Effect of ornithine decarboxylase inhibitor on tetragastrin treatment of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.
The effects of combined administration of tetragastrin and the ornithine decarboxylase inhibitor 1,3-diaminopropane (DAP) on the incidence and number of gastric cancers induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the BUdR labelling indices of the fundic and antral mucosae, were investigated in inbred Wistar rats. Rats were given drinking water containing 2.5 g/l of DAP ad libitum and received alternate-day injections of 1 mg/kg body weight of tetragastrin in depot form after 25 weeks of oral treatment with MNNG. At week 52, prolonged administration of tetragastrin alone resulted in a significant reduction in the incidence and number of gastric cancers and a significant increase or decrease in the labelling indices of the fundic and antral mucosae, respectively. Concomitant administration of tetragastrin and DAP had no effect on the inhibition by tetragastrin of gastric carcinogenesis. With this treatment, the labelling index was significantly reduced in the fundic mucosa but not in the antral mucosa. These results suggest that ODC inhibitor does not attenuate tetragastrin inhibition of gastric carcinogenesis, and that anti-trophic action of tetragastrin on antral mucosa may be related to tetragastrin inhibition of gastric carcinogenesis.


Anti-Inflammatory and Antioxidant Actions of Copaiba Oil Are Related to Liver Cell Modifications in Arthritic Rats.
The present study investigated the action of copaiba oil (Copaifera reticulata) on the systemic inflammation, oxidative status, and liver cell metabolism of rats with adjuvant-induced arthritis. The later is an experimental autoimmune pathology that shares many features with the human rheumatoid arthritis. Holtzman rats were distributed into the following groups: control (healthy) rats; control rats treated with copaiba oil at the doses of 0.58 and 1.15 g · kg-1 , arthritic rats, and arthritic rats treated with copaiba oil (0.58 and 1.15 g · kg-1 ). The oil was administrated orally once a day during 18 days after arthritis induction. Both doses of copaiba oil improved the paw edema and the dose of 0.58 mg · kg-1 improved the swollen adrenals and lymph nodes besides decreasing the plasmatic myeloperoxidase activity (-30%) of arthritic rats. Copaiba oil (1.15 g · kg-1 ) abolished the increases of protein carbonyl groups and reactive oxygen species in the liver and both doses increased the liver GSH content and the catalase activity in arthritic rats. Copaiba oil (1.15 g · kg-1 ) decreased glycolysis (-65%), glycogenolysis (-58%), and gluconeogenesis (-30%) in the liver of arthritic animals. However, gluconeogenesis was also diminished by the treatment of control rats, which presented lower body weight gain (-45%) and diminished number of hepatocytes per liver area (-20%) associated to higher liver weight (+29%) and increased hepatocyte area (+13%). The results reveal that copaiba oil presented systemic anti-inflammatory and antioxidant actions in arthritic rats. These beneficial effects, however, were counterbalanced by harmful modifications in the liver cell metabolism and morphology of healthy control rats. J. Cell. Biochem. 118: 3409-3423, 2017. © 2017 Wiley Periodicals, Inc.


2 μm passively mode-locked thulium-doped fiber lasers with Ta2AlC-deposited tapered and side-polished fibers.
In this work, mode-locked thulium-doped fiber lasers operating in the 2 µm wavelength region were demonstrated using tantalum aluminum carbide (Ta2AlC)-based saturable absorbers (SAs) utilizing the evanescent wave interaction. The Ta2AlC MAX Phase was prepared by dissolving the Ta2AlC powder in isopropyl alcohol and then deposited onto three different evanescent field-based devices, which were the tapered fiber, side-polished fiber, and arc-shaped fiber. Flame-brushing and wheel-polishing techniques were used to fabricate the tapered and arc-shaped fibers, respectively, while the side-polished fiber was purchased commercially. All three SA devices generated stable mode-locked pulses at center wavelengths of 1937, 1931, and 1929 nm for the tapered, side-polished, and arc-shaped fibers. The frequency of the mode-locked pulses was 10.73 MHz for the tapered fiber, 9.58 MHz for the side-polished fiber, and 10.16 MHz for the arc-shaped fiber. The measured pulse widths were 1.678, 1.734, and 1.817 ps for each of the three SA devices. The long-term stability of the mode-locked lasers was tested for each configuration over a 2-h duration. The lasers also showed little to no fluctuations in the center wavelengths and the peak optical intensities, demonstrating a reliable, ultrafast laser system.


Integrating different tools and technologies to advance drinking water quality exposure assessments.
Contaminants in drinking water are a major contributor to the human exposome and adverse health effects. Assessing drinking water exposure accurately in health studies is challenging, as several of the following study design domains should be addressed as adequately as possible. In this paper, we identify the domains Time, Space, Data Quality, Data Accessibility, economic considerations of Study Size, and Complex Mixtures. We present case studies for three approaches or technologies that address these domains differently in the context of exposure assessment of drinking water quality: regulated contaminants in monitoring databases, high-resolution mass spectrometry (HRMS)-based wide-scope chemical analysis, and effect-based bioassay methods. While none of these approaches address all the domains sufficiently, together they have the potential to carry out exposure assessments that would complement each other and could advance the state-of-science towards more accurate risk analysis. The aim of our study is to give researchers investigating health effects of drinking water quality the impetus to consider how their exposure assessments relate to the above-mentioned domains and whether it would be worthwhile to integrate the advanced technologies presented into planned risk analyses. We highly suggest this three-pronged approach should be further evaluated in health risk analyses, especially epidemiological studies concerning contaminants in drinking water. The state of the knowledge regarding potential benefits of these technologies, especially when applied in tandem, provides more than sufficient evidence to support future research to determine the implications of combining the approaches described in our case studies in terms of protection of public health.


Assessment of a new RNA stabilizing reagent (Tempus Blood RNA) for minimal residual disease in onco-hematology using the EAC protocol.
Standardization efforts of real time quantitative PCR (RQ-PCR), such as the Europe Against Cancer (EAC) protocol, are actually essential. However, all the stages of the preanalytical phase (blood collection, conservation and procedures of cellular separation) which influence the ex vivo expression of many genes are not controlled. Various kits for stabilizing the RNA at the time of blood collection were developed: PAXgene Blood kit (Qiagen) and the new Tempus Blood RNA kit (Applied Biosystems). PAXgene Blood was already validated to monitor minimal residual disease (MRD) in onco-hematologic pathologies. In order to evaluate the Tempus Blood RNA kit, it was compared to unstabilized EDTA blood/Ficoll/TRIzol protocol and PAXgene Blood kit. The RNAs extracted by the different methods were assessed for quantity, quality and detection of control genes (GUS and ABL) and fusion gene transcripts BCR-ABL and TEL-AML1 by RQ-PCR. Our study shows that using the EAC protocol, the new Tempus Blood RNA kit allows the detection of fusion gene transcript with the same sensitivity as the two other protocols. Altogether, our data suggest the possible use of such a technology for MRD follow-up in myeloproliferative diseases and acute leukemias. So, further multicentric studies on leukemic patients should be performed to validate this technique in these applications.


Anti-Müllerian hormone predicts positive sperm retrieval in men with idiopathic non-obstructive azoospermia-findings from a multi-centric cross-sectional study.
Is it possible to identify a reliable marker of successful sperm retrieval (+SR) in men with idiopathic non-obstructive azoospermia (iNOA) undergoing microdissection testicular sperm extraction (mTESE)? A higher likelihood of +SR during mTESE is observed in men with iNOA and lower preoperative serum anti-Müllerian hormone (AMH) levels, with good predictive accuracy achieved using an AMH threshold of <4 ng/ml. AMH has been previously linked to +SR in men with iNOA undergoing mTESE prior to ART. A multi-centre cross-sectional study was carried out with a cohort of 117 men with iNOA undergoing mTESE at three tertiary-referral centres. Data from 117 consecutive white-European men with iNOA presenting for primary couple's infertility associated with a pure male factor at three centres were analysed. Descriptive statistics was applied to compare patients with negative (-SR) versus +SR at mTESE. Multivariate logistic regression models were fitted to predict +SR at mTESE, after adjusting for possible confounders. Diagnostic accuracy of the factors associated with +SR was assessed. Decision curve analyses were used to display the clinical benefit. Overall, 60 (51.3%) men had an -SR and 57 (48.7%) had a +SR at mTESE. Patients with +SR had lower levels of baseline AMH (P = 0.005) and higher levels of estradiol (E2) (P = 0.01). At multivariate logistic regression analysis, lower levels of AMH (odds ratio: 0.79; 95% CI: 0.64-0.93, P = 0.03) were associated with +SR at mTESE, after adjusting for possible confounders (e.g. age, mean testicular volume, FSH, and E2). A threshold of AMH <4 ng/ml achieved the highest accuracy for +SR at mTESE, with an AUC of 70.3% (95% CI: 59.8-80.7). Decision curve analysis displayed the net clinical benefit of using an AMH <4 ng/ml threshold. There is a need for external validation in even larger cohorts, across different centres and ethnicities. Systematic reviews and meta-analysis to provide high level of evidence are lacking in the context of AMH and SR rates in men with iNOA. Current findings suggest that slightly more than one in two men with iNOA had -SR at mTESE. Overall, men with iNOA with lower levels of AMH had a significantly higher percentage of successful SR at surgery. A threshold of <4 ng/ml for circulating AMH ensured satisfactory sensitivity, specificity, and positive predictive values in the context of +SR at mTESE. This work was supported by voluntary donations from the Urological Research Institute (URI). All authors declare no conflict of interest. N/A.


miR-324-5p Contributes to Cell Proliferation and Apoptosis in Pancreatic Cancer by Targeting KLF3.
Pancreatic cancer cells are characterized by high cell proliferation and low cell apoptosis, but the factors involved in these processes remain to be further studied. In this study, we report that miR-324-5p regulates the proliferation and apoptosis of pancreatic cancer cells through regulating the expression of Krüppel-like factor 3 (KLF3). In both pancreatic cancer tissues and cell lines, the levels of miR-324-5p are significantly increased. Inhibition of miR-324-5p represses cell proliferation but promotes cell apoptosis, whereas overexpression of miR-324-5p exerts the opposite effect. Furthermore, we identified KLF3, a factor regulating pancreatic cancer cell proliferation and apoptosis, as a new direct downstream target of miR-324-5p. Our results suggest that miR-324-5p plays an important role in pancreatic cancer cell proliferation and apoptosis via downregulating the expression of KLF3.


Tumour-to-tumour metastasis of laryngeal leiomyosarcoma to an axillary hibernoma.
Tumour-to-tumour metastasis is a rare, but well-recognised occurrence. This case report documents the metastasis of a primary laryngeal leiomyosarcoma to a hibernoma. We believe that this is the first recorded case of leiomyosarcoma metastasising to another neoplasm, and the first recorded case of a hibernoma acting as a recipient tumour for metastasis. This case study emphasises the importance of re-imaging a known benign mass in the presence of new symptoms in a patient with underlying malignancy, to ensure prompt diagnosis and management of potentially treatable metastasis. The imaging findings including whole body magnetic resonance imaging (MRI) staging, macroscopic and histological features are presented.


Rhodococcus equi: equine neutrophil chemiluminescent and bactericidal responses to opsonizing antibody.
The opsonic capacity of serum containing R. equi-specific antibody was compared with antibody-deficient sera using luminol-dependent chemilumenscence (LDCL) and bactericidal assays. These assays incorporated peripheral blood polymorphonuclear neutrophilic leukocytes (PMNL) exposed to R. equi opsonized with neonatal equine pre-colostral serum (control) or serum from foals with R. equi infections (principal). All sera were complement inactivated at 56 degrees C for 30 min. Bacteria were obtained from the lung of a foal with R. equi pneumonia. Neutrophils were obtained from one adult horse for LDCL and another for bactericidal assays. Chemiluminescence of PMNL exposed to R. equi opsonized with control or principal sera was measured in a liquid scintillation counter. Mean peak LDCL within 1 h was significantly (P less than 0.01) higher with principal sera (2.4 X 10(5) cpm) than with control sera (0.018 X 10(5) cpm). A radioisotope bactericidal assay was used to determine the effect of control or principal sera on PMNL capacity to kill R. equi. Mean peak percent kill of R. equi by PMNL within 2 h was significantly (P less than 0.01) higher with principal sera (95.2%) than with control sera (54.6%). Enzyme-linked immunosorbent assay (ELISA) values for R. equi-specific antibody were determined on all sera. Mean ELISA values were significantly (P less than 0.01) higher for principal sera (71.8) than for controls (0.0). This investigation documents the presence and biological effectiveness of opsonic activity in complement-inactivated sera from foals with R. equi infections and R. equi-specific antibody.


Some correlates of Al-Anon group membership.
A husband's membership in A.A. was related to greater marital happiness, superior ability as a father and less severe drinking problems.


The effects of colchicine and its derivates on the collagen biosynthesis in vitro.
Recent evidence shows that colchicine decreases collagen production and favourably influences some fibroproductive processes in experimental animal and clinical practice. In our study we investigated the influence of two colchicine derivates--demecolcine and desacetylcolchiceine--on the synthesis of collagen and non-collagen proteins in new born rat skin after the incubation of tissues slices with 14C-proline for 2 h. Collagen was separated in fractions soluble in either 0.45 M NaCl or 2% semi-carbazide that in an insoluble residue. Demecolcine (10(-3)--5.10(-5) M), desacetylcolchiceine (10(-2)--5.10(-4) M), as well as colchicine (10(-4)-10(-6)), inhibited the synthesis of soluble collagen, depending on the drug concentration in the incubation media. Higher concentrations of tested agents also decreased the formation of insoluble collagen. Significant inhibition of non-collagen protein synthesis was ascertained only in the presence of desacetylcolchiceine.


Psychotropic medication use and future unexplained and injurious falls and fracture amongst community-dwelling older people: data from TILDA.
Psychotropic medications (antidepressants, anticholinergics, benzodiazepines, 'Z'-drugs and antipsychotics) are frequently identified as Falls Risk Increasing Drugs. The aim of this study is to clarify the association of psychotropic medication use with future falls/fracture amongst community-dwelling older people. Participants ≥ 65 years from TILDA were included and followed from Waves 1 to 5 (8-year follow-up). Incidence of falls (total falls/unexplained/injurious) and fracture was by self-report; unexplained falls were falls not caused by a slip/trip, with no apparent cause. Poisson regression models reporting incidence rate ratios (IRR) assessed the association between medications and future falls/fracture, adjusted for relevant covariates. Of 2809 participants (mean age 73 years), 15% were taking ≥ 1 psychotropic medication. During follow-up, over half of participants fell, with 1/3 reporting injurious falls, over 1/5 reporting unexplained falls and almost 1/5 reporting fracture. Psychotropic medications were independently associated with falls [IRR 1.15 (95% CI 1.00-1.31)] and unexplained falls [IRR 1.46 (95% CI 1.20-1.78)]. Taking ≥ 2 psychotropic medications was further associated with future fracture (IRR 1.47 (95% CI 1.06-2.05)]. Antidepressants were independently associated with falls [IRR 1.20 (1.00-1.42)] and unexplained falls [IRR 2.12 (95% CI 1.69-2.65)]. Anticholinergics were associated with unexplained falls [IRR 1.53 (95% CI 1.14-2.05)]. 'Z'-drug and benzodiazepine use were not associated with falls or fractures. Psychotropic medications, particularly antidepressants and anticholinergic medications, are independently associated with falls and fractures. Regular review of ongoing need for these medications should therefore be central to the comprehensive geriatric assessment.


Association of urinary organophosphate esters level with sex steroid hormones levels in adult males: A nationwide study, NHANES 2013-2014.
Exposure to environmental pollution via different mechanisms is associated with multiple endocrine dysfunctions. Organophosphate esters (OPEs) are endocrine-disrupting chemicals that affect sex steroid hormones. We aimed to study the effect of OPEs and their metabolites, such as diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), and dibutyl phosphate (DBUP), on sex steroid hormones in males. This cross-sectional analytical study analyzed data from the 2013-2014 National Health and Nutrition Examination Survey among 763 male participants aged ≥20 years. The relationships between the metabolites of OPEs and total testosterone, estradiol, sex hormone-binding globulin, and the ratio of total testosterone to estradiol (a parameter derived from total testosterone and estradiol) were evaluated using multivariate linear regression models that were adjusted for potential confounders. A total of 763 participants, with a mean age of 44.59 (±15.59) years, were enrolled. Of these, 65.7% participants had non-Hispanic white ancestry, 9.83% had non-Hispanic black ancestry, and 15.97% had Hispanic ancestry. Participants with higher urinary level of DPHP had a lower level of total testosterone and estradiol. Moreover, higher urinary levels of BDCPP were associated with higher estradiol. According to our study, which is based on a representative population of US adults, exposure to OPEs was significantly associated with altered sex hormone levels (total testosterone and estradiol). Further studies focused on the underlying mechanisms regarding the association between each metabolite and sex steroid hormones are required.


Can older patients adopt and maintain a ketogenic diet? An observational study in support of clinical trials in older patients.
Ketogenic diets appear promising for obesity, diabetes, cancer, and other illnesses. Because older patients are more likely to contend with such illnesses and because of a paucity of dietary outcomes among these patients, we examined ketogenic diets in older patients.This multisite study focused on patients (≥65 years of age) on a ketogenic diet. Medical records were identified with the keywords "keto," "ketogenic," and "Atkins." Records were reviewed in detail with extraction of direct quotations to substantiate observations.We report on 200 consecutive patients with a median age of 70 years. Reasons for diet included weight loss, diabetes, and cancer; the majority remained on the diet for >1 month. In 134 (67%: 95% confidence interval: 60, 73%), the ketogenic diet appeared beneficial: 93 of 117 (79%) who sought weight loss lost weight ("She has lost 15 pounds and plans to lose another 8"); 36 of 67 (54%) who sought glucose control appeared to achieve the latter ("He has gone on a ketogenic diet and has been able to bring his sugars down significantly"); and 5 of 8 (63%) who sought improved cancer outcomes appeared to derive them ("He attributes part of the control of his cancer and increased QOL to adopting the keto for cancer diet"). Adverse events occurred in 30 patients (15%): dyslipidemia (n = 14), constipation (n = 9), sub-therapeutic international normalized ratio (n = 3), pancreatitis (n = 2), diarrhea (n = 1), and fatigue (n = 1).Trials that test ketogenic diets for a variety of illnesses should enroll older adults.


The effects of prior knowledge on the encoding of episodic contextual details.
A positive relationship between prior knowledge and item memory is a consistent finding in the literature. In the present study, we sought to determine whether this relationship extends to episodic details that are present at the time of encoding, namely source memory. Using a novel experimental design, we were able to show both between- and within-subjects effects of prior knowledge on source memory. Specifically, the results revealed that the degree of prior knowledge positively predicted memory for source specifying contextual details. In addition, by including two conditions in which attention was divided either at encoding or retrieval, we were able to show that prior knowledge influences memory by affecting encoding processes. Overall, the data suggest that a priori knowledge within a specific domain allows attentional resources to be allocated toward the encoding of contextual details.


Drilling from the intercondylar area for treatment of osteochondritis dissecans of the knee joint.
We demonstrate a new method in which a drilling is made from the intercondylar space, and its efficacy in treating osteochondritis dissecans (OCD) of the knee in skeletally immature patients with relatively stable lesions with an intact articular surface, in cases where there was failure of initial non-operative management. The lesions of 16 knees of 12 patients with OCD of the femoral condyles failed to heal by conservative treatment for more than 3 months (average 5-6 months) and thereafter were arthroscopically treated with drilling from not the transarticular but the intercondylar bare area without damaging the articular surface. Eight lesions involved the medial femoral condyle, and eight involved the lateral femoral condyle. The average follow-up was 16 months. All lesions healed after drilling, and the average time of healing was 4 months by X-ray and 7 months by MRI. The average Lysholm score improved from an average of 70.4 points at preoperation to an average of 97.8 points after operation. The results of the Hughston Rating Scale were similar: 10 of the 12 patients showed excellent results and the remaining two patients good results. We advocate our new and less invasive procedure of drilling from the bare area of the intercondylar space for OCD in the knee joint of skeletally immature patients who have had failure of initial non-operative management.


Cysteine usage in Sulfolobus spindle-shaped virus 1 and extension to hyperthermophilic viruses in general.
Fuselloviridae are ubiquitous crenarchaeal viruses found in high-temperature acidic hot springs worldwide. The type virus, Sulfolobus spindle-shaped virus 1 (SSV1), has a double-stranded DNA genome that contains 34 open reading frames (ORFs). Fuselloviral genomes show little similarity to other organisms, generally precluding functional predictions. However, tertiary protein structure can provide insight into protein function. We have thus undertaken a systematic investigation of the SSV1 proteome and report here on the F112 gene product. Biochemical, proteomic and structural studies reveal a monomeric intracellular protein that adopts a winged helix DNA binding fold. Notably, the structure contains an intrachain disulfide bond, prompting analysis of cysteine usage in this and other hyperthermophilic viral genomes. The analysis supports a general abundance of disulfide bonds in the intracellular proteins of hyperthermophilic viruses, and reveals decreased cysteine content in the membrane proteins of hyperthermophilic viruses infecting Sulfolobales. The evolutionary implications of the SSV1 distribution are discussed.


Molecular and clinicopathological features of appendiceal mucinous neoplasms.
Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered.


Tributylphosphine-catalyzed cycloaddition of aziridines with carbon disulfide and isothiocyanate.
Aziridines underwent cyclization reaction with carbon disulfide and isothiocyanate in the presence of organophosphine to afford thiazolidinone derivatives in good to high yields. The mechanistic study revealed that organophosphine serves as a catalyst in the reaction.


Differential regulation of respiratory chain subunits by a CREB-dependent signal transduction pathway. Role of cyclic AMP in cytochrome c and COXIV gene expression.
In vertebrate organisms, the molecular mechanisms by which extracellular signals regulate mitochondrial function and biogenesis are largely unknown. We have previously identified multiple cis-acting elements in both cytochrome c and cytochrome oxidase subunit IV (COXIV) genes that are likely targets for the regulated expression of respiratory chain components. We now demonstrate that cytochrome c but not COXIV mRNA is induced by cAMP through a mechanism involving transcriptional activation. Maximal induction occurs within 3 h and does not require de novo protein synthesis. The differential response of these genes is mediated by two distinct cAMP response elements (CREs) in the cytochrome c promoter region. Both elements function independently to drive cAMP-dependent expression from a heterologous promoter and within the proper cytochrome c promoter context. In addition, the binding properties of both elements to nuclear factors were characterized by competition DNase I footprinting, methylation interference footprinting, site-directed mutagenesis, and UV-induced DNA-protein cross-linking. The results are all consistent with the specific recognition of both CREs by CRE binding protein (CREB). A highly purified preparation of recombinant CREB formed a specific complex with each of the cytochrome c CREs identical to that formed with a crude nuclear fraction. In addition, the trans-activation of cytochrome c gene expression by recombinant CREB and protein kinase A in transfected cells was completely dependent on functional CREs within the promoter. These results establish that respiratory chain gene expression can be regulated directly by cAMP through a CREB-dependent signal transduction pathway.


Inappropriate use of urinary catheters in patients admitted to medical wards in a university hospital.
The prevalence and predisposing factors were determined for inappropriate urinary catheterization (UC) among inpatients in medical wards. A cross-sectional study was conducted including all patients aged ≥ 18 years admitted to medical wards in a 1300-bed tertiary-care centre, and who had a urinary catheter in place on the day of the survey. Of 380 patients observed, 46 (12.1%) had a urinary catheter in place. Twelve of them (26.1%) were inappropriately catheterized. The most common indication for inappropriate UC was urine output monitoring in a cooperative, non-critically ill patient. Inappropriateness was associated with increased age, poor functional status, urinary incontinence, dementia, and admission from a long-term care facility. Further educational efforts should be focused on improving catheterization prescribing practices by physicians.


Leadless pacemaker perforations: Clinical consequences and related device and user problems.
Cardiac perforation during leadless pacemaker implantation is more likely to require intervention than perforation by a transvenous lead. This study reports the consequences of Micra pacemaker perforations and related device and operator use problems based on information the manufacturer has submitted to the Food and Drug Administration (FDA). FDA's Manufacturer and User Facility Device Experience (MAUDE) database was searched for Micra perforations. Data extracted included deaths, major adverse clinical events (MACEs), and device and/or operator use problems. Between 2016 and July 2021, 563 perforations were reported within 30 days of implant and resulted in 150 deaths (27%), 499 cardiac tamponades (89%), 64 pericardial effusions (11%), and 146 patients (26%) required emergency surgery. Half of perforations were associated with 139 (25%) device problems, 78 (14%) operator use problems, and 62 (11%) combined device and operator use problems. Inadequate electrical measurements or difficult positioning were the most frequent device problems (n = 129); non-septal implants and perforation of other structures were the most frequent operator use problems (n = 69); a combined operator use and device problem resulted in 62 delivery system perforations. No device or operator use problem was identified for 282 perforations (50%), but they were associated with 78 deaths, 245 tamponades, and 57 emergency surgeries. The Micra perforations reported in MAUDE are often associated with death and major complications requiring emergency intervention. Device and use problems account for at least half of perforations. Studies are needed to identify who is at risk for a perforation and how MACE can be avoided or mitigated.


Preparation and physicochemical characterization of a solid dispersion of (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T) and polyvinylpyrrolidone.
Ischemic brain injury is a major disease which threatens human health and safety. (3, 5, 6-trimethylpyrazin-2-yl) methyl 3-methoxy-4-[(3, 5, 6-trimethylpyrazin-2-yl) methoxy] benzoate (VA-T), a newly discovered lead compound, is effective for the treatment of ischemic brain injury and its sequelae. But the poor solubility of VA-T leads to poor dissolution and limited clinical application. In order to improve the dissolution of VA-T, the pharmaceutical technology of solid dispersions was used in the present study. VA-T/polyvinylpyrrolidone (PVP) solid dispersion was prepared by the solvent method. The dissolution studies were carried out and solid state characterization was evaluated by differential scanning calorimetry (DSC), infrared spectroscopy (IR), x-ray diffraction (XRD) and scanning electron microscopy (SEM). The dissolution rate of VA-T was significantly improved by solid dispersion compared to that of the pure drug and physical mixture. The results of DSC and XRD indicated that the VA-T solid dispersion was amorphous. The IR spectra showed the possible interaction between VA-T and PVP was the formulation of hydrogen bonding. The SEM analysis demonstrated that there was no VA-T crystal observed in the solid dispersions. The ideal drug-to-PVP ratio was 1:5. In conclusion, the solid dispersion technique can be successfully used for the improvement of the dissolution profile of VA-T.


Laboratory managers' perceptions of the impact of teaching on the clinical laboratory.
To determine managers' perceptions of the impact of teaching students on the clinical laboratory, including: productivity, costs, recruitment/new employee orientation, staff morale/attitude, and staff professionalism. Managers' views on responsibility for teaching and reasons for not having students were also determined. Written survey, randomized sampling. Five hundred laboratory managers certified by the National Credentialing Agency. Participants completed a forced-choice written survey consisting of demographic information and statements assessing the impact of teaching. Managers agreed with impact statements on professionalism, recruitment, and new employee orientation. They were also in agreement that clinical teaching is essential. Neutral responses were obtained for impact statements related to laboratory productivity, costs, and staff morale and attitude. Over 90% of respondents who presently had students or who had had students at one time indicated that they hired their graduates. Laboratory managers understand the importance of clinical education and the benefits to recruitment, new employee orientation, and staff professionalism. Managers are undecided about the effects of teaching on laboratory costs and staff productivity.


Trafficking and Oligomeric Regulation of Platelet-Activating Factor Acetylhydrolase Type II.
Platelet-activating factor acetylhydrolase type II, PAFAH-II, is an intracellular phospholipase A2 enzyme present in various tissues and cells. PAFAH-II hydrolyzes a known phospholipid-derived mediator, platelet-activating factor, as well as oxidatively fragmented phospholipids in cellular membranes. Although the crystal structure of PAFAH-II remains unsolved, homology modeling has provided insight into the components of its structure that are necessary for membrane localization and binding. PAFAH-II contains an N-terminal myristoyl tail as well as two hydrophobic helices that help to control the oligomeric state and the association of the enzyme to membranes. This chapter presents an overview of the experimental methods and results that have developed our current understanding of the trafficking of PAFAH-II to the cellular membranes, as well as the enzyme's natural oligomeric states related to its function.


Transient synovitis of the hip as a complication of chickenpox in infant: Case study.
Chickenpox has many rare complications; transient synovitis is one of the very painful and self-limiting rare complications. This patient suffered from transient synovitis associated with chickenpox. After being diagnosed, it was managed by diclofenac sodium suppositories. Physicians must be able to correlate all of the possible complications of chickenpox in order to avoid misdiagnoses.


Usefulness of an anesthetic conserving device (AnaConDa™) in sevoflurane anesthesia.
The anesthetic conserving device (AnaConDaTM) is a disposable vaporizer that can save consumption of inhalational anesthetic used in low sevoflurane concentration. This study was performed to investigate whether AnaConDa when used at high sevoflurane concentration (1.5% to 2.0%) could save sevoflurane consumption and hasten emergence from anesthesia without any adverse effects. Thirty patients for ear surgery were equally divided into AnaConDa and control groups. Anesthesia was induced with intravenous anesthetics. After intubation sevoflurane inhalation started by infusion at 25 mL/h in the AnaConDa group and by inhalation of 2.0% (conventional vaporizer setting) in the control group. During anesthesia, end-tidal sevoflurane concentration was kept between 1.5 and 2.0% in both groups. The time to first detection of end-tidal sevoflurane, the time to sevoflurane concentration reached 1.5%, sevoflurane consumption, and emergence time were compared between the two groups. Adverse effects were checked. Sevoflurane consumption was smaller, time to first detection of end-tidal sevoflurane was longer, time to sevoflurane concentration reached 1.5% was longer, emergence time was shorter, and decrease of end-tidal sevoflurane concentration after stop of administration was faster in the AnaConDa group significantly. Clear Water accumulation with no smell in the filter was observed in 12 of 15 patients in the AnaConDa group. In general anesthesia with sevoflurane 1.5% to 2.0%, AnaConDa could save sevoflurane consumption and fasten emergence from anesthesia compared to conventional vaporizer, while water accumulation in the filter should be cautioned.


Benign recurrent aseptic meningitis (Mollaret's meningitis): case report and clinical review.
Benign recurrent aseptic meningitis (Mollaret's meningitis) is rare. Only five cases have been reported in this country. This article reports another case and briefly reviews the characteristic manifestations of this disorder.


DOX: A new computational protocol for accurate prediction of the protein-ligand binding structures.
Molecular docking techniques have now been widely used to predict the protein-ligand binding modes, especially when the structures of crystal complexes are not available. Most docking algorithms are able to effectively generate and rank a large number of probable binding poses. However, it is hard for them to accurately evaluate these poses and identify the most accurate binding structure. In this study, we first examined the performance of some docking programs, based on a testing set made of 15 crystal complexes with drug statins for the human 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). We found that most of the top ranking HMGR-statin binding poses, predicted by the docking programs, were energetically unstable as revealed by the high theoretical-level calculations, which were usually accompanied by the large deviations from the geometric parameters of the corresponding crystal binding structures. Subsequently, we proposed a new computational protocol, DOX, based on the joint use of molecular Docking, ONIOM, and eXtended ONIOM (XO) methods to predict the accurate binding structures for the protein-ligand complexes of interest. Our testing results demonstrate that the DOX protocol can efficiently predict accurate geometries for all 15 HMGR-statin crystal complexes without exception. This study suggests a promising computational route, as an effective alternative to the experimental one, toward predicting the accurate binding structures, which is the prerequisite for all the deep understandings of the properties, functions, and mechanisms of the protein-ligand complexes.


A new strategy to minimize humidity influences on acoustic wave ultraviolet sensors using ZnO nanowires wrapped with hydrophobic silica nanoparticles.
Surface acoustic wave (SAW) technology has been widely developed for ultraviolet (UV) detection due to its advantages of miniaturization, portability, potential to be integrated with microelectronics, and passive/wireless capabilities. To enhance UV sensitivity, nanowires (NWs), such as ZnO, are often applied to enhance SAW-based UV detection due to their highly porous and interconnected 3D network structures and good UV sensitivity. However, ZnO NWs are normally hydrophilic, and thus, changes in environmental parameters such as humidity will significantly influence the detection precision and sensitivity of SAW-based UV sensors. To solve this issue, in this work, we proposed a new strategy using ZnO NWs wrapped with hydrophobic silica nanoparticles as the effective sensing layer. Analysis of the distribution and chemical bonds of these hydrophobic silica nanoparticles showed that numerous C-F bonds (which are hydrophobic) were found on the surface of the sensitive layer, which effectively blocked the adsorption of water molecules onto the ZnO NWs. This new sensing layer design minimizes the influence of humidity on the ZnO NW-based UV sensor within the relative humidity range of 10-70%. The sensor showed a UV sensitivity of 9.53 ppm (mW/cm2)-1, with high linearity (R 2 value of 0.99904), small hysteresis (<1.65%) and good repeatability. This work solves the long-term dilemma of ZnO NW-based sensors, which are often sensitive to humidity changes.


Tumor necrosis factor microsatellite alleles in patients with rheumatoid arthritis in Taiwan.
To investigate the association of tumor necrosis factor (TNF) microsatellite alleles with the pathogenesis of rheumatoid arthritis (RA) in Taiwan. The TNF a, b, c, d, and e microsatellites were determined in 112 patients with RA and 99 healthy controls by using polymerase chain reaction (PCR) and electrophoresis with sequencing gel. All of these patients and controls had known HLA-DR genotypes and TNF-308 polymorphisms. The phenotypic frequency of TNFa9 was significantly higher in DR4(-) RA patients than in DR4(-) controls. However, the phenotypic frequency of TNFb6 was significantly higher in RA patients than in controls in the presence of HLA-DR4. The phenotypic frequency of TNFa3-e1 was significantly lower in DR4(+) RA patients than in DR4(+) controls, while a negative linkage disequilibrium was noted between TNFa3-e1 and HLA-DR4. TNF microsatellite alleles were not related to the prevalences of bone erosion, rheumatoid nodule, sicca syndrome, pulmonary fibrosis, and seropositivity of rheumatoid factor (RF) in patients with RA. The associations of TNF microsatellites with the susceptibility to RA in Taiwan are not completely independent of the HLA-DR associations. The association of TNFb6 with the susceptibility to RA depends on the presence of HLA-DR4, and the correlation of TNFa9 to RA depends on the absence of HLA-DR4. The negative association of TNFa3-e1 with RA may be secondary to the negative linkage disequilibrium between TNFa3-e1 and HLA-DR4. Moreover, TNFb6 and HLA-DR4 have a synergistic effect on the susceptibility to RA. TNFa3-e1 and TNF-308A have a synergistic effect on preventing from RA. The TNF microsatellite alleles are not related to the clinical manifestations and severity of RA patients in Taiwan.


Psychometric properties of the Hospital Survey on Patient Safety Culture, HSOPSC, applied on a large Swedish health care sample.
A Swedish version of the USA Agency for Healthcare Research and Quality "Hospital Survey on Patient Safety Culture" (S-HSOPSC) was developed to be used in both hospitals and primary care. Two new dimensions with two and four questions each were added as well as one outcome measure. This paper describes this Swedish version and an assessment of its psychometric properties which were tested on a large sample of responses from personnel in both hospital and primary care. The questionnaire was mainly administered in web form and 84215 forms were returned (response rate 60%) between 2009 and 2011. Eleven per cent of the responses came from primary care workers and 46% from hospital care workers. The psychometric properties were analyzed using both the total sample and the hospital and primary care subsamples by assessment of construct validity and internal consistency. Construct validity was assessed by confirmatory (CFA) and exploratory factor (EFA) analyses and internal consistency was established by Cronbachs's α. CFA of the total, hospital and primary care samples generally showed a good fit while the EFA pointed towards a 9-factor model in all samples instead of the 14-dimension S-HSOPSC instrument. Internal consistency was acceptable with Cronbach's α values above 0.7 in a major part of the dimensions. The S-HSOPSC, consisting of 14 dimensions, 48 items and 3 single-item outcome measures, is used both in hospitals and in primary care settings in Sweden for different purposes. This version of the original American instrument has acceptable construct validity and internal consistency when tested on large datasets of first-time responders from both hospitals and primary care centres. One common instrument for measurements of patient safety culture in both hospitals and primary care settings is an advantage since it enables comparisons between sectors and assessments of national patient safety improvement programs. Future research into this version of the instrument includes comparing results from patient safety culture measurements with other outcomes in relation to safety improvement strategies.


Chain-length dependence of the kinetics of the hyaluronan hydrolysis catalyzed by bovine testicular hyaluronidase.
Hyaluronan (HA) has various biological functions that are strongly dependent on its chain length. In some cases, as in inflammation and angiogenesis, long and short chain-size HA effects are antagonistic. HA hydrolysis catalyzed by hyaluronidase (HAase) is believed to be involved in the control of the balance between longer and shorter HA chains. Our studies of native HA hydrolysis catalyzed by bovine testicular HAase have suggested that the kinetic parameters depend on the chain size. We thus used HA fragments with a molar mass ranging from 8x10(2) g mol(-1) to 2.5x10(5) g mol(-1) and native HA to study the influence of the chain length of HA on the kinetics of its HAase-catalyzed hydrolysis. The initial hydrolysis rate strongly varied with HA chain length. According to the Km and Vm/Km values, the ability of HA chains to form an efficient enzyme-substrate complex is maximum for HA molar masses ranging from 3x10(3) to 2x10(4) g mol(-1). Shorter HA chains seem to be too short to form a stable complex and longer HA chains encounter difficulties in forming a complex, probably because of steric hindrance. The hydrolysis Vm values strongly suggest that as the chain length decreases the HAase increasingly catalyses transglycosylation rather than hydrolysis. Finally, two HA chain populations, corresponding to HA chain molar masses lower and higher than approximately 2x10(4) g mol(-1), are identified and related to the bi-exponential character of the model we have previously proposed to fit the experimental points of the kinetic curves.


DNA hybridization, cladistics, and the phylogeny of phalangerid marsupials.
Single-copy DNA/DNA hybridization experiments and numerical cladistic analyses of anatomical characters were used to investigate relationships among nine phalangerid (Marsupialia) species from four different genera. Both rate-dependent and rate-independent analyses of molecular data indicate that species of Trichosurus from one clade and that Strigocuscus, Phalanger, and Spilocuscus form a second. Within the latter group, Spilocuscus is excluded from a Strigocuscus-Phalanger clade, which, in turn, is not fully resolved on a jackknife strict consensus tree. Minimum-length Dollo, Wagner, and Camin-Sokal parisomy trees based on 35 anatomical characters, in contrast, suggest placement of Strigocuscus with Trichosurus rather than with Spilocuscus and Phalanger. However, there are two derived characters that support the alternative arrange of Strigocuscus with Spilocuscus and Phalanger and one character that further unites Strigocuscus and Phalanger. Thus, DNA hybridization results are not inconsistent with the distribution of derived character states among anatomical characters, only with minimum-length trees based on character data.


Healthy sibling donor anxiety and pain during bone marrow or peripheral blood stem cell harvesting for allogeneic transplantation: results of a randomised study.
This study reports the first comparison of healthy donor subjective well-being during two alternative procedures of hematopoietic stem cells harvesting for allogeneic transplantation. Among the 105 donors included between September 1996 and October 1998 in the SFGM French randomised trial aiming to compare allogeneic bone marrow (BM) transplantation and blood cell (BC) transplantation, 64 donors (33 in BC and 31 in BM groups) were relevant for the analysis. They had received a set of self-administered questionnaires to complete during the collection process, aiming to measure anxiety (assessed using the Spielberger's State-Trait Anxiety Inventory) and pain induced by the procedure (evaluated using a visual analogical scale). Results showed that no harvest procedure is free from pain even if none was more painful than the other. Levels of anxiety before the collection procedure were high in both groups and significantly so for BC donors. Although BC collection induces at least similar levels of pain and anxiety as does BM collection, they were of a different kind, and the short-term impact of G-CSF stimulation on the well-being of BC donors has to be taken into account in improving quality of care in the allogeneic setting.


A molecular device: A DNA molecular lock driven by the nicking enzymes.
As people are placing more and more importance on information security, how to realize the protection of information has become a hotspot of current research. As a security device, DNA molecular locks have great potential to realize information protection at the molecular level. However, building a highly secure molecular lock is still a serious challenge. Therefore, taking advantage of the DNA strand displacement and enzyme control technology, we constructed a molecular lock with a self-destructive mechanism. This molecular lock is mainly composed of logic circuits and takes nicking enzymes as inputs. To build this molecular lock, we first constructed a series of cascade circuits, including a YES-YES cascade circuit and a YES-AND cascade circuit. Then, an Inhibit logic gate was constructed to explore the inhibitory properties between different combinations of two nicking enzymes. Finally, using the characteristics of mutual inhibition between several enzymes, a DNA molecular lock driven by three nicking enzymes was constructed. In this molecular device, only the correct sequence of nicking enzymes can be input to ensure the normal operation of the molecular lock. Once the wrong password is entered, the device will be destroyed and cannot be recovered, which effectively prevents intruders from cracking the lock through exhaustive methods. The molecular lock has the function of simulating an electronic keyboard, which can realize the protection of information at the molecular level, and provides a new implementation method for building more advanced and complex molecular devices.


Synergistic effect of paeonol and cisplatin on oesophageal cancer cell lines.
Paeonol, a phenolic component from the root bark of Paeonia moutan, has shown great promise in antitumour activities in our previous studies. The present study was designed to investigate whether paeonol has synergistic effect with cisplatin on the growth-inhibitory of human oesophageal cancer cell lines and the possible mechanism. Cell viability was measured by MTT assay. Drug-drug interactions were analysed by the coefficient of drug interaction. Apoptosis was detected by acridine orange fluorescence staining and flow cytometry assay. Bcl-2, Bax and caspase-3 expression was assayed by immunohistochemical staining. A synergistic inhibitory effect on viability of the two cell lines was observed after combination of paeonol with various concentrations of cisplatin. Further study showed the combination induced greater apoptosis than the groups treated with paeonol or cisplatin alone. The expression of Bcl-2 was decreased and that of Bax was increased in treatment groups, especially in the combination group, with the ratio of Bcl-2/Bax decreased correspondingly. And the combination also resulted in greater activation of caspase-3 than did either agent alone. Paeonol, in combination with cisplatin, had a significantly synergistic growth-inhibitory effect on oesophageal cell line, which may be related to apoptosis induction.


Productive Performance, Egg Quality and Yolk Lipid Oxidation in Laying Hens Fed Diets including Grape Pomace or Grape Extract.
An experiment was conducted to assess in laying hens the effect of including grape pomace (GP, at 30 or 60 g/kg) or grape extract (GE, at 0.5 or 1.0 g/kg) on egg production, feed conversion ratio, protein and polyphenol digestibility, egg weight, egg quality, yolk fatty acid profile and oxidative stability of yolk lipids. No differences were detected among diets for egg production (83.8%, on average) or egg mass (56.8 g/d, on average). However, the average egg weight was lower (p = 0.004) for dietary treatments GP 30, GP 60 and GE 0.5 (67.5 g, on average) than for control hens (68.5 g). Accordingly, in hens fed the GP diets the proportion of XL eggs was lower (p = 0.008) than in control hens, while the proportion of M eggs was higher (p < 0.001) in hens fed the diets GP 30, GP 60 and GE 0.5 than in the control group. The dietary inclusion of both GP and GE decreased daily feed intake (120.9 vs. 125.3 g/d, p < 0.001) and the feed conversion ratio (2.09 vs. 2.18, p = 0.01). Feeding GP at 60 g/kg or GE reduced excreta protein digestibility (54.7 vs. 62.8%, p < 0.001), whereas all GP and GE diets showed higher excreta polyphenol digestibility than the control treatment (57.2 vs. 41.0%, p < 0.001). While yolk colour score was increased with all grape diets (8.12 vs. 7.34, p < 0.001), the dietary inclusion of GP, either at 30 or 60 g/kg, and that of GE at 1.0 g/kg increased the Haugh units of the albumen (80.8 vs. 76.4 Haugh units, p = 0.001). Shell thickness remained unaffected by dietary treatments (365.2 μm, on average). When included in the diet at 60 g/kg, GP reduced the proportion of saturated fatty acids in the yolk (31.6 vs. 32.9%, p = 0.001) and that of monounsaturated fatty acids (39.5 vs. 41.4%, p < 0.001), while it increased the percentage of polyunsaturated fatty acids (28.9 vs. 25.7%, p < 0.001). In fresh eggs, no significant differences were found for the malondialdehyde (MDA) concentration (0.146 mg/kg, on average). In stored eggs, the MDA amount was lower in the eggs of the laying hens fed GP at 60 g/kg than in the eggs of the control hens (1.14 vs. 1.64 mg/kg, p = 0.025). In conclusion, the inclusion of grape pomace, either at 30 or 60 g/kg, and grape extract at 1.0 g/kg in the diet of laying hens improved some egg quality traits, but feeding grape pomace resulted in a lower average weight of eggs. Nevertheless, feeding laying hens with diets containing grape pomace resulted in a higher antioxidant potential in egg yolk than dietary inclusion of grape extract.


Axl/Gas6 pathway positively regulates FLT3 activation in human natural killer cell development.
Activation of the fibromyalgia syndrome-like tyrosine kinase 3 (FLT3) by its ligand, FLT3 ligand (FL), strongly augments the development of natural killer (NK) cells from human CD34⁺ hematopoietic progenitor cells (HPCs) in the presence of IL-15, compared with NK-cell development in the presence of IL-15 alone. In this study, we observed that blocking the receptor tyrosine kinase Axl/Gas6 pathway with a soluble Axl-IgG1 Fc fusion protein (Axl-Fc) in the presence of FL significantly diminished the absolute number of CD3⁻ CD56⁺ NK cells derived from human CD34⁺ HPCs. Axl-Fc reduced the expression levels of the IL-2/15 receptor β chain (CD122) and γ chain (CD132) induced by activation of FLT3 and consequently reduced the frequency of NK precursor cells responding to IL-15. Furthermore, Axl-Fc diminished FL-induced FLT3 phosphorylation and impeded the physical interaction between Axl and FLT3 in CD34⁺ HPCs. Collectively, our data suggest that the Axl/Gas6 pathway contributes to normal human NK-cell development at least in part via its positive regulatory effect on FLT3 signaling in CD34⁺ HPCs.


Thirty years of the vegetative state: clinical, ethical and legal problems.
The vegetative state is the rarest form of disability in patients now frequently rescued from life-threatening severe brain damage by resuscitation and intensive care. Many doctors have never seen such cases, yet it provokes great interest among professionals and the public because of the paradox of a person who is awake yet not aware. The commonest cause is head injury and it is more common in countries with a high incidence of severe head injury. The most consistent brain damage is in the subcortical white matter of the cerebral hemispheres and in the thalami; although the cerebral cortex is often severely damaged, it may be relatively spared. Diagnosis depends on prolonged expert observation to determine that there is no evidence of awareness in spite of a wide range of reflex responses, some of which may involve cortical activity. Functional imaging confirms that there is some residual cortical function in many vegetative patients. Mistaken diagnosis is less likely since the recent definition of clinical criteria for the vegetative state and for the minimally conscious state. Many patients recover consciousness and even regain independence after a month in a vegetative state after head injury, but few do so after non-traumatic insult. The longer the state persists the less likely the recovery, and eventually permanence can be declared. Patients can survive for many years in a vegetative state. Many consider that indefinite survival in a vegetative state is of no benefit to the patient and that there is no moral or legal obligation to continue life-sustaining treatment, including artificial nutrition and hydration. Ethical issues include how to respect the autonomy of the legally incompetent patient, and uphold the right to refuse unwanted treatment. Many cases have been brought to court in several North American, Northern European and some other jurisdictions where it has been ruled that it is legally permissible to withdraw life-sustaining treatment once a patient is declared permanently vegetative, and such withdrawal seems likely to be what that person would want done.


Prognostic significance of EGFR and Her-2 in oral cavity cancer in betel quid prevalent area cancer prognosis.
Although several studies have found overexpression of epidermal growth factor receptor (EGFR) proteins EGFR and Her-2 in head and neck cancers, the clinical relevance of the finding varies. We examined the expression and clinical association of these molecules with oral squamous cell carcinoma in an area where betel chewing is prevalent. EGFR and Her-2 proteins were measured in 59 paired (grossly normal and cancer) tissues by an enzyme immunoassy method. The cutoff value for gene overexpression was defined as the level of mean expression in normal tissue plus two s.d. A total of 59% of the patients consumed alcohol, 90% smoked tobacco, and 90% chewed betel quid. Of the patients assayed, 34 (58%) and 24 (41%) had EGFR and Her-2 overexpression, with average 3.5- and 1.5-fold elevations. EGFR overexpression has been shown to be statistically associated with T stage, N stage, overall TMN stage, primary tumour depth, lymph node extra-capsular spread, and poor survival. Her-2 overexpression, however, did not demonstrate a similar association with clinicopathological parameters or therapeutic outcome. On multivariant analysis, EGFR overexpression (P=0.041) and N stage (P=0.024) were the only independent factors for overall survival. These results indicate that the molecular targeting therapy to EGFR may be a treatment for oral cavity cancer in the betel quid-chewing prevalent area.


Double trouble: Concomitant unmasking and paradoxical immune reconstitution inflammatory syndrome in a patient with newly diagnosed HIV.
Immune reconstitution inflammatory syndrome (IRIS) is a complication encountered in patients with HIV due to immune function recovery following the initiation of antiretroviral therapy. IRIS can be divided into two forms: paradoxical (recurrence of clinical signs of a previously treated opportunistic infection) and unmasking (uncovering of a previously undiagnosed and asymptomatic infection). We present the rare case of a 48-year-old man diagnosed with AIDS after presenting with cryptococcal meningitis who, shortly after initiation of ART, developed both unmasking IRIS due to Mycobacterium avium complex (MAC), and subsequently paradoxical IRIS to his prior cryptococcal meningitis infection. To our knowledge, cases in the medical literature describing "double IRIS" remain scarce.


Posterior cingulate cortical lesions eliminate learning-related unit activity in the anterior cingulate cortex.
The frequency of multi-unit neuronal firing in response to tonal conditional stimuli increases, and the neuronal responses become discriminative in character, in the anterior and posterior subfields of the cingulate cortex (Brodmann's Area 24 and 29, respectively) during the course of discriminative avoidance conditioning in rabbits. Bilateral electrolytic lesions of the dorsal subicular complex eliminated the training-induced excitatory response in both cortical subfields, suggesting that subiculocortical projection fibers are essential for this effect. Yet, available data indicate that the subicular projection reaches only Area 29, not Area 24. Here we test the hypothesis that the subicular influence attains Area 24 via a synaptic relay in Area 29. The results showed in keeping with the hypothesis, that bilateral aspirative or electrolytic lesions in Area 29 eliminated the training-induced neuronal responses in Area 24. As in the case of subicular lesions, the Area 29 lesions increased the amplitude of the macropotentials in Area 24. These results are discussed in relation to a model of the interactions of the cingulate cortex, hippocampus and the limbic thalamic nuclei during learning.


Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9.
In the human paired box-containing (PAX) gene family, only two members, PAX-3 and PAX-6, which are associated with Waardenburg's syndrome and aniridia, respectively have been mapped to human chromosomes. We have now isolated cosmids for six additional human PAX genes (PAX-1,-2,-5,-7,-8,-9) and a polymerase chain reaction fragment for PAX-4. PAX-9 is a novel family member which is closely related in its paired domain to PAX-1. The chromosomal location of all cloned PAX genes was determined by analysis of somatic cell hybrids and (except PAX-4) by fluorescence in situ hybridization to metaphase chromosomes. PAX-1 and PAX-7 map to chromosomal regions containing previously assigned disease loci.


The dopamine D2 receptor: new surprises from an old friend.
Drugs acting at dopamine D2 receptors (D2R) are commonly used to alleviate symptoms produced by diseases such as Parkinson's disease, schizophrenia, and depression. A limitation to the use of these drugs is that they sometimes afflict patients with severe side effects. This review discusses recent evidence for several proteins that represent novel mediators of the downstream consequences of D2R activation, since selective targeting of particular D2R-mediated signaling pathways could lead to the development of improved treatments for these devastating diseases.


Mutation, sequence analysis, and association studies of alpha-synuclein in Parkinson's disease.
A mutation within the alpha-synuclein gene on human chromosome 4 has been reported to segregate with PD in an Italian family. We screened a sample of familial cases of PD for mutation in the alpha-synuclein gene. None of the familial cases of PD carried a mutation within the alpha-synuclein gene, and no association was detected between PD and alleles of a dinucleotide repeat marker within the alpha-synuclein gene. We conclude that variation within the alpha-synuclein gene does not play a significant role in the risk for PD in our sample.


The Association Between Angiographically Derived Radial Wall Strain and the Risk of Acute Myocardial Infarction.
The radial wall strain (RWS) is a novel angiography-based method to assess the biomechanical property of the coronary artery and whether it can predict future acute myocardial infarction (AMI) events remains to be elucidated. This study aimed to investigate the association between angiography-derived RWS and future AMI events in mild to intermediate lesions. We performed a matched case-control analysis nested in a retrospective cohort of patients who had received prior angiography (the index procedure) at least 1 month before and were hospitalized again for repeat angiography. Patients with at least 1 de novo mild to intermediate lesion identified at the index procedure and eligible for RWS analysis were enrolled. The study identified cases with target lesion-related AMI diagnosed at the repeat angiography, matching each case to 3 control subjects without AMI. Altogether 44 patients with lesion-related AMI and 132 matched controls were enrolled. The median diameter stenosis of the overall interrogated lesions was 34.0%. The baseline maximum RWS (RWSmax), which was defined as the highest RWS in the stenotic segment, was significantly higher in lesions responsible for AMI than those that remained quiescent (median 13% vs 10%; P < 0.001). RWSmax was predictive of lesion-related AMI, with an area under the curve of 0.83 (95% CI: 0.76-0.90; P < 0.001) and an optimal cutoff >12%. RWSmax >12% was found to be independently associated with subsequent AMI events with a risk ratio of 7.25 (95% CI: 3.94-13.37; P < 0.001). Among angiographically mild to intermediate lesions, a high-strain pattern identified by angiography-derived RWS was associated with an increased risk of AMI events.


Abdominal amyloidosis: spectrum of radiological findings.
Amyloidosis is a disease characterized by the deposition of fibrillar protein amyloid of beta-structure in organs or tissues. It is usually classified as either a primary disease or secondary to a co-existent condition, such as rheumatoid arthritis, tuberculosis, or neoplasm (particularly multiple myeloma or renal cell carcinoma). Amyloid protein deposition can be seen in a variety of organs though it occurs with higher frequency in the gastrointestinal tract, kidney, and heart. Amyloidosis can have a wide spectrum of manifestations in nearly every abdominal organ. Some of these, for example, multiple cystic submucosal masses of the stomach, amyloidosis of the gallbladder, and dirty soft tissue infiltration of the subcutaneous fat, have not yet been covered in the radiological literature. The combination of various imaging techniques and the identification of characteristic computed tomography (CT) hepatic features may help in the differentiation of amyloidosis from other infiltrative diseases; however, confirmative diagnosis can usually only be achieved by tissue biopsy.


Detailed characterization of Pinus ponderosa sporopollenin by infrared spectroscopy.
In plant spores and pollen, sporopollenin occurs as a structural polymer with remarkable resistance to chemical degradation. This recalcitrant polymer is well-suited to analysis by non-destructive infrared spectroscopy. However, existing infrared characterization of sporopollenin has been limited in scope and occasionally contradictory. This study provides a comprehensive structural analysis of sporopollenin in the Pinus ponderosa pollen exine using infrared spectroscopy, including detailed band assignments, descriptions of chemical reactivity, and comparison to multiple reference substances. We observe that the infrared spectral characteristics of sporopollenin prepared by enzymatic digestion of the polysaccharide-based intine are largely consistent with a copolymer of aliphatic lipids and trans-4-hydroxycinnamic acid, without distinct contributions from α-pyrone or carotenoid substructures.


Human-like tele-health robotics for older adults - A preliminary feasibility trial and vision.
The global increase of the aging population presents major challenges to healthcare service delivery. Further, the COVID-19 pandemic exposed older adults' vulnerability to rapid deterioration of health when deprived of access to care due to the need for social distancing. Robotic technology advancements show promise to improve provision of quality care, support independence for patients and augment the capabilities of clinicians to perform tasks remotely. This study explored the feasibility and end-user acceptance of using a novel human-like tele-robotic system with touch feedback to conduct a remote medical examination and deliver safe care. Testing of a remotely controlled robot was conducted with in-person clinician support to gather ECG readings of 11 healthy participants through a digital medical device. Post-study feedback about the system and the remote examinations conducted was obtained from study participants and study clinicians. The findings demonstrated the system's capability to support remote examination of participants, and validated the system's perceived acceptability by clinicians and end-users who all reported feeling safe interacting with the robot and 72% preferred remote robotic exam over in-person examination. This paper discusses potential implications of robot-assisted telehealth for patients including older adults who are precluded from having in-person medical visits due to geographic distance or mobility, and proposes next steps for advancing robot-assisted telehealth delivery.


Quantitative proteomics reveals the molecular mechanism of Aeromonas hydrophila in enoxacin stress.
Aeromonas hydrophila is an aquatic pathogen that has been of increasing concern in cultivation fisheries because of antibiotics resistance; however, its intrinsic antibiotics resistance mechanism remains elusive. In this study, a label-free-based proteomics method was used to compare differential protein abundances in response to enoxacin (ENX) stress in A. hydrophila. The results showed a total of 96 proteins were altered, with 43 increased and 53 decreased. Subsequent bioinformatics analysis showed that 11 SOS response-related proteins increased and four chemotaxis proteins decreased in response to ENX stress. Further antibiotics susceptibility assay showed that SOS response inhibitors such as baicalein and curcumin significantly enhanced the bactericidal capacity when compounded with ENX but not with chlortetracycline. These findings indicate the importance of SOS response in quinolones resistance. Moreover, the survival rates of five related knock-out strains (ΔuvrA, ΔahyR, ΔompW, ΔcheV, and ΔhgpB) were compared in response to different doses of ENX. Finally, the auto-inducer 1 (AI-1) quorum sensing system may negatively regulate ENX resistance in A. hydrophila. Overall, our data provide insight into the quinolones resistance mechanism and indicate that an effective SOS response inhibitor compound with ENX may be a promising strategy for the treatment of quinolones-resistant A. hydrophila. BIOLOGICAL SIGNIFICANCE: Bacterial antibiotics resistance has become a very serious public health problem, whereas its intrinsic mechanism remains elusive. To investigate the antibiotics resistant characteristics of fish pathogenic Aeromonas hydrophila, we compared the differential protein abundances in response to enoxacin (ENX) stress using proteomics method in this study. Our bioinformatics analysis showed that SOS response-related proteins increased and chemotaxis proteins decreased in response to ENX stress. Further assays showed that SOS response inhibitors such as baicalein and curcumin significantly enhanced the bactericidal capacity when compounded with ENX but not with chlortetracycline. Moreover, the antibiotics susceptibility of five related knock-out strains were valued in different doses of ENX. Overall, our data provide insight into the quinolones resistance mechanism and indicate that SOS response process and quorum sensing may involve in ENX resistance in A. hydrophila.


[Cyclotropia in macula translocation. Possible eye muscle surgery solutions].
Macular translocation for treatment of age-related maculopathy often necessitates surgical counter-rotation of the external eye muscles. Excyclorotatory effects can be attained generally by various surgical methods on all extraocular eye muscles. If procedures on different muscles are combined, anterior segment perfusion has to be maintained. The results of 29 operations were analysed in order to examine the excyclorotatory effects of 4 different combined surgical approaches. In 23 patients a partial transposition of all 4 m. recti together with a high dose combined operation on both oblique muscles yielded a mean effect of 21.6 degrees excyclorotation. In four patients a vertical transposition of the horizontal m. recti in opposite directions together with a high dose combined operation on both oblique muscles led to a mean excyclorotation of 22 degrees. A full tendon transposition of the superior oblique muscle to the nasal part of the orbit in one case combined with a downward transposition of the medial rectus muscle resulted in an excyclorotation of 37 degrees, in another case combined with an anterior margin advancement of the inferior oblique muscle led to an excyclorotation of 35 degrees. All approaches yielded mean counter-rotatory effects over 20 degrees. The indications are discussed under the aspects of the possibility of a one-step correction of horizontal or vertical angles, dosage, induction of inconcomitancies and operation time.


Tissue kallikrein and bradykinin B2 receptor in human uterus in luteal phase and in early and late gestation.
This study was addressed to evaluate the temporospatial pattern of key components of the kallikreinkinin system in human uterus in luteal phase (n = 7), early pregnancy (isolated spontaneous abortions, n = 11; ectopic pregnancies, n = 9), idiopathic preterm deliveries (n = 5), and term gestations (n = 12). Tissue kallikrein mRNA and protein and the type 2 bradykinin receptor (B2R) protein were expressed in luminal and glandular epithelium and in endothelial cells of stromal and myometrial blood vessels, while tissue kallikrein mRNA and B2R, but not tissue kallikrein protein, were observed in decidual cells and in arteriolar and myometrial muscle. A greater signal intensity for tissue kallikrein mRNA and protein and of B2R protein was observed in the early pregnancy samples. The sites and variations of the tissue kallikrein mRNA and protein and of the B2R protein in the human uterus and in fallopian tubes during the luteal phase and in pregnancy coincide with those described for other vasoactive effectors such as nitric oxide, prostacyclins, growth factors, and renin. The uterine localization of the main enzyme and receptor of the tissue kallikrein-kinin system in key sites for embryo attachment, implantation, placentation, maintenance of placental blood flow, and parturition supports the notion that the kallikreinkinin system participates in these processes, probably through vasodilation, increased vasopermeability, enhanced matrix degradation, stimulation of cell proliferation, and myometrial contractility.


Perioperative discontinuation of intravenous bisphosphonate therapy reduces the incidence and severity of bisphosphonate-related osteonecrosis of the jaw: A randomized, controlled, prospective experimental study in rats.
To evaluate the effects of intravenous bisphosphonate discontinuation on incidence and severity of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Seventy rats were randomly divided into 7 groups. In control and S0 groups, weekly injection of saline and 0.06 mg/kg zoledronate (respectively) for 4 weeks, tooth extraction, continuation of injections for 2 months and euthanasia were performed. In group S1, zolendronate injection for 4 weeks, tooth extraction, zolendronate discontinuation for 2 months, and euthanasia were done. For groups S2, S3, S4, and S5, zolendronate injections for 4 weeks, drug holiday for 1-4 months (respectively) before and 2 months after tooth extraction, and euthanasia were performed. Presence of bone exposure, osteonecrosis, and new bone formation were clinically and histologically evaluated. The rate of BRONJ in control, S0, S1, S2, S3, S4, and S5 groups was 0%, 85%, 80%, 65%, 60%, 50%, and 40%, respectively. In control group, epithelial healing, bone formation, and absence of osteonecrosis; and in S0 group, unhealed epithelium, osteonecrosis, and impaired bone formation were histologically observed. In study groups, prolongation of drug holiday caused diminished osteonecrosis, and improved bone and epithelial healing. Zolendronate discontinuation significantly decreased the incidence and severity of BRONJ in rats.


Scaling up quality-assured psychotherapy: The role of therapist competence on perinatal depression and anxiety outcomes.
To examine: (1) the psychometric properties of two therapist competence measures-multiple choice questionnaire (MCQ) and standardized role-plays; (2) whether therapist competence differed between non-specialist (NSPs) and specialist (SPs) providers; and (3) the relations between therapist competence and patient outcomes among perinatal patients receiving brief psychotherapy. This study is embedded within the SUMMIT Trial-a large, ongoing psychotherapy trial for perinatal women with depressive and anxiety symptoms. We assessed the: (1) psychometric properties of therapist competence measures using Cronbach's alpha and inter-class correlation; (2) differences in therapist competence scores between n = 23 NSPs and n = 22 SPs using a two-sample t-test; and (3) relations between therapist competence measures and perinatal patient outcomes through a linear regression model. Internal consistency for role-play was acceptable (α = 0.71), whereas MCQ was excellent (α = 0.97). Role-play showed good inter-rater reliability (ICC = 0.80) and scores were higher for SPs compared with NSPs (t(2,38) = -2.86, p = 0.0069) and associated with outcomes of anxiety (B = 1.52, SE = 0.60, p = 0.01) and depressive (B = 0.96, SE = 0.55, p = 0.08) symptom scores. Our study highlights the importance of demonstrating psychological treatment skills through standardized role-plays over knowledge-based competence to predict perinatal patient outcomes. Using well-defined evidence-based tools is critical for deploying NSPs to provide high-quality psychotherapy and increase accessibility to psychological treatments for perinatal populations worldwide.


Providing oral care in haematological oncology patients: nurses' knowledge and skills.
In the international literature, the most commonly recommended intervention for managing oral mucositis is good oral care, assuming that nurses have sufficient knowledge and skills to perform oral care correctly. The aim of the present study was to investigate if knowledge and skills about oral care improve when education in oral care is provided to nurses in charge of patients who are at risk of oral mucositis. This intervention study consists of a baseline test on the knowledge and skills of nurses of the haematology wards of two different hospitals. Oral care education sessions were given in one hospital and follow-up tests were performed in both hospitals. Nursing records were examined and observations of nurses performing oral care were made at baseline as well as at follow-up. The results show significant differences in the scores for knowledge and skills before and after the education, whereas there was no difference in scores at the two points in time for the comparison hospital, where no education had taken place. The records test showed no differences at baseline or follow-up for the two groups. Observations showed that nurses who followed the education session implemented the oral care protocol considerably better than those who did not attended. Education in oral care has a positive influence on the knowledge and skills of nurses who care for patient at risk of oral mucositis, but not on the quality of oral care documentation.


Use of pulsed Doppler tissue imaging to assess regional left ventricular diastolic dysfunction in hypertrophic cardiomyopathy.
In this study, regional diastolic patterns and their relations with transmitral Doppler inflow were investigated in hypertrophic cardiomyopathy (HC) by pulsed Doppler tissue imaging (DTI). Doppler echocardiography and DTI of basal septum and lateral wall (apical 4-chamber view) were performed in 20 patients (15 men and 5 women) with HC and in 10 healthy subjects (7 men and 3 women). Diabetes, hypertension, coronary artery and valvular disease, mitral regurgitation, New York Heart Association functional classes III to IV, sinus tachycardia, atrial fibrillation, and inadequate echocardiograms were exclusion criteria. Peak velocity and time-velocity integral of early and late waves and their ratios, and deceleration and isovolumic relaxation times were determined by standard Doppler and by DTI at the septal and lateral wall levels. The 2 groups were comparable for age, heart rate, blood pressure, and ejection fraction. Transmitral peak velocity and time-velocity integral E/A ratios were reduced (both p <0.05) and deceleration and isovolumic relaxation times prolonged (both p <0.00001) in HC. Septal DTI showed lower peak velocity and time-velocity integral e/a ratios (p <0.00001 and p <0.001, respectively) and lengthened regional deceleration (p <0.01) and isovolumic (p <0.001) relaxation times. DTI of the lateral wall showed a prolongation of deceleration and isovolumic relaxation times (both p <0.01). By dividing HC according to transmitral E/A, 8 patients with E/A <1 had lower DTI septal e/a ratio (p <0.01) and prolonged septal deceleration and isovolumic relaxation times (both p <0.01) but no changes in DTI pattern of lateral wall than 12 patients with E/A > 1. In conclusion, DTI is useful and complementary to standard Doppler imaging to characterize diastolic properties in HC, reflecting a typical pattern of intramyocardial impaired relaxation at the level of hypertrophied septum and also providing information about the degree of this regional impairment. The lateral wall presents minor changes in diastolic times, which indicate how diastolic asynchrony is not confined to the hypertrophied segment in HC.


Low birthweight and post partum endometritis-myometritis.
The study aims at confirming or rejecting the hypothesis of an association between birthweight and post partum uterine infection. A case-referent study was performed on 51 puerperal women with clinical signs of endometritis-myometritis. To each case an otherwise healthy puerperal woman was recruited and matched for age, parity and days after delivery. The proportion of women having had newborns with birthweight < 2500 g was 20/49 among cases and 2/50 among referents (odds ratio 16.6; 95% CI 3.5-152.3). Preterm births were registered in 15/50 cases and 2/49 referents (odds ratio 10.1; 95% CI 2.1-94.5). The average gestational age at delivery was approximately 2 weeks shorter among cases than among referents (37.5 versus 39.5 weeks). Low birth weight was ten times more prevalent among women with puerperal infection than among healthy puerperal women. The findings indicate that giving birth to a low birth weight baby is strongly associated with ensuing puerperal infection, possibly by a subclinical antenatal intrauterine infection, predisposing to both adverse fetal and maternal outcomes of pregnancy.


Healing of osteoporotic bone defects by baculovirus-engineered bone marrow-derived MSCs expressing MicroRNA sponges.
Fractures associated with osteoporosis are a worldwide health problem. To augment osteoporotic bone healing, we aimed to develop a cell/gene therapy approach in combination with miRNA manipulation. We unraveled aberrant overexpression of miR-140* and miR-214 in the bone marrow-derived MSCs isolated from ovariectomized (OVX) rats (OVX-BMSCs). To suppress the miRNA levels, we constructed hybrid baculovirus vectors expressing miRNA sponges to antagonize miR-140* or miR-214. Engineering OVX-BMSCs with the hybrid vectors persistently attenuated the cellular miR-140*/miR-214 levels, which promoted the OVX-BMSCs osteogenesis and augmented the ability of OVX-BMSCs to repress osteoclast maturation in vitro. Notably, suppressing miR-214 exerted more potent osteoinductive effects. In the osteoporotic rat models with a critical-size bone defect at the femoral metaphysis, implanting the OVX-BMSCs ectopically expressing BMP2 failed to heal the defect, which underscored the difficulty to heal osteoporotic bone defects. Nonetheless, allotransplantation of the miR-214 sponges-expressing OVX-BMSCs healed the defect and ameliorated the bone quality (density, trabecular number, trabecular thickness and trabecular space) at 4 weeks post-implantation. Co-expressing BMP2 and miR-214 sponges in OVX-BMSCs further synergistically substantiated the healing. The baculovirus-engineered OVX-BMSCs that expressed miR-214 sponge, with or without BMP2 expression, thus paved a new avenue to the treatment of osteoporotic bone defects.


Insulin therapy associated relative hypoglycemia during critical illness.
In critically ill diabetes patients, relative hypoglycemia (RH) (a decrease in glucose ≥30% below pre-admission levels, as estimated by HbA1c) is associated with greater mortality and absolute hypoglycemia. We investigated the epidemiology and outcomes of RH when it was associated with insulin therapy. We performed retrospective analysis of a cohort of critically ill patients with diabetes who received insulin in the intensive care units (ICUs) of a tertiary hospital. The primary outcome was 28-day mortality with respect to insulin therapy associated relative hypoglycemia (ITARH). ITARH occurred in 184 (42%) of insulin-treated patients. ITARH was associated with a higher HbA1c (8.6% vs 6.6%, p < 0.001), a higher glycemic variability index (121 vs 75.1 mmol2/L2/h/week, p < 0.001) and more absolute hypoglycemia (18.5% vs 3.94%, p < 0.001). Its frequency peaked about 5 h after initiation of insulin therapy. ITARH was associated with a greater risk of subsequent hypoglycemia (adjusted HR 3.5, 95% CI 1.7-6.8) but not mortality (HR 1.2, 95% CI 0.7-2.2). ITARH is common in insulin treated critically ill diabetes patients and associated with poorer glycemic control. Unlike reports of RH in general, it is not associated with mortality, suggesting that the prognostic implications of RH differ according to its context.


Associations of Workplace Violence With Cardiovascular Disease Among United States Workers: Findings From a National Survey.
Recent research indicates a potential association between workplace violence and an increased risk of cardiovascular disease (CVD) in the working-age population. However, the relevant evidence in the United States is sparse. Thus, this study was conducted to explore the possible relationship between workplace violence and CVD among United States workers. We utilized cross-sectional data from the 2015 National Health Interview Survey, which included a representative sample of 18 380 workers, to investigate the associations between workplace violence and the prevalence of CVD using logistic regression. Workplace violence was determined based on self-reported threats, bullying, or harassment at work over the past 12 months, supplemented with additional information regarding frequency. CVD included all forms of heart disease and stroke. A total of 1334 workers reported experiences of workplace violence, and 1336 workers were diagnosed with CVD. After adjustment for covariates, participants who reported any instance of workplace violence had significantly higher odds of having CVD (odds ratio [OR], 1.76; 95% confidence interval [CI], 1.35 to 2.30) than those who reported no such violence. Furthermore, the highest odds of CVD (OR, 1.80; 95% CI, 1.23 to 2.63) were observed among those frequently exposed to workplace violence. Even occasional exposure to workplace violence was associated with 74% excess odds of CVD. Our study indicates an association between workplace violence and CVD in United States workers, exhibiting a dose-response pattern.


An analytical investigation of critical factors to prioritize coalfields for Underground Coal Gasification - Bangladesh case.
In recent decades, many countries have shown a growing interest in Underground Coal Gasification (UCG) as a potential clean and environmental-friendly means of harnessing coal energy for power generation, and production of hydrogen, diesel fuel, etc. While Bangladesh may have good UCG potential that can be utilized to alleviate the country's current energy scarcity, this avenue has remained completely untapped up to now. In this work, the possibility of UCG implementation in five (05) indigenous discovered coalfields of the country was evaluated for the first time by using the preference selection index (PSI) method. This novel technique was considered to prioritize coalfields for gauging UCG potential. The PSI method is chosen over numerous traditional multi-criteria decision-making (MCDM) techniques, because it selects the best alternative from given alternatives without deciding the relative importance between attributes. The study indicated Jamalganj coalfield as the most suitable for implementing the UCG technique with a 93.6% potential. The second priority is Khalaspir coalfield with around 70.0% prospect and the other three coalfields - Dighipara (64.7%), Barapukuria (63.5%), and Phulbari (58.3%) may have UCG suitability in decreasing order of preference. The deduction is expected to assist the cogitation of energy-sector researchers and facilitate the decision-making of relevant authorities, policy makers, planners, and entrepreneurs.


Chronic intracerebroventricular infusion of the antiopioid peptide, Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), downregulates mu opioid binding sites in rat brain.
Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe-NH2 (NPFF), an endogenous mammalian antiopioid peptide, has been shown by other laboratories to attenuate the acute antinociceptive effects of morphine, the development of morphine tolerance, and naloxone-induced withdrawal in morphine-dependent rats. The present study determined the effect of chronic NPFF on mu opioid receptors and mRNA for the endogenous opioids dynorphin and enkephalin. Rats received ICV infusions of either saline or NPFF (5 micrograms/h) for 13 days via Alzet 2002 osmotic minipumps. Homogenate binding studies, which used whole brain membranes, demonstrated that NPFF decreased the Bmax of mu binding sites (labeled by [3H][D-Ala2-MePhe4,Gly-ol5]enkephalin) from 262 +/- 12 to 192 +/- 12 fmolmg protein, and increased the Kd from 1.1 to 2.3 nM. Quantitative receptor autoradiography and in situ hybridization experiments were conducted with sections collected at the level of the striatum. The density of mu opioid binding sites labeled by [3H][D-Ala2-MePhe4,Gly-ol5]enkephalin was decreased in all brain areas measured except the corpus callosum, and there was no change in dynorphin mRNA or enkephalin mRNA in the caudate, the nucleus accumbens, or the ventral pallidum. Rats chronically administered ICV morphine sulfate (20 micrograms/h) for 14 days developed tolerance to morphine and a low degree of dependence, as measured by naloxone-precipitated withdrawal. Chronic administration of NPFF concurrently with morphine sulfate did not significantly alter naloxone-induced withdrawal signs or the development of morphine tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)


Association of embryo aneuploidy and sperm DNA damage in unexplained recurrent implantation failure patients under NGS-based PGT-A cycles.
Recurrent implantation failure (RIF) is one of the most common conditions affecting In Vitro Fertilization (IVF)/Intracytoplasmic sperm injection (ICSI) outcomes. Aneuploidy embryos, one of the main types of embryos-related factors, was reported to be a major contributor to RIF. The present study aimed to examine the association between sperm DNA fragmentation index (DFI) and outcomes of next-generation sequencing (NGS)-based preimplantation genetic testing for aneuploidy (PGT-A) in unexplained RIF patients. This study analyzed 119 couples with unexplained RIF who underwent 119 PGT-A cycles between January, 2017 and March, 2022. The 119 males were divided into 3 groups according to their sperm DFI levels: Group1 (low, DFI ≤ 15%, n = 50), Group2 (medium, 15% < DFI < 30%, n = 41) and Group3 (high, DFI ≥ 30%, n = 28). Sperm DFI was measured by sperm chromatin structure analysis (SCSA) technique. Trophectoderm biopsy on day 5 or 6 were performed with NGS technique. The following outcomes of PGT-A were analyzed and compared: fertilization, good-quality embryos, aneuploidy rate, miscarriage, live birth and newborn defects. The component of aneuploidy embryos was significantly higher in high DFI group (42.71%) than that of medium group (28.39%) and low group (27.80%). The miscarriage rate of high DFI group (27.27%) and medium group (14.29%) is significantly higher than that of low group (0.00%). No significant differences were found regarding fertility, good-quality embryo rate, pregnancy rate, live birth rate or newborn defects among three groups. The sperm DNA damage is associated with blastocyst aneuploidy and miscarriage rate in unexplained RIF cases. Embryo selection by PGT-A and efforts to decrease sperm DFI before IVF/ICSI treatments should be considered for those male patients with high DFI.


Rheolytic thrombectomy with Angiojet in thrombus-containing lesions.
The AngioJet thrombectomy device removes thrombus by creating a negative pressure and causing fragmentation of the thrombus. The objective was to study the safety and efficacy of this thrombectomy device during coronary interventions and to report the results of our experience. We studied 72 patients (mean age, 64.9 +/- 12.6 years; 79% males) who had an AngioJet procedure during coronary intervention; 33 (46%) had vein graft intervention. All patients had angiographic thrombus. Most patients presented either with unstable angina (54%) or acute myocardial infarction (32%) within 24 hr. The procedural success was high with AngioJet (93%). TIMI grade 3 flow was achieved in 79% of lesions treated with AngioJet. In-hospital mortality was 1.4%, death/Q-wave myocardial infarction was 4.2%, and the composite endpoint of death and Q-wave myocardial infarction/revascularization was 5.6% for patients undergoing AngioJet. Subgroup analysis of patients with vein graft intervention demonstrated high procedural success in those undergoing AngioJet (91%). At 1-year follow-up of the successful percutaneous interventions with AngioJet, the mortality, death/Q-myocardial infarction, and composite endpoint rates were 10%, 13.3%, and 35.5%, respectively. Long-term event-free survival was worse in vein graft interventions. The incidence of death, death/myocardial infarction, or composite endpoints at 1 year was 16%, 19%, and 46%, respectively. High procedural success can be achieved with the AngioJet thrombectomy device in lesions containing thrombus. It is effective in both native coronary arteries and vein graft interventions. However, the long-term outcome of patients with vein graft intervention was worse.


[Neuronal organisation of the central part of the brain amygdaloid body].
Characteristics of neurons in amygdala central division were investigated and compared with the data available in literature on the similar parameters of the cells in its anterior and posterior divisions. Silver nitrate impregnation of neurons using Golgi method was used in this work. Classification and measurements of neurons were performed using Leontovich method (1978). Peculiarities of representation and quantitative characteristics of long-axonal and short-axonal neurons in amygdala central division were shown.


Preparation of Biotubes with vascular cells component by in vivo incubation using adipose-derived stromal cell-exuding multi-microporous molds.
Biotubes, prepared using in-body tissue architecture (IBTA) technology, have adequate mechanical properties and excellent biocompatibility for vascular grafts. However, they have thin walls, lack vascular constructing cells, and are composed of subcutaneous connective tissues consisting mainly of collagen and fibroblasts. This study aimed to prepare Biotubes with a vascular-like structure including an endothelial cell lining and a smooth muscle cell by IBTA using adipose-derived vascular stromal cell (ADSCs)-exuding specially designed multiporous tubes (outer diameter 5 mm, length 24 mm, pore size 500 μm, pore number 180, cell number/tube >3.0 × 10(6)). ADSCs were separated from rat subcutaneous fat, suspended in a Matrigel™ solution at 4 °C, and then filled into the tubes. After the tubes were embedded into dorsal subcutaneous pouches of the same rats for 2 weeks, robust Biotubes with a wall thickness of >600 μm were formed surrounding the tubes. The luminal layer of the obtained Biotubes was dominated by the cells positive for an endothelial marker. Almost the entire intima, with a thickness of about 400 μm, was occupied with cells positive for a smooth muscle marker. Both cells were derived from ADSCs. Biotube walls were constructed by fusing ADSC-derived vascular constructing cells exuded from the tubes and fibroblasts and collagen from the surrounding connective tissue. A robust Biotubes with vascular cells component, were formed after only 2 weeks of subcutaneous incubation of ADSCs-exuding multiporous tubes.