[Electroencephalographic assessment of dosage and sleep-profile in a hypnotic Triazolothienodiazepine (author's transl)].
We 941, a Triazolodiazepine, has satisfying hypnotic properties. The optimum dosage lies nearly at 0.3 mg. In this dosage the sleep-begin is shortened, the number of nightly wakeness is decreased and the total sleep-time is extended, while the sleep-profile remains unchanged. A normal cycling can be taken as a sign of qualitative good sleep. The REM-percentage is diminished insignificantly and increases again under the continuated therapy. The percentage of deep sleep increases by 0.3 mg. The subjective presentations confirm the melioration of sleep. In higher dosages troubles occur as decrease of deep-sleep stage and deteriorations of feeling. Remarkable is the withdrawal effect after 1.0 mg with an initial and a dissociated REM. However, such strong disturbances couldn't be observed in the carried on therapy with 0.3 mg.


Implications of median sensory study to the thumb and deltoid/biceps motor unit recruitment on identifying C6 root avulsion in upper neonatal brachial plexus palsy.
Anatomic representation suggests that a median sensory nerve conduction study recording the thumb (median D1 NCS) may effectively assess upper neonatal brachial plexus palsy (NBPP). We sought to determine the feasibility of technique, establish reference data, and assess its ability to: (a) identify focal upper plexus lesions; and (b) identify C6 root avulsion. In a secondary analysis, we explored the association between absence/presence of motor unit action potentials (MUAPs) during needle electromyography (EMG) of the deltoid and biceps brachii muscles and C6 avulsion status. A retrospective chart review was performed of surgical patients with severe upper NBPP who ultimately underwent surgical reconstruction (between 2017 and 2020). Median D1 sensory nerve action potential (SNAP) amplitude ranges were determined in affected and contralateral limbs and analyzed by C6 root avulsion status. Also, presence/absence of MUAPs during EMG of the deltoid and biceps brachii was compared between C6 avulsion patients and controls. Thirty-eight patients were included in our analysis. A median D1 NCS study was readily performed, showing a contralateral limb mean amplitude of 27.42 μV (range, 3.8-54.7 μV). Most patients had a low ipsilateral median D1 SNAP amplitude, regardless of C6 avulsion status. Detectable MUAPs in either deltoid or biceps brachii on EMG were atypical in C6 root avulsion. The median D1 NCS identifies upper NBPP, but does not distinguish C6 avulsions from post-ganglionic lesions, likely due to the frequent co-occurrence of post-ganglionic axonal disruption. The presence of MUAPs on deltoid/biceps brachii EMG suggests C6 avulsion is unlikely.


Stem cell plasticity, beyond alchemy.
Cell plasticity is a central issue in stem cell biology. Differentiated somatic nuclei have the flexibility to dedifferentiate when transferred into oocytes or when fused to pluripotent embryonic stem cells. Recent publications also claim that somatic stem cells can convert into developmentally unrelated cell types both in vivo and ex vivo without such drastic cell manipulations. Some of these claims are still controversial, making it difficult for us to determine the reality of somatic stem cell plasticity. Indeed, we have heard enough about the "potentials" of cell plasticity; how much do we know about mechanisms? A fundamental issue in current stem cell biology is to understand the mechanisms underlying cell plasticity. In this short review, we overview three research fields related to cell plasticity: nuclear transfer, transdifferentiation, and cell fusion, with an emphasis on studies of molecular mechanisms underlying cell plasticity.


Trochanteric fractures: Tip-Apex distance, Calcar Tip-Apex distance, and Chang criteria-a multiple variable analysis.
Failure of osteosynthesis is a common complication of the nailing of trochanteric fractures which typically occurs through form of cut-out. Tip-Apex distance (TAD), Calcar Tip-Apex distance (CalTAD), and Chang criteria are validated variables to predict failure of cephalomedullary nailing. This is a retrospective study which analyzes treatment of trochanteric fractures from 2018 to 2020 (n = 296) evaluating postoperative radiographs and factors of mechanical failure. Our objective was to assess correlation among these variables and their influence on mechanical failure, either individually or creating a new score. Our results support the CalTAD and Chang's criteria as valid predictors of mechanical failure. Furthermore, they empathize the importance of fracture reduction and proper placement of cervical screw. To our knowledge, this is the first study performing multivariate analysis including these 3 variables.


Impact of 13-Valent Pneumococcal Conjugate Vaccine on Invasive Pneumococcal Disease Among Adults With HIV-United States, 2008-2018.
People with HIV (PWH) are at increased risk for invasive pneumococcal disease (IPD). Thirteen-valent pneumococcal conjugate vaccine (PCV13) was recommended for use in US children in 2010 and for PWH aged 19 years or older in 2012. We evaluated the population-level impact of PCV13 on IPD among PWH and non-PWH aged 19 years or older. We identified IPD cases from 2008 to 2018 through the Active Bacterial Core surveillance platform. We estimated IPD incidence using the National HIV Surveillance System and US Census Bureau data. We measured percent changes in IPD incidence from 2008 to 2009 to 2017-2018 by HIV status, age group, and vaccine serotype group, including serotypes in recently licensed 15-valent (PCV15) and 20-valent (PCV20) PCVs. In 2008-2009 and 2017-2018, 8.4% (552/6548) and 8.0% (416/5169) of adult IPD cases were among PWH, respectively. Compared with non-PWH, a larger proportion of IPD cases among PWH were in adults aged 19-64 years (94.7%-97.4% vs. 56.0%-60.1%) and non-Hispanic Black people (62.5%-73.0% vs. 16.7%-19.2%). Overall and PCV13-type IPD incidence in PWH declined by 40.3% (95% confidence interval: -47.7 to -32.3) and 72.5% (95% confidence interval: -78.8 to -65.6), respectively. In 2017-2018, IPD incidence was 16.8 (overall) and 12.6 (PCV13 type) times higher in PWH compared with non-PWH; PCV13, PCV15/non-PCV13, and PCV20/non-PCV15 serotypes comprised 21.5%, 11.2%, and 16.5% of IPD in PWH, respectively. Despite reductions post-PCV13 introduction, IPD incidence among PWH remained substantially higher than among non-PWH. Higher-valent PCVs provide opportunities to reduce remaining IPD burden in PWH.


Association between accelerometer-measured amplitude of rest-activity rhythm and future health risk: a prospective cohort study of the UK Biobank.
The health effects of rest-activity rhythm are of major interest to public health, but its associations with health outcomes remain elusive. We aimed to examine the associations between accelerometer-measured rest-activity rhythm amplitude and health risks among the general UK population. We did a prospective cohort analysis of UK Biobank participants aged 43-79 years with valid wrist-worn accelerometer data. Low rest-activity rhythm amplitude was defined as the first quintile of relative amplitude; all other quintiles were classified as high rest-activity rhythm amplitude. Outcomes of interest were defined using International Classification of Diseases 10th Revision codes and consisted of incident cancer and cardiovascular, infectious, respiratory, and digestive diseases, and all-cause and disease-specific (cardiovascular, cancer, and respiratory) mortality. Participants with a current diagnosis of any outcome of interest were excluded. We assessed the associations between decreased rest-activity rhythm amplitude and outcomes using Cox proportional hazards models. Between June 1, 2013, and Dec 23, 2015, 103 682 participants with available raw accelerometer data were enrolled. 92 614 participants (52 219 [56·4%] women and 40 395 [42·6%] men) with a median age of 64 years (IQR 56-69) were recruited. Median follow-up was 6·4 years (IQR 5·8-6·9). Decreased rest-activity rhythm amplitude was significantly associated with increased incidence of cardiovascular diseases (adjusted hazard ratio 1·11 [95% CI 1·05-1·16]), cancer (1·08 [1·01-1·16]), infectious diseases (1·31 [1·22-1·41]), respiratory diseases (1·26 [1·19-1·34]), and digestive diseases (1·08 [1·03-1·14]), as well as all-cause mortality (1·54 [1·40-1·70]) and disease-specific mortality (1·73 [1·34-2·22] for cardiovascular diseases, 1·32 [1·13-1·55] for cancer, and 1·62 [1·25-2·09] for respiratory diseases). Most of these associations were not modified by age older than 65 years or sex. Among 16 accelerometer-measured rest-activity parameters, low rest-activity rhythm amplitude had the strongest or second- strongest associations with nine health outcomes. Our results suggest that low rest-activity rhythm amplitude might contribute to major health outcomes and provide further evidence to promote risk-modifying strategies associated with rest-activity rhythm to improve health and longevity. National Natural Science Foundation of China and China Postdoctoral Science Foundation.


High prevalence of VanA-type vancomycin-resistant Enterococci in Austrian poultry.
Fecal samples from humans and food-producing animals were analyzed for the presence of vancomycin-resistant enterococci (VRE). The VRE carriage rate in humans was 6%, and there was a predominance of VanC-type resistance. Enterococcus faecium with vanA-mediated resistance was frequent in broiler chickens (42%) but rare in cattle and pig samples.


A 10-year follow-up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node dissection or axillary clearance.
We compare long-term outcomes in patients with node negative early stage breast cancer treated with breast radiotherapy (RT) without the axillary RT field after sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND). We hypothesize that though tangential RT was delivered to the breast tissue, it at least partially sterilized occult axillary nodal metastases thus providing low nodal failure rates. Between 1995 and 2001, 265 patients with AJCC stages I-II breast cancer were treated with lumpectomy and either SLND (cohort SLND) or SLND and ALND (cohort ALND). Median follow-up was 9.9 years (range 8.3-15.3 years). RT was administered to the whole breast to the median dose of 48.2 Gy (range 46.0-50.4 Gy) plus boost without axillary RT. Chi-square tests were employed in comparing outcomes of two groups for axillary and supraclavicular failure rates, ipsilateral in-breast tumor recurrence (IBTR), distant metastases (DM), and chronic complications. Progression-free survival (PFS) was compared using log-rank test. There were 136/265 (51%) and 129/265 (49%) patients in the SLND and ALND cohorts, respectively. The median number of axillary lymph nodes assessed was 2 (range 1-5) in cohort SLND and 18 (range 7-36) in cohort ALND (P < 0.0001). Incidence of AFR and SFR in both cohorts was 0%. The rates of IBTR and DM in both cohorts were not significantly different. Median PFS in the SLND cohort is 14.6 years and 10-year PFS is 88.2%. Median PFS in the ALND group is 15.0 years and 10-year PFS is 85.7%. At a 10-year follow-up chronic lymphedema occurred in 5/108 (4.6%) and 40/115 (34.8%) in cohorts SLND and ALND, respectively (P = 0.0001). This study provides mature evidence that patients with negative nodes, treated with tangential breast RT and SLND alone, experience low AFR or SFR. Our findings, while awaiting mature long-term data from NSABP B-32, support that in patients with negative axillary nodal status such treatment provides excellent long-term cure rates while avoiding morbidities associated with ALND or addition of axillary RT field.


Real-world Outcomes With Cumulative Bortezomib Dose and Efficacy in the Treatment of Transplant-ineligible Multiple Myeloma With Cyclophosphamide, Bortezomib, and Dexamethasone.
Higher cumulative dose of bortezomib, a key component of Multiple Myeloma (MM) treatment regimens, has been shown to improve outcomes in MM patients, but must be balanced with toxicities including peripheral neuropathy. In this study, we studied the effect of cumulative bortezomib dose on survival, depth of response, and discontinuation rate in transplant ineligible MM patients. Data from 70 patients treated with Cyclophsophamide, Bortezomib, and Dexamethasone (CyBorD) in a single Canadian center were grouped according to above vs below median cumulative bortezomib dose and analyzed for progression-free survival (PFS), overall survival (OS), depth of response, and discontinuation rate. There was a trend for lower discontinuation rate (45.7% vs. 68.6%, P = .052) and significantly lower rate of neuropathy-related discontinuation (5.7% vs. 22.9%, P = .035) in patients who received higher than 43.1 mg/m² of bortezomib. The higher-dose group showed a trend for higher rate of complete response (14.3% vs. 5.7%, P = .225) and significantly higher rate of very good partial response or better (77.1% vs. 51.4%, P = .024). There was significantly longer PFS (24.3 vs. 9.1 months, P = .012) and a trend for longer OS (22.4 vs. 61.3 months, P = .061) in the higher-dose group. In landmark analysis after 180 days, PFS (23.5 vs. 24.3 months, P = .941) and OS were similar in both groups. Higher cumulative bortezomib dose showed a lower rate of discontinuation, longer survival, and deeper response. Determining risk of treatment intolerance remains important for treatment.


Development and Validation of RP-HPLC and an Ecofriendly HPTLC Method for Simultaneous Determination of Felodipine and Metoprolol Succinate, and their Major Metabolites in Human Spiked Plasma.
Felodipine is a calcium channel blocker used together with metoprolol succinate for treatment of hypertension. Two chromatographic methods were developed for simultaneous determination of felodipine (FEL) and metoprolol succinate (MET), and their major metabolites, dehydrofelodipine and metoprolol acid, respectively. The first method was RP-HPLC which comprised separation of the studied components by gradient elution using a Phenomenex C8 column and a mobile phase composed of water (adjusted to pH 3.5 with o-phosphoric acid)-acetonitrile - methanol (45:40:15, by volume) for the first 6 min and (30:60:10, by volume) for the next 4 min at a flow rate of 1 mL/min followed by UV detection of the eluted peaks at 225 nm. The second method was an HPTLC method where separation was achieved using a mobile phase consisting of toluene-ethyl acetate-methanol-ammonia-formic acid (10:5:2.5:0.3:0.1, by volume) and scanning of the separated bands at 225 nm. Validation of the developed methods was done according to ICH guidelines. Successful application of the developed methods was carried out for determination of the studied drugs in human spiked plasma and in Logimax® tablets. The developed RP-HPLC and HPTLC methods can be further applied for quality control testing of the studied drugs. RP-HPLC and HPTLC methods for determination of FEL, MET and their major metabolites. The developed methods were successfully applied for determination of FEL and MET in Logimax® tablets.


Cell wall dynamics: novel tools and research questions.
Years ago, a classic textbook would define plant cell walls based on passive features. For instance, a sort of plant exoskeleton of invariable polysaccharide composition, and probably painted in green. However, currently, this view has been expanded to consider plant cell walls as active, heterogeneous, and dynamic structures with a high degree of complexity. However, what do we mean when we refer to a cell wall as a dynamic structure? How can we investigate the different implications of this dynamism? While the first question has been the subject of several recent publications, defining the ideal strategies and tools needed to address the second question has proven to be challenging due to the myriad of techniques available. In this review, we will describe the capacities of several methodologies to study cell wall composition, structure, and other aspects developed or optimized in recent years. Keeping in mind cell wall dynamism and plasticity, the advantages of performing long-term non-invasive live-imaging methods will be emphasized. We specifically focus on techniques developed for Arabidopsis thaliana primary cell walls, but the techniques could be applied to both secondary cell walls and other plant species. We believe this toolset will help researchers in expanding knowledge of these dynamic/evolving structures.


In vitro production of desired sex ovine embryos modulating polarity of oocytes for sex-specific sperm binding during fertilization.
The present study aimed to modulate the oxidative status-mediated polarity of the oocytes for sex-specific sperm fertilization to generate desired sex embryos. In vitro embryos were produced at different oxidative status, varying O2 concentrations, and without/with L-carnitine in maturation and culture media. The majority of the embryos produced at high oxidative stress were males whereas; low oxidative status favoured female embryos production. Low O2 doubled the proportion of female embryos (10.59 vs 21.95%); however, L-carnitine supplementation in media increased approximately seven-folds of the female embryos (12.26 vs. 77.62%) production. Oocytes matured at high oxidative status were in the repolarized state favouring positively charged Y sperm fertilization to produce significantly more male embryos. Low oxidative status favoured negatively charged X sperm fertilization to the oocytes in the depolarized state to produce more female embryos. Intracellular ROS was significantly low in female embryos than in males; however, female embryos were more stressful than males. The study concluded that the oxidative status-mediated alteration in pH of the medium to modulate the intracellular positive ions is the main critical factor to influence the sex of embryos through sex-specific sperms fertilization to the oocytes as per their polarity.


Teriparatide [PTH(1-34)] strengthens the proximal femur of ovariectomized nonhuman primates despite increasing porosity.
OVX monkeys treated for 18 months with 1 or 5 microg/kg/d teriparatide [PTH (1-34)] had significantly stronger proximal femora relative to ovariectomized controls. Teriparatide enhancement of cortical area, cortical width, and trabecular bone volume seemed to more than compensate for the dose-dependent increase in cortical porosity. Beneficial effects of teriparatide treatment on the proximal femur persisted beyond the treatment period and may extend to the marrow. We conducted a detailed quantitative analysis of the effects of teriparatide on the proximal femur of ovariectomized monkeys. Teriparatide increased bone mass, enhanced structural architecture, and strengthened the hip, despite increasing cortical porosity. Monkeys were treated with vehicle (sham or OVX controls), 1 microg/kg/day teriparatide [parathyroid hormone (1-34); PTH1], or 5 microg/kg/day teriparatide (PTH5) for 18 months or for 12 months followed by 6 months of treatment withdrawal (PTH1W and PTH5W, respectively). Excised proximal femora were analyzed by microCT, conventional histomorphometry, and biomechanics. The femoral neck showed significant reduction in trabecular bone volume (BV/TV) for OVX compared with sham, whereas PTH1 BV/TV was restored to sham levels and PTH5 BV/TV was greater than sham and OVX. The withdrawal groups had BV/TVs intermediate between sham and OVX. PTH1 had trabecular number (Tb.N) greater than OVX, and PTH5 Tb.N was greater than sham and OVX. The withdrawal groups had Tb.Ns intermediate between sham and OVX. No differences between groups were observed for trabecular orientation or trabecular thickness. Teriparatide dose-dependently increased bone formation rate and activation frequency in the femoral neck. Cellular composition analyses suggested a tendency of ovariectomy to increase adiposity of marrow by 100%, whereas PTH tended to reduce adipocyte number and increase osteoblast number compared with OVX. Analyses of the cortex showed dose-dependent elevation of cortical porosity, which was consistent with enhanced bone turnover with treatment. Cortical porosity was reduced after withdrawal of teriparatide, because PTH1W cortical porosity was lower than OVX, whereas PTH5W cortical porosity was intermediate between sham and OVX. Increased cortical porosity did not weaken the proximal femora. Biomechanics showed that ovariectomy weakened proximal femora compared with sham, but PTH1, PTH5, and PTH1W were stronger than OVX and not different from sham. PTH5W strength was intermediate between sham and OVX. Therefore, teriparatide had beneficial effects on the proximal femur, despite increasing cortical porosity. Cortical porosity did not adversely affect the mechanical integrity of the proximal femora, because enhanced cortical area and trabecular bone volume more than compensated for the porosity. Much of the beneficial effects of teriparatide were retained after 6 months withdrawal from treatment. PTH effects on the femoral neck were not limited to bone but may include inhibition of OVX-stimulated adiposity of the marrow.


Effects of root canal sealers on lipopolysaccharide-induced expression of cyclooxygenase-2 mrna in murine macrophage cells.
Cyclooxygenase-2 (COX-2) is a useful biomarker of the inflammatory potential of biomaterials in vitro. In this study we investigate the effects of soluble extracts from 3 selected root canal sealers (AH26, Sealapex, and N2 Universal) on COX-2 mRNA expression in cultured murine macrophage cells. Root canal sealers and the addition of lipopolysaccharide (LPS) both produced significant increases in COX-2 mRNA expression in RAW 264.7 macrophages. In addition, both Sealapex and N2 Universal produced a synergistic 6- to 8-fold increase in COX-2 mRNA expression, whereas AH26 did not demonstrate synergy with LPS. These results suggest that LPS and certain root canal sealers have a synergistic effect on the inflammatory responses of macrophages. Under the conditions of this in vitro study, the results suggest that one potential mechanism of periapical inflammatory reactions might be the synergistic effects of certain root canal sealers on LPS-induced COX-2 expression by macrophage cells.


Granzymes, IL-16, and poly(ADP-ribose) polymerase 1 increase during wildfire smoke exposure.
Given the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health-particularly in specific immunologic pathways-is crucial. Exposure to air pollutants is associated with cardiorespiratory disease; however, immune and epithelial barrier alterations require further investigation. We sought to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers by using proteomics and immune cell phenotyping. A San Francisco Bay area cohort (n = 15; age 30 ± 10 years) provided blood samples before (October 2019 to March 2020; air quality index = 37) and during (August 2020; air quality index = 80) a major wildfire. Exposure samples were collected 11 days (range, 10-12 days) after continuous exposure to wildfire smoke. We determined alterations in 506 proteins, including zonulin family peptide (ZFP); immune cell phenotypes by cytometry by time of flight (CyTOF); and their interrelationship using a correlation matrix. Targeted proteomic analyses (n = 15) revealed a decrease of spondin-2 and an increase of granzymes A, B, and H, killer cell immunoglobulin-like receptor 3DL1, IL-16, nibrin, poly(ADP-ribose) polymerase 1, C1q TNF-related protein, fibroblast growth factor 19, and von Willebrand factor after 11 days' average continuous exposure to smoke from a large wildfire (P < .05). We also observed a large correlation cluster between immune regulation pathways (IL-16, granzymes A, B, and H, and killer cell immunoglobulin-like receptor 3DL1), DNA repair [poly(ADP-ribose) 1, nibrin], and natural killer cells. We did not observe changes in ZFP levels suggesting a change in epithelial barriers. However, ZFP was associated with immune cell phenotypes (naive CD4+, TH2 cells). We observed functional changes in critical immune cells and their proteins during wildfire smoke exposure. Future studies in larger cohorts or in firefighters exposed to wildfire smoke should further assess immune changes and intervention targets.


The isolation of fibrinogen monomer dramatically influences fibrin polymerization.
Fibrin polymerization begins with the thrombin-catalyzed cleavage of fibrinopeptides from fibrinogen and proceeds through several assembly steps to form an insoluble fibrin clot. Using dynamic light scattering (DLS), we found that purified fibrinogens are polydisperse, containing small amounts of fibrinogen complexes. In order to characterize the impact of these complexes, we used gel filtration chromatography to isolate monomers from three fibrinogens: plasma, recombinant, and recombinant variant Aα251. SDS-PAGE analysis showed that the polypeptides in the monomers were indistinguishable from those in the initial fibrinogen. DLS showed the fibrinogen monomers were monodisperse. We used turbidity to follow polymerization and found the polymerization of fibrinogen monomers was markedly different from the polymerization of the initial fibrinogen; the final optical density (OD) was significantly higher for monomers. Moreover, the polymerization curve for fibrinogen monomers was independent of the polymerization curves of the fibrinogen samples without gel filtration. For example, monomers isolated from two recombinant fibrinogen preparations polymerized similarly even though the final OD increased 2-fold for one preparation and 3-fold for the other. Scanning electron microscopy of the fibrin clots verified the turbidity data; monomer clots had thicker fibers. We conclude that fibrinogen complexes alter the kinetics of polymerization and impair the assembly of monomers into protofibrils and fibers.


An enzymatic determination of D-glucaric acid by conversion to pyruvate.
A method was developed for determination of D-glucaric acid by treatment with a bacterial extract containing glucarate dehydratase and ketodeoxyglucarate aldolase. This led to the quantitative formation of pyruvate, which was then assayed by use of lactate dehydrogenase. Measurements of D-glucarate in individual samples of human urine by this technique were compared with those by the commonly used method of beta-glucuronidase inhibition, and gave values for D-glucarate content which were about 25% higher, but with otherwise good correlation.


A prospective hospital-based study on C-reactive protein as a response predictor of antidepressant treatment in drug naïve patients with major depressive disorder.
C-reactive protein (CRP) is an acute phase reactant that is implicated in the pathogenesis of major depressive disorder (MDD), due to its role in the execution of various important neurological events, including neurogenesis, mediation of neural plasticity, and synaptic transmission. This study was conducted to determine the relationship between the level of CRP to remission rates after antidepressant therapy. Fifty patients of first episode MDD with no past history of antidepressant exposure and other medical comorbidity were recruited after obtaining consent for Escitalopram therapy. The CRP levels of the patients were evaluated on the day of recruitment and depressive symptoms were monitored using Montgomery-Asberg Depression Rating Scale at weeks 0, 3, 6, and 12. The patients with low (≤10 mg/l) and high (>10 mg/l) CRP levels were compared for time taken to achieve remission using Kaplan-Meier survival analysis. The Kaplan-Meier survival analysis showed a significantly higher proportion of patients with low CRP levels attained remission than patients with higher CRP levels (Log-rank = 7.594; dF = 1; P = 0.006). The age, compliance to pharmacotherapy, and disability did not significantly affect the remission rates of the patients. Our study confirms that higher levels of CRP can lead to poorer remission rates in patients with MDD after antidepressant therapy and can predict treatment resistance.


Partial complex seizures in children: an analysis of 69 seizures in 24 patients using EEG FM radiotelemetry and videotape recording.
The electroencephalographic and clinical manifestations of 69 partial complex seizures in 24 pediatric patients recorded during EEG-FM radiotelemetry and videotape monitoring were reviewed. The seizure could be divided into 3 electro-clinical types. Type I attacks were characterized by an initial motionless stare often followed by automatisms and associated with initial lateralized EEG changes. Type II attacks began with automatic behavior and had bilateral, diffuse changes on the EEG initially. Type II attacks began with a loss of body tone followed by automatisms and with bilateral EEG changes initially. This study demonstrates that both the clinical and electroencephalographic aspects of partial complex seizures in children are similar to those reported in adults. This similarity may be secondary to the early maturation of the limbic structures.


Marginal utility of montelukast for persistent asthma.
The efficacy of a new pharmacologic agent for asthma, in this instance the leukotriene receptor antagonist montelukast, is determined in controlled trials in research subjects. The utility of a new drug is determined by multiple uncontrollable factors in individual patients. To assess the utility of montelukast in the management of persistent asthma. Observational, retrospective. Suburban multispecialty medical clinic. From April 1998, montelukast was prescribed for 110 patients with persistent but controlled asthma, primarily for the corticosteroid-sparing effect. Outcomes after 1 year were determined from audits of medical records and responses to questionnaires. At least 56% of patients continued receiving montelukast for the entire year. However, compared to those patients who had discontinued montelukast therapy, those who continued receiving it had no difference in the use of inhaled or systemic corticosteroid or inhaled beta(2)-agonist therapy. Montelukast had marginal utility in the management of these adult patients with controlled persistent asthma.


sST2 as a value-added biomarker in heart failure.
Soluble suppression of tumorigenicity-2 (sST2) is a biomarker widely investigated during the last few years. Its role has become clear in pathological conditions such as fibrosis and inflammation. From translational research to laboratory medicine, considerable efforts have been made to elucidate the features of sST2 biomarker and to consider its contribution to HF management. In this review, we summarized the results from recent works concerning sST2, and particularly we focused on the interest of sST2 in conditions for which classical biomarkers value interpretation is misleading. Indeed, despite other HF biomarkers, sST2 was proved to be independent from common comorbidities such as renal dysfunction and hypertension. Thus, sST2 showed promise for a combined strategy with natriuretic peptides, mainly for specific categories of patients. Particular attention was paid to findings on sST2 in HF with preserved ejection fraction (HFpEF), a form of HF for which reliable and specific biomarkers are awaited. Finally, a place is reserved to sST2 kinetics from basal to follow up values in order to improve clinical decision making and to customize patient treatments.


Deux modèles de population dans un environnement périodique lent ou rapide.
Two problems in population dynamics are addressed in a slow or rapid periodic environment. We first obtain a Taylor expansion for the probability of non-extinction of a supercriticial linear birth-and-death process with periodic coefficients when the period is large or small. If the birth rate is lower than the mortality for part of the period and the period tends to infinity, then the probability of non-extinction tends to a discontinuous limit related to a "canard" in a slow-fast system. Secondly, a nonlinear S-I-R epidemic model is studied when the contact rate fluctuates rapidly. The final size of the epidemic is close to that obtained by replacing the contact rate with its average. An approximation of the correction can be calculated analytically when the basic reproduction number of the epidemic is close to 1. The correction term, which can be either positive or negative, is proportional to both the period of oscillations and the initial fraction of infected people.


Colonization and infection in surgical intensive care patients--a prospective study.
Nosocomial infections are a major problem in intensive care patients. Thirty-nine patients, requiring intensive care for 5 days or more (mean 15.8 days) were prospectively investigated, to determine the relation between colonisation and nosocomial infection. Thrice weekly, cultures from the oropharynx, respiratory and digestive tract were obtained. Colonization with aerobic gram-negative microorganisms of the oropharynx, respiratory and digestive tract significantly increased during the stay in the Intensive Care Unit. In 29 patients (74%) 78 nosocomial infections were diagnosed. The most frequent nosocomial infections were pneumonia (26 patients, 66.6%), catheter-related bacteraemia (11 patients, 28.2%), and wound infections (7 patients, 17.9%). In 59 instances (75.6%), colonization with the same potential pathogenic microorganism preceded the nosocomial infection. The overall mortality was 25.6% (10 patients), bacteraemia with aerobic gram-negative microorganisms being the cause of death in 7 patients.


Agricultural Use of Insecticides Alters Homeostatic Behaviors and Cognitive Ability in Lymnaea stagnalis.
Lymnaea stagnalis is an ecologically important, stress-sensitive, freshwater mollusk that is at risk for exposure to insecticides via agricultural practices. We provide insight into the impact insecticides have on L. stagnalis by comparing specific behaviors including feeding, locomotion, shell regeneration, and cognition between snails collected at two different sites: one contaminated by insecticides and one not. We hypothesized that each of the behaviors would be altered in the insecticide-exposed snails and that similar alterations would be induced when control snails were exposed to the contaminated environment. We found no significant differences in locomotion, feeding, and shell regeneration of insecticide-exposed L. stagnalis compared with nonexposed individuals. Significant changes in feeding and shell repair were observed in nonexposed snails inhabiting insecticide-contaminated pond water. Most importantly, snails maintained and trained in insecticide-contaminated pond water did not form configural learning, but this cognitive deficit was reversed when these snails were maintained in insecticide-free pond water. Our findings conclude that insecticides have a primarily negative impact on this higher form of cognition in L. stagnalis. Environ Toxicol Chem 2023;42:2466-2477. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Rapid kinetic techniques.
The elementary steps in complex biochemical reaction schemes (isomerization, dissociation, and association reactions) ultimately determine how fast any system can react in responding to incoming signals and in adapting to new conditions. Many of these steps have associated rate constants that result in subsecond responses to incoming signals or externally applied changes. This chapter is concerned with the techniques that have been developed to study such rapidly reacting systems in vitro and to determine the values of the rate constants for the individual steps. We focus principally on two classes of techniques: (1) flow techniques, in which two solutions are mixed within a few milliseconds and the ensuing reaction monitored over milliseconds to seconds, and (2) relaxation techniques, in which a small perturbation to an existing equilibrium is applied within a few microseconds and the response of the system is followed over microseconds to hundreds of milliseconds. These reactions are most conveniently monitored by recording the change in some optical signal, such as absorbance or fluorescence. We discuss the instrumentation that is (commercially) available to study fast reactions and describe a number of optical probes (chromophores) that can be used to monitor the changes. We discuss the experimental design appropriate for the different experimental techniques and reaction mechanisms, as well as the fundamental theoretical concepts behind the analysis of the data obtained.


Nutrition in the intensive care unit and early recovery influence functional outcomes for survivors of critical illness: A prospective cohort study.
Patients who are critically ill may receive suboptimal nutrition that leads to weight loss and increased risk of functional deficits. Our overarching hypothesis is that nutrition in the intensive care unit (ICU) and the early recovery phase associates with functional outcomes at short-term follow-up. We enrolled adult patients who attended the University of Kentucky ICU recovery clinic (ICU-RC) from November 2021 to June 2022. Patients participated in muscle and functional assessments. Nutrition intake and status during the ICU stay were analyzed. The Subjective Global Assessment and a nutrition questionnaire were used to identify changes in intake, ongoing gastrointestinal symptoms, and patient's access to food at the ICU-RC appointment. Forty-one patients enrolled with a median hospital length of stay (LOS) of 23 days. Patients with 0 days of nil per os (NPO) status throughout hospitalization had a shorter LOS (P = 0.05), were able to complete the five times sit-to-stand test (P = 0.02), and were less likely to experience ICU-acquired weakness (P = 0.04) at short-term follow-up compared with patients with ≥1 day of NPO status. Twenty (48%) patients reported changes in nutrition intake in early recovery compared with before hospitalization. Eight (20%) patients reported symptoms leading to decreased intake and four (10%) reported access to food as a barrier to intake. Barriers to nutrition exist during critical illness and persist after discharge, with almost half of patients reporting a change in intake. Inpatient nutrition intake is associated with functional outcomes and warrants further exploration.


Mechanisms of scale formation and carbon dioxide partial pressure influence. Part I. Elaboration of an experimental method and a scaling model.
Scale formation in industrial or domestic installations is still an important economic problem. The existence of a metastable domain for calcium carbonate supersaturated solutions and its breakdown are observed under conditions rarely well defined. In most cases it is the pH rise caused by the carbon dioxide loss that involves calcium carbonate precipitation. Before studying this problem, we suggest in this first part, a new model for the evolution of the calcocarbonic system that takes into account the hydrated forms of CaCO3: CaCO3 amorphous, CaCO3 x 6H2O (ikaite) and CaCO3 x H2O (monohydrate). According to this model, the precipitation of any one of these hydrated forms could be responsible for the breakdown of the metastable state. After this first step, the solids evolve into dehydrated forms. At first, the metastable domain spread of the calcium carbonate supersaturated solutions was studied by the elaboration of computer programs in which the formation of CaCO3(0)(aq) ion pairs was taken into account. These ion pairs are supposed to evolve through dehydration to form the various calcium carbonate solid form precursors. This thermodynamic study was then compared to the experimental methods of the critical pH. Here the pH rise was caused by adding sodium hydroxide under different conditions for sodium hydroxide addition speed, agitation mode and ageing of solutions. For the highest speed of sodium hydroxide addition, the CaCO3 ionic product reached the value of the amorphous calcium carbonate solubility product, and the reaction of the amorphous calcium carbonate precipitation was of the homogenous type. Decreasing the reagent's addition speed caused an extension of the titration time. Then, the breakdown of the metastable state was obtained with the CaCO3 x H2O heterogeneous precipitation. This clearly illustrates the probable ageing of the precursors of the solid states that are considered in this model.


Coupling of headspace solid phase microextraction with ultrasonic extraction for the determination of chlorinated pesticides in bird livers using gas chromatography.
In the present study a combined analytical method involving ultrasonic extraction (USE), sulfuric acid clean-up and headspace solid-phase microextraction (HS-SPME) was developed for the determination of chlorinated pesticides (CPs) in bird livers. Extraction of CPs from 1g of liver was performed by ultrasonication for 30 min using 20 mL of solvent mixture (n-hexane:acetone (4:1, v/v)). The extract was subsequently subjected to a clean-up step for lipid removal. A comparative study on several clean-up procedures prior to the HS-SPME enrichment step was performed in order to achieve maximum recovery and optimal clean-up efficiency, which would provide suitable limits of detection in the gas chromatographic analysis. For this purpose, destructive (sulfuric acid or sodium hydroxide treatment) and non-destructive (alumina column) clean-up procedures has been assayed. The treatment of the extract with 40% (v/v) H2SO4 prior to HS-SPME process showed the best performance since lower detection limits and higher extraction efficiencies were obtained. The method detection limit ranged from 0.5 to 1.0 ng g(-1) wet weight and peak areas were proportional to analyte concentrations (r2>0.990) in the range of 5-500 ng g(-1) wet wt. The method was found to be reproducible (R.S.D.<10%) and effective under the operational conditions proposed and was applied successfully to the analysis of CPs in liver tissues of various bird species from Greece.


A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat.
This study combined two neurodevelopmental manipulations, neonatal MK-801 treatment and isolation rearing, to produce a 'two-hit' model and determine whether two hits induce a more robust behavioural phenotype of an animal model of aspects of schizophrenia compared with individual manipulations alone. The effect of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK-801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10 and were assigned to group or isolation rearing at weaning (PND 21). From PND 77, they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were subjected to three prepulse inhibition (PPI) tests, a locomotor activity assessment and a novel object recognition task. MK-801-treated rats reared in isolation displayed robust PPI disruptions which were consistently manifested in all three tests. PPI deficits were also detected in saline-treated rats reared in isolation but not in all tests. Only the two-hit rats demonstrated hyperlocomotion and impaired object recognition memory. Clozapine restored PPI anomalies in the two-hit rats. The two-hit model showed greater psychotic-like effects than either neonatal MK-801 or isolation rearing alone. The preliminary predictive validity shown with clozapine suggests this model may be useful for predicting the efficacy of putative antipsychotics.


Obesity-Related Single-Nucleotide Polymorphisms and Weight Gain Following First-Line Antiretroviral Therapy.
We studied the association of obesity-related single-nucleotide polymorphisms (OR-SNPs) with weight gain after antiretroviral therapy (ART) in people with human immunodeficiency virus (HIV; PWH). Participants were ART-naive PWH from the Spanish HIV Research Cohort who started ART from 2014 onward and had blood/DNA deposited in the cohort Biobank. The primary outcome was change in weight at 96 weeks after starting ART. We genotyped 14 OR-SNPs from a meta-analysis of genome-wide association studies of body mass index (BMI) loci. Changes over time in weight and BMI were studied using adjusted linear mixed models. A total of 1021 PWH were included. The mean weight gain over 96 weeks was 2.90 (95% confidence interval, 2.54-3.26) kg. Factors associated with higher weight gain were female sex, birth in sub-Saharan Africa, prior AIDS, CD4+ <200 cells/µL, HIV-RNA >100 000 copies/mL, negative hepatitis C virus serology, and use of tenofovir alafenamide. A significant association was found between ZC3H4 rs3810291 GG genotype and BCDIN3D/FAIM2 rs7138803 GG genotype polymorphisms and weight and BMI increase. The estimated adjusted mean (standard error [SE]) of weight gain was 4.26 (0.56) kg in ZC3H4 rs3810291 GG carriers and 2.66 (0.19) kg in AA/AG carriers (P = .007). Likewise the estimated weight gain at 96 weeks was 3.35 (0.29) kg in BCDIN3D/FAIM2 rs7138803 GG carriers and 2.51 (0.24) kg in AG/AA carriers (P = .020). Genetic factors may play a role in weight gain after ART initiation. Further work is needed to replicate our findings and understand how the identified SNPs lead to higher weight gain in this context.


Detection of glucagon in pancreatic A-cells by monoclonal antibodies.
The production of a mouse monoclonal antibody from a hybrid myeloma and its use for the detection of glucagon in tissue sections is reported. The hybrid clone isolated after fusion of mouse myeloma cells with hyperimmune spleen cells from a mouse previously immunized with porcine glucagon allowed us a standardized and permanent source of monoclonal antibodies in a culture cell system. The monoclonal antibody (3 GL 31) specifically reacts with pancreatic A-cells in several species including pig, rabbit, tupaia belangeri and sheep. No immunoreactivity is observed against gut cells and neurons.


Penetrating injuries to the vertebral artery: interventions and outcomes from US Trauma Centers.
Penetrating injuries to the vertebral artery are rare and incompletely studied. Operative, angioembolic, and nonoperative strategies are management options, although the association between management strategy and outcomes is unknown. This study endeavored to define the epidemiology, management strategy, and outcomes after penetrating injuries to the vertebral artery presenting to trauma centers nationwide. Patients with veterbral artery injuries were identified from the National Trauma Data Bank (NTDB) (2016-2017) using ICD-10-CM codes. Only those with penetrating mechanisms of injury were included in the study. Transferred patients were excluded. Study groups were defined by management strategy (Operative management, OM; angioembolization, AE; and nonoperative management, NOM). Patient demographics, injury characteristics, and outcomes were compared between groups using univariate analysis. Multivariate analysis with logistic regression was used to examine independent risk factors for mortality and stroke. Penetrating injuries to the vertebral artery were rare (n = 476, < 1% of NTDB patient population). Median age was 28 [IQR 21-37] years and 81% (n = 385) of patients were male. Interpersonal violence was the most common injury intent (n = 374, 79%). Most patients were managed with NOM (n = 409, 86%), with AE and OM utilized less frequently (8% and 6%, respectively). Stab wounds were the most frequent mechanism of injury among patients managed with OM (62%), while gunshot wounds were most common among patients managed with NOM (84%) or AE (79%). Multivariate analysis of risk factors for stroke revealed only associated carotid artery injury (OR 4.236, 95% CI 1.284-13.970, p = 0.018) and AE (OR 6.342, 95% CI 1.417-28.399, p = 0.016) were independent predictors. Independent risk factors for mortality were advanced age (OR 1.026, 95% CI 1.001-1.052, p = 0.044); elevated ISS (OR 1.030, 95% CI 1.008-1.052, p = 0.006); and associated traumatic brain injury (OR 3.020, 95% CI 1.333-6.843, p = 0.008). Higher ED GCS was independently associated with reduced mortality (OR 0.788, 95% CI 0.731-0.849, p < 0.001). Vertebral artery injuries after penetrating mechanisms are infrequent in the United States. Patients with these injuries tend to be young adult men who were injured by gunshot wounds as a result of interpersonal violence. The majority of these injuries were managed nonoperatively, with operative intervention required most commonly for patients injured by stab wounds. Risk factors for both stroke and mortality were principally due to patient factors and associated injuries. Increased risk of stroke among patients managed with angioembolization will need to be further investigated with future study to determine if this risk is imparted from the management strategy itself or from underlying injury characteristics.


Effect of 200μG/day of vitamin K1 on the variability of anticoagulation control in patients on warfarin: a randomized controlled trial.
Controversy exists whether low-dose vitamin K supplementation can improve anticoagulation control in patients with unstable anticoagulation under warfarin. In a single- centre randomized, double-blind, placebo-controlled study, we evaluated the effectiveness of 200 μg/day of vitamin K1 in patients with unstable control under warfarin. Effectiveness of Vitamin K1 supplementation was primarily assessed by the percentage (%) of Time-in-Therapeutic-Range (TTR) and secondarily by the standard deviation (SD) of the patient's INR values; the proportion of out-of-range INRs; and the number of dose changes on warfarin. Their change scores were obtained by subtracting the mean value in the 6 months pre-randomization from the mean value in the 6 months post-randomization. Multivariable linear-regressions identified factors associated with anticoagulation instability. Fifty out of 54 patients were analyzed (intervention: n=26; placebo: n=24). Most indications (87%) for anticoagulation were venous thromboembolism (VTE). The intervention was associated with a greater reduction in the change scores for the SD of INRs between the pre and post-randomization periods compared with placebo. The mean change score was -0.259±0.307 with the intervention and -0.046±0.345 with placebo (p=0.026). There was no effect on the change scores of the (%) TTR (p=0.98), the number of INRs out-of-range (p=0.58) and the number of dose changes (p=0.604). Factors independently associated with increased variability in the SD of INRs were increased alcoholic drinks/week (p=0.017), dosing errors (p=0.0009) and missed INR appointments (p=0.035). Vitamin K1 supplementation reduces the SD of INRs as an indicator of the variability in anticoagulation control in patients treated with warfarin for VTE.


Stapes ankylosis in a family with a novel NOG mutation: otologic features of the facioaudiosymphalangism syndrome.
To report the phenotype-genotype correlation in a Belgian family that was ascertained to have a novel missense mutation in the NOG gene mapping to chromosome 17q22. To describe the phenotype, a retrospective case study was performed based on the otologic, audiologic, ophthalmologic, and radiologic data of the mutation carriers of the NOG gene. Tertiary referral center. All members of a Belgian kindred who carried the novel missense mutation in the NOG gene (NOG, Trp205Cys [W205C]; 1426G>C). Diagnostic otologic and ophthalmologic examination, audiometric analysis, and radiologic imaging. Phenotype-genotype correlations. All five mutation carriers had a typical facies. Bilateral proximal symphalangism and hyperopia were present in 80%. Five of 10 ears also had progressive early-onset conductive hearing loss caused by stapes ankylosis. So far, 14 independent NOG mutations have been identified. The autosomal dominant disorder described in the present family was caused by a novel NOG missense mutation (NOG, Trp205Cys [W205C]; 1426G>C). The phenotype correlated well with the facioaudiosymphalangism syndrome. The mutation carriers demonstrated progressive multiple joint fusions, hyperopia, early-onset conductive deafness, and a typical facies.


New insights into the pathogenesis of Hirschsprung's associated enterocolitis.
The management of Hirschsprung's disease (HD) has made dramatic strides over the last 20 years. Research into the embryological development and migration of ganglion cell has enabled a greater understanding of the pathogenesis of the disease. Coupled with new techniques in surgery, such as laparoscopy-assisted pull-through and the transanal pull-through, this knowledge has led to improved outcomes for children with HD. However, although our appreciation of Hirschsprung's associated enterocolitis and its aetiology has increased, there are continued references in the literature to a multitude of theories of pathogenesis. The purpose of this review is to delineate the theories and demonstrate the evidence supporting or otherwise contradicting each other.


Sialadenitis of the anterior mandibular vestibule: A subset of burning mouth syndrome.
Burning Mouth syndrome (BMS) is a relatively common oral neurosensory disorder known for oral burning pain. In that there is a relative absence of oral clinical findings and systemic causation, the diagnosis of BMS is challenging. Sialadenitis of the anterior mandibular vestibule appears to be a subset of BMS. The lip component of chronic orofacial pain is potentially an important concern with regard to the diagnosis and treatment of chronic orofacial pain. Discussion regarding the etiology, diagnosis, and therapy of this condition is provided.


Alleviating monoterpene toxicity using a two-phase extractive fermentation for the bioproduction of jet fuel mixtures in Saccharomyces cerevisiae.
Monoterpenes are a diverse class of compounds with applications as flavors and fragrances, pharmaceuticals and more recently, jet fuels. Engineering biosynthetic pathways for monoterpene production in microbial hosts has received increasing attention. However, monoterpenes are highly toxic to many microorganisms including Saccharomyces cerevisiae, a widely used industrial biocatalyst. In this work, the minimum inhibitory concentration (MIC) for S. cerevisiae was determined for five monoterpenes: β-pinene, limonene, myrcene, γ-terpinene, and terpinolene (1.52, 0.44, 2.12, 0.70, 0.53 mM, respectively). Given the low MIC for all compounds tested, a liquid two-phase solvent extraction system to alleviate toxicity during fermentation was evaluated. Ten solvents were tested for biocompatibility, monoterpene distribution, phase separation, and price. The solvents dioctyl phthalate, dibutyl phthalate, isopropyl myristate, and farnesene showed greater than 100-fold increase in the MIC compared to the monoterpenes in a solvent-free system. In particular, the MIC for limonene in dibutyl phthalate showed a 702-fold (308 mM, 42.1 g L(-1) of limonene) improvement while cell viability was maintained above 90%, demonstrating that extractive fermentation is a suitable tool for the reduction of monoterpene toxicity. Finally, we estimated that a limonane to farnesane ratio of 1:9 has physicochemical properties similar to traditional Jet-A aviation fuel. Since farnesene is currently produced in S. cerevisiae, its use as a co-product and extractant for microbial terpene-based jet fuel production in a two-phase system offers an attractive bioprocessing option.


Selenium requirement for the growth of Clostridium sporogenes with glycine as the oxidant in stickland reaction systems.
Clostridium sporogenes was found to have an absolute requirement for selenium to utilize glycine but not proline as oxidant in Stickland-type fermentations. No glycine reductase activity was detectable in cells from media without added selenium. The data indicate that this organism could be used for microbiological assays for very low levels of selenium in certain forms.


The effect of continuous positive airway pressure (CPAP) on the quality of life in patients with multiple system atrophy.
To evaluate the effect of continuous positive airway pressure (CPAP) on the quality of life (QoL) in patients with multiple system atrophy (MSA) and their caregivers. We reviewed the electronic medical records of patients with MSA treated with CPAP (n = 15). After CPAP treatment, we checked the patient global impression of change (PGI-C) scale for sleep complaints and QoL for six patients who continued to use CPAP. QoL was also assessed for five caregivers of these patients. A total of 15 patients (6 women) were included. The mean age was 63.6 ± 8.1 years old and the mean disease duration was 4.9 years. The mean duration of CPAP treatment was 22.1 ± 10.6 months and the average compliance was 90%. Three patients died during CPAP treatment, and two patients discontinued CPAP after tracheostomy. For six patients who continued to use CPAP, sleep complaints minimally improved. Five patients reported an improved QoL, and all five caregivers reported improved caregivers' QoL. This study showed that the use of CPAP has a beneficial effect on sleep complaints and QoL of patients with MSA and their caregivers.


Defining chiropractic professional identity: A concept analysis.
The concept of professional identity within chiropractic is often discussed and debated, however in the field to date, there is no formal definition of chiropractic professional identity (CPI). This article aims to create a coherent definition of CPI and to formalise the conceptual domains that may encompass it. Using the Walker and Avant (2005) process, a concept analysis methodology was employed to clarify the diffuse concept of CPI. This method initially involved selecting the concept (CPI), determining the aims and purpose of the analysis, identifying concept uses, and defining attributes. This was achieved from a critical literature review of professional identity across health disciplines. Chiropractic-related model, borderline and contrary cases were used to exemplify characteristics of CPI. The antecedents required to inform CPI, consequences of having, and ways to measure the concept of CPI were evaluated. From the concept analysis data, CPI was found to encompass six broad attributes or domains: knowledge and understanding of professional ethics and standards of practice, chiropractic history, practice philosophy and motivations, the roles and expertise of a chiropractor, professional pride and attitude, and professional engagement and interaction behaviours. These domains were not mutually exclusive and may overlap. A conceptual definition of CPI may bring together members and groups within the profession and promote intra-professional understanding across other disciplines. The CPI definition derived from this concept analysis is: 'A chiropractor's self-perception and ownership of their practice philosophies, roles and functions, and their pride, engagement, and knowledge of their profession'.


Recent Advance in the Development of Singlet-Fission-Capable Polymeric Materials.
Singlet fission (SF) is a spin-allowed process in which a higher-energy singlet exciton is converted into two lower-energy triplet excitons via a triplet pair intermediate state. Implementing SF in photovoltaic devices holds the potential to exceed the Shockley-Queisser limit of conventional single-junction solar cells. Although great progress has been made in exploiting the underlying mechanism of SF over the past decades, the scope of materials capable of SF, particularly polymeric materials, remains poor. SF-capable polymer is one of the most potential candidates in the implementation of SF into devices due to their distinct superiorities in flexibility, solution processability and self-assembly behavior. Notably, recent advancements have demonstrated high-performance SF in isolated donor-acceptor (D-A) copolymer chains. This review provides an overview of recent progress in the development of SF-capable polymeric materials, with a significant focus on elucidating the mechanisms of SF in polymers and optimizing the design strategies for SF-capable polymers. Additionally, the paper discusses the challenges encountered in this field and presents future perspectives. It is expected that this comprehensive review will offer valuable insights into the design of novel SF-capable polymeric materials, further advancing the potential for SF implementation in photovoltaic devices.


Hemodynamic differences between Pipeline and coil-adjunctive intracranial stents.
Modern coil-adjunctive intracranial stent designs have increased metal surface coverage to construct putative 'flow diverter lights.' This is rooted in the assumption that flow diversion is linearly correlated with metal surface coverage rather than being a threshold to be reached by device porosity and design. To evaluate this assumption, by performing computational flow analysis on three aneurysm models treated with low metal surface coverage stents (ATLAS and Enterprise), a Pipeline flow diverter, and the LVIS Blue stent. Computational flow analysis was performed on virtual deployment models entailing deployment of an ATLAS, Enterprise, LVIS Blue, or Pipeline. The impact of device deployment on velocity vectors at the neck, maximum wall shear stress, inflow rate into the aneurysm, and turnover time was determined. Velocity vector plots demonstrated low magnitude, localized inflow jets for Pipeline only; asymmetric, selectively high inflow jets were seen for LVIS Blue, and broader velocity vector clusters were seen for Atlas and Enterprise. Reduction in wall shear stress as compared with baseline was significant for all devices and greatest for the Pipeline. Mean peak wall shear stress was significantly lower for LVIS Blue in comparison with ATLAS or Enterprise but significantly lower for Pipeline than for LVIS Blue. Reduction of inflow rate into the aneurysm was significant for LVIS Blue and Pipeline but significantly lower for Pipeline than for LVIS Blue. Turnover time was statistically similar for ATLAS, Enterprise, and LVIS Blue, but significantly increased for Pipeline. Considerable differences in peak wall shear stress, inflow rates, and turnover time between flow diverters, moderate- and low-porosity stents reinforce the assumption that effective flow diversion represents a threshold in device design, encompassing metal surface coverage only in part.


Health Care Use by Muslim Patients During Ramadan.
Health care utilization during Ramadan has not been examined in the United States. A retrospective review of billing and electronic health record data for Muslims (n = 2,919) and non-Muslims (n = 184,803) in primary care practices in Eastern Massachusetts. Muslim patients were younger, less educated, less often commercially insured, more likely to have Medicare, and less likely to be primary English speakers (p < .0001 for all comparisons). In multivariate models, during Ramadan, Muslims, compared with non-Muslims, had a higher rate of primary care visits (incidence rate ratio [IRR], 1.06; 95% confidence interval [CI], 1.01-1.11), emergency department visits (IRR, 1.60; 95% CI, 1.34-1.91), and hospitalizations (IRR, 1.18; 95% CI, 1.03-1.34). Important demographic differences exist between Muslim and non-Muslim patients. Muslims, compared with non-Muslims, had higher health care utilization during Ramadan.


Involvement of protein kinase C in the regulation of assembly-disassembly of neurofilaments in vitro.
Protein kinase C phosphorylated the major mammalian neurofilament protein (NF-L) with approximately 3 mol phosphate per mol protein. The phosphorylated NF-L no longer formed the filaments. Sequential analysis of the tryptic phosphopeptides, together with the known primary sequence, revealed that Ser-12, Ser-27, Ser-33 and Ser-51 were phosphorylated by protein kinase C. These findings contribute toward elucidation of mechanisms regulating the functions of neurofilaments.


Psychosocial correlates of neurodevelopmental disabilities in 2- to 3-year-olds.
Canada's National Longitudinal Study of Children and Youth survey data provide insights into chronic health conditions in children. Children with neurodevelopmental disabilities (NDD) are at increased risk for adverse behavioral outcomes. We examined data from 3 cycles of Canada's National Longitudinal Survey of Children and Youth for the presence of epilepsy (Epi), cerebral palsy (CP), and intellectual disability (ID) in 2- to 3-year-olds. We then examined the relationship of NDD to composite measures of behavior: hyperactivity-inattention (HI), prosocial behaviors (PS), emotional disorder-anxiety (EA), physical aggression oppositional behavior (AO), and separation anxiety (SA). There were 15 children with Epi, 25 with CP and 28 with ID in a sample of 10,879, which represented a population of 756,848 2- to 3-year-old Canadian children. Comparison of mean scores of the NDD groups and controls (Welch's ANOVA), indicated statistically significant differences in HI, PS, EA, and SA at the p < 0.001 level. Post hoc analysis showed significant intergroup differences. Children with epilepsy did not differ from controls on any of the behavioral measures. However, in comparison to controls, children with intellectual disability had higher EA and SA scores and lower PS scores, and those with cerebral palsy had lower PS scores. Children with NDD show differences in behavioral outcomes at a very early age when compared with controls. Screening for these behaviors and early intervention programs may help avoid longer term psychiatric comorbidity associated with these disabilities.


Can a metabolism-targeted therapeutic intervention successfully subjugate SARS-COV-2? A scientific rational.
As a process entailing a high turnover of the host cell molecules, viral replication is required for a successful viral infection and requests virus capacity to acquire the macromolecules required for its propagation. To this end, viruses have adopted several strategies to harness cellular metabolism in accordance with their specific demands. Most viruses upregulate specific cellular anabolic pathways and are largely dependent on such alterations. RNA viruses, for example, upregulate both glycolysisand glycogenolysis providing TCA cycle intermediates essential for anabolic lipogenesis. Also, these infections usually induce the PPP, leading to increased nucleotide levels supporting viral replication. SARS-CoV-2 (the cause of COVID-19)that has so far spread from China throughout the world is also an RNA virus. Owing to the more metabolic plasticity of uninfected cells, a promising approach for specific antiviral therapy, which has drawn a lot of attention in the recent years, would be the targeting of metabolic changes induced by viruses. In the current review, we first summarize some of virus-induced metabolic adaptations and then based on these information as well as SARS-CoV-2 pathogenesis, propose a potential therapeutic modality for this calamitous world-spreading virus with the hope of employing this strategy for near-future clinical application.


The effect of inhaled salbutamol on the outcomes of transient tachypnea of the newborn.
Transient tachypnea of the newborn (TTN) is a self-limiting disease that results from a reduction in the rate of lung fluid clearance in neonates. A delay in lung fluid absorption in neonates disrupts the transition from intrauterine to extrauterine life. Use of beta-adrenergic antagonists, such as salbutamol, accelerates lung fluid clearance. The current study aimed to evaluate the effect of inhaled salbutamol on the clinical progression of TTN treatment. In the current triple-blind clinical trial, a total of 148 inpatients diagnosed with TTN were randomly divided into 2 groups. The treatment group (n = 74) received inhaled salbutamol and the placebo group (n = 74) received inhaled normal saline. The drug administration was started 6 h after birth and continued in the case of continued respiratory distress and the need for oxygen as adjuvant therapy for up to 72 h maximum after the initiation of treatment. To evaluate the response to treatment with inhaled salbutamol, we assessed the respiratory rate (RR), heart rate (HR), fraction of inspired oxygen (FIO2) level, and O2 saturation at intervals of 30 min as well as 1 h and 4 h after drug administration. The results were compared between the groups. The results of the current study indicated a significant difference between the treatment and placebo groups in the treatment duration, hospitalization duration, need for continuous positive airway pressure therapy (CPAP), and time of oral feeding initiation. In addition, no complication was observed during the treatment. It is noteworthy that, following the improvement of disease symptoms and reduction of hospitalization. This reduction may decrease the treatment costs and anxiety of parents, which was associated with proper mental and economic outcomes. Although, in the current study, drug administration was continued for 72 h maximum, the prescription of at most 4 doses of salbutamol may have had maximum efficiency in the remediation process. To evaluate the therapeutic role of inhaled salbutamol, further studies are recommended.


Analysis of molecular structure, spectroscopic properties (FT-IR, micro-Raman and UV-vis) and quantum chemical calculations of free and ligand 2-thiopheneglyoxylic acid in metal halides (Cd, Co, Cu, Ni and Zn).
In this study, molecular geometries, experimental vibrational wavenumbers, electronic properties and quantum chemical calculations of 2-thiopheneglyoxylic acid molecule, (C6H4O3S), and its metal halides (Cd, Co, Cu, Ni and Zn) which are used as pharmacologic agents have been investigated experimentally by FT-IR, micro-Raman and UV-visible spectroscopies and elemental analysis. Meanwhile the vibrational calculations were verified by DFT/B3LYP method with 6-311++G(d,p) and LANL2DZ basis sets in the ground state, for free TPGA molecule and its metal halide complexes, respectively, for the first time. The calculated fundamental vibrational frequencies for the title compounds are in a good agreement with the experimental data.


American College of Medical Genetics and Genomics: standards and guidelines for documenting suspected consanguinity as an incidental finding of genomic testing.
Genomic testing, including single-nucleotide polymorphism-based microarrays and whole-genome sequencing, can detect long stretches of the genome that display homozygosity. The presence of these segments, when distributed across multiple chromosomes, can indicate a familial relationship between the proband's parents. This article describes the detection of possible consanguinity by genomic testing and the factors confounding the inference of a specific p-arental relationship. It is designed to guide the documentation of suspected consanguinity by clinical laboratory professionals and to alert laboratories to the need to establish a reporting policy in conjunction with their ethics review committee and legal counsel.


Synthesis, spectra and biomimetic properties of copper(II)-copper(II) and copper(II)-zinc(II) binuclear complexes with CuN5 chromophores.
X-band electron spin resonance (ESR) and UV-vis spectra of a homobinuclear [(Bipy)2Cu-E-Im-Cu(Bipy)2](BF4)3 and a heterobinuclear [(Bipy)2Cu-E-Im-Zn(Bipy)2](BF4)3 complexes, E-Im=2-ethylimidazolate ion have been described as possible models for superoxide dismutase (SOD). Magnetic moment and ESR spectral measurements of the homobinuclear complex have shown an antiferromagnetic exchange interaction. From pH-dependent ESR and UV-vis spectral measurements studies, these complexes have been found to be stable over 8.5-10.5 pH range. These complexes catalyze the dismutation of superoxide (O2-) at biological pH. All the observations indicate that these complexes act as good possible models for superoxide dismutase.


Considerations on the temperature dependence of the gas-liquid chromatographic retention.
A discussion on the temperature dependence of the partition coefficient K is developed. This discussion embraces topics such as the limitations of conventional thermodynamic approaches followed in the chromatographic literature, qualitative theoretical notions arising from molecular thermodynamics and the experimental information that is accessible through modern capillary gas chromatography. It is shown that the heat capacity difference of solute transfer for flexible molecules has at least one maximum in the chromatographic range of temperature. As a consequence, a great amount of experimental data is required for a correct thermodynamic interpretation of the chromatographic retention.


Comparative efficacy of antiviral therapy in preventing vertical transmission of hepatitis B: a network meta-analysis.
Antiviral drugs are safe and effective in the third trimester to prevent intrauterine transmission of hepatitis B virus, and are recommended for hepatitis B virus (HBV) infected gravid mothers (between weeks 28 and 32) with high viral load, followed by postnatal hepatitis B immunization in the newborn. We estimated the comparative efficacy of antiviral drugs for prevention of vertical transmission of HBV, through a network meta-analysis of clinical trials. We conducted a comprehensive search of MEDLINE, EMBASE and published proceedings from major liver meetings from January 1980 to November 2014. We conducted pair-wise meta-analyses and Bayesian framework using Markov chain Monte Carlo methods, combining direct and indirect evidence for any given pair of treatments. Seventeen clinical trials involving 2764 newborns of hepatitis B surface antigen seropositive mothers were eligible for analysis. There were no clinical trials involving tenofovir or entecavir. On pair-wise meta-analyses, telbivudine (hazard ratio, HR 0.12, 95% confidence interval (CI) 0.04-0.37; I(2) = 0%), and Lamivudine (HR 0.40, 95% CI 0.24-0.65; I(2) = 0%), were more effective than placebo in reducing vertical transmission of HBV in high viremic hepatitis B e antigen (HBeAg)-positive chronic Hepatitis B Chinese patients. Sensitivity analyses limited to studies with HBeAg seropositive mothers revealed similar results. Based on a Bayesian network meta-analysis of clinical trials, combining direct and indirect treatment comparisons, telbivudine appears to be more effective than Lamivudine for preventing vertical transmission of HBV infection. Trials assessing the efficacy of tenofovir or entecavir compared to placebo or other antiviral drugs are lacking.


Perineal herniorrhaphy with pedunculated tunica vaginalis communis in dogs: Description of the technique and clinical case series.
Perineal hernia (PH) in dogs is caused by the separation of the anal septal muscles and the displacement of pelvic/abdominal organs under the perineal skin. Reconstruction of the pelvic septum by surgical repositioning is the only curative treatment. To describe the procedure and outcomes of surgical repair using the pedunculated tunica vaginalis communis (TVC) for PH in dogs. Intact male dogs diagnosed with PH were included in this study. For surgery, each dog was positioned in the Trendelenburg position. Castration was performed with the open technique, followed by colopexy and cystopexy via laparotomy. The remaining bilateral TVCs transposed to the opening of PH were used for the perineal herniorrhaphy. Intraoperative findings, complications, and outcomes were evaluated and recorded. Eight dogs [median age 10.5 years (range, 9-13 years); median body weight 4.9 kg (range, 1.6-12.3 kg)] were treated using the TVC surgical technique. Perineal herniorrhaphy with the TVC was feasible in all dogs. The median operation time was 105.5 min (range, 46-149 min) in unilateral PH, and 92 and 122 min in two dogs with bilateral PH. Short-term postoperative complications during hospitalization did not occur in six dogs, whereas the residual two dogs had a temporary local infection as a minor complication. Postoperative recurrence occurred in one dog (13%) on postoperative day 136. Our study suggests that the herniorrhaphy technique using the pedunculated TVC is an alternative option for the repair of PH in dogs.


Older people's preferences regarding programme formats for managing concerns about falls.
to explore the preferences of community-dwelling older persons regarding different programme formats for managing concerns about falls. cross-sectional study of 5,755 community-dwelling people aged ≥ 70 years in the Netherlands. a questionnaire assessed people's willingness to participate per programme format (n=6), i.e. a programme at home, via telephone, via home visits and telephone consultations, via television or via Internet. of the 2,498 responders, 62.7% indicated no interest in any of the formats. The willingness to participate per programme format varied between 21.5 (at home) and 9.4% (via Internet). Among people interested in at least one of the formats (n=931), higher levels of fall-related concerns were associated with increased preference for a programme with home visits. Poor perceived health and age ≥ 80 years were associated with less preference for a group programme. Higher educated people were more in favour of a programme via Internet compared with their lower educated counterparts. the majority of community-dwelling older people are not likely to participate in any of the six proposed programme formats for managing concerns about falls. However, when diverse formats of effective programmes will be made available, uptake and adherence may be increased since programme preferences are associated to specific population characteristics.


Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia.
To determine whether circulating markers of oxidative stress are elevated in pre-eclampsia when appropriate precautions are taken to prevent in vitro oxidation A prospective study. Nuffield Department of Obstetrics and Gynaecology, Oxford and The William Harvey Institute, London. Three groups of women: those with pre-eclampsia (n = 19), control pregnant women (n = 19) matched for gestation, age and parity and a group of non pregnant individuals of reproductive age (n = 7). Citrated plasma was stored at -80 degrees C with 20 micromol beta hydroxytoluene to prevent auto-oxidation. Plasma samples were assayed for levels of 8 epi-prostaglandin F2alpha, lipid hydroperoxides, malondialdehyde and also the lipid soluble antioxidant vitamin E. There were no differences in 8 epi-prostaglandin F2alpha, lipid peroxide or malondialdehyde levels between the groups of women with pre-eclampsia and those acting as pregnant controls. However, lipid hydroperoxides and malondialdehyde were significantly raised in both pre-eclampsia and normal pregnancy, compared with nonpregnant women. Vitamin E levels were similar in women with pre-eclampsia and those with a normal pregnancy, but in both groups levels were significantly higher than in nonpregnant women. Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia.


Unilateral percutaneous cannulation and endoaortic balloon management in robotic-assisted cardiac surgery: The least invasive approach.
Totally endoscopic, robotic-assisted cardiac surgery has been increasingly utilized for valvular surgery. Peripheral cannulation with endoaortic balloon occlusion offers a safe approach for initiation of cardiopulmonary bypass during such procedures. We present a step-by-step demonstration of unilateral percutaneous femoral cannulation, endoaortic balloon positioning, and decannulation in a patient undergoing totally endoscopic, robotic-assisted mitral valve repair.


The influence of data-driven versus conceptually-driven processing on the development of PTSD-like symptoms.
Ehlers and Clark [(2000). A cognitive model of posttraumatic stress disorder. Behaviour Research and Therapy, 38, 319-345] propose that a predominance of data-driven processing during the trauma predicts subsequent PTSD. We wondered whether, apart from data-driven encoding, sustained data-driven processing after the trauma is also crucial for the development of PTSD. Both hypotheses were tested in two analogue experiments. Experiment 1 demonstrated that relative to conceptually-driven processing (n=20), data-driven processing after the film (n=14), resulted in more intrusions. Experiment 2 demonstrated that relative to the neutral condition (n=24) and the data-driven encoding condition (n=24), conceptual encoding (n=25) reduced suppression of intrusions and a trend emerged for memory fragmentation. The difference between the two encoding styles was due to the beneficial effect of induced conceptual encoding and not to the detrimental effect of data-driven encoding. The data support the viability of the distinction between data-driven/conceptually-driven processing for the understanding of the development of PTSD.


Factors that contribute to satisfaction or dissatisfaction in stepfather-stepchild relationships.
Factors contributing to satisfaction and dissatisfaction in stepfather-stepchild relationships. A qualitative multicase study of six stepfathers. Four themes emerged: previous experiences as parents, other relationships within the family, issues that required negotiating, discipline of the children. Previous experience as parents, good relationships with other family members, similarity in values between parents, and inclusion in the disciplinary process increased stepfathers' satisfaction.


HISTONE DEACETYLASE 9 transduces heat signal in plant cells.
Heat stress limits plant growth, development, and crop yield, but how plant cells precisely sense and transduce heat stress signals remains elusive. Here, we identified a conserved heat stress response mechanism to elucidate how heat stress signal is transmitted from the cytoplasm into the nucleus for epigenetic modifiers. We demonstrate that HISTONE DEACETYLASE 9 (HDA9) transduces heat signals from the cytoplasm to the nucleus to play a positive regulatory role in heat responses in Arabidopsis. Heat specifically induces HDA9 accumulation in the nucleus. Under heat stress, the phosphatase PP2AB'β directly interacts with and dephosphorylates HDA9 to protect HDA9 from 26S proteasome-mediated degradation, leading to the translocation of nonphosphorylated HDA9 to the nucleus. This heat-induced enrichment of HDA9 in the nucleus depends on the nucleoporin HOS1. In the nucleus, HDA9 binds and deacetylates the target genes related to signaling transduction and plant development to repress gene expression in a transcription factor YIN YANG 1-dependent and -independent manner, resulting in rebalance of plant development and heat response. Therefore, we uncover an HDA9-mediated positive regulatory module in the heat shock signal transduction pathway. More important, this cytoplasm-to-nucleus translocation of HDA9 in response to heat stress is conserved in wheat and rice, which confers the mechanism significant implication potential for crop breeding to cope with global climate warming.


Artificial intelligence-assisted cryoEM structure of Bfr2-Lcp5 complex observed in the yeast small subunit processome.
Eukaryotic ribosome is maturated through an elaborate process that includes modification, processing and folding of pre-ribosomal RNA (pre-rRNAs) by a series of ribosome assembly intermediates. More than 70 factors participate in the dynamic assembly and disassembly of the small subunit processome (90S) inside nucleolus, leading to the early maturation of small subunit. The 5' domain of the 18S rRNA is the last to be incorporated into the stable 90S prior to the cleavage of pre-rRNA at the A1 site. This step is facilitated by the Kre33-Enp2-Bfr2-Lcp5 protein module with the participation of the DEAD-box protein Dbp4. Though structures of Kre33 and Enp2 have been modeled in previously observed 90S structures, that of Bfr2-Lcp5 complex remains unavailable. Here, we report an AlphaFold-assisted structure determination of the Bfr2-Lcp5 complex captured in a 3.99 Å - 7.24 Å cryoEM structure of 90S isolated from yeast cells depleted of Pih1, a chaperone protein of the 90S core assembly. The structure model is consistent with the protein-protein interaction results and the secondary structures of recombinant Bfr2 and Bfr2-Lcp5 complex obtained by Circular Dichroism. The Bfr2-Lcp5 complex interaction mimics that of exosome factors Rrp6-Rrp47 and acts to regulate 90S transitions.


Improving adherence to unguided Internet-based therapy for obsessive-compulsive disorder: A randomized controlled trial.
Adherence to internet-based cognitive-behavioral therapy (iCBT) is often low, possibly reducing its potential. The current study set out to test whether adherence and effects of unguided iCBT for obsessive-compulsive disorder (OCD) could be improved by varying the degree of autonomy in which modules are completed (free choice vs. fixed order). We randomized 151 individuals with OCD to either an unguided iCBT with a fixed (iCBTfixed) or a free-choice (iCBTfree+) order of the modules. We assessed participants at baseline (t0), eight weeks (t1), and 16 weeks (t2). Primary outcomes were adherence (utilization time, modules completed) and change in OCD severity (Y-BOCS). Secondary outcomes included depression, self-esteem, and treatment satisfaction. We calculated intent-to-treat (ITT) and complete case (CC) analyses. Analyses showed that both iCBT programs significantly reduced OCD severity. While groups did not differ on the ITT analyses, for the CC analyses, a greater improvement was found in the iCBTfixed in comparison to the iCBTfree+ group regarding OCD severity and quality of life, with medium effect sizes from t0 to t1 (ηp2 = 0.067-0.077). Time of utilization and number of modules completed did not differ between groups. No placebo control group, short follow-up period, self-report assessment. iCBT is effective in improving OCD. Despite similar adherence in the fixed versus the free-choice module order, the study offers tentative evidence that a fixed order of content is associated with better effects. More research on the effects of adherence on outcome is necessary.


Immunohistochemical localization of α2-adrenergic receptors in the neonatal rat cochlea and the vestibular labyrinth.
The α2-adrenergic receptors (α2-ARs), which mediate physiological responses to noradrenaline and adrenaline, are encoded by three different genes but all are coupled to the Gi/Go subfamily of G proteins. The present study investigated the localization of three subtypes, i.e., α2a-, α2b-, and α2c-ARs, in cochlea and vestibular labyrinth in rat in the early postnatal period by immunohistochemistry. The results showed that α2-ARs were widely distributed in regions, including the organ of Corti, spiral ganglion neurons, stria vascularis, crista ampullaris, Scarpa's ganglion, utricle, and Reissner's membrane. Furthermore, the cellular locations of α2-ARs between different cell subtypes as well as receptor subtypes and different observed time points also had diversity. α2a-AR mainly targeted to nuclei at postnatal ages (P)3. While at P(8), only ganglion neurons maintained this character whereas other cell types expressed α2a-AR mainly in plasma membrane. The α2b- and α2c-ARs exhibited predominantly in plasma membrane. Compared with P(8), α2c-AR was not present at stria vascularis at P(3). Overall, our observations indicated that there was region-specific regulation of α2-ARs development in cochlea and vestibular labyrinth. In addition, the extensive expressions of α2-ARs established a significant foundation for the exploration of the function of α2-ARs in cochlea and vestibular labyrinth.


Cytokeratins expressed in experimental rat bronchial carcinomas.
Cytokeratin expression in rat lung tumors was studied using polypeptide-specific monoclonal antibodies (MAbs) to human cytokeratins 4, 5, 7, 8, 10, 13, 14, 18 and 19. Experiments were performed on tumor fragments derived from 5 experimental rat squamous-cell lung tumors and one adenocarcinoma, as well as on cell lines obtained from the same tumors. The aims of this study were to investigate the differentiation profile of the rat tumor tissue and established tumor cell lines based on light and electron microscopical features and on cytokeratin phenotype, to characterize the tumor type and degree of differentiation of the lung tumors maintained during passaging in experimental animals, and to compare the cytokeratin expression pattern in transplanted tumors with that of the cultures derived from these tumors. Our results indicate that, in general, the antibodies used cross-react with rat cytokeratins and that these MAbs can be used to phenotype rat lung carcinomas. Both the tumor fragments and the cultured cells revealed a similar pattern of cytokeratin expression. In addition, the degree of differentiation was maintained upon prolonged culturing in vitro. MAbs to cytokeratin sub-types can therefore be used to distinguish the main sub-types of rat lung tumors and can give an indication about the degree of differentiation.


Degradation of dansyl polyamines on high-performance thin-layer chromatographic plates.
Using high-performance thin-layer chromatography with in situ quantitation to measure dansylated polyamines in the range of 1-20 pmol, we found that dansylated polyamines apparently react with the silica gel of the plates. The fluorescence of the dansyl polyamines diminished with increase in the time interval between application of a sample to the plate and start of the chromatographic separation. Conversely, the fluorescence at the site of application increased with the length of the time interval, indicating the formation of polar reaction products. If this reaction is not accounted for, considerable errors in quantitation of dansyl polyamines may occur.


Organization, replication and modification of the human genome: differential methylation of two classes of HeLa nuclear DNA separated on Ag+--Cs2SO4 gradients.
HeLa nuclear DNA sediments as a single peak, in neutral CsCl, while it is separated in a heavier and a lighter components, in alkaline Ag+--Cs2SO4. The heavy fraction, on the average, represents about 20% of the total DNA. CsCl analytical ultracentrifugation shows that heavy DNA bands at 1.715 g/cm3 and contains 53% GC (10% of the total GC), whereas light DNA bands at 1.703 g/cm3 and contains 40% GC (32% of the total GC). Coherently, Tm values in 0.1 x SSC are 82.5 degrees C, for heavy DNA, and 72.5 degrees C, for light DNA. After treatment with [3H-methyl-S-adenosyl-L-methionine in isolated nuclei, the concentration of labelled 5-methylcytosine was found to be highest in the more dense regions of the heavy peak and in the less dense regions of the light peak. Exposure to ultrasound modifies the quantitative relationship of the two peaks and improves the separation of supermethylated AT- and GC-rich DNAs. Four possible triplets as sites for DNA-methylase recognition are discussed.


Transport of L-histidine by human diploid fibroblasts in culture.
The transport of L-histidine has been characterized in skin derived diploid human fibroblasts, cultured under strictly controlled conditions. The transport measurements were made on cells grown to subconfluency after 60 to 90 min timed preincubation. The data, at substrate concentrations ranging from 0.050 to 10 mmol/l, were analyzed by a computer program. A saturable transport system (Km = 0.25 mmol/l, Vmax = 17 nmol/mg protein per min) and a nonsaturable component of influx (Kd = 1.6 +/- 0.4 nmol/mg protein/min per mmol) were found. L-Histidine displayed no Na+ requirement at either low or high concentrations. Inhibition analysis demonstrated that L-histidine uptake at low concentration was poorly inhibited by amino acids known to be effective inhibitors of system A. The largest fraction of L-histidine uptake was inhibited by 2-amino-bicyclo (2,2,1)-heptane-2-carboxylic acid (BCH), leucine, and tryptophan. These results indicated that L-histidine is transported in human fibroblasts mainly by the Na+ independent system L. The differences between this cell type and others studied previously are discussed.


Direct Measurement of Cerebrospinal Fluid Production in Mice.
The emerging interest in brain fluid transport has prompted a need for techniques that provide an understanding of what factors regulate cerebrospinal fluid (CSF) production. Here, we describe a methodology for direct quantification of CSF production in awake mice. We measure CSF production by placing a catheter in a lateral ventricle, while physically blocking outflow from the 4th ventricle. Using this methodology, we show that CSF production increases during isoflurane anesthesia, and to a lesser extent with ketamine/xylazine anesthesia, relative to the awake state. Aged mice have reduced CSF production, which is even lower in aged mice overexpressing amyloid-β. Unexpectedly, CSF production in young female mice is 30% higher than in age-matched males. Altogether, the present observations imply that a reduction in CSF production might contribute to the age-related risk of proteinopathies but that the rate of CSF production and glymphatic fluid transport are not directly linked.


Determining a sampling regime for PCR detection of respiratory tract viral infection at coronial post-mortem examinations.
Death due to respiratory infection is commonly encountered at autopsy. With only one opportunity to obtain samples for identification of a causative agent, it is important to ensure that sampling regimes are optimized to provide the greatest detection, without the expense and redundancy that can arise from over-sampling. This study was performed retrospectively using data from Coronial autopsies over the period 2012-2019 from which swabs from the nasopharyngeal region, trachea and lung parenchyma, in addition to samples of lung tissue, had been submitted for multiplex PCR detection of respiratory pathogens. From 97 cases with all four samples, there were 24 with at least one positive result for viral infection. Some cases had multiple positive results and a total of 27 respiratory tract viruses were identified, of which rhinovirus, influenza A virus and respiratory syncytial virus were the most common. Seventeen of the 27 viral infections (63%) were identified in all four samples. However, in nearly all cases (96%) the nasopharyngeal swab detected the infective agent when the multiplex PCR panel had detected infection in any of the four sample types. A nasopharyngeal swab is considered to be an optimal sample for detection of respiratory tract viral infection. As the samples analyzed were acquired before the appearance of the COVID-19 virus, the applicability of this finding for COVID-19 screening is not established.


High-dose methadone maintenance in pregnancy: maternal and neonatal outcomes.
This study assesses the effect of higher doses of methadone during pregnancy on maternal and fetal outcomes. We retrospectively reviewed clinical data for 81 mothers who received methadone and their 81 offspring. The cohort was divided into high-dose (>/=100 mg) and low-dose (<100 mg) groups. There were no differences in the rate of medication treatment for neonatal abstinence symptoms or days of infant hospitalization between the high-dose (mean, 132 mg) and low-dose (mean, 62 mg) groups. Despite longer histories of opiate abuse, the high-dose group had less illicit drug use at delivery. The whole cohort, which received an average of 101 mg/d, had an 81% rate of negative toxicology screens at delivery. High doses of methadone were not associated with increased risks of neonatal abstinence symptoms but had a positive effect on maternal drug abuse. Arbitrarily limiting methadone dose as a way of minimizing the risks of neonatal abstinence symptoms may be unwarranted.


Dengue virus serotype 2 genotype III evolution during the 2019 outbreak in Mato Grosso, Midwestern Brazil.
DENV-2 was the main responsible for a 70% increase in dengue incidence in Brazil during 2019. That year, our metagenomic study by Illumina NextSeq on serum samples from acute febrile patients (n = 92) with suspected arbovirus infection, sampled in 22 cities of the state of Mato Grosso (MT), in the middle west of Brazil, revealed eight complete genomes and two near-complete sequences of DENV-2 genotype III, one Human parvovirus B19 genotype I (5,391 nt) and one Coxsackievirus A6 lineage D (4,514 nt). These DENV-2 sequences share the aminoacidic identities of BR4 lineage on E protein domains I, II and III, and were included in a clade with sequences of the same lineage circulating in the southeast of Brazil in the same year. Nevertheless, 11/34 non-synonymous mutations are unique to three strains inthis study, distributed in the E (n = 6), NS3 (n = 2) and NS5 (n = 3) proteins. Other 14 aa changes on C (n = 1), E (n = 3), NS1 (n = 2), NS2A (n = 1) and NS5 (n = 7) were first reported in a genotype III lineage, having been already reported only in other DENV-2 genotypes. All 10 sequences have mutations in the NS5 protein (14 different aa changes). Nine E protein aa changes found in two sequences, six of which are unique, are in the ectodomain; where the E:M272T change is on the hinge of the E protein at domain II, in a region critical for the anchoring to the host cell receptor. The NS5:G81R mutation, in the methyltransferase domain, was found in one strain of this study. Altogether, these data points to an important evolution of DENV-2 genotype III lineage BR4 during this outbreak in 2019 in MT. Genomic surveillance is essential to detect virus etiology and evolution, possibly related to immune evasion and viral fitness changes leading to future novel outbreaks.


Supporting Breastfeeding Mothers by Transforming Library Space: A Nursing Mothers Room Project.
Librarians at Rowland Medical Library collaborated with individuals from across the campus of the University of Mississippi Medical Center (UMMC) to transform an unused library office to a nursing mothers room. This project resulted in a functional and attractive room for breastfeeding students and employees to pump breast milk.