Improved survival of ischemic cutaneous and musculocutaneous flaps after vascular endothelial growth factor gene transfer using adeno-associated virus vectors.
A major challenge in reconstructive surgery is flap ischemia, which might benefit from induction of therapeutic angiogenesis. Here we demonstrate the effect of an adeno-associated virus (AAV) vector delivering vascular endothelial growth factor (VEGF)165 in two widely recognized in vivo flap models. For the epigastric flap model, animals were injected subcutaneously with 1.5 x 10(11) particles of AAV-VEGF at day 0, 7, or 14 before flap dissection. In the transverse rectus abdominis musculocutaneous flap model, AAV-VEGF was injected intramuscularly. The delivery of AAV-VEGF significantly improved flap survival in both models, reducing necrosis in all treatment groups compared to controls. The most notable results were obtained by administering the vector 14 days before flap dissection. In the transverse rectus abdominis musculocutaneous flap model, AAV-VEGF reduced the necrotic area by >50% at 1 week after surgery, with a highly significant improvement in the healing process throughout the following 2 weeks. The therapeutic effect of AAV-VEGF on flap survival was confirmed by histological evidence of neoangiogenesis in the formation of large numbers of CD31-positive capillaries and alpha-smooth muscle actin-positive arteriolae, particularly evident at the border between viable and necrotic tissue. These results underscore the efficacy of VEGF-induced neovascularization for the prevention of tissue ischemia and the improvement of flap survival in reconstructive surgery.


A pilot study of bevacizumab combined with etoposide and cisplatin in breast cancer patients with leptomeningeal carcinomatosis.
Elevated vascular endothelial growth factor (VEGF) was associated with poor prognosis in leptomeningeal carcinomatosis and anti-angiogenic therapy was found to prolong the survival of mice in preclinical studies. This prospective pilot study investigated the efficacy of anti-VEGF therapy plus chemotherapy in patients with leptomeningeal carcinomatosis originating from breast cancer. Eligible patients were scheduled to receive bevacizumab combined with etoposide and cisplatin (BEEP) every 3 weeks for a maximum of 6 cycles or until unacceptable toxicity. The primary objective was the central nervous system (CNS)-specific response rate, which was defined as disappearance of cancer cells in the cerebrospinal fluid (CSF) and an improved or stabilized neurologic status. The impact of VEGF inhibition on etoposide penetration into the CSF was analyzed. Eight patients were enrolled. The CNS-specific response rate was 60% in 5 evaluable patients. According to intent-to-treat analysis, the median overall survival of the eight patients was 4.7 months (95% confidence interval, CI, 0.3-9.0) and the neurologic progression-free survival was 4.7 months (95% CI 0-10.5). The most common grade 3/4 adverse events were neutropenia (23.1%), leukopenia (23.1%), and hyponatremia (23.1%). The etoposide concentrations in the CSF were much lower than those in plasma, and bevacizumab did not increase etoposide delivery to the CSF. BEEP exhibited promising efficacy in breast cancer patients with leptomeningeal carcinomatosis. Additional studies are warranted to verify its efficacy and clarify the role of anti-angiogenic therapy in this disease. ClinicalTrials.gov identifying number NCT01281696 .


The inferior frontal sulcus: Cortical segregation, molecular architecture and function.
The inferior frontal sulcus is conceptualized as the landmark delineating ventro-from dorsolateral prefrontal cortex. Functional imaging studies report activations within the sulcus during tasks addressing cognitive control and verbal working memory, while their microstructural correlates are not well defined. Existing microstructural maps, e.g., Brodmann's map, do not distinguish separate areas within the sulcus. We identified six new areas in the inferior frontal sulcus and its junction to the precentral sulcus, ifs1-4, ifj1-ifj2, by combined cytoarchitectonic analysis and receptor autoradiography. A hierarchical cluster analysis of receptor densities of these and neighbouring prefrontal areas revealed that they form a distinct cluster within the prefrontal cortex. Major interhemispheric differences were found in both cyto- and receptorarchitecture. The function of cytoarchitectonically identified areas was explored by comparing probabilistic maps of the areas in stereotaxic space with their functions and co-activation patterns as analysed by means of a coordinate-based meta-analysis. We found a bilateral involvement in working memory, as well as a lateralization of different language-related processes to the left hemisphere, and of music processing and attention to the right-hemispheric areas. Particularly ifj2 might act as a functional hub between the networks. The cytoarchitectonic maps and receptor densities provide a powerful tool to further elucidate the function of these areas. The maps are available through the Human Brain Atlas of the Human Brain Project and serve in combination with the information on the cyto- and receptor architecture of the areas as a resource for brain models and simulations.


Cochlear, auditory brainstem responses in Type 1 diabetes: relationship with metabolic variables and diabetic complications.
Few studies have analysed the presence of hearing abnormalities in diabetes. We assessed the presence of subclinical auditory alterations and their possible association with early vascular and neurological dysfunction in young adults with Type 1 diabetes of long duration. Thirty-one patients with Type 1 diabetes (mean age 33 ± 2.3 years, disease duration 25.7 ± 4.2 years) and 10 healthy controls underwent pure tone audiometry (PTA), distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) analyses. Associations with metabolic variables and chronic complications were explored. Compared with healthy controls, patients with diabetes had significantly higher mean hearing thresholds, although still within the normoacusic range. DPOAE intensities at medium frequencies (2.8-4 kHz) were significantly lower in patients with diabetes. In ABR, in addition to waves I, III and V, we observed the appearance of a visible wave IV in patients with diabetes compared with controls (prevalence 61% vs. 10%, P < 0.05), and its appearance was related to a prolonged I-V interval (4.40 ± 0.62 ms vs. 4.19 ± 0.58 ms, P < 0.05). Diastolic blood pressure was higher in people with abnormal DPOAE (P < 0.05), whereas systolic blood pressure correlated with wave V and interpeak I-V interval latencies. A trend towards an association between evidence of wave IV and the presence of somatic neuropathy or abnormal cardiovascular autonomic tests was observed. Young adults with long-term Type 1 diabetes have subclinical abnormalities in qualitative auditory perception, despite normal hearing thresholds, which might reflect neuropathic and/or vascular alterations.


[Nuclear ribonucleoproteins containing messenger RNA. 12. Fluorescence studies of the secondary structure of pre-mRNA in nuclear RNP-particles].
Secondary structure of pre-mRNA in nuclear ribonucleoprotein particles (30S-particles) was examined using fluorescent dyes: acridine orange, acriflavine and ethidium bromide. Comparison of ethidium bromide and acriflavine adsorption isotherms for RNP-particles and free RNA and a study of acridine orange dimerization on binding to RNP revealed that 70% of pre-mRNA in 30S-particles is accessible for the dye binding. Dye molecules were adsorbed on double-stranded sequences (11--12% of the total amount of RNA in 30S-particles) and on the single-stranded parts of RNA (58--59% of 30S-particles), the rest part of RNA was unaccessible for the dye binding. A method involving measurements of acriflavine fluorescence quantum yields was used for the determination of nucleotide composition of double-stranded parts of RNA in the 30S-particles. AU-nucleotide content thus obtained was approximately 50%, as was established also for free pre-mRNA. Na+ ions weaken the interaction between the protein and pre-mRNA in 30S particles and increase mobility of double-stranded parts of this nucleic acid.


Staphylococcal enterotoxin B enhances a flare-up reaction of murine contact hypersensitivity through up-regulation of interferon-gamma.
We often see aggravation of eczematous skin lesions associated with bacterial infection, but the mechanism of this phenomenon is unclear. Staphylococcus aureus is known to colonize on the eczematous lesion and produce some exotoxins, which act as bacterial superantigens. To investigate the potential role of superantigens in chronic dermatitis, we investigated the effect of staphylococcal enterotoxin B (SEB) on the skin reaction, the proliferative response and the cytokine production of local lymph node cells in the mouse model of contact hypersensitivity reaction. Sensitized BALB/c mice were repeatedly challenged with dinitrofluorobenzene (DNFB), and intravenously injected with SEB and dinitrobenzne sulfonic acid sodium salt (DNBS). The ear swelling response was measured after DNBS injection. Cervical lymph node cells of those mice were cultured with DNBS in vitro. Their proliferative responses and the production of cytokines were assessed. SEB markedly enhanced the flare-up reaction of ear swelling induced by DNBS, the proliferative response of lymph node cells and the production of IFN-gamma. In contrast, the production of IL-5 was decreased. The present study may provide some clues for elucidating the mechanism involved in the exacerbation of dermatitis associated with staphylococcal infection.


Deep Learning Methods for Lung Cancer Segmentation in Whole-Slide Histopathology Images-The ACDC@LungHP Challenge 2019.
Accurate segmentation of lung cancer in pathology slides is a critical step in improving patient care. We proposed the ACDC@LungHP (Automatic Cancer Detection and Classification in Whole-slide Lung Histopathology) challenge for evaluating different computer-aided diagnosis (CADs) methods on the automatic diagnosis of lung cancer. The ACDC@LungHP 2019 focused on segmentation (pixel-wise detection) of cancer tissue in whole slide imaging (WSI), using an annotated dataset of 150 training images and 50 test images from 200 patients. This paper reviews this challenge and summarizes the top 10 submitted methods for lung cancer segmentation. All methods were evaluated using metrics using the precision, accuracy, sensitivity, specificity, and DICE coefficient (DC). The DC ranged from 0.7354 ±0.1149 to 0.8372 ±0.0858. The DC of the best method was close to the inter-observer agreement (0.8398 ±0.0890). All methods were based on deep learning and categorized into two groups: multi-model method and single model method. In general, multi-model methods were significantly better (p 0.01) than single model methods, with mean DC of 0.7966 and 0.7544, respectively. Deep learning based methods could potentially help pathologists find suspicious regions for further analysis of lung cancer in WSI.


Comparison of time domain and frequency domain variables from the signal-averaged electrocardiogram: a multivariable analysis.
The relative values of the unprocessed signal-averaged electrocardiogram (ECG) and time domain analysis and frequency domain analysis of the signal-averaged ECG were compared in 36 patients with sustained monomorphic ventricular tachycardia and a remote myocardial infarction, in 29 asymptomatic patients with a remote myocardial infarction and in 23 normal subjects. Area ratios of the energy spectra derived from fast Fourier transform analysis were calculated using six separate 140 ms intervals starting at 0, 40, 50 and 60 ms after QRS onset; 40 and 50 ms before QRS end and a variable length interval starting 40 ms before QRS end and extending to the T wave. Total filtered QRS duration, late potential duration and root mean square voltage of the terminal QRS complex were measured from the filtered vector magnitude signal-averaged ECG. The total QRS duration was also measured from the X, Y, Z leads of the unfiltered signal-averaged ECG. Seven variables were significantly different in univariate tests between myocardial infarction patients with and without ventricular tachycardia: three fast Fourier transform area ratios with the sampling interval starting at 1) QRS onset (p = 0.007), 2) 40 ms after QRS onset (p = 0.02), and 3) 60 ms after QRS onset (p less than 0.0001); and all four time domain variables at 1) total filtered QRS duration (p less than 0.0001), 2) late potential duration (p = 0.0001), 3) root mean square terminal QRS voltage (p = 0.0001), and 4) QRS duration from the unprocessed signal-averaged ECG (p less than 0.0001). Of these seven variables, only the fast Fourier transform area ratio starting at QRS onset was significantly different between patients with myocardial infarction without ventricular tachycardia and normal subjects. In multi-variable analysis, the total filtered vector magnitude QRS duration, a time domain variable that includes the late potential, was the only independent factor that separated patients with myocardial infarction with and without associated ventricular tachycardia.


LncRNA NEAT1 Promotes Proliferation, Migration and Invasion via Regulating miR-296-5p/CNN2 Axis in Hepatocellular Carcinoma Cells [Retraction].
[This retracts the article DOI: 10.2147/OTT.S228917.].


Anti-N SARS-CoV-2 assays for evaluation of natural viral infection.
The 2019 coronavirus (COVID-19) epidemic, required the development of different diagnostic tests. While reverse transcriptase real-time PCR (RT-PCR) remains the first-line test of choice in acute infection diagnosis, anti-N antibodies serological assays provide a valuable tool to differentiate natural SARS-CoV-2 immunological response from that induced by vaccination, thus the goal of our study was to evaluate three serological tests agreement for these antibodies detection. Three anti-N different tests were examined in 74 sera from patients referred or not COVID infection: immunochromatographic rapid test (Panbio™ COVID-19 IgG/IgM Rapid Test Device Abbott, Germany), ELISA kit (NovaLisa® SARS-CoV-2 IgG and IgM NovaTech Immunodiagnostic GmbH, Germany) and ECLIA immunoassay (Elecsys® Anti-SARS-CoV-2 Roche Diagnostics, Manheim, Germany). Qualitative comparison of the three analytical methods revealed a moderate agreement between ECLIA immunoassay and immunochromatographic rapid test (Cohen kappa coefficient κ = 0.564). Correlation analysis indicated weak positive correlation between total Ig (IgT) detected by ECLIA immunoassay and IgG by ELISA test (p < 0.0001), the analysis of ECLIA IgT and IgM ELISA detected, showed no statistical correlation. Comparison between of three analytical systems available for anti-N SARS-CoV-2 IgG and IgM antibodies showed a general agreement when compared to detect total and G class immunoglobulins, while doubtful or discordant results have been highlighted for IgT and IgM class. Anyway, all the tests examined provide reliable results to assess the serological status of SARS-CoV-2 infected patients.


The acceptability and feasibility of using a 3D body size scale to initiate conversations about weight in toddlerhood: a mixed-methods study.
Health Care Professionals struggle to initiate conversations about overweight in toddlerhood. A novel 3D body size scale (3D BSS) may facilitate engagement with this topic during pediatric appointments. To explore barriers and facilitators to using the 3D BSS through a mixed-methods design. For the qualitative phase, parents of toddlers (n = 38) participated in semi-structured interviews introducing the 3D BSS of 4-5-year-old children. For the quantitative phase, pre- and post-interview questionnaires were administered to ascertain the acceptability of the 3D BSS. Parents rated the 3D BSS as "very" (n = 20, 52.6%) to "moderately" (n = 12, 31.6%) acceptable. Thematic analysis revealed four barriers to acceptability: i) the sensitive nature of child weight, ii) the belief that weight does not determine health, iii) the visual normalisation of overweight and iv) the need to account for individual variation in growth patterns. However, these barriers could be overcome through three facilitators: i) the provision of expert guidance ii) the value of simple tools, and iii) tailoring conversations to familial needs. Parents considered the 3D BSS an acceptable visual resource to discuss child weight during routine appointments. However, the acceptability of the tool was conditional on a sensitive, collaborative, and tailored delivery approach.


Fetal Doppler Hypoxic index for the prediction of abnormal fetal heart rate at delivery in chronic fetal distress.
To design a Doppler Hypoxic index (HI), which takes into account both the duration and the intensity of fetal flow redistribution (i.e. hypoxia) for predicting the occurrence of abnormal fetal heart rate (FHR) at delivery. Sixty-six pregnancies with hypertension and/or growth retardation (IUGR) were investigated (age: 23+/-5 years; primigravidas: 30%, CS 59%; hospitalisation: 10+/-8 days, IUGR (<10 c) 82%, intensive care 23%, fetal death 1). Umbilical (URI) and cerebral (CRI) Doppler resistance indices, and the C/U ratio (CRI/URI) were measured every 2 days from admission to delivery. HI was calculated by summing the daily %C/U reduction (in % from normal cut-off limit 1.1) over the period of observation (or mean C/U reduction in % from 1.1 x number of days of observation). Doppler C/U and HI were compared with fetal heart rate (FHR) traces, and perinatal data. HI > 160% was associated with abnormal FHR in 80% of the cases (PPV = 87%, NPV = 88%). HI > 160% predicted the occurrence of abnormal FHR 8+/-6 days before they happened. A combination of intensity and duration of the fetal flow redistribution (i.e. hypoxia) evaluated by Doppler is correlated with the occurrence of abnormal fetal heart rate.


Detection of HBeAg and anti-HBe in acute hepatitis B by a sensitive radioimmunoassay.
A solid-phase radioimmunoassay using anti-HBe-coated polysterence beads and iodine-125-labeled anti-HBe of human origin was developed for the detection of HBeAg. Anti-HBe could be determined by a blocking test. Both assays were about 500-fold more sensitive than immunodiffusion. Few nonspecific positive results for HBeAg could be recognized in the anti-HBe test by increase in cpm over that of the negative control. HBeAg was not found in acute hepatitis A and non A-non B hepatitis or in a control group of accident patients. On admission to the hospital 12 of 48 (25%) acute hepatitis B patients from Greece and 17 of 20 (85%) acute hepatitis B patients from Germany were HBeAg-positive. All 39 initially HBeAg negative sera were already anti-HBe positive. Tests of the acute stage and follow-up sera of the 20 German patients indicated that HBeAg is regularly present in the incubation period and early acute phase of hepatitis B. After onset of disease the antigen is cleared from the serum very rapidly in uncomplicated cases and is usually followed by the appearance of anti-HBe. Like anti-HBc, anti-HBe can serve as a tool for the diagnosis of hepatitis B after the disappearance of HBsAg.


Effects of pregnancy on the contents of water, taurine, and total amino nitrogen in rat cerebral cortex.
Plasma osmolality and the levels of water, taurine, and total amino nitrogen (detected as ninhydrin-positive substances) have been measured in the cerebral cortices of nonpregnant and 19-day pregnant Wistar rats. Plasma osmolality fell by 11 mosmol/kg during pregnancy. Brain water content remained unaltered, but levels of taurine and ninhydrin-positive substances fell by 48.5 and 21.9%, respectively. It is suggested that one way in which brain cells are prevented from swelling during the mild hypoosmolality of pregnancy is through loss of cellular amino nitrogen, particularly taurine.


Using quotients as a mentor to facilitate the success of underrepresented students.
Choosing a mentor requires a certain level of introspection for both the mentor and the mentee. The dynamics of mentorship may change depending on the academic status of the mentee. Regardless, mentors should help their trainees grow both academically and professionally. The success of an individual in the fields of science, technology, engineering, mathematics, and medicine (STEMM) depends on more than intellectual capacity; a holistic view encompassing all factors that contribute to scientific achievement is all-important. Specifically, one new method scientists can adopt is quotients, which are scales and techniques that can be used to measure aptitude in a specific area. In this paper, we focus on these factors and how to grow one's adversity quotient (AQ), social quotient (SQ), and personal growth initiative scale (PGIS). We also look at how mentors can better understand the biases of their trainees. In addressing this, mentors can help trainees become more visible and encourage other trainees to become allies through reducing biases.


The effects of fatty acids in propylene glycol on the percutaneous absorption of alendronate across the excised hairless mouse skin.
The effects of fatty acids at various concentrations in propylene glycol (PG) on the in vitro permeation of alendronate from solution formulations and formulated pressure-sensitive adhesive (PSA) transdermal delivery systems through excised hairless mouse skin were investigated. Caprylic acid, capric acid, lauric acid, oleic acid and linoleic acid at concentrations of 3, 6 and 10% were employed as a fatty acid. The highest maximum permeation flux was obtained with 3% capric acid in PG followed by 6% capric acid and 3% oleic acid from solution formulations; the enhancement factor by the addition of 3% capric acid to PG was 20.5 compared to PG alone. On the contrary, from PSA transdermal delivery systems, the highest enhancement factor of 2.9 was attained with 6% caprylic acid in PG compared to PG alone. The maximum permeation flux and lag time from PSA transdermal delivery systems by the addition of 6% caprylic acid to PG were 195.68+/-26.6 ng/cm2/h and 0.6+/-0.3h whereas PG without fatty acids showed 67.3+/-5.8 ng/cm2/h and 0.5+/-0.4h, respectively. The PSA transdermal delivery systems initially provided very high permeation rate followed by a gradual decrease regardless of the fatty acids. The highest release rate was also obtained with the formulation containing 6% caprylic acid in PG although release rates were not matched with permeation rates perfectly. In conclusion, for effective transdermal delivery system of alendronate, 6% caprylic acid in PG could be employed.


LC-MS analysis of Hep-2 and Hek-293 cell lines treated with Brazilian red propolis reveals differences in protein expression.
Red propolis, an exclusive variety of propolis found in the northeast of Brazil has shown to present antitumour activity, among several other biological properties. This article aimed to help to evaluate the underlying molecular mechanisms of the potential anticancer effects of red propolis on tumour, Hep-2, and non-tumour cells, Hek-293. Differentially expressed proteins in human cell lines were identified through label-free quantitative MS-based proteomic platform, and cells were stained with Giemsa to show morphological changes. A total of 1336 and 773 proteins were identified for Hep-2 and Hek-293, respectively. Among the proteins here identified, 16 were regulated in the Hep-2 cell line and 04 proteins in the Hek-293 line. Over a total of 2000 proteins were identified under MS analysis, and approximately 1% presented differential expression patterns. The GO annotation using Protein Analysis THrough Evolutionary Relationships classification system revealed predominant molecular function of catalytic activity, and among the biological processes, the most prominent was associated to cell metabolism. The proteomic profile here presented should help to elucidate further molecular mechanisms involved in inhibition of cancer cell proliferation by red propolis, which remain unclear to date.


Naloxone augments electrophysiological signs of selective attention in man.
Previous research on the behavioural functions of endogenous opioid systems in rodents suggested a possible opioid role in the regulation of attention. This proposal was consistent with reports that opiate administration in man impairs the ability to concentrate while opiate antagonists augment behavioural and electrophysiological indices of arousal and attention. We examined the effects of the opiate antagonist naloxone on electrophysiological measures of attention in normal human subjects, using a paradigm which dissociates selective information processing from concurrent processes of general arousal or alertness that may be present. We now report electrophysiological evidence that naloxone improves the selectivity of auditory attention in the presence of competing sources of stimuli. These findings indicate a role for the endogenous opioid systems in the regulation of selective attention in man.


Effects of porta-systemic shunting and ammonia infusion on cerebral blood flow autoregulation in the rat.
Portacaval shunting of blood, hyperammonemia, and impaired cerebral blood flow (CBF) autoregulation are assumed to be involved in the development of high intracranial pressure (ICP) in liver failure. In this study, we determined whether CBF autoregulation is impaired by portacaval anastomosis and hyperammonemia. Four groups of pentobarbital-sedated and mechanically ventilated rats were investigated after construction of a portacaval anastomosis or following sham operation. Half of the rats received either infusion of ammonia (55 micromol/kg/minute) or saline for 180 minutes. Arterial pressure and ICP was monitored, and lower limit of CBF autoregulation was determined. Lower limit of autoregulation was preserved in all four groups of studied animals; vehicle lower limits were 40 +/- 2.3, 40 +/- 2, 54 +/- 1, and 51 +/- 3 mmHg in sham-operated rats, sham rats receiving ammonia infusion, portacaval anastomosis-vehicle animals, and portacaval anastomosis-hyperammonemia animals, respectively. The lower limit of auto regulation was higher in portacaval anastomosis rats (p = 0.01) compared to the sham- operated rats. Hyperammonemia in portacaval anastomosis rats did not aggravate this. Portacaval anastomosis and hyperammonemia does not impair the lower limit of CBF autoregulation. However, shunting of portal blood to the systemic circulation shifts the lower limit of autoregulation to higher blood pressure values, making the brain more sensitive to episodes of arterial hypotension.


Retracted: A Study on Parents' Attitudes towards Middle School Students' Online Learning Based on Statistical Analysis.
[This retracts the article DOI: 10.1155/2022/4848738.].


Hepatocellular carcinoma surveillance - utilization, barriers and the impact of changing aetiology.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of α-fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity. In this Review, we discuss the current status of HCC surveillance and the remaining challenges, including the changing aetiology of liver disease. We also discuss strategies to improve the utilization and quality of surveillance for HCC.


Associations between clinicians' emotional responses, therapeutic alliance, and patient suicidal ideation.
Mental health clinicians frequently experience intense negative emotional responses to suicidal patients, which have been related to treatment outcome. This study examines the therapeutic alliance as a mediator of the relationship between clinicians' negative emotional responses at the initial encounter and patients' suicidal ideation (SI) concurrently and 1 month later. We assessed 378 adult psychiatric outpatients (62.7% female; mean age = 39.1 ± 14.6 years) and their 61 treating clinicians. Following the initial encounter, self-report questionnaires assessed clinicians' emotional responses to their patients, patients' and clinicians' perception of the therapeutic alliance, and patients' SI. The SI was reassessed 1 month after the initial visit. Multilevel mediation analyses were performed. Patients' (but not clinicians') perception of the therapeutic alliance mediated the relationship between clinicians' negative emotional responses to patients and patients' SI 1 month following the initial visit (indirect effect estimate = 0.015; p < .001). The association between clinicians' negative emotional response and patients' prospective SI appears to be transmitted, at least partly, through the patients' perception of the poorer early quality of the therapeutic alliance. Thus, clinicians' awareness and management of their emotional states appear essential both for the identification of suicidal risk and to enhance therapeutic alliance and treatment outcomes.


DPP-4 inhibitors and heart failure: a potential role for pharmacogenomics.
There remains an ongoing controversy regarding the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors and the risk of developing heart failure (HF). In addition, none of the animal studies suggested a mechanism for the DPP-4 inhibitors and HF risk. To date, advances in pharmacogenomics have enabled the identification of genetic variants in DPP-4 gene. Studies have shown that genetic polymorphisms in the gene encoding DPP-4 may be associated with potential pathways involved in HF risk. This review discusses the contradictory findings of DPP-4 inhibitors and HF and a potential role for pharmacogenomics. Pharmacogenomics of DPP-4 inhibitors is promising, and genetic information from randomized control trials is urgently needed to gain a full understanding of the safety of DPP-4 inhibitors and the risk of HF.


Eye injuries from merchandise display hooks.
Four patients had ocular or ocular adnexal injuries, which resulted from store merchandise display hooks. Ocular and periocular injuries from display hooks include conjunctival, eyelid, and canalicular lacerations, as well as penetrating brain injury. Display hooks are commonly used in retail establishments and pose a high risk when placed below eye level.


Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes.
Our present report deals with the preparation of hitherto unreported 7-([carbonyl-14C]-acetyl)paclitaxel 4 and two new bioactive 7-substituted fluorescent taxoids (FITC 9 and rhodamine 11), as well as evaluation towards their applications as biological probes. The results in this report demonstrate that (a) the new paclitaxel derivatives 4, 9, 11 could be prepared with good yields starting from paclitaxel; (b) the [14C]acetylation step was found to be better by using [14C]acetic anhydride rather than [14C]sodium acetate; (c) the radiochemical purity of 4 was 96% and its specific activity was 48 mCi/mmol; (d) the cytotoxicity of 4 was close to that of paclitaxel whereas 9, 11 were far less active than paclitaxel, but these cytotoxic levels were good enough for their biological applications; (e) the drug-quantitation by flow cytometric analysis using 9 and 11 was proved to be equally efficient with respect to the radioactivity-based determination employing 4; (f) the intracellular fluorescence mapping by 9 and 11 was found to be effective and the microtubule network pattern was visible in both the cases; (g) the overall fluorescence imaging efficiency was better with 11 while the intensity of fluorescence was higher with 9; (h) staining of nucleolus was observed in fluorescence studies of both 9 and 11. Based on these results, the newly prepared paclitaxel derivatives can be considered as efficient biological probes and should find further use in relevant applications.


Soft Tissue Metastases in Head and Neck Cutaneous Squamous Cell Carcinoma.
Soft tissue metastases (STM) in head and neck cutaneous squamous cell carcinoma (HNcSCC) are non-nodal based metastases to the parotid and cervical soft tissues of the head and neck. This is a unique subgroup of regional metastases amongst patients with cSCC and have been shown to be associated with poor prognosis. Detailed studies of this subgroup are lacking in the literature. A retrospective cohort analysis was performed to characterize the prognostic significance of STM in HNcSCC based on individual clinicopathological features. Patients with HNcSCC with STM were identified from the Sydney Head and Neck Cancer Institute database. Clinicopathological characteristics were extracted from the histopathological reports. Recurrence and follow-up data were analyzed to determine disease-free and overall survival using the Kaplan-Meier method and Cox proportional hazards models. After excluding all patients with lymph node metastasis with no STM, there were 200 patients identified (161 parotid, 32 cervical, and seven with concurrent parotid and cervical STM) with a 5-year overall survival of 36%. In univariable analysis, age of patients, size of the deposits, location of the deposits, and patients that were not offered adjuvant radiotherapy have worse overall survival. However, on multivariable analysis, age and the number of STM deposits were independent factors that predict for worse survival. The presence of STM in patients with HNcSCC is associated with poor prognosis. Increasing number of STM deposits, as well as involved margin of the regional excision, negatively impacted on the overall prognosis. Level III - retrospective cohort study. Laryngoscope, 131:E1209-E1213, 2021.


Neuromuscular efficiency of the multifidus muscle in pilates practitioners and non-practitioners.
Pilates exercises help stabilize the vertebral segments by recruiting the abdominal and spinal muscles. Pilates training may increase joint stability and improve neuromuscular efficiency (NME). This study aimed to evaluate NME of the multifidus (MU) muscle through electromyography (EMG) analysis and torque test, applied to practitioners and non-practitioners of Pilates. Participants included thirty women: Pilates practitioners (n = 15) and non-practitioners (n = 15). They were tested for trunk extension. Their right and left MU muscles were submitted to EMG to estimate NME. Results concerning torque, EMG, and NME from all participants were compared. Statistical analysis concerning isometric torque peak (p = 0.0275) and NME (p = 0.0062) showed significant difference (Student t test; p < 0.05) between practitioners and control. No significant difference (p = 0.3387) in EMG was observed. Our results suggest Pilates exercises is effective in training spinal muscles to improve NME in women.


Seminal vesicle cyst and ipsilateral renal agenesis. Case report.
Cysts of the seminal vesicles are rare, and associated anomalies of the ipsilateral kidney are frequent. We report a case of a monolocular cystic mass in the seminal vesicle bed in a young male with recurrent epididymitis, with emphasis on the ultrasonographic and CT features. The embryological background is briefly mentioned.


Therapeutic plasma exchange for COVID-19-associated hyperviscosity.
Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID-19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID-19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID-19-associated hyperviscosity. Six critically ill COVID-19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4-1.8 cP) underwent daily TPE for 2-3 treatments. TPE decreased plasma viscosity in all six patients (Pre-TPE median 3.75 cP, range 2.6-4.2 cP; Post-TPE median 1.6 cP, range 1.5-1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre-TPE median 739 mg/dL, range 601-1188 mg/dL; Post-TPE median 359 mg/dL, range 235-461 mg/dL); D-dimer levels in all six patients (Pre-TPE median 5921 ng/mL, range 1134-60 000 ng/mL; Post-TPE median 4893 ng/mL, range 620-7518 ng/mL); and CRP levels in five of six patients (Pre-TPE median 292 mg/L, range 136-329 mg/L; Post-TPE median 84 mg/L, range 31-211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE. This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID-19-associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID-19.


Ulcerative colitis of the neovagina as a postsurgical complication of persistent cloaca.
Persistent cloaca is characterized by a common vestibule connected to the bladder, uterus, and rectum and a single perineal orifice to the exterior. Treatment can involve vaginal reconstruction with sigmoid/descending colon. We report a case of an 8-year-old girl who, as an infant, underwent vaginoplasty using sigmoid colon for persistent cloaca and developed a fulminant colitis that also affected the colonic neovagina 2 years after her reconstruction.


Direct examination vs culture of biopsy specimens for the diagnosis of keratomycosis.
In two patients with fungal keratitis, direct examination of corneal biopsy specimens showed positive fungal elements, but cultures of biopsy specimens failed to disclose fungal growth. We compared the value of direct examination and culture of biopsy specimens in the diagnosis of keratomycosis in rabbits with experimental fungal keratitis caused by Fusarium solani, Aspergillus fumigatus, and Candida albicans. Cultures disclosed seven specimens (70%) positive for Candida and eight (80%) for Fusarium and Aspergillus keratitis, whereas direct examination showed positive fungal elements of Fusarium, Aspergillus, and Candida in all specimens.


Outbreak of gastric mucormycosis associated with the use of wooden tongue depressors in critically ill patients.
To describe a nosocomial outbreak of gastric mucormycosis caused by Rhizopus microsporus var. rhizopodiformis in five adult patients admitted to an intensive care unit (ICU). Epidemiological surveillance study. A 12-bed polyvalent ICU of an acute care teaching hospital in Pamplona, Spain. Five patients admitted to the ICU requiring artificial ventilation, diagnosis on admission severe pneumonia in four patients and one polytrauma patient, within a 14-week period, were diagnosed with gastric mucormycosis based on microbiological and/or histopathological characteristics. Upper gastrointestinal bleeding was the presenting manifestation in 80% of patients. Filamentous fungi isolated at the microbiology laboratory of the hospital were examined at the national Mycology Reference Laboratory in Madrid. Rhizopus microsporus var. rhizopodiformis growth was detected in gastric aspiration samples, environmental samples, wooden tongue depressors used to prepare oral medications (and given to patients through a nasogastric catheter), and in some tongue depressors stored in unopened boxes unexposed to the ICU environment. All depressors were purchased from the same supplier. R. microsporus was not isolated from batches purchased at different times from the same supplier and from another supplier. The outbreak terminated when contaminated tongue depressors were withdrawn from use. Wooden tongue depressors contaminated by R. microsporus var. rhizopodiformis used to prepare oral medications caused an outbreak of fungal gastritis with an attributable mortality of 40%. Wooden material should not be used in the hospital setting.


Intraperitoneal application of fibrinogen gluing in the rat for adhesions prophylaxis.
The suitability of fibrinogen gluing for prophylaxis of intraperitoneal adhesions was investigated experimentally. Small bowel slings, traumatized previously, were covered by a layer of fibrinogen 2-3 mm thick to see whether formation of adhesions could be prevented. In the experiments 50 rats of both sexes were observed over 21 days. Following mechanical traumatization of the terminal ileum the visceral peritoneum was coated with fibrinogen, whereas animals of the control group did not receive fibrinogen coating. Macroscopic and microscopic findings after 1, 3, 7, 14 and 21 days yielded the following results: 1. Fibrinogen dissolution and resorption occurred for 3-14 days following operation. 2. On autopsy, all animals of the control group showed massive, extended adhesions; two of the controls died on the 6th postoperative day from peritonitis. 3. None of the treated animals exhibited extended adhesions. 4. Histological examinations revealed regeneration of the injured serosa and healing of the bowel wall below the fibrinogen coating. 5. Fibrinogen applied to intact peritoneal serosa (without injury) is entirely resorbed without formation of adhesions.


[Change in the content of inorganic ions in the hemolymph of freshwater mollusks infected with trematode parthenitae].
Changes in the concentration of ions of sodium, potassium, calcium and chlorine in the haemolymph of Lymnaea stagnalis and Planorbis corneus were studied during their infection with sporocysts and rediae of trematodes. Statistically reliable disturbances in the ion balance caused by the infection were established.


Isolation of alkaloidal and glycosidal fractions from leaves of Trigonella foenum-graecum L. cv. Desi indigenous to Pakistan for antiprostaglandin evaluation as substitute of nonsteroidal anti-inflammatory drugs.
Trigonella foenum graecum (fenugreek) has been in use for a long time as a traditional medicine and natural food additive. The reported gastro-protective property makes it unique among other herbs. Seeds and leaves have been shown to exert significant antiatherogenic, antidiabetic, antianorexic, antioxidant, anticarcinogenic, antihyperlipidemic, galactogogue and anti-inflammatory effects in several animal and human models. But its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs needs to be confirmed. Nonsteroidal anti-inflammatory drugs (NSAIDs) are in common use in treating inflammation associated with a variety of ailments, fever and pain such as menstrual cramps, back pain, arthritic pain and headaches. Their toxicity profile includes the risk of severe gastro-intestinal adverse events like increased bleeding tendency, ulceration, perforation, etc. Conventional NSAIDs have also been reported to reduce the glomerular filtration rate (GFR) by affecting afferent arterioles in nephrons. Exacerbated potassium levels were noted in patients using NSAIDs concomitantly with antihypertensive drugs belonging to the angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) classes. In this context, the need of the hour is to discover and isolate new compounds from the reported medicinal plants for evaluation of antiprostaglandin potential and safety profile in terms of the hepato-renal system. These compounds may be used as substitutes for NSAIDs in the future management of inflammation and pain with therapeutic equivalency and organ safety. In this scenario, the present study aimed to assess the antiprostaglandin potential of alkaloidal and glycosidal fractions from the leaves of Trigonella foenum-graecum L. cv. Desi variety, indigenous to Pakistan, in albino mice along with safety profile. The herb has been used as folk medicine since ancient times for treating inflammation and pain. Alkaloidal and glycosidal fractions were separated from a methanol extract of leaves of the fenugreek Desi variety. After separation of fractions, their subsiding effects on carrageenan-induced inflammation, air pouch exudate prostaglandin-E2 levels, Brewer's yeast induced pyrexia and acetic acid induced abdominal constrictions were assessed in adult male albino mice. The safety profile of fractions was assessed by measuring their effects on mice sera hepato-renal biomarkers. Alkaloidal fraction of T. foenum Desi variety was found to be significantly effective in reducing inflammation, air pouch exudate PGE2 levels, fever (≤37 °C) and pain by inhibiting writhes (up to 96.58%) Gradual inhibition of paw edema was observed 1-6 h post-dose, with maximum reduction percentages of 62.82% and 62.57% for 100 mg and 200 mg, respectively. Both fractions did not disturb the normal physiology of the hepato-renal system by showing normal biomarker values. In summary, the results demonstrate the potent antiprostaglandin potential of the alkaloidal fraction of gastroprotective fenugreek "Desi" leaves with hepato-renal system safety and hence justify its use as a substitute for ulcerative nonsteroidal anti-inflammatory drugs.


Using mercury stable isotope fractionation to identify the contribution of historical mercury mining sources present in downstream water, sediment and fish.
Ecosystems downstream of mercury (Hg) contaminated sites can be impacted by both localized releases as well as Hg deposited to the watershed from atmospheric transport. Identifying the source of Hg in water, sediment, and fish downstream of contaminated sites is important for determining the effectiveness of source-control remediation actions. This study uses measurements of Hg stable isotopes in soil, sediment, water, and fish to differentiate between Hg from an abandoned Hg mine from non-mine-related sources. The study site is located within the Willamette River watershed (Oregon, United States), which includes free-flowing river segments and a reservoir downstream of the mine. The concentrations of total-Hg (THg) in the reservoir fish were 4-fold higher than those further downstream (>90 km) from the mine site in free-flowing sections of the river. Mercury stable isotope fractionation analysis showed that the mine tailings (δ202Hg: -0.36‰ ± 0.03‰) had a distinctive isotopic composition compared to background soils (δ202Hg: -2.30‰ ± 0.25‰). Similar differences in isotopic composition were observed between stream water that flowed through the tailings (particulate bound δ202Hg: -0.58‰; dissolved: -0.91‰) versus a background stream (particle-bound δ202Hg: -2.36‰; dissolved: -2.09‰). Within the reservoir sediment, the Hg isotopic composition indicated that the proportion of the Hg related to mine-release increased with THg concentrations. However, in the fish samples the opposite trend was observed-the degree of mine-related Hg was lower in fish with the higher THg concentrations. While sediment concentrations clearly show the influence of the mine, the relationship in fish is more complicated due to differences in methylmercury (MeHg) formation and the foraging behavior of different fish species. The fish tissue δ13C and Δ199Hg values indicate that there is a higher influence of mine-sourced Hg in fish feeding in a more sediment-based food web and less so in planktonic and littoral-based food webs. Identifying the relative proportion of Hg from local contaminated site can help inform remediation decisions, especially when the relationship between total Hg concentrations and sources do not show similar covariation between abiotic and biotic media.


Time to desaturation in the 6-min walking distance test predicts 24-hour oximetry in COPD patients with a PO2 between 60 and 70mmHg.
The 6-min walking distance (6MWD) test is a useful tool for assessing patients with chronic obstructive pulmonary disease (COPD), but little is known about the changes in oxygen saturation that occur during the test. To predict the oximetry profile during daily living activities by the time to desaturation in the 6MWD test in COPD-affected patients. We studied 67 COPD patients with moderate hypoxemia performing a 6MWD test and a 24-hour ambulatory pulse oximetry (24-hr PO). We determined the time to desaturation (SatO290%) in the 6MWD test, in the daytime, nighttime and 24-hr PO. We then estimated the time to desaturation that better predicts desaturation in diurnal, nocturnal and 24-hour oximetries using the ROC type II analysis. The patients who desaturated after 3'30min have a 100% probability not to desaturate during diurnal, nocturnal and 24-hr PO. Those patients who desaturated during the first minute of the 6MWD test have a 74% probability to desaturate in these oximetries. The time to desaturation in the 6MWD test can discriminate early desaturators who desaturate during their daily living activities and late desaturators who do not desaturate. Ambulatory oximetry would thus only be necessary in patients with a time to desaturation that ranges between 1 and 3'30''.


Heart failure in pressure overload hypertrophy. The relative roles of ventricular remodeling and myocardial dysfunction.
We sought to explore the relative contributions of ventricular remodeling and myocardial dysfunction to heart failure in pressure overload hypertrophy (POH). The mechanism that underlies heart failure in POH is adverse left ventricular (LV) chamber remodeling or decreased myocardial function, or a combination of these. Twenty weeks after suprarenal aortic banding in rats, animals with POH were classified as those with heart failure (POH-HF) or those with no heart failure (POH-NHF). The LV chamber and myocardial systolic and diastolic functions were determined from in vivo and ex vivo experiments. The LV mass was similar in both POH groups. Chamber remodeling in the POH-HF group was characterized by marked LV enlargement with a normal relative wall thickness (eccentric remodeling), whereas remodeling in the POH-NHF group was characterized by a normal chamber size and increased relative wall thickness (concentric remodeling). The LV systolic function, as determined in vivo from the end-systolic pressure-diameter relationship and ex vivo from the pressure-volume relationship, was lower in the POH-HF group than in the POH-NHF and sham-operated control groups. In contrast, myocardial function was similar in both POH groups, as determined in vivo from the stress-midwall fractional shortening relationship and myocardial systolic stiffness, and ex vivo from the slope of the LV systolic stress-strain relationship. The diastolic chamber stiffness constant was lower in the POH-HF group than in the POH-NHF group, but the myocardial stiffness constant was similar in the two POH groups. The two POH groups differed primarily in their remodeling process, which led to a chronically compensated state in one group and to heart failure in the other. Hence, heart failure in POH is more closely related to deleterious LV remodeling than to depressed myocardial function.


COVID-19 vaccination in correctional systems in the United States.
Overcrowding and limited ability to social distance contribute to high rates of COVID-19 outbreaks in correctional facilities. Despite the Centers for Disease Controls' recommendations, incarcerated persons and correctional staff report a high prevalence of vaccine-hesitance. We sought to identify reasons underlying COVID-19 vaccine hesitation and refusal in correctional systems. We used Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines to design the review. We searched PubMed abstracts and reviewed literature relevant to COVID-19 vaccine uptake and hesitancy in correctional systems of the United States (n = 23). Reasons for vaccine hesitancy among incarcerated people and correctional staff include efficacy, safety concerns, lack of information, and distrust. Findings reveal higher vaccine hesitancy among young and Black residents whereas facilities in close collaborations with state health departments exhibited higher vaccination rates. Correctional facilities must prioritize communication and education to improve the current state of vaccine hesitancy.


Off-pump right atrial thrombectomy for heparin-induced thrombocytopenia with thrombosis.
This report describes a 72-year-old woman with atrial fibrillation who presented with lower extremity ischemia secondary to thromboembolism. After lower extremity thrombectomy, the patient developed heparin-induced thrombocytopenia with thrombosis (HITT). Her postoperative course was complicated by recurrent supraventricular and ventricular tachycardia, secondary to a mobile thrombus in the right atrium extending into the right ventricle. Because administration of heparin was contraindicated, the patient underwent off-pump right atrial thrombectomy during a brief period of inflow occlusion. Postoperatively, she was placed on lepirudin. Her platelet count normalized without any further thrombotic episodes, and she was discharged on warfarin.


[Evaluation of a primary care self-management project].
To evaluate a "Primary Care Self-Management Project" started in 1992. An observational and semi-experimental study with sub-designs: post-test, pretest/post-test with one group, pre-test/post-test with a non-equivalent control group and multiple temporal series. An urban area. The nine Primary Care teams (PCT) in Vitoria-Gasteiz. A decentralised budget for self-management was assigned to each PCT, which included Chapter I, staff replacements and Chapter II, Stores, Laboratory, Radiology and Maintenance. 1. Cost control and adjustment of each PCT to the assigned budget. There was an overall saving of 1.8% of the total decentralised budget (96,959,988 pesetas). Six of the nine PCTs fulfilled their assigned budgets. 2. The increase in professional motivation was partially measured by looking at short-term spells off work in the Absence from Work index. In the PCT this index fell 31% from 1991 to 1992, from 4.2 to 2.9%. Among the County's other staff this index remained practically stable, falling only from 5.1 to 4.8%. 3. Higher productivity and better budget use was measured by looking at replacement costs, which went down 7.2% from 1991 to 1992. The proportion of cost arising from replacements for scheduled activities went from 57.9% in 1991 to 39.1% in 1992. Self-management, at least within the scope of this study, has positive effects on various aspects of the PCTs' work.


Single-dose pharmacokinetics of 2 or 3 tablets of biphasic immediate-release/extended-release hydrocodone bitartrate/acetaminophen (MNK-155) under fed and fasted conditions: two randomized open-label trials.
Biphasic immediate-release (IR)/extended-release (ER) hydrocodone bitartrate (HB)/acetaminophen (APAP) 7.5/325-mg tablets are formulated with gastroretentive ER drug delivery technology that has been associated with clinically meaningful food effects in other approved products. Two phase 1 studies evaluated potential effects of food on single-dose pharmacokinetics of IR/ER HB/APAP tablets. These were single-center, open-label, randomized, single-dose, 3-period crossover studies in healthy volunteers (aged 18-55 years). IR/ER HB/APAP was administered as a single 2-tablet dose (study 1) or 3-tablet dose (study 2) under fed (high- and low-fat) and fasted conditions. Area under the plasma concentration-time curve from 0 h to time t (AUC0-t) and from time 0 extrapolated to infinity (AUC0-inf) and maximum observed plasma concentration (Cmax) of hydrocodone and APAP under fed versus fasted conditions were compared using analysis of variance. A 90% confidence interval of the geometric least squares mean ratio fully contained within 80 to 125 % indicated no treatment difference. Safety and tolerability were assessed. Forty of 48 participants in study 1 and 21 of 30 in study 2 completed all treatments. In both studies, under fed (high- or low-fat meal) versus fasted conditions, 90% CIs for AUC0-t and AUC0-inf for both hydrocodone and APAP were entirely contained within the bioequivalent range (80-125%), indicating that high- and low-fat meals did not affect the extent of exposure. In both studies, a high-fat meal did not affect the Cmax for hydrocodone. Hydrocodone Cmax was not affected by a low-fat meal in study 1 but increased by approximately 19% in study 2. A high-fat meal decreased APAP Cmax by approximately 20 % (study 1) and 13 % (study 2); a low-fat meal decreased APAP Cmax by 22% (study 1) and 21% (study 2). Approximately 50% of participants in both studies reported ≥1 treatment-emergent adverse event (TEAE), with no notable difference based on food intake. There were no serious or severe AEs. The most common TEAEs were nausea, vomiting, and dizziness. Pharmacokinetic and safety findings were similar regardless of food intake. TEAEs were consistent with those reported with low-dose combination opioids. IR/ER HB/APAP can be administered without regard to food. ClinicalTrials.gov NCT02561650 and NCT02561741 .


Surfactant protein gene expression in metastatic and micrometastatic pulmonary adenocarcinomas and other non-small cell lung carcinomas: detection by reverse transcriptase-polymerase chain reaction.
Reverse transcriptase (RT)-PCR with primers specific for surfactant protein A (SP-A), B (SP-B), C (SP-C), and D (SP-D) genes was applied to detect metastatic non-small cell lung carcinomas. Forty-one paratracheal and subcarinal lymph nodes obtained from 41 patients with non-small cell lung carcinomas, 11 lymph nodes from 11 patients with extrapulmonary adenocarcinomas, and eight control lymph nodes from patients without cancer were analyzed using RT-PCR. PCR products corresponding to SP-B gene products were found in all eight control lymph nodes, offering evidence of SP-B gene expression in cells of lymphatic tissue. SP-A, SP-C, and/or SP-D transcripts were detected in 11 (84.6%) of 13 lymph nodes with histologically identifiable metastases of pulmonary adenocarcinomas and in 10 (55.5%) of 18 lymph nodes that were tumor free on routine histological examination. These findings provide evidence of micrometastatic nodal involvement which remains undetectable by conventional light microscopy but can be evaluated by surfactant RT-PCR. Gene expression of SP-A and SP-C was restricted to metastatic pulmonary adenocarcinomas but SP-D gene activity has been also detected in two of four metastases of pulmonary large cell carcinomas, one adenosquamous carcinoma, and nine extrapulmonary adenocarcinomas as well.


The effect of gabapentin premedication on postoperative nausea, vomiting, and pain in patients on preoperative dexamethasone undergoing craniotomy for intracranial tumors.
In patients undergoing craniotomy, the incidence of postoperative nausea and vomiting (PONV) is 55% to 70% and that of moderate to severe postoperative pain is 60% to 84%. We hypothesized that gabapentin plus dexamethasone would be superior, compared with placebo and dexamethasone in reducing the incidences of PONV and pain after craniotomy. Patients undergoing craniotomy received either placebo (group D) or gabapentin (600 mg) (group GD) premedication orally, 2 hours before induction of anesthesia. In addition, all patients received 4 mg of intravenous dexamethasone on the morning of surgery and continued receiving it after every 8 hours. The 24-hour incidence of nausea, emesis, or PONV (nausea, emesis, or both) (primary outcome) and postoperative pain scores (secondary outcome) were analyzed with the χ test and the Wilcoxon rank-sum test as applicable. A significant difference was observed between the groups in the incidence of nausea (odds ratio [OR], 0.23; 95% confidence interval [CI], 0.07, 0.80; P=0.02), PONV (OR, 0.3; 95% CI, 0.08, 0.8; P=0.02), and the requirement for antiemetics (OR, 0.30; 95% CI, 0.09, 0.9; P=0.03). The number of emetic episodes were also reduced in group GD, but this did not assume statistical significance (OR, 0.34; 95% CI, 0.10, 1.1; P=0.06). However, there was no significant difference in either the postoperative pain scores or the opioid consumption between the 2 groups. A dosage of 600 mg of gabapentin plus 4 mg of dexamethasone significantly reduced the 24-hour incidence of nausea and PONV. However, there was no reduction in either the postoperative pain scores or opioid consumption.


Timing and type of immune checkpoint therapy affect the early radiographic response of melanoma brain metastases to stereotactic radiosurgery.
Growing evidence suggests that immunotherapy and radiation therapy can be synergistic in the treatment of cancer. This study was performed to determine the effect of the relative timing and type of immune checkpoint therapy on the response of melanoma brain metastases (BrMets) to treatment with stereotactic radiosurgery (SRS). Seventy-five melanoma patients with 566 BrMets were treated with both SRS and immune checkpoint therapy between 2007 and 2015 at a single institution. Immunotherapy and radiosurgery treatment of any single lesion were considered concurrent if SRS was administered within 4 weeks of immunotherapy. The impact of the timing and type of immunotherapy on the lesional response was determined with the Wilcoxon rank-sum test, which was used to compare the median percent lesion volume change 1.5, 3, and 6 months after SRS treatment, with significance determined by P = .0167 according to the Bonferroni correction for multiple comparisons. Concurrent use of immunotherapy and SRS resulted in a significantly greater median percent reduction in the lesion volume at 1.5 (-63.1% vs -43.2%, P < .0001), 3 (-83.0% vs -52.8%, P < .0001), and 6 months (-94.9% vs -66.2%, P < .0001) in comparison with nonconcurrent therapy. The median percent reduction in the lesion volume was also significantly greater for anti-programmed cell death protein 1 (anti-PD-1) than anti-cytotoxic T-lymphocyte-associated protein 4 (anti-CTLA-4) at 1.5 (-71.1% vs -48.2%, P < .0001), 3 (-89.3% vs -66.2%, P < .0001), and 6 months (-95.1% vs -75.9%, P = .0004). The administration of immunotherapy within 4 weeks of SRS results in an improved lesional response of melanoma BrMets in comparison with treatment separated by longer than 4 weeks. Anti-PD-1 therapy also results in a greater lesional response than anti-CTLA-4 after SRS. Cancer 2016;122:3051-3058. © 2016 American Cancer Society.


Role of C-Reactive Protein and Erythrocyte Sedimentation Rate in the Diagnosis and Monitoring of Treatment Response in Treatment Naïve Subjects with Chronic Pulmonary Aspergillosis.
The role of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) for diagnosing chronic pulmonary aspergillosis (CPA) remains unknown. Herein, we investigate the diagnostic performance of serum ESR and CRP in CPA. We retrospectively analyzed the data of treatment-naïve subjects with CPA and diseased controls (post-tuberculosis lung disease on CT thorax). We treated CPA subjects with six months of oral itraconazole. Our primary objective was to evaluate the sensitivity and specificity of ESR and CRP in diagnosing CPA. The key secondary objective was to study the change in the inflammatory markers with treatment. We included 434 subjects and 20 diseased controls. The sensitivity and specificity of ESR (n = 434) and CRP (at cut-off value of 10 mg/L, n = 308) in diagnosing CPA were 42.9% and 65%, and 52.3% and 65%, respectively. Both ESR and CRP had erratic trend following treatment. ESR and CRP declined or remained stable in approximately 60% of subjects but increased in approximately 40% of the subjects despite treatment. Serum CRP and ESR have limited utility in diagnosing and following subjects with CPA.


Impact of Autologous Stem Cell Transplantation on Blood Pressure and Renal Function in Multiple Myeloma Patients.
Autologous stem cell transplantation (ASCT) reverses kidney failure in one-third of multiple myeloma (MM) patients, which may lead to blood pressure (BP) improvement. We evaluate the long term impact of ASCT on BP and renal function in MM patients. We studied 192 MM patients that underwent ASCT. We compared BP readings and glomerular filtration rate (GFR) at 4 weeks before ASCT, on day of ASCT and post-ASCT at 30, 100 and 180 days. Mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) on day of ASCT and at both 30 and 100 days post-ASCT was significantly lower as compared to pre-ASCT SBP and DBP. There was a significantly higher mean GFR at day of ASCT and 30 days post-ASCT and significantly lower mean GFR at 180 days post-ASCT as compared to pre-ASCT. White patients had similar patterns to the total group for SBP, DBP, and GFR except for SBP which was still significantly lower and GFR which was not significantly different at 180 days. African-American patients showed no significant reductions in the mean values of SBP and DBP and no significant increases for GFR in follow-up after day of ASCT. Furthermore, the mean value of GFR was significantly lower at 180 days post-ASCT. ASCT in MM patients had a positive impact on SBP and DBP and GFR but the impact was minimal for African-American patients. We recommend that clinicians consider closer follow-up of BP and kidney function and more intense therapy in African-Americans with MM.


How accurately does the public perceive differences in transport risks? An exploratory analysis of scales representing perceived risk.
This paper probes the extent to which the public accurately perceives differences in transport risks. The paper is based on a survey of a random sample of the Norwegian population, conducted in September 2003. In the survey, respondents were asked: "How safe do you think it is to travel by means of (bus, train, etc.)?" Answers were given as: very safe, safe, a little unsafe, and very unsafe. A cursory examination of the answers suggested that the Norwegian public was quite well informed about differences in the risk of accident between different modes of transport, as well as between groups formed according to age and gender for each mode of transport. This paper probes the relationship between statistical estimates of risk and summary representations of perceived risk more systematically. It is found that the differences in fatality rate between different modes of transport are quite well perceived by the Norwegian public, irrespective of the way in which perceived risk is represented numerically. The relationship between statistical estimates of risk and numerical representations of perceived risk for each mode of transport is more sensitive to the choice of a numerical representation of perceived risk. A scale in which the answer "very safe" is assigned the value of 0.01 and the answer "very unsafe" is assigned the value of 10 is found to perform quite well. When the perception of risk is represented numerically according to this scale, a positive correlation between statistically estimated risk and perceived risk is found in seven of the eight comparisons that were made to determine how well variation in accident rates according to age and gender for car occupants, car drivers, cyclists and pedestrians are perceived.


Prospects in straw disintegration for biogas production.
The pretreatment methods for enhancing biogas production from oat straw under study include hot maceration, steam explosion, and pressure shockwaves. The micropore area (9, 55, and 64 m(2) g(-1)) inhibitor formations (0, 15, and 0 mL L(-1)) as well as the overall methane yields (67, 179, and 255 CH4 VS t(-1)) were robustly analyzed. It was confirmed that the operating conditions of the steam explosion must be precisely tailored to the substrate. Furthermore, it was beneficial to prepend the hot maceration before the steam explosion and the pressure shockwaves. The second alternative may give increased methane yields (246 in comparison to 273 CH4 VS t(-1)); however, the application of pressure shockwaves still faces limitations for deployment on a commercial scale.


Identification of disulfidptosis-related subtypes, characterization of tumor microenvironment infiltration, and development of a prognosis model in colorectal cancer.
Colorectal cancer is the second leading cause of cancer-related deaths, which imposes a significant societal burden. Regular screening and emerging molecular tumor markers have important implications for detecting the progression and development of colorectal cancer. Disulfidptosis is a newly defined type of programmed cell death triggered by abnormal accumulation of disulfide compounds in cells that stimulate disulfide stress. Currently, there is no relevant discussion on this mechanism and colorectal cancer. We classified the disulfidptosis-related subtypes of colorectal cancer using bioinformatics methods. Through secondary clustering of differentially expressed genes between subtypes, we identified characteristic genes of the disulfidptosis subtype, constructed a prognostic model, and searched for potential biomarkers through clinical validation. Using disulfidptosis-related genes collected from the literature, we classified colorectal cancer patients from public databases into three subtypes. The differentially expressed genes between subtypes were clustered into three gene subtypes, and eight characteristic genes were screened to construct a prognostic model. The disulfidptosis mechanism has important value in the classification of colorectal cancer patients, and characteristic genes selected based on this mechanism can serve as a new potential biological marker for colorectal cancer.


Pharmacokinetic Profile of Doxycycline in Koala Plasma after Weekly Subcutaneous Injections for the Treatment of Chlamydiosis.
Six mature, male koalas (Phascolarctos cinereus), with clinical signs of chlamydiosis, were administered doxycycline as a 5 mg/kg subcutaneous injection, once a week for four weeks. Blood was collected at standardised time points (T = 0 to 672 h) to quantify the plasma doxycycline concentrations through high-pressure liquid chromatography (HPLC). In five koalas, the doxycycline plasma concentration over the first 48 h appeared to have two distinct elimination gradients; therefore, a two-compartmental analysis was undertaken to describe the pharmacokinetic (PK) profile. The average ± SD maximum plasma concentration (Cmax) was 312.30 ± 107.74 ng/mL, while the average time ± SD taken to reach the maximum plasma concentration (Tmax) was 1.68 ± 1.49 h. The mean ± SD half-life of the distribution phase (T1/2 α) and the elimination phase (T1/2 β) were 10.51 ± 7.15 h and 82.93 ± 37.76 h, respectively. The average ± SD percentage of doxycycline binding to koala plasma protein was 83.65 ± 4.03% at three different concentrations, with a mean unbound fraction (fu) of 0.16. Using probability of target attainment modelling, doxycycline plasma concentrations were likely to inhibit 90% of pathogens with the doxycycline minimum inhibitory concentration (MIC) of 8.0-31.0 ng/mL, and the reported doxycycline MIC to inhibit Chlamydia pecorum isolates at the area under the curve/minimum inhibitory concentration (AUC/MIC) target of ≥24. All koalas were confirmed to be negative for Chlamydia pecorum using loop-mediated isothermal amplification (LAMP), from ocular and penile urethra swabs, three weeks after the last doxycycline injection.


Detection of Epstein-Barr virus DNA from a lymphoma-like lesion of the uterine cervix.
The case of a 60-year-old woman in whom a lymphoma-like lesion of the cervix was found during an episode of silent Epstein-Barr virus (EBV) infection is presented. Fractional curettage was performed because of abnormal endometrial smear. The endocervical curettage specimens were diagnosed as highly suggestive of malignant lymphoma, but microscopic examination of a subsequent hysterectomy specimen revealed a benign lymphoid hyperplasia. Those were retrospectively interpreted as a lymphoma-like lesion of the cervix. In the absence of clinical symptoms of infectious mononucleosis, the results of serologic tests for EBV revealed an active EBV infection. EBV DNA was demonstrated in nuclei of large lymphoid cells in endocervical curettage specimens by in situ hybridization. She is alive and well 32 months postoperatively. When female patients with lymphoma-like lesions of the lower genital tract are encountered, examinations for EBV are recommended.


Imitating Architectural Mortise-Tenon Structure for Stable Ni-Rich Layered Cathodes.
Ni-rich layered oxides are the most promising cathodes for Li-ion batteries, but chemo-mechanical failures during cycling and large first-cycle capacity loss hinder their applications in high-energy batteries. Herein, by introducing spinel-like mortise-tenon structures into the layered phase of LiNi0.8 Co0.1 Mn0.1 O2 (NCM811), the adverse volume variations in cathode materials can be significantly suppressed. Meanwhile, these mortise-tenon structures play the role of the expressway for fast lithium-ion transport, which is substantiated by experiments and calculations. Moreover, the particles with mortise-tenon structures usually terminate with the most stable (003) facet. The new cathode exhibits a discharge capacity of 215 mAh g-1 at 0.1 C with an initial Coulombic efficiency of 97.5%, and capacity retention of 82.2% after 1200 cycles at 1 C. This work offers a viable lattice engineering to address the stability and low initial Coulombic efficiency of the Ni-rich layered oxides, and facilitates the implementation of Li-ion batteries with high-energy density and long durability.


Roles of human periodontal ligament stem cells in osteogenesis and inflammation in periodontitis models: Effect of 1α,25-dihydroxyvitamin D3.
Periodontitis is a chronic inflammatory disease caused by Porphyromonas gingivalis and other bacteria, and human periodontal ligament stem cells (hPDLSCs) are a promising candidate for the treatment of periodontal supporting tissue defects. This study aimed to investigate the effect of 1α,25-dihydroxyvitamin D3 [1,25(OH)2VitD3] on osteogenic differentiation of hPDLSCs in an in vitro periodontitis model and whether it can improve inflammatory status. hPDLSCs were in vitro isolated and identified. After treatment with 1,25(OH)2VitD3 and ultrapure pure Porphyromonas gingivalis lipopolysaccharide (LPS-G), the viability of hPDLSCs was detected using Cell Counting Kit-8, the expressions of osteogenic markers and inflammatory genes using Western blotting and quantitative reverse transcription PCR (qRT-PCR), the levels of inflammatory factors in cells using enzyme linked immunosorbent assay (ELISA), and the fluorescence signal intensity of osteoblastic markers and inflammatory genes in cells using immunofluorescence assay. It was found that 1,25(OH)2VitD3 reversed the inhibition of hPDLSCs proliferation by LPS-G; LPS-G exhibited inhibitory effect on ALP, Runx2, and OPN expressions, and such inhibitory effect was significantly weakened when co-acting with 1,25(OH)2VitD3. Meanwhile, LPS-G upregulated the expressions of inflammatory genes IL-1β and Casp1, whereas 1,25(OH)2VitD3 antagonized such an effect and improved the inflammatory status. In conclusion, 1,25(OH)2VitD3 can reverse the inhibitory effect of LPS-G on hPDLSCs proliferation and osteogenic differentiation and suppress LPS-G-induced upregulation of inflammatory gene expressions.


Work and psychiatric illness: the significance of the posthospitalization occupational environment for the course of psychiatric illnesses.
The value of the reintegration and rehabilitation of inpatients vocationally was studied. Certain of the vocational experiences (unemployment and stressful working conditions) of former psychiatric inpatients were examined, with attention being paid to their stabilizing or destabilizing effect on symptomatic behaviour. A cohort of 230 first-time admissions for treatment of various disorders were interviewed while hospitalized and 1 year later. A 20-item list prepared by INFAS was used for indexing stressful working conditions. Psychopathological states were assessed with the help of the Present State Examination of Wing et al. (1973). The results indicate that mentally ill persons (especially those with organic or affective disorders), when confronted with unemployment after discharge from hospital, will usually respond by developing new or worse syndromes. Stressful working conditions appear to have very different effects in schizophrenia and affective disorders, viz. deterioration and amelioration of psychopathological syndromes respectively.


Standoff detection of high explosive materials at 50 meters in ambient light conditions using a small Raman instrument.
We have designed and demonstrated a standoff Raman system for detecting high explosive materials at distances up to 50 meters in ambient light conditions. In the system, light is collected using an 8-in. Schmidt-Cassegrain telescope fiber-coupled to an f/1.8 spectrograph with a gated intensified charge-coupled device (ICCD) detector. A frequency-doubled Nd : YAG (532 nm) pulsed (10 Hz) laser is used as the excitation source for measuring remote spectra of samples containing up to 8% explosive materials. The explosives RDX, TNT, and PETN as well as nitrate- and chlorate-containing materials were used to evaluate the performance of the system with samples placed at distances of 27 and 50 meters. Laser power studies were performed to determine the effects of laser heating and photodegradation on the samples. Raman signal levels were found to increase linearly with increasing laser energy up to approximately 3 x 10(6) W/cm2 for all samples except TNT, which showed some evidence of photo- or thermal degradation at higher laser power densities. Detector gate width studies showed that Raman spectra could be acquired in high levels of ambient light using a 10 microsecond gate width.


Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO.
This study is aimed at investigating the novel use of minocycline for cardiac protection during ischemia/reperfusion (I/R) injury, as well as its mechanism of action. Minocycline is a tetracycline with anti-inflammatory properties, which is used clinically for the treatment of diseases such as urethritis and rheumatoid arthritis. Experimentally, minocycline has also been shown to be neuroprotective in animal models of cerebral ischemia and to delay progression and improve survival in mouse models of neurodegenerative diseases. We studied 62 rat intact hearts exposed to I/R and cell cultures of neonatal and adult rat ventricular myocytes. Minocycline significantly reduced necrotic and apoptotic cell death, both in neonatal and adult myocytes, not only when given prior to hypoxia (p < 0.001), but also at reoxygenation (p < 0.05). Moreover, in the intact heart exposed to I/R, in vivo treatment with minocycline promoted hemodynamic recovery (p < 0.001) and cell survival, with reduction of infarct size (p < 0.001), cardiac release of creatine phosphokinase (p < 0.001), and apoptotic cell death (p < 0.001). In regard to its antiapoptotic mechanism of action, minocycline significantly reduced the expression level of initiator caspases, increased the ratio of XIAP to Smac/DIABLO at both the messenger RNA and protein level, and prevented mitochondrial release of cytochrome c and Smac/DIABLO (all, p < 0.05). These synergistic actions dramatically prevent the post-ischemic induction of caspase activity associated with cardiac I/R injury. Because of its safety record and multiple novel mechanisms of action, minocycline may be a valuable cardioprotective agent to ameliorate cardiac dysfunction and cell loss associated with I/R injury.


Women alcoholics' responses to Scale 4 of the MMPI.
Responses to three items of Scale 4 of the MMPI accounted for the significant difference between the mean scores of women alcoholics and women psychiatric outpatients. Factor analysis of alcoholics' responses yielded six interpretable factors.


Ethical aspects of social freezing.
The term "social freezing" is used to degrade the reason for freezing eggs to the level of a wish instead of a need. The main problem is that the distinction between "social" and "medical" freezing is very difficult to make and many applications do not fit nicely into one of the categories. The rejection of these applications also suffers from a number of inconsistencies. Given the difficulties in separating the two models, it is proposed that all applications, regardless of the reason, should be evaluated with the same criteria: efficiency, safety and justice.


Flies eggs: a new method for the estimation of short-term post-mortem interval?
Three modeling methods were used to estimate the time for laying of Lucilia sericata eggs (Diptera, Calliphoridae) after measurements of hatching times at several constant temperatures. These models were tested first under controlled conditions with 19 profiles of fluctuating temperatures, and on the other hand under field conditions on mice. All three models were allowed to determine the time of laying within a period of about 2h, and consequently this determines the time of death, as this species lays immediately after death under favorable conditions. Rearing of eggs sampled on a corpse may therefore contribute to the determination of a short post-mortem interval (PMI).


Structural details of cellulose nanocrystals/polyelectrolytes multilayers probed by neutron reflectivity and AFM.
Neutron reflectivity measurements and AFM observations were used as complementary techniques to investigate multilayered films consisting of alternating sheets of rigid cellulose nanocrystals and flexible poly(allylamine hydrochloride) (PAH) prepared by the layer-by-layer assembly technique. Both techniques showed that smooth films with a high load of cellulose could be obtained. After deposition, the cellulose component occurred as a double layer with different densities: 50% and 25% for the lower and upper layer, respectively. A linear growth of the multilayer and the presence of a Bragg peak on neutron reflectivity curves indicated the formation of a well-ordered structure resulting from entropy-driven assembly and smoothening effect of the flexible PAH macromolecules. The possible alignment of the nanocrystals when anisotropic suspensions were used is also shown and opens the route to an improved control of the architecture of these multilayers.


Characteristics associated with suboptimal viral suppression at delivery in human immunodeficiency virus-1-infected pregnant women.
This study was undertaken to determine clinical characteristics and factors associated with suboptimal viral suppression at delivery in human immunodeficiency virus (HIV)-infected women. All HIV-infected women who delivered at a single urban tertiary care center from January 1999 to June 2004 were studied. Women were divided into 2 groups based on HIV viral load (VL) proximate to delivery: VL < 1000 copies per milliliter and VL > or = 1000 copies per milliliter. Demographic and clinical factors were analyzed and compared between the 2 groups. A total of 146 women had adequate data available for analysis: 102 (69.9%) had VL < 1000 copies per milliliter and 44 (30.1%) had VL > or = 1000 copies per milliliter at delivery. Women with a viral load > or = 1000 copies per milliliter at delivery were more likely to have a baseline viral load VL > or = 10,000 copies per milliliter (66.7% vs 32%, P < .001) and less likely to report medication adherence, (50% vs 87.8%, P < .001). Our findings support the concept that in addition to antiviral medical therapy, intervention to improve adherence and maintaining a low baseline VL are key components to VL suppression in pregnancy.


Are Patients More Susceptible to Viral Illness Immediately Following Hip and Knee Arthroplasty? An Analysis of Influenza Diagnoses Using Multiple Administrative Databases.
Elective surgery elicits a systemic immune response and may result in transient immunosuppression in certain patients. It is currently unknown whether patients are at increased risk for viral infection and associated illness in the immediate postoperative period following total joint arthroplasty (TJA). Four large administrative datasets (Medicare 5% and 100% standard analytic files, Humana claims, and Mariner Database) were analyzed to identify patients who underwent total knee arthroplasty (TKA) and total hip arthroplasty (THA) from 2005 to 2017. The influenza vaccination status of each patient was defined using the presence or absence of a code for vaccination. The incidence of an influenza diagnosis was recorded in both vaccinated and unvaccinated patients during peak influenza season following the date of surgery and compared to a cohort of vaccinated patients who did not undergo surgery. The incidence of postoperative influenza diagnoses in TKA and THA patients was similar to that of vaccinated patients who did not undergo TJA at all time points. The results were largely consistent across all datasets. Large administrative databases fail to show an increased incidence of influenza in patients who have recently undergone TJA. While the lack of signal in the data is reassuring, these findings are limited by the nature of large administrative datasets and the accuracy of coding for influenza. Further studies will be necessary to fully understand an individual patient's postoperative risk for contracting a viral illness. Level III.


Natriuretic peptide clearance receptor alleles and susceptibility to abdominal adiposity.
To test the association of the C(-55)A polymorphism of the natriuretic peptide clearance receptor (NPRC) with blood pressure (BP), overweight/obesity, and body fat distribution in a large male adult population. The study population was from a cross-sectional and follow-up study of 787 untreated male participants in the 1994 to 1995 follow-up examination of the Olivetti Heart Study in Naples (356 of whom were examined previously in 1975). BP and anthropometric measures were taken, and biochemical assays were performed. The NPRC gene polymorphism C(-55)A was evaluated by polymerase chain reaction and HgaI digestion. In the whole study population, there was no difference in BP, BMI, and biochemical tests among genotypes. Considering an A(-55) recessive model of inheritance, the AA subjects had lower BMI and waist circumference and lower prevalence of overweight, obesity, and abdominal adiposity as compared with the CC+CA subjects. On reviewing the characteristics of the subgroup previously examined in 1975, the AA subjects had already lower BMI, and their 20-year rate of overweight and obesity was lower than the CC+CA subjects; no difference was observed in the rate of hypertension. Male subjects carrying the A(-55)A NPRC genotype had a significantly lower prevalence of overweight, obesity, and abdominal adiposity. They also had a lower 20-year rate of overweight compared with CC+CA individuals. These findings from a large unselected and untreated male population are in keeping with the recent evidence of a powerful lipolytic and lipomobilizing activity of natriuretic peptides.


Childhood obesity and socioeconomic status: a novel role for height growth limitation.
To assess prevalence and socioeconomic context of overweight and obesity in a cohort of Scottish children. Cross-sectional study. Primary schools in Dundee, Angus, and Fife, Eastern Scotland, UK. A total of 1240 boys and 1214 girls aged between 4-10 y. Weight, height and body mass index (weight/height2). Overall overweight or obesity prevalence was 24.6%, while prevalence of obesity alone was 6.1%. Individuals from schools with a high level of low-income families were 65% more likely to be overweight as judged by BMI. However, these children weighed the same as more affluent children of the same age, but were 1.26 cm shorter. These data confirm the continued increase in childhood obesity in the UK and reveal a role for height-growth limitation in the absence of overall growth restriction, among children from low-income groups. This observation raises important questions regarding socioeconomic environmental factors in promoting the currently increasing levels of obesity.


Methamphetamine dependence and human immunodeficiency virus risk behavior.
We examined human immunodeficiency virus (HIV)-related risk behaviors among methamphetamine (MA)-dependent users. Secondary data analysis was performed on data from a large clinical trial: The Methamphetamine Treatment Project (N = 784). All MA-dependent participants were enrolled in an outpatient treatment program, receiving either a standardized psychosocial protocol (Matrix model) or treatment-as-usual. HIV-related risk behavior, including injection and unsafe sexual practices, was assessed using the AIDS Risk Assessment at baseline, treatment discharge, and 6, 12, and 36 months following treatment participation. Results indicated that HIV risk behaviors substantially decreased over time. Treatment factors (retention and completion) and frequency of MA use were both positively associated with increased reduction of HIV risk behaviors. The findings suggested that treatment of MA dependence is promising for reducing behaviors that have been shown to transmit HIV.


Risk factors for and role of OprD protein in increasing minimal inhibitory concentrations of carbapenems in clinical isolates of Pseudomonas aeruginosa.
This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of Pseudomonas aeruginosa. Consecutive clinical isolates of P. aeruginosa were collected. The MicroScan WalkAway system detected more than fourfold increases in the MICs of carbapenems in P. aeruginosa isolates serially recovered from some patients during their clinical course. The clinical risk factors associated with this increase were examined by multiple logistic regression analysis. Western blot analysis and nucleotide sequencing of the oprD gene of 19 clonally related and paired P. aeruginosa isolates from the same patients were undertaken to examine the mechanisms underlying the increase in MICs. The results showed that prior use of carbapenems (OR, 2.799; 95 % CI, 1.088-7.200; P=0.033) and the use of ventilators or tracheostomies (OR, 2.648; 95 % CI, 1.051-6.671; P=0.039) were risk factors for increased carbapenem MICs. Analysis of the underlying mechanisms revealed that loss of functional OprD protein due to mutation of the oprD gene tended to occur in P. aeruginosa isolates with imipenem MICs of more than 8 µg ml-1; a reduction in OprD expression was observed in P. aeruginosa isolates with imipenem MICs of 4 or 8 µg ml-1. This difference in the resistance mechanism was not correlated with the MICs of meropenem. This difference in the resistance mechanism of P. aeruginosa indicates a critical breakpoint at an imipenem MIC of 8 µg ml-1, in accordance with EUCAST criteria. Reducing carbapenem use will prevent P. aeruginosa clinical isolates from developing resistance to carbapenems.


Perceptions of Cardiac Rehabilitation Participants Regarding their Health Behaviors and Information Needs during the COVID-19 Pandemic in Brazil.
COVID-19 has impacted how people receive health care for many conditions, including cardiovascular diseases. To examine perceptions of cardiac rehabilitation (CR) participants regarding their health behaviors and information needs during the COVID-19 pandemic in Brazil. In this cross-sectional study, a 27-item questionnaire, developed by the investigators, was administered online to participants from two CR programs. Questions included health literacy (HL; using the Brief Health Literacy Screening Tool), technology use, perceptions before and during the COVID-19 pandemic, and information needs. Pearson correlation coefficients, paired t-tests, and ANOVA were used as appropriate. P < 0.05 was considered statistically significant for all tests. Overall, 159 (25.5%) CR participants answered the questionnaire. Of these, 89.9% had limited or marginal HL and 96.2% reported having internet access at home. Patients are mainly concerned about their family's health and their own, as well as how the coronavirus is dangerous to their health and how it has changed their lifestyle. Participants perceived that the quality of their health behaviors significantly decreased during the pandemic. The pandemic also changed information needs of CR participants as new needs emerged, such as the control of anxiety levels, staying motivated to live healthily during a pandemic, and how COVID-19 can impact their health condition. Participants with adequate HL significantly perceived the severity of the disease and having access to information significantly more than those with limited HL. Our results highlighted the impact of the pandemic on CR participants' perceptions regarding their health behaviors and information needs, which can be influenced by HL levels.


Distinct forms of hepatic androgen 6 beta-hydroxylase induced in the rat by indole-3-carbinol and pregnenolone carbonitrile.
The ability of indole-3-carbinol (IC), an anticarcinogen present in cruciferous vegetables, to induce CYP1A1, CYP1A2, CYP2B1/2, CYP2E1 and CYP3A1/2 in female rat liver was determined by Western analysis using monoclonal antibodies and compared to effects produced by pregnenolone carbonitrile in animals of both sexes. The ontogeny of induction of these cytochrome P450 isozymes in response to oral administration of IC was also investigated. An inverse correlation was observed between the 6 beta-hydroxylation of androsterone (A) and the induction by IC of CYP3A1/2, the P450 isozyme responsible for the bulk of hepatic 6 beta-hydroxylation of 4-androstenedione (AD). The effect of inhibitors on the formation of 6 beta-OHA from A or AD was also determined and shown to differ from their action on the P450 isozymes involved in the formation of the 6 beta-hydroxylated derivatives of AD or lithocholic acid. The results indicate that the enzyme induced by IC is distinct from the CYP3A1/2 which catalyzes hydroxylations at position 6 beta, allylic in AD but not in the fully saturated ring system of A. The increased hepatic conversion of A to its biologically less active 6 beta-OHA metabolite after treatment of female rats with IC could possibly contribute to the anticarcinogenic action of indole carbinols. It is also proposed that the action of multiple inducers present in cruciferous and other vegetables might produce androgen metabolic profiles very different from those produced by individual components isolated from them.


Differences in association between birth parameters and blood pressure in children from preschool to high school.
We aimed to investigate the association between birth parameters with blood pressure (BP) among preschool- and school-aged children. Two separate childhood datasets were used: (1) 1295 children aged 3-6 years were examined during 2007-2009; and (2) 1741 and 2353 children aged 6 and 12 years, respectively, were examined during 2004-2006. Birth parameter data were obtained from parental records. BP was measured using standard protocols. Among 6-year-old children, each 1 kg decrease in birth weight was associated with a 1.33- and 1.20-mm Hg higher systolic and diastolic BP, respectively, after multivariable adjustment. In 6-year-old children, a decrease of 1 week in gestational age was independently associated with a 0.33- and 0.37-mm Hg higher systolic and diastolic BP, respectively. Six-year-old children in the low birth weight category (≤ 2499 g) versus those in the normal/high birth weight category (≥ 2500 g) had significantly higher systolic BP (P<0.0001). Girls in the low birth weight category versus those in the normal/high weight category had higher systolic BP (P=0.02). Significant associations were not observed among preschool-aged children and preadolescents. Birth weight and gestational age were strongly associated with BP among 6-year-old children, particularly girls, but not among preschoolers or preadolescents.


Movement disorders in cell surface antibody mediated autoimmune encephalitis: a meta-analysis.
Autoimmune encephalitis (AE) is an increasingly recognized neuroinflammatory disease entity in which early detection and treatment leads to the best clinical outcomes. Movement disorders occur in AE but their characteristics are not well defined. To identify the frequency, classification, and prognostic significance of movement disorders in AE. We conducted a systematic review and random-effects meta-analysis of movement disorders in cell surface antibody mediated AE. The frequency of any movement disorder as well as the classification of movement disorders in AE serotypes was determined. We looked at adults 18 years and older and included publications that described at least 10 cases. We used the following four electronic databases: Medline (Ovid), EMBASE (Ovid), APA Psychinfo, and Cochrane library. A total of 1,192 titles and abstracts were reviewed. Thirty-seven studies were included in the final meta-analysis. At least one kind of movement disorder was present in 40% of the entire AE cohort, 53% with anti-NMDA receptor antibodies, 33% with anti-CASPR2 antibodies, 30% with anti-LGI1 antibodies and 13% with anti-GABA receptor antibodies. Dyskinesia was the commonest movement disorder in anti-NMDA antibody mediated AE and faciobrachial dystonic seizures were most frequent in anti-LGI1 antibody mediated AE. Patients with a movement disorder tended to have a higher mortality. The risk of bias in the included studies was mostly moderate or high. Movement disorders are common in AE and their identification, in conjunction with other clinical and paraclinical features, may facilitate earlier diagnosis. The prognostic implications of movement disorders in AE warrant further dedicated study. https://www.crd.york.ac.uk/prospero/, identifier: CRD42023386920.