Feasibility of using Clinical Practice Research Datalink data to identify patients with chronic obstructive pulmonary disease to enrol into real-world trials.
To assess the feasibility of using Clinical Practice Research Datalink (CPRD) data for identifying populations of patients with chronic obstructive pulmonary disease (COPD) eligible for a hypothetical pragmatic trial. A retrospective multidatabase cohort study using CPRD primary care and linked secondary care data to describe the characteristics of populations of patients with COPD. Patients' demographic and lifestyle factors, comorbidity profile, spirometry measurements and treatment changes were evaluated, as was the distribution of follow-up time and types of losses during follow-up. Characteristics were evaluated using descriptive statistics. A total of 322 991 patients from 1148 primary care practices in the United Kingdom across two CPRD primary care databases, CPRD GOLD and CPRD Aurum, were potentially eligible to participate in a hypothetical trial using CPRD, starting on 31 December 2017. Patients with COPD in CPRD GOLD and CPRD Aurum were comparable in terms of age (median age 70 vs. 68 years), gender (50% vs. 52% male), disease severity (e.g., 25% vs. 24% Medical Research Council [MRC] dyspnoea score grades 3-5) and history of respiratory conditions (e.g., 43% vs. 38% asthma). High proportions of patients with COPD in CPRD GOLD and CPRD Aurum were available on 31 December 2012 for follow-up at 1, 2, and 5 years (92%, 85% and 67%, respectively). Patients and data from CPRD GOLD and CPRD Aurum were comparable across key aspects relevant to COPD trials. A pragmatic trial using CPRD to recruit patients with COPD is scientifically feasible.


Neuroscience: Glutamate neurons in the medial septum control wakefulness.
Despite intensive research efforts, biologists still do not have a clear picture of the brain circuitry that controls behavioural arousal. However, new research has identified a novel septo-hypothalamic circuit that functions to promote wakefulness.


Successful recruitment to a study of first-episode psychosis by clinicians: a qualitative account of outcomes and influences on process.
Abstract Background: Strategies proposed to promote recruitment of representative samples to trials and mental health research have focused on researchers external to clinical services. How clinicians approach recruitment as researchers and particularities of recruiting people with first episode of psychosis warrant investigation. To describe recruitment, by clinicians, of people with first-episode psychosis (FEP) and factors influencing process and enrolment. Observational study nested within longitudinal examination of trauma and outcomes for patients experiencing first psychotic episode. Data collected during 20 scheduled meetings of clinicians recruiting from services in Australia. Timely recruitment of 60 young people demonstrates that clinicians can successfully engage patients in research. Success depends on satisfaction of organisational preconditions and clinician motivation grounded in considering the study worthwhile. Pre-selection of participants was informed by judgments about health, insight and quality of the therapeutic alliance. Patients' decisions were influenced by family support, acceptance of diagnosis and altruism. Honoraria had variable effect. Clinicians are well placed to recruit when appropriately supported, and people with FEP are willing to engage in research that fits their personal circumstances. Research should examine the meaning of participation in such studies and ways participation could support recovery.


Prostacyclin and thromboxane in diabetic children.
Plasma concentrations of a stable metabolite of prostacyclin, 6-keto-prostaglandin Fla (6-keto-PGF1a), and the ability of platelets to generate thromboxane B2 (TxB2), a metabolite of thromboxane A2, during spontaneous clotting of the blood were measured in 40 diabetic children and 16 healthy controls. The diabetics' platelets generated TxB2 to a lesser extent than those of controls, whereas no difference was seen in plasma 6-keto-PGF1a concentration. The balance and duration of diabetes were not related to TxB2 or 6-Keto-PGF1a. The results do not support the theory that an absolute or relative prostacyclin deficiency could trigger the onset of diabetic vascular complications.


IQGAP1 regulation and roles in cancer.
IQGAP1 is a key mediator of several distinct cellular processes, in particular cytoskeletal rearrangements. Recent studies have implicated a potential role for IQGAP1 in cancer, supported by the over-expression and distinct membrane localisation of IQGAP1 observed in a range of tumours. IQGAP1 is thought to contribute to the transformed cancer cell phenotype by regulating signalling pathways involved in cell proliferation and transformation, weakening of cell:cell adhesion contacts and stimulation of cell motility and invasion. In this review we discuss these different functional and regulatory roles of IQGAP1 and its homologues in relation to their potential impact on tumourigenesis.


Predictive value of serum matrix metalloproteinase 9 combined with tissue inhibitor of metalloproteinase 1 for post-stroke cognitive impairment.
Post-stroke cognitive impairment (PSCI) seriously affects the quality of life of patients. Identifying early predictors of PSCI to realize timely intervention of PSCI can provide effective information for patient rehabilitation and follow-up treatment, and has important clinical significance for delaying its progression to dementia. Montreal Cognitive Assessment (MoCA) and National Institutes of Health Stroke Scale (NIHSS) were used to assess patients' cognitive and neurological function separately. ELISA was used to analyze serum tissue inhibitor of metalloproteinase 1 (TIMP 1) and matrix metalloproteinase 9 (MMP 9) levels of patients on admission. 180 patients with first-ever acute ischemic stroke (AIS) were included in the study. After three months of follow-up, 78 patients were diagnosed with PSCI, and 102 patients did not have PSCI. MMP 9 and TIMP 1 were elevated in PSCI patients on admission relative to non-PSCI groups, and they were positively correlated with patients' NIHSS scores on admission (p < 0.001). Serum levels of MMP 9 and TIMP 1 in PSCI patients were negatively correlated with MoCA scores at the end of the 3-month follow-up (p < 0.001). Serum MMP 9 (p < 0.001), TIMP 1 (p = 0.02) and combined detection (p < 0.001) of AIS patients at admission appear to have predictive value for the diagnosis of PSCI three months later. Serum MMP 9 and TIMP 1 levels in stroke patients were statistically predictive of PSCI.


The effect of thyrocalcitonin and growth hormones on bone metabolism.
The use of the hormone, thyrocalcitonin, has been shown to change the bone metabolism so that resorption is decreased and calcium increased. The growth hormone seems to add to bone mass and indirectly prevents resorption. The combination of growth hormone and calcitonin seems to cause an unusual amount of resorption. This research has shown that metallic endosteal blade implants are not automatically successful even in short spans with additional support from two abutment teeth. It is true that the type of occlusion of the squirrel monkey is different from that of man, but the prosthetic devices that were placed in these animals can be validly compared to similar devices placed in man. While the hygiene cannot be practiced effectively by the animal, the psychogenic and emotional problems of man offset this disadvantage. Also, the diet of the monkey is not as traumatic to a prosthesis as is man's. Two of the most important criteria for implant success have not proved satisfactory: (1) no pocket depth beyond 3 mm. and (2) negative radiographic pathosis around the implant. While this study was not meant to be one of criticism or evaluation of metallic implants, it should be noted that thyrocalcitonin and the growth hormone, individually used, played an important part in retarding bone resorption around the blade. Autogenous bone grafts for residual alveolar ridge restoration often fail due to rapid osseous resorption and volume loss. The maintenance of osseous elements in the autogenous bone grafts when calcitonin had been administered was quite revealing. This might be the chemotherapeutic basis for the many conditions involving bone that dentists are called upon to treat.


Hematological, biochemical effects, and self-reported symptoms in pesticide retailers.
This study evaluates the effects of exposure to pesticides on the health of pesticide retailers. The study population comprised 83-male pesticide retailers and 98 controls. Serum butyrylcholinesterase levels and complete blood analysis were performed in a certified laboratory and each subject completed a structured questionnaire. Butyrylcholinesterase activity and hematological parameters such as hemoglobin and hematocrit were significantly lower in pesticide retailers than in control subjects. In contrast, platelet count as well as hepatic parameters such as glutamic-pyruvate transaminase and gamma-glutamyl transpeptidase activities was higher in pesticide retailers. Furthermore, pesticide retailers experienced burning sensations in the skin more frequently than controls. These preliminary results suggest the importance of evaluating further toxicological biomarkers in these populations.


Age-related changes in bone density, geometry and biomechanical properties of the proximal femur: CT-based 3D hip structure analysis in normal postmenopausal women.
The geometry as well as bone mineral density (BMD) of the proximal femur contributes to fracture risk. How and the extent to which they change due to natural aging is not fully understood. We assessed BMD and geometry in the femoral neck and shaft separately, in 59 normal Japanese postmenopausal women aged 54-84 years, using clinical computed tomography (CT) and commercially available software, at baseline and 2-year follow-up. This system detected significant reductions over the 2-year interval in total BMD (%change/year = -0.900 ± 0.257, p < 0.0005), cortical cross-sectional area (CSA) (-0.800 ± 0.423%/year, p < 0.05) and cortical thickness (-1.120 ± 0.453%/year, p < 0.01) in the femoral neck. In the femoral shaft, cortical BMD decreased significantly (-0.642 ± 0.188%/year, p < 0.005). Regarding biomechanical parameters in the femoral neck, the cross-sectional moment of inertia (CSMI) and section modulus (SM) decreased (-1.38 ± 3.65%/year, p < 0.01 and -1.37 ± 2.96%/year, p < 0.005) and the buckling ratio (BR) increased significantly (1.48 ± 4.81%/year, p < 0.05), whereas no changes were found in the femoral shaft. The distinct patterns of age-related changes in the geometry and biomechanical properties in the femoral neck and shaft suggest that improved geometric measures are possible with the current non-invasive method using clinical CT.


Estimation of the physiological mechanical conditioning in vascular tissue engineering by a predictive fluid-structure interaction approach.
The in vitro replication of physiological mechanical conditioning through bioreactors plays a crucial role in the development of functional Small-Caliber Tissue-Engineered Blood Vessels. An in silico scaffold-specific model under pulsatile perfusion provided by a bioreactor was implemented using a fluid-structure interaction (FSI) approach for viscoelastic tubular scaffolds (e.g. decellularized swine arteries, DSA). Results of working pressures, circumferential deformations, and wall shear stress on DSA fell within the desired physiological range and indicated the ability of this model to correctly predict the mechanical conditioning acting on the cells-scaffold system. Consequently, the FSI model allowed us to a priori define the stimulation pattern, driving in vitro physiological maturation of scaffolds, especially with viscoelastic properties.


Development of three-dimensional integral-type reconstruction formula for magnetic resonance elastography.
The viscoelasticity (storage modulus and loss modulus) of living tissues is known to be related to diseases. Magnetic resonance elastography (MRE) is a quantitative method for non-invasive measuring viscoelasticity. The viscoelasticity is calculated from the elastic wave images using an inversion algorithm. The estimation accuracy of the inversion algorithm is degraded by background noise. This study aims to propose novel inversion algorithms that are applicable for noisy elastic wave images. The proposed algorithms are based on the Voigt-type viscoelastic equation. The algorithms are designed to improve the noise robustness by avoiding direct differentiation of measurement data by virtue of Green's formula. Similarly, stabilization is introduced to the curl-operator which works to eliminate the compression waves in measurement data. To clarify the characteristics of the algorithms, the proposed algorithms were compared with the conventional algorithms using isotropic and anisotropic voxel numerical simulations and phantom experimental data. From the results of the numerical simulations, normalized errors of stiffness of proposed algorithms were 3% or less. The proposed algorithms mostly showed better results than the conventional algorithms despite noisy elastic wave images. From the gel phantom experiment, we confirmed the same tendency as the characteristics of the algorithms observed in the numerical simulation results. We have developed a novel inversion algorithm and evaluated it quantitatively. The results confirm that the proposed algorithms are highly quantitative and noise-robust methods for estimating storage and loss modulus regardless of noise, voxel anisotropy, and propagation direction. Therefore, the proposed algorithms will appropriate to various three-dimensional MRE systems.


Citrobacter rodentium-host-microbiota interactions: immunity, bioenergetics and metabolism.
Citrobacter rodentium is an extracellular enteric mouse-specific pathogen used to model infections with human pathogenic Escherichia coli and inflammatory bowel disease. C. rodentium injects type III secretion system effectors into intestinal epithelial cells (IECs) to target inflammatory, metabolic and cell survival pathways and establish infection. While the host responds to infection by activating innate and adaptive immune signalling, required for clearance, the IECs respond by rapidly shifting bioenergetics to aerobic glycolysis, which leads to oxygenation of the epithelium, an instant expansion of mucosal-associated commensal Enterobacteriaceae and a decline of obligate anaerobes. Moreover, infected IECs reprogramme intracellular metabolic pathways, characterized by simultaneous activation of cholesterol biogenesis, import and efflux, leading to increased serum and faecal cholesterol levels. In this Review we summarize recent advances highlighting the intimate relationship between C. rodentium pathogenesis, metabolism and the gut microbiota.


Presence of endometrioma decreased blastocyst formation rate but not impair Assisted Reproductive Technology (ART) outcome.
This study aims to assess the impact of endometrioma on patients who undergo ART treatment due to endometriosis. A retrospective study was conducted on women ≤ 40 years of age who underwent ART treatment at an academic medical center between January 2014 and December 2020. Two-hundred-and-eight women had received IVF/ICSI treatment due to endometriosis and there were 89 patients presence of endometrioma. Patients were further divided into primary endometrioma, recurrent endometrioma and those having received cystectomy for endometrioma prior to IVF/ICSI. The control group included 624 infertile women without endometriosis. In the endometrioma subgroup (B) the blastocyst formation rate was significantly lower when compared with the endometriosis (A) and control groups (C). The cumulative live birth rates (CLBRs) (60.5% versus 49.4% versus 56.9%, p = 0.194 in A versus B, p = 0.406 in A versus C, p = 0.878 in B versus C) were comparable. Multiple logistic regression analysis revealed that female age, total FSH dose and blastocyst formation rate were the significant variables in predicting CLBR (OR 0.89, CI 0.80-0.99, p < 0.025, OR 0.68 CI 0.53-0.88, p = 0.003 and OR 30.04, CI 9.93-90.9, p < 0.001, respectively). The CLBRs were comparable at 47.1%, 60% and 57.9% in the primary endometrioma, s/p cystectomy and recurrent endometrioma group. Although the blastocyst formation rate was lower in the endometrioma group, CLBR was not worse than those who were in the endometriosis or control group. Cystectomy for endometrioma did not alter IVF/ICSI outcomes if the ovarian reserve was comparable. Recurrent endometrioma did not worsen IVF/ICSI outcomes than primary endometrioma.


Kinetic study of acid depolymerization of chitosan and effects of low molecular weight chitosan on erythrocyte rouleaux formation.
In this study, the depolymerization of chitosan was carried out in an acetic acid aqueous solution and was followed by viscometry for molecular weight determination. It was found that the depolymerization rate increased with elevated temperatures and with high acid concentrations. Based on FTIR analysis, the chitosan was depolymerized randomly along the backbone; no other structural change was observed during the acid depolymerization process. Revealed in the TGA study, the degradation temperature and char yield of LMWCs (low molecular weight chitosan) were molecular weight dependent. The blood compatibility of LMWCs was also investigated: rouleaux formation was observed when erythrocyte contacted with LMWCs, which showed that LMWCs are able to interfere with the negatively charged cell membrane through its polycationic properties. Furthermore, as regards a kinetics investigation, the values of M(n) (number-average molecular weight) were obtained from an experimentally determined relationship. The kinetics study showed that the complex salt, formed by amine on chitosan and acetic acid, acted as catalyst. Finally, the activation energy for the hydrolysis of the glycosidic linkage on chitosan was calculated to be 40kJ/mol; the mechanism of acid depolymerization is proposed. In summary, LMWCs could be easily and numerously generated with acid depolymerization for further biological applications.


A Radiographic Measurement of the Anterior Epidural Space at L4-5 Disc Level.
To observe the morphology character of the anterior epidural space at the L4-5 disc level and to provide an anatomical basis for safely and accurately performing a percutaneous endoscopic lumbar discectomy (PELD). Fifty-five cases with L5 S1 lumbar disc herniation were included in this study, and cases with L4-5 disease were excluded. When the puncture needle reached the epidural space at the L5 S1 level, iohexol was injected at the pressure of 50 cm H2 O during the PELD, then C-Arm fluoroscopy was used to obtain standard lumbar frontal and lateral images. The widths of epidural space at the level of the L4 lower endplate, the L5 upper endplate, as well as the middle point of the L4-5 disc were measured from the lumbar lateral X-ray film. Epidural space at the L4-5 disc plane performs like a trapezium chart with a short side at the head end and a long side at the tail end in the lumbar lateral X-ray radiograph, while the average widths of epidural space were 10.2 ± 2.5, 12.3 ± 2.3, and 13.8 ± 2.6 mm at the upper, middle, and lower level of the L4-5 disc. Understanding the morphological characteristics of epidural space will contribute to improving the safety of the tranforaminal percutaneous endoscopy technique.


Crystal orientation mapping and microindentation reveal anisotropy in Porites skeletons.
Structures made by scleractinian corals support diverse ocean ecosystems. Despite the importance of coral skeletons and their predicted vulnerability to climate change, few studies have examined the mechanical and crystallographic properties of coral skeletons at the micro- and nano-scales. Here, we investigated the interplay of crystallographic and microarchitectural organization with mechanical anisotropy within Porites skeletons by measuring Young's modulus and hardness along surfaces transverse and longitudinal to the primary coral growth direction. We observed micro-scale anisotropy, where the transverse surface had greater Young's modulus and hardness by ∼ 6 GPa and 0.2 GPa, respectively. Electron backscatter diffraction (EBSD) revealed that this surface also had a higher percentage of crystals oriented with the a-axis between ± 30-60∘, relative to the longitudinal surface, and a broader grain size distribution. Within a region containing a sharp microscale gradient in Young's modulus, nanoscale indentation mapping, energy dispersive spectroscopy (EDS), EBSD, and Raman crystallography were performed. A correlative trend showed higher Young's modulus and hardness in regions with individual crystal bases (c-axis) facing upward, and in crystal fibers relative to centers of calcification. These relationships highlight the difference in mechanical properties between scales (i.e. crystals, crystal bundles, grains). Observations of crystal orientation and mechanical properties suggest that anisotropy is driven by microscale organization and crystal packing rather than intrinsic crystal anisotropy. In comparison with previous observations of nanoscale isotropy in corals, our results illustrate the role of hierarchical architecture in coral skeletons and the influence of biotic and abiotic factors on mechanical properties at different scales. STATEMENT OF SIGNIFICANCE: Coral biomineralization and the ability of corals' skeletal structure to withstand biotic and abiotic forces underpins the success of reef ecosystems. At the microscale, we show increased skeletal stiffness and hardness perpendicular to the coral growth direction. By comparing nano- and micro-scale indentation results, we also reveal an effect of hierarchical architecture on the mechanical properties of coral skeletons and hypothesize that crystal packing and orientation result in microscale anisotropy. In contrast to previous findings, we demonstrate that mechanical and crystallographic properties of coral skeletons can vary between surface planes, within surface planes, and at different analytical scales. These results improve our understanding of biomineralization and the effects of scale and direction on how biomineral structures respond to environmental stimuli.


Renal effects of antipyretic analgesics.
Most antipyretic analgesics can cause acute nephrotoxic effects, including acute tubular necrosis, acute interstitial nephritis, glomerular toxicity, and functional changes, such as "salicyl edema," following large doses of sodium salicylate. Most functional changes are related to acute suppression of prostaglandin synthesis, "the acute prostaglandin-effect," and have been primarily noted with the use of indomethacin. The association between prolonged and excessive consumption of compound analgesics and the development of renal disease and renal failure, characterized by renal papillary necrosis, is now well established. Studies in several countries have shown that the incidence of analgesic nephropathy as an indication for dialysis and transplantation corresponds to the per capita consumption of phenacetin in compound analgesics. Analgesic nephropathy, which is part of a wider clinical syndrome, the analgesic syndrome, is uncommon following the use of single analgesics. Analgesic nephropathy and the analgesic syndrome are discussed in detail, including the development of uroepithelial tumors.


The relationship between the waist-to-height ratio and glucose and lipid metabolism in Han adolescents.
To evaluate the relationship between waist-to-height ratio (WHtR) and glucose and lipid metabolism in Han adolescents aged 13-15 years. A study was conducted on 1665 Han adolescents aged 13-15 years. Measurements included height, weight, waist circumference, fasting plasma glucose(FPG), triglyceride and high-density lipoprotein cholesterol. The subjects were divided into two groups according to WHtR. Compared with the control group (n=1340,WHtR<0.46), the abdominal obesity group(n=325,WHtRe"0.46) had significantly higher levels of body mass index (BMI) (26.3+/-3.6 vs 18.9+/-2.3), WHtR (0.51+/-0.04 vs 0.40+/-0.03), FPG (4.99+/-0.48 vs 4.86+/-0.46), and triglyceride (1.21+/-0.62 vs 0.87+/-0.41), and a lower level of high-density lipoprotein cholesterol (1.26+/-0.27 vs 1.46+/-0.30) (P<0.01). Logistic regression analysis showed that after controlling for age, sex and BMI, the elevated FPG and dyslipidemia risk odds ratios of the abdominal obesity group were 1.954 (95% CI:1.250 approximately 3.054) and 2.012 (95% CI:1.204 approximately 3.362) (P<0.01) respectively. When clustered, the odds ratio of elevated FPG and dyslipidemia was 6.659 (95% CI: 1.337 approximately 33.159) (P<0.01). The waist-to-height ratio is an appropriate measure to assess dyslipidemic-diabetic adolescents and should be used to guide early intervention with the aim of future prevention of these linked diseases.


Coding of Sexual Assault by Emergency Physicians: A Nationally Representative Study.
Sexual assault is a public health problem that affects many Americans and has multiple long-lasting effects on victims. Medical evaluation after sexual assault frequently occurs in the emergency department, and documentation of the visit plays a significant role in decisions regarding prosecution and outcomes of legal cases against perpetrators. The American College of Emergency Physicians recommends coding such visits as sexual assault rather than adding modifiers such as "alleged." This study reviews factors associated with coding of visits as sexual assault compared to suspected sexual assault using the 2016 Nationwide Emergency Department Sample. Younger age, female gender, a larger number of procedure codes, urban hospital location, and lack of concurrent alcohol use are associated with coding for confirmed sexual assault. Implications of this coding are discussed.


Time trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in the UK 2009-2018: a retrospective cohort study.
To describe recent trends in the incidence of clinically diagnosed type 2 diabetes and pre-diabetes in people seen in UK general practice. A retrospective cohort study using IQVIA Medical Research Data looking at people newly diagnosed with type 2 diabetes and pre-diabetes through primary care registers in the UK between 1 January 2009 and 31 December 2018. A cohort of 426 717 people were clinically diagnosed with type 2 diabetes and 418 656 people met the criteria for a diagnosis of pre-diabetes in that time period. The incidence of clinically diagnosed type 2 diabetes per 1000 person years at risk (PYAR) in men decreased from a peak of 5.06 per 1000 PYAR (95% CI 4.97 to 5.15) in 2013 to 3.56 per 1000 PYAR (95% CI 3.46 to 3.66) by 2018. For women, the incidence of clinically diagnosed type 2 diabetes per 1000 PYAR decreased from 4.45 (95% CI 4.37 to 4.54) in 2013 to 2.85 (2.76 to 2.93) in 2018. The incidence rate of pre-diabetes tripled by the end of the same study period in men and women. Between 2009 and 2018, the incidence rate of new clinical diagnoses of type 2 diabetes recorded in a UK primary care database decreased by a third from its peak in 2013-2014, while the incidence of pre-diabetes has tripled. The implications of this on timely treatment, complication rates and mortality need further longer term exploration.


Binaural interaction in brainstem potentials of human subjects.
Binaural interaction in the short-latency averaged auditory evoked potentials (AEPs) can be assessed from the binaural difference waveform (BD). The BD is derived by computing the difference between the AEP evoked by simultaneous clicks from both earphones and the sum of two other AEPs: one evoked by clicks from the right earphone alone and the other evoked by clicks from the left earphone alone. Once the contributions of acoustic cross talk and the middle ear reflex are eliminated, the BD can be considered to represent neural binaural interaction. This interaction begins after wave III and has its first major peak during the dowmslope of wave V. The more localizing value than the AEPs alone since the BD probably represents a subpopulation of generators of the AEPs, which show binaural interaction at the single cell level.


Xenon-induced inhibition of synchronized bursts in a rat cortical neuronal network.
Xenon (Xe) and other inert gases produce anesthesia via an inhibitory mechanism in neuronal networks. To better understand this mechanism, we measured the electrical signals from cultured rat cortical neuronal networks in a multi-electrode array (MEA) under an applied Xe pressure. We used the MEA to measure the firing of the neuronal network with and without Xe gas pressurized to 0.3MPa. The MEA system monitored neuronal spikes on 16 electrodes (each 50×50μm(2)) at a sampling rate of 20kHz. The embryo rat cortical cells were first cultured on MEAs without Xe for approximately 3weeks, at which time they produced synchronized bursts that indicate maturity. Then, with an applied Xe pressure, the synchronized bursts quickly ceased, whereas single spikes continued. The Xe-induced inhibition-recovery of neuronal network firing was reversible: after purging Xe from the system, the synchronized bursts gradually resumed. Thus, Xe did not inhibit single neuron firing, yet reversibly inhibited the synaptic transmission. This finding agrees with the channel-blocker and a modified-hydrate hypothesis of anesthesia, but not the lipid-solubility hypothesis.


Feasibility of tailored follow-up for patients with early breast cancer.
As the number of breast cancer survivors increases, this study prospectively examined whether tailored follow-up with differentiated number of visits per risk group, based on a prognostic index for local recurrence, is feasible and acceptable for patients and professionals. Between March 2007 and March 2010, 180 breast cancer patients (pT1-2N0-2cM0) were included. Primary endpoint was feasibility of tailored follow-up, based on the number of follow-up visits, patient satisfaction, anxiety and attitude towards follow-up. Secondary endpoints were reasons for visits, incidence, time to detection of local recurrences and the use of alternative care. In the second and third year of follow-up, the results show a 22% reduction in visits per patient in the low-risk group compared to the intermediate-risk group; 2.8 versus 3.6 visits. The majority of interval visits in both groups was initiated by the professional. No significant differences were found in attitude towards follow-up, patient satisfaction, anxiety and depression, alternative health care use or local recurrences between the risk groups. In conclusion, implementation of a tailored follow-up programme with decreased number of visits for low-risk patients is feasible and acceptable to patients. Appointing one coordinating professional, possibly a nurse practitioner, could further reduce the number of follow-up visits.


PFAPA syndrome in siblings. Is there a genetic background?
"PFAPA syndrome" is an autoinflammatory entity composed of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. There have been many reports of children with the disease, but only occasionally have been described in siblings, and no specific genetic mutation has been determined yet. Corticosteroids are the mainstay in the treatment of the acute attacks. The role of surgery in long-term follow-up (tonsillectomy with or without adenoidectomy) is controversial. We report two brothers affected with the syndrome, in whom corticosteroids as the only treatment led to an improvement. A genetic work-up was performed, making very unlikely other possible syndromes of recurrent fever. PFAPA syndrome is the most common recurrent periodic fever disorder described in childhood. Its genetic background has not been elucidated yet. Our contribution with two siblings affected with PFAPA syndrome further support the genetic basis for the entity.


Differentiation of cultured neuroblastoma induced by staurosporine and cyclic AMP: methods for assessing a neuronal phenotype.
In cultured neuronal cells, neurite outgrowth provides a prominent morphological marker for assessing neurotrophic activity derived from different sources. Permanent cell lines are often used for such studies; however, the process of differentiation should be evaluated biochemically or electrophysiologically to determine whether the affected cells acquire a neuronal phenotype. We have reported that low-dose staurosporine acts synergistically with cyclic AMP to induce neuronal differentiation in a human neuroblastoma cell line. This protocol describes a method for examining phenotypic changes in cultured cells.


Comparison of Tenofovir Disoproxil Fumarate and Entecavir in the Prophylaxis of HBV Reactivation.
Current guidelines recommend starting antiviral prophylaxis to prevent hepatitis B virus (HBV) reactivation in patients receiving immunosuppressive treatments (IST). The aim of this study was to compare the efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) for prophylaxis. Patients, who were HBsAg and/or anti-HBc IgG positive and scheduled to receive IST for oncologic and hematologic diseases, were enrolled into the study. Those who were already receiving an antiviral treatment for HBV or had an associated HIV, hepatitis C, D were excluded. The remaining patients with a prophylaxis indication according to the AGA guideline were randomized to receive either ETV (0.5 mg/day) or TDF (245 mg/day). Prophylaxis was continued for 6-12 months after completion of IST. Patients were followed up for 1 year after completion of prophylaxis. The HBV reactivation rates and side effects of the drugs were compared. The study group included 120 patients. There was no significant difference between the demographic data, viral serologic parameters and reactivation risk profiles of the ETV (n = 60) and TDF (n = 60) groups. Forty-one patients in the ETV and 36 in the TDF group completed the antiviral prophylaxis, and no HBV reactivation was observed. HBV reactivation was observed in 4 of 37 patients (10.8%) in the ETV group and 5 of 35 (14.3%) patients in the TDF group (including one with flare) during the follow-up after completion of prophylaxis. Ten patients in the ETV group (16.7%) and 14 patients (23.3%) in the TDF group experienced side effects (p = 0.77). One patient in the TDF group had to switch to ETV due to severe itchy, maculopapular rash-like lesions. ETV and TDF had a similar efficacy in the prophylaxis of HBV reactivation in patients undergoing IST, with none of the patients experiencing reactivation.


Sex-linked difference in DNA content of a polytene chromosome in Prodiamesa (Chironomidae).
The chironomid Prodiamesa olivacea possesses 3 pairs of chromosomes. The underreplication of the right arm in the polytene 3rd was presented earlier and is here shown to affect in females the cell nuclei of salivary glands. Malpighian tubules and the hindgut. The same somatic nucleic in males exhibit also a polytene 3rd with specific characteristics inasmuch as it contains half the relative DNA value of the female nuclei (3% instead of 6% complemental portion). - In male meiocytes the two partners in each of the 3 diakinetic bivalents were recognized to be homomorphic. In view of this morphological criterium the polytene situation in males must be due either to an unknown elimination process or to the underreplication of both right arms and further one left arm of the 3rd chromosomes. The latter model interprets the elements of the 3rd pair as differently polytenizing heterosomes in P. olivacea.


The Role of Community Health Agents in Promoting Social Change in Peru.
Community health agents (CHAs) provide basic health services and increase health care access thereby improving health outcomes for peri-urban regions in Peru. Few studies analyze the effect that becoming a CHA has on women's interpersonal interactions. We aim to explore the impact CHAs may have on gender and social norms through their roles as trusted leaders in male-dominated communities. We conducted six 90-minute group discussions with CHAs working in Huancayo and Trujillo, Peru. We designed the discussions to extract data about family and community norms that changed as a result of working as a CHA. A total of 53 female CHAs participated in six discussion groups. CHAs reported shifting family support (a change in how their family supported them in their role as a CHA), gaining status within their family (feeling more valued for their knowledge and experience), and shifting family gender roles (men and boys taking on more household responsibilities) as a result of their work. CHAs also reported a change in community norms and felt they were more valued and respected within their communities as women leaders. Working as a CHA creates an opportunity to enact social change through altering family dynamics and community perceptions. Moreover, empowering women to become CHAs not only generates tangible benefits in community health, but can help create social change that ultimately improves the lives of women and realize their human rights.


Measuring the accuracies of motor unit firing times and action potential waveforms derived from surface electromyographic decomposition.
This study included spike trigger averaging (STA) procedures to examine the acceptability of the Precision Decomposition (PD) III derived motor unit action potential (MUAP) trains that met the >90% accuracy criteria from the reconstruct-and-test. MUs met the >90% accuracy criteria from the reconstruct-and-test with STA procedures then applied. Y-intercepts and slopes were calculated for the firing rate- and MUAP amplitude-recruitment threshold relationships. Gaussian noise (1% of the SD of the mean interspike interval) was added to the firing times with the changes in MUAPs quantified. A total of 455 MUs were decomposed with 155 MUs removed as a result of the reconstruct-and-test. Five additional MUs were excluded via the STA criteria. The MUAP waveforms deteriorated with the inclusion of Gaussian noise. There were differences in the derived action potentials amplitudes of higher-threshold MUs between the PD III algorithm and the STA procedure. There was excellent agreement among the slopes and y-intercepts between the relationships that included or excluded MUs that did not meet the STA criteria. There was good agreement between the MUAP amplitude-recruitment threshold relationships derived from the PD III and STA procedure. The addition of the STA procedures did not alter the MU-derived relationships.


Gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin primes cortical microglia to tissue injury.
Recent studies have shown that the aryl hydrocarbon receptor (AhR) is expressed in the brain's native immune cells, known as microglia. However, while the impact of exposure to AhR ligands is well studied in the peripheral immune system, the impact of such exposure on immune function in the brain is less well defined. Microglia serve dual roles in providing synaptic and immunological support for neighboring neurons and in mediating responses to environmental stimuli, including exposure to environmental chemicals. Because of their dual roles in regulating physiological and pathological processes, cortical microglia are well positioned to translate toxic stimuli into defects in cortical function via aberrant synaptic and immunological functioning, mediated either through direct microglial AhR activation or in response to AhR activation in neighboring cells. Here, we use gene expression studies, histology, and two-photon in vivo imaging to investigate how developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a high-affinity and persistent AhR agonist, modulates microglial characteristics and function in the intact brain. Whole cortical RT-qPCR analysis and RNA-sequencing of isolated microglia revealed that gestational and lactational TCDD exposure produced subtle, but durable, changes in microglia transcripts. Histological examination and two-photon in vivo imaging revealed that while microglia density, distribution, morphology, and motility were unaffected by TCDD exposure, exposure resulted in microglia that responded more robustly to focal tissue injury. However, this effect was rectified with depletion and repopulation of microglia. These results suggest that gestational and lactational exposure to AhR ligands can result in long-term priming of microglia to produce heightened responses towards tissue injury which can be restored to normal function through microglial repopulation.


Piperine alleviates acute pancreatitis: A possible role for FAM134B and CCPG1 dependent ER-phagy.
Acute pancreatitis was a common acute abdominal disease characterized by pancreatic acinar cell death and inflammation. Endoplasmic reticulum autophagy (ER-phagy) coud maintain cell homeostasis by degrading redundant and disordered endoplasmic reticulum and FAM134B and CCPG1 was main ER-phagy receptors. As a natural alkaloid, piperin is found in black pepper and has anti-inflammatory properties, whose effect on ER-phagy in pancreatitis has not been studied. The objective of this study was to demonstrate the pivotal role of FAM134B and CCPG1 dependent ER-phagy for alleviating acute pancreatitis and explore the molecular mechanism of piperine in alleviating acute pancreatitis. In this study we investigated the role of ER-phagy in acute pancreatitis and whether piperine could alleviate pancreatitis through ER-phagy regulation. We first detected endoplasmic reticulum stress (ER-stress) and ER-phagy in different degrees of acute pancreatitis. Then we used ER-stress and autophagy regulators to explore the relationship between ER-stress and ER-phagy in acute pancreatitis and their regulation of cell death. Through using FAM134B-/- and CCPG1-/-, we investigated the mechanism of piperine in the treatment of acute pancreatitis. In this study, we confirmed that with the progression of acute pancreatitis, the pancreatic endoplasmic reticulum stress increased continuously, but the ER-phagy increased first and then was inhibited. Meanwhile, in acute pancreatitis, ER-stress and ER-phagy interacted: endoplasmic reticulum stress can induce ER-phagy, but serious ER-stress would inhibit ER-phagy; and ER-phagy could alleviate ER-stress. Next, we found that piperine reduced ER-stress by enhancing FAM134B and CCPG1 dependent ER-phagy, thereby alleviating pancreatic injury. Impaired ER-phagy was both a cause and a consequence of ER-stress in AP mice, which contributed to the transition from AP to SAP. Piperine targeting ER-phagy provided a new insight into the pharmacological mechanism of piperine in treating AP.


Parent training intervention for autism symptoms, functional emotional development, and parental stress in children with autism disorder: A randomized clinical trial.
Today, early interventions to treat autistic children through parent training interventions is of outmost importance. Interventions are focused on developmental or behavioral approaches and are mostly individual or group ones. In the present study, both proposed approaches in the form of structured individual and group parent training sessions among Iranian families are investigated. This study was a randomized clinical trial which was performed in 2019-2020 in Tehran. Forty four 3-5 year-old children with autism participated in the study and were assigned to experimental (n = 22) and control (n = 22) groups through block randomization method. To evaluate the effectiveness of therapy on autism symptoms, Gilliam Autism Rating and Functional Emotional Assessment Scales were used. Also, Parenting Stress Index and Quality of Life Questionnaire were implemented to investigate the secondary effects of the therapy. After 12 therapy sessions, both groups took the posttest and 3 months later, follow up evaluations were performed. The treatment group manifested significant improvement regarding autism symptoms in both the posttest and follow up (ŋ2 = .77, P < .05) as well as Functional Emotional Development (ŋ2 = .62, P < .05). Comparing the means indicates that the experimental group mean score is significantly higher in quality of life and lower in parenting stress than the control group's. Parent training is effective on autism symptoms and functional emotional development. Regarding the fact that the follow-up phase coincided with Covid-19 pandemic and quarantine, it can be concluded that the therapy has been successful in maintaining the attained capabilities.


Selective antitumor activity of drug-free TPGS nanomicelles with ROS-induced mitochondrial cell death.
D-a-tocopheryl polyethylene glycol succinate (TPGS) as a FDA-approved safe adjuvant has shown an excellent application in the targeting delivery of antitumor drugs and overcoming multidrug resistance. Beside, TPGS can result in apoptogenic activity toward many tumor types because it can induce mitochondrial dysfunction. Therefore, TPGS can serve as an antineoplastic agent. However, the current research on the selective antitumor activity of TPGS is ignored. To reveal the issue, herein we develop a mitochondria-targeting drug-free TPGS nanomicelles with the hydrodynamic diameter of about 100 nm and outstanding serum stability by weak interaction-driven self-assembly of the amphiphilic TPGS polymer. Moreover, such drug-free TPGS nanomicelles intravenously injected into tumor-bearing mice exhibit long blood circulation time, superior tumor enrichment, and inhibit the tumor growth via inducing excessive reactive oxygen species (ROS) generation within tumor cells. Further in vitro and in vivo researches jointly demonstrate that drug-free TPGS nanomicelles have more significant antitumor effect on HeLa cells compared with that of other tumor cells. On the contrary, drug-free TPGS nanomicelles display the low toxicity toward normal cells and tissues. Taken together, these new findings confirm that TPGS drug-free nanomicelles represent simple, multifunctional, safe, and efficient antineoplastic agents, which can be expected to bring new light on the development of drug-free polymers for tumor therapy.


Association of Angiotensin-Converting Enzyme gene polymorphism in Pakistani women with the atypical steroidogenesis in Polycystic ovarian syndrome: A case-control study.
Polymorphism in the angiotensin-converting enzyme gene (ACE) is responsible for elevated ACE concentrations in plasma. High ACE levels induce insulin resistance and hyperandrogenism, which are the main attributes of polycystic ovary syndrome (PCOS). Therefore, it was hypothesized that I/D polymorphism plays a role in the pathogenesis of PCOS. A case-control study was designed to investigate the association of I/D polymorphism of the ACE gene with PCOS in Pakistani women of reproductive age. ACE I/D polymorphism was assessed in 252 women of age group 16-40 years. For genotypic analysis, PCR amplification of genomic DNA was carried out. Statistical analysis was performed to interpret the results using SPSS software. Our study showed that PCOS women were more likely to have a high body mass index and waist circumferences. Most PCOS patients had menstrual irregularities 99.3%, hirsutism 75.2% and cysts in ovaries 66.6%, along with other hyperandrogenic conditions (P-value = 0.001). The genotypic and allelic frequencies were significantly different between patients and controls. There was a significant association of three genotypes with the ratio of LH: FSH among PCOS patients (P = 0.05). Anthropometric characters, comorbidities, clinical symptoms, and PCOS conditions showed no statistical significance with ACE polymorphism. ACE I/D polymorphism was not found associated with clinical conditions of PCOS in women of reproductive age. However, it was associated with atypical steroidogenesis. So, it indicates that ACE I/D polymorphism aggravates the pathogenesis of PCOS.


Chemical probes for biological systems.
According to the latest definition in use by the NIH Molecular Libraries Screening Centers Network, a compound to be nominated as a chemical probe should have, on the one hand, an affinity below 100 nM for the primary target and, on the other hand, at least tenfold selectivity against related targets. Taking drugs as the ultimate product of an affinity and selectivity optimization process, it is found that only 14.4% of them would actually qualify as chemical probes under those criteria. Therefore, if chemical probes are expected to give rise to new medicines, strict adherence to the current probe definition might result in many compounds of potential therapeutic interest being overlooked.


Looking for genetic effects of polluted anthropized environments on Caiman crocodilus crocodilus (Reptilia, Crocodylia): A comparative genotoxic and chromosomal analysis.
The Amazon aquatic ecosystems have been modified by the human population growth, going through changes in their water bodies and aquatic biota. The spectacled alligator (Caiman crocodilus crocodilus) has a wide distribution and adaptability to several environments, even those polluted ones. This study aimed to investigate if a Caiman species living in urban streams of Manaus city (Amazonas State, Brazil) is affected by environmental pollution. For that, it was used classical and molecular cytogenetic procedures, in addition to micronucleus and comet assays. Although the karyotype macrostructure remains unaltered (2 n = 42 chromosomes; 24 t + 18 m/sm; NF = 60), the genotoxic analysis and the cytogenetic mapping of repetitive DNA sequences demonstrated that polluted environments alter the genome of the specimens, affecting both the chromosomal organization and the genetic material.


Supplementing Garlic Nanohydrogel Optimized Growth, Gastrointestinal Integrity and Economics and Ameliorated Necrotic Enteritis in Broiler Chickens Using a Clostridium perfringens Challenge Model.
Necrotic enteritis (NE) caused by Clostridium perfringens (C. perfringens) results in impaired bird growth performance and increased production costs. Nanotechnology application in the poultry industry to control NE outbreaks is still not completely clarified. Therefore, the efficacy of dietary garlic nano-hydrogel (G-NHG) on broilers growth performance, intestinal integrity, economic returns and its potency to alleviate C. perfringens levels using NE challenge model were addressed. A total of 1200 male broiler chicks (Ross 308) were assigned into six groups; four supplemented with 100, 200, 300 or 400 mg of G-NHG/kg diet and co-challenged with C. perfringens at 21, 22 and 23 d of age and two control groups fed basal diet with or without C. perfringens challenge. Over the total growing period, the 400 mg/kg G-NHG group had the most improved body weight gain and feed conversion efficiency regardless of challenge. Parallel with these results, the mRNA expression of genes encoding digestive enzymes (alpha 2A amylase (AMY2A), pancreatic lipase (PNLIP) and cholecystokinin (CCK)) and intestinal barriers (junctional adhesion molecule-2 (JAM-2), occludin and mucin-2 (Muc-2)) were increased in groups fed G-NHG at higher levels to be nearly similar to those in the unchallenged group. At 14 d post challenge, real-time PCR results revealed that inclusion of G-NHG led to a dose-dependently decrease in the C. perfringens population, thereby decreasing the birds' intestinal lesion score and mortality rates. Using 400 mg/kg of G-NHG remarkably ameliorated the adverse effects of NE caused by C. perfringens challenge, which contributed to better growth performance of challenged birds with rational economic benefits.


Up-regulation of calcitonin gene-related peptide protects streptozotocin-induced diabetic hearts from ischemia/reperfusion injury.
Diabetic hearts are vulnerable to ischemia/reperfusion (I/R) injury. Pretreatment with exogenous calcitonin gene-related peptide (CGRP) exerts a cardioprotective effect against myocardial I/R injury. Our previous study found that the CGRP level was decreased in diabetic hearts. This study aimed to investigate whether up-regulation of CGRP could reduce I/R injury in diabetic hearts. Adenovirus encoding the CGRP gene (Ad-CGRP) was injected intramyocardially in mice with or without streptozotocin (STZ) treatment. Three days after injection, the hearts were subjected to in vivo and in vitro I/R. Myocardial infarct size, cardiac function, lactate dehydrogenase (LDH) level in plasma and effluents, and cell mitochondrial function were measured. After ischemia (30 min) and reperfusion (24h) in vivo, diabetes mellitus (DM) mice had greater myocardial infarct size than their nondiabetic counterparts, and released more LDH in plasma. However, CGRP gene transfer reduced myocardial infarct size and plasma LDH level in both non-DM and DM hearts. After 30 min global ischemia and 40 min reperfusion in vitro, the DM hearts demonstrated increased left ventricular end-diastolic pressure (LVEDP) and effluent LDH level, and decreased left ventricular developed pressure (LVDP), coronary flow (CF), as well as cell mitochondrial function, when compared with the non-DM hearts. Again, CGRP gene transfer could protect against I/R injury in both non-DM and DM hearts. Adenovirus-mediated up-regulation of CGRP gene expression protects diabetic hearts against I/R injury.


Comparing the incommensurable: where science and politics collide.
Arguments about the possibility that cognitive variables may play a causal role in human behavior are unlikely to be resolved in favor of one side or the other, because they set against each other two incommensurable views of human agency. Contemporary cognitive models of psychology are based on an implicitly dualist view of human behavior, assuming the existence of a nonmaterial mental realm which has the capacity to act on the material world. Critics, by comparison, frequently argue from an epiphenomenalist position. While there may be sound scientific reasons for rejecting self-efficacy theory, and particularly for rejecting the utility of the concept that behavior is caused by efficacy expectations, this paper argues that epistemic criteria are frequently less important than a sense that a theory is compatible with a particular world view. I argue that cognitive theories are accepted by the psychological mainstream because their dualist basis accords with deeply held cultureal beliefs about the relationship between the person and the world. However, the social and political consequences of such models are rarely articulated, and there is a need for psychologists to develop a more explicit understanding of the relationship between psychological theories and their broader implications.


Clinical investigation on abnormal glucose tolerance in liver cirrhosis.
The changes of blood glucose, serum insulin, serum free fatty acid and its fatty acid composition following oral glucose load were observed in twenty-nine cirrhotic patients. The insulin secretory response was significantly lower in the cirrhotic patients with overt diabetes than in those without overt diabetes. There were no definite relation between serum free fatty acid level or its composition and glucose intolerance. These results suggest that the diabetic state in most of the cirrhotic patients with overt diabetes is due to essential diabetes and that serum free fatty acid livel and its composition are not important factors contributory to the glucose intolerance in liver cirrhosis.


The treatment of ulcers on legs with split-thickness skin grafts: report of a simple technique.
The placing of split-thickness skin grafts on chronic ulcers on legs in the usual way is tedious and time consuming. An effective technique that is simply and quickly done is described and illustrated herein. At least two weeks of hospitalization is required to insure complete healing.


Inhaled epinephrine and oral theophylline-ephedrine in the treatment of asthma.
Inhaled and oral over-the-counter bronchodilators are used for self-therapy by asthmatic patients. To evaluate their safety and efficacy, we compared epinephrine and theophylline combined with ephedrine with inhaled metaproterenol and the placebo. Twelve asthmatic patients were studied in a randomized, double-blind, placebo-controlled, crossover trial comparing forced expiratory volume in 1 second (FEV1) after two inhalations of epinephrine (0.2 mg/inh), 1 minute apart, followed in 15 minutes by theophylline (130 mg) with ephedrine (24 mg) versus two inhalations of metaproterenol (0.65 mg/inh), 1 minute apart, versus placebo inhaler and tablets. Onset of FEV1 greater than 15% above baseline values occurred within 15 seconds after inhalations for 100% of epinephrine-treated patients, 92% of metaproterenol-treated patients, and 33% of placebo-treated patients. FEV1 responses were significantly greater (P less than .05) for epinephrine at 0.66 to 1.66 minutes compared with the responses of metaproterenol, and epinephrine and theophylline that was combined with ephedrine compared with metaproterenol beginning at 2 hours. Mean duration of activity was 5.7 hours for the epinephrine- and theophylline with ephedrine-treated patients, 4.9 hours for metaproterenol-treated patients, and 2 hours for the placebo group. There were statistically significant differences for patients receiving epinephrine and theophylline with ephedrine versus the placebo group (P less than .001), metaproterenol patients versus the placebo group (P = .02), and patients receiving epinephrine and theophylline with ephedrine versus metaproterenol-treated patients (P less than .05). Compared with inhaled metaproterenol, inhaled epinephrine followed in 15 minutes by a theophylline-ephedrine tablet had a significantly earlier onset, longer duration of action, numerically greater peak effect, and patient preference.(ABSTRACT TRUNCATED AT 250 WORDS)


Hybrid capacitive deionization of NaCl and toxic heavy metal ions using faradic electrodes of silver nanospheres decorated pomegranate peel-derived activated carbon.
Capacitive deionization (CDI) is an evolving technology for eradicating salt and toxic heavy metal ions from brackish wastewater. However, traditional CDI electrodes have lower salt adsorption capacity and inadequate adsorption of selective metal ions for long-term operations. Herein, Ag nanospheres incorporated pomegranate peel-derived activated carbon (Ag/P-AC) was prepared and implied to the CDI process for removing NaCl, toxic mono-, di-, and trivalent metal ions. Morphological analysis revealed that the 80-100 nm-sized Ag nanospheres were uniformly decorated on the surfaces of P-AC nanosheets. The Ag/P-AC has a higher specific surface area (640 m2 g-1), superior specific capacitance (180 F g-1 at 50 mV s-1) and a lower charge transfer resistance (0.5 Ω cm2). CDI device was fabricated by Ag/P-AC as an anode, which adsorbed anions and P-AC as cathode for adsorption of positively charged ions at 1.2 V in an initial salt concentration of 1000 mg L-1. An asymmetric Ag/P-AC//P-AC exhibited a maximum NaCl adsorption capacity of 36 mg g-1 than symmetric P-AC//P-AC electrodes (22.7 mg g-1). Furthermore, Pb(II), Cd(II), F-, and As(III) ions were successfully removed from simulated wastewater by using Ag/P-AC//P-AC based CDI system. These asymmetric CDI-electrodes have an excellent prospect for the removal of salt and toxic contaminants in industrial wastewater.


Melatonin and enterochromaffine cells.
As a result of investigations active biosynthesis of melatonin was found in enterochromaffin cells of gastrointestinal tract. It is suggested to unify epiphysis and enterochromaffine cells into a united functionally active neuroendocrine system, which plays an important role in the control of rhythms of biological processes in the body.


A quantitative approach for sealing capacity evaluation of caprock in candidate of aquifer gas storage.
The gas sealing capacity of caprock (SCC) is one of the key factors that determine whether aquifer trap can be constructed into underground gas storage (UGS). However, no standard protocol for evaluating SCC of candidate aquifers has been proposed. Based on the core observation, laboratory experiment, and well logging data, the sealing capacity of the target aquifer caprock of Permian mudstone in D5 block of Litan sag, China, is quantitatively evaluated. The important parameters of mineral brittleness, permeability, breakthrough pressure (BP), mechanical brittleness, thickness, and areal extent that affect the SCC are determined. The results of specific tests and data statistics show that the caprock of D5 block is a low permeability rock with a permeability of 10-4 mD, and the BP of undisturbed rock is greater than 38 MPa. Although the brittle mineral quartz is abundant with an average of 38.38%, the mechanical brittleness is not strong under formation conditions. The direct caprock has a thickness of greater than 50 m, and on the top of it is a high-quality indirect caprock that complements the physical closure. The results of a mathematical evaluation model show that except for the sealing index of sample 2, all the other samples have optimal sealing capacity. The field interference test shows that the optimal sealing capacity of the caprock meets the requirements of the construction of underground gas storage (UGS). The rationality of the comprehensive evaluation model can provide a reference for similar evaluation projects in the future.


Evaluation of an implementation support package to increase community mental health clinicians' routine delivery of preventive care for multiple health behaviours: a non-randomised controlled trial.
People with a mental health condition are more likely to engage in risk behaviours compared to people without. Delivery of preventive care to improve such behaviours is recommended for community mental health services, but inadequately implemented. This study assessed the effectiveness of an implementation support package on clinicians' delivery of preventive care (assessment, advice, referral) for four risk behaviours (tobacco smoking, harmful alcohol consumption, physical inactivity, inadequate fruit and vegetable intake) compared to no implementation support. The participatory approach to developing the support package, and fidelity of the implementation strategies, are also described. A non-randomised controlled trial was undertaken in 2019-2020 with two community mental health services (control and target) in one health district in New South Wales, Australia. A 4-month support package consisting of multiple implementation strategies was delivered to one site following a two-phase participatory design process. Five implementation strategies were proposed to service managers by researchers. After consultation with managers and clinicians, the final implementation support package included four strategies: training and education materials, enabling resources and prompts, client activation material, and audit and feedback. Client-reported receipt of the three elements of preventive care for the four risk behaviours was collected from a cross-sectional sample of clients who had recently attended the service at baseline (6 months) and follow-up (5 months). Logistic regression models examined change in receipt of preventive care to assess effectiveness. A total of 860 client surveys were completed (control baseline n = 168; target baseline n = 261; control follow-up n = 164; and target follow-up n = 267). Analyses revealed no significant differential changes in preventive care receipt between the target and control sites from baseline to follow-up, including across the four primary outcomes: assessed for all behaviours (OR = 1.19; 95% CI 0.55, 2.57; p = 0.65); advised for all relevant risk behaviours (OR = 1.18; 95% CI 0.39, 3.61; p = 0.77); referred for any relevant risk behaviour (OR = 0.80; 95% CI 0.40, 1.63; p = 0.55); and complete care (OR = 3.11; 95% CI 0.62, 15.63; p = 0.17). Fidelity of the implementation strategies was limited as one of the four strategies (audit and feedback) was not delivered, components of two strategies (enabling resources and prompts, and client activation material) were not delivered as intended, and one strategy (education and training) was delivered as intended although some components were offered late in the implementation period. The implementation support package was ineffective at increasing preventive care delivery. Further investigation is required to determine optimal participatory design methods to develop effective implementation strategies, including those that support delivery of care in community mental health settings within the ongoing context of uncertain environmental challenges. Australian and New Zealand Clinical Trials Registry ACTRN12619001379101.


Health service engagement, side effects and concerns among men with anabolic-androgenic steroid use: a cross-sectional Norwegian study.
Recreational use of anabolic-androgenic steroids (AAS) is a public health concern world-wide associated with a range of physical and psychological side effects. Still, people who use AAS tend to be reluctant to seek treatment. This study aims to explore use characteristics, treatment-seeking behaviour, side effects and associated health concerns among men with AAS use. The study includes cross-sectional self-report data from 90 men with a current or previous use of AAS exceeding 12 months, where 41 (45.6%) had sought treatment at least once during their lifetime, and 49 (54.4%) had not. Health service engagement was examined with descriptive statistics on reasons for contacting health services, transparency about AAS use, satisfaction with health services and reasons for not seeking treatment. Furthermore, experienced side effects and health concerns were compared between the treatment seeking and the non-treatment seeking group, using two-sample t-tests and Chi2 or Fisher exact tests for numerical and categorical variables, respectively. All 90 AAS-using men reported side effects from AAS use. Treatment seekers were significantly younger, experienced more side effects including gynecomastia, excessive sweating, fatigue, depression and anxiety, and expressed more concern for testosterone deficiency. Preventive health check-up was the most common reason for seeking treatment (n = 22, 53.7%), and 38 men (93%) were transparent about AAS use during consultations with health professionals. The main reported reasons for not seeking healthcare services were that the experienced side effects were not considered to be of treatment demanding nature (n = 39, 79.6%) and the belief that healthcare providers had scarce knowledge about AAS use and its health impacts (n = 12, 24.5%). Reluctance to seek treatment among people who use AAS, despite having associated side effects and health concerns, may contribute to continued health risks. It is important to fill the knowledge gap on how to reach and treat this new patient group, and policy makers and treatment providers need to be educated on how to meet their treatment needs.


Continuous transport of Pacific-derived anthropogenic radionuclides towards the Indian Ocean.
Unusually high concentrations of americium and plutonium have been observed in a sediment core collected from the eastern Lombok Basin between Sumba and Sumbawa Islands in the Indonesian Archipelago. Gamma spectrometry and accelerator mass spectrometry data together with radiometric dating of the core provide a high-resolution record of ongoing deposition of anthropogenic radionuclides. A plutonium signature characteristic of the Pacific Proving Grounds (PPG) dominates in the first two decades after the start of the high yield atmospheric tests in 1950's. Approximately 40-70% of plutonium at this site in the post 1970 period originates from the PPG. This sediment record of transuranic isotopes deposition over the last 55 years provides evidence for the continuous long-distance transport of particle-reactive radionuclides from the Pacific Ocean towards the Indian Ocean.


Stochastic analysis of gene expression.
In this chapter, stochasticity in gene expression is investigated using Ω-expansion technique. Two theoretical models are considered here, one concern the stochastic fluctuations in a single-gene network with negative feedback regulation, and the other the additivity of noise propagation in a protein cascade. All of these theoretical analyses may provide a basic framework for understanding stochastic gene expression.


In-situ development of boron doped g-C3N4 supported SBA-15 nanocomposites for photocatalytic degradation of tetracycline.
In this study, versatile boron-doped graphitic carbon nitride (gCN) incorporated mesoporous SBA-15 (BGS) composite materials were prepared by thermal polycondensation method using boric acid & melamine as a B-gCN source material and SBA-15 as mesoporous support. The prepared BGS composites are utilized sustainably using solar light as the energy source for the continuous flow of photodegradation of tetracycline (TC) antibiotics. This work highlights that the photocatalysts preparation was carried out with an eco-friendly strategy, solvent-free and without additional reagents. To alter the amount of boron quantity (0.124 g, 0.248 g, and 0.49 g) have to prepare three different composites using a similar procedure, the obtained composites viz., BGS-1, BGS-2 and BGS-3, respectively. The physicochemical property of the prepared composites was investigated by X-ray diffractometry, Fourier-transform infrared spectroscopy, Raman, Diffraction reflectance spectra, Photoluminescence, Brunauer-Emmett-Teller and transmission electron microscopy (TEM). The results shows that 0.24 g boron- loaded BGS composites degrade TC up to 93.74%, which is much higher than the rest of the catalyst. The addition of mesoporous SBA-15 incresed the specific surface area of the g-CN, and heteroatom of boron increased the interplanar stracking distance of g-CN, enlarged the optical absorption range, reducing the energy bandgap and enhanced the photocatalytic activity of TC. Additionally, the stability and recycling efficiency of the representative photocatalysts viz., BGS-2 was observed to be good even at the fifth cycle. The photocatalytic process using the BGS composites demonstrated to be capable candidate for the removal of tetracycline biowaste from aquesous media.


Self-induced Elizabethkingia meningoseptica endophthalmitis: a case report.
Endophthalmitis is a sight-threatening condition defined as any inflammation of the internal ocular spaces. It is classified as either endogenous or exogenous depending on the route of infection. Exogenous endophthalmitis results from direct inoculation as a complication of intra-ocular surgery, penetrating ocular trauma, intra-ocular foreign bodies, corneal ulceration and following a breach of ocular barriers from a periocular infection. We report a rare case of exogenous endophthalmitis with both unusual etiology and microbiology. A 41-year-old Caucasian man with a history of depressive illness presented to our eye department with painful acute visual loss on a background history of chronic uveitis. Ocular examination revealed a dense fibrinous panuveitis with a suspicion of a focal lesion in the posterior segment. Microbiological sampling from his anterior chamber and posterior segment revealed a culture of Elizabethkingia meningoseptica. On closer questioning, he volunteered the occurrence of multiple episodes of deliberate needle ocular penetration. Following vitrectomy for associated retinal detachment, a final Snellen visual acuity of 6/60 was obtained. Elizabethkingia meningoseptica endophthalmitis is a rare condition, and visual results to date are poor.


Prognostic value of preoperative chemotherapy for thymic epithelial tumors: A propensity-matched analysis based on the SEER database.
The aim of this study was to assess the impact of preoperative chemotherapy on long-term survival (≥1 month) in patients with thymic epithelial tumors (TETs) and conditions suitable for chemotherapy using data from surveillance, epidemiology, and end-result databases. This retrospective study controlled for confounding factors by propensity score matching (PSM), analyzed overall survival (OS) and cancer-specific survival (CSS) by Kaplan-Meier methods, and analyzed factors affecting the prognosis of patients undergoing surgery for thymic epithelial tumors by univariate and multifactorial Cox regression. A total of 2,451 patients who underwent surgery for TETs were identified from the Surveillance, Epidemiology, and End Results database. Preoperative chemotherapy significantly improved OS and CSS in patients with stage III/IV TETs compared to patients without preoperative chemotherapy. Subgroup analysis showed that patients younger than 60 years of age with TETs, patients with thymic carcinoma, and patients with TETs with multiple cancers were more likely to benefit from preoperative chemotherapy. This study found that preoperative chemotherapy is a viable option for advanced thymoma with favorable overall and cancer-specific survival rates, but patient history and physical condition should be fully considered in conjunction with diagnostic imaging findings to assess patient tolerance to chemotherapy.


Embryo production after superovulation of bovine donors with a reduced number of FSH applications and an increased eCG dose.
This study evaluated embryo production after superovulation (SO) with a reduced number of FSH applications and increased eCG dose in 26 Bos taurus × Bos indicus donors. On Day 0, donors received an intravaginal device (CIDR) with 1.9 g of progesterone plus 2.5 mg of estradiol benzoate and 50 mg of progesterone via IM. On Day 4, donors were randomly allotted to one of three SO treatments: 1) 455 IU of Folltropin +400 IU of eCG (n = 9), 2) 350 IU of Folltropin +600 IU of eCG (n = 9), and 3) 500 IU of Pluset + 600 IU of eCG (n = 8). In treatment 455 IU of Folltropin +400 IU of eCG, donors received eight IM Folltropin injections in decreasing dose 12 h apart from Day 4 to Day 7. On Day 6, at the same time as the Folltropin, donors received via IM 25 mg of dinoprost tromethamine (PGF2a). On Day 7, the CIDR was removed, and together with the Folltropin, donors received 200 IU of eCG via IM. In treatment 350 IU of Folltropin +600 IU of eCG, donors received four IM Folltropin injections in decreasing dose 12 h apart on Days 4 and 5. On Day 6, donors received via IM 600 IU of eCG in the morning and two doses of 25 mg of PGF2a 12 h apart. On Day 7, the CIDR was removed. Donors from treatment 500 IU of Pluset +600 IU of eCG received four IM Pluset injections in decreasing dose 12 h apart on Days 4 and 5. On Day 6, donors received via IM 600 IU of eCG in the morning and two doses of 25 mg of PGF2a 12 h apart. On Day 7, the CIDR was removed. In the morning of Day 8, donors from the three treatments received 0.25 mg of GnRH via IM. Artificial insemination was performed on Day 8 (pm) and Day 9 (am). Embryos were collected on Day 15. Variables evaluated were number of CL before embryo collection, number of structures recovered, transferable embryos, degenerate embryos and unfertilized oocytes, recovery rate, and viability rate. There was no difference in any variable among treatments (P > 0.05). In conclusion, replacement of four Folltropin or Pluset injections from a conventional eight FSH-injection SO protocol, by a single injection of 600 IU of eCG, is a good alternative to reduce donor handling without decreasing yield of transferable embryos.


Editorial Commentary: Biology and Biomechanics Must Be Carefully Balanced for a Durable Rotator Cuff Repair.
Arthroscopic rotator cuff repair strategies have evolved over 3 decades, but suture anchor design, anchor configuration, and stitches have been largely driven by repair biomechanics. In recent years there has been a shift toward repair strategies that enhance the biology of tendon repair. Double-row and transosseous equivalent suture anchor repair constructs demonstrate excellent time zero mechanical properties, but the resulting increased repair tension and tendon compression may compromise tendon healing. Modern single-row repairs employing medialized triple-loaded suture anchors, simple stitches, and lateral marrow venting avoid some of the problems associated with double-row repairs and demonstrate excellent short-term healing and clinical results. The most robust repair fails if the tendon does not heal. Biology and biomechanics must be carefully balanced.


Efficacy and Safety of the Fixed-Dose Versus Variable-Dose of 4-PCC for Vitamin K Antagonist Reversal: A Comprehensive Systematic Review and Meta-Analysis.
The optimal dosing strategy of four-factor prothrombin complex concentrate (4F-PCC) for vitamin K antagonists (VKAs) reversal is unknown. We conducted systematic search on the PubMed, SCOPUS, and Embase databases from inception to December 2020 for clinical studies that compared the fixed-dose versus variable-dose of 4-PCC for VKAs reversal with at least one reported clinical outcome. The treatment effects were expressed as relative ratios (RR) with 95% confidence intervals (CIs) and pooled by a random-effects model. Ten studies, including 988 patients, were included. Fixed-dose 4-PCC was associated with lower rate of mortality (RR= 0.65, 95% CI 0.47 to 0.9, p= 0.009), comparable rate of thromboembolic event (TEE) (RR= 1.10, 95%CI 0.44 to 2.80, p= 0.826), and lower goal INR reached (RR= 0.87, 95%CI 0.78 to 0.96, p= 0.007). Less 4-PCC cumulative dose, shorter duration of order-to-needle time, similar hospital length of stay, the comparable time required for INR reversal, higher post-4-PCC INR, and a higher need for additional dose were observed in fixed-dose. The use of a fixed-dose of 4-PCC may be considered an effective and safe dosing strategy for VKAs reversal in various clinical situations. However, further well-designed, controlled studies should be conducted focusing on clinical outcomes to determine the optimal dose of 4-PCC for VKAs reversal.


Adaptive Ionization-Induced Tunable Electric Double Layer for Practical Zn Metal Batteries over Wide pH and Temperature Ranges.
The violent side reactions of Zn metal in aqueous electrolyte lead to sharp local-pH fluctuations at the interface, which accelerate Zn anode breakdown; thus, the development of an optimization strategy to accommodate a wide pH range is particularly critical for improving aqueous Zn metal batteries. Herein, we report a pH-adaptive electric double layer (EDL) tuned by glycine (Gly) additive with pH-dependent ionization, which exhibits excellent capability to stabilize Zn anodes in wide-pH aqueous electrolytes. It is discovered that a Gly-ionic EDL facilitates the directed migration of charge carriers in both mildly acidic and alkaline electrolytes, leading to the successful suppression of local saturation. It is worth mentioning that the regulation effect of the additive concentration on the inner Helmholtz plane (IHP) structure of Zn electrodes is clarified in depth. It is revealed that the Gly additives without dimerization can develop orderly and dense vertical adsorption within the IHP to effectively reduce the EDL repulsive force of Zn2+ and isolate H2O from the anode surface. Consequently, they Zn anode with tunable EDL exhibits superior electrochemical performance in a wide range of pH and temperature, involving the prodigious cycle reversibility of 7000 h at Zn symmetric cells with ZnSO4-Gly electrolytes and an extended lifespan of 50 times in Zn symmetric cells with KOH-Gly electrolytes. Moreover, acidic Zn powder||MnO2 pouch cells, and alkaline high-voltage Zn||Ni0.8Co0.1Mn0.1O2 cells, and Zn||NiCo-LDH cells also deliver excellent cycling reversibility. The tunable EDL enables the ultrahigh depth of discharge (DOD) of 93%. This work elucidates the design of electrolyte additives compatible in a wide range of pH and temperature, which might cause inspiration in the fields of practical multiapplication scenarios for Zn anodes.


Clinician activism and ethical restraints in providing treatment: preventive as opposed to reconstructive approaches.
There is seldom controversy when faced with treatment decisions for a child born with a birth defect. Occasionally, the situation arises in which a decision to withhold treatment must be made. Under most circumstances the responsibility for making such decisions rests with the child's parents or guardians, since it is generally felt that these individuals are the best advocates for the child's best interests. In order to make such difficult decisions, the parents are dependent upon the guidance and counseling of health professionals, especially the physicians most closely involved in each case. The ultimate decisions made by parents are dependent upon open and unambiguous communication with their children's clinicians as well as open communications among the caregivers themselves. The role of the clinician as an advocate for treatment and nontreatment of children is dependent upon clear unbiased communication and the desire to do what is in the best interest for each patient.


Intravertebral cleft sign on fat-suppressed contrast-enhanced MR: correlation with cement distribution pattern on percutaneous vertebroplasty.
Filling intravertebral clefts during percutaneous vertebroplasty (PVP) is considered to be important for optimal pain control. It is often difficult to detect clefts on non-contrast MR and some fractures show a solid pattern distribution of injected cement without a cleft sign on non-contrast MR. In this study, we evaluated usefulness of fat-suppressed contrast-enhanced MR to predict a solid pattern distribution of injected cement on PVP. Twenty-six patients with 35 vertebral compression fractures due to osteoporosis were studied. We performed sagittal T1-weighted, T2-weighted and fat-suppressed contrast-enhanced T1-weighted images prior to PVP. First we evaluated the presence of fluid-filled or gas-containing clefts on non-contrast MR. Next we evaluated contrast-enhanced MR of the same vertebrae for the presence of cleft-shaped unenhanced areas within the diffuse enhancement area. We correlated MR findings with cement distribution patterns of injected cement. Based on MR findings, 35 osteoporotic fractures were divided into 3 types. Type 1 (11 fractures, 31%): There were no clefts on non-contrast MR and no unenhanced areas on contrast-enhanced MR; Type 2 (13, 37%): There were no clefts on non-contrast MR but there were unenhanced areas on contrast-enhanced MR; Type 3 (13, 37%): There were clefts on non-contrast MR and unenhanced areas on contrast-enhanced MR. Of 35 osteoporotic fractures, thirteen vertebral fractures (37%) were noted to contain clefts on non-contrast MR, while 24 vertebral fractures (69%) contained unenhanced areas on contrast-enhanced MR. Cement distributed as a solid pattern within clefts or unenhanced areas in all fractures with them. Fat-suppressed contrast-enhanced MR is useful to predict a solid pattern distribution of injected cement prior to PVP.


European Governments' Responses to the COVID-19 Pandemic during the First Wave: Resetting Governance Systems to Cope More Effectively with Future Shocks.
The emergence of the current global crisis induced by the rapid spread of the COVID-19 pandemic brings about an urgent need to rethink and reshape recovery strategies adapted to this specific challenging context. Neglecting this reconfiguration could lead to system lockdown, affecting all sectors, both on medium and long term. The coronavirus has penetrated various countries with different degrees of intensity, thus being spatially diversified; even within the same country, with the same lockdown measures, an enormous variety in cases is encountered. Subsequently, even if crises may manifest heterogeneously and the long-term impact of implementing recovery policies cannot be accurately known ex ante by governments, institutions could adapt themselves to changing circumstances and respond promptly and appropriately to emerging shocks only if their functioning framework had been well set up by the outbreak of the crisis. Considering these aspects, the main questions that this paper aims to answer are: How effective have governmental measures in European countries been in combating the COVID-19 crisis?; Could the solutions offered by the European states' governments have an influence on diminishing the intensity of negative effects of a possible more serious return of this health crisis? What more could national authorities and international actors do to control the epidemiological evolution of SARS-CoV-2? Is a generic European Union policy helpful or should there be a case for local policy? Based on these issues, a comprehensive picture of the differences between the East and the West of Europe in terms of some medical, socio-economic, institutional and cultural factors will be outlined, in order to emphasize which of the two groups better-handled the COVID-19 situation in the first wave, covering the lockdown period (March 1, 2020 - June 1, 2020) and the relaxation period (June 1, 2020 - September 1, 2020); at the same time, some policy recommendations on how governments should more effectively manage future similar crises to generate a higher resilience of the systems will be provided.


Relatively low and moderate pre-fracture serum 25-hydroxyvitamin D levels associated with the highest survival in elderly hip fracture patients in Finland: a minimum 3-year follow-up.
The association between serum 25-hydroxyvitamin D level and post-fracture mortality indicates beneficial relatively high serum 25-hydroxyvitamin D concentrations. A 1-year cohort study on 245 hip fracture patients in Finland indicated the lowest 3-year mortality and highest survival among patients with serum 25-hydroxyvitamin D level of 50-74 nmol/L. To explore pre-fracture serum 25-hydroxyvitamin D level as a factor associated with post-fracture survival among a cohort of hip fracture patients in Finland. A prospectively collected cohort of hip fracture patients (n = 245, 70% women) from two hospitals was followed for 3.2 post-hip fracture years. Serum 25-hydroxyvitamin D was measured in admission to the hospital and classified: < 50, 50-74, 75-99, and ≥ 100 nmol/L. Survival was analyzed with a Bayesian multivariate model. Relative survival was explored with the life table method according to serum 25-hydroxyvitamin D. Mortality according to serum 25-hydroxyvitamin D level and to the hospital was calculated. Mortality in the patients with serum 25-hydroxyvitamin D level of 50-74 nmol/L was significantly lower than in all other patients together at every post-fracture year. The most important factors for survival were age under 85 years; living in an actual/private home; serum 25-hydroxyvitamin D level of 50-74 nmol/L, followed by 75-99 nmol/L; ASA classes 1-2 and 3; and female sex. The mean age of patients with serum 25-hydroxyvitamin D level of 50-99 nmol/L was significantly higher than in other levels. Relative survival was highest in men, women, and patients in hospital B with serum 25-hydroxyvitamin D level of 50-74 nmol. The highest 3-year survival and the lowest mortality in this cohort appeared in patients with pre-fracture serum 25-hydroxyvitamin D level of 50-74 nmol/L. This result differs from similar studies and is lower than the recommended level of 25-hydroxyvitamin D among hip fracture patients. The results should be examined in future research with larger data.


What influences adolescents to continuously use e-cigarettes?
The use of e-cigarettes is rapidly increasing in adolescents. Health care providers pay attention to e-cigarette users because of the risk of developing addiction and problematic behavior. Based on ecological perspective, this study investigated factors influencing continued e-cigarette use. We classified 1556 current e-cigarette users into experimental and continued users using the Korean national representative data. Data were analyzed using the chi-square test and logistic regression based on a complex sample analysis. Among current e-cigarette users, 55.1% were continued users. Adolescents who use e-cigarettes because of the belief that they are less harmful than cigarettes, concealment, easy purchase, and adding various flavors had a high risk of continued use. Continued users were more likely to have a higher weekly allowance, lower rate of living with family, and higher chance of smoking parents and exposure to passive smoking at home. Continued e-cigarette use was influenced by interpersonal and environmental factors, such as ease of purchase and addition of flavoring substances. Improving the environment of adolescents can prevent continued use of e-cigarettes.


Detection of HCV antibodies in oral fluid.
Although conventionally the detection of HCV antibodies is carried out on serum, the collection of oral fluid is non-invasive, safe and cost effective. In this study, the efficacy of the detection of HCV antibodies in oral fluid was assessed. 73 anti-HCV positive and 73 anti-HCV negative paired serum/oral fluid samples, drawn from patients visiting a Belgian academic hospital, were tested using the modified Ortho HCV 3.0 and LIA confirmation assay. Performing the test on oral fluid with the modified protocol, 61/73 anti-HCV positive samples were tested positive, while 73/73 anti-HCV negative samples were tested negative, giving a sensitivity and specificity of 83.6% (95% CI: 72.7-90.9%) and 100.0% (95% CI: 93.8-100.0%), respectively. Comparing S/CO of concordantly positive and negative samples, the cut-off point was lowered by 30% resulting in a sensitivity of 89.0% (95% CI: 79.0-94.8%) while the specificity remained 100.0% (95% CI: 93.8-100.0%). The confirmation assay was carried out as described by the manufacturer, diluting the oral fluid 1:10. Testing paired samples gave a concordance of 85.6% (125/146), yielding no more accurate results. These findings suggested that the modified ELISA method for anti-HCV detection in oral fluid can be used for epidemiological surveys.


Alpha-Synuclein and LRRK2 in Synaptic Autophagy: Linking Early Dysfunction to Late-Stage Pathology in Parkinson's Disease.
The lack of effective disease-modifying strategies is the major unmet clinical need in Parkinson´s disease. Several experimental approaches have attempted to validate cellular targets and processes. Of these, autophagy has received considerable attention in the last 20 years due to its involvement in the clearance of pathologic protein aggregates and maintenance of neuronal homeostasis. However, this strategy mainly addresses a very late stage of the disease, when neuropathology and neurodegeneration have likely "tipped over the edge" and disease modification is extremely difficult. Very recently, autophagy has been demonstrated to modulate synaptic activity, a process distinct from its catabolic function. Abnormalities in synaptic transmission are an early event in neurodegeneration with Leucine-Rich Repeat Kinase 2 (LRRK2) and alpha-synuclein strongly implicated. In this review, we analyzed these processes separately and then discussed the unification of these biomolecular fields with the aim of reconstructing a potential "molecular timeline" of disease onset and progression. We postulate that the elucidation of these pathogenic mechanisms will form a critical basis for the design of novel, effective disease-modifying therapies that could be applied early in the disease process.


Building a Low-cost Standalone Electrochemical Instrument Based on a Credit Card-sized Computer.
A low-cost, standalone electrochemical instrument was built from a credit card-sized computer and inexpensive A/D and D/A converter chips. The instrument is capable of cyclic voltammetry and constant potential electrolysis, with the potential range of -4 to +4 V and the current range of 1 μA to 20 mA.


Effects of Preoperative Motor Status on Intraoperative Motor-evoked Potential Monitoring for High-risk Spinal Surgery: A Prospective Multicenter Study.
Prospective multicenter observational study. To evaluate transcranial motor-evoked potentials (Tc-MEPs) baseline characteristics of lower limb muscles and to determine the accuracy of Tc-MEPs monitoring based on preoperative motor status in surgery for high-risk spinal disease. Neurological complications are potentially serious side effects in surgery for high-risk spine disease. Intraoperative spinal neuromonitoring (IONM) using Tc-MEPs waveforms can be used to identify neurologic deterioration, but cases with preoperative motor deficit tend to have poor waveform derivation. IONM was performed using Tc-MEPs for 949 patients in high-risk spinal surgery. A total of 4454 muscles in the lower extremities were chosen for monitoring. The baseline Tc-MEPs was recorded immediately after exposure of the spine. The derivation rate was defined as muscles detected/muscles prepared for monitoring. A preoperative neurological grade was assigned using the manual muscle test (MMT) score. The 949 patients (mean age 52.5 ± 23.3 yrs, 409 males [43%]) had cervical, thoracic, thoracolumbar, and lumbar lesions at rates of 32%, 40%, 26%, and 13%, respectively. Preoperative severe motor deficit (MMT ≤3) was present in 105 patients (11%), and thoracic ossification of the posterior longitudinal ligament (OPLL) was the most common disease in these patients. There were 32 patients (3%) with no detectable waveform in any muscles, and these cases had mostly thoracic lesions. Baseline Tc-MEPs responses were obtained from 3653/4454 muscles (82%). Specificity was significantly lower in the severe motor deficit group. Distal muscles had a higher waveform derivation rate, and the abductor hallucis (AH) muscle had the highest derivation rate, including in cases with preoperative severe motor deficit. In high-risk spinal surgery, Tc-MEPs collected with multi-channel monitoring had significantly lower specificity in cases with preoperative severe motor deficit. Distal muscles had a higher waveform derivation rate and the AH muscle had the highest rate, regardless of the severity of motor deficit preoperatively.Level of Evidence: 3.


Radiofrequency Ablation Provides Rapid and Durable Pain Relief for the Palliative Treatment of Lytic Bone Metastases Independent of Radiation Therapy: Final Results from the OsteoCool Tumor Ablation Post-Market Study.
The OsteoCool Tumor Ablation Post-Market Study (OPuS One) was a prospective, multi-national, single-arm study to investigate safety and effectiveness of radiofrequency ablation (RFA) for palliation of painful lytic bone metastases with 12 months of follow-up. RFA has demonstrated effective palliation of osseous metastases in small clinical studies with short-term follow-up; however, a long-term assessment with robust subject numbers is lacking. Prospective assessments were conducted at Baseline, 3 days, 1 week, and 1, 3, 6, and 12-months. Pain and quality of life were measured prior to RFA and postoperatively using the Brief Pain Inventory, European Quality of Life-5 Dimension, and European Organization for Research and Treatment of Cancer Care Quality of Life Questionnaire for palliative care. Radiation, chemotherapy and opioid usage, and related adverse events were collected. 206 subjects were treated with RFA at 15 institutions in OPuS One. Worst pain, average pain, pain interference and quality of life significantly improved at all visits starting 3 days post-RFA and sustained to 12 months (P < 0.0001). Post hoc analysis found neither systemic chemotherapy nor local radiation therapy at the index site of RFA influenced worst pain, average pain, or pain interference. Six subjects had device/procedure-related adverse events. RFA for lytic metastases provides rapid (within 3 days) and statistically significant pain and quality of life improvements with sustained long-term relief through 12 months and a high degree of safety, independent of radiation. 2B, PROSPECTIVE, NON-RANDOMIZED, POST-MARKET STUDY: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Emission and environmental distribution of decabromodiphenyl ethane (DBDPE) in China from 2006 to 2026: Retrospection, forecasting, and implications for assessment and management.
Decabromodiphenyl ethane (DBDPE) is the main alternative to decabromodiphenyl ether (deca-BDE) in commercial use. However, there is increasing evidence show that DBDPE is a potential persistent organic pollutant, and it has been found ubiquitously in environmental media across China in recent years. Monitoring studies have not been able to determine the overall levels and temporal trends of DBDPE contamination in China, and have been unable to explain how emission patterns can affect their environmental distribution. Therefore, this study estimated the temporal variance of DBDPE emissions and environmental concentrations in five regions of China from 2006 to 2026 using the PROduction-To-EXposure (PROTEX) mass balance model. The results showed that Guangdong Province was the greatest DBDPE pollution hotspot in China due to emissions from plastics manufacturing and e-waste disposal; there was also severe pollution in Shandong Province, where almost all the DBDPE in China is produced. The DBDPE concentrations in indoor and outdoor environments increased substantially in all regions during 2006-2021. Furthermore, in Guangdong Province and Shandong Province, the ratio of indoor/outdoor air concentrations was greater than or close to 1, indicative of significant outdoor emission sources of DBDPE. In contrast, the ratios for the Beijing-Tianjin-Hebei region, East China, and Southwest China were below 1 due to the indoor use of electronic equipment containing DBDPE. The temporal trends of these ratios indicated that DBDPE contamination has gradually spread from high-concentration environments with strong emission sources to low-concentration environments. The outcomes of this study have important implications for the risk assessment of DBDPE use in China and can be used to establish contamination-mitigation actions.