Factors associated with prolonged wound drainage after hemiarthroplasty for hip fractures in elderly.
The aim of this study was to determine the incidence of prolonged wound drainage (PWD) and the amount of drainage fluid after hip hemiarthroplasty (HA) and to investigate the risk factors for the development of PWD associated with the patient, fracture and surgical treatment. Data from 313 patients who underwent HA were prospectively analysed. The mean drainage time and drainage amount of patients with PWD were calculated. Patient demographic data, pre-operative ASA scores and anticoagulation status, presence of diabetes, fracture type, surgical approach, femoral stem type, cable usage, amount of drain output, blood transfusion quantity, time from injury to surgery, time from surgery to discharge and patient blood tests were investigated. The incidence of PWD after HA was 8.9% (28 patients). The mean drainage time in patients with PWD was 4.9 ± 1.85 (3-9) days, and the mean collected total fluid volume was 51.1 ± 26.9 (21-132) mL. PWD was more commonly observed in the lateral approach group (p < 0.001) and morbidly obese patients (p < 0.001). In the PWD group, the mean post-operative first-day haemoglobin value was lower (p < 0.001), more blood transfusions were required (p < 0.001) and the amount of drainage output from the closed suction drain (CSD) was higher (p < 0.001). The duration of hospitalization was longer in patients with PWD (p < 0.001). Lateral approach, morbid obesity and increased drainage output were found to be associated with PWD in logistic regression analysis. Lateral approach, morbid obesity and increased drainage output were found to be risk factors for the occurrence of PWD.


Knowledge and Attitudes of Men in Bahrain Toward Prostate Cancer.
Bahrain has one of the highest rates of prostate cancer in the Middle East, when compared to neighboring countries. Therefore, a seminal study was undertaken, investigating the knowledge and attitudes of Arabic men over 50 years and older, who are in the highest risk group for prostate cancer. A secondary objective was to apply inter-professional student learning of research though the inclusion of medical and nursing students in the research team. A descriptive research design with data collection through a researcher-administered questionnaire. Study participants included 74 men, predominantly of Arabic origin. Whereas the results of this study are generally reflective of the international literature, the study also provides some new and interesting insights into the perspectives of Arabic men. The findings highlight the importance of a culturally sensitive, health awareness programme for men's health and prostate cancer in Bahrain. The study supports the important role of nurses in men's health promotion and disease prevention. An expansion in community nursing roles could facilitate the development of nursing specialist roles in the area of prostate disease prevention. An enhancement of undergraduate nursing student research learning occurs through active engagement with researchers in research projects, where students participate in preparing for research ethics approval, data collection, data analysis and writing for publication. Inter-professional learning is a very valuable experience in lowering traditional barriers between medicine and nursing.


[Pathogenesis and treatment of migraine (neuroendocrinologic aspect)].
In 24 women with simple and ophthalamic migraine the authors employed neuropeptide 8-arginine-vasopressin under control of plasma levels of ACTH and cortisol and rheoencephalographic parameters. The authors observed a marked clinical effect, normalization of hypothalamoadrenal function and improvement in the cerebral hemodynamics.


The Role of Anterior Thalamic Deep Brain Stimulation as an Alternative Therapy in Patients with Previously Failed Vagus Nerve Stimulation for Refractory Epilepsy.
Deep brain stimulation (DBS) has provided new treatment options for refractory epilepsy; however, treatment outcomes of DBS in refractory epilepsy patients previously treated with vagus nerve stimulation (VNS) have not been clarified. Herein, treatment outcomes of DBS of the anterior nucleus of the thalamus (ANT-DBS) in patients who had previously experienced VNS failure are reported. Seven patients who had previously experienced VNS failure underwent ANT-DBS device implantation. VNS was turned off before DBS device implantation. Monthly seizure counts starting from baseline to 12-18 months after DBS were analyzed. Five (71.3%) of the 7 patients experienced a >50% reduction of seizure counts after DBS; 1 responder reached a seizure-free status after DBS therapy. Of the 2 nonresponders, 1 subject showed improvement in seizure strength and duration, which lessened the impact of the seizures on the patient's quality of life. This is the first study in which favorable outcomes of ANT-DBS surgery were observed in individual patients with refractory epilepsy who had not responded to prior VNS. Further studies with a larger number of subjects and longer follow-up period are needed to confirm the feasibility of ANT-DBS in patients who have previously experienced VNS failure.


Steam sterilization and internal count sheets: assessing the potential for cytotoxicity.
Count sheets, when placed in contact with surgical instruments during steam sterilization, can transfer ink to the instruments. To explore whether this poses a safety concern, stainless steel instruments were placed on top of completely inked paper and subjected to steam sterilization, extracted, and tested for cytotoxicity. Preprinted labels were examined in a similar fashion. Extracts from stainless steel devices exposed to ink, toner, or labels showed no significant cytotoxic response, although the ink residue on the devices after steam sterilization is difficult to remove and detrimental to the instrument. Placing a barrier between the count sheet and the devices facilitates reuse of the instruments.


[Phase-frequency characteristics of afferent activity and depolarization of primary afferents during passive displacement of the hindlimb of the cat].
Frequency response characteristics of afferent activity and primary afferent depolarization (PAD) evoked by this activity were investigated in decerebrated cats during passive movement of hindlimb in ankle joint. At the frequencies of 0.2-1.7 Hz the lead of the level of depolarization was determined by the value of phase changes of afferent activity. Above 1.7 Hz a phase lag of the level of depolarization was observed. This lag was caused by the dynamic properties of PAD generation system.


Collapse of Viabahn stent-graft secondary to rheolytic thrombectomy: a rare complication of the AngioJet device.
There is increased use of percutaneous mechanical thrombectomy for treatment of occluded dialysis access. The AngioJet rheolytic thrombectomy device is one such device available. Reports have shown safety and efficacy of these techniques with relatively few complications. We describe a case report of a collapsed Viabahn endoprosthesis in an arteriovenous fistula during treatment with an AngioJet device.


Alexithymia and chronic diseases: the state of the art.
Alexithymia is a disorder of the regulatory mechanism of the emotion elaboration; it is characterized by difficulties in differentiating and describing feelings. Research indicates that alexithymia can be considered as a possible risk factor for a variety of medical conditions as it may increase susceptibility to disease development. The interest in alexithymia has increased considerably over the past decade. The present review was aimed at providing a state of the art of recent research on alexithymia in patients with chronic diseases. We reviewed most relevant papers on alexithymia and its relationships with chronic diseases. Numerous investigations have been conducted in the fields of clinical research, cognitive psychology, neurobiology, and psycho-neuro endocrinology. Some researchers link alexithymia with insecure parental attachment and adverse childhood experiences. Alexithymia seems to be associated with different pathologies and it seems to be an element of co-morbidity associated with an increased risk of mortality. Moreover has been underlined the role of alexithymia in influencing illness behaviours and as a consequence it influences clinical and patients reported outcomes. Several processes or mechanisms by which alexithymia may influence health and illness have been explored. Present research findings on alexithymia suggest important implications for the management of chronic diseases.


Centriolar distal appendages activate the centrosome-PIDDosome-p53 signalling axis via ANKRD26.
Centrosome amplification results into genetic instability and predisposes cells to neoplastic transformation. Supernumerary centrosomes trigger p53 stabilization dependent on the PIDDosome (a multiprotein complex composed by PIDD1, RAIDD and Caspase-2), whose activation results in cleavage of p53's key inhibitor, MDM2. Here, we demonstrate that PIDD1 is recruited to mature centrosomes by the centriolar distal appendage protein ANKRD26. PIDDosome-dependent Caspase-2 activation requires not only PIDD1 centrosomal localization, but also its autoproteolysis. Following cytokinesis failure, supernumerary centrosomes form clusters, which appear to be necessary for PIDDosome activation. In addition, in the context of DNA damage, activation of the complex results from a p53-dependent elevation of PIDD1 levels independently of centrosome amplification. We propose that PIDDosome activation can in both cases be promoted by an ANKRD26-dependent local increase in PIDD1 concentration close to the centrosome. Collectively, these findings provide a paradigm for how centrosomes can contribute to cell fate determination by igniting a signalling cascade.


Comparing the Effects of Mobile-Based Education and Booklet-Based Education on Iranian Mothers' Perception on Antibiotics: A Quasi-Experimental Study.
The aim of this study was to investigate the effect of mobile-based education in comparison with booklet-based education on mothers' perception on antibiotics. This quasi-experimental study was performed on 160 mothers of children aged 1 to 6 years (80 in the experimental group and 80 in the control group) who referred to the urban community health centers in Iran. Both groups were taught about the proper use of antibiotics. The experimental group was taught using a mobile application and the control group was taught using a booklet. The Parental Perception on Antibiotics (PAPA) scale was used to collect data at the beginning and two to four weeks after the educational intervention. The data were analyzed using SPSS version 19. The results showed that 91.9% of mothers used the knowledge of nurses or other health care providers and 86.3% used their previous experience as the source of information about antibiotics. Also, mothers' perceptions about antibiotics in the subscales of knowledge and beliefs, behaviors, adherence and awareness about antibiotics resistance in the experimental group improved significantly compared to the control group (p < 0.05). Mobile-based education was more effective in improving mothers' perception on antibiotics than booklet-based education. Health care providers can use mobile-based educational method for different groups of society to promote health in various fields.


[Percutaneously implanted permanent vena cava filter: follow-up of 117 consecutive patients].
Retrospective review of indication, insertion technique and problems, complications and effectiveness of 5 different filter designs implanted during a period of 5 years. MATERIALS, PATIENTS AND METHODS: We inserted one Filcard-filter, 4 Antheor DC 3 perm.-filters, 17 Trigon/Cardial-filters, 28 Titan-Greenfield-filters (modified hook) and 65 LGM 30 D/U Vena Tech-filters via a femoral (n = 111) or a jugular (n = 4) approach in 115 of 117 patients. Indication was acute deep thrombosis of the iliac or femoral vein with and without pulmonary embolism (PE) in patients with contraindication to, or unsuccessful, anticoagulation therapy or lysis. Follow-up was possible in 92 patients. In two of 117 patients the filter could not be implanted due to dissection of the left iliac vein. In the other 115 patients we achieved an orthograde position of the filter in 78%, 22% of the filters tilted more than 15 zero and 25% had been opened incompletely. We noticed late filter dislocation in 4 cases, deep vein thrombosis of the access vein in two cases, one haematoma of the insertion site, three asymptomatic perforations of filter struts through the caval wall, 14 filter induced thromboses of the vena cava (15.2%) and 13 recurrent PE (14.1%), fatal in 5 cases (5.4%). The implantation of vena caval filters as a prophylaxis of PE is easy and of low risk. Because of the relatively high rate of recurrent PE (14.1%) in our series after implantation, the effectiveness must be judged critically.


Exercise right ventricular ejection fraction predicts right ventricular contractile reserve.
Right ventricular (RV) contractile reserve shows promise as an indicator of occult RV dysfunction in pulmonary vascular disease. We investigated which measure of RV contractile reserve during exercise best predicts occult RV dysfunction and clinical outcomes. We prospectively studied RV contractile reserve in 35 human subjects referred for right heart catheterization for known or suspected pulmonary hypertension. All underwent cardiac magnetic resonance imaging, echocardiography, and supine invasive cardiopulmonary exercise testing with concomitant RV pressure-volume catheterization. Event-free survival was prospectively adjudicated from time of right heart catheterization for a 4-year follow-up period. RV contractile reserve during exercise, as measured by a positive change in end-systolic elastance (Ees) during exertion, was associated with elevation in pulmonary pressures but preservation of RV volumes. Lack of RV reserve, on the other hand, was tightly coupled with acute RV dilation during exertion (R2 = 0.76, p< 0.001). RV Ees and dilation changes each predicted resting RV-PA dysfunction. RV ejection fraction during exercise, which captured exertional changes in both RV Ees and RV dilation, proved to be a robust surrogate for RV contractile reserve. Reduced exercise RV ejection fraction best predicted occult RV dysfunction among a variety of resting and exercise RV measures, and was also associated with clinical worsening. RV ejection fraction during exercise, as an index of RV contractile reserve, allows for excellent identification of occult RV dysfunction, more so than resting measures of RV function, and may predict clinical outcomes as well.


Interaction of caffeine-, IP3- and vanadate-sensitive Ca2+ pools in acinar cells of the exocrine pancreas.
Previous studies have shown the existence of functionally distinguishable inositol 1,4,5-trisphosphate- (IP3) sensitive and IP3-insensitive nonmitochondrial intracellular Ca2+ pools in acinar cells of the exocrine pancreas. For further characterization of Ca2+ pools, endoplasmic reticulum (ER) membrane vesicles were separated by Percoll gradient centrifugation which allowed us to distinguish five discrete fractions designated P1 to P5 from the top to the bottom of the gradient. Measuring Ca2+ uptake and Ca2+ release with a Ca2+ electrode, we could differentiate three nonmitochondrial intracellular Ca2+ pools: (i) an IP3-sensitive Ca2+ pool (IsCaP), vanadate- and caffeine-insensitive, (ii) a caffeine-sensitive Ca2+ pool (CasCaP), vanadate- and IP3-insensitive, and (iii) a vanadate-sensitive Ca2+ pool (VasCaP), neither IP3- nor caffeine-sensitive, into which Ca2+ uptake is mediated via a Ca2+ ATPase sensitive to vanadate at 10(-4) mol/liter. A fourth Ca2+ pool is neither IP3- nor caffeine- or vanadate-sensitive. Percoll fraction P1 contained essentially the IsCaP, CasCaP and VasCaP and was mainly used for studies on Ca2+ uptake and Ca2+ release. When membrane vesicles were incubated in the presence of caffeine (2 x 10(-2) mol/liter), Ca2+ uptake up to the steady state [Ca2+] did not appear to be altered as compared to the control Ca2+ uptake. However, in control vesicles spontaneous Ca2+ release occurred after the steady state had been reached, whereas caffeine-pretreated vesicles did not spontaneously release Ca2+. Addition of IP3 at steady state [Ca2+] induced similar Ca2+ release followed by Ca2+ reuptake in both caffeine-pretreated and control vesicles. However, when caffeine was acutely added at steady state, Ca2+ was released from all Ca2+ pools including the IsCaP. Following Ca2+ reuptake after IP3 had been added, a second addition of IP3 to control vesicles induced further but smaller Ca2+ release, and a third addition resulted in a steady Ca2+ efflux by which all Ca2+ that had been taken up was released. This steady Ca2+ release started at a Ca2+ concentration between 5.5-8 x 10(-7) mol/liter and could also be induced by the IP3 analogue inositol 1,4,5-trisphosphorothioate (IPS3) or by addition of Ca2+ itself. Ruthenium red (10(-5) mol/liter) inhibited both caffeine-induced as well as Ca2(+)-induced but not IP3-induced Ca2+ release. Heparin (100 micrograms/ml) inhibited IP3- but not caffeine-induced Ca2+ release. The data indicate the presence of at least three separate Ca2+ pools in pancreatic acinar cells: the IsCaP, CasCaP and VasCaP. During Ca2+ uptake these Ca2+ pools appear to be separate.(ABSTRACT TRUNCATED AT 400 WORDS)


Observations, in vitro, on N-nitrosation by intracellular extracts of some microorganisms isolated from palm wine.
Soluble fractions of sonicates derived from cell suspensions of some bacteria and yeasts, which contaminate palm sap, enhanced nitrosamine formation when each fraction was incubated, under sterile conditions, at a pH of 7.0 +/- 0.2, with either diphenylamine, dimethylamine or diethylamine and sodium nitrite and glucose as substrates. The intrinsic factor in the extracts, which was responsible for the N-nitrosation reactions, was heat labile and might be an enzyme; a so-called 'N-nitrosatase'.


Randomized controlled trial of once-daily tenofovir, lamivudine, and lopinavir/ritonavir versus remaining on the same regimen in virologically suppressed HIV-infected patients on their first PI-containing HAART regimen.
To assess the effects of switching to once-daily (QD) lopinavir/ritonavir (LPV/r)-based combination therapy in HIV-infected patients who are virologically suppressed (HIV viral load <50 copies/mL) on their first protease inhibitor (PI)-containing regimen. In this 48-week, prospective, open-label, randomized study, patients were either switched to once-daily LPV/r, tenofovir (TDF), and lamivudine (3TC) (QD arm) or remained on their existing regimen (control arm). The primary endpoint of the study was the proportion of patients maintaining virologic suppression following 48 weeks of treatment. Fifty and 22 patients were randomized to the QD and control arms, respectively. At week 48, there was no significant difference in virological suppression between the QD and control arms using intent-to-treat (missing = failure) analysis (p = .44). There was no significant difference in discontinuation rates between the two arms (p = .66). Significantly more patients randomized to the QD arm reported gastrointestinal adverse events compared with the control arm (p = .009). There were no study drug-related serious adverse events. For patients who are already virologically suppressed on their first PI-containing regimen, switching to a QD regimen of TDF+3TC+LPV/r resulted in similar rates of virologic suppression when compared with staying on existing therapy.


Metabolic cost calculations of gait using musculoskeletal energy models, a comparison study.
This paper compares predictions of metabolic energy expenditure in gait using seven metabolic energy expenditure models to assess their correlation with experimental data. Ground reaction forces, marker data, and pulmonary gas exchange data were recorded for six walking trials at combinations of two speeds, 0.8 m/s and 1.3 m/s, and three inclines, -8% (downhill), level, and 8% (uphill). The metabolic cost, calculated with the metabolic energy models was compared to the metabolic cost from the pulmonary gas exchange rates. A repeated measures correlation showed that all models correlated well with experimental data, with correlations of at least 0.9. The model by Bhargava et al. (J Biomech, 2004: 81-88) and the model by Lichtwark and Wilson (J Exp Biol, 2005: 2831-3843) had the highest correlation, 0.95. The model by Margaria (Int Z Angew Physiol Einschl Arbeitsphysiol, 1968: 339-351) predicted the increase in metabolic cost following a change in dynamics best in absolute terms.


Efficacy and safety of PLDR-IMRT for the re-irradiation of recurrent NPC: A prospective, single-arm, multicenter trial.
Salvage treatment of locoregionally recurrent nasopharyngeal carcinoma (NPC) requires weighing the benefits of re-irradiation against increased risks of toxicity. Here, we evaluated the outcomes of patients treated with intensity-modulated-based pulsed low-dose-rate radiotherapy (PLDR-IMRT) to enhance the curative effect of salvage treatment and reduce RT-related SAEs. A prospective clinical trial was conducted from March 2018 to March 2020 at multiple institutions. NPC patients who experienced relapse after radical therapy were re-irradiated with a median dose of 60 Gy (50.4-70 Gy)/30 f (28-35 f) using PLDR-IMRT. Thirty-six NPC patients who underwent PLDR-IMRT for locoregional recurrence were identified. With a median follow-up of 26.2 months, the objective response rate (ORR) of the entire cohort was 91.6%. The estimated mPFS duration was 28 months (95% CI: 24.9-31.1), and the estimated mLRFS duration was 30.4 months (95% CI: 25.2-35.5). The overall survival (OS) rate for all patients was 80.6%, the progression-free survival (PFS) rate was 75% and the cancer-specific survival (CSS) rate was 88.9% at 1 year. The LRFS and DMFS rates were 88.9% and 91.7%, respectively, at 1 year. A combination of systematic therapies could provide survival benefits to patients who experience NPC relapse (p < 0.05), and a Karnofsky performance status (KPS) score of ≥90 was a favorable factor for local control (p < 0.05). The incidence of acute SAEs (grade 3+) from PLDR was 22.2%, and the incidence of chronic SAEs was 19.4% among all patients. PLDR-IMRT combined with systematic therapy can effectively treat patients with locoregionally recurrent nasopharyngeal carcinoma and causes fewer adverse events than the rates expected with IMRT.


Demystifying the Mysteries: Sexual Dimorphism in Primary Teeth.
One of the critical steps in the process of identification is the sex determination of an unknown individual. Many studies have shown that sex can be determined using the human skeleton, especially by examining the pelvis and skull. Odontometric analysis of the human sexual variation has been less investigated, especially of primary dentition. To verify the presence of sexual dimorphism in primary teeth of local population of Faridabad, Haryana, India. The research was performed on dental casts of 500 children (250 boys and 250 girls, age range 3-5 years). Mesiodistal and buccolingual crown dimensions of maxillary and mandibular primary teeth were measured with a digital Vernier's caliper and were analysed for sexual dimorphism. Mann-Whitney-U test was used to check the statistical significance of difference in tooth dimensions among boys and girls. Differences were found in the mean values of mesiodistal and buccolingual diameters of primary teeth, in which boys generally had larger crown diameters than girls. Primary teeth may be used as an additional tool for sex identification of juvenile skeletons where other dimorphic features are not much developed.


Cationic compounds used in lipoplexes and polyplexes for gene delivery.
Gene transfer represents an important advance in the treatment of both genetic and acquired diseases. Many cationic lipids and cationic polymers naturally occurred or synthesized have been used for gene transfer. They have the advantages over viral gene transfer as non-immunogenic, easy to produce and not oncogenic. These cationic compounds, however, have the major limitations of inefficient transfection and toxicity to cells. For overcoming these problems, many new cationic compounds were developed since the first cationic lipid, DOTMA, was found usage in gene therapy. This article reviews cationic lipids for gene therapy from chemistry viewpoint and we classify these compounds as monovalent cationic lipids, polyvalent cationic lipids, cationic polymers, guanidine containing compounds, cationic peptides and cholesterol containing compounds, and hope to provide suggestions on the development of this variety of cationic compounds through the discussion.


8-Carbon oxylipins inhibit germination and growth, and stimulate aerial conidiation in Aspergillus nidulans.
Germination of Aspergillus nidulans conidia in liquid cultures was progressively inhibited at inoculum loads above 1×10(5)conidiamL(-1). High conidial densities also inhibited growth of neighbouring mycelia. The eight-carbon oxylipin 1-octen-3-ol was identified as the main inhibitor in a fraction also containing 3-octanone and 3-octanol. These three oxylipins also increased the conidiation rate of dark-grown surface cultures, but had no effect on liquid cultures. 3-octanone was the most conidiogenic compound. The action of 3-octanone required functional forms of developmental activators fluG, flbB-D and brlA, and was not additive to the conidiogenic effect of stress stimuli such as osmotic stress or carbon starvation. Oxylipins were produced shortly after hyphae made contact with the atmosphere and were most effective on aerial mycelia, indicating that they perform their signalling function in the gas phase.


Development of a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the detection of Sugarcane mosaic virus and Sorghum mosaic virus in sugarcane.
A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed for detecting Sugarcane mosaic virus (SCMV) and Sorghum mosaic virus (SrMV) in sugarcane. Six sets of four primers corresponding to the conserved coat protein gene were designed and tested for each virus. Three primer sets designed for detecting SCMV and four for detecting SrMV were successful in the RT-LAMP assay. The effective primer sets were not only specific for their target virus, but also able to detect multiple virus strains. The magnesium sulfate concentration of the reaction solution was optimized, with both viruses requiring a minimum of 5mM for detection. The sensitivity of this RT-LAMP assay was less than that of conventional and real-time RT-PCR.


Assessment of the microbiome during bacteriophage therapy in combination with systemic antibiotics to treat a case of staphylococcal device infection.
Infectious bacterial diseases exhibiting increasing resistance to antibiotics are a serious global health issue. Bacteriophage therapy is an anti-microbial alternative to treat patients with serious bacterial infections. However, the impacts to the host microbiome in response to clinical use of phage therapy are not well understood. Our paper demonstrates a largely unchanged microbiota profile during 4 weeks of phage therapy when added to systemic antibiotics in a single patient with Staphylococcus aureus device infection. Metabolomic analyses suggest potential indirect cascading ecological impacts to the host (skin) microbiome. We did not detect genomes of the three phages used to treat the patient in metagenomic samples taken from saliva, stool, and skin; however, phages were detected using endpoint-PCR in patient serum. Results from our proof-of-principal study supports the use of bacteriophages as a microbiome-sparing approach to treat bacterial infections. Video abstract.


Effects of particle size and acid addition on the remediation of chromite ore processing residue using ferrous sulfate.
A bench-scale treatability study was conducted to assess the effects of particle size and acid addition on the remediation of chromite ore processing residue (COPR) using ferrous sulfate. The remediation scheme entailed the chemical reduction of hexavalent chromium [Cr(VI)] and the mitigation of swell potential. Leaching tests and the EQ3/6 geochemical model were used to estimate the acid dosage required to destabilize Cr(VI)-bearing and swell-causing minerals. The model predicted greater acid dosage than that estimated from the batch leaching tests. This indicated that mass transfer limitation may be playing a significant role in impeding the dissolution of COPR minerals following acid addition and hence hindering the remediation of COPR. Cr(VI) concentrations determined by alkaline digestion for the treated samples were less than the current NJDEP standard. However, Cr(VI) concentrations measured by X-ray absorption near edge structure (XANES) were greater than those measured by alkaline digestion. Greater Cr(VI) percentages were reduced for acid pretreated and also for smaller particle size COPR samples. Upon treatment, brownmillerite content was greatly reduced for the acid pretreated samples. Conversely, ettringite, a swell-causing mineral, was not observed in the treated COPR.


Rurality Effect on Michigan Newborn Hearing Screening.
Evaluate the effect of rurality on newborn hearing screen outcomes in Michigan. Patients in the Michigan Department of Health and Human Services (MDHHS) Newborn Hearing Screening database that failed or did not receive their initial screen from 2015 to 2020 were evaluated. Using the U.S. Department of Agriculture Rural-Urban Continuum Codes (RUCC), patients were assigned a 1-9 code based on the population of their zip code, with 1 being the most urban and 9 being the most rural and outcomes between these patients were compared. There were 34,928 patients initially identified. Patients that had follow-up testing after a failed NBHS had a slightly higher RUCC than those that did not follow-up, 2.3 versus 2.2, respectively (p < 0.001). There was a significant difference between those that refused screening, with a mean RUCC of 4.2, and those that had a failed initial screen having a mean RUCC of 2.1 (p < 0.001). Similarly, those with equipment failure had a higher mean RUCC, 2.8, compared to those that had screening completed (p < 0.001). More rural areas are more likely to refuse a newborn hearing screen as well as have equipment failure options. There was no difference in rurality scores of those that had a follow-up screen after a failure and those that did not. IV Laryngoscope, 2023.


Epigenetic alterations of miR-155 and global DNA methylation as potential mediators of ochratoxin A cytotoxicity and carcinogenicity in human lung fibroblasts.
Ochratoxin A (OTA) is a well-known mycotoxin that adversely affects different human cells. Inhalational exposure to OTA and subsequent pulmonary diseases have been previously reported, yet its potential carcinogenicity and underlying molecular mechanisms have not been fully elucidated. This study aimed to evaluate the OTA-induced cytotoxicity and the epigenetic changes underlying its potential carcinogenicity in fetal lung fibroblast (WI-38) cells. OTA cytotoxicity was assessed by MTT assay; RT-qPCR was used to determine the expression of BAX, BCL-2, TP53, and miR-155, while ELISA was used for measuring 5-methyl cytosine percentage to assess global DNA methylation in OTA-treated versus control cells. WI-38 cells demonstrated sensitivity to OTA with IC50 at 22.38 μM. Though BAX and Bcl-2 were downregulated, with low BAX/BCL-2 ratio, and TP53 was upregulated, their fold changes showed decline trend with increasing OTA concentration. A significant dose-dependent miR-155 upregulation was observed, with dynamic time-related decline. Using subtoxic OTA concentrations, a significant global DNA hypermethylation with significant dose-dependent and dynamic alterations was identified. Global DNA hypermethylation and miR-155 upregulation are epigenetic mechanisms that mediate OTA toxicity on WI-38 cells. BAX downregulation, reduced BAX/BCL-2 ratio together with miR-155 upregulation indicated either the inhibition of TP53-dependent apoptosis or a tissue specific response to OTA exposure. The aforementioned OTA-induced variations present a new molecular evidence of OTA cytotoxicity and possible carcinogenicity in lung fibroblast cells.


Changes in the amount of cytochrome P450s in rat hepatic microsomes with starvation.
The effects of starvation on the composition of 12 different cytochrome P450s in rat hepatic microsomes were studied with a specific antibody. Changes in the metabolic activity of the microsomes were studied at the same time. P450 DM (P450j) was induced 2.5-fold by a 48-h starvation and its increase reflected the increase of metabolic activity of hepatic microsomes toward aniline, 7-ethoxycoumarin, and N-nitrosodimethylamine. P450 K-5, the major renal cytochrome P450 in untreated male rat, was also induced 2.5-fold by a 48-h starvation. P450 UT-2 (P450h) and P450 UT-5 (P450g), typical male-specific forms, decreased with starvation. P450 UT-2 had high testosterone 2 alpha- and 16 alpha-hydroxylation activities. These activities of hepatic microsomes were reduced with the decrease in P450 UT-2. P450 PB-1, testosterone 6 beta-hydroxylase, was increased time-dependently by starvation. P450 UT-4 (RLM2), a minor male-specific form, was not changed by starvation. P450 PB-2 (P450k), present in both sexes, was changed little by starvation. P450 PB-4 (P450b) and P450 PB-5 (P450e) are strongly induced in rat liver by phenobarbital in coordinate fashion. Starvation increased P450 PB-4 12-fold but reduced P450 PB-5 to 22% of the control level. P450 MC-1 (P450d) was decreased by starvation. P450 MC-5 (P450c) was barely detected in control rats and was not changed by starvation. P450 IF-3 (P450a), rich in immature rats, was increased by starvation, accompanied by an increase in testosterone 7 alpha-hydroxylation activity in the hepatic microsomes. We further investigated whether new cytochrome P450s appeared upon starvation by comparison of chromatographic profiles of cytochrome P450 from starved rats with those of cytochrome P450 from control rats using HPLC. Three new cytochrome P450s were detected in the starved rats. These cytochrome P450s were purified to homogeneity. One of them was P450 DM, judging from spectral properties, catalytic activity, and the NH2-terminal sequence. The two other forms were designated P450 3b and 4b. The minimum molecular weights of P450 3b and 4b were 53,000 and 52,000, respectively, and their CO-reduced absorption maxima were at 449 and 452 nm, respectively. P450 3b metabolized aminopyrine, N-nitrosodimethylamine, 7-ethoxycoumarin, and lauric acid, but with low activity. P450 4b was efficient in lauric acid omega- and (omega-1)-hydroxylation only. The spectral properties, catalytic activity, peptide map, and NH2-terminal sequence of P450 4b agreed with those of P450 K-5. P450 3b was a new cytochrome P450, judged by these criteria.


The association between fluoride in water and blood pressure in children and adolescents.
The objective of this study was to determine the association between water and plasma fluoride and blood pressure (BP) among children and adolescents. Our study population was individuals of 8-18 years in the 2013-2016 National Health and Nutrition Examination Survey. We performed a multivariable linear and logistic regression analysis to examine the relationship between fluoride and BP. In a linear regression analysis for systolic BP (SBP) (mm Hg) adjusting for age, sex, race, and poverty, fluoride in water (mg/L) was significant with a coefficient of -0.44 (p = 0.046) among adolescents (12-18 years). Additional adjustments for race, poverty, serum levels of cotinine, and BMI remained significant. While an inverse relationship was found in children (8-11 years), none were significant. Fluoride in plasma was not significant across all ages. The odds ratio of high BP for an increase in water fluoride also was not significant. Higher concentrations of fluoride in water were associated with low SBP only among adolescents. Fluoride alone cannot be responsible for BP as several biological metabolic processes may influence its physiological effects. Fluoride consumption should be considered in conjunction with these processes. The high fluoride in drinking water was statistically significantly associated with low systolic BP in children and adolescents. The odds ratio of high BP for an increase in fluoride in drinking water was not significant. Our study contributes to the existing literature by providing individualized data and results on an individual level.


Factors related to the practice of vacuum-assisted birth: findings from provider interviews in Kigoma, Tanzania.
Vacuum-assisted birth is not widely practiced in Tanzania but efforts to re-introduce the procedure suggest some success. Few studies have targeted childbirth attendants to learn how their perceptions of and training experiences with the procedure affect practice. This study explores a largely rural cohort of health providers to determine associations between recent practice of the procedure and training, individual and contextual factors. A cross-sectional knowledge, attitudes and practice survey of 297 providers was conducted in 2019 at 3 hospitals and 12 health centers that provided comprehensive emergency obstetric care. We used descriptive statistics and binary logistic regression to model the probability of having performed a vacuum extraction in the last 3 months. Providers were roughly split between working in maternity units in hospitals and health centers. They included: medical doctors, assistant medical officers (14%); clinical officers (10%); nurse officers, assistant nurse officers, registered nurses (32%); and enrolled nurses (44%). Eighty percent reported either pre-service, in-service vacuum extraction training or both, but only 31% reported conducting a vacuum-assisted birth in the last 3 months. Based on 11 training and enabling factors, a positive association with recent practice was observed; the single most promising factor was hands-on solo practice during in-service training (66% of providers with this experience had conducted vacuum extraction in the last 3 months). The logistic regression model showed that providers exposed to 7-9 training modalities were 7.8 times more likely to have performed vacuum extraction than those exposed to fewer training opportunities (AOR = 7.78, 95% CI: 4.169-14.524). Providers who worked in administrative councils other than Kigoma Municipality were 2.7 times more likely to have conducted vacuum extraction than their colleagues in Kigoma Municipality (AOR = 2.67, 95% CI: 1.023-6.976). Similarly, providers posted in a health center compared to those in a hospital were twice as likely to have conducted a recent vacuum extraction (AOR = 2.11, 95% CI: 1.153-3.850), and finally, male providers were twice as likely as their female colleagues to have performed this procedure recently (AOR = 1.95, 95% CI: 1.072-3.55). Training and location of posting were associated with recent practice of vacuum extraction. Multiple training modalities appear to predict recent practice but hands-on experience during training may be the most critical component. We recommend a low-dose high frequency strategy to skills building with simulation and e-learning. A gender integrated approach to training may help ensure female trainees are exposed to critical training components.


A right scrotal abscess and foreign body ingestion in a schizophrenic patient.
A 38-year-old man with a history of schizophrenia presented with pain and swelling of his testicles, with the right side worse than the left. Physical examination was remarkable for a very firm, large, right-sided scrotal mass. Testicular ultrasound was suspicious for neoplasm or abscess. On the pelvic computed tomography (CT) scan, which was obtained as part of a metastatic cancer work-up, two metallic foreign bodies were identified in the pelvis. On further questioning, the patient admitted to ingesting the nails 2 days prior, in a suicide attempt. We review the evaluation of unilateral scrotal pain and swelling, and incidental foreign body ingestion.


Patients as team members: Factors affecting involvement in treatment decisions from the perspective of patients with a chronic condition.
Active patient involvement in treatment decisions is seen as a feature of patient-centred care that will ultimately lead to better healthcare services and patient outcomes. Although many factors have been identified that influence patient involvement in treatment decisions, little is known about the different views that patients have on which factors are most important. This study explores the views of patients with a chronic condition on factors influencing their involvement in treatment decisions. Q-methodology was used to study the views of patients. Respondents were asked to rank a set of 42 statements from the least important to the most important for active patient involvement in treatment decision-making. The set of 42 statements was developed based on a literature search and a pilot in which two external researchers, 15 patients and four healthcare professionals participated. A total of 136 patients with one of three major chronic conditions were included: diabetes types 1 and 2, respiratory disease (i.e., chronic obstructive pulmonary disease and asthma) and cancer (i.e., breast cancer and prostate cancer). Data were collected in a face-to-face interview setting in the Netherlands. Four distinct views on the factors influencing active patient involvement were identified among patients with a chronic condition. (1) Enabled involvement: the extent to which patients are facilitated and empowered to participate will lead to patient involvement. (2) Relationship-driven involvement: the relationship between patients and healthcare professionals drives patient involvement. (3) Disease impact-driven involvement: the severity of disease drives patient involvement. (4) Cognition-driven involvement: knowledge and information drive patient involvement. From the patients' perspective, this study shows that there is no one-size-fits-all approach to involving patients more actively in their healthcare journey. Strategies aiming to enhance active patient involvement among patients with a chronic condition should consider this diversity in perspectives among these patients. Patients are the respondents as this study researches their perspective on factors influencing patient involvement. In addition, patients were involved in pilot-testing the statement set.


Systematic review of stepped wedge cluster randomized trials shows that design is particularly used to evaluate interventions during routine implementation.
To describe the application of the stepped wedge cluster randomized controlled trial (CRCT) design. Systematic review. We searched Medline, Embase, PsycINFO, HMIC, CINAHL, Cochrane Library, Web of Knowledge, and Current Controlled Trials Register for articles published up to January 2010. Stepped wedge CRCTs from all fields of research were included. Two authors independently reviewed and extracted data from the studies. Twenty-five studies were included in the review. Motivations for using the design included ethical, logistical, financial, social, and political acceptability and methodological reasons. Most studies were evaluating an intervention during routine implementation. For most of the included studies, there was also a belief or empirical evidence suggesting that the intervention would do more good than harm. There was variation in data analysis methods and insufficient quality of reporting. The stepped wedge CRCT design has been mainly used for evaluating interventions during routine implementation, particularly for interventions that have been shown to be effective in more controlled research settings, or where there is lack of evidence of effectiveness but there is a strong belief that they will do more good than harm. There is need for consistent data analysis and reporting.


Intervention of 3-aminobenzamide against Dextran Sulphate Sodium induced colitis in mice: Investigations on molecular mechanisms.
Various preclinical and clinical studies reported that Poly [ADP-ribose] polymerase 1 plays significant role in all acute and chronic inflammatory diseases with different etiopathogenesis. The present study aims to investigate the protective effect of 3-aminobenzamide in Dextran Sulphate Sodium induced ulcerative colitis and associated molecular mechanisms. Ulcerative colitis in male BALB/c mice was induced using Dextran sulphate sodium (3 %w/v) for 3 cycles with 7 days recovery period in-between. 3-aminobenzamide was administered at the doses of 5, 10 and 20 mg/kg starting from the Ist week of remission period and was continued till the termination of the experiment. The effect of 3-aminbenzamide was evaluated using biochemical parameters, histopathological evaluations, ELISA, immunohistochemistry, immunofluorescence and Western blot analysis. All the doses of 3-aminobenzamide (5 mg/kg; 10 mg/kg and 20 mg/kg) ameliorated the severity of ulcerative colitis by modulating various molecular targets such as poly[ADP-ribose] polymerase 1, nuclear factor kappa-light-chain-enhancer of activated B cells, NLR family pyrin domain containing 3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, cysteine aspartases, interleukin-1β, proliferating cell nuclear antigen, sirtuin 1, adenosine monophosphate-activated protein kinase, tumour necrosis factor-α and catalase. However, the lower doses (5 and 10 mg/kg) exerted more prominent effects in comparison to the high dose (20 mg/kg). Further, 3-aminobenzamide treatment restored the intestinal integrity by increasing the expression of occludin and significantly ameliorated ulcerative colitis associated elevated lipopolysaccharides, oxidative and nitrosative stress, cellular damage and apoptosis. Lower doses of 3-aminobenzamide showed more prominent protective effects against ulcerative colitis associated damage as compared to higher dose.


Use of neoadjuvant versus adjuvant chemotherapy for hormone receptor-positive breast cancer: a National Cancer Database (NCDB) study.
Neoadjuvant chemotherapy (NAC) is a well-established therapeutic option for patients with locally advanced disease often allowing downstaging and facilitation of breast conserving therapy. With evolution of better targeted treatment regimens and awareness of improved outcomes for significant responders, use of NAC has expanded particularly for triple negative and HER2-positive (HER2+) breast cancer. In this study, we explore utility of neoadjuvant chemotherapy for hormone receptor-positive HER2-negative (HR+ HER2-) patients. Patients with HR+ HER2- breast cancer treated with chemotherapy before or after surgery were identified from 2010 to 2015 in the NCDB. Multivariable regression models adjusted for covariates were used to determine associations within these groups. Among 134,574 patients (clinical stage 2A, 64%; 2B, 21%; 3, 15%), 105,324 (78%) had adjuvant chemotherapy (AC) and 29,250 (22%) received NAC. Use of NAC increased over time (2010-2015; 13.2-19.4% and PR = 1.34 for 2015; p < 0.0001). Patients were more likely to receive NAC with cT3, cT4, and cN+ disease. Patients less likely to receive NAC were age ≥ 50, lobular carcinoma, increased Charlson-Deyo score, and government insurance. Complete response (pCR) was noted in 8.3% of NAC patients. Axillary downstaging occurred in 21% of patients, and predictors included age < 50 years, black race, poorly differentiated grade, invasive ductal histology, and either ER or PR negativity. NAC use among HR+ HER2- breast cancer patients has expanded over time and offers downstaging of disease for some patients, with pCR seen in only a small subset, but downstaging of the axilla in 21%. Further analysis is warranted to determine the subgroup of patients with HR+ HER2- disease who benefit from this approach.


Comparing posaconazole and itraconazole for antifungal prophylaxis in critically ill lung transplant recipients: Efficacy and plasma concentrations.
Posaconazole and itraconazole are commonly used for systemic antifungal prophylaxis after lung transplantation. The aim of this study on critically ill lung transplant recipients was to assess the rate of adequate plasma concentrations and the frequency of fungal-induced transitions from antifungal prophylaxis to therapy after the administration of either posaconazole or itraconazole for systemic prophylaxis. Critically ill lung transplant recipients with postoperative posaconazole or itraconazole prophylaxis and therapeutic drug monitoring from February 2016 to November 2019 were retrospectively included in the study. Positive fungal cultures or Aspergillus antigen tests resulting in a transition from antifungal prophylaxis to therapy were analyzed from the first day of prophylaxis until 7 days after the last sample for each patient. Adequate plasma concentrations were defined as ≥500 µg/L for itraconazole and ≥700 µg/L for posaconazole. Two hundred seventy-five samples from 73 patients were included in the analysis. Overall, 60% of the posaconazole and 55% of the itraconazole concentrations were subtherapeutic. Administration of posaconazole suspension resulted significantly (P < .01) more often in subtherapeutic concentrations than tablets (68% vs 10%). Patients treated with posaconazole showed less positive fungal records resulting in a transition from prophylaxis to therapy than patients treated with itraconazole (10% vs 33%, P-value: .029). The detection of a fungal pathogen was not associated with the measured plasma concentrations or the achievement of the target concentrations. Our findings suggest that posaconazole should be used instead of itraconazole for systemic prophylaxis in critically ill lung transplant recipients.


Angioedema with severe acute abdominal pain: Think of hereditary angioedema.
Angioedema can be either mast cell-(histamine-)mediated or bradykinin-mediated. Treatment approaches for the two types are very different, making differential diagnosis critical. Severe acute abdominal pain caused by intestinal angioedema is commonly misdiagnosed, especially when associated with bradykinin-mediated angioedema. After describing a typical clinical scenario and diagnostic journey of a patient with recurrent, undiagnosed abdominal pain due to hereditary angioedema (HAE), a rare variant of bradykinin-mediated angioedema, we delve into the classification and differential diagnosis of the various types of angioedema and provide an overview of appropriate management with an emphasis on the bradykinin-mediated types. Bradykinin-induced angioedema may be inherited or acquired and is infrequent compared to mast cell-mediated angioedema. HAE is a rare disease characterized by recurrent attacks of non-urticarial, nonpruritic edema usually affecting the face, respiratory tract, extremities, gastrointestinal tract, and genitalia. Unlike mast cell-mediated angioedema, painful abdominal symptoms are prevalent in bradykinin-mediated angioedema and are sometimes the only manifestation of an attack, increasing the likelihood of initial misdiagnosis as appendicitis or other forms of acute abdomen. It is important for gastroenterologists to be vigilant for the possibility of angioedema pathology in patients presenting with undiagnosed, recurrent, abdominal symptoms to facilitate accurate diagnosis and effective treatment.


Effect of vitamin E on 2-deoxy-D-glucose uptake in human fibroblast cultures.
2-Deoxy-D-glucose (2-DOG) uptake was tested in human fibroblast cultures in the presence and absence of vitamin E. Addition of 10 micrograms/ml vitamin E to the culture medium significantly reduced this uptake for 2-DOG concentrations of 0.005 to 10 mmol/liter (P less than or equal to 0.01). The decrease of 2-DOG uptake was inversely proportional to the rise in 2-DOG concentration (P less than or equal to 0.01). The presence of vitamin E reduced by 71% the average cellular level of lipid peroxides (expressed as thiobarbituric acid reactive substances) and caused a small but significant decrease in the cholesterol concentration (P less than or equal to 0.01). These last results might explain the decrease in 2-DOG uptake observed in the presence of vitamin E.


Localization of active sites in the neuromuscular junction of the frog.
Spontaneous quantal discharges at the frog neuromuscular junction were simultaneously monitored with three glass microelectrodes. Two extracellular electrodes were located at the synaptic cleft a few microns apart from each other so that each quantal discharge occurring nearby evoked signals in both electrodes. From the observed ratios of the signal amplitudes it is inferred that quantal discharges exclusively occur at discrete sites. The distance between active sites is in the same range as that between "active zones" seen from electron micrographs.


Heavy metals in urban ambient PM10 and soil background in eight cities around China.
The ambient PM(10) and background soil samples were collected and analyzed with ICP-AES in eight cities around China to investigate the levels of ten heavy metals (Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, and Pb). The mean concentrations of ten heavy metals in PM(10) of the eight cities of China followed the order of Zn > Pb > Mn > Cu > Ni > Cr > Co > V. The metals in the ambient PM(10) and soil were compared in each city to evaluate the heavy metal mass fraction from anthropogenic sources in ambient air. The CD values in these cities were all above 0.2, indicating that the ingredients spectrums of PM(10) and soil vary markedly. Most heavy metals were enriched in PM(10), except Fe and Ti. The results showed that almost all the cities suffer important heavy metal pollution from anthropogenic sources. The eight cities were also grouped according to their similarity in heavy metals of ambient PM(10) by cluster analysis to investigate the relationship between the heavy metals and the pollution sources of each city. The conclusion was that the eight cities were divided into three clusters which had similar industrial type and economy scale: the first cluster consisted of Shenzhen, Wuxi, and Guiyang; followed by Jinan and Zhengzhou as the second grouping; and the third group had Taiyuan, Urumqi, and Luoyang.


Endoplasmic reticulum stress-controlled autophagic pathway promotes polystyrene microplastics-induced myocardial dysplasia in birds.
In complex ecosystems, birds are generally long-lived and occupy high trophic positions, making them good bioindicators for monitoring environmental contaminants. The effects of microplastics (MPs) on myocardial development in bird is currently unknown. Chicks, as a high trophic level terrestrial bird, may be more affected by MPs exposure and. Therefore, we established an in vivo model of chicks exposed to different concentrations of polystyrene microplastics (PS-MPs) and selected 12-day-old chicken embryos in vitro to extract primary cardiomyocytes to further investigate the potential molecular mechanisms of the effect of PS-MPs on myocardial development in birds. Histopathological observations revealed that the PS-MPs treated exhibited loose and irregular myocardial arrangement, large cell gaps and broken myocardial fiber bundles. More mechanistically, TnnT2, Nkx2-5, Gata4, TBX5 and ACTN2 were down-regulated, endoplasmic reticulum (ER) stress markers GRP78, PERK, eIF2α, IRE1, ATF4, ATF6 and CHOP were overexpressed, autophagy-related genes LC3, ATG5, Beclin1 and P62 were down-expressed after PS-MPs exposure, and the addition of 4PBA effectively deregulated the above aberrant expression. Hence, our report indicated that PS-MPs induced myocardial dysplasia in birds is mainly attributed to the ER stress-mediated autophagic pathway. This provided data supporting the protection of birds from the health risks of MPs pollution. More critically, the study of cardiac developmental toxicity in birds may help to better explain or solve the problem of MPs pollution in complex ecosystems.


A Bifunctional Spin Label for Ligand Recognition on Surfaces.
In situ monitoring of biomolecular recognition, especially at surfaces, still presents a significant technical challenge. Electron paramagnetic resonance (EPR) of biomolecules spin-labeled with nitroxides can offer uniquely sensitive and selective insights into these processes, but new spin-labeling strategies are needed. The synthesis and study of a bromoacrylaldehyde spin label (BASL), which features two attachment points with orthogonal reactivity is reported. The first examples of mannose and biotin ligands coupled to aqueous carboxy-functionalized gold nanoparticles through a spin label are presented. EPR spectra were obtained for the spin-labeled ligands both free in solution and attached to nanoparticles. The labels were recognized by the mannose-binding lectin, Con A, and the biotin-binding protein avidin-peroxidase. Binding gave quantifiable changes in the EPR spectra from which binding profiles could be obtained that reflect the strength of binding in each case.


Barriers to orthopaedic practice--why surgeons do not put into practice what they have learned in educational events.
All orthopaedic and trauma surgeons attend educational events throughout their careers. Many surgeons find that when they return to practice they are unable to put into effect those things that they have learned. This study focussed on 708 surgeons from 2 different cultural backgrounds (developed and developing world) who attended 7 separate trauma Educational events. Surgeons were contacted by e-mail at least 6 weeks after the event and asked if they had encountered any Barriers, which had prevented them from putting into practice what they had learned at the event. If Barriers had been encountered they were asked to categorize them and state if they were able to overcome them. Barriers affect nearly every learner and learners are usually unable to overcome them. The study identified what barriers exist for implementation of acquired knowledge, how they vary with the degree of experience of the surgeon and his or her cultural background. The commonest barrier amongst all surgeons is not having contact with a suitable patient to treat with their new knowledge and skills. Inability to get access to equipment and facilities is a major barrier for many surgeons especially in the developing world. This has profound implications for organizers of educational events that will need to incorporate strategies into their educational planning to help surgeon learners avoid or overcome barriers.


Use of hand-held laser scanning in the assessment of craniometry.
The intra- and inter-examiner reliability was evaluated for hand-held 3D laser scanning technology when it was combined with localization of landmarks for craniometry. The data from the laser surface scanning were compared with those of conventional direct measuring. Using thirty unidentified skulls requested for individual identification, measurements were taken of the line distances from lambda to 26 landmarks, and also for seven breadth parameters. For the laser surface scanning, two examiners performed replicate measurements with an interval of 1 week. In the conventional direct measuring, the first examiner took replicate measurements with a 1-week interval. To assess intra- and inter-examiner reliabilities, the intraclass correlation coefficient was used. Analysis of variance with repeated measures for each parameter was performed to compare the conventional method with the 3D scanning method. Both the 3D scanning and conventional methods showed excellent intra-examiner reliabilities, and the 3D laser scanning method also showed excellent inter-examiner reliability. A statistical difference between the two examiners was found only in nasal breadth in the 3D laser scanning method. There was no significant difference between the two measuring methods, though the 3D laser scanning method tended to give a slightly lower reading. Collectively, the 3D laser scanning method with point localization is a useful method with excellent reliability, and it can replace the conventional direct measuring method in craniometry.


Serological and molecular study of Leptospira in pediatric patients at a tertiary care centre of northern India.
Leptospirosis is considered as one of the most neglected zoonotic tropical diseases. Animals and humans acquire this infection through direct contact with contaminated urine or body fluids of infected animals. This prospective study was undertaken to know the proportion of leptospirosis in pediatric patients presented with acute febrile illness at the Post Graduate Department of Microbiology, King George's Medical University, Lucknow, Uttar Pradesh. Blood samples were collected over a period of one year from January to December 2018 from 70 pediatric patients aged up to 0-12 years presented with febrile illness for 3-14 days. Out of the 70 samples, 7 (10%) samples were found positive by IgM ELISA, 4 (5.7%) samples were positive by MAT and 3(4.3%) were found positive by PCR. Risk factors such as contact with infected animals and contaminated environment were highly associated with seropositivity of leptospirosis. Clinical symptoms such as fever, chills, myalgia, headache, abdominal pain and cough were significantly associated (p < 0.05) with the seropositivity of leptospirosis.


Serum lipid abnormalities in heart transplant recipients: predominance of HDL2-like particles in the HDL pattern.
Accelerated coronary atherosclerosis is a major risk limiting long-term survival after heart transplantation and is commonly associated with dyslipoproteinemia even in subjects who were not dyslipoproteinemic before intervention. The purpose of this study was to analyse the abnormalities in the lipid profiles of 2 different groups of heart-transplanted males: 18 subjects with underlying ischemic heart disease (IHD) and 19 subjects with non-obstructive cardiomyopathy of unknown aetiology (CM). Both groups were compared to 33 healthy males. All patients were under immunosuppressive therapy including prednisone, cyclosporin A and azathioprine. A moderate hyperlipidemia was found in all transplant recipients, associated with high HDL-cholesterol concentrations in the CM group (1.80 +/- 0.37 vs. 1.29 +/- 0.23 mmol/l) and normal HDL-cholesterol levels in the IHD group (1.40 +/- 0.23 mmol/l). HDL subfractionation showed a marked increase in HDL2-cholesterol (CM: 1.12 +/- 0.32; IHD: 0.69 +/- 0.28; control: 0.40 +/- 0.17 mmol/l) while HDL3-cholesterol was significantly lower than in the control group. Analysis of HDL particle sizes showed in all transplant subjects an increase of an intermediate size particle HDL2a (diameter 9.0 +/- 0.10 nm) which is a minor form in control subjects. In the CM group, both the common HDL2b (10.2 +/- 0.13 nm) and HDL2a were abundant in 13 of 17 patients. The pattern was more heterogeneous in the IHD group but witnessed to a high frequency of HDL2a particles either alone (5/14) or associated with larger HDL2b (4/14) or with small HDL3 (4/14).(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of serum free thyroxine indices and "corrected" thyroxine tests.
A dual competitive protein-binding assay for serum thyroxine (T4) is described. The assay is called the "corrected" T4 index and can be performed simultaneously with the determination of total T4. This method correlated significantly with the free T4 index and the effective T4 ratio. The "corrected" T4 index was compared for precision and diagnostic accuracy with the effective T4 ratio and two different free T4 indices. Improved modifications of the thyroxine and triiodothyronine Sephadex uptake tests, used for calculation of the free T4 indices, are also reported. In spite of better precision, the "corrected" T4 index and effective T4 ratio gave twice as many incorect classifications of both hyper- and hypothyroidism as the free T4 indices. Previous reports on the effective T4 ratio and other basically similar tests might give an overly optimistic view of what can be expected in routine clinical practice. The free T4 index, which is a good estimate of the free T4 concentration, may still be the thyroid function test of choice when serum T4 and clinical impression are not in conformity.


Novel nanocomposite of biochar-zerovalent copper for lead adsorption.
In this study, a composite of zerovalent copper-biochar was investigated for its ability to remove lead from water. The prepared material was characterized by using scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), X-ray diffractomter (XRD), and X-ray photoelectron spectroscopy (XPS). The pH effect on adsorption of lead was investigated within the range of 2-8 and the effect of temperature was studied at 303, 308, 313, and 318 K. The kinetics of lead adsorption on biochar composite was evaluated and the equilibrium time of 12 hr was established. To further evaluate the nature of adsorption, Langmuir model was tested and the adsorption capacities were evaluated for lead adsorption on the surface of copper biochar composite. The activation energy, entropy, and enthalpy values indicated the adsorption phenomenon to be chemisorptive and spontaneous in nature. Comparison of adsorption capacities with the reported adsorbents in the literature concluded zerovalent copper-biochar composite to be an efficient adsorbent for the removal of lead in the experimental conditions under study. RESEARCH HIGHLIGHTS: Highly efficient composite of zerovalent copper with biochar was synthesized for lead adsorption. XPS and XRD shows the presence of zerovalent copper in the biochar composite. pH and temperature were the main governing factors in the adsorption process. Adsorption capacity for lead is higher than many of the reported adsorbents.


Longitudinal Monitoring of DNA Viral Loads in Transplant Patients Using Quantitative Metagenomic Next-Generation Sequencing.
Immunocompromised patients are prone to reactivations and (re-)infections of multiple DNA viruses. Viral load monitoring by single-target quantitative PCRs (qPCR) is the current cornerstone for virus quantification. In this study, a metagenomic next-generation sequencing (mNGS) approach was used for the identification and load monitoring of transplantation-related DNA viruses. Longitudinal plasma samples from six patients that were qPCR-positive for cytomegalovirus (CMV), Epstein-Barr virus (EBV), BK polyomavirus (BKV), adenovirus (ADV), parvovirus B19 (B19V), and torque teno-virus (TTV) were sequenced using the quantitative metagenomic Galileo Viral Panel Solution (Arc Bio, LLC, Cambridge, MA, USA) reagents and bioinformatics pipeline combination. Qualitative and quantitative performance was analysed with a focus on viral load ranges relevant for clinical decision making. All pathogens identified by qPCR were also identified by mNGS. BKV, CMV, and HHV6B were additionally detected by mNGS, and could be confirmed by qPCR or auxiliary bioinformatic analysis. Viral loads determined by mNGS correlated with the qPCR results, with inter-method differences in viral load per virus ranging from 0.19 log10 IU/mL for EBV to 0.90 log10 copies/mL for ADV. TTV, analysed by mNGS in a semi-quantitative way, demonstrated a mean difference of 3.0 log10 copies/mL. Trends over time in viral load determined by mNGS and qPCR were comparable, and clinical thresholds for initiation of treatment were equally identified by mNGS. The Galileo Viral Panel for quantitative mNGS performed comparably to qPCR concerning detection and viral load determination, within clinically relevant ranges of patient management algorithms.


Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.
The aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.


5HTT polymorphisms are associated with job stress in Japanese workers.
Recently, the number of workers who suffer from job stress was increasing in Japan because of a prolonged recession, increasing number of elderly workers, and structural reorganization of companies. On the other hand, polymorphism associated with depression or alcoholism was detected. Relationship between job stress and these polymorphisms were investigated. Brief job stress questionnaire was assessed for 243 employees who worked at a manufacturing company and a local hospital in Japan (mean age 40.8 years). Alcohol consumption and smoking habit were assessed as lifestyle factors. DNA samples were prepared to detect polymorphisms of 5HTT, aldehyde dehydrogenase 2 (ALDH2), D2 dopamine receptor (DRD2), and cytochrome p450 2A6 (CYP2A6) genes. The level of depressed mood by job stress was significantly higher among carriers of two short alleles of the 5HTT regulatory region compared with carriers of one or two long alleles (Mann-Whitney U, p<0.05). In a logistic regression analysis, the s/s allele of the 5HTT had a tendency to be a risk of depressed mood. When subjects had high supervisor's support, depressed mood was significantly lower irrespective of 5HTT polymorphism. Job stress may elicit biological responses that contribute to depressed mood in relation to 5HTT polymorphism.


Poststroke depression and functional outcome: a critical review of literature.
Depression is a frequent complication of stroke with a prevalence of 25% to 79%, depending on the setting, assessment tool, and time poststroke. Patients with poststroke depression (PSD) show far less recovery from functional impairments compared with nondepressed patients with stroke. Many stroke patients have significant physical disability and an inability to carry out activities of daily living. This, in turn, adversely affects quality of life. Poststroke functional disability has been considered predictive of depression after stroke in some literature. However, studies differ on the relative contribution of functional impairment to PSD. The purpose of this article is to synthesize the literature on the relationship between PSD and functional outcome. This synthesis will help identify gaps in knowledge to further direct future studies and provide knowledge for clinicians to improve care and recovery after stroke.


Lead, cadmium, arsenic and mercury in canned tuna fish marketed in Tehran, Iran.
Fifty-four canned tuna fish samples corresponding to 10 widely used different brands were purchased from local markets in Tehran, Iran during 2012-2013 and analysed on heavy metals. Mercury was determined by a direct mercury analyser without any sample preparation. For analysis of other elements samples were digested using a microwave apparatus. Lead and cadmium were determined by graphite furnace atomic absorption spectrometry and arsenic via hydride vapour generation. All samples had arsenic and mercury contamination. Arsenic levels showed a range of 0.25-1.42 mg kg(-1), which might be due to lack of national and international limits for arsenic in canned tuna fish. Lead and cadmium were measured in a small number of samples with a mean of 0.053 ± 0.058 mg kg(-1) and 0.013 ± 0.015 mg kg(-1), respectively. Results obtained for these heavy metals in all samples were lower than the corresponding limits, whereas arsenic and mercury contents might raise some attention.


Nonlinear indentation of single human erythrocytes under application of a localized mechanical force.
Despite the accepted notion that erythrocytes are uniquely deformable cells, the apparent Young's modulus values reported in the literature do not differ so much from those of other cells. We devised to measure the local deformability of living immobilized human erythrocytes at a low force, in contact-free mode, using an application of Scanning Ion Conductance Microscopy (SICM) previously developed in our laboratory. Reversible indentations were induced by forces of up to few hundreds pN. The indentation did not grow linearly with the force. The apparent Young's modulus varied from 0.2 to 1.5 kPa applying forces from 20 to 500 pN on a cell surface area of about 0.2 μm2, exhibiting a progressive stiffening at increasing force. Control measurements showed that A549 cells exhibit a constant value of the apparent Young's modulus (about 2 kPa) for forces up to about 800 pN. These findings show that SICM is a suitable tool to investigate cell mechanical properties, when forces in the range of tens of pN are required, in the absence of mechanical contact between probe and sample. The nonlinear deformation of the erythrocyte has to be taken into account in modeling the complex regulation mechanism of the microvascular beds.


Prediction of adherence and control in diabetes.
This study aims to predict adherence to diabetic treatment regimens and sustained diabetic control. During two clinic visits that were 2 months apart, 63 adult outpatients completed measures of diabetic history, current treatment, diabetic control, adherence, and self-efficacy about adherence to treatment. Results showed that self-efficacy was a significant predictor of later adherence to diabetes treatment even after past levels of adherence were taken into account. Posttest levels of adherence in turn were significantly associated with posttest %HbA1c after control for illness severity. A stepwise multiple regression to predict %HbA1c at post entered pretest measures of diabetic control, treatment type, and self-efficacy, which together predicted 50% of the variance. Results are related to self-efficacy theory and implications for practice are discussed.


The SerpinB1 knockout mouse a model for studying neutrophil protease regulation in homeostasis and inflammation.
SerpinB1 is a clade B serpin, or ov-serpin, found at high levels in the cytoplasm of neutrophils. SerpinB1 inhibits neutrophil serine proteases, which are important in killing microbes. When released from granules, these potent enzymes also destroy host proteins and contribute to morbidity and mortality in inflammatory diseases including emphysema, chronic obstructive pulmonary disease, cystic fibrosis, arthritis, and sepsis. Studies of serpinB1-deficient mice have established a crucial role for this serpin in Pseudomonas aeruginosa infection by preserving lung antimicrobial proteins from proteolysis and by protecting lung-recruited neutrophils from a premature death. SerpinB1⁻/⁻ mice also have a severe defect in the bone marrow reserve of mature neutrophils demonstrating a key role for serpinB1 in cellular homeostasis. Here, key methods used to generate and characterize serpinB1⁻/⁻ mice are described including intranasal inoculation, myeloperoxidase activity, flow cytometry analysis of bone marrow myeloid cells, and elastase activity. SerpinB1-knockout mice provide a model to dissect the pathogenesis of inflammatory disease characterized by protease:antiprotease imbalance and may be used to assess the efficacy of therapeutic compounds.


Comparison of different analytical methods to evaluate the heat shock protein (HSP) response in fruits. Application to tomatoes subjected to stress treatments.
Heat shock proteins (HSP) are synthesized in living tissues exposed to transient increase in temperature and play a central role in the protective response against heat and other stresses. In fruits, this response to heat treatment provides resistance to a physiological alteration known as chilling injury. Despite the physiological importance of this group of proteins, publications comparing different methodological alternatives for their analysis are rather scarce. In the present paper, we conducted a comparative study using different electrophoretic and immunological techniques to evaluate the HSP response in fruits. Proteins were extracted from tomato fruit exposed to an HSP-inducing temperature (38 °C) for different times (0, 3, 20, and 27 h). Different alternatives of analysis (SDS-PAGE, SDS-PAGE followed by IEF, Western blot, and dot blot) were performed, and their potential application discussed. The study was complemented with a practical application, in which tomatoes were subjected to heat and anaerobic treatments and then stored in a chill-inducing temperature. This application evidences the relevance of knowing the level of proteins attained by stress treatments which correlates with the acquired tolerance.


Seizure prediction using EEG spatiotemporal correlation structure.
A seizure prediction algorithm is proposed that combines novel multivariate EEG features with patient-specific machine learning. The algorithm computes the eigenspectra of space-delay correlation and covariance matrices from 15-s blocks of EEG data at multiple delay scales. The principal components of these features are used to classify the patient's preictal or interictal state. This is done using a support vector machine (SVM), whose outputs are averaged using a running 15-minute window to obtain a final prediction score. The algorithm was tested on 19 of 21 patients in the Freiburg EEG data set who had three or more seizures, predicting 71 of 83 seizures, with 15 false predictions and 13.8 h in seizure warning during 448.3 h of interictal data. The proposed algorithm scales with the number of available EEG signals by discovering the variations in correlation structure among any given set of signals that correlate with seizure risk.


Recruitment and retention of WIC participants in a longitudinal dietary intervention trial.
This paper describes strategies and outcomes of techniques to recruit and retain low-income women served by the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) in a longitudinal dietary intervention trial. Community engagement strategies, methods to recruit and retain participants, and recruitment and retention rates are reported. Demographic and lifestyle predictors of loss to follow-up, contacts required to reach participants at each data collection point, participant reactions to the recruitment and retention strategies used, and reasons for drop out (assessed among those who discontinued their study involvement) also were examined. Of 1281 eligible women, 744 were enrolled (58% recruitment rate); retention rates were 87%, 70%, and 55%, respectively, 2 weeks and 3 and 6 months post-intervention. Being unmarried, younger, and having low baseline vegetable intake predicted loss to follow-up. Between 4 and 5 contact attempts and 1 and 2 completed contacts were required to reach participants at each data collection point. Participants endorsed recruiting women while waiting for WIC appointments (as they were accessible, perceived the information provided as informative, and wanted to pass the time) and by word of mouth. Lacking time and loss of interest were commonly reported reasons for not completing assessments and dropout. To improve retention, shortening telephone assessments, conducting the assessments in person, and increasing the amount of incentives were recommended. Despite using recommended strategies, recruitment and retention rates were modest. Research is needed to identify and test approaches to effectively engage WIC-enrolled adults in health intervention trials.


White matter microstructure and the variable adult outcome of childhood attention deficit hyperactivity disorder.
Changes in cerebral cortical anatomy have been tied to the clinical course of attention deficit hyperactivity disorder (ADHD). We now ask if alterations in white matter tract microstructure are likewise linked with the adult outcome of childhood ADHD. Seventy-five young adults, 32 with ADHD persisting from childhood and 43 with symptom remission were contrasted against 74 never-affected comparison subjects. Using diffusion tensor imaging, we defined fractional anisotropy, a metric related to white matter microstructure, along with measures of diffusion perpendicular (radial) and parallel (axial) to the axon. Analyses were adjusted for head motion, age and sex, and controlled for multiple comparisons and medication history. Tract-based analyses showed that greater adult inattention, but not hyperactivity-impulsivity, was associated with significantly lower fractional anisotropy in the left uncinate (standardized β=-0.37, t=3.28, p=0.002) and inferior fronto-occipital fasciculi (standardized β=-0.37, t=3.29, p=0.002). The ADHD group with symptoms persisting into adulthood had significantly lower fractional anisotropy than the never-affected controls in these tracts, differences associated with medium to large effect sizes. By contrast, the ADHD group that remitted by adulthood did not differ significantly from controls. The anomalies were found in tracts that connect components of neural systems pertinent to ADHD, such as attention control (inferior fronto-occipital fasciculus) and emotion regulation and the processing of reward (the uncinate fasciculus). Change in radial rather than axial diffusivity was the primary driver of this effect, suggesting pathophysiological processes including altered myelination as future targets for pharmacological and behavioral interventions.


The treatment of alcoholism in France.
Despite a recent decline in per capita alcohol consumption, alcoholism remains a serious public health problem in France. Pharmacotherapy is used to make withdrawal from alcohol easier and to help maintain abstinence. The recent development of effective pharmacologic treatments for alcoholism has increased interest in this approach to therapy. To determine the most appropriate form of pharmacotherapy for treating alcohol dependence, a meta-analysis of randomized controlled studies published between 1960 and 1993 was performed. We found that several pharmacotherapeutic agents had demonstrated safety and efficacy on different periods of follow-up, including acamprosate (long term), naltrexone (intermediate term), fluoxetine and citalopram (short term). Studies of zimeldine, nialamide, L-dopa, viloxazine, and tetrabamate failed to demonstrate efficacy for these agents in the treatment of alcoholism. Results were ambiguous or mixed for lithium, phenytoin, bromocriptine, apomorphine, and buspirone. Continued research is needed to identify the most appropriate patients to receive treatment with specific forms of pharmacotherapy.


Transcription factor networks of oligodendrogliomas treated with adjuvant radiotherapy or observation inform prognosis.
Recent international sequencing efforts have allowed for the molecular taxonomy of lower-grade gliomas (LGG). We sought to analyze The Cancer Genome Atlas (TCGA, 2015) gene expression datasets on molecularly defined oligodendrogliomas (IDH-mutated and 1p/19q-codeleted) patients treated with adjuvant radiation or those observed to discover prognostic markers and pathways. mRNA expression and clinical information of patients with oligodendroglioma were taken from the TCGA "Brain Lower Grade Glioma" provisional dataset. Transcription factor network reconstruction and analysis were performed using the R packages "RTN" and "RTNsurvival." Elastic net regularization and survival modeling were performed using the "biospear," "plsRCox," "survival" packages. From our cohort of 137 patients, 65 received adjuvant radiation and 72 were observed. In the cohort that received adjuvant radiotherapy, a transcription factor activity signature, that correlated with hypoxia, was associated with shorter disease-free survival (DFS) (median = 45 months vs 108 months, P < .001). This increased risk was not seen in patients who were observed (P = .2). Within the observation cohort, a transcription factor activity signature was generated that was associated with poor DFS (median = 72 months. vs 143 months., P < .01). We identified a transcription factor activity signature associated with poor prognosis in patients with molecular oligodendroglioma treated with adjuvant radiotherapy. These patients would be potential candidates for treatment intensification. A second signature was generated for patients who were more likely to progress on observation. This potentially identifies a cohort who would benefit from upfront adjuvant radiotherapy.


Adiposity and the development of dyslipidemia in APOE ε2 homozygous subjects: A longitudinal analysis in two population-based cohorts.
Familial dysbetalipoproteinemia (FD), characterized by remnant lipoprotein accumulation and premature cardiovascular disease, occurs in homozygous carriers of the APOE ε2 allele, but genetic predisposition alone does not suffice for the clinical phenotype. Cross-sectional studies suggest that a second metabolic hit - notably adiposity or insulin resistance - is required, but the association between these risk factors and development of FD has not been studied prospectively. For this study, we evaluated 18,987 subjects from two large prospective Dutch population-based cohorts (PREVEND and Rotterdam Study) of whom 118 were homozygous APOE ε2 carriers. Of these, 69 subjects were available for prospective analyses. Dyslipidemia - likely to be FD - was defined as fasting triglyceride (TG) levels >3 mmol/L in untreated subjects or use of lipid lowering medication. The effect of weight, body mass index (BMI), waist circumference, type 2 diabetes mellitus and non-TG metabolic syndrome on development of dyslipidemia was investigated. Eleven of the 69 ε2ε2 subjects (16%) developed dyslipidemia - likely FD - during follow-up. Age-, sex- and cohort-adjusted risk factors for the development of FD were BMI (OR 1.19; 95%CI 1.04-1.39), waist circumference (OR 1.26 95%CI 1.01-1.61) and presence of non-TG metabolic syndrome (OR 4.39; 95%CI 1.04-18.4) at baseline. Change in adiposity during follow-up was not associated with development of dyslipidemia. Adiposity increases the risk of developing an FD-like lipid phenotype in homozygous APOE ε2 subjects. These results stress the importance of healthy body weight in subjects at risk of developing FD.


MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice.
The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Therefore, BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with MHTP by intranasal or oral routes. Treated animals showed a decrease (p < 0.05) of sneezing, nasal rubbings, and histamine nasal hyperactivity. Besides, MHTP presented binding energy and favorable interaction for adequate anchoring in the histamine H1 receptor. MHTP treatment inhibited the eosinophil migration into the nasal (NALF) and the bronchoalveolar (BALF) fluids. Histological analysis showed that the alkaloid decreased the inflammatory cells in the subepithelial and perivascular regions of nasal tissue and in the peribronchiolar and perivascular regions of lung tissue. The MHTP treatment also reduced the pulmonary hyperactivity by decreasing the smooth muscle layer hypertrophy and the collagen fiber deposition in the extracellular matrix. The immunomodulatory effect of the alkaloid was due to the decrease of cytokines like IL-5 and IL-17A (type 2 and 3), TSLP (epithelial), and the immunoregulatory cytokine, TGF-β. These MHTP effects on granulocytes were dependent on the p38/ERK1/2 MAP kinase signaling pathway axis. Indeed, the synthetic alkaloid reduced the frequency of activation of both kinases independent of the NF-κB (p65) pathway indicating that the molecule shut down the intracellular transduction signals underlie the cytokine gene transcription.


Casting a wide net for endocrine disruptors.
The number of chemicals identified as endocrine disruptors continues to rise, and, yet, many assays intended to prioritize them for further action cannot gauge their impact on cells. Stossi and colleagues present new high-throughput screening methods that inform estrogen receptor biology, leading to questions about "safe alternatives" for one compound, bisphenol A.


Elevated ectodomain of type 23 collagen is a novel biomarker of the intestinal epithelium to monitor disease activity in ulcerative colitis and Crohn's disease.
Impaired intestinal epithelial barrier is highly affected in inflammatory bowel disease. Transmembrane collagens connecting the epithelial cells to the extracellular matrix have an important role in epithelial cell homeostasis. Thus, we sought to determine whether the transmembrane type 23 collagen could serve as a surrogate marker for disease activity in patients with Crohn's disease and ulcerative colitis. We developed an enzyme-linked immunosorbent assay to detect the ectodomain of type 23 collagen (PRO-C23) in serum, followed by evaluation of its levels in both acute and chronic dextran sulphate sodium colitis models in rats and human inflammatory bowel disease cohorts. Serum from 44 Crohn's disease and 29 ulcerative colitis patients with active and inactive disease was included. In the acute and chronic dextran sulphate sodium-induced rat colitis model, the PRO-C23 serum levels were significantly increased after colitis and returned to normal levels after disease remission. Serum levels of PRO-C23 were elevated in Crohn's disease (p < 0.05) and ulcerative colitis (p < 0.001) patients with active disease compared to healthy donors. PRO-C23 differentiated healthy donors from ulcerative colitis (area under the curve [AUC]: 0.81, p = 0.0009) and Crohn's disease (AUC: 0.70, p = 0.0124). PRO-C23 differentiated ulcerative colitis patients with active disease from those in remission (AUC: 0.75, p = 0.0219) and Crohn's disease patients with active disease from those in remission (AUC: 0.68, p = 0.05). PRO-C23 was elevated in rats with active colitis, and inflammatory bowel disease patients with active disease. Therefore, PRO-C23 may be used as a surrogate marker for monitoring disease activity in ulcerative colitis and Crohn's disease.


Further investigations on serum ultrafiltrate as medium for tissue respiration in vitro.
Serum ultrafiltrate was shown to be able to sustain in vitro the oxygen consumption of various tissue slices, attaining values very close to those reached in vivo. Serum ultrafiltrate also exerted its stimulating effect on homogenate, and maintained this activity for some time, after dilution, after lyophilization and after boiling; finally it was not species-specific. Serum ultrafiltrate was also more efficient than Eagle's Minimum Essential Medium in supporting tissue respiration. Preliminary data, obtained from gel fractionating serum ultrafiltrate, suggested that the metabolic activity should be ascribed to a sum of small single effects due to the single fractions of serum ultrafiltrate.


Perinatal hypoxic ischemic encephalopathy affects the proportion of GABA-immunoreactive neurons in the cerebral cortex of the rat.
The hypothesis was tested whether perinatal hypoxic ischemia leads to a preferential degeneration of the GABAergic inhibitory neurons in the cerebral cortex which, in turn, could account for the reported higher risk of developing epilepsy later in life. To that end rat pups, aged 12-13 days, were made hypoxic by employing a combination of unilateral ligation of one of the carotid arteries and a 90-min exposure to 8% O2. After recovery periods of 3, 7, 35 and 150 days, the animals were sacrificed by perfusion fixation and the brains embedded in Epon. Transverse semi-thin sections were alternately stained with an antibody against GABA and with Toluidine blue. By using an unbiased morphometric method (the disector) the number of GABA-immunoreactive (GABA-IR) neurons and the total number of nerve cells per unit volume of tissue were estimated in corresponding neocortical areas in the ipsilateral (damaged) and contralateral ('control') hemisphere. For all animals with post-ischemic survival times of 3 and 7 days GABA-IR cells constituted a lower proportion of the total number of nerve cells in the damaged than in the 'control' cortical areas. This finding was consistent with the outcome of an earlier in vitro study. By contrast, in all animals with a survival time of 35 and 150 days, the proportion of GABA-IR neurons was higher on the damaged than on the 'control' side. This switch in the direction of the left/right differences, apparently depending on the length of the post-ischemic survival time, was statistically significant. No lateralization in the proportion of GABA-IR cells was detected in the cerebral cortex of the control rats. These observations, therefore, do not support the hypothesis that perinatal hypoxic ischemia ultimately leads to a preferential loss of GABAergic neurons in the cerebral cortex.


Aberrant maturation and connectivity of prefrontal cortex in schizophrenia-contribution of NMDA receptor development and hypofunction.
The neurobiology of schizophrenia involves multiple facets of pathophysiology, ranging from its genetic basis over changes in neurochemistry and neurophysiology, to the systemic level of neural circuits. Although the precise mechanisms associated with the neuropathophysiology remain elusive, one essential aspect is the aberrant maturation and connectivity of the prefrontal cortex that leads to complex symptoms in various stages of the disease. Here, we focus on how early developmental dysfunction, especially N-methyl-D-aspartate receptor (NMDAR) development and hypofunction, may lead to the dysfunction of both local circuitry within the prefrontal cortex and its long-range connectivity. More specifically, we will focus on an "all roads lead to Rome" hypothesis, i.e., how NMDAR hypofunction during development acts as a convergence point and leads to local gamma-aminobutyric acid (GABA) deficits and input-output dysconnectivity in the prefrontal cortex, which eventually induce cognitive and social deficits. Many outstanding questions and hypothetical mechanisms are listed for future investigations of this intriguing hypothesis that may lead to a better understanding of the aberrant maturation and connectivity associated with the prefrontal cortex.


Malnutrition-associated high bleeding risk with low thrombogenicity in patients undergoing percutaneous coronary intervention.
Although antithrombotic treatments are established for coronary artery disease (CAD), they increase the bleeding risk, especially in malnourished patients. The total thrombus-formation analysis system (T-TAS) is useful for the assessment of thrombogenicity in CAD patients. Here, we examined the relationships among malnutrition, thrombogenicity and 1-year bleeding events in patients undergoing percutaneous coronary intervention (PCI). This was a retrospective analysis of 300 consecutive CAD patients undergoing PCI. Blood samples obtained on the day of PCI were used in the T-TAS to compute the thrombus formation area under the curve. We assigned patients to two groups based on the geriatric nutritional risk index (GNRI): 102 patients to the lower GNRI group (≤98), 198 patients to the higher GNRI group (98<). The primary endpoint was the incidence of 1-year bleeding events defined by Bleeding Academic Research Consortium criteria types 2, 3, or 5. The T-TAS levels were lower in the lower GNRI group than in the higher GNRI group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the lower GNRI group compared with the higher GNRI group. The combined model of the GNRI and the Academic Research Consortium for High Bleeding Risk (ARC-HBR) had good calibration and discrimination for bleeding risk prediction. In addition, having a lower GNRI and ARC-HBR positivity was associated with 1-year bleeding events. A lower GNRI could reflect low thrombogenicity evaluated by the T-TAS and determine bleeding risk in combination with ARC-HBR positivity.