Definition, general principles and expected benefits of enhanced recovery in surgery.
A multimodal approach to promoting recovery from surgery was first described by Henrik Kehlet in 1995. This approach has since been significantly developed and refined, and is now referred to as Enhanced Recovery in Surgery (ERS). The goal of ERS is to enable a patient to regain his/her pre-surgery physical and psychological state after a surgical procedure - notably by reducing the stress and the inflammatory response inevitably triggered by surgery. ERS protocols include anesthesia-related items (such as reducing the use of morphine) and surgical items (such as the use of minimally invasive routes, and limiting the postoperative use of drains and probes). Each step is essential - from patient information, education and adherence during the preoperative phase to involvement of the family circle and the attending physician with a view to early discharge. The term ERS corresponds to a set of principles for optimizing pre-, per- and postoperative care, the aim of which is to improve the post-operative course and the patient's experience by decreasing per- and postoperative complications and accelerating a return to the patient's pre-operative physical and psychological state. The use of ERS protocols is associated with a lower complication rate and a shorter hospital stay, regardless of the patient's age and comorbidities.


Long-term effects of popular dietary approaches on weight loss and features of insulin resistance.
High-carbohydrate (HC)-high-fibre diets are recommended for weight loss and for treating and preventing diseases such as diabetes and cardiovascular disease. We report a randomised trial comparing high-fat (HF) and high-protein (HP) diets with the conventional approach. A total of 93 overweight insulin-resistant women received advice following randomisation to HF, HP or HC dietary regimes, to achieve weight loss followed by weight maintenance over 12 months. Weight, body composition and measures of carbohydrate and lipid metabolism were investigated. Retention rates were 93% for HP and 75% for HC and HF. Features of the metabolic syndrome improved in all groups during the first 6 months, to a greater extent on HF and HP than an HC. During the second 6 months the HF group had increases in waist circumference (mean difference 4.4 cm (95% CI 3.0, 5.8)), fat mass (2.3 kg (1.5, 3.1)), triglycerides (0.28 mmol/l (0.09, 0.46)) and 2 h glucose (0.70 mmol/l (0.22, 1.18)). Overall there was substantial sustained improvement in waist circumference, triglycerides and insulin in the HP group and sustained but more modest changes on HC. Dietary compliance at 12 months was poor in all groups. HP and HC approaches appear to be appropriate options for insulin-resistant individuals. When recommending HP diets appropriate composition of dietary fat must be ensured. HC diet recommendations must include advice regarding appropriate high-fibre, low glycaemic index foods.


TruNeo: an integrated pipeline improves personalized true tumor neoantigen identification.
Neoantigen-based personal vaccines and adoptive T cell immunotherapy have shown high efficacy as a cancer treatment in clinical trials. Algorithms for the accurate prediction of neoantigens have played a pivotal role in such studies. Some existing bioinformatics methods, such as MHCflurry and NetMHCpan, identify neoantigens mainly through the prediction of peptide-MHC binding affinity. However, the predictive accuracy of immunogenicity of these methods has been shown to be low. Thus, a ranking algorithm to select highly immunogenic neoantigens of patients is needed urgently in research and clinical practice. We develop TruNeo, an integrated computational pipeline to identify and select highly immunogenic neoantigens based on multiple biological processes. The performance of TruNeo and other algorithms were compared based on data from published literature as well as raw data from a lung cancer patient. Recall rate of immunogenic ones among the top 10-ranked neoantigens were compared based on the published combined data set. Recall rate of TruNeo was 52.63%, which was 2.5 times higher than that predicted by MHCflurry (21.05%), and 2 times higher than NetMHCpan 4 (26.32%). Furthermore, the positive rate of top 10-ranked neoantigens for the lung cancer patient were compared, showing a 50% positive rate identified by TruNeo, which was 2.5 times higher than that predicted by MHCflurry (20%). TruNeo, which considers multiple biological processes rather than peptide-MHC binding affinity prediction only, provides prioritization of candidate neoantigens with high immunogenicity for neoantigen-targeting personalized immunotherapies.


Are perfectionism dimensions risk factors for anxiety symptoms? A meta-analysis of 11 longitudinal studies.
Over 50 years of theory and research implicates perfectionism in anxiety. However, it is unclear which (if any) perfectionism dimensions are risk factors for anxiety. To address this, we conducted a meta-analysis testing whether socially prescribed perfectionism, concern over mistakes, doubts about actions, self-oriented perfectionism, and personal standards predict increases in anxiety. Our literature search yielded 11 relevant studies for inclusion, composed of children, adolescents, undergraduates, community adults, and psychiatric patients. Meta-analysis using random-effects models revealed concern over mistakes (r+ = .11), doubts about actions (r+ = .13), and personal standards (r+ = .08), but not socially prescribed perfectionism or self-oriented perfectionism, displayed significant small positive relationships with follow-up anxiety, after controlling for baseline anxiety. Research is needed to understand the conditions under which the connection between perfectionism and anxiety becomes stronger (e.g., stress).


The reduction of platelet thrombi on damaged vessel wall by a thromboxane synthetase inhibitor in rabbits.
The role of thromboxane A2 (TXA2) in platelet-vessel wall interaction was investigated using 1-benzylimidazole (1-BI), a selective thromboxane synthetase inhibitor. 1-BI (0.9 mM) will reduce the aggregatory response of rabbit platelets to 0.2 mM arachidonate by 50% and their production of TXA2 by 84%. The effect of 1-BI on platelet thrombus formation was evaluated in vivo on New Zealand white male rabbits using the autologous indium-111 labeled platelet technique. After injection of autologous 111In-platelets, 10 cm of the abdominal aorta was de-endothelialized with a balloon catheter. Three hours later the animals were sacrificed and injured and uninjured segments of the aorta removed. The radioactivity and dry weight of the tissue were determined. The radioactivity/gm of tissue was greater for the injured tissue than for the uninjured tissue. 1-BI at 10 mg/kg reduced the specific platelet accumulation at the injured site (n = 5; 4.8 +/- 0.3 X 10(5) cpm/gm) compared to the controls (n = 10; 11.7 +/- 2.1 X 10(5) cpm/gm). Platelet accumulation on the injured tissue was further reduced by increasing the dosage to 30 mg/kg. Thirty minutes after 1-BI administration (30 mg/kg), platelets were less sensitive to arachidonate-induced aggregation (a 67% decrease) and TXA2 production was decreased 82%. Alterations in platelet sensitivity persisted for up to 3 hours. These findings indicate that TXA2 plays an important role in platelet-vessel wall interaction.


Effects of feeding and light cycles on activity rhythms of maternally isolated rat pups.
Motor activity of infant rat pups was measured continuously between days 3 and 18 of postnatal age. Mother-reared rats on a 12:12 LD cycle exhibited significant rhythmic activity in the circadian range as early as day 5 of postnatal age. Some of the pups reared in isolation from maternal and sibling contact and kept on 12:12 LD cycles, feeding cycles, or combinations of feeding, temperature, and LD cycles also showed rhythmic activity but it was less persistent and of a lower amplitude than the rhythms of the mother-reared group. In the isolated rat pups nocturnal partitioning of activity was strengthened in the presence of both a light-dark cycle and a feeding cycle but only when the feeding resembled more natural nursing rhythms. In animals kept on constant light and a feeding cycle, activity occurred slightly more often during the 12-hr interval of decreased food intake. The addition of a temperature cycle--cooler nocturnal temperature--decreased the proportions of nocturnal motor activity. These results indicate that feeding and light-dark cycles may contribute to the synchronization of activity rhythms during the early postnatal period.


Diagnostic histologique et moléculaire des cancers de l'ovaire - recommandations pour la pratique clinique Saint-Paul 2021: Histological and molecular diagnosis of ovarian.
Oncogenetic testing is now part of standard management in high grade ovarian cancer, including at least mutational status of BRCA1/BRCA2 genes. If necessary, tumor genetic testing is followed by constitutional testing to either confirm the constitutional origin of variants identified in BRCA1/2 genes or detect variants in other predisposition genes. The whole process including prescription of tumoral testing, retrieval of analysis report and communication of results must be formalized, as well as information on possible consequences of the results for the patient and her family. Tumor material must meet criteria of size and cellularity to allow high-quality analysis. These samples are processed during the preanalytical phase with two major steps : time of cold ischemia and fixation. Only pathogenic (Class V) and likely pathogenic (Class IV) variants shown in tumor tissue are mentioned in the report. Currently, only BRCA1 and BRCA2 genes are routinely studied but, in the future, analysis will be extended to other genes involved in homologous recombination repair. In patients without BRCA mutation, other biomarkers reflecting sensitivity to PARP inhibitors, such as HRD scores (homologous recombination deficiency) that appeared recently, will have to be implemented in routine practice in order to better select patients for these treatments and choose optimal therapy.


ADAM-mediated ectodomain shedding of HB-EGF in receptor cross-talk.
All ligands of the epidermal growth factor receptor (EGFR) which has important roles in development and disease, are shed from the plasma membrane by metalloproteases. The ectodomain shedding of EGFR ligands has emerged as a critical component in the functional activation of EGFR in the interreceptor cross-talk. Identification of the sheddases for EGFR ligands using mouse embryonic cells lacking candidate sheddases (a disintegrin and metalloprotease; ADAM) has revealed that ADAM10, -12 and -17 are the sheddases of the EGFR ligands in response to various shedding stimulants such as GPCR agonists, growth factors, cytokines, osmotic stress, wounding and phorbol ester. Among the EGFR ligands, heparin-binding EGF-like growth factor (HB-EGF) is a representative ligand to understand the pathophysiological roles of the ectodomain shedding in wound healing, cardiac diseases, etc. Here we focus on the ectodomain shedding of HB-EGF by ADAMs, which is not only a key event of receptor cross-talk but also a novel intercellular signaling by the carboxy-terminal fragment (CTF signal).


Safety and efficacy of hyperosmolar irrigation solution in shoulder arthroscopy.
A hyperosmolar irrigation solution has been reported to be safe and have potential benefits for use during shoulder arthroscopy in an animal model study. In this study, the clinical effects of a hyperosmolar solution were compared with a standard isotonic solution when used for shoulder arthroscopy. A prospective, double-blind, randomized controlled trial was performed to compare isotonic (273 mOsm/L) and hyperosmolar (593 mOsm/L) irrigation solutions used for arthroscopic rotator cuff repair. Primary outcomes focused on the amount of periarticular fluid retention based on net weight gain, change in shoulder girth, and pain. All patients were tracked through standard postsurgical follow-up to ensure no additional complications arose. Patients were contacted at 1 year to assess American Shoulder and Elbow Surgeon score, visual analog scale pain score, and the Single Assessment Numeric Evaluation shoulder scores RESULTS: Fifty patients (n = 25/group) were enrolled and completed the study. No statistically significant differences were noted between cohorts in demographics or surgical variables. The hyperosmolar group experienced significantly less mean weight gain (1.6 ± 0.82 kg vs. 2.25 ± 0.77 kg; P = .005), significantly less change in shoulder girth (P < .05), and a significantly lower immediate postoperative visual analog scale pain score (P = .036). At 1 year postoperatively, the differences between groups for American Shoulder and Elbow Surgeons, visual analog scale pain, and Single Assessment Numeric Evaluation were not significant (P > .2). A hyperosmolar irrigation solution provides a safe and effective way to decrease periarticular fluid retention associated with arthroscopic rotator cuff surgery without any adverse long-term effects. Use of a hyperosmolar irrigation solution for shoulder arthroscopy has potential clinical benefits to surgeons and patients.


Splenic hydatid cyst perforating into the colon manifesting as acute massive lower gastrointestinal bleeding: an unusual presentation of disseminated abdominal echinococcosis.
Hydatid disease can occur in all viscera and soft tissues, although the liver and the lungs are the organs most commonly involved. Isolated splenic involvement with the disease is extremely rare. Splenic hydatid cysts may suppurate, fistulise to adjacent organs, or rupture into the peritonaeal cavity. However, acute, massive lower gastrointestinal bleeding due to splenocolic communication resulting from splenic echinococcal cyst has not been previously reported. We present a 77-year-old woman with disseminated abdominal echinococcosis, and active lower gastrointestinal bleeding due to splenocolic fistula resulting from splenic hydatid cyst. She was treated successfully with en-bloc excision of the spleen and splenic flexure of the colon.


Antibiotics in the management of PROM and preterm labor.
A significant fraction of preterm birth results from subclinical intrauterine infection. It is presumed that ascending bacterial colonization of the decidua results and either uterine contractions or membrane weakening that results in the clinical presentation of preterm labor or PROM. Those with overt infection require delivery. However, it is plausible that adjunctive antibiotic treatment during therapy for preterm labor and PROM remote from term could result in pregnancy prolongation and reductions in gestational age-dependent and infectious newborn morbidities. Data support adjunctive antibiotic treatment during conservative management of PROM remote from term. Such treatment should include broad-spectrum agents, typically intravenous therapy initially, and continue for up to 7 days if undelivered. Such treatment should be reserved for women presenting remote from term where significant improvement in neonatal outcomes can be anticipated with conservative management. Alternatively, current evidence suggests that antibiotic treatment in the setting of preterm labor with intact membranes does not consistently prolong pregnancy or improve newborn outcomes. Given this, and the concerning findings from the ORACLE II trial of antibiotics for preterm labor, this treatment should not be offered in the setting of preterm labor with intact membranes. Although one could speculate that women with preterm labor and with either a short cervical length for a positive fetal fibronectin screen might benefit from antibiotic therapy, no well-designed, randomized, controlled trials addressing this issue have been completed. Therefore, antibiotic therapy for women in preterm labor should be reserved for usual clinical indications, including suspected bacterial infections, GBS prophylaxis, and chorioamnionitis.


Anti-hyperalgesic and anti-inflammatory effects of ketorolac tromethamine gel using pulsed ultrasound in inflamed rats.
The aim of this study was to determine if a ketorolac tromethamine (KT) gel solution could be administered in vivo via phonophoretic transdermal delivery using pulsed ultrasound by examining its anti-hyperalgesic and anti-inflammatory effects in a rat carrageenan inflammation model. 1% carrageenan was injected into the plantar surface of the right hindpaw of a rat, and anti-hyperalgesic and anti-inflammatory effects of KT via phonophoretic transdermal delivery were examined. The changes in the mechanical and thermal hyperalgesia, nociceptive flexor reflex (NFR), as well as the swelling changes were determined. According to the anti-hyperagesia and anti-inflammation tests, which were used to determine the change in the pain threshold, NFR and swelling showed that the group given the phonophoretic transdermal delivery of KT exhibited significantly more noticeable anti-hyperalgesic and anti-inflammatory effects than those treated with the simple application of a KT gel. The transdermal application of KT gel using phonophoresis had significant anti-hyperalgesic and anti-inflammatory effects. These findings suggest that the transdermal administration of a KT gel using phonophoresis using pulsed ultrasound might be useful for treating acute inflammation and pain.


Mobile gamma cameras in breast cancer care - a review.
Currently, due to progress in detection and to extended screening, surgeons have to deal with increasing numbers of non-palpable lesions in breast cancer. These lesions can be treated by radio-guided surgery in the lumpectomy associated with sentinel lymph node (SLN) procedures. Thanks to advances in detector technology, mini gamma cameras are now available, that can perform real-time lymphoscintigraphy during surgery, or at bedside. In this article, we review the clinical literature on these dedicated cameras used in breast cancer surgery. The goal is to show how these cameras are used in breast cancer treatment and in SLN biopsy and what kind of benefits they offer. We conducted our search on MEDLINE and EMBASE databases. We performed a comprehensive review to identify clinical studies or cases using mobile gamma cameras in breast cancer surgery. We collected 14 articles published between January 2000 and March 2012. We analysed the use of the mobile cameras and the obtained results. Mobile gamma cameras seem to be useful imaging tools either used pre-operatively or during surgery. They assist surgeons with accurate localization of SLNs and/or radio-labelled tumours, and in verification that all radioactive nodes have been excised.


Effectiveness of a multiple health-behaviour-change intervention in increasing adherence to the Mediterranean Diet in adults (EIRA study): a randomized controlled hybrid trial.
The present study describes the effectiveness of a complex intervention that addresses multiple lifestyles to promote healthy behaviours in increasing adherence to the Mediterranean diet (MD). METHODS: Cluster-randomised, hybrid clinical trial controlled with two parallel groups. The study was carried out in 26 primary Spanish healthcare centres. People aged 45-75 years who presented at least two of the following criteria were included: smoker, low adherence to the MD or insufficient level of physical activity. The intervention group (IG) had three different levels of action: individual, group, and community, with the aim of acting on the behaviours related to smoking, diet and physical activity at the same time. The individual intervention included personalised recommendations and agreements on the objectives to attain. Group sessions were adapted to the context of each healthcare centre. The community intervention was focused on the social prescription of resources and activities performed in the environment of the community of each healthcare centre. Control group (CG) received brief advice given in the usual visits to the doctor's office. The primary outcome was the change, after 12 months, in the number of participants in each group with good adherence to the MD pattern. Secondary outcomes included the change in the total score of the MD adherence score (MEDAS) and the change in some cardiovascular risk factors. Three thousand sixty-two participants were included (IG = 1,481, CG = 1,581). Low adherence to the MD was present in 1,384 (93.5%) participants, of whom 1,233 initiated the intervention and conducted at least one individual visit with a healthcare professional. A greater increase (13.7%; 95% CI, 9.9-17.5; p < 0.001) was obtained by IG in the number of participants who reached 9 points or more (good adherence) in the MEDAS at the final visit. Moreover, the effect attributable to the intervention obtained a greater increase (0.50 points; 95% CI, 0.35 to 0.66; p < 0.001) in IG. A complex intervention modelled and carried out by primary healthcare professionals, within a real clinical healthcare context, achieved a global increase in the adherence to the MD compared to the brief advice. ClinicalTrials.gov Identifier: NCT03136211. Retrospectively registered on 02/05/2017 https://clinicaltrials.gov/ct2/show/NCT03136211.


Fresh Frozen Plasma Use in a Neonatal Unit in South Africa.
Despite limited evidence, fresh frozen plasma (FFP) transfusions are a relatively common neonatal procedure. Quantify FFP usage in our unit; determine indications for transfusions and compliance with published guidelines. Data were retrospectively collected on infants who received FFP from January 2009 to December 2013. Admissions totalled 10 912 infants during the study period. In total, 113 case notes were reviewed and 142 FFP transfusions were administered. Infants receiving FFP had a high mortality rate (54.87%) and an increased odds ratio for mortality 17.9 (95% confidence interval 12.0-26.6). In total, 75% FFP transfusions were compliant with guidelines. The difference between pre- and post-transfusion coagulation profile in 36.3% of infants was not statistically significant. FFP was often used in accordance with published guidelines in our neonatal unit. However, the appropriate use and effectiveness of FFP in improving neonatal outcomes undermines the rationale for FFP usage in current guidelines.


Review of the genus Vekunta Distant from China, with descriptions of two new species (Hemiptera, Fulgoromorpha, Derbidae).
The derbid genus Vekunta Distant, 1906 is reviewed. Two new species, V.bambusana sp. n. and V.pentaprocessusa sp. n., are described and illustrated from the southwest of China to give the genus twenty-nine species in China. A checklist and a key to species of the genus from China are also provided.


Prospective evaluation of 6895 groin hernia repairs in women.
Although 8 per cent of groin hernia repairs are performed in women, there is little published literature relating specifically to women. This study compared differences in outcome between women and men after groin hernia repair. Data collected prospectively in the Swedish Hernia Register between 1992 and 2003 were analysed, including 6895 groin hernia repairs in women and 83 753 in men. A higher proportion of emergency operations was carried out in women (16.9 per cent) than men (5.0 per cent), leading to bowel resection in 16.6 and 5.6 per cent respectively. During reoperation femoral hernias were found in 41.6 per cent of the women who were diagnosed with a direct or indirect inguinal hernia at the primary operation. The corresponding proportion for men was 4.6 per cent. The hernia repair was not classified as a standard operation (e.g. Shouldice, Lichtenstein, Plug/Mesh, TAPP/TEP) in 38.2 per cent of women and 11.2 per cent of men. Women had a significantly higher risk of reoperation for recurrence than men, and techniques associated with the lowest risk for reoperation in men had the highest risk in women. A greater proportion of women than men require emergency groin hernia repair, with consequently higher rates of bowel resection, complications and death. Surgical techniques developed for use in men may put women at unnecessary risk.


Design, synthesis, and biophysical properties of a helical Abeta1-42 analog: Inhibition of fibrillogenesis and cytotoxicity.
The aggregation of amyloid beta-peptide (Abeta) into beta-sheet-rich aggregates is a crucial step in the etiology of Alzheimer's disease. Helical forms of Abeta have been suggested to be intermediates in the aggregation process of the peptide in aqueous phase, micelles and membranes. A stable helical Abeta analog would be useful to investigate the role of helical intermediates in fibrillization by Abeta. Here we designed a helical analog by simply cross-linking the Cys residues of A30C, G37C-Abeta1-42 with 1,6-bismaleimidohexane. The analog assumed a weak alpha-helical conformation in model membranes mimicking lipid raft microdomains of neuronal membranes under conditions in which the wild-type Abeta1-42 formed a beta-sheet, indicating the cross-linking locally induced a helical conformation. Furthermore, addition of equimolar helical Abeta analog significantly reduced the amyloid formation and cytotoxicity by Abeta1-42. Thus, our helical Abeta1-42 is not only a model peptide to investigate the role of helical intermediates in fibrillization by Abeta, but also an inhibitor of Abeta-induced cytotoxicity.


Oral and inhaled glucocorticoid use and risk of Achilles or biceps tendon rupture: a population-based case-control study.
Tendinotoxicity of glucocorticoids (GC) has been shown, but evidence on how this translates into clinical practice remains scarce. To explore the association between oral or inhaled GC use and the risk of Achilles or biceps tendon rupture (ATR/BTR). We identified patients aged 18 to 89 years with incident ATR or BTR (1995-2013) for a matched (1:4) case-control analysis using the UK-based Clinical Practice Research Datalink. We stratified oral GC use by indication, timing and duration of use, continuous versus intermittent use, cumulative dose, and average daily dose. We stratified inhaled GC use by timing and number of prescriptions. Among 8,202 cases, we observed increased odds ratios (ORs) around 3.0 for continuous oral GC use, which declined shortly after therapy cessation (similarly across indications). Odds ratios increased with average daily dose (≥ 10 mg/day, OR 4.05, 95% CI 2.32-7.08) and were elevated after one cycle of high-dose oral GC (≥ 20 mg/day). There was no effect of inhaled GC at any level of exposure. Our results provide evidence that oral GC therapy increases the risk of tendon rupture in a dose-response relationship. A single short-term high-dose GC treatment course may be sufficient transiently to increase the risk of tendon rupture.


The neuroprotective role of prolonged normobaric oxygenation applied during ischemia and in the early stage of reperfusion in cerebral ischemic rats.
Recanalization is the main treatment option for ischemic stroke. However, prognosis remains poor for about half of patients after recanalization, possibly due to the "no-reflow" phenomenon at the early phase of recanalization. Normobaric oxygenation (NBO) during ischemia can reportedly maintain the partial pressure of oxygen and exert a protective effect in ischemic brain tissue. This study investigated whether prolonged NBO treatment during ischemia and the early phase of reperfusion (i/rNBO) has neuroprotective effects and to elucidate the underlying mechanisms in rats with middle cerebral artery occlusion plus reperfusion. NBO treatment significantly elevated the level of O2 in the atmosphere and arterial blood without altering the level of CO2. The infarcted cerebral volume was significantly reduced by application of i/rNBO as compared to iNBO (applied during ischemia) or rNBO (applied at the early phase of reperfusion), indicating better protective effects of i/rNBO. i/rNBO more effectively suppressed s-nitrosylation of MMP-2 (amplifying inflammation) as compared to iNBO and rNBO, dramatically downregulated the cleavage of poly(ADP-ribose)polymerase-1 (PARP-1, acting as the substrate of MMP-2), and suppressed neuronal apoptosis, as determined by the TUNEL assay and staining for NeuN. These results demonstrated that application of i/rNBO in the early stage of reperfusion significantly alleviated neuronal apoptosis via suppression of the MMP-2/PARP-1 pathway. The mechanism underlying the neuroprotective role of i/rNBO involved prolonged NBO treatment for cerebral ischemia, suggesting that i/rNBO may allow expansion of the time window for NBO application in stroke patients following vascular recanalization.


Sterol content of foods of plant origin.
Available data on phytosterols from the world's literature have been compiled and summarized. There still exists a paucity of data on the quantities of plant sterols in many foods. More extensive data are available on the relative sterol composition. Our compilation shows that plant oils are excellent sources of phytosterols. Nuts and seeds contain moderate levels, and fruits and vegetables generally contain the lowest concentrations of plant sterols. Analyses of the minor sterols, namely, the delta5- and delta7-phytosterols, have become available only recently.


Efficacy and safety of mineral trioxide aggregate (MTA) pulpotomy for caries-exposed permanent teeth in children: a systematic review and meta-analysis.
This study aimed to evaluate the effect of mineral trioxide aggregate (MTA) pulp capping for caries-exposed permanent teeth. However, the efficacy of MTA in the treatment of children's gums is still controversial, and different studies have shown different efficacy. Therefore, it is necessary to systematically review the efficacy and safety of MTA pulp incision in the treatment of pediatric caries using meta methods. We used meta-analysis to compare differences in the efficacy of MTA and calcium hydroxide (CH) for treating caries in permanent teeth. The mean treatment success rate of MTA for reversible and irreversible pulpitis groups was calculated, and the effect of apical opening condition and surgical type on success rate were investigated. A total of 15 studies were included, and meta-analysis showed that there was a significant statistical difference between the MTA group and CH group in efficacy [odds ratio (OR) =1.87, 95% confidence interval (CI): 1.28, 2.73, P=0.001, I2=63%, Z=3.25], success rate (OR =3.20, 95% CI: 1.93, 5.30, P<0.00001, I2=0%, Z=4.52), influence of apical foramen condition on success rate (OR =1.77, 95% CI: 1.14, 2.73, P=0.01, I2=15%, Z=2.56), and surgical procedure on success rate (OR =2.64, 95% CI: 1.65, 4.23, P<0.0001, I2=45%, Z=4.05). Our results showed that MTA pulpotomy was superior to CH. Nonclosure of apical openings and complete coronal pulpotomy may be more beneficial than partial pulpotomy.


Analysis of derivatised steroids by matrix-assisted laser desorption/ionisation and post-source decay mass spectrometry.
Neutral steroids are difficult to analyse using desorption ionisation methods coupled with mass spectrometry (MS). However, steroids with an unhindered ketone group can readily be derivatised with the Girard P (GP) reagent to give GP hydrazones. Steroid GP hydrazones contain a quaternary nitrogen atom and are readily desorbed in the matrix-assisted laser desorption/ionisation (MALDI) process, giving an improvement in sensitivity of two orders of magnitude. Steroids without a ketone group, but with a 3beta-hydroxy-Delta5 function, can be readily converted to 3-oxo-Delta4 steroids and subsequently derivatised to GP hydrazones for MALDI analysis. In addition to giving strong [M]+ ions upon MALDI, steroid GP hydrazones give informative post-source decay (PSD) spectra. By using the accurate mass of the precursor-ion measured by MALDI-MS, in combination with the structural information encoded in its PSD spectrum, steroid structures can readily be determined.


A "hateful epileptic" patient in the burn unit.
An interdisciplinary team discussed the case of a 31-year-old woman who sustained second- and third-degree burns while having a seizure. She was a difficult patient who elicited a good deal of negative feelings from the staff. The interview raised the possibility of this burn having been a suicidal attempt, and the subsequent discussion centered on effective ways of relating to her pathologic defense mechanisms. The need for a comprehensive approach that took into consideration the biologic, psychologic, and social aspects of her needs became evident to all the participants.


Practice Changing Updates in Perioperative Medicine Literature 2022. A Systematic Review.
Perioperative medicine is a rapidly growing multidisciplinary field with significant advances published each year. In this review, we highlight important perioperative publications in 2022. A multi-database literature search from January to December of 2022 was undertaken. Original research articles, systematic reviews, meta-analyses, and guidelines were included. Abstracts, case reports, letters, protocols, pediatric and obstetric articles, and cardiac surgery literature were excluded. Two authors reviewed each reference using the Distiller SR systematic review software (Evidence Partners Inc., Ottawa, Ont, Canada). A modified Delphi technique was used to identify 8 practice-changing articles. We identified another 10 articles for tabular summaries. We highlight why these articles have the potential to change clinical perioperative practice and areas where more information is needed.


Measurement of pH, electrolytes and electrophoretic studies of tear proteins in tears of patients with dacryoliths: a novel concept for dacryoliths.
Dacryolithiasis is one of the causes of acquired nasolacrimal duct obstruction, although its origin is unclear. The purpose of this study was to investigate the differences in tear constituents between patients with nasolacrimal duct obstruction with dacryoliths and those without dacryoliths. In a prospective case-control study, undiluted tears were collected from 30 eyes from 30 patients with partial acquired nasolacrimal duct obstruction (PANDO) consisting of 17 PANDO patients with dacryoliths and 13 PANDO patients without dacryoliths. The pH, and the Na(+), K(+), Cl(-), total calcium and total protein concentrations were determined. The composition of the tear proteins was assessed by cellulose acetate electrophoresis. In the tear samples from 17 eyes with PANDO/dacryoliths, the mean +/- SD K(+) level was 15.6 +/- 3.1 mEq/l. In the tear samples from 13 PANDO controls, the mean +/- SD K(+) level was 19.8 +/- 4.9 mEq/l. The difference between the two groups was statistically significant (p = 0.02). In the tear samples from PANDO/dacryolith patients, the mean +/- SD total protein level was 129.0 +/- 72.9 mg/dl. In the tear samples from the PANDO controls the mean +/- SD total protein level was 261.6 +/- 132.5 mg/dl. The difference between the two groups was statistically significant (p = 0.00). In the tear protein fractions from electrophoresis, a low level of lysozyme was observed in the PANDO/dacryolith samples compared with the PANDO control samples (p = 0.03). The tears from patients with PANDO due to dacryoliths showed a change in the concentrations of electrolytes and protein, particularly lysozyme, compared with that of the patients with PANDO without dacryoliths, which may be related to the pathogenesis of dacryoliths.


Mical modulates Tau toxicity via cysteine oxidation in vivo.
Tau accumulation is clearly linked to pathogenesis in Alzheimer's disease and other Tauopathies. However, processes leading to Tau fibrillization and reasons for its pathogenicity remain largely elusive. Mical emerged as a novel interacting protein of human Tau expressed in Drosophila brains. Mical is characterized by the presence of a flavoprotein monooxygenase domain that generates redox potential with which it can oxidize target proteins. In the well-established Drosophila Tauopathy model, we use genetic interactions to show that Mical alters Tau interactions with microtubules and the Actin cytoskeleton and greatly affects Tau aggregation propensity and Tau-associated toxicity and dysfunction. Exploration of the mechanism was pursued using a Mical inhibitor, a mutation in Mical that selectively disrupts its monooxygenase domain, Tau transgenes mutated at cysteine residues targeted by Mical and mass spectrometry analysis to quantify cysteine oxidation. The collective evidence strongly indicates that Mical's redox activity mediates the effects on Tau via oxidation of Cys322. Importantly, we also validate results from the fly model in human Tauopathy samples by showing that MICAL1 is up-regulated in patient brains and co-localizes with Tau in Pick bodies. Our work provides mechanistic insights into the role of the Tau cysteine residues as redox-switches regulating the process of Tau self-assembly into inclusions in vivo, its function as a cytoskeletal protein and its effect on neuronal toxicity and dysfunction.


Type 1 diabetes in insulin-treated adult-onset diabetic subjects.
The frequency of autoimmune features was compared in adult-onset diabetic subjects either requiring insulin treatment within 12 months of diagnosis or progressing to insulin therapy after a latency of at least 5 years. Adult-onset insulin-treated diabetic subjects were sampled from the population-based Canterbury Diabetes Registry (n = 1580). There were 237 (15%) registrants who met the study criteria of age < 75 years at 1 January 1993, age at diagnosis of diabetes > or = 45 years and duration of diabetes between 5 and 15 years; 101 subjects commenced insulin 5-15 years after diagnosis (group 1) and 80 subjects commenced insulin within 1 year of diagnosis (group 2). C-peptide levels, islet cell antibodies (ICA) and antibodies against glutamic acid decarboxylase (anti-GAD) were determined in all individuals from group 1 (n = 27) and group 2 (n = 23) who agreed to be recruited to the study. The group 1 and group 2 samples did not differ significantly in their demographic characteristics, nor were they different from the two groups from which they were drawn (mean age, 64.2 years; age at diagnosis, 53.5 years; duration of diabetes, 10.7 years; body mass index, 28.6 kg/m2). Overall, 12 of the 50 (24%) study subjects tested positive for anti-GAD; 43% (10) of group 2 subjects were anti-GAD positive compared with only 7.4% (2) of group 1 subjects (P < 0.01). Postprandial C-peptide levels were significantly lower in group 2 subjects compared with group 1 subjects (627 vs 1124 pM, P < 0.05). All subjects were ICA negative. These observations suggest that autoimmune destruction of beta-cells explains early requirement for insulin in adult-onset diabetes.


How technology facilitates tourism education in COVID-19:case study of nankai University.
School closures follows the sudden outbreak of COVID-19. In order to minimize the negative impact on learning and teaching, MOOCs, SPOC and live broadcasting have been taken as the responsive measures of universities in China. Taking tourism education of Nankai University as an example, the paper illustrates the operation of distance and online teaching during the epidemic, and analyzes the prons and cons of adopted approaches in order to provide practical reference to online education in other countries as well.


Comparative study of physiological and anatomical triage in major incidents using a new simulation model.
To develop and evaluate a simulation model making it possible to evaluate the accuracy and efficiency of different triage methods; to compare the results of physiological and anatomical triage performed by medical staff with different levels of skills with the use of this model. A simulation model was created based on patient cards giving sufficient physiological data as a base for physiological triage and anatomical data as description of findings at exposure, providing a base for anatomical triage. Three groups with different skills in disaster medicine, nurse students (n = 23), ambulance nurses (n = 20), and surgeons (n = 30), performed triage based on the patient cards. The outcome was given as potential avoidable mortality. The results of the triage for the two methods were compared to the result of the same triage performed by an expert group. Differences in triage: Within the groups, the difference between the two triage methods was only significant for the surgeons (p < 0.001), who had a better result using the anatomical triage. For the "physiological triage," there were no significant differences between the three groups. Regarding the results for the "anatomical triage," there were significant differences between both the nurse students and the surgeons (p < 0.001) and the ambulance nurses and the surgeons (p < 0.05). Results in distribution of patients and potential avoidable mortality: Within the groups, the difference between the two methods was significant for all the groups (nurse students, p < 0.01; ambulance nurses, p < 0.01; and surgeons, p < 0.001). They all had a better outcome with anatomical triage (nurse students, 6.1 percent; ambulance nurses, 6.1 percent; and surgeons 19.5 percent less mortality than physiological triage). The group that made the best outcome from physiological triage was the ambulance nurses who had a significantly better result than both nurse students (p < 0.01) and surgeons (p < 0.001). The mean mortality rate for ambulance nurses was 31.1 percent, nurse students, 37 percent, and surgeons was 38.1 percent. Regarding the anatomical triage, there was a significant difference (p < 0.001) between the groups of nurse students (30.9 percent mortality) and surgeons (18.9 percent mortality). The differences between the rest of the groups were also significant (p < 0.05). The model developed for this study made it possible to compare different methods of triage and also triage performed by staff of different levels of training and experience. Anatomical triage for all test groups in this study gave significantly better results than physiological triage regarding calculated outcome and this difference increased with increasing experience.


Aggressive elimination of precancerous lesions of the vocal cords to avoid risk of cancer.
Several studies show that early histological classification and excision of precancerous lesions of the vocal cords reduces the risk of cancer development. National Danish guidelines have not been established. The purpose of this study was to describe a Danish series of patients with precancerous lesions of the vocal cords and to estimate the risk of malignant transformation. This was a retrospective cohort study, including a total of 101 patients with histologically verified precancerous lesions of the vocal cords who were treated from 1997 to 2007 at Odense University Hospital (OUH). Among the 101 patients, 18 (18%) were diagnosed with mild dysplasia, 16 (16%) with moderate dysplasia, 35 (35%) with severe dysplasia and 32 (32%) with carcinoma in situ (CIS) at the initial examination at OUH. Fifteen patients (15%), all males, developed invasive cancer. Among these, one patient was initially diagnosed with mild dysplasia, one with moderate dysplasia, seven with severe dysplasia and six with CIS. In 11 of the 15 patients (73%), cancer occurred within one year from the time of diagnosis of the precancerous lesion, whereas four cancers occurred years later. The malignant transformation rate is comparable with other recent series. A strategy with elimination of all visible pathology is preferable. not relevant. not relevant.


Methotrexate and mortality in patients with rheumatoid arthritis: a prospective study.
Methotrexate is the most frequent choice of disease-modifying antirheumatic therapy for rheumatoid arthritis. Although results of studies have shown the efficacy of such drugs, including methotrexate, on rheumatoid arthritis morbidity measures, their effect on mortality in patients with the disease remains unknown. Our aim was to prospectively assess the effect on mortality of methotrexate in a cohort of patients with rheumatoid arthritis. Our cohort included 1240 patients with rheumatoid arthritis seen at the Wichita Arthritis Center, an outpatient rheumatology facility. Patients' details were entered into a computerised database at the time of their first clinic visit. We also obtained and recorded demographic, clinical, laboratory, and self-reported data at each follow-up visit (average interval 3.5 months). We estimated the mortality hazard ratio of methotrexate with a marginal structural Cox proportional hazards model. 191 individuals died during follow-up. Patients who began treatment with methotrexate (n=588) had worse prognostic factors for mortality. After adjustment for this confounding by indication, the mortality hazard ratio for methotrexate use compared with no methotrexate use was 0.4 (95% CI 0.2-0.8). Other conventional disease-modifying antirheumatic drugs did not have a significant effect on mortality. The hazard ratio of methotrexate use for cardiovascular death was 0.3 (0.2-0.7), whereas that for non-cardiovascular deaths was 0.6 (0.2-1.2). Our data indicate that methotrexate may provide a substantial survival benefit, largely by reducing cardiovascular mortality. This survival benefit of methotrexate would set a standard against which new disease-modifying antirheumatic drugs could be compared.


Successful Ayurvedic Management of Dermatophytosis-A case report.
Fungal infections are quite common in day-to-day practice. The available conventional treatments include various topical and systemic anti-pruritic and anti-fungal agents which are associated with high rates of treatment failure and adverse effects. Fungal infections manifest a great challenge to clinicians due to higher rate of recurrences and if not treated early, can lead to the development of more extensive diseases. In Ayurveda, this condition has resemblance with Dadru kustha. The characteristics of Dadrukustha are circumscribed erythematous, scaly plaques due to dematophytes infection. It is a type of Kshudra kushta, tridosaja vyadhi with dominance of pitta and kaphadosha, having characteristic features such as presence of utsannamandal (elevated circular skin lesion), kandu (itching), raga (erythyma), and pidaka (eruptions). In this case report, a 62-year old male patient suffering from tinea corporis on and off for one year was treated effectively with Ayurvedic medicines. Significant changes were observed in the skin lesion and in the patient symptoms after 42 days of regular treatment. Post-treatment follow-up after 1 month did not reveal any signs of recurrences of lesions. Ayurvedic medicines offer an effective approach to manage tinea corporis.


The Therapeutic Potential of Stem Cells for Bronchopulmonary Dysplasia: "It's About Time" or "Not so Fast" ?
While the survival of extremely premature infants has improved over the past decades, the rate of complications - especially for bronchopulmonary dysplasia (BPD) - remains unacceptably high. Over the past 50 years, no safe therapy has had a substantial impact on the incidence and severity of BPD. This may stem from the multifactorial disease pathogenesis and the increasing lung immaturity. Mesenchymal Stromal Cells (MSCs) display pleiotropic effects and show promising results in neonatal rodents in preventing or rescuing lung injury without adverse effects. Early phase clinical trials are now underway to determine the safety and efficacy of this therapy in extremely premature infants. This review summarizes our current knowledge about MSCs, their mechanism of action and the results of preclinical studies that provide the rationale for early phase clinical trials and discuss remaining gaps in our knowledge.


[PROK1, prognostic marker of embryo implantation?].
In spite of improvements in assisted reproductive technology (ART) during the last 30 years, the rate of pregnancy remains constrained, as only about 25 % of embryo transfer lead to successful pregnancies, even with an average of two embryos replaced. Embryo selection is currently based on the establishment of morphokinetic scores, a method that obviously exhibits limitations. Therefore, the assessment of embryo development potency by criteria of higher predictive value is mandatory in order to increase the rates of pregnancy. Nowadays, there is increasing evidence that angiogenic factors might contribute to the success of the implantation and to the pregnancy outcome. Among these factors, prokineticin 1 (PROK1) and its receptors (PROKRs) constitute new targets that showed over the last ten years strong biological features directly linked to ovarian physiology, endometrial receptivity, embryo implantation and thus successful pregnancies. In ART, the rates of circulating PROK1 were reported in 2012 as significantly linked to the quality of embryonic cohort, as well as to the rates of pregnancy. Our preliminary data suggest a high potential of this cytokine in the success of implantation and pregnancy, and strongly overtones the emergency to investigate the value of its measurement in conditioned media of oocytes and embryo cultures in ART.


Mechanical stress activates proinflammatory cytokines and antioxidant defense enzymes in human dental pulp cells.
This study was conducted to investigate the effects of mechanical stress, particularly cyclic strain, on proinflammatory cytokines as well as antioxidant properties and their interactions with cellular defense systems in human dental pulp (HDP) cells. Exposure of HDP cells to mechanical strain induced inflammatory cytokines such as interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-6, as well as antioxidant genes such as heme oxygenase-1, superoxide dismutases, reduced nicotinamide adenine dinucleotide phosphate quinone oxidoreductase-1, and glutathione peroxidases. In addition, treatment with N-acetylcysteine, indomethacin, and heme oxygenase-1 inhibitors blocked reactive oxygen species production, antioxidant response element (ARE) gene expression, and Nrf2 accumulation that occurred in response to mechanical stress. These data demonstrate that mechanical strain activates inflammatory cytokines and oxidative stress, which then act in concert to induce the Nrf2-/ARE-mediated antioxidant enzymes. Therefore, we suggest that the activation of a compensatory adaptation or defense antioxidant system might represent a novel mechanism for protecting HDP cells against mechanical stress.


Assessment of physician-patient trust in the obstetrics and gynecology departments in Poland and Greece.
To evaluate patient trust in their physicians of the obstetrics and gynecology departments. We used the Trust in Physician Scale comprising 11-items. Data were collected from 150 women hospitalized in the obstetrics and gynecology departments in Poland and 109 in Greece. Of the surveyed, 25.3% from Poland and 47.4% from Greece did not doubt their doctors' proper care. Almost 90% of the respondents from Poland and 58.8% from Greece agreed with the statement "I trust my doctor very much, that is why I always comply with his/her advice". More than 68% of the patients from Poland and 56.9% from Greece were convinced that "if my physician tells me something, this has to be the truth": Almost 77% of patients from Poland and 43.1% from Greece declared trust in their physicians therapy. Eighty-four percent of women from Poland and 49.55% from Greece were convinced that their doctor is a true expert in the treatment of their diseases. Nearly 97% of the patients from Poland and 35.8% from Greece did not declare fear of their physician not keeping the professional secret. The Trust in Physician Scale is an appropriate tool for assessing levels of patient trust in their gynecologist. Patients reported a relatively high degree of trust in their gynecologists. Women from Greece more often than from Poland did not trust their physicians, and declared that doctors did not do all for their care.


Screening and identification of mimotopes of the major shrimp allergen tropomyosin using one-bead-one-compound peptide libraries.
The one-bead-one-compound (OBOC) combinatorial peptide library is a powerful tool to identify ligand and receptor interactions. Here, we applied the OBOC library technology to identify mimotopes specific to the immunoglobulin E (IgE) epitopes of the major shellfish allergen tropomyosin. OBOC peptide libraries with 8-12 amino acid residues were screened with serum samples from patients with shellfish allergy for IgE mimotopes of tropomyosin. Twenty-five mimotopes were identified from the screening and their binding reactivity to tropomyosin-specific IgE was confirmed by peptide ELISA. These mimotopes could be divided into seven clusters based on sequence homology, and epitope mapping by EpiSearch of the clustered mimotopes was performed to characterize and confirm the validity of mimotopes. Five out of six of the predicted epitopes were found to overlap with previously identified epitopes of tropomyosin. To further confirm the mimicry potential of mimotopes, BALB/c mice were immunized with mimotopes conjugated to keyhole limpet hemocyanin and assayed for their capacity to induce tropomyosin-specific antibodies. BALB/c mice that received mimotope immunization were found to have an elevated level of tropomyosin-specific immunoglobulin G, but not mice that received an irrelevant mimotope. This study pioneers the successful application of the OBOC libraries using whole sera to screen and identify multiple shrimp allergen mimotopes and validates their mimicry potential using in vitro, in vivo, and in silico methods.Cellular & Molecular Immunology advance online publication, 14 september 2015; doi:10.1038/cmi.2015.83.


Physician vaccination practices in mild to moderate inborn errors of immunity and retrospective review of vaccine completeness in IEI: results from the Canadian Immunization Research Network.
Safety and effectiveness concerns may preclude physicians from recommending vaccination in mild/moderate inborn errors of immunity (IEI). This study describes attitudes and practices regarding vaccination among physicians who care for patients with mild/moderate B cell or mild/moderate combined immunodeficiencies (CID) and vaccination completeness among patients diagnosed with IEIs. Canadian physicians caring for children with IEI were surveyed about attitudes and practices regarding vaccination in mild/moderate IEI. Following informed consent, immunization records of pediatric patients with IEI evaluated before 7 years of age were reviewed. Vaccine completeness was defined at age 2 years as 4 doses of diphtheria-tetanus-pertussis (DTaP), 3 doses pneumococcal conjugate (PCV), and 1 dose measles-mumps-rubella (MMR) vaccines. At 7 years 5 doses of DTP and 2 doses MMR were required. Forty-five physicians from 8 provinces completed the survey. Most recommended inactivated vaccines for B cell deficiency: (84% (38/45) and CID (73% (33/45). Fewer recommended live attenuated vaccines (B cell: 53% (24/45), CID 31% (14/45)). Of 96 patients with IEI recruited across 7 centers, vaccination completeness at age 2 was 25/43 (58%) for predominantly antibody, 3/13 (23%) for CID, 7/35 (20%) for CID with syndromic features, and 4/4 (100%) for innate/phagocyte defects. Completeness at age 7 was 15%, 17%, 5%, and 33%, respectively. Most physicians surveyed recommended inactivated vaccines in children with mild to moderate IEI. Vaccine completeness for all IEI was low, particularly at age 7. Further studies should address the reasons for low vaccine uptake among children with IEI and whether those with mild-moderate IEI, where vaccination is recommended, eventually receive all indicated vaccines.


Tetracycline suppresses ATP gamma S-induced CXCL8 and CXCL1 production by the human dermal microvascular endothelial cell-1 (HMEC-1) cell line and primary human dermal microvascular endothelial cells.
Tetracyclines (TCN) have powerful anti-inflammatory properties in addition to their anti-microbial effects. These anti-inflammatory effects are thought to play a role in inhibiting cutaneous inflammation in patients with rosacea and acne; however, the mechanism(s) of this action remains poorly understood. We have previously shown that adenosine-5'-triphosphate (ATP)gamma S, a hydrolysis-resistant ATP analogue, augments secretion of pro-inflammatory messengers by a human dermal microvascular endothelial cell line (HMEC-1). ATP released by the sympathetic nerves during stress may stimulate release of pro-inflammatory chemokines by dermal vessel endothelial cells, resulting in recruitment of inflammatory cells and exacerbation of inflammatory skin disease. Here we demonstrate that TCN inhibits ATP gamma S-induced release of pro-inflammatory mediators by HMEC-1 cells and primary human dermal microvascular endothelial cells. TCN dose-dependently inhibited ATP gamma S-induced augmentation of CXCL8 (interleukin-8) and CXCL1 (growth-regulated oncogene-alpha) production by HMEC-1 cells and primary human dermal endothelial cells in vitro. TCN and ATP gamma S did not affect HMEC-1 cell viability as determined by trypan-blue exclusion and cell counts. Inhibition of production of inflammatory mediators by endothelial cells may be one mechanism by which TCN improves inflammatory skin diseases. The ability to inhibit release of inflammatory mediators induced in HMEC-1 cells by purinergic agonists may be a useful way to screen for potential therapeutic agents for cutaneous inflammation.


Cavernous sinus fistulas: carotid cavernous fistulas and dural arteriovenous malformations.
Direct and indirect carotid cavernous sinus fistulas are uncommon vascular anomalies that result in increased pressure in the cavernous sinus. The subsequent changes in blood flow lead to orbital venous congestion, cranial neuropathies, and glaucoma. The following review summarizes knowledge of the clinical features, natural history, diagnostic testing, and therapy for carotid cavernous sinus fistulas.


Characterization of cis-platinum-induced Sertoli cell dysfunction in rodents.
The present study examined the effects of dosage and frequency of cis-platinum administration on various aspects of Sertoli cell function and its correlation with the status of spermatogenesis in rats 1 and 9 weeks after the initial drug administration. Adult male Sprague-Dawley rats were administered cis-platinum (10 mg/kg) intraperitoneally as a single dose or as five daily doses of 2 mg/kg. Electron microscopic observation of testicular tissues fixed in the presence of lanthanum revealed that cis-platinum administration resulted in leakage of the Sertoli cell tight junctions. This occurred as early as 24 hr after the five daily injections, and persisted at least 40 days. Testicular androgen-binding protein (ABP) content was not significantly affected by either treatment regimen after 1 or 9 weeks of recovery. On the other hand, serum ABP values were significantly elevated after 9 weeks of recovery. In addition, the increased sodium and decreased potassium concentrations in seminiferous tubular fluid noted in cis-platinum-treated animals were also indicative of abnormal Sertoli cell secretory function. Degeneration of spermatogenic cells was noted as early as 5 days after the last drug administration; and partial restoration of spermatogenesis was noted after 40 days of recovery. We conclude that in rats both morphological and biochemical properties of Sertoli cells are affected by cis-platinum administration. These changes in Sertoli cell function may be responsible for the cis-platinum-induced impairment of spermatogenesis in these animals.


Structural basis of terephthalate recognition by solute binding protein TphC.
Biological degradation of Polyethylene terephthalate (PET) plastic and assimilation of the corresponding monomers ethylene glycol and terephthalate (TPA) into central metabolism offers an attractive route for bio-based molecular recycling and bioremediation applications. A key step is the cellular uptake of the non-permeable TPA into bacterial cells which has been shown to be dependent upon the presence of the key tphC gene. However, little is known from a biochemical and structural perspective about the encoded solute binding protein, TphC. Here, we report the biochemical and structural characterisation of TphC in both open and TPA-bound closed conformations. This analysis demonstrates the narrow ligand specificity of TphC towards aromatic para-substituted dicarboxylates, such as TPA and closely related analogues. Further phylogenetic and genomic context analysis of the tph genes reveals homologous operons as a genetic resource for future biotechnological and metabolic engineering efforts towards circular plastic bio-economy solutions.


The pooled incidence of post-stroke seizure in 102 008 patients.
Post-stroke seizures and epilepsy may worsen the recovery and increase the disability of stroke patients during their daily lives. However, few meta-analysis studies have been conducted on post-stroke seizures incidence. We carried on a meta-analysis on the incidence rate of post-stroke seizures and associated factors. We searched the Medline, Embase, Web of Science, Science Citation Index, and Cochrane Library electronic databases (1990-2013) to identify observational studies of post-stroke seizures. Two authors independently extracted the related information from all included studies. We calculated the pooled incidence by meta-analysis using the software R version 12.3. A total of 34 longitudinal cohort studies involving 102 008 patients were included in our meta-analysis. The pooled incidence rate of post-stroke seizures was found to be 0.07 [95% confidence interval (CI), 0.05-0.09] while the rate of post-stroke epilepsy (PSE) was 0.05 (95% CI, 0.04-0.06). The incidence of post-stroke seizures in hemorrhagic stroke (0.10, 0.08-0.13) was much higher than in ischemic stroke (0.06, 0.04-0.08) and when the cortical region was involved (0.15, 0.10-0.21). Our meta-analysis showed that seizures occurred in about 6.93% of people with stroke. Seizures occurred more commonly after hemorrhagic stroke and when stroke occurred in the cortical region.


Online screening of nitric oxide scavengers in natural products using high performance liquid chromatography coupled with tandem diode array and fluorescence detection.
Nitric oxide (NO) is an important cellular signaling molecule with extensive physiological and pathophysiological effects. NO scavengers have the potential to treat inflammation, septic shock and other related diseases, and numerous examples have been chemically synthesized or isolated from natural products. The chemical diversity of natural products, however, means that a huge effort is necessary to efficiently screen and identify bioactive compounds, especially NO scavengers. In this article, we propose an effective analytical method to screen for NO scavengers in three natural products using an online system that couples high performance liquid chromatography with tandem diode array and fluorescence detection (HPLC-DAD-FLD). Eighteen compounds from radix of Scutellaria baicalensis Georgi and green tea displayed significant NO scavenging activity whereas components of Pueraria lobata (Willd.) Ohwi had no discernable activity. The structures of the active compounds were elucidated using Agilent Accurate-Mass Q-TOF LC/MS system. Preliminary analysis of structure-activity relationships indicated that, in flavonoids, a 2,3-double bond and a 3-H atom or a 3-OH group are essential for activity. In tannins, poly-hydroxyl groups are important for NO scavenging activity. Method validation indicated that the newly developed method is both reliable and repeatable. The online method that we present provides a simple, rapid and effective way to identify and characterize NO scavengers present in natural products.


Opioid peptides modulate the response of neurons of the superficial laminae of the rat spinal dorsal horn to GABA.
The modulatory effects of methionine-enkephalin (M-ENK) and selective opioid-receptor agonists on GABA-activated whole-cell currents were investigated in neurons acutely dissociated from the superficial laminae of the rat spinal dorsal horn using nystatin-perforated patch recording configuration under voltage-clamp conditions. The results show that: (1). GABA acted on GABA(A) receptors and elicited inward Cl(-) currents (I(GABA)) at -60 mV; (2). M-ENK depressed I(GABA) in approximately 65% of the tested neurons and potentiated I(GABA) in approximately 15% of the neurons tested; (3). the agonists of mu-, kappa-, and delta-opioid receptors-[D-AIa(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO), dynorphin-A (Dyn-A), and [D-Pen(2),D-Pen(5)]-enkephalin (DPDPE) also depressed the I(GABA), and the order of agonist potency was DAMGO>Dyn-A>DPDPE; and (4) naloxone blocked the inhibitory effects of M-ENK on I(GABA). The antagonists of mu-, kappa-, and delta-opioid receptors-beta-funaltrexamine (beta-FNA), nor-binaltorphimine (nor-BNI), and naltrindole (NTI) prevented the DAMGO-, Dyn-A-, and DPDPE-induced depression of I(GABA). The results suggest that M-ENK downregulates I(GABA) principally through mu- and kappa-opioid receptors, and thus exerts its modulating effects indirectly on the transmission of noxious information at the spinal level.


[Characteristics of the transmission of hepatitis B virus infection to infants from their mothers--chronic HBsAg carriers with anti-HBe present].
A series of long-term prospective studies was carried out to investigate the possibilities and manifestations of perinatal infection in Moscow. The observations included 45 mothers, chronic carriers of HBsAg, and their 48 babies. In most of the mothers (31 out of 41), HBs antigenemia was accompanied by the presence of anti-HBe. No persisting HBsAg carrier state was ever detected in the newborns, although in 9 out of 48 babies transitory ephemeral infection was recorded with minimal clinico-biochemical disorders in 6 and complete lack of any such disorders in 3. The above results are compared with the observations in the countries of South-East Asia, West Africa, Europe and the USA. The causes of significant differences in the epidemiological role of perinatal infection in different world regions are discussed. The primary role of anti-HBe formation, ecological, and genetic factors is emphasized.


An interneuronal chemoreceptor required for olfactory imprinting in C. elegans.
Animals alter their behavioral patterns in an experience-dependent manner. Olfactory imprinting is a process in which the exposure of animals to olfactory cues during specific and restricted time windows leaves a permanent memory ("olfactory imprint") that shapes the animal's behavior upon encountering the olfactory cues at later times. We found that Caenorhabditis elegans displays olfactory imprinting behavior that is mediated by a single pair of interneurons. To function in olfactory imprinting, this interneuron pair must express a G protein-coupled chemoreceptor family member encoded by the sra-11 gene. Our study provides insights into the cellular and molecular basis of olfactory imprinting and reveals a function for a chemosensory receptor family member in interneurons.


Histone H1: Lessons from Drosophila.
Eukaryotic genomes are structured in the form of chromatin with the help of a set of five small basic proteins, the histones. Four of them are highly conserved through evolution, form the basic unit of the chromatin, the nucleosome, and have been intensively studied and are well characterized. The fifth histone, histone H1, adds to this basic structure through its interaction at the entry/exit site of DNA in the nucleosome and makes an essential contribution to the higher order folding of the chromatin fiber. Histone H1 is the less conserved histone and the less known of them. Though for long time considered as a general repressor of gene expression, recent studies in Drosophila have rejected this view and have contributed to uncover important functions on genome stability and development. Here we present some of the most recent data obtained in the Drosophila model system and discuss how the lessons learnt in these studies compare and could be applied to all other eukaryotes.


Early X-irradiation of rats--II. Effect on granule cells and their dendrodendritic synapses in the olfactory bulb.
Low, repeated doses of X-rays from a Co60 source were used to impair the development of the granule cells and their dendritic terminals in the olfactory bulb, and the resulting effect was studied under light and electron microscopes at 9 days of age. Irradiation of rats from embryonic day 18 (in utero) to postnatal day 5 resulted, among others, in maldevelopment of the (internal) granule cell and external plexiform layers. This was accompanied by a decrease in the number and the density of the granule cells, and the remaining granule cells contained less ribosomes, regardless of their position within the layer. This implies that both supposed subtypes of granule cells were effected. In the external plexiform layer, a reduced number of mature dendrodendritic synapses and signs of harmed granule gemmules were observed. The results suggest that intrauterinal plus postnatal irradiation with low, repeated doses of X-rays may be an effective tool impairing the development of prenatally forming neurons.


The mts1 gene and control of tumor metastasis.
The main stream of biology today is the analysis of the molecular mechanisms of major biological phenomena through studies of the genes governing these processes and their protein products. An example is the problem of tumor metastasis which is extremely important both theoretically and practically. Here we describe the data obtained on the detection, cloning, structure and transcription control of the mts1 gene, that encodes metastasin 1, a protein which seems to play an important role in the control of metastasis in mouse tumors. In particular, the experiments on tumor cell transfection with constructions containing either a sense or antisense mts1 sequence under a strong promoter/enhancer element show the direct dependence of the metastatic phenotype on the expression of the mts1 gene at least in some systems. Gene mts1 encodes a protein belonging to the family of Ca(2+)-binding proteins and may be involved in the control of cell motility in different types of cells, such as macrophages and T-lymphocytes. The relationship between mts1 and other genes up- and down-regulated in metastatic cells is discussed.


Calculated decisions: Pediatric appendicitis risk calculator (pARC)
The pediatric appendicitis risk calculator quantifies appendicitis risk in pediatric patients with abdominal pain, possibly better than the pediatric appendicitis score.


Lead shot incarceration in appendix: an unusual cause of appendicular foreign body.
A previously fit man was investigated for right-sided abdominal pain and an appendicular foreign body (FB) caused by ingested lead shot was found. He had associated urinary tract infection causing his symptoms and hence was treated conservatively. We present this rare case, followed by discussion of the causes, investigations, clinical significance and management of appendicular FBs.


Operationalization of a nursing model for psychiatric nursing research.
Theoretical substruction provides a framework for deriving and operationalizing study variables related to abstract constructs identified in nursing theories. Moreover, substruction demonstrates the suitability of nursing models for empirical investigation and clinical application. In this paper, theoretical substruction is used to illustrate the significance of Schlotfeldt's health-seeking model for nursing research and practice. From Schlotfeldt's model, study variables are derived and the theoretical-empirical consistency of an exemplary research design examining hypothesized relationships among study variables is described. The research design, grounded in explicit nursing theory, illustrates the investigation of phenomena of concern to the nursing discipline and promises results that will contribute to nursing knowledge development.


Manipulation of Mitophagy by "All-in-One" nanosensitizer augments sonodynamic glioma therapy.
Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors. ACHL: Angiopep-2-modified liposomes loaded with Ce6 and hydroxychloroquine; ACL: Angiopep-2-modified liposomes loaded with Ce6; BBB: blood brain barrier; Ce6: chlorin e6; CHL: liposomes loaded with Ce6 and hydroxychloroquine; CL: liposomes loaded with Ce6; CNS: central nervous system; DDS: drug delivery system; EB: Evans blue; FUS: focused ultrasound; HCQ: hydroxychloroquine; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MBs: microbubbles; MTG: MitoTracker Green; MTR: MitoTracker Red; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS: phosphate-buffered saline; PDI: polydispersity index; PINK1: PTEN induced kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; SDT: sonodynamic therapy; SQSTM1: sequestome 1; TA: terephthalic acid; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling; US: ultrasound; UTMD: ultrasound-targeted microbubble destruction.


Relationship between functional ability and physical fitness in juvenile idiopathic arthritis patients.
To determine the relationship between aerobic and anaerobic physical fitness and functional ability in children with juvenile idiopathic arthritis (JIA). Eighteen children with JIA (age 7 to 14 yr., 3 male/15 female) performed a maximal aerobic exercise test and a Wingate anaerobic exercise test. Functional ability was concurrently assessed using the Childhood Health Assessment Questionnaire (CHAQ). A low relationship between aerobic fitness and functional ability was found (r = 0.0 to 0.4, p > 0.05, except for eating r = 0.46, p < 0.05). The correlations between anaerobic physical fitness and functional ability in JIA patients were strong (r = 0.5 to 0.75, p < 0.05). This indicated a good relationship between anaerobic fitness and functional ability. The strong association between anaerobic physical fitness and functional ability showed the importance of anaerobic physical fitness for children with JIA.


Analyses of Genetic Diversity in the Endangered "Berrenda" Spanish Cattle Breeds Using Pedigree Data.
Pedigree analyses of two endangered cattle breeds were performed in order to study the structure and the genetic variability in their populations. Pedigree data were analyzed from 12,057 individuals belonging to the "Berrenda en Negro" cattle breed (BN) and 20,389 individuals belonging to the "Berrenda en Colorado" cattle breed (BC) that were born between 1983 and 2020. BN and BC reference populations (RP) were set up by 2300 and 3988 animals, respectively. The generation interval in BN and BC reference populations was equal to 6.50 and 6.92 years, respectively. The pedigree completeness level was 82.76% in BN and 79.57% in BC. The inbreeding rates were 4.5% in BN and 3.4% in BC, respectively. The relationship among animals when they were born in different herds was 1.8% in BN and 5% in BC; these values increased to 8.5% and 7.7%, respectively when comparing animals that were born in the same herd. The effective number of founding herds was 23.9 in BN and 60.9 in BC. Number of ancestors needed to explain 50% of genes pool in the whole population was 50 and 101, in BN and in BC, respectively. The effective population size based on co-ancestries was 92.28 in BN and 169.92 in BC. The genetic variability has been maintained in both populations over time and the results of this study suggest that measures to promote the conservation of the genetic variability in these two breeds would go through for the exchange of breeding animals among farms and for monitoring the genetic contributions before implementing any selective action.


Machine Learning Algorithms to Predict Breast Cancer Recurrence Using Structured and Unstructured Sources from Electronic Health Records.
Recurrence is a critical aspect of breast cancer (BC) that is inexorably tied to mortality. Reuse of healthcare data through Machine Learning (ML) algorithms offers great opportunities to improve the stratification of patients at risk of cancer recurrence. We hypothesized that combining features from structured and unstructured sources would provide better prediction results for 5-year cancer recurrence than either source alone. We collected and preprocessed clinical data from a cohort of BC patients, resulting in 823 valid subjects for analysis. We derived three sets of features: structured information, features from free text, and a combination of both. We evaluated the performance of five ML algorithms to predict 5-year cancer recurrence and selected the best-performing to test our hypothesis. The XGB (eXtreme Gradient Boosting) model yielded the best performance among the five evaluated algorithms, with precision = 0.900, recall = 0.907, F1-score = 0.897, and area under the receiver operating characteristic AUROC = 0.807. The best prediction results were achieved with the structured dataset, followed by the unstructured dataset, while the combined dataset achieved the poorest performance. ML algorithms for BC recurrence prediction are valuable tools to improve patient risk stratification, help with post-cancer monitoring, and plan more effective follow-up. Structured data provides the best results when fed to ML algorithms. However, an approach based on natural language processing offers comparable results while potentially requiring less mapping effort.


Mitochondrial Dynamics: ER Actin Tightens the Drp1 Noose.
Drp1 is an oligomeric GTPase essential for mitochondrial division. A recent study has proposed a new model whereby machinery localized to the endoplasmic reticulum drives polymerization of actin, which then acts as a platform for Drp1 oligomerization and hydrolysis at mitochondrial constriction sites.


Kounis Syndrome Associated With Takotsubo Syndrome in an Adolescent With Peutz-Jeghers Syndrome.
We describe the case of a 15-year-old female patient with Peutz-Jeghers syndrome who presented with vomiting and abdominal pain secondary to ileoileal invagination. Initial analgesic treatment was not effective, and subsequent tramadol infusion resulted in clinical manifestations compatible with Kounis and Takotsubo syndromes. However, the patient had an excellent recovery. (Level of Difficulty: Advanced.).


A novel homogeneous irradiation fiber probe for whole bladder wall photodynamic therapy.
We designed and fabricated a novel fiber probe that homogeneously illuminates the urinary bladder cavity for photodynamic therapy (PDT) of bladder cancer, which is known to occur in multifocal areas and to proliferate diffusely in the bladder mucosa. One end of a quartz multicore fiber was twisted and conically shaped, and the sharpened apex of the fiber end was rounded in order to provide light of which the fluence distribution approximates the three-dimensional shape of the bladder cavity of rats. The superiority of the developed fiber probe (homogenous irradiation fiber probe: HIFiP) to a control fiber with a flat cleaved end (CF) in Photofrin®-PDT using a rat orthotopic bladder cancer model was evaluated. Percentage of irradiated area to the whole area of the mucosal surface of the bladder was 36% in the case of the CF, while it was 69% in the case of HIFiP (P = 0.04). A greater PDT effect was seen in rats with HIFiP-PDT, the volume of tumors (5.0 mm(3)) being less than half of that in the CF group (11.8 mm(3); P = 0.02). HIFiP succeeded in delivering light homogenously to a wide area of the bladder cavity, resulting in enhancement of the PDT effect on bladder cancer.


Late recurrence of pineal germinoma.
Cerebral germinomas and their occasional recurrences can usually be cured by irradiation, chemotherapy, or a combination of the two treatment modalities. Late recurrences, as in our case, are distinctly rare. This patient presented at age 24 with a calcified tumor in the pineal area. The radiological diagnosis was germinoma. No tissue diagnosis was obtained. Radiation therapy was given, and there was a complete response. The patient's symptoms reappeared 13 years later. Imaging studies revealed a lesion in the anterior corpus callosum. A germinoma was diagnosed by stereotactic biopsy. Because of complications attributed to the initial course of radiation therapy, no further radiation was given. Five courses of chemotherapy resulted in a partial remission lasting six months. The patient later died because of massive tumor progression with intracerebral, intraventricular, cerebellar, and meningeal dissemination. As this case illustrates, exceptional recurrences of cerebral germinomas may appear even many years after adequate initial treatment with radiation and chemotherapy.


Volume Doubling Times of Pulmonary Metastases in Patients With Bone and Soft-Tissue Sarcomas: Associations With Subsequent New Metastases and Survival After Metastasectomy.
BACKGROUND. Pulmonary metastases of bone and soft-tissue sarcoma are common and have a high recurrence rate after metastasectomy. Factors associated with postmetastasectomy recurrence are not well studied. OBJECTIVE. The purpose of this study was to investigate the association of the volume doubling time (VDT) of pulmonary metastases with the subsequent development of new pulmonary nodules and survival after metastasectomy in patients with bone or soft-tissue sarcoma. METHODS. This retrospective study included patients with bone or soft-tissue sarcoma who, between January 2010 and December 2020, underwent first complete metastasectomy of pulmonary nodules visualized on two sequential preoperative CT scans. Semiautomatic volumetric segmentation of the pulmonary metastases was performed on the two CT scans, and VDTs were calculated. VDT was compared between patients with and without subsequent new metastases after metastasectomy. Cox proportional hazards regression analyses were performed to determine risk factors for recurrence-free survival (RFS) after metastasectomy and for postmetastasectomy overall survival (OS). RESULTS. Forty patients (21 women, 19 men; mean age, 51.1 ± 14.3 [SD] years) were included. Of these patients, 23 (57.5%) developed new metastatic nodules after metastasectomy, and 10 (25.0%) died during follow-up. Median VDT was shorter in patients with, versus those without, new metastases after metastasectomy (56 vs 140 days, p = .002). Only four of 23 patients with new metastases had VDT of 140 days or more. In multivariable analysis, older age (hazard ratio [HR], 1.06; p = .004), female sex (HR, 2.80; p = .03), and VDT less than 140 days (HR, 4.22; p = .01) were independent predictors of worse RFS. Also in multivariable analysis, only older age (HR, 1.17; p = .005) and VDT less than 50 days (HR, 8.60; p = .02) were independent predictors of worse OS. OS was significantly worse in patients with VDT less than 140 days (10 deaths among 27 patients) than in patients with VDT of 140 days or more (no deaths in 13 patients) (p = .01). CONCLUSION. In patients with bone and soft-tissue sarcoma, shorter VDT of pulmonary metastases is independently associated with subsequent new metastases after metastasectomy and worse OS. CLINICAL IMPACT. VDT of pulmonary nodules may be considered in patient selection for pulmonary metastasectomy and in postoperative patient management.


Binding of fibronectin to Escherichia coli isolated from bovine mastitis from different geographical regions.
Seventy strains of Escherichia coli, isolated from bovine mastitis in Australia, Denmark, Norway and the U.S.A., were tested for their ability to bind fibronectin. Fifty-three strains (76%) interacted with iodinated fibronectin at a level exceeding 5% of the total radioactivity added. Binding of the amino-terminal (29 kD) fragment of fibronectin was tested for 15 strains, and 6 strains (40%) bound greater than 5%. Bacteria binding the 29 kD fragment at greater than or equal to 19% of the added protein, consistently showed "high" attachment to bovine skin fibroblasts. These cells were shown by immunofluorescence to produce extracellular matrix containing fibronectin. Strains binding lower amounts of fibronectin or 29 kD fragment adhered poorly to these fibroblasts.


Geoclimatic risk factors for childhood asthma hospitalization in southwest of Iran.
Asthma is a chronic respiratory disease resulting from a complex interaction between genetic and environmental factors. Among environmental factors, climatic and geographical variations have an important role in increasing asthma hospitalization. The current study aimed to investigate the effect of geoclimatic factors on the occurrence of childhood asthma hospitalization in Fars province, southwest Iran. We mapped the addresses of 211 hospitalized patients with childhood asthma (2016-2019) and investigated the effects of different temperature models, mean annual rainfall and humidity, number of frosty and rainy days, evaporation, slope, and land covers on the occurrence of childhood asthma hospitalization using a geographical information system. The Kriging and Spline methods have been used for generating interpolated models. Data were analyzed using logistic regression. In the multivariate model, urban setting was recognized as the most important childhood asthma hospitalization predictor (p < 0.001, odds ration [OR] = 35.044, confidence interval [CI] = 9.096-135.018). The slope was considered the determinant of childhood asthma hospitalization when analyzed independently and its increase was associated with decreased childhood asthma hospitalization (p = 0.01, OR = 0.914, CI = 0.849-0.984). In the current study, the urban setting was the most important risk factor associated with increased childhood asthma hospitalization.


Bilateral serous retinal detachments in the H.E.L.L.P. syndrome.
The first case of the H.E.L.L.P. syndrome with ophthalmic signs is described. This syndrome of pregnancy is characterized by Haemolysis, Elevated Liver enzymes and Low Platelets in association with upper abdominal pain. Diagnosis and treatment is often delayed, while a non-obstetric cause for these findings is sought. The present report adds serous retinal detachments in association with sub-retinal opacities to the signs which should raise suspicion of this syndrome.


Intrathecal delivery and its applications in leptomeningeal disease.
Intrathecal delivery (IT) of opiates into the cerebrospinal fluid (CSF) for anesthesia and pain relief has been used clinically for decades, but this relatively straightforward approach of bypassing the blood-brain barrier has been underutilized for other indications because of its lack of utility in delivering small lipid-soluble drugs. However, emerging evidence suggests that IT drug delivery be an efficacious strategy for the treatment of cancers in which there is leptomeningeal spread of disease. In this review, we discuss CSF flow dynamics and CSF clearance pathways in the context of intrathecal delivery. We discuss human and animal studies of several new classes of therapeutic agents-cellular, protein, nucleic acid, and nanoparticle-based small molecules-that may benefit from IT delivery. The complexity of the CSF compartment presents several key challenges in predicting biodistribution of IT-delivered drugs. New approaches and strategies are needed that can overcome the high rates of turnover in the CSF to reach specific tissues or cellular targets.


p53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1.
The p53 tumour suppressor has an important role in cancer cells. Here we show that p53 regulates expression of major histocompatibility complex I on the cell surface. We show that the tumour cell line HCT116, which lacks p53 exhibits significantly lower major histocompatibility complex I expression than its wild-type counterpart. Using a combination of chromatin immunoprecipitation sequencing and gene expression analysis, we demonstrate that p53 upregulates expression of endoplasmic reticulum aminopeptidase 1 by binding to its cognate response element in the ERAP1 gene. Silencing of p53 decreases endoplasmic reticulum aminopeptidase 1 protein levels and therefore major histocompatibility complex I expression. We further show that this mechanism operates in A549 cells infected with H1N1 influenza virus, in which H1N1 activates p53, leading to endoplasmic reticulum aminopeptidase 1 upregulation and a corresponding increase in major histocompatibility complex I expression. Our study suggests a previously unrecognized link between p53 function and the immunosurveillance of cancer and infection.


Simultaneous determination of psychotropic drugs in human urine by capillary electrophoresis with electrochemiluminescence detection.
Amitriptyline, doxepin and chlorpromazine are often used as psychotropic drugs in treatment of the various mental diseases, and are also partly excreted by kidney. This work developed a simple, selective and sensitive method for their simultaneous monitoring in human urine using capillary electrophoresis coupled with electrochemiluminescence (ECL) detection based on end-column ECL reaction of tris-(2,2'-bipyridyl)ruthenium(II) with aliphatic tertiary amino moieties. Acetone was used as an additive to the running buffer to obtain their absolute separation. Under optimized conditions the proposed method displayed a linear range from 5.0 to 800 ng mL(-1) for the three drugs with the correlation coefficients more than 0.995 (n=8). Their limits of detection were 0.8 ng mL(-1) (3.6 fg), 1.0 ng mL(-1) (4.5 fg) and 1.5 ng mL(-1) (6.8 fg) at a signal to noise ratio of 3, respectively. The relative standard deviations for five determinations of 20 ng mL(-1) amitriptyline, doxepin and chlorpromazine were 1.7%, 4.2% and 3.6%, respectively. For practical application an extract step with 90:10 heptane/ethyl acetate (v/v) was performed to eliminate the influence of ionic strength in sample. The recoveries of amitriptyline, doxepin and chlorpromazine at different levels in human urine were between 83% and 93%, which showed that the method was valuable in clinical and biochemical laboratories for monitoring amitriptyline, doxepin and chlorpromazine.


Myositis ossificans after total hip replacement and perioperative muscle ischemia.
It has been suggested that muscle ischemia could contribute to myositis ossificans and that the ischemia could result from prolonged retraction during surgery. Biopsy specimens of the gluteus medius muscle were taken at the beginning and the end of 30 primary total hip arthroplasties and the intracellular lactate and phosphocreatine (PCr) measured. Postoperative myositis ossificans was classified according to Brooker after 1 year, and the surface of the heterotopic bone projected above the greater trochanter in an anteroposterior roentgenogram was measured by planimetry. The findings suggest that muscle ischemia is not an important cause of myositis ossificans after hip arthroplasty, but elevated levels of lactate and lowered levels of intracellular PCr may occur as nonspecific responses to tissue trauma that through other mechanisms may lead to ossification.


The effect of perioperative psychological intervention on fatigue after laparoscopic cholecystectomy: a randomized controlled trial.
Fatigue is one of the main complaints after surgery and may last longer than physical symptoms. It prevents return to normal function and activity. Relaxation interventions, performed prior to abdominal surgery, have been shown to reduce pain, wound erythema, and systemic cortisol levels. However, there is a lack of data on the impact of this intervention on patient well-being, functional recovery, activities of daily living, and fatigue after discharge from hospital. The study was a randomised single-blinded trial. Patients who were to undergo elective laparoscopic cholecystectomy for any indication between April 2008 and May 2010 were screened for inclusion. Those in the intervention group attended a standardised 45 min relaxation session with a health psychologist and were given relaxation exercise CDs to take home. The control group did not have the intervention. Patients were followed for 30 days. Fatigue was measured using the identity-consequence fatigue scale. Seventy-five patients were randomised. Fifteen patients were excluded after randomization for various reasons; hence, 60 patients were followed up and analysed. Both groups had similar fatigue at baseline. There was improved fatigue and consequence of fatigue on postoperative day 30 in the intervention group. There was no difference in fatigue at any other time point postoperatively. This was the first interventional study targeting fatigue after laparoscopic cholecystectomy by using a brief psychological relaxation intervention. It has shown a reduction of fatigue and impact of fatigue at 30 days postoperatively in the intervention group.


Effect of home reliner on occlusal relationships and oral mucosa: viscoelastic analyses by smoothed particle hydrodynamics simulation.
For decades, many reports have expressed negative opinions about home reliner (HR), because it may result in residual ridge resorption. Recently, some clinical studies evaluated HR. However, the effect of HR on occlusal relationships and the oral mucosa remains unclear. Here, we dynamically analyzed the situation in which a patient applies HR to an upper complete denture. We numerically simulated the effect of HR on occlusal relationships and the oral mucosa. In the simulation, the thickness of HR was set to 2mm as a proper amount and 4mm as an excessive amount. The loading points were set at the center of the right and left occlusal surfaces of the denture. Compared with the case without using HR, at proper amounts (2mm on the right and left sides), HR suppressed the depression of the ill-fitting denture, and stress on the oral mucosa was decreased. In the excessive HR model (4mm on the right and left sides), the vertical occlusal dimension was increased, and stress on the oral mucosa originally fitted with the denture base was increased. When the denture was modeled in an inclined position (2mm on the left side and 4mm on the right side), stress on the oral mucosa on the left buccal side was markedly increased. It was found that when an improper amount of HR was applied, the occlusal vertical dimension increased and the oral mucosa was pressured more than that under non-HR conditions.


Single Loading Low Dose MgSo4 Regimen: A Simple, Safe and Effective Alternative to Pritchard's Regimen for Indian Women.
Magnesium sulphate is the anticonvulsant of choice in prevention and control of eclamptic convulsions. Pritchard's regimen is the most popular time-tested regimen used. However, owing to concerns of toxicity, several low dose regimens have been introduced considering the lower body mass index of Asian women. To compare the efficacy and safety of a single loading low dose MgSo4 regimen with the Pritchard's regimen. Seventy cases of eclampsia and imminent eclampsia were allocated to the control and study groups each. The former received the Pritchard's regimen while the latter was treated with single loading low dose of magnesium sulphate. Recurrent convulsion rates, maternal and perinatal outcomes of both regimens were evaluated and compared using unpaired t-test and Chi-square test for continuous and categorical variables, respectively. The mean serum magnesium levels were significantly lower in the study group at 30 minutes and 4 hours of initiation of therapy. The single loading low dose regimen was equally efficacious in prevention (96.6% vs 100%, p = 0.934) and control (97.6% vs 97.8%, p = 0.358) of eclamptic fits as compared to the Pritchard's regimen. The feto-maternal outcomes were also comparable. The single loading low dose MgSo4 regimen is an effective and safe alternative to the Pritchard's regimen, especially tailored to the small built Indian women.


Bioassay-guided isolation of antimicrobial benzopyrans and phloroglucinol derivatives from Hypericum species.
Recently the crude methanol extracts of six Hypericum species were analysed against a panel of microorganisms and it was found that H. caprifoliatum Cham. & Schlecht., H. myrianthum Cham. & Schlecht. and H. polyanthemum Klotzsch ex Reichardt were the most active. This paper reports the activity of the hexane, chloroform and methanol fractions of these plants as well as the activity of some isolated compounds against Staphylococcus aureus determined by bioautographic procedures.