximab, rituximab maintained efficacy with a median OS of 3.10 vs. 2.11 years (HR 0.70, 0.54-0.91). The rate of secondary malignancies was 0.5 and 3.9% for hematological and 7 and 8% for non-hematological malignancies for CHOP and R-CHOP patients, respectively. We present mature results of a pooled MCL cohort, demonstrating prolonged FFS, OS and DOR for the combined immuno-chemotherapy, confirming the standard of care in first line treatment.


Effects of TCDD on vitamin A status and liver microsomal enzyme activities in a TCDD-susceptible and a TCDD-resistant rat strain.
To investigate the relationship between vitamin A status and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality, the influence of TCDD on tissue and serum vitamin A levels was determined in the most TCDD-susceptible (Long-Evans) and the most TCDD-resistant (Han/Wistar) rat strains. The TCDD LD50 values of these two strains differ by a factor of more than 300. Groups of three rats per strain were used in a dose-response study (given single ip doses of 0, 4, 40, 400, 800 or 1600 micrograms TCDD/kg body weight and killed on day 11) and in a time-course experiment (given single ip doses of 0, 4 and, in the case of Han/Wistar rats only, 1600 micrograms TCDD/kg body weight, and killed on days 4, 11, 23, 50 and 76). The strains showed similar response over the 76-day study with respect to vitamin A levels in the liver, kidneys, testicles and serum after exposure to a sublethal dose of TCDD (4 micrograms/kg body weight). In contrast, TCDD doses lethal to the Long-Evans strain only (40-1600 micrograms/kg, day 11) markedly increased kidney and serum vitamin A levels in Han/Wistar rats, while they were practically without effect in Long-Evans rats. Hepatic cytochrome P-450 concentration, and the activities of 7-ethoxyresorufin O-deethylase, ethylmorphine N-demethylase, and uridine diphosphate glucuronosyltransferase (towards p-nitrophenol) were affected by the TCDD doses in much the same manner in both strains. These findings show that the correlations between TCDD lethality and changes in vitamin A status found among species of laboratory animals do not hold for Long-Evans and Han/Wistar strains of rat.


Do reproduction and parenting influence personality traits? Insights from threespine stickleback.
Although one of the hallmarks of personality traits is their consistency over time, we might expect personality traits to change during life history shifts. Becoming a parent is a major life history event, when individuals undergo dramatic behavioural and physiological changes. Here we employ a longitudinal experiment to ask whether personality changes in response to the experience of parenting in male threespine sticklebacks, Gasterosteus aculeatus. Life history theory predicts that males should be less risk averse after successfully parenting, and the neuroendocrinology of parenting suggests that parenting could reorganize the hormonal landscape and behaviour of fathers. We randomly assigned males to either an experimental group (reproduced and parented) or a control group (did not reproduce and parent), and repeatedly measured a personality trait ('boldness') and 11-ketotestosterone levels (11-kT, the major androgen in fishes) in individual males. In the control group, males became bolder over time. However, in the experimental group, boldness did not change. Furthermore, 11-kT changed dramatically in the experimental group, and changes in 11-kT in parents were associated with boldness after parenting ceased. Our study is one of the first to assess proximate and ultimate explanations for changes in personality as a function of reproduction and parenting.


Ganglioneuroblastoma arising in a Mature Cystic Teratoma of Ovary: Report and Literature review of an uncommon neoplasm.
•Somatic neoplasms in Mature Cystic Teratoma are uncommon; Ganglioneuroblastoma is rare, this is 2nd reported case.•Due to rarity, it can pose a diagnostic challenge for Pathologists, and management and staging conundrum for Gynecologists.•Morphological differentials include immature teratoma, glial neoplasms arising in teratoma, and carcinoid.


Parent & Family Influences on Adopting Healthy Weight-Related Behaviors: Views and Perceptions of Obese African-American Female Adolescents.
RTI International is acknowledged for supporting the time of Susan McRitchie, Keeley Pratt and Susan Sumner to participate in the design, execution, or analysis of this study. East Carolina University would like to acknowledge Brittney France for being a triangulated investigator for the qualitative analysis and to the Pitt Memorial Hospital Foundation for financial support of the healthy lifestyles camp. Our purpose was to evaluate the views of obese African-American (AA) female adolescents concerning parent and family factors relating to obesity and a healthy lifestyle. Obese AA female adolescents enrolled in a residential healthy lifestyle program completed inventories measuring family functioning and perceptions of parenting styles, and participated in focus groups to identify themes regarding parent and family involvement in healthy lifestyle change. The majority of participants' mothers were scored as "inductive/authoritative" and fathers were "indulgent". Mothers reportedly were seen as more likely to encourage dieting to control weight than fathers. Common themes of the focus groups included a desire for family involvement, identification of family behaviors that were supportive as well as those which were perceived as unhelpful. Though generalizability of these results is limited by a homogenous small sample size, our results suggest that obese adolescents seeking weight loss treatment desire significant family involvement in their efforts.


[Differentiated expression of the viral genome in mammalian cells transformed by the Rous sarcoma virus].
In hybridization of 3H-DNA-product of Rous sarcoma virus with the RNA isolated from mammalian cells transformed by the virus concerned, it was found, that the virus-specific RNA, isolated from cryptovirogenic cells RVP-3, differs in nucleotide sequences from virogenic cells XC, XPO and TWERC.


Duplex ultrasonographic study of the renal arteries before and after renal artery stenting.
The aim of our study was to evaluate feasibility and accuracy of colour-coded duplex US in the detection of renal artery stenosis before and after stenting. Eighty-four patients (23 women, 61 men; mean age 64 years) with significant renal artery stenosis were studied with Doppler US, before and after stenting. A combined anterior and translumbar approach was used to visualise the renal arteries. Renal artery stenosis and in-stent restenosis were proved by the increase of renal peak systolic velocity (PSV) and reno-aortic ratio (RAR). Laboratory-specific threshold values of PSV and RAR were used to assess sensitivity and specificity of Doppler US. The renal arteries were visualised in all patients (feasibility 100%). A statistically significant difference of PSV and RAR was demonstrated between patent and stenotic renal arteries, before stenting, and between stenotic and stented renal arteries. No difference was demonstrated in cases of in-stent restenosis ( n=21). Before stenting, sensitivity of PSV and RAR was 93%, whereas specificity rates were 92 and 96%, respectively. After stenting sensitivity and specificity rates were, respectively, 90 and 93% for PSV, and 95 and 95% for RAR. Doppler US represents a feasible and reliable technique in the detection of renal artery stenosis and in-stent restenosis, although laboratory-specific threshold values are required to improve its accuracy.


M by Fritz Lang (Germany, 1931) Phenomenology of Evil: a serial killer and his social group.
In 1931 an unknown murderer of little girls (Peter Lorre) is terrorizing the city of Berlin. We see him entice a new victim, the little Elsie Beckmann, who is coming home from school: whistling a tune by Grieg, he buys her a balloon from a blind beggar. When her corpse is discovered, the police undertake a major mobilization aimed at seeking the serial killer in the criminal underworld; meanwhile, the ever more terrified population starts to see the dangerous murderer in everyone. Since the roundups and incursions into the seediest parts of town disturb the gangsters' activities, the leaders of organized crime, headed by Schränker (Gustav Gründgens), take it upon themselves also to hunt down the solitary child-killer, engaging the community of beggars. Every corner of the city is catalogued and sifted by the dual activity of the police and the gangsters. The 'monster', a former psychiatric patient, mild and harmless in manner, is finally tracked down via two parallel routes: the clue of a cigarette packet enables Inspector Lohmann (Otto Wernicke) to track down the serial killer's address, while the blind beggar recognizes the whistled tune. The murderer is identified by a 'slap' from a young criminal which leaves an M marked in chalk on a shoulder of the man's overcoat. Thus he is caught and undergoes a kind of trial at the hands of the gangsters who tie him up in order to lynch him, but they are interrupted by the arrival of the forces of law and order.


A novel antioxidant phenanthrenoid dimer from Juncus acutus L.
A novel phenanthrenoid symmetrical dimer 8,8'-bidehydrojuncusol [1,1',6,6'-tetramethyl-5,5'-divinyl-8,8'-biphenanthrene-2,2',7,7'-tetraol], a related phenanthrenoid monomer, a phenolic chromone, and five flavonoids derivatives have been isolated from the halophyte Juncus acutus L., Juncaceae. The structure of the dimeric phenanthrenoid was determined on the basis of spectroscopic analyses, including 2D NMR spectroscopy, and by spectral correlations. The new dimer and the other isolated compounds bearing four phenolic hydroxy groups showed the significant in vitro antioxidant activity comparable with that of ascorbic acid using 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulphonate] (ABTS) radical cation decolourisation assay. On the basis of the results from an in vitro anti-inflammatory assay using lipopolysaccharide-stimulated RAW264.7 macrophage cells linked with immunoblot analysis, it was found that dimerisation of dehydrojuncusol [1,6-dimethyl-5-vinyl-8-phenanthrene-2,7-diol] molecule nearly nullified its inhibitory effect on the expression of the pro-inflammatory inducible nitric oxide synthase (iNOS) protein.


Postnatal loss of methyl-CpG binding protein 2 in the forebrain is sufficient to mediate behavioral aspects of Rett syndrome in mice.
Mutations in the methyl-CpG binding protein 2 (MeCP2) gene cause Rett syndrome (RTT), a neurodevelopmental disorder that is accompanied by a broad array of behavioral phenotypes, mainly affecting females. Methyl-CpG binding protein 2 is a transcriptional repressor that is widely expressed in all tissues. To investigate whether the postnatal loss of MeCP2 in the forebrain is sufficient to produce the behavioral phenotypes observed in RTT, we have generated conditional MeCP2 knockout mice. These mice display behavioral abnormalities similar to RTT phenotypes, including hindlimb clasping, impaired motor coordination, increased anxiety, and abnormal social behavior with other mice. These mice, however, have normal locomotor activity and unimpaired context-dependent fear conditioning, suggesting that the behavioral deficits observed are the result of loss of MeCP2 function in postnatal forebrain and not the result of generalized global deficits. These data highlight the important role of MeCP2 in the forebrain and suggest that even partial loss of MeCP2 expression in these brain regions is sufficient to recapitulate features of RTT.


Associations between symptoms, modern health worries, and somatosensory amplification in patients with building-related symptoms.
The objective of the present study was to investigate the associations between somatosensory amplification, modern health worries (MHWs), and symptoms among patients with building-related symptoms (BRS). Patients with self-reported and medically confirmed BRS (n = 83) were included in this cross-sectional study. The Somatosensory Amplification Scale (SSAS) was used to quantify the tendency to amplify somatic sensations and perceive them as unpleasant and dangerous. Concerns about harmful effects of modern technologies were assessed with the Modern Health Worries Scale (MHWS). Symptoms commonly found in different forms of environmental intolerance were assessed with the Environmental Hypersensitivity Symptom Inventory (EHSI). Patients with BRS were characterized by more frequent and more severe environmental hypersensitivity symptoms compared to a reference population. Females and those with co-morbid self-reported chemical intolerance reported even more symptoms. MHWS and SSAS scores showed weak to moderate associations with symptoms, even after adjusting for socio-economic variables. However, neither the mean MHWS score or the SSAS score of our sample differed from normative scores. Patients with BRS are not characterized by elevated levels of MHWs and somatosensory amplification, thus other, psychosocial and/or environmental, factors may have contributed to the development of the condition. However, the associations between severity of symptoms and MHWs and somatosensory amplification suggest that psychosocial characteristics may substantially influence symptom experience in this group.


Controlled microfluidic interfaces.
The microfabrication technologies of the semiconductor industry have made it possible to integrate increasingly complex electronic and mechanical functions, providing us with ever smaller, cheaper and smarter sensors and devices. These technologies have also spawned microfluidics systems for containing and controlling fluid at the micrometre scale, where the increasing importance of viscosity and surface tension profoundly affects fluid behaviour. It is this confluence of available microscale engineering and scale-dependence of fluid behaviour that has revolutionized our ability to precisely control fluid/fluid interfaces for use in fields ranging from materials processing and analytical chemistry to biology and medicine.


Should Albumin be Considered for Prehospital Resuscitation in Austere Environments? A Prospective Randomized Survival Study in Rabbits.
The new guidelines for prehospital care of combat casualties in shock recommend administration of whole blood or blood components to increase blood pressure to a permissible hypotensive level (i.e., hypotensive resuscitation [HR]). We investigated if 2 h of HR using limited volumes of whole blood, plasma, or albumin would lead to full recovery and long-term survival of rabbits subjected to severe hemorrhagic shock (HS). Following instrumentation, laparotomy was performed on IV-anesthetized spontaneously breathing New Zealand white rabbits (3.0 kg -3.5 kg). Next, ∼40% of rabbits' blood volume was removed producing HS (mean arterial pressure [MAP]∼20 mm Hg). Fifteen minutes later, rabbits were resuscitated with a limited volume (12.5 mL/kg) of rabbit whole blood (fresh whole blood [FWB]), rabbit fresh frozen plasma (FFP), or 5% human albumin (ALB) to a target pressure (MAP) of 60 mm Hg (n=8/grp) and monitored for 2 h. Liver bleeding time was measured at baseline and 10 min after HR. Subsequently, animals were fully resuscitated (blood + lactated Ringer [LR]), surgically repaired, and recovered for 8 days. An untreated group (n = 6) was also included. Following HS, lactate and base deficit levels were increased to 8.2 ± 1.6 and 12.9 ± 3.1 mM respectively with no difference among groups. A lower volume of FWB volume was required to reach the target MAP (P < 0.05 vs. ALB) but MAP declined during the HR period (P < 0.01 vs. ALB). FWB provided higher hematocrit and platelets but it did not reduce lactate level faster than other fluids. Beside higher fibrinogen, no differences were found in hemostatic or resuscitative effects of FFP versus ALB. Bleeding time was prolonged with ALB and FFP fluids but unchanged with FWB. Untreated rabbits died during shock or shortly after. All treated rabbits except one recovered and lived for 8 days with normal blood tests and similar tissue histology. Two hours of HR using a limited volume of FWB, FFP, or ALB led to full recovery and long-term survival of rabbits subjected to HS. Apart from bleeding time, no clinically significant differences were found among the three fluids. Five percent human albumin solutions are isotonic, iso-oncotic, ready-to-use, stable, and compatible with all blood types and should be considered for prehospital resuscitation where blood products are not available or not accepted.


Fine-needle aspiration of the breast: the outpatient management of breast lesions.
Fine-needle aspiration of the breast has become a well-accepted diagnostic tool for the management of breast lesions. When employed on an ambulatory basis it is both accurate and cost-effective. This study of a series of patients managed over a 2-year period demonstrates the use of this technique in an ambulatory gynecologic practice. Results demonstrate this to be a very rapidly accomplished, effective procedure that is very well accepted by the patients. Results are generally available within 24 hours and permit both the physician and the patient to accurately predict the course of management. In addition, it allows the primary physician to accurately determine which patients will require in-hospital management and which may safely undergo ambulatory, office-based biopsy of solid lesions. Experience shows this to be a valuable diagnostic tool that can be safely utilized by the practicing gynecologist.


Involvement of opioid system in antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251 after physical stress in mice.
Cannabinoid inverse agonists possess antidepressant-like properties, but the mechanism of this action is unknown. Numerous studies have reported the interaction between opioid and cannabinoid pathways. In this study, acute foot-shock stress was used in mice to investigate the involvement of the opioid pathway in the antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251. Stress was induced by intermittent foot-shock stimulation for 30 min. Then, using the forced swimming test (FST) and tail suspension test (TST), the immobility time was measured. Results show that the immobility time was significantly prolonged in animals subjected to foot-shock stress, compared with non-stressed controls (P < 0.01). Also, the serum corticosterone level was significantly increased after stress induction (P < 0.001). Administration of AM-251 (0.5 and 0.3 mg/kg, intraperitoneally (i.p.)), significantly decreased the immobility time of stressed mice in the FST (P < 0.001 and P < 0.01, respectively) and TST (P < 0.01 and P < 0.05, respectively). The lowest dose of AM-251 (0.1 mg/kg), naltrexone (0.3 mg/kg), and morphine (1.0 mg/kg) did not show any significant effect on stressed animals (P > 0.05). Co-administration of AM-251 with sub-effective dose of naltrexone decreased the effective dose of this cannabinoid inverse agonist, to 0.1 mg/kg (P < 0.01). On the other hand, administration of the sub-effective dose of morphine reversed the anti-immobility effect of AM-251 (0.5 mg/kg; P < 0.001). In conclusion, the present study for the first time reveals the possible role of opioid signalling in the antidepressant-like properties of AM-251 in a foot-shock stress model.


Hinge-bending motion of D-allose-binding protein from Escherichia coli: three open conformations.
Conformational changes of periplasmic binding proteins are essential for their function in chemotaxis and transport. The allose-binding protein from Escherichia coli is, like other receptors in its family, composed of two alpha/beta domains joined by a three-stranded hinge. In the previously determined structure of the closed, ligand-bound form (Chaudhuri, B. N., Ko, J., Park, C., Jones, T. A., and Mowbray, S. L. (1999) J. Mol. Biol. 286, 1519-1531), the ligand-binding site is buried between the two domains. We report here the structures of three distinct open, ligand-free forms of this receptor, one solved at 3.1-A resolution and two others at 1.7-A resolution. Together, these allow a description of the conformational changes associated with ligand binding. A few large, coupled torsional changes in the hinge strands are sufficient to generate the overall bending motion, with only minor disruption of the individual domains. Integral water molecules appear to act as structural "ball bearings" in this process. The conformational changes of the related ribose-binding protein follow a distinct pattern. The observed differences between the two proteins can be interpreted in the context of changes in sequence and in crystal packing and provide new insights into the nature of hinge bending motion in this class of periplasmic binding proteins.


A novel metabolic-related gene signature for predicting clinical prognosis and immune microenvironment in head and neck squamous cell carcinoma.
Metabolic reprogramming is not only an essential hallmark in the progression of head and neck squamous cell carcinoma (HNSCC), but also an important regulator of cancer cell adaptation to tumor microenvironment (TME). However, the potential mechanism of metabolic reprogramming in TME of HNSCC is still unknown. The head and neck squamous cell carcinoma with survival information were obtained the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. The metabolic-related genes were identified by differential analysis and survival analysis. Univariate and multivariate Cox regression analyses were applied to determine an overall estimate of metabolic-related risk signature and related clinical parameters. The sensitivity and specificity of the risk signature were evaluated by time-dependent receiver operation characteristic (ROC) curves. TME immune cell infiltration mediated by metabolic-related genes was explored by gene set enrichment analysis (GSEA) and correlation analysis. Seven metabolic-related genes (SMS, MTHFD2, HPRT1, DNMT1, PYGL, ADA, and P4HA1) were identified to develop a metabolic-related risk signature. The low-risk group had a better overall survival compared to that of the high-risk group in the TCGA and GSE65858 cohorts. The AUCs for 1-, 3-, and 5-year overall survival were 0.646 vs. 0.673, 0.694 vs. 0.639, and 0.673 vs. 0.573, respectively. The AUC vale of risk score was 0.727 vs. 0.673. The low-risk group was associated with immune cell infiltration in the TME. The metabolic-related risk signature were constructed and validated, which could involve in regulating the immune cell infiltration in the TME and act as an independent biomarker that predicted the prognosis of HNSCC.


Combinational effect of PPARγ agonist and RXR agonist on the growth of SGC7901 gastric carcinoma cells in vitro.
In order to investigate the inhibitory effects and mechanisms of troglitazone (TGZ), a peroxisome proliferator-activated receptor γ (PPARγ) agonist, and retinoid X receptor (RXR) agonist (9-cis-retinoic acid (RA)) on gastric carcinoma cells SGC7901, SGC7901 cells were treated with TGZ and 9-cis-RA, respectively, or in combination. Then, the cell growth, apoptosis, morphological changes, and the expression of PPARγ, RXRγ, Bcl-2, and Bax were detected by MTT assay, flow cytometry, HE staining, immunocytochemistry staining, and Western blot assay, respectively. Our results showed that the growth of SGC7901 cells was inhibited and the cells got sparser at the concentrations of 50 μmol/L TGZ, 20 μmol/L 9-cis-RA, or combination of TGZ (25 μmol/L) and 9-cis-RA (10 μmol/L). Immunocytochemistry and Western blot showed that after 72 h, the expression of PPARγ, RXRγ, and Bax were upregulated; Bcl-2 was downregulated compared with the negative control group. These data indicated that PPARγ agonist and RXR agonist could inhibit the proliferation of SGC7901 cells via inducing the apoptosis, which involved the increase in the level of Bax/Bcl-2. The combination of RXR agonist and PPARγ agonist could induce the maximal inhibitory effects on tumor growth and apoptosis via promoting the formation of RXR/PPARγ heterodimer.


The effect of tamoxifen on the lipid profile in women: A systematic review and meta-analysis of randomized controlled trials.
The effect of tamoxifen administration on serum lipids in females remains unclear. The studies which have explored this topic have produced conflicting results, probably due to discrepancies in the length of the intervention, differences in baseline variables or other factors. To answer this research question, we decided to conduct this systematic review and meta-analysis to assess the effects of tamoxifen on the lipid profile in women. A comprehensive search was conducted in Web of Science, Scopus, PubMed/Medline and Embase, from the inception of these databases up to June 2021. We used a random effects meta-analysis to generate the combined results. The overall findings were generated from 18 eligible trials. As compared to placebo, tamoxifen led to a notable reduction of the total cholesterol (TC) (WMD: -23.03 mg/dL, 95% CI: -25.94 to -20.12, P˂0.001), and the low-density lipoprotein-cholesterol (LDL-C) (WMD: -18.68 mg/dL, 95% CI: -24.31 to -13.04, P˂0.001). However, tamoxifen did not alter triglycerides (TG) concentrations (WMD: +1.06 mg/dL, 95% CI: -11.08 to 13.20, P = 0.864) significantly. A pronounced reduction of the high-density lipoprotein-cholesterol (HDLC) was noted in the RCTs with a duration of ≤52 weeks (WMD: -2.06 mg/dL) and when tamoxifen was administered in participants with a BMI ≥25 kg/m2 (WMD: -1.42 mg/dL). Notable reductions in TC (WMD: -23.57 mg/dL) and LDL-C (WMD: -19.21 mg/dL) was detected when the dose of tamoxifen was ≥20 mg/day. Moreover, a significant reduction of TC (WMD: -20.23 mg/dL) and LDL-C (WMD: -24.13 mg/dL) was observed in the RCTs with a duration of ≤52 weeks. Tamoxifen can alter the lipid profile in females, particularly by decreasing TC, LDL-C and HDLC. Tamoxifen can further reduce TC and LDL-C if the dose of administration is ≥20 mg/day, the treatment duration is ≤52 weeks and if it prescribed in subjects with dyslipidemia.


Synthesis, structural analysis, and properties of highly twisted alkenes 13,13'-bis(dibenzo[a,i]fluorenylidene) and its derivatives.
The rotation of a C = C bond in an alkene can be efficiently accelerated by creating the high-strain ground state and stabilizing the transition state of the process. Herein, the synthesis, structures, and properties of several highly twisted alkenes are comprehensively explored. A facile and practical synthetic approach to target molecules is developed. The twist angles and lengths of the central C = C bonds in these molecules are 36-58° and 1.40-1.43 Å, respectively, and confirmed by X-ray crystallography and DFT calculations. A quasi-planar molecular half with the π-extended substituents delivers a shallow rotational barrier (down to 2.35 kcal/mol), indicating that the rotation of the C = C bond is as facile as that of the aryl-aryl bond in 2-flourobiphenyl. Other versatile and unique properties of the studied compounds include a broad photoabsorption range (from 250 up to 1100 nm), a reduced HOMO-LUMO gap (1.26-1.68 eV), and a small singlet-triplet energy gap (3.65-5.68 kcal/mol).


Dietary Ruminant Enteric Methane Mitigation Strategies: Current Findings, Potential Risks and Applicability.
This review examines the current state of knowledge regarding the effectiveness of different dietary ruminant enteric methane mitigation strategies and their modes of action together with the issues discussed regarding the potential harms/risks and applicability of such strategies. By investigating these strategies, we can enhance our understanding of the mechanisms by which they influence methane production and identify promising approaches for sustainable mitigation of methane emissions. Out of all nutritional strategies, the use of 3-nitrooxypropanol, red seaweed, tannins, saponins, essential oils, nitrates, and sulfates demonstrates the potential to reduce emissions and receives a lot of attention from the scientific community. The use of certain additives as pure compounds is challenging under certain conditions, such as pasture-based systems, so the potential use of forages with sufficient amounts of plant secondary metabolites is also explored. Additionally, improved forage quality (maturity and nutrient composition) might help to further reduce emissions. Red seaweed, although proven to be very effective in reducing emissions, raises some questions regarding the volatility of the main active compound, bromoform, and challenges regarding the cultivation of the seaweed. Other relatively new methods of mitigation, such as the use of cyanogenic glycosides, are also discussed in this article. Together with nitrates, cyanogenic glycosides pose serious risks to animal health, but research has proven their efficacy and safety when control measures are taken. Furthermore, the risks of nitrate use can be minimized by using probiotics. Some of the discussed strategies, namely monensin or halogenated hydrocarbons (as pure compounds), demonstrate efficacy but are unlikely to be implemented widely because of legal restrictions.


Quinolone resistance and biofilm formation capability of uropathogenic Escherichia coli isolates from an Iranian inpatients' population.
Uropathogenic Escherichia coli (UPEC) is a major pathogen of the urinary tract infection (UTI), and biofilm formation is crucial as it facilitates the colonization in the urinary tract. We aimed to investigate the antibiotic susceptibility pattern, biofilm formation capability, distribution of quinolone resistance genes, and phylogenetic groups among UPEC isolates from an Iranian inpatients' community. A collection of 126 UPEC obtained from hospitalized patients with symptomatic UTI at 3 teaching hospitals during 2016 were included. Antibiogram of all isolates against quinolone and fluoroquinolones was performed using the disk diffusion method. Phylogenetic groups and qnr A, B, and S genes were assessed by PCR. Susceptibility pattern showed that more than 50% and 81% of the isolates were resistant to fluoroquinolones and quinolones, correspondingly. The frequency of qnrS and qnrB genes was 22% and 13.5%, correspondingly. Our result indicated no significant association between the presence of fluoroquinolone genes and antibiotic resistance to them. The frequent common phylogroup was B2 (84.1%), followed by D (10.3%), A (3.2%) and B1 (2.4%) groups. Indeed, 80.2% of the isolates were biofilm producers, so that 42.1%, 16.7% and 21.4% of them were classified as weak, moderate and strong producers, respectively. Our results showed considerable fluoroquinolone and quinolone resistance among UPEC along with a remarkable rate of biofilm-producing isolates from symptomatic hospitalized patients, making them a serious health concern in the region. This survey highlights the need for awareness on quinolone resistance and careful prescription of them by physicians.


A fluorometric assay to determine labile copper(II) ions in serum.
Labile copper(II) ions (Cu2+) in serum are considered to be readily available for cellular uptake and to constitute the biologically active Cu2+ species in the blood. It might also be suitable to reflect copper dyshomeostasis during diseases such as Wilson's disease (WD) or neurological disorders. So far, no direct quantification method has been described to determine this small Cu2+ subset. This study introduces a fluorometric high throughput assay using the novel Cu2+ binding fluoresceine-peptide sensor FP4 (Kd of the Cu2+-FP4-complex 0.38 pM) to determine labile Cu2+ in human and rat serum. Using 96 human serum samples, labile Cu2+was measured to be 0.14 ± 0.05 pM, showing no correlation with age or other serum trace elements. No sex-specific differences in labile Cu2+ concentrations were noted, in contrast to the total copper levels in serum. Analysis of the effect of drug therapy on labile Cu2+ in the sera of 19 patients with WD showed a significant decrease in labile Cu2+ following copper chelation therapy, suggesting that labile Cu2+ may be a specific marker of disease status and that the assay could be suitable for monitoring treatment progress.


Novel Aceclofenac Cocrystals with l-Cystine: Virtual Coformer Screening, Mechanochemical Synthesis, and Physicochemical Investigations.
Current work focuses on the improvement of the solubility and dissolution of ACF by the cocrystal approach. Aceclofenac (ACF) is one of the commonly used Nonsteroidal Anti-Inflammatory Drug (NSAID) representing a variety of therapeutic applications including management of pain, inflammation, rheumatoid arthritis, and osteoarthritis, etc. But very low solubility and dissolution rate of ACF compromise its therapeutic utility. Now a day's cocrystallization technique has emerged as a novel technique for modulation of the said problems. The Specific objectives of this research work were mechanochemical synthesis, characterization, and performance evaluation of aceclofenac cocrystal. ACF was screened with various pharmaceutically acceptable coformers (Selected from GRAS and EAFUS list) using MOPAC software and physical screening method to find out novel cocrystals of ACF with enhanced solubility and dissolution rate. Novel cocrystals (multi-component crystalline solid) of ACF with l-cystine were prepared by a neat grinding method and by liquid assisted grinding method. The synthesized cocrystals (ACF-l-CYS NG and ACF-l-CYS LAG) were characterized carefully by Differential Scanning Calorimetry (DSC), Infrared Spectroscopy (IR), and Powder XRay Diffraction (PXRD) to verify the formation of the cocrystals. Pharmaceutically significant properties such as powder dissolution rate, solubility, and stability of the prepared cocrystals were evaluated. Compared to pure ACF, the prepared cocrystals showed superior solubility and dissolution rate. The prepared cocrystals were found to be stable and non-hygroscopic under study conditions. The cocrystallization technique was successfully utilized to increase the solubility and dissolution rate of aceclofenac.


Forensic facial reconstruction: Nasal projection in Brazilian adults.
The nose has a marked cognitive influence on facial image; however, it loses its shape during cadaveric decomposition. The known methods of estimating nasal projection using Facial Reconstruction are lacking in practicality and reproducibility. We attempted to relate the points Rhinion, Pronasale and Prosthion by studying the angle formed by straight lines that connect them. Two examiners measured this angle with the help of analysis and image-processing software, Image J, directly from cephalometric radiographs. The sample consisted of 300 males, aged between 24 and 77 years, and 300 females, aged 24 to 69 years. The proposed angle ranged from 80° to 100° in both sexes and all ages. It was considered possible to use a 90° angle from projections of the Rhinion and Prosthion points in order to determine the Pronasale position, as well as to estimate the nasal projection of Brazilian adults.


Risk factors for developing synchronous esophageal neoplasia in patients with head and neck cancer.
This study investigated the risk factors for synchronous esophageal neoplasia in patients with head and neck squamous cell carcinoma (HNSCC). All 315 consecutive patients with newly diagnosed HNSCC received endoscopic esophageal screening with image-enhanced endoscopy. Sixty-nine patients (21.9%) had synchronous esophageal neoplasia, 37 (53.6%) with superficial neoplasia and 21 (30.4%) with multiple esophageal lesions. Univariate analysis revealed age <50 years, drinking alcohol, and location of index HNSCC were significant risk factors for developing synchronous esophageal neoplasia. In multivariate analysis, drinking alcohol (odds ratio [OR], 3.792; p = .0035), index oropharynxgeal cancers (OR, 3.618; p = .0045) and hypopharyngeal cancers (OR, 2.627; p = .0029) were independent risk factors. Drinking alcohol was clearly dose-response related (p = .001). Alcohol consumption and index tumor location are associated with the development of synchronous esophageal neoplasia in patients with HNSCC. Because of the high prevalence, routine endoscopic examination of the esophagus should be recommended, especially in patients with the risk factors identified.


Clostridium difficile testing algorithms using glutamate dehydrogenase antigen and C. difficile toxin enzyme immunoassays with C. difficile nucleic acid amplification testing increase diagnostic yield in a tertiary pediatric population.
We evaluated the performance of the rapid C. diff Quik Chek Complete's glutamate dehydrogenase antigen (GDH) and toxin A/B (CDT) tests in two algorithmic approaches for a tertiary pediatric population: algorithm 1 entailed initial testing with GDH/CDT followed by loop-mediated isothermal amplification (LAMP), and algorithm 2 entailed GDH/CDT followed by cytotoxicity neutralization assay (CCNA) for adjudication of discrepant GDH-positive/CDT-negative results. A true positive (TP) was defined as positivity by CCNA or positivity by LAMP plus another test (GDH, CDT, or the Premier C. difficile toxin A and B enzyme immunoassay [P-EIA]). A total of 141 specimens from 141 patients yielded 27 TPs and 19% prevalence. Sensitivity, specificity, positive predictive value, and negative predictive value were 56%, 100%, 100%, and 90% for P-EIA and 81%, 100%, 100%, and 96% for both algorithm 1 and algorithm 2. In summary, GDH-based algorithms detected C. difficile infections with superior sensitivity compared to P-EIA. The algorithms allowed immediate reporting of half of all TPs, but LAMP or CCNA was required to confirm the presence or absence of toxigenic C. difficile in GDH-positive/CDT-negative specimens.


Pregnancy-associated endometrial expression of antileukoproteinase gene is correlated with epitheliochorial placentation.
Uterine expression of the mRNA encoding antileukoproteinase (ALP) is highest in pig uterus during mid- to late pregnancy, suggesting a stage of pregnancy-dependent role for this elastase/cathepsin G protease inhibitor in feto-maternal interactions. To examine a potential relationship between uterine synthesis of ALP and the type of placentation in mammalian species, the expression of ALP mRNA and/or protein in pregnant mares, cows, rats, and mice was evaluated. Genomic DNA and mRNA hybridization analyses were performed using a porcine ALP cDNA as probe. The concentration of ALP protein in reproductive tissues was determined by RIA using a polyclonal antibody raised against a synthetic peptide (ALP 16P) corresponding to amino acid residues 21-36 of the porcine ALP protein. A single ALP mRNA transcript of approximately 0.8 kb in length was detected in equine and bovine uterine tissues. The relative abundance of ALP mRNA in equine endometrium increased between days 125-170 (mid-pregnancy), and then decreased by day 215 of pregnancy. Similarly, the steady state levels of ALP mRNA in bovine endometrium and myometrium were higher during mid- to late than during early pregnancy. The levels of ALP mRNA in bovine fetal cotyledon were low and did not change significantly with stage of pregnancy. No hybridization was detected to pregnant rat endometrial tissues, although high stringency Southern blot analysis of porcine, bovine, and rat genomic DNAs using porcine ALP cDNA as probe predicted a high degree of nucleotide sequence homology in their respective ALP genes.(ABSTRACT TRUNCATED AT 250 WORDS)


Study on Spontaneous Combustion Characteristics and Oxidation Kinetic Parameters of Lignite at Different Oxygen Concentrations.
The spontaneous combustion parameters of lignite at different oxygen concentrations and temperatures were studied by temperature-programmed oxidation experiments. The characteristic parameters, tendency, oxygen consumption rate, kinetic parameters of oxidation reaction, and heat release intensity of coal's spontaneous combustion were studied. The results show that the variation of export oxygen volume fraction of coal samples under different oxygen concentrations is similar. It has a general s-shaped downward trend. The change trend of the CO concentration of the coal sample export is basically the same at different oxygen concentrations. The CO concentration at the outlet of the coal sample increases with the increase in coal temperature. The CO concentration at 0-200 °C increased exponentially with the coal temperature. The distribution pattern of CO/CO2 ranging from 0 to 320 °C was similar at different oxygen concentrations. With the increase of coal temperature, CO/CO2 first increases and then decreases after reaching the extreme point. The change curve of CH4 with coal temperature under different oxygen concentrations meets the exponential change rule. At different oxygen concentrations, the concentration of ethylene at 0-300 °C changes exponentially, but at 300-400 °C there is no rule. When the oxygen concentration is 20.9%, according to the comprehensive judgment index method and cross temperature method, the comprehensive determination of the spontaneous combustion trend of coal samples is grade II. Under different oxygen concentrations, the oxygen consumption rate of coal increases with the increase of temperature; the oxygen consumption rate increases with the increase of oxygen concentration at the same temperature. The activation energy of coal samples increases with the decrease of oxygen supply concentration or the increase of temperature. The thermal strength of the coal sample is consistent with the change trend of the oxygen consumption rate. The heat release intensity of coal samples conforms to an exponential function and polynomial function in the early and late stages, respectively.


Laminar Differences in the Targeting of Dendritic Spines by Cortical Pyramidal Neurons and Interneurons in Human Dorsolateral Prefrontal Cortex.
Activation of specific neural circuits in different layers of the primate dorsolateral prefrontal cortex (DLPFC) is essential for working memory, a core cognitive function. Recurrent excitation between pyramidal neurons in middle and deep layers of the DLPFC contributes to the laminar-specific activity associated with different working memory subprocesses. Excitation between cortical pyramidal neurons is mediated by glutamatergic synapses on dendritic spines, but whether the relative abundance of spines receiving cortical inputs differs between middle and deep cortical layers in human DLPFC is unknown. Additionally, GABAergic inputs to spines sculpt pyramidal neuron activity. Whether dendritic spines that receive a glutamatergic input from a cortical pyramidal neuron are targeted by GABAergic interneurons in the human DLPFC is unknown. Using triple-label fluorescence confocal microscopy, we found that 1) the density of spines receiving an input from a cortical pyramidal neuron is greater in the middle than in the deep laminar zone, 2) dendritic spines dually innervated by a cortical pyramidal neuron and an interneuron are present in the human DLPFC, and 3) the density of spines dually innervated by a cortical pyramidal neuron and an interneuron is also greater in the middle than in the deep laminar zone. Ultrastructural analyses support the presence of spines that receive a cortical pyramidal neuron synapse and an interneuron synapse in human and monkey DLPFC. These data support the notion that the DLPFC middle laminar zone is particularly endowed with a microcircuit structure that supports the gating, integrating and fine-tuning of synaptic information in recurrent excitatory microcircuits.


IL-21-driven neoplasms in SJL mice mimic some key features of human angioimmunoblastic T-cell lymphoma.
SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4(+) T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (TFH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R)-deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of TFH cells, lower serum levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21-dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of TFH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated levels of transcripts for IL21, IL21R, and a series of genes associated with TFH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling.


Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy.
The slit diaphragm is an adhesion and signalling protein complex linking the interdigitating podocyte foot processes in the kidney glomerulus, and mutations in slit diaphragm-associated genes result in severe proteinuria. Here we report a genetic association analysis of four slit diaphragm genes, LRRC7, KIRREL, NPHS2 and ACTN4, in a Finnish diabetic nephropathy cohort. A total of 40 single nucleotide polymorphisms (SNPs) were genotyped in 1103 patients with type 1 diabetes. The patients were classified according to their renal status, and the genotype data were analysed in a cross-sectional case-control setting. To confirm positive associations, four SNPs were genotyped in 1,025 additional patients with type 1 diabetes. No associations with diabetic nephropathy were observed for any of the analysed SNPs. The SNPs were not associated with the time from the onset of diabetes to the diagnosis of nephropathy or with glomerular filtration rate or AER as quantitative variables. In a sex-specific sub-analysis, the variants rs979972 and rs749701 in the first intron of ACTN4 were nominally associated with diabetic nephropathy in females, with odds ratios of 1.81 (95% CI 1.18-2.79, p = 0.007) and 1.93 (95% CI 1.26-2.96, p = 0.003) respectively. Our study has not found any evidence that common variants in LRRC7, KIRREL, NPHS2 and ACTN4 contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes.


Penile gangrene associated with extensive Kaposi's sarcoma in patients with the acquired immunodeficiency syndrome.
Kaposi's sarcoma (KS) of the penis is a well-recognized manifestation of the acquired immunodeficency syndrome. Extensive KS of the genitalia progressed and caused penile gangrene in 2 cases. Management is palliative with urinary diversion via percutaneous suprapubic cystostomy.


[Lower urinary tract dysfunction in Guillain-Barre syndrome].
Guillain-Barré syndrome (GBS) as acute inflammatory demyelinating polyradiculoneuropathy frequently leads to lower urinary tract dysfunction. The available knowledge in the medical literature is limited and good recommendations for diagnosis and therapy are rare. In this study, 189 patients with GBS were screened for lower urinary tract dysfunction. In symptomatic patients, a urodynamic study was performed. Detrusor contractility, post-void residual, and changes of the symptoms over time were studied. Overall Barthel index and urinary control Barthel index as well as the relationship of time after onset of the disease and post-void residual were studied as possible screening criteria for urodynamic assessment. According to the urinary control Barthel index (BI), 115 of 189 patients (61%) presented lower urinary tract symptoms sometime during the course of disease. In 28 patients, these symptoms were temporary during the acute phase. At the time of urological assessment, 87 patients had lower urinary tract symptoms. At the end of rehabilitation, 37 had no symptoms anymore (BI 10), 20 were able to control micturition to a certain extent (BI 5), and 30 had no lower urinary tract control (BI 0). There was a significant negative correlation between post-void residual volume and overall BI (ρ -0.5823, p < 0.0001) and BI for urinary tract control (ρ -0.6430, p < 0.0001). Overall BI and BI for urinary tract control are suitable screening criteria for urodynamic assessment.


Changes in the composition of membrane phospholipids during the cell cycle of Escherichia coli.
Phospholipid concentrations have been estimated throughout the successive cell cycle in synchronously growing culture of E. coli B/r. Total phospholipid phosphorus was shown to be doubled in the period of time between two cell divisions, whereas during the division itself it did not change. Phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) exhibit a stepwise increase during the cell cycle. It should be noted that the phase of accumulation of these lipids could shift depending on the duration of the cell cycle. The fall in level of PE was followed by a short-term increase (5-10 min). At the same time the level of cardiolipin was observed to be significantly increased.


Ingestion of A Common Plant's Leaves Leads to Acute Respiratory Arrest and Paralysis: A Case Report.
Nicotiana glauca is a plant known to cause acute toxicity upon ingestion or dermal exposure due to the nicotinic alkaloid, anabasine. Nicotinic alkaloids cause toxicity by acting as agonists on nicotinic-type acetylcholine receptors (nAChRs). Initial stimulation of these receptors leads to symptoms such as tachycardia, miosis, and tremors. The effects of high doses of nicotinic alkaloids are biphasic, and eventual persistent depolarization of nAChRs at the neuromuscular junction occurs. This causes apnea, paralysis, and cardiovascular collapse. In this report, we present a case of respiratory arrest due to nicotinic alkaloid poisoning from the ingestion of Nicotiana glauca. The diagnosis was suspected after the patient's family gave a history of the patient ingesting a plant prior to arrival. They were able to also provide a physical sample of the plant. The phone application, "Plant Snap", determined the plant species and helped confirm the diagnosis. This case describes how modern technology and thorough history taking can combine to provide the best possible patient care.