Increased of serum high-mobility group box chromosomal protein 1 correlated with intestinal mucosal barrier injury in patients with severe acute pancreatitis.
Secondary infections are the leading cause of death in patients with severe acute pancreatitis (SAP). The gut represents the main source of pancreatic contamination and related septic complications. High-mobility group box chromosomal protein 1 (HMGB1) was recently identified to play an important role in the SAP intestinal mucosal barrier dysfunction. To investigate the correlation of high-mobility group box 1 (HMGB1) with intestinal barrier injury and infections in patients with severe acute pancreatitis (SAP). The serum levels of HMGB1, amylase, lipase, and biochemical indicators were measured in 80 patients with SAP at the time of admission. Furthermore, relationship between their serum HMGB1 levels and intestinal barrier injury, infection and other clinical factors were analyzed. The mean value of serum HMGB1 levels was significantly higher in patients with SAP (6.02 ± 2.42 ng/mL) than that in healthy volunteers (1.87 ± 0.63 ng/mL). Serum HMGB1 levels were significantly positively correlated with the Ranson score. The HMGB1 levels were higher in patients with infection during the clinical course, the HMGB1 levels in non-survivors were higher than those in survivors, and positively correlated with DAO activity, L/M ratio, the concentration of endotoxin (R = 0.484, P <0.01). HMGBl level of patients with severe acute pancreatitis was significantly increased, and can be used as an important indicator to determine the intestinal barrier dysfunction and infection.


Bringing Global Health Home: The Case of Global to Local in King County, Washington.
The article describes the experience of testing successful global health interventions in the cities of SeaTac and Tukwila, Washington-2 very diverse, underserved communities outside of Seattle that experience significant health disparities compared with surrounding areas in King County. Topics covered include an overview of the partnership that established Global to Local, the process of engaging Seattle-based global health institutions in identifying global health strategies to test, identifying communities experiencing health disparities that might benefit from global health-inspired interventions, engaging those local communities to understand the perceived drivers of poor health outcomes, tailoring global interventions to the local context, launching programs, and the successes and challenges that have emerged throughout this process. Global health strategies that were tested and are reported on in the article include the use of community health workers to support chronic disease prevention and management, partnering with and building the capacity of local organizations and institutions, linking public health and primary care by addressing the social determinants of health in a primary care and community setting, and using mobile phones to transform practices for managing type 2 diabetes. The paper concludes that based on the early learnings of this approach, there is value in looking to tested and proven global health strategies to address health disparities in underserved communities in the United States and calls for further exploration of this approach by other actors.


The Effect of Arthroscopic Extra-Articular Entire Coracohumeral Ligament Release for Patients with Recalcitrant Frozen Shoulder.
The thickened coracohumeral ligament (CHL) is an important part of the typical manifestations and magnetic resonance imaging of frozen shoulder. However, only a few clinical studies with limited cases on arthroscopic extra-articular entire CHL release exist in the literature. This study was to evaluate the effect of arthroscopic extra-articular entire CHL release for patients with recalcitrant frozen shoulder. From February 2014 to February 2020, 81 cases of recalcitrant frozen shoulder patients treated with surgery in a single-center shoulder department and followed for more than 2 years were analyzed. Arthroscopic 360° capsular release was performed with intra-articular partial release (IPR group) or additional extra-articular entire release (IPR + EER group) of CHL. The same rehabilitation program was performed after surgery in both groups. Visual analogue scale (VAS) for pain, range of motion (ROM), and the Constant-Murley scoring system was evaluated before operation, at 3 months after operation, 6 months after operation, and the final follow-up. T-test, Mann-Whitney U-test and chi-squared test were used to compared data. There were 39 patients in the IPR group, with an average follow-up of 29.2 months. A total of Forty-two patients in the IPR + EER group completed a mean follow-up of 25.7 months. All incisions healed in stages. There were significant differences in Constant-Murley shoulder score, VAS score, and ROM before operation and at the final follow-up in both groups (both P < 0.001). The VAS score of the IPR + EER group was lower than that of the IPR group at 3 months after surgery (P < 0.05), and 6 months after operation (P < 0.05). External rotation, internal rotation, and abduction of ROMs and Constant-Murley shoulder score were significantly greater in the IPR + EER group at 3 months (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively) and 6 months after operation (P < 0.001, P < 0.05, P < 0.001, P < 0.05, respectively). At the last follow-up, there was no significant difference in forward flexion, internal rotation, and abduction of ROMs, VAS, and the Constant-Murley shoulder score between the IPR and IPR + EER groups. The external rotation of the IPR + EER group was still greater than that of the IPR group at the last follow-up (P < 0.001). Arthroscopic extra-articular entire coracohumeral ligament release could solve early pain of shoulder joint, recover shoulder joint functions effectively, and achieve a satisfactory efficacy in the treatment of recalcitrant frozen shoulder.


Serological typing of reference strains and clinical isolates of Streptococcus mutans by agglutination reactions and/or radioimmunoassay.
Rabbit antisera were prepared against eight different serotypes of Streptococcus mutans. After absorption with heterologous serotype strains the antisera were able to distinguish 21 reference strains of different serotypes of S. mutans by simple agglutination reactions and radioimmunoassay, both using intact whole cells. The reference serotypes a, b, d and g were differentiated by specific agglutination using the corresponding monospecific antiserum. Strains of serotypes c, e, f and h were discriminated by differential agglutination using anti-c, anti-e, anti-f or anti-h serum respectively, but the antisera cross-reacted slightly with other serotype strains. Using these antisera a total of 261 clinical isolates of S. mutans from human dental plaques were serotyped by agglutination reactions, in addition to which radioimmunoassay and the classical immunodiffusion tests in agar were also used in some cases. The results were quite consistent in the three methods. The predominant strain was of serotype c (187), followed by serotype f (28), g (10), d (5), e (4) and b (1). 26 strains were untypable and there were no serotype a or h strains.


Helicobacter pylori: diseases, tests and treatment.
Gastroduodenal disease associated with Helicobacter pylori infection are reviewed as well as the diagnostic approach. Generally, there are by and large two ways in which a diagnosis of infection by Helicobacter pylori can be made: by using either an invasive or non-invasive procedure. The invasive procedures involve endoscopy and biopsy Biopsy is essential since the mucosa may often appear macroscopically normal but, nevertheless, be inflamed. Once a biopsy is obtained histological examination, culture, polymerase chain reaction, detection of the presence of urease activity can be detected. The non-invasive tests that can be used to diagnose the infection are: serology, detection of labelled metabolic products of urea hydrolysis either in the breath (13CO2, 14CO2), the urine or the blood, detection of Helicobacter pylori antigen in stool specimen. At present, no single test is sufficiently reliable to definitely detect colonisation by Helicobacter pylori, and a combination of two is recommended, if feasible. Choice of the test to be used is not straightforward and relies on a series of situations, i. e., clinical setting and local expertise and availability, that the clinician must consider to obtain the best diagnostic yeld. The challenge of Helicobacter pylori eradication is not very easy to obtain. The possible scenario and the use of a new proton pump inhibitor (esomeprazole) are reviewed and discussed.


Suppressing effect of cysteamine on the TSH-stimulated mitotic activity of the rat thyroid follicular cells in vivo.
We have examined the effect of the thiol agent-cysteamine, known to deplete the hypothalamus, the pancreas, the gut of somatostatin--on the basal and TSH-stimulated mitotic activity of the thyroid follicular cells (TFC) in adult male rats in vivo. The animals of different groups were administered cysteamine alone (300 mg/kg BW, s.c.), TSH alone (2IU, i.p.), or cysteamine with TSH jointly, the former agent being injected 2 hrs prior to the latter. In order to evaluate the thyroid mitotic activity, the metaphase-arrest technique was used in the study. It was shown that: 1. TSH significantly increased the mitotic activity of TFC, as compared to controls, 2. cysteamine alone had no effect on the TFC proliferation, 3. unexpectedly, cysteamine, when administered 2 hrs prior to TSH, suppressed the stimulatory effect of TSH on the mitotic activity of TFC.


Do differences in diagnostic criteria for late fetal growth restriction matter?
Criteria for diagnosis of fetal growth restriction differ widely according to national and international guidelines, and further heterogeneity arises from the use of different biometric and Doppler reference charts, making the diagnosis of fetal growth restriction highly variable. This study aimed to compare fetal growth restriction definitions between Delphi consensus and Society for Maternal-Fetal Medicine definitions, using different standards/charts for fetal biometry and different reference ranges for Doppler velocimetry parameters. From the TRUFFLE 2 feasibility study (856 women with singleton pregnancy at 32+0 to 36+6 weeks of gestation and at risk of fetal growth restriction), we selected 564 women with available mid-pregnancy biometry. For the comparison, we used standards/charts for estimated fetal weight and abdominal circumference from Hadlock, INTERGROWTH-21st, and GROW and Chitty. Percentiles for umbilical artery pulsatility index and its ratios with middle cerebral artery pulsatility index were calculated using Arduini and Ebbing reference charts. Sensitivity and specificity for low birthweight and adverse perinatal outcome were evaluated. Different combinations of definitions and reference charts identified substantially different proportions of fetuses within our population as having fetal growth restriction, varying from 38% (with Delphi consensus definition, INTERGROWTH-21st biometric standards, and Arduini Doppler reference ranges) to 93% (with Society for Maternal-Fetal Medicine definition and Hadlock biometric standards). None of the different combinations tested appeared effective, with relative risk for birthweight <10th percentile between 1.4 and 2.1. Birthweight <10th percentile was observed most frequently when selection was made with the GROW/Chitty charts, slightly less with the Hadlock standard, and least frequently with the INTERGROWTH-21st standard. Using the Ebbing Doppler reference ranges resulted in a far higher proportion identified as having fetal growth restriction compared with the Arduini Doppler reference ranges, whereas Delphi consensus definition with Ebbing Doppler reference ranges produced similar results to those of the Society for Maternal-Fetal Medicine definition. Application of Delphi consensus definition with Arduini Doppler reference ranges was significantly associated with adverse perinatal outcome, with any biometric standards/charts. The Society for Maternal-Fetal Medicine definition could not accurately detect adverse perinatal outcome irrespective of estimated fetal weight standard/chart used. Different combinations of fetal growth restriction definitions, biometry standards/charts, and Doppler reference ranges identify different proportions of fetuses with fetal growth restriction. The difference in adverse perinatal outcome may be modest, but can have a significant impact in terms of rate of intervention.


Elucidation of microbial nitrogen-transformation mechanisms in activated sludge by comprehensive evaluation of nitrogen-transformation activity.
Using prepared nitrifying sludge, anaerobic ammonia oxidization (anammox) sludge and two heterotrophic ammonia oxidization bacterial (AOB) species as inocula, this study elucidated the effect of oxygen conditions, assay media, and selective metabolic inhibitors on various microbial nitrogen (N)-transformation activities including aerobic chemolithotrophic ammonia and nitrite oxidization, aerobic heterotrophic ammonia oxidization, anammox, and aerobic and anoxic denitrification. The oxygen conditions and assay media effectively differentiated among almost all ammonia removal pathways except for separating aerobic chemolithotrophic ammonia oxidization from aerobic heterotrophic ammonia oxidization. A final allylthiourea concentration of 10mg·L-1 was optimal for accurate determination of aerobic heterotrophic ammonia oxidization activity in the presence of aerobic chemolithotrophic AOB. Finally, this study developed a simple and reliable method to individually determine and compare the comprehensive N-transformation activity characteristics of several activated sludge samples from different origins, and to elucidate the major microbial N-transformation mechanisms for ammonia removal and N2 production.


Evaluation of the One-Hour ¹³C-Propionate Breath Test in 49 Patients from a Single Center in Japan to Detect Vitamin B₁₂ Deficiency.
BACKGROUND Given the unavailability of reliable biomarkers for vitamin B₁₂ (VB₁₂) deficiency in clinical settings, the usefulness of the ¹³C-propionate breath test (PBT), utilizing VB₁₂ as a coenzyme of methylmalonyl-CoA in propionate metabolism, as a diagnostic modality for VB₁₂ deficiency has been studied. However, a collection time of 2 h reduces its convenience. Hence, we evaluated the effectiveness of 1-h PBT for detecting VB₁₂ deficiency in 49 patients with suspected VB₁₂ deficiency. MATERIAL AND METHODS We collected 100-200 mL breath gas every 10 min until 1 h after the administration of 1 g of ¹³C-propionate from 49 patients (31 men, 18 women; median age, 70 years) with clinically suspected VB₁₂ deficiency and calculated the ¹³CO₂ recovered in the breath per hour as the recovery rate (RR [%dose/h]) from ¹³CO₂/¹²CO₂ using infrared isotope spectrometry. We compared the RRs between groups: (1) with serum VB₁₂ levels ≥145 pg/mL and <145 pg/mL, (2) with mean corpuscular volume ≤100 fL and >100 fL, and 3) pre- and post-VB₁₂ supplementation. RESULTS The RRs peaked within 30 min. The RRs at 20 min (RR20) and 30 min (RR30) were significantly lower in macrocytotic patients (41.28 vs 50.07, p=0.026 and 37.82 vs 43.93, P=0.003). The RR30 was higher in the supplemented patients (41.93 vs 32.84, P=0.024). There was no significant difference in RRs between the patients with normal and low serum VB₁₂ levels. CONCLUSIONS The 1-h PBT can be a diagnostic modality for VB₁₂ deficiency because 1 h is a sufficient collection time.


Methadone alters transcriptional programs associated with synapse formation in human cortical organoids.
Opioid use disorder (OUD) among pregnant women has become an epidemic in the United States. Pharmacological interventions for maternal OUD most commonly involve methadone, a synthetic opioid analgesic that attenuates withdrawal symptoms and behaviors linked with drug addiction. However, evidence of methadone's ability to readily accumulate in neural tissue, and cause long-term neurocognitive sequelae, has led to concerns regarding its effect on prenatal brain development. We utilized human cortical organoid (hCO) technology to probe how this drug impacts the earliest mechanisms of cortico-genesis. Bulk mRNA sequencing of 2-month-old hCOs chronically treated with a clinically relevant dose of 1 μM methadone for 50 days revealed a robust transcriptional response to methadone associated with functional components of the synapse, the underlying extracellular matrix (ECM), and cilia. Co-expression network and predictive protein-protein interaction analyses demonstrated that these changes occurred in concert, centered around a regulatory axis of growth factors, developmental signaling pathways, and matricellular proteins (MCPs). TGFβ1 was identified as an upstream regulator of this network and appeared as part of a highly interconnected cluster of MCPs, of which thrombospondin 1 (TSP1) was most prominently downregulated and exhibited dose-dependent reductions in protein levels. These results demonstrate that methadone exposure during early cortical development alters transcriptional programs associated with synaptogenesis, and that these changes arise by functionally modulating extra-synaptic molecular mechanisms in the ECM and cilia. Our findings provide novel insight into the molecular underpinnings of methadone's putative effect on cognitive and behavioral development and a basis for improving interventions for maternal opioid addiction.


Full thoracoscopic approach for surgical management of invasive pulmonary aspergillosis.
Invasive pulmonary aspergillosis (IPA) is a frequent and serious infection occurring in patients with hematologic malignancies and allogenic stem cell transplant (SCT) recipients, causing a high mortality rate. We report the use of full thoracoscopic management in 19 patients. Nineteen patients (mean age 27 years) with diagnosed or probable IPA were operated on. Seventeen had an hematologic malignancy and 2 had a refractory aplastic anemia. Nine patients had undergone an allogenic SCT that was complicated by a graft-versus-host disease in 5 patients. In 3 patients, SCT was pending. All patients had preoperative systemic antifungal therapy for at least 2 weeks. Fifteen patients had only one lesion, whereas 4 had two lesions. Eight patients had an absolute neutrophil count less than 3,000 and 2 less than 1,000, and 9 were thrombopenic (platelet count <60,000) at the day of surgery. Wedge resections were performed in 7 patients and lobectomies were performed for the other 12. For the latter, an open approach via posterolateral thoracotomy was decided upon in only 1 patient. For the other 11 lobectomies, a mini-thoracotomy was needed in 3 cases for intraoperative difficulties. Conversion to conventional thoracotomy was necessary for 2 of these patients. In total, out of the 19 patients, 15 had a total endoscopic approach, 3 had a thoracotomy, and 1 had a video-assisted approach. There was no intraoperative mortality. In the group of wedge resections, no intraoperative or postoperative complication occurred. In the lobectomy group, three hemorrhages occurred during dissection of the pulmonary artery in the fissure, leading to conversion to a mini-thoracotomy in 2 patients and to a classic posterolateral thoracotomy in 1 patient. There were two minor complications: one pneumothorax and one mild pleural effusion. In these debilitated and immunocompromised patients, a full thoracoscopic resection of fungal infection is feasible, even for lobectomies. It allows a simpler postoperative course and minimizes sequelae.


Rickettsia raoultii and Rickettsia sibirica in ticks from the long-tailed ground squirrel near the China-Kazakhstan border.
Spotted fever group (SFG) rickettsiae cause infection in humans, domestic animals and wildlife. To date, no rickettsial agents have been reported in hard ticks from the long-tailed ground squirrel (Spermophilus undulatus). A total of 50 adult ticks and 48 nymphs were collected from S. undulatus in the border region of northwestern China. Tick species (identified according to morphological and molecular characteristics) included Dermacentor nuttalli, Dermacentor silvarum and Ixodes kaiseri. Based on the cytochrome c oxidase subunit I (COI) haplotype analysis, I. kaiseri from S. undulatus belongs to an ancestral. In addition, all tick samples were analyzed for the presence of rickettsiae by PCR amplification and sequencing of six genetic markers. Rickettsia raoultii and Rickettsia sibirica subsp. sibirica were shown to occur in adults and nymphs of D. nuttalli and D. silvarum. Rickettsia sibirica subsp. sibirica was also detected in an I. kaiseri adult. Dermacentor silvarum and I. kaiseri were found for the first time on S. undulatus. Rickettsia raoultii and R. sibirica subsp. sibirica were detected in two Dermacentor and one Ixodes species, respectively, suggesting that these rickettsiae circulate in the region of the China-Kazakhstan border by hard ticks infesting S. undulatus.


The Use of Enteric Contrast in the Emergency Setting.
Historically, computed tomography of the abdomen and pelvis had been performed routinely with enteric contrast to help improve diagnostic accuracy. However, the utility of enteric contrast has been called into question recently, particularly in the high-patient-volume setting of the emergency department. This article reviews the role of enteric contrast in the emergency setting. Particular emphasis is given to specific clinical scenarios in which enteric contrast provides value. These include the identification of abdominal postsurgical complications such as anastomotic leaks and fistulas, detection of penetrating bowel injuries, evaluation of acute appendicitis, and assessment of small-bowel obstructions.


The role research gap years play in a successful dermatology match.
A new trend includes taking a dedicated year away from medical school to complete a research fellowship. There is minimal data on the benefit of a gap year. We aimed to identify if a gap year makes a dermatology applicant more successful in The Match. Dermatology applicants who applied to Mayo Clinic Arizona for the 2018-2019 application cycle and Mayo Clinic Rochester, Arizona, and Florida for the 2019-2020 application cycle were surveyed. In total, 291 dermatology applicants completed the initial survey, and 236 completed the follow-up survey. Ninety applicants took a gap year, 198 applicants did not. There was no significant difference in match rates. When comparing match rates at top dermatology residency programs, 40.6% of gap-year applicants matched to these residencies versus 19.0% of no gap-year applicants (P < 0.01). Applicants should weigh the opportunity costs before pursuing research gap years as they may not be universally helpful. Applicants who want to match at a top dermatology program may benefit from a research gap year. This data may have limited generalizability outside of the United States.


Results of a colpocytologic mass screening and in-patient casework: comparison by age groups.
This paper reports the results of cervico-vaginal examinations performed on the women (7,098) resident in the municipality of Bollate (mass screening) and the women (1,416) hospitalized in the Gynecologic ward in the same period (in-patients). Age distribution, prevalence of initial and invasive forms, and prevalence according to age groups have been considered. The results are: 1) any kind of lesion is more frequent among in-patient than mass-screening subjects; 2) the prevalence of benign displasia, incipient, in situ and invasive carcinoma per age group, considered per quinquennium, shows a three-phase trend, both in mass screening and in-patient cases; 3) the time of evolution is different for cervicocarcinoma in the different age groups of incipience. Periodic checks are a useful means of precocious diagnosis of cervicocarcinoma; the frequency of checks should vary according to patient age.


Measurement of pH and calcium ions release from different calcium hydroxide pastes at different intervals of time: Atomic spectrophotometric analysis.
To evaluate the effect of different vehicles on pH and release of calcium ions from calcium hydroxide (CH) paste from apical third of root canals. 40 single rooted extracted human mandibular premolars were instrumented with RevoS files (MicroMega) up to ISO size 40. The teeth were divided into 4 groups on the basis of vehicle as follows: Group I - calcium hydroxide mixed with 2% chlorhexidine; Group II - calcium hydroxide mixed with propylene glycol; Group III - calcium hydroxide mixed with glycerine; and Control - calcium hydroxide mixed with double distilled water. Each group had two subgroups (n = 5) on the basis of the calcium hydroxide delivery. Subgroup A - calcium hydroxide paste placed with spiral filler (Lentulospiral) subgroup B - calcium hydroxide paste placed with flat wire filler (Paste Inject). pH and calcium ion release was evaluated at 24 h, 48 h, 7th day, 15th day and 30th day using a pH meter and atomic absorption spectrophotometer respectively. The calcium release from various groups was highest for CH+glycerine (Group III) followed by CH+chlorhexidine (Group I), CH+propylene glycol (Group II) and CH+double distilled water (control). At all the intervals the differences in calcium ion release among the groups were statistically significant (p < 0.05), except on day 7. Delivery technique did not have a significant effect on calcium ion release. Highest pH values were recorded from CH+glycerine group at day 30 for both the delivery systems, however rise in pH from day 1 to day 30 were non-significant in all groups with both delivery systems. Demonstrable changes in calcium ion release occurred from the calcium hydroxide mixed with various vehicles and CH+glycerine group showed the maximum calcium ion release at all intervals and highest pH day 30.


A research tool for general practitioners.
In this paper a research tool for general practitioners is described, that will be used in a network of community-based primary care practices in order to collect the necessary data for research purpose. The research tool is coupled to a commercial information system for general practitioners. The research tool supports coding strongly. The way in which the research tool is designed is described and examples of the use of windowing techniques are given.


Pressure inhibition of the Koebner reaction by capillary occlusion.
A 38-year-old male with extensive psoriasis received a linear experimental abrasion. Immediate pressure was applied for 24 hours to the central portion of the traumatized site. During a psoriatic relapse 5 weeks later, Koebnerization occurred in the abraded areas but spared the site where pressure had been previously applied. The mechanism is not known but may be due to a local suppressive effect of pressure on inflammation.


Enantioselective gas chromatographic assays with electron-capture detection for methoxyphenamine and its three primary metabolites in human urine.
Sensitive and enantioselective gas chromatographic assays have been developed and applied to the quantitation in human urine of the enantiomers of methoxyphenamine and its three primary oxidative metabolites, namely, N-desmethylmethoxyphenamine, O-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine. The separation of the various analytes was achieved through the combined use of high-resolution gas chromatography coupled with electron-capture detection and employing a capillary OV-225 column. The formation of diastereometric derivatives involved the chiral acylating reagent N-heptafluorobutyryl-L-prolyl chloride. The assays for methoxyphenamine and O-desmethylmethoxyphenamine were linear over the range 0.25-2.0 micrograms/ml for each analytes' enantiomers, while in the case of the enantiomers for N-desmethylmethoxyphenamine and 5-hydroxymethoxyphenamine linearity was shown over the ranges 0.094-0.75 and 0.188-1.5 micrograms/ml, respectively. The mean coefficients of variation in all cases were less than 4%.


Validation of a self-administered form for recording food intake in hospital patients.
Validation a self-administered form used by patients to record their food intake and compare the recorded data with the observed intake. Data were obtained from an unselected cross-sectional group of hospitalized patients. Forty-five adult men and women volunteered to participate. Five of these dropped out. Observed intake at breakfast, lunch and dinner was obtained by recording the servings of food before they were served to the patients and subtracting weighed leftovers. At meal times the patients recorded food items eaten in fractions of amount served to the nearest 25%. Inpatients from five different wards at Rikshospitalet, Oslo. There was a significant under-reporting of the number of foods served (P < 0.005) resulting in a significant underestimation of energy 231 kJ (P < 0.02). There was good agreement between the patients and the observers for the portions of most foods (Kappa 0.44-0.92, P < 0.00001). The differences in amount had little influence on the difference in total energy. The difference in number of foods correlated with the difference in energy (r = 0.68, P < 0.001) and with the difference in protein (r = 0.50, P < 0.01). Patients with an underestimation of energy above 20% had forgotten seven or more food items. For most patients, the self-administered form adapted to the hospital menu appears to have acceptable validity, but for some patients it was unacceptable, mainly owing to food items being omitted and not because of incorrect estimate of amounts of food.


Prognostic assessment in coronary artery disease: role of radionuclide angiography.
Left ventricular function is one of the most important determinants, if not the most important determinant, of outcome in patients with coronary artery disease. The ability of radionuclide angiography to assess resting and exercise ejection fraction accurately and reproducibly has been shown to be a critical determinant of survival in large-scale studies of survivors of myocardial infarction, as well as patients with chronic stable angina. In addition, several centers have demonstrated that the exercise ejection fraction is an extremely valuable (and perhaps the most valuable) noninvasive parameter in predicting survival among patients with coronary artery disease. The prognostic insights gained from the exercise ejection fraction add incremental predictive information to the coronary anatomic information obtained from coronary arteriography, especially in patients with multivessel disease and those with left ventricular dysfunction at rest.


Sonographic fetal asymmetry predicts shoulder dystocia.
The purpose of this study was to evaluate the performance of a sonographic measurement of fetal asymmetry, abdominal diameter minus biparietal diameter (AD - BPD), in the prediction of shoulder dystocia (SD) in a patient population that was unselected for diabetes mellitus (DM) status. Patients who underwent sonographic estimations of fetal biometric measurements within 14 days of vaginally delivered live-born singleton neonates weighing 3400 g or greater at a tertiary care institution were included in this retrospective cohort. The mean AD - BPD was retrospectively compared in deliveries complicated by SD with those without SD by the Student t test. A receiver operating characteristic curve was generated to determine the optimal cutoff for SD prediction. Test performance characteristics of AD - BPD were determined. Of 5204 deliveries, 332 met inclusion criteria. Shoulder dystocia complicated 23 deliveries (6.9%). The mean AD - BPD was significantly higher in the dystocia group (2.39 versus 1.97; P = .0002). With an AD - BPD of 2.6 cm or greater, the risk rates of SD were 25% for unselected patients and 38.5% with DM. An AD - BPD of 2.6 cm or greater identifies a subset of patients with and without DM at risk for SD.


Cliv-92-Loaded Glycyrrhetinic Acid-Modified Chitosan Nanoparticles for Enhanced Hepatoprotection-Preparation, Characterization, and In Vivo Evaluation.
Cliv-92 is a mixture of three structurally similar coumarinolignoids and a proven hepatoprotective agent. Low aqueous solubility and poor bioavailability are notable hindrances for its further use. Therefore, glycyrrhetinic acid-linked chitosan nanoparticles loaded with Cliv-92 were prepared for active targeting to the liver. The nanoparticles were prepared by the ionic gelation method to avoid the use of toxic solvents/rigorous agitation. The method of preparation was optimized using a central composite design with independent variables, namely polymer: drug ratio (3:1, w/w), crosslinker concentration (0.5%), and stirring speed (750 rpm). The optimized nanoparticles had a mean particle size of 185.17 nm, a polydispersity index of 0.41, a zeta potential of 30.93 mV, and a drug loading of 16.30%. The prepared formulation showed sustained release of approximately 63% of loaded Cliv-92 over 72 h. The nanoparticles were freeze-dried for long-term storage and further characterized. The formulation was found to be biocompatible for parenteral delivery. In vivo imaging study showed that optimized nanoparticles were preferentially accumulated in the liver and successfully targeting the liver. The present study successfully demonstrated the improved pharmacokinetic properties (≈12% relative bioavailability) and efficacy profile (evidenced by in vivo and histopathological studies) of fabricated Cliv-92 nanoparticles.


Molecular Variability and Host Distribution of 'Candidatus Phytoplasma solani' Strains from Different Geographic Origins.
The knowledge of phytoplasma genetic variability is a tool to study their epidemiology and to implement an effective monitoring and management of their associated diseases. 'Candidatus Phytoplasma solani' is associated with "bois noir" disease in grapevines, and yellowing and decline symptoms in many plant species, causing serious damages during the epidemic outbreaks. The epidemiology of the diseases associated with this phytoplasma is complex and related to numerous factors, such as interactions of the host plant and insect vectors and spreading through infected plant propagation material. The genetic variability of 'Ca. P. solani' strains in different host species and in different geographic areas during the last two decades was studied by RFLP analyses coupled with sequencing on vmp1, stamp, and tuf genes. A total of 119 strains were examined, 25 molecular variants were identified, and the variability of the studied genes was linked to both geographic distribution and year of infection. The crucial question in 'Ca. P. solani' epidemiology is to trace back the epidemic cycle of the infections. This study presents some relevant features about differential strain distribution useful for disease monitoring and forecasting, illustrating and comparing the phytoplasma molecular variants identified in various regions, host species, and time periods.


Naive and memory B cells in T-cell-dependent and T-independent responses.
This review focuses on the properties and roles of distinct subsets among the primary and the memory B lymphocytes regarding their contribution to helper-T-cell-dependent and -independent antibody responses. The naive/memory B cell functions are explained in the context of current concepts on the basic mechanisms of humoral immunity. Differences between murine and human B cells are also discussed.


[Clinical chemistry and preventive medicine (author's transl)].
In a workshop conference of the German Society for Clinical Chemistry, clinical chemical parameters, which are important in preventive medicine, were discussed for three common diseases, diabetes mellitus, gout and chronic liver diseases. In addition the analytical and diagnostic reliability was evaluated for each of these parameters.


Solidago canadensis as a bioaccumulator and phytoremediator of Pb and Zn.
Canadian goldenrod (Solidago canadensis L.) is a plant that grows in a variety of environmental conditions. It shows high capability to spread in various habitats, including fallow lands and brownfield land. The research aimed at analyzing the content of Pb and Zn in the underground (roots, rhizomes) and aboveground parts (stems, leaves, inflorences) of Solidago canadensis (SC) originating from two locations that are clearly different in terms of metal content in soil. Statistically significant differences were determined in the content of Pb and Zn in soil and particular morphological parts of the plant, depending on the sampling location. It has been shown that in the conditions of increased (compared with natural) Pb and Zn content in the soil, SC may serve as a bioaccumulator of these metals. It was determined that SC can be used as a phytostabilizer of Pb and Zn in soils heavily contaminated with these elements. The content of Zn in the aboveground parts of SC indicates that this plant can also be used for phytoextraction of soils contaminated with this metal.


Acute effects of different proprioceptive neuromuscular facilitation stabilization techniques on the balance of elderly women.
To compare the acute effects of rhythmic stabilization (RS) and stabilizer reversal (SR) techniques of PNF on the balance of sedentary elderly women. Women aged (≥70) were allocated into three groups: RS, SR and control (CR). The experimental groups (RS and SR) performed balance exercises with the addition of rhythmic stabilization techniques (RS group) or with stabilizers reversal (SR group) for 15 min. The CR group performed the exercises without adding the PNF stabilization techniques. Participants performed the Time Up and Go (TUG) test, the Functional Reach Test (FRT) and static and dynamic stabilometry pre and post intervention. Kruskal-Wallis and Mann-Whitney tests were used for comparison between groups and post hoc analysis, respectively, with p ≤ 0.05. For the effect size measurements, the r for Wilcoxon and Mann-Whitney signal were used. For functional tests intra-group analysis, a reduction in TUG time and an increase in FRT range (p ≤ 0.05) were observed in RS e SR groups. Stabilometry analysis showed a significant difference only for the RS group, with reduced average velocity of the centre of pressure (COP), and an increased in the left foot pressure. A single RS or SR session reduced the TUG time and the range distance in the FRT in elderly women. A single session of the RS technique was also able to reduce the mean velocity of the COP and the maximum pressure on the left foot. This study shows an easy-to-apply methods without additional materials that can help prevent falls in the elderly.


Acupuncture to alleviate chemotherapy-induced nausea and vomiting in pediatric oncology - a randomized multicenter crossover pilot trial.
We investigated whether acupuncture as a supportive antiemetic approach reduces the need for antiemetic rescue medication during highly emetogenic chemotherapy in pediatric oncology. We report on a multicenter crossover study at 5 tertiary hospitals in Germany. Twenty-three children (13.6 y,+/- 2.9) receiving highly emetogenic chemotherapy for treatment of solid malignant tumors were included. Patients were randomly allocated to receive acupuncture treatment during either the second or third identical chemotherapy course together with standard antiemetic medication. The main outcome measure was the amount of additional antiemetic medication during chemotherapy. Secondary outcome measure was the number of episodes of vomiting per course. Fourty-six chemotherapy courses with or without acupuncture were compared. The need for rescue antiemetic medication was significantly lower in acupuncture courses compared to control courses (p=0.001) Episodes of vomiting per course were also significantly lower in courses with acupuncture (p=0.01). Except for pain from needling (4/23) no side effects occurred. Patients acceptance of acupuncture was high. Acupuncture as applied here seems to be effective in preventing nausea and vomiting in pediatric cancer patients.


The anti-apoptotic effect of fluid mechanics preconditioning by cells membrane and mitochondria in rats brain microvascular endothelial cells.
Exercise preconditioning is a simple and effective way to prevent ischemia. This paper further provided the mechanism in hemodynamic aspects at the cellular level. To study the anti-apoptotic effects of fluid mechanics preconditioning, Cultured rats brain microvascular endothelial cells were given fluid intervention in a parallel plate flow chamber before oxygen glucose deprivation. It showed that fluid mechanics preconditioning could inhibit the apoptosis of endothelial cells, and this process might be mediated by the shear stress activation of Tie-2 on cells membrane surface and Bcl-2 on the mitochondria surface.


Anti-tumor effects of dual PI3K-HDAC inhibitor CUDC-907 on activation of ROS-IRE1α-JNK-mediated cytotoxic autophagy in esophageal cancer.
PI3K-Akt pathway activation and the expression of histone deacetylases (HDACs) are highly increased in esophageal cancer, suggesting that inhibition of such targets may be a viable therapeutic strategy. Herein, we aimed to evaluate the anti-tumor effect of CUDC-907, a dual PI3K-HDAC inhibitor, in esophageal squamous cell carcinoma (ESCC). The anti-tumor effects of CUDC-907 in ESCC were evaluated using cell counting kit-8, flow cytometry, and western blot. mRNA-sequencing was used to explore the mechanism underlying CUDC-907 anti-tumor effects. The relations of reactive oxygen species (ROS), lipocalin 2 (LCN2), and CUDC-907 were determined by flow cytometry, rescue experiments, and western blot. The activation of the IRE1α-JNK-CHOP signal cascade was confirmed by western blot. The in vivo inhibitory effects of CUDC-907 were examined by a subcutaneous xenograft model in nude mice. CUDC-907 displayed effective inhibition in the proliferation, migration, and invasion of ESCC cells. Through an mRNA-sequencing and functional enrichment analysis, autophagy was found to be associated with cancer cells death. CUDC-907 not only inhibited the PI3K-Akt-mTOR pathways to result in autophagy, but also induced ROS accumulation to activate IRE1α-JNK-CHOP-mediated cytotoxic autophagy by downregulating LCN2 expression. Consistently, the in vivo anti-tumor effects of CUDC-907 accompanied by the downregulated expression of p-mTOR and LCN2 and upregulated expression of p-IRE1α and LC3B-II were evaluated in a xenograft mouse model. Our findings suggested the clinical development and administration of CUDC-907 might act as a novel treatment strategy for ESCC. A more in-depth understanding of the anti-tumor effect of CUDC-907 in ESCC will benefit the clinically targeted treatment of ESCC.


Insulin-induced hypoglycemia does not impair the surge of luteinizing hormone secretion in the proestrous rat.
To know whether insulin-induced hypoglycemia (IIH), which has been shown to inhibit pulsatile luteinizing hormone (LH) secretion, also affects the surge of LH secretion, adult female rats were injected with insulin (5 units/rat) or saline intravenously at 1300 or 1600 h on the day of proestrus and serum concentrations of LH and blood glucose were determined during the period from 1100 to 2100 h. The injection of insulin at neither 1300 nor 1600 h affected the surge of LH secretion, but it significantly decreased the blood glucose. Together with our recent hypothesis that the pulsatile and surge of LH secretion are controlled by separate gonadotropin-releasing hormone (GnRH) mechanisms, we conclude that the GnRH surge generator is less sensitive to IIH than the GnRH pulse generator.


Serum IgG4 anti-Fab antibodies in rheumatoid arthritis are constitutively expressed.
IgG4 comprises a significant proportion of the total anti-Fab antibody (aFABA) response in many but not all patients with rheumatoid arthritis (RA). Analyses of the dynamics of IgG aFABA subclass expression in 11 RA patients for periods of up to 11 months demonstrated that IgG4 aFABA was restricted to 6 of the 11 RA patients' sera initially studied and comprised approximately 25% (or more) of the total IgG aFABA response. Quantities of IgG4 aFABA in subsequent, serially obtained serum samples from these patients remained stable throughout the study period, whereas the remaining RA patients whose initial sera possessed small quantities of serum IgG4 aFABA failed to generate any augmented IgG4 aFABA response during the study. Elevated expression of IgG4 aFABA did not appear to be a consequence of a generalized polyclonal gammopathy or a generalized increase in autoantibody expression, though patients with higher total IgG4 serum levels expressed significantly greater quantities of IgG4 aFABA. These results indicate that the differential expression of IgG4 aFABA among RA patients reflects constitutive production within a subset of RA patients in whom IgG4 appears to comprise a significant proportion of the total IgG aFABA response.


Fetal Repair of Neural Tube Defects.
Myelomeningocele is the most common congenital neurologic defect, and the only nonlethal disease addressed by fetal surgery. A randomized control trial has established amelioration of the Arnold-Chiari II malformation, reduced ventriculoperitoneal shunt rate, and improvement in distal neurologic function in patients that receive in utero repair. Long-term follow-up of these school-age children demonstrates the persistence of these effects. The use of stem cells in fetal repair is being investigated to further improve distal motor function.


Author Correction: Telomeres in cancer: tumour suppression and genome instability.
In the original Fig. 2a, telomeres are erroneously depicted having blunt ends following resection and CST-mediated fill-in. Instead, telomeres retain 3' overhangs, as depicted below.


Environmental epigenetics and effects on male fertility.
Environmental exposures to factors such as toxicants or nutrition can have impacts on testis biology and male fertility. The ability of these factors to influence epigenetic mechanisms in early life exposures or from ancestral exposures will be reviewed. A growing number of examples suggest environmental epigenetics will be a critical factor to consider in male reproduction.


Stuttering-like hesitation in speech during acute/post-acute phase of immune-mediated encephalitis.
Neurogenic stuttering may be evident after a lesion/dysfunction of wider neural networks. Here we present a case of acquired stuttering as the consequence of immune-mediated encephalitis. The case of a 71-year old male who complained about the progressive onset of stuttering and disequilibrium as the consequence of immune-mediated encephalitis, is here reported. Administration of corticosteroid methylprednisolone was useful to recover from impairments. An in depth analysis of the electroencephalography (relative power of brain rhythms and source localization) during different phases of the disease/treatment was also realized. The patient showed a stuttering-like slowed speech with blocks and repetitions, especially at the beginning of words/sentences, with associated movements of the oro-facial muscles. Speech and general motor skills resulted slowed in their preparation/execution phases. Electroencephalography showed a "slowed" pattern, with delta/theta waves mainly in the prefrontal cortex and in sensorimotor networks. This case reports a probable immune-mediated encephalitis that resulted in acquired stuttering. The effect of "slowed" oscillatory brain activity on motor skills requesting sequencing and fine coordination (e.g. speech) could result in less "synchronized" systems, easily prone to disruptions.


Temperature corrected thrombelastography in hypothermic patients.
Thrombelastograms and other coagulation studies are performed at 37 degrees C, regardless of the patient's body temperature. This prospective study of 45 patients undergoing orthotopic liver transplantation was conducted to evaluate the effect on the thrombelastogram performed at the patient's actual body temperature compared with a control thrombelastogram heated in the standard fashion to 37 degrees C. Thrombelastograms were obtained after the induction of anesthesia and at various times throughout the operation when clinically indicated. A freshly drawn sample of the patient's blood was divided into two aliquots and run simultaneously on two thrombelastographs; one thrombelastograph was modified with a thermostat to perform the test at the patient's body temperature and the other was unmodified to serve as a control. The temperature of the patients in this study ranged from 36.9 degrees C to 32 degrees C. The variables of the thrombelastogram measured were: r (reaction time in minutes), r + K (coagulation time in minutes), alpha (coagulation rate in degrees), and MA (maximum amplitude in millimeters). Whenever the patient's body temperature was less than 37 degrees C, statistically significant prolongation of the reaction time, coagulation time, and decrease in the clot formation rate occurred compared with control variables at 37 degrees C. Overall means were as follows: r for control, 8.24 +/- 0.28 min; r for temperature corrected, 9.32 +/- 0.27 min; r + K for control, 15.4 +/- 0.65 min; r + K for temperature corrected, 17.5 +/- 0.81 min; and alpha for control, 39.8 +/- 1.22 degrees; alpha for temperature corrected, 37.7 +/- 1.23 degrees.(ABSTRACT TRUNCATED AT 250 WORDS)


Coupling-oxidation process promoted ring-opening degradation of 2-mecapto-5-methyl-1,3,4-thiadizaole in wastewater.
As an important raw material and intermediate of widely used antibiotics cefazolin and cefazedone, 2-mecapto-5-methyl-1,3,4-thiadizaole (MMTD) in antibiotic wastewater is hardly decyclized during wastewater treatment, posing great risk to the environment. This work proposed a green "coupling-oxidation" process to enhance ring-opening of MMTD during antibiotic wastewater treatment. In particular, the significant role of humic substances (HS) as pre-coupling reagent was emphasized. Real HS and different model HS, especially quinones, not only efficiently pre-coupled MMTD (>95%) but also promoted the MMTD removal by MnO2 (from 72.4% to 92.4%). Mass spectrometric analysis indicated that MMTD pre-coupled to HS would be oxidized with ring opening to environmental-friendly sulfonated HS, while direct oxidation of MMTD produced MMTD dimers or sulfonated MMTD that would not undergo ring opening. Theoretical calculations indicated that pre-coupling to HS enabled the ring-opening oxidation by increasing the nucleophilicity and decreasing ring-opening barrier of thiadiazole. Based on the density function theory (DFT), the global nucleophilicity index (Nu) followed the trend of HS-MMTD > MMTD dimer > sulfonated MMTD, while the ring-opening barrier followed the trend of HS-MMTD (274 kJ/mol) < first ring of MMTD dimers (286 kJ/mol) < MMTD (338 kJ/mol). Theoretical calculations further confirmed that the cross-coupled HS-MMTD intermediate was more likely to be decyclized than intermediates from direct oxidation. Moreover, nitrogen, acetaldehyde group, sulfate and CO2 were the products of thiadiazole ring degradation. Pre-coupling of MMTD with HS provides a new idea and strategy in developing a green and sustainable scheme for wastewater treatment.


Insulin resistance, dietary fat intake and blood pressure predict left ventricular diastolic function 20 years later.
Our knowledge on the development of left ventricular diastolic dysfunction is scarce. Thus, we aimed to investigate the relationship between left ventricular diastolic function and a wide variety of cardiovascular risk factors, including dietary factors using both cross-sectional and longitudinal data with 20 years follow-up. A population-based cohort of 505 50-year-old men was examined with determinations of blood pressure, insulin, glucose and fatty acid composition of serum cholesterol esters. A reinvestigation 20 years later also included hyperinsulinaemic euglycaemic clamp, 7-day diet record and Doppler echocardiography with determination of left ventricular diastolic function (early (E) and late (A) peak mitral velocities and left atrial diameter). Blood pressure both at age 50 and 70 was negatively correlated to the E/A ratio (r=-0.15, p<0.001 and r=-0.23, p<0.001) at age 70. Insulin resistance at age 50 and 70 were negatively correlated to the A-wave and left atrial diameter at follow-up. A fatty acid profile indicating a diet high in saturated fats at age 50 was correlated to an increased left atrial diameter 20 years later and the dietary intake of fat was negatively correlated to the E/A ratio (r=-0.09, p<0.05) at age 70. All findings were independent of myocardial infarction and cardiovascular medication. Apart from blood pressure, insulin resistance and dietary fat intake predicted left ventricular diastolic function after 20 years. These findings suggest that both hemodynamic and metabolic factors may play a role for left ventricular diastolic function and disclose new possibilities for prevention of left ventricular diastolic dysfunction.


Loop mediated isothermal amplification (LAMP) assay for detection of coconut root wilt disease and arecanut yellow leaf disease phytoplasma.
The coconut root wilt disease (RWD) and the arecanut yellow leaf disease (YLD) are two major phytoplasma associated diseases affecting palms in South India. Greatly debilitating the palm health, these diseases cause substantial yield reduction and economic loss to farmers. A rapid and robust diagnostic technique is crucial in efficient disease management. We established phytoplasma 16S rDNA targeted loop mediated isothermal amplification (LAMP) and real time LAMP based diagnostics for coconut RWD and arecanut YLD. The LAMP reaction was set at 65 °C and end point detection made using hydroxynaphthol blue (HNB) and agarose gel electrophoresis. Molecular typing of LAMP products were made with restriction enzyme HpyCH4 V. Conventional PCR with LAMP external primers and sequencing of amplicons was carried out. Real time LAMP was performed on the Genei II platform (Optigene Ltd., UK). An annealing curve analysis was programmed at the end of the incubation to check the fidelity of the amplicons. The phytoplasma positive samples produced typical ladder like bands on agarose gel, showed colour change from violet to blue with HNB and produced unique annealing peak at 85 ± 0.5 °C in the real time detection. Restriction digestion produced predicted size fragments. Sequencing and BLASTN analysis confirmed that the amplification corresponded to phytoplasma 16S rRNA gene. LAMP method devised here was found to be more robust compared to conventional nested PCR and hence has potential applications in detection of phytoplasma from symptomatic palm samples and in rapid screening of healthy seedlings.


Intraductal ultrasound for the evaluation of patients with biliary strictures and no abdominal mass on computed tomography.
Endoscopic retrograde cholangiopancreatography (ERCP) is the diagnostic procedure of choice in patients with biliary strictures and no culprit mass lesion on abdominal imaging, but it is limited in its diagnostic accuracy. The aim of this prospective study was to determine the value of intraductal ultrasound (IDUS) in distinguishing between benign and malignant biliary strictures in this clinical setting. Sixty-one patients with painless jaundice and no mass lesion on abdominal computed tomography, who were found to have a biliary stricture at ERCP, underwent IDUS with a high-frequency (20-MHz) wire-guided probe. Histopathological confirmation or clinical follow-up was used to establish the final diagnosis. The diagnostic performances of IDUS, ERCP, and IDUS plus ERCP in the identification of malignant strictures were evaluated. Forty-three patients had malignant strictures and 18 had benign strictures. ERCP produced 25 false-negative diagnoses, 22 of which were identified as malignant by IDUS. IDUS provided seven false-negative and three false-positive diagnoses. The proportion of patients with malignant strictures who tested positive with IDUS was 2.06 times that of ERCP (95 % CI, 1.37 - 3.10; 83.3 % vs. 40.5 %, P = 0.0004). When used in conjunction, IDUS increased the accuracy of ERCP from 58 % to 90 %. Patients with operable lesions on IDUS and no contraindication to surgery underwent resection; most patients with pancreatic parenchymal invasion on IDUS underwent EUS, which identified a pancreatic mass in more than 50 % of cases. Patients with negative IDUS and a low clinical suspicion for malignancy were treated endoscopically, while a more aggressive work-up was performed in all patients with high pretest probability, regardless of the IDUS results. IDUS is a valuable adjunct to ERCP in the characterization of biliary strictures in patients who present with painless jaundice in the absence of a culprit mass on abdominal imaging.


The caper (Capparis L.): ethnopharmacology, phytochemical and pharmacological properties.
Caper (Capparis L.), a shrub plant with a large natural distribution, is used in traditional medicines to cure various illnesses. Phytochemicals studies have shown the presence of many beneficial compounds such as spermidine, rutin, quercetin, kaempferol, stigmasterol, campesterol, tocopherols, and carotenoids. Biological studies reveal important antimicrobial, anti-oxidative, anti-inflammatory, immunomodulatory and antiviral properties. The presented review summarizes information concerning the morphology, ethnopharmacology, phytochemistry, and biological activities of caper plants.


Correlation study of scanning acoustic microscope reflection coefficients and image brightness intensities of micrographed osteons.
Scanning acoustic microscopy (SAM) of Haversian bone at high frequency clearly shows differences in the brightness (gray) levels of individual osteons, which were observed to correspond to the differences in reflection coefficients measured with the SAM technique: the darker the bony regions on the SAM micrographs, the lower the SAM reflection coefficient values, and vice versa. We studied the correlation between differences in brightness and the related reflection coefficients of osteons on undecalcified transverse sections of goat tibial diaphysis using a 400-MHz burst mode lens on the Olympus UH3 SAM. Results showed that there was a strong linear correlation between brightness intensities and the corresponding reflection coefficients, with a correlation coefficient r = 0.99 ( P << 0.001) using gray level 210 as cutoff. This result suggested that the image brightness intensity of osteonic bone could be measured retrospectively to provide information on the stiffness of the corresponding bone matrix.


Methods to reduce variability in E. Coli-based cell-free protein expression experiments.
Cell-free protein synthesis (CFPS) is an established biotechnology tool that has shown great utility in many applications such as prototyping proteins, building genetic circuits, designing biosensors, and expressing cytotoxic proteins. Although CFPS has been widely deployed, the many, varied methods presented in the literature can be challenging for new users to adopt. From our experience and others who newly enter the field, one of the most frustrating aspects of applying CFPS as a laboratory can be the large levels of variability that are present within experimental replicates. Herein we provide a retrospective summary of CFPS methods that reduce variability significantly. These methods include optimized extract preparation, fully solubilizing the master mix components, and careful mixing of the reaction. These have reduced our coefficient of variation from 97.3% to 1.2%. Moreover, these methods allow complete novices (e.g. semester rotation undergraduate students) to provide data that is comparable to experienced users, thus allowing broader participation in this exciting research area.


Virtual Education During COVID-19: Exploring Factors Associated With E-Learning Satisfaction Among Saudi Nursing Students.
Because of the COVID-19 pandemic, education and learning processes have been shifted to a completely virtual, online format. Students' satisfaction has been linked to better learning outcomes. The purpose was to determine factors associated with students' satisfaction with e-learning among Saudi nursing students. A cross-sectional, correlational descriptive study was conducted among 139 nursing students from different nursing programs in Saudi Arabia using a self-reported online survey. Previous experience with and readiness for e-learning influenced students' overall satisfaction with e-learning and satisfaction with assessment. Only readiness for e-learning was associated with satisfaction with teaching and generic skills and learning experiences. This study may enhance faculty members' understandings of factors influencing students' satisfaction with e-learning. Therefore, the urgent national distance education plan may need further development to meet students' needs.


Quantitative and rapid detection of morphine and hydromorphone at the point of care by an automated giant magnetoresistive nanosensor platform.
Opioids, such as morphine and hydromorphone, are common pain management drugs with a high risk for addiction and adverse effects when delivered in large doses or administered too frequently. Point-of-care (POC) tools provide a solution to combat these negative outcomes through active monitoring of opioid concentrations in clinical settings. We demonstrate that giant magnetoresistive (GMR) nanosensors offer a quantitative, sensitive, and rapid solution for low-cost, sample-to-answer opioid detection at the POC. We show the robust nature of GMR nanosensors by developing a competitive morphine assay and characterizing it in saliva, blood, and plasma. We then implemented the assay on a fully automated POC GMR platform and demonstrated its duality to detect either morphine or hydromorphone using only 180 μL of direct saliva without the need for pre-processing. In 35 min from sample addition to result, the automated platform was controlled via smartphone and had seamless transmission of results via Bluetooth. The fully automated POC assay had a limit of detection of 3.43 ng/mL for morphine and 3.49 ng/mL for hydromorphone. The low-cost, 80-plex GMR nanosensor array coupled with the automated POC platform enables future development of multiplexed drug screening tools that can be deployed in clinical settings using a wide variety of non-invasive matrices.


New Keys to Early Diagnosis: Muscle Echogenicity, Nerve Ultrasound Patterns, Electrodiagnostic, and Clinical Parameters in 150 Patients with Hereditary Polyneuropathies.
Hereditary neuropathies are of variable genotype and phenotype. With upcoming therapies, there is urgent need for early disease recognition and outcome measures. High-resolution nerve and muscle ultrasound is a dynamic, non-invasive, well-established tool in the field of inflammatory and traumatic neuropathies. In this study, we defined nerve and muscle ultrasound parameters as recognition and progression markers in 150 patients with genetically confirmed hereditary neuropathies, including Charcot-Marie-Tooth (CMT) disease (CMT1A, n = 55; other CMT1/4, n = 28; axonal CMT, n = 15; CMTX, n = 15), hereditary neuropathy with liability to pressure palsies (HNPP, n = 16), hereditary transthyretin-amyloidosis (ATTRv, n = 14), and Fabry's disease (n = 7). The CMT1A, followed by the CMT1/4 group, had the most homogeneous enlargement of the nerve cross-sectional areas (CSA) in the ultrasound pattern sum (UPSS) and homogeneity score. Entrapment scores were highest in HNPP, ATTRv amyloidosis, and Fabry's disease patients. In demyelinating neuropathies, the CSA correlated inversely with nerve conduction studies. The muscle echo intensity was significantly highest in the clinically most affected muscles, which was independent from the underlying disease cause and correlated with muscle strength and disease duration. Further correlations were seen with combined clinical (CMTES-2) and electrophysiological (CMTNS-2) scores of disease severity. We conclude that nerve ultrasound is a helpful tool to distinguish different types of hereditary neuropathies by pattern recognition, whereas muscle ultrasound is an objective parameter for disease severity. The implementation of neuromuscular ultrasound might enrich diagnostic procedures both in clinical routines and research.


Ebola and Marburg virus VP35 coiled-coil validated as antiviral target by tripartite split-GFP complementation.
Ebola virus (EBOV) and Marburg virus (MARV) are highly pathogenic viruses in humans, against which approved antivirals are lacking. During EBOV and MARV infection, coiled-coil mediated oligomerization is essential for the virion protein 35 (VP35) polymerase co-factor function and type I interferon antagonism, making VP35 coiled-coil an elective drug target. We established a tripartite split-green fluorescent protein (GFP) fluorescence complementation (FC) system based on recombinant GFP-tagged EBOV and MARV VP35, which probes VP35 coiled-coil assembly by monitoring fluorescence on E. coli colonies, or in vitro in 96/384-multiwell. Oligomerization-defective VP35 mutants showed that correct coiled-coil knobs-into-holes pairing within VP35 oligomer is pre-requisite for GFP tags and GFP detector to reconstitute fluorescing full-length GFP. The method was validated by screening a small compound library, which identified Myricetin and 4,5,6,7-Tetrabromobenzotriazole as inhibitors of EBOV and MARV VP35 oligomerization-dependent FC with low-micromolar IC50 values. These findings substantiate the VP35 coiled-coil value as antiviral target.


Clinical profile and prognostic factors of alcoholic cardiomyopathy in tribal and non-tribal population.
Alcoholic cardiomyopathy (ACM) is a leading cause of non-ischaemic dilated cardiomyopathy (DCM) in tribal and non-tribal population. However, no study has been done depicting the correlation between clinical profile and prognosis of ACM in tribal and non-tribal population. This study also defines the long-term outcome and prognostic markers of ACM. We studied 290 patients with ACM who were evaluated in our institute between January 2013 and December 2016. The primary endpoint of the study was all-cause mortality. Statistical analysis was done by using Kaplan-Meier survival curves for the assessment of all-cause mortality and Cox regression for the assessment of risk factors. After a median follow-up period of 3.75 years (IQR: 3-4 years), 50 patients with ACM (37.3%) died among tribal population while 14 patients (9%) died among non-tribal population. Independent predictors of all-cause mortality in ACM identified by Cox regression were left ventricular ejection fraction (LVEF) (HR: 0.883; 95% CI 0.783 to 0.996; p=0.043), QRS duration (HR: 1.010; 95% CI 1.007 to 1.017; p=0.005) and Child-Turcotte-Pugh (CTP) Scoring (HR: 12.332; 95% CI 6.999 to 21.728; p<0.001) at admission. The Kaplan-Meier survival probability estimate was 95.1% at 1 year and all-cause mortality was found to be higher in patients with QRS>120 ms, LVEF ≤35%, CTP Grade B/C than patients with QRS≤120 ms, LVEF >35% and CTP Score A, respectively (log-rank χ²=55.088, p<0.001; log-rank χ²=32.953, p<0.001; log-rank χ²=139.764, p<0.001, respectively). Our study indicated increased morbidity and mortality in tribal population. LVEF, QRS duration and CTP Scoring at the time of presentation were found to be the independent prognostic markers of patients with ACM.


Effect of melatonin on intracranial pressure and brain edema following traumatic brain injury: role of oxidative stresses.
Traumatic brain injury (TBI) is one of the main causes of brain edema and increased intracranial pressure (ICP). In the clinic it is essential to limit the development of ICP after TBI. In the present study, the effects of melatonin on these parameters at different time points and alterations of oxidant factors as one of the probable involved mechanisms have been evaluated. Albino N-Mary rats were divided into five groups of sham, TBI, TBI + vehicle, TBI + Mel5 and TBI + Mel20. Brain injury was induced by Marmarou method. Melatonin was injected i.p. at 1, 24, 48 and 72 h after brain trauma. Brain water and Evans blue dye contents as well as oxidant/antioxidant factors were measured 72 h after TBI. ICP and neurological scores were determined at -1, 1, 24, 48 and 72 h post-TBI. Brain water and Evans blue dye contents in melatonin-treated groups decreased as compared to the TBI + vehicle group (p <0.001). Veterinary coma scale (VCS) at 24, 48 and 72 h after TBI showed a significant increase in melatonin groups (TBI + Mel5: p <0.01 and TBI + Mel20: p <0.001) in comparison to the TBI + vehicle group. ICP at 24, 48 and 72 h after TBI decreased in melatonin groups as compared to the TBI + vehicle group (p <0.001). Superoxide dismutase and glutathione peroxidase activities showed a significant increase, whereas malondialdehyde level in these groups was significantly lower in melatonin groups in comparison to the TBI + vehicle group (p <0.001). Melatonin decreases brain edema, BBB permeability and ICP, but increases VCS after TBI. These effects are probably due to inhibition of oxidative stress.


Chemical effect on the K shell x-ray fluorescence parameters of some Ce compounds.
Chemical effects on the Kβ/Kα x-ray intensity ratios, fluorescence yields wK and vacancy transfer probabilities ηKL for some Ce compounds were investigated. In this study, the samples were excited by 59.54 keV γ-rays from a 5Ci (241)Am annular radioactive source. K x-rays emitted by samples were counted by an HPGe detector with a resolution of 182 eV at 5.9 keV. The experimental values were compared with the theoretical and other experimental values. The aim of these measurements was to characterize the dependence of the line position and line width with the chemical environment changes.


Crystal structure of the GAF-B domain from human phosphodiesterase 10A complexed with its ligand, cAMP.
Cyclic nucleotide phosphodiesterases (PDEs) catalyze the degradation of the cyclic nucleotides cAMP and cGMP, which are important second messengers. Five of the 11 mammalian PDE families have tandem GAF domains at their N termini. PDE10A may be the only mammalian PDE for which cAMP is the GAF domain ligand, and it may be allosterically stimulated by cAMP. PDE10A is highly expressed in striatal medium spiny neurons. Here we report the crystal structure of the C-terminal GAF domain (GAF-B) of human PDE10A complexed with cAMP at 2.1-angstroms resolution. The conformation of the PDE10A GAF-B domain monomer closely resembles those of the GAF domains of PDE2A and the cyanobacterium Anabaena cyaB2 adenylyl cyclase, except for the helical bundle consisting of alpha1, alpha2, and alpha5. The PDE10A GAF-B domain forms a dimer in the crystal and in solution. The dimerization is mainly mediated by hydrophobic interactions between the helical bundles in a parallel arrangement, with a large buried surface area. In the PDE10A GAF-B domain, cAMP tightly binds to a cNMP-binding pocket. The residues in the alpha3 and alpha4 helices, the beta6 strand, the loop between 3(10) and alpha4, and the loop between alpha4 and beta5 are involved in the recognition of the phosphate and ribose moieties. This recognition mode is similar to those of the GAF domains of PDE2A and cyaB2. In contrast, the adenine base is specifically recognized by the PDE10A GAF-B domain in a unique manner, through residues in the beta1 and beta2 strands.


Multiple types of Na(+) currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia.
Small (<25 microm in diameter) neurons of the dorsal root ganglion (DRG) express multiple voltage-gated Na(+) channel subtypes, two of which being resistant to tetrodotoxin (TTX). Each subtype mediates Na(+) current with distinct kinetic property. However, it is not known how each type of Na(+) channel contributes to the generation of action potentials in small DRG neurons. Therefore, we investigated the correlation between Na(+) currents in voltage-clamp recordings and corresponding action potentials in current-clamp recordings, using wild-type (WT) and Na(V)1.8 knock-out (KO) mice, to clarify the action potential electrogenesis in small DRG neurons. We classified Na(+) currents in small DRG neurons into three categories on the basis of TTX sensitivity and kinetic properties, i.e., TTX-sensitive (TTX-S)/fast Na(+) current, TTX-resistant (TTX-R)/slow Na(+) current, and TTX-R/persistent Na(+) current. Our concurrent voltage- and current-clamp recordings from the same neuron revealed that the action potentials in WT small DRG neurons were mainly dependent on TTX-R/slow Na(+) current mediated by Na(V)1.8. It was surprising that a large portion of TTX-S/fast Na(+) current was switched off in WT small DRG neurons due to a hyperpolarizing shift of the steady-state inactivation (h (infinity)), whereas in KO small DRG neurons which are devoid of TTX-R/slow Na(+) current, the action potentials were generated by TTX-S/fast Na(+) current possibly through a compensatory shift of h (infinity) in the positive direction. We also confirmed that TTX-R/persistent Na(+) current mediated by Na(V)1.9 actually regulates subthreshold excitability in small DRG neurons. In addition, we demon strated that TTX-R/persistent Na(+) current can carry an action potential when the amplitude of this current was abnormally increased. Thus, our results indicate that the action potentials in small DRG neurons are generated and regulated with a combination of multiple mechanisms that may give rise to unique functional properties of small DRG neurons.


Dietary enzyme and zinc bacitracin reduce colonisation of layer hens by the intestinal spirochaete Brachyspira intermedia.
Brachyspira intermedia strain HB60 was used to experimentally infect 40 individually caged 22-week-old laying hens. Another 10 control birds were sham-inoculated with sterile broth. All chickens received an experimental layer diet based on wheat. The infected birds were randomly divided into four groups of 10, with the diet for each group containing either 50 ppm zinc bacitracin (ZnB), 100 ppm ZnB, 256 ppm of dietary enzyme (Avizyme), 1302), or no additive. Birds were kept for 6 weeks after infection, and faecal excretion of B. intermedia, faecal water content, egg numbers, egg weights and body weights were recorded weekly. Control birds remained uninfected throughout the experiment. B. intermedia was isolated significantly less frequently from the groups of experimentally infected birds receiving ZnB at 50 ppm or enzyme than from those receiving 100 ppm ZnB or no treatment. Infected birds had a transient increase in faecal water content in the week following challenge, but no other significant production differences were detected amongst the five groups of birds in subsequent weeks. It was not established how the ZnB at 50 ppm and the dietary enzyme reduced the ability of the spirochaete to colonise, but it may have been by bringing about changes in the intestinal microflora and/or the intestinal microenvironment.


Nasotracheal intubation versus tracheostomy for intermittent positive pressure ventilation in neonatal tetanus.
Fifty-two neonates with tetanus who required muscle paralysis and IPPV were managed alternatively with naso-tracheal intubation or tracheostomy. The complications of the two techniques were compared. Planned extubation caused less problems in the intubated than in the tracheostomized children, and secondary infection occurred less often. Accidental extubation, however, was a significant hazard in the intubated child.


High methylmercury uptake by green algae in Lake Titicaca: Potential implications for remediation.
Anthropogenic pressure in the high altitude lakes such as Titicaca and Uru (Bolivia) may favor the production of methylmercury (MeHg) known to accumulate in trophic chains. Periphyton associated with emerged aquatic plants (totoras) from the lake shores accumulates and demethylates MeHg providing a potential cost-effective water treatment technique. In this laboratory study, we measured the MeHg uptake kinetics of a consortium of green algae isolated from Lake Titicaca totora's periphyton. The most abundant algal consortium, composed of Oedogonium spp., Chlorella spp., Scenedesmus spp., was exposed to rising MeHg concentrations (from 5 to 200 ng·L-1) to assess their maximum potential capacity for MeHg accumulation. Various algal biomass concentrations were tested to choose the optimal one. Results provided a net MeHg uptake rate by this algal consortium of 2.38 amol ng-1·h-1·nM-1 (the total uptake was 2863 ng MeHg·g-1) for an initial concentration of 200 ng MeHg·L-1 with an algal biomass concentration of 0.02 g·L-1. This initial MeHg concentration is 1000 times higher than the one measured in the eutrophic Cohana Bay of Lake Titicaca, which shows the high accumulation potential of these green algae. Our data suggest that periphyton has a high potential for the treatment of Hg contaminated waters in constructing wetlands in the Andean Altiplano.


Evolution of polycyclic aromatic hydrocarbons in the surface sediment of southern Jiaozhou Bay in northern China after an accident of oil pipeline explosion.
The 2013 "Qingdao oil pipeline explosion" contaminated about 2.5 km of shoreline in the Jiaozhou Bay area and aroused widespread concern because of the serious casualties even though it was not the most severe oil-spill contamination in China. To evaluate the long-term impact, we collected thirty-three surface sediment samples after 3 years of the accident, with sixteen polycyclic aromatic hydrocarbons (PAHs) detected. Spatial-temporal variation in PAHs revealed that a minimal impact might still be present after 3 years. Source analysis combined with a one-way ANOVA showed that pyrolytic sources were consistently predominant. The environmental impact was already minimal 3 years later and negligible thereafter. Although the cancer risk has decreased over the years, there has always been a potential hazard to human for specific occupation, with all of the risk values exceeded 10-6. This study offers a reference for assessing the long-term impact of oil spills in similar bay areas.


Clinical-pathological findings induced by Histophilus somni isolated in subacute cardiac death in feedlot cattle.
The purpose of this report is to provide information about the different presentations of cardiac and extra-cardiac histophilosis and, to assess the antimicrobial (ATM) susceptibility of Histophilus somni isolated from these cardiac lesions to different ATM agents commonly used for treating bovine bacterial respiratory pathogens. Eight feedlot calves, which died after suffering from food rejection, apathy, hyperthermia, cough and nasal mucous discharge, and lack of response to ATM therapy, were studied. Cardiac lesions observed at necropsy included valvular/mural endocarditis, myocardial infarction, and necrotizing myocarditis, miliar non-suppurative myocarditis, myocardic necrotic sequestrum, and/or pericarditis. Histopathological, bacteriological and molecular studies confirmed the presence of a fastidious microorganism in the affected organs. H. somni showed no resistance to most ATM tested (ceftiofur, gamithromycin, enrofloxacin, florfenicol, tilmicosin). The results obtained in this study confirmed that H. somni was the main cause of the subacute cardiac lesions associated with hyperthermia, apathy and respiratory signs observed in cattle examined in this research. These presentations must be considered by veterinary practitioners in order to establish a rational therapeutic.


Lead, Mercury, and Cadmium Concentrations in Blood Products Transfused to Neonates: Elimination Not Just Mitigation.
Lead (Pb), mercury (Hg), and cadmium (Cd) are identified as potent developmental neurotoxicants. Neonates are the main group receiving multiple blood transfusions. The exposure of neonates to these heavy metals (HMs) can occur through blood transfusions. This study aimed to determine the concentrations of lead (Pb), mercury (Hg), and cadmium (Cd) in various blood products (plasma, platelets, packed red blood cells (pRBCs), and whole blood (WB)) to explore the probability of concurrent exposure of these HMs and to identify the metal load per transfusion with risk assessment. Residual bloods from blood bank bags were collected after neonatal transfusion. Pb, Hg, and Cd concentrations were determined in 120 samples of blood products by inductively coupled plasma mass spectrometry (ICP-MS). Pb and Cd levels were over the normal levels in 19.2 and 5.9% of all blood units, respectively. In 35 and 0.8% of blood units, the Pb and Cd concentrations, respectively, were higher than that recommended for transfusions in premature neonates. The anticipated safe value was surpassed by 2.5% for Cd of all transfusions, primarily because of WB. However, Hg was detected only in 5.8% of all samples and their concentrations were within the normal range. The concurrent neonatal exposure to Pb, Hg, and Cd was statistically significant. Hazard quotients of Hg and Cr were >1 and Pb cancer risk was 2.41 × 10-4. To the best of our knowledge, this study is the first report examining Pb, Hg, and Cd in blood products other than WB and pRBCs using ICP-MS. This study demonstrated the exposure of neonates to Pb, Hg, and Cd during transfusion with a considerable amount of Pb. It confirms the significant concurrent exposure to the three HMs, which maximize their potential developmental neurotoxicity with a high probability of developing non-carcinogenic and carcinogenic health effects.


Suppression of polyclonal human B cell activation by IgG binding factors: interference with the maturation of Ig-containing cells into Ig-secreting cells.
Human IgG binding factors (IgG BF) were prepared by immunopurification on IgG immunosorbents from cell-free supernatants of unstimulated peripheral blood mononuclear cells (PB MNC). The suppressive effects of IgG BF was studied using PB MNC stimulated by pokeweed mitogen or by nocardia delipidated cell mitogen. At the end of the culture three parameters of B cell activation were measured: (1) the numbers of IgM-, IgG-, or IgA-containing cells (CC) using direct immunofluorescence, (2) the numbers of IgM, IgG, or IgA plaque-forming cells (PFC) using a Protein A hemolytic plaque assay, and (3) the concentrations of IgM, IgG, or IgA in culture supernatants using an enzyme-linked immunosorbent assay. Addition of IgG BF at the third day of culture resulted in a selective decrease of IgG CC, while IgM CC and IgA CC were increased or unchanged. Conversely, IgG BF induced a nonselective diminution of the number of PFC and of the amount of secreted Ig of the three major Ig classes. Therefore the results demonstrate two distinct effects of IgG BF: (1) an isotype-specific suppression of cells producing IgG, demonstrated by the parallel decrease of IgG CC and IgG PFC, and (2) a blocking of the late stages of B cell maturation evidenced by the discrepancy between normal or elevated Ig CC and decreased Ig PFC of the IgM and IgA classes.


More attentional focusing through binaural beats: evidence from the global-local task.
A recent study showed that binaural beats have an impact on the efficiency of allocating attention over time. We were interested to see whether this impact affects attentional focusing or, even further, the top-down control over irrelevant information. Healthy adults listened to gamma-frequency (40 Hz) binaural beats, which are assumed to increase attentional concentration, or a constant tone of 340 Hz (control condition) for 3 min before and during a global-local task. While the size of the congruency effect (indicating the failure to suppress task-irrelevant information) was unaffected by the binaural beats, the global-precedence effect (reflecting attentional focusing) was considerably smaller after gamma-frequency binaural beats than after the control condition. Our findings suggest that high-frequency binaural beats bias the individual attentional processing style towards a reduced spotlight of attention.


An evaluation of a chronic disease prevention program in the Republika Srpska (RS) of Bosnia and Herzegovina.
In 2002 the Republika Srpska of Bosnia and Herzegovina adopted goals for reducing the burden of chronic disease through a new screening program in its publicly funded health centers ("Dom Zdravljas"). This study evaluated the first year of program implementation. The evaluation used in-depth interviews with 25 key stakeholders and in-person interviews with 1004 citizens. We found that many health care providers and citizens were unaware of the program. In addition, there was inadequate financing for the program, because the Health Insurance Fund does not collect revenue for uninsured citizens, more than 20 per cent of the population. We recommend improved co-ordination among public and private organizations involved in implementation; increased promotion of the program with health care providers and citizens; and increased financial resources for providing screening for uninsured citizens.


Cost Considerations for Robotic Surgery.
Transoral robotic surgery (TORS) is a rapidly growing diagnostic and therapeutic modality in otolaryngology-head and neck surgery, having already made a large impact in the short time since its inception. Cost-effectiveness analysis is complex, and a thorough cost-effectiveness inquiry should analyze not only financial consequences but also impact on the health state of the patient. The cost-effectiveness of TORS is still under scrutiny, but the early data suggest that TORS is a cost-effective method compared with other available options when used in appropriately selected patients.


Psychosocial differences as predictors for recovery from chronic low back pain following manipulation, stabilizing exercises and physician consultation or physician consultation alone.
Three psychosocial profile groups are introduced in the Multidimensional Pain Inventory for chronic pain patients. Patients with the dysfunctional profile have shown a more favourable outcome after multidisciplinary treatments, due to the suggested effects of specific psychosocial treatment elements. In this study we explored, among patients with chronic low back pain, whether the Multidimensional Pain Inventory patient profile groups might respond differently to treatment without planned psychosocial elements. Of 204 voluntarily recruited patients with chronic low back pain, 102 were randomized to a combined manipulation, exercise and physician consultation group (called the combination group) and 102 to a consultation-alone group. Although all subjects showed improvement during follow-up both on the Oswestry index and the Visual Analogue Scale, the dysfunctional profile patients in the combination group improved the most. Their high pre-treatment ratings on Oswestry and Visual Analogue-scales fell at the 5- and 12-month follow-ups to the same level as those of the adaptive copers or interpersonally distressed patients, and they were on a significantly lower level than the dysfunctional profile patients in consultation group during follow-up. All dysfunctional profile patients also showed a decrease in affective distress, equally in combination and consultation groups. We suggest that dysfunctional profile patients are more sensitive to respond even to treatment without any specific psychosocial elements. This should be considered when evaluating any treatment effects. Among dysfunctional profile patients, pain-related anxiety and decreased acceptance of pain may contribute to their sensitivity to treatment.


Insulin and vanadium protect against osteoarthritis development secondary to diabetes mellitus in rats.
Diabetic complications such as cardiovascular disease and osteoarthritis (OA) are among the common public health problems. The effect of insulin on OA secondary to diabetes has not been investigated before in animal models. Therefore, we sought to determine whether insulin and the insulin-mimicking agent, vanadium can protect from developing OA in diabetic rats. Type 1 diabetes mellitus (T1DM) was induced in Sprague-Dawley rats and treated with insulin and/or vanadium. Tissues harvested from the articular cartilage of the knee joint were examined by scanning electron microscopy, and blood samples were assayed for oxidative stress and inflammatory biomarkers. Eight weeks following the induction of diabetes, a profound damage to the knee joint compared to the control non-diabetic group was observed. Treatment of diabetic rats with insulin and/or vanadium differentially protected from diabetes-induced cartilage damage and deteriorated fibrils of collagen fibers. The relative biological potencies were insulin + vanadium >> insulin > vanadium. Furthermore, there was about 2- to 5-fold increase in TNF-α (from 31.02 ± 1.92 to 60.5 ± 1.18 pg/ml, p < 0.0001) and IL-6 (from 64.67 ± 8.16 to 338.0 ± 38.9 pg/ml, p < 0.0001) cytokines and free radicals measured as TBARS (from 3.21 ± 0.37 to 11.48 ± 1.5 µM, p < 0.0001) in the diabetic group, which was significantly reduced with insulin and or vanadium. Meanwhile, SOD decreased (from 17.79 ± 8.9 to 8.250.29, p < 0.0001) and was increased with insulin and vanadium. The relative potencies of the treating agents on inflammatory and oxidative stress biomarkers were insulin + vanadium >> insulin > vanadium. The present study demonstrates that co-administration of insulin and vanadium to T1DM rats protect against diabetes-induced OA possibly by lowering biomarkers of inflammation and oxidative stress.


Design and synthesis of new potent, silent 5-HT1A antagonists by covalent coupling of aminopropanol derivatives with selective serotonin reuptake inhibitors.
Hybrid molecules built up by covalent coupling of aminopropanol derivatives (especially pindolol) with antidepressant drugs like fluoxetine, paroxetine or milnacipran were found to be potent and silent 5-HT1A antagonists (KB < 1 nM for 7c and 9a).


Comparison of antibody responses following natural infection with Severe Acute Respiratory Syndrome Coronavirus 2 or receipt of CoronaVac or ChAdOx1 (AZD1222) vaccination in Chiang Mai, Thailand.
In Thailand, early vaccination initiatives for SARS-CoV-2 relied on CoronaVac (Sinovac Life Sciences) and ChAdOx1 (Oxford-AstraZeneca) vaccines. However, the data of immunogenicity of these two vaccines in Thai populations is limited. This real time, head-to-head comparative study was conducted to investigate antibody (Ab) responses to SARS-CoV-2 following infection or receipt of either CoronaVac or ChAdOx1 vaccination in Chiang Mai, Thailand. Sera was collected within two months from participants having a history of documented SARS-CoV-2 infection or at one month after the second dose of CoronaVac vaccine. Sera from participants with a history of receiving one dose of ChAdOx1 vaccination was collected twice, at one month following each vaccine dose. Neutralizing antibodies (NAbs) were assessed using the surrogate neutralization test and anti-spike protein antibodies were assessed using an in-house enzyme-linked immunosorbent assay. The prevalence of NAbs against SARS-CoV-2 was 92.1 %, 95.7 %, 64.1 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. The inhibition rate in individuals receiving two doses of ChAdOx1 vaccine (90.8%) was significantly higher than individuals who had recovered from natural infection (71.7%) or individuals who had received two doses of CoronaVac vaccine (66.7%). The prevalence of anti-spike Abs was 97.4 %, 97.8 %, 97.4 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. Significantly higher levels of anti-spike Abs were observed in the ChAdOx1 group after two doses of vaccination (1975 AU/mL) compared to those who had recovered from natural infection (468.5 AU/mL) and individuals who had received CoronaVac (554.4 AU/mL). Neutralizing activity had a statistically significant positive correlation with levels of anti-spike Abs. ChAdOx1 vaccine may provide superior immunogenicity than CoronaVac and natural infection.


Nonverbal communication and play correlates of language development in autistic children.
The aim of this study was to determine the social and cognitive correlates of language acquisition in autistic children. Functional and symbolic play skills were shown to be associated with language abilities in a sample of young autistic children (mean CA 54.5 months), thereby replicating previous findings. Certain types of nonverbal communication skills were also shown to be significant correlates of language development in this group of autistic children. These involved the ability to use gestures to coordinate visual attention between social partners with respect to objects or events. The play and nonverbal communication variables were not significantly correlated, suggesting that these variables reflect independent psychological factors associated with language development in young autistic children.


Stability of the mandible after bilateral sagittal split osteotomy: Comparison between positioning screws and plate.
Relapse is one of the complications of orthognathic surgery. In this study, we compared the stability of mandibular bilateral sagittal split osteotomy by using two different methods of fixation. In Group 1, eight patients with prognathic mandible underwent BSSO and set back average of 6.0 mm. The method of fixation was positioning screws. In Group 2, eight patients with prognathic mandible underwent BSSO and set back average of 6.0 mm. The method of fixation was plate and monocortical screws. In Group 3, eight patients with retrognathic mandible underwent BSSO and advancement average of 6.0 mm. The method of fixation was positioning screws. In Group 4, eight patients with retrognathic mandible underwent BSSO and advancement average of 6.0 mm. The method of fixation was plate and monocortical screws. The results showed in terms of advancement that there was no significant difference between the groups after one year. However, in terms of set back, this study showed significant difference.


Determination of the electromotive force of active sodium transport in frog skin epithelium (Rana temporaria) from presteady-state flux ratio experiments.
The presteady-state influxes and effluxes of sodium across frog skin epithelium have been determined as a function of time while all electrophysiological parameters were maintained constant. The fluxes measured were resolved in the fractions which have passed a pathway through the cells and those that have used a paracellular pathway. The procedure is based on the theory that all presteady-state flux ratios have to be equal to the steady-state flux ratio if only one pathway is involved. The flux ratios for the transcellular route were used to calculate the electromotive force of the sodium pump. The calculation hinges on the assumptions (a) that both influx and efflux have to pass through the sodium pump and (b) that single file diffusion of sodium is not taking place anywhere along the path. The validity of both assumptions is discussed. Our calculated values for the electromotive force of the sodium pump EaNa vary between 146 and 200 mV, which is in agreement with the energy of the ATP/ADP system. There is a distinct indication that, as the electrochemical gradient for sodium opposing the transport is being increased, the emf increases towards an asymptotic value around 200 mV. The relation between the value of EaNa and the cellular phosphorylation potential for ATP is discussed.


Intestinal obstruction caused by the strangulation of a Treves' field pouch hernia from a Meckel's diverticulum - A case report.
The etiology for intestinal obstruction is often difficult to determine especially in a young patient with a virgin abdomen. Differential diagnosis may include congenital abnormalities such as a more common Meckel's diverticulum but also a rarer mesenteric type internal hernia. Although the definite diagnosis is not as important in an acute setting and diagnosis is often made postoperatively, the preoperative differential diagnosis including the two should be considered for successful management. We report a case of a 16-year-old young female who has a history of abdominal complaints but treated successfully conservatively. She eventually presented to us with suspicion of intestinal obstruction and image study confirmed an internal hernia. Operative findings showed a Meckel's diverticulum with tip adherent leading to the strangulation of a Treves' field pouch hernia. The encapsulated small bowel resulted in an intestinal obstruction of the terminal ileum. Meckel's diverticulum is a common congenital abnormality but often asymptomatic. Treves' field of the mesentery is also a congenital abnormality but a much rarer finding often only impressed if herniation of the bowel is involved. However, both can lead to an abdominal emergency. Intestinal obstruction is often an emergent situation and prompt surgery is usually required. The exact etiology may not be obvious preoperatively especially in a young patient with a virgin abdomen, but differential diagnosis like Meckel's diverticulum and Treves' filed hernia should be important for successful management.