Proteins in aqueous humor from cataract patients with and without pseudoexfoliation syndrome.
The aim of this study was to investigate the protein content in aqueous humor in eyes with and without pseudoexfoliations (PEX) and to evaluate the quantitative proteomics method, isobaric tagging for relative and absolute protein quantification (iTRAQ), in combination with two separation methods followed by matrix-assisted Laser desorption/ionization (MALDI) mass spectrometry and tandem mass spectrometry (MS/MS). During cataract surgery, samples of aqueous humor were collected from 20 eyes with PEX and from 18 control eyes. The relative concentrations of proteins in the pooled samples of ten PEX eyes and eight controls were evaluated after trypsin digestion and Labeling of the peptides with (iTRAQ) reagent. Two separation methods, Liquid chromatography (LC) and capillary electrophoresis (CE) were used, followed by MALDI mass spectrometry and MS/MS. Furthermore, 1D gel electrophoresis was performed on the remaining ten pooled PEX samples and ten control samples. The gel material was separated by nano-liquid chromatography (nano-LC) followed by Linear-ion-trap quadrupole Fourier transformation ion cyclotron resonance (FT-ICR). Fifty four proteins were identified in the LC runs and 24 with CE. The relative concentrations of beta-crystallines B2 and S were raised and those of angiotensinogen and osteopontin Lowered in the PEX sample compared to the control. The trends regarding beta-crystallines B2, angiotensinogen and osteopontin were confirmed by the 1D gel electrophoresis.


Investigating Markers of the NLRP3 Inflammasome Pathway in Alzheimer's Disease: A Human Post-Mortem Study.
Neuroinflammatory mechanisms with glial cell activation have been implicated in the pathogenic process of Alzheimer's disease (AD). Activation of the NLRP3 inflammasome is an essential component of the neuroinflammatory response. A role for NLRP3 activation in AD is supported by both in vitro and in vivo preclinical studies with little direct investigation of AD brain tissue. RNA expression of genes of three glial cell markers, HLA-DRA, AIF-1 and GFAP; the components of the NLRP3 inflammasome NLRP3, ASC, and caspase-1; and downstream pre-inflammatory cytokines IL-1 β and IL-18, were investigated in the temporal cortex of AD patients and age- and sex-matched controls. Protein expression of GFAP was also assessed. Increases in both mRNA and protein expression were observed for GFAP in AD. There were no significant changes in other NLRP3 activation markers between groups. Our results indicate the involvement of astrocyte activation in AD, particularly in more severe patients. We found no evidence for the specific involvement of the NLRP3 inflammasome.


Case report 680. Intraosseous meningioma of the sphenoid bone.
Two cases of intraosseous meningioma of the calvaria with hyperostosis are presented and compared with the appearance on plain films and CT of en plaque meningioma, metastatic disease from such primary sites as prostatic cancer, and fibrous dysplasia. It is emphasized that intraosseous meningioma in the calvaria is relatively uncommon, occurring most often in the sphenoid bone (probably because of its numerous articulations). The relationship of the development of intraosseous meningioma to the entrapment of dura containing arachnoid cells is discussed in considering the cause of such lesions, and it is stressed that calvarial fractures and cranial sutures may contribute to the entrapment of arachnoidal tissue and later the formation of a meningioma.


[Assessment of drug treatment for hypertension in a health centre as a function of associated chronic pathologies and degree of control of the hypertension].
To assess the suitability of whatever hypertension medication is prescribed for the associated pathology in each patient, and to analyse the monitoring of blood pressure figures. A cross-sectional descriptive study.Setting. Urban health centre. The target population were the hypertension patients being treated with medication and monitored at the health centre. Stratified random sampling by quotas of the total number with hypertension was performed. The sample numbered 219 patients. The clinical history of each patient selected was reviewed. To evaluate the hypertension treatment, we established three levels of suitability with regard to the accompanying pathology of each patient (suitable, intermediate, unsuitable), using the 1999 Hypertension Protocol of the Spanish Society of Family and Community Medicine. Out of 219 cases, treatment was suitable in 71 (32.4%), intermediate in 91 (41.6%), and unsuitable in 57 (26%). The most frequently indicated drug group was the angiotensin converting enzyme inhibitor (ACEI) group and, jointly, ACEI and diuretics. Regarding the monitoring of blood pressure: 66.5% had very good monitoring, 23.2% partial and 9% poor. Most treatments are at an intermediate level of suitability: without beneficial or undesirable effects on the associated pathology. This makes us think we need to optimize the drug indicators for hypertension.


The effect of docetaxel (taxotere) on human gastric cancer cells exhibiting low-dose radiation hypersensitivity.
Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells in the G(2)/M phase of the cell cycle. Some previous studies suggested that HRS might result from the abrogation of the early G(2) checkpoint arrest. First we tested whether HRS occurs in gastric cancer-derived cells, and whether pre-treatment of cells with low docetaxel concentrations can enhance the magnitude of HRS in gastric cancer cells. The results demonstrated HRS at ~0.3 Gy and the synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other drug/dose combinations. The synergistic effect was associated with a significant docetaxel-induced G(2) accumulation. Next, we evaluated in time-course experiments ATM kinase activity and proteins associated with the induction and maintenance of the early G(2) checkpoint. The results of multi-immunoblot analysis demonstrate that HRS does not correlate with the ATM-dependent early G(2) checkpoint arrest. We speculate that G(2) checkpoint adaptation, a phenomenon associated with a prolonged cell cycle arrest, might be involved in HRS. Our results also suggest a new approach for the improvement the effectiveness of docetaxel-based radiotherapy using low doses per fraction.


Progressive motor and respiratory metabolism deficits in post-weaning Mecp2-null male mice.
The methyl-CpG binding protein 2 (Mecp2) gene encodes a nuclear transcriptional modulator highly expressed in post-mitotic neurons. Mutations of this gene cause a large spectrum of neurological disorders in humans. Several lines of mice harboring a constitutional deletion of Mecp2 are available. The use of these models is crucial to understand the basis of Mecp2-related pathologies. However, most of the studies performed using these lines focused on different postnatal time points. The aim of the present study was to provide a more complete description of the behavioral phenotype of the Mecp2(tm1.1Bird) mice. To this aim, we used a modified version of the SHIRPA protocol and a set of sensorimotor tests and respiratory metabolism measurements, in a longitudinal study of the Mecp2-null male mice (Mecp2(-/y)) from three weeks (weaning) to eight weeks of age. Our data document, for the first time, the sequential appearance of the in vivo deficits in this mouse line. The observed deficits initially concern major parameters (such as body weight), and are followed by involuntary and sensitive defects (reflexes). Subsequently, motor functions and respiratory metabolism are severally impaired. A detailed description of these gradual defects may help to identify their neuronal origin and to elaborate novel therapeutic strategies.


Promoting LPG usage during pregnancy: A pilot study in rural Maharashtra, India.
Household air pollution from the combustion of biomass and coal is estimated to cause approximately 780,000 premature deaths a year in India. The government has responded by promoting uptake of liquefied petroleum gas (LPG) by tens of millions of poor rural families. Many poor households with new LPG stoves, however, continue to partially use traditional smoky chulhas. Our primary objective was to evaluate three strategies to transition pregnant women in rural Maharashtra to exclusive use of LPG for cooking. We also measured reductions in kitchen concentrations of PM2.5 before and after our interventions. Our core intervention was a free stove, 2 free LPG cylinders (one on loan until delivery), and repeated health messaging. We measured stove usage of both the traditional and intervention stoves until delivery. In households that received the core intervention, an average of 66% days had no indoor cooking on a chulha. In an adjacent area, we evaluated a conditional cash transfer (CCT) based on usage of LPG in addition to the core intervention. Results were less successful, due to challenges implementing the CCT. Pregnant women in a third nearby area received the core intervention plus a maximum of one 14.2 kg cylinder per month of free fuel. In their homes, 90% of days had no indoor cooking on a chulha. On average, exclusive LPG use decreased kitchen concentrations of PM2.5 by approximately 85% (from 520 to 72 μg/m3). 85% of participating households agreed to pay the deposit on the 2nd cylinder. This high purchase rate suggests they valued how the second cylinder permitted continuous LPG supply. A program to increase access to second cylinders may, thus, be a straightforward way to encourage use of clean fuels in rural areas.


Lithium does not alter the renal response to a pressor dose of tyramine in man.
Renal clearance of lithium has been used as a marker of proximal tubular function in man. Recently, lithium pre-treatment has been shown to interfere with the natriuretic actions of some natriuretic agents in man. We have therefore investigated the effects of oral lithium carbonate (500 mg) on the natriuretic response to a pressor dose of tyramine (15 micrograms kg-1 min-1) in six normal volunteers. Lithium had no effect on baseline sodium excretion, nor did it affect the tyramine-induced increase in blood pressure and subsequent natriuresis. These results show that oral lithium carbonate (500 mg) does not appear to interfere with the pressure natriuretic response to tyramine in man.


Free-Roaming Cat (Felis Catus) Management and Welfare Policies in Two University Campuses in Beirut, Lebanon: Strengths, Weaknesses, and Opportunities.
Little information has been reported about the welfare and management of free-roaming animals in Middle Eastern countries. Here we describe a case study of free-roaming cat (Felis catus) management policies in two universities in Beirut, Lebanon whereby cats are immensely valued for their presence and the benefits they bring to students and employees. Guided by concern for animal welfare, the innovative, humane approaches by the universities include arranging adoptions, discouraging pet abandonment, food provision, health monitoring, nurturing a social responsibility consciousness among young people, formal endorsement of animal rights and humane treatment in student conduct expectations, sterilization, and veterinary care. The policies serve as blueprint for universities and other institutions across the globe to adopt proactive approaches to free-roaming cat management as well take responsibility for the welfare of all animals on campus (rather than only for ethical conduct in use of animals in scientific research). They also inspire students, as the next generation, to safeguard animals and the environment.


Effects of Different Allotments of Avocados on the Nutritional Status of Families: A Cluster Randomized Controlled Trial.
Avocados are a nutrient-dense plant-food, but limited trial-derived evidence exists about the effects of avocado intake on family nutritional status. We investigated the impact of two levels of avocado allotment, plus a standard nutrition education intervention on the nutritional status of Hispanic/Latino families. Seventy-two families consisting of at least three members of ≥5 years of age and residing in the same home, free of severe chronic disease, not on specific diets, and self-identified of Hispanic heritage, were randomized to one of two levels of avocado allotment (low = 3/week/family or high = 14/week/family) for 6 months plus 12 bi-weekly nutrition education sessions. The primary outcomes included change in a family's total energy and macro- and micronutrient intakes. Primary analysis was intention-to-treat with unpaired, two-sided t-tests to assess mean changes between groups at 6 months. At 6 months, the high avocado allotment group had a significant reduction in energy intake, carbohydrate, animal and vegetable protein, saturated and polyunsaturated fat, calcium, magnesium, sodium, potassium, iron, and vitamin D intakes (all p < 0.05). A high allotment of avocados significantly reduced self-reported energy intake by 29% kcal/family/day, compared to a 3% kcal/family/day reduction in families who received a low allotment. Culturally-appropriate plant-food interventions may alter the nutritional status of at-risk families.


Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling.
Oxidative stress plays a crucial role in neurodegeneration. Therefore, reducing oxidative stress in the brain is an important strategy to prevent neurodegenerative disorders. Thunbergia laurifolia (Rang-jued) is well known as an herbal tea in Thailand. Here, we aimed to determine the protective effects of T. laurifolia leaf extract (TLE) on glutamate-induced oxidative stress toxicity and mitophagy-mediated cell death in mouse hippocampal cells (HT-22). Our results reveal that TLE possesses a high level of bioactive antioxidants by LC-MS technique. We found that the pre-treatment of cells with TLE prevented glutamate-induced neuronal death in a concentration-dependent manner. TLE reduced the intracellular ROS and maintained the mitochondrial membrane potential caused by glutamate. Moreover, TLE upregulated the gene expression of antioxidant enzymes (SOD1, SOD2, CAT, and GPx). Interestingly, glutamate also induced the activation of the mitophagy process. However, TLE could reverse this activity by inhibiting autophagic protein (LC3B-II/LC3B-I) activation and increasing a specific mitochondrial protein (TOM20). Our results suggest that excessive glutamate can cause neuronal death through mitophagy-mediated cell death signaling in HT-22 cells. Our findings indicate that TLE protects cells from neuronal death by stimulating the endogenous antioxidant enzymes and inhibiting glutamate-induced oxidative toxicity via the mitophagy-autophagy pathway. TLE might have potential as an alternative or therapeutic approach in neurodegenerative diseases.


Microcirculation and blood rheology in patients with cerebrovascular disorders.
We estimated hemorheological parameters of vein blood samples and cutaneous microvascular blood flow in patients with acute ischemic stroke and in controls. The worsened blood rheological properties were registered in patients with stroke: the enhanced whole blood viscosity was due to the substantial increase of plasma viscosity and the impairment of microrheological blood properties: elevated erythrocyte aggregability and decreased deformability compared to the healthy group. The decrease of oxygen consumption fixed by rheological methods and by laser Doppler flowmetry led us to conclude that the tissue hypoxia took place in patients with stroke. The regulatory mechanisms aimed to maintain blood supply to tissue were activated under cerebral infarction and the impact of unfavorably changed rheological blood properties was markedly enhanced. Revealed close interrelations between rheological and microcirculation parameters testified the important role of hemorheological factors in maintenance of microvascular blood flow and oxygen delivery to tissue.


Biotin Alone or a Science-Driven Nutraceutical Multi-Targeted Approach?
It is with great fervor that I revisit the article published in Journal of Drugs in Dermatology by Soleymani et al, titled "The Infatuation With Biotin Supplementation: Is There Truth Behind Its Rising Popularity? A Comparative Analysis of Clinical Efficacy versus Social Popularity."1 First, I'd like to thank the authors for raising awareness of the overuse of biotin for hair loss and reminding us of the struggle we are faced with daily when debunking quick-fix myths propagated by media infatuation.


In vivo induction of terminal differentiation of malignant myelopoietic progenitor cells by CSF-inducing biological response modifiers.
We have investigated the mechanisms by which colony-stimulating factor (CSF)-inducing biological response modifiers (BRM) may have beneficial effects on tumor-bearing hosts undergoing anti-tumor therapy. First, we have documented that treatment of mice with the chemically defined BRM maleic anhydride divinyl ether copolymer (MVE-2), which induces CSF secretion by macrophages (M phi) and bone marrow cells (BMC), significantly increased growth and differentiation of normal myelopoietic cells and counteracted the myelosuppressive effects of cyclophosphamide (CY). Second, we established that MVE-2 may exert CSF-mediated antitumor effects on certain leukemic tumor cells. Serum from mice pretreated in vivo with MVE-2, which contained CSF, induced terminal differentiation of cloned tumor cells from the CSF responsive WEHI-3B D+ subline in vitro, but not from the WEHI-3B D- subline, which is unresponsive to CSF. In vivo experiments showed that treatment of mice bearing the WEHI-3B D+ tumor first with CY and three days later with the CSF inducer MVE-2, significantly increased their survival time and rendered 20% to 50% of the tumor-bearing mice disease free. No such effects were obtained in mice bearing the WEHI-3B D- tumor. Thus, the induction of CSF or other differentiation factors by some BRMs may result in therapeutic effects against certain leukemias based on at least two distinct mechanisms: In addition to their restorative effects on normal bone marrow functions, CSF-inducing BRMs may also prevent further leukemogenesis by induction of terminal differentiation of leukemic cells.


Magnetic resonance imaging based classification of anatomic relationship between the cochleovestibular nerve and anterior inferior cerebellar artery in patients with non-specific neuro-otologic symptoms.
In this study, we aimed to assess anatomical relationship between the anterior inferior cerebellar artery (AICA) and cochleovestibular nerve (CNV) in patients with non-specific cochleovestibular symptoms using magnetic resonance imaging (MRI). One-hundred and forty patients with non-specific neuro-otologic symptoms were assessed using cranial and temporal MRI. Classification was performed according to four different types of anatomical relationship observed between the AICA and CVN. In type 1 (point compression), the AICA compresses only a limited portion of the CVN. In type 2 (longitudinal compression), the AICA approaches the CVN as both traverse parallel to each other. In type 3 (loop compression), the vascular loop of the AICA encircles the CVN. In type 4 (indentation), the AICA compresses the CVN so as to make an indentation in the nerve. The anatomical relationship between the CVN and AICA was encountered in 19 out of 140 (13.6%) patients (20 ears). The VCC was unilateral in 18 patients (94.7%) and bilateral in one patient (5.3%). There was no other vascular structure causing VCC to the CVN except for vertebral artery that was seen in 2 out of 140 patients (1.4%). These were unilateral cases. There were tinnitus, vertigo or dizziness, hearing loss, and both hearing loss and vertigo in 5 (25%), 13 (65%), 1 (5%) and 1 (5%) ears of 20 patients, respectively. There was no relationship between the cochleovestibular symptoms and type of compression (p>0.05). Neurovascular relationship between the CVN and AICA can be imaged properly using MR and MR based classification may help reporting this relationship in a standard way. Although, MR images can show the anatomical relationship accurately, diagnosis of vascular conflict should not be based on imaging findings alone.


Variability and Determinism in Motor Behavior
In investigations into perception-action systems, variability of observable behavior may be considered to (a) interfere with inquiry, (b) be neither detrimental nor particularly useful to inquiry, or (c) play a crucial role in inquiry. The authors underscore recent suggestions that alternative (c) is a preferred strategy for the study of many motor behaviors. In tutorial fashion, the authors review the concepts of variability and determinism with respect to postural and rhythmic movements. Study of the variability of those behaviors has revealed crucial features suggestive of underlying mechanisms and control, such as particular blends of noise and determinism (piecewise determinism). It has also revealed general lessons (for example, more variable does not mean more random and more controllable does not mean more deterministic) that may extend to other classes of perceptual behavior.


Endoluminal treatment of peripheral chronic total occlusions using the Crosser® recanalization catheter.
Revascularization of lower extremity chronic total occlusions (CTOs) is technically challenging. The Crosser® recanalization catheter was designed to facilitate distal vessel intraluminal entry that is both rapid and safe. We present our experience with the Crosser device as primary therapy for peripheral CTOs. Subjects undergoing evaluation for arterial insufficiency at our institution between 2008-2010 who were noted to have a CTO in the lower extremity by duplex ultrasonography and who subsequently underwent Crosser recanalization were enrolled. Clinical characteristics, ankle-brachial indices, Rutherford-Becker symptom category, and angiographic CTO parameters were collected. Primary technical success was intraluminal delivery of the guidewire into the distal vessel solely by the Crosser device. Secondary technical success was assisted delivery using the Outback LTD® re-entry device. Safety endpoints were the occurrence of dissections, thromboembolism, and perforations related to the Crosser device. Statistical analysis was performed to find independent predictors for failure to achieve Crosser recanalization. Fifty-six subjects with 73 CTOs were enrolled. The mean Crosser use time was 17.6 ± 12.7 minutes. The overall primary and secondary technical success rates for Crosser recanalization were 76.7% and 87.7%, respectively. Technical success was highest for CTOs located in the aorto-iliac (90.0%) and tibial (95.2%) arterial segments. There were no perforations related to the Crosser device. For successful cases, the mean ABI improved significantly from pre- to post-intervention (0.57 ± 0.13 to 0.89 ± 0.15, p < 0.001). The only predictors for failure were lesion length longer than 100 mm (p = 0.04) and calcification within 10 mm of the exit cap (p = 0.02). The Crosser device is safe and shows excellent efficacy in facilitating guidewire distal lumen entry, especially for aorto-iliac and tibial occlusions. The technical success rate for the femoral and popliteal occlusions is comparable to those reported with other recanalization techniques.


Does Preoperative Activity Level Affect Postoperative Outcomes Following Total Hip Arthroplasty?
Many patients electing to undergo total hip arthroplasty (THA) value continuing active lifestyles when considering treatment options. Addressing these concerns requires evaluating the effect of preoperative activity level on patient-reported outcomes and improvement following THA. Three hundred thirty-five patients (368 hips) who underwent THA with a minimum 6-month (mean 533 ± 271 days) follow-up completed preoperative and postoperative University of California, Los Angeles (UCLA) activity score along with various patient-reported measures of function, pain, and mental state. Preoperative UCLA score divided patients into inactive, mild, and active groups. Analysis of covariance controlling for age, sex, body mass index, surgical approach, implant, bilateral cases, conversions, and follow-up time evaluated differences among groups for postoperative outcomes with subsequent Tukey-Kramer pairwise comparisons. Mildly active patients (73:139 male:female) had better postoperative outcomes than inactive patients (40:70 male:female) for UCLA score, EuroQol Visual Analog Scale (EQVAS), Hip Outcome Score (HOS), 12-item Short-Form (SF-12) Physical, and Visual Analog Pain Scale (average/now/worst) (P values <0.001/<0.001/<0.001/<0.001/0.003/<0.001/<0.001). Active patients (32:14 male:female) had better postoperative outcomes than inactive patients for UCLA score, EQVAS, HOS, SF-12 Physical, and Visual Analog Pain Scale Worst (P values <0.001/0.024/0.001/0.001/0.017). No postoperative outcome differences existed between active and mild patients. Inactive patients displayed greater outcome improvements than mildly active patients for UCLA score, Harris Hip Score, and International Hip Outcome Tool (P values <0.001/<0.001/0.013) and active patients for UCLA score, EQVAS, HOS, International Hip Outcome Tool, and SF-12 Physical (P values <0.001/0.008/0.013/0.022/0.004). Inactive patients achieve greater measure improvements following THA. Active patients achieve better absolute outcomes than inactive patients; however, increasing activity levels do not incrementally improve patient-reported outcome measures. Patients similarly improve pain and mental health regardless of activity level.


CE: Original Research: Work-Related Stress and Positive Thinking Among Acute Care Nurses: A Cross-Sectional Survey.
: Background: Acute care nurses work in highly taxing environments, and as such are vulnerable to work-related stress, burnout, and attrition. Yet some nurses appear to flourish even in the presence of such stress, perhaps because of differences in their cognitive processes. Positive thinking, a set of skills that can be learned, has been linked to increased well-being, physical health, and longevity. But at this writing, there has been scant research investigating the use of positive thinking among nurses. To assess the relationship between perceptions of work-related stress and the use of positive thinking among acute care nurses. A cross-sectional survey consisting of the Expanded Nursing Stress Scale, the Positive Thinking Skills Scale (PTSS), and a demographic questionnaire was administered to a convenience sample of 298 RNs, which included nurses already working for an eight-campus health care system and newly hired nurses during orientation. Compared to the established group, the incoming RNs were generally younger, had less education, and reported higher levels of both work-related stress and positive thinking. Linear regression analysis revealed that an increase in perceived stress was predictive of an increase in positive thinking. The PTSS, which had not been previously tested among nurses, was found to be reliable and valid. This is the first U.S. study to evaluate the use of positive thinking in managing work-related stress among acute care nurses. The data suggest that positive thinking skills are being used to cope with such stress. But the mean PTSS scores for both groups were only slightly above midline, suggesting that nurses' use of positive thinking as a coping skill can be improved through formal training and education.


A density functional theory based estimation of the anharmonic contributions to the free energy of a polypeptide helix.
We have employed density functional theory to determine the temperature dependence of the intrinsic stability of an infinite poly-L-alanine helix. The most relevant helix types, i.e., the α- and the 3(10)-helix, and several unfolded conformations, which serve as reference for the stability analysis, have been included. For the calculation of the free energies for the various chain conformations we have explicitly included both, harmonic and anharmonic contributions. The latter have been calculated by means of a thermodynamic integration approach employing stochastic Langevin molecular dynamics, which is shown to provide a dramatic increase in the computational efficiency as compared to commonly employed deterministic molecular dynamics schemes. Employing this approach we demonstrate that the anharmonic part of the free energy amounts to the order of 0.1-0.4 kcal/mol per peptide unit for all analysed conformations. Although small, the anharmonic contribution stabilizes the helical conformations with respect to the fully extended structure.


Your client credibility: are your pharmacy practices helping or hindering?
When recommending a specific pharmaceutical, more has to be taken into account than whether the API is indicated for the illness in question. Based on the preceding discussion, product source can have a tremendous impact on efficacy, on therapeutic success, and on practitioners' credibility in the eyes of their clients. However, product source goes beyond simple credibility, encompassing professional ethics and liability. In answering the Ethical question of the month--December 2001 "Should private veterinary practitioners be allowed to produce autogenous vaccines or compound antimicrobial products for use in food producing animals?" Rollin concluded, "one cannot envision a clearer case of unethical behavior." The reality is that quality assurance, efficacy, potency, and safety are not defined for compounded products, and should veterinarians choose to script or dispense one, the responsibility for its quality, efficacy, potency, and safety falls squarely on their shoulders. Ultimately, this also translates into 100% liability should an ADR, illness, or lack of effect, befall the patient. While having access to ELDU and compounded products is crucial in facilitating the treatment of the various diseases that veterinarians face, the regulatory freedom that gives them this choice carries heightened responsibilities when electing this option. In a nutshell, ethical and responsible principles of pharmacy dictate that a veterinarian's first choice should be a veterinary-licensed pharmaceutical for the indication in question. Should this not exist, ELDU of a licensed product with clinically derived therapeutic protocols should be the next choice. Compounded pharmaceuticals should only be used when no licensed (those sporting a DIN) product exists, and extreme cautions should be exercised when using transdermal formulations. Liability dictates that this decision be undertaken with informed consent of the owner and with appropriate due diligence when selecting a compounding service provider. Various articles have been written that provide the veterinarian with guidance when making this decision.


Impact of surgery on quality of life in Crohn's disease.
Health-related quality of life (HRQOL) status is an important component in assessing the impact of disease and its treatments in patients with chronic disorders. We recently validated a HRQOL questionnaire in French patients with inflammatory bowel disease. The aim of this study was to evaluate prospectively the impact of surgery on HRQOL in patients operated on for Crohn's disease (CD). Twenty-six patients (14 women, 12 men; median age 28.5 yr) undergoing an elective ileocolonic resection for CD were studied. The HRQOL questionnaire comprised a general questionnaire of 36 items (Medical Outcomes Study-Short Form 36), to which was added a sleep module, and a specific questionnaire of 28 items (Rating Form of Inflammatory Bowel Disease Patient Concerns), to which were added three independent items because of their pertinence in the French population. HRQOL was assessed immediately preoperatively and 3 months postoperatively. HRQOL was improved postoperatively compared with the immediate preoperative status in almost all scales. Patient concerns and worries decreased after surgery. However, ranking was unchanged for the five most intense concerns: having an ostomy bag, having surgery, energy level, uncertainty of the disease, and pain or suffering. HRQOL is greatly improved after surgery for CD, and this reassuring message might be delivered to our patients. In addition, the questionnaire showed the ability to detect clinical changes over time. This attests to its potential use in research.


The relationship between self-report of depression and media usage.
Depression is a debilitating condition that adversely affects many aspects of a person's life and general health. Earlier work has supported the idea that there may be a relationship between the use of certain media and depression. In this study, we tested if self-report of depression (SRD), which is not a clinically based diagnosis, was associated with increased internet, television, and social media usage by using data collected in the Media Behavior and Influence Study (MBIS) database (N = 19,776 subjects). We further assessed the relationship of demographic variables to this association. These analyses found that SRD rates were in the range of published rates of clinically diagnosed major depression. It found that those who tended to use more media also tended to be more depressed, and that segmentation of SRD subjects was weighted toward internet and television usage, which was not the case with non-SRD subjects, who were segmented along social media use. This study found that those who have suffered either economic or physical life setbacks are orders of magnitude more likely to be depressed, even without disproportionately high levels of media use. However, among those that have suffered major life setbacks, high media users-particularly television watchers-were even more likely to report experiencing depression, which suggests that these effects were not just due to individuals having more time for media consumption. These findings provide an example of how Big Data can be used for medical and mental health research, helping to elucidate issues not traditionally tested in the fields of psychiatry or experimental psychology.


Hepatitis B associated monoclonal gammopathy that resolved after successful liver transplant.
Monoclonal gammopathy of undetermined significance (MGUS) has been most commonly associated with diseases like multiple myeloma, Waldenstrom's macroglobulinemia, primary systemic amyloidosis, HIV, and other lymphoproliferative disorders. There has been an isolated report of MGUS in patients coinfected with HIV and Hepatitis B, as the work by Amara et al. in 2006. Here, we report a case of IgA-kappa light chain gammopathy secondary to Hepatitis B infection, which resolved after liver transplantation. To our knowledge, this is the first reported case of M protein spike seen in the context of Hepatitis B infection only.


Whole Blood Holding Time Prior to Plasma Processing Alters microRNA Expression Profile.
MicroRNAs (miRNAs) can exhibit aberrant expression under different physiological and pathological conditions. Therefore, differentially expressed circulating miRNAs have been a focus of biomarker discovery research. However, the use of circulating miRNAs comes with challenges which may hinder the reliability for their clinical application. These include varied sample collection protocols, storage times/conditions, sample processing and analysis methods. This study focused on examining the effect of whole blood holding time on the stability of plasma miRNA expression profiles. Whole blood samples were collected from healthy pregnant women and were held at 4°C for 30 min, 2 h, 6 h or 24 h prior to processing for plasma isolation. Plasma RNA was extracted and the expression of 179 miRNAs were analyzed. Unsupervised principal component analysis demonstrated that whole blood holding time was a major source of variation in miRNA expression profiles with 53 of 179 miRNAs showing significant changes in expression. Levels of specific miRNAs previously reported to be associated with pregnancy-associated complications such as hsa-miR-150-5p, hsa-miR-191-5p, and hsa-miR-29a-3p, as well as commonly used endogenous miRNA controls, hsa-miR-16-5p, hsa-miR-25-3p, and hsa-miR-223-3p were significantly altered with increase in blood holding time. Current protocols for plasma-based miRNA profiling for diagnostics describe major differences in whole blood holding periods ranging from immediately after collection to 26 h after. Our results demonstrate holding time can have dramatic effects on analytical reliability and reproducibility. This highlights the importance of standardization of blood holding time prior to processing for plasma in order to minimize introduction of non-biological variance in miRNA profiles.


Loneliness Status and Related Factors among the Hakka Elderly in Fujian, China: Based on the Health Ecological Model.
There are few studies estimating the loneliness of the Hakka elderly in China. This study aims to examine the loneliness status and related factors among the Hakka elderly in Fujian, China. The short-form UCLA Loneliness Scale (ULS-8) was used to assess the loneliness of the Hakka elderly. Factors associated with loneliness were classified as individual indicators, behavioral indicators, interpersonal indicators, and social indicators according to the health ecological model (HEM). Hierarchical linear regression models were established to identify the main factors that were most predictive of loneliness. A sample of 1,262 Hakka elderly people was included in this study. Females (β = 0.631, P=0.012), those with ≥2 chronic diseases (β = 1.340, P < 0.001), those who were currently living in rural areas (β = 4.863, P < 0.001) or suburban areas (β = 2.027, P < 0.001), those with parents both died (β = 0.886, P=0.001), and those with the Urban Employees Basic Medical Insurance (UEBMI; β = 0.852, P=0.030) obtained a higher score of ULS-8. Those exercised regularly (β = -2.494, P < 0.001), those had leisure activities (β = -1.937, P < 0.001), those ate healthy (β = -1.270, P < 0.001), and those with better self-rated financial status and higher education level received a lower score of ULS-8. There are differences in loneliness among different Hakka elderly population subgroups, and healthy behaviors and lifestyles may reduce the loneliness of the Hakka elderly. Relevant interventions should be implemented in a targeted manner, focusing on susceptible populations. This is most evident among those who were female, living in rural areas, with parents both died, with lower education, and with multiple chronic diseases.


[Professional dysadaptation syndrome in anesthetists-resuscitators].
The professional dysadaptation syndrome (PDS) has just recently been recognized in Russian medicine and regarded as a response to long-term professional stresses. PDS has a high tropicity for educated anesthetists-resuscitators (AR) whose profession is socionomic and high-technonomic. Irrespective of the length of service, psychoemotional stress in AR is significantly higher than that in surgeons. Typical PDS, the so-called alexithymia, the psychological characteristics of a personality, which includes a difficulty in defining and describing his/her own emotions, was identified in 82% of anesthetics and in only 57% of surgeons. Alexithymia is considered as a risk factor of cardiovascular and gastrointestinal diseases. Its correction assumes psychotherapeutic care in the conventional forms. However, only 7.6% of the respondents agreed to be questioned.


Evaluation of filtering techniques to extract movement intention information from low-frequency EEG activity.
Low-frequency electroencephalographic (EEG) activity provides relevant information for decoding movement commands in healthy subjects and paralyzed patients. Brainmachine interfaces (BMI) exploiting these signals have been developed to provide closed-loop feedback and induce neuroplasticity. Several offline and online studies have already demonstrated that discriminable information related to movement can be decoded from low-frequency EEG activity. However, there is still not a well-established procedure to guarantee that this activity is optimally filtered from the background noise. This work compares different configurations of non-causal (i.e., offline) and causal (i.e., online) filters to classify movement-related cortical potentials (MRCP) with six healthy subjects during reaching movements. Our results reveal important differences in MRCP decoding accuracy dependent on the selected frequency band for both offline and online approaches. In summary, this paper underlines the importance of optimally choosing filter parameters, since their variable response has an impact on the classification of low EEG frequencies for BMI.


Slow Crystal Growth of Cubic Ice with Stacking Faults in a Glassy Dilute Glycerol Aqueous Solution.
Control of ice formation is an important issue as catastrophic ice growth influences our life activities and many industrial systems. We prepared a homogeneous glass of a dilute glycerol aqueous solution by a pressure liquid cooling vitrification method and examined the effect of solute on the ice formation of solvent water using a powder X-ray diffraction method. The solvent water immediately after the crystallization is composed of nanosized pure cubic ice (ice Ic). The crystal growth of ice Ic with stacking faults is much slower than that of pure water. The presence of glycerol molecules dispersing homogeneously may hinder crystal growth. The macroscopic segregation occurs rapidly during the transformation from stacking disordered ice to hexagonal ice. The results suggest that ice formation can be controlled by changing the solute type and concentration. This study has implications for thawing technology in cryobiology and frozen food engineering.


An unusual case of anuria: spontaneous perirenal hematoma in a solitary kidney.
A 71-year-old woman with a solitary kidney who developed acute renal failure with anuria secondary to a spontaneous perirenal hematoma is described. Serum creatinine peaked at 335.9 micromol/L and BUN at 26.4 mmol/L, but neither surgery nor dialysis treatment was performed because renal function gradually improved. In this syndrome, first described by Wunderlich in 1856, anuria was not previously reported. Conservative management must always be considered rather than emergency surgery, which usually results in nephrectomy.


Autoimmune myasthenia gravis in a ferret.
A 7-month-old neutered male ferret was evaluated for episodic pelvic limb weakness of 2 weeks' duration. Neurologic examination revealed flaccid tetraparesis with decreased spinal reflexes suggestive of a neuromuscular disease. Results of hematologic and CSF analyses, thoracic radiography, and abdominal ultrasonography were unremarkable. Electrodiagnostic testing revealed subtle spontaneous activity localized to pelvic limb interosseous muscles, unremarkable motor nerve conduction velocities, and lower than typical compound muscle action potential (CMAP) amplitude for tibial nerve stimulation only. A severe decremental response of the CMAP was detected with repetitive nerve stimulation (45.5% at the third ulnar nerve). An esophagogram revealed mild megaesophagus. Intravenous neostigmine methylsulfate administration resulted in immediate resolution of muscle weakness. Cross-reacting anti-acetylcholine receptor (AChR) antibodies were detected in serum (0.35 nmol/L) by use of a canine- and feline-specific muscle extract. Clinical signs and ancillary test results were diagnostic of acquired myasthenia gravis. Pyridostigmine bromide was administered (1 mg/kg [0.45 mg/lb], PO, q 8 h), resulting in complete remission of clinical signs. However, 1 month after the diagnosis, the ferret was euthanized because of recurrence of weakness despite anticholinesterase treatment. To the authors' knowledge, this is the first report of acquired myasthenia gravis in a ferret and the first identification of anti-AChR antibodies in this species. Autoimmune myasthenia gravis should be considered in ferrets when weakness and flaccid paresis suggest a neuromuscular disease. Electrodiagnostic testing, anticholinesterase challenge, and AChR antibody titer determination were helpful for diagnosis of this condition.


Effect of hyperbaric oxygen treatment on myogenic transcriptional factors in regenerating rat masseter muscle.
Hyperbaric oxygen (HBO) treatment was shown to be beneficial as an additional treatment for ischemic muscles in crush injuries and ischemia-reperfusion injuries. The purpose of this study was to assess the influence of hyperbaric oxygen treatment on transcriptional myogenic factors during muscle regeneration. Those factors (MyoD, myf5, myogenin, mrf4) are essential for determination and differentiation of skeletal muscle tissue and together with several other factors control gene expression during myogenesis. The process of regeneration in rat masseter muscle was provoked with injection of local anesthetic bupivacaine hydrochloride. Following injection, the animals were treated once daily in hyperbaric chamber from one to ten days and than sacrificed. Immunohistochemical and Western blot analysis of frozen masseter muscle samples showed a transient upregulation of myoD and myogenin transcriptional factors in the muscles of hyperbaric oxygen treated rats and of rats that have not been treated after the injury. HBO treatment had no effect on the expression of MyoD and myogenin transcriptional factors in the regenerating rat masseter muscle.


Surgical treatment of displaced acetabular fractures.
Acetabular fractures are severe injuries, generally caused by high-energy trauma, most frequently from traffic accidents or falls from heights. Fractures of the extremities, head injuries, chest, abdomen and pelvic ring injuries are most commonly associated injuries. The purpose of this study was to evaluate the results of open reduction and internal fixation of acetabular fractures. The open anatomical reduction of the articular surface combined with a rigid internal fixation and early mobilisation have become the standard treatment of these injuries. We conducted a retrospective analysis of 22 patients of average age 43.13 years. The patients were treated by open reduction and internal fixation at the Orthopaedic Clinic of Nis from 2005-2009. The follow-up was 12 to 60 months, with the average of 21.18 months after surgery. All injured patients were operated on between 4 and 11 days (5.7 days on the average). According to the classification by Judet and Letournel, 15 (68.18%) patients had an elementary acetabular fracture, whereas 7 (31.82%) patients had associated fracture. A satisfactory postoperative reduction implying less than 2 mm of displacement was achieved in 19 (86.36%) patients. The radiological status of the hip joint, determined according to Matta score, was excellent in 15 (68.18%) patients, good in 4 (18.18%) patients and moderate in 3 (13.63%) patients. According to Merle d'Aubigné Scale, the final functional results of the treatment of all operated patients were excellent in 12 (54.54%) patients, good in 7 (31.81%) patients and moderate in 3 (13.63%) patients. Surgical treatment of dislocated acetabular fractures requires an open reduction and a stable internal fixation. Excellent and good results can be expected only if anatomical reduction and stable internal fixation are achieved.


The regulatory role of microRNA-1187 in TNF-α-mediated hepatocyte apoptosis in acute liver failure.
In the current study, we aimed at elucidating the regulatory mechanisms through which microR-1187 (miR-1187) participates in hepatocyte apoptosis in acute liver failure (ALF). An ALF model was induced with D-galactosamine (D-GalN) plus lipopolysaccharide (LPS) in BALB/c mice. The hepatic miRNA expression profile was detected by microarray analysis and verified by quantitative real-time PCR (qRT-PCR). The possible underlying mechanism was investigated in vitro using an embryonic murine hepatocyte cell line (BNLCL2) and miR-1187 mimic. Caspase-8 protein was detected by Western blotting and cell apoptosis was assayed by flow cytometry. Hepatic miR-1187 was down-regulated in ALF mice based on microarray data (P<0.001) and verified by qRT-PCR (P<0.01). Target scan revealed that caspase-8 was the putative target of miR-1187. In an in vitro study, miR-1187 showed the highest up-regulation in BNLCL2 cells transfected with the miR-1187 mimic at a 50 nM concentration for 12 h compared with cells transfected with the non-specific mimic (P<0.001). miR-1187 was down-regulated (P<0.01) but caspase-8 mRNA (P<0.01) as well as protein (P<0.05) were up-regulated in the BNLCL2 cells treated with D-GalN/TNF. Furthermore, overexpressed miR-1187 reduced caspase-8 expression at both the mRNA and protein levels significantly (P<0.01 and P<0.05 respectively), and significantly attenuated the apoptotic rate of BNLCL2 cells (P<0.05). We show that miR-1187 regulates hepatocyte apoptosis by targeting caspase-8. miR-1187 may serve as a potential therapeutic target for the treatment of ALF.


Increased success of blind nasotracheal intubation through the use of nasogastric tubes as a guide.
We were able to improve the success rate of blind nasotracheal intubation by using nasogastric tubes as a guide during intubation, first, for passing the endotracheal tube through the nasal cavity, and second, passing it from the pharynx to the larynx. By adding both sedation by modified neuroleptanalgesia (NLA) and topical and transtracheal administration of lidocaine, our technique became safer and smoother. We have completed 36 cases without accident, with an average time for intubation of 8.25 min. The Rüsh spiral tube was thought to be the most suited to this form of intubation because of the 90 degrees cut of its tip, its high-volume cuff, and its flexibility in all directions. These features are useful for hearing breath sounds, raising the tip of the tube by inflation of the cuff, and advancing the tube in a turning motion.


Posterior versus direct anterior approach in total hip arthroplasty: difference in patient-reported outcomes measured with the Forgotten Joint Score-12.
When the postoperative outcome of primary total hip arthroplasty (THA) was compared with the direct anterior approach (DAA) and the posterior approach (PA), there was no significant difference of the clinical outcome at 6 months to 1 year after surgery in many studies. This study was performed to compare the medium-term outcome of THA via the DAA or PA and clarify which approach achieves better quality of life (QOL). We investigated 61 hips receiving primary THA (30 via DAA and 31 via PA), using hip function scores such as the Harris Hip Score (HHS) and patient-reported outcomes such as the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Japanese Orthopaedic Association Hip Disease Evaluation Questionnaire (JHEQ), and the Forgotten Joint Score-12 (FJS). The mean duration of postoperative follow-up was 36.8 months in the DAA group and 40.5 months in the PA group. There was no difference in preoperative or postoperative HHS between the two groups. Although there was no difference of postoperative WOMAC and JHEQ, the postoperative FJS-12 score was significantly higher in the DAA group than in the PA group (75.2 ± 15.9 versus 60.1 ± 24.4, p = 0.01). When forgetting the artificial joint in daily life is the target, better QOL can be achieved by performing THA via the DAA.


Influence of the coronavirus 2 (SARS-Cov-2) pandemic on acute appendicitis.
Acute appendicitis (AA) is the most common abdominal surgical emergency. No specific studies have been found that evaluate the impact of the coronavirus 2 (SARS-Cov-2) pandemic on AA and its surgical management. An analysis was made on the influence of this new pathology on the clinical course of AA. Retrospective observational study was conducted on patients operated on for AA from January to April 2020. They were classified according to the time of the appendectomy, before the declaration of the state of alarm (Pre-COVID-19), and after its declaration (Post-COVID-19) in Spain, one the most affected countries in the world. An evaluation was made of demographic variables, duration of symptoms, type of appendicitis, surgical time, hospital stay, and postoperative complications. The study included 66 patients (41 Pre-COVID-19; 25 Post-COVID-19) with mean age of 10.7 ± 3 and 9.3 ± 3.1; P = .073, respectively. Fever was found in a higher number of post-COVID-19 patients (52 vs 19.5%; P = .013), as well as a higher CRP (72.7 ± 96.2 vs 31.3 ± 36.2 mg/dL; P = .042). This group presented with a higher proportion of complicated appendicitis when compared to Pre-COVID-19 (32 vs 7.3%; P = .015). The mean hospital stay was longer in the Post-COVID-19 group (5.6 ± 5.9 vs 3.2 ± 4.3 days; P = .041). No differences were found in the time of onset of symptoms or surgical time. The SARS-Cov-2 pandemic influenced the time of diagnosis of appendicitis, as well as its course, and mean hospital stay. Peritonitis was more frequently seen. As a result of the significant circumstances, delaying diagnosis and treatment of AA during SARS-Cov-2 pandemic, inappropriate management of this common surgical disorder has been noticed.


Can a Commercial Video Game Prevent Depression? Null Results and Whole Sample Action Mechanisms in a Randomized Controlled Trial.
Depressive symptoms and disorders are major public health concerns, affecting many adolescents and young adults. Despite extensive research, depression prevention programs for youth show limited effectiveness. Moreover, the maximal potential of youth psychotherapy - on which depression prevention programs are based - may have been reached. Commercial video games may offer an engaging alternative vehicle for youth to practice emotional and social skills vital to mental health. The current study investigated the potential for the commercial video game Journey to prevent the exacerbation of depressive symptoms. A pre-registered randomized controlled trial tested the effectiveness of Journey as an indicated depression prevention approach compared to a control game condition and a passive control condition (Dutch Trial Register: NL4873, https://www.trialregister.nl/trial/4873). Additionally, potential action mechanisms for depression prevention using video games were examined. Participants aged 15 to 20 years old with elevated depressive symptoms (n = 244, M age = 17.11, SD age = 1.76, 66.4% female) were given 4 weeks to play Journey (M duration = 3 h 20 min) or the control game, Flower (M duration = 2 h 36 min). Results showed no beneficial effects of playing the commercial video game, Journey, on youth's change in depressive symptoms above and beyond the active and passive control conditions up to 12-months after the intervention. Additionally, no action mechanisms were found specifically for Journey. Nevertheless, over the whole study, participants decreased in depressive symptoms, became less sensitive to rejection, and experienced more hope and optimism. Moreover, participants who during the study decreased in rejection sensitivity or rumination or who increased in hope and optimism or in distraction and problem solving showed the strongest decrease in depressive symptoms. Although results do not support the use of the studied commercial game as an effective indicated depression prevention strategy, our results do suggest that rejection sensitivity, hope, optimism, rumination, distraction, and problem solving are promising targets for future depression prevention efforts. We conclude with important lessons for future research on games to promote mental health. Particularly, encouraging careful consideration of research designs to explore for whom and how potential action mechanisms and associated game mechanics may be effective.


Tartric acid-based linker for the solid-phase synthesis of C-terminal peptide alpha-oxo aldehydes.
A novel linker, based on the anchoring of (+)-dimethyl 2,3-O-isopropylidene-D-tartrate to PEGA or PEG-PS solid supports, was developed for the solid-phase synthesis of C-terminal peptide alpha-oxo aldehydes. Peptide elongation was performed using the 9-fluorenylmethoxycarbonyl/t-Bu chemistry. The peptide and the 1,2-diol were deprotected on the solid phase. Then, a periodic oxidation of the fully deprotected peptidyl-resin led to the simultaneous cleavage of the product from the solid support and to the generation of the alpha-oxo aldehyde moiety. The methodology allowed the distance between the alpha-oxo aldehyde and the peptide to be easily modulated. The C-terminal peptide alpha-oxo aldehydes synthesized in this study were found to be useful partners in hydrazone, thiazolidine, and oxime chemical ligations.


Triple Emission of 5'-(para-R-Phenylene)vinylene-2-(2'-hydroxyphenyl)benzoxazole (PVHBO). Part II: Emission from Anions.
This paper is the second part of a study on the effects of a substituted 5'-phenylenevinylene (PV) functionality on the emission properties of 2-(2'-hydroxyphenyl)benzoxazole (HBO)─a dye that is known for excited-state intramolecular proton transfer. The topical compounds are referred to as PVHBOs, each of which is a structural fusion of HBO and a 4-hydroxy-4'-R-stilbene fluorophore that occurs at the hydroxyphenyl moiety. Therefore, the resulting fusion fluorophore manifests the properties of one component or the other, as governed by its interactions with the environment. In part I (the preceding paper), PVHBOs are divided into two groups depending on whether the R substituent is electron-donating/neutral (group I) or electron-withdrawing (group II). The difference in absorption and emission properties between groups I and II is explained based on observations from spectroscopic experiments (both steady-state and time-resolved) and quantum chemical calculations. In the current paper, the same set of tools is applied to characterize the photophysical properties of the conjugate bases─that is, the anions─of PVHBOs. The emission energy of the anion of any group I compound, where the R substituent is either electron-donating or neutral, is situated between those of the neutral enol and keto forms. The emission of the anion of any given group II compound, on the other hand, has a lower energy than both the enol and keto emissions. The frontier molecular orbitals (i.e., HOMO, LUMO, and LUMO + 1) of a PVHBO localized on either HBO or stilbenoid are impacted by the substituent R and the solvent/additive differently, which leads to the differences in the optical properties of group I and II PVHBOs in both neutral and anion forms.


Autoimmune diseases in humans, e.g. autoimmune rheumatic diseases.
In spite of increasing evidence that viruses and especially retroviruses could act as etiologic factors in autoimmune and especially autoimmune rheumatic diseases, clear-cut evidence for an involvement of these agents is still missing. Findings, which, for example, indirectly support the hypothesis that retroviruses might play a part, are the demonstration of antibodies to the gp24 in SLE and Sjögren's patients as well as the description of retroviral antigens in the inflamed synovium of rheumatoid arthritis patients. Furthermore, evidence comes from animal models that viruses, such as the Visna or Caprine arthritis encephalitis virus, induced chronic inflammatory diseases in sheep and goats. More recently, a mouse model for rheumatoid arthritis and Sjögren's syndrome was reported in mice transgenic for HTLV-1tax. It is hoped that, especially from the experimental animal models, the possible role of retroviruses as etiological factors in autoimmune rheumatic diseases can be clarified.


Factors affecting reproduction and the importance of adult size on reproductive output of the midge Chironomus tentans.
We conducted two separate tests to evaluate the influence of several factors that could affect estimation and interpretation of effects on reproductive output of Chironomus tentans in sediment toxicity tests. Specifically, the influence of adult size, mating frequency in males (male), and age of both males and females (female) at first mating on mating success (number of successful matings), fecundity (number of eggs/female), percentage hatch, and number of offspring (number of hatched eggs) was assessed. In the first experiment, the influence of adult size on reproductive output was determined by growing midges fed a low (0.29 mg/individual/d) and a high (0.42 mg/individual/d) amount of food to produce small (S) and large (L) adults, respectively. The adults were then mated in one of four scenarios: S male x S female, S male x L female, L male x S female, and L male x L female. An increase in male weight at a constant female weight had no significant effect on fecundity, whereas an increase in female weight yielded 49.5 and 60.7% increases in fecundity when mated with low- and high-fed males, respectively. Similarly, mean number of offspring (fecundity x percent hatch) increased by 19.8 and 48.3% when male weight was increased and female weight was held constant and by 141.9 and 180.4% when female weight was increased and male weight was held constant. In the second experiment, conducted at a single feeding rate, fecundity increased significantly with an increase in female weight but not male weight. The number of offspring was not significantly influenced by adult weight. The age of males or females at first mating, the frequency with which males were mated (up to seven consecutive days), and the proportion of males successfully mating had no effect on fecundity or number of offspring; however, large increases in variability about mean estimates were observed in some endpoints for older males. These results suggest that adult female size is the most important factor affecting reproductive output in C. tentans, and that enhanced performance of the life-cycle test with respect to all reproductive endpoints might be achieved if males are not mated for more than five consecutive days.


[The incidence of postoperative nausea and vomiting is not effected by routinely applied manual pre-oxygenation during induction of anesthesia].
To evaluate whether routine pre-intubation positive pressure mask ventilation (PPMV) influences the incidence of postoperative nausea and vomiting (PONV). Prospective, randomised single blinded study. 669 ASA class I-III patients of either sex (number calculated as follows: incidence of PONV = 30%, group difference = 25%, a-error < 5%, statistical power = 90%) scheduled for elective surgery (no eye, neck, nose or ear surgery) of at least 30 min duration. Approval by the local ethical committee and informed written consent was obtained. After preoxygenation (3 min) and induction of anesthesia with fentanyl (1-2 micrograms.kg-1 b.w.) and thiopental (5 mg.kg-1 b.w) patients were divided into two groups: group 1 patients (without PPMV, n = 333) received succinylcholine 30s after thiopental followed by tracheal intubation. Group 2 patients (with PPMV, n = 336) were ventilated by mask for at least 30s after thiopental injection, followed by succinylcholine and, after another 120s of PPMV, tracheal intubation. All anesthetics were performed by 15 anesthesiologists (8 certified staff members, 7 residents). Primary endpoint: incidence of PONV during the first 24 h postoperatively. Secondary end point: relation between PONV and medical qualification of the anesthesiologists. significant difference in PONV between groups. contingency tables with chi-square and Fisher's exact test, Kruskal-Wallis-test (for categorical variables); ANOVA with post-hoc Scheffe (for continuous variables), p < 0.05. No difference was found in the incidence of nausea (30.6% vs. 28%, p = 0.5) or vomiting (20.1% vs. 17%, p = 0.32) regardless whether the patients received PPMV or not. Women were nearly three times more likely to suffer from PONV (35.2% vs. 13.8%, p < 0.0001). Distribution of age, weight, height, anesthetic duration and surgical procedures were comparable between groups. The degree of medical qualification did not influence the incidence of PONV (p = 0.543). Since neither routine pre-intubation positive pressure mask ventilation nor the medical qualification of the anesthesilogist affect the incidence of PONV neither variable needs to be taken into account in studies concerning PONV.


Free-living marine nematodes from San Antonio Bay (Río Negro, Argentina).
The dataset of free-living marine nematodes of San Antonio Bay is based on sediment samples collected in February 2009 during doctoral theses funded by CONICET grants. A total of 36 samples has been taken at three locations in the San Antonio Bay, Santa Cruz Province, Argentina on the coastal littoral at three tidal levels. This presents a unique and important collection for benthic biodiversity assessment of Patagonian nematodes as this area remains one of the least known regions. In total 7,743 specimens of free-living marine nematodes belonging to two classes, eight orders, 37 families, 94 genera and 104 species were collected.


Comparison of the Abundance and Community Structure of N-Cycling Bacteria in Paddy Rhizosphere Soil under Different Rice Cultivation Patterns.
Eco-agricultural systems aim to reduce the use of chemical fertilizers in order to improve sustainable production and maintain a healthy ecosystem. The aim of this study was to explore the effects of rice-frog farming on the bacterial community and N-cycling microbes in paddy rhizosphere soil. This experiment involved three rice cultivation patterns: Conventionally cultivated rice (CR), green rice-frog farming (GR), and organic rice-frog farming (OR). The rice yield, paddy soil enzyme activities, physicochemical variables and bacterial and N-cycling bacterial abundances were quantitatively analyzed. Rice-frog cultivations significantly increased soil protease, nitrate and reductase activity. Additionally, the nirS gene copy number and the relative abundance of denitrifying bacteria also increased, however urease activity and the relative abundance of nitrifying bacteria significantly decreased. The bacterial community richness and diversity of OR soil was significantly higher than that of the GR or CR soil. Nitrogen use efficiency (NUE) of GR was highest. The N-cycling bacterial community was positively correlated with the total carbon (TC), total nitrogren (TN) and carbon to nitrogen (C:N) ratio. The present work strengthens our current understanding of the soil bacterial community structure and its functions under rice-frog farming. The present work also provides certain theoretical support for the selection of rational rice cultivation patterns.


Japan's dilemma: how to cope with an aging population.
Future demographic trends in Japan are reviewed, with an emphasis on demographic aging. "It is clear the aging of its population will have an impact on Japan's labor practices, saving and consumption patterns, and demand for public and private resources." The author concludes that "given Japan's past experience in adapting to all types of adversity...its response to demographic shifts will likely enable it to continue its remarkable economic growth."


Fluctuation ratios in the absence of microscopic time reversibility.
We study fluctuations in diffusion-limited reaction systems driven out of their stationary state. Using a numerically exact method, we investigate fluctuation ratios in various systems which differ by their level of violation of microscopic time reversibility. Studying a quantity that for an equilibrium system is related to the work done to the system, we observe that under certain conditions oscillations appear on top of an exponential behavior of transient fluctuation ratios. We argue that these oscillations encode properties of the probability currents in state space.


Restriction endonucleases whose sites are predictable from the amino acid sequence offer an improved strategy for typing bovine rotaviruses.
Variation in the third base of a codon hampers genotypic characterization, particularly of RNA viruses. Some restriction endonucleases, however, have a recognition site with a variable base at the third position and will always cleave when a certain amino acid pair occurs (such as glycine-proline for Sau96I and glutamic or aspartic acid followed by serine usually for HinfI). We developed a restriction fragment length polymorphism (RFLP) procedure based on these enzymes for P-typing bovine group A rotaviruses (BRV). Employing this procedure 20 BRV local strains, isolated in tissue culture as well as the original faecal sample, could be typed in one of three patterns. More variability was observed when restriction endonucleases were employed whose cleavage sites cannot be predicted from the amino acid sequence (TaqI and Tsp509I). These RFLP results agreed with the PCR-VP4 typing assay, neutralization tests, and nucleotide sequence analysis. RFLP with Sau96I and HinfI provided quick and objective P-typing of strains and could detect multiple genotypes in the same sample.


Transepithelial pressure pulses induce nucleotide release in polarized MDCK cells.
The release of nucleotides is involved in mechanosensation in various epithelial cells. Intriguingly, kidney epithelial cells are absolutely dependent on the primary cilium to sense changes in apical laminar flow. During fluid passage, the renal epithelial cells are subjected to various mechanical stimuli in addition to changes in the laminar flow rate. In the distal part of the collecting duct, the epithelial cells are exposed to pressure changes and possibly distension during papillary contractions. The aim of the present study was to determine whether nucleotide release contributes to mechanosensation in kidney epithelial cells, thereby establishing whether pressure changes are sufficient to produce nucleotide-mediated responses. Madin-Darby canine kidney (MDCK) cells grown on permeable supports were mounted in a closed double perfusion chamber on an inverted microscope. The intracellular Ca(2+) concentration ([Ca(2+)](i)) was monitored with the Ca(2+)-sensitive fluorescence probe fluo 4. Transepithelial pressure pulses of 30-80 mm Hg produced a transient increase in [Ca(2+)](i) of MDCK cells. This response is independent of the primary cilium, since it is readily observed in immature cells that do not yet express primary cilia. The amplitudes of the pressure-induced Ca(2+) transients varied with the applied chamber pressure in a quantity-dependent manner. The ATPase apyrase and the P2Y antagonist suramin significantly reduced the pressure-induced Ca(2+) transients. Applying apyrase or suramin to both sides of the preparation simultaneously nearly abolished the pressure-induced Ca(2+) response. In conclusion, these observations suggest that rapid pressure changes induce both apical and basolateral nucleotide release that contribute to mechanosensation in kidney epithelial cells.


Genetic testing for warfarin therapy initiation.
To review the literature regarding the efficacy of genetic testing for determining the appropriate initial dose of warfarin and the effect that this testing has on the safety and efficacy of therapy. Searches of MEDLINE (1966-May 2008) and Cochrane Database (1993-May 2008) were conducted using the search terms warfarin, anticoagulation, pharmacogenomics, pharmacogenetics, CYP2C9, VKORC1, and interindividual variability. Limits included articles written in English with human subjects. Additional data were identified through bibliographic reviews. All English-language articles identified from the data sources were evaluated. Studies were eligible for inclusion if they evaluated the efficacy of pharmacogenomic testing to improve outcomes with initiation of warfarin therapy. The use of warfarin presents numerous challenges in clinical practice. Four studies (N = 38, 48, 200, 297) evaluating the efficacy of genetic testing for determining the initial dose of warfarin therapy have been published. Results show that time to therapeutic international normalized ratio (INR) and time to stable warfarin dose are similar regardless of genotype. When conventional warfarin dosing was compared with pharmacogenomic-based dosing, no significant difference was seen between groups in terms of time spent within the target INR range (41.5% vs 41.7%; no p value reported). Similar results were found in a subsequent study in which patients receiving conventional dosing were outside their target INR range 33.1% of the time compared with 30.7% of the time for patients whose dose was guided by pharmacogenomics (p = 0.47). There is growing evidence that variant alleles for CYP2C9 and VKORC1 genotypes account for a proportion of the variability seen in warfarin dosing. The currently available literature related to the use of pharmacogenomic testing in the initiation of warfarin therapy does not show improved outcomes in either safety or efficacy with warfarin therapy and therefore does not support the routine use of pharmacogenomic testing when initiating warfarin therapy.


Immunocytochemical Localization of Phosphoribulose Kinase in the Cyanelles of Cyanophora paradoxa and Glaucocystis nostochinearum.
The distribution of phosphoribulose kinase (PRK) in the cyanelles of Cyanophora paradoxa Korschikoff and Glaucocystis nostochinearum Itzigsohn was studied by protein A-gold immunoelectron microscopy. In both endocyanomes, antiserum against PRK heavily labeled the thylakoid region of the cyanelles, whereas little or no label was present over the carboxysomes. Antiserum against ribulose 1,5-bisphosphate carboxylase/oxygenase by contrast heavily labeled the carboxysomes of each endocyanome. In vitro studies of PRK distribution in cell-free extracts of C. paradoxa showed that 93% of the enzyme was in the soluble fraction. Quantitative immunoelectron microscopy showed that more than 99% of the PRK in the cyanelle of C. paradoxa was localized in the thylakoid region. We conclude that the carboxysomes of cyanelles like the carboxysomes of autotrophic prokaryotes and the pyrenoids of green algal chloroplasts do not contain phosphoribulose kinase.


Peripheral arterial disease in general and diabetic population.
Peripheral arterial disease (PAD) is stenosis or occlusion of peripheral arterial vessels by atherosclerotic plaque. It may present as intermittent claudication, rest pain and impotence. PAD of the lower limbs is the third most important site of atherosclerotic disease after coronary heart disease and cerebrovascular disease. Increasing age, family history, smoking, hypertension, dyslipidemia and more decisively diabetes are significant risk factors. PAD is a clinical condition that has often been neglected, underdiagnosed, undertreated and has a serious outcome. It may lead to nonhealing wounds, gangrene and amputation of the lower limbs. Hence, early identification of patients at risk of PAD and timely referral to the vascular surgeon in severe cases is crucial.


The effect of probe to skin contact force on Cutometer MPA 580 measurements.
The purpose of this study is to test the hypothesis that increasing the force applied on the skin by the Cutometer MP580 probe will result in a decrease in the skin elasticity measures. Specifically, this study assessed the probe intrinsic weight plus the addition of a light mass (10 g and 20 g), a moderate mass (50 g and 100 g) and a high mass (200 g and 500 g) on skin elasticity measures. Primary outcome measures Uv, Ur, Uf, Ue and Ua, along with calculated measures Uv/Uf, Ua/Uf and Ur/Uf were assessed under each loading condition. A general linear model ANOVA with repeated measures was used to assess for differences in each outcome measure between each loading condition. Thirty-two patients were enrolled and all completed the testing. For all primary variables except Uv (p < 0.001), there was no statistically significant effect of adding a light mass to the probe. There was a significant effect of the addition of a moderate and heavy mass for all variables (p < 0.005) except Ue/Uf. These results suggest that the addition of a low mass results in no significant effect on outcome measures. However, if moderate-to-heavy additional force is applied to the probe, the outcome measures are significantly altered. Of all the variables, Ue/Uf appears to be influenced the least by alterations in force. Users should ensure light contact is made between the skin and probe during testing to avoid a false alteration in outcome measures of skin elasticity.


Heterogeneity's ruses: some surprising effects of selection on population dynamics.
"As a cohort of people, animals, or machines ages, the individuals at highest risk tend to die or exit first. This differential selection can produce patterns of mortality for the population as a whole that are surprisingly different from the patterns for subpopulations or individuals. Naive acceptance of observed population patterns may lead to erroneous policy recommendations if an intervention depends on the response of individuals. Furthermore, because patterns at the individual level may be simpler than composite population patterns, both theoretical and empirical research may be unnecessarily complicated by failure to recognize the effects of heterogeneity."


Biosynthesis of ribulose-1,5-bisphosphate carboxylase in spinach leaf protoplasts.
Spinach leaf (Spinacia oleracea L. var. Kyoho) protoplasts sustain protein-synthesizing activity as measured by the incorporation of [(14)C]-leucine into the protein fraction both in the light and in the dark. By the immunoprecipitation of ribulose-1,5-bisphosphate (RuP(2)) carboxylase with rabbit antibody raised against the purified spinach enzyme preparation, it was found that approximately 7% of the total radiocarbon incorporated into the protein fraction in the light was in the carboxylase molecules. However, there was no measurable net increase observed in the content of the enzyme protein in the experimental conditions employed. It was found that both chloramphenicol and cycloheximide inhibited the incorporation of [(14)C]leucine into RuP(2) carboxylase and its constituent subunits, as measured by the immunoprecipitation of the enzyme molecule and its subunits, A and B.


Epiploic appendagitis: the great mimicker.
Epiploic appendagitis is a benign, self-limited, clinicopathological, and radiological entity that has become more commonly recognized. The clinical presentation resembles a variety of other medical and surgical intra-abdominal conditions and may easily be confused with many of them. Computed tomography (CT) demonstrates characteristic features that help make the diagnosis in most cases, thus avoiding unneeded treatment or surgery. Here, we discuss a case series of five patients who presented with abdominal pain and were ultimately diagnosed with epiploic appendagitis.


Naphthalene removal from aqueous systems by Sagittarius sp..
Naphthalene is a polyaromatic hydrocarbon (PAH) present in many sediment-water systems. The uptake of naphthalene by an aquatic plant, arrowhead (Sagittaria sp.), was studied in a series of batch systems and continuous flow systems. Batch experiments were conducted in a fed-batch mode, and naphthalene was administered in consecutive spike doses. Results from batch experiments indicated that the rate of naphthalene removal by arrowhead in the presence of light was 0.114+/-0.061 h(-1), at a 90% confidence interval. Naphthalene removal by arrowhead occurred even in the absence of light, although this rate was about 25% of that in the presence of light. Results indicated that repeated exposures to naphthalene for a single arrowhead plant may decrease its capacity for naphthalene uptake, particularly after the first exposure. Naphthalene tended to deposit out in CSTRs where no arrowhead was present, indicating that while the naphthalene may not have been present in the water column, it was not removed from the system. Results from CSTR experiments indicated that under well-mixed quasi-steady state conditions, naphthalene removal by arrowhead in the presence of light was about 40%. Photolytic degradation of naphthalene in the absence of arrowhead was about 15%, when additional mixing was provided to simulate scouring.


Ayurvedic medicine: patients in peril from plumbism.
Heavy metals are commonly incorporated into Ayurvedic preparations as ashes or 'bhasmas'. A widely disseminated belief within Ayurvedic medicine is that these heavy metals can be valuable therapeutic components. Western toxicology refutes this contention. We report eight cases of lead poisoning occurring in or near the Auckland region of New Zealand. In all cases, poisoning was attributable to consumption of Ayurvedic 'herbal medicines'. Whole blood lead levels ranged from 1.5 to 6.9 micromol/L. Six patients had symptomatic lead poisoning, requiring treatment with chelation therapy. A high index of suspicion is required to detect lead poisoning, which should be suspected in people taking Ayurvedic remedies, especially if they have associated anaemia or abdominal symptoms.


Helicopter Transport of Trauma Patients Improves Survival Irrespective of Transport Time.
Helicopter transport of trauma patients remains controversial. We examined the survival rates of patients undergoing helicopter versus ground transport to a Level 1 trauma center. Retrospective analysis was performed on trauma patients treated between 2014 and 2017. Student's t-test was used to compare air versus ground transport times. A logistic regression was then used to examine the association of transportation type on survival controlling for demographics, mechanism of injury, transport time, field intubation, and injury severity. Of 3967 patients identified, 69.6% (2762) were male, and the average age was 40 years. Most patients suffered blunt injuries (86.8%, 3445), while the remaining had penetrating injuries (11.6%, 459) or burns (1.6%, 63). The majority of patients were transferred by ground (3449) with only 13% (518) transferred by air. Patients transported by air had increased Injury Severity Score (ISS) with a median of 17 (IQR 9-24) versus 9 (IQR 5-14), increased length of stay (LOS) at 6 days versus 3 (P < .001), and increased mortality at 12.6% vs 6.5% (P < .001). Patients transported by air arrived 16.6 ± 6.7 minutes faster compared with ground for the zip codes examined. When adjusting for the mechanism of injury, ISS, age, gender, intubation status, and transport time, air transport was associated with an increased likelihood of survival (odds ratio [OR] = 1.57, 95% CI = 1.06-2.40). In our analysis of 3967 patients, those transported by air had a significant improvement in the likelihood of survival compared with those transported by ground even when adjusting for both ISS and time.


Accumulation of Perfluoroalkylated Substances in Oceanic Plankton.
The bioaccumulation of perfluoroalkylated substances (PFASs) in plankton has previously been evaluated only in freshwater and regional seas, but not for the large oligotrophic global oceans. Plankton samples from the tropical and subtropical Pacific, Atlantic and Indian Oceans were collected during the Malaspina 2010 circumnavigation expedition, and analyzed for 14 ionizable PFASs, including perfluorooctanoate (PFOA), perfluorooctanesulfonate (PFOS) and their respective linear and branched isomers. PFOA and PFOS concentrations in plankton ranged from 0.1 to 43 ng gdw-1 and from 0.5 to 6.7 ng gdw-1, respectively. The relative abundance of branched PFOA in the northern hemisphere was correlated with distance to North America, consistent with the historical production and coherent with previously reported patterns in seawater. The plankton samples showing the highest PFOS concentrations also presented the largest relative abundances of branched PFOS, suggesting a selective cycling/fractionation of branched PFOS in the surface ocean mediated by plankton. Bioaccumulation factors (BAFs) for plankton were calculated for six PFASs, including short chain PFASs. PFASs Log BAFs (wet weight) ranged from 2.6 ± 0.8 for perfluorohexanesulfonic acid (PFHxS), to 4.4 ± 0.6 for perfluoroheptanoic acid (PFHpA). The vertical transport of PFASs due to the settling of organic matter bound PFAS (biological pump) was estimated from an organic matter settling fluxes climatology and the PFAS concentrations in plankton. The global average sinking fluxes were 0.8 ± 1.3 ng m-2d-1 for PFOA, and 1.1 ± 2.1 ng m-2d-1 for PFOS. The residence times of PFAS in the surface ocean, assuming the biological pump as the unique sink, showed a wide range of variability, from few years to millennia, depending on the sampling site and individual compound. Further process-based studies are needed to constrain the oceanic sink of PFAS.


[Sick rate of scabies among people in the city of Katowice].
The incidence of scabies disease was analysed among women, men and children in Katowice in 1993-1997. The materials came from the Municipal Hospital of Dermatology and from the Clinic of Dermatology in Katowice. From the analysis of materials follows that the precentage of infected women and men was low in the studied period and fuctuated between 0.5 % and 1.8 %. Higher percentage appeared among children. The precentage of hospitalized children was higher (9.4 %-12.6 %) than at children from the clinic (2-2.4 %). The most cases concerned children between 1 and 5 years old.


[Embryo transfer: a critical step in assisted reproduction].
The advances and development of new procedures and techniques related to embryo development, and its final outcome, the embryo transfer; have increased significantly the pregnancy rate through this reproductive assisted technique. The embryo transfer is probably the last part in in-vitro fertilization programs and the success should be determined through the technical approach and procedure's characteristics. The use and standardization of the current techniques during the embryo transfer process allow increasing the success in pregnancy and implantation rates in a short period of time in the current Assisted Reproduction Programs.


Prevalence of smoking and high blood pressure, two major risk factors for non-communicable diseases: the SuRF NCD (surveillance of risk factors of non-communicable disease) report 2012.
Introduction: In recent years non-communicable diseases (NCDs) risk factors such as tobacco consumption and high blood pressure (BP) have been increased. This study aimed to determine the frequency of risk factors of the main NCDs among inhabitants of Rafsanjan city. Methods: Our study is a part of NCD surveillance in Iran (SuRF NCD). A total of 640 people enrolled and divided in four age groups in urban and rural areas in Rafsanjan (a city in Kerman province). Data were collected using the standardized stepwise protocol for NCD risk factor surveillance of the World Health Organization (WHO). This study focused on hypertension (HTN) and smoking. Results: A total of 640 people (46.9% male and 53.1% female) participated in this cross-sectional study. The prevalence of HTN was 198 per 1000 population. 4.8% of those were below the age of 44, and 15% between 45 and 70 years old. Mean systolic BP was 127 ± 15.6 in male and 118 ± 19.65 in female and the statistical difference was significant (t = 5.55, P < 0.001). 79 (14.1%) of hypertensive live in urban and 32 (5.7%) live in rural areas (χ2 = 8.004, P = 0.005). The prevalence of current smokers was 112 per 1000 population; among them 56 (88.9%) were daily smokers. The mean age for starting smoking was 21.11 ± 7.16 years. Conclusion: Modifying risk factors such as HTN and smoking behavior through primary and secondary prevention programs by enhancing awareness and knowledge of lay people, improvement screening and treatment interventions, particularly for the youth is highly recommended.


Burden of skin cancer in Colombia.
Levels of incidence and mortality of skin cancer in Colombia and Latin America are largely unknown. Present the available information from official and gray literature and governmental databases to grasp the magnitude and characteristics of skin cancer in Colombia (middle-income Latin American country). Narrative review based on a literature search (2005-2020), gray literature and cancer registry and governmental warehouse data, calculation of proportions and age-standardized incidence (ASIR) and mortality rates (ASMR), expressed per 100,000 person-years. ASIR of cutaneous melanoma in Colombia is around 3, corresponding ASMR between 0.7 and 0.8. Distinctive features are the high proportion and rates for acral melanomas, and the advanced stage at diagnosis in the general population but not in private clinics. For non-melanoma skin cancer, ASIR is at least around 35-40, ASMR 0.8. Among the wealthy Colombians, melanoma features are similar to those of high incidence countries (but of lower magnitude), whereas the majority of the population present distinct features with a much higher proportion of acral melanomas, very late stages at diagnosis, and poor prognosis. More advanced melanomas seem to have a relation with lower socioeconomic status. Non-melanoma skin cancer is common, with very high mortality rates at levels even above those of predominantly fair-skinned populations, implying high fatality rates for non-melanoma skin cancers. This could indicate a late diagnosis or difficulties in access to treatment, illustrating the need for primary and secondary prevention to reduce the burden of disease and improve the prognosis of this common cancer.


Animal models of multiple endocrine neoplasia.
Multiple endocrine neoplasia (MEN) syndromes are autosomal dominant diseases with high penetrance characterized by proliferative lesions (usually hyperplasia or adenoma) arising in at least two endocrine tissues. Four different MEN syndromes have been so far identified: MEN type 1 (MEN1), MEN2A (also referred to as MEN2), MEN2B (or MEN3) and MEN4, which have slightly varying tumor spectra and are caused by mutations in different genes. MEN1 associates with loss-of-function mutations in the MEN1 gene encoding the tumor suppressor menin. The MEN2A and MEN2B syndromes are due to activating mutations in the proto-oncogene RET (Rearranged in Transfection) and are characterized by different phenotypic features of the affected patients. MEN4 was the most recent addition to the family of the MEN syndromes. It was discovered less than 10 years ago thanks to studies of a rat strain that spontaneously develops multiple endocrine tumors (named MENX). These studies identified an inactivating mutation in the Cdkn1b gene, encoding the putative tumor suppressor p27, as the causative mutation of the rat syndrome. Subsequently, germline mutations in the human ortholog CDKN1B were also found in a subset of patients with a MEN-like phenotype and this led to the identification of MEN4. Small animal models have been instrumental in understanding important biochemical, physiological and pathological processes of cancer onset and spread in intact living organisms. Moreover, they have provided us with insight into gene function(s) and molecular mechanisms of disease progression. We here review the currently available animal models of MEN syndromes and their impact on the elucidation of the pathophysiology of these diseases, with a special focus on the rat MENX syndrome that we have been characterizing.


Twitter Mentions Influence Academic Citation Count of Shoulder and Elbow Surgery Publications.
Background Social media use among scholars and journals is growing and has augmented the academic impact of published articles in several areas of medicine. However, the influence of social media postings on academic citations of shoulder and elbow surgery publications is not known. In this study, we sought (1) to quantify the adoption of Twitter use for the dissemination of research publications by three prominent shoulder and elbow surgery journals and (2) to determine the correlation between Twitter mentions and academic citations in shoulder and elbow surgery publications. Methodology A total of 396 original research articles from three shoulder and elbow surgery journals (Journal of Shoulder and Elbow Surgery (JSES), Shoulder & Elbow, and JSES International) published in 2018 were assessed 34 to 45 months after print publication. For each article, the total number of Twitter mentions were obtained using Altmetric Bookmarklet and grouped into those tweeted by authors, an official outlet, or a third party. Article citation data was obtained using the Google Scholar search engine. Pearson correlation was used to determine the association between the number of Twitter mentions and citation count. Results Of all articles, 51% (202/396) had at least one Twitter mention. Of all Twitter mentions, 12.7% (367/2,879) occurred within the first week of online publication dates, while 51.5% (1,482/2,879) occurred between online and print publication dates. Articles mentioned on Twitter had 1.3-fold more Google Scholar citations (17.7 ± 15.2) than articles with no Twitter mentions (14.0 ± 15.7) (p = 0.017). The number of Twitter mentions had a weakly positive correlation with academic citation count (r = 0.25; p < 0.001). No significant difference in academic citation rates was found between articles tweeted by authors or official outlets when compared to articles tweeted by a third party only (p = 0.97 and p = 0.34, respectively). Conclusions Approximately half of shoulder and elbow surgery publications are shared on Twitter, with the majority of the activity occurring prior to their print publication date. The finding that tweeted articles have more academic citations within three years of release suggests that social media activity seems to amplify the academic impact of shoulder and elbow surgery publications.


[Physiological characteristics of single K+ channel currents (Ik) in cerebellar cortical neurons of neonatal rat].
The characteristics of single K+ channels in cultured cerebellar granule neurons of neonatal rat were studied by the cell- attached and inside-out configurations of patch clamp technique. The results are as follows: the predominant conductance of single channel was 25PS, the currents amplitude, the mean open time and the open probability were dependent of membrane potential, the open time distribution histograms were fitted by two exponential components, the channel activity was not inactivated during 20 s period, independent of calcium and blocked by tetraethylammonium. These results indicated that the single channel was a delayed rectifier (Ik). It is suggested that the non-inactivating channel with conductance of 25pS which exists in the cerebellar granule cell might be a new subtype of Ik channel.


Epidemiology and Risk Factors Associated with Developing Bacterial Meningitis among Children in Gaza Strip.
Bacterial meningitis is still the leading cause of high morbidity and mortality among the children. The present study was conducted to determine the epidemiology, clinical characteristics of bacterial meningitis and to evaluate the risk factors associated with developing the infection. This cross sectional study was conducted in three hospitals of Gaza strip -Palestine during the period 2009. All the children with clinical diagnosis of meningitis /meningoencephalitis admitted to these hospitals were included in the study. They were subjected to clinical examination as well as CSF bacteriological and serological investigations. During the period (2009), 1853 patients were admitted to the hospitals with suspect of meningitis by pediatricians, 73 (3.9%) proved by culture to be acute bacterial meningitis, of these patients 62% were males and 38% were females. The common isolated pathogens were Neisseria meningitides (47.9%), Streptococcus pneumonia (15.1%), Haemophilus influenza (13.7%), E. coli (11.0%), Enterobacter spp. (6.8%), Citrobacter spp. (2.7%), Providencia spp. (1.4%), and Pseudomonas aeruginosa (1.4%). The common recorded symptoms were fever (78%), neck stiffness (47%), vomiting (37%), poor feeding (19%), and irritability (16%). Statistical analysis showed that there was statistical significance associated developing of infection with malnutrition (low hemoglobin level), high house crowdness and irritability (P-value <0.05). The ANOVA statistical analysis showed that S. pneumonia has an impact on developing low hemoglobin level and leukocytosis. N. meningitides is still dominant and needs vaccination. The risk factors should be taken into consideration in any future plan.


Cardiovascular effects of the macrolide antibiotic tilmicosin, administered alone and in combination with propranolol or dobutamine, in conscious unrestrained dogs.
Tilmicosin(TM), a macrolide antibiotic and active ingredient in formulated Micotil 300 (Eli Lilly and Co., Indianapolis, IN, USA), is the active ingredient in a formulated animal product used for the treatment of respiratory tract infections in cattle. Owing to the concern of governmental regulatory agencies over the possibility of an accidental injection of the antibiotic to a livestock handler, the cardiovascular effects of sub lethal doses of TM were evaluated in conscious mixed-breed dogs. Left ventricular function, systemic arterial blood pressure, and heart rate (HR) responses to TM alone and in combination with propranolol(P) or dobutamine HCl(DOB) were evaluated. Dogs were instrumented with indwelling micromanometers implanted in the left ventricular chamber and in the thoracic aorta. Cardiovascular variables were recorded, and the peak value of the first derivative of left ventricular pressure (dp/dt(max)) was used as an index of left ventricular inotropic state. Six treatments were randomly assigned to each of the six dogs using a Latin square design. The six treatments were vehicle, TM alone (2.5 mg/kg of body weight), TM immediately followed by P, and TM immediately followed by 1 of 3 dosages of DOB infused for approximately 45 min. Additionally, doses of TM alone (0.25, 1.0, 2.5, and 5.0 mg/kg) were administered to complete a dose-response curve. TM caused dose dependent decreases in (dp/dt(max)) and aortic pulse pressure. HR increased dose-dependently. Left ventricular end-diastolic pressure increased at the 2.5 and 5.0 mg/kg dosages. Left ventricular systolic pressure was reduced dose-dependently at the 2.5 and 5.0 mg/kg dosages. Treatment with P exacerbated the negative inotropic effect and the decrease in left ventricular systolic pressure, but did not attenuate the tachycardia associated with TM treatment. DOB attenuated the changes in ventricular inotropic state in a dose-dependent manner. DOB infusion also restored left ventricular systolic pressure at dosages of 3 or 10 micrograms/min/kg. Our data indicate that toxic doses of TM may have a negative inotropic effect in conscious dogs. HR increased in a dose-dependent manner and was not the result of beta 1-receptor stimulation. DOB reversed some, but not all, of the effects caused by TM administration.