Describing Hawai'i's nursing home physicians: the results of a survey.
Despite a growing need for physicians providing care to nursing home patients, the characteristics of physicians providing such care are not well described. A survey was sent to adult primary care physicians in Hawai'i; respondents' demographic data were obtained. Associations between physician characteristics, level of nursing home experience, and island of practice were analyzed using chi square and multivariate logistic regression models. Of 806 physicians, 388 (48%) returned surveys. Controlling for years of experience and other demographic factors, having nursing home experience was associated with physician age (40 years and over compared with under 40 years; OR 3.5, 95% Confidence Interval (CI) 1.4-8.5), Family Medicine specialty (compared with Internal Medicine, General Practice or Other; OR 4.0, 95% CI 1.4-11.4), private practice type (compared with employed, other, and trainee physicians; OR 2.3, 95% CI 1. 1-4.6), and practice location (neighbor islands compared with Oahu, OR 4.5, 95% CI 1.1-17.8). Physicians practicing on the neighbor islands were more likely to be aged 40 years and older (OR 3.9, 95% CI 1.4-10.3), and white (ethnicity compared with all other ethnicities, OR 4.1, 95% CI 2.1-7.7). The association of higher physician age with both nursing home experience and neighbor island practice has important implications for the training of physicians to provide nursing home care in Hawai'i.


Fractures in thalassemia.
Fractures occur frequently in patients with homozygous beta-thalassemia. A study was made of the fractures noted in a group of patients who were followed at the Thalassemia Clinic at The New York Hospital-Cornell Medical Center. Results indicate that these patients often sustain fractures which are multiple and which frequently heal with resultant deformities.


Helicobacter pylori infection and insulin resistance in diabetic and nondiabetic population.
Helicobacter pylori (HP) is a common worldwide infection with known gastrointestinal and nongastrointestinal complications. One of the gastrointestinal side effects posed for this organism is its role in diabetes and increased insulin resistance. The aim of this study was to evaluate the association between HP and insulin resistance in type 2 diabetic patients and nondiabetics. This cross-sectional study was carried out from May to December 2013 on 211 diabetic patients referred to diabetes clinic of Shahid Beheshti Hospital of Qom and 218 patients without diabetes. HP was evaluated using serology method and insulin resistance was calculated using HOMA-IR. The prevalence of H. pylori infection was 55.8% and 44.2% in diabetics and nondiabetics (P = 0.001). The study population was divided into two HP positive and negative groups. Among nondiabetics, insulin resistance degree was 3.01 ± 2.12 and 2.74 ± 2.18 in HP+ and HP- patients, respectively (P = 0.704). Oppositely, insulin resistance was significantly higher in diabetic HP+ patients rather than seronegative ones (4.484 ± 2.781 versus 3.160 ± 2.327, P = 0.013). In diabetic patients, in addition to higher prevalence of HP, it causes a higher degree of insulin resistance.


Mirrizi Syndrome and Markedly Elevated Levels of Carbohydrate Antigen 19-9 in the Absence of Malignant Disease.
Elevated carbohydrate antigen 19-9 (CA19-9) beyond 1000 U/L occurs in nonneoplastic conditions which is causing questioning of the use of CA19-9 as a marker for screening. We report a case where a 51-year-old male with Mirrizi Syndrome (MS) presented with markedly increased CA19-9 level (4,618 U/mL). MS is a rare complication characterized by compression of the common bile or hepatic duct caused by an impacted gallstone in the cystic duct or neck of the gallbladder. Biliary epithelial cells secrete CA19-9: it is hypothesized that increased proliferation of such cells caused by inflammation leads to increased secretion. CA19-9 should not be used as a diagnostic tool, but rather for surveillance.


Biosynthesis, characterisation and antimicrobial activity of silver nanoparticles using Hibiscus rosa-sinensis petals extracts.
Green synthesis of metallic nanoparticles has lured the world from the chemical and physical approaches owing to its rapid, non-hazardous and economic aspect of production mechanism. In this study, silver nanoparticles (AgNPs) were synthesised using petal extracts of Hibiscus rosa-sinensis. The AgNPs displayed characteristic surface plasmon resonance peak at around 421 nm having a mean particle size of 76.25±0.17 nm and carried a charge of -41±0.2 mV. The X-ray diffraction patterns displayed typical peaks of face centred cubic crystalline silver. The surface morphology was characterised by scanning electron microscopy and atomic force microscopy. Fourier transform infrared spectroscopy studies confirmed the surface modifications of the functional groups for the synthesis of AgNPs. Furthermore, the synthesised AgNPs displayed proficient antimicrobial activity against pathogenic strains of Vibrio cholerae, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus.


Dynamic contrast-enhanced magnetic resonance imaging of tumor-induced lymph flow.
The growth of metastatic tumors in mice can result in markedly increased lymph flow through tumor-draining lymph nodes (LNs), which is associated with LN lymphangiogenesis. A dynamic magnetic resonance imaging (MRI) assay was developed, which uses low-molecular weight gadolinium contrast agent to label the lymphatic drainage, to visualize and quantify tumor-draining lymph flow in vivo in mice bearing metastatic melanomas. Tumor-bearing mice showed greatly increased lymph flow into and through draining LNs and into the bloodstream. Quantitative analysis established that both the amount and the rate of lymph flow through draining LNs are significantly increased in melanoma-bearing mice. In addition, the rate of appearance of contrast media in the bloodstream was significantly increased in mice bearing melanomas. These results indicate that gadolinium-based contrast-enhanced MRI provides a noninvasive assay for high-resolution spatial identification and mapping of lymphatic drainage and for dynamic measurement of changes in lymph flow associated with cancer or lymphatic dysfunction in mice. Low-molecular weight gadolinium contrast is already used for 1.5-T MRI scanning in humans, which should facilitate translation of this imaging assay.


Primary Unilateral Small Cell Neuroendocrine Carcinoma of the Kidney in a Dog.
Primary small cell carcinomas are rare in domestic animals. A mass measuring 15 × 20 × 9 cm was detected in the left abdominal cavity of a 7.5-year-old female golden retriever. The cut surface of the excised mass showed a tumour replacing the left kidney. Microscopically, the mass was composed of polymorphic, small basophilic cells with a high nuclear to cytoplasmic ratio and round, oval or short slender fusiform nuclei with condensed or finely granular chromatin, absent or inconspicuous nucleoli, and scant, faintly eosinophilic cytoplasm with poorly defined cytoplasmic borders. Immunohistochemically, most of the neoplastic cells were immunoreactive for thyroid transcription factor 1 and CD56, moderately positive for vimentin and weakly or sparsely labelled for chromogranin A, synaptophysin, Wilms' tumour 1 protein, neuron-specific enolase, pan-cytokeratin (CK) AE1/AE3 and epithelial membrane antigen. The tumour cells were negative for glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule 1, CK7, CK20, CD3, CD45 and CD99. These findings indicated a neuroendocrine origin of the tumour. To the best of author's knowledge, this is the first report of a small cell neuroendocrine carcinoma originating as a primary tumour in the kidney of a dog.


Duodenal adipose tissue is associated with obesity in baboons (Papio sp): a novel site of ectopic fat deposition in non-human primates.
Ectopic fat is a recognized contributor to insulin resistance and metabolic dysfunction, while the role of fat deposition inside intestinal wall tissue remains understudied. We undertook this study to directly quantify and localize intramural fat deposition in duodenal tissue and determine its association with adiposity. Duodenal tissues were collected from aged (21.2 ± 1.3 years, 19.5 ± 3.1 kg, n = 39) female baboons (Papio sp.). Fasted blood was collected for metabolic profiling and abdominal circumference (AC) measurements were taken. Primary tissue samples were collected at the major duodenal papilla at necropsy: one full cross section was processed for hematoxylin and eosin staining and evaluated; a second full cross section was processed for direct chemical lipid analysis on which percentage duodenal fat content was calculated. Duodenal fat content obtained by direct tissue quantification showed considerable variability (11.95 ± 6.93%) and was correlated with AC (r = 0.60, p < 0.001), weight (r = 0.38, p = 0.02), leptin (r = 0.63, p < 0.001), adiponectin (r = - 0.32, p < 0.05), and triglyceride (r = 0.41, p = 0.01). The relationship between duodenal fat content and leptin remained after adjusting for body weight and abdominal circumference. Intramural adipocytes were found in duodenal sections from all animals and were localized to the submucosa. Consistent with the variation in tissue fat content, the submucosal adipocytes were non-uniformly distributed in clusters of varying size. Duodenal adipocytes were larger in obese vs. lean animals (106.9 vs. 66.7 µm2, p = 0.02). Fat accumulation inside the duodenal wall is strongly associated with adiposity and adiposity related circulating biomarkers in baboons. Duodenal tissue fat represents a novel and potentially metabolically active site of ectopic fat deposition.


Multimodal learning of pheromone locations.
Memorizing pheromonal locations is critical for many mammalian species as it involves finding mates and avoiding competitors. In rodents, pheromonal information is perceived by the main and accessory olfactory systems. However, the role of somatosensation in context-dependent learning and memorizing of pheromone locations remains unexplored. We addressed this problem by training female mice on a multimodal task to locate pheromones by sampling volatiles emanating from male urine through the orifices of varying dimensions or shapes that are sensed by their vibrissae. In this novel pheromone location assay, female mice' preference toward male urine scent decayed over time when they were permitted to explore pheromones vs neutral stimuli, water. On training them for the associations involving olfactory and whisker systems, it was established that they were able to memorize the location of opposite sex pheromones, when tested 15 days later. This memory was not formed either when the somatosensory inputs through whisker pad were blocked or when the pheromonal cues were replaced with that of same sex. The association between olfactory and somatosensory systems was further confirmed by the enhanced expression of the activity-regulated cytoskeleton protein. Furthermore, the activation of main olfactory bulb circuitry by pheromone volatiles did not cause any modulation in learning and memorizing non-pheromonal volatiles. Our study thus provides the evidence for associations formed between different sensory modalities facilitating the long-term memory formation relevant to social and reproductive behaviors.


Effectiveness of strontium-doped brushite, bovine-derived hydroxyapatite and synthetic hydroxyapatite in rabbit sinus augmentation with simultaneous implant installation.
Various bone substitutes have been applied in sinus augmentation (SA) to overcome insufficient bone height at the posterior maxilla region caused by pneumatized sinus and severe alveolar bone resorption after teeth loss. However, their effectiveness in SA needs to be further elucidated. In this study, strontium-doped brushite (Sr-DCPD), a new bone substitute, together with bovine-derived hydroxyapatite (bHA) and synthetic hydroxyapatite (sHA) was used in rabbit maxillary SA with simultaneous implant installation. The sinus space-keeping capacity, resorption rate, osteoconductivity, and mechanical properties of regenerated bone, were evaluated by micro-computed tomography (CT), histological analysis, and mechanical testing. Sr-DCPD exhibited the best osteoconductivity and new bone formation (<4 weeks), but its final bone regeneration and removal torque of implants at week 12 were the lowest, mainly due to its poor space-keeping capacity and fast resorption. bHA exhibited the best space-keeping capacity and slowest resorption rate, but relative lower final bone volume and mechanical properties, while sHA showed good space-keeping capacity, slower resorption rate, and the best final bone formation and mechanical properties. sHA was most effective for SA and bHA was also an acceptable bone substitute; however, Sr-DCPD was least effective and not suitable in SA by itself.


Educational requirements of nurses providing care to children with complex needs in the community.
The number of children with complex care needs has increased in recent decades and many of them are cared for in the community. Nurses may require additional training and education to provide optimal care to these children. To establish whether nurses providing care to children with complex needs in the community feel prepared for their role and whether they require additional education and/or training, and to identify the essential skills and knowledge required to provide care to children with complex needs in the community. A quantitative descriptive study was conducted with nurses employed by private providers to care for children with complex needs in the community across the Republic of Ireland. The study used an existing online survey validated through a literature review, an expert panel review and a pilot study. A total of 62 nurses responded, 53% of them (n=33) stating that their current education met their requirements when caring for children with complex needs in the community. There was a small positive correlation between the number of years of nursing experience and whether respondents thought their educational requirements were being met. More experienced respondents identified a need for continuing education and less experienced respondents identified a need for community placements during preregistration education. Assisted ventilation, non-invasive ventilation and tracheostomy care were the three top subject areas in terms of the usefulness of their inclusion in an educational programme designed to enhance the knowledge and skills of nurses providing care to children with complex needs in the community. The findings reinforce the need for specific training and continuing education for specialist nurses caring for children with complex needs and their families in the community.


Stimulatory Effects of Flusilazole on Virulence of Sclerotinia sclerotiorum.
Flusilazole, a member of the demethylation inhibitor fungicides, is highly efficacious for control of Sclerotinia sclerotiorum. To achieve judicious applications of flusilazole, its hormetic effects on virulence of S. sclerotiorum were investigated. Flusilazole sprayed at concentrations from 0.02 to 0.5 μg/ml caused statistically significant (P < 0.05) stimulatory effects on virulence of S. sclerotiorum to potted rapeseed plants, and the maximum stimulation magnitudes were 11.0 and 10.7% for isolates GS-7 and HN-24, respectively. Studies on the time course of the infection process showed that a stimulatory effect on virulence could be discerned at 18 h postinoculation, indicating a direct stimulation mechanism rather than an overcompensation for initial inhibitions. In order to determine whether the stimulations were caused mainly by effects of flusilazole on S. sclerotiorum or on rapeseed plants, mycelia grown on flusilazole-amended potato dextrose agar (PDA) media were inoculated on leaves of rapeseed plants without spraying the fungicide. Mycelium radial growth on PDA supplemented with flusilazole at concentrations from 0.005 to 0.16 μg/ml was inhibited by 10.11 to 48.7% for isolate GS-7 and by 4.1 to 24.9% for isolate HN-24. Observations with a scanning electron microscope showed that flusilazole in PDA at 0.04 and 0.08 μg/ml caused slightly deformed mycelia and twisted mycelial tips. Nevertheless, after inoculating on leaves of potted rapeseed plants, virulence of the inhibited mycelia was statistically significantly (P < 0.05) greater than that of the nontreated control, and the maximum stimulation magnitudes were 16.2 and 19.8% for isolates GS-7 and HN-24, respectively. Studies on a physiological mechanism for virulence stimulations showed that tolerance to hydrogen peroxide did not increase significantly for mycelia grown on flusilazole-amended PDA, thus excluding the possibility of tolerance to reactive oxygen species as a potential mechanism for virulence stimulations.


Purification and properties of a beta-mannanase from alfalfa seeds.
A beta-mannanase (EC 18.104.22.168) has been purified from germinating Alfalfa seeds by successive chromatography steps; on hydroxyapatite, DEAE-cellulose and ECTEOLA-cellulose. The enzyme preparations were homogeneous as judged by gel electrophoresis. A 5000-fold increase in specific activity (from the crude extract) was obtained. The purified enzyme has a molecular weight of 40 000. Several of its properties were determined: pH optimum 5.2 and optimal temperature of activity 50 degrees C. The hydrolysis of galacto- and gluco-mannans (with various ratio of mannose to galactose and glucose) as well as that of mannooligosaccharides was studied in detail. A prefered point of attack at the third position from the non-reducing end was shown. Comparative results from the hydrolysis of intact galactomannans, of galactomannans previously hydrolysed by galactosidase, suggest that galactose hinders the accessibility of the mannan backbone to the enzyme.


[Study of the heart conduction system in atrioventricular disorders].
A His electrogram was registered with a Castillo tripolar catheter in seven patients with atrio-ventricular discordance and transposition of the great arteries (corrected transposition). They all had ventricular septal defect, six had pulmonary stenosis. two had atrial septal defect, and only one patient presented first degree AV block. The QRS was of normal duration, 4 had RBBB morphology in the left precordials. Two with ASD and VSD had a prolonged P/A interval. In one, the His recording was polyphasic with a prolonged H-V (55 msec) and two others showed a wide polyphasic His potential (25 and 26msec), with a prolonged H-V. These 3 cases with prolonged His had a minor degree of RBBB. The remaining 3 showed normal AV conduction. In all, the Purkinje electrogram was registered. The duration of the Pu potential and the Pu-V were normal. Corrected transposition shows a high incidence of slow AV conduction, frequently not detectable in the usual electrocardiogram in agreement with previous anatomo-pathological studies. The distal block would explain the frequency of complete AV block with low cardiac output and frequent sudden death in this type of heart disease. The distal block would compel us to take e more agressive steps in its treatment. Atrial septal defect with slowing of the intra-arial conduction is not detected in the electrocardiogram.


Microbial dynamics and flagellate grazing during transition to winter in Lakes Hoare and Bonney, Antarctica.
The planktonic microbial communities of Lakes Hoare and Bonney were investigated during transition into winter. We hypothesized that the onset of darkness induces changes in the functional role of autotrophic and heterotrophic microplankton. Bacteria decreased in Lake Hoare during March-April, while in Lake Bonney bacterial abundances varied. Heterotrophic nanoflagellates (HNAN), phototrophic nanoflagellates (PNAN) and ciliates showed no marked decline with the onset of winter. PNAN outnumbered HNAN in both lakes. Grazing rates of HNAN in Lake Hoare ranged up to 30.8 bacteria per cell day(-1). The HNAN community grazed between 3.74 and 36.6 ng of bacterial carbon day(-1). Mixotrophic PNAN had grazing rates up to 15.2 bacteria per cell day(-1), and their daily community grazing exceeded bacterial production. In Lake Bonney East, PNAN grazing rates ranged up to 12.48 bacteria per cell day(-1) and in Lake Bonney West up to 8.16 bacteria per cell day(-1). As in Lake Hoare, the mixotrophic PNAN grazing rates (up to 950 ng C day(-1)) usually exceeded bacterial production. HNAN grazing rates were generally similar to those in Lake Hoare. As winter encroaches, these lakes move progressively towards heterotrophy and probably function during the winter, enabling populations to enter the short austral summer with actively growing populations.


Management of the neck after alternating chemoradiotherapy for advanced head and neck cancer.
To investigate neck control probability and the value of nodal response at completion of alternating chemoradiotherapy, a group of 43 patients was reviewed. Patients were treated with 60 Gy alternated with four cycles of cisplatin and fluorouracil. All patients had lymph nodes positive for squamous cell carcinoma from various primary sites, underwent computed tomography (CT) for staging and evaluation of response, and were treated at a single institution. Patients with bilateral lymph nodes (N2c) were further staged according to the side of dominant neck disease. After chemoradiotherapy alone, 2-year neck control probabilities (NCP) are 86+/-13%, 58+/-10%, and 0 for N1, N2a/b, and N3 neck stages, respectively (p = .038). Two-year NCP for 25 complete responders is 85+/-8%, whereas, at the same time interval, it is 17+/-9% for 18 partial responses (p<.0001). Within patients with N1-2a/b neck disease, 21 complete responders had a 2-year NCP of 92+/-8%. Five (11%) heminecks in four patients developed severe (Radiation Therapy Oncology Group [RTOG] grade > 2) subcutaneous late reactions. For patients with N1-2a/b neck disease, response at the end of treatment as evaluated by both physical exam and CT is a reliable criterion to select patients for complementary surgery even after chemoradiotherapy. For N3 disease, planned neck dissection regardless of response seems warranted.


A comparative study on the antifungal effect of potassium sorbate, chitosan, and nano-chitosan against Rhodotorula mucilaginosa and Candida albicans in skim milk acid-coagulated (Karish) cheese.
Yeasts are common contaminants in the cheese industry, which frequently arise from raw milk, the surrounding environment, and equipment, resulting in economic losses in addition to health hazards. This study aimed to compare the antifungal effect of chitosan and nano-chitosan as natural preservatives with a commonly used chemical preservative (potassium sorbate) against Rhodotorula mucilaginosa and Candida albicans. Laboratory Karish cheese was manufactured with the addition of potassium sorbate, chitosan, nano-chitosan, and their combinations at different concentrations. The survival of R. mucilaginosa and C. albicans was monitored in different treatments (CR, PR1, PR2, CR1, CR2, NR1, NR2, MR, CC, PC1, PC2, CC1, CC2, NC1, NC2, MC) during storage in a refrigerator with continuous measurement of pH. The impact of using these antifungal agents on the organoleptic parameters of Karish cheese during storage was also evaluated. There was a significant decrease in the count of yeasts in all treatments from the 3rd day of storage, while the mixture of 0.1% potassium sorbate (MR) and 2% chitosan (MC) improved the antifungal effect of chitosan with a lower potassium sorbate concentration and showed the best antifungal effects against both R. mucilaginosa and C. albicans. This combination reduced the yeast count from 8.92 and 9.57 log10 colony-forming unit (CFU)/g in MR and MC treatments, respectively, until it became undetectable on the 9th day of storage, which was earlier than for all other treatments. It was noted that the addition of chitosan nanoparticles (ChNPs) at either 0.25% (NR1 and NC1) or 0.5% (NR2 and NC2) during the manufacturing of Karish cheese significantly lowered the counts of R. mucilaginosa and C. albicans compared with chitosan with a higher molecular weight, but significantly lower than potassium sorbate until 6th day of storage as all treatments of chitosan nanoparticles became significantly higher than potassium sorbate treatments. After 9 days of storage, NR2 and NC2 treatments showed the most significant decreases in count (3.78 and 4.93 log10 CFU/g, respectively), indicating better stability of ChNPs. At the end of the storage period, PR2, PC2, CR2, and CC2 showed significantly high pH values among the groups of 4.8, 5.0, 4.8, and 5.1, respectively. The overall acceptability was significantly higher in treated Karish cheese samples than in the control group, especially at the end of the storage period. Potassium sorbate, chitosan, and ChNPs are effective antifungal preservatives against R. mucilaginosa and C. albicans. In addition, the combination of chitosan with potassium sorbate showed synergistic antifungal activity. These additives also preserve the sensorial criteria longer than for cheese without preservatives.


Efficacy and Safety of Aspirin Combined with Low-Dose P2Y12 Receptor Antagonists in East Asian Patients Undergoing PCI.
Previous studies have indicated that low-dose new generation of P2Y12 receptor antagonists may be more suitable compared with clopidogrel at a standard dose for the dual antiplatelet therapy (DAPT) for East Asian patients receiving percutaneous coronary intervention (PCI). However, there remains no consensus in clinical practice. Thus, in this study, we aimed to determine the efficacy and safety of low-dose P2Y12 receptor antagonists, compared to clopidogrel at a standard dose, in DAPT in East Asian patients after PCI. We systematically searched literatures for randomized controlled trials (RCT) comparing low-dose P2Y12 receptor antagonists with standard-dose clopidogrel for the treatment of East Asian patients undergoing PCI. The endpoints of efficacy include major adverse cardiac events (MACEs), all-cause mortality, and the number of target vessel revascularization. The indicators of safety include major and minor bleeding events. Heterogeneity was evaluated by I2 statistic test. Begg's and Egger's tests were used to evaluate publication bias. In total, 2,747 subjects from 8 RCT studies were included. Low-dose new P2Y12 receptor antagonists, that is, ticagrelor or prasugrel, showed significantly lower incidence of MACEs, as compared with standard-dose clopidogrel, in the East Asian patients who are in DAPT after undergoing PCI. Further, no difference was noted for the risk of major and minor bleeding events. In East Asian patients undergoing PCI and receiving DAPT, the use of low-dose P2Y12 receptor antagonists, ticagrelor or prasugrel, has been determined to be superior than clopidogrel at standard dose; this has been evidenced by a lower incidence of MACEs without increasing the risk of bleeding.


Antibodies to the HIV-1 V3 loop in serum from infected persons contribute a major proportion of immune effector functions including complement activation, antibody binding, and neutralization.
Previous studies have shown that the V3 region of the HIV envelope is both critical to viral functions and immunogenic. However, the relative contribution of anti-V3 antibodies in the sera of infected individuals in mediating immune effector functions directed at whole intact virus and infected cells has not been determined. This study used peptides corresponding to several regions of the HIV envelope as inhibitors of antibody binding and antibody effector functions directed at virions and virus-infected cells in order to assess the relative importance of V3-specific antibodies in sera from infected persons. Approximately 40% of the antibody in serum which could bind to native viral proteins on HIVMN-infected cells was blocked by a peptide corresponding to the central 15 amino acids of the V3 loop. In contrast, little if any blocking of serum antibody binding was observed with peptides corresponding to flanking regions of HIVMN V3 or three regions of gp41. Since antiviral antibody can also activate immune effector functions, we determined whether peptides could block antibody-dependent activation of the complement system by HIV-infected cells or free virus. Surprisingly, the V3 loop peptide blocked 75-95% of complement activation on HIV-infected cells. While the V3 loop peptide also blocked a substantial portion of the neutralizing activity in serum from infected persons for free virus it was again more effective in inhibiting complement-mediated effects on free virus. Accordingly, antibody-dependent, complement-mediated virolysis was inhibited by 61-79%. The results of these experiments indicate that (1) a substantial portion (30-40%) of the antibody in sera from infected persons that is capable of binding to HIV-infected cells and HIV virions is V3-specific, and (2) these V3-specific antibodies are particularly important for complement activation on infected cells and virions. This indicates that the central portion of the V3 loop, while constituting less than 3% of the amino acid sequence of the HIV envelope, apparently provides a major gp160 site for immune effector functions, especially complement activation.


Precision nutrition in the context of bariatric surgery.
Bariatric surgery (BS) is the most effective long-term treatment for severe obesity. This review summarizes the main nutritional deficiencies before and after BS, as well as current dietary and supplementation recommendations to avoid them. Likewise, we have reviewed all those aspects that in recent years have been shown to be related to postoperative weight loss (WL) and its subsequent maintenance, such as hormonal changes, dietary patterns, changes in food preference, adherence to recommendations and follow-up, genetic factors and microbiota, among others. Despite all the knowledge, nutritional deficiencies and weight regain after BS are frequent. It is essential to continue studying in this field in order to establish more precise recommendations according to the individual characteristics of patients. It is also a major objective to understand more deeply the role of the factors involved in WL and its maintenance. This will allow the development of precision treatments and nutrition for patients with obesity, optimizing their benefit after BS.


Comparison of outcomes after single-port laparoscopic cholecystectomy in relation to patient body mass index.
Single-port laparoscopic cholecystectomy may contribute to a paradigm shift in the field of laparoscopic cholecystectomy surgery by providing patients with benefits beyond those observed after other surgical procedures. This study was designed to evaluate clinically meaningful differences in operative outcomes between obese and nonobese patients after single-port laparoscopic cholecystectomy. Data were collected retrospectively from 172 patients who had undergone single-port laparoscopic cholecystectomy performed by the same surgeon at a single medical center between January and December 2011. For the outcome analysis, patients were divided into nonobese and obese patient groups according to their body mass index (<25 kg/m2 vs ≥25 kg/m2). Demographic and clinical data did not differ significantly between obese patients (n=65) and nonobese patients (n=107). In addition, statistically significant differences pertaining to most measured surgical outcomes including postoperative hospital stay, bile spillage, additional port use, and open conversion were not detected between the groups. However, the two groups differed significantly regarding operative time such that nonobese patients had shorter operative times than obese patients (P<.05). The results of this study showed that operative time for single-port laparoscopic cholecystectomy was the only difference between obese and nonobese patients. Given this result, body mass index may not be as relevant a factor in patient selection for single-port laparoscopic cholecystectomy as previously thought.


Impact of Blood Pressure, Lesion Level, and Physical Activity on Aortic Augmentation Index in Persons with Spinal Cord Injury.
Individuals with chronic spinal cord injury (SCI) are at a heightened risk of cardiovascular disease (CVD) resulting from autonomic nervous system dysfunction, physical inactivity, and increased inflammatory processes. Arterial stiffness (AS) is recognized as an independent risk factor for CVD and, specifically, pulse wave analysis (PWA) has proven to be a useful tool to predict and track structural arterial changes that reflect arteriosclerosis. The augmentation index (AI) can be used to estimate AS and is derived from the amplitude and timing of the blood pressure (BP) wave reflection in a peripheral artery. Recently, AS has been shown to be increased in persons with SCI compared with the uninjured population; however, possible contributors to increased AS in the SCI population have not been fully explored. In this study, increased radial artery AI is demonstrated in persons with high cord lesions (above T6) compared with individuals with low cord lesions (T7 and below) and uninjured controls. The association between age and AI was not significant in the SCI population; however, there was a direct association between AI and level of injury. Further, AI was inversely associated with seated systolic blood pressure (SBP) and was increased in individuals who reported orthostatic hypotension (OH) and in those who were physically inactive. In conclusion, individuals with higher cord lesions have more severe cardiovascular autonomic disruption, leading to orthostatic BP dysregulation and physical inactivity, which appear to contribute independently to increased AS in these individuals.


Comparison of isolation methods of exosomes and exosomal RNA from cell culture medium and serum.
Exosomes are cell-derived vesicles and are abundant in biological fluids; they contain RNA molecules which may serve as potential diagnostic biomarkers in 'precision medicine'. To promote the clinical application of exosomal RNA (exoRNA), many isolation methods must be compared and validated. Exosomes in cell culture medium (CCM) and serum may be isolated using ultracentrifugation (UC), ExoQuick or Total Exosome Isolation Reagent (TEI), and exoRNA may be extracted using TRIzol-LS, SeraMir, Total Exosome RNA Isolation (TER), HiPure Liquid RNA/miRNA kit (HLR), miRNeasy or exoRNeasy. ExoRNA was assessed using NanoDrop, Bioanalyzer 2100, quantitative polymerase chain reaction and high-throughput sequencing. UC showed the lowest recovery of particles, but the highest protein purity for exosome isolation. For isolation of exoRNA, we found that combinations of the TEI and TER methods resulted in high extraction efficiency and purity of small RNA obtained using CCM. High yield and a narrow size distribution pattern of small RNA were shown in exoRNA isolated by exoRNeasy from serum. In RNA profile analysis, the small RNA constituent ratio, miRNA content and amount varied as a result of methodological differences. This study showed that different methods may introduce variations in the concentration, purity and size of exosomes and exoRNA. Herein we discuss the advantages and disadvantages of each method and their application to different materials, therefore providing a reference according to research design.


Ectopic thyroid nodular goiter presenting as a porta hepatis mass.
An ectopic thyroid goiter was found in a 58-year-old woman who presented with abdominal and low back pain, diarrhea, and generalized weakness. Initial workup, including abdominal CT scan, revealed a mass extending from the duodenum to the porta hepatis. After resection and upon pathologic examination of the tissue, nodular arrangement of thyroid follicles and colloid lakes with focal hyperplastic and nodular goiter changes were identified.


Dermatophytes from urban soils in João Pessoa, Paraíba, Brazil.
A total of 68 soil samples was collected from "favelas" (slums), schools, public squares, beaches and vacant lots in the city of João Pessoa-PB, Brazil. A search for dermatophytes in these soils was carried out by using the Vanbreuseghem technique. As a result, 48 strains and 6 dermatophytes species were isolated. Trichophyton terrestre (25.0%), Microsporum gypseum (20.8%) and Anthroderma gypsea (2.1%) were identified among the geophilic species, and T. mentagrophytes var. mentagrophytes (37.5%) among the zoophilic species and T. tonsurans (4.2%), among the anthropophilic species. The growth of 75% of dermatophytes occurred in alkaline pH (7.02-9.00) and their presence in the soil should not be underestimated, since some of the identified species are aetiological agents of dermatophytoses in humans and animals.


Endovascular therapy of inflammatory aortic aneurysms: a meta-analysis.
To report a meta-analysis of results from endovascular aneurysm repair (EVAR) of inflammatory aortic aneurysms (IAA). A comprehensive literature review was performed to identify all studies reporting the results of EVAR in patients with IAA. To be included in the analysis, an article had to provide a minimum follow-up of 6 months, information about primary technical success, details of immediate and long-term complications, and evaluation of at least one of the basic outcome criteria: changes in aneurysm sac diameter, periaortic fibrosis (PAF), and/ or renal impairment. All studies were reviewed by 2 independent observers for the inclusion criteria. Data were retrieved on the technical and clinical success, outcome criteria, mortality in follow-up, and reinterventions from 14 articles selected from among 701 initially identified. The 14 articles encompassed 46 patients (45 men [97.8%]; mean age 65 years, range 59-75) with a mean follow-up of 18 months after endovascular repair of IAAs located in the abdominal aorta. The primary technical success rate was 95.6% (44/46) and the 30-day clinical success rate was 93.4% (43/46). The median aneurysm sac diameter regression was 11 mm. Of 43 patients with PAF prior to the intervention, 22 (51.2%) patients showed complete regression, 18 (41.8%) remained unchanged, and 3 (7.0%) showed progression after EVAR. Renal impairment disappeared in 11 (45.8%) of 24 patients. Reinterventions were reported in 8 patients. The procedure-related and follow-up mortality rates were 0% and 13.0%, respectively. EVAR of IAA is feasible, excludes the aneurysm effectively, and reduces PAF and renal impairment in most patients with very low periprocedural and midterm mortality and an acceptable reintervention rate.


Histological characteristics of respiratory system in Brown Norway rat.
It is well known that the Brown Norway (BN) rat strain exhibits airway hyperresponsiveness to exposure to allergens or some chemicals. We investigated the histological characteristics of the trachea and lungs of this strain (10-week-old and retired animals) and compared them with those of age-matched Fischer 344 (F344) rat strain. No histological differences between two strains in tracheal epithelial cells were detected, but differences in the distribution and development of submucosal glands were clarified by the observation of serial sections cut at intervals of 100 microns. Submucosal glands of BN strain were larger in the number and better-developed than those of F344 strain, especially in the middle and lower trachea. Similar results were also obtained in scanning electron microscopic observation of resin casts. There were no significant differences between two strains in the lectin histochemical characteristics of the cytoplasm of glandular epithelial cells. No age-related changes in these morphological characteristics in the two strains were observed. These results suggest that mucin from submucosal glands is quantitatively different but qualitatively similar in the two strains. In addition, microgranuloma mainly composed of histiocytes and eosinophils was observed in the lungs of the BN strain rats.


Cryo-Electron Tomography of the Herpesvirus Procapsid Reveals Interactions of the Portal with the Scaffold and a Shift on Maturation.
Herpes simplex virus 1 (HSV-1) requires seven proteins to package its genome through a vertex in its capsid, one of which is the portal protein, pUL6. The portal protein is also thought to facilitate assembly of the procapsid. While the portal has been visualized in mature capsids, we aimed to elucidate its role in the assembly and maturation of procapsids using cryo-electron tomography (cryoET). We identified the portal vertex in individual procapsids, calculated a subtomogram average, and compared that with the portal vertex in empty mature capsids (A-capsids). The resulting maps show the portal on the interior surface with its narrower end facing outwards, while maintaining close contact with the capsid shell. In the procapsid, the portal is embedded in the underlying scaffold, suggesting that assembly involves a portal-scaffold complex. During maturation, the capsid shell angularizes with a corresponding outward movement of the vertices. We found that in A-capsids, the portal translocates outward further than the adjacent capsomers and strengthens its contacts with the capsid shell. Our methodology also allowed us to determine the number of portal vertices in each capsid, with most having one per capsid, but some none or two, and rarely three. The predominance of a single portal per capsid supports facilitation of the assembly of the procapsid.IMPORTANCE Herpes simplex virus 1 (HSV-1) infects a majority of humans, causing mostly mild disease but in some cases progressing toward life-threatening encephalitis. Understanding the life cycle of the virus is important to devise countermeasures. Production of the virion starts with the assembly of an icosahedral procapsid, which includes DNA packaging proteins at a vertex, one of which is the dodecameric portal protein. The procapsid then undergoes maturation and DNA packaging through the portal, driven by a terminase complex. We used cryo-electron tomography to visualize the portal in procapsids and compare them to mature empty capsids. We found the portal located inside one vertex interacting with the scaffold protein in the procapsid. On maturation, the scaffold is cleaved and dissociates, the capsid angularizes, and the portal moves outward, interacting closely with the capsid shell. These transformations may provide a basis for the development of drugs to prevent HSV-1 infections.


Nitric Oxide-Scavenging, Anti-Migration Effects, and Glycosylation Changes after Hemin Treatment of Human Triple-Negative Breast Cancer Cells: A Mechanistic Study.
The enhanced expression of nitric oxide (•NO) synthase predicts triple-negative breast cancer outcome and its resistance to different therapeutics. Our earlier work demonstrated the efficiency of hemin to scavenge the intra- and extracellular •NO, proposing its potency as a therapeutic agent for inhibiting cancer cell migration. In continuation, the present work evaluates the effects of •NO on the migration of MDA-MB-231 cells and how hemin modulates the accompanied cellular behavior, focusing on the corresponding expression of cellular glycoproteins, migration-associated markers, and mitochondrial functions. We demonstrated for the first time that while •NO induced cell migration, hemin contradicted that by •NO-scavenging. This was in combination with modulation of the •NO-enhanced glycosylation patterns of cellular proteins with inhibition of the expression of specific proteins involved in the epithelial-mesenchymal transition. These effects were in conjunction with changes in the mitochondrial functions related to both •NO, hemin, and its nitrosylated product. Together, these results suggest that hemin can be employed as a potential anti-migrating agent targeting •NO-scavenging and regulating the expression of migration-associated proteins.


The endocytic recycling regulator EHD1 is essential for spermatogenesis and male fertility in mice.
The C-terminal Eps15 homology domain-containing protein 1 (EHD1) is ubiquitously expressed and regulates the endocytic trafficking and recycling of membrane components and several transmembrane receptors. To elucidate the function of EHD1 in mammalian development, we generated Ehd1-/- mice using a Cre/loxP system. Both male and female Ehd1-/- mice survived at sub-Mendelian ratios. A proportion of Ehd1-/- mice were viable and showed smaller size at birth, which continued into adulthood. Ehd1-/- adult males were infertile and displayed decreased testis size, whereas Ehd1-/- females were fertile. In situ hybridization and immunohistochemistry of developing wildtype mouse testes revealed EHD1 expression in most cells of the seminiferous epithelia. Histopathology revealed abnormal spermatogenesis in the seminiferous tubules and the absence of mature spermatozoa in the epididymides of Ehd1-/- males. Seminiferous tubules showed disruption of the normal spermatogenic cycle with abnormal acrosomal development on round spermatids, clumping of acrosomes, misaligned spermatids and the absence of normal elongated spermatids in Ehd1-/- males. Light and electron microscopy analyses indicated that elongated spermatids were abnormally phagocytosed by Sertoli cells in Ehd1-/- mice. Contrary to a previous report, these results demonstrate an important role for EHD1 in pre- and post-natal development with a specific role in spermatogenesis.


Characterization of an operon required for growth on cellobiose in Clostridioides difficile.
Cellobiose metabolism is linked to the virulence properties in numerous bacterial pathogens. Here, we characterized a putative cellobiose PTS operon of Clostridiodes difficile to investigate the role of cellobiose metabolism in C. difficile pathogenesis. Our gene knockout experiments demonstrated that the putative cellobiose operon enables uptake of cellobiose into C. difficile and allows growth when cellobiose is provided as the sole carbon source in minimal medium. Additionally, using reporter gene fusion assays and DNA pulldown experiments, we show that its transcription is regulated by CelR, a novel transcriptional repressor protein, which directly binds to the upstream region of the cellobiose operon to control its expression. We have also identified cellobiose metabolism to play a significant role in C. difficile physiology as observed by the reduction of sporulation efficiency when cellobiose uptake was compromised in the mutant strain. In corroboration to in vitro study findings, our in vivo hamster challenge experiment showed a significant reduction of pathogenicity by the cellobiose mutant strain in both the primary and the recurrent infection model - substantiating the role of cellobiose metabolism in C. difficile pathogenesis.


Survivors of bursal B cell production and emigration.
The bursa of Fabricius is the site of primary B cell generation in the chicken. Analysis of the rate of bursal cell emigration demonstrated that about 1% of the blood B cell pool was replaced per hour by bursal emigrants. Surgical bursectomy distinguished three populations of blood B cells. About 60% of blood B cells in 3-wk-old chickens were short lived, with a lifespan of 2 to 3 d, and included most bursal emigrants. These cells migrate directly from the bursal follicular cortex to the periphery, express the LT2 antigen, and are proposed to represent a diversified repertoire of B cell specificities that have emigrated from the bursa in the absence of interaction with environmentally derived antigens in the follicular medulla. About 35% of blood B cells were much longer lived cells, having a lifespan exceeding 2 wk. These cells represent about 10% of bursal emigrants, which do not express the LT2 antigen and do not divide in the peripheral blood following emigration from the bursa. This population may represent cells that have undergone positive selection in the bursa by interacting with environmentally derived antigens and should, therefore, contain a restricted repertoire of B cell specificities. The third population, about 5% of blood B cells, were short-lived cells that represent the progeny of postbursal B cell production. The frequency of these cells progressively increases with time, taking over from the short-lived bursal emigrants as the bursa involutes, likely as a diversified repertoire of B cell specificities.


Transcriptional responses and flavor volatiles biosynthesis in methyl jasmonate-treated tea leaves.
Tea (Camellia sinensis) has long been consumed worldwide for its amazing flavor and aroma. Methyl jasmonate (MeJA), which acts as an effective elicitor among the plant kingdom, could mostly improve the quality of tea aroma by promoting flavor volatiles in tea leaves. Although a variety of volatile secondary metabolites that contribute to aroma quality have been identified, our understanding of the biosynthetic pathways of these compounds has remained largely incomplete. Therefore, information aboaut the transcriptome of tea leaves and, specifically, details of any changes in gene expression in response to MeJA, is required for a better understanding of the biological mechanisms of MeJA-mediated volatiles biosynthesis. Moreover, MeJA treatment could exaggerate the responses of secondary metabolites and some gene expression which offer a better chance to figure out the mechanism. The results of two-dimensional gas-chromatograph mass-spectrometry showed that the terpenoids content in MeJA-treated tea leaves increased, especially linalool, geraniol, and phenylethyl alcohol. More importantly, we carried out RNA-seq to identify the differentially expressed genes (DEGs) related to volatiles biosynthesis pathways induced by MeJA treatment (0 h, 12 h, 24 h and 48 h) in tea leaves. We identified 19245, 18614, 11890 DEGs respectively in the MeJA_12h, MeJA_24 h and MeJA_48 h samples. The α-Lenolenic acid degradation pathway was firstly responded resulting in activating the JA-pathway inner tea leaves, and the MEP/DOXP pathway significantly exaggerated. Notably, the expression level of jasmonate O-methyltransferase, which is associated with the central JA biosynthesis pathway, was increased by 7.52-fold in MeJA_24 h tea leaves. Moreover, the genes related to the terpenoid backbone biosynthesis pathway showed different expression patterns compared with the untreated leaves. The expression levels of 1-deoxy-D-xylulose-phosphate synthase (DXS), all-trans-nonaprenyl-diphosphate synthase, geranylgeranyl reductase, geranylgeranyl diphosphate synthase (type II), hydroxymethylglutaryl-CoA reductase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase increased by approximately 2-4-fold. The results of two-dimension gas-chromatography mass-spectrometry analysis suggested that exogenous application of MeJA could induce the levels of volatile components in tea leaves, especially the geraniol, linalool and its oxides. Moreover, the transcriptome analysis showed increased expression of genes in α-Lenolenic acid degradation pathway which produced massive jasmonic acid and quickly activated holistic JA-pathway inner tea leaves, also the terpenoid backbones biosynthesis pathway was significantly affected after MeJA treatment. In general, MeJA could greatly activate secondary metabolism pathways, especially volatiles. The results will deeply increase our understanding of the volatile metabolites biosynthesis pathways of tea leaves in response to MeJA.


Women's decision making about whether or not to use breast cancer chemoprevention.
Minimal research is available that examines how women at high risk for breast cancer make choices about chemoprevention. We examined how women decide whether to use chemoprevention within the Study of Tamoxifen and Raloxifene (STAR), a non-placebo arm prevention trial. We used in-depth, semi-structured interviews and qualitative analysis. We interviewed 28 participants who chose to take chemoprevention and 23 STAR eligible women who declined participation and chemoprevention. Most participants perceived themselves at heightened risk for and anxious about developing breast cancer and believed taking either trial medication was a reasonable way to reduce risk. More than half of non-participants did not perceive themselves at heightened risk for and felt little anxiety about breast cancer. More than half of non-participants felt at greater risk for developing other diseases. While breast cancer risk can be calculated with a fair degree of accuracy, its impact on women's choices about chemoprevention is likely best assessed in tandem with women's feelings about developing breast cancer, whether within the context of a clinical trial or not.


Budesonide: safety and efficacy aspects of its long-term use in children.
Fifty-two asthmatic children aged 4 to 13 years (mean 9.6) were enrolled in this open 12-month study of budesonide, 200 mcg bid, administered by tube-spacer inhaler (INHALET, ASTRA DRACO). The aim of the study was to assess long-term safety, as well as efficacy, of budesonide in children whose asthma was not adequately controlled by their current therapy. Children attended the clinic every three months for assessment of lung function and height. In addition, an adrenal function test and routine clinical chemistry and haematology were performed. Parents completed diary cards once each week, recording the child's PEF, asthma symptoms, beta 2-agonist consumption and other medication (no prophylactic drugs or other inhaled steroids were allowed and oral steroids were used for emergency treatment only). There were significant increases in all clinic lung function tests (baseline to last visit) and in diary card PEF (first 3 months vs last 3 months). These were accompanied by decreases in asthma symptoms and use of beta 2-agonists or other medication. There was no indication that growth was affected by study treatment and basal adrenal function (basal cortisol) did not change significantly throughout the study. The adrenal response to Synacthen had actually increased significantly by the end of the study. No serious adverse events were associated with budesonide treatment. In conclusion, regular budesonide therapy was associated with a significant improvement in lung function and symptoms over one year. Budesonide was well-tolerated by the children and appeared to have no adverse influence on either growth or adrenal function.


[The first experience of TAPP and TEP allohernioplasty in patients with inguinal hernias at CRH].
To improve the outcomes in patients with inguinal hernias by application of advanced minimally invasive procedures. The article describes an experience of 59 laparoscopic allohernioplasties in 48 patients at the central regional hospital. There were bilateral hernias in 11 cases. Transabdominal preperitoneal (n=49) and extraperitoneal (n=10) placement of polypropylene mesh graft were used. Intraoperative complications such as sigmoid colon lesion occurred in 2 patients with sliding left-sided hernia. Mortality was absent. Mean hospital-stay was 5.4 days, 12-month examination after discharge did not show any recurrent hernias. Positive results of TAPP and TEP hernia repair justify their application as minimally invasive techniques in patients with various inguinal hernias at CRH if appropriate technical training and motivation of surgical team are present.


Probiotic Lactobacillus rhamnosus GG (LGG) and prebiotic prevent neonatal inflammation-induced visceral hypersensitivity in adult rats.
Increasing evidence indicates a positive effect of probiotics on the nervous system. The objective of this study was to determine if probiotic Lactobacillus rhamnosus GG (LGG) and/or prebiotics polydextrose/galactooligosaccharide (PDX/GOS) can alter the colonic sensitivity in a neonatal rat model of chronic visceral hyperalgesia and to determine whether altered sensitivity is associated with changes in neurotransmitter levels in the brain. Chronic visceral hyperalgesia was induced in rats by intracolonic administration of zymosan for 3 days during postnatal day 14-16 (P14-P16). After weaning (P21), these pups were divided into groups that received either (1) control diet (CD), (2) PDX/GOS, (3) LGG, or (4) PDX/GOS + LGG. These diets were continued until visceral sensitivity was tested at P60. The viscero-motor response (VMR) to graded colorectal distension (CRD) was determined by measuring the electromyographic (EMG) activity from the abdominal external oblique muscles. The levels of neurotransmitters and biogenic amines were quantified in the frontal cortex, subcortex, brain stem, and cerebellum. At P60, the VMR to CRD in the neonatal zymosan-treated rats was significantly higher than neonatal saline-treated rats. In contrast, neonatal zymosan-treated rats that received PDX/GOS or LGG did not exhibit visceral hyperalgesia. The levels of serotonin, noradrenaline, and dopamine were significantly altered in LGG-treated rats compared to other groups. Results document that in rats LGG can attenuate neonatally induced chronic visceral pain measured in adulthood. Prolonged intake of LGG alters some key brain neurotransmitters and biogenic amines that could be involved in pain modulation.


Relationship between thickness of fibrosis and epithelial dysplasia in oral submucous fibrosis.
Although oral submucous fibrosis is characterized by fibrosis of the subepithelial connective tissue, the overlying epithelial changes contribute to malignant transformation. Therefore, the aim of the study was to evaluate the relationship between thickness of fibrosis and epithelial changes in oral submucous fibrosis. The relationship between thickness of fibrosis and presence or absence of epithelial dysplasia was evaluated in 107 biopsies containing histopathologically-confirmed oral submucous fibrosis. The results were analyzed using Student's t-test or χ(2) -test. Fifty-seven percent (61/107) of oral submucous fibrosis lesions showed a non-dysplastic overlying epithelium, while 43% (46/107) showed varying degrees of epithelial dysplasia. The mean thickness of fibrosis of non-dysplastic lesions was 0.91±0.41 mm (mean ± standard deviation) and ranged from 0.25 to 1.9 mm. However, the mean thickness of fibrosis of dysplastic lesions was 1.17 ± 0.52 mm and ranged from 0.48 to 3 mm. The results revealed a significant increase in the incidence of epithelial dysplasia as the thickness of fibrosis increased (P = 0.004). As such, the lesions that showed increased fibrosis were more likely to present with epithelial dysplasia. The advancement of fibrosis increases the risk of development of epithelial dysplasia in oral submucous fibrosis.


MS-KIF18A, a kinesin, is associated with estrogen receptor.
The study of MS-KIF18A kinesin protein is focused on its cellular distribution and association with a cargo protein. Indirect immunofluorescence (IF) analyzed the intracellular distribution of endogenous MS-KIF18A and the transfected enhanced green fluorescence protein (eGFP)-MS-KIF18A in osteogenic cells. In both cases, the proteins were localized at the plasma membrane, cytosol, and nucleus. Bioinformatics analysis suggested interactions between MS-KIF18A and estrogen receptor (ERalpha) which were further elucidated by immunoprecipitation (IP). We identified interaction between endogenous MS-KIF18A with 66 and 46 kDa isoforms of ERalpha in MBA-15 cells. Moreover, MS-KIF18A and 66 kDa ERalpha complex has been demonstrated between ectopically expressed proteins in COS-7 cells. We have shown that anti-MS-KIF18A antibody immunoprecipitated the ERalpha and pERK in cells challenged with 17beta-estrogen (17beta-E2). The hormone activation induced mitogen-activated protein kinases (MAPK) pathway and increased p-ERK. The activation was interfered when cells were pre-treated with either ICI-182,780 or MAPK inhibitor PD98059 prior the challenge with 17beta-E2 that resulted in a decrease in association between MS-KIF18A and p-ERK1/2. The obtained results suggest a role for the proteins in a non-genomic response of MBA-15 cells challenged with 17beta-E2. This study presents a novel interaction between MS-KIF18A and ER that may have important physiological and pharmacological implications for estrogen action in various cells.


Plasticity in Adult Mouse Visual Cortex Following Optic Nerve Injury.
Optic nerve (ON) injury is an established model of axonal injury which results in retrograde degeneration and death of retinal ganglion cells as well anterograde loss of transmission and Wallerian degeneration of the injured axons. While the local impact of ON crush has been extensively documented we know comparatively little about the functional changes that occur in higher visual structures such as primary visual cortex (V1). We explored the extent of adult cortical plasticity using ON crush in aged mice. V1 function of the contralateral hemisphere was assessed longitudinally by intrinsic signal imaging and 2-photon calcium imaging before and after ON crush. Functional imaging demonstrated an immediate shift in V1 ocular dominance towards the ipsilateral, intact eye, due to the expected almost complete loss of responses to contralateral eye stimulation. Surprisingly, within 2 weeks we observed a delayed increase in ipsilateral eye responses. Additionally, spontaneous activity in V1 was reduced, similar to the lesion projection zone after retinal lesions. The observed changes in V1 activity indicate that severe ON injury in adulthood evokes cortical plasticity not only cross-modally but also within the visual cortex; this plasticity may be best compared with that seen after retinal lesions.


[Measles outbreaks in the Bern canton].
Currently, overall vaccination coverage against measles among infants ranges between 77% and 89% in Switzerland. Experience in other countries has shown that this level of vaccination is not sufficient to prevent measles outbreaks, especially among schoolchildren. During 1992 surveillance for measles outbreaks in closed populations was conducted in the Canton of Berne. Outbreaks were investigated for vaccine efficacy. Two measles outbreaks in schoolchildren were observed during the study period. In 2 Bernese suburban schools 6 measles cases in children (median age 12.5 years) occurred over a period of 37 days. One of the cases had been vaccinated. Vaccination rate in the healthy control children was 89.7%. Estimated vaccine efficacy was 97.7% (95% confidence interval [CI]: 68%, 99%). The second outbreak occurred in a rural region and comprised 21 measles cases (median age 7.5 years) within 43 days. 10 (47.6%) of the cases attended the same school. None of the cases had been vaccinated. Of the healthy control children 82.6% had received measles vaccine. Estimated vaccine efficacy was 100% (CI: 87%, 100%). These two measles outbreaks were due to failure to vaccinate rather than low vaccine efficacy. Surveillance for measles cases is currently not sufficient for the detection of measles outbreaks in our population. Laboratory confirmation of measles, especially in vaccinated persons, has become more important in a time of relatively low measles incidence.


Mitomycin C and bleomycin in the treatment of far-advanced cervical cancer: a Southwest Oncology Group pilot study.
Under the auspices of the Southwest Oncology Group, Wayne State University tested a schedule using bleomycin and mitomycin C that was previously reported to give a response rate of 88%. In our patients the same regimen produced similar toxic effects but a far different response rate of 15.8% (one complete remission and two partial remissions). The only discernible difference in the two patient groups was the amount of radiation given prior to chemotherapy.


A method for constructing case-mix indexes, with application to hospital length of stay.
This article presents the methodological development of an index for case-mix adjustment of hospital data exemplified by our construction of an index for studying length of stay. We describe the development and evaluation of this index, including internal and external validation procedures, and show an example of its use in a policy-relevant context by applying it to the analysis of length-of-stay differences between investor-owned and voluntary hospitals. Some advantages of this approach to adjusting for case mix are applicability to many hospital or patient output measurements/diagnostic scheme situations; usefulness in reducing heterogeneity in other case-mix adjustments, e.g., the Diagnosis-Related Group (DRG) approach; interpretation possibilities; production of a single score for each patient/hospital; statistical approach allowing more accurate and reliable interpretation of hospital and patient output measurements, ability to deal with hospital deaths; and consideration of the complete set of secondary diagnoses. We also suggest other possible uses of this approach.


Age-related changes in central effects of corticotropin-releasing factor (CRF) suggest a role for this mediator in aging anorexia and cachexia.
Hypothalamic corticotropin-releasing factor (CRF) lays downstream to catabolic melanocortins and at least partly mediates their catabolic effects. Age-related changes in the melanocortin system (weak responsiveness in middle-aged and a strong one in old rats) have been shown to contribute to middle-aged obesity and later to aging anorexia and cachexia of old age groups. We hypothesized that catabolic (anorexigenic and hypermetabolic) CRF effects vary with aging similarly to those of melanocortins. Thus, we aimed to test whether age-related variations of CRF effects may also contribute to middle-aged obesity and aging anorexia leading to weight loss of old age groups. Food intake, body weight, core temperature, heart rate, and activity were recorded in male Wistar rats of young, middle-aged, aging, and old age groups (from 3 to 24 months) during a 7-day intracerebroventricular CRF infusion (0.2 μg/μl/h) in a biotelemetric system. In addition, CRF gene expression was also assessed by quantitative RT-PCR in the paraventricular nucleus (PVN) of intact animals of the same age groups. The infusion suppressed body weight in the young, aging, and old rats, but not in middle-aged animals. Weak anorexigenic and hypermetabolic effects were detected in the young, whereas strong anorexia (without hypermetabolism) developed in the oldest age groups in which post mortem analysis showed also a reduction of retroperitoneal fat mass. CRF gene expression in the PVN increased with aging. Our results support the potential contribution of age-related changes in CRF effects to aging anorexia and cachexia. The role of the peptide in middle-aged obesity cannot be confirmed.


Health-related quality of life outcomes following adult cochlear implantation: A prospective cohort study.
The benefits of cochlear implantation extend beyond improved speech recognition and into overall health-related quality of life (HRQoL). Several measures of HRQoL, categorized as generic or disease specific, have been used in the cochlear implant literature. The clinical utility of generic HRQoL measures have been reported to be variable by previous investigators. The degree to which HRQoL correlates to speech perception is largely unknown. A prospective single-subject design at a large tertiary care center. Self-reported HRQoL was measured at the preoperative and 12-month post-activation test intervals. The measures of HRQoL included a generic form, (Medical Outcome Study Short Form; SF-36), and disease specific form (Nijmegen Cochlear Implant Questionnaire; NCIQ). Speech recognition was measured at the preoperative, 6- and 12-months post-activation test intervals using the Consonant-Nucleus-Consonant (CNC) monosyllabic word test. A total of 61 patients (mean 67 years; range 30-87 years) were included in the final analysis. Average speech recognition on the CNC word test was 10% pre-operatively, and 66.7% at 12-months post-activation. The HRQoL scores improved significantly for seven of the eight subdomains of the NCIQ, and one of the nine domains of the SF-36. Cochlear implantation significantly improves HRQoL, regardless of age. Disease specific measures, such as the NCIQ, are better able to demonstrate differences in HRQoL compared to general health surveys.


[The use of fibrin glue in the surgery of breast carcinoma].
Twenty-four patients operated on for breast carcinoma with associated axillary node dissection were randomly assigned to two protocols. In the first group fibrin glue was applied intraoperatively, in the second group no complementary treatment was accomplished. The aim of the study was to evaluate the effect of fibrin glue in reducing postoperative axillary sero-lymphatic secretion. In the fibrin glue group a significant reduction of postoperative axillary secretion was observed.


MicroRNA-206 Reduces Osteosarcoma Cell Malignancy In Vitro by Targeting the PAX3-MET Axis.
This study was undertaken to explore how miR-206 represses osteosarcoma (OS) development. Expression levels of miR-206, PAX3, and MET mRNA were explored in paired OS and adjacent tissue specimens. A patient-derived OS cell line was established. miR-206 overexpression and knockdown were achieved by lentiviral transduction. PAX3 and MET overexpression were achieved by plasmid transfection. Treatment with hepatocyte growth factor (HGF) was utilized to activate c-Met receptor. Associations between miR-206 and PAX3 or MET mRNA in OS cells were verified by AGO2-RNA immunoprecipitation assay and miRNA pulldown assay. OS cell malignancy was evaluated in vitro by cell proliferation, metastasis, and apoptosis assays. PAX3 and MET gene expression in OS cells was assayed by RT-qPCR and Western blot. Activation of PI3K-AKT and MAPK-ERK in OS cells were assayed by evaluating Akt1 Ser473 phosphorylation and total threonine phosphorylation of Erk1/2, respectively. Expression levels of miR-206 were significantly decreased in OS tissue specimens, compared to adjacent counterparts, and were inversely correlated with expression of PAX3 and MET mRNA. miR-206 directly interacted with PAX3 and MET mRNA in OS cells. miR-206 overexpression significantly reduced PAX3 and MET gene expression in OS cells in vitro, resulting in significant decreases in Akt1 and Erk1/2 activation, cell proliferation, and metastasis, as well as increases in cell apoptosis, while miR-206 knockdown showed the opposite effects. The effects of miR-206 overexpression on OS cells were reversed by PAX3 or MET overexpression, but only partially attenuated by HGF treatment. miR-206 reduces OS cell malignancy in vitro by targeting PAX3 and MET gene expression.


Potential for human immunodeficiency virus parenteral transmission in the Middle East and North Africa: an analysis using hepatitis C virus as a proxy biomarker.
The Middle East and North Africa (MENA) region has endured several major events of infection parenteral transmission. Recent work has established the utility of using hepatitis C virus (HCV) as a proxy biomarker for assessing the epidemic potential for human immunodeficiency virus (HIV) parenteral transmission. In this review, we use data on the prevalence of HCV infection antibody (seroprevalence) among general population and high risk population groups to assess the potential for HIV parenteral transmission in MENA. Relatively low prevalence of HCV infection in the general population groups was reported in most MENA countries indicating that parenteral HIV transmission at endemic levels does not appear to be a cause for concern. Nonetheless, there could be opportunities for localized HIV outbreaks and transmission of other blood-borne infections in some settings such as healthcare facilities. Though there have been steady improvements in safety measures related to parenteral modes of transmission in the region, these improvements have not been uniform across all countries. More precautions, including infection control training programs, surveillance systems for nosocomial infections and wider coverage and evaluation of hepatitis B virus immunization programs need to be implemented to avoid the unnecessary spread of HIV, HCV, and other blood-borne pathogens along the parenteral modes of transmission.


Longitudinal associations between psychedelic use and meditation practices in the United States and the United Kingdom.
Previous research has proposed that there may be potential synergies between psychedelic and meditation interventions, but there are still knowledge gaps that merit further investigation. Using a longitudinal observational research design with samples representative of the US and UK adult population with regard to sex, age, and ethnicity (N = 9732), we investigated potential associations between self-reported psychedelic use and meditation practice. The follow-up survey was completed by 7667 respondents (79% retention rate), with 100 respondents reporting psychedelic use during the 2-month study period (1.3% of follow-up respondents). In covariate-adjusted regression models, psychedelic use during the study period was associated with greater increases in the number of days of mindfulness meditation practice in the past week (B = 0.40, p = 0.004). Among those who reported psychedelic use during the study period, covariate-adjusted regression models revealed that the subjective experience of insight during respondents' most intense psychedelic experience in that period was also associated with greater increases in the number of days of mindfulness and loving-kindness or compassion meditation practice in the past week (B = 0.42, p = 0.021; B = 0.38, p = 0.017). Notably, more days of loving-kindness or compassion meditation practice in the past week at baseline was associated with less severe subjective feelings of death or dying during respondents' most intense psychedelic experience in the study period (B = -0.29, p = 0.037). Psychedelic use might lead to greater engagement with meditation practices such as mindfulness meditation, while meditation practices such as loving-kindness or compassion medication might buffer against certain challenging experiences associated with psychedelic use.


Design of an integration platform between the water-energy nexus and a business model applied for sustainable development.
Setting out an international standard schema for the water-energy-food (WEF) nexus and providing accurate data with realistic reports for investment through a simple application is essential for our real world. This research presents a tool to help anyone who wants to invest in environmental projects, especially water, energy, or food projects. The user can directly connect to a database of environmental data applying WEF nexus principles. This paper is looking for a mechanism to apply the WEF nexus concept through a web-based platform implementing unified concepts and terminology, setting basic criteria and standards, and making the data available, consistent, and homogeneous. Based on the problem statement, the purpose of this research is to implement a cross-application for sustainable development, including WEF nexus concepts, taking into consideration the interlinkage between the three resources integrated with a business model or financial study for projects. In addition, we have determined organizational perspectives of WEF nexus, including government entities, non-governmental organizations, and the private sector, and consolidated all the concepts into one set of WEF standards. Increasing the awareness of WEF nexus will help to establish a new generation of researchers who believe in the WEF nexus concepts and who will coordinate with developers and expert consultants to convert the WEF standards to programming coding.


The Macrolide Toxin Mycolactone Promotes Bim-Dependent Apoptosis in Buruli Ulcer through Inhibition of mTOR.
Mycolactone, the macrolide exotoxin produced by Mycobacterium ulcerans, is central to the pathogenesis of the chronic necrotizing skin disease Buruli ulcer (BU). Here we show that mycolactone acts as an inhibitor of the mechanistic Target of Rapamycin (mTOR) signaling pathway by interfering with the assembly of the two distinct mTOR protein complexes mTORC1 and mTORC2, which regulate different cellular processes. Inhibition of the assembly of the rictor containing mTORC2 complex by mycolactone prevents phosphorylation of the serine/threonine protein kinase Akt. The associated inactivation of Akt leads to the dephosphorylation and activation of the Akt-targeted transcription factor FoxO3. Subsequent up-regulation of the FoxO3 target gene BCL2L11 (Bim) increases expression of the pro-apoptotic regulator Bim, driving mycolactone treated mammalian cells into apoptosis. The central role of Bim-dependent apoptosis in BU pathogenesis deduced from our experiments with cultured mammalian cells was further verified in an experimental M. ulcerans infection model. As predicted by the model, M. ulcerans infected Bim knockout mice did not develop necrotic BU lesions with large clusters of extracellular bacteria, but were able to contain the mycobacterial multiplication. Our findings provide a new coherent and comprehensive concept of BU pathogenesis.


Identification of a putative RNA helicase (HRH1), a human homolog of yeast Prp22.
In the budding yeast Saccharomyces cerevisiae, a number of PRP genes known to be involved in pre-mRNA processing have been genetically identified and cloned. Three PRP genes (PRP2, PRP16, and PRP22) were shown to encode putative RNA helicases of the family of proteins with DEAH boxes. However, any such splicing factor containing the helicase motifs in vertebrates has not been identified. To identify human homologs of this family, we designed PCR primers corresponding to the highly conserved region of the DEAH box protein family and successfully amplified five cDNA fragments, using HeLa poly(A)+ RNA as a substrate. One fragment, designated HRH1 (human RNA helicase 1), is highly homologous to Prp22, which was previously shown to be involved in the release of spliced mRNAs from the spliceosomes. Expression of HRH1 in a S. cerevisiae prp22 mutant can partially rescue its temperature-sensitive phenotype. These results strongly suggest that HRH1 is a functional human homolog of the yeast Prp22 protein. Interestingly, HRH1 but not Prp22 contains an arginine- and serine-rich domain (RS domain) which is characteristic of some splicing factors, such as members of the SR protein family. We could show that HRH1 can interact in vitro and in the yeast two-hybrid system with members of the SR protein family through its RS domain. We speculate that HRH1 might be targeted to the spliceosome through this interaction.


Twenty-year evaluation of the New Jersey LCS Rotating Platform Knee Replacement.
Clinical results of the initial cemented and cementless series of 233 New Jersey Low Contact Stress Rotating Platform Knee Replacements in 184 patients surviving at least 10 years were analyzed using a strict knee scoring scale. The study showed excellent (46.7%) and good (53.3%) results in primary cemented rotating platform knee replacements, and excellent (68.1%), good (29.8%), and fair (2.1%) results in primary cementless rotating platform knee replacements. Radiographic evaluation at a minimum 10-year follow-up showed stable fixation of all components, no gross migration but significant osteolysis requiring bearing exchange, and bone grafting in three cementless rotating platform knee replacements (1.8%) in three patients who underwent previous surgeries at an average 10.2 years from the index surgery. Survivorship of the patients who underwent primary cemented rotating platform knee replacements with end points of revision for any mechanical reason or a poor clinical knee score was 97.7% at 10 and 20 years. Survivorship of the patients who underwent cementless rotating platform knee replacements with end points of revision for any mechanical reason or a poor clinical knee score was 98.3% at 10 and 18 years.


Influence of wing bands and behavior of Anastrepha fraterculus (Diptera: Tephritidae) by the presence of Megafreya sutrix (Araneae: Salticidae).
The objective of this study was to evaluate the influence of wing bands and the behavior of Anastrepha fraterculus in the presence of Megafreya sutrix. The first experiment used specimens of M. sutrix (n = 40), 20 males and 20 females of A. fraterculus and Musca domestica. The second experiment used 20 individuals of M. sutrix (10 males and 10 females) and 120 of A. fraterculus (20 males and 20 females) for each treatment. Marks were made on the wings of the flies: a group with painted wing bands (n = 40) with their wings fully painted; another with highlighted wing bands (n = 40) and normal bands (n = 40). Recordings were made for 15 min or until the fly was preyed upon. The analyses were performed through observation of the recordings and Chi-square test with Yates correction for continuity. The values found for predation of A. fraterculus were significant when compared to M. domestica when evaluating the predation factor, showing that, A. fraterculus is less predated than M. domestica. It was found that the wing patterns did not influence the predatory behavior of M. sutrix.


A human papillomavirus testing system in women with abnormal Pap results: a comparison study with follow-up biopsies.
To evaluate the efficacy of INFORM HPV using the SurePath collection method in women whose Pap tests indicated abnormal results. Ninety-two women from the gynecology clinics at The University of Texas M.D. Anderson Cancer Center who had Pap tests and underwent follow-up biopsies were selected for the study. This included 51 women with atypical squamous cells of undetermined significance (ASCUS), 23 women with low-grade squamous intraepithelial lesion (LSIL), 15 women with high-grade squamous intraepithelial lesion (HSIL) and 3 women with negative Pap results. The INFORM HPV, an in situ hybridization assay, testing for oncogenic types of HPV was performed, and the results were compared with follow-up biopsies. The positive rate of the INFORM HPV increased with higher grades of cytology diagnoses. The sensitivity of the INFORM HPV testing for predicting high-grade cervical intraepithelial neoplasia (CIN 2/3) also increased with higher grades of cytology diagnoses. A negative predictive value (NPV) of 94.9% and a specificity of 80.4% for predicting CIN 2/3 were observed in the ASCUS group. Using SurePath Pap specimens, the INFORM HPV lacks sufficient sensitivity and NPV for predicting CIN 2/3 in women with ASCUS. Therefore, use of the test as a triage tool is limited.


Early implementation of full-practice authority: A survey of Massachusetts nurse practitioners.
In January 2021, Massachusetts granted nurse practitioners (NPs) full-practice authority (FPA). Little is known about how FPA changes the day-to-day work of NPs. To examine changes in practice barriers and care delivery in the early stages of FPA. Descriptive analysis of a web-based survey of clinically active NPs in Massachusetts from October to December 2021, using Fisher exact tests to examine the associations between the perception that FPA improved work and other variables. Survey response rate was 50.3% ( N = 147). Overall, 79% of NPs believe that clinical work is unchanged by FPA. Practicing outside institutions is a significant predictor of FPA improving work ( p < .05). Larger proportions of respondents feel that efficiency (22%), patient centeredness (20%), and timeliness (20%) are improved by FPA compared with effectiveness (16%), equity (14%), and safety (10%). Almost half of those reporting that FPA improves overall care also report improved efficiency (50%, p < .0001), but only 22% report improved safety ( p < .05). Of those believing that FPA improved work, a minority no longer need physician review of new controlled substance prescriptions (29%, p < .01), a practice agreement (32%, p < .05), or physician signature on clinical documentation (22%, p < .05). Almost 1 year after FPA was passed in Massachusetts, the large majority of NPs report no changes in their day-to-day work, suggesting that FPA implementation is slow. Concerted efforts by regulators, employers, and individual NPs are needed to ensure that legislated FPA is effectively implemented inside organizations and among payers.


Multicultural competency in research: examining the relationships among multicultural competencies, research training and self-efficacy, and the multicultural environment.
Research on multicultural competencies has mainly focused on the practice dimension of psychology training and practice. Little theoretical or empirical research has examined multicultural research training and self-efficacy. In this study, 119 psychology graduate students filled out a Web survey focusing on the research training environment, research self-efficacy, multicultural competency, the multicultural environment, and social desirability. Results showed that multicultural competency, research training, and the multicultural environment were related to multicultural research self-efficacy. Hierarchical regressions showed that multicultural competency predicted students' research anxiety; social desirability predicted multicultural research utility, multicultural competency, and the research training environment; and multicultural competency predicted students' confidence in research and perceptions that their graduate training programs were multicultural. Implications are discussed.


One stage revision single-bundle anterior cruciate ligament reconstruction with impacted morselized bone graft following a failed double-bundle reconstruction.
Although double-bundle anterior cruciate ligament (ACL) reconstruction has theoretical benefits such as more accurate reproduction of ACL anatomy, it is technically more demanding surgery. This report describes the case of a one stage revision single-bundle ACL reconstruction after primary double-bundle ACL reconstruction. A professional dancer had an ACL previously reconstructed with a double-bundle technique, but the femoral tunnels were malpositioned resulting in residual laxity and rotational instability. The previous femoral tunnel positions were vertical and widened. The previous vertical tunnels were filled with impacted bone graft and a revision single-bundle ACL reconstruction was performed via the new femoral tunnel with a 2 O'clock position between the previous two tunnels. After 10 months of postoperative rehabilitation, the patient returned to professional dancing with sound bony union and without any residual instability.


Decreased beta-amyloid and increased abnormal Tau deposition in the brain of aged patients with leprosy.
We examined the brains of 37 leprosy patients (mean age, 76.3 +/- 7.8 years), 5 patients with Alzheimer-type dementia (mean age, 79.0 +/- 9.5 years), and 23 age-matched non-dementia controls (mean age, 77.6 +/- 5.4 years). The frequency of beta-amyloid (A beta)-positive cases was lower (27.0%) in leprosy patients (n = 37) than in controls (47.8%; P = 0.05, Z = 1.49). When senile plaque subtypes were examined, type III (classical) plaques were significantly fewer (P < 0.05) in leprosy subjects compared with controls. Interestingly, neurofibrillary tangles in the temporal cortex were much more frequent in leprosy patients than in controls (P < 0.05). However, hippocampal CA3 pyramidal neurons in leprosy patients were well preserved. These data indicate that 1) leprosy patients have a low risk of A beta deposition but a high risk of abnormal tau deposition, 2) abnormal tau deposition is unrelated to A beta deposition in leprosy, and 3) neuronal loss is unrelated to abnormal tau deposition. It is not clear at present whether the result is related to the disease process itself, antileprosy treatment, environmental factors, or the genetic background in leprosy patients.


The Human Virome: Implications for Clinical Practice in Transplantation Medicine.
Advances in DNA sequencing technology have provided an unprecedented opportunity to study the human virome. Transplant recipients and other immunocompromised hosts are at particular risk for developing virus-related pathology; thus, the impact of the virome on health and disease may be even more relevant in this population. Here, we discuss technical considerations in studying the human virome, the current literature on the virome in transplant recipients, and near-future applications of sequence-based findings that can further our understanding of viruses in transplantation medicine.


Synchronous Seminoma in Abdominopelvic and Inguinal Testes: A Rare Presentation with Unusual Morphology.
The development of testes occurs in the abdomen during fetal life, after which they migrate into the scrotal sacs during the third trimester. During their descent, they may get arrested anywhere along the tract. Risk of testicular cancer is higher in patients with undescended testes, abdominal testis being more prone than inguinal. Seminoma is the commonest cancer in undescended testis. However, synchronous seminoma involving bilateral cryptorchid testis is rare. Present case is uncommon due to synchronous involvement of abdominopelvic and inguinal testes in extended age. It also exhibited unusual morphology with marked heterogeneity grossly as well as microscopically, instead of a common homogenous appearance.


Physiological synchrony and shared flow state in Javanese gamelan: positively associated while improvising, but not for traditional performance.
The experience of shared flow refers to the optimal balance between challenge and ability for a given task, resulting from interpersonal action in a group situation. The performance of Javanese gamelan is an ideal setting to investigate shared flow, due to the requirement that all performers on varying instrumental parts work harmoniously, allowing for shared flow and its native equivalent, ngeli. To minimise the disruption of flow, while still measuring it continuously, one way to assess a person's state is by measuring physiological responses of the sympathetic (i.e., fight-or-flight) system, namely heart rate and skin conductance. Flow has been related to physiological signatures, and shared actions in music-making have been related to synchronised physiology. However, to our knowledge, no study yet has directly investigated the links between shared physiology and shared flow. Therefore, this study aimed to assess the associations between flow states, physiological synchrony, and Javanese gamelan playing. Subsequently, we tested for differences between advanced and beginner groups playing traditional gamelan pieces and improvising. Firstly, a factor analysis revealed a two-factor solution of Awareness and Absorption for self-reported shared flow. Next, using inter-subject correlation to assess synchrony and circular shuffling to infer significance, we found a greater proportion of significance in traditional playing compared to improvised playing for the experienced group, and the opposite for the beginner group. Lastly, linear mixed models revealed largely positive associations between synchronised physiology and shared flow during improvised playing, and negative associations during traditional playing, regardless of experience levels. This study demonstrates methodological possibilities for the quantitative study of shared flow in music-making contexts, and potential differences in shared flow experience in improvised and traditional, or prescribed, playing.


[Differential diagnosis and prognosis of primary and post-myocarditis cardiomyopathy in childhood].
It is still difficult to differentiate between the various stages of myocarditis and primary dilated cardiomyopathy (DCM). Hence, we analyzed the history, as well as the laboratory and virological data of 22 children with a dilated, poorly functioning left ventricle, aged 2 months to 16.7 years (m = 4.2 y), on whom we had performed endomyocardial biopsies about 4 months after the beginning of the illness. Specimens were investigated by light and electron microscopy and, in addition immunoserological (n = 15) and immunohistological investigations (n = 7) were performed. On the basis of cellular infiltration in the histological examination we diagnosed resolving/resolved myocarditis in 6 patients and DCM in 15 patients. Previous respiratory infection or sudden onset were found in 40-50% of patients in both groups. Antimyolemmal and antisarcolemmal antibodies showed no preference. Follow-up (3.1 +/- 2.8 years) of the patients showed equal mortality (33% vs. 38%) in the post-myocarditis and DCM group. Complete normalization of all findings in 3 patients of the DCM group makes the classification among the post-myocarditis group probable, which would, then give a lower mortality rate (22% vs. 46%) and a chance of restitution in 55% of cases. In any one specific case all the diagnostic methods do not allow undoubted distinction between both entities. The prognosis of myocarditis seems to be better than that of DCM in childhood.


Technological feasibility of the 2 fibers/cc asbestos standard in asbestos textile facilities.
The technical feasibility of developing dust control practice which would bring the asbestos industry into compliance with the OSHA I fibers/cc standard, scheduled to become effective July 1, 1976, has been questioned since its promulgation. This paper presents the results of industrial hygiene surveys, including the results of 243 asbestos air samples, conducted at two asbestos textile production facilities which have achieved the 2 fibers/cc standard. Both facilities use nonconventional production techniques. Conclusions drawn from the investigations express the need for: (1) a study of new products; (2) a tool to motivate consumers to switch to the new products when appropriate; and (3) legislation which will protect all domestic producers of asbestos textiles from certain producers who do not have to absorb the added expense of meeting the OSHA standard.


Patient Perspectives on the Cost of Hand Surgery.
Health-care expenditures in the U.S. are continually rising, prompting providers, patients, and payers to search for solutions to reduce costs while maintaining quality. The present study seeks to define the out-of-pocket price that patients undergoing hand surgery are willing to pay, and also queries the potential cost-cutting measures that patients are most and least comfortable with. We hypothesized that respondents would be less accepting of higher out-of-pocket costs. A survey was developed and distributed to paid, anonymous respondents through Amazon Mechanical Turk. The survey introduced 3 procedures: carpal tunnel release, cubital tunnel release, and open reduction and internal fixation of a distal radial fracture. Respondents were randomized to 1 of 5 out-of-pocket price options for each procedure and asked if they would pay that price. Respondents were then presented with various cost-saving methods and asked to select the options that made them most uncomfortable, even if those would save them out-of-pocket costs. There were 1,408 respondents with a mean age of 37 years (range, 18 to 74 years). Nearly 80% of respondents were willing to pay for all 3 of the procedures regardless of which price they were presented. Carpal tunnel release was the most price-sensitive, with rejection rates of 17% at the highest price ($3,000) and 6% at the lowest ($250). Open reduction and internal fixation was the least price-sensitive, with rejection rates of 11% and 6% at the highest and lowest price, respectively. The use of older-generation implants was the least acceptable cost-cutting measure, at 50% of respondents. The present study showed that most patients are willing to pay a considerable amount of money out of pocket for hand surgery after the condition, treatment, and outcomes are explained to them. Furthermore, respondents are hesitant to sacrifice advanced technology despite increased costs.


Can the Wild Perennial, Rhizomatous Rice Species Oryza longistaminata be a Candidate for De Novo Domestication?
As climate change intensifies, the development of resilient rice that can tolerate abiotic stresses is urgently needed. In nature, many wild plants have evolved a variety of mechanisms to protect themselves from environmental stresses. Wild relatives of rice may have abundant and virtually untapped genetic diversity and are an essential source of germplasm for the improvement of abiotic stress tolerance in cultivated rice. Unfortunately, the barriers of traditional breeding approaches, such as backcrossing and transgenesis, make it challenging and complex to transfer the underlying resilience traits between plants. However, de novo domestication via genome editing is a quick approach to produce rice with high yields from orphans or wild relatives. African wild rice, Oryza longistaminata, which is part of the AA-genome Oryza species has two types of propagation strategies viz. vegetative propagation via rhizome and seed propagation. It also shows tolerance to multiple types of abiotic stress, and therefore O. longistaminata is considered a key candidate of wild rice for heat, drought, and salinity tolerance, and it is also resistant to lodging. Importantly, O. longistaminata is perennial and propagates also via rhizomes both of which are traits that are highly valuable for the sustainable production of rice. Therefore, O. longistaminata may be a good candidate for de novo domestication through genome editing to obtain rice that is more climate resilient than modern elite cultivars of O. sativa.


Herpes simplex virus type 2-specific CD8 cytotoxic T lymphocyte cross-reactivity against prevalent HLA class I alleles.
Clonally expressed T-cell receptor alphabeta heterodimers are able to bind many different major histocompatibility complex/peptide combinations. This promiscuity is thought to be required for adequate surveillance against microbial and malignancy-associated antigens. After transplantation, T cells may react with nonself structures, contributing to graft-versus-host disease, in the case of hematopoietic stem cell transplantation, or graft failure, when the host immune system is preserved. We describe 2 distinct HLA A*0201-restricted, cytotoxic CD8 T-cell responses to the prevalent chronic pathogen, herpes simplex virus type 2, that cross-react with cells bearing specific alleles of the common HLA B44 family. Transfection of human or primate renal epithelial cells with HLA class I complementary DNA confirmed these results. Given the prevalence of this viral infection and the HLA alleles involved, it is possible that this cross-reactivity may be involved in clinically significant events.