Search

OBJECTIVE To evaluate role of molecular (endothelin-1, soluble Fas-L, NT-proBNP, TNF-α, interleukin-1β,) and genetic factors (NOS3 (rs1799983), EDNRA (C + 70G, rs5335), NADPH oxidase (C242T, rs4673), p53 protein (polymorphic marker-Arg72Pro exon 4, rs1042522), NOS3 (Glu298Asp, rs1799983), Caspase 8 (CASP8, rs3834129 and rs1045485), interleukin-1β gene (Il-1β, rs1143634), TNF-α gene (rs1800629), SOD2 (rs4880), GPX1 (rs1050450) in development of anthracycline-induced cardiotoxicity (AIC) in women without cardiovascular diseases. METHODS A total of 176 women with breast cancer and without cardiovascular diseases who received anthracyclines were enrolled in the study. After the 12 months of chemotherapy (CT), all patients were divided into two groups: group 1 (n = 52) comprised patients with AIC, group 2 (n = 124) comprised those without it. RESULTS Based on ROC-analysis, levels of endothelin-1 of ≥9.0 pg/mL (AUC of 0.699), sFas-L of ≥98.3 ng/mL (AUC of 0.990), and NT-proBNP of ≥71.5 pg/mL (AUC of 0.994;) were identified as a cut-off values predicting AIC during 12 months after CT. Whereas, NT-proBNP and sFas-L were more significant predictors than endothelin-1 (p

The aim of the study is to develop a validated, rapid, simple and low-cost method for estimating ofloxacin and benzyl alcohol in a combined dosage. Materials and methods: Materials which were used ofloxacin pure substance and benzyl alcohol pure substance which were determined by UV spectrophotometer using ethanol 95% as a solvent and a blank. Results and discussion: Ofloxacin shows the absorption maxima at 300.0 ± 2.0 nm in ethanol 95% with an apparent concentration absorptivity of (30 to 90) µg/ml and benzyl alcohol shows the absorption maxima at 312.0 ± 2.0 nm in ethanol 95% with an apparent concentration absorptivity of (60 to 200) µg/ml, it was found that in the selected range of application of the method there is a directly proportional relationship between the concentration of ofloxacin and benzyl alcohol respectively, in the measured samples and the analytical signal, linear dependence is characterized by high correlation coefficients (R> 0.999)for both of drugs, which is considered acceptable for establishing strict linearity. Conclusion: The method has been verified as it has been proven simple, fast, accurate and low-cost method and does not require any expensive equipment for the analysis of Ofloxacin and benzyl alcohol separately and in a pharmaceutical mixture.

Although it is well established that individuals with psychopathic traits commit more crimes than individuals without psychopathic traits, the association between psychopathy and success in the cri...

A recent report in the journal, Neurology, documents age-normalized, nation-specific (e.g., United States and Western Europe), progressive decrease of dementia, beginning about 25 years ago. This observation has, thus far, not had explanation. We begin our proposed explanation with the following previous disease construct. (1) Some dementia is caused by innate immune over-response to infections. (2) The innate immune over-response occurs via excessive conversion of amyloid protein to α-sheet conformation. (3) This conversion evolved to inhibit invading microbes by binding microbe-associated α-sheet, e.g., in hyper-expanded capsid intermediates of some viruses. The rarity of human α-sheet makes this inhibition specific for microbial invaders. As foundation, here we observe directly, for the first time, extreme, sheet-like outer shell thinness in a hyper-expanded capsid of phage T3. Based on phage/herpesvirus homology, we propose the following. The above decrease in dementia is caused by varicella-zoster virus (VZV) vaccination, USFDA-approved about 25 years ago; VZV is a herpesvirus and causes chickenpox and shingles. In China and Japan, a cotemporaneous non-decrease is explained by lower anti-VZV vaccination. Co-assembly extension of α-sheet is relatively independent of amino acid sequence. Thus, we project that additional dementia is suppressible by vaccination against other viruses, including other herpesviruses.

There is a paucity of qualitative research on children’s and adolescents’ perceptions of their sexual abuse experiences. This paper aims to describe the narrative types and consequences of sexual abuse stories among ten female Filipino children and adolescents. Data were collected through semi-structured interviews and analyzed using dialogical narrative analysis. Results show that three narrative types appear in the stories of the survivors. These are the tragic resistance narrative, rescued slave narrative, and heroic saga narrative, and each of these narratives has idiosyncratic effects on the identities, affiliations, disclosure, and adjustment processes of the participants. The results show how symbolic cultural structures can have far-reaching consequences on sexually abused children and adolescents.

The report presents the results of the development of dental films with ketorolac trometamine based on the natural biodegradable polymers from the groups of sodium alginates and xanthan gums in combination with lightly crosslinked acrylic polymer carbopol. Physicochemical properties, such as moisture, mucoadhesion, thickness, tensile strength, disintegration in phosphate buffer were determined in obtained samples of this dosage form. A comparison of physicochemical properties of experimental samples and commercial model of dental film has allowed establishing the perspective composition of complex matrix of films with ketorolac trometamine for use in dentistry.

Optimal management of Type 2 diabetes mellitus (Type 2 DM) is impeded by widespread nonadherence to efficacious medication regimens. Cardiovascular disease (CVD) is the most common cause of morbidity and mortality among persons with Type 2 DM. In this work we evaluated the relationship between CVD and medication adherence to antihypertensives, oral hypoglycemic agents, and antidepressants among patients with Type 2 DM. We also sought to understand how patients perceived barriers to and facilitators of adherence to medications. Adherence to medications was measured in 72 primary care patients from the West Philadelphia area using electronic monitoring (Medication Event Monitoring System caps) over 12 weeks. Standard questions assessed the presence of CVD. Participants answered open-ended questions about barriers to and facilitators of medication adherence. Participants who had CVD were significantly less likely to achieve ≥80% adherence to an antidepressant, oral hypoglycemic agent, and antihypertensive medications at 12 weeks. Participants identified four themes related to medication adherence: Interference from Psychosocial Demands, Need for Technological Innovation, Awareness of Disease Severity, and Integrating Community Linkages. Interventions to improve medication adherence among persons with Type 2 DM in underserved communities may aim to address social determinants of health, create community linkages, emphasize disease severity and utilize apps which are integrated with existing primary care services.

Background Chronic stress is implicated in behavioral and health issues in cats, but methods for recognition, evaluation, and measurement of stress are lacking. Cortisol concentration is typically used as an indicator of stress. Objectives To evaluate use of an enzyme immunoassay to quantitate hair and nail cortisol concentrations (HCC and NCC) in cats and evaluate associations between HCC and NCC and behavioral, physical, and environmental correlates of chronic stress in cats. Animals Forty‐eight adult, owned or community cats. Methods Cross‐sectional study. Nail clippings and hair were collected from cats. Medical history and cat daily lifestyle questionnaires were completed by owners or caretakers. A commercial laboratory performed cortisol extraction and quantification using a validated enzyme immunoassay kit. Correlational and regression analyses were used to evaluate associations between HCC and NCC and behavioral, environmental, and medical factors. Results Hair and nail cortisol concentrations were significantly associated (r s = 0.70; P

Objective Our immediate objective is to determine whether infectivity of lytic podophage T3 has a relatively high persistence in the blood of a mouse, as suggested by previous data. Secondarily, we determine whether the T3 surface has changed during this mouse passage. The surface is characterized by native agarose gel electrophoresis (AGE). Beyond our current data, the long-term objective is optimization of phages chosen for therapy of all bacteremias and associated sepsis. Results We find that the persistence of T3 in mouse blood is higher by over an order of magnitude than the previously reported persistence of (1) lysogenic phages lambda and P22, and (2) lytic phage T7, a T3 relative. We explain these differences via the lysogenic character of lambda and P22, and the physical properties of T7. For the future, we propose testing a new, AGE-based strategy for rapidly screening for high-persistence, lytic, environmental podophages that have phage therapy-promoting physical properties.

Background Feline herpesvirus-1 (FHV-1) infection can result in serious morbidity and mortality, especially in kittens. Immunotherapy using liposome-toll-like receptor (TLR) ligand complexes (LTC) has been shown to activate innate immune responses. Objectives To determine in kittens whether mucosal administration of LTC before FHV-1 inoculation would decrease severity of clinical signs and decrease quantities of FHV-1 DNA in materials collected on oropharyngeal swabs. Animals Nineteen, 14-week-old, purpose-bred kittens. Methods Pilot clinical trial with 2 groups of kittens allocated to either an LTC or control group. The LTC were administered into both nares and the oropharynx of the 12 LTC group kittens, and all 19 kittens were inoculated with FHV-1 24 hours later. Clinical scores were determined daily for 28 days, and oropharyngeal mucosal materials were collected every 7 days to assess FHV-1 DNA quantities for comparison between groups. Results Conjunctivitis was more common in kittens in the control group on Days 15-28 (P = .01) and Days 1-28 (P = .02). Total respiratory scores were higher in the LTC group on days 15-28 (P = .03). The LTC group had significantly decreased FHV-1 DNA on swabs when compared to the control group on some postinoculation days, using 2 methods of calculation. Conclusions and clinical importance Administration of LTC to kittens was shown to decrease FHV-1 DNA and some manifestations of illness in kittens when administrated 24 hours before inoculation, suggesting clinical benefit.

Background Nonspecific induction of local innate immune responses by mucosally administered immunotherapy is a new approach to protection from upper respiratory tract infections. Therefore, a new liposome-toll-like receptor complex (LTC) immune stimulant was developed and investigated for its ability to activate innate immune responses in cats, both in vitro and in vivo, as part of an initial evaluation of LTC for use as an immunotherapeutic agent in cats. Objectives We hypothesized that LTC could activate innate immune responses in cats after topical application to nasal and oropharyngeal mucosal surfaces. Animals Mucosal immune responses to topical administration of LTC were assessed in 7 healthy, purpose-bred cats, and in vitro responses were assessed using blood samples from healthy cats. Methods Cytokine and cellular immune responses to LTC were evaluated in blood samples, nasal lavage specimens, and pharyngeal swabs from cats, using reverse transcriptase polymerase chain reaction assays, ELISA assays, and flow cytometry. Results Liposome-TLR complexes rapidly activated leukocytes in vitro, including upregulation of costimulatory molecule expression and cytokine production. Topical administration of LTC in healthy cats triggered rapid recruitment of monocytes to the nasal and oropharyngeal mucosa. Conclusions and clinical importance Liposome-TLR complexes were found to effectively activate innate immune responses in cats after mucosal administration. These findings suggest that LTC have potential for use as a new mucosally administered immunotherapy for nonspecific protection from viral and bacterial respiratory tract infections.

Cardiovascular disease remains the leading cause of mortality accounting up to 40% of all deaths, but, currently, cancer is prominent cause of death globally. Anthracyclines are the cornerstone of chemotherapy in women with breast cancer. However, its clinical use is limited by their cardiotoxic effects that can trigger heart failure development. Vascular toxicity of chemotherapy may be linked with endothelial dysfunction because anthracycline damage of endothelial cells can lead to the development and progression of cardiomyopathy by decreasing the release and activity of endothelial factors and, ultimately, endothelial cell death. These processes suppress anti-inflammatory and vascular reparative functions and initiate the development of future cardiovascular events. Recent studies have shown that chemotherapy may induce toxicity in the vascular endothelium and is accompanied by systemic endothelial dysfunction in patients with diagnosed cardiovascular diseases. Because the initial endothelial cell insult is likely asymptomatic, there is often a long delay between the termination of doxorubicin therapy and the onset of vascular disorders. In this case, genetic susceptibility factor will help to identify susceptible patients in the future. The objectives of this study were to evaluate prognostic role of molecular (endothelin-1) and genetic factors (gene polymorphisms of endothelial nitric oxide (NO) synthase (NOS3, rs1799983), endothelin-1 receptor type A (EDNRA, C+70G, rs5335) and NADPH oxidase (C242T, rs4673) in development of endothelial dysfunction and anthracycline-induced cardiotoxicity in women without cardiovascular diseases.

We review some aspects of the rapid isolation of, screening for and characterization of jumbo phages, i.e., phages that have dsDNA genomes longer than 200 Kb. The first aspect is that, as plaque-supporting gels become more concentrated, jumbo phage plaques become smaller. Dilute agarose gels are better than conventional agar gels for supporting plaques of both jumbo phages and, prospectively, the even larger (>520 Kb genome), not-yet-isolated mega-phages. Second, dilute agarose gels stimulate propagation of at least some jumbo phages. Third, in-plaque techniques exist for screening for both phage aggregation and high-in-magnitude, negative average electrical surface charge density. The latter is possibly correlated with high phage persistence in blood. Fourth, electron microscopy of a thin section of a phage plaque reveals phage type, size and some phage life cycle information. Fifth, in-gel propagation is an effective preparative technique for at least some jumbo phages. Sixth, centrifugation through sucrose density gradients is a relatively non-destructive jumbo phage purification technique. These basics have ramifications in the development of procedures for (1) use of jumbo phages for phage therapy of infectious disease, (2) exploration of genomic diversity and evolution and (3) obtaining accurate metagenomic analyses.

The production of volatile organic compounds (VOCs) during programmed cell death (PCD) is still insufficiently studied and their implication in the process is not well understood. The present study demonstrates that the release of VOSCs with presumed antioxidant capacity (methanethiol, dimethylsulfide and dimethyldisulfide) accompanies the cell death in chemical-stressed tobacco BY-2 suspension cultured cells. The cells were exposed to cell death inducers of biotic nature mastoparan (MP, wasp venom) and camptothecin (CPT, alkaloid), and to the abiotic stress agent CdSO4. The VOCs emission was monitored by proton-transfer reaction mass spectrometry (PTR-MS). The three chemicals induced PCD expressing apoptotic-like phenotype. The identified VOSCs were emitted in response to MP and CPT but not in presence of Cd. The VOSCs production occurred within few hours after the administration of the elicitors, peaked up when 20-50 % of the cells were dead and further levelled off with cell death advancement. This suggests that VOSCs with antioxidant activity may contribute to alleviation of cell death-associated oxidative stress at medium severity of cell death in response to the stress factors of biotic origin. The findings provide novel information about cell death defence mechanisms in chemical-challenged BY-2 cells and show that PCD related VOSCs synthesis depends on the type of inducer.

Surgical management of postamputation orthopedic disease (PAOD) in canine amputees has rarely been documented, and no reports describing outcome of stifle surgery in canine amputees are available. The objective of this multisite retrospective case series was to describe cases and evaluate satisfaction with and outcome of postamputation orthopedic surgery in canine amputees. Data was obtained through medical records and owner survey responses; data included signalment, amputation cause, diagnosis, surgical treatment, timeframes, and outcome assessment. Outcome was categorized as acceptable or unacceptable, and complications were classified as catastrophic, major, or minor. Eleven thoracic limb amputees and 6 pelvic limb amputees with surgically treated PAOD were identified. Surgically treated PAOD was reported at a median of 9.7 months (range 0.5-110 months) after amputation. All 17 amputees were treated for pelvic limb disease, predominantly for cranial cruciate ligament disease that occurred in 11 of 17 dogs. Major complications following orthopedic surgeries performed in 3 thoracic limb amputees consisted of infection (n = 2) and uncontrolled pain (n = 1). No major complications were reported following orthopedic surgeries performed in pelvic limb amputees. Acceptable mid-to-long-term outcome was achieved in 16 of the 17 canine amputees. Surgical treatment of pelvic limb disease did not appear to be associated with a high number of major complications in this case series. These findings suggest that orthopedic surgery, specifically stifle surgery, in canine amputees might be considered a feasible treatment option. Although there are inherent methodological limitations of retrospective studies and owner surveys, our case series provides new information that might help guide surgical treatment decisions in canine amputees suffering from orthopedic disease. Prospective studies using objective outcome measures evaluating surgical management of PAOD are necessary to confirm the provided information.

In this work, the involvement of programmed cell death (PCD) in the wound-induced postharvest browning disorder and senescence in butterhead lettuce (Lactuca sativa L.) fresh-cuts was studied. At the wounded (cut, bruised) sites, rapid browning, loss of chlorophyll and massive cell death, accompanied with accumulation of reactive oxygen species and increased electrolyte leakage occurred in a narrow strip of tissue adjacent the injury. The dead cell morphology (protoplast and nuclei shrinkage) together with the biochemical and physiological changes resembled necrotic PCD type. With a slight delay post-wounding, senescence associated with similar cell death features was initiated in distant non-wounded sites. In addition to necrotic PCD, both in wounded and senescing tissue, the appearance of empty cell corpses was observed, indicating that part of the cells might undergo vacuolar PCD (self-digestion of cellular content after vacuole collapse). The wounding-induced local cell death at the primary site of damage suggested that PCD may serve as a mechanism to seal-off the wound by building a physical barrier of dead cells. However, the cell death at sites remote from the wound suggests the distribution of long-distance senescence-inducing wound messengers. Trichomes in unwounded tissue often were the first to show H2O2 accumulation and dead cells; thereafter, the elevated H2O2 and cell death appeared in connecting cells and senescence progressed over larger areas. This suggests that trichomes may contribute to mediating the wound signalling leading to subsequent senescence. Our findings demonstrate that PCD is an integral part of the wound syndrome in fresh-cut lettuce.

Tele-technologies may be able to increase access to evidence-based exercise interventions for adults aging with long-term mobility disabilities. This population experiences substantial barriers in attending such programs in person, including lack of transportation to classes, inaccessible buildings where classes are held, and lack of appropriate modifications offered for this population of older adults. It is critical to overcome such barriers to ensure this population has an opportunity to receive the benefits of evidence-based programs. In this study we are translating an in-person evidence-based tai chi intervention, Tai Chi for Arthritis, to an online platform using videoconferencing software for those aging with long-term mobility disabilities. We will describe our approach of including users from the target population and industry representatives (videoconferencing software developer, Tai Chi for Arthritis program developer as well as local master trainer) in the adaptation of the intervention and present the key findings from doing so.

Blood-borne therapeutic phages and phage capsids increasingly reach therapeutic targets as they acquire more persistence, i.e., become more resistant to non-targeted removal from blood. Pathogenic bacteria are targets during classical phage therapy. Metastatic tumors are potential future targets, during use of drug delivery vehicles (DDVs) that are phage derived. Phage therapy has, to date, only sometimes been successful. One cause of failure is low phage persistence. A three-step strategy for increasing persistence is to increase (1) the speed of lytic phage isolation, (2) the diversity of phages isolated, and (3) the effectiveness and speed of screening phages for high persistence. The importance of high persistence-screening is illustrated by our finding here of persistence dramatically higher for coliphage T3 than for its relative, coliphage T7, in murine blood. Coliphage T4 is more persistent, long-term than T3. Pseudomonas chlororaphis phage 201phi2-1 has relatively low persistence. These data are obtained with phages co-inoculated and separately assayed. In addition, highly persistent phage T3 undergoes dispersal to several murine organs and displays tumor tropism in epithelial tissue (xenografted human oral squamous cell carcinoma). Dispersal is an asset for phage therapy, but a liability for phage-based DDVs. We propose increased focus on phage persistence—and dispersal—screening.

Background Healthcare workers play an important role in responding to the needs of the millions of children and adolescents who experience sexual abuse around the globe. A supportive child and adolescent-centered initial response is crucial for the physical and emotional wellbeing of survivors. Objective In 2017, the World Health Organization (WHO) published clinical guidelines for responding to child and adolescent sexual abuse. The review described in this paper informed the development of good practice statements on how best to deliver health care to survivors. Participants and setting This review examined the values and preferences of children and adolescents who were sexually abused, and of their caregivers and healthcare workers, regarding: 1) initial response to children and adolescents who have been sexually abused; and 2) obtaining medical history, conducting physical examination, and documenting examination findings. Methods Searches were conducted in Scopus, Pubmed, and the WHO’s Global Index Medicus (1 January, 1995-15 July 2016). All articles in English that indicated preferences of survivors, caregivers and/or healthcare workers in ensuring empathetic and trauma-informed care were included. Results Sixty-two articles were included and analyzed thematically. Key findings included the importance of providing care to survivors in a manner that respects the child or adolescent’s autonomy and wishes, ensures privacy and confidentiality, and makes services and facilities appropriate and welcoming. Conclusions Findings indicate how evidence-based recommendations can be delivered in a child or adolescent-centred and trauma-informed manner.

Suaahara, a nutrition-enhancement program in Nepal, conducted participatory community theater (CT) dramas with the goal of improving nutrition-related practices. To evaluate CT, a pre/posttest with randomized intervention and matched control sites was used. Dramas were conducted in Nawalparasi, Bajhang, and Sindhupalchowk Districts to represent the mountain, hill, and terai/plains regions. Within each study district, two intervention sites were randomly selected and two matched comparison sites were identified for inclusion in the study. At both baseline and endline, 600 individuals aged 18-59 (100 men and 100 women/district × 3 districts) were interviewed in the control sites and 600 in the intervention sites (1200 total respondents). Multivariate logistic analysis controlling for background characteristics found that CT attendance was significantly and positively associated with improved nutrition-related knowledge (adjusted odds ratio ratio [aORR] 10.2, p 0.001) and communication (aORR 2.4, p 0.001), hand washing after cleaning a defecating child (aORR 1.49, p 0.05), feeding children eggs (aORR 1.83, p 0.01), and feeding children meat and/or fish (aORR 2.10, p 0.01). This is the first study to rely on a pre/post matched intervention-control design to assess CT effects in a low-income setting. By testing the "difference-in-differences"-or the difference between intervention groups at baseline and endline minus that between controls at baseline and endline-the argument that the effects can be causally attributed to the intervention itself is strengthened. These findings support the continued and expanded use of CT to improve nutrition-related knowledge, communication, efficacy, and feeding practices as a valuable community-based, public health approach.

The paper reports the synthesis and in vivo pharmacological studies of a series of N-alkyl-1,5-benzodiazepine-2-ones. In this work, 19 novel benzodiazepine derivatives have been prepared and characterized by spectroscopic methods including 2D nuclear magnetic resonance techniques. Crystal structure of 1-benzyl-8-methyl-4-phenyl-1H-benzo[b][1,4]diazepin-2(3H)-one has also been determined by X-ray diffraction. Prediction of activity spectra for substances prediction and docking studies onto human serum albumin were conducted. Two compounds under these investigation showed high antihypoxic, tranquilizing, and anticonvulsant activity in vivo.

People with disabilities acquired in early to mid-life are living longer, contributing to growing numbers of older adults who are aging with disability, an understudied population likely to be underserved.This paper demonstrates the usefulness of the TechSAge Minimum Battery as a holistic assessment of health for people aging with disabilities.Survey data of socio-demographic and health characteristics were collected from 176 older adults with long-term vision, hearing, and/or mobility disabilities. A series of descriptive and bivariate analyses were conducted to illustrate the heterogeneity of the sample. An in-depth analysis of the subsample with vision difficulty was conducted to highlight the tool's value in assessing detailed contextual information for a specific disability.Prevalence of health conditions (M = 4.1; SD = 2.5), prescription medications (M = 4.1; SD = 3.9), and serious functional difficulties (M = 1.6; SD = 0.85) indicated a fair degree of comorbidity, but with considerable variation in number and type among individuals. Subjective health ratings were high overall, but lower scores were correlated with additional comorbidities (r = -0.31-0.40, p =.001). Analyses of the subsample with vision difficulty demonstrated heterogeneity in functional capacity, degree of impairment, duration, and use of supportive aids.Findings highlighted the heterogeneity among people aging with disability and demonstrated the importance of capturing multi-dimensional factors inclusive of an individual's capacity, context, and personal factors, which the Minimum Battery provides in an integrated assessment. Potential healthcare applications of the tool are discussed with implications for bridging aging and disability services.

Objective To conduct a comprehensive mapping of published indicators for monitoring and evaluation (M&E) of sexual and reproductive health (SRH) services and outcomes in humanitarian settings. Methods A systematic search of the peer-reviewed and grey literature published between January 2008 and May 2018 was conducted to identify all references describing indicator sets for M&E of SRH services and outcomes in humanitarian settings. The databases MEDLINE, Web of Science, and Global Health, as well as 85 websites of relevant organizations involved in humanitarian response were searched. Characteristics of identified indicator sets and data from individual indicators was extracted. Findings Of 3278 records identified, 20 met the review’s inclusion criteria and 9 existing indicator sets were identified. A total of 179 relevant indicators were included in the mapping, and removal of duplicates yielded 132 unique indicators. Twenty-seven percent fell within the maternal health domain, followed by the HIV/AIDS domain (26%) and the gender-based violence domain (23%). The distribution of indicators by type (process/output, outcome, impact) was balanced overall but varied substantially across domains. The most commonly used data collection platforms were facility-based systems or population-based surveys. Domains covered and indicator definitions were inconsistent across indicator sets. Conclusion Results demonstrate the need to standardize data collection efforts for M&E of SRH services and outcomes in humanitarian settings and to critically appraise the extent to which different domains should be covered. A core list of indicators is essential for assessing response status over time as well as across countries.

Objective Our immediate objective is to test the data-suggested possibility that in-agarose gel bacterial propagation causes gel fiber dislocation and alteration of cell distribution. We also test the further effect of lowering water activity. We perform these tests with both Gram-negative and Gram-positive bacteria. Data are obtained via electron microscopy of thin sections, which provides the first images of both bacteria and gel fibers in gel-supported bacterial lawns. The long-term objective is analysis of the effects of in-gel propagation on the DNA packaging of phages. Results We find that agarose gel-supported cells in lawns of Escherichia coli and Lysinibacillus (1) are primarily in clusters that increase in size with time and are surrounded by gel fibers, and (2) sometimes undergo gel-induced, post-duplication rotation and translation. Bacterial growth-induced dislocation of gel fibers is observed. One reason for clustering is that clustering promotes growth by increasing the growth-derived force applied to the gel fibers. Reactive force exerted by gel on cells explains cell movement. Finally, addition to growth medium of 0.94 M sucrose causes cluster-associated E. coli cells to become more densely packed and polymorphic. Shape is determined, in part, by neighboring cells, a novel observation to our knowledge.

Persistent infection of Anaplasma phagocytophilum (AP) after treatment and immunosuppression has not been studied in dogs infected with AP after Ixodes scapularis infestation. This descriptive pilot study evaluated 6 laboratory-reared beagles that were persistently positive for AP antibodies after infestation with wild-caught I. scapularis. After 20 weeks, 3 of 6 dogs were administered doxycycline orally for 28 days, and all 6 dogs were then administered prednisolone at 2.2 mg/kg orally for 14 days. Blood was collected from all 6 dogs and evaluated by complete blood count, AP antibodies, and AP DNA at the beginning of the study and on Week 24 through Week 28. Blood was collected from 5 of the dogs on Week 48. No dogs developed recognizable clinical signs of illness or clinically relevant complete blood count abnormalities. During Week 26 through Week 28, all 6 dogs were negative for AP DNA. On Week 48, the 2 doxycycline treated dogs available for testing were negative for AP DNA and antibodies; the 3 untreated dogs were negative for AP DNA but positive for AP antibodies. In this model, the prednisolone protocol used did not activate AP in dogs with chronic, vector-induced infection. Since PCR evidence of AP infection resolved in both groups of dogs, the effect doxycycline had in eliminating AP infection from I. scapularis-exposed dogs will require further study.

A 7-month-old female domestic shorthair cat was diagnosed with chronic regenerative hemolytic anemia characterized by increased osmotic fragility of unknown etiology. At 13 months of age, the cat was evaluated for acute collapse. The cat was icteric with severe hyperbilirubinemia but no hematocrit changes. Severe obtundation and lateral recumbency progressed to tetraparesis and loss of proprioception in all 4 limbs, and a cerebellar or brainstem lesion was suspected. Postmortem examination revealed suppurative cholangiohepatitis and acute neuronal necrosis in the nuclei of the brainstem and cerebellum, consistent with bilirubin encephalopathy. This is the first known occurrence of cholangiohepatitis and bilirubin encephalopathy in an adult cat with chronic hemolytic anemia. Although rare, bilirubin encephalopathy should be considered a possible sequela to hyperbilirubinemia in adult patients. It remains unknown whether increased osmotic fragility was related to the cholangiohepatopathy.

The professional literature on gatekeeping in social work education has grown; however, there remains a dearth in the literature regarding how educators truly work to engage students who are experiencing a psychiatric disability or other emotional problem. This qualitative study explored the experiences of 26 social work educators from 22 colleges and universities in the United States. Practice wisdoms emerged as interwoven strategies which encourage proactive interventions that accentuate students’ strengths through socially just opportunities. Identified strategies include having an awareness of psychosocial and environmental stressors that students may be experiencing, recognizing warning signs, approaching students, and building appropriate faculty–student relationships.

We present a procedure that allows a reliable determination of the elastic (Young's) modulus of soft samples, including living cells, by atomic force microscopy (AFM). The standardized nanomechanical AFM procedure (SNAP) ensures the precise adjustment of the AFM optical lever system, a prerequisite for all kinds of force spectroscopy methods, to obtain reliable values independent of the instrument, laboratory and operator. Measurements of soft hydrogel samples with a well-defined elastic modulus using different AFMs revealed that the uncertainties in the determination of the deflection sensitivity and subsequently cantilever's spring constant were the main sources of error. SNAP eliminates those errors by calculating the correct deflection sensitivity based on spring constants determined with a vibrometer. The procedure was validated within a large network of European laboratories by measuring the elastic properties of gels and living cells, showing that its application reduces the variability in elastic moduli of hydrogels down to 1%, and increased the consistency of living cells elasticity measurements by a factor of two. The high reproducibility of elasticity measurements provided by SNAP could improve significantly the applicability of cell mechanics as a quantitative marker to discriminate between cell types and conditions., This work was supported by grants to D.N., T.L., N.C., and J.J.U. (Spanish Ministry of Economy and Competitiveness FIS-PI14/00280), M.L. and J.B. (National Science Center NCN DEC-2011/01/M/ST3/00711), H.O. (Deutsche Forschungsgemeinschaft, Koselleck 68/1 and Centre of Excellence, Cells in Motion (CIM), University of Münster, Germany), S.B. and F.L. (ANR-10-EQPX-04-01) and A.D., E.T.H., R.G. (CSD2010-00024, ERC-AdG-340177). A.P. thanks the Dept. of Physics of the University of Milano for financial support under the project “Piano di Sviluppo dell’Ateneo per la Ricerca 2014”, actions: “A. Upgrade of instrumentation”, and “B. Support to young researchers”. We acknowledge the support of the International AFMBioMed Conference Association.

Non-disclosure of significant or emotionally charged information can have psychological and physical health consequences. Widowhood in Nepal is highly stigmatised and therefore is a sensitive topic. This study sought to understand why and to whom women do not disclose their status as widows. Thematic content analysis of 31 in-depth interviews and 6 focus groups was conducted with primarily high-caste widows of reproductive age from the Kathmandu Valley, Surkhet, Chitwan and Kavre districts of Nepal. A codebook was developed based upon recurring concepts and applied to all transcripts using Atlas.ti. Due to discomfort or stigmatisation, many women concealed their status as widows in the community through behaviours impacting their daily lives. Non-disclosure to children was frequently described, often as a way to protect them from psychological sequelae. Concealment of widowhood is a coping strategy Nepali women use to shield themselves against societal stigma and to manage bereavement in their children. Efforts are needed to support widows in dealing with mental health issues related to disclosure and the psychosocial impact on their children.

Background Consumption of herbal supplements in the developed world remains high. Cimicifuga racemosa (C. racemosa) extract, or black cohosh, is widely used as a hormone replacing and an anti-inflammatory agent, and has been shown to cause idiosyncratic hepatitis. The mechanism of acute liver injury in those cases is unclear. To date, hepatotoxic effects of C. racemosa have been studied mostly in vitro and in animal models. Data on human tissue is extremely limited, and mostly confined to histological findings of explanted livers. Methods We evaluated clinical data and examined surgical diagnostic liver biopsy specimens obtained from two female patients, who developed acute submassive liver necrosis, following consumption of C. racemosa. Both patients presented with acute elevation of liver enzymes, cholestasis, absence of reactivity to hepatitis A, B and C antibodies, and weak non-specific positivity for autoimmune serological markers. Initial histological interpretation of the biopsies, with focus on hepatic parenchyma and portal tracts, was done by light microscopy, followed by special stain series and immunohistochemical studies, including Cam 5.2, AE1/AE3, reticulin, α-actin, sirius red, and PAS with diastase. Areas of prominent lymphocytic infiltration of the periportal liver plate, observed microscopically, were further evaluated by electron microscopy (EM). 4HNE adduction study, an immunofluorescent assay, was performed to detect products of the oxidative damage and their localization in the liver parenchyma. Results Oxidative damage was evident by accumulation of 4HNE protein adducts in the cytoplasm of hepatocytes, secondary lysosomes and macrophages. We hypothesize that the adducted proteins, accumulated in the liver parenchyma, serve as autoantigens, which provoke an autoimmune response, and cause migration of lymphocytes to the affected regions. The formation of immunological synapses between hepatocytes and lymphocytes, predominantly T-lymphocytes, is demonstrated by electron microscopy. The autoimmune response induces piecemeal, or troxis necrosis of hepatocytes, a well described biological phenomenon, where lymphocytes gradually remove hepatocytes in a piecemeal fashion, slowly consuming them and leaving fragments of liver cells, or nubbins of anuclear cytoplasm of liver cell, at the interface between lymphocytes and hepatocytes. Conclusion The pattern of pathological injury of liver cells in both patients, following consumption of black cohosh, is identical to troxis necrosis, seen during autoimmune hepatitis. Recognition of the possibility of the acute hepatic injury by the herbal supplement black cohosh is essential for early accurate diagnosis, and timely patient management.

DNA packaging of phages phi29, T3 and T7 sometimes produces incompletely packaged DNA with quantized lengths, based on gel electrophoretic band formation. We discover here a packaging ATPase-free, in vitro model for packaged DNA length quantization. We use directed evolution to isolate a five-site T3 point mutant that hyper-produces tail-free capsids with mature DNA (heads). Three tail gene mutations, but no head gene mutations, are present. A variable-length DNA segment leaks from some mutant heads, based on DNase I-protection assay and electron microscopy. The protected DNA segment has quantized lengths, based on restriction endonuclease analysis: six sharp bands of DNA missing 3.7–12.3% of the last end packaged. Native gel electrophoresis confirms quantized DNA expulsion and, after removal of external DNA, provides evidence that capsid radius is the quantization-ruler. Capsid-based DNA length quantization possibly evolved via selection for stalling that provides time for feedback control during DNA packaging and injection.

We designed a new complex drug with antiallergic effect containing, in addition to the main component loratadine, a phytocomplex for an extra therapeutic effect. A collection of plants with sedative activity is chosen and the optimal agent for extraction of bioactive compounds (40% ethanol) and optimal degree of plant fragmentation are determined. Chemical composition of the sedative tea is evaluated by reverse phase HPLC. The marker components of the species are detected: xanthohumol and isoxanthohumol - Humulus lupulus cone components, Mentha piperita rosmarinic acid, and scutellareine, Menyanthes trifolia element - quercetin-3-rutinoside, and caffeic acid. Standardization of the species by the absolute graduation method in conversion to quercetin-3-rutinoside is suggested.

Group exercise classes have the potential to provide physical, cognitive, and emotional health benefits, through the physical activity performed as well as the social interaction among class participants. Substantial barriers exist for adults aging with lower-body mobility disabilities to engage in group exercise classes, including lack of transportation to classes, inaccessible buildings where classes are held, and lack of appropriate modifications offered for this population of older adults. Just as telehealth interventions have reduced barriers to healthcare, telewellness interventions can reduce barriers to engaging in wellness activities, such as group exercise classes. We will discuss a research study employing teleconferencing software to translate an evidence-based group tai chi class for adults aging with lower-body mobility disabilities. We will present the adaptation requirements identified to test the efficacy of a telewellness intervention for improving increasing social interaction and positive health behaviors (i.e., physical exercise frequency) for adults aging with disabilities.

Background The objective of this study is to assess if there were any changes in liver biopsies after treatment with S-adenosyl- l -methionine(SAMe) in alcoholic liver disease patients. Methods Liver biopsies of 14 patients were randomized for SAMe treatment at week 0 (biopsy #1) and at 24 weeks (biopsy #2). Patients received 1.2 g of SAMe or placebo by mouth daily and stopped alcohol intake. Biopsies were semi-quantitatively scored for: steatosis, inflammation, necrosis, fibrosis, apoptosis by TUNEL stain, percent fibrosis per square field, smooth muscle actin stain, Kupffer cells, polymorphonuclear leukocytes, lipogranules, lymphocytes, balloon cell formation, Mallory–Denk bodies, and duct metaplasia. Results Comparing treatment arm to placebo arm, no significant difference was found between biopsy #1 and biopsy #2. However, when both study arms were grouped together, there was decrease in smooth muscle actin stain, where the P-value = 0.027. Conclusion Treatment with SAMe did not show a statistically significant difference in the characteristics studied. However, when both the treatment and placebo arm data were grouped together to increase the n and power, there was a decrease in the smooth muscle actin stain, reflecting a decrease in stellate cells activation, likely due to the alcohol abstinence. This study suggests that it may not be beneficial to wait for more definitive treatment, like liver transplant in alcoholic liver disease patients, since the liver tissue remained largely with the same degree of pathology six months out, regardless of treatment.

Phospholipase D (PLD) and its product phosphatidic acid (PA) are incorporated in a complex metabolic network in which the individual PLD isoforms are suggested to regulate specific developmental and stress responses, including plant programmed cell death (PCD). Despite the accumulating knowledge, the mechanisms through which PLD/PA operate during PCD are still poorly understood. In this work, the role of PLD alpha 1 in PCD and the associated caspase-like proteolysis, ethylene and hydrogen peroxide (H2O2) synthesis in tomato suspension cells was studied. Wild-type (WT) and PLD alpha 1-silenced cell lines were exposed to the cell death-inducing chemicals camptothecin (CPT), fumonisin B1 (FB1) and CdSO4. A range of caspase inhibitors effectively suppressed CPT-induced PCD in WT cells, but failed to alleviate cell death in PLD alpha 1-deficient cells. Compared to WT, in CPT-treated PLD alpha 1 mutant cells, reduced cell death and decreased production of H2O2 were observed. Application of ethylene significantly enhanced CPT-induced cell death both in WT and PLD alpha 1 mutants. Treatments with the PA derivative lyso-phosphatidic acid and mastoparan (agonist of PLD/PLC signalling downstream of G proteins) caused severe cell death. Inhibitors, specific to PLD and PLC, remarkably decreased the chemical-induced cell death. Taken together with our previous findings, the results suggest that PLD alpha 1 contributes to caspase-like-dependent cell death possibly communicated through PA, reactive oxygen species and ethylene. The dead cells expressed morphological features of PCD such as protoplast shrinkage and nucleus compaction. The presented findings reveal novel elements of PLD/PA-mediated cell death response and suggest that PLD alpha 1 is an important factor in chemical-induced PCD signal transduction.

Dogs infected with canine parvovirus (CPV) can develop severe enteritis that requires supportive care until voluntary food and water consumption return. An oral recuperation fluid (ORF) may assist in the overall recovery from CPV. The hypotheses of the study were that dogs with naturally infected CPV would prefer the ORF to water and that dogs consuming the ORF would have a more rapid return to voluntary appetite and improved caloric intake during the initial recovery period compared with dogs consuming water. A total of 28 dogs with CPV were enrolled. Dogs were excluded if voluntary food or water intake was present at the time of study enrollment. Dogs were randomized to either an ORF or water group. The designated fluid was offered twice daily, followed by offering the opposite fluid 1 hour later if the designated fluid was refused. Dogs also received a standardized supportive treatment protocol. Beginning on day 2, all dogs were offered a gastrointestinal diet q8h, staggered with the fluid intake trials. A total of 40% (6/15) of dogs with CPV consumed the ORF as their designated fluid, and 31% (4/13) of dogs with CPV consumed water as their designated fluid ( P = .71). For those dogs who refused their designated fluid, 56% (5/9) of the dogs consuming ORF ultimately consumed water, and 22% (2/9) of the dogs consuming water also consumed the ORF ( P = .33). Dogs who consumed the ORF demonstrated a more rapid return to voluntary appetite (median = 1.5 days [range: 1-3]) compared with those that consumed water (median = 4.25 days [range: 1.5-5.5], P = .01) or neither fluid (median = 2 days [range: 1.5-5.5], P = .03). Additionally, those dogs consuming the ORF demonstrated greater caloric intake [median = 100% resting energy requirement (RER), range: 61%-100%] compared with those that consumed water (median = 19% RER; range: 9%-100%; P = .004) or neither fluid (median = 37% RER; range: 3-100; P = .05). This study suggests that some dogs with CPV voluntarily consume an ORF during the recovery phase of their illness and that consumption of the ORF may foster a more rapid return of voluntary appetite as well as improved caloric intake. Additional studies are warranted to further assess additional effects of this ORF during recovery from CPV.

Proteasome inhibition is a novel treatment for several hematological malignancies. However, resistance to the proteasome inhibitor bortezomib (BTZ, Velcade) is an emerging clinical impediment. Mutations in the β5 subunit of the proteasome, the primary target of BTZ, have been associated with drug resistance. However, the exact mechanism by which these mutations contribute to BTZ resistance, is still largely unknown. Toward this end, we here developed BTZ-resistant multiple myeloma (8226) and acute lymphoblastic leukemia (CCRF-CEM) cell line models by exposure to stepwise increasing concentrations of BTZ. Characterization of the various BTZ-resistant cells revealed upregulation of mutant β5 subunit of the proteasome. These newly identified β5-subunit mutations, along with previously described mutations, formed a mutation cluster region in the BTZ-binding pocket of the β5 subunit, that of the S1 specificity pocket in particular. Moreover, we provide the first evidence that the mechanism underlying BTZ resistance in these tumor cells is impaired binding of BTZ to the mutant β5 subunit of the proteasome. We propose that proteasome subunit overexpression is an essential compensatory mechanism for the impaired catalytic activity of these mutant proteasomes. Our findings further suggest that second-generation proteasome inhibitors that target the α7 subunit of the proteasome can overcome this drug resistance modality. © 2012 Macmillan Publishers Limited All rights reserved.

Piecemeal necrosis of the liver is thought to lead to liver cell necrosis. However the process does not lead to necrosis but rather lead to gradual progressive piecemeal removal of liver cell cytoplasm by T lymphocytes which are sensitized to antigens presented on the liver cell surface to form the immunologic synapse. The cytoplasm is taken up by the T cell and digested by the lysosome in the lymphocyte. By this mechanism the liver cell gradually disappears like the Cheshire cat in Alice in Wonderland.