Sequential alterations in gastric biopsies and tumor tissues support the multistep process of carcinogenesis.
Gastric cancer is the second leading cause of cancer related death worldwide. In the UAE, recent data show an increase in the number of patients with gastric cancer highlighting the need for greater understanding of its pathogenesis. Gastric cancer is generally believed to develop on a background of chronic atrophic gastritis which eventually leads to intestinal metaplasia, dysplasia and finally invasive carcinoma. Recently this multistep process of carcinogenesis has been challenged. Therefore, the aim of this study is to define alterations in antral mucosal biopsies and cancer tissues to investigate whether they could be used to assemble a tissue array supporting the multistep model of carcinogenesis. Gastric mucosal tissues were obtained from informed individuals undergoing endoscopy (for upper gastrointestinal symptoms) and gastrectomy (for adenocarcinoma) in Tawam Hospital. All tissues were processed for microscopic examination. Eighty nine antral biopsies were categorized as: normal (33%), mild superficial gastritis (34%) and severe atrophic gastritis (33%). About 5% of the latter exhibited evidence of intestinal metaplasia. Cancer tissues obtained from three patients were microscopically examined in three regions: safe resected margin, tumor edge and tumor center. Progressive changes in mucosal thickness, dysplasia and cellular transformation were observed, and when compared with alterations in biopsies, all appeared to represent a continuum of progression toward invasive adenocarcinoma. In conclusion, the tissue array presented in this study supports the multistep process of gastric carcinogenesis and will be helpful in examining the expression pattern of tumor markers or molecules that could help in the early detection of gastric cancer.


High pressure growth of nanocrystalline silicon films.
Nanocrystalline silicon thin films were grown using gaseous mixture of 5% silane (SiH4) diluted in hydrogen (H2) and argon (Ar) in a radio frequency (13.56 MHz) plasma enhanced chemical vapor deposition technique. These films were deposited as a function of pressure and were characterized using AFM, Laser Raman, UV-VIS transmission, photoluminescence and electrical conductivity techniques. AFM micrographs shows that these films contain nanocrystallites of 30-60 nm size. Laser Raman peaks at 520 cm(-1) and photoluminescence peaks at 2.75 and 2.85 eV have been observed. The crystalline fraction in these films was varied from 30% to 80% with the variation of deposition pressure from 2 Torr to 8 Torr. There is an optimum pressure of 4 Torr where the maximum growth of nanocrystalline phases was observed. It has been found that nanocrystallites in these film enhanced the optical band gap and electrical conductivity. Also a voltage-current (V-I) probe was used to evaluate the various electrical parameters of the plasma used to deposit the nc-Si:H films for the present investigation. Growth via a SiH3 precursor, diffusion of hydrogen in the sub-surface and argon etching of weak bonds are some of the processes that may be involved in the nano crystallization process.


Bone imaging in metastatic breast cancer.
Bone is the most common site to which breast cancer metastasizes. Imaging-by skeletal scintigraphy, plain radiography, computed tomography, or magnetic resonance imaging-is an essential part, and positron emission tomography or single-photon emission computed tomography have a potential of evaluating bone metastases, but no consensus exists as to the best modality for diagnosing the lesion and for assessing its response to treatment. Imaging bone metastases is problematic because the lesions can be osteolytic, osteoblastic, or mixed, and imaging modalities are based on either direct anatomic visualization of the bone or tumor or indirect measurements of bone or tumor metabolism. Although bone metastases can be treated, their response to treatment is considered "unmeasurable" according to existing response criteria. Therefore, the process by which oncologists and radiologists diagnose and monitor the response of bone metastases needs revision, and the current inability to assess the response of bone metastases excludes patients with breast cancer and bone disease from participating in clinical trials of new treatments for breast cancer. In this review of the MEDLINE literature, we discuss the pros and cons of each modality for diagnosing bone metastases and for assessing their response to treatment and we present a practical approach for diagnosis and assessment of bone metastasis.


Limited Effectiveness of Diabetes Risk Assessment Tools in Seniors' Facility Residents.
Undiagnosed diabetes can create significant management issues for seniors. To evaluate the effectiveness of two diabetes risk surveys-the Canadian Diabetes Risk Assessment Questionnaire (CANRISK) and the Finnish Diabetes Risk Score (FINDRISC)-to identify elevated blood glucose levels in seniors. A cross-sectional study was conducted in senior living facilities in Edmonton, Alberta, Canada. Those with known diabetes, without capacity, considered frail, or unable to communicate in English were excluded. Participants completed the CANRISK and FINDRISC surveys and had their glycated hemoglobin A1c (HbA1c) measured. Correlations between seniors with elevated risk on the surveys and an HbA1c value of 6.5% or higher or 6.0% and higher were assessed. In this study, 290 residents participated; their mean age was 84.3 ± 7.3 years, 82 (28%) were men, and their mean HbA1c level was 5.7% ± 0.4%. Mean CANRISK score was 29.4 ± 8.0, and of the 254 (88%) considered to be moderate or high risk, 10 (4%) had an HbA1c level of 6.5% or higher and 49 (19%) had an HbA1c level of 6.0% or higher. Mean FINDRISC score was 10.8 ± 4.2, and of the 58 (20%) considered to be high or very high risk, 4 (7%) had an HbA1c level of 6.5% or higher and 15 (26%) had an HbA1c level of 6.0% or higher. The area under the receiver-operating characteristic curve was 0.57 (95% confidence interval 0.42-0.72) for the CANRISK survey identifying participants with an HbA1c level of 6.5% or higher and 0.59 (95% confidence interval 0.51-0.67) for identifying participants with an HbA1c level of 6.0% or higher. Similar characteristics were observed for the FINDRISC survey. In this group of seniors with no known diabetes history, mean HbA1c level approximated that in the general population and neither survey effectively identified those with elevated blood glucose levels. These findings should be confirmed in a larger study; nevertheless, routine use of these surveys as a diabetes screening strategy does not appear to be warranted at this time.


Identification of Food-Derived Isoflavone Sulfates as Inhibition Markers for Intestinal Breast Cancer Resistance Proteins.
Potential inhibition of the breast cancer resistance protein (BCRP), a drug efflux transporter, is a key issue during drug development, and the use of its physiologic substrates as biomarkers can be advantageous to assess inhibition. In this study, we aimed to identify BCRP substrates by an untargeted metabolomic approach. Mice were orally administered lapatinib to inhibit BCRP in vivo, and plasma samples were assessed by liquid chromatography/time of flight/mass spectrometry with all-ion fragmentation acquisition and quantified by liquid chromatography with tandem mass spectrometry. A differential metabolomic analysis was also performed for plasma from Bcrp -/- and wild-type mice. Plasma peaks of food-derived isoflavone metabolites, daidzein sulfate (DS), and genistein sulfate (GS) increased after lapatinib administration and in Bcrp -/- mice. Administration of lapatinib and another BCRP inhibitor febuxostat increased the area under the plasma concentration-time curve (AUC) of DS, GS, and equol sulfate (ES) by 3.6- and 1.8-, 5.6- and 4.1-, and 1.6- and 4.8-fold, respectively. BCRP inhibitors also increased the AUC and maximum plasma concentration of DS and ES after coadministration with each parent compound. After adding parent compounds to the apical side of induced pluripotent stem cell-derived small intestinal epithelial-like cells, DS, GS, and ES in the basal compartment significantly increased in the presence of lapatinib and febuxostat, suggesting the inhibition of intestinal BCRP. ATP-dependent uptake of DS and ES in BCRP-expressing membrane vesicles was reduced by both inhibitors, indicating inhibition of BCRP-mediated DS and ES transport. Thus, we propose the first evidence of surrogate markers for BCRP inhibition. SIGNIFICANCE STATEMENT: This study performed untargeted metabolomics to identify substrates of BCRP/ABCG2 to assess changes in its transport activity in vivo by BCRP/ABCG2 inhibitors. Food-derived isoflavone sulfates were identified as useful markers for evaluating changes in BCRP-mediated transport in the small intestine by its inhibitors.


Allied health transdisciplinary models of care in hospital settings: A scoping review .
Improving the productivity of the allied health workforce is a global priority in response to the increasing incidence of chronic disease, associated healthcare costs, and insufficient workforce volume. Team-based healthcare, specifically allied health transdisciplinary teams, might be a solution to improve the utilization of workforce while maintaining high-quality and value-based healthcare. Allied health transdisciplinary teams can be a valuable solution in settings where care is delivered by different allied health professionals. Transdisciplinary teams embrace overlapping skills and blur traditional professional boundaries, allowing one professional to deliver certain aspects of care without eroding the skills and knowledge that each profession offers. The objective of this scoping review is to systematically examine and map the characteristics, outcomes, facilitators, and barriers of contemporary allied health transdisciplinary models of care that have been implemented in hospital settings. The scoping review was guided by the Joanna Briggs Institute methodology and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Three screening rounds were completed by two independent reviewers. Included sources were synthesized using descriptive and tabular analysis. Nine studies that evaluated hospital-based allied health transdisciplinary teams were included. One study was a randomized controlled trial, five were experimental quantitative studies, two utilized qualitative analyses, and one was a conference abstract. Most studies reported improvements in time-efficiency, quality of care, and positive stakeholder perceptions. One study reported labor and capital cost savings. Barriers and facilitators of transdisciplinary teams were categorized by the authors as person/interpersonal, workflow, organizational or implementation factors. This review presents some evidence that demonstrates the potential of hospital-based allied health transdisciplinary teams, however high-quality evidence is scarce. Further primary research should focus on stakeholder perceptions, and labor and capital cost outcomes.


Functional Profiling of Transcription Factor Genes in Neurospora crassa.
Regulation of gene expression by DNA-binding transcription factors is essential for proper control of growth and development in all organisms. In this study, we annotate and characterize growth and developmental phenotypes for transcription factor genes in the model filamentous fungus Neurospora crassa We identified 312 transcription factor genes, corresponding to 3.2% of the protein coding genes in the genome. The largest class was the fungal-specific Zn2Cys6 (C6) binuclear cluster, with 135 members, followed by the highly conserved C2H2 zinc finger group, with 61 genes. Viable knockout mutants were produced for 273 genes, and complete growth and developmental phenotypic data are available for 242 strains, with 64% possessing at least one defect. The most prominent defect observed was in growth of basal hyphae (43% of mutants analyzed), followed by asexual sporulation (38%), and the various stages of sexual development (19%). Two growth or developmental defects were observed for 21% of the mutants, while 8% were defective in all three major phenotypes tested. Analysis of available mRNA expression data for a time course of sexual development revealed mutants with sexual phenotypes that correlate with transcription factor transcript abundance in wild type. Inspection of this data also implicated cryptic roles in sexual development for several cotranscribed transcription factor genes that do not produce a phenotype when mutated.


On the prevalence of M. avium subspecies paratuberculosis DNA in the blood of healthy individuals and patients with inflammatory bowel disease.
Mycobacteria, such as M. leprae and M. tuberculosis infect billions of humans. However, because of appropriate immune responses and antibiotic therapy, overt mycobacterial diseases occur far less frequently. M. avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants, an affliction evocative of inflammatory bowel disease (IBD). Several agents used to treat IBD (5-ASA, methotrexate, azathioprine and its metabolite 6-MP) have recently been shown to be antiMAP antibiotics. We herein evaluate the prevalence of MAP DNA in healthy individuals and compare them with IBD patients on antiMAP antibiotics. We studied 100 healthy individuals (90 blood donors) and 246 patients with IBD. IS900 MAP DNA was identified using a nested primer PCR in the buffy coat of blood. Positive signal was confirmed as MAP by DNA sequence analysis. PCR positive results frequencies were compared according to medications used. Significance was accepted at p<0.05. 47% (47/100) healthy controls and 16% (40/246) IBD patients were IS900 positive (p<0.0001). MAP DNA was identified in 17% of 143 patients receiving mesalamine and 6% of 16 receiving sulfasalazine. None of the IBD patients receiving methotrexate (n = 9), 6-MP (n = 3), ciprofloxacin (n = 5) or Tacrolimus (n = 3) had MAP DNA detectable in their blood. We found a disquietingly large percentage of healthy individuals have MAP DNA in their blood, the significance of which remains to be determined. Counter-intuitively, the incidence of MAP DNA was significantly lower in patients with IBD. Agents with the most potent in vitro antiMAP activity were associated with clearance of blood MAP DNA. We posit that the use antiMAP antibiotics was responsible for the decreased prevalence of MAP DNA in patients with IBD.


A comparison of the morphological, histochemical and biochemical features of embryonic chick sternal chondrocytes in vivo with chondrocytes cultured in three-dimensional collagen gels.
Disaggregated chondrocytes from embryonic chick whole sterna proliferate in three-dimensional collagen gels forming mixtures of cartilage nodules (chondroids) and columns of cells. A typical matrix elaborated by the cells is composed of collagen type II and chondroitin and keratan sulphate proteoglycans. The cells of the chondroids are small and uniform whilst those in the columns are larger (hypertrophic) and have a vacuolated cytoplasm. Disaggregated cells from the caudal portion of the sternum (which in vivo contains small uniform cells and does not calcify) tend to form chondroids in culture whilst cells from the cephalic portion (which in vivo contains large hypertrophic cells and whose matrix calcifies) tend to form columns of hypertrophic cells. Only the cultures containing hypertrophic cells synthesise collagen type X and only the hypertrophic cells contain alkaline phosphatase. Collagen type X and alkaline phosphatase may therefore be coregulators of the calcification of hypertrophic cartilage matrix.


Transfer RNA Modification.
Transfer RNA (tRNA) from all organisms on this planet contains modified nucleosides, which are derivatives of the four major nucleosides. tRNA from Escherichia coli/Salmonella enterica contains 31 different modified nucleosides, which are all, except for one (Queuosine[Q]), synthesized on an oligonucleotide precursor, which through specific enzymes later matures into tRNA. The corresponding structural genes for these enzymes are found in mono- and polycistronic operons, the latter of which have a complex transcription and translation pattern. The syntheses of some of them (e.g.,several methylated derivatives) are catalyzed by one enzyme, which is position and base specific, but synthesis of some have a very complex biosynthetic pathway involving several enzymes (e.g., 2-thiouridines, N6-threonyladenosine [t6A],and Q). Several of the modified nucleosides are essential for viability (e.g.,lysidin, t6A, 1-methylguanosine), whereas deficiency in others induces severe growth defects. However, some have no or only a small effect on growth at laboratory conditions. Modified nucleosides that are present in the anticodon loop or stem have a fundamental influence on the efficiency of charging the tRNA, reading cognate codons, and preventing missense and frameshift errors. Those, which are present in the body of the tRNA, have a primarily stabilizing effect on the tRNA. Thus, the ubiquitouspresence of these modified nucleosides plays a pivotal role in the function of the tRNA by their influence on the stability and activity of the tRNA.


Polycythemia vera among participants of a nuclear weapons test.
Two cases of polycythemia vera and two cases of suspected polycythemia vera were found among 3,217 nuclear test participants present during the detonation of the nuclear device, "Smoky," on Aug 31, 1957, and traced through December 1981. The observed occurrence of four cases of polycythemia vera in a group this size significantly exceeds that expected. However, the small individual whole-body doses of radiation reported for these four participants makes the association with ionizing radiation tenuous, although this was the only known unusual risk factor.


IL‑6/STAT3/miR‑34a protects against neonatal lung injury patients.
The present study aimed to investigate the protective role of the interleukin (IL)‑6/signal transducer and activator of transcription 3 (STAT3)/microRNA (miR)‑34a signaling pathway in patients with neonatal lung injury (NLI) and the underlying molecular mechanisms of these effects. It was demonstrated that miR‑34a serum expression was significantly upregulated in patients and mice with NLI. Meanwhile, IL‑6 and phosphorylated‑STAT3 protein expression, and tumor necrosis factor (TNF)‑α, IL‑1β and IL‑18 activity levels in NLI mice were significantly induced compared with the normal control group. The promotion of IL‑6 protein expression resulted in significantly increased TNF‑α, IL‑1β and IL‑18 activity levels, phosphorylated‑STAT3 and p65 protein expression, and miR‑34a expression in NLI mice compared with the corresponding normal control groups. In A549 cells treated with lipopolysaccharides, the promotion of miR‑34a protein expression significantly increased TNF‑α, IL‑1β and IL‑18 activity levels, and induced transcription factor p65 protein expression compared with the corresponding negative control groups. Collectively, the data of the present study indicate that IL‑6R/STAT3/miR‑34a possesses a protective role in patients with neonatal lung injury.


Strengthening the safety net for online seniors: factors influencing differences in health information seeking among older internet users.
Earlier studies clearly have shown that older adults are going online and accessing health information, but they are not a monolithic group. The goal of this study is to identify different types of older online Americans and to examine their online health information attitudes and behaviors. A total of 424 individuals age 55+ responded to an online survey. Three types of users were found based on demographic and computer-use factors: power users, well-to-do, and older men. Two types were found based on health attitudes and behaviors: health traditionalists and health technologists. The study found interesting relationships among these groups and also explored their use and evaluation of specific types of health-related websites and their motivations for going online. Suggestions are made for extending this research to other populations and further exploring the theoretical model of senior's online health interactions (SOHI) that drives the study.


Survey to evaluate diagnosis and management of headache in primary care: Headache Management Pattern programme.
The Headache Management Pattern (HMP) programme was designed to evaluate the current clinical situation regarding the diagnosis, treatment and referral of headache in a European primary care setting. A total of 705 GPs (from Germany, Portugal and Belgium), who regularly treated migraine patients, completed a questionnaire relating to four different case scenarios described in terms of symptoms, signs and medical history. Each GP completed clinical decision-trees which were created following IHS diagnostic criteria and published treatment guidelines. Of those questioned, 90% accurately diagnosed a new migraine case and 54% prescribed early intervention with a triptan. However, 23.7% prescribed an NSAID, despite a past history of failed headache relief, and 7.2% indicated that they would refer their patients to a specialist. In the case of a patient whose migraine was deteriorating, 55% of GPs counselled early intervention with a triptan. For chronic migraine sufferers, 42.6% of GPs chose to refer them to a specialist, whilst about one-third made appropriate adjustments to the patient's treatment. The final case, tension-type headache, proved the most difficult scenario to assess, with only 26% of those questioned reaching an adequate diagnosis. Between-country differences in clinical practice may result from local reimbursement policy, treatment guidelines, and different healthcare systems/facilities (e.g., access to specialised care)--all of which could influence the results obtained. A questionnaire such as the HMP programme inherently has limited depth, and the sampling procedure (GPs with triptan knowledge from three countries) needs to be considered when interpreting the results. Nevertheless, the survey provides important information relating to the management of headache in primary care, highlighting the need for both continuing medical education and also improved referral to specialist care.


TCF7L2 variation and proliferative diabetic retinopathy.
Proliferative diabetic retinopathy (PDR) is the most severe vision-threatening complication of diabetes. For investigation of genetic association between TCF7L2 and PDR in Caucasian type 2 diabetes mellitus (T2DM) and its functional consequences, 383 T2DM patients with PDR (T2DM-PDR) and 756 T2DM patients without diabetic retinopathy (T2DM-no DR) were genotyped with rs7903146 in TCF7L2. We found that risk allele (T) frequency of rs7903146 was significantly higher in T2DM-PDR patients (allelic P = 2.52E-04). In lymphoblastoid cells induced to undergo endoplasmic reticulum (ER) stress by treatment of tunicamycin, higher fold change of TCF7L2 and VEGFA mRNA levels were observed in rs7903146-TT cells than in rs7903146-CC cells (P = 0.02 for TCF7L2; P = 0.004 for VEGFA), suggesting that ER stress plays a role in PDR pathogenesis. Silencing TCF7L2 resulted in decreased mRNA levels of both TCF7L2 and VEGFA (P < 0.001). Retinas of oxygen-induced retinopathy mice (a model for PDR) had higher TCF7L2 and VEGFA mRNA levels than those of controls (P = 2.9E-04 for TCF7L2; P = 1.9E-07 for VEGFA). Together, data from our study show that TCF7L2-rs7903146 is associated with PDR in Caucasian T2DM and suggest that TCF7L2 promotes pathological retinal neovascularization via ER stress-dependent upregulation of VEGFA.


Multiple effects of 2,3-butanedione monoxime.
2,3-Butanedione monoxime, also known as diacetyl monoxime, is a nucleophilic agent which dephosphorylates acetylcholinesterase poisoned with organophosphates. This "chemical phosphatase" activity stimulated studies of the effect of 2,3-butanedione monoxime on phosphorylation-dependent cellular processes. As a result of these studies, we know that the drug affects a number of mechanisms including muscle contraction, ionic current flow and synaptic transmission. Furthermore, it may be used as a component of cardioplegic solutions since it protects cardiac tissue exposed to certain ischaemic conditions. While this MiniReview reveals the diversity of its cellular actions, there continues to be unresolved questions regarding its molecular mechanism.


Near surface properties of mixtures of propylammonium nitrate with n-alkanols 2. Nanotribology and fluid dynamics.
Colloid probe friction force microscopy (FFM) has been used to study the lubricity of propylammonium nitrate (PAN) mixed with n-alkanols confined between sliding silica and mica surfaces. Mixtures of PAN with butanol, hexanol, octanol and dodecanol were investigated for various n-alkanol volume fractions to elucidate the effect of n-alkanol hydrocarbon chain length and concentration on shear forces. For all n-alkanols friction decreases with n-alkanol vol%. The trends in friction reduction with n-alkanol vol% do not correlate with changes in the bulk phase viscosity or the near surface nanostructure, and colloid probe atomic force microscope (AFM) fluid dynamic measurements showed that none of the mixtures shear thin. Thus, the reduction in friction is attributed to the n-alkanol disrupting solvophobic interactions between boundary layer propylammonium ions adsorbed to the mica and near surface liquid layers. The lowest friction is obtained for pure dodecanol, which is attributed to the dodecanol forming a robust boundary layer. Friction for the other pure n-alkanols is higher because the lateral attractions between adsorbed n-alkanols are too weak to facilitate the formation of a strong boundary layer, commensurate with the decreased hydrocarbon chain length.


Unilateral Right-Sided Ultrasound-Guided Erector Spinae Plane Block for Post-Laparoscopic Cholecystectomy Analgesia: A Randomized Control Trial.
Post-laparoscopic cholecystectomy (LC) pain control is still an issue postoperatively. We investigated the effectiveness of the unilateral right-side ultrasound-guided erector spinae plane block (ESPB) on post-LC pain intensity and opioid consumption. This is a parallel-arm randomized control trial on 62 adult patients with an American Society of Anesthesiologists (ASA) physical status ≤ 2 who underwent LC. The patients were randomized into 2 groups (the block group [BG] and the control group [CG]; n = 31 per group). BG received a single-shot right-sided T7 ESPB with 20 mL of 0.2% ropivacaine at arrival time in the post-anesthesia care unit (PACU). CG) received no regional anesthesia. Both groups received patient-controlled intravenous fentanyl and rescue meperidine for analgesia. The primary outcome was the pain intensity determined using a Numerical Rating Scale (NRS) in the first 24 hours after surgery. Secondary outcomes included total fentanyl and meperidine consumption within 24 hours. Median pain scores were significantly higher in CG at rest and with coughing up to 12 hours after surgery compared with BG. Pain scores were higher in CG with a cough at 24 hours compared with BG (median 1 [interquartile range (IQR) 1, 2] vs. 1 [1, 0]; P = 0.0005). Total fentanyl consumption and meperidine consumption within 24 hours were significantly lower in BG compared with CG (median 60 µg [IQR 60, 90] vs 250 µg [90, 300]; P < 0.0001 and median 20 µg [IQR 10, 20] vs 25 [20, 25]; P = 0.002, respectively). A single-shot, right-sided, unilateral ESPB decreases post-LC opioid consumption and pain.


Selection of CD8+ T cells with highly focused specificity during viral persistence in the central nervous system.
The relationships between T cell populations during primary viral infection and persistence are poorly understood. Mice infected with the neurotropic JHMV strain of mouse hepatitis virus mount potent regional CTL responses that effectively reduce infectious virus; nevertheless, viral RNA persists in the central nervous system (CNS). To evaluate whether persistence influences Ag-specific CD8+ T cells, functional TCR diversity was studied in spleen and CNS-derived CTL populations based on differential recognition of variant peptides for the dominant nucleocapsid epitope. Increased specificity of peripheral CTL from persistently infected mice for the index epitope compared with immunized mice suggested T cell selection during persistence. This was confirmed with CD8+ T cell clones derived from the CNS of either acutely (CTLac) or persistently (CTLper) infected mice. Whereas CTLac clones recognized a broad diversity of amino acid substitutions, CTLper clones exhibited exquisite specificity for the wild-type sequence. Highly focused specificity was CD8 independent but correlated with longer complementarity-determining regions 3 characteristic of CTLper clonotypes despite limited TCR alpha/beta-chain heterogeneity. Direct ex vivo analysis of CNS-derived mononuclear cells by IFN-gamma enzyme-linked immunospot assay confirmed the selection of T cells with narrow Ag specificity during persistence at the population level. These data suggest that broadly reactive CTL during primary infection are capable of controlling potentially emerging mutations. By contrast, the predominance of CD8+ T cells with dramatically focused specificity during persistence at the site of infection and in the periphery supports selective pressure driven by persisting Ag.


Thermal degradation behavior and flame retardant properties of PET/DiDOPO conjugated flame retardant composites.
PET/DIDOPO conjugated flame retardant composites were prepared by melt blending of styrene bridged DOPO (DIDOPO) into polyethylene terephthalate (PET). The flame retardancy, rheological behavior, and thermal degradation behavior of the composite were characterized by vertical combustion test (UL-94), limit oxygen index test (LOI), rotational rheometer, and thermogravimetry (TG). The results showed that the flame retardant composite with V-0 grade was obtained when the amount of DIDOPO is 12.5wt%, and the corresponding LOI value was 56.87% higher than that of PET. The thermogravimetry-fourier infrared spectroscopy (TG-FTIR) test results showed that DIDOPO could promote the degradation of PET/DIDOPO materials, and release phosphorus-containing free radicals to quench the flame, therefore slowing down the combustion process, and mainly playing the key flame retardant role in gas-phase.


Using Geographic Information Science to Explore Associations between Air Pollution, Environmental Amenities, and Preterm Births.
The study uses geographic information science (GIS) and statistics to find out if there are statistical differences between full term and preterm births to non-Hispanic white, non-Hispanic Black, and Hispanic mothers in their exposure to air pollution and access to environmental amenities (green space and vendors of healthy food) in the second largest city in New England, Worcester, Massachusetts. Proximity to a Toxic Release Inventory site has a statistically significant effect on preterm birth regardless of race. The air-pollution hazard score from the Risk Screening Environmental Indicators Model is also a statistically significant factor when preterm births are categorized into three groups based on the degree of prematurity. Proximity to green space and to a healthy food vendor did not have an effect on preterm births. The study also used cluster analysis and found statistically significant spatial clusters of high preterm birth volume for non-Hispanic white, non-Hispanic Black, and Hispanic mothers.


Experimental study of vascularized bone: quantitative analysis of bone scintigraphy and histology.
The purpose of this study was the sequential evaluation of vascularized bone by quantitative analysis of bone scintigraphy with Tc-99m methylene diphosphonate (MDP). The correlation between the uptake of Tc-99m MDP and the morphologic behavior of vascularized bone was investigated, simultaneously with bone labeling, contact microradiogram (CMR), and histology of an undecalcified sample. In this experiment, 41 adult female rabbits were used. An island tibia pedicled with the popliteal vessels was used as the model of vascularized bone. The maximum uptake of Tc-99m MDP was observed at two to four postoperative weeks. When bone marrow was partially exposed, the uptake was significantly large. On the basis of this experimental study, the degree of Tc-99m MDP uptake seemed to depend primarily on the osteoblastic activity of vascularized bone. The newly-formed bone was observed mainly at periosteal sites.


Bimodal degradation of MLL by SCFSkp2 and APCCdc20 assures cell cycle execution: a critical regulatory circuit lost in leukemogenic MLL fusions.
Human chromosome 11q23 translocations disrupting MLL result in poor prognostic leukemias. It fuses the common MLL N-terminal approximately 1400 amino acids in-frame with >60 different partners without shared characteristics. In addition to the well-characterized activity of MLL in maintaining Hox gene expression, our recent studies established an MLL-E2F axis in orchestrating core cell cycle gene expression including Cyclins. Here, we demonstrate a biphasic expression of MLL conferred by defined windows of degradation mediated by specialized cell cycle E3 ligases. Specifically, SCF(Skp2) and APC(Cdc20) mark MLL for degradation at S phase and late M phase, respectively. Abolished peak expression of MLL incurs corresponding defects in G1/S transition and M-phase progression. Conversely, overexpression of MLL blocks S-phase progression. Remarkably, MLL degradation initiates at its N-terminal approximately 1400 amino acids, and tested prevalent MLL fusions are resistant to degradation. Thus, impaired degradation of MLL fusions likely constitutes the universal mechanism underlying all MLL leukemias. Our data conclude an essential post-translational regulation of MLL by the cell cycle ubiquitin/proteasome system (UPS) assures the temporal necessity of MLL in coordinating cell cycle progression.


Regulation of experimental allergic encephalomyelitis. II. Appearance of suppressor cells during the remission phase of the disease.
Lewis rats are susceptible to experimental autoimmune encephalomyelitis (EAE). Most rats recover from paralysis and are subsequently resistant to the disease. In an adoptive transfer system, we found that lymph node cells (LNC) from rats that had recovered from EAE protect syngeneic recipients from the disease when the latter are challenged with encephalitogenic myelin basic protein and adjuvant after receiving donor cells. Suppression is antigen-specific and requires viable LNC. In contrast to the suppressor cells we previously studied in tolerized rats, which were nonadherent T lymphocytes, the suppressor cells found in rats that have recovered from EAE adhere to glass wool. However, they are not retained on Sephadex G-10 columns to which macrophages adhere. Suppressor activity is enriched in the nylon wool-adherent LNC population (which consists of approximately 80% Ig+ cells). Our findings suggest that activation of adherent suppressor cells may be implicated in recovery from EAE. These may be adherent T cells, or B cells that produce anti-BP blocking antibodies.


A novel amperometric biosensor based on banana peel (Musa cavendish) tissue homogenate for determination of phenolic compounds.
In this study the biosensor was constructed by immobilizing tissue homogenate of banana peel onto a glassy carbon electrode surface. Effects of immobilization materials amounts, effects of pH, buffer concentration and temperature on biosensor response were studied. In addition, the detection ranges of 13 phenolic compounds were obtained with the help of the calibration graphs. Storage stability, repeatability of the biosensor, inhibitory effect and sample applications were also investigated. A typical calibration curve for the sensor revealed a linear range of 10-80 microM catechol. In reproducibility studies, variation coefficient and standard deviation were calculated as 2.69%, 1.44 x 10(-3) microM, respectively.


Hepatitis C virus reinfection following treatment among people who use drugs.
Most new cases of hepatitis C virus (HCV) infections in the developed world are associated with injection drug use. However, treatment for people who inject drugs (PWID) is controversial, as successful treatment risks being followed by new infection. Reinfection after sustained virologic response has been reported, but is the risk so great that treatment should be withheld from this large HCV population? Preliminary evidence suggests that the reinfection incidence is low, but studies to date have been limited by small sample size and few cases of reinfection. In this review, we assess data from studies among PWID of HCV reinfection following treatment to give a reasonable estimate on how frequently reinfection appears and try to characterize those most at risk, The observation that spontaneous clearance of HCV reinfection following treatment occurs is suggestive of a partial protective immunity against persistent infection.


Human larynx carcinoma cells resistant to cis-diamminedichloroplatinum(II): cross-resistance patterns.
In our previous study we developed two lines of human larynx carcinoma HEp2 cells resistant to cis-diamminedichloroplatinum(II) (CDDP) due to acute (CA3 cells), or continuous (CK2 cells) treatments with increased CDDP concentrations. CA3 line was 2.3-fold resistant, and CK2 line 3.7-fold resistant to CDDP as compared to the parental cells. In this study the sensitivity of CDDP resistant and parental cells to several antitumor drugs was examined using clonogenic survival assay. CK2 cells were 1.7-fold more resistant to vincristine than parental cells, while CA3 cells exhibited resistance to vincristine only at higher concentrations of this drug. Verapamil, an inhibitor of P-glycoprotein, was not able to reverse the resistance of CK2 cells to vincristine, indicating that this cross-resistance did not involve P-glycoprotein. As compared to the parental cells, CK2 cells were 2.1-fold resistant, and CA3 cells 1.7-fold resistant to mitomycin C. CK2 cells were 2-fold more resistant to 5-fluorouracil than the parental cells, while CA3 cells did not exhibit any change in the sensitivity to this drug. CA3 cells were 0.4-fold sensitive to epoxide and 0.53-fold sensitive to doxorubicin, while CK2 cells had the same sensitivity to these drugs as the parental cells. Our results showed that treatment schedule determines the response of CDDP resistant human larynx carcinoma cells to additional drugs, suggesting the complexity of the judicious choice of the drugs in the combined modality treatments of cancer.


End-of-Life care in a community garden: Findings from a Participatory Action Research project in regional Australia.
This article presents findings from research that explored how a community garden might function as a place of end-of-life and bereavement support. Adopting Participatory Action Research (PAR) methods, and informed by Third Place theory and notions of therapeutic landscape, creative consultations were held in the Garden and people's homes. The findings provide insights into the nature of informal care as it is played out in the liminal garden space, between home and institution. The results illuminate the therapeutic landscape of community gardens, and contribute new understandings to the fields of PAR, health geography and end-of-life care.


Morphological description of the alimentary canal and adnexal glands in Amazilia tzacatl, Amazilia saucerottei, Amazilia amabilis and Anthrachotorax nigricollis species.
The hummingbird family (Trochilidae) includes the smallest and most metabolically active vertebrates. They have a high energy demand because of their extraordinarily high metabolic rates during hovering while looking for food. The morphology of the digestive apparatus is related to the feeding habits of the species. The anatomy and histology of the digestive apparatus in these birds have not been thoroughly described except for their tongue. Therefore, this study aimed to describe the gross anatomy and histology of the alimentary canal and adnexal glands in four species from the hummingbird family: Amazilia tzacatl (n = 2), Amazilia saucerottei (n = 1), Amazilia amabilis (n = 1) and Anthracothorax nigricollis (n = 1). The alimentary canal was found to be very short. The epithelium of the oesophagus and crop showed variable degrees of keratinization and parakeratotic areas as normal conditions. A dorsal crop was observed as a differential characteristic of these birds. Like other birds, the ventricular mucosa in hummingbirds was covered and protected by the cuticle and showed a tunica muscularis constituted by three muscle layers. There was no isthmus between the proventriculus and ventriculus. The intestine presents a well-differentiated duodenum and jejunum. However, no ileum nor caeca were identified. The intestinal villi length, base width, crypt depth and area showed differences among the specimens studied among the small and large intestines. In addition, variations in thickness were observed in the smooth muscle tunica along the intestine. In all the studied species, the liver was composed of two lobes (right and left), and no gall bladder was observed during gross inspection or in histological sections. Finally, the pancreas was observed as a diffused organ forming islets related to all the small intestines. Some anatomical differences were observed among the studied species, mainly concerning Anthracothorax nigricollis. Hummingbirds showed very interesting and distinctive morphological characteristics. Hummingbirds possess unique and intriguing morphological characteristics. Future comparative studies related to the anatomy, histology and function of the digestive apparatus of hummingbirds are required. Expanding our understanding of the digestive morphophysiology in these bird species is crucial. However, it is necessary to conduct more comprehensive studies encompassing a wider range of hummingbird species and including a larger number of individuals to obtain more conclusive findings.


[Community structure of rotifer in Mingzhu Lake of Chongming Island, Shanghai].
A comprehensive survey on the quantitative distribution, community structure, species composition, dominant species, and species diversity of rotifer was conducted in the Mingzhu Lake of Chongming Island, Shanghai in January-December, 2008. There were 27 species of rotifer in the Lake, belonging to 8 families and 11 genera. The dominant species were Polyarthra trigla, Trichocerca pusilla, Brachionus calyciflorus, Brachionus forficula, and Philodina sp. The rotifer had an average annual density of (1505.42 +/- 1304.63) ind x L(-1), and an average annual biomass of (2.012 +/- 2.146) mg x L(-1). The Shannon-Wiener diversity index, evenness index, and richness index of rotifer community in the Lake were relatively low, while the dominance index was rather high, indicating that the community structure of the rotifer was unstable. The E/O value wes 1.61 +/- 1.46 on average, and the Q(B/T) values wes 1.23 +/- 0.84 on average. Water temperature was the main factor affecting the rotifer distribution. Biological assessment of water quality suggested that the Mingzhu Lake was on eutrophication.


Acute endovascular management of a subclavian artery injury.
Traumatic injuries to the subclavian vessels are relatively uncommon and surgical repair may be technically challenging. With the increasing availability of endovascular techniques for nontraumatic arterial disease, an increase in the use of stenting for traumatic vascular injuries can be expected. This report describes the fifth successful endovascular repair with stenting of a pseudoaneurysm of the subclavian artery as a result of blunt trauma, and the first American report of such repair used in the acute or immediate management of blunt subclavian artery injury.


Ambulatory discharge after transradial coronary intervention: Preliminary US single-center experience (Same-day TransRadial Intervention and Discharge Evaluation, the STRIDE Study).
Although the safety and cost-effectiveness of same-day discharge after uncomplicated transradial percutaneous coronary intervention (TR-PCI) is well established in Europe and Asia, such data are not available for US patients. All patients who underwent TR-PCI at our high-volume US medical center between 2004 and 2007 were included in this study. The primary end point was in-hospital adverse clinical outcomes between 6 and 24 hours postprocedure. A total of 450 patients were included in this study (aged 59 +/- 11 years). Of these, 13% were female, 27% were diabetic, 6% had peripheral vascular disease, and 5% had chronic kidney disease. Procedural indications included stable angina (49%), unstable angina (31%), non-ST elevation myocardial infarction (NSTEMI) (17%), and ST elevation myocardial infarction (STEMI) (3%). All patients received an intra-arterial cocktail of heparin, verapamil, and nitroglycerin, and 13% of patients received glycoprotein IIb/IIIa inhibitors. Seven percent of patients had 3-vessel disease, 3% had bypass grafts stenoses, and 20% had class B(2)/C lesions. Procedural success rate was 96%. A total of 24 (5.3%) postprocedural complications were observed; however, none occurred between hours 6 to 24, the time differential between same-day and next-day discharge. Thirteen patients (2.9%) experienced significant complications within the first 6 hours (MI, urgent repeat revascularization, and ventricular tachycardia). Eleven (2.4%) spontaneously resolved minor access complications developed. There were 12 same-day discharges according to the operators' discretion; none required readmission. Although a low incidence of complications did occur, none would have been impacted by same-day discharge. Those observed before 6 hours would have prevented early discharge, and those occurring after 24 hours would have been unaffected by routine next-day discharge. This observational study demonstrated the safety and feasibility for a prospective evaluation of ambulatory TR-PCI in an American practice setting.


Clinical pharmacology of atypical antipsychotics: an update.
This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects.


Sexual health of male cardiac patients - present status and expectations of patients with coronary heart disease.
Due to the pathogenetic association between erectile disorders and cardiovascular diseases, cardiologists consult many patients with erectile dysfunction (ED). The aim of the study was to evaluate sexual function in patients with coronary heart disease (CHD) and the use of sexual knowledge in cardiology practice, both current use and that expected by patients. One thousand one hundred and thirty-six patients (average age: 60.73 ±9.20) underwent a dedicated survey which encompassed demographic data and the presence of modifiable ED risk factors. The presence of ED was assessed using the International Index of Erectile Function (IIEF-5) Questionnaire. Sexual problems were discussed by cardiologists with 45 (3.96%) patients. The frequency of initiating the topic was significantly associated with the respondents' education level (p = 0.0031); however, it was not associated with the patients' age, duration of CHD, presence of ED, or modifiable risk factors. Four hundred and sixteen (36.62%) respondents indicated that they expect their cardiologist to take an interest in their ED. Nine hundred and twenty-six (81.51%) patients claimed good sexual function to be important or very important to them. Attitude to sexual function was significantly associated with age (p < 0.0001), duration of CHD (p = 0.0018), education (p = 0.0011), presence of ED (p = 0.0041), diabetes (p = 0.0283) and hyperlipidaemia (p = 0.0014). The low frequency with which cardiologists initiate the topic of ED is in contrast to the expectations of patients with CHD. The majority of these patients regard good sexual maintenance as an important part of their life.


Hemolytic disease of the fetus and newborn: rapid review of postnatal care and outcomes.
Advances in postnatal care for hemolytic disease of the fetus and newborn (HDFN) have occurred over the past decades, but little is known regarding the frequency of postnatal treatment and the clinical outcomes of affected neonates. Most studies reporting on HDFN originate from high-income countries or relatively large centers, but important differences between centers and countries may exist due to differences in prevalence and available treatment options. We therefore aimed to evaluate the postnatal treatment landscape and clinical outcomes in neonates with Rhesus factor D (Rh(D))- and/or K-mediated HDFN and to provide recommendations for future research. We conducted a rapid literature review of case reports and series, observational retrospective and prospective cohort studies, and trials describing pregnancies or children affected by Rh(D)- or K-mediated HDFN published between 2005 and 2021. Information relevant to the treatment of HDFN and clinical outcomes was extracted. Medline, ClinicalTrials.gov and EMBASE were searched for relevant studies by two independent reviewers through title/abstract and full-text screening. Two independent reviewers extracted data and assessed methodological quality of included studies. Forty-three studies reporting postnatal data were included. The median frequency of exchange transfusions was 6.0% [interquartile range (IQR): 0.0-20.0] in K-mediated HDFN and 26.5% [IQR: 18.0-42.9] in Rh(D)-mediated HDFN. The median use of simple red blood cell transfusions in K-mediated HDFN was 50.0% [IQR: 25.0-56.0] and 60.0% [IQR: 20.0-72.0] in Rh(D)-mediated HDFN. Large differences in transfusion rates were found between centers. Neonatal mortality amongst cases treated with intrauterine transfusion(s) was 1.2% [IQR: 0-4.4]. Guidelines and thresholds for exchange transfusions and simple RBC transfusions were reported in 50% of studies. Most included studies were from middle- to high-income countries. No studies with a higher level of evidence from centers in low-income countries were available. We noted a shortage and inconsistency in the reporting of relevant data and provide recommendations for future reports. Although large variations between studies was found and information was often missing, analysis showed that the postnatal burden of HDFN, including need for neonatal interventions, remains high. PROSPERO 2021 CRD42021234940. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021234940 .


Enantioselective fluorescent recognition of amino alcohols by a chiral tetrahydroxyl 1,1'-binaphthyl compound.
The tetrahydroxyl derivative of BINOL, (S)- or (R)-1, and its analogues are synthesized. (S)- or (R)-1 can be used to conduct the enantioselective recognition of chiral amino alcohols. In comparison with BINOL, the two additional hydroxyl groups of (S)- or (R)-1 have increased the binding of this compound with the amino alcohols and significantly improved the fluorescence quenching efficiency. The fluorescence responses of (S)- or (R)-1 toward amino alcohols are compared with those of its analogues (R)-4 and (R)-6. It shows that the interaction of the central naphthyl hydroxyl groups of (S)- or (R)-1 with the substrates is responsible for the observed fluorescence quenching, and the two additional alkyl hydroxyl groups increase the quenching efficiency.


Application of randomized response techniques for investigating cannabis use by Spanish university students.
Cannabis is the most widely used illicit drug in developed countries, and has a significant impact on mental and physical health in the general population. Although the evaluation of levels of substance use is difficult, a method such as the randomized response technique (RRT), which includes both a personal component and an assurance of confidentiality, provides a combination which can achieve a considerable degree of accuracy. Various RRT surveys have been conducted to measure the prevalence of drug use, but to date no studies have been made of the effectiveness of this approach in surveys with respect to quantitative variables related to drug use. This paper describes a probabilistic, stratified sample of 1146 university students asking sensitive quantitative questions about cannabis use in Spanish universities, conducted using the RRT. On comparing the results of the direct question (DQ) survey and those of the randomized response (RR) survey, we find that the number of cannabis cigarettes consumed during the past year (DQ = 3, RR = 17 approximately), and the number of days when consumption took place (DQ = 1, RR = 7) are much higher with RRT. The advantages of RRT, reported previously and corroborated in our study, make it a useful method for investigating cannabis use. Copyright © 2016 John Wiley & Sons, Ltd.


Glycaemic variability and pancreatic β-cell dysfunction.
The importance of glycaemic variability (GV) as a factor in the pathophysiology of cellular dysfunction and late diabetes complications is currently a matter of debate. However, there is mounting evidence from in vivo and in vitro studies that GV has adverse effects on the cascade of physiological processes that result in chronic β-cell dysfunctions. Glucose fluctuations more than sustained chronic hyperglycaemia can induce excessive formation of reactive oxygen (ROS) and reactive nitrogen species (RNS), ultimately leading to apoptosis related to oxidative stress. The insulin-secreting β-cells are particularly susceptible to damage imposed by oxidative stress. Evidence from experiments, using isolated pancreatic islets or β-cell lines, has linked intermittent high glucose, which mimicks GV under diabetic conditions, to significant impairment of β-cell function. Several clinical studies reported a close association between GV and β-cell dysfunction, although the deleterious effects are difficult to demonstrate. Notwithstanding, early therapeutic interventions in patients with type 1 as well as type 2 diabetes, using different strategies of optimising glycaemic control, have shown that favourable outcomes on recovery and maintenance of β-cell function correlated with reduction of GV. The purpose of the present review is to discuss the detrimental effects of GV and associations with β-cell function as well as upcoming therapeutic strategies directed towards minimising glucose excursions, improving β-cell recovery and preventing progressive β-cell loss. Measuring GV has importance for management of diabetes, because it is the only one component of the dysglycaemia that reflects the degree of dysregulation of glucose homeostasis.


Immunoglobulin levels in psychiatric patients.
In a study of 19 schizophrenic patients, 7 nonschizophrenic patients, and 31 controls, the authors found significantly higher mean serum levels of 1) immunoglobulin A in schizophrenic women then in control women and in schizophrenic blacks than in either schizophrenic whites or black controls. 2) immunoglobulin D in schizophrenic blacks than in schizophrenic whites, 3) immunoglobulin M in controls than in nonschizophrenic patients, and 4) immunoglobulin G (IgG) in schizophrenics whose urine was positive for phenothiazines than in schizophrenics whose urine was negative for phenothiazines. High serum levels of IgG were associated with no or mild hallucinations and low levels with moderate or severe hallucinations. Black female patients had significantly more severe hallucinaions than white female patients. The authors discuss the possible implications of these findings.


Accuracy of a routine real-time PCR assay for the diagnosis of Pneumocystis jirovecii pneumonia.
Pneumocystis jirovecii is a common cause of life-threatening pneumonia among immunocompromised patients. Using 400 fresh bronchoalveolar lavage samples, we compared prospectively routine direct immunofluorescence assay (DFA) and a real-time PCR assay, performed on a LightCycler system, for the detection of P. jirovecii. Among the 66 PCR positive samples, 31 were positive by DFA. No patient was found as having the pattern "PCR--ve/DFA+ve". The semi-quantification of the P. jirovecii DNA was represented by the cycle threshold (Ct). Using DFA as the gold standard, the sensitivity of the PCR was 100% for Ct > or = 28 and the specificity was 100% for Ct < 22. Between these two points, the results could be discrepant. The patients of the "22 < or = Ct < 28" group presented more frequently with a radiological interstitial syndrome than the "Ct > or = 28" group, and presented less frequently with HIV-infection and elevated lactate dehydrogenase (LDH) assay than in the "Ct < 22" group. A negative PCR allowed us to exclude the P. jirovecii pneumonia. The real-time PCR assay seems to be an accurate diagnosis method and could replace the DFA. The semi-quantitative results should be helpful to distinguish colonized, subclinically infected and P. jirovecii pneumonia patients.


Accumulation and suppressive function of regulatory T cells in malignant ascites: Reducing their suppressive function using arsenic trioxide in vitro.
Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As2O3) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro. In this study, lymphocytes were separated from malignant ascites and T-cell subsets were detected via flow cytometry. Forkhead box P3 (FoxP3) expression was assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In addition, cytokines, including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ), were measured by enzyme-linked immunosorbent assay (ELISA). Abundant Tregs were observed in ascites lymphocytes, which and exhibited a significantly increased frequency compared with that in the peripheral blood of patients. Furthermore, As2O3 treatment significantly reduced Treg numbers and Foxp3 mRNA levels in vitro (P<0.05). IFN-γ levels in the supernatant of ascites-derived TILs were increased by As2O3, whereas IL-10 and TGF-β levels were significantly reduced (P<0.05). As2O3 may induce selective depletion and inhibit immunosuppressive function of Tregs, and may enhance the cytotoxic activity of ascites-derived TILs.


Activity and conformational changes of horseradish peroxidase in trifluoroethanol.
The effect of trifluoroethanol (TFE) on horseradish peroxidase (HRP) was determined using activity assay and spectral analysis including optical absorption, circular dichroism (CD), and intrinsic fluorescence. The enzyme activity increased nearly twofold after incubation with 5-25% (v/v) concentrations of TFE. At these TFE concentrations, the tertiary structure of the protein changed little, while small changes occurred at the active site. Further increases in the TFE concentration (25-40%) decreased the enzyme activity until at 40% TFE the enzyme was completely inactivated. The alpha-helix content of the protein increased at high TFE concentrations, while near-UV CD, Soret CD, and intrinsic fluorescence indicated that the tertiary structure was destroyed. Polyacrylamide gel electrophoresis results indicated that the surface charge of the enzyme was changed at TFE concentrations greater than 20%, and increasing concentrations of TFE reduced the enzyme molecular compactness. A scheme for the unfolding of HRP in TFE was suggested based on these results. The kinetics of absorption change at 403 nm in 40% TFE followed a two-phase course. Finally, HRP incubated with TFE was more sensitive to urea denaturation, which suggested that the main effect of TFE on HRP was the disruption of hydrophobic interactions.


Designing, characterization, and immune stimulation of a novel multi-epitopic peptide-based potential vaccine candidate against monkeypox virus through screening its whole genome encoded proteins: An immunoinformatics approach.
The current monkeypox virus (MPXV) spread in the non-epidemic regions raises global concern. Presently, the smallpox vaccine is used against monkeypox with several difficulties. Conversely, no next-generation vaccine is available against MPXV. Here, we proposed a novel multi-epitopic peptide-based in-silico potential vaccine candidate against the monkeypox virus. The multi-epitopic potential vaccine construct was developed from antigen screening through whole genome-encoded 176 proteins of MPXV. Afterward, ten common B and T cell epitopes (9-mer) having the highest antigenicity and high population coverage were chosen, and a vaccine construct was developed using peptide linkers. The vaccine was characterized through bioinformatics to understand antigenicity, non-allergenicity, physicochemical properties, and binding affinity to immune receptors (TLR4/MD2-complex). Finally, the immune system simulation of the vaccine was performed through immunoinformatics and machine learning approaches. The highest antigenic epitopes were used to design the vaccine. The docked complex of the vaccine and TLR4/MD2 had shown significant free binding energy (-98.37 kcal/mol) with a definite binding affinity. Likewise, the eigenvalue (2.428517e-05) from NMA analysis of this docked complex reflects greater flexibility, adequate molecular motion, and reduced protein deformability, and it can provoke a robust immune response. The designed vaccine has shown the required effectiveness against MPXV without any side effects, a significant milestone against the neglected disease.


Evaluation of PIK3CA mutations as a biomarker in Chinese breast carcinomas from Western China.
PIK3CA gene encodes the p110 α catalytic subunit of the oncoprotein phosphatidylinositol 3-kinase (PI3 K) which regulates many biological processes such as cell proliferation, differentiation, migration and survival through the activation of various signaling pathways. In this study, we have investigated the possible somatic mutations in PIK3CA gene in invasive ductal breast carcinomas of Chinese women from Western China. Genomic DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) tissue samples. The hotspot mutations in PIK3CA gene of exon 9 and exon 20 were studied by pyrosequencing. The sequencing identified two hotspot mutations in exon 20 of one cancer samples at p. H1047L (c. 3140A > T) and eight cancer sample at p. H1047R (c. 3140A > G). No mutation in exon 9 of PIK3CA gene was found in these breast cancer tissue samples. PIK3CA mutations showed surprising clinicopathological features in breast cancer patients, as incidence of lymph node invasiveness is increased in the patients with PIK3CA mutation. In addition, all the patients showed tumor size bigger than 3 cm in diameter. It is important that for early detection and early treatment for BC in developing countries or areas like Western China, and for people to provide popularization education using scientific knowledge in cancer fields. This study identified PIK3CA mutations in breast carcinoma patients of Western China that will enable a more rapid molecular diagnosis, and provide a stronger rationale evidence for development of precision therapeutic approaches as well as promising therapeutic targets for breast cancer treatment or patient management.


[An optimal method for cryopreservation of microamount round spermatids of the mouse].
To search for an optimal protocol and freezing conditions for the cryopreservation of microamount round spermatids of the mouse. We compared the survival rates of frozen-thawed microamount round spermatids of the mouse achieved by vitrification or standard slow freezing with different concentrations of glycerol (5, 7, or 9%) and different lengths of equilibrium time (0, 15, 30, 45, or 60 min). Under the conditions of 7% glycerol and 30 min equilibrium, both vitrification and standard slow freezing achieved high survival rates of spermatids, and the former obtained an even higher rate than the latter ([72.9 ± 15.4]% vs [58.2 ± 17.7]%, P < 0.05). A high rate of frozen-thawed microamount round spermatids of the mouse can be achieved by vitrification under the conditions of 7% glycerol and 30 min equilibrium.


The design and application of effective written instructional material: a review of published work.
This review will consider the evidence base for the format of educational material drawing on academic papers and the practice of the design industry. The core issues identified from the review are drawn together in guidelines for educational posters, text and web based material. The review deals with the design of written material both for use in leaflets and books as well as the impact of factors such as font type and size as well as colour on poster design. It sets these aspects of educational material within a research framework, which looks at impact on learning and subsequent change in practice. These issues are examined through a practical example of a poster designed for a regional gastroenterology meeting.


Rice bran triterpenoids improve postprandial hyperglycemia in healthy male adults: a randomized, double-blind, placebo-controlled study.
Compared to white rice, brown rice induces a lower glycemic response in healthy and diabetic humans. This effect is partly attributed to the higher amounts of water- or oil-soluble bran components and dietary fiber in brown rice. We hypothesized that dietary supplementation with oil-soluble rice bran triterpenoids (RBTs; triterpene alcohol and sterol prepared from rice bran) might reduce the incidence of postprandial hyperglycemia in healthy humans. We examined the acute effects of a single RBT-supplemented meal on the postprandial blood glucose responses of healthy male adults in a double-blind, randomized, placebo-controlled, crossover trial. Nineteen subjects consumed a test meal containing either placebo- or RBT-supplemented olive oil. Blood biomarkers were evaluated in a fasting state and up to 240 min postprandially. Compared to the placebo-supplemented meal, the RBT-supplemented meal significantly suppressed the increase in postprandial blood glucose level. A subclass analysis revealed that RBT-supplemented oil significantly reduced blood glucose increases in subjects with higher postprandial blood glucose elevations. Postprandial increases in blood insulin, glucose-dependent insulinotropic peptide (GIP), and glucagon-like peptide-1 (GLP-1) levels did not differ between the groups. These results suggest that RBT consumption improves postprandial hyperglycemia in healthy humans, especially those with higher postprandial glucose increases.


Head and neck cancer: carcinoma of unknown primary.
Carcinoma of unknown primary is uncommon, estimated to represent only 3% to 5% of all head and neck cancers. Squamous cell carcinoma accounts for 70% to 90% of these lesions, most commonly from sites in the upper aerodigestive tract, including tonsils, base of tongue, nasopharynx, and piriform sinus. Magnetic resonance, computed tomography (CT), and positron emission tomography all play a role in the assessment of patients with an unknown primary. The location of a metastatic lymph node may give an indication of the primary tumor site, and knowledge of lymph node drainage patterns is important for anyone evaluating these patients. Magnetic resonance and CT are both used for evaluation for extracapsular nodal disease, perineural tumor spread, osseous skull base or perivertebral space involvement, and vascular invasion, findings that seriously impact treatment and prognosis. Positron emission tomography/CT also plays a significant role in detecting primary tumor sites and identifying distant metastatic disease.


First established pregnancy and birth after induction of ovulation with recombinant human follicle stimulating hormone during in vitro fertilization-embryo transfer and intracytoplasmic sperm injection.
This case report describes the first established pregnancy and birth in the Philippines after induction of ovulation with recombinant follicle stimulating hormone (rec FSH) during In Vitro Fertilization-Embryo Transfer (IVF-ET) and Intracytoplasmic Sperm Injection (ICSI) in a Filipino woman with pelvic endometriosis who underwent right oophorectomy for endometrioma 1 year prior to IVF-ET and ICSI. Husband's semenalysis revealed adequate volume with 10% normal forms. Gonadotrophin releasing hormone agonist (Lupron) 375 mg subcutaneous was given for 2 cycles. 100 IU B.I.D. (a total of 2200 IU) of rec FSH was administered intramuscularly daily with single preovulatory follicle seen upon transvaginal ultrasonographic examination of 10,000 IU of human chorionic gonadotrophin, after which a viable singleton pregnancy was revealed at a gestational age of 8 weeks. The course of pregnancy until term was uneventful and ended with abdominal delivery at a gestational age of 37.3 weeks secondary to poor Fetopelvic Index with oligohydramnios. A healthy girl was born and pediatric examination did not demonstrate any abnormality.


CORRELATION OF INCREASED SERUM ADIPSIN WITH INCREASED CARDIOVASCULAR RISKS IN ADULT PATIENTS WITH GROWTH HORMONE DEFICIENCY.
Objective: Adult growth hormone deficiency (AGHD) patients have an increased cardiovascular morbidity and mortality. Adipsin is an adipokine that is significantly correlated with metabolic disease, especially in people with obesity. The objective of our study was to compare AGHD patients with healthy subjects to evaluate whether adipsin levels are closely related to glycolipid metabolism and cardiovascular risks in AGHD patients. Methods: Our study included 88 AGHD patients and 88 age-, weight-, and body mass index (BMI)-matched healthy subjects. Anthropometric parameters such as BMI, waist circumference, and blood pressure were measured. Biochemical indicators such as serum adipsin, lipids, and fasting insulin levels were determined. Results: Adipsin levels in AGHD patients were significantly increased compared to levels of the control group (11,567.29 ng/mL, interquartile [9,856.46 to 13,360.60 ng/mL]) versus (9,127.86 ng/mL, interquartile [8,061.82 to 10,647.06 ng/mL], P = .000). Increased serum adipsin levels are correlated with cardiovascular risk factors such as a higher waist-to-hip ratio, serum lipids levels, and insulin resistance. Adipsin levels were inversely related to insulin-like growth factor 1 (IGF-1) (r = -0.6363, P<.0001) and insulin-like growth factor binding protein 3 levels (r = -0.498, P<.0001). The odds ratio (OR) for AGHD in the highest quartile was found to be 4.491 times the ratio in the lowest quartile (OR = 4.491, P = .048). Additionally, adipsin was found to be the most independent factor to influence IGF-1 levels in AGHD subjects. Conclusion: The serum levels of adipsin were significantly correlated with glucolipid metabolism disorder with a growth hormone deficiency status. Furthermore, serum levels of adipsin might be a good marker for the occurrence and development of cardiovascular diseases in AGHD patients. Abbreviations: AGHD = adult growth hormone deficiency; ASCVD = atherosclerotic cardiovascular disease; BMI = body mass index; DBP = diastolic blood pressure; FINS = fasting insulin; FPG = fasting plasma glucose; GH = growth hormone; HOMA-IR = homeostatic model to assess insulin resistance index; hsCRP = high-sensitivity C-reactive protein; IGF-1 = insulin-like growth factor 1; IGFBP-3 = insulin-like growth factor binding protein 3; LAP = lipid accumulation products; LDL = low-density lipoprotein; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; WC = waist circumference; WHR = waist-to-hip ratio; OR = odds ratio.


Practice guidelines for teledermatology in Australia.
Despite the potential of teledermatology to increase access to dermatology services and improve patient care, it is not widely practised in Australia. In an effort to increase uptake of teledermatology by Australian dermatologists and support best practice, guidelines for teledermatology for the Australian context have been developed by The University of Queensland's Centre for Online Health in collaboration with The Australasian College of Dermatologists' E-Health Committee. The guidelines are presented in two sections: 1. Guidelines and 2. Notes to support their application in practice, when feasible and appropriate. Content was last updated March 2020 and includes modalities of teledermatology; patient selection and consent; imaging; quality and safety; privacy and security; communication; and documentation and retention of clinical images. The guidelines educate dermatologists about the benefits and limitations of telehealth while articulating how to enhance patient care and reduce risk when practicing teledermatology.


Avoiding emotional bonds: an examination of the dimensions of therapeutic alliance among cannabis users.
There is a growing need to provide treatment for cannabis users, yet engaging and maintaining this population in treatment is particularly difficult. Although past research has focused on the importance of therapeutic alliance on drug treatment outcomes, this is the first study to examine the dimensions of therapeutic alliance for cannabis users compared with users of alcohol or other drugs in a naturalistic setting. The acceptability of Internet-delivered interventions for drug and alcohol treatments is also investigated. Participants (n = 77) included clients who were receiving outpatient drug and alcohol treatment at a publicly funded health service, including a Specialist Cannabis Clinic. The results indicated that one particular domain of alliance, Bond, was consistently lower, from both client and clinician perspectives, for current cannabis users relative to those not currently using cannabis. Client perceptions of Bond decreased as the severity of cannabis use increased (r = -0.373, p = 0.02). Cannabis Clinic clients did not report a significantly lower Bond with their clinicians, suggesting that specialized cannabis services may be better placed to provide appropriate treatment for this population than embedding cannabis treatment within traditional drug and alcohol treatment teams. In addition, Internet/computer-based treatments may be one potential way to engage, transition, or retain cannabis users in treatment.


Reduction of Endothelial Nitric Oxide Increases the Adhesiveness of Constitutive Endothelial Membrane ICAM-1 through Src-Mediated Phosphorylation.
Nitric oxide (NO) is a known anti-adhesive molecule that prevents platelet aggregation and leukocyte adhesion to endothelial cells (ECs). The mechanism has been attributed to its role in the regulation of adhesion molecules on leukocytes and the adhesive properties of platelets. Our previous study conducted in rat venules found that reduction of EC basal NO synthesis caused EC ICAM-1-mediated firm adhesion of leukocytes within 10-30 min. This quick response occurred in the absence of alterations of adhesion molecules on leukocytes and also opposes the classical pattern of ICAM-1-mediated leukocyte adhesion that requires protein synthesis and occurs hours after stimulation. The objective of this study is to investigate the underlying mechanisms of reduced basal NO-induced EC-mediated rapid leukocyte adhesion observed in intact microvessels. The relative levels of ICAM-1 at different cell regions and their activation status were determined with cellular fractionation and western blot using cultured human umbilical vein ECs. ICAM-1 adhesiveness was determined by immunoprecipitation in non-denatured proteins to assess the changes in ICAM-1 binding to its inhibitory antibody, mAb1A29, and antibody against total ICAM-1 with and without NO reduction. The adhesion strength of EC ICAM-1 was assessed by atomic force microscopy (AFM) on live cells. Results showed that reduction of EC basal NO caused by the application of caveolin-1 scaffolding domain (AP-CAV) or NOS inhibitor, L-NMMA, for 30 min significantly increased phosphorylated ICAM-1 and its binding to mAb1A29 in the absence of altered ICAM-1 expression and its distribution at subcellular regions. The Src inhibitor, PP1, inhibited NO reduction-induced increases in ICAM-1 phosphorylation and adhesive binding. AFM detected significant increases in the binding force between AP-CAV-treated ECs and mAb1A29-coated probes. These results demonstrated that reduced EC basal NO lead to a rapid increase in ICAM-1 adhesive binding via Src-mediated phosphorylation without de novo protein synthesis and translocation. This study suggests that a NO-dependent conformational change of constitutive EC membrane ICAM-1 might be the mechanism of rapid ICAM-1 dependent leukocyte adhesion observed in vivo. This new mechanistic insight provides a better understanding of EC/leukocyte interaction-mediated vascular inflammation under many disease conditions that encounter reduced basal NO in the circulation system.


[The acquired flatfoot: mid-term results of the medial displacement calcaneal-osteotomy with flexor digitorum longus transfer].
The present retrospective study investigates the mid-term results after medial displacement calcaneal osteotomy combined with flexor digitorum longus transfer for the treatment of acquired flatfoot deformity due to posterior tibial tendon insufficiency at stage II (Johnson and Strom Classification). 30 feet in 29 patients (6 male, 23 female) with an average age of 58 years (from 43 to 68 years) had surgery between 1995 and 2001. All feet were examined at an average follow-up of 58.5 months (range 35-97 months) and were evaluated with the American-Orthopaedic-Foot and Ankle Society (AOFAS) Hindfoot-Score. The average AOFAS-Score was 88.8+/-10.7 points (range 48 to 100) at final follow-up. The AOFAS-pain-subscale score was 34+/-6.2 points. At the latest follow-up were 14 feet (47%) painfree, 14 feet (47%) noted mild pain and 2 feet (6%) had daily pain. One foot (3%) had pain due to subluxation of the musculus flexor digitorum longus tendon, in another one pain was caused by a contract Chopart joint (3%). Further complications were painful prominent hardware (17%) and neuralgia of the sural nerve (7%). The authors conclude that the combination of the medial calcaneal displacement osteotomy with flexor digitorum longus transfer may provide optimal results in patients with adult acquired flatfoot deformity and posterior tibialis tendon dysfunction.


[Ethics, science and utilitarianism].
We begin this article with the distinction between Deontology, Moral and Ethics. We also review the concept and the relevance of Bioethics, as the "science of survival", and as part of Ethics, a section of Philosophy. We tried to answer two further questions considering the role of Science in orienting Ethics, or the possible place of utilitarianism in controlling Ethics. The author discusses some new aspects of the doctor/patient relationship, and their evolution in the last 100 years, as well as the relations between patients and Health care institutions. Some ethical problems were also raised related to the beginning and the end of life. Finally the author reflects on the difficulties of defining ethical concepts in the near future.


[The recycling of EGF-receptor complexes in A431 cells].
As was demonstrated elsewhere (L. V. Teslenko et al., 1987), the epidermal growth factor (EGF) can recycle after internalization by A431 cells in membrane-bound state. In the present study, direct evidence on recycling of EGF-receptor complexes is presented using a covalently crosslinking reagent. The recycling was shown to occur via peripheral endosomes as well as through para-Golgi endosomes. It was found that among EGF degradation inhibitors tested only primaquine (300 microM) was able to decrease significantly the rate of recycling. The lowering of the temperature to 17 degrees C led to blocking the EGF degradation as well as to inhibiting the recycling. The data obtained suggested that the recycling of EGF-receptor complexes is relatively independent of their degradation.


Physiological changes in hemostasis associated with acute exercise.
Acute exercise enhances fibrinolytic (FA), factor VIII coagulant and factor VIII ristocetin cofactor activities, and increases the concentration of factor VIII-related antigen. Little is known concerning the mechanisms of these changes. To investigate possible relationships between exercise-induced changes in blood lactate, 2,3-diphosphoglycerate (DPG), and the hemostatic variables, a branching multistage treadmill protocol was used to exercise male volunteers to a maximum effort. Blood samples were drawn before, immediately post-, and 8 min postexercise. All hemostatic variables were significantly (P less than 0.05) increased postexercise. Highest values for factor VIII coagulant, factor VIII-related antigens and factor VIII ristocetin cofactor were observed at 8 min postexercise. Significant (P less than 0.001) correlations were found postexercise for lactate with factor VIII coagulant (r = 0.64), while no association between pre-, post-, or 8 min postexercise. Postexercise lactate demonstrated a significant correlation (r = +0.81), which was strengthened by including the preexercise high-density lipoprotein (HDL) concentrations (r = +0.87). Consequently, the expected postexercise FA may be calculated from the observed values for postexercise lactate and preexercise HDL. The correlations of lactate with postexercise FA and with postexercise factor VIII coagulant may reflect a common stimulus for these exercise-induced changes.


Adenoviruses 16 and CV23 efficiently transduce human low-passage brain tumor and cancer stem cells.
Most clinical protocols involving adenovirus (Ad) vectors for gene therapy use a vector based on serotype 5 (Ad5). We believe that this serotype is not suitable for all gene therapy applications and that alternative vectors based on other serotypes should be developed. We have compared the ability of Ad5, Ad11p, Ad16p, and a chimpanzee Ad (CV23) to infect human low-passage brain tumor cells as well as primary glioma cells sorted into a CD133(+) and CD133(-) population. Cancer stem cells have been shown to reside in the CD133(+) population of cells in human glioma tumors and they are of considerable interest in glioma therapy. Ad16p and CV23 infected the low-passage brain tumor cell lines and also the CD133(+) and CD133(-) primary tumor cells most efficiently. Interestingly, as the passage number of the cells increased, the infection capacity of Ad5 increased significantly, whereas this was not seen for CV23. To ensure the therapeutic effect of Ad vectors on brain tumors, the vector must be capable of addressing both the CD133(+) cancer stem cells and the CD133(-) cells of the tumor. In particular, Ad16 and CV23 are meeting this challenge.


Release of corrosion products by F-75 cobalt base alloy in the rat. I: Acute serum elevations.
The release of corrosion products by implants has become a matter of concern. Using a microsphere model, the release of chromium, cobalt, and nickel, secondary to implantation of various surface area exposures of F-75, a cast cobalt-chromium alloy, was studied over a 30 day period in the rat. Dose related elevations were observed in the serum concentration of chromium and cobalt but not of nickel, with the maxima being achieved at 3 days after metal implantation followed by declines in concentration. The chromium elevation, approximately twelvefold for a surface area to body weight (SA/BW) ratio of 300 X is similar to that previously reported in patients receiving total hip replacement arthoplasties . However, the cobalt elevation, twentyfold for a SA/BW ratio of 300 X, has not been previously observed. These serum concentration changes are as yet unexplained, but are probably not due to fibrous capsule maturation or alloy repassivation .


Developmental diversity of amphibians.
The current model amphibian, Xenopus laevis, develops rapidly in water to a tadpole which metamorphoses into a frog. Many amphibians deviate from the X. laevis developmental pattern. Among other adaptations, their embryos develop in foam nests on land or in pouches on their mother's back or on a leaf guarded by a parent. The diversity of developmental patterns includes multinucleated oogenesis, lack of RNA localization, huge non-pigmented eggs, and asynchronous, irregular early cleavages. Variations in patterns of gastrulation highlight the modularity of this critical developmental period. Many species have eliminated the larva or tadpole and directly develop to the adult. The wealth of developmental diversity among amphibians coupled with the wealth of mechanistic information from X. laevis permit comparisons that provide deeper insights into developmental processes.


CD4+ T cells are important for clearance of DA strain of TMEV from the central nervous system of SJL/J mice.
DA and other TO subgroup strains of Theiler's murine encephalomyelitis virus synthesize a protein called L* which interferes with DA virus clearance from the central nervous system of susceptible SJL mice, thereby fostering virus persistence and a late demyelinating disease. By using CD4 (-/-) and CD8 (-/-) mice as well as adoptive transfer studies we demonstrate that susceptible mouse strains are capable of clearing DA virus through a CD4+ T cell-dependent activity that is inhibited by L*.


Complete nucleotide sequence of an attenuated hepatitis A virus: comparison with wild-type virus.
The complete nucleotide sequence of an attenuated hepatitis A virus, HAV HM-175/7 MK-5, was determined from cloned cDNA. This virus was derived from wild-type HAV HM-175 after 32 passages in African green monkey kidney cells. The resultant cell culture-adapted virus is attenuated for chimpanzees. This virus was passaged an additional three times in monkey kidney cells to obtain sufficient virus for molecular cloning and was designated HM-175/7 MK-5. Three overlapping cDNA clones were obtained that together spanned the entire genome. Comparison of the nucleotide sequence of cDNA from wild-type virus (propagated in marmoset liver in vivo) with attenuated virus (grown in cell culture) showed 24 nucleotide changes distributed throughout the genome. Five base deletions occurred in the 5' noncoding region, and 12 of the 16 base substitutions in the coding region resulted in amino acid changes. Amino acid changes occurred in viral capsid proteins VP1 and VP2 and several of the nonstructural proteins. Thus, a small number of nucleotide changes are responsible for adaptation to cell culture and attenuation of HAV strain HM-175.


Demographic variation and risk factors regarding breast cancer among females in Southern Punjab, Pakistan.
To explore epidemiology, clinical profiles and contribution of reproductive and non-reproductive risk factors in breast cancer development. The case-control study was conducted from October 2017 to March 2018 at Quaid-i-Azam University, Islamabad, Pakistan, and comprised breast cancer patients and age-matched controls recruited from the Bahawalpur Institute of Nuclear Medicine and Oncology, and the Bahawal Victoria Hospital, Bahawalpur. Socio-demographic data, family history of cancer, reproductive health and lifestyle factors were recorded using a structured questionnaire. Data was analysed using SPSS 21 and Stata/IC 14.1. Of the 326 women, 163(50%) each were cases and controls. The mean age for both the groups was identical at 46.04±10.62 years. Positive family history and hypertension were significantly linked to increased breast cancer risk (p<0.05), while intense physical activity, increased anthropometric measurements and breastfeeding per child in months were inversely associated with the risk (p<0.05). Established risk factors for breast cancer were reaffirmed.


[Transformation of bar gene to tetraploid of Isatis indigotica].
The transgenic tetraploid of Isatis indigotica mediated by Agrobacterium tumefaciens was obtained. To transfer the plant binary expression vector pCAMBIA 3300 carrying bar gene, the Agrobacterium tumefaciens strain EHA 105 was used as engineering bacterium. The results of PCR indicated that the bar gene had been transferred into and merged with the genome of Isatis indigotica. This study will make foundation for improvement of other characters of this species with genetic engineering.


[Pharmacologic modification of vigilance in the postnarcotic phase-- naloxone or physostigmine?].
The usefulness of physostigmine in reversing post-narcotic depression after general anaesthesia is well proven; so is that of naloxone, a specific opioid analgetics antagonist, in reversing neuroleptic anaesthesia effects. Morphine-like analgetics are widely used as premedication agents, too; on the other hand, physostigmine reverses opioids as well as other psychotropic and narcotic agents. For that reason, positive post-narcotic physostigmine effects could be due to its anti-opioid potency as well. In a double-blind, randomised study, physostigmine and naloxone were evaluated using a clinically based vigilance protocol, and compared with saline solution. Naloxone did not have remarkable advantages as compared with placebo, while physostigmine led to a significantly higher level of vigilance; moreover, that level was reached sooner. The positive effects of physostigmine in restoring a sufficient level of vigilance after general anaesthesia are, in respect of our findings, unrelated to its antagonism to morphine-like analgetics.


Apoptosis, autophagy & endoplasmic reticulum stress in diabetes mellitus.
The prevalence of diabetes mellitus (DM) is increasing secondary to increased consumption of food and decreased physical activity worldwide. Hyperglycaemia, insulin resistance and hypertrophy of pancreatic beta cells occur in the early phase of diabetes. However, with the progression of diabetes, dysfunction and loss of beta cells occur in both types 1 and 2 DM. Programmed cell death also named apoptosis is found to be associated with diabetes, and apoptosis of beta cells might be the main mechanism of relative insulin deficiency in DM. Autophagic cell death and apoptosis are not entirely distinct programmed cell death mechanisms and share many of the regulator proteins. These processes can occur in both physiologic and pathologic conditions including DM. Besides these two important pathways, endoplasmic reticulum (ER) also acts as a cell sensor to monitor and maintain cellular homeostasis. ER stress has been found to be associated with autophagy and apoptosis. This review was aimed to describe the interactions between apoptosis, autophagy and ER stress pathways in DM.


Novel functions for Period 3 and Exo-rhodopsin in rhythmic transcription and melatonin biosynthesis within the zebrafish pineal organ.
Entrainment of circadian clocks to environmental cues such as photoperiod ensures that daily biological rhythms stay in synchronization with the Earth's rotation. The vertebrate pineal organ has a conserved role in circadian regulation as the primary source of the nocturnal hormone melatonin. In lower vertebrates, the pineal has an endogenous circadian clock as well as photoreceptive cells that regulate this clock. The zebrafish opsin protein Exo-rhodopsin (Exorh) is expressed in pineal photoreceptors and is a candidate to mediate the effects of environmental light on pineal rhythms and melatonin synthesis. We demonstrate that Exorh has an important role in regulating gene transcription within the pineal. In developing embryos that lack Exorh, expression of the exorh gene itself and of the melatonin synthesis gene serotonin N-acetyl transferase 2 (aanat2) are significantly reduced. This suggests that the Exorh protein at the cell membrane is part of a signaling pathway that positively regulates transcription of these genes, and ultimately melatonin production, in the pineal. Like many other opsin genes, exorh is expressed with a daily rhythm: mRNA levels are higher at night than during the day. We found that the transcription factor Orthodenticle homeobox 5 (Otx5) activates exorh transcription, while the putative circadian clock component Period 3 (Per3) represses expression during the day, thereby contributing to the rhythm of transcription. This work identifies novel roles for Exorh and Per3, and gives insight into potential interactions between the sensory and circadian systems within the pineal.


Where are italian anesthesiologists and intensive care specialists publishing? A quantitative analysis of publication activity.
With the continuing worldwide shortage of anesthesiologists, the demands of clinical duties allow very little time for research activities. Every dedicated biomedical center should provide doctors and scientists with the proper environment to facilitate education, clinical practice and research activities and promote publication in international peer-review journals. In this observational study, the Scopus database was searched for publications ( 2004-2009 ) to identify the most prolific authors among Italian anesthesiologists and intensive care specialists working in Italy. We then identified the journals that most frequently hosted Italian writers. The top 20 authors published between 30 and 76 papers each (mean 51) in the last 5 years. Intensive Care Medicine (112 papers, 14%), Minerva Anestesiologica (92 papers, 11%), Critical Care Medicine (55 papers, 7%), Journal of Cardiothoracic and Vascular Anesthesia (32 papers, 4%), and European Journal of Anesthesiology (32 papers, 4%) most frequently hosted Italian authors. Despite its obvious limitations such as the choice of a single database (Scopus), the absence of important qualitative indicators (e.g. impact factor, citation index), the inclusion of any type of publication (a letter to the editor or reviews counted like a randomized controlled study) and the possible exclusion of important scholars, this is the most up-to-date and comprehensive attempt to perform a quantitative analysis of publishing in Italy. Each of the 20 indexed Journals that most frequently hosted Italian authors only accepts manuscripts in English and has impact factor.


Risk factors for sporadic infection with Salmonella Infantis: a matched case-control study.
This matched case-control study investigated the risk factors for sporadic Salmonella Infantis infection in 263 affected children and 263 age-, gender- and neighbourhood-matched controls. Information about exposure to potential risk factors was obtained via telephone interview and evaluated by conditional logistic regression analysis. Age groups ≤ 1 year (n=77) and >1 year (n = 186) were analysed separately. Of those aged ≤ 1 year, breastfeeding was a significant protective factor against infection [matched odds ratio (mOR) 0.24, 95% confidence interval (CI) 0.10-0.59, P < 0.01]. In the older group, consumption of eggs (mOR 1.87, 95% CI 1.00-3.49, P = 0.05) was a significant risk factor and thawing chicken in water (mOR 2.55, 95% CI 0.94-6.91, P = 0.07) was borderline risk factor, while consumption of carrots (mOR 0.46, 95% CI 0.26-0.83, P < 0.01), drinking tap water (mOR 0.44, 95% CI 0.22-0.85, P = 0.02), religious lifestyle (mOR 0.40, 95% CI 0.21-0.74, P < 0.01) and having a high number of children in the household (mOR 0.72, 95% CI 0.58-0.88, P < 0.01) were significant protective factors. Consumers should avoid eating undercooked eggs and food handlers should be educated regarding proper handling and cooking of eggs. Breastfeeding should be strongly encouraged by public health authorities. The public must be educated on stringent hygiene practices, especially proper cooking of eggs to reduce infection rates.