The Clinical Utility of Preoperative Thyroglobulin for Surgical Decision Making in Thyroid Disease.
Serum thyroglobulin (Tg) levels are used to monitor for differentiated thyroid cancer (DTC) recurrence and have been correlated with posttreatment disease burden. The clinical significance of Tg in the preoperative setting to predict the risk of DTC is unclear. Our aim is to examine the clinical utility of preoperative Tg levels in those undergoing thyroidectomies for DTC or benign disease. From a prospectively collected database, we identified 385 patients who underwent thyroidectomy from 01/14 to 12/19 and had preoperative Tg levels available. Preoperative Tg levels were compared by preoperative indication for surgery, Bethesda category of biopsied nodules, presence of DTC on surgical pathology, and number of metastatic lymph nodes. There was no difference in mean preoperative Tg level when comparing indication for surgery (P = 0.2) or Bethesda classification (P = 0.4). Mean preoperative Tg levels were lower in patients with DTC (238 ± 77) compared to without DTC (532 ± 97) on final pathology (P = 0.02). Among 188 DTC patients who had lymph nodes removed, there was no significant correlation between the preoperative Tg level and number of positive lymph nodes on final pathology (P = 0.4). Preoperative serum Tg levels were lower in patients with DTC compared to those with benign disease on final pathology and did not correlate with extent of lymph node metastasis in patients with DTC. We found that serum Tg levels obtained in the preoperative setting do not predict DTC or lymph node metastasis and, therefore, do not inform the extent of surgery for differentiated thyroid cancer.


Mild COVID-19 infection does not alter the ovarian reserve in women treated with ART.
Does mild COVID-19 infection affect the ovarian reserve of women undergoing an assisted reproductive technology (ART) protocol? A prospective observational study was conducted between June and December 2020 at the ART unit of Tenon Hospital, Paris. Women managed at the unit for fertility issues by in-vitro fecundation, intracytoplasmic sperm injection (IVF/ICSI), fertility preservation, frozen embryo transfer or artificial insemination, and with an anti-Müllerian hormone (AMH) test carried out within 12 months preceding ART treatment, were included. All the women underwent a COVID rapid detection test (RDT) and AMH concentrations between those who tested positive (RDT positive) and those who tested negative (RDT negative). The study population consisted of 118 women, 11.9% (14/118) of whom were COVID RDT positive. None of the tested women presented with a history of severe COVID-19 infection. The difference between the initial AMH concentration and AMH concentration tested during ART treatment was not significantly different between the COVID RDT positive group and COVID RDT negative group (-1.33 ng/ml [-0.35 to -1.61) versus -0.59 ng/ml [-0.15 to -1.11], P = 0.22). A history of mild COVID-19 infection does not seem to alter the ovarian reserve as evaluated by AMH concentrations. Although these results are reassuring, further studies are necessary to assess the effect of COVID-19 on pregnancy outcomes in women undergoing ART.


Normal Oral Flora and the Oral Ecosystem.
The oral ecosystem comprises the oral flora, so-called oral microbiome, the different anatomic microniches of the oral cavity, and its bathing fluid, saliva. The oral microbiome comprises a group of organisms and includes bacteria, archaea, fungi, protozoa, and viruses. The oral microbiome exists suspended in saliva as planktonic phase organisms or attached to oral surfaces as a plaque biofilm. Homeostasis of the plaque biofilm and its symbiotic relationship with the host is critical for oral health. Disequilibrium or dysbiosis within the plaque biofilms is the initiating event that leads to major oral diseases, such as caries and periodontal disease.


Integrated case management for work-related upper-extremity disorders: impact of patient satisfaction on health and work status.
An integrated case management (ICM) approach (ergonomic and problem-solving intervention) to work-related upper-extremity disorders was examined in relation to patient satisfaction, future symptom severity, function, and return to work (RTW). Federal workers with work-related upper-extremity disorder workers' compensation claims (n = 205) were randomly assigned to usual care or ICM intervention. Patient satisfaction was assessed after the 4-month intervention period. Questionnaires on clinical outcomes and ergonomic exposure were administered at baseline and at 6- and 12-months postintervention. Time from intervention to RTW was obtained from an administrative database. ICM group assignment was significantly associated with greater patient satisfaction. Regression analyses found higher patient satisfaction levels predicted decreased symptom severity and functional limitations at 6 months and a shorter RTW. At 12 months, predictors of positive outcomes included male gender, lower distress, lower levels of reported ergonomic exposure, and receipt of ICM. Findings highlight the utility of targeting workplace ergonomic and problem solving skills.


Sirt1 Overexpression Inhibits Fibrous Scar Formation and Improves Functional Recovery After Cerebral Ischemic Injury Through the Deacetylation of 14-3-3ζ.
Cerebral ischemic stroke is one of the leading causes of human death. The fibrous scar is one of major factors influencing repair in central nervous system (CNS) injury. Silencing information regulator 2-related enzyme 1 (Sirt1) can regulate peripheral tissue and organ fibrosis. However, it is unclear how the fibrous scar forms and is regulated and it is unknown whether and how Sirt1 regulates the formation of the fibrous scar after cerebral ischemic stroke. Therefore, in the present study, we examined the effects of Sirt1 on the formation of the fibrotic scar after middle cerebral artery occlusion/reperfusion (MCAO/R) injury in vivo and on the transforming growth factor β1 (TGF-β1)-induced meningeal fibroblast fibrotic response in vitro, and we explored the molecular mechanisms underlying the Sirt1-regulated fibrosis process in vitro. We found that MCAO/R injury induced fibrotic scar formation in the ischemic area, which was accompanied by the downregulation of Sirt1 expression. The overexpression of Sirt1 reduced the infarct volume, improved Nissl body structure and reduced neurons injury, attenuated formation of fibrotic scar, upregulated growth associated protein43 (GAP43) and synaptophysin (SYP) expression, and promoted neurological function recovery. Similarly, Sirt1 expression was also downregulated in the TGF-β1-induced fibrosis model. Sirt1 overexpression inhibited fibroblast migration, proliferation, transdifferentiation into myofibroblasts, and secretion of extracellular matrix(ECM) by regulating the deacetylation of lysine at K49 and K120 sites of 14-3-3ζ in vitro. Therefore, we believe that Sirt1 could regulate fibrous scar formation and improve neurological function after cerebral ischemic stroke through regulating deacetylation of 14-3-3ζ.


Impacts of charcoal characteristics on sorption of polycyclic aromatic hydrocarbons.
Sorption of three polycyclic aromatic hydrocarbons (PAHs, phenanthrene, anthracene and pyrene) on three charcoals and their precursor substance (sawdust) was studied. The charcoals obtained by heating at 400 degrees C for different periods were different in chemical composition and structure. Sorption characteristics were described by a Polanyi-Dubinin-Manes model combined with poly-parameter linear free energy relationships. The results revealed that though partition could not be neglected for sawdust and charcoal containing large sawdust residue, adsorption controlled the sorption of PAHs on matured charcoals, where pi-pi electron donor-acceptor (EDA) exerted as the main molecular-scale interactions. Charring elevated partition coefficients (K(oc)) of the three PAHs more than one order of magnitude, which ranged from 10(5.74) to 10(6.58) on charcoals (for PAHs at equilibrium concentration C(e)=0.005S(w)). Adsorption increased with the aromaticity of the charcoals, however, polar aromatic structure may stimulate sorption of PAHs due to the presence of pi-pi EDA interactions.


Rheumatoid syndrome associated with lung interstitial disorder in a dental technician exposed to ceramic silica dust. A case report and critical literature review.
Exposure to silica minerals is associated with silicosis and autoimmune disorders, especially systemic scleroderma. Evidence of this association has been increasingly reported in the last decade. The aim of this paper is to discuss, on the basis of a literature review, the case of a 28-year-old female dental technician who suffered from episodes of weakness, arthralgia, pain, swelling and stiffness of the fingers, dyspnoea with cough, a positive Waaler-Rose reaction, increased rheumatoid factor and normal ESR. She was a non-smoker. A rheumatoid syndrome with lung interstitial disorder, associated with silica exposure from dental ceramic products, was diagnosed. The patient had the HLA-A2-A31, HLA-B51-B18 and HLA-DR3-DR11 haplotypes, some of which are associated with autoimmune disease susceptibility. A 6-month follow-up, with adequate protection and without treatment, showed disappearance of the symptomatology and negative tests for Waaler-Rose reaction and rheumatoid factor. Exposure to silica should, therefore, be sought in the history of any patient with autoimmune or lupus-like syndrome and pulmonary changes. Symptoms associated with silica dust exposure from dental ceramic products should be recognised as being due potentially to an occupational disease, and dental technicians should be protected as workers at risk.


Effects of peridural block: V. Properties, circulatory effects, and blood levels of etidocaine and lidocaine.
Ten healthy, unpremedicated, male volunteers, aged 21-33 years, were given 20 ml 1 per cent etidocaine with 5 mug/ml epinephrine for peridural analgesia via a catheter placed L2. On a different occasion they were given 20 ml 2 per cent lidocaine with 5 mug/ml epinephrine in the same manner. Initial onset of sensory analgesia to pin prick was faster for etidocaine (7 min) than for lidocaine (9 min). Analgesia lasted significantly longer after etidocaine with respect to both two-segment regression (177 plus or minus SE min vs. 114 plus or minus 8 min) and total duration (379 plus or minus 22 min vs. 190 plus or minus 8 min). Onset of maximal motor blockade was significantly faster with etidocaine (15.4 plus or minus 2.5 min) than with lidocaine (31.7 plus or minus 3.3 min); blockade lasted longer with etidocaine (331 plus or minus 25 min vs. 167 plus or minus 13 min). Changes in mean arterial pressure cardiac output, central venous pressure, limb blood flows, total peripheral resistance, and stroke volume were similar with the two drugs, although those after etidocaine were more prolonged as a result of the longer blockade. Mean maximum arterial concentrations of etidocaine were 0.96 plus or minus 0.05 SE mug/ml (plasma) and 0.55 plus or minus 0.03 mug/ml (whold blood), achieved at 17 plus or minus 2 min. Mean maximum arterial concentrations of lidocaine were 2.22 plus or minus 0.09 mug/ml (plasma) and 1.85 plus or minus mug/ml (whold blood), achieved at 24 plus or minus 2 min. No sign of central toxicity was observed with either drug, although subjects receiving lidocaine tended to sleep, which was not the case with etidocaine. Hematologic screening, blood chemistries, and urinalyses performed 24 hours before and after each study showed no abnormality.


Monitoring approaches to assess bioaccessibility and bioavailability of metals: matrix issues.
Bioavailability and bioaccessibility are complex issues that determine whether or not adverse effects are to be expected when organisms or plants are exposed to contaminants. Clearly, the determinants of bioavailability and bioaccessibility must be understood if one is to monitor or, ultimately, predict the effects of metals. On the basis of a dynamic conceptual model, this article offers an analysis of the physicochemical and biological determinants underlying bioavailability and bioaccessibility. This analysis is used as the basis for a general monitoring strategy for assessing potentially and actually available and accessible metal fractions in the environmental matrices of water, soil, and sediment. We conclude that, lack of a universal expression of bioavailable and bioaccessible metal fractions precludes the presentation of a detailed monitoring strategy that is broadly applicable. Instead, we recommend that a critical assessment of the endpoints of determination become the basis for a need-specific monitoring strategy.


Integrated rational and evolutionary engineering of genome-reduced Pseudomonas putida strains promotes synthetic formate assimilation.
Formate is a promising, water-soluble C1 feedstock for biotechnology that can be efficiently produced from CO2-but formatotrophy has been engineered in only a few industrially-relevant microbial hosts. We addressed the challenge of expanding the feedstock range of bacterial hosts by adopting Pseudomonas putida as a robust platform for synthetic formate assimilation. Here, the metabolism of a genome-reduced variant of P. putida was radically rewired to establish synthetic auxotrophies that could be functionally complemented by expressing components of the reductive glycine (rGly) pathway. We adopted a modular engineering approach, dividing C1 assimilation in segments composed of both heterologous activities (sourced from Methylobacterium extorquens) and native biochemical reactions. Modular expression of rGly pathway elements enabled growth on formate as carbon source and acetate (predominantly for energy supply), and adaptive laboratory evolution of two lineages of engineered P. putida formatotrophs lead to doubling times of ca. 15 h. We likewise identified emergent metabolic features for assimilation of C1 units in these evolved P. putida populations. Taken together, our results consolidate the landscape of useful microbial platforms that can be implemented for C1-based biotechnological production towards a formate bioeconomy.


Total respiratory system compliance after thoracoplasty.
Recent attention has been directed towards the deleterious effects of the sequelae of pulmonary tuberculosis on respiratory function. Thus, a study was undertaken to find out to what extent the deformity of thorax after thoracoplasty increases the mechanical work of breathing. Compliance of the total respiratory system (Crs) was measured with a pressure-type body plethysmograph in nine post-thoracoplasty tuberculosis patients, 15 patients with pulmonary tuberculosis and three patients with pleural diseases. Mean Crs in nine post-thoracoplasty tuberculosis patients was 0.0861 cmH2O-1, and that in six patients with moderately advanced pulmonary tuberculosis was 0.0841 cmH2O-1. Mean Crs (0.1301 cmH2O-1) in nine patients with a minimum lesion of tuberculosis was not different from the reference Crs values reported to date by several authors. Crs was significantly correlated with vital capacity, but not with functional residual capacity. There was no difference in specific Crs between post-thoracoplasty tuberculosis patients and patients with moderately advanced pulmonary tuberculosis. Crs of patients with a pleural disease was smaller than Crs of patients with a minimal lesion of pulmonary tuberculosis. The deformity of thorax after thoracoplasty caused a decrease of Crs. However, ventilation is not as severely impaired as anticipated from the degree of thorax deformity on chest X-ray film, providing that movement of the diaphragm is unrestricted.


A needed amendment that explains too much and resolves little.
Baumard's application of Life History Theory to explain the origins of economic growth is a needed amendment to incentive-based explanations of modern economics. However, even though it is grounded in evolution, the theory does not do enough to specify the relevant evolutionary mechanisms. As such, it accommodates too many alternative historic scenarios, yet remains unable to explain divergent regional patterns of economic growth.


Synthesis of 5-amino-N'-(9H-fluoren-9-ylidene)-8-nitro-7-aryl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide derivatives based on heterocyclic ketene aminals.
A new class of tetrahydroimidazo[1,2-a]pyridine derivatives has been successfully prepared via a five-component domino reaction using cyanoacetohydrazide, 9-fluorenone, aromatic aldehydes, 1,1-bis(methylthio)-2-nitroethene and ethylenediamine in ethanol at reflux. The new efficient cascade approach involves a sequence of N,N-acetal formation, Knoevenagel condensation, Michael addition, imine-enamine tautomerization and N-cyclization as key steps. The merit of this protocol is highlighted by its available and economical starting compounds, operational simplicity, clean reaction profile and tolerance of a wide diversity of functional groups.


Plasma zinc response to a breakfast meal or fasting in elderly women.
The aim of this study was to determine whether the postprandial decline in plasma zinc concentration is altered by aging. Eleven women, between the ages of 65 and 82 yr, participated in two separate experimental protocols: a high carbohydrate breakfast trial and a fasting trial. Plasma zinc concentrations were measured from blood samples obtained at 8:00 AM (baseline fasting) and at 30-min intervals until 1:00 PM during each trial. Following the breakfast meal, plasma zinc concentrations declined 14% from 75 +/- 1 to 65 +/- 2 micrograms/dL (p < 0.05), reaching a nadir 2.7 +/- 0.2 h after the meal. This decline was significantly (p < 0.0001) greater than the 3.6% fall observed during the fasting trial. Postprandial changes in the plasma zinc concentrations were correlated with postprandial changes in serum glucose (r = -0.43, p < 0.001), serum insulin (r = -0.17, p < 0.01), and serum phosphorus (r = 0.32, p < 0.005). These data show that plasma zinc concentrations decline following food intake in elderly women in the same manner as previously described for younger adult women.


Towards Process Mining in Radiology: Utilization of IHE SOLE.
Audit trails of health information systems are not useful for business analytics. To show how recent developments can be utilized to enable process mining in radiology. The SWIM lexicon is used to code the workflow steps. Seven activities with their corresponding RadLex codes. The semantic enrichment of audit trails is an important step in operationalizing and improving the workflows in radiology.


'The thief of womanhood': women's experience of polycystic ovarian syndrome.
Previous research on polycystic ovarian syndrome (PCOS) has overwhelmingly been conducted within a medical or psychiatric framework, and has failed to explore women's own experience of the syndrome. Interviews were conducted with 30 women with PCOS recruited through a national self-help organisation. Thematic analysis of the interviews revealed pervasive reports of feeling 'freakish', 'abnormal', and not 'proper' women. These feelings were related to three symptoms commonly experienced by women with PCOS: 'excess' hair growth; irregular, absent or disrupted periods; and infertility. Smooth hairless bodies and faces, regular menstruation and the capacity to bear children were associated with femininity, and as a result of their symptoms women expressed feeling 'different' from other women and less 'feminine'. The results are discussed within a feminist framework and suggest that polycystic ovarian syndrome is a deeply stigmatising condition, 'a theft of womanhood', with far reaching implications for all women, whether or not they conform to 'feminine' norms.


Assessment by Using a Water-Soluble Contrast Enema Study of Radiologic Leakage in Lower Rectal Cancer Patients With Sphincter-Saving Surgery.
This study evaluated the efficacy of a water-soluble contrast enema (WCE) in predicting anastomotic healing after a low anterior resection (LAR). Between January 2000 and March 2012, 682 consecutive patients underwent a LAR or an ultra-low anterior resection (uLAR) and were followed up for leakage. Clinical leakage was established by using physical and laboratory findings. Radiologic leakage was identified by using retrograde WCE imaging. Abnormal radiologic features on WCE were categorized into four types based on morphology: namely, dendritic, horny, saccular, and serpentine. Of the 126 patients who received a concurrent diverting stoma, only two (1.6%) suffered clinical leakage due to pelvic abscess. However, 37 patients (6.7%) in the other group suffered clinical leakage following fecal diversion (P = 0.027). Among the 163 patients who received a fecal diversion, 20 showed radiologic leakage on the first WCE (eight with and 12 without a concurrent diversion); 16 had abnormal features continuously until the final WCE while four patients healed spontaneously. Eleven of the 16 patients (69%), by their surgeon's decision, underwent a stoma restoration based on clinical findings (2/3 dendritic, 3/4 horny, 5/7 saccular, 1/2 serpentine). After stoma reversal, only 2 of the 11 (19%) complained of complications related to the rectal anastomosis. WCE is helpful for detecting radiologic leakage before stoma restoration, especially in patients suffering clinical leakage after an uLAR. However, surgeons appear to opt for stoma restoration despite the persistent existence of radiologic leakage in cases with particular features on the WCE.


Evaluation of adenosine agonists as potential analgesics.
Adenosine agonists, N6-cyclohexyladenosine (CHA), N6-cyclopentyladenosine (CPA), N6-phenylisopropyladenosine (PIA), 5'-N-ethylcarboxamidoadenosine (NECA), 5'-N-methylcarboxamidoadenosine (MECA) and 2-chloroadenosine (CADO), produced a dose-related inhibition of acetylcholine (ACh)-induced writhing in mice. The antinociceptive potency of adenosine agonists was comparable to that of morphine. Adenosine agonists were 10-1000 times more potent when given i.c.v. than p.o., suggesting a central site of action. Theophylline antagonized the antinociceptive activity of R-PIA in the writhing assay, suggestive of an adenosine receptor-mediated event. The sedative/ataxic properties of adenosine agonists were evaluated using a rotorod assay. Adenosine agonists impaired performance on the rotorod in doses comparable to and in some cases lower than those active in the ACh writhing assay. The results of the present study suggest that adenosine agonists attenuate nociceptive responding to a chemical stimulus through a central purinergic mechanism. The ability of adenosine agonists to inhibit ACh-induced writhing may be secondary to their sedative/ataxic properties.


Assessment of Tumor Response in Mice with Ovarian Peritoneal Carcinomatosis using Doppler Ultrasound of the Superior Mesenteric Artery and Celiac Trunk.
The goal of the work described here was to assess the performance of Doppler ultrasound (US) of the superior mesenteric artery (SMA) and celiac trunk (CT) in the evaluation of tumor response in female mice with ovarian peritoneal carcinomatosis treated either with bevacizumab or with carboplatin. Compared with untreated mice, carboplatin-treated mice had a lower weight (23.3 ± 2.0 vs. 27.9 ± 2.9 g, p < 0.001), peritoneal carcinomatosis index (PCI, 11 ± 3 vs. 28 ± 6, p < 0.001), Ki67-positive staining surfaces (p < 0.001), vascular density (p < 0.001), mean blood flow velocity (mBFVel) in the SMA (7.0 ± 1.4 vs. 10.9 ± 1.8 cm/s, p < 0.001) and CT (8.0 ± 1.8 vs. 14.3 ± 4.6 cm/s, p < 0.001) and no ascites. Weight and mBFVel were similar in bevacizumab-treated and untreated mice. The mBFVels in the SMA and CT correlated with the PCI used as an estimation of the tumor burden, R = 0.70 (p < 0.0001) and R = 0.65 (p < 0.0001), respectively. Doppler US allows non-invasive assessment of the effects of anticancer therapy in ovarian peritoneal carcinomatosis-induced mice.


Association between HLA-A1,B8 in children with extrinsic asthma and IgA deficiency.
The tissue types, immunoglobulin levels, and the presence of circulating autoantibodies were investigated in 57 children. Fifteen of these children suffered from bronchial asthma and, in addition, had no or very little IgA in their serum and saliva (Group 1 patients). Another fifteen children with asthma but normal immunoglobulin levels in serum and saliva (Group 2 patients), seven patients with selective IgA deficiency but without allergic diseases (Group 3 patients), and twenty healthy children served as controls. Sixty per cent of the Group 1 patients had the phenotype HLA-A1,B8, whereas this tissue type was found only in 27, 14 and 15 per cent, respectively, of the Group 2 and Group 3 patients and the healthy children. Furthermore, high IgM- and IgE levels were observed in most Group 1 patients, and in five of these patients (33 per cent) autoantibodies were present in the serum. In addition, eczema and glomerulonephritis occurred rather frequently in this group of patients. Conversely, normal immunoglobulin levels and absence of circulating autoantibodies were found in the remaining three groups of children. The results emphasize the heterogeneity of the IgA deficiency syndrome, and the question is raised as to whether the tissue type HLA-A1,B8 observed in most Group 1 patients reflects the abnormal immune reactivity of these patients.


Community-based programmes to prevent falls in children: a systematic review.
We systematically reviewed the literature to examine the evidence for the effectiveness of community-based interventions to reduce fall-related injury in children aged 0-16 years. We performed a comprehensive search of the literature using the following study selection criteria: community-based intervention study; target population was children aged 0-16 years; outcome measure was fall-related injury rates; and either a community control or historical control was used in the study design. Quality assessment and data abstraction were guided by a standardized procedure and performed independently by two authors. Only six studies fitting the inclusion criteria were identified in our search and only two of these used a trial design with a contemporary community control. Neither of the high quality evaluation studies showed an effect from the intervention and while authors of the remaining studies reported effective falls prevention programmes, the pre- and post-intervention design, uncontrolled for background secular trends, makes causal inferences from these studies difficult. There is a paucity of research studies from which evidence regarding the effectiveness of community-based intervention programmes for the prevention of fall-related injury in children could be based.


Optimal load for a torque-velocity relationship test during cycling.
Lower limbs' neuromuscular force capabilities can only be determined during single sprints if the test provides a good fit of the data in the torque-velocity (T-V) and power-velocity (P-V) relationships. This study compared the goodness of fit of single sprints performed against traditional (7.5% of the body mass) vs. optimal load (calculated based on the force production capacity and ergometer specificities), and examined if reducing the load in fatigued state enhances T-V and P-V relationship goodness of fit. Thirteen individuals performed sprints before (PRE) and after (POST) a fatiguing task against different loads: (1) TRAD: traditional, (2) OPT: optimal, and (3) LOW-OPT: optimal load reduced according to fatigue levels. At PRE, OPT sprints presented a higher R2 of the T-V relationship (0.92 ± 0.06) and lower time to reach maximal power (Pmax) (48 ± 9%) when compared with TRAD sprints (0.89 ± 0.06 and 66 ± 22%, respectively, p < 0.01). At POST, the range of velocity spectrum was greater in the LOW-OPT (33 ± 4%) vs. TRAD (24 ± 3%) and OPT (26 ± 8%, p < 0.007). Similarly, the time to reach Pmax was lower in the LOW-OPT (46 ± 12%) vs. TRAD (76 ± 24%) and OPT (70 ± 24%, p < 0.006). Sprints performed against an OPT load and reducing the OPT load after fatigue improve the fit of data in the T-V and P-V curves. Sprints load assignment should consider force production capacities rather than body mass.


Exploring the distributional environmental justice implications of an air quality monitoring network in Los Angeles County.
Non-governmental air quality monitoring networks include low-cost, networked air pollution sensors hosted at homes and schools that display real-time pollutant concentration estimates on publicly accessible websites. Such networks can empower people to take health-protective actions, but their unplanned organization may produce an uneven spatial distribution of sensors. Barriers to acquiring sensors may disenfranchise particular social groups. To test this directly, we quantitatively examine if there are social inequalities in the distribution of sensors in a non-governmental air quality monitoring network (PurpleAir) in Los Angeles County, California. We paired sociodemographic data from the American Community Survey and estimates of PM2.5 concentrations from the USEPA's Downscaler model at the census tract level (n = 2203) with a sensors per capita (SPC) variable, which is based on population proximity to PurpleAir sensors (n = 696) in Los Angeles County. Findings from multivariable generalized estimating equations (GEEs) controlling for clustering by housing age and value reveal patterns of environmental injustice in the distribution of PurpleAir sensors across Los Angeles County census tracts. Tracts with higher percentages of Hispanic/Latino/a and Black residents and lower median household income had decreased SPC. There was a curvilinear (concave) relationship between the percentage of renter-occupants and SPC. Sensors were concentrated in tracts with greater percentages of adults and seniors (vs. children), higher occupied housing density, and higher PM2.5 pollution. Results reveal social inequalities in the self-organizing PurpleAir network, suggesting another layer of environmental injustice such that residents of low-income and minority neighborhoods have reduced access to information about local air pollution.


SDH-deficient renal cell carcinoma: A case report associated with a novel germline mutation.
The highly syndromic nature of succinate dehydrogenase-deficient RCCs constitutes their active surveillance and molecular profiling the alpha and omega.


Polyploid tubular cells initiate a TGF-β1 controlled loop that sustains polyploidization and fibrosis after acute kidney injury.
Polyploidization of tubular cells (TC) is triggered by acute kidney injury (AKI) to allow survival in the early phase after AKI, but in the long run promotes fibrosis and AKI-chronic kidney disease (CKD) transition. The molecular mechanism governing the link between polyploid TC and kidney fibrosis remains to be clarified. In this study, we demonstrate that immediately after AKI, expression of cell cycle markers mostly identifies a population of DNA-damaged polyploid TC. Using transgenic mouse models and single-cell RNA sequencing we show that, unlike diploid TC, polyploid TC accumulate DNA damage and survive, eventually resting in the G1 phase of the cell cycle. In vivo and in vitro single-cell RNA sequencing along with sorting of polyploid TC shows that these cells acquire a profibrotic phenotype culminating in transforming growth factor (TGF)-β1 expression and that TGF-β1 directly promotes polyploidization. This demonstrates that TC polyploidization is a self-sustained mechanism. Interactome analysis by single-cell RNA sequencing revealed that TGF-β1 signaling fosters a reciprocal activation loop among polyploid TC, macrophages, and fibroblasts to sustain kidney fibrosis and promote CKD progression. Collectively, this study contributes to the ongoing revision of the paradigm of kidney tubule response to AKI, supporting the existence of a tubulointerstitial cross talk mediated by TGF-β1 signaling produced by polyploid TC following DNA damage.NEW & NOTEWORTHY Polyploidization in tubular epithelial cells has been neglected until recently. Here, we showed that polyploidization is a self-sustained mechanism that plays an important role during chronic kidney disease development, proving the existence of a cross talk between infiltrating cells and polyploid tubular cells. This study contributes to the ongoing revision of kidney adaptation to injury, posing polyploid tubular cells at the center of the process.


Verification of the C-terminal intramolecular beta-sheet in Abeta42 aggregates using solid-state NMR: implications for potent neurotoxicity through the formation of radicals.
Structural analysis of 42-residue amyloid beta (Abeta42) aggregates using rotational resonance in solid-state NMR verified that C(beta) and/or C(gamma) of Met-35 and the carboxyl carbon of Ala-42 are proximal enough to form an intramolecular antiparallel beta-sheet in the C-terminus. The S-oxidized radical cation at Met-35, an ultimate radical species responsible for neurotoxicity, could be stabilized by the carboxylate anion at the C-terminus, resulting in aggregation to cause long-term oxidative stress.


It Is All in the Genes: A Story of Unexpected Survival in a 67-Year-Old Male with Metastatic Pancreatic Cancer.
We describe a case report of a 67-year-old male with PDAC who experienced an exceptional survival outcome during systemic therapy and its implications in precision medicine. We hypothesize that his outcomes are attributable, in part, to a germline BRCA2 deletion and somatic GNAS substitution. Retrospective single-patient chart review was performed at the London Regional Cancer Program, as well as a structured literature search spanning all years in PubMed of BRCA and GNAS mutations in pancreatic cancer. The case described herein represents a 67-year-old male who survived over 27 months after third-line treatment with gemcitabine, docetaxel, and capecitabine (GTX) chemotherapy for metastatic PDAC after progression on gemcitabine and Abraxane and then on FOLFIRINOX. His survival far exceeded the median overall survival metrics. Genetic testing revealed a pathogenic heterozygous germline BRCA2 6643delT p.(Tyr2215Thrfs∗14) frameshift mutation and somatic GNAS 2531G > A p.(Arg844His) mutation. This case highlights the urgent need to expand our knowledge of cancer biology to advance personalized cancer treatment and therapy development.


Biomechanical Stability Analysis of a Stand-alone Cage, Static and Rotational-dynamic Plate in a Two-level Cervical Fusion Construct.
To test the following hypotheses: (i) anterior cervical discetomy and fusion (ACDF) using stand-alone interbody spacers will significantly reduce the range of motion from intact spine; and (ii) the use of a static or a rotational-dynamic plate will significantly augment the stability of stand-alone interbody spacers, with similar beneficial effect when compared to each other. Eleven human cadaveric subaxial cervical spines (age: 48.2 ± 5.4 years) were tested under the following sequence: (i) intact spine; (ii) ACDF at C4 -C5 using a stand-alone interbody spacer; (iii) ACDF at C5 -C6 and insertion of an interbody spacer (two-level construct); and (iv) randomized placement of either a two-level locking static plate or a rotational-dynamic plate. Insertion of stand-alone cage at C4 -C5 and C5 -C6 caused a significant decrease in the range of motion compared to intact spine (P < 0.05). Placement of both the locking and the rotational dynamic plate further reduced the range of motion at C4 -C5 and C5 -C6 compared to stand-alone cage (P < 0.01). No significant differences in range of motion restriction at either C4 -C5 or C5 -C6 were found when the two plating systems were compared (P > 0.05). Cervical stand-alone interbody spacers caused significant restriction in the range of motion. Both plates significantly augmented the stability of stand-alone interbody spacers, with similar stabilizing effect.


No association between a common type 2 diabetes risk gene variant in the melatonin receptor gene (MTNR1B) and mortality among type 2 diabetes patients.
The minor G risk allele in the common melatonin receptor gene (MTNR1B, rs10830963) has been associated with an increased risk of myocardial infarction among patients with type 2 diabetes (T2D). Furthermore, activating the melatonin receptor 1B through melatonin has been shown to promote cell proliferation, which could be hypothesized to increase cancer risk. Cardiovascular disease (CVD) and cancer are common causes of death among patients with T2D. Using data from 14 736 patients with T2D who participated in the UK Biobank investigation, we hypothesized an additive effect of the G risk allele on all-cause mortality, CVD mortality, and cancer mortality. As shown by Cox regression adjusted for confounders such as age, glucose-lowering medication, and socioeconomic status, no significant trend between the number of G risk alleles and mortality outcomes was found during the follow-up period of 11.1 years. Our negative findings do not speak against the role of this gene variant in the development of T2D, as repeatedly shown by previous large-scale studies. Instead, they may suggest that rs10830963 is less relevant for mortality risk in patients with T2D.


Retracted: Construction and Analysis of Performance Evaluation Index System for Chinese Small and Medium-Sized Enterprises Based on Fuzzy Hierarchical Analysis Model.
[This retracts the article DOI: 10.1155/2022/1230786.].


The influence of surface energy on the wetting behaviour of the spore adhesive of the marine alga Ulva linza (synonym Enteromorpha linza).
The environmental scanning electron microscope has been used to image the adhesive pads secreted by zoospores of the marine alga Ulva linza as they settle on a range of self-assembled and grafted monolayers of different wettability, under natural, hydrated conditions. Results reveal that the diameter of the adhesive pad is strongly influenced by surface wettability, the adhesive spreading more (i.e. wetting the surface better) on the more hydrophilic surfaces. This is in direct contrast to previous observations on the spreading of marine bioadhesives and is in apparent contradiction to the predictions of the Young-Dupre equation for three-phase systems. In this paper, we attempt an explanation based upon thermodynamic analysis of the wetting properties of hydrophilic proteins.


Trends and directions in developmental research.
Perhaps one of the most dramatic fundamental changes in our views of child development has been the relatively recent shift from Freud's view of the infant as an individual struggling to avoid displeasure to Piaget's view of an individual who from the first day of life is essentially an active initiator of all kinds of interactions with his or her environment. Subsequent interactional research shifted the focus again to the interaction among biologic, psychological, and environmental factors. Within this context, infant behavior has probably been the largest single expanding area of child development research in recent years. Some discernible trends and directions of special interest to the clinician will be noted here.


Search and Rescue in the Pacific West States.
The training practices and the level of medical oversight of search and rescue (SAR) organizations in the US National Park Service (NPS) Pacific west region is not known. A database of SAR teams in the NPS Pacific west region was assembled using public sources. SAR team leaders received an electronic survey between May and December 2019. A descriptive analysis characterizing team size, technical and medical training protocols, and medical oversight was completed. Results are reported as median (interquartile range, range). Of the 250 SAR teams contacted, 39% (n=97) completed our survey. Annual mission volume was 25 (10-50, 1-200). Team size was 30 members (22-58, 1-405). SAR teams most frequently trained in helicopter operations (77%), low-angle rope rescue (75%), and avalanche rescue (43%). Nearly all teams (99%) had members with some medical training: first aid or cardiopulmonary resuscitation (89%), emergency medical technicians (75%), registered nurses or midlevel providers (52%), and physicians (40%). SAR members administered field medical care (84%), often in coordination with EMS (77%). Medical direction was present on a minority of teams (45%), most frequently by a provider specialized in emergency medicine (68%). Expanded medical procedures were permitted on 21% of SAR teams. SAR teams across the NPS Pacific west region had composition and training standards similar to those surveyed previously in the US intermountain states. Healthcare professionals were present on most teams, typically as team members, not as medical directors. Few SAR teams use medical protocols in remote care environments.


In vitro susceptibility of methicillin-resistant and methicillin-susceptible strains of Staphylococcus aureus to two different cold atmospheric plasma sources.
Staphylococcus aureus may be the most important wound pathogen and causative for most of surgical site infections. As many anti-staphylococcal drugs are useless because of resistance, novel antimicrobial strategies are strongly needed and may be provided by cold atmospheric plasma (CP), which is being currently investigated for antiseptic efficacy. To test the antimicrobial properties of CP against Staphylococcus aureus, 168 methicillin-susceptible isolates (MSSA) and 50 methicillin-resistant isolates (MRSA) were treated with two technically different plasma sources [an atmospheric pressure plasma jet (APPJ) and a dielectric barrier discharge plasma (DBD)] in vitro. CP treatment allowed a reproducible and significant growth reduction of MRSA and MSSA. However, MRSA was significantly less susceptible to treatment with DBD than was MSSA, while no difference between MRSA and MSSA was found using APPJ. As the initial physical antiseptic on skin, CP may be suitable for rapid decolonization of microbial pathogens in vivo. Each device must undergo validated efficacy testing prior to clinical application, as device related differences may occur.


Effects of dietary supplementation of bacteriophage cocktail on health status of weanling pigs in a non-sanitary environment.
The study evaluated the effects of bacteriophage cocktail (BP) and ZnO administered during weaning time for piglets exposed to a non-sanitary environment. The bacteriophages were designed to eliminate Escherichia coli (K88, K99 and F41), Salmonella (typhimurium and enteritidis), and Clostridium perfreingens (types A and C). Forty 21-day-old crossbreed piglets were assigned to four treatments, including the PC (sanitary environment), NC (non-sanitary environment), BP (NC plus 108 pfu/kg BP), and ZO (NC plus 2,500 mg/kg ZnO). Piglets in the NC, BP and ZO were kept in a non-sanitary environment for 14 d, which was contaminated with the feces of infected pigs. Pigs in the BP and ZO treatments had a higher final body weight compared with the NC. The NC treatment showed the highest concentration of inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α in the plasma. The administration of BP and ZO showed lower myeloperoxidase concentrations compared with the NC. The NC treatment showed a lower concentration of superoxide dismutase in serum compared with the PC. Among the treatments in non-sanitary environment, the NC treatment showed a higher concentration of malondialdehyde compared with the ZO. The PC treatment showed a lower concentration of butyric acid in the feces compared with the BP treatment. Among non-sanitary treatments, the villus height in the duodenum was greater in the BP and ZO compared with the NC. The lower abundance of Proteobacteria phylum was observed in the BP and PC treatments compared with the NC. The highest relative abundance of Eubacterium was recorded in the BP treatment. The abundance of Megasphaera and Schwartzia was higher in the NC pigs compared with the BP piglets. The abundance of Desulfovibrio was lower in the supplemented treatments (BP and ZO) compared with non-supplemented (NC and PC). The abundance of Cellulosilyticum genera was higher in the BP and ZO treatments rather than in the NC. The piglets in the NC treatment had the highest abundance of Escherichia-Shigella, followed by the PC and ZO treatments. In conclusion, these results suggest that the supplementation of bacteriophage cocktail could effectively control Proteobacteria phylum, Clostridium spp. and coliforms population and mitigated the adverse influences of weaning stress in piglets.


Self-reported oral health and quality of life: a latent growth curve analysis.
The longitudinal associations between oral health (OH) and physical and mental health-related quality of life (HRQoL) are unclear. This study examined the relationship of self-reported OH with the trajectories of physical and mental HRQoL in Hong Kong at 3, 9, and 15 months after the measurement period using a latent growth curve model. This study included 5,710 participants recruited in the FAMILY project cohort study during March-October 2009. Self-report OH was measured using a five-point single-item scale, and HRQoL was measured using the physical component scale (PCS) and mental component scale (MCS) of Short Form 12. Latent growth curve model was used to compute the relationship of self-reported OH with the trajectories on HRQoL over time, adjusted for age and sex. The latent growth curve model gave good fit to both the PCS (normed fit index (NFI) = 0.98, comparative fit index (CFI) = 0.99, and standardized root mean square residual (SRMR) = 0.03) and MCS (NFI = 0.97, CFI = 0.98, and SRMR = 0.03). Better self-reported OH was associated with higher PCS and MCS at the baseline. The longitudinal association with PCS remained constant over time (coefficient = -0.02, p = 0.07) but that with MCS diminished over time with baseline oral health status (coefficient = -0.04, p = 0.002). Better self-reported OH status was associated with higher level of physical and mental HRQoL, and with negative change in mental HRQoL.


Treatment of migraine with intramuscular chlorpromazine.
We undertook a prospective, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of intramuscular parenteral chlorpromazine (CPZ) in the treatment of the acute migraine attack. Thirty-six patients who presented to the emergency department with migraine headache were given either CPZ (1 mg/kg) or a saline placebo and were observed for one hour. Of those receiving CPZ, nine of 19 (47.4%) had sufficient relief from their headache to carry on with their activities of daily living, compared with four of 17 (23.5%) of the control group. This difference was not statistically significant. However, the drug was more often effective than a placebo in giving some relief from the headache (P less than .005) and in relieving nausea significantly more often than placebo (P less than .001). The only significant side effects were drowsiness (P less than .01), and an asymptomatic drop in blood pressure (10 mm Hg systolic) (P less than .05). This controlled study demonstrates that CPZ is a safe medication that provides some relief from migraine headaches, but it is less efficacious than suggested in earlier reports.


Neuronal PAC1 receptors mediate delayed activation and sensitization of trigeminocervical neurons: Relevance to migraine.
The pathogenesis of migraine is not well understood. To dissect the relative contributions of endogenous peripheral and central mechanisms in triggering migraine, we examined the effects of two pharmacologically similar, but clinically different, vasodilator neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide 38 (PACAP-38), on dural meningeal vessels and the response properties of central trigeminovascular neurons. Both VIP and PACAP-38 caused short-lived meningeal vasodilation mediated by VPAC2 receptors, which did not coincide with activation of central trigeminovascular neurons. Only PACAP-38 caused delayed activation and sensitization of central trigeminovascular neurons, similar to its delayed effects in inducing migraine headache. After a 90-min delay, PACAP-38 induced a robust increase in ongoing spontaneous firing and hypersensitivity to intra- and extracranial somatosensory stimulation, which did not coincide with meningeal vasodilation. Only intravenous delivery of a PAC1 receptor antagonist inhibited the peripheral meningeal vasodilatory effects of dural trigeminovascular nociception, whereas only central (intracerebroventricular) administration of the PAC1 receptor antagonist inhibited dural nociceptive-evoked action potentials in central trigeminovascular neurons. Our data suggest that the endogenous mechanisms of migraine pathogenesis are located within the central nervous system, likely in the trigeminocervical complex, and that the dural meninges and their primary afferent innervation are less likely to contribute to migraine initiation. Furthermore, the PAC1 receptor may be an appropriate molecular target for migraine therapeutics.


Ankle sprain complications: MRI evaluation.
Sprains are disruptions of the ligamentous anatomy about a joint. The ankle sprain is one of the most common injuries seen in podiatric and orthopedic practice. It usually is incurred from an inversion force on the ankle, but eversion forces also can traumatize the ankle. Many times, this injury is taken for granted because of the frequency of its presentation. The patient usually is given appropriate initial care, but the patient can experience continued or residual pain. Podiatrists have found this problem is common and have come to recognize that secondary or accessory injuries occur that slow the natural recovery of this injury.


Circadian profile of plasma cortisol and aldosterone in post-traumatic comatose patients under high-dose dexamethasone treatment.
Six comatose patients hospitalized in an intensive care unit immediately following an acute trauma with severe brain injury (road or industrial accident) were examined through out three consecutive 24-h cycles in the first week after trauma, when receiving intramuscularly 12 mg daily of dexamethasone-21-phosphate. Intravenous or enteral nutrition was supplied continuously. Plasma cortisol and aldosterone were measured on blood samples drawn at 4-h intervals. Data were analyzed both by conventional chronograms and by rhythmometric analysis according to the Cosinor procedures. A normally-synchronized circadian pattern of plasma cortisol was recognizable in all cases in the face of the lack of consciousness and of the pharmacological administration of dexamethasone. Acrophase was located at 08:56, with a 95% confidence region vastly overlapping the corresponding region of the controls. By contrast, the circadian pattern of plasma aldosterone appeared to be disrupted; irregular fluctuations were recorded along the entire day. The Cosinor analysis did not detect a significant rhythm of plasma aldosterone during the examined 24-h cycles. Data obtained with the present investigation demonstrate that comatose patients within a few days after severe head injury and given high-dose corticoid treatment do maintain the normal circadian organization of the plasma cortisol, whereas loose that of the plasma aldosterone. Our findings are compatible with the concept that glucocorticoid rhythmicity is particularly resistant to acute injury; the mineralocorticoid rhythmicity appears more labile probably as a consequence of the plurifactorial modulation.


Differential uptake of 2-fluoro-2-deoxyglucose by normal and transformed chicken and mouse fibroblasts as a function of glucose concentration.
Recently, [18F]-2-fluorodeoxyglucose, a positron emitter, has found an important application in certain metabolic studies using external scanning techniques. We have studied [14C]-2-fluorodeoxyglucose, [3H]-2-deoxyglucose and [14C]-D-glucose uptake in normal and transformed chicken and mouse fibroblasts to determine whether such external scanning techniques might be applicable to detect in vivo tumoral localisations. In this in vitro model, with glucose concentrations in the culture medium below that of normal animal blood, transformed cells showed a higher uptake of all three hexose tracers than did normal cells. However, at physiological glucose concentrations there was no differential uptake of these hexoses. Therefore our results suggest that [18F]-fluorodeoxy-glucose would be of no help in the in vivo detection of tumour localisations by external positron scanning unless in vitro and in vivo cell behavior differs considerably.


Open study of the safety and efficacy of a single oral dose of cefixime for the treatment of gonorrhea in pregnancy.
The intent of this study was to determine the efficacy and tolerance of single dose oral cefixime use in the treatment of pregnant women with endocervical gonococcal carriage. A retrospective review of clinic records over a 3 year period identified patients treated with a single 400 mg dose of cefixime for gonorrhea during pregnancy. Side effects and subsequent gonococcal carriage were noted. Pregnant women (n = 102) treated with cefixime were reviewed. A cure rate of 95.2% was found. Side effects were reported in three patients: two had nausea and vomiting and one had diarrhea. A single 400 mg oral dose of cefixime was effective for the treatment of gonorrhea and was well tolerated by the pregnant women.


Synthesis and characterization of 6-O-(N-heptylcarbamoyl)-methyl-alpha-D-glucopyranoside, a new surfactant for membrane studies.
A new surfactant, 6-O-(N-heptylcarbamoyl)-methyl-alpha-D-glucopyranoside (HECAMEG, molar mass 335.38 g), was synthesized by a simple and low cost procedure from methyl-alpha-D-glucopyranoside. This surfactant is characterized by a high solubility in water (even at 0 degree C), ultraviolet light transparency in the region useful for protein detection, and a high critical micellar concentration (CMC = 19.5 mM), permitting fast elimination by dialysis. Furthermore, the surfactant is colorimetrically titratable by the anthrone technique and its weak interference in protein titration by the Lowry et al. procedure and the bicinchoninic method is easy to overcome. Two membrane proteins (NADH oxidase and succinate dehydrogenase) and a soluble enzyme (lactoperoxidase) retained full activity in the presence of HECAMEG below or above its CMC. The partial inhibition of beta-lactamase (soluble form) by HECAMEG above the CMC was probably only apparent and due to an interference of the surfactant with the substrate rather than a direct effect on the enzyme. HECAMEG was capable of extracting up to 75% of bacteriorhodopsin from the purple membrane of Halobacterium halobium in a nondenatured form as indicated by the spectral properties of the protein. It also solubilized spiralin from the Spiroplasma melliferum membrane with a great selectivity and efficiency, without detectable loss of antigenic properties. These data show that HECAMEG is a very mild surfactant, useful for membrane protein studies.


Whole body vibration in the static modified push-up position in untrained healthy women stimulates neuromuscular system potentiating increased handgrip myogenic response.
To investigate the acute effect of whole-body vibration (WBV) on handgrip strength (HS) and electromyographic activity of the flexor digitorum superficialis muscle of healthy women in the static push-up position. Twenty-eight women received four experimental tests in a randomized order: A) Control - rest in seating position with feet on the floor and hands in the supine position on the lower limbs. There was no vibration stimulus; B) Placebo - push-up position with their hands on the vibratory platform that remained disconnected, but with a sonorous stimulus mimicking the vibration; C) Low vibration and D) High vibration - push-up position with their hands on the vibratory platform using one of the vibratory stimulus intensity: low vibration: 25 Hz/2 mm/49.30 m s-2; or high vibration: 45 Hz/2 mm/159.73 m s-2. Participants remained 5 min in each situation. HS and electromyography (EMG) were performed at baseline and after all four experimental tests. The index of neural efficiency (i.e. the ratio between EMG and HS) was also calculated to determine the efficiency of muscle contraction. Statistical analysis was performed by ANOVA two-way design mixed test with Tukey's post hoc test, being considered significant p < 0.05. High vibration increased HS compared with all the other experimental tests (p = 0.0006, F = 6.03). There was a reduction of EMG activity of the flexor digitorum superficialis muscle only after high vibration (p = 0.0135, F = 6.22), which was accompanied by lower values of the index of neural efficiency after intervention (between-group difference, p = 0.0002, F = 0.674). WBV in the push-up position has an acute positive effect on HS accompanied by a lower index of neural efficiency, providing a better efficiency of muscle contraction.


Giant cell tumor in Paget's disease of bone: familial and geographic clustering.
Four patients with benign giant cell tumor and one patient with probable benign giant cell tumor associated with Paget's disease of bone are reported. The familial and geographic clustering of these cases is unique in that three patients were related and all patients traced ancestral roots to the same area of southern Italy. Tumors arose from the cranial or facial bones in three patients and from vertebral bodies in two patients. All caused symptoms by local compression, and treatment by curettage or radiotherapy was successful in all patients. Three separate tumors in one patient shrank dramatically in response to treatment with high doses of dexamethasone, and one patient whose tumor caused spinal cord compression showed marked improvement in neurologic function on therapy with dexamathasone.


Investigating changes in atmospheric aerosols properties over the Indo-Gangetic Plain during different phases of COVID-19-induced lockdowns.
Impact of COrona VIrus Diseases 2019 (COVID-19) restrictive measures on aerosol optical depth (AOD) and black carbon (BC) concentration is investigated for the western, central, and eastern Indo-Gangetic Plain (IGP) using satellite-based observations. Due to COVID-19-induced lockdown measures, a noticeable decline in AOD and BC concentrations was observed across the IGP when compared to pre-lockdown period of 2020 and the lockdown concurrent period of 2015-2019. During the total lockdown period, a maximum drop in AOD and BC was observed in the central IGP (26.5 % and 10.1 %), followed by western IGP (24.9% and 5.2%) and eastern IGP (23.2 % and 4.9 %) with respect to the same period of 2015-2019. We have removed seasonal influences on aerosol properties during the COVID-19 lockdown, by taking average seasonal variations during the period of 2015-2019 as reference and projecting the hypothetical AOD and BC for the lockdown period under normal scenario. The difference between the hypothetical AOD and BC (under normal scenario) and the retrieved AOD and BC for the lockdown period is the absolute percentage change in AOD and BC concentration due to the lockdown alone. This elimination of seasonal influence is a novel approach. Central IGP showed an absolute decrease in AOD and BC of 38.5% and 18.2% during the lockdown period followed by western IGP (34.6% and 7.7%) and eastern IGP (25.9% and 11.5%). The observed absolute reduction in AOD, 26-39 %, is significantly higher than the global average reduction in AOD of 2-5%. CALIPSO-derived aerosol sub-types over major location of the western, central, and eastern IGP suggests prevalence of anthropogenic activities during pre- and post-lockdown periods. During the lockdown, IGP was influenced by aerosols from natural sources, with mineral dust and polluted dust in the western and central IGP, and aerosols from marine regions in the eastern IGP. Replenishment of aerosols within the boundary layer were far quicker when compared to total column during post-lockdown. Overall, the study reveals a reduction in anthropogenic emissions during the COVID-19-induced lockdowns, leading to temporary improvements in air quality over the IGP. Our study presents a comprehensive analysis of COVID-19 lockdown impact on aerosols properties over the IGP and highlights unprecedented reductions in AOD (~ 40 %) and BC (~ 20 %), due to imposition of lockdown and subsequent cessation of aerosol sources, by removing seasonal influences.


Luteinizing hormone bioactivity and variable responses to clomiphene citrate in chronic anovulation.
In 18 women with infertility and chronic anovulation with normal gonadotropins, three different responses were observed to increasing doses (250 to 750 mg) of clomiphene citrate (CC). Follicle development and ovulation in 8, follicle development but no ovulation without human chorionic gonadotropin (hCG) in 6, and no response to CC in 4. Serum concentrations of bioactive luteinizing hormone (bioactive-LH), immunoactive (immunoactive-LH), follicle-stimulating hormone, and estradiol (E2) were measured and follicle growth was assessed by daily ultrasound. Findings were compared with 8 normal ovulatory controls. Folliculogenesis on CC therapy, based on our data, was 78%; however, only 44% ovulated spontaneously, 34% required hCG for follicle rupture. There were no apparent hormonal indicators to predict responders from nonresponders. The absence of an LH surge in the presence of follicles and sustained high E2 concentrations in 34% of patients may be associated with a decreased E2 sensitivity at the hypothalamic-pituitary level. Ultrasound easily identified patients who responded to CC with folliculogenesis but did not initiate an LH surge. Follicle rupture was achieved promptly by hCG administration.


TSH response to TRH and family history of alcoholism.
The thyrotropin (TSH) response to intravenous thyrotropin-releasing hormone (TRH) was evaluated in 10 sons of alcoholic fathers (FHP group) and 10 matched controls (FHN group). No differences were observed between the two groups in basal TSH, peak TSH levels, on the incidence of TSH-blunting to TRH. Though there was a trend for a less intense TSH response over time after the TRH infusion, the difference between the family groups was not significant. These results are not consistent with some previous reports of an increased percentage of blunted TSH response to TRH for children of alcoholics. The clinical and research implications of these findings are discussed.


Influence of individual characteristics on static rotational knee laxity using the Rotameter.
The purpose of this study was to evaluate the influence of individual characteristics on rotational knee laxity in healthy participants. Our second aim was to verify whether the contralateral knee of patients with a non-contact ACL injury presents greater rotational knee laxity than a healthy control group. Sixty healthy participants and 23 patients having sustained a non-contact ACL injury were tested with a new Rotameter prototype applying torques up to 10 Nm. Multiple linear regressions were performed to investigate the influence of gender, age, height and body mass on rotational knee laxity and to establish normative references for a set of variables related to rotational knee laxity. Multiple analyses of covariance were performed to compare the contralateral knee of ACL-injured patients and healthy participants. Being a women was associated with a significantly (P < 0.05) higher rotational knee laxity, and increased body mass was related to lower laxity results. In the multiple analyses of covariance, gender and body mass were also frequently associated with rotational knee laxity. When controlling for these variables, there were no differences in measurements between the contralateral leg of patients and healthy participants. In the present setting, gender and body mass significantly influenced rotational knee laxity. Furthermore, based on these preliminary results, patients with non-contact ACL injuries do not seem to have excessive rotational knee laxity. Retrospective comparative study, Level III.


Intracochlear schwannoma: Imaging diagnosis.
Intralabyrinthine schwannomas (ILS) are rare benign tumors, often responsible for hearing loss. MRI is important in establishing the diagnosis. We present the example of a 48-year-old lady who reported a 3-years history of right-sided sensorineural deafness. MRI demonstrated a loss of the normal hypersignal of the second turn of the right cochlea compatible with intracochlear schwannoma.


Males from populations with higher competitive mating success produce sons with lower fitness.
Female mate choice can result in direct benefits to the female or indirect benefits through her offspring. Females can increase their fitness by mating with males whose genes encode increased survivorship and reproductive output. Alternatively, male investment in enhanced mating success may come at the cost of reduced investment in offspring fitness. Here, we measure male mating success in a mating arena that allows for male-male, male-female and female-female interactions in Drosophila melanogaster. We then use isofemale line population measurements to correlate male mating success with sperm competitive ability, the number of offspring produced and the indirect benefits of the number of offspring produced by daughters and sons. We find that males from populations that gain more copulations do not increase female fitness through increased offspring production, nor do these males fare better in sperm competition. Instead, we find that these populations have a reduced reproductive output of sons, indicating a potential reproductive trade-off between male mating success and offspring quality.


Acoustic Trauma Causes Cochlear Pericyte-to-Myofibroblast-Like Cell Transformation and Vascular Degeneration, and Transplantation of New Pericytes Prevents Vascular Atrophy.
Acoustic trauma disrupts cochlear blood flow and damages sensory hair cells. Damage and regression of capillaries after acoustic trauma have long been observed, but the underlying mechanism of pathology has not been understood. We show herein that loud sound causes change of phenotype from neural/glial antigen 2 positive/α-smooth muscle actin negative to neural/glial antigen 2 positive/α-smooth muscle actin positive in some pericytes (PCs) on strial capillaries that is strongly associated with up-regulation of transforming growth factor-β1. The acoustic trauma also reduced capillary density and increased deposition of matrix proteins, particularly in the vicinity of transformed PCs. In a newly established in vitro three-dimensional endothelial cell (EC) and PC co-culture model, transformed PCs induced thicker capillary-like branches in ECs and increased collagen IV and laminin expression. Transplantation of exogenous PCs derived from neonatal day 10 mouse cochleae to acoustic traumatized cochleae, however, significantly attenuated the decreased vascular density in the stria. Transplantation of PCs pretransfected with adeno-associated virus 1-vascular endothelial growth factor-A165 under control of a hypoxia-response element markedly promotes vascular volume and blood flow, increased proliferation of PCs and ECs, and attenuated loud sound-caused loss in endocochlear potential and hearing. Our results indicate that loud sound-triggered PC transformation contributes to capillary wall thickening and regression, and young PC transplantation effectively rehabilitates the vascular regression and improves hearing.


Role of the COOH-terminal domains of meprin A in folding, secretion, and activity of the metalloendopeptidase.
Secreted forms of the alpha subunit of recombinant mouse meprin A include an NH2-terminal prosequence, a catalytic domain, and three COOH-terminal domains designated as MAM (meprin, A-5 protein, receptor protein-tyrosine phosphatase mu), MATH (meprin and TRAF homology), and AM (after MATH). In this study, the importance of these COOH-terminal domains for biosynthesis of secreted, activable forms of the protease was investigated. Transcripts of the meprin subunit truncated after the protease (alpha(1-275)), MAM (alpha(1-452)), and MATH (alpha(1-528)) domains or with individual domains deleted (DeltaMAM, DeltaMATH, and DeltaAM), were transfected into human embryonic kidney 293 cells. The wild-type subunit, DeltaMATH, DeltaAM, alpha(1-452), and alpha(1-528) were secreted into the media, although the DeltaAM mutant was secreted at very low levels. The DeltaMATH and alpha(1-452) mutants were not activable by limited proteolysis. The alpha(1-528) mutant was as active as wild-type meprin alpha against a bradykinin substrate, but had no activity against azocasein, and it, as all other mutants, was more vulnerable to extensive degradation by proteases than the wild-type protein. Pulse-chase experiments revealed that the DeltaMAM and alpha(1-275) mutants were rapidly degraded within cells. Treatment with lactacystin, a specific inhibitor of the proteasome, significantly decreased the degradation, indicating that the mutants lacking the MAM domain are degraded by the proteasome as misfolded proteins. These results indicate that the MAM domain is necessary for correct folding and transport through the secretory pathway, the MATH domain is required for folding of an activable zymogen, and the AM domain is important for activity against proteins and efficient secretion of the protein. The work demonstrates the interdependence of the domains for correct folding of an activable, stable, mature enzyme.


Controllable genetic manipulation of apoptosis of cells in culture.
Apoptosis of mammalian cell is under the control of a wide range of intracellular and extracellular factors-amongst them proteases, protein kinases, cytokines and the protein products of oncogenes and tumour suppressor genes. The c-myc proto-oncogene encodes an essential component of the cell's proliferative machinery and its deregulated expression is implicated in many cancers. Under certain conditions, c-Myc also acts as a potent inducer of apoptosis. We have developed a 'switchable' chimaeric c-Myc protein whose activity is dependent on the synthetic ligand, 4-hydroxytamoxifen. In cells expressing this switchable c-Myc, proliferation and apoptosis in cultured fibroblasts can be regulated by addition of 4-hydroxytamoxifen. We have further demonstrated the utility of a switchable gene transcription system for the induction of proteins with pro-apoptotic effect. Myc-induced apoptosis is inhibited by the action of certain cytokines or by expresson of exogenous proteins with anti-apoptotic potential such as Bcl-2. We show that inhibition of p53 using dominant negative molecules inhibits apoptosis induced by DNA damage but has little effect on Myc-induced apoptosis. Finally, we have also been able to modulate a relatively late stage in apoptosis using inhibitors of cysteine proteases. Our data suggest a model in which the integrated activities of several proteins with diverse molecular functions may determine whether a particular cell undergoes apoptosis but that, once the actual catalytic machinery is engaged, the apoptotic process is irreversible.


Reductions in methotrexate and folate influx in methotrexate-resistant lines of Leishmania major are independent of R or H region amplification.
The methotrexate (MTX) and folate transport properties of five MTX-resistant lines of Leishmania major have been examined. These resistant lines all show a decreased Vmax for MTX influx, with no change in apparent affinity (Kt). The Vmax of folate influx is also proportionately decreased without alteration in Kt, supporting our proposal that there is a single carrier mediating influx of both ligands. Amplifications of two regions of DNA, the R region (encoding dihydrofolate reductase-thymidylate synthase) and the H region (Beverley, S.M., Coderre, J.A., Santi, D.V., and Schimke, R.T. (1984) Cell 38, 431-439), were also observed. In a given line, the amplifications occurred singly, in combination, or not at all. No other regions of amplification were detected. The phenotype of reduced MTX transport was moderately stable in the highly resistant R1000 line, being retained for more than 200 generations in the absence of MTX in vitro and during one passage through an infected mouse; in contrast, R- and H-amplified DNA were less stable. The lack of correlation of R and H amplification with reduced MTX transport suggests that alterations in transport are not causally mediated by gene amplification in Leishmania, but are a separate mode of MTX resistance. The onset of decreased MTX transport was also examined; wild-type Leishmania developed a reduced Vmax of MTX influx within 24 h following exposure to 1 microM MTX, which is extremely unstable in the absence of drug pressure. A comparable decrease in the Vmax of influx is seen in cells exposed to MTX in media in which cytotoxicity is eliminated. As the folate/MTX transporter is regulated by exogenous folate, these data suggest that the initial rapid decrease in MTX transport may be a cellular regulatory response, in contrast to that found within the R1000 line which resembles a more stable genetic mutation.


Synthesis of magnetic orderly mesoporous α-Fe2O3 nanocluster derived from MIL-100(Fe) for rapid and efficient arsenic(III,V) removal.
A calcination time regulation method has been unprecedentedly used to adjust the orderly meso-structure of novel α-Fe2O3 nanoclusters derived from MIL-100(Fe) (MIL: Materials of Institute Lavoisier). The as-synthesized magnetic orderly mesoporous α-Fe2O3 nanoclusters were characterized by XRD, SEM, TEM, TGA, N2 adsorption-desorption isotherms, VSM, Zeta potential, FTIR and XPS. The 6h calcinated α-Fe2O3 nanocluster exhibited the optimal properties, including the high specific surface area and the orderly mesoporous properties, which facilitate the arsenic(III,V) adsorption capacity. The maximum adsorption capacities of As(III) and As(V) were 109.89 and 181.82mgg-1, respectively, and adsorption equilibrium can be reached just within 30min. The kinetics intra-particle diffusion model and adsorption isotherms reveal that the adsorption rate is controlled by pore diffusion and the adsorption process belongs to Langmuir monolayer adsorption. These results indicate that the orderly mesoporous structure of α-Fe2O3 nanoclusters plays a key role in rapid and efficient adsorption for arsenic(III,V). Meanwhile, adsorption mechanism verifies that arsenic can react with active sites (Fe-OH) to form complexes by Fe-O-As bond. Moreover, α-Fe2O3 nanocluster can be separated easily due to its excellent magnetism. Above all, the magnetism orderly mesoporous α-Fe2O3 nanocluster is a promising adsorbent for emergent treatment of arsenic in practice.


Urinary tract infection is associated with 2.4-fold increased risk of surgical site infection in hip fracture surgery: systematic review and meta-analysis.
There is no consensus regarding whether urinary tract infection (UTI) should be screened for or treated in hip fracture patients. To assess the relationship between perioperative UTI and surgical site infection (SSI) in hip fracture patients, and the relationship between urinary catheterization and SSI in these patients. PubMed, Embase, CINAHL and Cochrane Library were searched to identify studies that evaluated the relationship between perioperative UTI and SSI and/or between urinary catheterization and SSI. Articles were included if they used the term UTI or specified UTI as symptomatic bacteriuria. A total of 4139 records were identified, with eight studies included. Meta-analysis of seven studies which evaluated perioperative UTI and SSI showed an SSI rate of 7.1% (95% confidence interval (CI): 3.8-13.2) among 1217 patients with UTI vs 2.4% (95% CI: 1.0-5.7) in 36,514 patients without UTI (OR: 2.41; 95% CI: 1.67-3.46; P < 0.001). In three studies which specifically defined UTI as symptomatic bacteriuria, the SSI rate among UTI patients was 5.7% (95% CI: 4.0-8.1) vs 1.1% (95% CI: 0.2-5.2) in those without UTI (OR: 3.00; 95% CI: 0.55-16.26; P = 0.20). One study evaluated urinary catheterization and SSI. Perioperative UTI is associated with a higher risk of SSI among hip fracture patients but the evidence is limited by the heterogeneity in the definition of UTI. We recommend considering the possibility of perioperative UTI in hip fracture patients, with treatment administered as necessary to reduce SSI rates.


Extra-anatomic revascularization and a new cannulation strategy for preoperative cerebral malperfusion due to severe stenosis or occlusion of supra-aortic branch vessels in acute type A aortic dissection.
Acute type A aortic dissection (ATAAD) with severe stenosis or occlusion of the true lumen of aortic arch branch vessels often leads to an increased incidence of severe postsurgical neurological complications and mortality rate. In this study, we aimed to introduce our institutional extra-anatomic revascularization and cannulation strategy with improved postoperative outcomes for better management of patients with cerebral malperfusion in the setting of ATAAD. Twenty-eight patients with ATAAD complicated by severe stenosis or occlusion of the aortic arch branch vessels, as noted on combined computed tomography angiography of the aorta and craniocervical artery, between January 2021 and June 2022 were included in this study. Basic patient characteristics, surgical procedures, hospitalization stays, and early follow-up results were analyzed. The median follow-up duration was 16.5 months (interquartile range: 11.5-20.5), with a 100% completion rate. The 30-day mortality rates was 7.1% (2/28 patients); two patients had multiple cerebral infarctions on preoperative computed tomography and persistent coma. Postoperative transient neurological dysfunction occurred in 10.7% (3/28) of the patients, and no new permanent neurological dysfunction occurred. Of all the patients, 3.6% (1/28) had novel acute renal failure. No other deaths, secondary surgeries, or serious complications occurred during the early follow-up period. Use of extra-anatomic revascularization and a new cannulation strategy before cardiopulmonary bypass is safe and feasible and may reduce the high incidence of postoperative neurological complications in patients with ATAAD and cerebral malperfusion.


Right ventricular expression of extracellular matrix proteins, matrix-metalloproteinases, and their inhibitors over a period of 3 years after heart transplantation.
Fibrillar collagens I and III, nonfibrillar collagen IV, and the glycoproteins fibronectin and laminin, are elements of the myocardial extracellular matrix (ECM). Alterations in the normal concentrations and ratios of these elements may reflect remodeling in response to physiologic stress. In the case of patients' post-heart transplantation (HTx), specific patterns of alteration may herald myocardial dysfunction. Right ventricular biopsies were taken from the same 28 HTx patients before implantation and 1 week, 2 weeks, and 1, 2, and 3 years after HTx. The above-noted five ECM proteins, six matrix metalloproteinases (MMPs) and two of their tissue inhibitors (TIMPs) were detected by immunohistochemistry and scored as cells per square millimeter or semiquantitatively. The total connective tissue fibers were detected by connective tissue stain and morphometry. Variations in these ECM components were followed in the same patient cohort over 3 years. In summary, during the first 2 weeks after HTx, a predominant increase in connective tissue occurred. Increases in MMP-8 and MMP-9 were found. By 3 years after transplantation, there was a decrease of connective tissue fibers and a significant reduction of all ECM components and an increase in MMPs and TIMPs. These findings may reflect a pattern of remodeling specific to the transplanted heart.


Orbitofrontal Cortex Value Signals Depend on Fixation Location during Free Viewing.
In the natural world, monkeys and humans judge the economic value of numerous competing stimuli by moving their gaze from one object to another, in a rapid series of eye movements. This suggests that the primate brain processes value serially, and that value-coding neurons may be modulated by changes in gaze. To test this hypothesis, we presented monkeys with value-associated visual cues and took the unusual step of allowing unrestricted free viewing while we recorded neurons in the orbitofrontal cortex (OFC). By leveraging natural gaze patterns, we found that a large proportion of OFC cells encode gaze location and, that in some cells, value coding is amplified when subjects fixate near the cue. These findings provide the first cellular-level mechanism for previously documented behavioral effects of gaze on valuation and suggest a major role for gaze in neural mechanisms of valuation and decision-making under ecologically realistic conditions.


Association between childhood nephrotic syndrome and hemophagocytic lymphohistiocytosis.
Hemophagocytic lymphohistiocytosis (HLH) is caused by an excessive activation of nonmalignant macrophages. Renal lesions have been described in association with, but always after, HLH diagnosis. We describe a previously healthy 26-month-old girl who presented originally with steroid-responsive nephrotic syndrome (NS), but after 4 months, on the first NS relapse, experienced numerous complications (many of them reported to accompany NS as single events). Clinical and laboratory signs of HLH evolved with time and led to deterioration of her condition and death, within 5 months of her original presentation. To our knowledge, this is the first report of NS antedating the presentation of HLH.


Biomechanical investigation of intra-articular cage and cantilever technique in the treatment of congenital basilar invagination combined with atlantoaxial dislocation: a finite element analysis.
Biomechanical effect of posterior intra-articular cages and cantilever technique on the congenital basilar invagination (BI) combined with atlantoaxial dislocation (AAD) was investigated and evaluated using finite element (FE) analysis. A 3D nonlinear occipitocervical segment C0-C3 FE models of congenital BI and AAD was established. Then, the FE model treated with C2 pedicle screw and occipital plate fixation coupled with intra-articular cages (Cage + C2PS + OP) was compared to that without intra-articular cages (C2PS + OP). The range of motion (ROM) of C0C1-C2 and the maximum von Mises stresses (MVMS) on the intra-articular cages, screw-plate system, and C2 endplate were calculated and compared to further analyze the stability of atlantoaxial joint and assess the collapse and fracture risks of intra-articular cages and screw-plate system. ROM of C0C1-C2 segment was reduced by 57.58%, 63.33%, 78.18%, and 75.90%, and the peak stresses of C2 pedicle screw and occipital plate were decreased by 84.86%, 72.90%, 73.24%, and 84.90% and 78.35%, 76.64%, 81.82%, and 89.49% for Cage + C2PS + OP model in flexion, extension, lateral bending, and axial rotation when compared with the C2PS + OP model under the same condition. The MVMS of intra-articular cages were 13.80 MPa, 40.26 MPa, 26.93 MPa, and 17.50 MPa and those of C2 endplate were 14.56 MPa, 34.80 MPa, 36.29 MPa, and 37.56 MPa in Cage + C2PS + OP model under same conditions. Posterior intra-articular cages and cantilever technique to treat BI-AAD can improve the stability of the atlantoaxial joint and reduce the risk of screw-plate breakage. The intra-articular cages can not only complement the height loss on account of atlantooccipital fusion but also provide stable support for posterior fixation fusion.


Full structure of the lipopolysaccharide of Pseudomonas aeruginosa immunotype 5.
The lipopolysaccharide (LPS) of the opportunistic human pathogen Pseudomonas aeruginosa immunotype 5 was delipidated by mild acid hydrolysis, and the products were separated by high-performance anion-exchange chromatography and analyzed by ESI MS and NMR spectroscopy. LPS species of three types were found, including those with an unsubstituted core and the core substituted with one O-polysaccharide repeating unit or with an O-polysaccharide of a variable number of repeating units. The core region is highly phosphorylated, the major species containing two monophosphate groups and one ethanolamine diphosphate group. Based on these and published data on the O-polysaccharide structure, the full structure of the LPS of P. aeruginosa immunotype 5 was established.


Cleaner degreasing of sheepskins by the Yarrowia lipolytica LIP2 lipase as a chemical-free alternative in the leather industry.
Conventional degreasing of skins and hides in the leather industry requires high amounts of organic solvents and detergents that cause environmental issues. In this study, the LIP2 lipase from the yeast Yarrowia lipolytica (YLLIP2) was shown to be effective in degreasing sheepskins, thus reducing the amount of harmful chemicals. Using 6 mg of lipase/kg of raw skin, successful degreasing was achieved in only 15 min at pH 8 and 30°C. ToF-SIMS mass spectra of chemically and enzymatically treated sheepskins are consistent with a selective elimination process for the enzymatic treatment. Comparative SEM microscopy, ATR-FTIR spectroscopy and physicochemical analyses showed better properties of the enzymatically treated leather than those of the chemical treatment. Effluent physicochemical parameters showed that the enzymatic treatment is a cleaner degreasing operation. Altogether, this work opens new horizons to use the YLLIP2 lipase as a more efficient alternative in the leather industry.


Pharmacological and clinical monitoring in children with acute lymphoblastic leukemia treated with a biogeneric PEG-l-asparaginase product.
l-Asparaginase (ASP) plays a crucial role in the treatment of childhood acute lymphoblastic leukemia (ALL). Currently, different ASP products are available in the market, including both native and pegylated drugs. Several biogeneric Escherichia coli ASP (GEN-ASP) products have been developed in response to shortages and expensiveness of the native E. coli ASP innovator compounds, but some concerns have been raised about their quality. Recently, a number of generic pegylated ASP products (GEN-PEG-ASP) have been marketed to substitute for the innovator product (PEG-ASP). Clinical courses and serum asparaginase activity (SAA) levels were monitored in 12 children with ALL, who were treated in our institution with two doses of a GEN-PEG-ASP product, given IV at 2500 IU/m2 during the remission induction phase. Results were compared with those obtained in a reference cohort of 35 patients treated in our institution, who received the innovator PEG-ASP product at same dosage and within the same chemotherapy background. Compared to the reference cohort treated with PEG-ASP, SAA levels were significantly lower in the 12 patients receiving GEN-PEG-ASP (p < .0001); a higher proportion of ASP-associated hypersensitivity reactions (2/12 vs. 0/35; p = .061) and silent inactivation (3/12 vs. 0/35; p = .014) were observed in comparison with the reference cohort. Our results highlighted different pharmacological profiles and different rates of hypersensitivity reactions and silent inactivation in the GEN-PEG-ASP cohort compared to those treated with the innovator product. Our findings suggest that a rigorous clinical attention and a thorough pharmacological monitoring are advisable in patients treated with GEN-PEG-ASP products.


Monotherapy of hypertension with angiotensin-converting enzyme inhibitors.
Angiotensin-converting enzyme (ACE) inhibitors are clearly effective treatment for all stages of hypertension. Since the introduction of captopril in 1981, numerous ACE inhibitors have been synthesized and are under investigation. Their exact antihypertensive mechanism of action remains unclear. Part of their effect may be mediated by vasodilator prostaglandins. Early studies with as much as 1,000 mg a day captopril demonstrated the agent's ability to reduce blood pressure, but only 10 percent of the severely hypertensive patients were controlled with monotherapy. Subsequent studies have demonstrated that patients with mild to moderate hypertension can be controlled with ACE inhibitor alone, although there is a tendency for the very low doses to lose their effect with time. Black patients are less readily controlled with monotherapy. Captopril has now been demonstrated to be effective in the hypertension of scleroderma and has reversed scleroderma renal crisis. ACE inhibitors are also effective for the treatment of severe congestive heart failure.


Application of synchrotron-radiation-based computer microtomography (SRICT) to selected biominerals: embryonic snails, statoliths of medusae, and human teeth.
Synchrotron-radiation-based computer microtomography (SRmicroCT) was applied to three biomineralised objects First, embryonic snails of the freshwater snail Biomphalaria glabrata, second, rhopalia (complex sense organs) of the medusa Aurelia aurita, and third, human teeth. The high absorption contrast between the soft tissue and mineralised tissues, i.e. the shell in the first case (consisting of calcium carbonate) and the statoliths in the second case (consisting of calcium sulphate hemihydrate), makes this method ideal for the study of biomineralised tissues. The objects can be non-destructively studied on a micrometre scale, and quantitative parameters like the thickness of a forming a snail shell or statolith crystal sizes can be obtained on a length scale of 1-2 mum. Using SRmicroCT, the dentin-enamel border can be clearly identified in X-ray dense teeth.


Gender differences in mental health: evidence from three organisations.
It is commonly observed that women report higher levels of minor psychiatric morbidity than men. However, most research fails to control for the gendered distribution of social roles (e.g. paid work and domestic work) and so does not compare men and women in similar positions. In this short report, we examine the distribution of minor psychiatric morbidity (measured by the 12 item General Health Questionnaire) amongst men and women working in similar jobs within three white-collar organisations in Britain, after controlling for domestic and socioeconomic circumstances. Data from self-completion questionnaires were collected in a Bank (n = 2,176), a University (n = 1,641) and the Civil Service (n = 6,171). In all three organisations women had higher levels of minor psychiatric morbidity than men, but the differences were not great; in only the Civil Service sample did this reach statistical significance. We conclude that generalisations about gender differences in minor psychiatric morbidity can be unhelpful, as these differences may vary depending on the context of the study.


Dose-dependent priming or desensitization induced by chemotactic agents in chemiluminescence experiments with canine and human neutrophils.
We explored whether receptor-specific desensitization in repeated stimulation offers an opportunity to identify chemotactic factors particularly in species, e.g. the dog, for which immunochemical methods to determine chemotactic factors are not commercially available. Complement fragment 5a and interleukin-8 act via distinct receptors. They were used as test agents for neutrophils in luminol-dependent chemiluminescence. These experiments led to the observation that exposure of human and canine neutrophils to low concentrations of a chemotactic agent shows an increased response when stimulated again with the same agent (priming). In the heterologous system even cross-priming could be observed after a second stimulation with another agent. The concentration at which priming rather than desensitization occurred were lower for homologous factor-cell combinations (<10-20 nM) than for heterologous combinations (<45-60 nM). The mechanism underlying this phenomenon is unknown. However, it raises the possibility that it subserves an important function in the recruitment and activation of cells by low agonist concentration. This study shows that despite the phenomenon of priming receptor-specific desensitization may be used to determine chemotactic agents in the homologous system.


Differences and similarities in the practice of medicine between australia and the United States of america: challenges and opportunities for the university of queensland and the ochsner clinical school.
In 2008, The University of Queensland (UQ) in Australia and the Ochsner Health System (OHS) in Louisiana entered into a partnership that will allow a cohort of United States (US) citizens to enroll in an Australian medical degree program in which students will study for their first 2 years of medical school in Brisbane, Australia, and then complete the final 2 years of clinical education at OHS in New Orleans. The program's goal is to create graduates eligible to practice in Australia, New Zealand, and/or the US. We reviewed the UQ School of Medicine-established Ochsner Clinical School (OCS) and the translation of the UQ clinical curriculum to the US. The curriculum presented both challenges and opportunities, revealing the similarities and differences in the practice of medicine between Australia and the US. This paper highlights some of them, in terms of the healthcare systems, the health professional workforce, and medical education. For example, the healthcare system and medical school curriculum in Australia have a strong focus on primary care. This new model in education may help train more primary care physicians for the US, providing physicians with a unique global perspective to face the future challenges of medical practice.


Genome-wide association study unravels genomic regions associated with chlorophyll fluorescence parameters in wheat (Triticum aestivum L.) under different sowing conditions.
Genome-wide association study identified 205 significant marker-trait associations for chlorophyll fluorescence parameters in wheat. Candidate gene mining, in silico expression, and promoter analyses revealed the potential candidate genes associated with the studied parameters. The present study investigated the effect of varied sowing conditions (viz., early, timely, and late) on different chlorophyll fluorescence parameters in diverse wheat germplasm set comprising of 198 lines over two cropping seasons (2020-2021 and 2021-2022). Further, a genome-wide association study was conducted to identify potential genomic regions associated with these parameters. The results revealed significant impacts of sowing conditions on all fluorescence parameters, with the maximum and minimum effects on FI (26.64%) and FV/FM (2.12%), respectively. Among the 205 marker-trait associations (MTAs) identified, 11 high-confidence MTAs were chosen, exhibiting substantial effects on multiple fluorescence parameters, and each explaining more than 10% of the phenotypic variation. Through gene mining of genomic regions encompassing high-confidence MTAs, we identified a total of 626 unique gene models. In silico expression analysis revealed 42 genes with an expression value exceeding 2 TPM. Among them, 10 genes were identified as potential candidate genes with functional relevance to enhanced photosynthetic efficiency. These genes mainly encoded for the following important proteins/products-ankyrin repeat protein, 2Fe-2S ferredoxin-type iron-sulfur-binding domain, NADH-ubiquinone reductase complex-1 MLRQ subunit, oxidoreductase FAD/NAD(P)-binding, photosystem-I PsaF, and protein kinases. Promoter analysis revealed the presence of light-responsive (viz., GT1-motif, TCCC-motif, I-box, GT1-motif, TCT-motif, and SP-1) and stress-responsive (viz., ABRE, AuxRR-core, GARE-motif, and ARE) cis-regulatory elements, which may be involved in the regulation of identified putative candidate genes. Findings from this study could directly help wheat breeders in selecting lines with favorable alleles for chlorophyll fluorescence, while the identified markers will facilitate marker-assisted selection of potential genomic regions for improved photosynthesis.


MoS2/SnS/CoS Heterostructures on Graphene: Lattice-Confinement Synthesis and Boosted Sodium Storage.
The development of high-efficiency multi-component composite anode nanomaterials for sodium-ion batteries (SIBs) is critical for advancing the further practical application. Numerous multi-component nanomaterials are constructed typically via confinement strategies of surface templating or three-dimensional encapsulation. Herein, a composite of heterostructural multiple sulfides (MoS2/SnS/CoS) well-dispersed on graphene is prepared as an anode nanomaterial for SIBs, via a distinctive lattice confinement effect of a ternary CoMoSn-layered double-hydroxide (CoMoSn-LDH) precursor. Electrochemical testing demonstrates that the composite delivers a high-reversible capacity (627.6 mA h g-1 after 100 cycles at 0.1 A g-1) and high rate capacity of 304.9 mA h g-1 after 1000 cycles at 5.0 A g-1, outperforming those of the counterparts of single-, bi- and mixed sulfides. Furthermore, the enhancement is elucidated experimentally by the dominant capacitive contribution and low charge-transfer resistance. The precursor-based lattice confinement strategy could be effective for constructing uniform composites as anode nanomaterials for electrochemical energy storage.


In vitro and in vivo antitrypanosomal activity of Xanthium strumarium leaves.
Antitrypanosomal activity of crude 50% ethanolic extract of Xanthium strumarium leaves was studied in vitro and in vivo. The extract exhibited trypanocidal activity at all four concentrations tested i.e. 5, 50, 500 and 1000 micrograms/ml, in vitro. In vivo trial revealed that the extract exerted antitrypanosomal effect at dosage of 100, 300 and 1000 mg/kg, intraperitoneally. At 100 and 300 mg/kg doses the survival period of the Trypanosoma evansi infected mice was significantly prolonged. However, the extract was found to be toxic to the animals at 1000 mg/kg dose.