Trends of notification rates and treatment outcomes of tuberculosis cases with and without HIV co-infection in eight rural districts of Uganda (2015 - 2019).
The End TB Strategy aims to reduce new tuberculosis (TB) cases by 90% and TB-related deaths by 95% between 2015 - 2035. We determined the trend of case notification rates (CNRs) and treatment outcomes of TB cases with and without HIV co-infection in rural Uganda to provide an interim evaluation of progress towards this global target in rural settings. We extracted retrospective programmatic data on notified TB cases and treatment outcomes from 2015 - 2019 for eight districts in rural Uganda from the District Health Information System 2. We estimated CNRs as the number of TB cases per 100,000 population. Treatment success rate (TSR) was calculated as the sum of TB cure and treatment completion for each year. Trends were estimated using the Mann-Kendall test. A total of 11,804 TB cases, of which 5,811 (49.2%) were HIV co-infected, were notified. The overall TB CNR increased by 3.7-fold from 37.7 to 141.3 cases per 100,000 population in 2015 and 2019 respectively. The increment was observed among people with HIV (from 204.7 to 730.2 per 100,000, p = 0.028) and HIV-uninfected individuals (from 19.9 to 78.7 per 100,000, p = 0.028). There was a decline in the TSR among HIV-negative TB cases from 82.1% in 2015 to 63.9% in 2019 (p = 0.086). Conversely, there was an increase in the TSR among HIV co-infected TB cases (from 69.9% to 81.9%, p = 0.807). The CNR increased among people with and without HIV while the TSR reduced among HIV-negative TB cases. There is need to refocus programs to address barriers to treatment success among HIV-negative TB cases.


Large-animal models of acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is characterized by an acute inflammatory response that compromises alveolar-capillary membrane integrity. Clinical symptoms include refractory hypoxemia, noncardiogenic edema, and decreased lung compliance. The purpose of this review is to summarize the different ARDS large-animal models in terms of similarity to the clinical disease and underlying pathophysiology. The repeated lavage, oleic acid, endotoxin, and smoke/burn ARDS models will be discussed in this review. While each model has significant benefits, none is without weaknesses. Thus, the choice of large-animal ARDS model must be carefully considered based upon the study focus and investigative team experience.


Parental knowledge and adolescent adjustment: substance use and health-related quality of life.
This study analyses two models (maternal and paternal) in which parental care and sources of parental knowledge moderated the relationship between parents' knowledge about their adolescents' lives and adolescents' substance use and health-related quality of life. The sample was made up of 15942 Spanish adolescents who participated in the 2006 edition of Health Behavior in School-aged Children Study. Results showed that increased parents' knowledge about their adolescents' lives reduced adolescents' substance use and increased their quality of life. With respect to the moderation relationship, a limited effect was found. However, parental care and sources of parental knowledge used by both parents generally had main effects on adolescents' substance use and health-related quality of life, with care being the most relevant variable in the health-related quality of life, while knowledge was the most relevant one for substance use.


Randomized phase II BGOG/ENGOT-cx1 study of paclitaxel-carboplatin with or without nintedanib in first-line recurrent or advanced cervical cancer.
Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor. The aim was to establish the role of nintedanib in addition to paclitaxel and carboplatin in first-line recurrent/metastatic cervical cancer. Double-blind phase II randomized study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin-paclitaxel with oral nintedanib 200 mg BID/placebo. The primary endpoint was progression-free survival (PFS) at 1.5 years and α = 0.15, β = 80%, one sided. 120 patients (62 N, 58C) were randomized. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favor of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However, N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Global health status during and at the end of the study was similar in both arms. The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.


Growth of very low birth weight infants after increased amino acid and protein administration.
To assess the impact of a high enteral protein nutrition strategy in human milk-fed very low birth weight (VLBW) infants (<1500 g) on growth during the first 5 weeks of life. Weight, length and head circumference of VLBW infants were recorded after introduction of a high protein strategy. Forty-three infants (median/interquartile range) of gestational age 27+6 weeks (26+0/29+6), birth weight 984 g (675/1130) were included. Parenteral nutrition was administered for 16 (14/18) days and the nutritional intakes achieved target values 4.3 g/kg/day protein (4.0/4.4); 128 kcal/kg/day energy (119/131). Human milk was fortified with 0.5-2.3 g/kg/day protein powder in addition to a fortifier. Near-intrauterine growth was observed: Weight gain from days 8-35: 17.6 g/kg/day (14.9/20.5); head growth from day 1-35: 0.70 cm/week (0.50/0.80); length growth from day 1-35: 1.0 cm/week (0.8/1.2). The total protein intake was shown to have a significant impact on infant's weight gain up to the 35th day of life. High protein nutrition enables similar to fetal growth weight gain and head growth of VLBW infants during the first 5 weeks of life. These data support recently published ESPGHAN recommendations.


The muscarinic M1 receptor modulates associative learning and memory in psychotic disorders.
Psychotic disorders are characterized by prominent deficits in associative learning and memory for which there are currently no effective treatments. Functional magnetic resonance imaging (fMRI) studies in psychotic disorders have identified deficits in fronto-temporal activation during associative learning and memory. The underlying pathology of these findings remains unclear. Postmortem data have suggested these deficits may be related to loss of muscarinic M1 receptor mediated signaling. This is supported by an in-vivo study showing improvements in these symptoms after treatment with the experimental M1/4 receptor agonist xanomeline. The current study tests whether reported deficits in fronto-temporal activation could be mediated by loss of M1 receptor signaling in psychotic disorders. Twenty-six medication-free subjects diagnosed with a psychotic disorder and 29 age-, gender-, and IQ-matched healthy controls underwent two functional magnetic resonance imaging (fMRI) sessions, one under placebo and one under selective M1 antagonist biperiden, while performing the paired associated learning task. M1 binding potentials (BPND) were measured in the dorsolateral prefrontal cortex (DLPFC) and hippocampus using 123I-IDEX single photon emission computed tomography. In the subjects with psychotic disorders DLPFC hypoactivation was only found in the memory phase of the task. In both learning and memory phases of the task, M1 antagonism by biperiden elicited significantly greater hyperactivation of the parahippocampal gyrus and superior temporal gyrus in subjects with a psychotic disorders compared to controls. Greater hyperactivation of these areas after biperiden was associated with greater hippocampal M1 receptor binding during learning, with no association found with M1 receptor binding in the DLPFC. M1 receptor binding in the DLPFC was related to greater functional sensitivity to biperiden of the cingulate gyrus during the memory phase. The current study is the first to show differences in M1 receptor mediated functional sensitivity between subjects with a psychotic disorder and controls during a paired associate learning and memory task. Results point to subjects with psychotic disorders having a loss of M1 receptor reserve in temporal-limbic areas.


Inhibition effect of miR-577 on hepatocellular carcinoma cell growth via targeting β-catenin.
To investigate the expression and the regulation effect of cell growth of microRNA-577 in hepatocellular carcinoma (HCC). qRT-PCR was applied to detect the relative expression of miR-577 in 70 paired HCC and matched tumor adjacent tissues collecting from resection between March 2011 and March 2014. Pearson chi-square test was used to analyze the relationship between the miR-577 expression and clinical features. The miR-577 mimics were transfected into HepG2 cells; cell cycles were detected by flow cytometry, cell proliferation was measured by MTT assay and BrdU incorporation assay, and cell apoptosis was determined by flow cytometry and caspase3/7 activity analysis. The expressions of β-catenin were measured by immunohistochemistry. Spearman correlation analysis was used to analyze the relationship between miR-577 and β-catenin. qRT-PCR and western-blot were used to detect the expression of β-catenin in transfected HepG2 cells. The relative expressions of miR-577 was significantly lower in HCC tissues compared to the matched normal tumor-adjacent tissues (P < 0.05). Low expression of miR-577 was significantly associated with large tumor size (≥5 cm, P < 0.05) and advanced tumor node metastasis stage (III+IV, P < 0.05). Transfection of miR-577 mimics could inhibit repress cell proliferation, enhance cell apoptosis and block the cell cycles in G0/G1 phase (P < 0.05). miR-577 in HCC group had a significant negative correlation relationship with the expression of downstream target of β-catenin (P < 0.05). Both the mRNA and protein expression in HepG2 cells were down-regulated after transfection (P < 0.05). Low expression of miR-577 is related to the malignant clinicopathological features in HCC tissues, and miR-577 may suppress HCC growth through down-regulating β-catenin.


Sprengel Deformity with Omovertebral Bone Encroaching the Spinal Canal Causing Progressive Cervical Myelopathy: A Technical Case Report.
An adult with Sprengel deformity and Klippel-Feil syndrome associated with an omovertebral bone has rarely been reported in literature. The omovertebral bone is an abnormal cartilaginous connection between the scapula and the cervical spine. Limited cases have previously been reported in the literature describing surgical intervention when neurologic deficits such as cervical myelopathy or radiculopathy are present. In the present case, an omovertebral bone extended into the cervical lamina resulting in cervical myeloradiculopathy requiring resection of the bony anomaly and cervicothoracic fusion. The omovertebral bone as an etiology for radiculopathy or myelopathy is rarely seen in an adult population, and surgical decompression and fusion should be considered with this constellation of anomalies.


Downregulation of microRNA‑33a promotes cyclin‑dependent kinase 6, cyclin D1 and PIM1 expression and gastric cancer cell proliferation.
Although microRNA‑33 (miR‑33) family members are known to be involved in the regulation and balancing of cholesterol metabolism, fatty acid oxidation and insulin signaling, their functions in carcinogenesis are controversial and the underlying mechanisms have remained elusive. Gastric cancer is the fourth most common malignancy in the world; however, the dysregulation and function of miR‑33 family members in gastric cancer have not been extensively studied. The present study reported that a miR‑33 family member, miR‑33a, was significantly downregulated in gastric cancer tissues and gastric cancer cell lines. Of note, the expression of miR‑33a was inversely correlated with pathological differentiation and metastasis as well as gastric cancer biomarker CA199. A cell‑counting kit‑8 assay showed that transfection of the SGC‑7901 gastric cell line with miR‑33a‑overexpression plasmid inhibited the capability of the cells to proliferate. Furthermore, overexpression of miR‑33a led to cell cycle arrest of SGC‑7901 cells in G1 phase. In addition, a luciferase reporter assay showed that miR‑33a directly targeted cyclin‑dependent kinase 6 (CDK6), cyclin D1 (CCND1) and serine/threonine kinase PIM‑1. In gastric cancer specimens, the reduced expression of miR‑33a was associated with increased expression of CDK‑6, CCND1 and PIM1. However, only PIM1 expression was significantly increased in cancer tissues compared with that in their adjacent tissues. The present study revealed that miR‑33a was downregulated in gastric cancer tissues and cell lines, while forced overexpression of miR‑33a decreased CDK‑6, CCND1 and PIM1 expression to inhibit gastric cancer cell proliferation by causing G1 phase arrest. miR‑33a overexpression may therefore resemble an efficient strategy for gastric cancer therapy.


Comparison of preoxygenation efficiency measured by the oxygen reserve index between high-flow nasal oxygenation and facemask ventilation: a randomised controlled trial.
High-flow nasal oxygenation and the oxygen reserve index (ORI), which is a non-invasive and innovative modality that reflects the arterial oxygen content, are used in general anaesthesia. This study compares the preoxygenation efficiency (measured by the ORI) of high-flow nasal oxygenation and facemask ventilation during the induction process. This single-centre, two-group, randomised controlled trial included 197 patients aged ≥ 20 years who underwent orotracheal intubation for general anaesthesia for elective surgery. The patients were randomly allocated to receive preoxygenation via facemask ventilation or high-flow nasal oxygenation. The ORI was measured and compared between both groups. The ORI increased during preoxygenation in all patients. At 1 min of preoxygenation, the ORI was significantly higher in the high-flow nasal oxygenation group (0.34 ± 0.33) than in the facemask ventilation group (0.21 ± 0.28; P = 0.003). The highest ORI was not significantly different between the two groups (0.68 ± 0.25 in the high-flow nasal oxygenation group vs. 0.70 ± 0.28 in the facemask ventilation group; P = 0.505). High-flow nasal oxygenation results in an oxygenation status similar to that provided by facemask ventilation during the induction process of general anaesthesia; therefore, high-flow nasal oxygenation is a feasible preoxygenation method. Clinicaltrials.gov (NCT04291339).


Treatment of a potentially lethal dose isoniazid ingestion.
A seven-year-old boy ingested 3,000 mg (125 mg/kg) of isoniazid. Initial blood levels of isoniazid were 250 micrograms/mL approximately six hours after ingestion. Despite IV treatment in the emergency department with 3,000 mg pyridoxine and a repeat of the same antidote one hour later in the intensive care unit, the high isoniazid blood levels and persistent metabolic acidosis and coma prompted a decision to increase drug clearance by hemodialysis. Clearance data confirmed the effectiveness of hemodialysis in removing the poison, and the clinical response was dramatic.


Interventions for adults with a history of complex traumatic events: the INCiTE mixed-methods systematic review.
People with a history of complex traumatic events typically experience trauma and stressor disorders and additional mental comorbidities. It is not known if existing evidence-based treatments are effective and acceptable for this group of people. To identify candidate psychological and non-pharmacological treatments for future research. Mixed-methods systematic review. Adults aged ≥ 18 years with a history of complex traumatic events. Psychological interventions versus control or active control; pharmacological interventions versus placebo. Post-traumatic stress disorder symptoms, common mental health problems and attrition. Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 onwards); Cochrane Central Register of Controlled Trials (CENTRAL) (from inception); EMBASE (1974 to 2017 week 16); International Pharmaceutical Abstracts (1970 onwards); MEDLINE and MEDLINE Epub Ahead of Print and In-Process & Other Non-Indexed Citations (1946 to present); Published International Literature on Traumatic Stress (PILOTS) (1987 onwards); PsycINFO (1806 to April week 2 2017); and Science Citation Index (1900 onwards). Searches were conducted between April and August 2017. Eligible studies were singly screened and disagreements were resolved at consensus meetings. The risk of bias was assessed using the Cochrane risk-of-bias tool and a bespoke version of a quality appraisal checklist used by the National Institute for Health and Care Excellence. A meta-analysis was conducted across all populations for each intervention category and for population subgroups. Moderators of effectiveness were assessed using metaregression and a component network meta-analysis. A qualitative synthesis was undertaken to summarise the acceptability of interventions with the relevance of findings assessed by the GRADE-CERQual checklist. One hundred and four randomised controlled trials and nine non-randomised controlled trials were included. For the qualitative acceptability review, 4324 records were identified and nine studies were included. The population subgroups were veterans, childhood sexual abuse victims, war affected, refugees and domestic violence victims. Psychological interventions were superior to the control post treatment for reducing post-traumatic stress disorder symptoms (standardised mean difference -0.90, 95% confidence interval -1.14 to -0.66; number of trials = 39) and also for associated symptoms of depression, but not anxiety. Trauma-focused therapies were the most effective interventions across all populations for post-traumatic stress disorder and depression. Multicomponent and trauma-focused interventions were effective for negative self-concept. Phase-based approaches were also superior to the control for post-traumatic stress disorder and depression and showed the most benefit for managing emotional dysregulation and interpersonal problems. Only antipsychotic medication was effective for reducing post-traumatic stress disorder symptoms; medications were not effective for mental comorbidities. Eight qualitative studies were included. Interventions were more acceptable if service users could identify benefits and if they were delivered in ways that accommodated their personal and social needs. Assessments about long-term effectiveness of interventions were not possible. Studies that included outcomes related to comorbid psychiatric states, such as borderline personality disorder, and populations from prisons and humanitarian crises were under-represented. Evidence-based psychological interventions are effective and acceptable post treatment for reducing post-traumatic stress disorder symptoms and depression and anxiety in people with complex trauma. These interventions were less effective in veterans and had less of an impact on symptoms associated with complex post-traumatic stress disorder. Definitive trials of phase-based versus non-phase-based interventions with long-term follow-up for post-traumatic stress disorder and associated mental comorbidities. This study is registered as PROSPERO CRD42017055523. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 43. See the NIHR Journals Library website for further project information.


Results of a randomized, multicenter, comparative trial of a single dose of cefotetan versus multiple doses of cefoxitin as prophylaxis in cesarean section.
In a multicenter, open, randomized, comparative trial, 308 women undergoing cesarean section were given a single 1 gm dose of cefotetan or three 2 gm doses of cefoxitin after cord clamping to reduce the incidence of postoperative infectious morbidity. Of the 286 evaluable patients, 195 received cefotetan and 91 received cefoxitin. Most patients were in active labor and one third had ruptured membranes. Microorganisms cultured from the endocervix or intraoperatively from the endometrium or abdominal wall operative sites were comparable for the two groups. In this multicenter study, the difference between the percentage of patients receiving cefotetan who did not develop clinical signs and symptoms of infection (93%) and the percentage of patients receiving cefoxitin (85%) considered clinical successes was statistically significant (p = 0.02, chi 2). The bacteriologic response rate for patients taking cefotetan was also significantly higher than that for patients taking cefoxitin (93% versus 85%, p = 0.03). Isolates recovered from the endocervix, endometrium, or operative site were comparable for the two groups. Both drugs were well tolerated. In this evaluation, cefotetan administered in a single dose of 1 gm was more effective as a prophylactic agent than multiple 2 gm doses of cefoxitin in the reduction of infectious morbidity in this large series of patients undergoing cesarean section.


Inhibition of lysophospholipase by cholesterol in rabbit aorta.
Lysophospholipase activity was measured in rabbit aorta using 1-[1-14C]palmitoyl-sn-glycero-3-phosphocholine as a substrate. The enzyme did not require Ca2+ for its activation and the maximal activation was attained in the presence of EGTA. Cholesterol dose-dependently inhibited the lysophospholipase activity in the soluble fraction and IC50 value was approximately 15 microM. Lineweaver-Burk plot revealed that cholesterol competitively inhibited lysophospholipase and Km values in the presence and absence of cholesterol (15.5 microM) were 12.3 and 2.8 microM, respectively. Vmax values were approximately 475 pmol/min.mg. The results suggest that cholesterol can interact with the enzyme per se, resulting in the inhibition of the lysophospholipase activity in rabbit aorta.


Co-encapsulation of PI3-Kδ/HDAC6 dual inhibitor and Navitoclax in Quatramer™ nanoparticles for synergistic effect in ER+ breast cancer.
Progression and metastasis of ER+ breast cancer depend on multiple signaling cascades. The available conventional treatment options have limited efficacy in ER+ breast cancer due to overexpression of AKT, c-Myc and BCL-2 proteins. Simultaneous targeting and inhibition of these targets in ER+ cancer may result in effective therapeutic outcomes. However, combining two or more free drug molecules to treat cancer leads to unsynchronised pharmacokinetics, toxicity, and eventual resistance development. To overcome these limitations, a novel nanoformulation of PI3-Kδ/HDAC6 dual inhibitor in combination with Navitoclax is developed using Pluronic modified PLA based hybrid block copolymer. The prepared dual drug loaded PI3-Kδ/HDAC6-NAV-NPs (1:3-NPs) have shown high encapsulation efficiency, hydrodynamic size, and polydispersity of ∼ 93 %, 159 ± 2.6 nm, and 0.19 ± 0.03, respectively. These PI3-Kδ/HDAC6-NAV-NPs exhibit slow and sustained release profiles of PI3-Kδ/HDAC6 inhibitor and NAV in phosphate buffer saline (PBS, pH 7.4). The in-vitro cytotoxicity studies done with PI3-Kδ/HDAC6-NAV-NPs in ER+ breast cancer cell lines have shown a synergistic effect with lower IC50 values compared to individual NAV-NPs and PI3-Kδ/HDAC6-NPs. The PI3-Kδ/HDAC6-NAV-NPs treatment (4 mg/kg, I.V., twice a week for three weeks) of ER+ breast cancer syngeneic mice tumor model resulted in complete tumor eradication without any overt toxicity. These results demonstrate that a unique formulation of a novel PI3-Kδ/HDAC6 dual inhibitor in combination with Navitoclax represents an approach for an efficient treatment option for ER+ breast cancer.


Fabrication of bimodal open-porous poly (butylene succinate)/cellulose nanocrystals composite scaffolds for tissue engineering application.
The design of porous tissue engineering scaffold with multiscale open-pore architecture (i.e., bimodal structure) promotes cell attachment and growth, which facilitates nutrient and oxygen diffusion. In this study, a porous poly (butylene succinate) (PBS)/cellulose nanocrystals (CNCs) composite scaffold with a well-defined controllable bimodal open-pore interconnected structure was successfully fabricated. The bimodal open-porous scaffold architecture was designed by synergistic control of temperature variation and a two-step depressurization in a supercritical carbon dioxide (Sc-CO2) foaming process. The microstructure and properties of the bimodal open-porous PBS/CNCs scaffold, such as morphology, open porosity, hydrophilic and degradation performance, and mechanical compression properties, were analyzed. In the experiments, the scaffold with unimodal pore structure was used for comparison. The results showed that the bimodal open-porous PBS5 scaffold displayed a well-defined bimodal open-pore structure composed of large pore (~68.9 μm in diameter) and small pore (~11.0 μm in diameter), with a high open porosity (~95.2%). In addition, the scaffolds exhibited good mechanical compressive properties (compressive strength of 2.76 MPa at 50% strain), hydrophilicity (water contact angle of 71.7 °C) and in vitro degradation rate. Moreover, in vitro biocompatibility was determined with NIH-3T3 fibroblast cells using MTT assay and live/dead cell viability assay. Results indicated that the obtained bimodal open-porous scaffolds had a good biocompatibility and the viability of cells grown on the scaffolds reached up to 98% after 7th day of culture. Therefore, our work provides new insights into the use of biodegradable polymeric composite scaffolds with bimodal open-pore structure and balanced properties in tissue engineering.


In vivo detection of lipid-based nano- and microparticles in the outermost human stratum corneum by EDX analysis.
Lipid-based particulate delivery systems have been extensively investigated in the last decade for both pharmaceutical and cosmetic skin application although their translocation across the skin is not yet clarified. The aim of this paper was to investigate on humans the ability of solid lipid nanoparticles (SLN) and solid lipid microparticles (SLM) to penetrate the outermost stratum corneum (SC) and to be modified upon contact with the cutaneous components by using the Tape Stripping Test coupled with the energy dispersive X-ray (EDX) analysis. SLN and SLM were prepared by the melt emulsification technique and loaded with nanosized titanium dioxide (TiO2) to become identifiable by means of X-ray emission. Following human skin application, the translocation of the particulate systems was monitored by the analysis of twelve repetitive stripped tapes using non-encapsulated metal dioxide as the control. Intact SLN as well as non-encapsulated TiO₂ were recorded along the largest SC openings until the 12th stripped tape suggesting the intercluster region as their main pathway. Evidences of a concurrent biodegradation process of the lipid matrix, as the result of SLN interaction with the lipid packing between the corneocyte clusters, were found in the deepest SC layers considered. On the contrary, SLM were retained on the skin surface without undergoing biodegradation so preventing the leaching and the subsequent SC translocation of the loaded TiO₂.


Electric scooter-related accidents: a possible protective effect of helmet use on the head injury severity.
Despite electric scooter use has proliferated in Italy since 2019, actionable data regarding injury incidence and patterns associated with electric scooter accidents are limited. This study aims at analyzing the rate, clinical, and demographic features of electric scooter accidents accessed to the Emergency Department (ED) of Fondazione Policlinico Universitario A. Gemelli IRCSS (Rome, Italy). This retrospective study included all patients older than 18 years riding an electric scooter in the ED from June 2019 to April 2022. Personal data, injury circumstances, helmet use, and health data were collected. Abbreviated Injury Scale (AIS) codes of all diagnoses were recorded, and the Injury Severity Score (ISS) was calculated for each patient. The analysis includes 92 patients admitted to the ED due to an e-scooter accident during the study period, with an increase in years. Thirty-two patients presented bone fractures especially concerning the extremities and the face districts. The median Injury Severity Score in the study cohort was 3, with the highest AIS represented by AIS Pelvic-Extremity and AIS External. Moreover, statistical significance was found between AIS Head-Neck and severity of trauma. E-scooters have become a familiar sight in cities worldwide recently, with many new companies renting them for use. But their arrival has also brought new safety concerns. Although most injuries reported are minor, the meager rate of helmet use is critical. Implementing compulsory helmet use for electric scooters for all ages could be a protective factor for being patient with head trauma on urban streets.


Neural mechanisms of drug stimuli: experimental approaches.
Drug discrimination methodology affords a behavioral end point that reflects actions of a drug at the cellular level. The stimulus control of behavior by drugs of many pharmacological classes satisfies criteria for a receptor-mediated phenomenon. Within many classes of drugs, order of relative of potency for discriminative effects correlates highly with the order of potency of the drugs in other procedures that involve interactions with a defined population of receptors. Examples include the morphine-like opioids and the benzodiazepines. Specific competitive antagonists are of paramount importance for defining neuronal substrates that subserve the discriminative effects of a drug. Quantitative pharmacological approaches can be used not only to define the receptor mediating the discriminative effects of a drug but also to assess the intrinsic activity of the drug at the receptor. The primary site of stimulus control of behavior by most drugs can be shown by indirect and direct means to be of central rather than peripheral origin; however, neuronanatomical localization of specific sites of drug action remains elusive. Attention is starting to be focused on endogenous neuropeptides, their discriminative stimulus properties and potential role in modulating discriminative effects of drugs. Some of the most important contributions of drug discrimination methodology may arise in the rapidly emerging area of peptide neuropharmacology.


Mechanisms of in vivo generation of cytotoxic activity against syngeneic tumours. I. Local differentiation of mature cytotoxic T lymphocytes in the rejection of tumours.
Mature cytotoxic T lymphocytes (CTL) were detected in the peritoneal cavity of syngeneic mice immunized intraperitoneally (i.p.) with mitomycin C (MC)-treated EL-4 or X5563 cells, but were not found in their spleens or lymph nodes. Mature CTL appeared among PE cells after transfer of spleen cells from those immune mice, along with MC-treated tumour cells, to the peritoneal cavity of syngeneic mice. These results lead us to the hypothesis that immature CTL primed in the spleen and lymph nodes may migrate to the site of tumour inoculation and differentiate into mature CTL after antigenic or non-specific stimulation at that site. Inability of primed CTL to differentiate to mature CTL in the spleen might be explained by the effect of splenic suppressor cells, since mature CTL became detectable in the spleen of immune mice by treatment with cyclophosphamide.


Immunohistochemical detection of the ras oncogene product p21 in advanced ovarian cancer. Lack of correlation with clinical outcome.
The monoclonal antibody RAP 5 immunoreactive with the ras gene product p21 was used in an immunohistochemical study of 57 patients with advanced ovarian cancer and in 28 normal ovaries. The pattern of the staining of various tumor specimens was similar to the germinal epithelium of normal ovaries, whereas the intensity of staining was more enhanced in carcinomas than in normal ovaries. However, we found a lack of correlation among staining intensity of RAP 5 and the histologic type, the histologic grade, the ploidy class, and the clinical outcome.


A Digital Architecture for a Network-Based Learning Health System: Integrating Chronic Care Management, Quality Improvement, and Research.
We collaborated with the ImproveCareNow Network to create a proof-of-concept architecture for a network-based Learning Health System. This collaboration involved transitioning an existing registry to one that is linked to the electronic health record (EHR), enabling a "data in once" strategy. We sought to automate a series of reports that support care improvement while also demonstrating the use of observational registry data for comparative effectiveness research. We worked with three leading EHR vendors to create EHR-based data collection forms. We automated many of ImproveCareNow's analytic reports and developed an application for storing protected health information and tracking patient consent. Finally, we deployed a cohort identification tool to support feasibility studies and hypothesis generation. There is ongoing uptake of the system. To date, 31 centers have adopted the EHR-based forms and 21 centers are uploading data to the registry. Usage of the automated reports remains high and investigators have used the cohort identification tools to respond to several clinical trial requests. The current process for creating EHR-based data collection forms requires groups to work individually with each vendor. A vendor-agnostic model would allow for more rapid uptake. We believe that interfacing network-based registries with the EHR would allow them to serve as a source of decision support. Additional standards are needed in order for this vision to be achieved, however. We have successfully implemented a proof-of-concept Learning Health System while providing a foundation on which others can build. We have also highlighted opportunities where sponsors could help accelerate progress.


Does interleukin-1 affect intracellular calcium in osteoblast-like cells (UMR-106)?
Interleukin-1 (IL-1) enhances bone resorption and formation in vitro, presumably through a primary action on osteoblasts, but the mechanism by which IL-1 activates bone cells is unknown. We investigated the possibility that the effect of IL-1 on osteoblasts is mediated through an increase in intracellular calcium [Ca++]i by studying the effects of purified human monocyte-derived IL-1 (hIL-1) and recombinant human IL-1 alpha (rhIL alpha) and beta (rhIL-1 beta) on [Ca++]i in the rat osteogenic sarcoma cell line UMR 106 using indo-1, a new-generation fluorescent Ca++-sensitive probe. hIL-1 (1 U/ml) resulted in an 85.5% rise in [Ca++]i over baseline that reached a peak after 30 seconds and returned to basal levels within 60 seconds. A similar transient rise in calcium was obtained upon exposure of the UMR cells to both the hIL-1 suspension buffer and to the concentration of fetal bovine serum present in the hIL-1 buffer. This effect was not abolished either by heat inactivation of both hIL-1 and serum or by pretreatment of hIL-1 with specific rabbit antihuman-IL-1 antibody. Moreover, exposure of the UMR cells to either rhIL-1 alpha or rhIL-1 beta or to a mixture of both at concentrations of 1 to 100 U/ml was not followed by any change in [Ca++]i. Our data do not support the idea that IL-1 can stimulate osteoblasts through a calcium-mediated pathway.


Consensus recommendations on exploring effective solutions for the rising cost of diabetes.
Diabetes remains asymptomatic for a long period of time and its real burden gets noticed only once the complications set in. The number of individuals affected with the disease is also on the rise and more so in the low income countries. This scenario calls for urgent precautionary measures that need to be undertaken to equip ourselves to fight against this chronic disease. Individuals with financial constraints cannot afford to access even the basic treatment facilities and thus stands the most burdened. The International Diabetes Federation calls for 'Eyes on Diabetes' for the society to focus on early screening and early intervention. The rising cost of diabetes results from delayed and denied treatment. The panel discussion organized as a part of 4th Annual global diabetes convention of Jothydev's Professional Education Forum (JPEF, 2016) facilitated a platform to address diabetes as a serious health concern that needs to be given immediate priority by the policymakers as well as public and also to discuss about the feasible measures that will help achieve cost effective and affordable diabetes treatment. This was followed by in-depth literature search and finally a set of recommendations have been arrived at by the key opinion leaders to realize the dream of affordable diabetes care to all deserving individuals.


Anatomical study of a human skull with multiple osteomas in a seventeenth-century Dutch still-life painting: bone morphology and artistic intention.
Skulls were frequently depicted in seventeenth-century Dutch still-life paintings. Skulls were interpreted as symbols of vanitas-meaning the evanescence of life-but their morphological features have received little attention. This study analyzed a skull with abnormal tumors in a seventeenth-century Dutch still-life painting by a renowned artist, Edwaert Collier (ca. 1642-1708), from anatomical, forensic, and pathological perspectives. The morphology of the cranium and teeth indicated that the skull likely belonged to a middle-aged female. We carefully diagnosed the abnormal masses as multiple osteomas on the skull and left femur, based on clinical studies and paleopathological literature, which reported lesions with a similar appearance to those observed in Collier's work. Furthermore, detailed observations of the cranial sutures and epiphyses of the long bones in his paintings revealed that the artist may have selected bones with a morphology that was suitable for the subject of vanitas. Collier repeatedly depicted the skull with metopism, the rare condition of having a persistent metopic suture in adulthood. A skull with a metopic suture is called Kreuzschädel, meaning the cross skull, because it forms a cruciform by connecting with the sagittal and coronal sutures. The artist might have chosen skulls with metopic sutures, which is reminiscent of the crucifixion of Christ, as an appropriate motif for the vanitas painting. This paper argues that anatomical analysis could explain the hidden meaning of the painting and disclose the fascinating collaborations between anatomy and art in the seventeenth-century Dutch Republic.


Comparative evaluation of marginal leakage of different types of silver amalgam alloys in vitro--a microfluoroscopic study.
A study was carried out in vitro to evaluate the amount of microleakage using seven different Silver amalgam alloy using Fluorescein dye. Among the high copper alloy used in this study, the admixed alloy showed least marginal leakage followed by the high copper lathecut alloy and the high copper spherical alloy. It was also observed that the marginal penetration of the conventional alloy are much more than the high copper alloy.


A rapid ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric method for the qualitative and quantitative analysis of the constituents of the flower of Trollius ledibouri Reichb.
A rapid ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometric (UPLC-ESI-MS/MS) method was developed for the qualitative and quantitative determination of the constituents of the flower of Trollius ledibouri Reichb. The analysis was performed on an AcQuity UPLCtrade mark BEH C18 column using gradient elution with a mobile phase of 0.1% acetic acid and acetonitrile over 20 min. A tandem quadrupole spectrometer operating in either full scan mode or in MS/MS mode for multiple reaction monitoring (MRM) was used for the qualitative and quantitative analysis of the constituents, respectively. According to the mass spectrometric fragmentation mechanism and UPLC-ESI-MS/MS data, the chemical structures of 15 constituents of the flower of T. ledibouri Reichb. were identified on-line without time-consuming isolation and four of them, 2''-O-beta-L-galactopyranosylorientin, 2''-O-beta-arabinopyranosylorientin, orientin and vitexin, were quantified. The limits of quantification of these four flavonoids were 540, 321, 515 and 220 microg g(-1) plant material, respectively. Four commercial samples from different sources were analyzed. The UPLC-ESI-MS/MS method for analyzing the constituents can be used to evaluate the quality of the flower of T. ledibouri Reichb.


Semiautomated QT interval measurement in electrocardiograms from a thorough QT study: comparison of the grouped and ungrouped superimposed median beat methods.
We postulated that it may be easier to identify earliest Q onset and latest T offset when the median beats from 12 leads are separated vertically by 5 to 10 mm (ungrouped superimposed median beat [SMB] method) rather than when their baselines closely (but rarely perfectly) overlap (grouped SMB method). Three readers manually adjudicated annotations placed by an automated algorithm, using grouped (gSMB) and ungrouped (uSMB) methods in 2658 electrocardiograms (ECGs) recorded in 38 subjects in a crossover design thorough QT study at predose and 6 time points postdosing with placebo or moxifloxacin. Placebo-subtracted, moxifloxacin-induced QTcF prolongation was comparable with both methods. Maximum QTcF prolongation was seen at 2 hours--10.5 milliseconds (90% confidence interval, 7.9-13.1 milliseconds) with gSMB and 12.9 milliseconds (90% confidence interval, 9.9-15.8 milliseconds) by uSMB. Both methods showed good agreement; mean QT was 4 milliseconds greater by uSMB. Interreader variability of absolute differences in QT measurements was 1 millisecond lower with the uSMB method (6.8 ± 5.7 milliseconds by gSMB and 5.9 ± 4.5 milliseconds by uSMB). Mean QT was 4 milliseconds longer, and interreader variability, 1 millisecond lower with uSMB. Otherwise, both methods were comparable and detected the moxifloxacin effect.


Memory in sub-clinical obsessive-compulsive checkers.
In a series of experiments we extended the research on possible memory deficits in subclinical obsessive-compulsive Ss who reported excessive checking. Using a variety of memory tests we compared 20 subclinical checkers to 20 Ss without obsessive-compulsive symptomatology. Contrary to hypothesis, checkers remembered self-generated words better than read words just as much as did normals, but they were more likely than normals to report thinking they had studied words that, in fact, had not been on the study list. Further, they more often confused whether they read or generated the words at study. Checkers did not appear to perseverate on already-recalled words on repeated free recall tests any more than did normals. However, checkers remembered fewer actions overall and more often misremembered whether they had performed, observed, or written these actions. Such memory deficits may contribute to the development of excessive checking.


Seasonal wing length dimorphism in a tropical seed bug: ecological significance of the short-winged form.
Short-winged forms of the bug, Jadera aeola, were discovered during the late dry season at a study site on Barro Colorado Island, Panama. They were smaller than long-winged adults not only in elytron and hindwing sizes but also in head, thorax, rostrum and hind femur dimentions. When newly emerged adults were kept under natural photothermal conditions, short-winged females started ovipositing earlier, produced more eggs, and died earlier than did long-winged females. This was partly due to the fact that long-winged adults usually enter diapause after adult energence (Tanaka et al. 1987b). Egg size was another factor contributing to the high egg production in the short-winged form; it was significantly smaller in the short-winged form than that in the long-winged form. Wing form was apparently environmentally induced because all off-spring of short-winged adults became long-winged. No short-winged form was obtained in the laboratory when nymphs were reared on different species of seeds at different photoperiods. Although the factor(s) responsible for determination of the wing form remains unknown, the ecological significance of this short-winged form seems clear, i.e. exploitation of the food resource left in the late dry season. Wing length dimorphism in J. aeola could be a response to unpredictable availability of the food resource determined by seed production of the host plants (Sapindaceae) and by the timing of the onset of a wet season.


High microplastics concentration in liver is negatively associated with condition factor in the Benguela hake Merluccius polli.
Microplastics (MPs) affect both marine and terrestrial biota worldwide for their harmful effects, which range from physical cell damage to physiological deterioration. In this research, microplastics were quantified from gills, liver and muscle of demersal Benguela hakes Merluccius polli (n = 94), caught by commercial trawling from northwest African waters. Plastic polymers were identified using Fourier Transformed-infraRed spectroscopy (FT-iR). Fulton's k condition factor and the degree of DNA degradation in liver were measured. None of the individuals were free of MPs, whose concentration ranged from 0.18 particles/g in muscle to 0.6 in liver. Four hazardous polymers were identified: 2-ethoxyethylmethacrylate, polyester, polyethylene terephthalate, and poly-acrylics. MP concentration in liver was correlated negatively with the condition factor, suggesting physiological damage. Positive association of MP concentration and liver DNA degradation was explained from cell breakage during trawl hauls during decompression, suggesting an additional way of MPs harm in organisms inhabiting at great depth. This is the first report of potential MPs-driven damage in this species; more studies are recommended to understand the impact of MP pollution on demersal species.


Ethnicity's Role in the Relationship Between Anxiety and Negative Interpretation Bias Among Clinically Anxious Youth: A Pilot Study.
Negative interpretation bias, a correlate of anxiety, is defined as an individual's tendency to interpret ambiguous events as negative or threatening. The current study examined associations between interpretation bias and anxiety symptoms in clinically anxious youth and potential moderators of these relationships. Thirty anxious youth and their parents participated in a clinical interview and reported on child anxiety symptoms. Youth completed implicit, explicit-personally irrelevant, and explicit-personally relevant interpretation bias measures. Child-reported anxiety was only associated with negative interpretation bias on the explicit-personally relevant measure and parent-reported social anxiety was negatively associated with positive bias on this measure. Hispanic individuals displayed marginally higher anxiety symptoms and significantly more intense negative interpretation on the implicit measure. While this pilot study revealed preliminary findings that Hispanic ethnicity may play a role in relationships between interpretation bias and anxiety, future work may further elucidate associations between interpretation bias, anxiety, and ethnicity in anxious youth.


Photoinduced electron-transfer in perylenediimide triphenylamine-based dendrimers: single photon timing and femtosecond transient absorption spectroscopy.
The excited state dynamics of two generations perylenediimide chromophores substituted in the bay area with dendritic branches bearing triphenylamine units as well as those of the respective reference compounds are investigated. Using single photon timing and multi-pulse femtosecond transient absorption experiments a direct proof of a reversible charge transfer occurring from the peripheral triphenylamine to the electron acceptor perylenediimide core is revealed. Femtosecond pump-dump-probe experiments provide evidence for the ground state dynamics by populating excited vibronic levels. It is found by the means of both techniques that the rotational isomerization of the dendritic branches occurs on a time scale that ranges up to 1 ns. This time scale of the isomerization depends on the size of the dendritic arms and is similar both in the ground and excited state.


Macular microvasculature in patients with thyroid-associated orbitopathy: a cross-sectional study.
The aim of this study was to evaluate macular blood flow in patients with thyroid-associated orbitopathy (TAO) as compared to healthy subjects. The inflammatory nature of the disease, as well as the vascular congestion caused by the increase in the volume of orbital soft tissue and extraocular muscles, rationalize the assessment of retinal blood flow changes in these patients. This is a cross-sectional study with the convenience sampling method. Macular flow density was assessed using optical coherence tomography angiography (OCTA) and compared between patients with TAO and healthy individuals. We also compared macular flow density in two subgroups of patients based on clinical activity score (CAS). Eighty-five cases, including 30 healthy individuals and 55 patients with TAO, participated. The foveal avascular zone (FAZ) area was significantly larger in the patient group than in the control. Patients with active TAO with CAS 3 or more had significantly larger FAZ areas than those with CAS less than 3 (p = 0.04). We showed that the FAZ area is larger in active TAO patients and can be considered a possible candidate feature for monitoring disease activity and thyroid-associated vasculopathy.


Rapid isolation of double stranded RNA segments from disulphide crosslinked polyacrylamide gels.
A simple method was developed to isolate dsRNA segments from disulphide crosslinked polyacrylamide gels. The dsRNA preparations from the P4 killer virus strain 77 of Ustilago maydis containing 7 genomic segments with molecular sizes ranging from 0.36 to 6.7 kbp, the 20 kbp dsRNA associated with the '447' cytoplasmic male sterility in Vicia faba and the 23 kbp genomic dsRNA of citrus tristeza virus (CTV) were separated on disulphide crosslinked polyacrylamide gels. After UV visualisation, the dsRNA bands were excised from the gel and dissolved using 2-mercaptoethanol. The dsRNA were then purified from the solubilized fractions by specific adsorption on microgranular cellulose and elution with a small volume of water. The method is rapid, simple and convenient for the isolation of all the tested dsRNAs segments.


Male mice exhibit better spatial working and reference memory than females in a water-escape radial arm maze task.
The present study examined sex differences in spatial working and reference memory in C57BL/6 mice. Males and females were tested in a version of the spatial 8-arm radial arm maze in which the motivating stimulus was escape from water. To test spatial working memory, four arms were baited with submerged escape platforms, each of which was removed after it was found. Four arms that never contained platforms assessed spatial reference memory. In addition to determining the number of working memory and reference memory errors made in each session, working memory errors made in each trial were analyzed to examine performance as the number of arms to be remembered (i.e. the working memory load) increased. Males committed significantly fewer working memory and reference memory errors than females throughout testing. Within a session, males committed fewer working memory errors than females as the working memory load increased. These sex differences were particularly evident during task acquisition. The data indicate that male C57BL/6 mice learn both the working and reference memory components of a water-escape motivated radial arm maze task better than female mice.


Relationship between menarcheal age and adult height.
Many factors contribute to the attainment of adult height, including genetic and environmental variables. To assess the relationship between menarcheal age and adult height, measured adult height and recalled menarcheal age were compared by regression analysis in 425 women. The overall regression equation, Height = 158.14 + .4321 (Age) - .1667 (Age - 13)2, was significant (P less than .003), as was the coefficient for the quadratic term (P not equal to .014). After exclusion of those in whom menarche occurred after age 16, the overall linear regression equation for the remaining 416 patients, Height = 153.95 + .7353 (Age), was still significant (P not equal to .001), but the coefficient for the quadratic term was not. These data suggest that menarcheal age significantly correlates with adult height as an independent variable.


Thermogravimetric analysis of the gasification of microalgae Chlorella vulgaris.
The gasification of microalgae Chlorella vulgaris under an atmosphere of argon and water vapor was investigated by thermogravimetric analysis. The data were interpreted by using conventional isoconversional methods and also by the independent parallel reaction (IPR) model, in which the degradation is considered to happen individually to each pseudo-component of biomass (lipid, carbohydrate and protein). The IPR model allows obtaining the kinetic parameters of the degradation reaction of each component. Three main stages were observed during the gasification process and the differential thermogravimetric curve was satisfactorily fitted by the IPR model considering three pseudocomponents. The comparison of the activation energy values obtained by the methods and those found in the literature for other microalgae was satisfactory. Quantification of reaction products was performed using online gas chromatography. The major products detected were H2, CO and CH4, indicating the potential for producing fuel gas and syngas from microalgae.


Attributed causes of excess mortality during the COVID-19 pandemic in a south Indian city.
Globally, excess deaths during 2020-21 outnumbered documented COVID-19 deaths by 9.5 million, primarily driven by deaths in low- and middle-income countries (LMICs) with limited vital surveillance. Here we unravel the contributions of probable COVID-19 deaths from other changes in mortality related to pandemic control measures using medically-certified death registrations from Madurai, India-an urban center with well-functioning vital surveillance. Between March, 2020 and July, 2021, all-cause deaths in Madurai exceeded expected levels by 30% (95% confidence interval: 27-33%). Although driven by deaths attributed to cardiovascular or cerebrovascular conditions, diabetes, senility, and other uncategorized causes, increases in these attributions were restricted to medically-unsupervised deaths, and aligned with surges in confirmed or attributed COVID-19 mortality, likely reflecting mortality among unconfirmed COVID-19 cases. Implementation of lockdown measures was associated with a 7% (0-13%) reduction in all-cause mortality, driven by reductions in deaths attributed to injuries, infectious diseases and maternal conditions, and cirrhosis and other liver conditions, respectively, but offset by a doubling in cancer deaths. Our findings help to account for gaps between documented COVID-19 mortality and excess all-cause mortality during the pandemic in an LMIC setting.


Anterior Percutaneous-Assisted Total Hip Arthroplasty: Surgical Technique and Early Outcomes.
Percutaneous-assisted arthroplasty was introduced to minimize complications traditionally associated with minimally invasive techniques, such as component malposition and periprosthetic fracture. Proponents of percutaneous-assisted techniques have more than 15 years of clinical utilization with good outcomes. This study reports our early experience, and outcomes, with an anterior percutaneous-assisted total hip arthroplasty (AnteriorPath). A retrospective evaluation of a single-surgeon experience with the first 46 patients undergoing AnteriorPath using a cannula for acetabular cup instrumentation was compared with a similar-sized cohort undergoing traditional direct anterior (DA) total hip arthroplasty. Patients needed at least 2 postoperative visits for inclusion. Baseline preoperative characteristics, operative time, component positioning, and 6-week all-cause complications were evaluated. P values <.05 were considered statistically significant. Longer operative times were experienced with the AnteriorPath vs DA THA (93.6 minutes ± 38.6 vs 79.6 minutes ± 23.2, respectively, P = .0503). There were no significant differences in component abduction (40.14° DA vs 41.95° AnteriorPath, P = .1058). A statistically significant difference was found in component anteversion (32.8° DA vs 27.25° AnteriorPath, P = .0039). There were higher rates of short-term complications in patients undergoing DA THA (9.09% DA vs 2.5% AnteriorPath). Early experience with an AnteriorPath demonstrates similar short-term outcomes compared with traditional DA THA. The use of a percutaneous technique has also allowed for a smaller incision, in-line acetabular cup reaming and impaction under direct visualization, and limited trauma to surrounding soft tissues. Further long-term studies with a larger sample size are needed to evaluate the potential benefits and complications of this novel technique.


The effects of adenine nucleotides on cutaneous afferent nerve activity.
1 The activity produced by the adenine nucleotides adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP) and by potassium, acetylcholine (ACh), 5-hydroxytryptamine (5-HT) and bradykinin when applied to an exposed blister base on the ear of anaesthetized rabbits or intra-arterially to anaesthetized cats was investigated in multiple strands dissected from the auricular-temporal and saphenous nerves of rabbits and cats, respectively. 2 In the rabbit preparation potassium and the adenine nucleotides produced activity in the nerve fibres. The effects of these substances were produced in comparable dose ranges; threshold effects being produced by potassium at a concentration of 13 mM and by ADP at a concentration of 4 mM. ACh, 5-HT and bradykinin were inactive at similar or higher concentrations. 3 In the cat preparation all the substances tested produced activity in the nerve fibres. The adenine nucleotides were comparatively less potent than ACh, 5-HT or bradykinin, but had greater potency than potassium. 4 It was concluded that the adenine nucleotides do possess effects on afferent nerve terminals or fibres and thus resemble other known algogenic substances such as potassium, ACh, 5-HT and bradykinin.


Preparation and characterization of polyethylene terephthalate-chamomile oil blends with enhanced hydrophilicity and anticoagulant properties.
New blend films based on polyethylene terephthalate (PET) with different concentrations (50, 100 and 200 µL) of chamomile oil (CAO) were prepared. The effect of oil on the dielectric properties, structural and surface properties of PET was studied. The wettability of the blend films was evaluated by contact angle measurements. In vitro platelet adhesion on the surface and coagulation assessment were conducted to evaluate the behavior of the new blends for blood contact applications. Results of the study indicate that the wettability of PET-CAO blends up to 100 µL has been enhanced relative to the pure PET as indicated by the decrease in contact angle measurements. The attenuation total reflection-Fourier transform infrared spectra of the blends confirmed the presence of chamomile oil in the polymer matrix and suggested the presence of interaction between them. The permittivity ε' values decreased by increasing oil content upto 100 µL. On the other hand, the values of dielectric loss ε″ were found to increase by increasing oil content to 100 µL after which it decreased. The delay in partial thromboplastin time (PTT) of the blood would validate the anti-coagulant property of PET-CAO blends. The results demonstrated that the PET-CAO blends with concentration of 100 µL could be considered as a promising candidate material in blood contact application.


A fluorescent probe for conformational changes in skeletal muscle G-actin.
Actin from rabbit skeletal muscle has been modified with the fluorescent label N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine (1,5-I-AEDANS). Under conditions where the actin is in the unpolymerized form (G-actin), the addition of Mg2+ or KCl results in enhancement of the fluorescence. Titration of the labeled G-actin with Mg2+ at varying concentrations of CaCl2 gives, by extrapolation, a value for the dissociation constant for Mg2+ of 35 microM in the absence of Ca2+ and a calculated value of 10 microM for Ca2+ in the absence of Mg2+. The two metal ions compete with each other. The fluorescence enhancement induced by Mg2+ is reversed by the addition of Ca2+ and both processes are time-dependent, indicating a reversible conformational change of G-actin as a consequence of addition of divalent metal. KCl also enhances the fluorescence of the labeled G-actin but does not appear to compete with the divalent metal ion. The enhancement of the fluorescence is very rapid and any conformational change induced by KCl is probably different from that induced by divalent metal ions. Finally, it is shown that loss of fluorescence of the labeled G-actin may be associated with inactivation of the actin.


Long-lasting molecular changes in human skin after repetitive in situ UV irradiation.
It is known that UV modulates the expression of paracrine factors that regulate melanocyte function in the skin. We investigated the consequences of repetitive UV exposure of human skin in biopsies of 10 subjects with phototypes 2-3.5 taken 1-4 years later. The expression of melanogenic factors (TYR, MART1, MITF), growth factors/receptors (SCF/KIT, bFGF/FGFR1, ET1/EDNRB, HGF, GM-CSF), adhesion molecules (beta-catenin, E-cadherin, N-cadherin), cell cycle proteins (PCNA, cyclins D1, E2) as well as Bcl-2, DKK1, and DKK3, were analyzed by immunohistochemistry. Most of those markers showed no detectable changes at > or = 1 year after the repetitive UV irradiation. Although increased expression of EDNRB protein was detected in 3 of 10 UV-irradiated subjects, there was no detectable change in the expression of ET1 protein or in EDNRB mRNA levels. In summary, only the expression of TYR, MART1, and/or EDNRB, and only in some subjects, was elevated at > or = 1 year after UV irradiation. Thus the long-term effects of repetitive UV irradiation on human skin did not lead to significant changes in skin morphology and there is considerable subject-to-subject variation in responses. The possibility that changes in the expression and function of EDNRB triggers downstream activation of abnormal melanocyte proliferation and differentiation deserves further investigation.


External validation of the recurrent falls risk scale in community-dwelling stroke individuals.
To externally validate the Recurrent Fall Risk Scale (ReFR) in community-dwelling stroke survivors. Cohort of stroke survivors with independent gait ability recruited from a reference outpatient stroke clinic. Besides sociodemographic and clinical data, the following scales were used: Modified Barthel Index (mBI), ReFR scale and National Institutes of Health Stroke Scale (NIHSS). Participants were followed up for 12 months to record the incidence of falls. Accuracy of the ReFR scale was measured by the area under the ROC curve. One hundred and thirteen individuals were recruited between April 2016 and November 2016: mean age 54 years (± 14), 55% women, median time since the last stroke 24 months (range 12 -48 months), posterior vascular territory affected in 35% of the sample. Median NIHSS was 3 (range 1 to 6), median mBI 49 (range 46-50), median ReFR 3 (range 2 to 5). During the follow-up period, 32 (33%) subjects had at least one fall and 18 (19%) were recurrent fallers (two or more falls). The accuracy of ReFR scale was 0.67 (95% CI = 0.54-0.79), p = 0.026. This study externally validated the ReFR as a tool to predict recurrent falls in individuals after stroke.


Przewalskone: a cytotoxic adduct of a danshenol type terpenoid and an icetexane diterpenoid via hetero-Diels-Alder reaction from Salvia przewalskii.
Przewalskone (1), an unprecedented adduct of two different terpenoid units via a hetero-Diels-Alder cycloaddition, was isolated from the roots of Salvia przewalskii. The structure and absolute configurations were elucidated by extensive analysis of NMR spectra and crystal X-ray diffractions. Compound 1 exhibited significant cytotoxicities against five human cancer lines in vitro (IC(50) 0.69-2.35 μM).


Preparation and characterization of novel beta-chitin-hydroxyapatite composite membranes for tissue engineering applications.
Beta-chitin is a biopolymer principally found in shells of squid pen. It has the properties of biodegradability, biocompatibility, chemical inertness, wound healing, antibacterial and anti-inflammatory activities. Hydroxyapatite (HAp) is a natural inorganic component of bone and teeth and has osteoconductive property. In this work, beta-chitin-HAp composite membranes were prepared by alternate soaking of beta-chitin membranes in CaCl2 (pH 7.4) and Na2HPO4 solutions for 2 h in each solution. After 1, 3 and 5 cycles of immersion, beta-chitin membranes were characterized using the SEM, FT-IR, EDS and XRD analyses. The results showed the presence of apatite layer on surface of beta-chitin membranes, and the amounts of size and deposition of apatite layers were increased with increasing number of immersion cycles. Human mesenchymal stem cells (hMSCs) were used for evaluation of the biocompatibility of pristine as well as composite membranes for tissue engineering applications. The presence of apatite layers on the surface of beta-chitin membranes increased the cell attachment and spreading suggesting that beta-chitin-HAp composite membranes can be used for tissue engineering applications.


Detection of Salmonella enterica in food using two-step enrichment and real-time polymerase chain reaction.
A new real-time polymerase chain reaction-based method was developed for the detection of Salmonella enterica in food. The method consisted of a novel two-step enrichment involving overnight incubation in buffered peptone water and a 5-h subculture in Rappaport-Vassiliadis medium, lysis of bacterial cells and a Salmonella-specific 5'-nuclease real-time PCR with an exogenous internal amplification control. Because a two-step enrichment was used, the detection limit for dead S. enterica cells in artificially contaminated ice cream and salami samples was high at 10(7 )CFU (25 g)(-1), eliminating potential false-positive results. When the method was evaluated with a range of 100 naturally contaminated food samples, three positive samples were detected by both the real-time PCR-based method and by the standard microbiological method, according to EN ISO 6579. When the real-time PCR-based method was evaluated alongside the standard microbiological method according to EN ISO 6579 with 36 food samples artificially contaminated at a level of 10(0 )CFU (25 g)(-1), identical results were obtained from both methods. The real-time PCR-based method involving a two-step enrichment produced equivalent results to EN ISO 6579 on the day after sample receipt. The developed method is suitable for rapid detection of S. enterica in food.


Familial aggregation in Alzheimer's disease: comparison of risk among relatives of early-and late-onset cases, and among male and female relatives in successive generations.
Although the morbid risk of Alzheimer's disease (AD) is increased among relatives of AD index cases, it is not yet clear whether the extent of familial aggregation is similar for probands of all ages, or for male and female relatives. The present study investigated the incidence of AD-like illness among 379 first-degree relatives of 79 probands in a continuing longitudinal study of AD. Cumulative incidence among relatives increased strikingly with age to 49% by age 87, and the risks observed did not differ appreciably among relatives of presenile-onset versus senile-onset probands. Risks were also similar among parents and sibs. Female relatives appeared to develop the disease earlier than males, but the age-specific risk curves for the two sexes did not differ significantly. These results should not be viewed as direct evidence for dominant genetic transmission of late-onset AD, but they suggest a rationale for formal genetic studies in late-onset (often apparently "sporadic") disease as well as earlier-onset ("familial") cases.


Microplastics in coastal farmed oyster (Crassostrea angulata) shells: Abundance, characteristics, and diversity.
One of the most concerning emerging pollutants is microplastics (MPs), which can infiltrate soft tissues of organisms by ingestion, adhesion, and fusing and may even become embedded in biominerals. However, very little evidence is available about MPs in biominerals found in the wild. This study detected the abundance and characteristics of MPs in the shells of farmed oysters (Crassostrea angulata) off the coast of Taiwan and discussed the distribution, accumulation, and diversity in the oyster shells. The results showed that MPs were ubiquitous in oyster shells, with an average abundance of 0.70 ± 0.40 MPs/g. MPs abundance was significantly (p < 0.01) higher in small oyster shells (shell length < 6.5 cm, weight 5-10 g) and inorganic (CaCO3) fraction (HCl digestion) than in large oyster shells (>6.5 cm, 10-25 g) and an organic fraction (H2O2 digestion), respectively. However, there was no significant difference in MPs abundance between the top and bottom shells (p > 0.05). MPs with a size <2 mm accounted for 78.5 %, fibrous MPs for 93.7 %, and rayon for 89.5 %. The MPs diversity integrated index (MPDII) in oyster shells was low (0.27), and the small and fibrous MPs seemed more easily embedded in biominerals. The findings confirm the presence of MPs in oyster shells in coastal environments. In addition, oyster shells may contain higher amounts of MPs than soft tissues 4-5 times, which needs to be confirmed. Further revealing the distribution and accumulation of MPs in water/terrestrial biominerals will help to understand the fate of MPs in the environment.


Porphyrin biosynthesis from prophobilinogen by duck blood hemolysate.
The formation of porphyrins from porphobilinogen by a duck blood hemolysate was examined. The system was found to form mainly protoporphyrin IX and hemin, and accumulated lesser amounts of uroporphyrins, hepatacarboxylic porphyrin, and coproporphyrins. By storage at -20 degrees the accumulation of uroporphyrins and heptacarboxylic porphyrin was increased. Both porphyrins were mainly the type III isomers. By addition of dithiothreitol the porphyrin pattern reversed to the original one formed by the fresh hemolysate. Addition of a number of amines also inhibited the decarboxylating system without affecting the original isomer distribution among the porphyrins. Addition of Fe2+ (3mM) did not affect the porphyrin pattern or the isomer distribution. Addition of Pb2+ (2.5 mM) partially inhibited the decarboxylating system, whereas at higher concentrations (4 mM) it increased the decarboxylation rate of the heptacarboxylic porphyrin. The obtained results are discussed in relation to porphyrin accumulation in porphyria cutanea tarda and in acquired hepatic porphyrias.


Germ cell-specific expression of GFP gene induced by chicken vasa homologue (Cvh) promoter in early chicken embryos.
In the present study, we cloned the promoter sequence of the chicken vasa homologue (Cvh) gene, and observed the induction of germ cell-specific gene expression regulated by Cvh promoter in vitro and in vivo. The 2,718-bp Cvh promoter sequence involved putative binding sites of transcription factors such as Oct-1, Nkx2-5, HNF-4 and v-Myb, and a putative CpG island. The reporter vectors, which expressed humanized recombinant green fluorescent protein (hrGFP) under the control of one of three lengths (827, 1,555 and 2,718 bp) of Cvh promoter, were transfected to the dispersed gonadal cells of 7-day incubated embryos in vitro. Every length of promoter-induced germ cell-specific hrGFP expression was verified by immunohistochemistry for germ cell-specific antigens, and the intensity of fluorescence was significantly higher in the transfected gonadal cells using 1,555- and 2,718-bp Cvh promoter compared with 827-bp promoter. These results suggested that the germ cell-specific and enhanced gene expression required at least a 1,555-bp sequence of the 5' flanking region of Cvh gene. In vivo transfection of the reporter vector with 1,555-bp Cvh promoter, which was performed by injecting liposome-DNA complex into the blood vessels of 2-day incubated embryos, also induced germ cell-specific hrGFP expression. The Cvh promoter could provide the basis for a methodology for the visualization, purification and genetical modification of germ cells, and might further contribute to our understanding of the development, proliferation, migration and differentiation of germ cells in the chicken.


Planarian homolog of puromycin-sensitive aminopeptidase DjPsa is required for brain regeneration.
Puromycin-sensitive aminopeptidase (PSA) belongs to the M1 zinc metallopeptidase family. PSA is the most abundant aminopeptidase in the brain and plays a role in the metabolism of neuropeptides including those involved in neurodegeneration. A cDNA DjPsa was identified from the planarian Dugesia japonica cDNA library. It contains a 639-bp open reading frame corresponding to a deduced protein of 212 amino acids. Whole mount in situ hybridization revealed that DjPsa is expressed in the brain and ventral nerve cords of intact and regenerating animals and demonstrates a tissue and stage-specific expression pattern of DjPsa in developing embryos and larvae. Knocking down DjPsa gene expression with RNA interference during planarian regeneration inhibits the brain reformation completely. The results suggest that DjPsa is required for planarian brain regeneration.


Persistence of the carrier status in haemorrhagic septicaemia (Pasteurella multocida serotype 6:B infection) in buffaloes.
Fifty-seven young buffaloes were experimentally infected or naturally exposed to haemorrhagic septicaemia (HS). Of these animals 32 became immune carriers. They were observed in groups for periods up to 360 days to monitor the appearance of pasteurellae in the nasopharynx and antibody status. In most animals pasteurellae appeared in the nasopharynx for a short period initially and disappeared. The organism reappeared intermittently and the longest observed period of reappearance was 215 days after exposure. All animals showed rising antibody titres with a peak lasting for 150 to 180 days and declining thereafter. Pasteurellae persisted in the tonsils and were isolated from 20 out of 27 carriers after slaughter. The longest period when isolation was made after slaughter was 229 days. The organism lodged in the tonsils was unaffected by antibacterial therapy using drugs to which the organism displayed in vitro sensitivity. It is concluded that in HS, carrier animals exist in an active as well as a latent state, the former appearing for short intermittent periods between long latent periods, when pasteurellae continue to remain in the tonsils which constitute a long-term reservoir.


CA 125 in normal tissues and carcinomas of the uterine cervix, endometrium and Fallopian tube. II. Immunoradiometric determination in secretions, tissue extracts and serum.
The study deals with the occurrence of cancer antigen 125 (CA 125) in the normal and neoplastic uterine cervix, endometrium and fallopian tube and its applicability as a tumour marker. CA 125 concentrations were measured in 52 secretion specimens, in cytosol fractions of 97 tissue biopsies and in serum from 47 women with nonmalignant disorders and from 334 patients with carcinomas. High quantities of CA 125 (780-454860 U/ml) were detected in cervical mucus, intra-uterine and tubal fluid, exceeding those in the corresponding serum samples by factors of up to 2000. CA 125 concentrations were 9-53 fold higher in cytosol fractions of normal and neoplastic glandular epithelia of the endocervix and endometrium than in those of cervical squamous epithelia and the cervical wall. Despite similarly high antigen concentrations in normal glandular epithelia and adenocarcinomas serum levels elevated to above 65 U/ml were only found in patients with malignant tumours. The positivity rates in serum increased with tumour extent and were 0-43% for primary and 63-79% for recurrent cervical, endometrial and tubal adenocarcinomas. During long-term follow-up, CA 125 serum concentrations were concordant with the clinical course in 10 out of 11 patients with progressive carcinomas. According to these results, the release of CA 125 into the peripheral blood is apparently dependent on the infiltrative growth and the mass of the tumour rather than on the local tissue concentrations. The clinical use of CA 125 is limited to the detection of advanced adenocarcinomas of the Müllerian duct.


SK&F 83822 distinguishes adenylyl cyclase from phospholipase C-coupled dopamine D1-like receptors: behavioural topography.
Effects of SK&F 83822 [3-allyl-6-chloro-7,8-dihydroxy-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine], an agonist at dopamine D1-like receptors which stimulate adenylyl cyclase but not phosphoinositide hydrolysis, were studied topographically so as to clarify differences between these receptors in the regulation of behaviour. Using cloned receptors, SK&F 83822 showed high, selective affinity for dopamine D1 and D5 over D2, D3, D4 and several non-dopamine receptors. SK&F 83822 induced little intense grooming, but readily induced sniffing, locomotion and rearing; seizures were evident at higher doses, characterised by tonic convulsions, forepaw myoclonus and explosive hyperlocomotion. The dopamine D1-like receptor antagonist SCH 23390 [R(+)-3-methyl-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine] readily antagonised these responses to SK&F 83822, particularly seizure activity. The dopamine D2-like receptor antagonist YM 09151-2 [cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide] did not alleviate seizures induced by SK&F 83822; YM 09151-02 did, however, attenuate SK&F 83822-induced sniffing, locomotion and rearing, and released vacuous chewing. These findings indicate that dopamine D1-like receptors linked to adenylyl cyclase can be differentiated from those not linked to adenylyl cyclase in terms of their roles in the topographical regulation of behaviour. For example, the seizure and vacuous chewing responses appear to involve dopamine D1-like receptors that stimulate adenylyl cyclase, while intense grooming involves those which do not.


The analysis of results of radon/thoron measurements performed with the use of nuclear track detectors.
Radon has been identified as one of the most important hazards, causing lung cancer. The most important isotope of radon is222Rn (3.83 d), while thoron220Rn (55 s) is treated as the less important isotope due to its short half-life. The radon/thoron hazard for people is related to inhalation of their decay products, but usually, only measurements of radon gas are done in dwellings. For such a purpose nuclear track detectors are used in most of the cases. Since several years simultaneous measurements are done to estimate thoron contribution to indoor radon and thoron exposure with the use of track detectors, too. Typically, a set of two detectors are applied and thoron concentrations are calculated on the basis of discriminative calculations. Unfortunately, very often results of these surveys are not accurate due to underestimation of the lower limit of detection (LLD) for thoron in the presence of elevated radon concentrations. Therefore an analysis of thoron LLDs in relationship to radon concentrations is presented.


Spatial and temporal expression patterns of selenoprotein genes during embryogenesis in zebrafish.
Selenium is important for embryogenesis in vertebrates but little is known about the expression patterns and biological functions of most selenoprotein genes. Taking advantage of the zebrafish model, systematic analysis of selenoprotein gene expression was performed by in situ hybridization on whole-mount embryos at different developmental stages. Twenty-one selenoprotein mRNAs were analyzed and all of them exhibited expression patterns restricted to specific tissues. Moreover, we demonstrated that highly similar selenoprotein paralogs were expressed within distinct territories. Therefore, tissue- and development-specific expression patterns provided new information for selenoproteins of unknown function.


Endovascular recanalization of symptomatic non-acute intracranial artery occlusion: Procedural and mid-term clinical outcomes in the anterior circulation.
Symptomatic non-acute intracranial arterial occlusion (NAICO) is not uncommon. We report a single-center experience of the feasibility and safety of endovascular treatment of anterior circulation NAICO and summarize the outcomes of patient groups with successful or failed recanalization. Patients who underwent endovascular therapy for intracranial arterial stenosis between January 2010 and May 2017 were retrospectively reviewed. Thirty-eight patients with symptomatic NAICO (symptom onset > 24 hours) in the anterior circulation were identified. Successful recanalization was achieved in 76.3% of patients (29/38). Intraprocedural events occurred in 10.5% (4/38), including intima dissection (n = 1), parent artery rupture (n = 1) and acute in-stent thrombosis (n = 2). Mean follow-up duration after successful recanalization was 36.5 months. One patient died 68 days after the procedure because of a newly developed posterior circulation stroke. Acute reocclusion was observed in two patients (6.7%); subacute or delayed reocclusion was observed in three patients (10%). Good final outcome (modified Rankin Scale score ≤ 2) was achieved in 25 of 28 patients (89.3%) at three months. Mean follow-up duration of the nine patients with failed recanalization was 41.4 months. Three patients underwent extra-intracranial bypass for worsening symptoms. The other six patients showed stable or improved neurological status with antiplatelet medications. Good final outcome was achieved in eight of nine patients (88.9%) at three months. Endovascular revascularization can be a viable option with an acceptable safety profile in selected patients with symptomatic NAICO in the anterior circulation. Further characterization of aborted cases would facilitate proper patient selection for endovascular treatment.


Crohn's disease associated CARD15 (NOD2) variants are not involved in the susceptibility to type 1 diabetes.
Three variants in the caspase recruitment domain 15/nucleotide-binding oligomerization domain 2 (CARD15/NOD2) gene have been shown to be associated with Crohn's disease (CD). There is a strong support for shared genetic determinants between various autoimmune and inflammatory diseases. In particular, linkage of type 1 diabetes (T1D) and other autoimmune and inflammatory diseases has been reported on chromosome 16, encompassing the region containing the CARD15 gene. We therefore considered this gene as a good candidate for the T1D locus mapped to this region, and we tested the three CARD15 variants in the susceptibility to T1D in two independent settings: family based association analysis in Scandinavian multiplex families that we previously showed to be linked to this region, and case/control association study in a large cohort of French diabetic patients. We found no evidence for association of these variants with T1D overall, nor in subgroups of patients with or without the major risk genotypes at HLA-DRB1, at insulin (INS), or positive or negative for autoantibodies specific to other autoimmune diseases. Our results do not support a role for CD-associated CARD15 variants in the susceptibility to T1D, and suggest that another gene is responsible for the shared susceptibility between autoimmune and inflammatory diseases mapping to this region.


TAK-242 attenuates acute cigarette smoke-induced pulmonary inflammation in mouse via the TLR4/NF-κB signaling pathway.
The present study determined the effect of TAK-242 on attenuating acute cigarette smoke induced pulmonary inflammation and attempted to dissect its underlying mechanisms of action. When administered to the C57BL/6J mice after a 3 days period of cigarettes exposure,TAK-242 significantly decreased the accumulation of macrophages, neutrophils, lymphocytes and DCs, and upregulation of IL-6, IL-8 and TNF-α in BAL fluid and lungs in a dose-dependent manner, except MCP-1, IL-1β and IFN-γ, which demonstrated that TAK-242 inhibits release of various inflammatory mediators induced by cigarette smoke. TAK-242 also significantly suppressed the expression of TLR4, MyD88 and the activation of NF-κB in lungs, suggesting that TAK-242-mediated inhibition occurred largely through the TLR4/NF-κB signal pathway. Our results support TAK-242 as a potent therapeutic agent in the treatment of cigarette smoke induced-pulmonary inflammation, and warrants further pharmaceutical investigation.


Low-temperature plasma ionization source for the online detection of indoor volatile organic compounds.
A simple-structure, low-power, and low-cost low temperature plasma (LTP) ionization source, coupled with mass spectrometry, for the online detection of indoor volatile organic compounds (VOCs) has been constructed in this work. Air, instead of noble gases, was employed as the discharging and carrier gas. And a custom-built AC high-voltage power supply with a total power consumption of 5 W, frequency of 2-4 kHz, and amplitude around 1-5 kV(p-p) was used. This LTP source is a soft ionization source. The initial performance of the ionization source has been evaluated by ionizing samples including alcohols, ketones, aldehydes and aromatics. These compounds cover most of the common air pollutants concerning people's health. It is well known that those plasmas generated by dielectric barrier discharge (DBD) produce significant amount of metastable species and electrons with mean energies greater than several electronvolt, but minimal fragmentation was observed in our work. Protonated ions are the dominant product for the VOCs detected after the ionization process. Further work has been conducted to confirm the detection feature of this source. The results are promising enough to ensure the novel LTP ionization source as an effective tool for the online detection of indoor VOCs.


Older patients are less prone to fast decline of renal function: a propensity-matched study.
Despite CKD is common among older patients, and although factors associated with CKD progression have been explored over decades, little is known about the decline of renal function specifically in older individuals. We included adult patients with CKD on conservative management in a propensity-score matched study 1:1 older (> 65 year) and young (≤ 65 yr). Factors associated with the slope of the decline of eGFR such as proteinuria, initial eGFR, diabetes, sex, and use of angiotensin-converting enzyme inhibitor/angiotensin receptor block (ACEI/ARB) were analyzed. Inclusion criteria were at least two consultations in the service and an initial eGFR lower than 45 ml/min/m2, in the period between January 2012 and December 2017. Crude analysis of eGFR decline shows a slower progression of older patients when compared to younger patients in both absolute change [- 2.0 (- 4.5, - 1.0) vs. -3.0 (- 7.0, - 1.0) ml/min/1.73m2, p < 0.001] and slope of eGFR reduction [- 2.2 (- 4.4, - 1.0) vs. 3.1 (- 6.7, - 1.2)) ml/min/1.73m2, p < 0.001]. Patients considered fast progressors (> 5 ml/min/1.73 m2/year decline in eGFR) were less likely to be older (35.2% young vs. 22.0% older, p < 0.001). Adjusted logistic multivariate regression confirmed that older patients had less odds ratio of eGFR decline, independently of the presence of proteinuria, diabetes, ACEI/ARB use, sex, baseline eGFR, baseline phosphate and baseline 25(OH) vitamin D. Older patients present slower CKD progression even after multiple adjustments. This information should be taken into consideration while treating these patients on conservative management and should be kept in mind while planning dialysis start.


Development, validation and method stability study of a LC-MS method to quantify leuprolide (Hormone analog) in human plasma.
A rapid, highly sensitive and simple high-performance liquid chromatographic-tandem mass spectrometric (LC-MS) assay is developed and validated for the quantification of leuprolide: a Gonadotropin Releasing Hormone analog (GnRH) in human plasma. Moreover, various parameters of the method stability are determined. After the addition of stable isotope (internal standard), the leuprolide was extracted from human plasma by a C18 solid phase micro extraction (MEPS) cartridge and directly injected into LC-MS/MS system. Chromatographic separation was achieved using a Waters Atlantis HILIC, C18, 150 × 2.1 mm, 5 μ column. Mobile phase was a mixture of acetate buffer (pH 3) and acetonitrile (25/75). Drug detection was performed by MS using electrospray ionization in positive mode. Multiple reaction monitoring (MRM) with a tandem mass spectrometer was used to detect the analytes. Precursor to product ion transitions of: m/z 605.5 → m/z 110.2 and m/z 609.1 → m/z 249.1 were used to quantify leuprolide and leuprolide-13C6-15N, respectively. Sample analysis time was 3 min for each injection. The assay exhibited a linear dynamic range of 0.0500-40 ng/ml for each analyte with a lower limit of quantification (LLOQ) of: 0.0500 ng/ml. Furthermore, a complete analytic validation was carried out, including tests on: The specificity, precision, accuracy, matrix effect and stability under different storage conditions. Importantly, the obtained results established: an acceptable precision and accuracy for concentration over standard curve range. Nevertheless, it is to emphasize the simplicity, rapidity and also the high precision and accuracy of this novel LC-MS method, offering useful information about solution stability. Finally, this work is a good alternative to quantify Leuprolide concentration in human blood, especially on human clinic trials step.


Effects of precipitation and temperature on precipitation use efficiency of alpine grassland in Northern Tibet, China.
Precipitation use efficiency (PUE) is crucial in understanding the coupling between ecosystem carbon and water cycling. In this study, we used a time series (2000-2013) dataset of net primary productivity (NPP) based on the Carnegie-Ames-Stanford Approach (CASA) model together with precipitation to reveal the spatial and temporal patterns of alpine grassland PUE in Northern Tibet. The mean annual PUE values of alpine meadow, alpine meadow steppe, alpine steppe, alpine desert steppe, and alpine desert were 0.48, 0.39, 0.36, 0.29 and 0.23 gc m-2 mm-1, respectively. The spatial patterns of PUE of alpine grassland demonstrated an initial increase in the arid region and a subsequent decrease in the humid region along the precipitation gradient and peaked at approximately 500 mm. To evaluate the temporal patterns, the sensitivity [Formula: see text] and the Pearson correlation coefficient [Formula: see text] between the PUE and climatic factors were calculated. The inter-annual variability of PUE exhibited a significant negative correlation with annual precipitation (P < 0.05), which implies that NPP had a lower sensitivity to precipitation in most regions. The relationship between PUE and the mean annual temperature is different for different regions. Our findings have an important role in understanding the impacts of precipitation availability on climate change and in the scientific management of the alpine grassland ecosystems.


Dual role of boron-doped diamond (BDD) anode in effluent organic matter degradation and ultrafiltration membrane fouling mitigation.
Ultrafiltration (UF) is effective in retaining macromolecules during tertiary treatment, but the membrane fouling caused by the effluent organic matter (EfOM) limits its application. This study employed electrochemical oxidation (EO) as a pretreatment method for UF in tertiary treatment to investigate the effects of anode materials on membrane fouling alleviation and EfOM degradation. Compared with the dimensionally stable (DSA) and platinum (Pt) anodes, EO with a boron-doped diamond (BDD) anode exhibited better performances for membrane fouling mitigation due to the higher hydroxyl radical production activity of the BDD anode. It was observed that the current density and electrolysis time were closely related to membrane fouling when using a BDD anode, where increasing the current density or electrolysis time led to a significant improvement of specific flux. The BDD-based pre-oxidation efficiently removed 64% DOC, 76% UV254, and 95% fluorescence organic matter in EfOM, among which the concentrations of DOC and UV254 were positively correlated with the total fouling index (TFI). Meanwhile, 70% SMX in the secondary effluent was removed by the BDD anode. Furthermore, the BDD anode also mitigated membrane fouling by decomposing high molecular weight organic matter into smaller fractions and enhancing the electrostatic repulsion between membrane and EfOM. Therefore, the BDD-based EO process is a promising pretreatment strategy for UF to alleviate membrane fouling and improve the permeate quality.


The impact and effect of emotional resilience on performance: an overview for surgeons and other healthcare professionals.
Medicine and surgery can be demanding professions with high levels of burnout, but few healthcare professionals are given training or education in the management of stress, and the ability of individuals to cope with work and other pressures is often taken for granted. Emotional resilience - the ability to recover from a stressful event, whether at work or at home - is influenced by factors that are both within and outside our control. In this review, we provide an overview of emotional resilience for surgeons and other healthcare professionals, and focus on the factors that can be modulated to help us cope with difficult or complex situations. We also discuss the importance of teamwork and camaraderie, which can easily be forgotten in busy working practice. A greater awareness and understanding of emotional resilience and ways to cope with stress and pressure at work are essential if we are to look after ourselves better, improve the work of our teams, and provide the best care for our patients.


Towards stress-resistant persons: a stress management approach to the treatment of anxiety.
With the reported increase in life stress in recent years, it is important to understand the relationship between such stress and health. It would be of further value if efficacious and time-limited approaches for coping with life stress were to be developed. This paper presents a brief history of the literature on stress, health, and illness. It focuses particular attention on persons who cope adequately with life stress--stress-resistant persons. It also outlines a four-step program to teach these effective copying skills to more vulnerable persons, and presents preliminary findings and the theoretical and clinical issues involved in its implementation.


An analysis of the associations of high-sensitivity C-reactive protein and uric acid with metabolic syndrome components in Korean adults by sex: a cross-sectional study using the Korea national health and nutrition examination survey 2016-2018.
Low-grade inflammation plays a role in the pathogenesis of metabolic syndrome (MetS), and measuring levels of inflammatory molecules, such as high-sensitivity C-reactive protein (hs-CRP), may indicate Mets progression. Serum uric acid (SUA) has also been identified as an independent risk factor for MetS. This study aimed to investigate the association between MetS components and levels of serum hs-CRP and SUA using representative and reliable data for the Korean population. This study used the data of the Korea National Health and Nutrition Examination Survey 2016-2018, a cross-sectional and nationally representative survey performed by the Korean Centers for Disease Control and Prevention. We analysed the data of 13,454 individuals. High hs-CRP levels were observed in 1,164 (8.7%) subjects while 3,296 (24.5%) subjects had high SUA levels. Moreover, hs-CRP was negatively correlated with serum high-density lipoprotein (HDL) (OR, 1.703; 95% CI, 1.431-2.027). When stratified by sex, this trend remained, but the correlation was stronger in women than in men. Furthermore, high SUA levels were significantly associated with hypertension (HTN) (OR, 1.399; 95% CI, 1.210-1.616), hypertriglyceridemia (OR, 1.735; 95% CI, 1.486-2.026), and low HDL (OR, 1.257; 95% CI, 1.106-1.429), but not with diabetes mellitus (DM) (OR, 0.478; 95% CI, 0.382-0.597). When grouped by sex, this trend remained, however, all MetS components were found to be more prevalent in women with high SUA. Our findings showed that low HDL was more prevalent in subjects with high hs-CRP, and high SUA levels were observed in subjects with HTN, hypertriglyceridemia, and low HDL. However, the prevalence of high SUA was lower in diabetic subjects.