[Laser biostimulation in the treatment of pleurisy].
Low-intensity lasers have been utilized in medicine in two ways: for local stimulation and for stimulation of acupuncture points. Literature data reveal that this method has been indiscriminately applied in psychiatry, rheumatology, gynecology, dermatology, otorhinolaryngology, in diverse acute and chronic pains, inflammations, vascular disorders, angina pectoris, bronchial asthma. Most commonly reported clinical effects are analgesia, spasmolytic and anti-inflammatory effects, as well as faster wound and bone healing. This prospective study analyses effects of laser biostimulation on patients with pleurisy. The analysis included 25 patients treated at the Institute of Lung Diseases in Sremska Kamenica during 2000, 2001 and 2002. Apart from conservative treatment, these patients were treated with laser biostimulation of acupuncture points and local region for ten days. During treatment, changes of present clinical signs, general symptoms, radiological findings, as well as changes of some relevant biochemical parameters were recorded. Results were compared with the control group which included the same number of patients, who differed from the examined group only by not being exposed to laser biostimulation. The examined group of patients with pleuritis presented with quicker resorption of pleural effusion, less pleural adhesions, more significant decrease of clinical symptoms, especially pain, as well as more significant increase of cortisol and immunoglobulin A and decrease of circulating immune complexes (CIC), leukocytes and sedimentation rate than the control group. Mechanisms of laser biostimulation in treatment of pleurisy were described in detail and the obtained results were correlated to those reported by other authors. 1. Patients with pleurisy undergoing laser stimulation presented with faster resorption of effusion and remission of the subjective symptoms, as well as significant decrease of biochemical acute inflammation parameters in the peripheral blood and therefore with faster recovery. 2. In patients with pleurisy laser treatment increases regenerative mechanisms of the pleural surface, thus decreasing the quantity of formed adhesions and resulting in better mobility of the diaphragm.


The effect of nucleotides on glutamate dehydrogenase from the mealworm fat body.
The effect of nucleotides: AMP, cAMP, ADP, ATP, GDP and GTP, on glutamate dehydrogenase (GDH) purified from the mealworm fat body was studied. Guanine nucleotides and ATP inhibited the enzyme strongly in both directions. GDH was partially protected from the inhibition by the addition of ADP to an assay medium. AMP and cAMP activated the enzyme slightly. The concerted effects of ADP and ATP indicate the importance of adenylate energy charge in the regulation of fat body GDH. It is suggested that GDH may play amphibolic role in the fat body and that the direction of GDH catalysed reaction is under strong influence of nucleotides. The enzyme may synthesize glutamate at high energy charge, but when the energy reserves are low, it oxidizes glutamate.


Patient-centered Engagement as a Mediator in the Associations of Healthcare Discrimination, Pain Care Denial, and Later Substance Use Among a Sample of Predominately African Americans Living with HIV.
Chronic pain is prevalent and often under-addressed among people with HIV and people who use drugs, likely compounding the stress of discrimination in healthcare, and self-medicating along with its associated overdose risk or other problematic coping. Due to challenges in treating pain and HIV in the context of substance use, collaborative, patient-centered patient-provider engagement (PCE) may be particularly important for mitigating the impact of pain on illicit drug use and promoting sustained recovery. We examined whether PCE with primary care provider (PCE-PCP) mediated the effects of pain, discrimination, and denial of prescription pain medication on later substance use for pain among a sample of 331 predominately African Americans with HIV and a drug use history in Baltimore, Maryland, USA. Baseline pain level was directly associated with a higher chance of substance use for pain at 12 months (Standardized Coefficient = 0.26, p < .01). Indirect paths were observed from baseline healthcare discrimination (Standardized Coefficient = 0.05, 95% CI=[0.01, 0.13]) and pain medication denial (Standardized Coefficient = 0.06, 95% CI=[0.01, 0.14]) to a higher chance of substance use for pain at 12 months. Effects of prior discrimination and pain medication denial on later self-medication were mediated through worse PCE-PCP at 6 months. Results underscore the importance of PCE interpersonal skills and integrative care models in addressing mistreatment in healthcare and substance use in this population. An integrated approach for treating pain and substance use disorders concurrently with HIV and other comorbidities is much needed. Interventions should target individuals at multiple risks of discriminations and healthcare professionals to promote PCE.


Evolutionary selection pressure and family relationships among connexin genes.
We suggest an extension of connexin orthology relationships across the major vertebrate lineages. We first show that the conserved domains of mammalian connexins (encoding the N-terminus, four transmembrane domains and two extracellular loops) are subjected to a considerably more strict selection pressure than the full-length sequences or the variable domains (the intracellular loop and C-terminal tail). Therefore, the conserved domains are more useful for the study of family relationships over larger evolutionary distances. The conserved domains of connexins were collected from chicken, Xenopus tropicalis, zebrafish, pufferfish, green spotted pufferfish, Ciona intestinalis and Halocynthia pyriformis (two tunicates). A total of 305 connexin sequences were included in this analysis. Phylogenetic trees were constructed, from which the orthologies and the presumed evolutionary relationships between the sequences were deduced. The tunicate connexins studied had the closest, but still distant, relationships to vertebrate connexin 36, 39.2, 43.4, 45 and 47. The main structure in the connexin family known from mammals pre-dates the divergence of bony fishes, but some additional losses and gains of connexin sequences have occurred in the evolutionary lineages of subsequent vertebrates. Thus, the connexin gene family probably originated in the early evolution of chordates, and underwent major restructuring with regard to gene and subfamily structures (including the number of genes in each subfamily) during early vertebrate evolution.


Suckling mouse model for detection of heat-stable Escherichia coli enterotoxin: characteristics of the model.
Although the suckling mouse assay is widely used for the detection of heat-stable Escherichia coli enterotoxin (ST), few data have been published concerning the reproducibility, optimal growth, and test conditions of this assay. Four strains of toxigenic E. coli known to elaborate both heat-labile enterotoxin and ST or ST alone were used to study these parameters. ST activity after heat treatment and the effect of purified choleragen were also examined. ST production was optimal in Casamino Acids-yeast extract media, but both Trypticase soy and brain heart infusion broths resulted in several false negative reactions. Growing cultures in roller tubes was the most reliable method of ST production. Shaking-flask cultures and stationary-grown cultures resulted in suboptimal ST production in several strains. Optimal mouse incubation time was 3 h, and fluid secretion did not rise thereafter. Adequate toxin production occurred after 16 to 24 h of incubation. The coefficient of variation of various toxins tested on many occasions varied between 10.5 and 15.7%. Toxin activity was stable for 6 months when frozen at - 20 C. There was no decrease in ST activity when heated at 65 C for 15 min, but a small decrease was observed in two of four strains after heating at 100 C for 30 min. Choleragen, tested at various doses and at multiple times, gave uniformly negative results. These studies indicate that when done under the proper conditions, the suckling mouse assay is a simple, rapid, and reproducible assay for E. coli ST.


Risk sensitivity as an evolutionary adaptation.
Risk aversion is a common behavior universal to humans and animals alike. Economists have traditionally defined risk preferences by the curvature of the utility function. Psychologists and behavioral economists also make use of concepts such as loss aversion and probability weighting to model risk aversion. Neurophysiological evidence suggests that loss aversion has its origins in relatively ancient neural circuitries (e.g., ventral striatum). Could there thus be an evolutionary origin to risk aversion? We study this question by evolving strategies that adapt to play the equivalent mean payoff gamble. We hypothesize that risk aversion in this gamble is beneficial as an adaptation to living in small groups, and find that a preference for risk averse strategies only evolves in small populations of less than 1,000 individuals, or in populations segmented into groups of 150 individuals or fewer - numbers thought to be comparable to what humans encountered in the past. We observe that risk aversion only evolves when the gamble is a rare event that has a large impact on the individual's fitness. As such, we suggest that rare, high-risk, high-payoff events such as mating and mate competition could have driven the evolution of risk averse behavior in humans living in small groups.


The G to A polymorphism at -597 of the interleukin-6 gene is extremely rare in southern Han Chinese.
Interleukin-6 (IL-6) is a cytokine involved in different physiologic and pathophysiologic processes including essential hypertension (EH). Associations of the IL-6 promoter region polymorphisms with circulating level of IL-6 have been reported in various studies. We detected the IL-6-597G/A polymorphism in 246 EH patients and 194 healthy controls from Jiangsu area (south of China). Individuals all carried the GG wild genotype, no GA or AA genotypes were found. Our results suggest that IL-6-597G/A polymorphism is extremely rare and unlikely to be contributing significantly to disease susceptibility in southern Han Chinese.


Protein conformational modulation by photons: a mechanism for laser treatment effects.
Responsiveness to low-level laser treatment (LLTT) at a wavelength of 450-910 nm has established it as an effective treatment of medical, veterinary and dental chronic pain, chronic inflammation conditions (arthritis and macular degeneration), wound repair, and lymphoedema, yet the mechanisms underlying the effectiveness of LLLT remain unclear. However, there is now sufficient evidence from recent research to propose an integrated model of LLLT action. The hypothesis presented in this paper is that external applications of photons (through laser at an appropriate dose) modulates the nervous system through an integrated mechanism. This stimulated mechanism involves protein-to-protein interaction, where two or more proteins bind together to facilitate molecular processes, including modification of proteins by members of SUMO (small ubiquitin-related modifier proteins) and also protein phosphorylation and tyrosination. SUMO has been shown to have a role in multiple nuclear and perinuclear targets, including ion channels, and in the maintenance of telomeres and the post-translational modification of genes. The consequence of laser application in treatment, therefore, can be seen as influencing the transmission of neural information via an integrated and rapid modulation of ion channels, achieved through both direct action on photo-acceptors (such as cytochrome c-oxidase) and through indirect modulation via enzymes, including tyrosine hydroxylase (TH), tyrosine kinases and tyrosine kinase receptors. This exogenous action then facilitates an existing photonic biomodulation mechanism within the body, and initiates ion channel modulation both in the periphery and the central nervous system (CNS). Evidence indicates that the ion channel modulation functions predominately through the potassium channels, including two pore leak channels (K2P), which act as signal integrators from the periphery to the cortex. Photonic action also transforms SUMOylation processes at the cell membrane, nucleus and telomeres via signalling processes from the mitochondria (which is the main target of laser absorption) to these targets. Under the hypothesis, these observed biological effects would play a part in the bystander effect, the abscopal effect, and other systemic effects observed with the application of low level laser (LLLT). The implications of the hypothesis are important in that they point to mechanisms that can account for the effectiveness of laser in the treatment and prevention of inflammatory diseases, chronic pain and neurodegenerative disorders.


PET/CT and histopathologic response to preoperative chemoradiation therapy in locally advanced rectal cancer.
The objective of this study was to investigate the possibility of using positron emission tomography/computer tomography to predict the histopathologic response in locally advanced rectal cancer treated with preoperative chemoradiation. The study included 30 patients with locally advanced rectal adenocarcinoma treated with a combination of radiotherapy and concurrent Uftoral (uracil, tegafur) and leucovorine. All patients were evaluated by positron emission tomography/computer tomography scan seven weeks after end of chemoradiation, and the results were compared to histopathologic tumor regression as the "standard." The pathologic response was quantified by tumor regression grade. Positron emission tomography/computer tomography correctly identified six of eight patients (specificity 75 percent) with complete pathologic response. However, the sensitivity of positron emission tomography/computer tomography was only 45 percent and the accuracy 53 percent. The positive and negative predictive values were 83 and 33 percent, respectively. We conclude that positron emission tomography/computer tomography performed seven weeks after the end of chemoradiation is not able to predict the histopathologic response in locally advanced rectal cancer. There is an obvious need for other complementary methods especially with respect to the low sensitivity of positron emission tomography/computer tomography.


Periodontal considerations for provisional restorations.
Provisional restorations can cause alterations of tooth form, surface continuity, and the relationship of the restored tooth to the adjacent and opposing teeth as well as the periodontal tissues. As the integrity of the periodontium is of mutual interest to both the periodontist and the restorative dentist, it is important that the potential damage caused by restorative procedures and materials be avoided. Ideally, the provisional restoration should be considered an acrylic progenitor of the final restoration in all aspects except the material from which it is fabricated, its longevity, and the nuances of color and translucency. It should not be replaced by the permanent restoration until all treatment objectives have been accomplished. In an integrated multidisciplinary approach to dental care, it is logical that periodontal treatment precede final restorative procedures. The establishment and maintenance of periodontal health is clearly predicated on an intact dentogingival unit and shallow sulcular dimensions that allow accessibility for removal of plaque. Provisional restorations, whether single or multiple, must conform to and complement the healthy gingival environment if periodontal health is to be sustained. Direct and frequent communication between the periodontist and restorative dentist is a prerequisite for predictable and satisfactory results.


[Sarcoidosis of the tongue. Apropos a case].
Here we present the case of a patient with lesion on the tongue, during more than 6 months, which in its self required different therapeutic measures and because of a benign evolution is remitted to this center for study, which concluded with an histological diagnosis of sarcoidosis, a granulomatous disease systemic in character which in this patient only affect the tongue which reminds us daily the necessity to remember this entity by internist, gastroenterologists and dentists.


Comparison of broad beam central axis depth dose curves from different accelerators using the universal depth dose curve model.
Electron beam central axis depth dose distribution can be transformed to fluence distributions with geometric depth replaced by a measure of the state of angular dispersion of the beam. A transformed central axis depth dose distribution was called a 'fluence curve.' The transformation was applied to a set of central axis depth dose curves calculated by Monte Carlo code for broad electron beams of energies ranging from 1 to 60 MeV in homogeneous phantoms of water, aluminium, and copper. For the energies and compositions likely to be encountered in external beam radiation therapy, the resulting fluence curves, were found to belong to a single parameter family. A collimator scatter parameter was introduced to take into account the initial angular dispersion produced by the collimator of an accelerator. Given the energy of the beam, the medium in which the beam is passing through, and the collimator scatter parameter, the fluence curve associated with the beam can easily be transformed back to a calculated depth dose curve. The collimator scatter parameter necessary to fit the depth dose curves measured on different accelerators was investigated. The results for the Clinac 18, LMR-13, Mevatron XII, Mevatron 80, Microtron, Sagittaire, Siemens Betatron, and the Therac 20 are presented.


Localization of a gene for familial recurrent arthritis.
To localize the gene for familial recurrent arthritis via a genome-wide linkage scan in an extended kindred with the disease. A 3-generation family in which 9 members were diagnosed with juvenile idiopathic arthritis (JIA) was ascertained. In this family the disease was of very early onset and included episodic inflammation leading to eventual destruction of joints, muscle, and skin. We treated this disorder as a distinct clinical entity that we have named "familial recurrent arthritis." A genome-wide linkage scan with polymorphic microsatellites at 10-15-cM resolution was initiated. The genome-wide scan generated a maximum 2-point logarithm of odds score with D15S211 (Zmax = 3.27 at thetamax = 0.0010). Haplotype reconstruction defined a candidate region of approximately 20 cM flanked proximally by D15S983 and distally by D15S127 on human chromosome 15. A gene for familial recurrent arthritis was localized to 15q22-24, as a result of a genome-wide linkage scan in a large, multiply affected kindred. Identification of the altered gene will provide insights into the pathogenesis of autoimmune joint destruction that is reminiscent of JIA.


[The use of laser-assisted scanning confocal microscopy for the detection of foreign particles in internal organ tissues].
The objective of this study was to evaluate the possibility and effectiveness of using laser-assisted scanning confocal microscopy for the detection of foreign particles in internal organ tissues for the purpose of forensic medical diagnosis of fatal cases of acute and chronic drug intoxication. Lung tissue samples stained with hematoxylin and eosin exhibited autofluorescent foreign particles localized in vascular lumen. Microphotographs and autofluorescence spectral profiles of the examined tissues are presented.


[New diagnostic and neuroendocrine approaches to the borderline syndrome].
The recent literature reflects a growing interest in Borderline Disorders. This paper summarizes the recent developments on nosological, genetical and biological aspects of the Borderline syndrome. Original neuroendocrine results from our group are presented and discussed. They suggest that an endogenomorphic depressive spectrum may be associated with the Borderline personality disorders.


Dissolution kinetics of soluble nondisintegrating disks.
An equation describing the isotropical dissolution of soluble nondisintegrating disks was developed. It was equivalent to the cube root law only if the height and diameter of the disk were equal. The dissolution kinetics of sodium chloride disks were examined, using a beaker equipped with a centrifugal stirrer as the dissolution chamber. The fit of the experimental data to the cube root law had a coefficient of variation of about 4-5%. It was demonstrated statistically that a fit to a square root of mass versus time relation was significantly better. With increasing porosity, the dissolution process proceeded faster than predicted on the basis of the diffusion-convection model. An explanation is proposed by assuming an increased effective dissolution surface.


Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias.
In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance. The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years). At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up. At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.


Dietary inflammatory index, risk of incident hypertension, and effect modification from BMI.
Previous studies have identified a positive association between the inflammatory potential of the diet and hypertension. It is not known if BMI is an effect modifier for this association, nor if the association is dose-respondent. This study aimed to assess the association between the dietary inflammatory index (DII) and the risk of hypertension, and assess any effect modification from BMI. Data from the E3N cohort study, a French prospective population-based study initiated in 1990 was used. From the women in the study, we included those who completed a detailed diet history questionnaire, and who did not have prevalent hypertension or cardiovascular disease at baseline, resulting in 46,652 women. The adapted DII was assessed with data from the dietary questionnaire. Hypertension cases were self-reported and verified through a drug-reimbursement database. Cox proportional hazard models were used to calculate hazard ratios. Spline regression was used to determine any dose-respondent relationship. During 884,267 person-years, 13,183 cases of incident hypertension were identified. The median DII in the population was slightly pro-inflammatory (DII = + 0.44). A highly pro-inflammatory diet (DII > 3.0) was associated with a slight increase in hypertension risk (HRQ1-Q5 = 1.07 [1.02, 1.13]). Evidence was observed for effect modification from BMI, with associations strongest amongst women in the 18.5-21.0 BMI range (HRQ1-Q5 = 1.17 [1.06, 1.29]). A weak dose-respondent relationship was observed. Evidence for a weak association between DII and hypertension was observed. Associations were stronger amongst healthy-lean women.


Effect of Artificial Aging on Mechanical and Tribological Properties of CAD/CAM Composite Materials Used in Dentistry.
With easy-to-process 3D printing materials and fast production, the quality of dental services can be improved. In the conventional procedure, the dentist makes temporary crowns directly in the patient's mouth, e.g., from the most commonly used bis-acrylic composites. Temporary crowns made directly in the office without the use of CAD/CAM are often of inferior quality, which directly results in impaired hygiene, poorer masticatory mechanics, greater deposition of plaque, calculus and sediment, and may adversely affect periodontal and gum health. The mechanical strength, resistance to aging and abrasion of 3D printing materials are higher than those of the soft materials used in conventional methods. This translates into durability. The patient leaves the surgery with a restoration of higher utility quality compared to the conventional method. The objective of the paper was to determine the influence of aging in artificial saliva of AM (additive manufacturing) orthodontic composites on their functional properties. For the purpose of the study, fillings well-known worldwide were selected. These were traditional UV-curable resins (M I, M II, M III, M V) and a hybrid material based on a UV-curable resin (M VI). Samples were stored in artificial saliva at 37 ± 1 °C in a thermal chamber for 6 months. Indentation hardness, frictional tests and sliding wear measurements were conducted. A comparison between various materials was made. Descriptive statistics, degradation coefficients, H2E, Archard wear and specific wear rate were calculated. The Weibull statistical test for indentation hardness was performed and Hertzian contact stresses for the frictional association were calculated for unaged (M I, M II, M III, M V, M VI) and aged (M I AS, M II AS, M III AS, M V AS, M VI AS) samples. M I exhibited the lowest average hardness among the unaged materials, while M III AS had the lowest average hardness among the aged materials. Comparably low hardness was demonstrated by the M I AS material. The coefficient of friction values for the aged samples were found to be higher. The lowest wear value was demonstrated by the M I material. The wear resistance of most of the tested materials deteriorated after aging. The M VI AS material had the highest increase in wear. According to the results provided, not only the chemical composition and structure, but also aging have a great impact on the indentation hardness and wear resistance of the tested orthodontic materials.


Familial aggregation of medial arterial calcification in Pima Indians with and without diabetes.
Little is known about medial arterial calcification (MAC) other than its association with age, sex, diabetes, and diabetes complications. Familial aggregation of this disorder was studied to determine the importance of potential genetic factors and to assess whether such familial aggregation was independent of that of diabetes. Members of 1,256 Pima Indian nuclear families with 3,339 offspring were examined radiologically for MAC of the feet. Multiple logistic regression analyses were used to compare the presence of the disorder in a parent with the presence of MAC in an offspring and to determine whether familial aggregation of MAC was independent of parental diabetes. Controlled for age, sex, diabetes, serum cholesterol, and blood pressure, offspring of one parent with MAC had 3.3 (95% CI 1.5-7.6) times the odds of MAC as did offspring of parents without MAC, and offspring with both parents affected had an even higher risk (odds ratio, 8.1; 95% CI 3.4-18.8). Controlled for offspring age and sex and for parental age and diabetes, parental MAC was associated with the disorder in offspring (P < 0.001), but the effect of parental diabetes on MAC in the offspring was not significant when controlled for parental MAC (P = 0.36). Furthermore, offspring of nondiabetic parents with MAC, controlled for age, sex, diabetes, and diabetes duration, had 1.7 (95% CI 0.9-3.1) times the odds of MAC than did offspring of diabetic parents with MAC. Independent of parental age and diabetes and offspring age, sex, diabetes, and diabetes complications, parental MAC confers an increased risk of MAC in offspring. These findings suggest that the factors responsible for the familial clustering of MAC may be different from those for diabetes.


Physiological Strain in French Vineyard Workers Wearing Protective Equipment to Conduct Re-Entry Tasks in Humid Conditions.
The proper use of personal protective equipment (PPE) plays an important role in reducing exposure to pesticides in vineyard farming activities, including re-entry tasks. However, discomfort from clothing systems may increase the physiological burden on workers. We compared the physiological burdens of vineyard workers wearing three different types of PPE during canopy management in field humid conditions while accounting for occupational, climatic, and geographical environments. The study was conducted in the Bordeaux vineyards of southern France during June 2012. A total of 42 workers from seven vineyards consented to field observations. The following PPE garments were randomly allocated: HF Estufa polyamide (Brisa®), Tyvek® Classic Plus, and Tychem® C Standard. Participant sociodemographic characteristics were collected using a structured questionnaire. Skin temperature and heart rate were monitored continuously using portable devices. Multivariate multilevel linear regression models were performed to account for the hierarchical structure of data. No significant difference was found for mean skin temperature during work. Regardless of the cardiac strain parameter considered, the Tyvek® Classic Plus garment produced the poorest results (P ≤ 0.03). Under the very humid conditions encountered during the field study, the thinness and breathability of the Tyvek® Classic Plus garment resulted in undergarment humidity, imposing additional physiological burden on vineyard workers. These results confirm that the idea of using generic coveralls in any farming activity is unsuitable. Compromises should be created between physiological costs and protection, depending on the agricultural task performed, the crop grown, and the environmental conditions encountered.


Dual crosslinked pectin-alginate network as sustained release hydrophilic matrix for repaglinide.
Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes.


Nutrition in oncology: the case of micronutrients (review).
In the course of cancer disease, many oncological patients develop tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients. The inadequate nutritional status and the cancer anorexia-cachexia syndrome related to it are clinically relevant, as the response to antineoplastic measures, such as radiation and chemotherapy, is diminished, their side effects aggravated and the patient's quality of life and prognosis negatively affected. Therefore, the supportive nutrition care of oncological patients is of central importance. In this context, vitamins, minerals and long-chain omega -3 fatty acids are becoming more and more relevant in oncology although the benefit of such supplements is discussed controversially. Starting from a description of the etiopathogenesis and the pathophysiological consequences of cancer-associated malnutrition, the present study provides an overview of the importance of micronutrients for oncological patients. In the case of reduced food intake and/or inappropriate food choice the use of a multi-vitamin-multimineral supplement administered in physiological doses, i.e. nutrient quantities approximately corresponding to the recommended daily allowances, can be generally recommended. However, to enhance postoperative wound healing, it seems that cancer patients require higher amounts of micronutrients than healthy individuals. Because vitamin D deficiency is highly prevalent in oncological patients, improvement of vitamin D status is of special interest.


Validation of reference genes for the normalization of RT-qPCR expression studies on human laryngeal cancer and hypopharyngeal cancer.
Selecting stably expressed reference genes is crucial for evaluating real-time quantitative polymerase chain reaction (RT-qPCR) data via the relative quantification method. In the present-day study, our aim was to select optimal reference genes (RGs) for the investigation of target gene (TG) expression profiling in cancerous human laryngeal and hypopharyngeal tissues. 12 cancerous laryngeal tissues and 10 cancerous hypopharyngeal tissues were investigated. The expression characteristics of 11 reference genes (18S rRNA, GAPDH, B2M, ACTB, TBP, ALAS1, RPL29, HMBS, HPRT1, GUSB, and PUM1), which were commonly used in RT-qPCR for the analysis of gene expression, were investigated using the geNorm, NormFinder, and BestKeeper algorithm programs. HMBS, ALAS1, and B2M were suggested as optimal RGs for studying human laryngeal and hypopharyngeal cancerous tissues together, laryngeal cancerous tissue by itself, and hypopharyngeal cancerous tissue by itself, respectively. If 2 or more reference genes are needed to achieve better standardization, 3 reference genes can optimally be used in combination to improve the accuracy of relative quantitation normalization. The recommended combinations for studying human laryngeal and hypopharyngeal cancerous tissues together, laryngeal cancerous tissue by itself, and hypopharyngeal cancerous tissue by itself were HMBS + HPRT1 + GUSB, ALAS1 + GUSB + HMBS, and B2M + HPRT1 + TBP, respectively. The recommended reference genes could be used to improve the accuracy of gene expression studies on the molecular mechanisms of cancerous human laryngeal and hypopharyngeal tissues. The selected combination of reference genes can effectively improve the accuracy of the relative quantitative diagnosis of gene expression levels, such as messenger RNA, circular RNA, and long-noncoding RNA.


Phonetics and phonology of thematic contrast in German.
It is acknowledged that contrast plays an important role in understanding discourse and information structure. While it is commonly assumed that contrast can be marked by intonation only, our understanding of the intonational realization of contrast is limited. For German there is mainly introspective evidence that the rising theme accent (or topic accent) is realized differently when signaling contrast than when not. In this article, the acoustic basis for the reported impressionistic differences is investigated in terms of the scaling (height) and alignment (positioning) of tonal targets. Subjects read target sentences in a contrastive and a noncontrastive context (Experiment 1). Prosodic annotation revealed that thematic accents were not realized with different accent types in the two contexts but acoustic comparison showed that themes in contrastive context exhibited a higher and later peak. The alignment and scaling of accents can hence be controlled in a linguistically meaningful way, which has implications for intonational phonology. In Experiment 2, nonlinguists' perception of a subset of the production data was assessed. They had to choose whether, in a contrastive context, the presumed contrastive or noncontrastive realization of a sentence was more appropriate. For some sentence pairs only, subjects had a clear preference. For Experiment 3, a group of linguists annotated the thematic accents of the contrastive and noncontrastive versions of the same data as used in Experiment 2. There was considerable disagreement in labels, but different accent types were consistently used when the two versions differed strongly in F0 excursion. Although themes in contrastive contexts were clearly produced differently than themes in noncontrastive contexts, this difference is not easily perceived or annotated.


Reactivity of human labial glands in response to cevimeline treatment.
Among the pathologies affecting the salivary glands, the Sjögren's syndrome (SS), an autoimmune disease, causes progressive destruction of the glandular tissue. The effect of SS is particularly evident on the labial glands and the morphological analysis of these minor glands is considered useful for diagnosis. Cevimeline hydrochloride (SNI), a selective muscarinic agonist drug, is one of the elective treatments for the hyposalivation due to SS, acting not only on major salivary glands, but also on labial glands since their secretion is primarily under parasympathetic control. Aim of this study is to describe the morphology of human labial glands treated with SNI by light, transmission, and high-resolution scanning electron microscopy. Moreover, a morphometric analysis was applied to the light and transmission electron microscopy micrographs to obtain data that were then compared with analogous data collected on control and carbachol-treated labial glands. Following SNI administration, the mucous tubules exhibited enlarged lumina, which were filled with a dense mucous secretion. Occasionally, small broken debris of the cells were retrieved into the lumen. In the mucous secretory cells, some mucous droplets fused to form a large vacuole-like structure. Similarly, the seromucous acini showed both dilated lumina and canaliculi. These above reported signs of secretion were confirmed through morphometric analysis and a milder action of SNI than carbachol on labial parenchyma was observed. This study confirmed that SNI also evoked secretion on labial glands and that its effect is more physiologic than that of the pan-muscarinic agonists.


[Successful caspofungin treatment of invasive refractory candidiasis in the extremely low birthweight neonate].
Multiresistant Candida septicaemia is an increasing problem in Neonatal Intensive Care Units worldwide. Caspofungin is a new antifungal drug licensed in Portugal for use in children since September 2008, with limited experience in newborns. Preterm female, 26 weeks gestational age, born by vaginal delivery, with 780g birthweight and Apgar score 8/9. The newborn developed a mucocutaneous candidiasis at day 8 of life which was treated with oral nystatin and topic clotrimazol. Clinical and laboratory deterioration occurred at day 15 of life with Candida albicans sepsis being diagnosed. Therapy with amphotericin B liposome was started but the clinical condition and candidemia persisted. Treatment with caspofungin was initiated at day 28 of life and continued for 28 days. There was an improvement of the clinical condition and the blood cultures became negative. The child was discharged at the 80th of life with no evident clinical problems. The long term follow-up revealed bilateral deafness. This case reveals that caspofungin may be a useful choice for invasive refractory candidiasis in the neonate, especially in the extremely low birthweight neonate and in life-threatening situations. Long term follow-up is of great importance in order to document adverse effects not apparent at the neonatal period.


Geographic Differences in Temporal Incidence Trends of Hepatitis C Virus Infection Among People Who Inject Drugs: The InC3 Collaboration.
We determined temporal trends (1985-2011) in hepatitis C virus (HCV) incidence and associated behavioral exposures for people who inject drugs (PWID) from the United States (Boston, Baltimore, and San Francisco), Canada (Montreal), the Netherlands (Amsterdam), and Australia (Sydney and Melbourne). Using population-based cohort data from HCV-negative PWID, we calculated overall and within-city HCV incidence trends, HCV rates by study enrollment period (1985-2011), and temporal trends in exposure behaviors. Poisson regression models estimated trends in HCV incidence over calendar-time. Survival models identified risk factors for HCV incidence across cities and estimated independent effects of city and calendar period on HCV infection risk. Among 1391 initially HCV-negative participants followed prospectively (1644.5 person-years of observation [PYO]), 371 HCV incident infections resulted in an overall incidence of 22.6 per 100 PYO (95% confidence interval [CI], 20.4-25.0). Incidence was highest and remained elevated in Baltimore (32.6/100 PYO), San Francisco (24.7/100 PYO), and Montreal (23.5/100 PYO), lowest in Melbourne and Amsterdam (7.5/100 PYO and 13.1/100 PYO, respectively), and moderate (21.4/100 PYO) in Sydney. Higher rates of syringe and equipment sharing and lower prevalence of opioid agonist therapy were associated with HCV incidence in cities with the highest incidence. Risk for infection dropped by 18% for every 3-year increase in calendar-time (adjusted hazard ratio, 0.8 [95% CI, .8-.9]) in the multivariable model. Differences in prevention strategies and injecting contexts may explain the ongoing high HCV incidence in these North American cities and emphasize the need for scale-up of opioid agonist therapy and increased coverage of needle and syringe programs in North America.


An investigation of the Venetian blind effect.
When a rectangular wave grating is binocularly viewed with a neutral density filter over one eye, an illusory rotation resembling that of a partially opened Venetian blind is perceived (Cibis and Haber, 1951). Using a binary classification task, in the first experiment, the probability of perceiving a rotation in a given direction was measured as a function of a factorial combination of inter-ocular contrast (see Note 1) and luminance ratios. The probability of a rotation in a given direction decreased monotonically with the luminance of the brighter bars when the grating contains a less than unity contrast. This result is inconsistent with (i) the model of the Venetian blind effect proposed by Cibis and Haber (1951), (ii) a mechanism based on irradiation with a compressive non-linearity (von Helmholtz, 1911/1924, pp. 186-193) and (iii) contemporary stereo-energy/cross-correlation models of stereopsis. In the second and third experiments, we tested the prediction that irradiation combined with an early compressive non-linearity in response implies a positive relationship between both the threshold contrast or average luminance disparity to perceive rotation and the magnitude of perceived rotation, and the blur width at the bar's edge. No support was found for the prediction. We propose an intensity difference model of the probability of perceiving a rotation in a given direction as a function of the interocular difference in luminance or contrast.


Characterization of surfaces involved in adherence of Legionella pneumophila to Fischerella species.
Legionella pneumophila adheres to the slime coat of Fischerella spp. This was shown by microscopic examination and by a decline in L. pneumophila CFU in samples removed from coincubation mixtures of both organisms. Binding of partially purified Fischerella slime by L. pneumophila was most efficient by young, less hydrophobic L. pneumophila cells than by older, more hydrophobic cells. Uptake of crystal violet and partitioning into hexadecane were used to measure hydrophobicity of L. pneumophila. Purified soluble Legionella antigen also bound to Fischerella slime, as shown by indirect immunofluorescence. Adherence was not specific for L. pneumophila, since a variety of gram-negative, gram-positive, and acid-fast bacteria also bound to Fischerella slime.


Dinuclear manganese(iii) complexes with bioinspired coordination and variable linkers showing weak exchange effects: a synthetic, structural, spectroscopic and computation study.
Three dimanganese(iii) complexes have been synthesised and fully characterised by standard spectroscopic methods and spectroelectrochemistry. Each MnIII ion is chelated by a salen type ligand (H2L), but there is variation in the bridging group: LMn(OOCCH[double bond, length as m-dash]CHCOO)MnL, LMn(OOCC6H4COO)MnL, and LMn(OOCC6H4C6H4COO)MnL. X-ray diffraction revealed an axial compression of each six-coordinate high-spin d4 MnIII ion, which is a Jahn-Teller-active ion. Temperature dependent magnetic susceptibility and variable temperature-variable field (VTVH) magnetisation measurements, as well as high-frequency and -field EPR (HFEPR) spectroscopy were used to accurately describe the magnetic properties of the complexes, not only the single-ion spin Hamiltonian parameters: g-values and zero-field splitting (ZFS) parameters D and E, but also the exchange interaction constant J between the two ions, which has been seldom determined for a di-MnIII complex, particularly when there is more than a single bridging atom. Quantum chemical calculations reproduced well the electronic and geometric structure of these unusual complexes, and, in particular, their electronic absorption spectra along with the spin Hamiltonian and exchange parameters.


A double-blind, dose-response study of the efficacy and safety of olmesartan medoxomil in children and adolescents with hypertension.
The current study investigated the efficacy and safety of olmesartan medoxomil in children with hypertension, defined as systolic blood pressure measured at or above the 95th percentile (90th percentile for patients with diabetes, glomerular kidney disease, or family history of hypertension) for age, gender, and height while off any antihypertensive medication. The active treatment phase was conducted in 2 periods, with 2 cohorts in each period (cohort A, 62% white; cohort B, 100% Black). In period 1, patients stratified by weight received low-dose (2.5 or 5 mg) or high-dose (20 or 40 mg) olmesartan medoxomil daily for 3 weeks. In period 2, patients maintained their olmesartan medoxomil dose or initiated placebo washout for an additional 2 weeks. Period 1 efficacy results showed a dose-dependent, statistically significant reduction in seated trough systolic and diastolic blood pressure for both cohorts, with mean blood pressure reductions numerically smaller in cohort B than in cohort A. The olmesartan medoxomil dose response remained statistically significant when adjusted for body weight. In period 2, blood pressure control decreased in those patients switching to placebo, whereas patients continuing to receive olmesartan medoxomil therapy maintained consistent blood pressure reduction. Adverse events were generally mild and unrelated to study medication. Olmesartan medoxomil was safe and efficacious in children with hypertension, resulting in significant blood pressure reductions.


The 340b Program, Contract Pharmacies, Hospitals, and Patients: An Evolving Relationship Impacting Health Care Delivery.
The 340B Drug Pricing Program, created by Congress in 1992 through the Veterans Health Care Act, has provided discounted drug prices to hospitals and other health care organizations serving a wide population of low-income patients. Some 340B programs use contract pharmacies, an arrangement whereby the hospital or health care organization signs a contract directly with a pharmacy to provide covered pharmacy services at discounted prices. The federal 340B Drug Pricing Program has provided access to reduced price prescription drugs to more than 35 000 individual health care facilities and sites certified by the US Department of Health and Human Services, and clinics have served more than 10 million people in all 50 states, plus commonwealths and US territories. The 340B program has increased profits for hospitals through contract pharmacies because they have still received the same reimbursement but acquired drugs at a lower rate.


European pig genetic diversity: a minireview.
An evaluation of the European pig diversity has been carried on by several countries, with the support of the European Union over the period of 1994 to 2000. This article presents an overview of the results of this investigation, focussing on two genetic marker techniques, namely microsatellites (MS) and amplification of fragment length polymorphism (AFLP). Nearly 200 loci were characterised on about 50 individuals from each of 59 to 71 breeds, according to the marker considered. The analysis of diversity, based on genetic distances, led to similar conclusions for the two marker types (MS and AFLP), in spite of a markedly lower total diversity of AFLP compared to MS. The analysis of the MS loci showed that the allelic diversity pattern among breeds was quasi-independent from the diversity pattern based on allele frequencies. Genetic distances showed no particular clustering of local with international breeds, confirming the genetic uniqueness of the European local breeds compared to mainstream international breeds. The taxonomy of the local breeds revealed a cluster of the Iberian type breeds, in contrast with a wider dispersal of the breeds from other countries. Phylogeny often disagreed with documented breeds' history, showing the complex migration/admixture patterns which underlie the breeds' relationships. Methodologies developed in this investigation as well as the database and the DNA depository created should provide support for further innovative research in the field of domestic animal diversity management.


Reduced sodium concentration and increased sodium-potassium pump activity of erythrocytes in human hypertension.
Erythrocyte Nai, Nai/Ki and ouabain-sensitive and ouabain-insensitive 86Rb uptake (K transport) were measured in whole blood of 16 normotensive and 19 hypertensive white male subjects, within seconds or minutes after withdrawal of blood. Erythrocyte Nai and Nai/Ki were reduced (p less than 0.05), and ouabain-sensitive 86Rb uptake was increased (p less than 0.01) in hypertensive subjects. In a separate group of hypertensive white male subjects, an inverse correlation was found between erythrocyte Nai/Ki and ouabain-binding sites per erythrocyte (r = 0.85, p less than 0.01, n = 9). The abnormalities of erythrocyte cation fluxes in hypertensive subjects are similar to those induced by aldosterone in vascular smooth muscle cells and by glucocorticoid administration in the erythrocytes of human subjects, suggesting similarities in pathogenesis.


Screening Guidelines for Thyroid Function in Children With Alopecia Areata.
The incidence of thyroid disease in children with alopecia areata (AA) has been widely studied with no consensus on whether a true association with AA exists. In addition, screening practices for thyroid dysfunction in children with AA vary widely among clinicians. To reduce health care costs, eliminate unnecessary testing, and standardize clinical practices, we sought to characterize thyroid function in children with AA to establish guidelines for screening. A single-site retrospective medical chart review was carried out in an outpatient pediatric dermatology clinic in a tertiary referral medical center between January 1, 2008 and January 1, 2016. The study included 298 patients (ages 0-21 years) who received a clinical diagnosis of AA and underwent thyroid function tests. Age at diagnosis of AA, duration of disease, severity, location, and type were documented. Past medical history and family medical history of patients were also recorded. Results of laboratory tests including thyrotropin (formerly thyroid-stimulating hormone [TSH]), free T4 (FT4), triiodothyronine (T3), thyroid peroxidase antibodies (TPO-Abs), and thyroglobulin antibodies (Tg-Abs). During the 8-year period, 298 patients with AA had thyroid function screening. Of those with thyroid screening, patterns of AA included patchy (68%), ophiasis (13%), totalis (9%), and universalis (10%). Severity was determined by percentage of hair loss on the scalp and were divided into mild (30.2%), moderate (32.9%), and severe (36.9%). A total of 59 (20%) patients had abnormalities on thyroid testing results. In this group of patients, hypothyroidism was the most frequent finding 29 (49%), with Hashimoto thyroiditis being the most common cause(24 [41%]). Other abnormalities included hyperthyroidism secondary to Grave disease (12 [20%]) and subclinical thyroid dysfunction (7 [12%]). Whereas age, duration of disease, pattern of alopecia, and diagnosis of autoimmune diseases had no significant association with abnormal thyroid findings, a personal history of Down syndrome (P = .004), atopy (P = .009), and family history of thyroid disease (P = .001) did. We recommend that routine thyroid function screening should be restricted to AA patients with a medical history of Down syndrome, personal history of atopy, a family history of thyroid disease, or clinical findings (goiter) suggestive of potential thyroid dysfunction in the individual patient.


A dose-response analysis of skin cancer from inorganic arsenic in drinking water.
A study of the prevalence of skin cancer among 40,421 persons consuming arsenic-contaminated drinking water in Taiwan was used for a cancer dose-response assessment of ingested arsenic. The numbers of persons at risk over three dose intervals and four exposure durations were estimated from the data in order to apply the method of maximum likelihood to a multistage-Weibull time/dose-response model. A constant exposure level since birth for each of the exposure categories was assumed. It was found that the cumulative hazard increases as a power of three in age, and is linear or quadratic (with a linear coefficient) in dose. Observations from a smaller epidemiologic survey in Mexico were similar to what would be predicted from the model of the Taiwan data. Assuming that the skin cancer risk from ingested arsenic in the American population would also be similar to the Taiwan population, an American male would have a lifetime risk of developing skin cancer of 1.3 x 10(-3) (3.0 x 10(-3] if exposed to 1 microgram/kg/day for a 76-year lifespan (median lifespan in the U.S.).


Flattened chains dominate the adsorption dynamics of loosely adsorbed chains on modified planar substrates.
Herein, the adsorption of polystyrene (PS) on phenyl-modified SiO2-Si substrates was investigated. Different from those for PS adsorption on a neat SiO2-Si substrate, the growth rate (vads) in the linear regime and hads/Rg (hads, thickness of flattened and loosely adsorbed layers on the substrate; Rg, radius of gyration) declined with increasing molecular weight (Mw) of PS and the phenyl content on the modified substrates, while the thickness of the flattened layer (hflat) and its coverage increased with increasing phenyl content. The results indicated that the adsorption of loose chains was controlled by the adsorption of flattened chains, as it only occurred in the empty contact sites remaining after the adsorption of flattened chains. Before approaching quasi-equilibrium (t < tcross), the number of flattened chain contact sites increased due to an enthalpically favorable process and, correspondingly, their spatial positions dynamically changed, which perturbed the adsorption of loose chains. When the adsorption of flattened chains reached quasi-equilibrium (t > tcross), the adsorption of loose chains was determined by the empty contact sites. The coverage of flattened chains and time to reach quasi-equilibrium were increased with more phenyl groups on the substrate, enhancing π-π interfacial interactions and resulting in a decreased adsorption rate and fewer loosely adsorbed chains. Mw-dependent vads and hads/Rg differed on phenyl-modified substrates compared to the neat SiO2-Si substrate owing to fewer empty contact sites for loose chains. The study findings improve our understanding of the mechanism responsible for the formation and structure of the adsorbed layer on solid surfaces.


IB2d: a Python and MATLAB implementation of the immersed boundary method.
The development of fluid-structure interaction (FSI) software involves trade-offs between ease of use, generality, performance, and cost. Typically there are large learning curves when using low-level software to model the interaction of an elastic structure immersed in a uniform density fluid. Many existing codes are not publicly available, and the commercial software that exists usually requires expensive licenses and may not be as robust or allow the necessary flexibility that in house codes can provide. We present an open source immersed boundary software package, IB2d, with full implementations in both MATLAB and Python, that is capable of running a vast range of biomechanics models and is accessible to scientists who have experience in high-level programming environments. IB2d contains multiple options for constructing material properties of the fiber structure, as well as the advection-diffusion of a chemical gradient, muscle mechanics models, and artificial forcing to drive boundaries with a preferred motion.


Differences in Spontaneous Interactions of Autistic Children in an Interaction With an Adult and Humanoid Robot.
Robots are promising tools for promoting engagement of autistic children in interventions and thereby increasing the amount of learning opportunities. However, designing deliberate robot behavior aimed at engaging autistic children remains challenging. Our current understanding of what interactions with a robot, or facilitated by a robot, are particularly motivating to autistic children is limited to qualitative reports with small sample sizes. Translating insights from these reports to design is difficult due to the large individual differences among autistic children in their needs, interests, and abilities. To address these issues, we conducted a descriptive study and report on an analysis of how 31 autistic children spontaneously interacted with a humanoid robot and an adult within the context of a robot-assisted intervention, as well as which individual characteristics were associated with the observed interactions. For this analysis, we used video recordings of autistic children engaged in a robot-assisted intervention that were recorded as part of the DE-ENIGMA database. The results showed that the autistic children frequently engaged in exploratory and functional interactions with the robot spontaneously, as well as in interactions with the adult that were elicited by the robot. In particular, we observed autistic children frequently initiating interactions aimed at making the robot do a certain action. Autistic children with stronger language ability, social functioning, and fewer autism spectrum-related symptoms, initiated more functional interactions with the robot and more robot-elicited interactions with the adult. We conclude that the children's individual characteristics, in particular the child's language ability, can be indicative of which types of interaction they are more likely to find interesting. Taking these into account for the design of deliberate robot behavior, coupled with providing more autonomy over the robot's behavior to the autistic children, appears promising for promoting engagement and facilitating more learning opportunities.


Activated androgen receptor downregulates E-cadherin gene expression and promotes tumor metastasis.
The loss of E-cadherin gene expression can cause the dysfunction of the cell-cell junction to trigger tumor metastasis. Members of the Snail family of transcription factors are repressors of the expression of the E-cadherin gene. In this study, we showed that the activated androgen receptor (AR) is a novel repressor of E-cadherin gene expression and can promote metastasis. Our results demonstrated that the activated AR could bind to the E-cadherin promoter in vitro and in vivo. The activated AR and HDAC1 had synergistic effects in downregulating E-cadherin gene expression. Treating cells with the AR ligand, dihydrotestosterone (DHT), triggered the reduction of E-cadherin expression and induced changes in cell morphology from an epithelial-like to a mesenchymal-like appearance. When nonmetastatic breast cancer cells expressing cytoplasmic AR were transplanted into mice and the mice were treated with DHT, tumors were detected at metastatic sites, whereas no tumors were detected in transplanted mice without DHT treatment. Furthermore, clinical data from breast cancer patients with invasive ductal carcinomas showed high levels of AR expression in the nuclei and low levels of E-cadherin expression. These results suggest that, similarly to Snail and Twist, the activated AR can downregulate E-cadherin expression to promote the activation of epithelial-mesenchymal transition and tumor metastasis.


Molecular and systems mechanisms of memory consolidation and storage.
Until recently, memory consolidation and storage had been traditionally viewed as a permissive process derived from learning-activated molecular signaling cascades which include activations of the NMDA receptors, CaMKII, PKC, PKA and other kinases, new protein synthesis and CREB-mediated gene expression, and subsequent structural modifications at certain synapses. However, the time-scale of such a cascade is incompatible with the timescale of systems-level memory consolidation. Furthermore, increasing evidence suggests that synaptic proteins and structures are not stationary, but rather are highly dynamical and subjected to metabolic turnovers which would cause drift in synaptic efficacy and subsequently unstable neural circuits. Recent experiments using inducible gene- or protein-knockout techniques reveal that post-learning NMDA receptor and CaMKII reactivations are required for the systems-level consolidation of both hippocampal-dependent and hippocampal-independent memories. Furthermore, the reactivations of the NMDA receptors are also necessary for the long-term storage of old memories in the neural circuits. Therefore, the NMDA receptor reactivation-mediated synaptic reentry reinforcement (SRR) process may represent the unifying cellular mechanism in linking the consolidation and storage of long-term memories from the molecular level to the systems-level.


p38 mitogen-activated protein kinase is activated and linked to TNF-alpha signaling in inflammatory bowel disease.
Inflammatory bowel diseases (IBD)--Crohn's disease and ulcerative colitis--are relapsing chronic inflammatory disorders which involve genetic, immunological, and environmental factors. The regulation of TNF-alpha, a key mediator in the inflammatory process in IBD, is interconnected with mitogen-activated protein kinase pathways. The aim of this study was to characterize the activity and expression of the four p38 subtypes (p38alpha-delta), c-Jun N-terminal kinases (JNKs), and the extracellular signal-regulated kinases (ERK)1/2 in the inflamed intestinal mucosa. Western blot analysis revealed that p38alpha, JNKs, and ERK1/2 were significantly activated in IBD, with p38alpha showing the most pronounced increase in kinase activity. Protein expression of p38 and JNK was only moderately altered in IBD patients compared with normal controls, whereas ERK1/2 protein was significantly down-regulated. Immunohistochemical analysis of inflamed mucosal biopsies localized the main expression of p38alpha to lamina propria macrophages and neutrophils. ELISA screening of the supernatants of Crohn's disease mucosal biopsy cultures showed that incubation with the p38 inhibitor SB 203580 significantly reduced secretion of TNF-alpha. In vivo inhibition of TNF-alpha by a single infusion of anti-TNF-alpha Ab (infliximab) resulted in a highly significant transient increase of p38alpha activity during the first 48 h after infusion. A significant infliximab-dependent p38alpha activation was also observed in THP-1 myelomonocytic cells. In human monocytes, infliximab enhanced TNF-alpha gene expression, which could be inhibited by SB 203580. In conclusion, p38alpha signaling is involved in the pathophysiology of IBD.


Mycoparasitic species of Sphaerellopsis, and allied lichenicolous and other genera.
Species of Sphaerellopsis (sexual morph Eudarluca) are well-known cosmopolitan mycoparasites occurring on a wide range of rusts. Although their potential role as biocontrol agents has received some attention, the molecular phylogeny of the genus has never been resolved. Based on morphology and DNA sequence data of the large subunit nuclear ribosomal RNA gene (LSU, 28S) and the internal transcribed spacers (ITS) and 5.8S rRNA gene of the nrDNA operon, the genus Sphaerellopsis is shown to belong to Leptosphaeriaceae in Dothideomycetes. Sphaerellopsis is circumscribed, and the sexually typified generic name Eudarluca treated as a synonym on the basis that Sphaerellopsis is more commonly used in literature, is the older generic name, and is the morph commonly encountered by plant pathologists in the field. A neotype is designated for Sphaerellopsis filum, and two new species are introduced, S. macroconidialis and S. paraphysata spp. nov. Species previously incorrectly placed in Sphaerellopsis are allocated to Neosphaerellopsis gen. nov. as N. thailandica, and to the genus Acrocalymma, as A. fici. The genus Rhizopycnis is nestled among species of Acrocalymma, and reduced to synonymy based on its morphology and DNA phylogeny, while Acrocalymmaceae is introduced as novel family to accommodate members of this genus in the Dothideomycetes. Furthermore, Sphaerellopsis proved to be phylogenetically closely allied to a lichenicolous complex of phoma-like taxa, for which the new genera Diederichomyces and Xenophoma are established. Several new combinations are introduced, namely D. xanthomendozae, D. ficuzzae, D. caloplacae, D. cladoniicola, D. foliaceiphila, and X. puncteliae combs. nov, while Paraphaeosphaeria parmeliae sp. nov. is newly described.


When is a "free" registrar in clinic not free?
To investigate whether using registrars (doctors undergoing higher specialist training, whose salary is reimbursed) rather than consultants in outpatient clinics saves money Development of a formula calculating the economic breakeven point and application to retrospective audit data from 273 outpatient consultations. General cardiology outpatient clinic in a secondary and tertiary referral NHS hospital. Outcomes Difference in probability of a registrar and a consultant making a diagnostic decision that completes a clinical episode. Use of UK costings for consultant salaries and outpatient attendances to determine the economic breakeven point. The formula showed that if a registrar's episode completing probability is 12 percentage points lower than that of a consultant, then using a registrar costs the hospital more. Real life data showed that episode completion probabilities are 43 percentage points lower for registrars than for consultants (26% versus 69%, 95% CI 32% to 54%, P<0.0001). It is wrong to assume that external reimbursement of registrar salaries makes them a money saving option for staffing clinics. The apparent service role of a registrar can be a disservice.


A Case of Myocarditis Presenting With a Hyperechoic Nodule After the First Dose of COVID-19 mRNA Vaccine.
Myocarditis and/or pericarditis have been reported as adverse events following coronavirus disease 2019 (COVID-19) messenger RNA vaccination, with most cases occurring within 1 week after the second dose. We report a rare case of myocarditis after the first dose of the BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine in a 17-year-old boy. Here, we describe the laboratory, electrocardiographic, and imaging findings of myocarditis.


Age, growth, and energy storage of the subterranean fish Triplophysa rosa (Cypriniformes: Nemacheilidae) from Chongqing, China.
This study explores the age, growth, and energy storage of Triplophysa rosa, a troglobitic cavefish. A total of 102 wild T. rosa specimens were collected in Wulong County, Chongqing, China, between 2018 and 2022, with otoliths used for age determination. The earliest mature individuals were determined to be 4.8 years old, while the maximum ages for females and males were estimated at 15.8 years and 12.2 years, respectively. The length (L, cm)-weight (W, g) relationship was found to be the same for both sexes, following the eq. W = 0.0046 L3.03. Von Bertalanffy growth models were applied to the total length-at-age data, resulting in an asymptotic length of 23.4 cm and a K-parameter of 0.060 year-1. The body content of protein, ash, and glycogen did not show a significant correlation with the total length of T. rosa. However, both lipid and energy content exhibited a significant increase with total length. The lipid content ranged from 40.5 to 167.1 mg g-1, while the energy content ranged from 4.50 to 11.39 kJ g-1, indicating high storage features of T. rosa. The results affirm that T. rosa exhibits life traits conducive to its population dynamics in cave conditions, characterized by slow growth, small size, and high lipid energy storage.


Short-term results of physiotherapy in patients with newly diagnosed degenerative cervical spine disease.
Degenerative cervical spine diseases are common, and physiotherapy is widely used as an initial form of treatment. We aimed to analyse the effects of the initial sessions of physiotherapy for patients who were newly diagnosed with degenerative cervical spine disorders. A prospective series of 30 patients with newly diagnosed degenerative cervical spine disease were referred to our department and followed up for the initial two sessions of physiotherapy. The patients were assessed after each session. Outcome parameters studied included pain using a visual analogue scale (VAS), neck range of movements and activities of daily living (ADL). Our study subjects comprised mainly females (60%) in their fifties (46.7%) who worked as clerks or secretaries (53.3%). There was an improvement in the patients' pain score (VAS) from a median of 8 to 4 after two visits to the physiotherapists. Slight improvement in the neck range of movements was also observed. Marked improvement was seen in ADL, especially in the ability to carry heavy objects. Physiotherapy is an effective initial option for patients with newly presented degenerative cervical spine disease. The results of this study can be used to advise patients on the short-term benefits of physiotherapy.


Histopathologic diagnosis of endometrial precancers: Updates and future directions.
Early detection of endometrial cancer, especially its precancers, remains a critical and evolving issue in patient management and the quest to decrease mortality due to endometrial cancer. Due to many factors such as specimen fragmentation, the confounding influence of endogenous or exogenous hormones, and variable or overlapping histologic features, identification of bona fide endometrial precancers and their reliable discrimination from benign mimics remains one of the most challenging areas in diagnostic pathology. At the same time, the diagnosis of endometrial precancer, or the presence of suspicious but subdiagnostic features in an endometrial biopsy, can lead to long clinical follow-up with multiple patient visits and serial endometrial sampling, emphasizing the need for accurate diagnosis. Our understanding of endometrial precancers and their diagnosis has improved due to systematic investigations into morphologic criteria, the molecular genetics of endometrial cancer and their precursors, the validation of novel biomarkers and their use in panels, and more recent methods such digital image analysis. Although precancers for both endometrioid and non-endometrioid carcinomas will be reviewed, emphasis will be placed on the former. We review these advances and their relevance to the histopathologic diagnosis of endometrial precancers, and the recently updated 2020 World Health Organization (WHO) Classification of Female Genital Tumors.


New approach to an old problem: Incorporating signal from gap-rich regions of ITS and rDNA large subunit into phylogenetic analyses to resolve the Peltigera canina species complex.
The Peltigera canina species complex consists of foliose lichenized bitunicate ascohymenial discomycetes forming section Peltigera within the genus Peltigera (Lecanoromycetes, lichen-forming Ascomycetes). To test the circumscription of highly polymorphic species and to resolve relationships among putative members of the P. canina complex, part of the nuclear ribosomal DNA large subunit (LSU rDNA) and the entire internal-transcribed spacer (ITS rDNA) were sequenced for 84 individuals representing 33 putative Peltigera taxa. Seventeen of the 25 taxa from the P. canina complex are well established and widely accepted. The remaining eight taxa have been proposed recently but are undescribed. A hypervariable region in ITS1 (ITS1-HR, sites 111-237 in our alignment) showed remarkable variation in length, especially in the P. canina complex, ranging from 8 to 126 bp, and contained several microsatellites. We describe here an alignment-free method to code such large gap-rich hypervariable regions for phylogenetic analyses. Variation among ITS1-HR sequences greatly contributed to species delimitation and species identification and can be a major asset to future population studies for specific species within section Peltigera. Sequences of ITS1-HR alone were sufficient to identify all existing species of Peltigera from the P. canina species complex and related sections Retifoveatae and Horizontales included in this study. However, only when INAASE (for short ambiguously aligned regions) and ITS1-HR coded characters were added to the combined analysis of nonambiguous LSU and ITS sites was it possible to reach the level of phylogenetic resolution and support necessary to disentangle the P. canina complex. We report here complete concordance between phylogenetically based and morphologically based species delimitation for 15 of the 17 species from the P. canina complex (P. canina, P. cinnamomea, P. degenii, P. evansiana, P. frigida, P. kristinssonii, P. laciniata, P. lambinonii, P. lepidophora, P. membranacea, P. monticola, P. ponojensis, P. praetextata, P. rufescens and P. ulcerata). Four of the eight newly proposed but undescribed taxa most likely represent new species (P. "fuscopraetextata", P. "neocanina", P. "neorufescens" and P. "scotteri") within the P. canina complex. We found that morphologically and chemically distinct P. didactyla s. str. and P. didactyla var. extenuata form two non-sister monophyletic entities, therefore the latter taxon should be recognized at the species level (P. extenuata). The North American and European populations of the morphologically uniform P. degenii might represent two sibling species because they were found to be genetically distinct and monophyletic. Two major monophyletic groups within the P. canina complex (CICADE = CInnamomea + CAnina + DEgenii group and PORUDI = POnojensis + RUfescens + DIdactyla group) seem to be correlated with different humidity preferences. Although some authors previously have suggested interspecies recombination within the P. canina complex, we did not find statistically significant evidence for this phenomenon based on LSU and ITS sequences.


Optomechanical Bell Test.
Over the past few decades, experimental tests of Bell-type inequalities have been at the forefront of understanding quantum mechanics and its implications. These strong bounds on specific measurements on a physical system originate from some of the most fundamental concepts of classical physics-in particular that properties of an object are well-defined independent of measurements (realism) and only affected by local interactions (locality). The violation of these bounds unambiguously shows that the measured system does not behave classically, void of any assumption on the validity of quantum theory. It has also found applications in quantum technologies for certifying the suitability of devices for generating quantum randomness, distributing secret keys and for quantum computing. Here we report on the violation of a Bell inequality involving a massive, macroscopic mechanical system. We create light-matter entanglement between the vibrational motion of two silicon optomechanical oscillators, each comprising approx. 10^{10} atoms, and two optical modes. This state allows us to violate a Bell inequality by more than 4 standard deviations, directly confirming the nonclassical behavior of our optomechanical system under the fair sampling assumption.


Injection of chemotherapeutic microspheres and glioma. IV: Eradicating tumors in rats.
Polymer microspheres can be easily injected into the brain to provide a local and sustained delivery of chemotherapeutics to a tumor or surrounding tissue subject to high rates of tumor recurrence following surgery. Building on previous studies that established the clear advantage of local, peritumoral injections of sustained release microspheres, the following experiments utilized two different approaches for maximizing the survival benefit in glioma-bearing rats. In the first experiment, a previously grown cortical tumor was debulked and animals received either one or two treatments with carboplatin-loaded microspheres (either 200 or 800 microg total carboplatin per treatment). In each case, the microspheres were injected along the perimeter of the resection cavity with each treatment separated by 20 days. Survival studies clearly demonstrated that two, temporally spaced injections were superior to a single series of injections. At the lowest dose tested (200 microg), median survival was increased an additional 40% over that in animals receiving one treatment. At the higher dose (800 microg), one third of the animals receiving two separate treatments were long-term survivors (> 150 days) and showed complete eradication of the tumor on histological examination. In the second experiment, we directly compared the efficacy produced by sustained release carboplatin or 1,3-bis[2-chloroethyl]-1-nitrourea (BCNU) alone versus injecting carboplatin and BCNU-loaded microspheres blended together as a single suspension. Carboplatin and BCNU both enhanced survival, with BCNU being significantly less effective than carboplatin. However, the greatest improvements in survival were seen when a blended suspension of carboplatin and BCNU microspheres was injected around the surgical cavity. In contrast, spatially alternating injections of BCNU and carboplatin microspheres was significantly less effective and the increase in survival was no greater than that achieved with BCNU alone. These data offer further support for the potential utility of local, sustained release chemotherapeutic microspheres for treating glioma. Moreover, they suggest that injectable chemotherapeutic microspheres may offer important advantages by (a) permitting multiple, temporally spaced injections to be made, as needed, and (b) providing the opportunity to deliver combinations of several different efficacious drugs directly to the tumor site to enhance survival beyond what can be achieved with delivery of any single chemotherapeutic agent.


8. Staffing problems in long-term care.
The deficiencies in services of the wide range of health personnel involved in long-term care are well known. Physician involvement at all stages of the long-term care process is necessary as well as that of trained nurses, medical specialists, therapists, dentists, pharmacists, and others, and a team approach is essential to evaluate patient needs and to determine staffing requirements to meet them. Basic to the improvement in the education of health care personnel and the staffing of all types of long-term care services are 1) the development and regular recording of information on the needs for health services of chronically ill and aged patients, emphasixing functional status and the nature of disabilities requiring assistance; 2) comprehensive medical-nursing-social evaluation of patients to determine appropriate placement and treatment; and 3) methods of classifying patient data to establish staffing requirements.


Effect of nicotine on growth and metabolism of Streptococcus mutans.
Streptococcus mutans is a key contributor to dental caries. Smokers have a higher number of caries-affected teeth than do nonsmokers, but the association among tobacco, nicotine, caries, and S. mutans growth has not been investigated in detail. Seven S. mutans strains--UA159, UA130, 10449, A32-2, NG8, LM7, and OMZ175--were used in the present study. The minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), minimum biofilm inhibitory concentration (MBIC), planktonic cell growth, biofilm formation, metabolism, and structure (determined using scanning electron microscopy) of the seven strains treated with different concentrations of nicotine (0-32 mg ml(-1)) were investigated. The MIC, MBC, and MBIC were 16 mg ml(-1) (0.1 M), 32 mg ml(-1) (0.2 M), and 16 mg ml(-1) (0.1 M), respectively, for most of the S. mutans strains. Growth of planktonic S. mutans cells was significantly repressed by 2.0-8.0 mg ml(-1) of nicotine. Biofilm formation and metabolic activity of S. mutans was increased in a nicotine-dependent manner up to 16.0 mg ml(-1) of nicotine. Scanning electron microscopy revealed that S. mutans treated with a high concentration of nicotine a had thicker biofilm and more spherical bacterial cells. In summary, nicotine enhances S. mutans biofilm formation and biofilm metabolic activity. These results suggest that smoking can increase the development of caries by fostering increased formation of S. mutans biofilm on tooth surfaces.


Accuracy of IOS in Full-Arch Dentate Patients Compared to CBCT Cast-Scanning. An In-Vivo Study.
Twenty fully-dentate patients were enrolled in the study.Full-arch maxillary and mandibular PVS impressions were acquired using stock metal trays and the dual mix technique. A full-arch maxillary and mandibular intraoral scanner (IOS) was also obtained using the Trios IOS. The impressions were cast and subsequently scanned using a Planmeca Promax cone beam computed tomography (CBCT) scanner. The casts were also scanned in a Desktop Scanner for reference(7series Dental Wings). DICOM files from the CBCT device were converted into stl files. The.stl files from the CBCT and IOS devices were compared for accuracy against the reference files from the Desktop Scanner using a 3D surface measurement software. Statistical analysis was carried out using SPSS software. Trios had a smaller error (median = 39μm) than CBCT (median = 62μm),a statistically significant difference between the 2 modalities (z=-4.6, p⟨0.005).Concerning the IOS, the anterior teeth presented with a smaller error (42±16μm) as opposed to the posterior teeth (47±16μm), a significant difference (t(39)=-2.4, p=0,019). There were no significant differences in IOS mean accuracy between maxilla and mandible or between left and right quadrants. Fullarch digitization using the Trios IOS is significantly more accurate compared to CBCT scanning of the relevant plaster models. Anterior teeth Trios IOS is statistically more accurate compared to posterior teeth IOS.


Tsallis Entropy for Cross-Shareholding Network Configurations.
In this work, we develop the Tsallis entropy approach for examining the cross-shareholding network of companies traded on the Italian stock market. In such a network, the nodes represent the companies, and the links represent the ownership. Within this context, we introduce the out-degree of the nodes-which represents the diversification-and the in-degree of them-capturing the integration. Diversification and integration allow a clear description of the industrial structure that were formed by the considered companies. The stochastic dependence of diversification and integration is modeled through copulas. We argue that copulas are well suited for modelling the joint distribution. The analysis of the stochastic dependence between integration and diversification by means of the Tsallis entropy gives a crucial information on the reaction of the market structure to the external shocks-on the basis of some relevant cases of dependence between the considered variables. In this respect, the considered entropy framework provides insights on the relationship between in-degree and out-degree dependence structure and market polarisation or fairness. Moreover, the interpretation of the results in the light of the Tsallis entropy parameter gives relevant suggestions for policymakers who aim at shaping the industrial context for having high polarisation or fair joint distribution of diversification and integration. Furthermore, a discussion of possible parametrisations of the in-degree and out-degree marginal distribution-by means of power laws or exponential functions- is also carried out. An empirical experiment on a large dataset of Italian companies validates the theoretical framework.


The Role of Thrombin and Cell Contractility in Regulating Clustering and Collective Migration of Corneal Fibroblasts in Different ECM Environments.
We previously reported that extracellular matrix composition (fibrin versus collagen) modulates the pattern of corneal fibroblast spreading and migration in 3-D culture. In this study, we investigate the role of thrombin and cell contractility in mediating these differences in cell behavior. To assess cell spreading, corneal fibroblasts were plated on top of fibrillar collagen and fibrin matrices. To assess 3-dimensional cell migration, compacted collagen matrices seeded with corneal fibroblasts were embedded inside acellular collagen or fibrin matrices. Constructs were cultured in serum-free media containing platelet-derived growth factor (PDGF), with or without thrombin, the Rho kinase inhibitor Y-27632, and/or the myosin II inhibitor blebbistatin. We used 3-dimensional and 4-dimensional imaging to assess cell mechanical behavior, connectivity and cytoskeletal organization. Thrombin stimulated increased contractility of corneal fibroblasts. Thrombin also induced Rho kinase-dependent clustering of cells plated on top of compliant collagen matrices, but not on rigid substrates. In contrast, cells on fibrin matrices coalesced into clusters even when Rho kinase was inhibited. In nested matrices, cells always migrated independently through collagen, even in the presence of thrombin. In contrast, cells migrating into fibrin formed an interconnected network. Both Y-27632 and blebbistatin reduced the migration rate in fibrin, but cells continued to migrate collectively. The results suggest that while thrombin-induced actomyosin contraction can induce clustering of fibroblasts plated on top of compliant collagen matrices, it does not induce collective cell migration inside 3-D collagen constructs. Furthermore, increased contractility is not required for clustering or collective migration of corneal fibroblasts interacting with fibin.


Targeting BCL-2 in B-cell lymphomas.
The B-cell leukemia/lymphoma-2 (BCL-2) family of proteins governs the intrinsic pathway of mitochondrial apoptosis. Dysregulation of BCL-2 has long been known to be a crucial part of the pathophysiology of B-cell lymphomas; however, several early attempts to target this pathway therapeutically were unsuccessful because of toxicity, lack of efficacy, or both. Recently, a highly potent and selective oral BCL-2 antagonist, venetoclax, was approved in chronic lymphocytic leukemia, where it has proven to be highly active, even in patients with high-risk del(17p) disease. Venetoclax has also demonstrated efficacy in other B-cell non-Hodgkin lymphoma subtypes, in particular mantle cell lymphoma and follicular lymphoma. Here, I review the history of targeting BCL-2 in B-cell lymphomas, and I discuss recent data on venetoclax used as monotherapy and in combination with monoclonal antibodies, chemotherapy, and other novel agents. I also discuss how genomic and functional approaches such as BH3 profiling may allow us to prioritize novel-agent combinations for further study in clinical trials. These approaches may also help us to understand resistance mechanisms to BCL-2-selective therapy and how to overcome resistance. Finally, I provide my perspective on how to move BCL-2-directed therapies forward toward a goal of developing well-tolerated, time-limited combination regimens with curative potential for patients with B-cell lymphomas.


The cardioprotective effect of an aqueous extract of fermented rooibos (Aspalathus linearis) on cultured cardiomyocytes derived from diabetic rats.
Diabetic cardiomyopathy (DCM) is a disorder of the heart muscle that contributes to cardiovascular deaths in the diabetic population. Excessive generation of free radicals has been directly implicated in the pathogenesis of DCM. The use of antioxidants, through dietary supplementation, to combat increased cellular oxidative stress has gained popularity worldwide. Aspalathus linearis (rooibos) is a popular herbal tea that contains a novel antioxidant, aspalathin. Literature has reported on the antidiabetic, anti-inflammatory and free radical scavenging effects of rooibos. However, its protective effect against DCM has not been established. Therefore, this study investigated whether chronic exposure to an aqueous extract of fermented rooibos (FRE) has an ex vivo cardioprotective effect on hearts obtained from streptozotocin (STZ) induced diabetic rats. Adult Wistar rats were injected with 40 mg/kg of STZ. Two weeks after STZ injection, cardiomyocytes were isolated and cultured. Cultured cardiomyocytes were treated with FRE (1 and 10 μg/ml), vitamin E (50 μg/ml), and n-acetyl cysteine (1mM) for 6h, before exposure to either hydrogen peroxide (H2O2) or an ischemic solution. Cardiomyocytes exposed to H2O2 or an ischemic solution showed a decrease in metabolic activity and glutathione content with a concomitant increase in apoptosis and intracellular reactive oxygen species. Pretreatment with FRE was able to combat these effects and the observed amelioration was better than the known antioxidant vitamin E. This study provides evidence that an aqueous extract of fermented rooibos protects cardiomyocytes, derived from diabetic rats, against experimentally induced oxidative stress and ischemia.


The Role of Plant Lectins in the Cellular and Molecular Processes of Skin Wound Repair: An Overview.
There is increasing pressure for innovative methods to treat compromised and difficult-to-heal wounds. Consequently, new strategies are needed for faster healing, reducing infection, hydrating the wound, stimulating healing mechanisms, accelerating wound closure, and reducing scar formation. In this scenario, lectins present as good candidates for healing agents. Lectins are a structurally heterogeneous group of glycosylated or non-glycosylated proteins of non-immune origin, which can recognize at least one specific monosaccharide or oligosaccharide specific for the reversible binding site. Cell surfaces are rich in glycoproteins (glycosidic receptors) that potentially interact with lectins through the number of carbohydrates reached. This lectin-cell interaction is the molecular basis for triggering various changes in biological organisms, including healing mechanisms. In this context, this review aimed to (i) provide a comprehensive overview of relevant research on the potential of vegetable lectins for wound healing and tissue regeneration processes and (ii) discuss future perspectives.


The enucleated arterially perfused cat eye. I. Effects on protein permeability.
Protein permeability of the ciliary epithelium of enucleated arterially perfused cat eyes was studied. Tracer concentrations of 125I-albumin, in an arterial perfusate solution consisting of a balanced salt solution (BSS) without added colloid, was found in the anterior chamber fluid (AH) in a percentage similar to the AH/plasma ratio found for protein in the living cat eye. Stimulation of AH formation by acetylcholine plus eserine increased protein permeability markedly and by a similar amount in eyes perfused either with BSS or with 100% serum. These data indicate that arterial perfusion of the enucleated eye with BSS alone induces no gross abnormality of the blood-aqueous barrier.


Contrasting patterns of temperature related mortality and hospitalization by cardiovascular and respiratory diseases in 52 Spanish cities.
Climate change is a severe public health challenge. Understanding to what extent fatal and non-fatal consequences of specific diseases are associated with temperature may help to improve the effectiveness of preventive public health efforts. This study examines the effects of temperature on deaths and hospital admissions by cardiovascular and respiratory diseases, empathizing the difference between mortality and morbidity. Daily counts for mortality and hospital admissions by cardiovascular and respiratory diseases were collected for the 52 provincial capital cities in Spain, between 1990 and 2014. The association with temperature in each city was investigated by means of distributed lag non-linear models using quasi-Poisson regression. City-specific exposure-response curves were pooled by multivariate random-effects meta-analysis to obtain countrywide risk estimates of mortality and hospitalizations due to heat and cold, and attributable fractions were computed. Heat and cold exposure were identified to be associated with increased risk of cardiovascular and respiratory mortality. Heat was not found to have an impact on hospital admissions. The estimated fraction of mortality attributable to cold was of greater magnitude in hospitalizations (17.5% for cardiovascular and 12.5% for respiratory diseases) compared to deaths (9% and 2.7%, respectively). There were noteworthy differences between temperature-related mortality and hospital admissions regarding cardiovascular and respiratory diseases, hence reinforcing the convenience of cause-specific measures to prevent temperature-related deaths.


Wafer-Scale Lateral Self-Assembly of Mosaic Ti3C2Tx MXene Monolayer Films.
Bottom-up assembly of two-dimensional (2D) materials into macroscale morphologies with emergent properties requires control of the material surroundings, so that energetically favorable conditions direct the assembly process. MXenes, a class of recently developed 2D materials, have found new applications in areas such as electrochemical energy storage, nanoscale electronics, sensors, and biosensors. In this paper, we present a lateral self-assembly method for wafer-scale deposition of a mosaic-type 2D MXene flake monolayer that spontaneously orders at the interface between two immiscible solvents. ReaxFF molecular dynamics simulations elucidate the interactions of a MXene flake with the solvents and its stability at the liquid/liquid interface, the prerequisite for MXene flakes self-assembly at the interface. Moreover, facile transfer of this monolayer onto a flat substrate (Si, glass) results in high-coverage monolayer films with uniform thickness and homogeneous optical properties. Multiscale characterization of the resulting films reveals the mosaic structure and sheds light on the electronic properties of the films, which exhibit good electrical conductivity over cm-scale areas.


Regenerative capacity of retinal cells and the maintenance of their differentiation.
Mechanisms underlying cell type stability and the capacity of retinal cells for transdifferentiation are discussed. It is shown that cells of amphibian pigmented epithelium can be transformed into retina or lens cells depending on the inducing cell type: the influence of retina enables them to be transformed into retina, the influence of lens epithelium, to lens cells (lentoids or lenses). This led to an attempt to discover the molecular character of cell action by means of transfilter induction in early gastrula ectoderm of Xenopus laevis. The results show that the induced cell types correspond to the main inducing cell type, around which a range of neighbouring cell types is produced; this has been shown for five different cell types. The inducing factors involved seem to show qualitative differences. It is probable that they play a stabilizing role in the maintenance of the differentiated state of tissues, since temporary dissociation into cells leads eye tissues to transdifferentiate into other types. Such molecular factors can play a significant role in the maintenance of the type of differentiation and also in conversion into other cell types. These mechanisms of maintenance are not restricted to interactions between molecules and cells, since membranes on the surface of the retina and pigmented epithelium contribute to their shaping and consequently to the stability of the cell type.