Phylogeography of the endemic grasshopper genus Betiscoides (Lentulidae) in the South African Cape Floristic Region.
Vicariance and dispersal are two important processes shaping biodiversity patterns. The South African Cape Floristic Region (CFR) is known for its high biotic diversity and endemism. However, studies on the phylogeography of endemic invertebrates in this biodiversity hotspot are still scarce. Here, we present a phylogenetic study of the flightless grasshopper genus Betiscoides, which is endemic to the CFR and strongly associated with restio plants (Restionaceae). We hypothesized that the genus originated in the southwestern part of the CFR, that differentiation within the genus is mainly an effect of vicariance and that the three known species only represent a minor fraction of the real genetic diversity of the genus. We inferred the phylogeny based on sequences of three mitochondrial and two nuclear genes from 99 Betiscoides specimens collected across the CFR. Furthermore, we conducted a SDIVA analysis to detect distributions of ancestral nodes and the possible spatial origin of these lineages. Strong differentiation among genetic lineages was shown. The ancestor of this genus was most likely distributed in the southwestern CFR. Five major lineages were detected, three of which were ancestrally distributed in the southwestern CFR. The ancestors of the two other lineages were distributed in the northern and eastern margins of the CFR. A total of 24 divergent evolutionary lineages were found, reflecting the geographical isolation of restio-dominated fynbos habitats. Dispersal played a more prominent role than expected in differentiation of Betiscoides. While the five main lineages were separated during a first phase via dispersal, differentiation occurred later and on smaller spatial scale, predominantly driven by isolation in montane refugia (i.e. vicariance). Our study also suggests that flightless insect taxa likely show high levels of differentiation in biodiversity hotspots with their taxonomy often being incomplete.


Low forced expiratory volume in one second is associated with the history of acute coronary syndrome in patients with organic coronary stenosis.
Chronic obstructive pulmonary disease often coexists with cardiovascular diseases and airflow limitation has been known as a risk of cardiovascular death. However, the association between airflow limitation and the history of acute coronary syndrome (ACS) in patients with coronary stenosis remains to be determined. Study subjects were 271 consecutive patients (age: 70.6±9.5 years, sex: 200 males) who underwent coronary angiography and in whom organic coronary stenosis was detected. We collected spirometric data from those patients and investigated the association of the pulmonary function and the history of ACS. We also compared the prevalence of airflow limitation of the present subjects with Japanese epidemiological data that had been previously published. Multivariate analysis with multiple logistic regression analysis showed that the reduced forced expiratory volume in one second (FEV1.0) less than 80% of predicted value was significantly associated with a history of ACS (odds ratio: 2.81, 95% CI: 1.27-6.20, p<0.02) independently of age, sex, body mass index, and classic coronary risk factors including smoking habit, diabetes mellitus, hypertension, and dyslipidemia. Furthermore, the airflow limitation was more prevalent in the present subjects than in the Japanese general population (25.8% vs. 10.9%, p<0.05). Reduced FEV1.0 is associated with a history of ACS in patients with coronary arterial stenosis irrespective of any coronary risk factors. Airflow limitation is more prevalent in patients with coronary stenosis than in the general population.


Tradeoff between risks through ingestion of nanoparticle contaminated water or fish: Human health perspective.
This study proposed a framework (termed as "nanoHealthRisk" hereafter) for incorporating i) interaction of nanoparticles (NPs) with fishes, ii) availability of NPs to the human digestive system, and iii) estimation of health risk due to fish consumption and inadvertent ingestion of NP-contaminated surface water, for the first time as per the literature review. The framework was applied for estimating health risks due to hypothetical exposures of pristine ZnO, CuO, and TiO2 NPs (without any surface functionalization) from fish tissues. Values of bio- concentration factors (BCF) of ZnO, CuO, and TiO2 NPs in fish and model distributions of bio-assimilation factor of ZnO, CuO and TiO2 NPs in the human digestive system were incorporated explicitly in the risk assessment of NPs for the first time. ZnO NP was observed to be transferred more to the human digestive system from aqueous matrix than the other two NPs. Maximum allowable values of NP posing no risk were found to be 0.115 mg/L, 0.152 mg/L, and 1.77 × 107 mg/L for pristine ZnO, CuO and TiO2 NP, respectively. At the environmental concentration range, exposures of studied NPs from aquatic environment under the assumptions used did not pose any health risk under the conditions studied in this study. More work is required to (1) Estimate bio-concentration factors of a mixture of NPs with other constituents in fish tissues, (2) Estimate dissolution of NP from fish tissue in human digestive media, (3) Generate new data to develop reference dose of NP for human health risk assessment, and (4) Study effect of NP fate in the water on health risk through fish consumption pathway. Until all above-mentioned aspects are not explicitly incorporated in the risk assessment framework, risk estimates do not represent the risk from environment completely. Thus, continuous monitoring of these NPs in the environment is required to protect health due to chronic exposure of small concentrations of NPs from an aqueous matrix.


Effect of Prescription Size on Opioid Use and Patient Satisfaction After Minor Hand Surgery: A Randomized Clinical Trial.
To determine the influence of initial prescription size on opioid consumption after minor hand surgeries. Secondary outcomes include efficacy of pain control, patient satisfaction, and refill requests. Retrospective studies have shown that opioid prescriptions for acute pain after surgical procedures are often excessive in size, which encourages misuse. This is the first prospective randomized trial on the influence of initial prescription size on opioid consumption in the setting of acute postsurgical pain. In a prospective randomized trial at a single-academic institution, patients were provided an initial prescription of either 10 or 30 hydrocodone/acetaminophen (5/325 mg) pills after surgery. Two hundred opioid-naive patients, aged 19 to 69, undergoing elective outpatient minor hand surgeries were enrolled over 9 months, with a follow-up period of 10 to 14 days. One hundred seventy-four patients were included in this analysis. Patients initially prescribed 30 pills (n = 79), when compared with patients initially prescribed 10 pills (n = 95), used significantly more opioid (P = <0.001, mean 11.9 vs 6.4 pills), had significantly more leftover medication (P = <0.001, mean 20.0 vs 5.2 pills), and were over 3 times more likely to still be taking opioid at follow-up (15% vs 4%). There was no significant difference in refills requested, or in patient satisfaction with postoperative pain control. Providing large opioid prescriptions for the management of acute pain after minor upper extremity surgeries increases overall opioid use when compared with smaller initial prescriptions. The size of initial opioid prescription is a modifiable variable that should be considered both in patient care and research design.


Development of a new tachykinin antagonist.
The mouse urinary bladder possesses a tachykinin receptor which responds to kassinin and eledoisin, but not to some other tachykinins. The action of kassinin, but not that of eledoisin, was blocked in a surmountable manner by a new tachykinin antagonist, D-Pro4, Val8, D-Trp (SP).


Interleukin-6 and prostate cancer: Current developments and unsolved questions.
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models. Experimental therapies have been proposed in order to block the IL-6/STAT3 signaling pathway. In this context, the anti-IL-6 antibody siltuximab (CNTO 328) has been demonstrated to inhibit growth of prostate tumors in vitro and in vivo and delays progression towards castration resistance. However, clinically, the anti-IL-6 antibody was not successful as a monotherapy in phase II studies in patients with metastatic PCa. IL-6 is implicated in regulation of cellular stemness by increasing phosphorylation of STAT3. The cytokine has also a role in development of resistance to the non-steroidal anti-androgen enzalutamide. Endogenous inhibitors of IL-6 are suppressors of cytokine signaling and protein inhibitors of activated STAT. Although they inhibit signal transduction through STAT3, they may also exhibit anti-apoptotic effects. On the basis of complexity of IL-6 action in PCa, an individualized approach is needed to identify patients who will benefit from anti-IL-6 therapy in combination with standard treatments.


Studies on the influence of host plants and effect of chemical stimulants on the feeding behavior in the muga silkworm, Antheraea assamensis.
The feeding habits of Antheraea assamensis, Helfer (Lepidoptera: Saturniidae) larvae towards the leaves of its four different host plants, Persea bombycina King ex. Hook (Laurales: Lauraceae), Litsea polhantha Jussieu, L. salicifolia Roxburgh ex. Nees and L. citrata Blume, and the chemical basis of feeding preference were investigated. Nutritional superiority of young and medium leaves with respect to soluble protein, total phenol and phenylalanine ammonia lyase activity was observed in the leaves of P. bombycina compared to other host plants. Attraction and feeding tests with detached leaves and artificial diet with different chemical stimulants revealed that a mixture of the flavonoids, myrcetin, and 7, 2', 4' trimethoxy dihydroxy flavone with sterol compound β-sitosterol elicited the most biting behavior by A. assamensis larvae. While linalyl acetate alone attracted larvae towards the leaves of the host plants, a mixture of caryophyllene, decyl aldehyde and dodecyl aldehyde was found to both attract them to the host leaves and cause biting behavior. Azaindole was found to deter them from the host plants.


A randomized controlled trial to compare anal dilatation with lateral subcutaneous sphincterotomy for anal fissure.
A prospective randomized trial has compared manual dilatation of the anus (MDA)during general anesthesia with lateral subcutaneous spincterotomy (LSS) during local anesthesia for the management of anal fissure in 156 patients. The two groups were similar with respect to age, sex and symptoms. There was no difference in the duration of time off work or early complications of treatment but, four months after operation, 93 per cent claimed to have been improved by MDA compared with 78 per cent after LSS (P less than 0.05). Recurrent fissure was recorded in 13 patients after LSS (29 per cent) compared with four (10 per cent) after MDA (P less than 0.02). There was a significant reduction in anal pressure at four months (P less than 0.02) after MDA, (123 +/- 31 to 97 +/-33) and LSS (127 +/- 36 to 104 +/- 32), but the anal pressure remained unchanged by operation in all patients where pressures were measured with recurrent fissure. These data indicate that MDA gives better results than LSS for treatment of anal fissure and that successful treatment is associated with a reduction in anal pressure.


Characteristics of Japanese Duchenne and Becker muscular dystrophy patients in a novel Japanese national registry of muscular dystrophy (Remudy).
Currently, clinical trials for new therapeutic strategies are being planned for Duchenne and Becker muscular dystrophies (DMD/BMD). However, it is difficult to obtain adequate numbers of patients in clinical trials. As solutions to these problems, patient registries are an important resource worldwide, especially in rare diseases such as DMD/BMD. We developed a national registry of Japanese DMD/BMD patients in collaboration with TREAT-NMD. The registry includes male Japanese DMD/BMD patients whose genetic status has been confirmed by genetic analysis. The registry includes patients throughout Japan. As of February 2012, 583 DMD and 105 BMD patients were registered. Most individuals aged less than 20 years. In terms of genetic mutations of registrants of DMD and BMD, deletion of exons was the most frequent (61.4% and 79.0%) followed by point mutations (24.5% and 14.3%) and duplications (13.6% and 4.8%), respectively. 43.6% of DMD are capable of walking, and 76.2% of BMD registrants are able to walk. 41.1% of DMD registrants in the database were treated using steroids. 29.5% of DMD and 23.8% of BMD registrants were prescribed one cardiac medicine at least. 22% of DMD used ventilator support, and non-invasive support was common. Small numbers of DMD and BMD registrants, only 3.9% and 1.0% of them, have received scoliosis surgery. 57 (9.8%) patients were eligible to clinical trial focused on 'skipping' exon 51. The Remudy has already demonstrated utility in clinical researches and standardization of patients care for DMD/BMD. This new DMD/BMD patient registry facilitates the synchronization of clinical drug development in Japan with that in other countries.


Generation of realistic synthetic data using Multimodal Neural Ordinary Differential Equations.
Individual organizations, such as hospitals, pharmaceutical companies, and health insurance providers, are currently limited in their ability to collect data that are fully representative of a disease population. This can, in turn, negatively impact the generalization ability of statistical models and scientific insights. However, sharing data across different organizations is highly restricted by legal regulations. While federated data access concepts exist, they are technically and organizationally difficult to realize. An alternative approach would be to exchange synthetic patient data instead. In this work, we introduce the Multimodal Neural Ordinary Differential Equations (MultiNODEs), a hybrid, multimodal AI approach, which allows for generating highly realistic synthetic patient trajectories on a continuous time scale, hence enabling smooth interpolation and extrapolation of clinical studies. Our proposed method can integrate both static and longitudinal data, and implicitly handles missing values. We demonstrate the capabilities of MultiNODEs by applying them to real patient-level data from two independent clinical studies and simulated epidemiological data of an infectious disease.


Mass and number of fibres in the pathogenesis of asbestos-related lung disease in rats.
Five groups of rats were treated by inhalation for 12 months, with the U.I.C.C. preparations of the 3 main commercially used asbestos types, chrysotile, crocidolite and amosite. The experiment was designed so that the effects of both fibre mass and fibre number could be examined. The results indicated that chrysotile dust caused far more lung fibrosis than either amphibole type even when the fibre numbers in the dust clouds were similar. All malignant pulmonary neoplasms found during this study occurred in animals treated with chrysotile. The fibre-number calculations used for the generation of dust clouds were evaluated using the parameters recommended by the Health and Safety Executive in 1976, by which all fibres over 5 microgram long are counted using a phase-contrast light microscopy. When fibre-length distributions were calculated using a scanning electron microscope, however, it was found that the chrysotile clouds used in this study contained many more fibres over 20 microgram long than either of the amphibole clouds. The results, therefore, support previous suggestions that long asbestos fibres are more dangerous than short. They also indicate that neither a single mass standard, nor the present fibre-number standards are satisfactory.


Complete Genome Sequence of Rhodococcus qingshengii N9T-4.
Rhodococcus qingshengii N9T-4 can grow on media without added carbon sources. Here, we report the complete nucleotide sequence of the N9T-4 genome, consisting of a chromosome (6,439,972 bp), a linear plasmid (pN9T4-1 [565,206 bp]), and two circular plasmids (pN9T-4-2 [99,662 bp] and pN9T-4-3 [30,419 bp]).


Clinical outcomes after one anastomosis gastric bypass versus sleeve gastrectomy in super-super-obese patients.
Bariatric surgery in super-super-obese (SSO) patients remains a continuous challenge due to intraabdominal fat masses, higher liver volume and existing comorbidities. A convenient procedure in SSO patients is one anastomosis gastric bypass (OAGB). The aim of this study was to compare the outcome of SSO patients undergoing OAGB in comparison to laparoscopic sleeve gastrectomy (LSG). We retrospectively reviewed data from SSO patients who underwent OAGB and LSG in our institution between 2008 and 2020. Primary endpoints included percentage total body weight loss and percentage BMI loss at 12, 24, and 36 months after the operation. Secondary endpoints were perioperative complications, procedure length, length of hospital stay and outcome of comorbidities. 243 patients were included in this study. 93 patients underwent LSG and 150 underwent OAGB. At any of the time points evaluated, weight loss in patients after OAGB was greater than in LSG patients, while procedure length was significantly shorter for OAGB than LSG (81.4 vs. 92.1 min, p-value < 0.001). Additionally, mean length of hospital stay was shorter in the OAGB group (3.4 vs. 4.5 days, p-value < 0.001). There were more severe complications (Clavien-Dindo ≥ 3a) in the LSG group (11.8% vs 2.7%, p-value = 0.005). In this retrospective analysis, OAGB was superior to LSG in terms of weight loss in SSO patients. Procedure length and hospital stay were shorter after OAGB in comparison to LSG and there were fewer severe complications. OAGB can therefore be regarded a safe and effective treatment modality for SSO patients.


Nitrogen concentration and mimicry in some New Zealand mistletoes.
The nitrogen concentration in photosynthetic organs of 41 pairs of mistletoes and their respective hosts was compared and found to be higher (in relation to that of their hosts) in cryptic mistletoes and lower in non-cryptic mistletoes. This supports the hypothesis that crypsis may have evolved as a mechanism for avoiding predation by vertebrate herbivores. There were no consistent differences between the nitrogen concentrations of hosts and mistletoes in trees and larger-leaved shrubs (whether native or introduced). The largest differences between mistletoes and their hosts were found on small-leaved divaricate shrubs (Coprosma ssp., Melicope simplex) where the nitrogen concentrations in cryptic mistletoes (Korthalsella spp.) were significantly higher than in their hosts, but significantly lower in prominent mistletoes (Loranthus micranthus, Tupeia antarctica) which apparently "advertise" their unpalatability. If crypsis in New Zealand mistletoes evolved as a protection against herbivory, then it must have evolved in the absence of mammalian herbivores, and the appropriate selection pressures could have been provided only by moas, extinct ratite birds. Otherwise, alternative explanations, such as differing relationships between water use and nitrogen uptake, must be sought for the observed associations of nitrogen concentration and cryptic mimicry in New Zealand mistletoes.


Identifying differentially expressed genes in pollen from self-incompatible "Wuzishatangju" and self-compatible "Shatangju" mandarins.
Self-incompatibility (SI) is one of the important factors that can result in seedless fruit in Citrus. However, the molecular mechanism of SI in Citrus is not yet clear. In this study, two suppression subtractive hybridization (SSH) libraries (forward, F and reverse, R) were constructed to isolate differentially expressed genes in pollen from "Wuzishatangju" (SI) and "Shatangju" (self-compatibility, SC) mandarins. Four hundred and sixty-eight differentially expressed cDNA clones from 2077 positive clones were sequenced and identified. Differentially expressed ESTs are possibly involved in the SI reaction of "Wuzishatangju" by regulating pollen development, kinase activity, ubiquitin pathway, pollen-pistil interaction, and calcium ion binding. Twenty five SI candidate genes were obtained, six of which displayed specific expression patterns in various organs and stages after self- and cross-pollination. The expression level of the F-box gene (H304) and S1 (F78) in the pollen of "Wuzishatangju" was 5-fold higher than that in "Shatangju" pollen. The F-box gene, S1, UBE2, UBE3, RNaseHII, and PCP were obviously up-regulated in pistils at 3 d after self-pollination of "Wuzishatangju", approximately 3-, 2-, 10-, 5-, 5-, and 2-fold higher, respectively than that at the same stage after cross-pollination of "Wuzishatangju" × "Shatangju" pistils. The potential involvement of these genes in the pollen SI reaction of "Wuzishatangju" is discussed.


Beneficial effects of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a superoxide dismutase mimetic, in carrageenan-induced pleurisy.
Peroxynitrite, a potent cytotoxic oxidant formed by the reaction of NO with superoxide anion, has been proposed to have major pathogenetic role in inflammatory process. Here we have investigated the therapeutic efficacy of Mn(III)tetrakis (4-benzoic acid) porphyrin (MnTBAP), a novel superoxide dismutase mimetic that possesses peroxynitrite scavenging effect, in rats subjected to carrageenan-induced pleurisy. In vivo treatment with MnTBAP (3 and 10 mg/kg 5 min before carrageenan) prevented in a dose-dependent manner the carrageenan-induced the degree of pleural exudation, polymorphonuclear migration in rats subjected to carrageenan-induced pleurisy. Lung myeloperoxidase (MPO) activity and histological organ injury was significantly reduced by MnTBAP. However, MnTBAP did not inhibit the inducible NO synthase in lung samples. Immunohistochemical analysis for nitrotyrosine, a footprint of peroxynitrite, revealed a positive staining in lungs from carrageenan-treated rats. No positive nitrotyrosine staining was found in the lungs of the carrageenan-treated rats that received MnTBAP (10 mg/kg) treatment. In addition, in vivo MnTBAP treatment significantly reduced in a dose-dependent manner peroxynitrite formation as measured by the oxidation of the fluorescent dye dihydrorhodamine 123, prevented the appearance of DNA damage, the decrease in mitochondrial respiration and partially restored the cellular level of NAD+ in ex vivo macrophages harvested from the pleural cavity of rats subjected to carrageenan-induced pleurisy. Our study demonstrates that the MnTBAP exerts multiple protective effects in carrageenan-induced pleurisy. We suggest peroxynitrite produced during the inflammatory process trigger DNA strand breakage and subsequent cellular dysfunction. Part of these anti-inflammatory effects may be related to: (1) reduction of superoxide formation due to the superoxide dismutase-like activity of the compound and (2) scavenging of peroxynitrite.


Exposure to physical and sexual violence prior to imprisonment predicts mental health and substance use treatments in prison populations.
The present study aimed to establish rates of exposure to physical or sexual violence (PSV) prior to imprisonment for prisoners in Spain and to explore whether people exposed to PSV access mental health treatment during imprisonment. In a sample of 2484 male and 225 female prisoners, socio-demographic variables, exposure to PSV prior to imprisonment and mental health treatments during imprisonment were assessed. Frequencies were calculated as per cent values with 95% confidence intervals (CI). The Risk Ratio (RR) of PSV and other socio-demographic variables to associate with mental health treatment during imprisonment was established. History of PSV was present in 35.2% (95% CI: 33.3-37.0) of the male and 40.0% (95% CI: 33.9-46.8) of the female prisoners. 70.7% (95% CI: 67.8-73.9) of the male and 76.9% (95% CI: 67.7-86.0) of the female prisoners with prior exposure to PSV were in mental health treatment during imprisonment. PSV was a significant predictor of mental health treatment during imprisonment in male (RR: 2.79; 95% CI 2.44-2.92) and female (RR: 1.94; 95% CI 1.76-2.23) prisoners. Most people with exposure to PSV prior to imprisonment access mental health treatment during imprisonment. Treatments may have to focus more on traumatic experiences.


Poly(ADPR)polymerase inhibition and apoptosis induction in cDDP-treated human carcinoma cell lines.
Poly(ADPR)polymerases' (PARPs) inhibitors potentiate the cytotoxic effects of chemotherapeutic agents like alkylating compounds and TOPO I poisons, while their action in combination with cisplatin still needs investigation. In fact, one of the earliest responses to DNA single- or double-strand breaks is the synthesis of poly(ADP-ribose) (PAR) by PARPs; these enzymes are components of DNA repair machineries and substrates of caspases. Cisplatin (cDDP) yields intra- and inter-strand DNA cross-links and several proteins that recognise cDDP-induced DNA damage, such as p53, are also targets of poly(ADP-ribosyl)ation. We compared the effects of treatments with cDDP and the PARPs inhibitor PJ34 in p53 mutated carcinoma cell lines (HeLa, KB, HT29) that exhibited differential sensitivities to the drugs, in terms of cell growth inhibition and onset of apoptosis. In cDDP-resistant HT29 cells we determined: (i) PJ34 potentiation of cDDP-induced cell growth inhibition; (ii) an increment of PARP-1 automodification following cDDP treatment. In cDDP-sensitive HeLa cells, we found that the drug induced apoptotic cell death associated with caspase-dependent PARP-1 proteolysis.


Willingness to pay for midwife-endorsed product: An Australian best-worst study.
This article examined the impact of midwife endorsement on stated choice preferences in one of the highest volume baby care product categories, diapers. An online survey was conducted testing 12 alternatives of which six were midwife endorsed. A total of 215 responses were analyzed using best-worst and multinomial logit modeling. Results indicate that package size, price, and brand are more sensitive predictors of stated choice preferences than midwife endorsement. Respondents were willing to pay 2.3% more for a diaper that was endorsed by midwives. These findings suggest that midwife endorsement should be pursued by health marketers.


Bioimpedance: a novel method for the determination of extravascular lung water.
Extravascular lung water (EVLW) can be measured using the double indicator dilution technique (DD). However, because this method is highly invasive and complicated, its clinical used has been limited. In theory, changes in thoracic conductivity, or bioimpedance (BI), can reflect changes in EVLW. However, past studies were unable to directly quantitate changes in EVLW since the contribution of dynamic variables such as ventricular volumes, hematocrit (HCT), and EVLW to this impedance signal could not be discerned. Recent studies have shown that a thermodilution pulmonary artery catheter mounted with a fast response thermistor accurately measures right ventricular end-diastolic volume (RVEDV). With changes in the RVEDV and HCT known, the contribution of EVLW to the bioimpedance signal may be isolated and used to more directly measure changes in EVLW. This hypothesis was tested by creating acute sepsis in seven pigs by infusion of Pseudomonas aeruginosa. Changes in EVLW from baseline were measured using DD at 30 min and at 1, 2, and 4 hr and compared with the change in EVLW computed from a mathematical model comprising the measured changes in BI, RVEDV, and HCT at the same time points. Changes in EVLW using DD and BI were significantly correlated over the length of the study (r = 0.85, P less than 0.01). In early sepsis (30 min), BI overestimated EVLW when compared with DD (P less than 0.05). However, at 1, 2, and 4 hr there was no significant difference between the two methods. In conclusion, the use of bioimpedance and a volumetric catheter may provide a relatively simple and reliable method for continuously monitoring changes in EVLW in the intensive care setting.


Combination injuries 3. The risk of pulp necrosis in permanent teeth with extrusion or lateral luxation and concomitant crown fractures without pulp exposure.
To analyze the influence of a crown fracture without pulp exposure on the risk of pulp necrosis (PN) in teeth with extrusion or lateral luxation. The study included 82 permanent incisors with extrusion from 78 patients (57 male, 21 female) and 179 permanent incisors with lateral luxation from 149 patients (87 male, 62 female). A total of 25 teeth with extrusion and 33 teeth with lateral luxation had suffered a concomitant crown fracture (infraction, enamel fracture or enamel-dentin-fracture). All the teeth were examined and treated according to a standardized protocol. The risk of PN was analyzed separately for teeth with immature and mature root development by the Kaplan-Meier method, the log-rank test and Cox regression (lateral luxation only). The level of significance was set at 5%. Risk factors included in the analysis were gender, age, crown fracture, and response to electric pulp test at the initial examination. A concomitant crown fracture significantly increased the risk of PN in teeth with lateral luxation. For teeth with immature root development (hazard ratio: 10 [95% confidence interval (CI): 1.1-100] P = 0.04), the overall risk increased from 4.7% (95% CI: 0-10.8) to 40% (95% CI: 2.8-77.2). For teeth with mature root development [hazard ratio: 2.4 (95% CI: 1.4-4.2) P < 0.001], the overall risk increased from 65.1% (95% CI: 55.2-75.1) to 93% (95% CI: 85.5-100). In teeth with extrusion and mature root development, the overall risk of PN increased from 56.5% (95% CI: 37.7-75.4) to 76.5% (95% CI: 58.9-94) in case of a concomitant crown fracture, but the difference was not statistically significant (P > 0.05). A concomitant crown fracture without pulp exposure significantly increased the risk of PN in teeth with lateral luxation. This risk factor may be used to identify teeth at increased risk of PN following lateral luxation injury.


Long non-coding RNA LINC00665 gastric cancer tumorigenesis by regulation miR-149-3p/RNF2 axis.
Recently, LINC00665 has been reported to be a pivotal regulator in kinds of malignancy, such as lung cancer and liver cancer. However, the functions and underlying mechanisms of LINC00665 in gastric cancer (GC) remain unclear. We recruited 49 paired GC tissue to explore LINC00665 expression by qRT-PCR. In vitro function assays were used to explore the roles of LINC00665 in GC progression. Moreover, the interaction among LINC00665, miR-149-3p and RNF2 was explored by bioinformatics analysis and luciferase reporter assay. In the present study, we found that LINC00665 expression was significantly elevated in GC tissues and cell lines. High LINC00665 expression was associated with TNM stage, histological grade, and poor prognosis of GC patients. Function assays showed that LINC00665 suppression significantly reduced GC cells viability and invasion ability in vitro. Mechanistic analysis showed that LINC00665 might serve as a ceRNA for miR-149-3p to regulate the expression of RNF2. Our current study revealed the LINC00665/miR-149-3p/RNF2 axis was involved in GC progression, providing novel insights into the treatment for GC.


QuEChERS sample pre-processing with UPLC-MS/MS: A method for detecting 19 quinolone-based veterinary drugs in goat's milk.
We develop and validate a method for the rapid determination and identification of 19 quinolones in goat's milk by combining the QuEChERS technique with ultra-performance liquid chromatography-tandem mass spectrometry. Plackett-Burman and Central Composite Design methods were used to select the parameters that best promote the extraction efficiency, which led to extraction with acetonitrile/5% formic acid, followed by phase separation with sodium citrate, disodium hydrogen citrate, Na2SO4, and NaCl as optimal. The supernatant was then extracted and cleaned by dispersive solid-phase extraction using C18 and Na2SO4 aided by low-temperature clean-up. The method was validated, with limits of quantification (LOQs) of 5 ppb, specificities of 1/5 LOQ, linearities (R2) > 0.9853, recoveries of 73.4-114.2%, repeatabilities < 15.0%, and intermediate precisions < 13.6%. The developed method was suitable for the routine analysis of quinolone residues in goat's milk and was used to test 10 goat milk samples produced in Taiwan.


Exploring consumer exposure pathways and patterns of use for chemicals in the environment.
Humans are exposed to thousands of chemicals in the workplace, home, and via air, water, food, and soil. A major challenge in estimating chemical exposures is to understand which chemicals are present in these media and microenvironments. Here we describe the Chemical/Product Categories Database (CPCat), a new, publically available (http://actor.epa.gov/cpcat) database of information on chemicals mapped to "use categories" describing the usage or function of the chemical. CPCat was created by combining multiple and diverse sources of data on consumer- and industrial-process based chemical uses from regulatory agencies, manufacturers, and retailers in various countries. The database uses a controlled vocabulary of 833 terms and a novel nomenclature to capture and streamline descriptors of chemical use for 43,596 chemicals from the various sources. Examples of potential applications of CPCat are provided, including identifying chemicals to which children may be exposed and to support prioritization of chemicals for toxicity screening. CPCat is expected to be a valuable resource for regulators, risk assessors, and exposure scientists to identify potential sources of human exposures and exposure pathways, particularly for use in high-throughput chemical exposure assessment.


Investigation of cytotoxic, genotoxic, mutagenic, and estrogenic effects of the flame retardants tris-(2-chloroethyl)-phosphate (TCEP) and tris-(2-chloropropyl)-phosphate (TCPP) in vitro.
The organophosphorus esters tris-(2-chloroethyl)-phosphate (TCEP) and tris-(2-chloropropyl)-phosphate (TCPP) have been widely used as flame retardants and fire preventing agents, e.g. in polyurethane foams. We investigated the cytotoxic, genotoxic, mutagenic, and estrogenic potentials of TCEP and TCPP, using different in vitro models. Cytotoxic effects were evaluated by neutral red uptake and genotoxicity with the alkaline single cell gel electrophoresis (Comet assay), both in V79 (hamster fibroblasts) cells. Mutagenicity was tested in the Ames assay with Salmonella typhimurium using the strains TA 97 a, 98, 100, 102, 104, 1535, 1537, and 1538, with and without metabolic activation by S9-rat liver homogenate. Estrogenic or anti-estrogenic effects were examined with the recombinant yeast reporter gene assay, and in human endometrial cancer Ishikawa cells by induction of alkaline phosphatase. In V79 cells TCEP was weakly cytotoxic at concentrations above 10 microM in the presence of S9-rat liver homogenate whereas TCPP showed cytotoxicity above 1mM in the presence of S9. Both substances did not induce DNA strand breaks in the alkaline version of the Comet assay neither without an external enzymatic metabolizing system, nor in the presence of S9-mix. Additionally, no mutagenic potential could be detected for TCEP and TCPP in eight Salmonella strains using concentrations up to 1mM in the presence and absence of S9. Hormonal activity shown as induction of estrogenic or anti-estrogenic effects could not be detected in the two in vitro test systems.


Evaluating corrected carotid flow time as a non-invasive parameter for trending cardiac output and stroke volume in cardiac surgery patients.
The corrected carotid flow time (ccFT) is derived from a pulsed-wave Doppler signal at the common carotid artery. Several equations are currently used to calculate ccFT. Its ability to assess the intravascular volume status non-invasively has recently been investigated. The purpose of this study was to evaluate the correlation and trending ability of ccFT with invasive cardiac output (CO) and stroke volume (SV) measurements. Eighteen cardiac surgery patients were included in this prospective observational study. ccFT measurements were obtained at three time points: after induction of anesthesia (T1), after a passive leg raise (T2), and post-bypass (T3). Simultaneously, CO and SV were measured by calibrated pulse contour analysis. Three different equations (Bazett, Chambers, and Wodey) were used to calculate ccFT. The correlation and percentage change in time (concordance) between ccFT and CO and between ccFT and SV were evaluated. Mean ccFT values differed significantly for the three equations (p < 0.001). The correlation between ccFT and CO and between ccFT and SV was highest for Bazett's (ρ = 0.43, p < 0.0001) and Wodey's (ρ = 0.33, p < 0.0001) equations, respectively. Concordance between ΔccFT and ΔCO and between ΔccFT and ΔSV was highest for Bazett's (100%) and Wodey's (82%) equations, respectively. Subgroup analysis demonstrated that correlation and concordance between SV and ccFT improved when assessed within limited heart rate (HR) ranges. The use of different ccFT equations leads to variable correlation and concordance rates between ccFT and CO/SV measurements. Bazett's equation acceptably tracked CO changes in time, while the trending capability of SV was poor.


Latex hypersensitivity/glove component reaction as a contributing factor to osteomyelitis of the hand: a case report and review of the literature.
A patient with a known glove-related allergy/irritation has been diagnosed with osteomyelitis of the left ring finger. The patient's susceptibility to bone and soft tissue infection is due to an open skin fissure and an eczematoid dermatitis due to a work-related glove reaction. This article is presented to alert readers of the Journal of the Louisiana State Medical Society to the possibility of encountering this unusual complication of latex glove wear and to familiarize them with irritant and allergic contact dermatitis. This report is relevant as the incidence of occupational-related glove reactions has risen and continues to rise.


Early Progression of Xanthogranulomatous Pyelonephritis in Children Might Be Dependent on Vimentin Expression.
BACKGROUND Xanthogranulomatous pyelonephritis (XP) is an extremely rare, severe, atypical form of chronic renal parenchymal inflammation accompanied by hydronephrosis and/or urolithiasis. The pathomechanism of XP is not yet fully understood. Microscopically, XP is indicated by the presence of multinucleated giant cells and lipid-laden macrophages, as well as inflammatory infiltration and intensive renal fibrosis. The lipid accumulation in kidney parenchyma may be secondary to the altered flow of low-density lipoprotein (LDL)-derived cholesterol particles inside the affected cells. Physiologically, the process of LDL-derived cholesterol transport from lysosomes to the sites of its esterification is dependent on vimentin, which is a molecule comprising the cytoskeleton in mesenchymal cells. CASE REPORT A 7-year old girl was hospitalized because of the finding of unexplained kidney lesions on an abdominal ultrasound examination (an enlarged and deformed collecting system of the right kidney with hyperechogenic, solid, staghorn lesions in the calyces). Three months earlier, the patient had experienced recurrent urinary tract infection. Based on the subsequent laboratory and imaging diagnostics, the final diagnosis of XP was established and the girl was qualified for right-sided nephrectomy Microscopic examination revealed numerous foci of granuloma formations with no evident exponents of dysplastic or neoplastic abnormalities. Significant CD68-positive cell infiltrations and scattered foam cells arranging the numerous foci of granuloma inflammation were noticed. Renal parenchyma, adjacent to granuloma lesions, presented a vimentin expression. CONCLUSIONS Vimentin expression in XP may confirm a focal character of chronic granuloma formation and may suggest the complexity of XP pathogenesis involving not only macrophage and fibroblast activation but also local lipid deregulation and fibrosis.


Dentistry for children during and post COVID-19 pandemic outbreak.
During and post COVID-19 pandemic outbreak, it is essential for safeguarding this viral infection control and prevention in pediatric dental practices. The role of parents and pediatric dentist and their dental team requires specific guidance to deal with dental problems of children in the dental operatory during and post-pandemic outbreak of COVID-19 disease. To report dentistry for children during and post COVID-19 pandemic outbreak. The present review highlights the clinical features, possible modes of transmission of COVID-19 in dental operatory, preventive strategies, emergencies that pose a significant challenge, and treatment strategies for dealing with children and parents during and post COVID-19 pandemic. Absolute measures for children during their visit to dental operatory, quality control for pediatric dental clinics, and additional preventive measures associated with examinations and management of dental problems in children have been covered in this insight.


Diagnostic and prognostic value of mitochondrial DNA minisatellites after stem cell transplantation.
Mitochondrial DNA has been used to investigate phylogenetic relationships and pathophysiologic roles in aging, degenerative diseases, and cancer. We investigated the prognostic usefulness of mitochondrial DNA minisatellite (mtMS) markers compared with nuclear short tandem repeat markers by evaluating the laboratory performance and clinical value of these markers in a large sample of patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with various simulated conditions in vitro and in serial follow-up samples. We examined the value of mtMS markers as a prognostic indicator in 100 patients with various hematologic disorders undergoing allo-HSCT, including 35 patients with longitudinal follow-up for 55 months. The mtMS markers showed high sensitivity and accuracy for the quantitative detection of chimerism compared with nuclear short tandem repeat markers, particularly in unrelated transplantation and under inappropriate sampling conditions. Longitudinal follow-up after allo-HSCT disclosed that chimerism precisely reflected the status of engraftment or relapse during the clinicopathological course. Moreover, changes in mtMS markers in recipients before allo-HSCT were associated with clinical outcomes. Our data indicate that mtMS markers have multiple functions in monitoring mixed chimerism and predicting prognosis after allo-HSCT.


A role of Ultrabithorax in morphological differences between Drosophila species.
The mechanisms underlying the evolution of morphology are poorly understood. Distantly related taxa sometimes exhibit correlations between morphological differences and patterns of gene expression, but such comparisons cannot establish how mechanisms evolve to generate diverse morphologies. Answers to these questions require resolution of the nature of developmental evolution within and between closely related species. Here I show how the detailed regulation of the Hox gene Ultrabithorax patterns trichomes on the posterior femur of the second leg in Drosophila melanogaster, and that evolution of Ultrabithorax has contributed to divergence of this feature among closely related species. The cis-regulatory regions of Ultrabithorax, and not the protein itself, appear to have evolved. This study provides experimental evidence that cis-regulatory evolution is one way in which conserved proteins have promoted morphological diversity.


Multisensory and Motor Representations in Rat Oral Somatosensory Cortex.
In mammals, a complex array of oral sensors assess the taste, temperature and haptic properties of food. Although the representation of taste has been extensively studied in the gustatory cortex, it is unclear how the somatosensory cortex encodes information about the properties of oral stimuli. Moreover, it is poorly understood how different oral sensory modalities are integrated and how sensory responses are translated into oral motor actions. To investigate whether oral somatosensory cortex processes food-related sensations and movements, we performed in vivo whole-cell recordings and motor mapping experiments in rats. Neurons in oral somatosensory cortex showed robust post-synaptic and sparse action potential responses to air puffs. Membrane potential showed that cold water evoked larger responses than room temperature or hot water. Most neurons showed no clear tuning of responses to bitter, sweet and neutral gustatory stimuli. Finally, motor mapping experiments with histological verification revealed an initiation of movements related to food consumption behavior, such as jaw opening and tongue protrusions. We conclude that somatosensory cortex: (i) provides a representation of the temperature of oral stimuli, (ii) does not systematically encode taste information and (iii) influences orofacial movements related to food consummatory behavior.


Assessment of patient engagement with a mobile application among service members in transition.
This article examines engagement with a mobile application ("mCare") for wounded Service Members rehabilitating in their communities. Many had behavioral health problems, Traumatic Brain Injury (TBI), and/or post-traumatic stress disorder (PTS). The article also examines associations between Service Members' background characteristics and their engagement with mCare. This analysis included participants who received mCare (n = 95) in a randomized controlled trial. mCare participants received status questionnaires daily for up to 36 weeks. Participant engagement encompasses exposure to mCare, percentage of questionnaires responded to, and response time. Participants were grouped by health status-that is, presence/absence of behavioral health problems, PTS, and/or TBI. Histograms and regression analyses examined engagement by participants' health status and background characteristics. Exposure to mCare did not differ by health status. Participants usually responded to ≥60% of the questionnaires weekly, generally in ≤10 h; however, participants with behavioral health problems had several weeks with <50% response and the longest response times. Total questionnaires responded to and response time did not differ statistically by health status. Older age and higher General Well-Being Schedule scores were associated with greater and faster response. The sustained response to the questionnaires suggests engagement. Overall level of response surpassed trends reported for American's usage of mobile applications. With a few exceptions, Service Members engaged with mCare irrespective of health status. Mobile health has the potential to increase the quantity and quality of patient-provider communications in a community-based, rehabilitation care setting, above that of standard care.


Synthesis and biological evaluation of simplified ajudazol derivatives reveal potent 5-lipoxygenase inhibition and considerable apoptotic activity in neuroblastoma cells.
Simplified analogues of the myxobacterial polyketide ajudazol were obtained by synthesis and evaluated for their biological activities. Potent simplified 5-lipoxygenase inhibitors were identified. Moreover, strong antiproliferative and apoptotic activities were observed in brain cancer cell lines at low nano- to micromolar concentrations.


Substitution Activated Precise Phototheranostics through Supramolecular Assembly of AIEgen and Calixarene.
Photodynamic therapy (PDT) is a promising noninvasive therapeutic technique and has attracted increasing interests in preclinical trials. However, the translation from laboratory to clinic often encounters the problem of undesired dark cytotoxicity of photosensitizers (PSs). Now, this challenge can be addressed by cascaded substitution activated phototheranostics using the host-guest strategy. Through electrostatical complexation of pyridinium-functionalized tetraphenylethylene, namely, TPE-PHO, and water-soluble calixarene, the dark cytotoxicity of TPE-PHO is dramatically inhibited. The nanoassemblies of the complex show enhanced biocompatibility and selectively locate at the cytoplasm in vitro. When TPE-PHO is competitively displaced from the cavity of calixarene by 4,4'-benzidine dihydrochloride at the tumor site, its dark cytotoxicity and photoactivity in tumor tissue are restored to give efficient PDT efficacy under light irradiation. The result from cell imaging reveals that TPE-PHO undergoes translocation from cytoplasm to mitochondria to kill the cancer cells during the cascaded supramolecular substitution process. In vivo tumor imaging and therapy are successfully implemented to evaluate the curative effect. Such a supramolecular strategy avoids tedious molecular synthesis and opens a new venue to readily tune the PS behaviors.


Cerebral cortical microfluorometry at isosbestic wavelengths for correction of vascular artifact.
Microfluorometric measurements of cerebral cortical mitochondrial respiration in vivo are obscured by hemodynamic and oximetric artifacts. Isosbestic fluorometry provides appropriate correction for these vascular phenomena and permits simultaneous evaluation of mitochondrial nicotinamide adenine dinucleotide redox state, microcirculatory volume, and hemoglobin oxygenation.


The characteristics and performance of hospitals that care for elderly Hispanic Americans.
The site of care may play an important role in health care disparities. We examined the 5 percent of U.S. hospitals with the highest proportion of elderly Hispanic patients and found that these hospitals cared for more than half of elderly Hispanics. These hospitals were more often for-profit, with higher rates of Medicaid patients and low nurse-staffing levels. They also provided a modestly lower quality of care for common medical conditions. Our finding that care for Hispanics is concentrated among a small number of hospitals provides an opportunity for targeted efforts to improve care for this group of Americans.


Super-size flies.
The increasing prevalence of obesity and other nutrition-related chronic diseases has prompted considerable efforts to understand their pathogenesis and treatment. One experimental approach is to overexpress, inactivate, or manipulate specific genes that regulate energy metabolism and fat storage. Many such techniques are fully established, routine tools in Drosophila and C. elegans, which provide elegant models for dissecting endocrine problems and metabolic pathways.


Influence of TPH2 and HTR1A polymorphisms on lifelong premature ejaculation risk among the chinese Han population.
Lifelong premature ejaculation (LPE) is one of the most common ejaculatory dysfunctions in men. The serotonin (5-HT) synthesis rate-limiting enzyme (TPH2) and receptor (HTR1A) in the 5-HT regulatory system may play a key role in the pathogenesis of LPE. However, there are few studies on the effects of TPH2 and HTR1A polymorphisms on LPE risk. We speculated that TPH2 and HTR1A polymorphisms may affect the occurrence and development of LPE in the Chinese Han population. In this study, 91 patients with LPE and 362 normal controls aged 18 to 64 years were enrolled in the male urology department of Hainan General Hospital in China from January 2016 to December 2018. The SNPs in HTR1A and TPH2, which are related to 5-HT regulation, were selected as indexes to genotype the collected blood samples of participants. Logistic regression was used to analyze the correlation between SNPs of HTR1A and TPH2 with LPE susceptibility, as well as the relationship with leptin, 5-HT and folic acid levels. The results revealed that HTR1A-rs6295 increased LPE risk in recessive model. Rs11178996 in TPH2 significantly reduced susceptibility to LPE in allelic (odds ratio (OR) = 0.68, 95% confidence interval (95% CI) = 0.49-0.96, p = 0.027), codominant (OR = 0.58, 95% CI = 0.35-0.98, p = 0.040), dominant (OR = 0.58, 95% CI = 0.36-0.92, p = 0.020), and additive (OR = 0.71, 95% CI = 0.52-0.98, p = 0.039) models. Grs11179041Trs10879352 could reduce the risk of LPE (OR = 0.44, 95% CI = 0.22-0.90, p = 0.024) by haplotype analysis. HTR1A-rs6295 and TPH2-rs11178996 are associated with LPE risk in the Chinese Han population based on the finding of this study.


Discussions About Obstetric Brachial Plexus Injuries.
Although patients with obstetric brachial plexus injuries (OBPI) have been recognized and treated for greater than 100 years there is much that is not understood or is mis-understood. I address 6 areas for discussion: the cause of OBPI and whether it matters to nerve surgeons; the value of the Narakas grading; whether surgeons should perform primary nerve surgery, especially in patients with incomplete OBPI; the cause and treatment of shoulder tightness; the cause and treatment of elbow contracture; and whether patients with OBPI need surgery in adulthood.


Functional consequences of brain exposure to saturated fatty acids: From energy metabolism and insulin resistance to neuronal damage.
Saturated fatty acids (FAs) are the main component of high-fat diets (HFDs), and high consumption has been associated with the development of insulin resistance, endoplasmic reticulum stress and mitochondrial dysfunction in neuronal cells. In particular, the reduction in neuronal insulin signaling seems to underlie the development of cognitive impairments and has been considered a risk factor for Alzheimer's disease (AD). This review summarized and critically analyzed the research that has impacted the field of saturated FA metabolism in neurons. We reviewed the mechanisms for free FA transport from the systemic circulation to the brain and how they impact neuronal metabolism. Finally, we focused on the molecular and the physiopathological consequences of brain exposure to the most abundant FA in the HFD, palmitic acid (PA). Understanding the mechanisms that lead to metabolic alterations in neurons induced by saturated FAs could help to develop several strategies for the prevention and treatment of cognitive impairment associated with insulin resistance, metabolic syndrome, or type II diabetes.


Phosphorylation of high-mobility-group chromatin proteins by protein kinase C from rat brain.
Chromosomal high-mobility-group (HMG) proteins have been examined as substrates for calcium/phospholipid-dependent protein kinase C. Protein kinase C from rat brain phosphorylated efficiently both HMG 14 and HMG 17 derived from calf thymus and the reactions were calcium/phospholipid-dependent. About 1 mol of 32P was incorporated per mol of HMG 14 and HMG 17. Phosphopeptide mapping suggested that the same major site was phosphorylated in both proteins at serine. The apparent Km values for HMG 14 and HMG 17 were about 5 microM. HMG 14, HMG 17 and the five histone H1 subtypes prepared from rat thymus, liver and spleen were phosphorylated by the kinase. HMG 14 and HMG 17 from transformed human lymphoblasts (Wi-L2) were also phosphorylated in a calcium/phospholipid-dependent manner. HMG 1 and HMG 2 from the tissues examined were found to be poor substrates for the kinase.


Human bladder carcinoma cell lines as indicators of oncogenic change relevant to urothelial neoplastic progression.
Analysis of human tumour-derived cell lines has previously resulted in the identification of novel transformation-related elements and provided a useful tool for functional studies of different genes. To establish the utility of such cell lines as indicators of change relevant to urothelial cancer, we have characterised the expression of five genes (p53, MDM2, Rb, E-cadherin, APC) within a panel of human bladder carcinoma cell lines. Using single-strand conformation polymorphism (SSCP) and direct sequencing, p53 mutations were identified in 7/15 (47%) cell lines reflecting events reported in bladder tumours. Immunohistochemical analysis of p53 in cultured cells and in paraffin-embedded sections of xenografts from the cell line panel revealed discordant results. An absence of p53 nuclear staining was associated with an exon 5 mutation in EJ and with multiple p53 mutations found in J82. Two cell lines positive for p53 staining in the absence of detectable mutation displayed overexpression of MDM2 (PSI, HT1197) in Western blot analysis. Loss or aberrant Rb expression was recorded in 5/15 (TCCSUP, SCaBER, 5637, HT1376, J82) cell lines. Absence of E-cadherin was recorded in 5/15 cell lines (TCCSUP, EJ, KK47, UM-UC-3, J82) with loss of alpha-catenin in immunoprecipitated E-cadherin complexes of CUBIII. Western blot analysis of APC revealed a truncated protein in 1/15 (CUBIII) cell lines. The characterisation of oncogenic events within this panel of human bladder carcinoma cell lines establishes a representation of change observed in bladder tumours and better defines the genotypic background in these experimental human cell models of neoplastic progression.


Seasonal changes of basic erythrocyte-metric parameters in Pelophylaxridibundus (Amphibia: Ranidae) from anthropogenically polluted biotopes in Southern Bulgaria and their role as bioindicators.
The purpose of this research work is to present data that show the seasonal changes (spring-summer-autumn) of basic erythrocyte-metric parameters (ЕL: Erythrocyte length, ЕW: Erythrocyte width, ЕL/ЕW, ES: Erythrocyte size; NL: Nucleus length, NW: Nucleus width, NL/NW; NS: Nucleus size, NS/ES: Nucleus-cytoplasmic ratio) in Pelophylax ridibundus populations from three biotopes located on two rivers in Southern Bulgaria (less disrupted biotope, with domestic sewage pollution and heavy metal pollution). Differences of high statistical significance were found among the different populations. Within the population living in conditions of domestic sewage pollution, for the entire period of the investigation the erythrocytes and their nuclei had an elliptical shape (a slight elongation of ellipses in autumn) and the biggest sizes (EL, EW, ES, NL and NS were constantly higher than the less disrupted biotope), NS/ES, became significantly smaller in autumn. Throughout the period of investigation, the values of all nine cellular and nuclear parameters were statistically-significantly the lowest in the population from the biotope with heavy metal pollution. The parameters: EL, ЕW, NL, NW and ES became significantly lower, progressively and statistically, during seasonal transitions. Cells and nuclei grew ovular in shape in comparison to the populations from the other two biotopes (this process was most pronounced in autumn) and NS/ES numbers were significantly decreased in summer and autumn.


The prevalence and characteristics of tinnitus in the youth population of the United States.
To evaluate the prevalence, characteristics, and associated risk factors of tinnitus in U.S. adolescents. Cross-sectional analyses of U.S. representative demographic and audiometric data, the National Health and Nutrition Examination Survey (NHANES) 2005 to 2008. The study population consisted of 3,520 individuals aged 12 to 19 years with complete tinnitus-related data. Tinnitus was defined as the presence of ringing or buzzing in the ears lasting for at least 5 minutes during the preceding 12 months. In addition, we defined a chronic tinnitus subgroup as being bothered by tinnitus for more than 3 months. Demographic and other data regarding tinnitus, smoking, body mass index (BMI), anemia, hypertension, history of ear infections, tympanostomy tube placement, otoscopy, tympanometry and hearing thresholds, history of firearm use, and recreational and occupational exposure to noise were extracted and analyzed. Overall, tinnitus lasting 5 minutes or more in the preceding 12 months was reported by 7.5% of the 12- to 19-year-old population. This represents about 2.5 million adolescents in the United States. The prevalence of chronic tinnitus was 4.7%, corresponding to about 1.6 million adolescents in the United States. Multivariable-adjusted analysis revealed that both overall and chronic tinnitus were associated with female gender, low income, exposure to passive smoking, type A tympanogram, and occupational and recreational noise exposure. History of ≥ 3 ear infections and history of tympanostomy tube placement were associated only with overall tinnitus. Tinnitus afflicts a substantial portion of the youth population. Further investigation of the association between tinnitus and the identified risk factors is warranted.


Pregnancy alters adrenergic mechanisms in uterine arterioles of rats.
Pregnancy is associated with altered vascular reactivity. However, the effect of pregnancy on the alpha- and beta-adrenergic responses in the uterine microcirculation remains to be determined. In late-pregnant (Day 20-21, n = 6) and virgin (n = 6) Sprague-Dawley rats, uterine radial arterioles (70-120 microm in internal diameter) were isolated. We studied in vitro arteriolar responses in a pressurized, no-flow state with videomicroscopy. alpha(2)-Adrenergic activation relaxed uterine arterioles; this relaxation was increased with pregnancy and was inhibited after endothelial denudation or inhibition of nitric oxide synthase. Pregnancy significantly increased the contractile response to the alpha(1)-adrenoceptor agonist phenylephrine but decreased the relaxation to the beta-adrenoceptor agonist isoproterenol. The contractile response to the protein kinase C activator phorbol ester and relaxation responses to both the adenylate cyclase activator forskolin and the endothelium-independent cyclic guanosine monophosphate-mediated vaso- dilator nitroprusside were preserved. These results suggest that pregnancy enhances the alpha(2)-adrenoceptor-mediated relaxation of uterine arterioles, probably because of an increase in the release of nitric oxide. The alpha(1)-adrenergic response is upregulated, whereas the beta-adrenergic response is impaired, in the uterine microcirculation of pregnant rats. Both alpha- and beta-adrenergic responses are important mechanisms for the regulation of uteroplacental perfusion. By use of an in vitromicrovascular technique, we have shown pregnancy-associated alteration in adrenergic responses in the uterine microcirculation of the rat.


The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease.
Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia. In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3±2.7% and 19.0±3.5% at 1 and 3 years versus 5.2±2.4% and 8.3±3.1%, log-rank P<0.001) and critical limb ischemia (19.1±4.8% and 31.6±6.3% at 1 and 3 years versus 10.8±2.5% and 16.0±3.2%, log-rank P<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%, P<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection. In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations.


Removal effects of a biomass bottom ash composite on tailwater phosphate and its application in a rural sewage treatment plant.
Tailwater phosphate from sewage treatment plants and biomass bottom ash (BA) from power plants has become a global concern for the sustainable environmental development and resource management. However, there are large gaps in the understanding of the removal mechanisms and application conditions of BA on tailwater phosphate. In this study, the removal effect and mechanism of BA and its composites were fully discussed using a series of experiments, including adsorption, desorption, characterization, and incubation experiments. It was found that the combination of BA and red soil at a rate of 4:1 (CBA) could remove 92.44% of phosphate from tailwater in 3-10 h. Its adsorption process was well fitted by the pseudo-second-order kinetic and Freundlich isotherm adsorption models. The mechanism of phosphate adsorption primarily included ligand exchange, physical adsorption, chemical precipitation, electrostatic attraction, and ion exchange. The CBA could be used as a better substrate for constructed wetlands because it was effective under wide application conditions, which varying pH values (4.0-8.0), initial concentrations of tailwater phosphate (0.5-5.0 mg L-1), and even extreme temperatures (heat and cold). Moreover, Hippuris vulgaris L. was optimized and combined with the CBA to deeply remove 57.45-76.06% of phosphate from a rural sewage treatment plant. The phosphate concentration after treatment could reach below the limit values of the Grade III or IV standard (GB 3838-2002), though the CBA contained and released phosphate. This study can help provide a recycling route for both BA and tailwater phosphate resources, extend the industrial chain of biomass power plants, and improve the surrounding water environment.


Bisexuality and Non-Suicidal Self-Injury (NSSI): A narrative synthesis of associated variables and a meta-analysis of risk.
Bisexual people have been found to be at increased risk of non-suicidal self-injury (NSSI) when compared to heterosexual and gay or lesbian people. The purpose of this review was to update the estimated risk of NSSI for bisexual people and to examine variables that have been associated with NSSI in this population. The protocol for this paper was pre-registered (CRD42019145299). An electronic search of PsycINFO, CINAHL Plus, PubMed, Ovid Online and Web of Science was undertaken from earliest available date to October 2019. Twenty-four eligible papers were identified. Meta-analyses, including moderator analysis, were conducted to ascertain NSSI risk and a narrative synthesis was undertaken of predictors and correlates. All studies were assessed for risk of bias. Bisexual people had up to six times the odds of engaging in NSSI compared to other sexualities. Mental health variables of anxiety and depression symptoms were found to be most commonly associated with NSSI for this population. The majority of studies had moderate risk of bias. This review demonstrates that bisexual people have an elevated risk of engaging in NSSI. Increased incidence of anxiety and depression and exposure to negative life events may explain this increased risk. Studies were found to be consistently cross-sectional in design and limited to western cultures. A limitation of this review was that only English language papers were included. Results are clinically relevant as they suggest early identification and prevention of NSSI can be achieved. Future research should examine bisexual people independently of others.


Effects of pleural effusion drainage in the mechanically ventilated patient as monitored by electrical impedance tomography and end-expiratory lung volume: A pilot study.
In patients with pleural effusion (PLE) monitored by Electrical Impedance Tomography (EIT) an increase in end-expiratory lung impedance (EELI) is observed following evacuation of the PLE. We aimed at differentiating the effect of fluid removal from lung reaeration and describe the change in ventilation distribution. Mechanically ventilated patients were monitored by EIT during PLE evacuation. End-expiratory lung volume (EELV) was measured concurrently. We included a calibration maneuver consisting of an increase in positive end-expiratory pressure (PEEP) by 5 cm H2O. The ratio ΔEELI/ΔEELV was used to compare changes of EELI and EELV in response to the calibration maneuver and PLE evacuation. At the same time we assessed distribution of ventilation using changes in tidal variation. PLE removal resulted in a 6-fold greater increase in ΔEELI/ΔEELV when compared to the calibration maneuver (r = 0.84, p < .05). We observed a relative increase in ventilation in the area of the effusion (mean 7.1%, p < .006) and an overall shift of ventilation to the dorsal fraction of the lungs (mean 8%, p < .0002). The increase in EELI in the EIT image after PLE removal was primarily due to the removal of the conductive effusion fluid.


Timing of manual placenta removal to prevent postpartum hemorrhage: is it time to act?
The length of the third stage of labor is an important risk factor for postpartum hemorrhage (PPH). Current practice recommends manual placenta removal, if not delivered spontaneously, within 30 min. The review reexamines the evidence to determine the optimal length of the third stage of labor. A MEDLINE search that associated the length of the third stage of labor with the risk of PPH was undertaken. A retrospective cohort study revealed the risk of a PPH became significant at 10 min (odds ratio = 2.1, 95% confidence interval: 1.6-2.6), and had doubled by 20 min (odds ratio = 4.3, 95% confidence interval: 3.3-5.5). A receiver operator curve determined the optimal length of the third stage of labor to prevent PPH was 18 min. A follow up randomized controlled trial showed that hemodynamic compromise secondary to a PPH can be reduced with manual placenta removal at 10 compared to 15 min (6.4 versus 19.2%, p = 0.001). The time interval of 15 min may be a more appropriate time interval to recommend placental removal to prevent PPH.


A new methodology combining QCM-D and proteomic profiling enables characterization of protein adsorption on 2D surfaces.
One of the critical features of biomedical material design is controlling the plasma protein adsorption to modulate the material behavior in biological media. Protein adsorption is highly influenced by the material surfaces and the proteins present in the biological medium. Thus, it is necessary to study protein-surface interactions that eventually take place on nanomaterials introduced into the body by the use of human plasma. However, very little information is available about human plasma interaction with planar surfaces under physiological conditions. Due to the limitation of the current characterization techniques to investigate the complicated interaction between the complex milieu of plasma proteins and planar materials, most efforts have focused on single proteins. To face this challenge, we have developed a new methodology based on the combination of quartz crystal microbalance with dissipation monitoring (QCM-D) and liquid chromatography coupled with mass spectrometry (LC-MS) to obtain information about protein-surface interactions on planar surfaces. First, QCM-D allowed us to determine the adsorbed protein mass and layer thickness. After detaching the proteins by a surfactant treatment, LC-MS analysis revealed the proteomic profile. Here, we have investigated three base materials, polystyrene (PS), gold (Au), and silica (SiO2) with or without precoating and compared the protein profiles.


The epidemiology of work-related injury admissions to hospitals in the Midland region of New Zealand.
To describe the epidemiological characteristics of patients with work-related injuries (WRI) admitted to hospitals in New Zealand's Midland Trauma System (MTS) during a four year period. A retrospective review was conducted of trauma registry records for adults (≥15years) admitted to four hospitals in the MTS as a result of WRI between 1 January 2012 and 31 December 2015. We describe the patterns of injury incidence by demographic characteristics, employment industry, mechanism of injury, body regions injured, injury severity score (ISS), month, day and time of injury, duration of hospital stay, domicile District Health Board (DHB), and discharge destination. The 2169 WRI trauma admissions, corresponded to an annualised rate of 205.8 per 100,000 workers or 234.3 per 100,000 full time employment employees (FTE). Injury rates were highest among males (238.0 per 100,000 workers) and those aged 15-24 years (227.1 per 100,000 workers), and lowest among Asians (83 per 100,000 workers). The highest injury rates occurred among the 'agriculture/forestry/fishing', 'manufacturing', and 'transport/postal/warehousing' industries. 'Contact with machinery' was the most common mechanism of injury, and the 'extremities or pelvic girdle' the most common body region injured. The in-hospital case fatality rate was <0.5%. The predominance of WRI in the 'agriculture/forestry/fishing' industries in the Midland region is consistent with national estimates. The high rate of injuries amongst males, young adults, and Māori requires further exploration.


Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis.
Tuberculosis (TB) is a global pandaemic, partially due to the failure of vaccination approaches. Novel anti-TB vaccines are therefore urgently required. Here we show that aerosol immunization of macaques with the Mtb mutant in SigH (MtbΔsigH) results in significant recruitment of inducible bronchus-associated lymphoid tissue (iBALT) as well as CD4(+) and CD8(+) T cells expressing activation and proliferation markers to the lungs. Further, the findings indicate that pulmonary vaccination with MtbΔsigH elicited strong central memory CD4(+) and CD8(+) T-cell responses in the lung. Vaccination with MtbΔsigH results in significant protection against a lethal TB challenge, as evidenced by an approximately three log reduction in bacterial burdens, significantly diminished clinical manifestations and granulomatous pathology and characterized by the presence of profound iBALT. This highly protective response is virtually absent in unvaccinated and BCG-vaccinated animals after challenge. These results suggest that future TB vaccine candidates can be developed on the basis of MtbΔsigH.


Autoimmune hepatitis exerts a profound, negative effect on health-related quality of life: A prospective, single-centre study.
Autoimmune hepatitis is a progressive chronic liver disease. Health-related quality of life in autoimmune hepatitis has not attracted much attention so far. We prospectively assessed various aspects of health-related quality of life in a well characterized group of patients with autoimmune hepatitis. In total, 140 patients with autoimmune hepatitis (mean age 40 ± 17 years) and 170 controls (mean age 36 ± 14 years) were included. Health-related quality of life was evaluated with following questionnaires: The Short Form (36) Health Survey, Modified Fatigue Impact Score, State-Trait Anxiety Inventory and Patient Health Questionnaire-9 assessing depression. Patients with autoimmune hepatitis showed a significant impairment of health-related quality of life in all, but one, domains of The Short Form (36) Health Survey. Autoimmune hepatitis was associated with pronounced physical fatigue (P < 0.001), anxiety (P < 0.001) and depression (P < 0.001). As compared to males, female patients demonstrated greater impairment of physical aspects of The Short Form (36) Health Survey and Modified Fatigue Impact Score. Twenty-seven patients (19%) had moderate (Patient Health Questionnaire-9 >10) and 14 (10%) moderately severe depression (Patient Health Questionnaire-9 >15). Depression showed a very strong correlation with chronic fatigue (R = 0.68; P < 0.001); physical and mental components of The Short Form (36) Health Survey (R = 0.52/0.68 respectively; P < 0.001) and anxiety (R = 0.47; P < 0.001). There was a trend towards better life's quality in patients treated with budesonide in some aspects of their health-related quality of life. Duration of the disease, age at diagnosis, liver fibrosis and the presence of cirrhosis were not associated with health-related quality of life. Health-related quality of life is significantly impaired in patients with autoimmune hepatitis. Depression seems to be a dominant symptom affecting their well-being, not associated with clinical and biochemical features of the disease.


Hydroxychloroquine Controversies: Clinical Trials, Epistemology, and the Democratization of Science.
The claim that anti-malaria drugs, chloroquine and hydroxychloroquine, can cure COVID-19 became a focus of fierce political battles that pitted promoters of these pharmaceuticals, Presidents Bolsonaro and Trump among them, against "medical elites." At the center of these battles are different meanings of effectiveness in medicine, the complex role of randomized clinical trials (RCTs) in proving such effectiveness, the task of medical experts and the state in regulating pharmaceuticals, patients' activism, and the collective production of medical knowledge. This article follows the trajectory of chloroquine and hydroxychloroquine as anti-COVID-19 drugs, focusing on the reception of views of their main scientific promoter, the French infectious disease specialist, Didier Raoult. The surprising career of these drugs, our text proposes, is fundamentally a political event, not in the narrow sense of engaging specific political fractions, but in the much broader sense of the politics of public participation in science.


Identification of ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3) as a regulator of N-acetylglucosaminyltransferase GnT-IX (GnT-Vb).
Our previous studies on a β1,6-N-acetylglucosaminyltransferase, GnT-IX (GnT-Vb), a homolog of GnT-V, indicated that the enzyme has a broad GlcNAc transfer activity toward N-linked and O-mannosyl glycan core structures and that its brain-specific gene expression is regulated by epigenetic histone modifications. In this study, we demonstrate the existence of an endogenous inhibitory factor for GnT-IX that functions as a key regulator for GnT-IX enzymatic activity in Neuro2a (N2a) cells. We purified this factor from N2a cells and found that it is identical to ectonucleotide pyrophosphatase/phosphodiesterase 3 (ENPP3), as evidenced by mass spectrometry and by the knockdown and overexpression of ENPP3 in cultured cells. Kinetic analyses revealed that the mechanism responsible for the inhibition of GnT-IX caused by ENPP3 is the ENPP3-mediated hydrolysis of the nucleotide sugar donor substrate, UDP-GlcNAc, with the resulting generation of UMP, a potent and competitive inhibitor of GnT-IX. Indeed, ENPP3 knockdown cells had significantly increased levels of intracellular nucleotide sugars and displayed changes in the total cellular glycosylation profile. In addition to chaperones or other known regulators of glycosyltransferases, the ENPP3-mediated hydrolysis of nucleotide sugars would have widespread and significant impacts on glycosyltransferase activities and would be responsible for altering the total cellular glycosylation profile and modulating cellular functions.


2,8-Dihydroxyadenine-induced nephropathy causes hexosylceramide accumulation with increased mTOR signaling, reduced levels of protective SirT3 expression and impaired renal mitochondrial function.
Chronic kidney disease (CKD) is accompanied by increased cardiovascular risk and heart failure (HF). In rodents, 2,8-dihydroxyadenine (DHA)-induced nephropathy is a frequently used CKD model. Cardiac and kidney tubular cells share high energy demand to guarantee constant contractive force of the heart or reabsorption/secretion of primary filtrated molecules and waste products by the kidney. Here we analyze time-dependent mechanisms of kidney damage and cardiac consequences under consideration of energetic pathways with the focus on mitochondrial function and lipid metabolism in mice. CKD was induced by alternating dietary adenine supplementation (0.2 % or 0.05 % of adenine) in C57BL/6J mice for 9 weeks. Progressive kidney damage led to reduced creatinine clearance, kidney fibrosis and renal inflammation after 3, 6, and 9 weeks. No difference in cardiac function, mitochondrial respiration nor left ventricular fibrosis was observed at any time point. Investigating mechanisms of renal damage, protective SirT3 was decreased in CKD, which contrasted an increase in protein kinase B (AKT) expression, mechanistic target of rapamycin (mTOR) downstream signaling, induction of oxidative and endoplasmic reticulum (ER) stress. This occurred together with impaired renal mitochondrial function and accumulation of hexosylceramides (HexCer) as an established mediator of inflammation and mitochondrial dysfunction in the kidney. 2,8-DHA-induced CKD results in renal activation of the mTOR downstream signaling, endoplasmic reticulum stress, tubular injury, fibrosis, inflammation, oxidative stress and impaired kidney mitochondrial function in conjunction with renal hexosylceramide accumulation in C57BL/6J mice.


Infantile onset progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene.
Pontocerebellar hypoplasia (PCH) encompasses a group of neurodegenerative disorders. There are ten known subtypes with common characteristics of pontine and cerebellar hypoplasia or atrophy, neocortical atrophy, and microcephaly. PCH is associated with anterior horn cell degeneration in PCH1a and PCH1b due to mutations in the VRK1 and EXOSC3 genes. Late onset PCH1 has been described in single case reports. The molecular etiology remains mostly unknown. We describe two siblings from a consanguineous Moslem Arabic family with a unique combination of progressive cerebellar atrophy and a SMA-like anterior horn cell degeneration due to a homozygous mutation in the PLA2G6 gene (NM_003560.2). The PLA2G6 gene encodes phospholipase A2 beta, which is involved in the remodeling of membrane phospholipids, signal transduction and calcium signaling, cell proliferation and apoptosis. Mutations in PLA2G6 are known to cause Neurodegeneration with brain iron accumulation 2 (NBIA2): Our patients have some similarities with NBIA2; both are characterized by rapidly progressive psychomotor regression and cerebellar atrophy. However, NBIA2 is not known to exhibit anterior horn cell degeneration. Our patients' phenotype is more consistent with late onset PCH1; thus, indicating that the spectrum of clinical and radiological presentations of PLA2G6 mutations should be extended and that this gene should be included in the molecular evaluation of patients with late onset PCH1.


Isolation of a novel morphinan 3-O-diglucuronide metabolite from dog urine.
Following oral administration of the narcotic antagonist nalmefene [17-(cyclopropylmethyl)-4,5 alpha-epoxy-6-methylenemorphinan-3,14-diol] labeled with 14C to the dog, approximately 50% of the dose was excreted in the urine as a highly polar water-soluble conjugate. Although this major metabolite could be hydrolyzed with beta-glucuronidase to yield nalmefene, the intact conjugate was chromatographically more polar on reversed-phase high-performance liquid chromatography (HPLC) than authentic nalmefene 3-O-glucuronide. Milligram quantities of the metabolite were subsequently isolated and subjected to fast atom bombardment (FAB) mass spectral and nuclear magnetic resonance (NMR) analyses. The conjugate was identified as nalmefene 3-O-beta-diglucuronide with a 1,2-beta linkage between the two glucuronic acids. It is unlikely that this novel form of conjugate is unique to nalmefene and it is probably a metabolite of other morphinans and/or similar drugs in the dog. Nalmefene 3-O-diglucuronide is not a metabolite of nalmefene in man.


Diagnosis and genotyping of Helicobacter pylori by polymerase chain reaction of bacterial DNA from gastric juice.
Efficient and accurate detection of Helicobacter pylori infection as well as identification of virulence-associated alleles are important for the treatment of gastroduodenal diseases caused by this gastric pathogen. The present study was performed to test the efficiency of gastric juice polymerase chain reaction (PCR) method for the rapid detection of H. pylori infection and to determine the bacterial genotypes without the need for culture, which is often not feasible especially in developing countries. DNA was extracted from gastric juice samples collected from 45 subjects and was used to amplify urease B gene (ureB) for H. pylori. Results obtained from this method were further confirmed by rapid urease test (RUT), histology and culture. Genotypes of the infected strains predicted from gastric juice PCR were compared to the genotype data obtained from the isolated strains. Among 45 cases, 32 were positive by RUT, 37 by histological examination, 25 by gastric juice PCR method, while culture yielded positive results for 19 samples. Except for one case, all the 19 culture-positive strains gave the same genotype with the gastric juice PCR result. It was found that the gastric juice PCR is more efficient for detection of multiple-strain infection as compared to genotype data obtained from strains isolated as pooled culture. This moderately sensitive technique could be employed with good efficiency, particularly in cases where it is difficult to obtain biopsy. Moreover, with this method bacterial genotype could be obtained.


Diagnostic Efficacy of BRAFV600E Immunocytochemistry in Thyroid Aspirates in Bethesda Category IV and Papillary Thyroid Carcinoma.
In papillary thyroid carcinoma (PTC), BRAFV600E is a common mutation and is associated with aggressive clinical behaviour. Immunocytochemistry (ICC) and molecular testing are recommended in the Bethesda System for Reporting Thyroid Cytopathology 2017 (TBSRTC) category III, IV and V. The current study aimed to evaluate the diagnostic efficacy of conventional FNAC versus FNAC with BRAFV600E immunostaining in cases of TBSRTC category IV, cases of suspicious for PTC and cases of PTC. The study included a prospective case series of 45 patients with clinically palpable thyroid nodules with TBSRTC category IV, category V (suspicious for PTC) and PTC. The corresponding histology specimens of all the 45 cases were also analyzed. Immunostaining for BRAFV600E was performed on FNAC cell blocks and their corresponding histology sections using anti-BRAF (VE1) clone (Ventana). The diagnostic efficacy of the BRAFV600E immunostaining was compared on cytological specimens with histological specimens. BRAFV600E immunostaining helped to improve the sensitivity of the cytology to confirm the PTC as a diagnostic aid for thyroid FNAs. Cytology alone had a sensitivity of 62.96% and a lower specificity of 60.70%. The combination of both the tests together provided 84.62% sensitivity and much higher specificity of 100%. PPV was also increased to 100% and NPV was raised 94.12%. The performance of BRAFV600E immunostaining on the cytological specimen is a rapid, simple and cost-effective test and could be considered in TBSRTC category IV and suspicious and malignant cases of PTC.


Quality of life after intensive care with the sickness impact profile.
a) to validate the structure of the Sickness Impact Profile scale (SIP) when applied to intensive care patients after discharge from the hospital; b) to explore the influence of age upon the various components of quality of life. Prospective study. Patients admitted to 36 Dutch ICUs. 6,247 patients out of 13,000 consecutive admissions to the ICUs answered a SIP questionnaire 6 months after discharge from the hospital. The 3,655 returned questionnaire were analyzed after aggregating the respondents into 6 age groups: from group 1: 17-29 up to group 4: > 70 years of age. Self-administration of SIP one year after discharge, measuring 5 independent categories (IC) and two dimensions: physical (PD) and psychosocial (PSD). The total SIP-score oscillated between 5.8 +/- 8.2 (group I) and 10.5 +/- 9.5 (group 4). Group 3 had also a high score (9.4 +/- 11.2). Overall, the quality of life of patients was dominated by dysfunction on the categories composing the physical dimension, with exception of patients with ages between 30 and 50 years, in which dysfunction on the categories composing the psychosocial dimension was dominant. The structure of the SIP in the study was similar to that described to the original instrument. The study validated the use of the SIP QOL-instrument on patients after intensive care. Age influenced consistently the various components of quality of life.


A comparison of skinfold thickness, body mass index, bioelectrical impedance analysis and dual-energy X-ray absorptiometry in assessing body composition in obese subjects before and after weight loss.
The assessment of body composition in obese subjects by anthropometric means (skinfolds), presents many difficulties. This study compares the estimates provided of fat free mass in 21 obese subjects (mean body mass index 36.6 +/- 1.2 kg/m(2)) using body mass index and skinfold thickness, with those obtained using the more recently developed techniques of bioelectrical impedance analysis and dual-energy X-ray absorptiometry. Despite highly significant correlations between some of the methods (r(2) = 0.94 for dual-energy X-ray absorptiometry versus bioelectrical impedance analysis), there was a considerable lack of agreement in the measurements, particularly when skinfold thickness was compared with dual-energy X-ray absorptiometry (limits of agreement -21.9 to -1.5 kg for fat free mass estimated from dual-energy X-ray absorptiometry and skinfold thickness) and even for dual-energy X-ray absorptiometry and bioelectrical impedance analysis (limits of agreement -10.7 to 0.4 kg). After weight loss the intermethod differences were reduced.


Safety and efficacy of a feed additive consisting of 25-hydroxycholecalciferol monohydrate produced with Saccharomyces cerevisiaeCBS 146008 for all ruminants (DSM Nutritional Products Sp. z.o.o.).
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of 25-hydroxycholecalciferol monohydrate produced with Saccharomyces cerevisiae CBS 146008 as a nutritional feed additive for all ruminants. The additive is already authorised for use with chickens for fattening, turkeys for fattening, other poultry and pigs. The Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive does not give raise to any safety concern regarding the production strain. The additive is safe for cattle for fattening and dairy cows at the maximum recommended use level of 0.1 mg 25-OH-D3/kg complete feed. This conclusion can be extended to other cattle categories and extrapolated to all ruminant species. The use of 25-OH-D3 in all ruminants under the proposed conditions of use is considered safe for the consumer. The additive is not irritant to the skin or eyes. No conclusion on its potential to be a skin sensitiser or on its effects on the respiratory system can be reached due to absence of data. The use of the additive under assessment at the recommended conditions of use is considered safe for the environment. 25-OH-D3 is an efficient source of vitamin D3 for all ruminants when used according to the proposed conditions of use.


Determination of Lead in Water Samples Using a New Vortex-Assisted, Surfactant-Enhanced Emulsification Liquid-Liquid Microextraction Combined with Graphite Furnace Atomic Absorption Spectrometry.
A low toxic solvent-based vortex-assisted surfactant-enhanced emulsification liquid-liquid microextraction (LT-VSLLME) combined with graphite furnace atomic absorption spectrometry was developed for the extraction and determination of lead (Pb) in water samples. In the LT-VSLLME method, the extraction solvent was dispersed into the aqueous samples by the assistance of vortex agitator. Meanwhile, the addition of a surfactant, which acted as an emulsifier, could enhance the speed of the mass-transfer from aqueous samples to the extraction solvent. The influences of analytical parameters, including extraction solvent type and its volume, surfactant type and its volume, pH, concentration of chelating agent, salt effect and extraction time were investigated. Under the optimized conditions, a good relative standard deviation of 3.69% at 10 ng L(-1) was obtained. The calibration graph showed a linear pattern in the ranges of 5-30 ngL(-1), with a limit of detection of 0.76 ng L(-1). The linearity was obtained by five points in the concentration range of 5-30 ngL(-1). The enrichment factor was 320. The procedure was applied to wastewater and river water, and the accuracy was assessed through the analysis of the recovery experiments.


Maternal cortisol is associated with neonatal amygdala microstructure and connectivity in a sexually dimorphic manner.
The mechanisms linking maternal stress in pregnancy with infant neurodevelopment in a sexually dimorphic manner are poorly understood. We tested the hypothesis that maternal hypothalamic-pituitary-adrenal axis activity, measured by hair cortisol concentration (HCC), is associated with microstructure, structural connectivity, and volume of the infant amygdala. In 78 mother-infant dyads, maternal hair was sampled postnatally, and infants underwent magnetic resonance imaging at term-equivalent age. We found a relationship between maternal HCC and amygdala development that differed according to infant sex. Higher HCC was associated with higher left amygdala fractional anisotropy (β = 0.677, p=0.010), lower left amygdala orientation dispersion index (β = -0.597, p=0.034), and higher fractional anisotropy in connections between the right amygdala and putamen (β = 0.475, p=0.007) in girls compared to boys. Furthermore, altered amygdala microstructure was only observed in boys, with connectivity changes restricted to girls. Maternal cortisol during pregnancy is related to newborn amygdala architecture and connectivity in a sexually dimorphic manner. Given the fundamental role of the amygdala in the emergence of emotion regulation, these findings offer new insights into mechanisms linking maternal health with neuropsychiatric outcomes of children.


Anxiety prevalence following spinal cord injury: a meta-analysis.
Meta-analysis. Prevalence estimates indicate that anxiety following spinal cord injury (SCI) is a common problem. However, methodological differences between studies may impact the clinical interpretation of these data. Data from 18 independent studies (Nparticipants=3158), which reported the prevalence of an anxiety disorder or associated symptoms, were identified from the Embase, PubMed and PsycInfo databases. Proportions were the primary effect size estimate. Confidence intervals, fail-safe Ns and the I(2) statistic were additionally calculated to identify the extent to which findings were robust and consistent across studies. Five per cent of participants met the criteria for either GAD or panic disorder, with Agoraphobia identified in 2.5%. These diagnostic data were, however, limited to two studies. Higher rates were noted for self-reported 'caseness' of anxiety, with 27% reporting clinically significant symptoms. Anxiety prevalence estimates varied across the individual self-report measures (range: 15-32%). Method of administration (range: 26-32%) did not impact significantly on these estimates nor did recruitment source, with similarly high anxiety levels reported by hospital (27%) and community (29%) samples. Early identification and treatment of anxiety are important in SCI rehabilitation, with a subgroup of individuals experiencing chronic symptoms. Further research is needed to establish guidelines for the interpretation of self-report data, including the use of clinical cutoffs.


Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant?
About 20% of the population suffers from "functional syndromes". Since these syndromes overlap greatly in terms of co-morbidity, pathophysiology (including aberrant autonomic activity) and treatment responses, common predisposing genetic factors have been postulated. We had previously showed that two common mitochondrial DNA (mtDNA) polymorphisms at positions 16519 and 3010 are statistically associated with the functional syndromes of migraine, cyclic vomiting syndrome and non-specific abdominal pain. Herein, among individuals with mtDNA haplogroup H (HgH), the presence of these two mtDNA polymorphisms were ascertained in additional functional syndromes: chronic fatigue syndrome, complex regional pain syndrome, sudden infant death syndrome, and major depressive disorder. Polymorphic prevalence rates were compared between disease and control groups, and within each disease group in participants with and without specific clinical findings. In all four conditions, one or both of the polymorphisms was significantly associated with the respective condition and/or co-morbid functional symptomatology. Thus, we conclude that these two mtDNA polymorphisms likely modify risk for the development of multiple functional syndromes, likely constituting a proportion of the postulated common genetic factor, at least among individuals with HgH. Pathophysiology likely involves broad effects on the autonomic nervous system.