Interaction between corticosterone and PER2 in regulating emotional behaviors in the rat.
Circadian rhythms play a prominent role in psychiatric health with disruption in rhythms associated with poor mental health. Corticosterone (CORT) is an important hormone in entraining the biological rhythms of many cells throughout the body and coordinating peripheral rhythms with the central master clock. Here, we tested the hypothesis that excess CORT during the circadian trough would lead to a flattening of period genes (Per1 and Per2) rhythms in limbic brain areas, and thus impact emotional behaviors. Male rats were injected daily with 2.5 mg/kg CORT or vehicle for 21 days at either ZT0 or ZT12 and sucrose preference, open field, and forced swim behaviors measured during the dark phase of the light cycle. After three weeks of injections, a reduction in sucrose preference was observed in animals injected with CORT at ZT0 and the reduction significantly correlated with reductions in Per2 mRNA expression in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST). No changes in behavior or period gene expression were observed in animals injected with CORT at ZT12. DsiRNA was used to directly reduce Per2 levels in either the CeA or BNST and behavior was assessed. Despite reductions in Per2 expression in the CeA, no behavioral changes were observed. In contrast, a reduction in Per2 expression in the BNST was sufficient to reduce sucrose preference. The results demonstrate that CORT significantly contributes to the circadian expression of Period genes in certain limbic brain areas and disruption in diurnal CORT or Per2 expression can lead to impaired emotional behavioral responses.


Endoscopic band ligation compared to thermal therapy for gastric antral vascular ectasia: A systematic review and meta-analysis.
Gastric antral vascular ectasia is an infrequent cause of gastrointestinal-related blood loss manifesting as iron-deficiency anemia or overt gastrointestinal bleeding, and is associated with increased healthcare burdens. Endoscopic therapy of gastric antral vascular ectasia most commonly involves endoscopic thermal therapy. Endoscopic band ligation has been studied as an alternative therapy with promising results in gastric antral vascular ectasia. The primary aim was to compare the efficacy of endoscopic band ligation and endoscopic thermal therapy by argon plasma coagulation for the management of bleeding gastric antral vascular ectasia in terms of the mean post-procedural transfusion requirements and the mean hemoglobin level change. Secondary outcomes included a comparison of the number of sessions needed for cessation of bleeding, the change in transfusion requirements, and the adverse events rate. PubMed, Medline, SCOPUS, Google Scholar, and the Cochrane Controlled Trials Register were reviewed. Randomized controlled clinical trials and retrospective studies comparing endoscopic band ligation and endoscopic thermal therapy in bleeding gastric antral vascular ectasia, with a follow-up period of at least 6 months, were included. Statistical analysis was done using Review Manager. Our search yielded 516 papers. After removing duplicates and studies not fitting the criteria of selection, five studies including 207 patients were selected for analysis. Over a follow-up period of at least 6 months, patients treated with endoscopic band ligation had significantly lower post-procedural transfusion requirements (MD -2.10; 95% confidence interval (-2.42 to -1.77)) and a significantly higher change in the mean hemoglobin with endoscopic band ligation versus endoscopic thermal therapy (MD 0.92; 95% confidence interval [0.39-1.45]). Endoscopic band ligation led to a fewer number of required sessions (MD -1.15; 95% confidence interval [-2.30 to -0.01]) and a more pronounced change in transfusion requirements (MD -3.26; 95% confidence interval [-4.84 to -1.68]). There was no difference in adverse events. Results should be interpreted cautiously due to the limited literature concerning the management of gastric antral vascular ectasia. Compared to endoscopic thermal therapy, endoscopic band ligation for the management of bleeding gastric antral vascular ectasia led to significantly lower transfusion requirements, showed a trend toward more remarkable post-procedural hemoglobin elevation, and a fewer number of procedures. Endoscopic band ligation may improve outcomes and lead to decreased healthcare burden and costs.


Implant Surgery Update for the General Practitioner: Dealing with Common Postimplant Surgery Complications.
It is essential for practitioners who place dental implants to be able to diagnose and treat common complications or know when to refer to a specialist. Common complications can include nerve injuries, infections, sinus membrane perforations, and edema. This article discusses these complications, incidence rates, tips to avoid common complications, and management options when a patient returns with a complication.


Human immunodeficiency virus exanthem.
The human immunodeficiency virus (HIV) exanthem can be the primary manifestation of HIV infection. We report three cases of an exanthematous skin eruption associated with acute HIV infection. HIV antigen (p24 core antigen) was present, whereas results of the HIV antibody test were negative.


Physiology of the SOS response: kinetics of lexA and recA transcriptional activity following induction.
The products of the lexA and recA genes play central roles in the regulation of the Escherichia coli SOS response. We have measured the rate of mRNA synthesis from each gene at intervals following various inducing treatments in order to obtain a more precise timing of the induction process. Further, we provide quantitative evidence for kinetics of decay from fully induced levels of mRNA synthesis to basal levels as the cells shut down the SOS response which are in agreement with previously published data on the expression of specific SOS functions. The induction kinetics of lexA and recA gene expression are parallel except for nalidixic acid (NAL) treatment, with the actual levels of lexA mRNA synthesis being about 10-fold lower than that of recA. Reestablishment of repression from RecA commenced over 30 min earlier than from lexA. These results are fully consistent with the model that the functions result from the increased gene expression.


Seismic resurfacing by a single impact on the asteroid 433 Eros.
Impact cratering creates a wide range of topography on small satellites and asteroids. The population of visible craters evolves with impacts, and because there are no competing endogenic processes to modify the surface, determining the various ways younger craters add to or subtract from the population is a fundamental aspect of small-body geology. Asteroid 433 Eros, the most closely studied small body, has regions of substantially different crater densities that remain unexplained. Here we show that the formation of a relatively young crater (7.6 km in diameter) resulted in the removal of other craters as large as 0.5 km over nearly 40 percent of the asteroid. Burial by ejecta cannot explain the observed pattern of crater removal. The limitation of reduced crater density to a zone within a particular straight-line distance through the asteroid from the centre of the large crater suggests degradation of the topography by seismic energy released during the impact. Our observations indicate that the interior of Eros is sufficiently cohesive to transmit seismic energy over many kilometres, and the outer several tens of metres of the asteroid must be composed of relatively non-cohesive material.


Desmoplastic trichilemmoma of the facial region mimicking invasive carcinoma.
Trichilemmoma is a hamartomatous proliferation arising from cells of hair follicle. Its desmoplastic variant simulates an invasive carcinoma. In this tumor, the cell of origin seems to be located in the superficial level of the hair follicle just below the basement membrane at the sebaceous gland level. We present a similar case which presented with an asymptomatic nodular lesion in the region above the upper lip on left side. Fine needle aspiration cytology raised the cytological possibility of a malignancy for which the lesion was excised. On histopathology the lesion was diagnosed as desmoplastic trichilemmoma. The case highlights the difficulty encountered in differentiating a benign adnexal tumor from malignant lesion based on cytology alone. Moreover, the extensive desmoplasia on histopathology raises the suspicion of invasive malignancy which requires to be carefully excluded. The superficial features of trichilemmoma and lack of cellular atypia is a useful diagnostic clue in such a situation. Positivity of CD34 can also be used to differentiate from basal cell carcinomas. The case reported here had a solitary lesion, but follow up is required for development of more lesions or multiple hamartomas in other organs as a part of Cowden's disease.


Study of functionality of cochlear outer hair cells in patients with retinitis pigmentosa.
Hearing functionality was studied in 30 patients affected by retinitis pigmentosa (RP) and 25 of their relatives. These patients were defined as normal-hearing on the basis of pure-tone threshold audiometric and acoustic immittance tests. The evoked otoacoustic emissions (EOEs) were studied in these normal hearing patients. EOEs are an extremely sensitive method to study the functionality of the outer hair cells of the organ of Corti. In RP patients and in their relatives the values of EOE (amplitude, intensity and frequency) were found to be statistically reduced compared to those of control subjects. The EOEs turned out to be clearly pathological in 60% of patients with RP and in 24% of their relatives. During the embryologic development there is one transitory axoneme in the outer hair cells of the organ of Corti. This axoneme is important for the organization of the stereocilia. The axonemes are found inside a few mature hair cells, including the photoreceptors. The alteration of cochlear outer hair cells in a high percentage of patients with RP and in some of their relatives seems to corroborate the hypothesis that, in many cases, retinitis pigmentosa may be due to a structural anomaly of the ciliated cells.


Assessing the compatibility of the management of standardized procedures with the complexity of a sociotechnical system: case study of a control room in an oil refinery.
Although the need for the management of complex socio-technical systems (STS) to be compatible with the nature of those systems is widely recognized, there are few guidelines on how to determine the actual extent of this compatibility. The purpose of this study is to assess how compatible the management of standardized procedures (SPs) is with the nature of a complex STS. To this end, a case study was made of a control room in an oil refinery, involving the following stages: (a) delimitation of the investigated STS; (b) description of the STS according to a set of characteristics of complex STS; (c) application of two types of questionnaires to thirty workers - one of them to assess their perceptions about the applicability of seven principles of SPs management in complex STS and the other to determine their perceptions about the actual use of these principles; and (d) a feedback meeting with workers to discuss the results of the assessment. The assessment is discussed in terms of its limitations, usefulness and ease of use of the data collection and analysis tools.


Organic matter composition and thermal stability influence greenhouse gases production in subtropical peatland under different vegetation types.
Peatlands are a major carbon (C) sink globally. Organic matter quality influence greenhouse gases production. However, little is known about how organic matter from different vegetation types, influences C composition and resultant greenhouse gases production in subtropical peatland. Anoxic incubation experiments were conducted using two types of peats with different botanical origin to assess C composition, CO2 and CH4 production. First peat had cypress dominance and the second knotted spikerush and water lily (spike + lily). Solid-state CPMAS 13C NMR determined C chemical stability, MESTA determined C thermal stability, stable isotopes for C source and gas chromatograph for carbon dioxide (CO2) and methane (CH4). The results indicated dominance of autochthonous C as indicated by δ13C signatures. Low thermal stable C (LTSC) dominated in litter, FL (fermentation layer) and spike + lily sediment, high thermal stable C was dominant in cypress peat. O-alkyl C strongly correlated with LTSC whereas aromatic C correlated negatively with R400 (LTSC:total C ratio). Generally, O-alkyl decreased and alkyl increased along litter-FL-peat continuum. Spike + lily peat exhibited initial stage of decomposition. Indicated by increased alkyl C, aromatic C and aromatic:O-alkyl ratio with increasing peat depth. Also, exhibited 3 times more CH4 and CO2 production compared to cypress peat that dominantly exhibited second stage of decomposition. O-alkyl C exhibited positive relationship with CH4 (P = 0.012, r2 = 0.57) and CO2 (P = 0.047, r2 = 0.41) production whereas R400 related positively with CH4 (P = 0.05, r2 = 0.40). Organic matter thermal and chemical composition varied between the peat types and thermally and chemically labile C influenced CO2 and CH4 production.


[Diagnosis and therapy of primary extranodal non-Hodgkin's lymphoma of the stomach].
In the period from 1970-1980 120 patients with NHL were treated. A primary stomach manifestation could be detected in 6.6%. Problems of pre-operative, endoscopic-bioptic diagnostics are discussed and recommendations for a therapeutic proceeding are given. The tumour is surgically removed at stage I and II, which is always followed by polychemotherapy. Primary polychemotherapy is used at stages III and IV. Patients at stage II achieved a complete remission, those at stage IV died within 6 months after diagnosis.


A quantitative sustainability assessment framework for petroleum refinery projects.
Petroleum refinery industry (PRI) projects are inherently unsustainable for the most part, because of their environmentally and socially negative potential effects; nonetheless, their development is inevitable due to their deep positive impact on economic development for stakeholders and the society at large. With these competing realities, it is extremely important to develop tools that can quantify the level of sustainability of various alternatives, so managers can make informed decisions about how to go forward with these projects. Due to the complexity of life cycle and sustainability assessment of PRI projects, in addition to their complicated multidisciplinary nature, indicator-based approaches are used oftentimes as sustainability assessment tools. In this paper, an indicator-based sustainability framework is proposed based on the literature review at the qualitative level to cover the pillars of sustainability (which is social, economic, and environmental). Then, a quantitative set of sustainability assessment factors is developed which tries to address global sustainability concerns and to reinforce the understanding of sustainability by utilizing quantitative means. UN sustainability indicators were used as the basis for the study, and the framework was developed further to reflect the specifics of PRI projects; the result of this step is 140 quantitative sustainability factors. To realize the highly relevant global concerns regarding sustainability assessment factors to be applied to PRI projects, the screening process has been done by Delphi technique in combination with Fuzzy set theory, to select the most important as well as relevant indicators which results in 101 relevant quantitative sustainability factors; then, a panel of experts has converted the screened quantitative factors to meaningful ones for PRI projects. The expert panel has then interpreted the list of factors, according to expert judgments. Finally, a comparative study has been done to see how the results will compare with those of frequently used systems. The results of the study are of primary importance due to their applicability in sustainable decision-making, as well as for future studies. The reinforced indicator-based sustainability framework will make a core, not only to assess existing plants with various characteristics but also for new refineries that are going to be developed based on sustainability principles.


Comparative epistemology: contours of a research program.
This article addresses the question whether and how literary documents can be used to further our understanding of a number of key issues on the agenda of the philosophy of biology such as "complexity" and "reductionism". Kant already granted a certain respectability to aesthetical experiences of nature in his third Critique. Subsequently, the philosophical movement known as phenomenology often used literary sources and literary techniques to criticize and question mainstream laboratory science. The article discusses a number of literary documents, from Moby-Dick to Jurassic Park, that explicitly stage a confrontation between scientific and non-scientific ways of experiencing and understanding the natural world. Special attention is given to the work of Michael Crichton. Its relevance for the philosophy of biology is pointed out.


Activities of cytochrome P450 1A2, N-acetyltransferase 2, xanthine oxidase, and cytochrome P450 2D6 are unaltered in children with cystic fibrosis.
The activities of hepatic cytochrome P450 (CYP) 1A2, N-acetyltransferase 2 (NAT-2), xanthine oxidase (XO), and CYP2D6 were evaluated in 12 young children (aged 3-8 years) with mild cystic fibrosis (CF) and 12 age-matched healthy control subjects by use of standard caffeine and dextromethorphan phenotyping methods. Subjects were given 4 oz of Coca-Cola (approximately 35 mg caffeine) (The Coca-Cola Company, Atlanta, Ga) and a single 0.5-mg/kg dose of dextromethorphan. Urine was collected for 8 hours after biomarker administration, and enzyme activity was assessed by use of previously validated caffeine and dextromethorphan molar ratios. CYP2D6 genotyping was also performed in 10 of 12 subjects with CF and 11 of 12 control subjects. There were no significant differences in the urinary molar ratios for any of the enzyme systems evaluated. These data suggest that CF does not alter the activities of CYP1A2, NAT-2, XO, and CYP2D6. Altered biotransformation of drugs in this patient population is likely enzyme- and isoform-specific and thus is apparent for only selected compounds that are substrates for enzymes other than CYP1A2, NAT-2, XO, and CYP2D6.


Evaluation of effect of two different functionalized nanoparticle photodynamic therapy on nanohardness of root dentin-An in vitro study.
The aim of this study was to evaluate the effect of functionalized nanoparticle photodynamic therapy on Nano hardness of root dentin METHODOLOGY: Fifty single rooted lower premolars were decoronated and sectioned into two halves. Then the samples were embedded horizontally in to the acrylic resin to expose the dentin surface. Baseline nanohardness was done at midroot level using a Nanohardness tester. Exposed dentin surfaces were immersed in the following irrigating solutions Post treatment nanohardness testing was done and results were analyzed statistically RESULTS: In general, all the samples in their respective groups had significant change in nanohardness following immersion in irrigant solutions except in NaOCl + EDTA and saline group. CSRB-np and PLGA-MBnp showed increased nanohardness (P = 0.005 and P = 0.007 respectively). Whereas NaOCl + EDTA + CHX showed decrease in nanohardness (P = 0.04). With regards to Modulus of elasticity (MOE), CSRB-np showed significant difference (P = 0.002) compared to the other groups. MOE increased in CSRB-np and PLGA-MBnp while it decreased in all the other groups. In this study, the improvement of nanohardness and modulus of elasticity following the immersion of root dentin in CSRB-np solution was demonstrated.


Antineoplastic agents. 397: Isolation and structure of sesterstatins 4 and 5 from Hyrtios erecta (the Republic of Maldives).
The wide ranging marine sponge Hyrtios erecta is the source of the spongistatins, a new class of macrocyclic lactone antineoplastic agents. Continuation of a detailed investigation of cancer cell growth inhibitory (P388 lymphocytic leukemia) fractions (trace) from H. erecta has revealed the presence (10(-5) to 10(-7)% yield) of cytotoxic pentacyclic sesterterpenes. Employing P388 leukemia and human tumor cell line-guided bioassay techniques, two new moderate inhibitors of cancer cells were isolated and named sesterstatins 4 (1a, P388 ED50 4.9 micrograms/mL) and 5 (1b, DU-145 prostate GI50 1.9 micrograms/mL). Similar to other sesterterpenes, sesterstatin 5 inhibited growth of a Gram-positive bacterium. High field (500 MHz) 2-D NMR techniques were primarily employed for initial structural assignments, and structural assignments were confirmed by X-ray crystal structure determination of sesterstatin 4 (1a) and 5 (1b).


Impact of pre-diabetes, well-controlled diabetes, and poorly controlled diabetes on anastomotic leakage after esophagectomy for esophageal cancer: a two-center retrospective cohort study of 1901 patients.
Diabetes is known to be associated with anastomotic leakage (AL) after esophagectomy. However, it is unknown whether well-controlled diabetes is also associated with AL. We conducted a two-center retrospective cohort database study of patients who underwent oncological esophagectomy (2011-2019). Patients were divided into four groups: normoglycemia, pre-diabetes, well-controlled diabetes (hemoglobin A1c [HbA1c] < 7.0%), and poorly controlled diabetes (HbA1c ≥ 7.0%). The occurrence of AL and length of stay were compared between groups using multivariable analyses. The relationship between categorical HbA1c levels and AL was also investigated in patients stratified by diabetes medication before admission. Among 1901 patients, 1114 (58.6%) had normoglycemia, 480 (25.2%) had pre-diabetes, 180 (9.5%) had well-controlled diabetes, and 127 (6.7%) had poorly controlled diabetes. AL occurred in 279 (14.7%) patients. Compared with normoglycemia, AL was significantly associated with both well-controlled diabetes (odds ratio 1.83, 95% confidence interval [CI] 1.22-2.74) and poorly controlled diabetes (odds ratio 1.95, 95% CI 1.23-3.09), but not with pre-diabetes. Preoperative HbA1c levels showed a J-shaped association with AL in patients without diabetes medication, but no association in patients with diabetes medication. Compared with normoglycemia, only poorly controlled diabetes was significantly associated with longer hospital stay after surgery, especially in patients with operative morbidity (unstandardized coefficient 14.9 days, 95% CI 5.6-24.1). Diabetes was associated with AL after esophagectomy even in well-controlled patients, but pre-diabetes was not associated with AL. Operative morbidity, including AL, in poorly controlled diabetes resulted in prolonged hospital stays compared with normoglycemia.


Synthesis and biological activity of carbamate-linked cationic lipids for gene delivery in vitro.
We have introduced a convenient synthesis method for carbamate-linked cationic lipids. Two cationic lipids N-[1-(2,3-didodecylcarbamoyloxy)propyl]-N,N,N-trimethylammonium iodide (DDCTMA) and N-[1-(2,3-didodecyl carbamoyloxy)propyl]-N-ethyl-N,N-dimethylammonium iodide (DDCEDMA), with identical length of hydrocarbon chains, alternative quaternary ammonium heads, carbamate linkages between hydrocarbon chains and quaternary ammonium heads, were synthesized for liposome-mediated gene delivery. Liposomes composed of DDCEDMA and DOPE in 1:1 ratio exhibited a lower zeta potential as compared to those made of pure DDCEDMA alone, which influences their DNA-binding ability. pGFP-N2 plasmid was transferred by cationic liposomes formed from the above cationic lipids into Hela and Hep-2 cells, and the transfection efficiency of some of cationic liposomes was superior or parallel to that of two commercial transfection agents, Lipofectamine2000 and DOTAP. Combined with the results of the agarose gel electrophoresis and transfection experiment, the DNA-binding ability of cationic lipids was too strong to release DNA from complex in the transfection, which could lead to relative low transfection efficiency and high cytotoxicity.


Optical imaging of HPV infection in a murine model.
The development of animal models of HPV infection has given investigators a new set of tools to expand basic knowledge of the early events of infection in vivo. The use of HPV pseudovirions, in which the viral genome has been replaced with a reporter pseudogenome, in combination with advanced imaging techniques has facilitated and simplified studies using these models. Herein we provide details for a murine model of cervicovaginal HPV infection in conjunction with several methods for imaging and quantitating the transduced genes, both ex vivo and in vivo.


Age- and dose-dependent effect of statin use on the risk of osteoporotic fracture in older adults.
Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporosis-related measurement has shown controversial results. In this study, we found an age, dose andduration-dependent osteoprotective effect of statins in general older population. Previous studies have revealed the protective effects of statins on bone but the association of statins use with osteoporotic fractures has shown controversial results. In this study with Korean National Health Insurance Service-Senior cohort database, a total of 365,656 elderly without previous history of osteoporosis and who were started on statin since January 1 2004 were included and observed until December 31 2012. Hazard rations (HR) for major osteoporotic fractures were calculated using the weighted Cox proportional hazards model with inverse-probability of treatment weighting method. During 6.27 years of follow-up period, 54,959 osteoporotic fractures occurred and the majority of fractures (69.5%) were vertebral fractures. Compared with non-users, statin use was associated with a decreased risk of all outcomes with adjusted HR (95% CI) of 0.77 (0.72-0.83; P < 0.001) for major osteoporotic fractures, 0.49 (0.38-0.62; P < 0.001) for hip fractures, and 0.70 (0.64-0.77; P < 0.001) for vertebral fractures. When outcomes were examined separately by sex, the results were broadly comparable in terms of patterns of risk reduction by statin use. The patients with statin initiated at age ≥ 80 years had the highest risk reduction for most outcomes relative to non-users. Higher cumulative dose of statin was negatively associated with the osteoporotic fracture risk; 0.97 (0.91-1.02) for 30-364 cumulative daily defined dose (cDDD), 0.45 (0.40-0.51) for 365-1,094 cDDD, and 0.22 (0.15-0.33) for ≥ 1,095 cDDD. Our results showed that statin use was associated with significant reduction in the risk of osteoporotic fractures in general older population.


A proposal for thyroid surgery: criteria to identify the references of endocrine surgery.
Indicators of effectiveness and quality of care are needed to improve the outcomes in many surgical fields. International and national studies in thyroid surgery have not clearly documented an association between number of cases and outcome quality, but it is essential for the figure of a highly experienced surgeon, able to provide proof of positive outcomes. Therefore, we try to underline the structural and technical requirements in thyroid surgery. Moreover, the need for an accreditation program is outlined.


[Surgical treatment of epithelial skin tumors and their precursors].
Squamous cell carcinomas of the skin and their precursors, actinic keratosis as well as basal cell carcinomas are classified as non-melanocytic skin cancer and belong to the group of epithelial skin tumors. This tumor entity is one of the most common forms of malignant cancer in western countries with an incidence of approximately 100-170 per 100,000 inhabitants per year in Europe. In German-speaking countries no exact numbers are available on the early forms of squamous cell carcinoma, actinic keratosis (carcinoma in situ); however, results from Great Britain show that at ages over 70 years old the prevalence of actinic keratosis is 34 % in men and 18 % in women. Because invasive epithelial cancer is very common and most commonly occurs in the head region, a safe but skin-sparing approach to surgical treatment is desirable. The safest procedure with respect to local recurrence is surgical excision with subsequent complete 3-dimensional histological preparation (micrographic surgery). With this method it is possible to excise tissue affected by tumor tissue in small steps. This facilitates defect coverage and leads to very good results as well as good esthetic results. The local recurrence rates are extremely low compared to alternative treatment methods, such as photodynamic therapy, topical application of imiquimod or cryosurgery and for the treatment of basal cell carcinoma, for example is 0.7 %. Dermatological operations are therefore interventions with a very high guarantee of tumor-free survival and functional and esthetic results.


[Changes of interleukin-1beta and tumor necrosis factor-alpha of right atrial appendages in patients with rheumatic valvular disease complicated with chronic atrial fibrillation].
To investigate whether atrial expression of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) of right atrial appendages are altered in patients with rheumatic valvular disease during chronic atrial fibrillation. A total of 48 patients with rheumatic heart disease were included. 27 patients had no history of atrial fibrillation, 21 patients had atrial fibrillation. Atrial tissue was obtained from the right atrial appendage during open heart surgery. The protein expression of IL-1beta and TNF-alpha was detected by immunohistochemistry method. The fibrosis of right atrial appendage was detected by Masson staining. The fibrosis of right atrial appendage was significantly increased in patients with chronic atrial fibrillation. The protein expression of IL-1beta and TNF-alpha were significantly increased in patients with chronic atrial fibrillation. The protein expression of IL-1beta and TNF-alpha were significantly increased in patients with rheumatic valvular disease during chronic atrial fibrillation. Inflammation may be one of the mechanisms for the development and persistence of atrial fibrillation.


Anti-inflammatory and neuroprotective effects of triptolide on traumatic brain injury in rats.
Traumatic brain injury (TBI) is characterized by neuroinflammation, brain edema, and cerebral damage leading to impairment of neurobehavioral function. Triptolide (PG-490), a diterpenoid component from Tripterygium wilfordii Hook F., has anti-inflammatory properties. Whether triptolide has neuroprotective functions when treating TBI is unclear. To investigate this possibility, Sprague-Dawley rats were treated with triptolide immediately after TBI had been induced by a controlled cortical impact procedure or after a sham procedure. TBI produced neuroinflammation when measured on day 1 after TBI, induced cerebral damage when measured on day 1 and day 3, and impaired neurobehavioral functioning over a 28-day observation period. Triptolide suppressed TBI-induced increases in contusion volume, cell apoptosis, edema and the levels of various pro-inflammatory mediators in the brain. Thriptolide reversed the TBI-induced decrease in brain levels of anti-inflammatory cytokine interleukin-10. Importantly, triptolide improved neurobehavioral outcomes regarding motor, sensory, reflex and balance function. We conclude that triptolide confers neuroprotection against TBI, at least in part, via its anti-inflammatory activity.


Ecological impact of doxycycline at low dose on normal oropharyngeal and intestinal microflora.
This study included 34 healthy volunteers (16 male and 18 female) aged 19-37 years, of whom 17 received doxycycline 40 mg capsules orally once daily (o.d.) and 17 received placebo 40 mg capsules orally o.d. for 16 weeks. Plasma, saliva and faecal samples were collected before drug administration and at 4, 8, 16 and 20 weeks. Plasma samples were assayed for doxycycline concentrations, and saliva and faecal samples were investigated for doxycycline concentrations and microbiological analyses. Plasma concentrations of doxycycline in the doxycycline group were as follows: baseline visit (2 h), 0.20-0.61 mg/L; 4-week visit, 0.30-1.04 mg/L; 8-week visit, 0.43-1.49 mg/L; 16-week visit, 0.32-1.12 mg/L; and 20-week visit 0 mg/L. No doxycycline was detected in plasma in the placebo group. No doxycycline concentrations in the saliva samples were found in the doxycycline or placebo groups at the five visits. Faecal concentrations of doxycycline in the doxycycline group were as follows: baseline visit, 0 mg/kg; 4-week visit, 0-3.71 mg/kg; 8-week visit, 0-1.85 mg/kg; 16-week visit, 0-4.10 mg/kg; and 20-week visit, 0 mg/kg. No doxycycline faecal concentrations were detected in the placebo group. Minor effects on the aerobic and anaerobic oropharyngeal microflora were observed both in the doxycycline and placebo groups. There were minor changes in the number of enterococci and Escherichia coli in the doxycycline and placebo groups. The anaerobic intestinal microflora in the doxycycline and placebo groups was not changed, and no Clostridium difficile strains were isolated.


Chronic complications in patients with newly diagnosed type 2 diabetes: prevalence and related metabolic and clinical features: the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 9.
We explored the presence of chronic complications in subjects with newly diagnosed type 2 diabetes referred to the Verona Diabetes Clinic. Metabolic (insulin secretion and sensitivity) and clinical features associated with complications were also investigated. The comprehensive assessment of microvascular and macrovascular complications included detailed medical history, resting ECG, ultrasonography of carotid and lower limb arteries, quantitative neurological evaluation, cardiovascular autonomic tests, ophthalmoscopy, kidney function tests. Insulin sensitivity and beta-cell function were assessed by state-of-the-art techniques (insulin clamp and mathematical modeling of glucose/C-peptide curves during oral glucose tolerance test). We examined 806 patients (median age years, two-thirds males), of whom prior clinical cardiovascular disease (CVD) was revealed in 11.2% and preclinical CVD in 7.7%. Somatic neuropathy was found in 21.2% and cardiovascular autonomic neuropathy in 18.6%. Retinopathy was observed in 4.9% (background 4.2%, proliferative 0.7%). Chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) was found in 8.8% and excessive albuminuria in 13.2% (microalbuminuria 11.9%, macroalbuminuria 1.3%).Isolated microvascular disease occurred in 30.8%, isolated macrovascular disease in 9.3%, a combination of both in 9.1%, any complication in 49.2% and no complications in 50.8%.Gender, age, body mass index, smoking, hemoglobin A1c and/or hypertension were independently associated with one or more complications. Insulin resistance and beta-cell dysfunction were associated with macrovascular but not microvascular disease. Despite a generally earlier diagnosis for an increased awareness of the disease, as many as ~50% of patients with newly diagnosed type 2 diabetes had clinical or preclinical manifestations of microvascular and/or macrovascular disease. Insulin resistance might play an independent role in macrovascular disease. NCT01526720.


[Aesthesiophysiological and neurophysiological principles of organisation of the visual system (author's transl)].
The neuronal flow of signals of the visual system and the cortical modulous characteristic are described. Possible and not yet possible correlations between neuronal activity and aesthesiophysiological experience, as well as the cortical visual projection chain and its plasticity, are discussed.


Pediatric suicide by violent means: a cry for help and a call for action.
Suicide is the second most common cause of death among adolescents and young adults. In the pediatric population, gunshot wounds (GSWs) and hangings are common mechanisms of pediatric suicide. Comorbid psychiatric illness is prevalent in this population, but psychiatric resource utilization after self-inflicted traumatic injury is not well characterized. We analyzed patients < 18 years old presenting to a level 1 pediatric trauma center after suicide attempt by GSW, hanging, or jumping from a height from 2009 to 2019. The primary outcome was psychiatric resource utilization. Secondary outcomes included prior emergency department (ED) visits to identify prior opportunities for intervention. Of 6538 pediatric trauma patients, there were 219 GSWs, 7 hangings, and 7 jumps from height, for a total of 233 patients. Of these, 14 presented following a suicide attempt (four GSWs, six hangings, and four jumps, total 6.0%). Half of these patients died due to their injuries. Self-inflicted GSWs had the highest mortality (75%). Most surviving patients were placed on involuntary psychiatric holds (n = 5/7, 71.4%), and three patients were discharged to an inpatient psychiatric hospital (n = 3/7, 42.9%). Five of the 14 patients had prior ED visits (35.7%), and of these, 60% were for suicidal ideation or suicide attempts. Among pediatric trauma patients, suicide attempts are rare, but are highly lethal, with the highest mortality rate seen in self-inflicted GSWs. Psychiatric resource utilization is high both during and after the hospitalization. Prior ED visits may represent opportunities for depression and suicidality screening in this at-risk population.


A statistical model for HIV-1 sequence classification using the subtype analyser (STAR).
HIV-1 antiretroviral drug resistance testing produces large amounts of HIV-1 protease and reverse transcriptase sequences. These provide an excellent resource to study the incidence, spread and clinical significance of HIV-1 subtypes. We have produced a program, Subtype Analyser (STAR) that rapidly and accurately subtypes HIV-1. Here we have determined a robust and statistically validated model for subtype assignment. We have significantly extended our HIV-1 subtyping tool (STAR), such that each query sequence when evaluated against subtype profile alignments, returns a discriminating score based on the ratio of subtype positive to negative amino acid positions. These scores were transformed into a Z-score distribution and evaluated. Of the 141 sequences used to define the subtype alignments, 98% were correctly reclassified. Inclusion of additional recombination detection within STAR increased the detection of known recombinant sequences to 95%. STAR is available as compiled (Linux Fedora 3) or source code from http://pgv19.virol.ucl.ac.uk/download/star_linux.tar firstname.lastname@example.com http://pgv19.virol.ucl.ac.uk/download/star_supplement


Specificity of the MAP kinase ERK2 for phosphorylation of tyrosine hydroxylase.
Short-term regulation of catecholamine biosynthesis involves reversible phosphorylation of several serine residues in the N-terminal regulatory domain of tyrosine hydroxylase. The MAP kinases ERK1/2 have been identified as responsible for phosphorylation of Ser31. As an initial step in elucidating the effects of phosphorylation of Ser31 on the structure and activity of tyrosine hydroxylase, the kinetics of phosphorylation of the rat enzyme by recombinant rat ERK2 have been characterized. Complete phosphorylation results in incorporation of 2mol of phosphate into each subunit of tyrosine hydroxylase. The S8A and S31A enzymes only incorporate a single phosphate, while the S19A and S40A enzymes incorporate two. Phosphorylation of S8A tyrosine hydroxylase is nine times as rapid as phosphorylation of the S31A enzyme, consistent with a ninefold preference of ERK2 for Ser31 over Ser8.


Custom titanium sleeve for surgical treatment of mechanically assisted crevice corrosion in the well-fixed, noncontemporary stem in total hip arthroplasty.
Adverse local tissue reaction associated with total hip replacement may occur when mechanically assisted crevice corrosion occurs at metal-metal modular junctions in which at least one of the components is fabricated from cobalt-chromium alloy. Complete removal of components may be associated with significant morbidity; when components are well fixed and in acceptable position, it may be appropriate to consider modular rather than complete revision. We have diagnosed mechanically assisted crevice corrosion in total hip arthroplasty patients with noncontemporary but well-fixed femoral components and found that modular conversion to a ceramic femoral head to remove a source of CoCr corrosion and fretting products was only possible by having a custom titanium sleeve manufactured. Surgical implantation with a revision style Biolox ceramic head (CeramTec, Plochingen, Germany) was then achieved.


Role of infection control practitioners in human immunodeficiency virus testing. APIC Bloodborne Pathogens Committee.
As a result of the HIV epidemic, the role of the ICP has changed; acute care settings have developed a variety of policies regarding patient and health care worker (HCW) HIV testing and issues related to the HIV-infected HCW. APIC conducted a survey to determine the extent to which ICPs were involved in HCW and patient HIV testing and counseling, the prevalence of routine HIV testing for patients, institutional policies on HIV testing of patients and HCWs, and the management of HIV infected HCWs. In 1990, a questionnaire was sent to ICPs in a simple random sample of 1300 acute care hospitals (approximately 20%) in the United States. Response rate was 52.8%. Of the 686 respondents, 54.8% provided counseling to the HCW after an exposure incident. ICPs were involved not only in HIV testing and counseling for patients and HCWs but also in institutional policy development for HIV-related issues. Most facilities (73.8%) obtained written consent for testing from the patient after an employee exposure. When a direct care giver was known to be HIV positive, 61.5% of the respondents evaluated each case individually. The ICP has a significant role in the development and implementation of institutional policies on HIV testing and counseling and on the management of HIV-infected workers. These findings affirm the need for APIC to provide educational opportunities on the issues related to HIV testing and counseling.


The current perspective of low-grade myelodysplastic syndrome in children.
Myelodysplastic syndrome (MDS) without increased blasts, i.e., low-grade MDS, is the most common subtype of pediatric MDS and has characteristics different from adult form of the disease. Although histological findings of bone marrow (BM) biopsies suggest that low-grade MDS is a morphologically distinctive entity, a subset of pediatric low-grade MDS may clinically overlap with aplastic anemia (AA), such as high likelihood of hypocellular marrow and normal karyotype. In addition, children with low-grade MDS are as likely to respond to immunosuppressive therapy as those with AA, which indicates that a part of these disorders might share a common pathogenesis, that is, T cell-mediated inhibition of hematopoiesis. In contrast, a small part of children with low-grade MDS experience disease progression to advanced MDS. Given that the clinical courses of pediatric low-grade MDS are heterogeneous, assessing prognostic values of clinical, morphological, histological and cytogenetic findings is critical. Thus far, monosomy 7 and multilineage dysplasia have been suggested as prognostic factors that could predict disease progression. Treatment strategy will be optimized based on more precise prognostic factors. In the future, molecular findings may also help prognostification in children with hypoplastic BM disorders.


Centripetal lens epithelial cell migration: a prospective study of the Alcon SA60AT intraocular lens.
To evaluate prospectively the incidence and severity of centripetal lens epithelial cell migration (CLECM) onto the anterior surface of the Alcon SA60AT intraocular lens (IOL). One hundred and four consecutive cases of SA60AT IOL implantations were prospectively evaluated. At the 1-month postoperative visit, best corrected visual acuity (BCVA) was obtained. Following maximal pupillary dilatation, the extent of CLECM was assessed using a simplified grading scale (0-4). The centrality of the lens within the capsular bag was recorded. Patients with the highest grade of CLECM were recalled for reassessment at a minimum of 3 months. Centripetal lens epithelial cell migration data were obtained on 99 patients. Of these, 94% demonstrated CLECM of varying severity at 1 month postoperatively. The severity was low grade in 54% of patients (29% grade 1, 24% grade 2), and high grade in 40% of patients (16% grade 3, 24% grade 4). BCVA results were good (91.9% 6/6 or better) and did not correlate with CLECM grade. Operative capsulorhexis size did not correlate with the severity of CLECM. The lens was well-centred in 91 of 92 patients in whom lens position was assessed. Twenty-three patients with grade 4 CLECM at 1 month were brought back for reassessment (3.5-13 months postoperatively) and 18 of these demonstrated complete regression of CLECM (to grade 0). There is a high incidence and severity of CLECM 1 month postoperatively using the Alcon SA60AT IOL. There was no significant correlation between CLECM grade and either BCVA at 1 month, capsulorhexis size or lens centration. CLECM appears to be a frequent, benign and transient event with this lens.


Fouling of proton exchange membrane (PEM) deteriorates the performance of microbial fuel cell.
The fouling characteristics of proton exchange membrane (PEM) in microbial fuel cell (MFC) and the resulting deterioration of MFC performance were explored in this study. It was observed that the ion exchange capacity, conductivity and diffusion coefficients of cations of PEM were reduced significantly after fouling. Imaging analysis coupled with FTIR analysis indicated that the fouling layer attached on PEM consisted of microorganisms encased in extracellular polymers and inorganic salt precipitations. The results clearly demonstrate that PEM fouling deteriorated the performance of MFCs and led to a decrease in electricity generation. Cation transfer limitation might play an important role in the deterioration of MFC performance because of the membrane fouling. This was attributed to the physical blockage of charge transfer in the MFC resulted from the membrane fouling. With the experimental results, the effect of membrane fouling on the electrical generation of MFCs was evaluated. It was found that the decreased diffusion coefficients of cations and cathodic potential loss after membrane fouling contributed mainly to the deterioration of the MFC performance.


Physical activity, sustained sedentary behavior, and pain modulation in women with fibromyalgia.
Fibromyalgia (FM) has been conceptualized as a disorder of the central nervous system, characterized by augmented sensory processing and an inability to effectively modulate pain. We previously reported that physical activity is related to brain processing of pain, providing evidence for a potential mechanism of pain management. The purpose of this study was to extend our work by manipulating pain modulation and determining relationships to both physical activity and sustained sedentary behavior. Eleven women with FM completed accelerometer measures of physical activity and underwent functional magnetic resonance imaging of painful heat, administered alone and during distracting cognitive tasks. Results showed that physical activity was significantly (P < .005) and positively related to brain responses during distraction from pain in regions implicated in pain modulation including the dorsolateral prefrontal cortex (DLPFC), the dorsal posterior cingulate, and the periaqueductal grey. A significant negative relationship occurred in the left anterior insula. For sedentary time, significant negative relationships were observed in areas involved in both pain modulation and the sensory-discriminative aspects of pain including the DLPFC, thalamus, and superior frontal and pre- and post-central gyri. These results suggest that physical activity and sedentary behaviors are related to central nervous system regulation of pain in FM. Our results support a promising benefit of physical activity and highlight the potentially deleterious effects of sustained sedentary behavior for pain regulation in FM. Studies aimed at increasing physical activity or reducing sedentary behavior and determining the impact of these on pain regulation are warranted.


Knowledge of diabetes and the practice of diabetes self-management during Ramadan fasting among patients with type 2 diabetes in Malaysia.
To assess the level of diabetes knowledge and its association with diabetes self-management practices during Ramadan fasting among patients with type 2 diabetes (T2D). A cross-sectional study was conducted involving a sample of Malaysian patients with T2D. Patients aged 18 years and above, and attending an outpatient diabetic unit of a government hospital were recruited between February and April 2021. A self-administered questionnaire was utilized to assess diabetes knowledge and diabetes self-management practices. A total of 306 participants completed the questionnaire. Most of them were females (54.2%) and above 55 years old (75.1%). Resultantly, knowledge of diabetes was considered average among 52% of the participants. Only 9.5% of them avoided the consumption of sweet foods during iftar. Practicing late suhoor (p = 0.012) and self-monitoring of blood glucose (SMBG) (p = 0.026) during Ramadan were significantly associated with a better diabetes knowledge score. Education level (p = 0.000), working status (p = 0.030), and monthly income (p = 0.000) were significantly associated with participants' knowledge level of diabetes. A higher proportion (72.2%) of the participants completed fasting for a month during Ramadan 2020. Meanwhile, hypoglycemia was the main reason (38.8%) for incomplete fasting. These findings reflect the need to improve patients' knowledge of diabetes and diabetes self-management practices, especially during Ramadan. Such objectives could be achieved by considering the associated factors identified in this study.


[Incidence and determinants of levodopa-induced dyskinesia in a retrospective cohort of Mexican patients with Parkinson's disease].
BACKGROUND. Levodopa-induced dyskinesia is one of the main complications and limitations of the treatment of patients with Parkinson's disease. To determine the incidence and risk factors involved in the development of dyskinesias in a retrospective cohort of Mexican patients with Parkinson's disease. We reviewed a total of 601 cases of Parkinson's disease patients treated at the National Institute of Neurology and Neurosurgery in the period between January 1990 and June 2010; 482 of them had history of exposure to levodopa. The follow-up was equivalent to 4,392 person-years. 154 patients had dyskinesias at some point in the evolution of the disease. The person-time incidence was 35 cases per 1,000 person-years. The onset of motor symptoms before 50 years of age and levodopa doses > or = 600 mg of levodopa were the main risk factors for early development of dyskinesia (HR of 1.01 [95% CI 1.0 to 1.01, p = 0.001] and HR 1.10 [95% CI 1.04 to 1.23, p = 0.04], respectively]. The main determinants of dyskinesias were present early age of onset of motor symptoms and the dose of levodopa. Knowledge of these factors will improve the management planning.


Comparison of the pharmacodynamic effects of furosemide and BAY g 2821 and correlation of the pharmacodynamics and pharmacokinetics of BAY g 2821 (muzolimine).
In a biometrically planned, double-blind study on 12 Oedema-free male patients the saluretic effect of muzolimine 30 mg was compared with furosemide 40 mg. The plasma level of muzolimine was determined and correlated with its pharmacodynamics. In terms of excretion during the 12-hour observation period muzolimine 30 mg had as great a cumulative effect as furosemide 40 mg. There was a significant difference in the time-response curve. During the first gwo hours furosemide 40 mg had more saluretic effect than muzolimine 30 mg. Between two and four hours there was no significant difference between the two substances. Between four and six hours, however, muzolimine was somewhat more effective than furosemide, although the difference did not reach the level of significance. After 6 h there was no longer any difference between the two compounds. The half-life of the fall in concentration of muzolimine in plasma was 3.7 up to 10 h after its administration. The time-response curve of the increased urine excretion correlated well with the time course of the concentration of muzolimine in plasma.


Pharmacokinetics of norethindrone in Indian Women.
Pharmacokinetics of norethindrone (NET) was evaluated in eleven women belonging to a low socio-economic group and in five womem belonging to the high socio-economic group after the administration of an oral dose of 0.35 mg NET minipill on an empty stomach. Blood samples were collected at different intervals of time over a period of 24 hours. Plasma NET was estimated by radioimmunoassay. In all women, peak levels of NET occurred within 1-2 hours and a semi-log plot of plasma NET levels showed a biexponential decline. The half-life of plasma NET clearance was relatively shorter in women of low socio-economic group with poor nutritional status as indicated by anthropometric indices, as compared to that in well nourished women of high socio-economic group. There was a significant positive correlation between weight/(height) 2x 100 index on the one hand and t1/2 (beta) on the other in all the women studied, thereby suggesting a role for nutritional status in the metabolic handling of NET.


Repeat infusion of recombinant tissue-type plasminogen activator in patients with acute myocardial infarction and early recurrent myocardial ischemia.
When conventional treatment of patients with early clinical reinfarction after thrombolytic therapy fails, mechanical revascularization may be attempted. An alternative strategy, repeat thrombolytic infusions, is reported. Fifty-two patients with acute myocardial infarction were treated with one or two additional thrombolytic infusions of recombinant tissue-type plasminogen activator (rt-PA) because of nonsustained ischemia after initial treatment with rt-PA or streptokinase. Thirty-five patients received the second infusion within 1 h of the first; 13 patients received the second infusion 1 to 72 h after the first and 4 patients received it later during their hospitalization. Bleeding complications occurred in 10 patients (19%); however, most of these were minor (no intracranial bleeding) and only 2 patients required blood transfusion. In 14 patients in whom the decrease in fibrinogen and plasminogen levels was measured after the first and second infusions, this decrease was only 25% and 63%, respectively--only slightly higher than the 22% and 53% decreases measured in 63 patients who had only one rt-PA infusion. In 44 patients (85%), the acute ischemia resolved completely within 1 h after initiation of the second infusion. In 23 patients (44%), pain and ST segment elevation did not recur and invasive coronary intervention was avoided. Thus, repeat rt-PA infusions can stabilize a substantial number of patients with acute reinfarction and, even when relief is temporary, repeat rt-PA infusions can minimize myocardial damage while patients await mechanical revascularization.


A slow orthostatic tremor of primary origin.
Orthostatic tremor (OT) is a high-frequency tremor (13-18 Hz) present in the legs when standing. Underlying disease is found in one-third of OT patients. We describe an 86-year-old man with progressive shaking of the legs while standing, which disappears immediately after sitting down or while walking. Polymyography confirmed a tremor of the legs (10-11 Hz) while standing. Magnetic resonance imaging (MRI) and neurologic examination showed no underlying disease. Primary OT can appear at a lower frequency of 10-11 Hz.


Assessment of self-care agency in chronically ill adolescents.
This study evaluates the reliability and validity of the Denyes' instrument to measure self-care agency in adolescents and identifies significant correlates of agency in a sample of chronically ill adolescents. This descriptive cross-sectional study used a convenience sample of 51 adolescents having asthma, diabetes, and convulsive disorders. Internal consistency estimates of questionnaire factors ranged from alpha 0.65 to 0.87 except in one instance (attitude toward health, 0.17). Construct and concurrent validity were supported as self-care agency factors were significantly related to health practices and status. Of multiple demographic variables, only gender demonstrated significant correlations with any self-care factors, whereas gender and disease type displayed a significant interaction effect across three factors. Although assessment of factor stability remains, the Denyes' instrument appears to be a potentially useful research and clinical assessment tool to measure self-care agency in adolescents with a severe chronic illness.


Preoperative short-term radiotherapy in rectal carcinoma. A preliminary report of a prospective randomized study.
Between 1980 and 1983, 373 patients with clinically resectable rectal adenocarcinoma entered a prospective randomized study aimed to evaluate the effect of short-term preoperative radiotherapy. Protocol violations were identified in 21 instances. Of the remaining 352 patients, 182 were randomized to surgical treatment only (S-group). Immediately, before surgery, 170 patients were irradiated to the pelvic region with 25 Gy (2500 rad) during a 5-day period (RT-group). Of these patients, 59% underwent abdominoperineal excision, 38% anterior resection, and 3% laparotomy only. At surgery distant metastases were discovered in 32 patients (9%). There were no significant differences between the groups in the distribution of age, sex, operative methods, and tumor stage according to the original Dukes' classification. During the follow-up time, ranging between 6 months and 3 years, tumor recurrence occurred in 35 patients, 19 in the S-group and 16 in the RT-group. Fifteen patients in the S-group had pelvic recurrence compared to 10 patients in the RT-group. Distant metastases occurred in six and eight patients, respectively. Two patients in each group had both pelvic and distant recurrence. There was no correlation between tumor recurrence and type of operation. Median time interval from diagnosis to pelvic recurrence was 10 months in the S-group and 16 months in the RT-group. Postoperative complications in the form of wound sepsis were slightly more common in the RT-group. In summary, the applied treatment regimen, is well-tolerated and apparently does not affect the Dukes' stage of the tumor. Although there is no statistically significant difference, there is a trend of less pelvic recurrence in patients receiving preoperative radiotherapy.


The situational contexts and subjective effects of co-use of electronic cigarettes and alcohol among college students: An ecological momentary assessment (EMA) study.
Understanding the co-use of e-cigarettes and alcohol, including the situational contexts and subjective effects associated with co-use in real-time is necessary for validating this behavior and informing intervention. Yet, the sparse literature has built upon retrospective data. This study recruited 686 college students who were currently using e-cigarettes from three campuses in the Midwest and South of U.S in Fall 2019-Fall 2021. An on-line survey was conducted to measure e-cigarette use patterns, GPA, e-cigarette and alcohol dependence symptoms, and respiratory symptoms. A 7-day ecological momentary assessment was used to collect real-time data on e-cigarette and alcohol use, situational contexts and subjective effects. Frequent drinking e-cigarette users reported more high-risk use behavior including consuming 6 + drinks/occasion and simultaneous use, and reported more e-cigarettes and alcohol related dependence symptoms and respiratory symptoms, compared to infrequent/non-drinker e-cigarette users. Alcohol quantity was positively associated with e-cigarette quantity among the high frequency drinking group. This study identified important use contexts that were associated with higher e-cigarette consumption including use of menthol or fruit flavored e-cigarettes, being in a car, and the presence of others. E-cigarette use and alcohol use both increased the levels of positive affect, physiological sensation, and craving for e-cigarettes, whereas only alcohol use significantly decreased negative affect. No interaction effects between e-cigarette use and alcohol use were found. The findings highlight the addiction and health risks associated with frequent co-use of e-cigarettes and alcohol, and also call for regulations on nontobacco flavorings in e-cigarette products.


A real-time stress classification system based on arousal analysis of the nervous system by an F-state machine.
Detection and labelling of an increment in the human stress level is a contribution focused principally on improving the quality of life of people. This work is aimed to develop a biophysical real-time stress identification and classification system, analysing two noninvasive signals, the galvanic skin response and the heart rate variability. An experimental procedure was designed and configured in order to elicit a stressful situation that is similar to those found in real cases. A total of 166 subjects participated in this experimental stage. The set of registered signals of each subject was considered as one experiment. A preliminary qualitative analysis of the signals collected was made, based on previous counselling received from neurophysiologists and psychologists. This study revealed a relationship between changes in the temporal signals and the induced stress states in each subject. To identify and classify such states, a subsequent quantitative analysis was performed in order to determine specific numerical information related to the above mentioned relationship. This second analysis gives the particular details to design the finally proposed classification algorithm, based on a Finite State Machine. The proposed system is able to classify the detected stress stages at three levels: low, medium, and high. Furthermore, the system identifies persistent stress situations or momentary alerts, depending on the subject's arousal. The system reaches an F1 score of 0.984 in the case of high level, an F1 score of 0.970 for medium level, and an F1 score of 0.943 for low level. The resulting system is able to detect and classify different stress stages only based on two non invasive signals. These signals can be collected in people during their monitoring and be processed in a real-time sense, as the system can be previously preconfigured. Therefore, it could easily be implemented in a wearable prototype that could be worn by end users without feeling to be monitored. Besides, due to its low computational, the computation of the signals slopes is easy to do and its deployment in real-time applications is feasible.


Candida albicans and Pseudomonas aeruginosa interactions: more than an opportunistic criminal association?
Pseudomonas aeruginosa and Candida albicans are frequently coexisting opportunistic pathogens, responsible for colonization and infection in predisposed patients. They share a virulence specificity relying on auto-inducing, cell density-dependent molecules named quorum-sensing (QS). C. albicans virulence depends on its QS that influences morphological switch from yeast to filamentous form. Similarly, the production of P. aeruginosa virulence factors depends partly on QS molecules. Interactions have been investigated and demonstrated in vitro. P. aeruginosa may kill C. albicans either by producing toxins, such as pyocyanin, or by direct contact on its biofilm-dependent filamentous form. Cross-kingdom communication is a more subtle interaction: C. albicans can adapt its morphology in the presence of P. aeruginosa QS molecules, and inhibit P. aeruginosa QS-dependent virulence factor secretion, through farnesol, one of its QS molecule. But the in vivo relevance of these interactions is still controversial, as models of airway colonization/infection by C. albicans followed by subsequent P. aeruginosa pneumonia give contradictory results, suggesting the probable involvement of the immune system as a third party player. Finally, the authors of clinical studies performed in ventilated patients, indicate that C. albicans colonization could be a risk factor for P. aeruginosa pneumonia. The clinical outcome of C. albicans and P. aeruginosa interaction is uncertain, the virulence modulation demonstrated in these interactions opens new possibilities for future anti-infectious therapeutics.


Toxicity and potential underlying mechanism of Karenia selliformis to the fish Oryzias melastigma.
Karenia selliformis can produce toxins such as gymnodimines, and form microalgal blooms causing massive mortality of marine life such as fish and shellfish, and resulting in serious economic losses. However, there are a few of studies on the toxic effects of K. selliformis on marine organisms and the underlying mechanisms, and it is not clear whether the toxins produced by K. selliformis affect fish survival through the food chain. In this study, a food chain was simulated and composed by K. selliformis-brine shrimp-marine medaka to investigate the possibility of K. selliformis toxicity transmission through the food chain, in which fish behavior, histopathology and transcriptomics changes were observed after direct or indirect exposure (through the food chain) of K. selliformis. We found that both direct and indirect exposure of K. selliformis could affect the swimming behavior of medaka, manifested as decreased swimming performance and increased "frozen events". Meanwhile, exposure to K. selliformis caused pathological damage to the intestine and liver tissues of medaka to different degree. The effect of direct exposure to K. selliformis on swimming behavior and damage to fish tissues was more severe. In addition, K. selliformis exposure induced significant changes in the expression of genes related to energy metabolism, metabolic detoxification and immune system in medaka. These results suggest that toxins produced by K. selliformis can be transferred through the food chain, and that K. selliformis can destroy the intestinal integrity of medaka and increase the absorption of toxins, leading to energy metabolism disorders in fish, affecting the metabolic detoxification capacity of the liver. Our finding provides novel insight into the toxicity of K. selliformis to marine fish.


Rhinoplasty in the Asian Patient.
The ubiquitous goal of rhinoplasty is to make a natural-looking and attractive nose that blends harmoniously with the face. Rhinoplasty among Asians includes characteristics that distinguish the procedure from its white counterpart. Anatomic differences of the Asian nose coupled with differences in aesthetic standards demand they be approached in a unique way. In this article, peculiar aspects of Asian rhinoplasty are addressed with emphasis on surgical techniques used to obtain reliable results.


Physiological adaptation of a mature adult walking the Alps.
Research on endurance locomotion has mainly focused on elite athletes rather than common middle-aged subjects. Our report describes the physiological and hematological adaptation of a healthy, active 62-year-old man who trekked alone along a 1300 km/3 month course of Alpine paths (Via Alpina). The following procedures were conducted: pre- and post-trekking and fortnightly field anthropometry (total and lean body mass), functional tests (isometric maximal voluntary force, spontaneous walking speed, relative metabolic cost, and peak oxygen consumption) and clinical chemistry/hematological measurements with laboratory instruments; daily self-administered effort measurements using portable devices along the route (walked distance, ascent, descent, time, metabolic consumption, and cost). Despite the tough trekking route, the subject completed the trek without any worsening of his performance, or any significant health or functional problems. In addition, his peak oxygen consumption increased by 13.2%. His successful adaptation may be attributed to his constant, repeated middle-intensity and extensive exercise and lengthy exposure to high altitude. The clinical chemistry/hematological measurements documented his physiological adaptation. In conclusion, we show how an active, middle-aged man can successfully face endurance trekking, not only without any harm to his health or functions but also with an increase in his capacity to support specific effort.


Pioglitazone increases the fractional catabolic and production rates of high-density lipoproteins apo AI in the New Zealand White Rabbit.
Pioglitazone is an agonist of the peroxisome proliferator-activated receptor gamma (PPARgamma) that raises HDL-cholesterol plasma in humans. Whether pioglitazone-mediated modifications in HDL-apolipoprotein AI (apo AI) turnover in vivo contribute to this effect has not been completely elucidated. Therefore, we performed kinetic studies of HDL-apo AI radiolabeled with 125I in male New Zealand White rabbits after 6 weeks of 0.6 (n = 8), 1.75 (n = 8), and 2.6 mg/kg/day (n = 7) pioglitazone and vehicle (n = 12) treatment. Fractional catabolic rate (FCR) of HDL-apo AI was significantly higher in 1.75 and 2.6 mg/kg pioglitazone-treated animals, as compared with control rabbits (0.057+/-0.014 and 0.049+/-0.01 versus 0.025+/-0.005 pools/h, respectively); these changes were associated to a similar increase in apo AI production rates (PR) (1.24+/-0.62 and 1.14+/-0.40 versus 0.53+/-0.17 mg/kg/h, p < 0.01). Consequently, apo AI plasma levels in pioglitazone-treated animals were similar to those of controls. The apo AI-FRC and -PR correlated with the relative proportion of the HDL3c subclass, as determined by polyacrylamide gradient electrophoresis. Our data demonstrate that pioglitazone markedly modifies apo AI kinetics and enhances the proportion of small HDL3c particles, despite the unchanged apo AI concentration. Whether or not the pioglitazone-induced structural changes of HDL contribute to the anti-atherosclerotic effects of the drug remains to be determined.


The neuroradiological findings in a case of cerebral tuberculoma.
This paper describes the neuroradioloigical findings in a case of cerebral tuberculoma. Computed tomography demonstrated a mass in contact with the cranial bone with marked contrast enhancement and accompanied by perifocal cerebral edema. External carotid angiography revealed a homogenous stain supplied from the middle meningeal artery. Furthermore, by radioisotope scan it appeared to be a region of increased uptake with a comparatively clear border and was thereby misdiagnosed as meningioma.


Alkaloid fraction of Uncaria rhynchophylla protects against N-methyl-D-aspartate-induced apoptosis in rat hippocampal slices.
Uncaria rhynchophylla is a medicinal herb which has sedative and anticonvulsive effects and has been applied in the treatment of epilepsy in Oriental medicine. In this study, the effect of alkaloid fraction of U. rhynchophylla against N-methyl-D-aspartate (NMDA)-induced neuronal cell death was investigated. Pretreatment with an alkaloid fraction of U. rhynchophylla for 1 h decreased the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices and also inhibited NMDA-induced enhanced expressions of apoptosis-related genes such as c-jun, p53, and bax. In the present study, the alkaloid fraction of U. rhynchophylla was shown to have a protective property against NMDA-induced cytotoxicity by suppressing the NMDA-induced apoptosis in rat hippocampal slices.


Applications of bupivacaine in the non-surgical treatments of strabismus: a review.
Bupivacaine (BUP) is an anesthetic from the family of aminoacyl anesthetics and has the highest myotoxicity among other groups of anesthetics. Intramuscular injection of BUP first causes acute libriform lysis and subsequently with the regeneration process, stronger myofibrils are formed within 3-4 weeks. Satellite cells, which are actually myogenic stem cells, are preserved in the early stage and during the destruction of muscle fibers. In fact, these cells are responsible for the subsequent regeneration of fibers. BUP is one of the few medicines that is able to increase muscle strength. In animal studies on rabbits, a decrease has been observed in the diameter of the global layer in the first week and an increase in type-I myosin occurs after 60 days, especially in the global muscle layer. There are numerous studies according to BUP injection for the non-surgical management of horizontal strabismus. To intensify the effects of the injection, botulinum toxin injection can also be used simultaneously in the antagonist muscles. In general, although the rate of improvement in strabismus varied among different studies, BUP injection alone corrects about 5-8 prism diopters. Together with botulinum toxin, BUP corrects about 15 prism diopters. The stability of this improvement is up to 10 years after injection. No significant difference has been observed in response rate between patients with esotropia and exotropia. Unlike the large molecule of botulinum toxin, which spreads slowly to its site of action, the BUP molecule is small and must be in direct contact with myofibrils before absorption into the bloodstream to exert its effect. Therefore, the injection volume should be about 3 cc with a concentration of 0.75 g per deciliter. Although BUP is promising non-surgical strabismus management, especially in small angle and residual horizontal strabismus, however, it has its own limitations. The need for direct infusion of a relatively large volume of BUP may be one of its major drawbacks that limits its usage in an office method.


Workshop to address gaps in regulation of minimally manipulated autologous cell therapies for homologous use in Canada.
In Canada, minimally manipulated autologous cell therapies for homologous use (MMAC-H) are either regulated under the practice of medicine, or as drugs or devices under the Food and Drugs Act, Food and Drug Regulations (F&DR) or Medical Device Regulations (MDR). Cells, Tissues and Organs (CTO) Regulations in Canada are restricted to minimally manipulated allogeneic products for homologous use. This leaves an important gap in the interpretation of existing regulations. The purposes of this workshop co-organized by the Stem Cell Network and the Centre for Commercialization of Regenerative Medicine (CCRM) were to discuss the current state of regulation of MMAC-H therapies in Canada and compare it with other regulatory jurisdictions, with the intent of providing specific policy recommendations to Health Canada. Participants came to a consensus on the need for well-defined common terminology between regulators and stakeholders, a common source of confusion and misinformation. A need for a harmonized national approach to oversight of facilities providing MMAC-H therapies based on existing standards, such as Canadian Standards Association (CSA), was also voiced. Facilities providing MMAC-H therapies should also participate in collection of long-term data to ensure patient safety and efficacy of therapies. Harmonization across provinces of the procedures and practices involving administration of MMAC-H would be preferred. Participants felt that devices used to process MMAC-H are adequately regulated under existing MDR. Overly prescriptive regulation will stifle innovation, whereas insufficient regulation might allow unsafe or ineffective therapies to be offered. Until a clear, balanced and explicit approach is articulated, regulatory uncertainty remains a barrier.


1,3,5-Pyrazoline Derivatives in CNS Disorders: Synthesis, Biological Evaluation and Structural Insights through Molecular Docking.
Anxiety and oxidative stress are the common disorders prevailing in the modern age. Many new pyrazoline derivatives have been synthesized and patented, but there is still continuous research in progress to explore antidepressant and antioxidant potential of pyrazoline scaffold. The present work was carried out to synthesize, characterize and evaluate the pharmacological potential of 1,3,5-Pyrazoline derivatives. Ten new 1,3,5-Pyrazoline derivatives were synthesized and characterized by IR, 1HNMR and mass spectral techniques. The synthesized pyrazoline derivatives were investigated for their in vivo antidepressant activity by Tail Suspension Test (TST) and in vitro antioxidant activity by FRAP and DPPH assay methods. The docking studies and in silico ADME and toxicity characteristics were also evaluated. Among the synthesized analogues, IVh showed the highest antidepressant activity with a significant reduction in the duration of immobility. The compound IVh emerged as the most potent antioxidant compound due to the presence of an electron releasing hydroxyl group. Docking studies of most potent compounds revealed good interaction points with the MAO-A enzyme. The compounds were found to obey Lipinski's Rule of Five and displayed the least in silico toxicity profile. The synthesized compounds were found to possess great potential in decreasing the duration of immobility in Swiss albino mice and scavenging free radicals. These compounds may serve as new leads for further drug exploration.


The Northwestern University Novel Urology Residency Curriculum: Updated Outcomes from a 13-Year Experience with Flexible Residency Training and Electives.
We evaluated educational outcomes and satisfaction following institution of a novel, flexible and urology-driven resident curriculum. A new urology resident curriculum was instituted at Northwestern University in 2006. Rotation schedules and resident electives were recorded annually. Operative case logs and American Urological Association In-Service Examination scores were collected prospectively. Residents and faculty rated satisfaction with the residency program on a 5-point Likert scale from "poor" to "outstanding." Differences in cases logged, In-Service Examination scores and satisfaction ratings under the new and prior curricula were compared. Curriculum changes included full 5-year urology oversight of the residency curriculum by the program director, 8 months of urology rotations in the first postgraduate year and 2 months of general surgery during the second postgraduate year. General surgery rotations were modified annually based on educational rationale and feedback. Cases logged per resident and In-Service Examination scores were comparable between old and new curricula groups. All residents matriculating under the new curriculum took and passed their written boards. The percentage of faculty and residents describing the program as "outstanding" increased from 50% in 2004‒2005 to 82% in 2017‒2018. Program satisfaction increased significantly when comparing the first and last 6 years (percent rating "outstanding": 56.1±2.1% vs 71.6±10.0%, p=0.028). After 13 years with the novel curriculum, resident case numbers and In-Service Examination scores remained similar while faculty/resident satisfaction increased. Direct control of general surgery rotations enabled adjustments based on educational rationale. These results demonstrate that a urology-directed and flexible residency program can be instituted without compromising learner outcomes.


Assessment of daily variation in pelvic anatomy in women with and without pelvic organ prolapse.
Symptoms of pelvic organ prolapse (POP) can affect quality of life and are reported to progress during the day, although this was never objectified. The aim of this study is to determine whether the pelvic anatomy changes during the day using upright magnetic resonance imaging (MRI), in POP patients and asymptomatic women. In this prospective study 15 POP patients and 45 asymptomatic women were included. Upright MRI scans were obtained three times per day. The distances from the lowest points of the bladder and cervix to a standardized reference (pelvic inclination correction system) line were determined. A principal component analysis was performed on the levator plate (LP) shape. Statistical differences between time points and the groups were determined for the bladder, cervix, and LP shape. For all women a significant decrease in bladder and cervix height of -0.2 cm (p<0.001) was seen between morning/midday and afternoon scans. A significant difference in bladder descent during the day between POP patients and asymptomatic women was found (p=0.004). Individual differences in bladder position in the POP group of up to 2.2 cm between the morning and afternoon scan were reported. There was a significant difference in LP shape (p<0.001) between the groups but there were no significant changes during the day. This study found no clinically relevant pelvic anatomy changes during the day. Still, on an individual level differences can be large, so repeating clinical examination at the end of the day can be recommended in patients when anamnesis and physical examination do not match.


Open dialogue about complementary and alternative medicine (CAM) integrated in conventional oncology care, characteristics and impact. A systematic review.
To systematically review evidence on the characteristics, experiences and impact of an open dialogue about complementary and alternative medicine (CAM) integrated in oncology care. We searched MEDLINE, EMBASE, AMED, Scopus, ProQuest Dissertations and Thesis, Cochrane Central Register, clinicaltrials.gov, forskningsdatabase.dk and PROSPERO. Two reviewers screened title, abstract and full-text articles. Each study was appraised using the Critical Appraisal Skills Programme (CASP) and synthesized narratively. PROSPERO registration CRD42019112242. We retrieved 4736 articles and included 5; 3 received 9 ½, 1 received 9, and 1 received 5 points on the CASP score. Predominately, the open dialogue was one or two individual, patient-centered, face-to-face consultations led by oncology physicians. In one study, it was a tele-phone consultation and in another it was structured counseling led by pharmacists. Integrated information and recommendations about CAM contributed to high level of satisfaction and improvement in concerns, quality of life and well-being. Integration of open dialogue about CAM in oncology care including acknowledging patients' preferences, values, wishes and knowledge, and providing information about CAM expands the opportunities for improving patients' health, quality of life and well-being. Open dialogue about CAM has potentials, but research on how it specifically helps patients, is needed.


A patient with Creutzfeldt-Jakob disease presenting with amyotrophy: a case report.
Creutzfeldt-Jakob disease (CJD) is an ultimately fatal, neurodegenerative disease caused by misfolded prion protein aggregation and accumulation. The development of amyotrophic features has been described in CJD, though rarely as an early or prominent feature. Consequently, the significance of amyotrophy in prion disease etiology remains unclear. Our patient, a healthy 70-year-old French/Algerian man, presented to our hospital following a work-related fall and was admitted with lower limb skeletal muscle atrophy and fasciculations; the fasciculations progressed to involve the trunk, upper limbs and face. Within days, he developed evidence of a progressive ascending neurological syndrome and subsequent brain involvement with supranuclear palsy of upgaze, catalepsy and death 36 days after symptom onset. Amyotrophy remained the principle feature of his disease. Dementia started to develop within 10 days of the onset of his amyotrophy. Prion disease was confirmed at postmortem. Our observations suggest an unusual form of prion disease with prominent early involvement of anterior horn cells, ascending prion propagation in the central nervous system and a grave prognosis.


Bioavailable IGF-1 and its relationship with endothelial damage in a bi-ethnic population: The SABPA study.
Insulin-like growth factor-1 (IGF-1) has vasculoprotective effects and can directly oppose endothelial dysfunction in several ways. To improve our understanding on the potential contribution of reduced IGF-1 to the development of vascular endothelial damage, we investigated the link between bioavailable IGF-1 and von Willebrand factor (vWF) as a marker of endothelial damage. We performed this study in black South African school teachers, known to be prone to hypertension. From the larger Sympathetic activity and Ambulatory Blood Pressure in Africans (SABPA) study we included 179 black and 207 white non-diabetic men and women (aged 44.5 ± 9.96 years). We measured ambulatory blood pressure and determined IGF-1, insulin-like growth factor binding protein 3 (IGFBP-3) and vWF antigen from blood samples. We used the molar IGF-1/IGFBP-3 ratio as an estimate of bioavailable IGF-1. Black individuals presented higher blood pressure and vWFag and lower IGF-1 than the white group (all p < 0.001). In multivariate-adjusted analyses, vWFag was inversely associated with IGF-1 (R(2) = 0.18; β = -0.17; p = 0.044) and IGF-1/IGFBP-3 (R(2) = 0.18; β = -0.17; p = 0.030) in blacks, with no associations in whites. Since IGF-1 is attenuated and vWFag elevated in diabetes, we included patients with diabetes (n = 38) and the aforementioned associations found in blacks remained robust. The inverse association between bioavailable IGF-1 and vWF in black South Africans suggests that suppressed IGF-1 may result in endothelial damage independent of traditional risk factors.


Assembly of the Kdp complex, the multi-subunit K+-transport ATPase of Escherichia coli.
Kdp, the high affinity ATP-driven K+-transport system of Escherichia coli, is a complex of the membrane-bound subunits KdpA, KdpB, KdpC and the small peptide KdpF. The assembly of this complex was studied by the analysis of mutants that expressed two of the three large subunits and inserted them into the cytoplasmic membrane. In the strains that do not express KdpC or KdpA the other two subunits did not copurify on dye-ligand affinity columns after solubilization with non-ionic detergent. In the mutant lacking KdpB the other two subunits copurified under the same conditions. It is concluded that KdpC forms strong interactions with the KdpA subunit, serving to assemble and stabilise the Kdp complex. A structure in which KdpC could be one of the connecting links between the energy-delivering subunit KdpB and the K+-transporting subunit KdpA is suggested by these data.


Novel Application of Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging for Diagnosis of External Hydrocephalus.
Although a subdural fluid collection frequently is observed, diagnostic methods that differentiate between the subdural collection caused by external hydrocephalus and that caused by subdural hygroma have not been established. Here, we report a case of external hydrocephalus caused by Gliadel-induced eosinophilic meningitis that has been previously reported in only 1 case and can be diagnosed by time-spatial labeling inversion pulse magnetic resonance imaging (time-SLIP MRI). A tumor located in the left temporal was detected incidentally in an 81-year-old man by examination of a head injury. The tumor was surgically resected and diagnosed as a high-grade glioma during the surgery; Gliadel wafers subsequently were implanted. Three weeks after the resection, the patient showed disturbed consciousness, and computed tomography revealed a subdural fluid collection. The out-flow of cerebrospinal through the resection cavity was detected by time-SLIP MRI. Cerebrospinal tests indicated high white blood cell counts and high protein levels, with more than 90% of the white blood cell count comprising eosinophils. Therefore, we suspected that the subdural fluid collection was caused by external hydrocephalus because of Gliadel-induced eosinophilic meningitis. We surgically removed the Gliadel wafers and subsequently performed a surgery to insert a ventriculoperitoneal shunt. Histologic examination indicated eosinophilic accumulation around the Gliadel wafers. The patient's symptoms improved after the insertion of a ventriculoperitoneal shunt. In the present case, time-SLIP MRI was a useful and noninvasive method for diagnosing external hydrocephalus which was caused by eosinophilic meningitis because of Gliadel-induced eosinophilic meningitis.


[Pneumatic dilation in the treatment of achalasia].
Pneumatic dilation and surgical myotomy are currently the procedures of choice to treat achalasia. The selection of one or other treatment depends on the experience of each center and patient preferences. To review the experience of pneumatic dilation in patients with achalasia in our center. We included all patients with a clinical, endoscopic and manometric diagnosis compatible with achalasia who underwent pneumatic dilation in a 19-year period. All dilations were routinely performed with a Rigiflex(®) balloon, usually at pressures of 250, 250 and 300mm Hg in three inflations of one minute, each separated by one minute. The success of the dilation was assessed on the basis of the patient's symptoms, the number of sessions, the need for surgery, and the presence of complications. A total of 171 patients were included, 53.2% men and 46.8% women, with a mean age of 51.53±17.78 years (16-87 years), from June 1993 to October 2012. A 35-mm balloon was used in 157 patients, a 30-mm balloon in 9 patients and a 40-mm balloon in 7 patients. A single dilation session was required in 108 patients, two sessions were required in 56 patients, with a mean time between the first and second sessions of 25.23±43.25 months (1-215 months), and 3 sessions were required in 7 patients with a mean time between the second and third sessions of 6.86±5.33 months (1-15 months). Outcome after dilation was successful in 81% of the patients. Of the 140 responders, 121 had complete response (complete disappearance of symptoms without recurrence) and 19 partial response (initial disappearance of symptoms with subsequent reappearance). Surgery (Heller myotomy) was required in 15.8% of the patients. Perforation occurred in 4 of the 171 patients as a complication of the technique; these perforations were satisfactorily resolved, two by conservative treatment and two by surgery. There was no mortality associated with the technique or its complications. In our series, pneumatic dilation had a high success rate. In most patients, a single session was required and the complications rate was low. These results show that this technique is safe and effective in these patients, avoiding a large number of surgical interventions.


Characterisation of micromonosporae from aquatic environments using molecular taxonomic methods.
Large numbers of strains assigned to the genus Micromonospora on the basis of typical colonial and pigmentation features were isolated from diverse aquatic sediments using a standard selective isolation procedure. Two hundred and six isolates and eight representatives of the genus Micromonospora were assigned to 24 multimembered groups based on a numerical analysis of banding patterns generated using BOX and ERIC primers. Representatives of multimembered groups encompassing isolated micromonosporae were the subject of 16S rRNA gene sequencing analyses. Good congruence was found between the molecular fingerprinting and 16S rRNA sequence data indicating that the groups based upon the former are taxonomically meaningful. Nearly all of the isolates that were chosen for the 16S rRNA gene sequencing analyses showed that the ecosystems studied are a rich source of novel micromonosporae. These findings have implications for high throughput screening for novel micromonosporae as BOX and ERIC fingerprinting, which is rapid and reproducible, can be applied as a robust dereplication procedure to indicate which environmental isolates have been cultured previously.


Apoptosis is involved in the senescence of endothelial cells induced by angiotensin II.
Vascular endothelial cells have a finite cell lifespan and eventually enter an irreversible growth arrest, cellular senescence. The functional changes associated with cellular senescence are thought to contribute to human aging and age-related cardiovascular disorders, e.g. atherosclerosis. In this study, induction of Angiotensin II (Ang II) promoted a growth arrest with phenotypic characteristics of cell senescence, such as enlarged cell shapes, increased senescence-associated beta-galactosidase (SA-beta-gal) positive staining cell, and depressed cell proliferation. Apoptotic changes were increased in senescent cells, with a small subset of the senescent cells showing aberrant morphology such as pronounced nuclear fragmentation or multiple micronuclei. The results suggest cell apoptosis is possibly an important factor in the process of pathologic and physiologic senescence of endothelial cells as well as vascular aging.


Rapid molecular identification of Neisseria meningitidis isolates using the polymerase chain reaction followed by single-stranded conformation polymorphism analysis.
Typing of Neisseria meningitidis strains is currently performed with conventional and molecular methods. Our objectives were: first, to develop a polymerase chain reaction (PCR) followed by single-stranded conformation polymorphism (SSCP) analysis of the PorA gene (VR1 region) to distinguish N. meningitidis subtypes and second, to evaluate the method for the identification and characterization of N. meningitidis in patient specimens. SSCP analysis of the VR1 region of the PorA1/2 gene from 126 N. meningitidis strains and 29 clinical samples identified seven SSCP types (SP-1 to SP-7); four strains were not typeable by the method. Classification according to the SSCP methods and serosubtype agreed for 122 of the 126 typeable strains (96.8%). For the 24-culture positive clinical samples, serosubtype and SSCP agreed in all cases. Five samples, which were culture-negative but obtained from children during an apparent outbreak of meningococcal disease in a primary school, presented identical SSCP classification for each sample (SP-2). PCR-SSCP is a rapid and cost-effective method for typing N. meningitidis strains that could provide important early information in the surveillance of suspected meningococcal outbreaks, particularly when culture-negative specimens constitutes the main source of material to analyze.


Effect of incubation temperature on acid production and proteolytic activity in milk by selected lactobacilli mutants.
Lactobacillus bulgaricus 59 and L. casei RTS and their respective nitrosoguanidine-induced mutants were estimated for titratable and volatile acidities, production of biacetyl and acetoin and for proteolytic activity. Both the mutants showed a marked increase in proteolytic activity as compared to the parents.


Functional characterization of age-dependent p16 epimutation reveals biological drivers and therapeutic targets for colorectal cancer.
Methylation of the p16 promoter resulting in epigenetic gene silencing-known as p16 epimutation-is frequently found in human colorectal cancer and is also common in normal-appearing colonic mucosa of aging individuals. Thus, to improve clinical care of colorectal cancer (CRC) patients, we explored the role of age-related p16 epimutation in intestinal tumorigenesis. We established a mouse model that replicates two common genetic and epigenetic events observed in human CRCs: Apc mutation and p16 epimutation. We conducted long-term survival and histological analysis of tumor development and progression. Colonic epithelial cells and tumors were collected from mice and analyzed by RNA sequencing (RNA-seq), quantitative PCR, and flow cytometry. We performed single-cell RNA sequencing (scRNA-seq) to characterize tumor-infiltrating immune cells throughout tumor progression. We tested whether anti-PD-L1 immunotherapy affects overall survival of tumor-bearing mice and whether inhibition of both epigenetic regulation and immune checkpoint is more efficacious. Mice carrying combined Apc mutation and p16 epimutation had significantly shortened survival and increased tumor growth compared to those with Apc mutation only. Intriguingly, colon tumors with p16 epimutation exhibited an activated interferon pathway, increased expression of programmed death-ligand 1 (Pdl1), and enhanced infiltration of immune cells. scRNA-seq further revealed the presence of Foxp3+ Tregs and γδT17 cells, which contribute to an immunosuppressive tumor microenvironment (TME). Furthermore, we showed that a combined therapy using an inhibitor of DNA methylation and a PD-L1 immune checkpoint inhibitor is more effective for improving survival in tumor-bearing mice than blockade of either pathway alone. Our study demonstrated that age-dependent p16 epimutation creates a permissive microenvironment for malignant transformation of polyps to colon cancer. Our findings provide a mechanistic rationale for future targeted therapy in patients with p16 epimutation.


Anti-HIV pronucleotides: decomposition pathways and correlation with biological activities.
The purpose of the present study was to compare the decomposition pathways in CEM cell extracts of various phenyl phosphoramidate derivatives of AZT. In addition, the structures of their metabolites were identified. Correlations with their anti-HIV activities in a thymidine kinase deficient (TK-) CEM cell line have been established with a rationale of designing phosphoramidate pronucleotides capable of delivering intracellularly their respective 5'-nucleoside monophosphate derivatives.