Continuous improvement in dietetics education with a regional advisory board: a model that works.
Continuous improvement has been a focus of business and health care for years. The Commission on Accreditation for Dietetics Education has also identified the need for continuous improvement in dietetics education programs and requires them to seek outside counsel to help accomplish it. Most dietetics education programs develop advisory boards to provide this outside counsel, but finding individuals to commit to an ongoing advisory board can be challenging. Dietetics internship directors from dietetics practicum programs throughout Arizona created the Arizona Dietetic Practicum Advisory Committee (AzDPAC), which uses suggestions from preceptors, interns, and committee members to generate ideas for improvement. Since the conception of AzDPAC both tangible and intangible outcomes have occurred. Tangible outcomes include better coordination among programs, development of a combined annual affiliate meeting, standardization of forms, creation of a combined "Clinical Bootcamp," development of a Web page describing all programs, and better networking among interns from different programs. In addition, AzDPAC improved cooperation and sharing of expertise and created an available group of peers for new directors. An advisory committee of regional program directors is a model that works in providing dietetics education programs with ongoing outside counsel and ideas for continuous improvement.


Effect of anaesthetic agents on the phagocytic function of human polymorphonuclear leukocytes through analysis with a phagocytic plaque method.
We examined the effects of the intravenous anaesthetic agents, thiamylal and ketamine, on the phagocytic function of polymorphonuclear leukocytes (PMN) in heparinized peripheral blood from healthy individuals using the phagocytic plaque method. Subclinical doses of thiamylal caused enhancement of the phagocytic activity of PMN and super-clinical doses of thiamylal inhibited phagocytic activity of PMN. Ketamine did not adversely affect phagocytic function at relevant therapeutic concentrations. The results presented in this manuscript indicate the phagocytic plaque method can provide a quantitative assessment of the phagocytic function of leukocytes. This method may prove useful in determining whether anaesthetic agents and other drugs adversely affect leukocyte function and hence help prevent the increased susceptibility to infection which can occur in anaesthetized patients. Conversely, the phagocytic plaque method may prove useful in the search for immune-enhancing drugs.


Regulation of the Escherichia coli secA gene is mediated by two distinct RNA structural conformations.
Expression from the secA gene, encoding a key component of the general secretory pathway of Escherichia coli, is influenced by the secretion status of the cell, autogenous translational repression, and translational coupling to the upstream gene, X. SecA binds to its mRNA in a region overlapping its ribosome binding site, thus competing with ribosomes that would initiate secA translation. Mapping of the geneX-secA mRNA secondary structure has demonstrated that the RNA can adopt two distinct conformations in solution. The first conformation arises from the base-pairing of the secA Shine-Dalgarno (SD) sequence with the geneX terminus. The second conformation, in which the secA SD sequence is no longer paired with the geneX terminus, contains a GC-rich stem upstream of the secA SD sequence. The presence of this GC-rich stem is supported by structure mapping of a mutant RNA containing a deletion in the geneX terminus. The former structure appears to be involved in translational coupling by directly linking the geneX and secA sequences, where geneX translation activates secA translational initiation through the unpairing and unmasking of the secA SD sequence. As indicated by SecA-RNA binding assays, the latter structure is probably involved in SecA binding and translational repression of the secA gene. The stabilizing effect of magnesium ions toward occlusion of the secA SD sequence supports the presence of RNA tertiary structure in this regulatory domain.


Distribution and dissipation pathways of nonylphenol polyethoxylates in the Yellow River: Site investigation and lab-scale studies.
Spatial distribution of nonylphenol polyethoxylates (NPEOs) and nonylphenol (NP) was investigated in a field study in Lanzhou Reach of the Yellow River. NPEOs and their metabolites were found in the river, with the maximum dissolved concentrations of 6.38 nmol/L for NPEOs, 0.19 nmol/L for nonylphenol ethoxy acetic acids (NPECs) and 0.79 nmol/L for NP, respectively. The maximum concentrations in the sediment and suspended particle samples were 1.50 and 5.09 nmol/g for NPEOs and NP, respectively. The effects of particles, light and microorganism on the dissipation of NPEOs in the river water were investigated based on lab-scale experiments. When natural particles were removed, 72% and 22% degradation of NPEOs were achieved at 120 h in non-sterile and sterile conditions with light, respectively. Different concentrations of NPECs were also observed in these experiments. When suspended particle matters (SPMs) were present, about 38-50% of NPEOs were sorbed to the particulate phase in only 1 h. As a result, the degradation of NPEOs and production of NPECs were inhibited. However, the combined sorption and degradation in the presence of SPMs resulted in lower dissolved NPEO concentrations than those in the absence of SPMs. Biodegradation was the most important pathway for NPEOs degradation in the river water, while NPECs seemed to be produced through both biological and abiological pathways.


Mid-aortic syndrome in two preterm infants.
We report mid-aortic syndrome (MAC) in two preterm infants. Both infants developed malignant hypertension refractory to medical therapy and died early in infancy. Thus far, this account is of the two youngest patients with MAC.


A retinoic acid-inducible GATA-binding protein binds to the regulatory region of J6 serpin gene.
Transcription of the J6 gene (a member of the serpin family) is induced in murine F9 teratocarcinoma cells 24-48 h after retinoic acid (RA) treatment. Previously, we have identified a region of the J6 5'-flanking region (-1050 to -738) that is involved in regulating transcription of this gene. In this report, we show that a RA-induced nuclear protein in the F9 cell extract recognizes the GAGATAG sequence which is repeated four times in this regulatory region of the J6 gene. The kinetics of RA induction of the GAGATAG-binding protein correlates with that of J6 mRNA, suggesting that the GAGATAG-binding protein may be involved in the transactivation of the J6 gene in RA-treated F9 cells. Competition experiments demonstrate further that the RA- induced GAGATAG-binding protein is related to the transcription factors GATA-1 and GATA-2. Furthermore, insertion of the RA regulatory region of the J6 gene into a thymidine kinase promoter/chloramphenicol acetyltransferase expression vector causes an increase in chloramphenicol acetyltransferase expression by 5-8-fold in human HeLa cells when co-transfected with human GATA-2 or GATA-3 expression vectors. This suggests that the J6 gene is likely to be transactivated by the GATA-2, GATA-3, or related transcription factor, which is activated by retinoic acid during F9 cell differentiation.


Left versus right intra-abdominal umbilical arteries: comparison of their Doppler waveforms.
The purpose of this study was to compare Doppler velocimetric indices between the left and right intra-abdominal umbilical arteries in normally grown and growth-restricted fetuses. In this cross-sectional study, Doppler indices of the intra-abdominal segment of the left and right umbilical arteries were measured lateral to the fetal bladder. Measurements, including the systolic to diastolic ratio and pulsatility index, were obtained from both anatomic locations. The Student t test was used to make comparisons. Differences between left and right Doppler indices were noted in 98% of patients, and these differences were greater than 20% in at least one-third. Overall, the left umbilical artery had a higher systolic to diastolic ratio (P = .025) and pulsatility index (P = .007) than the right umbilical artery. The laterality of the umbilical artery, whether on the left or right side of the fetus, influences important Doppler blood flow parameters.


Molecular cloning and expression of Chimonanthus praecox farnesyl pyrophosphate synthase gene and its possible involvement in the biosynthesis of floral volatile sesquiterpenoids.
Farnesyl pyrophosphate (FPP) synthase catalyzes the biosynthesis of FPP, which is the precursors of sesquiterpenoids such as floral scent volatiles, from isopentenyl pyrophosphate (IPP) and dimethylallyl pyrophosphate (DMAPP). cDNA encoding wintersweet (Chimonanthus praecox L.) FPP synthase was isolated by the RT-PCR and RACE methods. The deduced amino acid sequence showed a high identity to plant FPP synthases. Expression of the gene in Escherichia coli yielded FPPS activity that catalyzed the synthesis of FPP as a main product. Tissue-specific and developmental analyses of the mRNA levels of CpFPPS and volatile sesquiterpenoids levels in C. praecox flowers revealed that the FPPS may play a regulatory role in floral volatile sesquiterpenoids of wintersweet.


[New approaches to intensive care for sepsis].
In Germany, the mortality from sepsis remains high, and up to 60,000 patients die from it each year. Thus, sepsis is the third most common cause of death. More deaths occur only from coronary heart disease and acute myocardial infarction. In the last 3-4 years, substantial progress in sepsis therapy has been made. Based on these achievements, there is hope of reducing sepsis mortality by 25% in the next few years. Implementing new medical evidence in this context into daily clinical intensive care remains a major hurdle. The early diagnosis of sepsis prior to the onset of clinical deterioration is of particular interest, because this would increase the possibility of early and specified treatment, which is in turn the major determining factor of mortality in septic patients.


Evaluation of the prognostic role of platelet-lymphocyte ratio in cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.
Whether platelet-lymphocyte ratio (PLR) is a prognostic factor for cancer patients treated with immunotherapy is under debate. In this study, we aimed to evaluate the relationship between PLR and survival of cancer patients treated with immune checkpoint inhibitors (ICIs). A systematical search was performed in databases including PubMed, Embase, and the Cochrane library to retrieve potential eligible clinical studies assessing the prognosis of cancer patients with high versus low PLR after immunotherapy, from the establishment of the database to June 2019. Quality evaluation of included studies was performed, and meta-analyses with regards to overall survival (OS) and progression-free survival (PFS) were conducted using RevMan 5.3 and STATA 11. A total of 12 eligible studies with 1340 cancer patients were included. Combined results showed that elevated PLR was a negative factor affecting the efficacy of ICIs in cancer patients. Patients with high PLR had a significantly shorter OS compared to those with low PLR (hazard ratio (HR) = 2.02, 95% confidence interval (CI): 1.46 to 2.80, P < 0.0001), as well as PFS (HR = 1.74, 95%CI: 1.27 to 2.38, P = 0.0006). Similar results were observed in sensitivity analyses. Subgroup analyses revealed that the prognostic role of PLR on OS and PFS was dependent on cancer type, region, and cutoff value. For NSCLC patients, the disease stage, ICIs agent, and line of treatment may not influence the prognostic role of PLR. PLR could be a routinely potential prognostic factor for ICIs. Low PLR may be associated with better survival for cancer patients when treated with immunotherapy.


Oxidized Low-Density Lipoprotein Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes by Modulating the TLR4/NF-κB Pathway.
This study was designed to investigate the apoptosis induced by oxidized low-density lipoprotein (ox-LDL) in cultured neonatal rat cardiomyocytes and explore the possible mechanisms. We evaluated whether ox-LDL-induced apoptosis depended in part on the activation of toll-like receptor-4(TLR4)/Nuclear factor κB (NF-κB) signaling pathway. Cells were cultivated with and without ox-LDL. Cell apoptosis was evaluated by flow cytometry. Immunofluorescence, western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to assess protein or mRNA expressions. Resatorvid (TAK-242), an exogenous synthetic antagonist for TLR4, was used to inhibit TLR4 signal transduction. Dose- and time-dependent apoptotic index of cardiomyocytes occurred after ox-LDL treatment. Incubation of cardiomyocytes with ox-LDL (50 μg/mL) for 24 hours increased TLR4 and NF-κB expressions significantly. Decrease of Bcl-2/Bax protein ratio, activation of caspase-3 and 9 were also detected. Ox-LDL-induced cardiomyocyte apoptosis, TLR4 and NF-κB expressions were attenuated by pretreatment with TAK-242. In conclusion, our findings indicate that the apoptosis induced by ox-LDL in cultured neonatal rat cardiomyocytes at least in part by modulating the TLR4/NF-κB signaling pathway.


Critical contribution of immunoproteasomes in the induction of protective immunity against Trypanosoma cruzi in mice vaccinated with a plasmid encoding a CTL epitope fused to green fluorescence protein.
Acquired immunity against infection with Trypanosoma cruzi is dependent on CD8(+)T cells. Here, to develop a vaccine strategy taking advantage of activated CD8(+)T cells, we constructed a DNA vaccine, designated pGFP-TSA1, encoding a fusion protein linking GFP to a single CTL epitope of TSA1, a leading candidate for vaccine against T. cruzi. C57BL/6 mice vaccinated with this plasmid showed suppressed parasitemia and prolonged survival. Vaccination with pGFP-TSA1 enhanced epitope-specific cytotoxicity and IFN-gamma secretion by CD8(+)T cells. Furthermore, the depletion of CD8(+)T cells prior to challenge infection with T. cruzi completely abolished this protection, indicating that CD8(+)T cells are the principal effector T cells involved. When mice deficient in the proteasome activator PA28alpha/beta or the immunoproteasome subunits LMP2 and LMP7 were used, the protective immunity against infection was profoundly attenuated. Our findings clearly demonstrate that vaccination with pGFP-TSA1 successfully induces protection dependent on CD8(+)T cell activation, in which immunoproteasomes play a crucial role. It is noteworthy to document that physical binding of the epitope and GFP is required for induction of this protection, since mice vaccinated with pTSA1-IRES-GFP failed to acquire resistance, probably because the epitope and GFP are separately expressed in the antigen-presenting cells.


Multiblock Copolymers Based on Highly Crystalline Polyethylene and Soft Poly(ethylene-co-butadiene) Segments: Towards Polyolefin Thermoplastic Elastomers.
Block copolymers based on polyethylene (PE) and ethylene butadiene rubber (EBR) were obtained by successive controlled coordinative chain transfer polymerization (CCTP) of a mixture of ethylene and butadiene (80/20) and pure ethylene. EBR-b-PE diblock copolymers were synthesized using the {Me2 Si(C13 H8 )2 Nd(BH4 )2 Li(THF)}2 complex in combination with n-butyl,n-octyl magnesium (BOMAG) used as both the alkylating and chain transfer agent (CTA). Triblock and multiblock copolymers featuring highly semi-crystalline PE hard segments and soft EBR segments were further obtained by the development of a bimetallic CTA, the pentanediyl-1,5-di(magnesium bromide) (PDMB). These new block copolymers undergo crystallization-driven organization into lamellar structures and exhibit a variety of mechanical properties, including excellent extensibility and elastic recovery in the case of triblock and multiblock copolymers.


[Undifferentiated bronchopulmonary carcinoma associated with scleroderma and hypertrichosis lanuginosa. A case report].
The development of a malignant tumor, as well as hypertrichosis lanuginosa as a paraneoplasic syndrome, in a patient afflicted with scleroderma is a very rare event. We present the clinical history of a patient afflicted with scleroderma, non-differentiated bronchopulmonary carcinoma adn hypertrichosis lanuginosa as paraneoplasic expression of the tumor.


Body composition variables and leptin levels in functional hypothalamic amenorrhea and amenorrhea related to eating disorders.
The purpose of the study was to identify diagnostic criteria that can distinguish between subjects with functional hypothalamic amenorrhea largely related to minimal energy deficiency and those in whom failure of adaptive response to stress prevails. We studied 59 young women with secondary amenorrhea related to modest eating disorders and 58 who complained of stressful events in their history. We assessed anthropometric measurements, body composition using dual energy X-ray absorptiometry (DEXA) and bioelectrical impedance analysis (BIA), and basal endocrine profile. Subjects with disordered eating had lower body mass index (BMI), fat mass (FM) measured with both techniques, lumbar mineral density and direct and indirect measures of lean mass. Leptin and free tri-iodothyronine(FT(3)) concentrations also proved lower in the group of subjects with eating disorders, although there was no significant difference in cortisol between the two groups. Leptin levels were positively associated not only with fat mass, but also with body cell mass indexed to height and phase angle, parameters studied with BIA as expression of active lean compartment. A multivariate model confirmed the utility of integrating endocrine data with the study of body composition. The use of bioelectrical impedance analysis proved to be, in clinical use, a valid diagnostic alternative to DEXA, especially considering body cell mass and phase angle.


Buoyancy effects on the scaling characteristics of atmospheric boundary-layer wind fields in the mesoscale range.
We have analyzed long-term wind speed time series from five field sites up to a height of 300 m from the ground. Structure function-based scaling analysis has revealed that the scaling exponents in the mesoscale regime systematically depend on height. This anomalous behavior is likely caused by the buoyancy effects. In the framework of the extended self-similarity, the relative scaling exponents portray quasiuniversal behavior.


Prevalence and trends of common mental disorders from 2007-2009 to 2019-2022: results from the Netherlands Mental Health Survey and Incidence Studies (NEMESIS), including comparison of prevalence rates before vs. during the COVID-19 pandemic.
Up-to-date information on the prevalence and trends of common mental disorders is relevant to health care policy and planning, owing to the high burden associated with these disorders. In the first wave of the third Netherlands Mental Health Survey and Incidence Study (NEMESIS-3), a nationally representative sample was interviewed face-to-face from November 2019 to March 2022 (6,194 subjects; 1,576 interviewed before and 4,618 during the COVID-19 pandemic; age range: 18-75 years). A slightly modified version of the Composite International Diagnostic Interview 3.0 was used to assess DSM-IV and DSM-5 diagnoses. Trends in 12-month prevalence rates of DSM-IV mental disorders were examined by comparing these rates between NEMESIS-3 and NEMESIS-2 (6,646 subjects; age range: 18-64 years; interviewed from November 2007 to July 2009). Lifetime DSM-5 prevalence estimates in NEMESIS-3 were 28.6% for anxiety disorders, 27.6% for mood disorders, 16.7% for substance use disorders, and 3.6% for attention-deficit/hyperactivity disorder. Over the last 12 months, prevalence rates were 15.2%, 9.8%, 7.1%, and 3.2%, respectively. No differences in 12-month prevalence rates before vs. during the COVID-19 pandemic were found (26.7% pre-pandemic vs. 25.7% during the pandemic), even after controlling for differences in socio-demographic characteristics of the respondents interviewed in these two periods. This was the case for all four disorder categories. From 2007-2009 to 2019-2022, the 12-month prevalence rate of any DSM-IV disorder significantly increased from 17.4% to 26.1%. A stronger increase in prevalence was found for students, younger adults (18-34 years) and city dwellers. These data suggest that the prevalence of mental disorders has increased in the past decade, but this is not explained by the COVID-19 pandemic. The already high mental disorder risk of young adults has particularly further increased in recent years.


Gustatory-salivary reflex: neural activity of sympathetic and parasympathetic fibers innervating the submandibular gland of the hamster.
Electrophysiological experiments were performed to clarify the neural control mechanisms subserving gustatory-salivary reflex in anesthetized and decerebrate hamsters. Efferent neural activities of postganglionic sympathetic and preganglionic parasympathetic fibers, innervating the submandibular gland, were recorded when taste stimuli were infused into the oral cavity. Neural activities of primary gustatory afferents were also recorded from the chorda tympani (innervating the anterior part of the tongue) and the glossopharyngeal nerve (innervating the posterior part of the tongue). The parasympathetic fibers showed a low rate of spontaneous discharges (about 0.3 Hz), and responded tonically in an excitatory manner to taste stimulation. The magnitude of parasympathetic activity was highly correlated with the magnitude of gustatory afferent responses of the chorda tympani rather than that of the glossopharyngeal nerve. On the other hand, the sympathetic fibers showed irregular burst discharges (1.5 burst/s), and the rate of burst discharges was increased in response to high concentrations of HCl (0.03 M) or NaCl (1 M) solutions. Deafferentation experiments suggest that the parasympathetic activity is mainly influenced by gustatory information via the chorda tympani, while the sympathetic activity can be evoked by both the chorda tympani and glossopharyngeal nerve.


Identification of compound heterozygous patients with primary hyperoxaluria type 1: clinical evaluations and in silico investigations.
Primary hyperoxaluria type 1 (PH1) is an autosomal recessive inherited disorder of glyoxylate metabolism in which excessive oxalates are formed by the liver and excreted by the kidneys. Calcium oxalate crystallizes in the urine, leading to urolithiasis, nephrocalcinosis, and consequent renal failure if treatment is not initiated promptly. Mutations in the AGXT gene which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase are responsible of PH1. In the present work, we aimed to analyze AGXT gene and in silico investigations performed in four patients with PH1 among two non consanguineous families. Exhaustive gene sequencing was performed after PCR amplification of coding exons and introns boundaries. Bioinformatic tools were used to predict the impact of AGXT variants on gene expression as well as on the protein structure and function. Direct sequencing of all exons of AGXT gene revealed the emergence of multiple mutations in compound heterozygous state in the two studied families. Two patients were compound heterozygous for the c.731 T > C, c.32C > T, c.1020A > G and c.33_34insC and presented clinically with recurrent urinary tract infection, multiple urolithiasis and nephrocalcinosis under the age of 1 year and a persistent hyperoxaluria at the age of diagnosis. The two other patients presenting a less severe phenotypes were heterozygous for c.731 T > C and homozygous for the c.32C > T and c.1020A > G or compound heterozygous for c.26C > A and c.65A > G variants. In Summary, we provided relevance regarding the compound heterozygous mutations in non consanguineous PH1 families with variable severity.


Demonstration of the percutaneous resorption of a lipophilic pesticide and its possible storage in the human body.
The kinetics of lindane concentration in the serum and the time-dependent urinary excretion of two groups, one with healthy subjects and one with scabies-infested subjects, were comparatively analyzed by gas chromatography. Both groups showed similar cumulative excretion curves at completely different lindane concentrations in the serum. Comparison of serum concentration in healthy females (high lindane concentration in serum) and healthy males (low serum concentration) to the urinary excretion showed similar results. There appears to be a serum 'threshold concentration', above which it is possible that lindane is no longer primarily excreted by the kidney. Based on these results recommendations are presented, for the practical use of such data in the treatment of scabies.


In vivo human melanoma cytokine production: inverse correlation of GM-CSF production with tumor depth.
Melanomas produce multiple cytokines which may influence their growth in vivo. Experimental evidence suggests that granulocyte macrophage-colony stimulating factor (GM-CSF) can induce a potent anti-melanoma response. whereas interleukin-8 (IL-8) may act as a growth factor in human melanoma. Little is currently known regarding the production of these cytokines by human melanoma in vivo. In this study we tested the hypothesis that endogenous production of GM-CSF and IL-8 can be correlated with the depth of human malignant melanoma surgical specimens. We examined 45 melanocytic human tissue samples consisting of 27 primary cutaneous melanomas, 9 metastatic melanomas, and 9 dysplastic nevi for in vivo GM-CSF and IL-8 production using immunohistochemistry. The majority of thin melanomas (< or = 0.76 mm) stained highly positive for GM-CSF with little or no staining for IL-8 whereas the medium (>0.76- < or = 4.0 mm) and thick (>4.0 mm) melanoma specimens showed little or no staining for GM-CSF and significant amounts of IL-8 staining. Metastatic melanoma as well as dysplastic nevi specimens had little or no GM-CSF and IL-8 staining. These results support the hypothesis that endogenous melanoma cytokines such as GM-CSF and IL-8 with opposing effects on tumor progression play an important role in melanoma growth and regulation.


SGOL1-AS1 enhances cell survival in acute myeloid leukemia by maintaining pro-inflammatory signaling.
Epigenetic dysregulation is a key feature of most acute myeloid leukemia (AML). Recently, it has become clear that long noncoding RNAs (lncRNAs) can play a key role in epigenetic regulation, and consequently also dysregulation. Currently, our understanding of the requirements and roles of lncRNAs in AML is still limited. Here, using CRISPRi screening, we identified the lncRNA SGOL1-AS1 as an essential regulator of survival in THP-1 AML cells. We demonstrated that SGOL1-AS1 interacts with chromatin-modifying proteins involved in gene repression and that SGOL1-AS1 knockdown is associated with increased heterochromatin formation. We also observed that loss of SGOLl-AS1 results in increased apoptosis and the downregulation of pro-inflammatory genes. In AML patients, high expression of SGOL1-AS1 correlates with both pro-inflammatory gene expression and poor survival. Altogether, our data reveal that SGOL1-AS1 is an essential regulator of cell survival in AML cell lines and a possible regulator of pro-inflammatory signaling in AML patients.


Lkb1 aggravates diffuse large B-cell lymphoma by promoting the function of Treg cells and immune escape.
Regulatory T cells (Tregs) induce immune responses and may contribute to immune escape in tumors. Accumulation of Tregs in tumors represents a critical barrier to anti-tumor immunity and immunotherapy. However, conflicting results describing the role of Tregs in lymphoma warrant further investigation. The precise features and mechanisms underlying the alteration in Tregs in diffuse large B-cell lymphoma (DLBCL) are not well understood yet. In this study, we analyzed the mechanism underlying the observed alterations in Tregs in DLBCL and examined the effect of Lkb1 expression on the immunosuppressive function of human Tregs. Flow cytometry and immunofluorescence were used to analyze the proportion of Tregs and effector Tregs in the peripheral blood and lymph nodes of patients with DLBCL and control group. In vitro culture assays were used to analyze the immunosuppressive function of Tregs in the two groups. Transcriptome sequencing was performed to analyze the differentially expressed genes in the two groups, and the transcription level and protein expression of Lkb1 in the two groups were detected using RT-PCR and WES microprotein technology. Lentiviral vectors were constructed to explore the functional changes of Tregs with stable upregulation and downregulation of Lkb1. Finally, a humanized murine lymphoma model was established to study the function of Lkb1 in Tregs in the pathogenesis of DLBCL. The number of Tregs was found to be dramatically increased in peripheral blood and tumor tissue in DLBCL patients compared with that in healthy controls, and decreased after treatment. Tregs from DLBCL patients exhibited multiple enhanced functions, including increased inhibition of CD8+cytotoxic T cells (CTL) against tumor cells, enhanced suppression of CD8+CTL secretion of granular enzyme, and suppression of CD8+CTL degranulation. Lkb1 was found to be upregulated in Tregs of DLBCL patients. Furthermore, Lkb1 contributes to Treg immunosuppressive function in DLBCL by regulating the mevalonate pathway. Finally, deletion of Lkb1 in Tregs suppressed tumor growth and promoted anti-tumor immunity in a DLBCL murine model. These findings confirmed that Lkb1-regulated Tregs are critical for immune escape in DLBCL, which emphasizes that Lkb1 is a potential target for the immunotherapy of DLBCL.


Evolution of outpatient parenteral antibiotic therapy.
The future will no doubt continue to promote safe, cost-effective therapies such as outpatient intravenous therapy. It is imperative that physicians trained and knowledgeable in the administration of outpatient intravenous antimicrobial drug administration continue to assume responsibility and leadership roles.


Identifying mechanisms by which Escherichia coli O157:H7 subverts interferon-γ mediated signal transducer and activator of transcription-1 activation.
Enterohemorrhagic Escherichia coli serotype O157:H7 is a food borne enteric bacterial pathogen that causes significant morbidity and mortality in both developing and industrialized nations. E. coli O157:H7 infection of host epithelial cells inhibits the interferon gamma pro-inflammatory signaling pathway, which is important for host defense against microbial pathogens, through the inhibition of Stat-1 tyrosine phosphorylation. The aim of this study was to determine which bacterial factors are involved in the inhibition of Stat-1 tyrosine phosphorylation. Human epithelial cells were challenged with either live bacteria or bacterial-derived culture supernatants, stimulated with interferon-gamma, and epithelial cell protein extracts were then analyzed by immunoblotting. The results show that Stat-1 tyrosine phosphorylation was inhibited by E. coli O157:H7 secreted proteins. Using sequential anion exchange and size exclusion chromatography, YodA was identified, but not confirmed to mediate subversion of the Stat-1 signaling pathway using isogenic mutants. We conclude that E. coli O157:H7 subverts Stat-1 tyrosine phosphorylation in response to interferon-gamma through a still as yet unidentified secreted bacterial protein.


Cellulose nanocrystal preparation from Gelidium amansii and analysis of its anti-inflammatory effect on the skin in vitro and in vivo.
Treated Gelidium amansii cellulose nanocrystal (TGa CNC) was prepared from treated Gelidium amansii (TGa) and evaluated for its anti-inflammatory effect on human keratinocytes and mice skin. Using three independent cell lines, TGa CNC showed no cytotoxicity in HaCaT, Beas-2B, and Raw 264.7 cells. A non-toxic dose of TGa CNC suppressed ultraviolet (UV) B-induced AP (activated protein)-1, and subsequent cyclooxygenase (COX)-2 gene and protein expression in HaCaT cells. TGa CNC suppressed translocation of c-Jun from the cytosol to the nucleus responds to UVB irradiation. Additionally, TGa CNC suppressed UVB-induced extracellular signal-regulated kinases (ERKs)1/2/MEK/2/B-Raf, c-Jun N-terminal kinase (JNK)1/2/MKK4/7, Akt, and epidermal growth factor receptor (EGFR) phosphorylation in HaCaT cells. Dorsal treatment of TGa CNC significantly suppressed acute UVB-induced increase in epidermal thickness and COX-2 expression in mice skin. Overall, these results indicate that TGa CNC exerts potent anti-inflammatory activity through the inhibition of abnormal COX-2 expression and mitogen-activated protein kinases (MAPK)s signaling pathways.


Frontalis-based island pedicle flaps for the single-stage repair of large defects of the forehead and frontal scalp.
Medium- to large-sized surgical defects of the forehead and frontal scalp provide a challenge for the reconstructive surgeon. To highlight the utility of a frontalis-based island pedicle flap (FIPF) for the single-stage, aesthetic reconstruction of such defects. The design and detailed surgical technique required for a FIPF are described. The long-term results are illustrated. FIPFs, despite significant tissue dissection, are readily performed under local anaesthesia and are well tolerated by patients. The FIPF adds to the dermatological surgeon's armamentarium in the reconstruction of large defects of the central forehead and frontal scalp.


Comparison of electrode position marking procedures on the cranial surface.
The study aimed to compare the conventional method of electrode marking with a new system, EPlacement, to improve accuracy and reduce the time burden on health care professionals. Ten health care professionals marked mannequin heads and adult volunteers using both methods. Time, accuracy, and usability of each method were analyzed. Three neurophysiological diagnostic tests were performed on mannequin heads: reversal pattern visual evoked potential (three electrodes required); somatosensory evoked potentials from the upper and lower extremities (five electrodes required); and standard intraoperative neurophysiological monitoring for spine surgery (nine electrodes required). Precision scanning of the mannequins with structured light and a printed hull were used to determine the actual locations of the electrodes of the 10/20 system. The new method based on the EPlacement device represents an improvement on conventional tape measure (TM) marking and may be considered within the group of advanced methods such as navigation systems since it leads to improvements of 34% (1.7 mm) for electrode positions in the Nasion-Inion and Left tragus-Right tragus lines and 77% (12.5 mm) for electrode positions using the approximate method. It reduces the time spent per test by an average of 1 min compared to the TM method. Health care staff survey results show a positive feedback regarding usability of the new method. The study showed that the EPlacement device improves accuracy, reduces time, and is easy to use compared to the conventional method of electrode marking. The EPlacement method can facilitate the complex task of electrode marking and ultimately contribute to improved patient outcomes. It has the potential to be widely accepted and implemented in clinical practice.


Facial implants.
By offering safe, long-term correction of volume depletion and contour defects, facial implants maintain a unique position in the armamentarium of the cosmetic surgeon. Careful patient assessment and selection of the appropriate implant type, size, and shape maximize results. Proper postoperative follow-up helps to treat any complications before they become a serious problem. Most patients have volume loss as part of their facial aging. Facial implants play an important role in panfacial rejuvenation.


Effectiveness of 2% CHG cloth bathing for reducing surgical site infections.
We conducted a prospective cohort study on the effectiveness of preoperative bathing with chlorhexidine gluconate (CHG) cloths for reducing surgical site infections. We hypothesized that use of CHG cloths as an adjunct to surgical prep would significantly reduce the endogenous flora of surgical patients and therefore reduce surgical site infections. Data from a control group of patients who had undergone general, vascular, and orthopedic surgery were used for comparison. Results indicated an overall reduction of infection in the group that received a 2% CHG bath before surgery. There also was a possible reduction in postoperative organ space infection, although the sample numbers were extremely small. To reduce surgical site infections, we suggest a nursing protocol of preoperative bathing with a 2% CHG cloth for patients undergoing general and vascular surgery, and an additional trial to investigate the use of preoperative CHG cloth baths in all surgical patient populations.


Effects of digital sleep interventions on sleep and psychological health during the COVID-19 pandemic: A systematic review and meta-analysis.
Various digital sleep interventions have been implemented to address sleep and psychological complications during the coronavirus disease 2019 (COVID-19) pandemic. However, the characteristics and effectiveness of digital sleep interventions on sleep and psychological outcomes for people with sleep problems during the COVID-19 pandemic are unknown. The protocol of this systematic review and meta-analysis was registered on PROSPERO (ID: CRD42022325662), seven databases were searched from December 2019 to June 2023. Reference lists from digital sleep reviews were also identified and selected. Two reviewers independently screened eligible articles and extracted data. Quality appraisal was undertaken by two independent reviewers using the Cochrane Risk-of-Bias Tools. Data synthesis was conducted using fixed- or random-effects model based on the results of the heterogeneity test. A total of 20 studies were identified, including nine randomised controlled trials (RCTs) and 11 non-RCTs, involving 3860 participants. Meta-analyses showed that digital sleep interventions significantly improve sleep quality, insomnia, and depression during the COVID-19 pandemic. Subgroup analysis showed that interventions of more than four weeks, healthcare workers as participants, and relaxation therapies may have the advantage of improving sleep quality. Most non-RCTs supported the efficacy of digital sleep interventions on sleep and psychological health. Digital sleep interventions during the COVID-19 pandemic had significant effectiveness in improving sleep and psychological outcomes for people with sleep problems. More structured and personalised digital sleep interventions should be designed, and other diverse digital technologies could be used to improve sleep and psychological disorders.


An analysis of problem areas and counseling experiences of gay white males.
An analysis of problem areas and counseling experiences of gay white males was performed in preparation for a larger study. Subjects were members of several gay organizations. A number of relationships among demographic variables and problem areas were found. Two factors, a general social functioning factor and a factor relating to acknowledging one's gayness to others (coming-out), accounted for almost 70% of the variance in a structure of problem areas. Approximately half of the respondents reported having had counseling experience. Of those reporting their satisfaction with the experience, the majority were satisfied. Results suggested that white, educated, middle-class gay males may not be underserved with respect to psychological service delivery.


Prophylactic Levetiracetam for Seizure Control After Cranioplasty: A Multicenter Prospective Controlled Study.
To study efficacy and safety of prophylactic levetiracetam (LEV) administration in adults undergoing cranioplasty. We prospectively enrolled and randomly divided 200 adults undergoing cranioplasty into 2 groups: LEV (prophylactic LEV for 24 weeks) and control (no prophylactic antiepileptic drugs). Demographic and clinical characteristics; occurrence of postoperative seizure; changes in IQ, memory quotient, and activities of daily living scores; and postoperative side effects during hospital stay were analyzed at 2-, 24-, and 48-week follow-up visits. Significant differences were found between groups in both early-stage seizures in the initial 2 weeks and late-stage seizures in the 3-24 weeks after cranioplasty (P < 0.05). Postoperative seizures occurred in 17.0% in the control group and 4.1% in the LEV group 48 weeks after cranioplasty, which was found to be significant (P = 0.0020). Patients with abnormal preoperative or postoperative electroencephalography (EEG) with spikes or sharp waves presented with an increased number of postoperative seizures compared with patients with normal EEG readings at 48 weeks. Significant differences were found between patients with postoperative seizures and patients without postoperative seizures in regard to changes in IQ, memory quotient, activities of daily living, and patient satisfaction scores (P < 0.01). No significant difference was found in side effects between the 2 groups. Postoperative seizure is a common complication of cranioplasty, especially in patients with preoperative or postoperative abnormal EEG with spikes or sharp waves. Prophylactic LEV administration significantly reduced postcranioplasty seizures during LEV usage and had few side effects.


Women's preferences for communication with the cervical screening programme: A qualitative study.
In Scotland, invitations and results for cervical screening are sent by post. We ask the question: is this an effective means of communication in the 21st century? Consideration of other ways of communicating with women may help to increase acceptability of the cervical screening programme. To explore perspectives of screening-eligible women, regarding methods for communication of invitations and results from the cervical screening programme to improve acceptability. A qualitative study design using semi-structured face-to-face or telephone interviews with women aged 25-65 years. Thirty interviews were directed using visual cues to generate discussion. Interviews were audio-recorded and transcribed verbatim. Thematic analysis of the data was conducted using a Framework approach. The main advantage of the postal system is its perceived formality; however, its lack of speed was a concern. Advantages of e-communication included speed and convenience; however, concerns such as lack of confidentiality and access were mentioned. Telephone communication was deemed impractical, while face-to-face communication was highly regarded. Furthermore, the majority of participants felt screening appointments set at a specific date and time may improve uptake. Overall, participants believed there is no universal solution regarding the issue of communication. At present, the postal system may be an appropriate method for invitation and results for cervical screening; however, there may be greater scope for preference of communication to improve the acceptability of the screening programme to women.


Direct inhibitory effect of erythromycin on human alimentary tract smooth muscle.
Erythromycin was found to stimulate motor activity in the upper gastrointestinal tract. However, in several smooth muscle preparations, it also elicited an inhibitory effect. Our aim was to study the effect of erythromycin in various human alimentary tract smooth muscles. Using force measurements, we assessed the effect of erythromycin on electrically and chemically evoked contractions of isolated muscle strips of human gallbladder, small intestine, and colon. The muscarinic receptor agonist carbachol evoked contraction in gallbladder, ileum, and colonic smooth muscle that were reduced by erythromycin at 10(-4) M to 72% +/- 24%, 77% +/- 22%, and 76% +/- 22% of control values, respectively. Erythromycin did not affect contractions evoked by noncholinergic agents. Erythromycin's inhibitory effects were not altered by nerve blockade, indicating a direct muscle effect. Eryrthromycin also reduced contractions evoked by electrical stimulation at frequencies of 5, 10, and 20 Hz in the human gallbladder, ileum, and colon preparations. These contractions were reduced by erythromycin in a reversible and dose-dependent manner. Erythromycin antagonized direct cholinergic effects on various smooth muscles from the human alimentary tract in a concentration-dependent manner.


Hepatitis E virus genotype 3 in humans and swine, Cuba.
This study was conduced to determinate the seroprevalence and risk factors associated to hepatitis E virus (HEV) exposition, in individuals who work in pig farms located at western of Artemise Province. The presence of HEV in human and swine samples and the phylogenetic analysis were evaluated. One hundred six workers (with an age range of 18-70years) were enrolled in this study. Two groups were defined, 69 employees with swine related occupations and 37 workers without contact with pigs. None had abroad travel history. Serum samples were tested for immunoglobulins (Ig) M, G and A against HEV. Individual fecal samples were obtained from 57 workers and 53 swine. All feces were tested for HEV RNA using reverse transcription PCR (RT-PCR). The amplification products were sequenced and phylogenetically analyzed by using MEGA5 software. A total of 38 (35.8%) (95% CI: 26.2-45.4) sera was positive for antibodies against HEV (anti-HEV). These were higher in persons who work in contact with swine compare as individuals with occupations without pig contact (40.5%, 28/69, 95% CI: 28.2-52.8, versus 27.0%, 10/37, 95% CI: 11.3-42.6, respectively). The prevalence of anti-HEV was higher in workers with an age range of 60-70years old and time-work 10-13years. HEV RNA was detected in 8 (14.0%) of 57 human fecal samples and 10 (18.8%) of 53 swine fecal samples. Phylogenetic analysis was performed on 7 amplification products obtained from 3 human and 4 swine fecal samples. Human and swine HEV sequences were closely related (94-99% nucleotide homology) and belonged to HEV genotype 3, subtype 3a.


Measuring men's opinions of prostate needle biopsy.
Needle biopsy of the prostate is an important, common, invasive procedure. Little is known about men's perceptions of it. The present study was designed to assess men's experience of prostate biopsy, to determine the feasibility of a randomized trial of interventions to alleviate distress during prostate biopsy, and to develop a pragmatic outcome measure for such a trial. Of 33 consecutive men undergoing prostate biopsy at a Sydney (Australia), tertiary referral urology centre 31 men were selected for study. A cross-sectional, observational was performed. Participants completed both a 24-item questionnaire assessing relevant symptoms, attitudes and emotional responses and a semistructured interview shortly after their prostate biopsy. Each item of the questionnaire was rated on an 11-point scale from 0 (no trouble at all), to 10 (worst they could imagine). The mean score for discomfort was 4.4 with 32% scoring > or =7; the mean score for pain was 4.2 with 29% scoring > or =7. The other most troubling aspects were: 'waiting for the result' (mean 4.4, 32% > or =7) and 'fear of the result' (mean 3.7, 32% > or =7). Seventy-one per cent of subjects stated that they would have been willing to participate in a randomized trial of interventions to make prostate biopsies less unpleasant. Thirteen of the 24 items were retained and refined for use as an outcome measure for subsequent trials. Many men experience pain, discomfort and anxiety during prostate needle biopsy and most would be willing to participate in trials of interventions to make it less unpleasant.


Multi-walled carbon nanotubes decrease neuronal NO synthase in 3D brain organoids.
Multi-walled carbon nanotubes (MWCNTs) might induce the dysfunction of neuronal NO synthase (nNOS) and impair the function of brains. But to the best of our knowledge, this conclusion was made by using laboratory animals or conventional nerve cell cultures; however, these models might not reflect the complex conditions of human brains. Recently, the development of 3D brain organoids (also known as organotypic cultures) derived from human induced pluripotent stem cells (iPSCs) provides a platform to investigate the behaviors of human brains in vitro. In this study, we investigated the toxicity of MWCNTs to 3D brain organoids which expressed the cortical layer markers. It was shown that MWCNTs induced cytotoxicity to 3D brain organoids but not in dose-dependent manner. Exposure to high level of MWCNTs (64 μg/mL) reduced the levels of intracellular NO but increased superoxide. As the mechanism, 64 μg/mL MWCNTs significantly reduced the protein level of nNOS. The nNOS regulators nuclear factor kappa-B (NF-κB) proteins were significantly induced by MWCNTs, whereas Kruppel-like factor 4 (KLF4) proteins were reduced particularly after exposure to low level of MWCNTs (16 μg/mL). The results from fluorescence micro-optical sectioning tomography (MOST) confirmed the decrease of nNOS proteins, not only at the out-layers that directly contacted MWCNTs, but also at the inner-layers. Combined, our results suggested that MWCNTs could decrease nNOS activity by inducing oxidative stress and modulating NF-κB-KLF4 pathway. This study also showed the potential of 3D brain organoids in mechanism-based toxicology studies.


[Diagnosis and treatment of bilateral testicular intratubular seminoma: a case report and review of literature].
To explore the diagnosis and treatment of testicular intratubular seminoma. One case of testicular intratubular seminoma was diagnosed with testicular biopsy. Epididymal sperm was aspirated and intracytoplasmic sperm injection ( ICSI) was performed. And local radiotherapy was conducted on the bilateral testes after fertilization. The result of testicular biopsy revealed bilateral testicular intratubular seminoma. Large numbers of sperms were found in the epididymal aspirate. ICSI did not succeed for the first time. The second ICSI succeeded. The local radiotherapy by 60Co had been conducted on the bilateral testes, and testicular tumor didn't develop further. Testicular intratubular seminoma is a type of intratubular germ cell neoplasia, with no clinical manifestations, and usually found in testicular biopsy. Earlier management promises better prognosis.


A potential model for studying the plasticity and reprogramming of human epidermal stem cells through preimplantation blastocyst microinjection.
Microinjection of adult stem cells (ASCs) into blastocysts provides a classic model for studying ASC plasticity. To explore the molecular mechanisms that govern the reprogramming of ASCs, we evaluated the experimental model through microinjection of human epidermal stem cells (hEpiSCs) into mouse blastocysts. Mouse blastocysts underwent regular embryogenesis after microinjection of allogeneic cells, confirmed by morphological observation and embryo cell counting. hEpiSCs survive and integrate into mouse embryos, by monitoring the migration of injected cells at 2, 4, 12, 16 and 24 h. In this xenogeneic system, hEpiSCs could be reprogrammed within 24 h, as evidenced by the silencing of CK15 and Integrin beta 1 gene expression, without activation of Oct4 and Nanog. Microinjection of hEpiSCs into mouse blastocysts provides an efficient model for studying the molecular mechanisms of their plasticity. Moreover, the possibility of inducing pluripotent stem cells without transgenes or viruses can be entertained.


The mediator couples transcription and splicing.
Transcription is coupled with pre-mRNA splicing in metazoans. In the current issue of Molecular Cell, Huang et al. (2012) show that Med23 interacts with the RNA binding protein hnRNP L to regulate alternative splicing, thus expanding Mediator's function beyond transcriptional control.


Self-inflicted eye injuries: a review.
To review the pathogenesis, clinical characteristics, and management of self-inflicted eye injuries. Review of the medical literature. Psychiatric theories of pathogenesis for self-inflicted behaviour include religious and sexual ideation, symbolism, guilt, and displacement. Biological theories include disorders of serotonergic, dopaminergic, and opiate neurotransmitters. Clinical characteristics of self-mutilators include acute or chronic psychoses, drug-induced psychoses, other psychiatric conditions, and certain organic states. The majority are young-to-early middle-aged male subjects, though it can also rarely occur in children. Management of self-inflicted eye injury requires close cooperation between ophthalmologists and psychiatrists as well as other medical specialists, to ensure quick resuscitation of the patient, prompt diagnosis and treatment of any injuries, and treatment of the underlying behaviour that led to the injuries. Self-inflicted eye injuries are a rare but important group of ophthalmic conditions that require close cooperation between different medical specialties to ensure optimum care of the often severely disturbed patient.


Cytotoxicity in feline leukemia virus subgroup-C infected fibroblasts is mediated by adherent bone marrow mononuclear cells.
The pathogenesis of retrovirus-induced erythroid aplasia in cats is unknown. In studies to define mechanisms of cytotoxicity associated with retroviral infections, bone marrow mononuclear cells (BMMC) from healthy specific pathogen-free cats were co-cultured with uninfected feline embryonic fibroblasts (FEA cells) and FEA cells infected with feline leukemia virus (FeLV) of subgroup A (FEA-A) or subgroup C (FEA-C). Moderate to marked cytotoxicity (CPE) developed in co-cultures of BMMC and FEA-C cells on Days 5 to 7 of incubation but not in co-cultures of BMMC and FEA-A or BMMC and uninfected cells (FEA-CT). Cytotoxicity was associated with adherent cells of light density (1.056) from bone marrow and peripheral blood, which were positive for alpha naphthyl butyrate esterase activity. Stimulation of adherent cells with phorbol ester or addition of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) caused similar CPE in FEA-CT cells. The TNF-alpha concentrations in the culture supernatants of BMMC+FEA-C were higher than those of BMMC+FEA-A or BMMC+FEA-CT, and addition of anti-TNF antibodies to the cultures blocked the CPE. These data support the hypothesis that macrophages exposed to FeLV-C cause CPE in co-cultures of BMMC and FEA cells by a mechanism involving TNF-alpha. It is suggested that TNF-alpha may be involved in the suppression of hematopoiesis in cats which develop FeLV-C induced erythroid aplasia.


Operant conditioning and assessment of stereopsis in young children.
Stereposis was assessed in 94 children ages 2--5 yr using random-dot stereograms (RDSs) and operant conditioning. After five traditional screening tests of stereopsis, all children were trained to perform a match-to-sample discrimination task involving RDSs with and without lateral disparity. An added feature of the operant RDS task was the availability of monocular cue-fading for children who failed initial RDS testing. The operant RDS test facilitated stereopsis-based responding more than the traditional clinical tests did. This finding is interpreted as indicating the importance of such factors as attention, motivation, and language ability in the assessment of stereopsis in young children.


Integration of transcriptome and proteome profiles in placenta accreta reveals trophoblast over-migration as the underlying pathogenesis.
Placenta accreta (PA) is a major cause of maternal morbidity and mortality in modern obstetrics, few studies have explored the underlying molecular mechanisms. In our study, transcriptome and proteome profiling were performed in placental tissues from ten participants including five cases each in the PA and control groups to clarify the pathogenesis of PA. We identified differential expression of 37,743 transcripts and 160 proteins between the PA and control groups with an overlap rate of 0.09%. The 33 most-significant transcripts and proteins were found and further screened and analyzed. Adhesion-related signature, chemotaxis related signatures and immune related signature were found in the PA group and played a certain role. Sum up two points, three significant indicators, methyl-CpG-binding domain protein 2 (MeCP2), podocin (PODN), and apolipoprotein D (ApoD), which participate in "negative regulation of cell migration", were downregulated at the mRNA and protein levels in PA group. Furthermore, transwell migration and invasion assay of HTR-8/SVneo cell indicated the all of them impaired the migration and invasion of trophoblast. A poor correlation was observed between the transcriptome and proteome data and MeCP2, PODN, and ApoD decreased in transcriptome and proteome profiling, resulting in increased migration of trophoblasts in the PA group, which clarify the mechanism of PA and might be the biomarkers or therapy targets in the future.


Establishment and characterization of a human cell line from a serous papillary endometrial carcinoma.
The cell line SPEC-1, derived from a human serous papillary endometrial carcinoma (SPEC), has been established and repetitively subcultured for over 18 months. SPEC is a clinically aggressive histologic variant of endometrial adenocarcinoma with a significantly poorer prognosis. The SPEC cells exhibit morphologic and ultrastructural characteristics of transformed epithelial cells. The cells were further characterized with regard to growth kinetics, histochemistry, karyotype, and tumorigenicity. These studies indicate that several properties of the SPEC cells in culture contrast markedly with those of both typical endometrial adenocarcinoma cell lines and normal endometrial epithelia, as described in the literature. The most significant of these differences concern cytogenetic and ultrastructural features. The implications of these unique characteristics are discussed with regard to the relationship they may have to the unusually aggressive biological behavior of this tumor cell type in vivo. This SPEC cell line should prove useful in future studies designed to determine important factors in the biological behavior of human tumor cells.


Transcription profile of DNA damage response genes at G₀ lymphocytes exposed to gamma radiation.
Ionizing radiation induces a plethora of DNA damages in human cells which may alter the level of mRNA expression. We have analyzed mRNA expression profile of DNA damage response genes involved in G(0)/G(1) check point pathway in whole blood to assess their radio-adaptive response, if any, to gamma radiation. Blood samples were collected from twenty-five random, normal, and healthy male donors with written informed consent and irradiated at doses between 0.1 and 2.0 Gy (0.7 Gy/min). DNA strand breaks were studied using comet assay, whereas DNA double-strand breaks were visualized using γH2AX as a biomarker. Dose response if any, at transcriptional level was studied for all these dose groups at 1 and 5-h post-irradiation. Adaptive response at transcriptional level was studied at three different priming doses (0.1, 0.3, and 0.6 Gy) separately followed by a challenging dose of 2.0 Gy after 4 h. For both the experiments, total RNA was isolated from PBMCs obtained from irradiated whole blood and reverse transcribed to cDNA. The level of mRNA expression of ATM, ATR, GADD45A, CDKN1A, P53, CDK2, MDM2, and Cyclin E was studied using real-time quantitative PCR. A significant dose-dependant increase in the percentage of DNA damage in tail was observed using comet assay. Similarly, increased number of foci was observed at γH2AX with increasing dose. At transcriptional level, a significant dose-dependent up-regulation at GADD45A, CDKN1A, and P53 genes up to 1.0 Gy was observed at 5-h post-irradiation (P ≤ 0.05). Radio-adaptive response at mRNA expression level was observed at CDK2, Cyclin E, and P53, whereas ATM, ATR, GADD45A, MDM2, ATM, and ATR have not shown any radio-adaptive changes in the expression profile. DNA damage response genes involved in G(0)/G(1) checkpoint pathway has important implications in terms of radiosensitivity in vivo and changes in the transcriptional profile might throw some new insights to understand the mechanism of adaptive response.


Microplastic accumulation by tube-dwelling, suspension feeding polychaetes from the sediment surface: A case study from the Norwegian Continental Shelf.
Sediment samples (0-1 cm) and tube-dwelling polychaetes from the Norwegian Continental Shelf and the Barents Sea were collected, including areas close to oil and gas installations and remote locations. Microplastics (≥45 μm) were found in quantifiable levels in 27 of 35 sediment samples, from 0.039 to 3.4 particles/gdw (dw = dry weight); and in 9 of 10 pooled polychaete samples, from 11 to 880 particles/gww (ww = wet weight). Concentrations were significantly higher in tube-dwelling polychaetes than sediments from the same locations (p<0.0097) by orders of magnitude. To quantify this factor increase in polychaetes, a Biota-Sediment Particle Enrichment Factor (BSPEF) is introduced, which ranged from 100 to 11000 gdw/gww (280-31000 gdw/gdw). Higher microplastic levels were observed in polychaete tube than in soft tissue (n=4). The feeding behavior and life cycle of tube-dwelling polychaetes could have an important influence on the transport, distribution and food-chain dynamics of microplastics on the seafloor.


2-Trifluoroacetylthiophene oxadiazoles as potent and selective class II human histone deacetylase inhibitors.
Trifluoroacetylthiophene carboxamides have recently been reported to be class II HDAC inhibitors, with moderate selectivity. Exploration of replacements for the carboxamide with bioisosteric pentatomic heteroaromatic like 1,3,4-oxadiazoles, 1,2,4-oxadiazoles and 1,3-thiazoles, led to the discovery that 2-trifluoroacetylthiophene 1,3,4-oxadiazole derivatives are very potent low nanomolar HDAC4 inhibitors, highly selective over class I HDACs (HDAC 1 and 3), and moderately stable in HCT116 cell culture.


Identification and fine mapping of AvrPi15, a novel avirulence gene of Magnaporthe grisea.
Avirulence of Magnaporthe grisea isolate CHL346 on rice cultivar GA25 was studied with 242 ascospore progenies derived from the cross CHL346 x CHL42. Segregation analysis of the avirulence in the progeny population was in agreement with the existence of a single avirulence (Avr) gene, designated as AvrPi15. For mapping the Avr gene, we developed a total of 121 microsatellite DNA markers [simple sequence repeat (SSR)], which evenly distributed in the whole-genome of M. grisea through bioinformatics analysis (BIA) using the publicly available sequence. Linkage analysis of the AvrPi15 gene with these SSR markers showed that six markers on chromosome 6, MS6-1, MS6-2, MS6-3, MS6-7, MS6-8 and MS6-10, were linked to the AvrPi15 locus. To further define the chromosomal location of the AvrPi15 locus, two additional markers, MS6-17 and STS6-6, which were developed based on the sequences of telomeric region 11 (TEL11), were subjected to linkage analysis. The results showed that MS6-17 and STS6-6 were associated with the locus by 3.3 and 0.8 cM, respectively. To finely map the Avr gene, two additional candidate avirulence gene (CAG) markers, CAG6-1 and CAG6-2, were developed based on the gene annotation of the sequence of TEL 11. Linkage analysis of the Avr gene with these two markers revealed that both of them completely cosegregated with the AvrPi15 locus. Finally, this locus was physically mapped into approximately 7.2-kb interval of the TEL11 by BIA using these sequence-ready markers. This is the key step toward positional cloning of the AvrPi15 gene.


Whole body autoradiographic study on the distribution of 14C-D-serine administered intravenously to rats.
The distribution of radioactivities in rats following intravenous administration of 14C-D- or -L-serine was investigated by whole body autoradiography. The radioactivities were distributed throughout the whole body in both cases with the greatest amount being found in the pancreas. D- and L- Serine levels in the pancreas were determined by high-performance liquid chromatography with a chiral column which revealed, for the first time, the existence of D-serine in the rat pancreas (12.6 +/- 7.90 nmol/g wet tissue) together with a much higher concentration (924 +/- 116 nmol/g) of L-serine. The results suggested that exogenous D-serine of dietary origin contributed at least in part to the D-serine levels found in mammalian tissues. The accumulation of radioactivity in the kidney, especially in the corticomedullary area, even at 24 hr after administration of 14C-D-serine suggested a possible link between acute necrosis of the renal proximal tubules and the administration of a large dose of D-serine [Am J Pathol 77: 269-282 (1974)].


Triplet and ground state potential energy surfaces of 1,4-diphenyl-1,3-butadiene: theory and experiment.
Relative energies of the ground state isomers of 1,4-diphenyl-1,3-butadiene (DPB) are determined from the temperature dependence of equilibrium isomer compositions obtained with the use of diphenyl diselenide as catalyst. Temperature and concentration effects on photostationary states and isomerization quantum yields with biacetyl or fluorenone as triplet sensitizers with or without the presence of O(2), lead to significant modification of the proposed DPB triplet potential energy surface. Quantum yields for ct-DPB formation from tt-DPB increase with [tt-DPB] revealing a quantum chain process in the tt --> ct direction, as had been observed for the ct --> tt direction, and suggesting an energy minimum at the (3)ct* geometry. They confirm the presence of planar and twisted isomeric triplets in equilibrium (K), with energy transfer from planar or quasi-planar geometries (quantum chain events from tt and ct triplets) and unimolecular decay (k(d)) from twisted geometries. Starting from cc-DPB, varphi(cc-->tt) increases with increasing [cc-DPB] whereas varphi(cc-->ct) is relatively insensitive to concentration changes. The concentration and temperature dependencies of the decay rate constants of DPB triplets in cyclohexane are consistent with the mechanism deduced from the photoisomerization quantum yields. The experimental DeltaH between (3)tt-DPB* and (3)tp-DPB*, 2.7 kcal mol(-1), is compared with the calculated energy difference [DFT with B3LYP/6-31+G(d,p) basis set]. Use of the calculated DeltaS = 4.04 eu between the two triplets gives k(d) = (2.4-6.4) x 10(7) s(-1), close to 1.70 x 10(7) s(-1), the value for twisted stilbene triplet decay. Experimental and calculated relative energies of DPB isomers on the ground and triplet state surfaces agree and theory is relied upon to deduce structural characteristics of the equilibrated conformers in the DPB triplet state.


India: Court upholds patent law denying patents for slightly modified versions of existing drugs.
In August 2007, the Madras High Court struck down a petition by the Swiss pharmaceutical company Novartis to declare the anti-evergreening provision in Indian patent law invalid. Evergreening is the practice of effectively extending the patent on a drug by filing a new patent for a marginal modification to that drug, such as a change in its shape, dosing range or color. The Court's decision is critical for global access to essential medicines in the form of affordable generic drugs from India


Crystal structure of the Oxytricha nova telomere end binding protein complexed with single strand DNA.
Telomeres are specialized protein-DNA complexes that compose the ends of eukaryotic chromosomes. Telomeres protect chromosome termini from degradation and recombination and act together with telomerase to ensure complete genome replication. We have determined the crystal structure of the two-subunit Oxytricha nova telomere end binding protein (OnTEBP) complexed with single strand telomeric DNA at 2.8 A resolution. The structure reveals four oligonucleotide/oligosaccharide-binding folds, three of which form a deep cleft that binds the ssDNA, and a fourth that forms an unusual protein-protein interaction between the alpha and beta subunits. This structure provides a molecular description of how the two subunits of OnTEBP recognize and bind ssDNA to form a sequence-specific, telomeric nucleoprotein complex that caps the very 3' ends of chromosomes.


IP3R deficit underlies loss of salivary fluid secretion in Sjögren's Syndrome.
The autoimmune exocrinopathy, Sjögren's syndrome (SS), is associated with secretory defects in patients, including individuals with mild lymphocytic infiltration and minimal glandular damage. The mechanism(s) underlying the secretory dysfunction is not known. We have used minor salivary gland biopsies from SS patients and healthy individuals to assess acinar cell function in morphologically intact glandular areas. We report that agonist-regulated intracellular Ca(2+) release, critically required for Ca(2+) entry and fluid secretion, is defective in acini from SS patients. Importantly, these acini displayed reduction in IP3R2 and IP3R3, but not AQP5 or STIM1. Similar decreases in IP3R and carbachol (CCh)-stimulated [Ca(2+)]i elevation were detected in acinar cells from lymphotoxin-alpha (LTα) transgenic (TG) mice, a model for (SS). Treatment of salivary glands from healthy individuals with LT α, a cytokine linked to disease progression in SS and IL14α mice, reduced Ca(2+) signaling. Together, our findings reveal novel IP3R deficits in acinar cells that underlie secretory dysfunction in SS patients.


Chloramphenicol acetyltransferase expression in marine Rhodobacter sp. NKPB 0021 by use of shuttle vectors containing the minimal replicon of an endogenous plasmid.
A vector, pUK318, was constructed to allow the expression of foreign genes in the marine photosynthetic bacterium Rhodobacter sp. NKPB 0021. This strain has been cured of its two endogenous plasmids. pUK318 consists of a 2.3-kb PstI-BamHI restriction fragment, containing a marine Rhodobacter plasmid replication region, cloned into pUC18. This fragment was derived from plasmid pRD31, a 3.1-kb endogenous plasmid purified from the marine strain Rhodobacter sp. NKPB 043402. A kanamycin resistance gene from Tn903 was cloned into the PstI restriction site to provide antibiotic selection. pUK318 was transferred to Rhodobacter sp. NKPB 0021 by transformation, and efficiencies of 7.2 x 10(-5) were obtained. Furthermore, pUK318 was stably maintained when transformants were grown either heterotrophically or photosynthetically in the absence of antibiotics. pUK318 was used to express the Escherichia coli chloramphenicol acetyl transferase (CAT) gene in Rb. NKPB 0021. Transformants expressed a maximum CAT activity of 1.12 mmol/min/g dry cells. In addition, the DNA region essential for pUK318 replication in Rb. NKPB 0021 was localized to a 1.36-kb HincII-PstI fragment. This is the first report of a plasmid vector containing a marine Rhodobacter-specific replicon that allows stable expression of foreign genes in the absence of antibiotic selection.


Tales from previous times: important eponyms in pediatric surgery.
The use of eponyms in medicine has a long and captivating tradition, which applies to pediatric surgery as well. Unfortunately, even though these eponyms are widely used, oftentimes the fascinating personalities and lives behind these names remain unrecognized or underappreciated, especially among residents, fellows and younger-generation pediatric surgeons. Therefore, in this article, we review 15 names that are frequently used as eponyms in modern pediatric surgery and hereby enlighten the personalities behind them. Given their particular frequency, we choose the following eponyms: Ramstedt pylorotomy, Nissen fundoplication, Murphy's sign and sequence, McBurney's sign and incision, Meckel's diverticulum, Kasai portoenterostomy, Ladd's procedure, Morgagni and Bochdalek hernia, Ravitch operation, Nuss procedure, Hirschsprung disease, Swenson pullthrough, Peña procedure and Wilms tumor. A detailed description of the historical importance of these personalities and their contribution to our field is given. Without the appropriate historical background, it is difficult for the current younger and next generation pediatric surgeons to grasp the full spectrum of the ongoing progress in our field. Therefore, our article conveys not only important insight into the past, but also provides young surgeons with an important historical perspective essential to understand the current and future developments in modern pediatric surgery.


Computer simulation of optimal lipped polyethylene liner orientation against prosthetic impingement.
Lipped or elevated acetabular liners are to improve posterior stability and are widely used in hip arthroplasty. However, concerns of increasing impingement exist when using such liners and optimal orientation of the elevated rim remains unknown. We aimed to identify the impact of lipped liner on the range of motion (ROM) before impingement and propose its optimal orientation. An isochoric three-dimensional model of a general hip-replacement prosthesis was generated, and flex-extension, add-abduction and axial rotation were simulated on a computer. The maximum ROM of the hip was measured before the neck impinged on the liner. Different combinations of acetabular anteversion angles ranging from 5 to 30 degrees, and lipped liner orientations from posterior to anterior were tested. When acetabular anteversion was 10 or 15 degrees, placing the lip of the liner in the posterosuperior of the acetabulum allowed satisfactory ROM in all directions. When acetabular anteversion was 20 degrees, extension and external rotation were restricted. Adjusting the lip to the superior restored satisfactory ROM. When acetabular anteversion was 25 degrees, only placing the lip into the anterosuperior could increase extension and external rotation to maintain satisfactory ROM. This study showed that optimal lipped liner orientation should depend on acetabular anteversion. When acetabular anteversion was smaller than 20 degrees, placing lip in the posterior allowed an optimally ROM. When acetabular anteversion was greater than 20 degrees, adjusting lip to the anterior allowed a comprehensive larger ROM to avoid early impingement.


Short-term efficacy of botulinum toxin a for refractory overactive bladder in the elderly population.
We determined the efficacy of intravesical botulinum toxin A injection for refractory overactive bladder in elderly patients. Patients 75 years or older with refractory urinary urgency were prospectively evaluated and offered treatment of symptoms with botulinum toxin A. A voiding log was obtained and urodynamics were performed before treatment. Patients underwent injection of 200 U botulinum toxin A (Botox(R)) into the detrusor muscle at 20 sites under cystoscopic guidance. Patients were followed postoperatively for evidence and duration of success, and treatment related complications. From January 2006 to June 2007, 18 females and 3 males with a mean age of 81.2 years (range 75 to 92) in whom detrusor overactivity was confirmed on urodynamics and who were refractory to or intolerant of antimuscarinics were treated with intravesical botulinum toxin A. Preoperatively the mean +/- SD number of daily voids was 11.4 +/- 1.67 and the mean number of pads per day was 4.0 +/- 0.89. One month after treatment 16 of the 21 patients (76%) reported greater than 50% improvement in symptoms after 1 injection. Specifically there was a significant improvement in the mean number of voids per day (5.19 +/- 0.83, p <0.001) and in the number of pads used daily (1.3 +/- 0.60, p <0.001). Two of the remaining 5 patients demonstrated greater than 50% improvement following repeat injection, while 3 did not show improvement after 2 injections. Mean time to deterioration was 7.12 months. There were no treatment related complications. Intravesical botulinum toxin A for detrusor overactivity in the elderly population appears to be efficacious and durable. Given its low incidence of adverse events, it should be considered a viable treatment option in this population.


Teenage pregnancy and timing of first marriage in Cameroon-What has changed over the last three decades, and what are the implications?
The consequences of teenage childbearing on the health of mothers and children, and on girls' schooling have been documented in many studies. The objectives of this study are to: 1) examine trends and differentials in teenage motherhood in Cameroon, with a distinction between premarital and marital teenage pregnancy; and 2) investigate trends and differentials in the length of time to marriage following a premarital teenage pregnancy. We use data from five demographic and health surveys (DHS) conducted in Cameroon between 1991 and 2018. Teenage pregnancy, defined as first pregnancy occurring before the age of 20 years, is recode as a trichotomous variable (0 = No teenage pregnancy; 1 = marital teenage pregnancy; 2 = premarital teenage pregnancy). Time from first premarital teenage pregnancy to first marriage is analyzed as a continuous variable. The percentage of women who experienced a marital teenage pregnancy declined from 39.6% to 26.4% between 1991 and 2018. After an initial drop between 1991 and 2004, premarital teenage pregnancy stabilized at about 25%. Women with intermediate levels of schooling were more likely to experience a premarital pregnancy than those with no schooling or higher secondary/tertiary education. The median length of time to first marriage following a premarital teenage pregnancy rose from 16 months in 1991 to 45 months in 2018. Further analysis suggests that marriage may be a more severe barrier to continued schooling than motherhood and that the desire to continue schooling is an important reason for postponing marriage for women who have given birth. Besides strengthening interventions to curb adolescent pregnancy, efforts should be made to support families, communities and schools to help adolescent mothers return to school, prevent future unintended pregnancies, and delay further family formation. Accessibility to youth-friendly FP/RH services should be addressed.


Evaluation of intracellular lipid bodies in Chlamydomonas reinhardtii strains by flow cytometry.
A comparative study of Chlamydomonas reinhardtii wild type CC124 and a cell wall-less mutant sta6-1 is described using FACS in conjunction with two different lipophilic fluorescent dyes, Nile Red and BODIPY 505/515. The results indicate that BODIPY 505/515 is more effective for the vital staining of intracellular lipid bodies and single cell sorting than Nile Red. While BODIPY 505/515 stained cells continued to grow after single cell sorting using FACS, Nile Red stained cells failed to recover from sorting. In addition, a comprehensive study was performed to establish a quantitative baseline for future studies for either lipid accumulation and/or microalgal growth by measuring various parameters such as cell count, size, fatty acid contents/composition, and optical/confocal images of the wild type and mutant.


Paediatric thyroidectomy: When and why? A 25-year institutional experience.
Thyroidectomy in paediatric patients is relatively uncommon. In this study, we reviewed our experience of thyroidectomy in children and identified risk factors associated with postoperative complications. We performed a retrospective analysis of paediatric patients who had thyroidectomy in our institution between April 1995 and January 2021. Demographic data, preoperative cytological findings, indications of surgery, surgical complications and histological results were analysed. A total of 87 paediatric patients with 92 thyroidectomy were identified. The indications for surgery were Graves' disease refractory to medical treatments (40.2%), benign thyroid nodules or multinodular goitre (26.4%), thyroid carcinoma (23.0%) and multiple endocrine neoplasm type 2A syndrome (10.3%). Patients presented with thyroid nodules or cervical lymph nodes had a 43.9% risk of malignancy. 66 total thyroidectomy were done with median operation time of 134 min(102-170), while 26 hemi-thyroidectomy were performed (Right side 12/92, Left side 14/92) with median operation time of 65 min(49-102). The median postoperative hospital stay was 2 days(1-4). Intraoperative neck dissection (p = 0.003), drain insertion (p = 0.001) and hypocalcaemia requiring medical treatment (p = 0.004) were associated with longer hospital stay. The median follow-up was 11.3 years (3.0-16.8). 32% patients had immediate postoperative hypocalcaemia and 8% patients had permanent hypoparathyroidism. Transient vocal cord palsy was found in 3 patients(3%) and all resolved within 5-month time upon reassessment direct laryngoscopy. The use of intraoperative recurrent laryngeal nerve monitoring was associated with less vocal cord palsy (p = 0.022). The median disease-free survival was 13.7 years(7.4-17.7) for patients operated for well-differentiated thyroid carcinoma(WDTC). amongst the 9 patients who had prophylactic total thyroidectomy for MEN2A syndrome, 44% were found to have medullary thyroid microcarcinomas on pathology. Surgical management of paediatric thyroid disease can be complex. Postoperative hypocalcaemia and vocal cord palsy were usually transient after total thyroidectomy. The use of intraoperative recurrent laryngeal nerve monitoring had resulted in less vocal cord palsy. Long-term disease-free survival of patients with thyroid cancer had been achieved with multi-disciplinary management in our centre. Retrospective Comparative Study; Level III.


Incidental demyelination in magnetic resonance imaging and 10-year risk of multiple sclerosis: A data lake cohort study.
There is an absence of data from large population-based cohort studies on the incidence of radiologically isolated syndrome (RIS). The incidence of RIS and the subsequent risk for multiple sclerosis (MS) were investigated. A population-based, retrospective cohort study was conducted using a data-lake-based analysis of digitalized radiology reports. All brain and spinal cord magnetic resonance imaging (MRI) in people aged 16-70 during the years 2005-2010 (n = 102,224) were screened using optimized search terms to detect cases with RIS. The subjects with RIS were followed up until January 2022. The cumulative incidence of RIS was 0.03% when all MRI modalities were included and 0.06% when only brain MRI was included according to MAGNIMS 2018 recommendation criteria. With the Okuda 2009 criteria, the respective figures were 0.03% and 0.05% (86% concordance). The overall risk for MS after RIS was similar, 32% by using the MAGNIMS and 32% by using the Okuda definition of RIS. Individuals aged <35.5 years exhibited the most significant predisposition to MS (80%), whilst those >35.5 years had less than 10% risk of MS. MS diagnosed after RIS constituted 0.8% of the incident MS cases in the population during 2005-2010. A population-wide context was provided for the incidence of RIS and its relationship to MS. MAGNIMS recommendations were only slightly more sensitive to detect RIS compared to the Okuda criteria. RIS has a subtle effect on the overall incidence of MS, yet the risk for MS in individuals under the age of 35.5 years is substantial.


A simplified stimulus value notation using preferred stimulus combinations for Goldmann quantitative perimetry.
In an effort to return to the simplicity intended by Goldmann, the authors propose adoption of a two-digit stimulus value (SV) nomenclature for defining targen area luminance and contrast on a properly standardized Goldmann-type perimeter. The system is designed to aid the examiner in target selection, mental interpolation and isopter construction, and to facilitate computer manipulation.


Fluorescence Readout of a Patch Clamped Membrane by Laser Scanning Microscopy.
In this chapter, we describe how to shield a patch of a cell membrane against extracellularly applied chemoattractant stimuli. Classical patch clamp methodology is applied to allow for controlled shielding of a membrane patch by measuring the seal resistivity. In Dictyostelium cells, a seal resistivity of 50 MΩ proved to be tight enough to exclude molecules from diffusing into the shielded membrane region. This allowed for separating a shielded and a non-shielded region of a cell membrane to study the spatiotemporal dynamics of intracellular chemotactic signaling events at the interface between shielded and non-shielded areas. The spatiotemporal dynamics of signaling events in the membrane was read out by means of appropriate fluorescent markers using laser scanning confocal microscopy.


Trichostatin A modulates the macrophage phenotype by enhancing autophagy to reduce inflammation during polymicrobial sepsis.
Sepsis is a syndrome of life-threatening organ dysfunction caused by dysregulated host responses to infection. Macrophage polarization is a key process involved in the pathogenesis of sepsis. Recent evidence has demonstrated that autophagy participates in the regulation of macrophage polarization in different phases of inflammation. Here, we investigated whether trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, promotes the macrophage M2 phenotype by enhancing autophagy to counteract excessive inflammation in a cecal ligation and puncture (CLP) mouse model. TSA stimulation increased the proportions of M2 marker (CD206, CD124 and CD23)-labeled RAW264.7 macrophages. Furthermore, with increasing TSA doses, autophagy was enhanced gradually. Interestingly, the autophagy activator rapamycin (Rap), also known as an mTOR inhibitor, unexpectedly decreased the proportions of M2 marker-labeled macrophages. However, TSA treatment reversed the Rap-induced decreases in CD206-labeled macrophages. Next, we stimulated different groups of RAW264.7 cells with the autophagy inhibitors MHY1485 or 3-methyladenine (3-MA). Inhibition of autophagy at any stage in the process suppressed TSA-induced macrophage M2 polarization, but the effect was not associated with mTOR activity. In vivo, TSA administration promoted peritoneal macrophage M2 polarization, increased LC3 II expression, attenuated sepsis-induced organ (lung, liver and kidney) injury, and altered systemic inflammatory cytokine secretion. However, 3-MA abolished the protective effects of TSA in CLP mice and decreased the number of M2 peritoneal macrophages. Therefore, TSA promotes the macrophage M2 phenotype by enhancing autophagy to reduce systemic inflammation and ultimately improves the survival of mice with polymicrobial sepsis.


Evaluating a modified behavioral skills training procedure for teaching poison prevention skills to children with autism.
Accidental poisonings can occur for children with disabilities as a result of ingesting household products, such as medications and cleaning chemicals, if the products are not stored safely. Behavioral approaches such as behavioral skills training (BST) have been used in previous research to teach safety skills to children with disabilities. However, research suggests that BST is not always effective for teaching safety skills to children with and without disabilities. Thus, the purpose of this study was to evaluate the efficacy of a modified BST package that incorporated a system of least prompts. A nonconcurrent multiple baseline design across participants was used to evaluate the effects of intervention with three 6-8-year-old children with autism. Results showed that BST with the prompt sequence increased poison prevention skills for all 3 participants and the skills maintained at follow-up.


Expanding diversity of glycan receptor usage by rotaviruses.
Rotaviruses are major etiologic agents of severe gastroenteritis in human and animals, infecting the mature intestinal epithelium. Their attachment to host cell glycans is mediated through the virion spike protein. This is considered to be crucial for successful host cell invasion by rotaviruses. Recent studies have greatly expanded our understanding of the diversity of glycans commonly recognized by rotaviruses, to include the ganglioside GM1a and histo-blood group antigens. Here, these new findings are integrated with advances in knowledge of spike protein structure, rotavirus entry mechanisms and innate intestinal immunity to provide an overview of the variety of rotavirus glycan receptors and their roles in cell penetration, host tropism and pathogenesis.


Lignans and sesquiterpenoids from Lactuca sibirica.
From aerial parts of Lactuca sibirica, two new and one known furofuran lignans were isolated, together with four known lactucin-like guaianolides. On the basis of spectral data, the new lignans were characterized as acylated glucopyranosides of 4alpha, 8alpha-dihydroxypinoresinol.


Theoretical study on ten Λ-S states of Si2(-) anion: potential energy curves, spectroscopy and spin-orbit couplings.
The potential energy curves (PECs) of seventeen Ω states generated from the ten Λ-S states of the Si2(-) anion are studied in detail using an ab initio quantum chemical method for the first time. The PECs are calculated for internuclear separations from 0.10 to 1.20 nm by the complete active space self-consistent field method, which is followed by the internally contracted multireference configuration interaction approach with the Davidson modification. The spin-orbit coupling is accounted for by the Breit-Pauli Hamiltonian. Core-valence correlation and scalar relativistic corrections are considered. Core-valence correlation corrections are included using an aug-cc-pCVTZ basis set. Scalar relativistic correction calculations are made with the third-order Douglas-Kroll Hamiltonian approximation at the level of a cc-pV5Z basis set. Obvious effect of core-valence correlation corrections on the PECs is observed, in particular for the two lowest (2)Πu and (2)Σg(+) Λ-S states. All the PECs are extrapolated to the complete basis set limit. The lowest (2)Πu Λ-S state is found to be the ground state of Si2(-) anion. The convergence observations of present calculations are made and the convergent behavior is discussed with respect to the basis set and level of theory. The effects of core-electron correlations on the energy splitting are studied by the all-electron aug-cc-pCVTZ basis set. Using these PECs, the spectroscopic parameters of Λ-S and Ω states involved are determined. The vibrational manifolds are evaluated for each Λ-S and Ω state of non-rotation Si2(-) anion. It shows that the spectroscopic parameters and molecular constants of ten Λ-S and seventeen Ω states reported here can be expected to be reliable predicted ones.


Differential scanning calorimetry to investigate G-quadruplexes structural stability.
Differential Scanning Calorimetry (DSC) is a straightforward methodology to characterize the energetics of thermally-induced transitions of DNA and other biological macromolecules. Therefore, DSC has been used to study the thermodynamic stability of several nucleic acids structures. G-quadruplexes are among the most important non-canonical nucleic acid architectures that are receiving great consideration. This article reports examples on the contribution of DSC to the knowledge of G-quadruplex structures. The selected case studies show the potential of this method in investigating the structure stability of G-quadruplex forming nucleic acids, and in providing information on their structural complexity. Indeed, DSC can determine thermodynamic parameters of G-quadruplex folding/unfolding processes, but it can also be useful to reveal the formation of multiple conformations or the presence of intermediate states along the unfolding pathway, and to evaluate the impact of chemical modifications on their structural stability. This article aims to show that DSC is an important complementary methodology to structural techniques, such as NMR and X-ray crystallography, in the study of G-quadruplex forming nucleic acids.


Patient-Provider Social Concordance and Health Outcomes in Patients with Type 2 Diabetes: a Retrospective Study from a Large Federally Qualified Health Center in Connecticut.
This study was conducted to better understand the relationship between patient-provider social concordance and cardiovascular risk factor control in patients with type 2 diabetes. A retrospective study was conducted on adult patients with type 2 diabetes receiving care at Community Health Center, Inc. between July 1, 2012, and June 30, 2013. We utilized a composite score comprised of four social dimensions-age, gender, language, and race/ethnicity-to determine patient-provider social concordance (SC) and used binary logistic regression to relate SC and other potentially influential covariates with cardiovascular outcomes of interest (HgA1c, LDL, BP control). Patients were more likely to have uncontrolled BP if they were in low or medium SC dyads with their providers (OR = 0.689, 95 % CI = 0.480, 0.989; OR = 0.673, 95 % CI 0.486, 0.931), and they were more likely to have controlled BP and LDL in the setting of care continuity with a regular provider (OR = 1.069, 95 % CI 1.005, 1.136; OR = 1.113, 95 % CI 1.048, 1.182). Certain health outcomes may be susceptible to patient-provider social concordance or discordance. Continuity of care may serve a protective role in offsetting effects of patient-provider social mismatching.


Directed percolation identified as equilibrium pre-transition towards non-equilibrium arrested gel states.
The macroscopic properties of gels arise from their slow dynamics and load-bearing network structure, which are exploited by nature and in numerous industrial products. However, a link between these structural and dynamical properties has remained elusive. Here we present confocal microscopy experiments and simulations of gel-forming colloid-polymer mixtures. They reveal that gel formation is preceded by continuous and directed percolation. Both transitions lead to system-spanning networks, but only directed percolation results in extremely slow dynamics, ageing and a shrinking of the gel that resembles synaeresis. Therefore, dynamical arrest in gels is found to be linked to a structural transition, namely directed percolation, which is quantitatively associated with the mean number of bonded neighbours. Directed percolation denotes a universality class of transitions. Our study hence connects gel formation to a well-developed theoretical framework, which now can be exploited to achieve a detailed understanding of arrested gels.


Ultrasound-Guided Ankle Lateral Ligament Stabilization.
Ultrasound (US) is an increasingly popular imaging modality currently used both in clinics and operating rooms. The purpose of this review is to appraise literature describing traditional lateral ankle stabilization techniques and discuss potential advantages of US-guided ankle lateral ligament stabilization. In addition, albeit limited, we will describe our experiences in perfecting this technique. To date, the modified open Broström-Gould technique remains as the gold standard surgical treatment for chronic ankle instability (CAI). In the past decade, modifications of this technique have been done, from a combination of arthroscopic and open procedure to an all-inside arthroscopic technique with a goal of minimizing wound complications, better outcomes, and earlier return to activity. Recently, the use of US as an adjunct to surgical procedures has gained popularity and several novel techniques have been described. The use of US in lateral ankle stabilization could allow accurate placement of the suture anchor at the anatomical attachment of the anterior talofibular ligament (ATFL) without iatrogenic damage to the neurovascular structures such as anterolateral malleolar artery, superficial peroneal nerve, and sural nerve. In summary, the use of US in ankle lateral ligament stabilization is a promising new micro-invasive technique. The theoretical advantages of US-guided ankle lateral ligament stabilization include direct visualization of desired anatomical landmarks and structures which could increase accuracy, decrease iatrogenic neurovascular damage, minimize wound complications, and improve outcomes.


Do pharmacist employers prefer or require board certification?
The pharmacy profession has promoted the value of board certification, yet the impact of board certification on employment opportunities for pharmacists is largely unknown. This study aims to report employer preferences for board certification as indicated on job listings. A national search for pharmacy job postings from November 16, 2018, to March 8, 2019 was performed by reviewing websites and attending conferences. For each listing, data on the status of required, preferred, or neither for board certification, type of specialty, and the practice setting were recorded. Employers listing a preference or requirement for board certification were asked to complete a questionnaire to ascertain reasons for requiring or preferring board certification. The study includes job listings from various non-community pharmacy employers. The outcome measures were to (1) assess if board certification is required/preferred by pharmacist employers, (2) determine if predominantly clinical versus nonclinical job listings include board certification as a requirement or preference, (3) differentiate practice area and specialty with regard to requirement or preference for board certification, and (4) evaluate reasons behind the requirement or preference. More employers did not prefer or require board certification compared with those who listed such preferences (51% vs. 49%). Employers of jobs with a predominantly clinical component were more likely to require or prefer board certification (53% vs. 27% [no clinical component]). The board certification most often requested was pharmacotherapy, followed by oncology and psychiatry. Most employers (98%) who prefer board certification and those who require board certification (79%) believe that credentialing verifies competence in a specialty practice (P = 0.03) and ensures acquisition of knowledge and skills within the specialized field (P = 0.03). More pharmacy employers do not require or prefer board certification. Employers are more likely to prefer or require board certification for predominantly clinical jobs.