Postural breathing pattern changes in patients with myotonic dystrophy.
We recorded by pneumotachography the breathing in nine patients with myotonic dystrophy (MD), both seated and supine and with eyes open in both positions. Irregular breathing (coefficient of variation >20% for VT and TTOT) was observed in six of the patients, two of whom showed irregularity in both positions whilst the remaining four had irregular breathing only when supine. In addition, in this latter group, irregularities first appeared in VT and only after a few minutes in TTOT. Whereas in the group exhibiting irregular breathing in both seated and supine positions, irregularities were observed throughout the recording. However, no significant difference in any ventilatory variable was observed as between the two postures. Rib cage (RC) and abdomen (AB) motions were recorded by uncalibrated respiratory inductance plethysmography. Although for MD patients the mean values of the RC/AB ratio lay within the normal range the relative decrease in value as between seated (0.78+/-0.52) and supine (0.31+/-0.13) position was less than in healthy subjects. These observations suggest that MD may cause deficiencies in several mechanisms. Analyses of the respiratory pattern in each patient may provide information leading to the identification of the impaired respiratory mechanisms.


Normal pressure "herniation".
Hydrocephalus with normal intracranial pressure has rarely been reported to result in herniation. Case report. A 52-year-old man became acutely comatose with extensor posturing and ventriculomegaly 17 days after experiencing a primary ventricular hemorrhage. An external ventricular drain revealed normal intracranial pressure. After 24 hours without improvement with the drain set at a level of 5 mm H2O, negative-pressure siphoning (50 mL of cerebrospinal fluid [CSF] removed) reduced ventricular size and led to dramatic clinical recovery. Normal pressure hydrocephalus can result in delayed brainstem herniation after ventricular hemorrhage. CSF siphoning in these patients can reverse the syndrome.


Are life episodes replayed during dreaming?
New phenomenological data demonstrate that integrated life episodes are incorporated in no more than 1-2% of dream reports. This appears to be at odds with the replay of temporally sequenced memory at the level of neuronal ensembles observed in some animals during sleep. This result will constrain emerging ideas on memory reactivation during sleep and the role of sleep in memory consolidation.


Utility of novel fetal echocardiographic morphometric measures of the aortic arch in the diagnosis of neonatal coarctation of the aorta.
Prenatal diagnosis of neonatal coarctation of the aorta (CoA) is challenging; there is a high false-positive rate, yet 60-80% are not identified prenatally. We aimed to identify novel fetal echocardiographic measures to improve prenatal identification of CoA. A retrospective review was conducted of subjects seen from 1/2007-1/2014 with prenatal suspicion for CoA and postnatal follow-up. The last fetal echocardiogram prior to delivery was evaluated for right/left ventricular dimensions, ascending (AAo), transverse (TAo), descending aorta (DAo), aortic isthmus (AoI), ductus arteriosus (DA), and main pulmonary artery diameters, and AoI and DA spectral Doppler. Three novel fetal measurements were performed: left common carotid-to-left subclavian artery distance (LCSA), AAo-DAo angle, and TAo-DAo angle. Postnatal data included diagnosis, surgical approach, and timing. Forty subjects were identified (mean gestational age at fetal echo 32.8 ± 4.2 weeks) with prenatal suspicion for CoA. Comparing subjects with (n = 20) and without CoA (n = 20), significant differences were detected for LCSA, AAo-DAo angle, and TAo-DAo angle (p < 0.0001). An LCSA >4.5 mm (sensitivity 80%,specificity 95%), AAo-DAo angle ≤20.31° (sensitivity 95%,specificity 100%) and TAo-DAo angle ≥96.15°(sensitivity 90%,specificity 100%) identified CoA. Fetal LCSA, AAo-DAo angle, and TAo-DAo angles are novel measures that can differentiate between subjects with and without CoA.


Coexistence of hERG current block and disruption of protein trafficking in ketoconazole-induced long QT syndrome.
Many drugs associated with acquired long QT syndrome (LQTS) directly block human ether-a-go-go-related gene (hERG) K(+) channels. Recently, disrupted trafficking of the hERG channel protein was proposed as a new mechanism underlying LQTS, but whether this defect coexists with the hERG current block remains unclear. This study investigated how ketoconazole, a direct hERG current inhibitor, affects the trafficking of hERG channel protein. Wild-type hERG and SCN5A/hNa(v) 1.5 Na(+) channels or the Y652A and F656C mutated forms of the hERG were stably expressed in HEK293 cells. The K(+) and Na(+) currents were recorded in these cells by using the whole-cell patch-clamp technique (23 degrees C). Protein trafficking of the hERG was evaluated by Western blot analysis and flow cytometry. Ketoconazole directly blocked the hERG channel current and reduced the amount of hERG channel protein trafficked to the cell surface in a concentration-dependent manner. Current density of the hERG channels but not of the hNa(v) 1.5 channels was reduced after 48 h of incubation with ketoconazole, with preservation of the acute direct effect on hERG current. Mutations in drug-binding sites (F656C or Y652A) of the hERG channel significantly attenuated the hERG current blockade by ketoconazole, but did not affect the disruption of trafficking. Our findings indicate that ketoconazole might cause acquired LQTS via a direct inhibition of current through the hERG channel and by disrupting hERG protein trafficking within therapeutic concentrations. These findings should be considered when evaluating new drugs.


Pneumopericardium-a life-threatening complication of central venous catheterisation.
A case of central venous catheterisation which was complicated by pneumoperi-cardium is presented. The clinical manifestations and management are described. Haemodynamic stability in this patient could not be achieved by conservative therapy and pericardiocentesis was necessary to save the patient.


Diarylsulfonamides as selective, non-peptidic thrombin inhibitors.
Based on the structures of aminopyridine thrombin inhibitors (1), a series of aminoalkyl- and guanidinoalkyl-substituted diarylsulfonamides were prepared. The most potent derivative, N-[3-(4-guanidinobutoxy)-5-methyl-phenyl]-benzenesulfonamide (6c) had Ki = 0.18 microM for thrombin and did not inhibit trypsin, plasmin, or factor Xa. Comparison of the X-ray structures of the thrombin/1b and the thrombin/6c complexes revealed important aspects which govern the binding of such diarylsulfonamides to thrombin.


Principles of evidence based medicine.
Health care professionals are increasingly required to base clinical decisions on the best available evidence. Evidence based medicine (EBM) is a systematic approach to clinical problem solving which allows the integration of the best available research evidence with clinical expertise and patient values. This paper explains the concept of EBM and introduces the five step EBM model: formulation of answerable clinical questions; searching for evidence; critical appraisal; applicability of evidence; evaluation of performance. Subsequent articles will focus on the principles and critical appraisal of randomised controlled trials, systematic reviews, and meta-analyses, and provide a practical demonstration of the five step EBM model using a real life clinical scenario.


Adrenergic nerves and 5-hydroxytryptamine-containing cells in the pulmonary vasculature of the aquatic file snake Acrochordus granulatus.
The adrenergic innervation of the pulmonary vasculature of the file snake Acrochordus granulatus was examined by use of glyoxylic acid-induced fluorescence. Perivascular plexuses of blue-green fluorescent nerves are observed around the common pulmonary artery, the anterior and posterior pulmonary arteries, the arterioles leading to the gas exchange capillaries of the lung, the venules draining the lung, and the anterior and posterior pulmonary veins. Adrenergic nerves are also associated with the visceral smooth muscle of the lung septa and other tissues. Thus, adrenergic control of pulmonary blood flow may occur either at the common pulmonary artery or more regionally within the lung. Regional control of blood flow in the elongate lung of this snake may be important in matching pulmonary perfusion with the distribution of respiratory gas. Glyoxylic acid-histochemistry and immunohistochemistry revealed that populations of cells located in the common pulmonary artery contain the indoleamine 5-hydroxytryptamine. Many of the cells are intimately associated with varicose blue-green fluorescent nerves. It is proposed that the 5-hydroxytryptamine-containing cells may be involved in intravascular chemoreception.


A Novel Point-of-Care Smartphone Based System for Monitoring the Cardiac and Respiratory Systems.
Cardio-respiratory monitoring is one of the most demanding areas in the rapidly growing, mobile-device, based health care delivery. We developed a 12-lead smartphone-based electrocardiogram (ECG) acquisition and monitoring system (called "cvrPhone"), and an application to assess underlying ischemia, and estimate the respiration rate (RR) and tidal volume (TV) from analysis of electrocardiographic (ECG) signals only. During in-vivo swine studies (n = 6), 12-lead ECG signals were recorded at baseline and following coronary artery occlusion. Ischemic indices calculated from each lead showed statistically significant (p < 0.05) increase within 2 min of occlusion compared to baseline. Following myocardial infarction, spontaneous ventricular tachycardia episodes (n = 3) were preceded by significant (p < 0.05) increase of the ischemic index ~1-4 min prior to the onset of the tachy-arrhythmias. In order to assess the respiratory status during apnea, the mechanical ventilator was paused for up to 2 min during normal breathing. We observed that the RR and TV estimation algorithms detected apnea within 7.9 ± 1.1 sec and 5.5 ± 2.2 sec, respectively, while the estimated RR and TV values were 0 breaths/min and less than 100 ml, respectively. In conclusion, the cvrPhone can be used to detect myocardial ischemia and periods of respiratory apnea using a readily available mobile platform.


A COMMENTARY ON IMPROVING CLOZAPINE ACCESSIBILITY AND REDUCING TREATMENT COST.
Clozapine is vastly underutilized in the United States and many other countries. The most commonly cited reason for this is the requirement for frequent blood monitoring, which continues for the duration of treatment. Despite the notoriety clozapine achieved early in its development, accumulated evidence has demonstrated that close blood monitoring beyond the first year of treatment yields minimal safety benefits. Many health care systems have relaxed clozapine blood monitoring requirements during the COVID-19 pandemic for practical reasons, and this presents an opportunity to implement permanent, long overdue changes in mandated monitoring that reflect what has been learned about the real risk for blood dyscrasias with clozapine.


Surface warming reacceleration in offshore China and its interdecadal effects on the East Asia-Pacific climate.
Since the late 1970s, sea surface temperatures (SSTs) have exhibited greater responses to global warming in the offshore area of China and adjacent seas (offshore China) than in the global ocean. This study identified a surface warming reacceleration in offshore China since 2011, following a well-known interdecadal shift from offshore surface warming to cooling in 1998. During the warming reacceleration period, the rate of increase in offshore China SSTs was twice the mean rate of global ocean surface warming, and the significantly warming area was primarily in the north, especially in the East China Sea. Concurrent with the ascending phase of the Interdecadal Pacific Oscillation, a large area of positive sea level pressure anomalies developed over the tropical Pacific. Accordingly, the surface southerly wind anomalies contributed to the recent surface warming in offshore China, especially in the East China Sea. With greater changes in the warming rate, the spatial mode of the circulation anomalies over East Asia and the western Pacific has shifted westward and has exerted more inshore influence during the recent warming reacceleration period than during the previous periods.


Influence of the dialysis membrane on outcome of ESRD patients.
Data from the US Renal Data System (USRDS) document a substantial reduction in the use of cellulosic membranes, from approximately 70% in 1990 to less than 20% in 1996. These changes have been accompanied by a reduction in the adjusted mortality of patients with end-stage renal disease (ESRD) in the United States. The possibility that this association between the changes in the nature of the membrane and clinical outcome represents a cause-and-effect relationship is discussed in terms of the known biochemical actions of complement activation, consequent neutrophil and monocyte activation, and clinical studies that have been published comparing membranes with different biocompatibilities. Together, these studies support a role for the changes in the biocompatibility of dialysis membranes in the improvement of ESRD patient mortality in the United States.


First-in-human safety, tolerability, and pharmacokinetics of SY-007, a prolonged action neuroprotective drug for ischemic stroke, in healthy Chinese subjects.
SY-007 is an interfering peptide designed to disrupt the cell death signaling of phosphatase and tensin homolog deleted on chromosome ten (PTEN) nuclear translocation during ischemic stroke. Preclinical studies indicated that rats treated with 1.5 mg/kg SY-007 in the middle cerebral artery occlusion (MACO) model had significantly reduced stroke lesion size even when administered 6 h after the stroke onset. The aim of this study was to evaluate the safety, tolerability, and pharmacokinetics of ascending doses of SY-007 administered intravenously in healthy Chinese subjects. A total of 78 healthy Chinese subjects were enrolled in the single ascending dose study (1-60 mg) and received a 15-min intravenous infusion SY-007 or placebo. Plasma concentrations of SY-007 were measured by a validated liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined using non-compartmental and compartment analyses. A model based on target-mediated drug disposition was applied. Model evaluation was performed through visual predictive checks and bootstrap analysis. Across doses of 1-60 mg, SY-007 was well tolerated. All adverse events (AEs) were mild or moderate in intensity, and all resolved without intervention. After infusion, SY-007 plasma concentrations decreased quickly with the mean terminal half-life was shorter than 0.78 h. The area under the concentration-time curve increased with a greater than dose-dependent manner from 1 to 30 mg and resulted in a dose-dependent increased from 30 to 60 mg. The nonlinear phenomenon was well described by a simplified target-mediated drug disposition (TMDD) model. Intravenous dosing of SY-007 appears to be safe up to a dose of 60 mg. Nonlinear pharmacokinetics was observed across the evaluated doses and TMDD might be the primary reason. The effective dose of SY-007 for neuroprotective effect in patients with ischemic stroke is expected to be 10-30 mg and was recommended for the later multiple ascending dose study of SY-007. Clinicaltrials.gov: NCT04111523.


Heterotopic ossification following musculoskeletal trauma: modeling stem and progenitor cells in their microenvironment.
Heterotopic ossification (HO), characterized by the formation of mature bone in the soft tissues, is a complication that can accompany musculoskeletal injury, and it is a frequent occurrence within the military population that has experienced orthopaedic combat trauma. The etiology of this disease is largely unknown. Our laboratory has developed strategies to investigate the cellular and molecular events leading to HO using clinical specimens that were obtained during irrigation and debridement of musculoskeletal injuries. Our approach enables to study (1) the cell types that are responsible for pathological transformation and ossification, (2) the cell- and tissue-level signaling that induces the pathologic transformation, and (3) the effect of extracellular matrix topography and force transduction on HO progression. In this review, we will report on our findings in each of these aspects of HO etiology and describe our efforts to recapitulate our findings in an animal model for traumatic HO.


Cardiovascular response to interval and continuous training in women.
Three groups of five women (age = 18--25 years) participated in a 12-week training program. Cardiovascular responses up to 85% VO2 max to interval (ITG) and continuous (CTG) training were studied in two groups, before training and after 4, 8, and 12 weeks of training four times per week. A control group was assessed before and after 6 and 12 weeks. Both exercise groups demonstrated significant increases in Cao2--Cvo2 after 8 weeks with only slight further increases after 12 weeks (CTG = 8.9%, ITG = 20.0% at 85% VO2 max). No significant changes were noted in either group in SV (+ 5 ml ITG, + 9 ml CTG) or in their Qc. These results indicated that, in response to high intensity training, women may demonstrate similar cardiovascular adaptations to training as have been observed for men.


The effect of systemically and topically applied drugs on ultraviolet-induced erythema in the rat.
1. Exposure of the skin of rats to u.v. light (greater than 295 nm) for 30 s or longer elicited a delayed erythema response, the rate of onset increasing with period of irradiation. The erythema was still present at 24 h and was replaced by scab formation in 48 hours. 2. Both topically applied steroidal and non-steroidal anti-inflammatory drugs reduced the erythema formation when administered immediately after u.v. exposure. Propyl gallate, an antioxidant with sun screening properties in man, also possessed topical anti-erythemic activity. 3. Both steroidal and non-steroidal anti-inflammatory drugs, systemically administered 1 h before u.v. exposure, reduced and erythema. However, the steroidal compounds were less effective than the non-steroids and reduced the intensity of erythema by less than 50%. Antagonists of 5-hydroxytryptamine (5-HT) reduced the erythema but several other drugs with different pharmacological activities were ineffective. 4. Neither topical nor systemic treatments of any of the drugs examined suppressed the scab formation at 48 hours. 5. These results and those using other selective blocking agents indicate that in the mediation of the erythema reaction prostaglandins may play a major role and 5-HT perhaps a minor one but that H1 histamine receptors and alpha- and beta-adrenoceptors have no significant role.


Seasonal variations in CDOM characteristics and effects of environmental factors in coastal rivers, Northeast China.
Colored dissolved organic matter (CDOM) is highly spatiotemporally varied due to the effects of complex environmental factors within a catchment or system. The seasonal nutritional status and potential risks of heavy metals in the coastal rivers of the Liaohe River basin were evaluated based on 40 water samples in January, April, May, and September. Meanwhile, the effects of environmental factors on CDOM, especially human activities, were quantitatively analyzed. The trophic state index (TSI) and the potential ecological risk index (RI) of heavy metals in the Liaohe River basin exhibited significant differences. The rivers were mesotrophic in January, lightly eutrophic in May, and highly eutrophic in April and September. An extremely high RI was shown in April and May, while a high RI was exhibited in September. CDOM exhibited great seasonal characteristics and showed significant seasonal correlations with environmental factors. Based on multiple general linear model analysis, total phosphorus (TP) was the most influential factor and significantly explained 62.1% of aCDOM(440) (p < 0.01) among the water parameters, followed by total alkalinity (38.3%). The percentages of built-up area exerted significantly positive effects on aCDOM(440) (R2 = 0.44), while distance from oil extraction sites significantly negatively affected aCDOM(440) (r = - 0.328, p < 0.05). Polluting enterprises showed non-significant correlation with CDOM (r = 0.314, p = 0.178).


The estimate of coronary incidence following different case finding procedures.
In the pool of two rural population groups made up of 1695 coronary-free men aged 40-59 years at entry and followed-up for 25 years, repeated field examination at 5, 10, 20 and 25 years after enrollment and mortality checking, allowed us to identify 256 first major coronary events (coronary deaths and definite myocardial infarction)--the basic procedure. An extra effort in data collection, involving checking hospital admissions and discharges, inquiries to general practitioners and some postal questionnaires, allowed us to identify 45 extra cases of non-fatal myocardial infarction--the special procedure. The reported incidence of a first major coronary event in 25 years increased in this way by 17.8%, from 15.1% to 17.7%. The 45 cases identified by the special procedure were younger and had more favourable levels of risk factors than the other 256. However the coefficients of six risk factors estimated by the Cox model (age, mean blood pressure, serum cholesterol, cigarette consumption, forced expiratory volume and arcus senilis) were rather similar, and all were significant in the solution that included the cases identified by the basic procedure, compared to the solution that included cases identified by both procedures.


Monitoring of unfractionated heparin using activated partial thromboplastin time: an assessment of the current nomogram and analysis according to age.
We frequently encounter high levels of activated partial thromboplastin time (aPTT) during heparin anticoagulation. The purpose of this study is, first, to investigate the rate of achieving and maintaining therapeutic aPTT in patients treated with heparin anticoagulation and second, to assess the adequacy the current nomogram. We included 197 patients who underwent anticoagulation with unfractionated heparin (UFH) according to the standard nomogram between September 2008 and May 2010. The primary endpoints were the rate of achieving a therapeutic range (TR) at the first sample, 24 hours, or 48 hours. We also compared heparin nomograms according to age (<70 years vs ≥70 years). Of the 197 patients, 131 had heparin loading. In the heparin loading group, there were 19.1% (n=25), 69.5% (n=91), and 90.1% (n=18) achieving TR at the first aPTT, 24 hours, and 48 hours, respectively. The therapeutic aPTT proportion was 39.2%, and the rate of peak level above 90 seconds was 93.1%. Peak levels of aPTT were higher in the older age group than in the younger age group (202.3 ± 124.2 versus 152.0 ± 78.9, p=0.007). Our results indicate a high rate of achieving therapeutic aPTT at 24 hous and 48 hours, but a low success rate for maintenance within the TR. Most patients had supratherapeutic aPTT of more than 90 seconds. Therefore, the TR of aPTT that matches heparin levels of 0.3 to 0.7 IU/mL measured by antifactor Xa assay should be determined. If not, we should consider adopting a new heparin dosing nomogram.


Exposures that may affect sperm DNA integrity: two decades of follow-up in a pregnancy cohort.
Prenatal lifestyle exposures are linked to alterations in conventional semen characteristics. Sperm DNA integrity is another marker of semen quality shown to be altered in mice prenatally exposed to chemicals. From a Danish pregnancy cohort established in 1984-1987, sons were selected for a follow-up study in 2005-2006. We examined associations between prenatal and current lifestyle exposures and DNA fragmentation index (DFI) among 337 men. Sons of overweight mothers had 22% (95% CI: -3; 52) higher DFI than sons of normal weight mothers and sons of parents with a TTP >12 months had 14% (95% CI: -4; 34) higher DFI than sons of parents with a TTP of 0-6 months. Abstinence time was positively associated with DFI (p<0.005). Overweight men had higher DFI compared to normal weight men, however, statistically insignificantly. In conclusion, results indicate that DFI is affected by prenatal exposures, but confidence limits are wide and results statistically insignificant.


Fe(III)-based metal-organic framework-derived core-shell nanostructure: Sensitive electrochemical platform for high trace determination of heavy metal ions.
A new core-shell nanostructured composite composed of Fe(III)-based metal-organic framework (Fe-MOF) and mesoporous Fe3O4@C nanocapsules (denoted as Fe-MOF@mFe3O4@mC) was synthesized and developed as a platform for determining trace heavy metal ions in aqueous solution. Herein, the mFe3O4@mC nanocapsules were prepared by calcining the hollow Fe3O4@C that was obtained using the SiO2 nanoparticles as the template, followed by composing the Fe-MOF. The Fe-MOF@mFe3O4@mC nanocomposite demonstrated excellent electrochemical activity, water stability and high specific surface area, consequently resulting in the strong biobinding with heavy-metal-ion-targeted aptamer strands. Furthermore, by combining the conformational transition interaction, which is caused by the formation of the G-quadruplex between a single-stranded aptamer and high adsorbed amounts of heavy metal ions, the developed aptasensor exhibited a good linear relationship with the logarithm of heavy metal ion (Pb2+ and As3+) concentration over the broad range from 0.01 to 10.0nM. The detection limits were estimated to be 2.27 and 6.73 pM toward detecting Pb2+ and As3+, respectively. The proposed aptasensor showed good regenerability, excellent selectivity, and acceptable reproducibility, suggesting promising applications in environment monitoring and biomedical fields.


Modulation of tumor-associated macrophage activity with radiation therapy: a systematic review.
Tumor-associated macrophages (TAMs) are the most represented cells of the immune system in the tumor microenvironment (TME). Besides its effects on cancer cells, radiation therapy (RT) can alter TME composition. With this systematic review, we provide a better understanding on how RT can regulate macrophage characterization, namely the M1 antitumor and the M2 protumor polarization, with the aim of describing new effective RT models and exploration of the possibility of integrating radiation with other available therapies. A systematic search in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was carried out in PubMed, Google Scholar, and Scopus. Articles from January 2000 to April 2020 which focus on the role of M1 and M2 macrophages in the response to RT were identified. Of the 304 selected articles, 29 qualitative summary papers were included in our analysis (16 focusing on administration of RT and concomitant systemic molecules, and 13 reporting on RT alone). Based on dose intensity, irradiation was classified into low (low-dose irradiation, LDI; corresponding to less than 1 Gy), moderate (moderate-dose irradiation, MDI; between 1 and 10 Gy), and high (high-dose irradiation, HDI; greater than 10 Gy). While HDI seems to be responsible for induced angiogenesis and accelerated tumor growth through early M2-polarized TAM infiltration, MDI stimulates phagocytosis and local LDI may represent a valid treatment option for possible combination with cancer immunotherapeutic agents. TAMs seem to have an ambivalent role on the efficacy of cancer treatment. Radiation therapy, which exerts its main antitumor activity via cell killing, can in turn interfere with TAM characterization through different modalities. The plasticity of TAMs makes them an attractive target for anticancer therapies and more research should be conducted to explore this potential therapeutic strategy.


Association of single nucleotide polymorphism rs6903956 on chromosome 6p24.1 with coronary artery disease and lipid levels in different ethnic groups of the Singaporean population.
A recent genome wide association study in the Chinese population has implicated rs6903956 within the ADTRP gene on chromosome 6p24.1 as a novel susceptibility locus for coronary artery disease (CAD). In this study, we evaluated the association of rs6903956 with CAD in the different ethnic groups of Singaporean population comprising Chinese, Malays and Asian Indians. The genotypes of the rs6903956 SNP were determined in 645 CAD patients and 755 control group Singaporean subjects by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). We then tested the association of this SNP with CAD and lipid profiles. The risk allele A of rs6903956 was associated significantly only in the Chinese with an odds ratio (OR) of 2.03 (95% CI 1.04-3.96, P=0.037) when analyzed by each ethnic group separately. In a meta-analysis with pooled subjects from all three ethnic groups, rs6903956 showed highly significant association with CAD both before (observed P=1.39e-04; OR=1.66; 95% CI 1.28-2.15) and after adjustment (P=4.63e-03; OR=1.86; 95% CI 1.21-2.87) for conventional risk factors of age, gender, BMI, smoking status and ethnicity. No significant association was observed between rs6903956 genotypes and lipid profiles in Chinese, Malays and Indians, suggesting that the association of this SNP with CAD is not mediated through plasma lipids. The SNP rs6903956 within the ADTRP gene on chromosome 6p24.1 is significantly associated with CAD in different ethnic groups of the Singaporean population.


Kluyveromyces fragilis SS-437: an associatively-profiled thermotolerant yeast.
The lactose-utilizing Kluyveromyces fragilis SS-437 was found to have an associative temperature profile, but a thermotolerant growth yield behaviour. Cardinal growth temperatures were: 3 degrees C minimum for growth; 41.5 degrees C optimum; 44.5 degrees C final maximum (growth and death rates equalize); 46.1 degrees C initial maximum (maximum limit for growth).


Mercury, lead and cadmium levels in the urine of 170 Spanish adults: a pilot human biomonitoring study.
Human biomonitoring is a well-recognized tool for estimating the exposure of human populations to environmental pollutants. However, information regarding biomarker concentrations of many environmental chemicals in the general population is limited for many countries. The Spanish Environment Ministry has recently funded a human biomonitoring study on the Spanish general population. This study aims to determine reference levels for several biomarkers, especially heavy metals, persistent organic pollutants (POPs) and cotinine, in urine, whole blood, serum and hair, and will involve 2000 volunteers throughout Spain. Samples were taken during 2009-2010 and analyses are currently underway. The results presented herein were obtained in a pilot study carried out in the Madrid region. The study group comprised 170 volunteers, of which 79% were female and 21% male (age: 23-66 years). All participants were asked to complete a questionnaire regarding diet and living habits and provides a morning urine sample. The geometric means for total mercury (Hg), lead (Pb) and cadmium (Cd) were 1.23, 1.11 and 0.25 μg/g creatinine, respectively. Levels of Pb and Hg were higher than those reported for the general population in the USA and Germany, whereas Cd was in the same range (CDC, 2009; Becker et al., 2003). The values reported here are similar to those reported in other Spanish studies.


Design and modelling of photobioreactor for the treatment of carpet and textile effluent using Diplosphaera mucosa VSPA.
The current study investigated the potential of one less explored microalgae species, Diplosphaera mucosa VSPA, for treating carpet and textile effluent in a conventionally designed 10 L bubble column photobioreactor. To the best of our knowledge, this is the first study to evaluate COD (chemical oxygen demand) removal efficiency by microalgae in carpet effluent. To evaluate D. mucosa VSPA's potential, its growth and bioremediation efficacy were compared to those of a well-known strain, Chlorella pyrenoidosa. D. mucosa VSPA outperformed C. pyrenoidosa in both effluents, with the highest biomass concentration reaching 4.26 and 3.98 g/L in carpet and textile effluent, respectively. D. mucosa VSPA also remediated 94.0% of ammonium nitrogen, 71.6% of phosphate phosphorus, and 91.9% of chemical oxygen demand in carpet effluent, approximately 10% greater than that of C. pyrenoidosa. Both species also removed more than 65% of colour from both effluents, meeting the standard set by governing bodies. Microalgae growth and substrate removal patterns in the photobioreactor were simulated using photobiotreatment and the Gompertz model. Simulation results revealed that photobiotreatment was the better-fit model, concluded based on the coefficient of regression value and the second-order Akaike information criterion test. Modelling studies can assist in increasing the performance and scale-up of the photobioreactor. The online version contains supplementary material available at 10.1007/s13205-023-03655-3.


Correlation between in vitro toxicity of pesticides and in vivo risk guidelines in support of complex operating site risk management: A meta-analysis.
In vitro cell systems can support hazard characterization and identify mechanisms involved in toxicity; however, using in vitro data for risk assessment still is challenging. As part of an effort to develop approaches for a complex operating site used for biocide packaging and distribution, we evaluated in vitro assays that could be used in a site management format. Across 66 studies, 108 pesticides were assessed on ten human-derived cell types at four endpoints. In vitro IC50s were compared to in vivo guidelines, NOEL/NOAELs, and ADIs using Spearman correlation and linear regression models. While human neuroblastoma cells (SH-SY5Y) were the most sensitive, HepG2 was the most used cell line in evaluating the toxicity of pesticides. Amongst the ten human cell lines, the IC50s derived from SH-SY5Y cells, using MTT-24 & 48 h (the most used assay) correlated (rho = 0.56-0.79; p < 0.05) with ADIs and NOEL/NOAELs. Although in vitro cell systems have some limitations, the correlation between in vitro data derived from SH-SY5Y cells and in vivo safety guidelines can provide site investigators with a tool to survey and prioritize areas and media of concern at complex operating sites impacted by pesticide mixtures.


Exploration of the interesting photovoltaic behavior of the fused benzothiophene dioxide moiety as a core donor with modification in acceptors for high-efficacy organic solar cells.
Non-fullerene-based chromophores with end-capped acceptor modification used in organic solar cells (OSCs) have proven to offer improved performance. Therefore, eight unique benzothiophene-based molecules (D2-D9) were designed by the end-capped acceptor manipulation of a reference molecule (R1). Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations at the B3LYP level were performed to investigate various parameters such as the optical properties, frontier molecular orbitals (FMOs), transition density matrix (TDM), binding energy, density of states (DOS), open-circuit voltage (V oc), and reorganization energies of electrons (λ e) and holes (λ h), to better understand the optoelectronic properties of the newly designed compounds. All the derivatives had broader absorption spectra of 737.562-700.555 nm with a reduced energy gap of 2.132-1.851 eV compared to those of the reference (719.082 nm), except for D8 and D9. A comparable value of V oc and lower reorganization energies were found in the derivatives compared to those of R1. Within the studied compounds, D3 was predicted to be a good optoelectronic material for environmentally friendly organic solar cells (EFOSCs) because of its superior optoelectronic capabilities, low-energy band gap (1.851 eV), highest λ max values of 794.516 and 744.784 nm in chloroform and the gas phase, respectively, and lowest transition energy (1.561 eV) than those of the reference and the other derivatives. Subsequently, end-capped acceptor modification was proven to be an effective method to achieve desired optoelectronic characteristics.


Diversified demand for health tourism matters: From a perspective of the intra-industry trade.
Previous studies on health tourism were limited to a small range of topics related to medical tourism. At present, the concept of health tourism has become profound because medical care has been altered from "disease-centered" to "health-centered". The main purpose of this study is to identify the key factors influencing the development of health tourism in China. To this end, in the first stage, an intra-industry trade theory was introduced and quantitative methods were applied to discover the important factors. In the second stage, multiple sources, including empirical studies, official data, research reports, and notably field investigations and case studies were incorporated to take in-depth discussions. The results indicated the foremost factors affecting the health tourism trade were total health expenditure per capita and the number of domestic health consumers. Notably, health tourism was substantially determined by the "willingness to spend on health" of domestic health consumers. In addition, Chinese health tourists were more likely to positively accept health tourism services in China. An important conclusion is that China should diversify health tourism offerings for different consumer groups. Once diversified products for health tourism are provided, the number of health tourism consumers will soar accordingly, which thus contributes to forming economies of scale, lowering the average costs of health treatment, increasing health tourism profit, and stimulating economic development.


Patient and Physician Race and the Allocation of Time and Patient Engagement Efforts to Mental Health Discussions in Primary Care: An Observational Study of Audiorecorded Periodic Health Examinations.
This study investigated racial differences in patient-physician communication around mental health versus biomedical issues. Data were collected from audiorecorded periodic health examinations of adults with mental health needs in the Detroit area (2007-2009). Patients and their primary care physicians conversed for twice as long, and physicians demonstrated greater empathy during mental health topics than during biomedical topics. This increase varied by patient and physician race. Patient race predicted physician empathy, but physician race predicted talk time. Interventions to improve mental health communication could be matched to specific populations based on the separate contributions of patient and physician race.


Imaging of Norway spruce early somatic embryos with the ESEM, Cryo-SEM and laser scanning microscope.
This article describes the surface structure of Norway spruce early somatic embryos (ESEs) as a typical culture with asynchronous development. The microstructure of extracellular matrix covering ESEs were observed using the environmental scanning electron microscope as a primary tool and using the scanning electron microscope with cryo attachment and laser electron microscope as a complementary tool allowing our results to be proven independently. The fresh samples were observed in conditions of the air environment of the environmental scanning electron microscope (ESEM) with the pressure from 550Pa to 690Pa and the low temperature of the sample from -18°C to -22°C. The samples were studied using two different types of detector to allow studying either the thin surface structure or material composition. The scanning electron microscope with cryo attachment was used for imaging frozen extracellular matrix microstructure with higher resolution. The combination of both electron microscopy methods was suitable for observation of "native" plant samples, allowing correct evaluation of our results, free of error and artifacts.


Production of large numbers of plasmacytoid dendritic cells with functional activities from CD34(+) hematopoietic progenitor cells: use of interleukin-3.
Plasmacytoid dendritic cells (pDC), a subset of dendritic cells characterized by a rapid and massive type-I interferon secretion through the Toll-like receptor pathway in response to viral infection, play important roles in the pathogenesis of several diseases, such as chronic viral infections (e.g., hepatitis C virus, human immunodeficiency virus), autoimmunity (e.g., psoriasis, systemic lupus erythematosus), and cancer. As pDC represent a rare cell type in the peripheral blood, the goal of this study was to develop a new method to efficiently generate large numbers of cells from a limited number of CD34(+) cord blood progenitors to provide a tool to resolve important questions about how pDC mediate tolerance, autoimmunity, and cancer. Human CD34(+) hematopoietic progenitor cells isolated from cord blood were cultured with a combination of Flt3-ligand (Flt3L), thrombopoietin (TPO), and one of the following cytokine: interleukin (IL)-3, interferon-β(IFN-β), or prostaglandin E2(PGE(2)). Cells obtained in the different culture conditions were analyzed for their phenotype and functional characteristics. The addition of IL-3 cooperates with Flt3L and TPO in the induction of pDC from CD34(+) hematopoietic progenitor cells. Indeed, Flt3L/TPO alone or supplemented with prostaglandin E2 or interferon-β produced smaller amounts of pDC from hematopoietic progenitor cells. In addition, pDC generated in Flt3L/TPO/IL-3 cultures exhibited morphological, immunohistochemical, and functional features of peripheral blood pDC. We showed that IL-3, in association with Flt3L and TPO, provides an advantageous tool for large-scale generation of pDC. This culture condition generated, starting from 2 × 10(5) CD34(+) cells, up to 2.6 × 10(6) pDC presenting features of blood pDC.


Structural Investigation of Uniform Ensembles of Self-Catalyzed GaAs Nanowires Fabricated by a Lithography-Free Technique.
Structural analysis of self-catalyzed GaAs nanowires (NWs) grown on lithography-free oxide patterns is described with insight on their growth kinetics. Statistical analysis of templates and NWs in different phases of the growth reveals extremely high-dimensional uniformity due to a combination of uniform nucleation sites, lack of secondary nucleation of NWs, and self-regulated growth under the effect of nucleation antibunching. Consequently, we observed the first evidence of sub-Poissonian GaAs NW length distributions. The high phase purity of the NWs is demonstrated using complementary transmission electron microscopy (TEM) and high-resolution X-ray diffractometry (HR-XRD). It is also shown that, while NWs are to a large extent defect-free with up to 2-μm-long twin-free zincblende segments, low-temperature micro-photoluminescence spectroscopy reveals that the proportion of structurally disordered sections can be detected from their spectral properties.


Automated Estimation of Mammary Gland Content Ratio Using Regression Deep Convolutional Neural Network and the Effectiveness in Clinical Practice as Explainable Artificial Intelligence.
Recently, breast types were categorized into four types based on the Breast Imaging Reporting and Data System (BI-RADS) atlas, and evaluating them is vital in clinical practice. A Japanese guideline, called breast composition, was developed for the breast types based on BI-RADS. The guideline is characterized using a continuous value called the mammary gland content ratio calculated to determine the breast composition, therefore allowing a more objective and visual evaluation. Although a discriminative deep convolutional neural network (DCNN) has been developed conventionally to classify the breast composition, it could encounter two-step errors or more. Hence, we propose an alternative regression DCNN based on mammary gland content ratio. We used 1476 images, evaluated by an expert physician. Our regression DCNN contained four convolution layers and three fully connected layers. Consequently, we obtained a high correlation of 0.93 (p < 0.01). Furthermore, to scrutinize the effectiveness of the regression DCNN, we categorized breast composition using the estimated ratio obtained by the regression DCNN. The agreement rates are high at 84.8%, suggesting that the breast composition can be calculated using regression DCNN with high accuracy. Moreover, the occurrence of two-step errors or more is unlikely, and the proposed method can intuitively understand the estimated results.


A Multimodality Electrochemical and Impedance Spectroscopy System-on-a-Chip With Temperature Sensing and Impedance-Boosting Techniques.
This article presents a multimodal electrochemical sensing system-on-chip (SoC), including the functions of cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and temperature sensing. CV readout circuitry achieves an adaptive readout current range of 145.5 dB through an automatic range adjustment and resolution scaling technique. EIS has an impedance resolution of 9.2 m Ω/√ Hz at a sweep frequency of 10 kHz and an output current of up to 120 μA. With an impedance boost mechanism, the maximum detectable load impedance is extended to 22.95 k Ω, while the total harmonic distortion is less than 1%. A resistor-based temperature sensor using a swing-boosted relaxation oscillator can achieve a resolution of 31 mK in 0-85 °C. The design is implemented in a 0.18 μm CMOS process. The total power consumption is 1 mW.


Rapid identification of Staphylococcus aureus in blood cultures by a combination of fluorescence in situ hybridization using peptide nucleic acid probes and flow cytometry.
Fluorescence in situ hybridization (FISH) using peptide nucleic acid probes (PNAs) allows the identification of Staphylococcus aureus from human blood culture samples. We present data revealing that the combination of PNA FISH and flow cytometry is a possible approach for the noncultural identification of staphylococci in blood cultures.


Combined effects of nano-TiO2 and hexavalent chromium towards marine crustacean Artemia salina.
There has been a significant increased concern of the impact of the toxicity of multiple contaminants in the marine environment. Thus, this study was aimed at determining whether the interaction between nano-TiO2 and Cr(VI) would modulate their toxic effects with the marine crustacean, Artemia salina. Nano-TiO2 agglomerated in artificial sea water (ASW) and readily formed micron-sized particles that settled down in the medium. The addition of Cr(VI) to nano-TiO2 aggravated their agglomeration through sorption of Cr(VI) onto nano-TiO2. This was reflected by a decrease in the residual concentration of Cr in the suspension. Acute toxicity tests performed using pristine nano-TiO2 (0.25, 0.5, 1, 2, and 4 mg/L) and Cr(VI) (0.125, 0.25, 0.5, and 1 mg/L) displayed a concentration dependent rise in the mortality of Artemia salina. To examine the effects of mixtures of nano-TiO2 and Cr(VI) on Artemia salina, two groups of experiments were designed. The former group studied the toxic effect of nano-TiO2 (0.5, 1, 2, and 4 mg/L) with a fixed concentration (0.125 mg/L) of Cr(VI). While the latter group studied the toxicity of Cr(VI) (0.25, 0.5, and 1 mg/L) with a fixed concentration (0.25 mg/L) of nano-TiO2. The toxic effects of nano-TiO2 was not significantly reduced at a fixed concentration of Cr(VI) but in contrast, a significant reduction in the Cr(VI) toxicity by fixed concentration of nano-TiO2 was observed. Toxicity data was well supported by an independent action model that proved the mode of action between nano-TiO2 and Cr(VI) to be antagonistic. Furthermore, ROS generation and measurement of antioxidant enzyme activities were also in line with toxicity results. From this study, the modification of Cr(VI) toxicity at fixed concentration of nano-TiO2 could have a huge impact on the reduction in Cr(VI) toxicity across trophic levels.


Extended base pair complementarity between U1 snRNA and the 5' splice site does not inhibit splicing in higher eukaryotes, but rather increases 5' splice site recognition.
Spliceosome formation is initiated by the recognition of the 5' splice site through formation of an RNA duplex between the 5' splice site and U1 snRNA. We have previously shown that RNA duplex formation between U1 snRNA and the 5' splice site can protect pre-mRNAs from degradation prior to splicing. This initial RNA duplex must be disrupted to expose the 5' splice site sequence for base pairing with U6 snRNA and to form the active spliceosome. Here, we investigated whether hyperstabilization of the U1 snRNA/5' splice site duplex interferes with splicing efficiency in human cell lines or nuclear extracts. Unlike observations in Saccharomyces cerevisiae, we demonstrate that an extended U1 snRNA/5' splice site interaction does not decrease splicing efficiency, but rather increases 5' splice site recognition and exon inclusion. However, low complementarity of the 5' splice site to U1 snRNA significantly increases exon skipping and RNA degradation. Although the splicing mechanisms are conserved between human and S.cerevisiae, these results demonstrate that distinct differences exist in the activation of the spliceosome.


Pituitary control of cholesterol metabolism in normal and LDL receptor knock-out mice: effects of hypophysectomy and growth hormone treatment.
The pituitary is important in the control of lipid metabolism and studies of hypophysectomized (Hx) rats have shown strong effects of growth hormone (GH) on bile acid synthesis, hepatic LDL receptor (LDLR) expression and on the sensitivity to dietary cholesterol. It is unclear if mice may be used in such studies. The aim of the current study was to evaluate if Hx mice may be used to further explore how GH modulates cholesterol and bile acid metabolism, and to define the importance of the LDLR in this regulation by studying LDLR-deficient mice (LDLRko). Experiments on three mouse strains showed that, following Hx, HDL were reduced and LDL increased. Cholesterol/fat feeding of Hx mice increased serum cholesterol levels 2- to 3-fold. Serum triglycerides were reduced 50% in Hx mice; a further 30% reduction was seen after dietary cholesterol/fat. A serum marker for CYP7A1-mediated bile acid synthesis (C4) increased 2-fold in intact mice on cholesterol/fat diet. In Hx mice C4 levels were reduced by 50% as compared to intact controls, but were unexpectedly increased to levels seen in normal mice upon cholesterol/fat feeding. Hx of LDLRko mice moderately increased LDL-cholesterol and reduced triglycerides and GH treatment attenuated these effects; serum C4 levels were increased by GH treatment in all groups. In conclusion, mice can be used to explore the role of the pituitary in lipid metabolism. CYP7A1 is generally reduced in Hx mice but has a normal stimulatory response following dietary cholesterol suggesting that faulty regulation of CYP7A1 is not important for the reduced resistance to dietary cholesterol in Hx mice. Further, the LDLR is only to a minor part involved in the pituitary regulation of serum cholesterol in mice.


Impact of ERAS compliance on the delay between surgery and adjuvant chemotherapy in hepatobiliary and pancreatic malignancies.
Multidisciplinary approach with adjuvant chemotherapy is the key element to provide optimal outcomes in pancreas and liver malignancies. However, post-operative complications may increase the interval between surgery and chemotherapy with negative oncologic effects. The aim of the study was to analyse whether compliance to Enhanced Recovery After Surgery (ERAS) pathway was associated with decreased interval to adjuvant chemotherapy. Retrospective analysis of all consecutive ERAS patients with surgery for hepatobiliary or pancreatic malignancies at the University Hospital of Lausanne between 2012 and 2016. Multivariate analysis was performed to assess the impact of ERAS compliance on time to chemotherapy. A total of 133 patients with adjuvant chemotherapy were included (n = 44 liver and n = 89 pancreatic cancer). Median compliance to ERAS was 61% (IQR 55-67) for the study population, and median delay to chemotherapy was 49 days (IQR 39-61). Overall, compliance ≥ 67% to ERAS induced a significant reduction in the interval between surgery and chemotherapy for young patients (< 65 years old) with or without severe comorbidities (reduction of 22 and 10 days, respectively). High compliance in young ASA3 patients with liver colorectal metastases was associated with an increase of 481 days of DFS. ERAS compliance ≥ 67% tends to be associated with a reduction in the delay to adjuvant chemotherapy for young patients with hepatobiliary and pancreatic malignancies. More prospective studies with strict adhesion to the ERAS protocol are needed to confirm these results.


Anti-centromere protein A antibodies in systemic sclerosis: Significance and origin.
Systemic sclerosis (SSc) is systemic, autoimmune, connective tissue disorder characterized by vascular abnormalities, collagen deposition (fibrosis), and the production of autoantibodies to nuclear proteins. About 20%-40% of patients have antibodies to centromere protein (CENP)-A or -B. Despite the known association of anti-CENP antibodies with certain clinical features of SSc, the role of these antibodies in SSc physiopathology is still poorly understood. To better understand the clinical significance and origin of these antibodies, we and others have been studying the epitopic motifs (amino acid contact sites) on CENP-A with the aim of determining whether other proteins can prime or be targeted by them. Here, we review published and ongoing studies aimed at defining the fine specificity and origin of anti-CENP-A antibodies. We describe progress made in identifying the CENP-A epitopic motif amino acids, and the discovery of one of these motifs in forkhead box protein E3 (FOXE-3), a transcription factor previously studied only for its role in the development of lens fiber cells. Moreover, we discuss preliminary evidence for a possible role of FOXE-3 in SSc pathogenesis and for the association of different subsets of anti-CENP-A antibodies, heterogeneously expressed among SSc patients, with some clinical correlates.


Mutagenic activity of promutagens in plants: indirect evidence of their activation.
This review summarizes data concerning mutagenic activity of promutagens in various plant in vivo assays. These data are compared with the present knowledge about the metabolism of xenobiotics and activation of promutagens in plants obtained by biochemical studies and by the separation of the activation process from the genetic endpoints assayed for the mutagenicity. The article documents a differential response of plant species in the endogenous transforming of various classes of promutagens into mutagens. Attention is devoted to the following types of promutagens: nitrosamines, polycyclic aromatic hydrocarbons and aromatic amines, aflatoxins, pyrrolizidine alkaloids, diallate, styrene, vinylchloride, ethanol, cycasin, nitrofurans, sodium azide, s-triazine herbicides, 1,2-dibromoethane and maleic hydrazide.


Ivabradine, the hyperpolarization-activated cyclic nucleotide-gated channel blocker, elicits relaxation of the human corpus cavernosum: a potential option for erectile dysfunction treatment.
To evaluate the effect of the If channel inhibitor, ivabradine on human corpus cavernosum (HCC) smooth muscle tone. HCC samples were obtained from erectile dysfunction(ED) patients (n = 12) undergoing penile prosthesis surgery. Concentration-response curves for ivabradine were exposed to various inhibitory and stimulatory agents. The relaxant and contractile responses to electrical field stimulation (EFS, 10 Hz and 80 Hz) were examined in the presence or absence of ivabradine (10 μM). HCN3 and HCN4 channel expression and localization were determined by Western blot and immunohistochemical analyses of HCC tissues. Increasing ivabradine concentrations dependently reduced the maximal contractile responses of isolated HCC strips induced by KCl (59.5 ± 2.5%) and phenylephrine (84.0 ± 9.8%), which was not affected by nitric oxide synthase and soluble guanylyl cyclase inhibitors after phenylephrine-induced contraction. Nifedipine and tetraethylammonium inhibited the maximum relaxation to ivabradine by 75% and 39.3%, respectively. Fasudil and sildenafil increased the relaxation response to ivabradine without altering the maximum response. Pre-incubation with ivabradine significantly increased relaxant responses to EFS (p < 0.01) and reduced the contractile tension evoked by EFS (72.3%) (p < 0.001). Ivabradine incubation did not affect the expression and localization of HCN3 and HCN4 channels in the HCC smooth muscle cells. Ivabradine exhibits a relaxant effect on HCC tissues, which is likely to be attributed to the blocking of L-type Ca2+ channels and the opening of K+ channels, independent of changes in the activation of the nitric oxide/cyclic guanosine monophosphate system. Inhibition of HCN channels localized in cavernosal smooth muscle cells may offer pharmacological benefits for patients with cardiovascular risk factors.


Increased fragmentation of urinary fibronectin in cancer patients detected by immunoenzymometric assay using domain-specific monoclonal antibodies.
Monoclonal antibodies (MoAbs) recognizing the distinct domains of human fibronectin had previously been established and they were used to construct several sandwich immunoenzymometric assays (IEMAs) for the structural analysis of fibronectin found in the urine of cancer patients. Urinary fibronectin (UFN) was immunodetectable only with FN12-8 and FN30-8 MoAbs against cell-binding domains and was less reactive with other IEMAs using MoAbs directed to terminal domains, indicating that UFN was almost completely fragmented and consisted mainly of cell-binding regions. The IEMA using MoAbs against cell-binding domains had sufficient immunoreactivities with the antigen fragmented by artificial proteolysis, but these fragments could hardly be detected by other IEMAs. UFN levels were significantly elevated in various cancer patients and extremely elevated in some patients with distant metastasis. It is presumed that UFN fragments which increase in cancer patients are generated by extracellular matrix destruction. Thus UFN levels and the ratio of the fragmented UFN level to the non-fragmented UFN level appear to be informative clinical indicators of tumor malignancy or metastatic ability in cancer patients.


Protein-dependent lipid lateral phase separation as a mechanism of human erythrocyte ghost resealing.
The hypothesis of a correlation between a 10 degrees-20 degrees C lipid phase transition and the resealing process of human erythrocyte membrane has been investigated. The conditions required to reseal human erythrocyte ghosts have been studied by measuring the amount of fluorescein-labeled dextran (FD) that is trapped into the membrane. Temperature per se was sufficient to induce membrane resealing: (1) at 5 mM sodium phosphate, pH 7.8 (5P8), resealing began at 12 degrees C; (2) at salt concentrations above 8 mM sodium phosphate, it occurred at lower temperature; and (3) in isotonic saline was detected just above 5 degrees C. The removal of peripheral membrane proteins from unsealed membranes by chymotrypsin at 0 degree C in 5P8 was followed by membrane resealing. This seems to imply that the presence of proteins is necessary to maintain the membrane unsealed. Protein-induced lateral phase separation of lipids may be a reasonable mechanism for the observed phenomena. In fact, the permeability of phosphatidylserine-phosphatidylcholine mixed liposomes to FD is modified by lipid lateral phase separation induced by pH or poly-L-lysine. Electron spin resonance studies of membrane fluidity by a spin labeled stearic acid showed a fluidity break around 11 degrees C, which may be due to a gel-liquid phase transition. Fluidity changes are abolished by chymotrypsin treatment. It is suggested that a lateral phase separation is responsible for the permeability of open ghosts to FD. Accordingly, disruption of phase separation apparently produces membrane reconstitution. In this respect peripheral proteins and particularly the spectrin-actin network, may play a major role in membrane resealing.


Long duration underwater glider dataset: Indian Ocean from Perth, Australia to Mirissa, Sri Lanka.
This data was collected using an underwater research vehicle, Slocum glider. The glider is an autonomous robot that is able to measure several water properties from surface to 1000 m depth. The duration of missions for underwater gliders are on the order of 1 month to over a year. Detailed here is the live satellite telemetered dataset as transmitted during mission. Dataset includes positional data, vehicle engineering, attitude, temperature, salinity, and depth averaged currents. Raw data as well as some derived variables from the raw data are included in this dataset. This data is transmitted every couple hours and comprises of a subset of the data stored on the vehicle's internal memory. The data is returned in segmented files which comprises of an underwater segment bookended by GPS positions. Because most analysis require longer time series, effort has been taken to conglomerate the segment datasets into a single continuous dataset stitching together the segments. The platform chosen for this is currently MATLAB. This data can provide the community with an example dataset of underwater glider data pertinent to a long duration and low energy glider mission. It also includes ocean measurements of temperature, salinity, and ocean currents. Built into the dataset object are various functions designed to help the user navigate and display a glider's collected data. The effort is being made to serve future datasets, 2017 and onward, via ERDAPP at the following location: http://slocum-data.marine.rutgers.edu/erddap/index.html Analyzed by the Applied Ocean Research article: Modeling for the Performance of Navigation, Control and Data Post-Processing of Underwater Gliders where it is used for flight efficiency analysis as well as ocean model comparisons.


A large abdominal intercostal hernia in a patient with vascular type Ehlers-Danlos syndrome: a surgical challenge.
A patient with vascular type Ehlers-Danlos syndrome developed a large abdominal intercostal hernia secondary to coughing. The tissue friability and associated risks for arterial ruptures and visceral perforations in these patients make hernia repair challenging. The hernia was successfully treated using a novel approach.


Nucleus Accumbens Shell Neurons Encode the Kinematics of Reward Approach Locomotion.
The nucleus accumbens (NAc) is considered an interface between motivation and action, with NAc neurons playing an important role in promoting reward approach. However, the encoding by NAc neurons that contributes to this role remains unknown. We recorded 62 NAc neurons in male Wistar rats (n = 5) running towards rewarded locations in an 8-arm radial maze. Variables related to locomotor approach kinematics were the best predictors of the firing rate for most NAc neurons. Nearly 18% of the recorded neurons were inhibited during the entire approach run (locomotion-off cells), suggesting that reduction in firing of these neurons promotes initiation of locomotor approach. 27% of the neurons presented a peak of activity during acceleration followed by a valley during deceleration (acceleration-on cells). Together, these neurons accounted for most of the speed and acceleration encoding identified in our analysis. In contrast, a further 16% of neurons presented a valley during acceleration followed by a peak just prior to or after reaching reward (deceleration-on cells). These findings suggest that these three classes of NAc neurons influence the time course of speed changes during locomotor approach to reward.


Aerobic exercise delays retinal ganglion cell death after optic nerve injury.
Aerobic exercise has been shown to play a crucial role in preventing neurological diseases and improving cognitive function. In the present study, we investigated the effect of treadmill training on retinal ganglion cells (RGCs) following optic nerve transection in adult rats. We exercised the rats on a treadmill for 5 d/week (30 min/d at a rate of 9 m/min) or placed control rats on static treadmills. After 3 weeks of exercise, the left optic nerve of each rat was transected. After the surgery, the rat was exercised for another week. The percentages of surviving RGCs in the axotomized eyes of inactive rats were 67% and 39% at 5 and 7 days postaxotomy, respectively. However, exercised rats had significant more RGCs at 5 (74% survival) and 7 days (48% survival) after axotomy. Moreover, retinal brain-derived neurotrophic factor (BDNF) protein levels were significantly upregulated in response to exercise compared with those in the axotomized eyes of inactive rats. Blocking BNDF signaling during exercise by intraperitoneal injections of ANA-12, a BDNF tropomyosin receptor kinase (TrkB) receptor antagonist, reduced the number of RGCs in exercised rats to the level of RGCs in the inactive rats, effectively abolishing the protection of RGCs afforded by exercise. The results suggest that treadmill training effectively rescues RGCs from neurodegeneration following optic nerve transection by upregulating the expression of BDNF.


Distinct expression of SARS-CoV-2 receptor ACE2 correlates with endotypes of chronic rhinosinusitis with nasal polyps.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry factors, ACE2 and TMPRSS2, are highly expressed in nasal epithelial cells. However, the association between SARS-CoV-2 and nasal inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been investigated. We thus investigated the expression of SARS-CoV-2 entry factors in nasal tissues of CRSwNP patients, and their associations with inflammatory endotypes of CRSwNP. The expression of ACE2 and TMPRSS2 was assessed in nasal tissues of control subjects and eosinophilic CRSwNP (ECRSwNP) and nonECRSwNP patients. The correlations between ACE2/TMPRSS2 expression and inflammatory indices of CRSwNP endotypes were evaluated. Regulation of ACE2/TMPRSS2 expression by inflammatory cytokines and glucocorticoids was investigated. ACE2 expression was significantly increased in nasal tissues of nonECRSwNP patients compared to ECRSwNP patients and control subjects, and positively correlated with the expression of IFN-γ, but negatively correlated with tissue infiltrated eosinophils, and expression of IL5 and IL13. IFN-γ up-regulated ACE2 expression while glucocorticoid attenuated this increase in cultured nasal epithelial cells. Genes co-expressed with ACE2 were enriched in pathways relating to defence response to virus in nasal tissue. TMPRSS2 expression was decreased in nasal tissues of CRSwNP patients compared to control subjects and not correlated with the inflammatory endotypes of CRSwNP. Glucocorticoid treatment decreased ACE2 expression in nasal tissues of nonECRSwNP patients, but not in ECRSwNP patients, whereas TMPRSS2 expression was not affected. These findings indicate that ACE2 expression, regulated by IFN-γ, is increased in nasal tissues of nonECRSwNP patients and positively correlates with type 1 inflammation.


Women's and male partners' socio-demographic and economic characteristics associated with contraceptive decision making in Nigeria.
Women's ability to make contraceptive decision can determine their contraceptive use which can improve their reproductive health and career. Improvement in such ability can increase contraceptive prevalence in Nigeria. However, factors that promote contraceptive decision-making among women are scarcely studied. This study examined factors associated with women's individual or joint contraceptive decision-making in Nigeria. Secondary (cross-sectional) data were analysed. The data were extracted from the individual recode file of the 2018 Nigeria Demographic and Health Survey (DHS). Partnered women (i.e., currently married or living with a partner) aged 15-49 years and currently using contraceptives before the survey were considered. They constituted 4,823 in total. Their data were analysed using frequency and percentage distributions of variables, Chi-square tests of independence and multinominal logistic regression. Findings reveal that 23% (1,125) of women made their own contraceptive decision, nearly 67% (3,213) were joint decision makers, and 10% (491) stated that their male partners had decided for them. The probability of solely making contraceptive decision and being a joint decision maker (relative to being a male partner's decision) was higher among women above 29 years and aged 30-34 years (than women aged 15-24 years) respectively as well as among the employed (than the unemployed) and among those from Yoruba ethnic group (than their counterparts from Hausa/Fulani/Kanuri/Beri Beri) respectively. The probability of being responsible for contraceptive decision (than being the male partner's decision) was higher among women from the Igbo group and women whose male partners desired more children (than those with the same number of desired children) respectively. The probability of being the main decision maker (relative to being the male partner) was lower among women in the poorer (RRR = 0.39; 95%CI = 0.21-0.73; p = 0.01), middle (RRR = 0.47; 95%CI = 0.25-0.90; p = 0.02) and richest (RRR = 0.41; 95%CI = 0.20-0.82; p = 0.01) groups respectively, than the poorest women. The probability of being a joint decision maker was higher among women with secondary education (than the uneducated), practised Christianity (than the Muslims/ others), and among those residing in the North West region (than those in North East) respectively. However, the probability of being a joint decision-maker was lower among women whose partners desire more children and those who did not know their partners' desires. Women's age, highest level of education, employment status, wealth index, ethnicity, religion, region of residence and male partners' desire for children are associated with contraceptive decision making respectively. There is a need for reproductive empowerment interventions in Nigeria that devise effective ways of improving contraceptive decision-making power of partnered women aged 15-24 years, unemployed, in the poorer and richest groups, from the Hausa/Fulani/Kanuri/Beri Beri ethnic group, practising Islam/ other religions, have the same fertility desire as their partners and those who do not know their male partner's desire for children respectively. Women whose partners desire more children should be empowered to participate effectively in contraceptive decision making.


Exploring common dialectical tensions constraining collaborative communication required for post-2020 conservation.
Contemporary conservation requires improved collaboration characterized by greater recognition and incorporation of multiple and diverse actors. Effective communication is central to this endeavour. However, the expression of concerns, perspectives, and the exchange of knowledge between actors and across multiple scales (i.e., collaborative communication), must navigate inevitable competing systems of meaning and motivation (i.e., dialectical tensions). Yet, a lack of understanding of how to improve collaborative communication within conservation interventions persists within the literature. Consequently, this paper reviews relevant literature to propose a framework that identifies common sources of dialectical tensions in collaborative conservation interventions that if managed effectively can improve required collaborative communication. The framework is then revised based on interviews conducted with 277 respondents in three African coastal-marine collaborative conservation interventions. Findings reinforce the effect of continued marginalization of certain actors' 'voices' within governance processes. More specifically, enabling collaborative communication requires managing several identified institutional-, agenda-, cultural-, and perception-based tensions. In particular, tensions emerging from formal-informal institutional interactions; gender-based exclusion; conflicting livelihood-ecological and economic-environmental agendas, and project-funder objectives; between indigenous/local-scientific knowledge and values; and perceived necessary-acceptable change. Furthermore, specific local-scale tensions identified included those associated with local-customary institutions; democratic-meritocratically elected local representatives; and exclusion based on cultural diversity. Consequently, these tensions require the 'co-creation' of communicative strategies amongst all actors to promote greater social equity that better aligns with local priorities to achieve 'positive' post-2020 ecological and social outcomes. Findings should be relevant to diverse conservation actors, and many others working within multi-stakeholder environmental interventions.


Dopamine "renal dose" versus fenoldopam mesylate to prevent ischemia-reperfusion injury in renal transplantation.
Low dose of dopamine is commonly used after kidney transplantation as a reno-protective agent, although its benefits are controversial. Dopamine may increase renal blood flow, decrease resistive index (RI), and induce urine output in normal kidneys. Many authors hypothesized that the vasculature of a denervated renal transplant may not respond to dopamine in the same fashion as healthy native kidneys, which led us to find other drugs to attenuate the ischemia-reperfusion (I/R) injury. Fenoldopam is a selective dopamine1 (DA1) receptor agonist, most of the activity of which resides in the R-enantiomer, which also shows weaker alpha 2-adrenoceptor antagonist activities. Fenoldopam produces a vasidilatory effect in vascular beds that are rich in vascular DA1 receptors, producing increased renal blood flow at doses that do not affect blood pressure. In addition to its renal vasodilator activity, fenoldopam is natriuretic, possibly resulting from a direct effect of DA1 receptors on the proximal convoluted tubule. In animals with spontaneous or drug-induced renal failure, fenoldopam improves renal function. The aim of this study was to investigate the possible effects of fenoldopan mesylate in recent kidney transplants. Creatinine, blood urea nitrogen, urine output, and renal vascular resistive index (IR) were measured using Doppler ultrasound. Two groups of patients with no statistical differences in demographic data were treated with dopamine or fenoldopan, showing no significant difference but a trend favoring the fenoldopan group.


[Methods of enteral nutritional intervention in the home].
The authors review indications and principles for providing home enteral nutrition. It is a method of nutritional support in ambulatory patients, which is effective, easy to administer and financially feasible.


Cabozantinib is well tolerated in acute myeloid leukemia and effectively inhibits the resistance-conferring FLT3/tyrosine kinase domain/F691 mutation.
Cabozantinib, a tyrosine kinase inhibitor of FMS-like tyrosine kinase 3 (FLT3), MET, AXL, vascular endothelial growth factor receptor, and KIT, is approved for use in multiple malignancies. We assessed the safety and tolerability of cabozantinib in AML, given up-regulation of multiple relevant pathways. Adults were eligible if they were 18 years old or older with relapsed/refractory AML or if they were 70 years old or older with newly diagnosed AML but were ineligible for conventional therapy. Cabozantinib was administered in 28-day cycles, and dose escalation occurred via cohorts. A pharmacodynamic evaluation of serial plasma samples via a plasma inhibitory assay (PIA) was used to assess FLT3-inhibitory activity in FLT3-mutant cell lines. Among 18 patients enrolled, 5 were found to harbor FLT3/ITD mutations. Sixteen patients (89%) had relapsed/refractory AML, and most were treated with 2 or more lines of prior treatment. No dose-limiting toxicities (DLTs) were detected at the first dose level (40 mg daily), but 2 patients experienced DLTs at the next level (60 mg daily). The remaining patients were then dosed at 40 mg daily, the maximum tolerated dose (MTD). Additional grade 2 or higher toxicities, possibly/probably related to cabozantinib, included fatigue, nausea, transaminitis, and electrolyte imbalance. No patients had a marrow response according to formal criteria, but 4 had peripheral blast reductions; 2 of these 4 patients transiently cleared circulating blasts. One patient experienced a reduction in marrow blasts, and 1 had stable disease. The FLT3-inhibitory activity of plasma samples, as assessed with the PIA, revealed potent and sustained inhibition in FLT3/ITD and, notably, F691 tyrosine kinase domain (TKD)-mutant cells. Cabozantinib is well tolerated in AML patients at an MTD of 40 mg daily and is a potent inhibitor of FLT3/ITD- and F691 TKD-altered tyrosine kinases. Cancer 2018;124:306-14. © 2017 American Cancer Society.


Amelioration of panadol-induced nephrotoxicity via down-regulation of Bax/Bcl2 ratio with some antioxidants.
Overdoses of Panadol (APAP) result in hepatic and renal toxicity. Up till now, there is no effective drug for APAP-enhanced nephrotoxicity. This work aims to explore the protective effects of N-acetylcysteine, Thymoquinone (THQ), Curcumin (CUR) and α-Lipoic acid (LA) either alone or in combination against APAP nephrotoxicity, focused on modulation of Bax/Bcl2 pathway. APAP was administrated at a single dose then treated with the fore mentioned antioxidants. APAP administration increased serum creatinine, urea, uric acid, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) levels compared to control group. There is a marked depletion of reduced glutathione (GSH) levels and superoxide dismutase activity (SOD), Bax level was overexpressed, whereas Bcl2 was downregulated in renal tissue. Histopathological examination of the kidney tissue supported these biochemical findings. Treatment with the fore mentioned anti-oxidants ameliorated most of the previous evaluated parameters and returned the kidney nearly to its normal architecture. The expression of Bax and Bcl2 is considered one of the mechanisms underlying APAP-induced nephrotoxicity. The administration of THQ along with CUR could be a promising antidote for APAP renal damage through their antioxidant potential.


Assessing toxicant emissions from e-liquids with DIY additives used in response to a potential flavour ban in e-cigarettes.
Electronic cigarettes (e-cigarettes) aerosolise liquids that contain nicotine, propylene glycol, glycerol and appealing flavours. In the USA, regulations have limited the availability of flavoured e-cigarettes in pod-based systems, and further tightening is expected. In response, some e-cigarette users may attempt to make their e-liquids (do-it-yourself, DIY). This study examined toxicant emissions from several aerosolised DIY e-liquids. DIY additives were identified by reviewing users' responses to a hypothetical flavour ban, e-cigarette internet forums and DIY mixing internet websites. They include essential oils, cannabidiol, sucralose and ethyl maltol. E-liquids with varying concentrations and combinations of additives and tobacco and menthol flavours were prepared and were used to assess reactive oxygen species (ROS), carbonyl and phenol emissions in machine-generated aerosols. Data showed that adding DIY additives to unflavoured, menthol-flavoured or tobacco-flavoured e-liquids increases toxicant emissions to levels comparable with those from commercial flavoured e-liquids. Varying additive concentrations in e-liquids did not have a consistently significant effect on the tested emissions, yet increasing power yielded significantly higher ROS, carbonyl and phenol emissions for the same additive concentration. Adding nicotine to DIY e-liquids with sucralose yielded increase in some emissions and decrease in others, with freebase nicotine-containing e-liquid giving higher ROS emissions than that with nicotine salt. This study showed that DIY additives can impact aerosol toxicant emissions from e-cigarettes and should be considered by policymakers when restricting commercially available flavoured e-liquids.


Cytogenetic effects of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in rat peripheral lymphocytes in vitro and in vivo.
3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a potent direct-acting Salmonella mutagen found in wood pulp chlorination effluents and chlorinated drinking water. In cultured rat peripheral lymphocytes, MX induced significant dose-related increases in sister-chromatid exchanges (SCEs) and chromosome aberrations at doses of 20-60 micrograms/ml and of 60-80 micrograms/ml, respectively. MX produced primarily chromatid-type as opposed to chromosome-type aberrations. The peripheral lymphocytes of male and female rats exposed to MX by gavage 5 days a week for 14-18 weeks showed significant dose-related increases in SCEs at both levels of exposure (30 and 45-75 mg/kg) in both sexes. The present results demonstrate for the first time that MX is genotoxic in vivo.


Management of chylous leakage after breast surgery: report of four cases.
Chylous leakage is a rare occurrence after breast surgery. Trauma to the thoracic duct and its main distribution may be the main cause of chylous leakage, but the cause of such an injury during breast surgery is unknown. We herein report the first case of chylous leakage from many minimal lymph ducts in a skin flap. In all, four cases of chylous leakage were observed out of 1 096 breast cancer patients who underwent axillary lymph node dissection. Of these four cases, three cases were successfully treated conservatively; however, surgical exploration was performed in the fourth case because of the large drainage volume. Furthermore, we reviewed the recently published studies on chylous leakage after breast surgery; 20 cases (our 4 cases included) have been reported in all. Of the 20 pooled cases, most were cured with conservative treatment and only three cases were cured with surgical treatment.


Properties of columns with several pyridinium and imidazolium ionic liquid stationary phases.
Recent advances in the development of new liquid phases (ILs) made it possible to use some classes of ILs as polar stationary liquid phases (SLP). In our days only alkylimidazolium- and alkylphosphonium-based ILs are widely used as polar SLP. In present work some other types of ILs - pyridinium and cyanopropyl/hydroxypropyl imidazolium were investigated as SLP. Columns with efficiencies 2000-2500 plates/m by high-pressure static method were prepared. Polarity and selectivity of these phases were measured. Selectivity was described in terms of intermolecular interactions by using Abraham solvatation parameter model. The set of the regularities between cation structure of ionic liquid and selectivity has been shown. The number and position of methyl groups in ionic liquid pyridinium ring were shown to have the sufficient influence on all type of molecular interactions. Finally the resolutions of test mixture for the several ionic liquid SLP were obtained. For columns with some ionic liquids the dependencies of the height equivalent to a theoretical plate (HETP) and sample loading capacity were obtained and compared with the conventional phases. It was found that the optimal efficiency for the IL columns is attained at lower carrier gas velocities in comparison with traditional phases. Nevetheless sample loading capacity of IL phases is comparable to those of conventional GC phases.


Atrophy of middle and short stereocilia on outer hair cells of guinea pig cochleas with experimentally induced hydrops.
Scanning electron microscopy was employed to investigate hair cell morphology at different stages in the development of experimentally induced hydrops in the guinea pig. A particular form of morpho-pathology, never before described, was identified as characteristic of hydropic cochleas. The pathology was characteristically identified as atrophy of the short and middle stereocilia on the outer hair cells while the inner hair cell stereocilia did not have such a pathology. The atrophy was restricted to the upper cochlear turns in remarkable correspondence with the low/middle frequency sensitivity loss and was detected only at the end of the period of fluctuating thresholds. These stereocilia perturbations appear therefore to be linked with the threshold fluctuations and represent the first evidence for a clear correlation between hair cell morphology and physiology in the experimental model of endolymphatic hydrops. Such a morphopathology might also be expected to occur in cochleas of Menière's patients but may have been overlooked in the past because of the discrete nature of the pathology.


Infertility knowledge and attitudes in urban high school students.
To assess knowledge and attitudes about infertility through a survey. Descriptive study with stratified random sampling. Eighteen high schools were selected in Toronto, Ontario, Canada. Seven hundred seventy-two students participated in the study. The mean age of students was 17.5 +/- 0.98 years. Females were 49.02% (n = 377) of the sample. The sample was ethnically diverse, consisting of >13 groups. None. The main outcome was infertility knowledge and attitudes. Secondary analysis compared gender and socioeconomic status. The majority (608; 79%) of high school students were familiar with the term infertility (95% confidence interval: 76%, 82%). More than 94% did not know that chlamydia or gonorrhea could lead to infertility. Seventy percent felt that protecting their fertility was important to them, with significantly more females feeling this way. There was a higher proportion of students from schools with low socioeconomic status who gave incorrect answers to knowledge-related questions and were unaware of the association between sexually transmitted infections and infertility. Although the majority of students value their fertility, knowledge about preventable factors causing infertility was limited. Increased efforts are needed to educate students on factors that may affect their fertility.


Clinical outcome and urodynamic changes of tailored transvaginal mesh surgery for pelvic organ prolapse: A mid-term 40 Months follow-up.
To evaluate the changes in clinical outcome and urodynamic parameters after tailored anterior transvaginal mesh (ATVM) surgeries in a mid-term follow-up. Between November 2011 and December 2015, women with ≥stage II pelvic organ prolapse (POP) who underwent ATVM surgeries were retrospectively reviewed. The data-reviewing timeframe was until December 2021. Clinical and urodynamic diagnoses regarding urinary symptoms were evaluated before and after the operation. A total of 160 women were included. Stress urinary incontinence decreased significantly after the operation (99% (159/160) vs. 43% (68/160), p < 0.01), as well as the pad weight (20.5 ± 2.7 vs. 9.4 ± 2.0, p < 0.001) and diagnosis of urodynamic stress incontinence (83% (132/160) vs. 51% (82/160), p < 0.01). Overactive bladder syndrome increased significantly after the operation (18% (29/160) vs. 28% (45/160), p = 0.03), even though the objective parameters, such as first and strong desire to void, bladder oversensitivity, and detrusor overactivity, were all improved after the operation. The pad weight was mostly improved significantly within the first postoperative 2 years. Eighteen (11%) women had global recurrent POP, and only one (0.6%) woman had true recurrence of cystocele. Twenty-four (15%) women had mesh extrusion, and two-thirds of them could be managed in an office setting. In women with advanced cystocele, the ATVM surgery provides a favorable anatomic reduction outcome with an acceptable mesh extrusion rate. The ATVM provides an anti-incontinence effect, both in subjective symptoms and objective parameters, but this effect might decline after postoperative 2 years.


Exosomes: A Potential Therapeutic Tool Targeting Communications between Tumor Cells and Macrophages.
Exosomes comprise extracellular vesicles (EVs) with diameters between 30 and 150 nm. They transfer proteins, RNA, and other molecules from cell to cell, playing an important role in the interactions between cells. The tumor microenvironment (TME) has been found to contain various cells and molecules that have an important impact on tumor development. In the TME, macrophages have been found to have an important relationship with tumor cells, with tumors recruiting and inducing macrophages to become tumor-associated macrophages (TAMs), which promote tumor development. Recently, exosomes have been found to play a critical role in the interaction between tumor cells and macrophages. Thus, in this review, we summarize the roles and mechanisms of exosomes in the interaction between tumor cells and macrophages and the potential methods by which exosomes are used to target the communication between tumor cells and macrophages to treat cancer.


Frequent immunoglobulin G4 expression in a common variant of primary cutaneous marginal zone B-cell lymphoma.
Immunoglobulin (Ig)G4 expression was recently observed in a proportion of primary cutaneous marginal zone B-cell lymphoma (PCMZL) with plasmacytic differentiation. IgG4-related disease is characterised by polyclonal lymphoplasmacytic infiltration with IgG4 expression, storiform fibrosis and obliterative phlebitis in histopathology. Here we report three cases of common variants of PCMZL with predominant and varied IgG4 expression, suggesting there is an underlying clonal progression between these two entities.


Climate warming and summer monsoon breaks drive compound dry and hot extremes in India.
Considering the severe impacts of compound dry and hot extremes, we examine the primary drivers of CDHEs during the summer monsoon in India. Using ERA5 reanalysis, we show that most of the CDHEs in India occur during the droughts caused by the summer monsoon rainfall deficit. Despite a decline in the frequency of summer monsoon droughts in recent decades, increased CDHEs are mainly driven by warming and dry spells during the summer monsoon particularly in the Northeast, central northeast, and west central regions. A strong land-atmospheric coupling during droughts in the summer monsoon season leads to frequent CDHEs in the Northwest and southern peninsular regions. Furthermore, regional variations in land-atmospheric coupling cause substantial differences in the CDHE occurrence in different parts of the country. Summer monsoon rainfall variability and increased warming can pose a greater risk of compound dry and hot extremes with severe impacts on various sectors in India.


Conversion total hip arthroplasty following extracapsular hip fracture fixation with a cephalomedullary device: a comprehensive review.
With the annual incidence of hip fractures and hip fracture fixation rising, the need for conversion total hip arthroplasty has also risen. About half of the 280,000 hip fractures that occur annually in the United States are extracapsular. Commonly extracapsular hip fractures are treated with either cephalomedullary nails (CMNs) or sliding hip screws (SHS). More recently, there has been a shift toward increased CMN use due to increased training with this fixation method as well as perioperative and biomechanical benefits. Given this shift, orthopedic surgeons need to understand the factors that lead to CMN failure. Failed CMN treatment leaves both patients and surgeons with few management options including revision fixation with or without osteotomy, conversion total hip arthroplasty, and conversion hemiarthroplasty. Surgeons must consider the patient and injury characteristics before deciding the best treatment plan. Conversion total hip arthroplasty is indicated in younger patients without femoral head and/or acetabular articular injury, degenerative joint disease, or avascular necrosis. Conversion total arthroplasty is a technically demanding and resource-intensive surgery associated with lower success rates and outcomes than primary total hip arthroplasty. Orthopedic surgeons should have thorough understanding of preoperative workup needed prior to surgery, implant selection associated with best outcomes, most common surgical approaches used, intraoperative considerations, and complications associated with conversion total hip arthroplasty. A comprehensive understanding of these concepts gives patients the best chance of having a successful outcome.


Inhaled nitric oxide and inhaled prostaglandin E1: effect on left ventricular contractility when used for treatment of experimental pulmonary hypertension.
Pulmonary hypertension (PHT) is a life-threatening complication after isolated heart and lung transplantation. Recent work has shown that inhaled nitric oxide (NO) in combination with inhaled prostaglandin E1 (PGE1) reduce pulmonary hypertension but their influence on cardiac contractility is less well defined. This study investigated left ventricular contractility as measured by the 'Preload Recruitable Stroke Work-Relation' (PRSW) in 24 anesthetized open chest pigs, 12 receiving in random order NO (50 ppm), PGE1 (20 microg/ml) and their combination compared to 12 controls. PHT was induced by embolization with glass beads (500 microm). Prior to induction of PHT, sonomicrometric crystals were placed on the heart to measure instantaneous cardiac dimensions. Instantaneous intraventricular pressure (micro-tip catheter) and intraventricular dimensions were recorded digitally, while intraventricular volumes were calculated from the intraventricular dimensions applying the cylindric ellipsoidal volume model for the left ventricle. PRSW was calculated from the instantaneous pressure and volume data during rapid vena caval occlusion by analysis of generated pressure-volume loops. All data were analyzed by MANOVA and corrected for heart rate (level of significance #: P < 0.05); PRSW-slope measures contractility, (PRSW-X-intercept did not change significantly). PRSW-change +/- SEM (in percent of initial PRSW after induction of PHT) was -14.6% +/- 4.4% versus 1.6% +/- 4.4% for NO versus Control (P = 0.004), -8.8% +/- 4.6% versus 1% +/- 3.3% (P = 0.18) for PGE1 versus Control and -5.7% +/- 4.4% versus 2.5% +/- 4.2% for NO + PGE1 versus Control (P = 0.33), respectively. In summary, application of NO 50 ppm significantly reduced left ventricular contractility while PGE1 20 microg/ml and the combination of NO and PGE1 did not. If NO is not available, the sole application of nebulized PGE1 (20 microg/ml) appears to be safe with respect to left ventricular contractility in the setting of PHT. The combination of NO and PGE1 for the treatment of pulmonary hypertension should be considered for clinical application in situations where a combination of pulmonary hypertension and decreased left ventricular function is present.


Diagnostic yield of array CGH in patients with autism spectrum disorder in Hong Kong.
Chromosomal microarray offers superior sensitivity for identification of submicroscopic copy number variants (CNV) and it is advocated to be the first tier genetic testing for patients with autism spectrum disorder (ASD). In this regard, diagnostic yield of array comparative genomic hybridization (CGH) for ASD patients is determined in a cohort of Chinese patients in Hong Kong. A combined adult and paediatric cohort of 68 Chinese ASD patients (41 patients in adult group and 27 patients in paediatric group). The genomic DNA extracted from blood samples were analysed by array CGH using NimbleGen CGX-135K oligonucleotide array. We identified 15 CNV and eight of them were clinically significant. The overall diagnostic yield was 11.8 %. Five clinically significant CNV were detected in the adult group and three were in the paediatric group, providing diagnostic yields of 12.2 and 11.1 % respectively. The most frequently detected CNV was 16p13.11 duplications which were present in 4 patients (5.9 % of the cohort). In this study, a satisfactory diagnostic yield of array CGH was demonstrated in a Chinese ASD patient cohort which supported the clinical usefulness of array CGH as the first line testing of ASD in Hong Kong.


Damage creation in swift heavy ion-irradiated calcite single crystals: Raman and infrared study.
Raman and Infrared studies were carried out on pristine and 100 MeV Ag(8+) ion irradiated calcite single crystals in the fluence range 1 x 10(11) to 1 x 10(13)ions/cm(2). Raman and Infrared modes were assigned according to factor theory analysis. It is observed that the intensities of the Raman and infrared bands decrease with increase of ion fluence. The decrease of these bands is attributed to breakage of carbonate ions and other details are discussed.


Subjective pleasure experience in patients with recent-onset schizophrenia: A preliminary report.
Little is known about subjective pleasure experience in recent-onset schizophrenia, and its relationship with neurocognitive functions. Twenty-seven recent-onset schizophrenia people and 26 controls completed the TEPS and neuropsychological tests. The results showed that schizophrenia people self-reported less anticipatory pleasure than controls. Semantic verbal fluency was apparently correlated with anticipatory pleasure.