Laparoscopic pyeloplasty with concomitant pyelolithotomy.
We present our experience with laparoscopic pyeloplasty plus pyelolithotomy in patients in whom stones were not the cause of ureteropelvic junction obstruction. A transperitoneal approach was used for laparoscopic pyeloplasty and pyelolithotomy in 19 patients (20 renal units). Before ureteropelvic junction repair stones were extracted through a small pyelotomy that was eventually incorporated into the final pyeloplasty incision. Stones in the renal pelvis were removed with rigid graspers under direct laparoscopic vision. A flexible cystoscope introduced through a port was used to extract stones in the calices. The renal pelvis was reconstructed based on the anatomy of the ureteropelvic junction. A median of 1 stone (range 1 to 28) was recovered. In 11, 8 and 1 patients the Anderson-Hynes dismembered pyeloplasty, Y-V plasty and the Heinecke Mickulicz procedure were performed, respectively. At 3 months 2 patients had residual calculi for a procedural stone-free rate of 90%. There was no evidence of obstruction in 18 of the 20 cases (90%), as confirmed by negative diuretic scan or radiological improvement of hydronephrosis. At a mean followup of 12 months (range 3 to 57) 2 additional patients had recurrent stones for an overall long-term stone-free rate of 80% (16 of 20). Laparoscopic pyelolithotomy is feasible when combined with pyeloplasty. Our results are comparable to those of stone removal during open pyeloplasty or percutaneous endopyelotomy. The advantages of open surgery appear to be maintained in this minimally invasive approach.


A Summary of Female Genital Mutilation/Cutting for the Pediatric and Adolescent Care Provider.
The World Health Organization defines female genital mutilation/cutting as any medically unnecessary procedure involving partial or total removal of the external female genitalia or other injury to the female genital organs. It is a violation of human rights and associated with serious complications and lifelong impact on health. This review article summarizes for the pediatric and adolescent care provider the incidence worldwide, the impact of cultural practices, appropriate screening and diagnosis, interventions, and treatment, along with legal and ethical issues.


Identification of two novel SALL1 mutations in chinese families with townes-brocks syndrome and literature review.
Townes-Brocks syndrome is a rare autosomal dominant genetic syndrome caused by mutations in SALL1. The clinical features of Townes-Brocks syndrome are highly heterogonous. Identification of new SALL1 mutations and study of the relation between SALL1 mutations and clinical features can facilitate diagnosis of Townes-Brocks syndrome. We collected clinical data and blood samples of the two patients and their family members for whole-exome sequencing and Sanger sequencing. Prediction analysis of the SALL1variation protein structure was achieved using Alphafold. The clinical materials and gene sequencing results were analyzed. The clinical materials and gene sequencing results were analyzed. The related literature of Townes-Brocks syndrome were searched and the genotype-renal phenotype analysis was performed combined with this two cases. Based on the clinical features and gene sequencing results, the two patients were diagnosed as Townes-Brocks syndrome. Two novel SALL1 mutations (c.878-887del and c.1240G > T) were identified, both of which were pathogenic mutations. The correlation between genotypes and renal phenotypes in Townes-Brocks syndrome patients caused by SALL1 mutation were summarized. This study identified two novel mutations and provided new insights into the correlation of genotypes and renal phenotypes of Townes-Brocks syndrome.


The effects of a typing task on the hand volume of the older worker.
Few studies have examined the relationship between changes in hand volume and typing. Volumetric evaluation documents the presence of an inflammatory response to activity. To study this relationship, researchers used a convenience sample of 31 participants who were aged 45 and older and worked full time where they typed at least one hour per day. Volumetric measurements were taken before a 15-minute typing activity, immediately after and 10 minutes after typing. Before typing, ergonomic adjustments were made to computer workstations, when necessary. Participants typed using an advanced speed test of the Mavis Beacon Teaches Typing program, which calculated adjusted words per minute. The data showed no significant (F = 0.321, p > 0.05) change in hand volume resulting from the typing activity. The amount of exercise provided in this study, a fifteen minute typing activity, did not result in changed hand volume.


Effects on neuromodulation, acupuncture, and aerobic exercises on migraine and tension-type headache outcomes: A systematic review and meta-analysis.
Headache disorders are common diseases that cause a social burden. This systematic review and meta-analysis aimed to evaluate the effects of various non-pharmacological treatments to address or prevent acute headaches, including neuromodulation, acupuncture, and aerobic exercises in patients with episodic migraine and tension-type headache (TTH). We performed a systematic search of the electronic databases PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, WANFANG MEDICINE ONLINE, and Chinese Medical Journal database using Stata/SE 14.0 to obtain weighted mean differences (WMDs). The outcomes included monthly headache days, headache intensity, headache duration, days per month of acute medication use, and the Medical Outcomes Study 36-Item Short-Form Health Survey. Of 872 identified articles, 27 were included in the meta-analysis. Neuromodulation was associated with reduced headache days (WMD: -1.274, 95% CI [-1.914, -0.634], P < .001), duration (WMD: -2.2, 95% CI [-3.32, -0.107], P < .001) and medication consumption (WMD: -1.808, 95% CI [-2.546, -1.071], P < .001) in cases of migraine. Acupuncture was associated with the alleviation of headache days (WMD: -0.677, 95% CI [-0.932, -0.422], P < .001) and intensity (WMD: -0.893, 95% CI [-1.573, -0.212], P = .01) in cases of migraine and acute medication use (WMD: -3.29, 95% CI [-4.86, -1.72], P < .001) in cases of TTH. Aerobic exercise was associated with reduced headache duration (WMD: -5.1, 95% CI [-8.97, -1.22], P = .01) in cases of TTH. The risk of bias for included articles was moderate. There is low- and moderate-quality evidence that neuromodulation, acupuncture, and aerobic exercises are associated with attenuated headache symptoms in patients with episodic migraine or TTH. However, high-quality studies are needed to draw more detailed conclusions.


Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study.
Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. Cancer Research UK, National Institute for Health Research.


Exploring outcomes from an innovative, pediatric-focused intervention with undergraduate nursing students.
To adapt to COVID-19 restrictions, a virtual pediatric skills day was developed to provide nursing students with practical experience prior to entering the pediatric clinical setting. Student assessment before and after participation indicate a virtual skills day is helpful in building student confidence prior to pediatric clinicals. This mixed-method study involved a cross-sectional approach with a six-item survey administered before and immediately after the virtual pediatric skills day intervention to undergraduate junior nursing students. Outcome measures included comfort and preparation for pediatrics and families of pediatric patients. After exploring outcomes from 93 students complete pre and post intervention measures, we addressed comfort themes including excited, nervous, and readiness while preparedness themes highlighted concerns with parental interactions, upset children, and COVID-19 restrictions. It is beneficial for nursing students to have clinical experiences with children prior to visiting a pediatric clinical setting. Such experiences decrease student stress and anxiety and allow meaningful opportunities to occur.


Computer assisted sperm analysis of motility patterns of postthawed epididymal spermatozoa of springbok (Antidorcas marsupialis), impala (Aepyceros melampus), and blesbok (Damaliscus dorcus phillipsi) incubated under conditions supporting domestic cattle in vitro fertilization.
The need for information on the reproductive physiology of different wildlife species is important for ex situ conservation using such methods as in vitro fertilization (IVF). Information on species reproductive physiology and evaluation of sperm quality using accurate, objective, repeatable methods, such as computer-assisted sperm analysis (CASA) for ex situ conservation has become a priority. The aim of this study was to evaluate motility patterns of antelope epididymal spermatozoa incubated for 4 h under conditions that support bovine IVF using CASA. Cauda epididymal spermatozoa were collected postmortem from testicles of springbok (N=38), impala (N=26), and blesbok (N=42), and cryopreserved in biladyl containing 7% glycerol. Spermatozoa were thawed and incubated in Capacitation media and modified Tyrode lactate (m-TL) IVF media using a protocol developed for domestic cattle IVF. The study evaluates 14 motility characteristics of the antelope epididymal sperm at six time points using CASA. Species differences in CASA parameters evaluated under similar conditions were observed. Several differences in individual motility parameters at the time points were reported for each species. Epididymal sperm of the different antelope species responded differently to capacitation agents exhibiting variations in hyperactivity. Motility parameters that describe the vigor of sperm decreased over time. Spermatozoa from the different antelope species have different physiological and optimal capacitation and in vitro culture requirements. The interspecies comparison of kinematic parameters of spermatozoa between the antelopes over several end points contributes to comparative sperm physiology which forms an important step in the development of species specific assisted reproductive techniques (ARTs) for ex situ conservation of these species.


Anaesthesia care with and without tracheal intubation during emergency endoscopy for peptic ulcer bleeding: a population-based cohort study.
Emergency upper gastrointestinal bleeding is a common condition with high mortality. Most patients undergo oesophagogastroduodenoscopy (OGD), but no universally agreed approach exists to the type of airway management required during the procedure. We aimed to compare anaesthesia care with tracheal intubation (TI group) and without airway instrumentation (monitored anaesthesia care, MAC group) during emergency OGD. This was a prospective, nationwide, population-based cohort study during 2006-13. Emergency OGDs performed under anaesthesia care were included. End points were 90 day mortality (primary) and length of stay in hospital (secondary). Associations between exposure and outcomes were assessed in logistic and linear regression models, adjusted for the following potential confounders: shock at admission, level of anaesthetic expertise present, ASA score, Charlson comorbidity index score, BMI, age, sex, alcohol use, referral origin (home or in-hospital), Forrest classification, ulcer localization, and postoperative care. The study group comprised 3580 patients under anaesthesia care: 2101 (59%) for the TI group and 1479 (41%) for the MAC group. During the first 90 days after OGD, 18.9% in the TI group and 18.4% in the MAC group died, crude odds ratio=1.03 [95% confidence interval (CI)=0.87-1.23, P=0.701], adjusted odds ratio=0.95 (95% CI=0.79-1.15, P=0.590). Patients in the TI group stayed slightly longer in hospital [mean 8.16 (95% CI=7.63-8.60) vs 7.63 days (95%=CI 6.92-8.33), P=0.108 in adjusted analysis]. In this large population-based cohort study, anaesthesia care with TI was not different from anaesthesia care without airway instrumentation in patients undergoing emergency OGD in terms of 90 day mortality and length of hospital stay.


Using AI and BES/MFC to decrease the prediction time of BOD5 measurement.
Biochemical oxygen demand (BOD) is one of the most important water/wastewater quality parameters. BOD5 is the amount of oxygen consumed in 5 days by microorganisms that oxidize biodegradable organic materials in an aerobic biochemical manner. The primary objective of this research is to apply microbial fuel cells (MFCs) to reduce the time requirement of BOD5 measurements. An artificial neural network (ANN) has been created, and the predictions we obtained for BOD5 measurements were carried out within 6-24 h with an average error of 7%. The outcomes demonstrated the viability of our AI MFC/BES BOD5 sensor in real-life scenarios.


An in vitro assessment of the physical properties of manually- mixed and encapsulated glass-ionomer cements.
The last decade has seen a variety of modifications of glass-ionomer cements (GICs), such as inclusion of bioactive glass particles and dispensing systems. Hence, the aim was to systematically evaluate effect of mixing modes and presence of reactive glass additives on the physical properties of several GICs. The physical properties of eight commercial restorative GICs; Fuji IX GP Extra (C&H), KetacTM Fill Plus Applicap (C&H), Fuji II LC (C&H), Glass Carbomer Cement and Equia® Forte Fil, capsulated versus manually mixed were assessed. 256 cylindrical specimens were prepared for compressive strength and microhardness, whilst 128 disc-shaped specimens were prepared for biaxial flexural strength tests. Fluid uptake and fluoride release were assessed. Data were analysed using one-way ANOVA and Games-Howell post-hoc tests (alpha = 0.05). Both encapsulated GIC/RMGICs exhibited significantly improved mechanical properties in comparison to manually mixed equivalents, which in turn showed higher fluid uptake and early fluoride release (p < 0.05). The glass carbomer cement exhibited improved mechanical properties post ageing and evidence of mineral deposits were apparent in the microstructure. The mixing mode and inclusion of reactive glass additives in cements had a statistically significant effect on physical properties of the selected GICs-RMGICs.


Impact Survey Results after SAFE Strategy Implementation in 15 Local Government Areas of Kebbi, Sokoto and Zamfara States, Nigeria.
To determine prevalence of trachoma after interventions in 15 local government areas (LGAs) of Kebbi, Sokoto and Zamfara States, Nigeria. A population-based impact survey was conducted in each LGA using Global Trachoma Mapping Project (GTMP) protocols. In each LGA, 25 villages were selected, except in Arewa LGA, where we selected 25 villages from each of four subunits to obtain finer-resolution prevalence information. Villages were selected with probability proportional to size. In each village, 25 households were enrolled and all consenting residents aged ≥1 year were examined by GTMP-certified graders for trachomatous inflammation-follicular (TF) and trachomatous trichiasis (TT). Information on sources of household water and types of sanitation facilities used was collected through questioning and direct observation. The number of households enrolled per LGA ranged from 623 (Kware and Tangaza) to 2488 (Arewa). There have been marked reductions in the prevalence of TF and TT since baseline surveys were conducted in all 15 LGAs. Eight of the 15 LGAs have attained TF prevalences <5% in children, while 10 LGAs have attained TT prevalences <0.2% in persons aged ≥15 years. Between 49% and 96% of households had access to water for hygiene purposes within 1 km of the household, while only 10-59% had access to improved sanitation facilities. Progress towards elimination of trachoma has been made in these 15 LGAs. Collaboration with water and sanitation agencies and community-based trichiasis surgery are still needed in order to eliminate trachoma by the year 2020.


Anti-inflammatory properties of a dual PPARgamma/alpha agonist muraglitazar in in vitro and in vivo models.
Peroxisome proliferator-activated receptor (PPAR) agonists are widely used drugs in the treatment of diabetes and dyslipidemia. In addition to their metabolic effects, PPAR isoforms PPARα and PPARγ are also involved in the regulation of immune responses and inflammation. In the present study, we investigated the effects of a dual PPARγ/α agonist muraglitazar on inflammatory gene expression in activated macrophages and on carrageenan-induced inflammation in the mouse. J774 murine macrophages were activated by lipopolysaccharide (LPS) and treated with dual PPARγ/α agonist muraglitazar, PPARγ agonist GW1929 or PPARα agonist fenofibrate. The effects of PPAR agonists on cytokine production and the activation of inducible nitric oxide synthase (iNOS) pathway were investigated by ELISA, Griess method, Western blotting and quantitative RT-PCR. Nuclear translocation, DNA-binding activity and reporter gene assays were used to assess the activity of nuclear factor kappa B (NF-kB) transcription factor. Carrageenan-induced paw oedema was used as an in vivo model of acute inflammation. Muraglitazar as well as PPARγ agonist GW1929 and PPARα agonist fenofibrate inhibited LPS-induced iNOS expression and NO production in activated macrophages in a dose-dependent manner. Inhibition of iNOS expression by muraglitazar included both transcriptional and post-transcriptional components; the former being shared by GW1929 and the latter by fenofibrate. All tested PPAR agonists also inhibited IL-6 production, while TNFα production was reduced by muraglitazar and GW1929, but not by fenofibrate. Interestingly, the anti-inflammatory properties of muraglitazar were also translated in vivo. This was evidenced by the finding that muraglitazar inhibited carrageenan-induced paw inflammation in a dose-dependent manner in mice as did iNOS inhibitor L-NIL and anti-inflammatory steroid dexamethasone. These results show that muraglitazar has anti-inflammatory properties both in vitro and in vivo and these effects reflect the agonistic action through both PPARα and PPARγ.


[3H]ketanserin binds to non-5-HT2 sites in rabbit cerebral cortex and neostriatum.
A characterization of [3H]ketanserin ([3H]KTS) binding in the frontal cortex (fCTX) and neostriatum (caudate-putamen, CPU) of rabbit was carried out to determine whether this ligand labels a non-serotoninergic receptor. The association and dissociation kinetics in fCTX were rapid, and could be fitted to two-site models, suggesting [3H]KTS is labeling two cortical sites. Using the serotonin-2 (5-HT2) antagonist mianserin to determine nonspecific binding, the saturation curves revealed a single high-affinity binding site. In contrast, when unlabeled ketanserin was used for nonspecific counts, the Scatchard plots were best fitted to a two-site model but the binding parameters of the high-affinity site were similar to that obtained in the presence of mianserin. The 5-HT2 antagonists mianserin, methysergide and ritanserin inhibited [3H]KTS binding in fCTX at nanomolar concentrations, however, the curves were best fitted to two-site models. In contrast, [3H]KTS binding to membrane preparations from the CPU could only be inhibited by high (micromolar) concentrations of these antagonists. Low micromolar concentrations of the monoamine uptake blockers GBR12909, desipramine, nomifensine, cocaine and fluoxetine competed with [3H]KTS in both fCTX and CPU. This study demonstrates that [3H]KTS labels a non-serotoninergic recognition site in the rabbit fCTX and CPU similar to that found in the rat neostriatum, i.e.: probably a monoamine transport site.


Operant conditioning of motor cortex neurons reveals neuron-subtype-specific responses in a brain-machine interface task.
Operant conditioning is implemented in brain-machine interfaces (BMI) to induce rapid volitional modulation of single neuron activity to control arbitrary mappings with an external actuator. However, intrinsic factors of the volitional controller (i.e. the brain) or the output stage (i.e. individual neurons) might hinder performance of BMIs with more complex mappings between hundreds of neurons and actuators with multiple degrees of freedom. Improved performance might be achieved by studying these intrinsic factors in the context of BMI control. In this study, we investigated how neuron subtypes respond and adapt to a given BMI task. We conditioned single cortical neurons in a BMI task. Recorded neurons were classified into bursting and non-bursting subtypes based on their spike-train autocorrelation. Both neuron subtypes had similar improvement in performance and change in average firing rate. However, in bursting neurons, the activity leading up to a reward increased progressively throughout conditioning, while the response of non-bursting neurons did not change during conditioning. These results highlight the need to characterize neuron-subtype-specific responses in a variety of tasks, which might ultimately inform the design and implementation of BMIs.


Rapid purification of human P-glycoprotein mutants expressed transiently in HEK 293 cells by nickel-chelate chromatography and characterization of their drug-stimulated ATPase activities.
P-glycoprotein containing 10 tandem histidine residues at the COOH end of the molecule was transiently expressed in HEK 293 cells and purified by nickel-chelate chromatography. The purified protein had an apparent mass of 170 kDa, and its verapamil-stimulated ATPase activity in the presence of phospholipid was 1.2 mumol/min/mg of P-glycoprotein. We then characterized P-glycoprotein mutants that exhibited altered drug-resistant phenotypes and analyzed the contribution of the two nucleotide binding folds to drug-stimulated ATPase activity. Mutation of residues in either nucleotide binding fold abolished drug-stimulated ATPase activity. The pattern of drug-stimulated ATPase activities of mutants, which conferred increased relative resistance to colchicine (G141V, G185V, G830V) or decreased relative resistance to all drugs (F978A), correlated with their drug-resistant phenotypes. By contrast, the ATPase activity of mutant F335A was significantly higher than that of wild-type enzyme when assayed in the presence of verapamil (3.4-fold), colchicine (9.1-fold), or vinblastine (3.7-fold), even though it conferred little resistance to vinblastine in transfected cells. These results suggest that both nucleotide-binding domains must be intact to couple drug binding to ATPase activity and that the drug-stimulated ATPase activity profile of a mutant does not always correlate with its drug-resistant phenotype.


Synthesis, NMR characterization and divergent biological actions of 2'-hydroxy-ceramide/dihydroceramide stereoisomers in MCF7 cells.
A straightforward method for the simultaneous preparation of (2S,3R,2'R)- and (2S,3R,2'S)-2'-hydroxy-ceramides (2'-OHCer) from (2S,3R)-sphingosine acetonide precursors and racemic mixtures of 2-hydroxy fatty acids (2-OHFAs) is described. The obtained 2'-OH-C4-, -C6-, -C12-, -C16-Cer and 2'-OH-C6-dhCer pairs of diastereoisomers were characterized thoroughly by TLC, MS, NMR, and optical rotation. Dynamic and multidimensional NMR studies provided evidence that polar interfaces of 2'-OHCers are extended and more rigid than observed for the corresponding non-hydroxylated analogs. Stereospecific profile on growth suppression of MCF7 cells was observed for (2'R)- and (2'S)-2'-OH-C6-Cers and their dihydro analogs. The (2'R)-isomers were more active than the (2'S)-isomers (IC(50) ∼3 μM/8 μM and IC(50) ∼8 μM/12 μM, respectively), surpassing activity of the ordinary C6-Cer (IC(50) ∼12 μM) and C6-dhCer (IC(50) ∼38 μM). Neither isomer of 2'-OH-C6-Cers and 2'-OH-C6-dhCers was metabolized to their cellular long chain 2'-OH-homologs. Surprisingly, the most active (2'R)-isomers did not influence the levels of the cellular Cers nor dhCers. Contrary to this, the (2'S)-isomers generated cellular Cers and dhCers efficiently. In comparison, the ordinary C6-Cer and C6-dhCer also significantly increased the levels of their cellular long chain homologs. These peculiar anabolic responses and SAR data suggest that (2'R)-2'-OHCers/dhCers may interact with some distinct cellular regulatory targets in a specific and more effective manner than their non-hydroxylated analogs. Thus, stereoisomers of 2'-OHCers can be potentially utilized as novel molecular tools to study lipid-protein interactions, cell signaling phenomena and to understand the role of hydroxylated sphingolipids in cancer biology, pathogenesis and therapy.


Analysis of Endocrine and Metabolic Indexes in Non-Obese Patients with Polycystic Ovary Syndrome and Its Compare with Obese Patients.
To compare the endocrine and metabolic indexes of obese and normal body mass index (BMI) polycystic ovary syndrome (PCOS) patients, and explore factors affecting the pathogenesis and progression of PCOS. This study included obese (n=79) and normal BMI (n=40) PCOS patients, and obese (n=30) and normal BMI (n=30) non-PCOS controls. Blood glucose, insulin (INS), blood lipids, sex hormones, and other metabolic and endocrine indicators were measured, and the correlations between the indicators were analyzed. HOMA-IR, 0min INS, 60min INS, 120min INS, 180min INS, FAI, TG, TC, LDL-C and sd-LDL in obese PCOS group were higher, while SHBG, LH, LH/FSH and HDL-C were lower than those in normal weight PCOS group (P <0.05). 120min PBG, HOMA-IR, FAI, T, LH, LH/FSH, AMH, TC and LDL-C in obese PCOS group were higher than those in obese control group (P <0.05). 0min PBG, 60min PBG, 120min PBG, 180min PBG, 0min INS, 60min INS, 120min INS, 180min INS, HOMA-IR, LH, LH/FSH and T in normal weight PCOS group were higher than those in normal weight control group (P <0.05). In both normal weight group and obesity group, HOMA-IR entered the regression equation with FAI as dependent variable, and the absolute value of HOMA-IR standardized partial regression coefficient was higher than that of hs-CRP and AMH. In PCOS patients, FAI in the obese and non-obese PCOS groups was positively correlated with HOMA-IR. Endocrine metabolic disorders in women with PCOS were more obvious than that in women with non-PCOS with matched BMI. The abnormality of glucose and lipid metabolism in obese PCOS patients is more serious than that in PCOS patients with normal BMI. Both obese and normal BMI PCOS patients were affected by hyperinsulinemia, and IR may play a key role in the pathogenesis and development of PCOS.


Neurodegeneration in amyotrophic lateral sclerosis: the role of oxidative stress and altered homeostasis of metals.
Amyotrophic lateral sclerosis is one of the most common neurodegenerative disorders, with an incidence of about 1/100,000. One of the typical features of this progressive, lethal disease, occurring both sporadically and as a familial disorder, is degeneration of cortical and spinal motor neurones. Present evidence indicates that loss of neurones in patients results from a complex interplay among oxidative injury, excitotoxic stimulation, dysfunction of critical proteins and genetic factors. This review focuses on existing evidence that oxidative stress is a major culprit in the pathogenesis of amyotrophic lateral sclerosis. An increase in reactive oxygen species and in products of oxidation has been observed both in post-mortem samples and in experimental models for ALS. This increase may be consequent to altered metabolism of copper and iron ions, that share the property to undergo redox cycling and generate reactive oxygen species. Metal-mediated oxidative stress would lead to several intracellular alterations and contribute to the induction of cell death pathways.


Laparoscopic cholecystectomy: intraoperative ultrasound of the extrahepatic biliary tree and the natural history of postoperative transabdominal ultrasound findings.
Laparoscopic cholecystectomy (LC) has been rapidly embraced as an alternative to conventional open cholecystectomy (OC). While LC is less invasive than OC, it is still a surgical procedure with potential complications such as retained bile duct stones, iatrogenic injury to the bile duct with or without bile leak, hemorrhage, intestinal injury, and abscess formation. This article discusses the feasibility of intraoperative transmural ultrasound of the extrahepatic biliary tree with a 6.2 French catheter-based ultrasound probe and reviews the natural history of postoperative changes in the liver and gallbladder bed with conventional transabdominal ultrasound.


Metabolic adaptation and ATP homeostasis in Pseudomonas fluorescens exposed to phosphate stress.
Phosphate (Pi) is essential for life as it is an integral part of the universal chemical energy adenosine triphosphate (ATP), and macromolecules such as, DNA, RNA proteins and lipids. Despite the core roles and the need of this nutrient in living cells, some bacteria can grow in environments that are poor in Pi. The metabolic mechanisms that enable bacteria to proliferate in a low phosphate environment are not fully understood. In this study, the soil microbe Pseudomonas (P.) fluorescens was cultured in a control and a low Pi (stress) medium in order to delineate how energy homeostasis is maintained. Although there was no significant variation in biomass yield in these cultures, metabolites like isocitrate, oxaloacetate, pyruvate and phosphoenolpyruvate (PEP) were markedly increased in the phosphate-starved condition. Components of the glycolytic, glyoxylate and tricarboxylic acid cycles operated in tandem to generate ATP by substrate level phosphorylation (SLP) as NADH-producing enzymes were impeded. The α-ketoglutarate (KG) produced when glutamine, the sole carbon nutrient was transformed into phosphoenol pyruvate (PEP) and succinyl-CoA (SC), two high energy moieties. The metabolic reprogramming orchestrated by isocitrate lyase (ICL), phosphoenolpyruvate synthase (PEPS), pyruvate phosphate dikinase (PPDK), and succinyl-CoA synthetase fulfilled the ATP budget. Cell free extract experiments confirmed ATP synthesis in the presence of such substrates as PEP, oxaloacetate and isocitrate respectively. Gene expression profiling revealed elevated transcripts associated with numerous enzymes including ICL, PEPS, and succinyl-CoA synthetase (SCS). This microbial adaptation will be critical in promoting biological activity in Pi-poor ecosystems.


Photostable pigments within the membrane of photoreceptors and their possible role.
In the majority of ommatidia of the fly, the membrane of the central rhabdomere contains--besides the rhodopsin--a photostable pigment. Due to its selective absorption in the blue spectral range, this pigment (possibly a carotene) could modify the spectral senstivity of the central receptor cells. It furthermore may change the fluidity of the microvillus membrane and hence affect the alignment of rhodopsin molecules. Indirect evidence for a possible role of the photostable pigment as an "antenna" -pigment for rhodopsin is discussed.


Sex differences in poly-victimization among youth experiencing homelessness prior to substance use treatment.
Poly-victimization is common among youth experiencing homelessness (YEH) and youth in substance use treatment. To date, studies have not examined poly-victimization among these two intersecting populations. To examine heterogeneity in lifetime victimization experiences among youth reporting homelessness at substance use treatment entry; identify demographic predictors of victimization class membership; and associations between victimization and clinical characteristics at treatment intake. 1270 adolescents and young adults reporting past 90-day homelessness in a nationwide substance use treatment data set. Latent Class Analysis (LCA) and logistic regression were used to examine heterogeneity in poly-victimization experiences, and associations with demographics and clinical characteristics for males and females. Four victimization classes emerged for males, and five victimization classes emerged for females. The prevalence of victimization and trauma characteristics were higher for females, except physical victimization, which was higher for males. Age, race/ethnicity, and sexual minority status were related to poly-victimization class membership, but not consistently across classes. Compared to low or single victimization classes, youth in the poly-victimization class had higher odds of post-traumatic stress disorder, major depressive disorder, and exchange sex (among females); Poly-victimization class membership was not associated with duration of recent homelessness or substance use disorder diagnoses, when compared to low/less complex victimization. High rates of lifetime victimization were found for YEH in substance use treatment, with rates generally higher among females. Trauma-informed interventions are needed to address complex victimization experiences and poor mental health among unstably housed youth in treatment.


Lymphocytic gastritis versus varioliform gastritis. A historical series revisited.
A historical series of varioliform gastritis published in 1978 by Lambert et al. (Digestion 1978; 17: 159-167) was revisited by two pathologists. The histological preparations from 35 patients were reread and interpreted in the light of endoscopic data found in the files. The results demonstrate a strict correlation between clinical diffuse varioliform gastritis and a recently recognized histopathological entity--lymphocytic gastritis, which is characterized by intense lymphocytic infiltration of the surface and foveolar epithelium. The rare discrepancies occur in Crohn's disease and in varioliform gastritis limited to part of the stomach, mostly the antrum.


Adolescent breast masses.
A retrospective experience with breast masses in 143 female and 22 male adolescents is reviewed: 104 females (71.7 per cent) had fibroadenomas and 1 (0.7 per cent) adenocarcinoma; all 22 males had gynecomastia. The significance of these findings is related to surgical therapy.


Antioxidant enzyme and malondialdehyde levels in patients with social phobia.
A growing body of reports have indicated that free radicals are involved in the etiopathogenesis of some neuropsychiatric disorders. In the present study, we aimed to evaluate whether antioxidant enzymes (superoxide dismutase; SOD, glutathione peroxidase; GSH-Px, and catalase; CAT) activity levels and malondialdehyde (MDA), a product of lipid peroxidation, were associated with social phobia (SP). Eighteen patients diagnosed with SP and 18 healthy controls were enrolled. A clinical evaluation and measurements of MDA, SOD, GSH-Px and CAT were performed. Additionally, all patients were assessed with the Liebowitz Social Anxiety Scale (LSAC). The mean MDA, SOD, GSH-Px and CAT levels in the patient group were significantly higher than those in the control group. There was a positive correlation between LSAC scores and MDA, SOD, GSH-Px and LSAC levels, and between the duration of illness, and MDA, SOD and CAT levels in the patient group. In conclusion, our results suggest that there may be a relationship between increased antioxidant enzyme levels and MDA, and SP.


The correlation of long non-coding RNAs IFNG-AS1 and ZEB2-AS1 with IFN-γ and ZEB-2 expression in PBMCs and clinical features of patients with coronary artery disease.
Aberrant expression of long non-coding RNAs (lncRNAs) can contribute to the pathogenesis of coronary artery disease (CAD). In this study, we aimed to evaluate the expression of lncRNA interferon γ-antisense 1 (IFNG-AS1), zinc finger E-box binding homeobox 2 antisense RNA 1 (ZEB2-AS1), and their direct target genes (IFN-γ and ZEB2, respectively) in peripheral blood mononuclear cell (PBMC) from CAD and healthy individuals. We recruited 40 CAD patients and 40 healthy individuals. After doing some bioinformatics analyses, the expressions of IFNG-AS1/ ZEB2-AS1 lncRNAs and IFN-γ/ ZEB2 in PBMCs were measured using quantitative real-time PCR. The possible correlation between the putative lncRNAs and disease severity was also assessed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive role of lncRNAs as diagnostic biomarkers in CAD patients. The expressions of IFNG-AS1 lncRNA as well as IFN-γ and ZEB2 genes were significantly reduced in CAD patients compared to healthy subjects. In contrast, the expression of ZEB2-AS1 was up-regulated in these patients. Linear regression analysis unveiled that there is a positive correlation between the expression of IFNG-AS1 and IFN-γ, also similarly, ZEB2-AS1 and ZEB2 in PBMCs of subjects. Moreover, the expression of IFNG-AS1 and ZEB2-AS1 correlated with the Gensini score. The area under the ROC curves ranged from 0.633-0.742 for ZEB2-AS1/ZEB2 and IFNG-AS1/IFN-γ, respectively. Our results indicated that the dysregulation of IFNG-AS1/IFN-γ and ZEB2-AS1/ZEB2 in PBMCs of CAD patients may be involved in CAD pathogenesis.


Comparison of two paediatric resuscitation charts for ease of use.
We have compared the ease and speed of use of two published paediatric resuscitation charts, the Burke and Bowden chart and the Oakley chart. Twenty general anaesthetists each answered 11 questions on resuscitation data for five paediatric patients of different weights, heights and ages. Data was recorded for the five patients using one chart and then repeated for the same patients using the second with the order of use of chart being randomised (n=100 patients for each chart). There were significantly fewer patients for whom mistakes were made with the Burke and Bowden chart compared to the modified Oakley chart (21 and 46, respectively, P < 0.001). Only one physician recorded the resuscitation data correctly for all five patients with each chart. The Burke and Bowden chart was also statistically significantly faster to use than the Oakley chart (52.7 s (range 31-103) versus 64 s (range 44-115), respectively (P < 0.001)). A change in format and content of each chart may be required to make them both more user friendly especially when used under stress.


Malformation syndrome with t(2;22) in a cancer family with chromosome instability.
A de novo unbalanced t(2;22)(q37;q11.2) [corrected], resulting in the deletion of the 22pter-q11 and 2q37-qter regions, was observed in a 12-year-old girl born with a congenital malformation syndrome and later displaying signs of neurologic impairment. Some of the clinical signs observed appear to overlap those found in subjects monosomic in the 22q11 region affected by the DiGeorge syndrome. The chromosomal rearrangement observed may be related to a familial cytogenetic instability that also gives rise to sustained cancer predisposition.


In vivo release of dopa and dopamine from genetically engineered cells grafted to the denervated rat striatum.
Fibroblastic 3T3 and endocrine RIN cells were genetically modified by infection with a recombinant retrovirus encoding the form I of human tyrosine hydroxylase (TH) and selection in tyrosine-free medium. These cells were grafted to rats unilaterally lesioned with 6-hydroxy-dopamine. Both cell types survived implantation into the striatum, expressed TH immunoreactivity, and as assessed by microdialysis 8-9 days after implantation, secreted high amounts of DOPA and/or dopamine into the surrounding host striatum. The modified 3T3 cells secreted large amounts of DOPA that was efficiently decarboxylated to dopamine by the host striatal tissue; the newly synthesized dopamine was stored only to a limited extent in the denervated striatum. The modified RIN cells synthesized dopamine that was stored intracellularly and released in a regulated fashion. The grafted DOPA-secreting cells produced 4-5 times higher extracellular dopamine levels than the dopamine-secreting cells, and they were more efficient in reducing apomorphine-induced rotation. No effect was observed with either cell type on amphetamine-induced turning behavior.


High-throughput sequencing of a single chromosome: a moth W chromosome.
Y and W chromosomes have mostly been excluded from whole genome sequencing projects. Due to the high amount of repetitive sequences they are 'difficult' to assemble and therefore need special treatment in the form of, e.g. adapted assembly programs, a range of different libraries, and accurate maps, if possible. A minimum requirement for these approaches is pure template DNA. We therefore microdissected the W chromatin of highly polyploid cells from the flour moth, Ephestia kuehniella, and used Roche/454 and Sanger sequencing to generate 72.6 Mbp of DNA sequence. Nominal coverage was 4.3× of the 16.7 Mbp of W chromosomal DNA. We used these data to assess the genetic content of the W chromosome. This approach allowed us to determine constituent families of transposable elements, microsatellites, and recent insertion sites of mitochondrial DNA. However, no conventional protein-coding gene has yet been found. The sequence collection is a rich source for the definition of W-specific PCR markers and the reconstruction of W chromosome loci, as a step towards full reconstruction of the chromosome.


The bad seed in Alzheimer's disease.
In this issue of Neuron, McGowan et al. report on a new mouse model of amyloid deposition as occurs in Alzheimer's disease. Unlike previous models in which overexpression of the amyloid precursor protein results in amyloid plaque formation, McGowan et al. have produced mice that overexpress only Abeta40 or Abeta42 and prove that Abeta42 is critical for the formation of amyloid deposits in vivo.


Bilateral simultaneous total knee arthroplasty.
One hundred thirty-two patients (264 knees) who had simultaneous bilateral total knee arthroplasty and 77 patients who had unilateral procedures were reviewed for statistical comparison of the two procedures with respect to pain, tibial and femoral radiolucency, and all other complications as well as average hospital stay and hospital costs. Both groups had posterior cruciate condylar total knee prostheses. There were no significant differences except for tibial radiolucency, which was significantly higher in the unilateral group. Bilateral total knee arthroplasty as a single procedure does not increase the risk of postoperative or follow-up complications and decreases the probability of complications such as phlebitis and pulmonary emboli, because only one operation is necessary. The average hospital cost and length of stay were lower in the simultaneous group (decreased by 20% and 46%, respectively), compared with twice that of the unilateral group.


Speech Outcomes of Treatment for Velopharyngeal Insufficiency: Combined Use of an Overlapping Intravelar Veloplasty and Dynamic Sphincter Pharyngoplasty.
Velopharyngeal insufficiency involving a large velopharyngeal gap and poor lateral wall movement is referred to as a "black hole" and remains a challenging problem for cleft surgeons. The effect of the pharyngeal flap on this form of velopharyngeal insufficiency is still debatable because a wide pharyngeal flap is associated with a high incidence of airway obstruction. The present study aimed to evaluate the speech outcomes of combined overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty for the treatment of velopharyngeal insufficiency. Between March 2016 and June 2019, 15 patients with velopharyngeal insufficiency were treated with a combination of overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty. Preoperative speech evaluation was performed on the basis of perceptual speech evaluation, nasometry, and nasoendoscopy. Postoperative speech evaluation using the same approach as that used preoperatively was performed after completion of speech therapy. All 15 patients achieved satisfactory velopharyngeal port closure and speech phonation after completion of speech therapy. No additional procedures were performed to improve velopharyngeal port closure and speech production. The preoperative and postoperative results of perceptual speech evaluation, nasometry, and nasoendoscopy evaluation were significantly different (P < 0.01). Combined treatment with overlapping intravelar veloplasty and dynamic sphincter pharyngoplasty can correct the velopharyngeal insufficiency "black hole" with highly reliable results and minimal risk of airway obstruction.


Positive predictive value of a single nucleotide polymorphism (SNP)-based NIPT for aneuploidy in twins: Experience from clinical practice.
Twins account for approximately 1 in 30 live births in the United States. However, there are limited clinical experience studies published in noninvasive prenatal testing (NIPT) for detecting aneuploidies in twins. This study reports the performance of an SNP-based NIPT in the largest cohort with known outcomes for high-risk aneuploidy results. This is a retrospective analysis of 18,984 results from commercial single-nucleotide polymorphism (SNP)-based NIPT tests performed in twins between October 2, 2017 and December 31, 2019. Follow-up for all 211 high-risk cases was solicited. Follow-up outcomes were obtained in 105 cases. Positive predictive values (PPVs) for high-risk results were 88.7% (63/71, 95% Confidence Interval [CI]: 79.0%-95.0%) for trisomy 21% and 72.7% (8/11, 95% CI: 39.0%-94.0%) for trisomy 18. The results were stratified into monozygotic (MZ) and dizygotic (DZ). The PPVs in MZ were 100% for both trisomy 21 (4/4, 95% CI: 40%-100%) and trisomy 18 (1/1, 95% CI: 2.5%-100%). No trisomy 13 cases were detected in the MZ group. The PPVs in DZ were 88.1% (59/67, 95% CI: 77.8%-94.7%), 70.0% (7/10, 95% CI: 34.8%-93.3%), and 66.7% (2/3, 95% CI: 9.4%-99.2%) for trisomy 21, trisomy 18, and trisomy 13, respectively. The performance of SNP-based NIPT in this large twin cohort was comparable to previously reported twin NIPT studies. SNP-based NIPT allows for zygosity-based PPV assessment.


Detection of antibodies to ovine lentivirus using a recombinant antigen derived from the env gene.
The Western blot assay was performed to characterize antibodies to the transmembrane glycoprotein (TGP) of ovine progressive pneumonia virus (OPPV) by using glutathione-S-transferase-TGP (GST-TGP) protein. The GST-TGP protein was efficiently expressed in Escherichia coli (E. coli) and was highly immunoreactive in the Western blot assay. This assay detected antibodies in 97% (103/106) of the sera from agarose gel immunodiffusion (AGID) positive OPP animals. Like human AIDS patients, antibodies to TGP appear to be one of the major serological markers in OPP infected animals.


Determinants of farmers' waste generation and disposal in rural areas of central China.
The treatment of agricultural waste plays an important role in the sustainability of agricultural production and the well-being of rural communities. The present study analyzes the existing sources of agricultural waste in rural communities, their current disposal, and the farmers' attitudes towards waste management. The data is based on a survey in 21 communities in agricultural areas in Shaanxi (N = 359 farmers interviewed). The results provide a description of the main agricultural waste in the region based on empirical data. The responses highlight the farmers' experience, reputation, and engagement at recycling domestic waste as the main variables shaping their attitudes towards agricultural waste disposal. Farmers prefer treating primarily biowaste, mostly used for biogas generation or crop fertilizer at the farms. Improving waste management facilities, accessibility and economic incentives are identified as the main factors that could increase recycling rates, as well as the importance of training campaigns and instructions related to waste handling and recycling. The analysis captured the general trends in agricultural waste treatment and future directions and provides a basis for better designing waste and management alternatives.


Not low hanging but still sweet: Metabolic proteomes in cardiovascular disease.
The application of proteomics in biology and medicine has reached a moment of truth. The demand of biologists for transformative insights into how cells work, plus the mandate of basic science research to ultimately impact clinical medicine, crystallize as a test on the rigor and reproducibility of any 'omics measurement. Studies like that by Boylston et al. indicate that proteomics can pass that test.


Characterization of non-taste & odor produced aerobic denitrification actinomycetes strains Streptomyces spp. isolated from reservoir ecosystem: Denitrification performance and carbon source metabolism.
The aerobic denitrification performance of actinomycetes was investigated. Two strains of actinomycetes were isolated and identified as Streptomyces sp. LJH-12-1 and Streptomyces diastatochromogenes LJH-12-2. Strain LJH-12-1 could remove 94% of organic carbon and 91% of total nitrogen. Meanwhile, strain LJH-12-2 could reduce 96% of organic carbon and 93% of total nitrogen. Two strains of actinomycetes revealed excellent carbon source metabolism activity. Moreover, the total nitrogen removal efficiencies were 69%, and 54%, respectively for strains LJH-12-1, and LJH-12-2 during the micro-polluted landscape raw water treatment. Futhermore, strains LJH-12-1 and LJH-12-2 could utilize aromatic proteins, soluble microbial products, and humic acid to drive aerobic denitrification processes in the landscape water bodies. These results will provide a new insight into applying aerobic denitrification actinomycetes to treat micro-polluted water bodies.


Chlorophyll and its degradation products in the two-spotted spider mite, Tetranychus urticae: observations using epifluorescence and confocal laser scanning microscopy.
Chlorophyll and chlorophyll degradation products were observed in the two-spotted spider mite (Tetranychus urticae) using epifluorescence microscopy (EFM) and confocal laser scanning microscopy (CLSM). A clear red fluorescence (EFM) and a fluorescence induced by a laser wavelength of 650 nm (CLSM) were observed. In the lateral caeca, in the ventriculus and in the excretory organ, a bright light blue fluorescence was observed in close association with chlorophyll by using EFM. The same material can be localized with CLSM by using a laser with a wavelength of 488 nm. By comparison with synthetic guanine, this bright fluorescence is supposed to be guanine. The presence of guanine fluorescence in the mite pellets confirms this hypothesis. A possible mechanism for guanine formation is discussed.


Second messenger-dependent protein kinases and protein synthesis regulate endogenous secretin receptor responsiveness.
1. The present study investigated the role of second messenger-dependent protein kinase A (PKA) and C (PKC) in the regulation of endogenous secretin receptor responsiveness in NG108-15 mouse neuroblastomaxrat glioma hybrid cells. 2. In whole cell cyclic AMP accumulation studies, activation of PKC either by phorbol 12-myristate 13-acetate (PMA) or by purinoceptor stimulation using uridine 5'-triphosphate (UTP) decreased secretin receptor responsiveness. PKC activation also inhibited forskolin-stimulated cyclic AMP accumulation but did not affect cyclic AMP responses mediated by the prostanoid-IP receptor agonist iloprost, or the A(2) adenosine receptor agonist 5'-(N-ethylcarboxamido) adenosine (NECA). 3. In additivity experiments, saturating concentrations of secretin and iloprost were found to be additive in terms of cyclic AMP accumulation, whereas saturating concentrations of NECA and iloprost together were not. This suggests compartmentalization of G(s)-coupling components in NG108-15 cells and possible heterologous regulation of secretin receptor responsiveness at the level of adenylyl cyclase activation. 4. Cells exposed to the PKA inhibitor H-89, exhibited a time-dependent increase in secretin receptor responsiveness compared to control cells. This effect was selective since cyclic AMP responses to forskolin, iloprost and NECA were not affected by H-89 treatment. Furthermore, treatment with the protein synthesis inhibitor cycloheximide produced a time-dependent increase in secretin receptor responsiveness. 5. Together these results indicate that endogenous secretin receptor responsiveness is regulated by PKC, PKA and protein neosynthesis in NG108-15 cells.


Which patients might benefit from platelet-rich plasma?
PRP has become a popular form of regenerative medicine. This review looks at the evidence for its use in various musculoskeletal conditions.


Infantile Refsum's disease (phytanic acid storage disease): a variant of Zellweger's syndrome?
The activity of phytanic acid oxidase is low in infantile and adult Refsum's disease, and in the cerebro-hepato-renal (Zellweger's) syndrome. The plasma of patients with the infantile but not the adult form of Refsum's disease contains increased amounts of pipecolic acid and of at least two abnormal bile acids, one of which has been identified as 3 alpha, 7 alpha, 12 alpha trihydroxy-5 beta-cholestan-26-oic acid. These changes are similar to those reported in the Zellweger syndrome and indicate that there may be similarities in the metabolic defects in Zellweger's syndrome and the infantile form of Refsum's disease.


Decoding motion direction using the topography of sustained ERPs and alpha oscillations.
The present study sought to determine whether scalp electroencephalogram (EEG) signals contain decodable information about the direction of motion in random dot kinematograms (RDKs), in which the motion information is spatially distributed and mixed with random noise. Any direction of motion from 0 to 360° was possible, and observers reported the precise direction of motion at the end of a 1500-ms stimulus display. We decoded the direction of motion separately during the motion period (during which motion information was being accumulated) and the report period (during which a shift of attention was necessary to make a fine-tuned direction report). Machine learning was used to decode the precise direction of motion (within ±11.25°) from the scalp distribution of either alpha-band EEG activity or sustained event-related potentials (ERPs). We found that ERP-based decoding was above chance (1/16) during both the stimulus and the report periods, whereas alpha-based decoding was above chance only during the report period. Thus, sustained ERPs contain information about spatially distributed direction-of-motion, providing a new method for observing the accumulation of sensory information with high temporal resolution. By contrast, the scalp topography of alpha-band EEG activity appeared to mainly reflect spatially focused attentional processes rather than sensory information.


Pain: the most common psychosomatic problem.
The individual who complains of pain often has a combined emotional and organic experience. Pain is the resultant symptom of organic factors, personal and developmental phenomena, as well as social and cultural characteristics of the individual. The individuals who complain of pain often have chronic histories of difficulty and disability thus creating a difficult treatment problem. The physician who faces such individuals must attend the psychological, social, and organic entities in order to adequately manage and help rehabilitate these distressed individuals.


Efficacy of recombinant adenovirus-mediated double suicide gene therapy in human keloid fibroblasts.
The recombinant adenovirus-mediated double suicide gene CDglyTK has been widely used for gene therapy of cancer. The biological behaviour of keloids is similar to that of cancer, in that they may extend beyond the site of injury, and do not subside. There are no effective strategies available for keloid therapy. Gene therapy is gaining greater importance in the field of plastic surgery, and the CDglyTK double suicide gene/prodrug system has been receiving greater attention. To show the lethal and bystander effects of a double suicide gene in keloid fibroblasts. Bcl-2 and BAX play an important role in the apoptosis induced by the double suicide gene. Recombinant adenovirus expression CDglyTK suicide genes were constructed using the modified AdEasy system. The lethal and bystander effects were measured after 48 h using the MTT assay. The morphological changes in fibroblasts were detected by haematoxylin and eosin staining, and apoptosis was detected by the terminal dUTP nick-end labelling assay. Bcl-2 and BAX were detected by immunohistochemistry and quantitative real-time PCR. CDglyTK could be constructed easily and relatively quickly. The lethal and bystander effects of CDglyTK were marked in keloid fibroblasts. Apoptosis was one of the main processes leading to fibroblast death in keloids, and Bcl-2 and BAX played an important role in the process of apoptosis. Together, the results support the notion that recombinant adenovirus-mediated CDglyTK double suicide gene therapy is effective in destroying keloid fibroblasts and provide a sound scientific rationale for keloid trials in vivo.


Optimizing anaerobic technology by using electrochemistry and membrane module for treating pesticide wastewater: Chemical oxygen demand components and fractions distribution, membrane fouling, effluent toxicity and economic analysis.
Optimization in performance and membrane fouling of an electrochemical anaerobic membrane bioreactor (R1) for treating pesticide wastewater was investigated and compared with a conventional anaerobic membrane bioreactor (R2). The maximum COD removal efficiency of R2 was 80.1%, 80.0%, 67.4%, 61.1% with HRT of 96, 72, 48 and 24 h, which of R1 was enhanced to 84.7%, 84.3%, 82.0% and 66.3%. These results demonstrated that the optimum HRT of R1 was shortened to 48 h, which of R2 required 72 h. R1 reduced the contents of particulate and colloidal COD, and the fraction of COD converted to sludge was 5.0-8.2% lower than that of R2. The fouling rate was 0.99-1.44 kPa/d and reduced by 31.0%-38.5% compared with R2. Detoxification was enhanced by 7.8-47.7% with the assistance of bio-electrochemistry. Ultimately, ensuring similar performance, R1 achieved a 65.6% improvement in environmental benefit, a 26.3% and 38.9% reduction in unit capital and operating costs.


Adjuvant chemotherapy in 2005: standards and beyond.
The 2003 St. Gallen consensus panel divided the many available adjuvant chemotherapy (CT) regimens into those with "standard efficacy" (ACx4, CMFx6) and those with "superior efficacy" (FA(E)Cx6, CA(E)Fx6, A(E)-->CMF, TACx6, ACx4--> paclitaxel (P)x4 or docetaxel (D)x4) but also greater complexity, toxicity and cost. This paper will summarize the latest information on long-term side effects of the "superior" regimens and 5-year benefits reported in taxane trials, including those of a "new" sequential regimen, FECx3--> docetaxelx3. Rapidly expanding evidence of marked heterogeneity in the magnitude of CT benefits according to the tumour oestrogen receptor (ER) status, a claim made for many years by IBCSG investigators, will be reviewed; it will lead to the conclusion that a revolution needs to take place in the way oncologists think about the CT added value and design adjuvant clinical trials. The conclusions proposed to the 2005 St. Gallen consensus panel are that: adequately dosed anthracycline-based CT regimens remain an acceptable standard for many women; a lower threshold for using taxanes in sequence or combination with anthracyclines (A) is justified in the presence of an ER-negative or low-ER tumour status, other aggressive biologic features (such as HER-2 overexpression), fear about A-induced cardiotoxicity; no recommendation can yet be made as far as the optimal taxane-A regimen, the best taxane or the best taxane schedule.


Perinatal intermittent hypoxia alters γ-aminobutyric acid: a receptor levels in rat cerebellum.
Perinatal hypoxia commonly causes brain injury in infants, but the time course and mechanisms underlying the preferential male injury are unclear. Intermittent hypoxia disturbs cerebellar γ-aminobutyric (GABA)-A receptor profiles during the perinatal period, possibly responding to transient excitatory processes associated with GABA(A) receptors. We examined whether hypoxic insults were particularly damaging to the male rodent cerebellum during a specific developmental time window. We evaluated cerebellar injury and GABA(A) receptor profiles following 5-h intermittent hypoxia (IH: 20.8% and 10.3% ambient oxygen, switched every 240s) or room-air control in groups of male and female rat pups on postnatal d 1-2, wk 1, or wk 3. The cerebella were harvested and compared between groups. The mRNA levels of GABA(A) receptors α6, normalized to a house-keeping gene GAPDH, and assessed using real-time reverse-transcriptase PCR assays were up-regulated by IH at wk 1, more extensively in male rats, with sex influencing the regulatory time-course. In contrast, GABA(A) α6 receptor protein expression levels, assessed using Western blot assays, reached a nadir at wk 1 in both male and female rats, possibly indicating involvement of a post-transcriptional mechanism. The extent of cerebellar damage and level of apoptosis, assessed by DNA fragmentation, were greatest in the wk 3 IH-exposed group. The findings suggest partial protection for female rats against early hypoxic insult in the cerebellum, and that down-regulation of GABA(A) receptors, rather than direct neural injury assessed by DNA fragmentation may modify cerebellar function, with potential later motor and other deficits.


The evaluation of JAK inhibitors on effect and safety in alopecia areata: a systematic review and meta-analysis of 2018 patients.
JAK inhibitors treat various autoimmune diseases, but an updated systematic review in treating alopecia areata is currently lacking. Evaluate the specific efficacy and safety of JAK inhibitors in alopecia areata by systematic review and meta-analysis. Eligible studies in PubMed, Embase, Web of Science, and Clinical Trials up to May 30, 2022, were searched. We enrolled in randomized controlled trials and observational studies of applying JAK inhibitors in alopecia areata. 6 randomized controlled trials with 1455 patients exhibited SALT50 (odd ratio [OR], 5.08; 95% confidence interval [CI], 3.49-7.38), SALT90 (OR, 7.40; 95% CI, 4.34-12.67) and change in SALT score (weighted mean difference [WSD], 5.55; 95% CI, 2.60-8.50) compared to the placebo. The proportion of 26 observational studies with 563 patients of SALT5 was 0.71(95% CI, 0.65-0.78), SALT50 was 0.54(95% CI 0.46-0.63), SALT90 was 0.33(95% CI, 0.24-0.42), and SALT score (WSD, -2.18; 95% CI, -3.12 to -1.23) compared with baseline. Any adverse effects occurred in 921 of 1508 patients; a total of 30 patients discontinued the trial owing to adverse reactions. Few randomized controlled trials met the inclusion criteria and insufficiency of eligible data. JAK inhibitors are effective in alopecia areata, although associated with an increased risk.


Adolescent risk-taking, cancer risk, and life course approaches to prevention.
Adolescent risk-taking may have long-term consequences for adult cancer risk. Behaviors such as smoking and sexual activity, commonly initiated during adolescence, may result--decades later--in cancer. Life course epidemiology focuses on unique vulnerabilities at specific development periods and their importance to later development of disease. A life course epidemiological perspective that integrates social and biological risk processes can help frame our understanding how specific adult cancers develop. Moreover, life course perspectives augment traditional public health approaches to prevention by emphasizing the importance of unique windows of opportunity for prevention.


Tuberosity healing in reverse shoulder arthroplasty in traumatology: Use of an offset modular system with bone graft.
Reverse shoulder arthroplasty (RSA) has become a common treatment in displaced proximal humeral fracture (PHF) in elderly patients due to inconstant results with osteosynthesis or hemiarthroplasty. RSA allows a good anterior elevation but rotational results are more random and depend on tuberosity healing. Use of an offset modular system (OMS) on the prothesis improve tuberosity healing and functional results. This retrospective cohort analysed radiological and clinical outcomes at least one year after the use of RSA Humelock II Reversed (Fx Solutions) after a displaced PHF Neer 3 or 4 in patients over 70 years. The first criterion was tuberosity healing with or without the use of the OMS device on radiographs. The second criterion was a clinical analysis of active range of motion (ROM), anterior elevation (AAE), external and internal rotations (ER, IR), Constant, DASH, SSV, VAS scores according to tuberosity healing. We also analysed radiological and clinical complications. We analysed from November 2013 to May 2018 thirty-four RSA. Mean age was 78±5,7 years, mean follow up was 18±7,2 months and the mean tuberosity healing rate was 79%. Mean ROM were: 117±24 (AAE), 18̊±18 (ER) and L2 (IR). On the first analysis, healing tuberosity with cage was present on 24 (92%) patients versus 3 (37,5%) without (p<0,005). The second analysis showed a non-significant improvement on ER, IR, Constant, DASH and SSV. Complications found were three removal of prothesis after infection, one axillary nerve lesion, one ulnar paraesthesia and one humeral loosening. The use of the OMS cage allows a better consolidation of tuberosities in a significant way but no significant clinical effects was highlighted due to a small patient number in the study. level III, retrospective cohort.


Upregulation of adhesion molecules on leukemia targets improves the efficacy of cytotoxic T cells transduced with chimeric anti-CD19 receptor.
T lymphocytes engineered to express chimeric antigen receptors (CARs) interact directly with cell surface molecules, bypassing MHC antigen presentation dependence. We generated human anti-CD19ζ CAR cytotoxic T lymphocytes and cytokine-induced killer cells and studied their sensitivity to the expression of adhesion molecules for the killing of primary B-lineage acute lymphoblastic leukemia (B-ALL) targets. Despite a very low basal expression of surface adhesion molecules, B-ALL blasts were lysed by the anti-CD19ζ-CAR transduced effectors as expected. We next investigated the regulatory role of adhesion molecules during CAR-mediated cytolysis. The blocking of these accessory molecules strongly limited the chimeric effector's cytotoxicity. Thereafter, B-ALL cells surface adhesion molecule level expression was induced by IFN-γ or by the combined use of CD40L and IL-4 and the cells were submitted to anti-CD19ζ-CAR transduced effectors lysis. Upregulation of adhesion molecules expression by blasts potentiated their killing. The improved cytotoxicity observed was dependent on target surface expression of adhesion molecules, particularly CD54. Taken together, these results indicate that adhesion molecules, and principally CD54, are involved in the efficiency of recognition by effector chimeric ζ. These observations have potential implications for the design of immunotherapy treatment approaches for hematological malignancies and tumors based on the adoption of CAR effector cells.


Accuracy and clinical relevance of an automated, algorithm-based analysis of facial signs from selfie images of women in the United States of various ages, ancestries and phototypes: A cross-sectional observational study.
Real-life validation is necessary to ensure our artificial intelligence (AI) skin diagnostic tool is inclusive across a diverse and representative US population of various ages, ancestries and skin phototypes. To explore the relevance and accuracy of an automated, algorithm-based analysis of facial signs in representative women of different ancestries, ages and phototypes, living in the same country. In a cross-sectional study of selfie images of 1041 US women, algorithm-based analyses of seven facial signs were automatically graded by an AI-based algorithm and by 50 US dermatologists of various profiles (age, gender, ancestry, geographical location). For automated analysis and dermatologist assessment, the same referential skin atlas was used to standardize the grading scales. The average values and their variability were compared with respect to age, ancestry and phototype. For five signs, the grading obtained by the automated system were strongly correlated with dermatologists' assessments (r ≥ 0.75); cheek skin pores were moderately correlated (r = 0.63) and pigmentation signs, especially for the darkest skin tones, were weakly correlated (r = 0.40) to the dermatologist assessments. Age and ancestry had no effect on the correlations. In many cases, the automated system performed better than the dermatologist-assessed clinical grading due to 0.3-0.5 grading unit differences among the dermatologist panel that were not related to any individual characteristic (e.g. gender, age, ancestry, location). The use of phototypes, as discontinuous categorical variables, is likely a limiting factor in the assessments of grading, whether obtained by automated analysis or clinical assessment of the images. The AI-based automatic procedure is accurate and clinically relevant for analysing facial signs in a diverse and inclusive population of US women, as confirmed by a diverse panel of dermatologists, although skin tone requires further improvement.


Interactive gerontechnology for fall prevention in the elderly: a descriptive study.
to develop interactive gerontechnology for the prevention of falls in the elderly at home. an exploratory and descriptive study that consisted of gerontechnology development and evaluation by experts and the target audience. For evaluation, researchers used the Agreement Index (AI), considering values greater than 80%. the three-dimensional virtual scale model was elaborated through the SketchUp program, with the distribution of rooms and floors, constituting Prototype 1 (P1). Fifty-four judges evaluated the P1, and all presented agreement above the established, with a minimum AI of 88% and a maximum of 100%, producing Prototype 2 (P2). Thirty elderly participants from a philanthropic institution evaluated Prototype 2. On all items, AI ranged from 83% a 100%, resulting in the final version. the product of this research reveals itself as an innovative and scientifically based tool aimed at preventing falls in the elderly.


Quality of life in children with sickle cell hemoglobinopathy.
To identify specific domains and traits that are most affected in patients with sickle cell anemia and traits with respect to normal children. Children attending the regional hemoglobinopathy center at IGMC, Nagpur in age group of 8-14 years were assessed. Of 52 children studied, 25 had sickle cell anemia (SCA), 12 had sickle cell trait (SCT) and 15 wre normal control. The (quality of life (QOL) was assessed using multidimensional interview based questionnaire. All domains, physical, psychosocial, cognitive and morbidity were affected. In SCA playing and mobility were most affected. There was feeling of sadness or disinterest and lack of support from teachers. The school attendance, vocational achievement perception, entertainment and participation in cultural activities were also affected. The intensity of weakness and pain was greater in SCA children who left that they were affected by a major illness. The unusual finding was that the SCT children also showed affection of all domains as compared to normal children, which was perhaps due to the stigma of the disease. QOL is affected in children with sickle cell disease (SCD) and to a lesser extent in SCT. Interventions to improve QOL should target the affected items. Improving awareness of the disease and its manifestation will help to alleviate the psychosocial affliction of children with SCT.


Differential modulation of the lipid metabolism as a model for cellular resistance to fumonisin B1-induced cytotoxic effects in vitro.
Differential sensitivity of primary hepatocytes and Chang cells to the cancer promoter fumonisin B1 (FB1)-induced cytotoxic effects were investigated in relation to changes in membrane lipid distribution. In contrast to primary hepatocytes, Chang cells were resistant to FB1-induced cytotoxic effects. This was associated with a high cholesterol (Chol) and sphingomyelin (SM) and low phosphatidylcholine (PC) content, resulting in a significant (P<0.05) decrease in phosphatidylethanolamine (PE)/PC ratio, increased Chol/total phosphoglyceride (TPG) ratios and low total polyunsaturated fatty acids (PUFA) content in PC and PE, suggesting a more rigid membrane structure. High levels of C18:1 and reduced polyunsaturated fatty acid (PUFA) levels are likely to provide selective resistance to FB1-induced oxidative stress. FB1-associated lipid changes included decreases in SM and Chol, increases in sphinganine (Sa) and PE with the increases in key saturated, monounsaturated, and PUFAs in PE as key role players in the differential responses to FB1-induced cell growth responses in cells.


Prostaglandin E2, a postulated mediator of neurovascular coupling, at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles.
There is considerable controversy regarding the vasoactive action of prostaglandin E2 (PGE2). On the one hand, indirect evidence implicates that astrocytic release of PGE2 contributes to neurovascular coupling responses mediating functional hyperemia in the brain. On the other hand, overproduction of PGE2 was also reported to contribute to cerebral vasospasm associated with subarachnoid hemorrhage. The present study was conducted to resolve this controversy by determining the direct vasoactive effects of PGE2 in resistance-sized human cerebral parenchymal arterioles. To achieve this goal PGE2-induced isotonic vasomotor responses were assessed in parenchymal arterioles isolated from fronto-temporo-parietal cortical tissues surgically removed from patients and expression of PGE2 receptors were examined. In functionally intact parenchymal arterioles lower concentrations of PGE2 (from 10-8 to 10-6 mol/l) caused significant, endothelium-independent vasorelaxation, which was inhibited by the EP4 receptor blocker BGC201531. In contrast, higher concentrations of PGE2 evoked significant EP1-dependent vasoconstriction, which could not be reversed by the EP4 receptor agonist CAY10598. We also confirmed previous observations that PGE2 primarily evokes constriction in intracerebral arterioles isolated from R. norvegicus. Importantly, vascular mRNA and protein expression of vasodilator EP4 receptors was significantly higher than that of vasoconstrictor EP1 receptors in human cerebral arterioles. PGE2 at low concentrations dilates whereas at higher concentrations constricts human cerebral parenchymal arterioles. This bimodal vasomotor response is consistent with both the proposed vasodilator role of PGE2 during functional hyperemia and its putative role in cerebral vasospasm associated with subarachnoid hemorrhage in human patients.


The three-dimensional effects of orthodontic treatment on the facial soft tissues--a preliminary study.
To examine the three-dimensional effects of extraction and non-extraction orthodontic treatment on the facial soft tissues. Department of Orthodontics, Royal London Hospital. Longitudinal study of two prospective cohorts of patients who were attending for orthodontic treatment. METHOD 12 patients were included in each group, in accordance with the selection criteria. Three-dimensional optical surface scans of these patients were obtained in the one month prior to having fixed appliances placed and this was repeated at the end of treatment. The average face of the non-extraction patients was of greater general dimensions than the extraction average, both at the start and the end of treatment. During the fixed appliance treatment, the vermilion of the upper lip became more protrusive to a similar extent in both groups in relation to the reference plane. The lower lip vermilion and the philtrum showed no change for either group over the treatment time. The labiomental fold area showed a slightly greater forward movement in the extraction group with treatment. Three-dimensional optical surface scanning allows data from the whole of the face to be assessed, as opposed to the lateral profile view used in the majority of the studies to date. The effects of the two types of treatment on the facial soft tissues were very similar, indicating that orthodontic treatment involving the extraction of teeth does not have a detrimental effect on the face.


Reference Intervals for Bone Histomorphometric Measurements Based on Data from Healthy Premenopausal Women.
This study has established the normal reference intervals for bone histomorphometric measurements derived from healthy premenopausal women, which is rarely available. We presented the static and dynamic bone histomorphometric data from trans-iliac bone biopsies in 62 healthy premenopausal women (19 blacks and 43 whites, ages 20-53 years). There were no significant differences in age and BMI between black and white women. Since there was no significant difference in bone remodeling between the two ethnic groups, we pooled data of all 62 premenopausal women to establish normal reference intervals for bone histomorphometry. The results provide normal reference intervals for both static and dynamic histomorphometric variables in cancellous and cortical bone of the ilium. None of the bone remodeling-related variables correlated with age or BMI. This study provides reference intervals for bone histomorphometric measurements in both cancellous and cortical bone of the ilium, which would be helpful in the evaluation of bone health in women.


Relationship Between Rhinitis, Nasal Obstruction and Hypothyroidism: A Follow Up Study with Pre-post Treatment with Levothyroxine.
Hypothyroidism is the most common form of thyroid disorder in India, while, Rhinitis and Nasal obstruction are frequent complaints treated on regular basis in ENT OPD. Studies show that there is relationship between Rhinitis and Nasal obstruction with hypothyroidism. To assess the improvement in symptoms associated with Rhinitis and nasal obstruction in patients with hypothyroidism after treating with levothyroxine. 50 patients presenting in ENT OPD with rhinitis and nasal obstruction and diagnosed with hypothyroidism were selected. Complete history was taken and clinical examination was performed, Nasal Obstruction Symptom Evaluation Score, (NOSE) and Peak nasal inspiratory flow rate (PNIF) were noted. Biochemically proven hypothyroid patients were treated with adequate dosage of Levothyroxine. The patients were followed up and the above-mentioned tests were repeated at regular intervals (1 month and 3 month), Changes in these readings were recorded and maintained. Significant difference was found in TSH level, NOSE questionnaire, and PNIF reading in patients with hypothyroidism after treatment with levothyroxine (P value < 0.001). This was most commonly noted to occur in young and middle-aged population of age 15 years to 50 years (88%). In our study - An attempt was made to correlate the symptomatology with hypothyroidism. Treatment with levothyroxine in patients with rhinitis, nasal obstruction and biochemically proven hypothyroidism was found to be effective in improvement of symptoms. It was found that there is significant association between hypothyroid status and rhinitis with nasal obstruction.


Purification and characterization of a cortical secretory vesicle membrane fraction.
A membrane fraction has been prepared by sucrose density gradient fractionation of purified cortical secretory vesicles from the eggs of the sea urchin Strongylocentrotus purpuratus. The purified cortical vesicle membrane fraction has a phospholipid to protein ratio of 1.76 and exhibits a morphology typical of biological membranes as seen by electron microscopy. The protein composition of the purified membranes was analyzed by SDS-polyacrylamide gel electrophoresis and shown to be distinct from that of eggs, cell surface complex, cortical vesicles, fertilization product, and yolk platelets. Alkaline extraction (pH 11.0) of peripheral membrane proteins increased the phospholipid to protein ratio to 2.55 and removed several polypeptides. Immunoblot analysis of the isolated cortical vesicle membrane fraction revealed low levels of contamination with two major cortical vesicle content proteins. Fractions enriched in egg plasma membranes and yolk platelet membranes also have been isolated and compared with the cortical vesicle membranes by SDS-polyacrylamide gel electrophoresis. The protein compositions of the three membrane fractions were found to contain very little overlap, indicating that the cortical vesicle membrane preparation is relatively free of contamination from these likely noncortical vesicle sources of membrane. Both the plasma membrane and cortical vesicle membrane samples were found by immunoblotting to contain actin.


Dietary exposure of the Qatari population to food mycotoxins and reflections on the regulation limits.
The article estimates the exposure of the population of Qatar to aflatoxins, fumonisins and ochratoxins, measured in food samples collected from the markets of Doha. The mycotoxin extractions were performed using the "Quick Easy Cheap Effective Rugged Safe" Method (QuEChERS) and the extract measured with LC-MS/MS. High contamination with aflatoxins was detected in Nuts and Spices (e.g. 534.15 ng/g and 371.6 ng/g respectively). The estimated daily intake (EDI) level was estimated using statistical data on average Qatari population. Additionally, the probability to exceed TDI was calculated for fumonisins and ochratoxins. The results indicate high exposure to aflatoxins (with alarming values of margin of exposure, i.e. MoE). The article points to the necessity of a regular assessment and reevaluation of the concentration limits allowed in food products accounting for statistics on the population (i.e. food consumption), economic growth of the country, and monitoring of mycotoxin contamination of food as much as technological, financial and human resources of a country allows.


Synapses on dendritic shafts exhibit a perforated postsynaptic density.
Synapses on dendritic shafts were examined in electron micrographs of serial sections obtained from the molecular layer of the rat dentate gyrus. Some of these synapses have been found to exhibit profiles of a discontinuous postsynaptic density (PSD). PSD reconstructions from serial sections were performed in a plane perpendicular to that of the sections. The results obtained indicate that profiles of discontinuous PSDs observed in random sections of dendritic shaft synapses are generated by sectioning of PSD plates that contain 1-3 holes or perforations. Earlier serial section studies of osmicated material have demonstrated that a proportion of axospinous synapses also exhibit a perforated PSD. It appears, therefore, that the presence of PSD perforations is a general phenomenon shared by subpopulations of different types of synapses, both those involving dendritic shafts and those involving dendritic spines.


Drug targeting of airway surface liquid: a pharmacological MRI approach.
Pharmacological MRI at 4.7 T was used to investigate the secretory response to Sylvestris pine oil stimuli in the rat airways, with the aim of developing an in vivo model in a small laboratory animal. The availability of such a model would greatly facilitate the drug discovery process using compounds active on airway surface liquid (ASL) production, and would make it possible to obtain information on chemoreceptoral mechanisms and to test the effects of environmental substances on the airways. T1- and T2-weighted images were acquired in the trachea and larynx before and at various times after exposure to pine oil. Several post-processing procedures were tested in order to improve the visibility of the secretory response and to measure the enhancement of the signal intensity of ASL. A semiautomatic application software was written to localize and to measure the volume involved in the secretory response to a compound administration. A significant effect of the pine oil administration on the secretory response was founded in trachea (p<0.01) and in the salivary glands (p<0.01). 3D reconstructions of MRI data and virtual endoscopy permitted a quick visualization of tracheal morphology and localization of the greatest response to stimulus. The study demonstrated that, despite technical problems due to the air/tissue interface and to the small dimensions of the experimental animals, the secretory response can be evaluated and the pharmacological MRI (phMRI) of the rat airways is feasible. The potential and the limitations of phMRI investigation in drug targeting of ASL are discussed.


Existence of different types of senile plaques between brain and spinal cord of TgCRND8 mice.
Conflicting findings exist regarding the formation of diffuse and dense-core β-amyloid (Aβ) plaques in Alzheimer's disease (AD). In the present study, we characterized Aβ plaque types in the brain and spinal cord of TgCRND8 mice, which express a transgene incorporating both the Indiana mutation (V717F) and the Swedish mutations (K670N/M671L) in the human amyloid-β protein precursor (APP) gene. By combining immunohistochemistry and thioflavin S staining, we were able to define dense-core and diffuse plaques in neocortex of the brain and spinal cord of 9 week-, 5 month-, 10 month- and 20-month-old TgCRND8 mice. The senile plaques in the neocortex were predominantly dense-core plaques, even in the youngest mice. However, diffuse plaques were instead detected in spinal cord of the mice, regardless of age. Our results that relative predominance of dense-core plaques in the neocortex and diffuse plaques in the spinal cord of TgCNRD8 mice of all disease durations argue against the notion that diffuse plaques may represent an early stage in the evolution of dense-core plaques. Furthermore, we also found that the ratio of Aβ42/Aβ40 of the brain was much higher than that of the spinal cord by Aβ ELISA assay. Our findings strongly indicate that diffuse and dense-core plaques may form via independent processes in AD and Aβ42 is more prone to form dense-core plaques than is Aβ40.


Modulating multi-functional ERK complexes by covalent targeting of a recruitment site in vivo.
Recently, the targeting of ERK with ATP-competitive inhibitors has emerged as a potential clinical strategy to overcome acquired resistance to BRAF and MEK inhibitor combination therapies. In this study, we investigate an alternative strategy of targeting the D-recruitment site (DRS) of ERK. The DRS is a conserved region that lies distal to the active site and mediates ERK-protein interactions. We demonstrate that the small molecule BI-78D3 binds to the DRS of ERK2 and forms a covalent adduct with a conserved cysteine residue (C159) within the pocket and disrupts signaling in vivo. BI-78D3 does not covalently modify p38MAPK, JNK or ERK5. BI-78D3 promotes apoptosis in BRAF inhibitor-naive and resistant melanoma cells containing a BRAF V600E mutation. These studies provide the basis for designing modulators of protein-protein interactions involving ERK, with the potential to impact ERK signaling dynamics and to induce cell cycle arrest and apoptosis in ERK-dependent cancers.


Polymerization characteristics of light- and auto-curing resins for individual splints.
The aim of this in vitro study was to assess different resins for occlusal splints regarding a number of polymerization characteristics. One autopolymerizing resin (Palapress) and four light-curing resins (Acrylight, Primosplint, Triad TranSheet Colorless and Pink) were tested for flexural strength, modulus of elasticity, water sorption, volumetric shrinkage, and conversion of double bonds. These resins were polymerized for 10 and 15 min in a light oven at frequencies between 320 and 400 nm or 400 and 500 nm, respectively. Data were treated statistically by ANOVA and by Scheffé test. Concerning flexural strength and modulus of elasticity, Triad TranSheet Colorless showed significantly greater values than Primosplint and Palapress (p<0.05). The light curing resins Acrylight and Primosplint featured significantly higher water sorption when cured for 10 min compared to all other resins (p<0.05). Acrylight displayed significantly higher volumetric shrinkage and a higher quantity of remaining double bonds compared to all other light-curing resins (p<0.05). Primosplint, Triad TranSheet Colorless and Pink showed significantly lower shrinkage values than autopolymerizing Palapress (p<0.05). For all light curing resins, polishing of the samples resulted in a significantly lower quantity of remaining double bonds (p<0.05) compared to unpolished samples. With respect to the polymerization properties evaluated, the light-curing resins reached similar material properties to the autopolymerizing resin or even surpassed them. Light-curing resins seem to be suitable for the fabrication of occlusal splints and can been seen as an alternative to autopolymerizing polymethylmethacrylates.


Alcohol use and abuse in the frail, homebound elderly: a clinical analysis of 103 persons.
We studied alcohol use and abuse in 103 frail, homebound elderly individuals cared for in a long-term home health care program from July 1991 to February 1992. Their average age was 80.63 years. Eighty-four percent were abstinent at the time of the study, including 25 (25%) past heavy drinkers. Two persons were current heavy drinkers and 14 continued to drink socially. Previous alcohol use or abuse was associated with a history of smoking, cardiovascular morbidity, social isolation, and anxiety or agitation. Current social drinking was associated with sedative-hypnotic use as well as smoking. Twenty-three of 25 past heavy drinkers remained sober on our programs without the use of formal alcohol treatment. Abstinence is known to increase with age, appears to be fostered by the homebound setting, is feasible for homebound elderly persons and is often accepted.


Compulsive respiratory stereotypies in children with autistic features: polygraphic recording and treatment with fenfluramine.
Syncopes due to compulsive respiratory stereotypies were studied in eight patients with autistic features. Most had been referred for episodes thought to be intractable epileptic seizures. Polygraphic recording showed two types of syncope, one induced by prolonged apnea and the other by a prolonged Valsalva maneuver. Fenfluramine, 1.5-3 mg/kg per day, was given in an open trial. In four of five cases with frequent Valsalva maneuvers, respiratory stereotypies and syncopes were suppressed for 2-18 months. Patients with periodic apneas were more severely retarded and had less clear benefit. Side effects consisted of dose-dependent sedation and mild weight loss which stabilized without interrupting treatment. We suggest that these syncopes are volitional and may be associated with pleasant sensations. A double-blind placebo-controlled trial of fenfluramine seems warranted in such patients.


Integrating hyperspectral imaging with machine learning techniques for the high-resolution mapping of soil nitrogen fractions in soil profiles.
Soil nitrogen (N) plays a central role in soil quality and biogeochemical cycles. However, little is known about the distribution and spatial variability of the different fractions of soil N within entire soil profiles. This study aimed to investigate the potential of laboratory-based hyperspectral imaging (HSI) spectroscopy to retrieve and map total N (TN), available N (AvailN), ammonium N (NH4-N), nitrate N (NO3-N), and microbial biomass N (MBN) in soil profiles at a high resolution. HSI images of eleven intact soil profiles of 100 ± 5 cm depth from three typical soil types were recorded. A variety of nonlinear machine learning techniques, such as artificial neural networks (ANN), cubist regression tree (Cubist), k-nearest neighbour (KNN), support vector machine regression (SVMR) and extreme gradient boosting (XGBoost), were compared with a partial least squares regression (PLSR) to determine the most suitable model for the prediction of the various soil N fractions. Overall, the results showed that nonlinear techniques performed better than PLSR in most cases, with a high coefficient of determination (R2) and low root mean square error (RMSE). Among the models, SVMR was found to be superior to the other tested models for TN (R2P = 0.94, RMSEP = 0.17 g kg-1), AvailN (R2P = 0.94, RMSEP = 13.35 mg kg-1), NO3-N (R2P = 0.82, RMSEP = 7.31 mg kg-1), and NH4-N (R2P = 0.70, RMSEP = 1.51 mg kg-1) based on independent validation, whereas MBN (R2P = 0.63, RMSEP = 6.62 mg kg-1) was predicted best by KNN. In addition, SVMR required less computational time and was less sensitive to spectral noise. It can therefore be concluded that HSI spectroscopy combined with SVMR is suitable for the high-resolution mapping of various soil N fractions in soil profiles.


Protein kinase A-dependent coupling of mouse prostacyclin receptors to Gi is cell-type dependent.
The ability of the prostacyclin (IP) receptor agonist cicaprost to activate Gs-, Gq/11- and Gi-mediated cell signalling pathways has been examined in Chinese hamster ovary (CHO) cells and human embryonic kidney 293 (HEK 293) cells expressing the cloned human (hIP) or mouse (mIP) prostacyclin receptor, and compared with data from NG108-15 and SK-N-SH cells that endogenously express rat/mouse and human IP receptors, respectively. Cicaprost stimulated [3H]cyclic AMP production with EC50 values of 1.5-22 nM, and stimulated [3H]inositol phosphate production (EC50 values 49-457 nM) in all but the SK-N-SH cells. Cicaprost failed to inhibit forskolin-stimulated [3H]cyclic AMP production in any of these cell lines. Therefore, although both human and mouse IP receptors couple to Gs and Gq/11-mediated signalling pathways in a cell type-dependent manner, we could find no evidence for IP receptor coupling to Gi.


Creutzfeldt-Jakob Disease Presenting with Abducens Nerve Palsy.
Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder with characteristic clinical and diagnostic features. We describe the unusual case of an elderly man who presented to our ophthalmology clinic with horizontal diplopia secondary to an abducens nerve (cranial nerve six) palsy and was subsequently diagnosed with CJD. Given the non-treatable nature of this disease, ophthalmologic management goals included symptomatic relief and quality of life improvement. Precautions related to the ophthalmologic management of CJD have also been addressed in this case report.


Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition.
Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652.