Hydrogels for delivery of therapeutic compounds

In some aspects, methacrylate co-polymers crosslinked with an enzymatically cleavable peptide linker are provided and may be used for the oral delivery of a therapeutic. The peptide linker may be cleavable by an enzyme in the small intestine and may allow for the delivery of a therapeutic protein or nucleic acid to the small intestine. Also provided are methods of using the polymers for the treatment of a disease.Board of Regents, University of Texas Syste

Persistent Elevated Expression of Cytokine Transcripts in Ganglia Latently Infected with Herpes Simplex Virus in the Absence of Ganglionic Replication or Reactivation

AbstractInfection of mouse trigeminal ganglia by herpes simplex virus induces cytokine expression that persists long after infectious virus or viral antigens become undetectable. To examine mechanisms underlying this phenomenon, we used a thymidine kinase mutant, dlsptk, which fails to replicate in ganglia and does not reactivate upon ganglionic explant. Using quantitative reverse transcriptase–polymerase chain reaction assays, we found that levels of interferon-γ and tumor necrosis factor-α transcripts in dlsptk-infected ganglia were lower than those in wild type-infected ganglia, but were significantly (eight- to 10-fold) higher than those in mock-infected ganglia from Day 3 to Day 100 postinfection. We also studied latency-associated transcript (LAT) negative mutants that exhibit increased expression of productive cycle transcripts in ganglia. Ganglia infected with these mutants contained levels of cytokine transcripts similar to those in wild type-infected ganglia; any increases in viral antigen expression mediated by the LAT deletion were not accompanied by increased cytokine expression. Thus, neither viral replication, the ability to reactivate, nor LAT expression in ganglia is required for persistent elevated cytokine expression. The results provide indirect evidence that low-level expression of viral productive cycle genes in neurons can provide signals that elicit cytokine expression

Barriers to help-seeking from healthcare professionals amongst women who experience domestic violence:A qualitative study in Sri Lanka

BACKGROUND: Domestic violence (DV) is a major global public health problem which is associated with significant adverse consequences. Although Sri Lankan women who experience DV receive treatment from healthcare professionals (HCPs) for DV related physical and psychological problems, disclosure of DV within health services is quite low. This study explored barriers to disclosure of DV to HCPs among Sri Lankan women who experience DV. METHOD: This qualitative study took place in the Central Province of Sri Lanka. Twenty women who had experienced DV were recruited from Gender Based Violence Centers (Mithuru Piyasa Centers) and a toxicology unit of the two selected hospitals. Participants were purposefully selected using maximum variation sampling technique. In-depth interviews were conducted until data saturation was reached. Interviews were recorded, and analyzed using thematic analysis. RESULTS: Survivor related barriers to help seeking included women’s lack of knowledge and perceptions about the role of HCPs, lack of confidence in HCPs, fear of repercussions, personal attitudes towards DV, and their love and loyalty towards the perpetrator. Women preferred it if HCPs initiated discussions about DV, and they valued it when HCPs could be confidential and protect their privacy, and give enough time for DV related issues during consultations. A perpetrator related barrier was the controlling behavior of the perpetrator. Social stigma and social and cultural norms about the role of women emerged as the socio-cultural constraints to disclosure. CONCLUSIONS: Barriers to help seeking for DV from HCPs exist at individual, healthcare level, and societal level. Community programs are needed to increase women’s access to healthcare services and interventions should be implemented to develop effective, preventive, and supportive strategies at the healthcare system level. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-022-13116-w

Families, children, migration and AIDS

Migration is very often a family affair, and often involves children, directly or indirectly. It may give rise to better quality of life for an entire family, or to bitter disappointment, and may also increase vulnerability to HIV and AIDS. This review, carried out for the Joint Learning Initiative on Children and AIDS, links the literature on “migration”, on “HIV and AIDS” and on “families”. Three themes are sketched: (1) As both HIV prevalence and circular migration increase, former migrant workers affected by AIDS may return to their families for care and support, especially at the end of life, often under crisis conditions. Families thus lose promising members, as well as sources of support. However, very little is known about the children of such migrants. (2) Following patterns of migration established for far different reasons, children may have to relocate to different places, sometimes over long distances, if their AIDS-affected parents can no longer care for them. They face the same adaptation challenges as other children who move, but complicated by loss of parent(s), AIDS stigma, and often poverty. (3) The issue of migrant families living with HIV has been studied to some extent, but mainly in developed countries with a long history of migration, and with little attention paid to the children in such families. Difficulties include involuntary separation from family members, isolation and lack of support, disclosure and planning for children's care should the parent(s) die and differences in treatment access within the same family. Numerous research and policy gaps are defined regarding the three themes, and a call is made for thinking about migration, families and AIDS to go beyond description to include resilience theory, and to go beyond prevention to include care

Salmonella Contamination of Swine Carcasses and Pork Products

This paper includes results from two separate studies: one surveyed the level of contamination at four points during the slaughter and processing of chilled pork; the second study surveyed ground pork from 17 companies representing five different segments of ground pork distribution. Regarding the carcass study, the highest percentage of Salmonella spp. isolated from the different sampling sites by a swab method, for both pork loin and ham surfaces, was 4.4% after the singeing step of the slaughter process. Overall, 1.7% of all pork samples showing positive isolations for Salmonella spp., however, there were no Salmonella spp. found in one of the three plants surveyed. Salmonella were isolated primarily from pork before fabrication and refrigerated storage. A continous reduction in the numbers of Salmonella spp. isolates was detected from the point of singeing to the point of fabrication. No Salmonella spp. were isolated from vacuumpackaged pork stored for 36 days at 2EC. The purpose of the ground pork project was to survey current sources of ground pork, and to determine the effects of different handling methods and raw material sources on the microbial quality of ground pork. There were no significant differences in the microbial counts, or prevalence of selected organisms, between the different types of companies from which the ground pork was obtained. Estimated variance among locations, samples and sample duplicates show that additional ground pork samples are needed to strengthen the results of this study

Evaluating deformation behavior of a TBC-System during thermal gradient mechanical fatigue by means of high energy X-ray diffraction

Applications of TBC-systems involve complex thermal mechanical loading pattern including transient thermal gradients across the coated system, which result in multiaxial stresses and stress gradients affecting the damage behavior. In an ongoing research, starting more than 10 years ago, the authors developed laboratory test facilities for evaluating the damage behavior of TBC-systems for gas turbine blades in aeroengines under realistic thermal mechanical loading conditions [1]. Fatigue tests involving thermal gradients have been conducted and damage behavior in dependence of load pattern and pre heat treatment has been intensively investigated on TBC-systems comprising a partially yttria stabilized zirconia (YSZ) topcoat and a MCrAlY bond coat both applied by electron physical vapor deposition (EB-PVD) onto nickel based super alloys serving as substrate [2]. Numerical analyses by means of FE-calculations did provide hypotheses explaining the observed damage behavior [3], but even though the results are plausible they did depend on reasonable assumptions on materials properties since reliable data on the properties of the thin coating layers are still lacking, especially for high temperatures. High energy X-ray diffraction can provide the requested information since it is possible to achieve information on the local deformation processes in each layer with high spatial resolution, and short acquisition times allow for in situ investigation of time dependent deformation processes. A new test facility based on concepts after [1] for cyclic thermal loading of tubular specimens and applying a controlled thermal gradient across the coated specimen’s wall has been developed for implementation into an electro-mechanical test machine at the advanced photon source (APS) at Argonne National Laboratory. A precision positioning rig allows for exact µm-positioning of the entire test machine with respect to the focused X-ray beam, and X-ray diffraction patterns were taken using a 2D detector, giving accurate 360° lattice parameter data [4]. Tests have been performed with varying thermal and mechanical load schemata intending to determine material properties from the respective strain response. The beam energy was 65 keV, and throughout all experiments the beam scanned through the coating layers with a window and step size of 30 µm. Strain data were acquired in plane parallel to the specimen’s length axis and out of plane. Results of the strain data evaluation will be presented and discussed. Exemplary results are: - Elastic properties of the YSZ showed a gradient across the coating thickness reflecting the microstructure gradient of the YSZ resulting from the EB-PVD process. - The YSZ strain was – below the deposition temperature - in plane compressive and out of plane tensile, which is a consequence of (i) the higher thermal expansion coefficient of YSZ with respect to the substrate and (ii) the cylindrical specimen geometry with the YSZ at the outer surface. [1] M. Bartsch, G. Marci, K. Mull, C. Sick, Adv. Eng. Mater. (1999), 1(2), 127–9 [2] M. Bartsch, B. Baufeld, S. Dalkilic, L. Chernova, M. Heinzelmann, Int. J. Fatigue (2008) 30, 211–8 [3] M. T. Hernandez, A. M. Karlsson, M. Bartsch, Surf. Coat. Technol. (2009) 203, 3549–58 [4] S.F. Siddiqui, K. Knipe, A. Manero, C. Meid, J. Wischek, J. Okasinski, J. Almer, A.M. Karlsson, M. Bartsch, S. Raghavan, Review of Scientific Instruments (2013) 84, 08390

Feasibility of hair sampling to assess levels of organophosphate metabolites in rural areas of Sri Lanka

AbstractMeasuring chronic pesticide exposure is important in order to investigate the associated health effects. Traditional biological samples (blood/urine) are difficult to collect, store and transport in large epidemiological studies in settings such as rural Asia. We assessed the acceptability of collecting hair samples from a rural Sri Lankan population and found that this method of data collection was feasible. We also assessed the level of non-specific metabolites (DAPS) of organophosphate pesticides in the hair samples. The median concentration (pg/mg) of each DAP was: diethyl phosphate: 83.3 (IQI 56.0, 209.4); diethyl thiophosphate: 34.7 (IQI 13.8, 147.9); diethyl dithiophosphate: 34.5 (IQI 23.4, 55.2); and dimethyl phosphate: 3 (IQI 3, 109.7). Total diethylphosphates were recovered in >80% of samples and were positively correlated with self-reported pesticide exposure

Psychiatric morbidity and suicidal behaviour in low- and middle-income countries: a systematic review and meta-analysis

Background: Psychiatric disorders are reported to be present in 80-90% of suicide deaths in high-income countries (HIC), but this association is less clear in low- and middle-income countries (LMIC). There has been no previous systematic review of this issue in LMIC. The current study aims to estimate the prevalence of psychiatric morbidity in individuals with suicidal behaviour in LMIC. Methods and findings: PubMed, PsycINFO, and EMBASE searches were conducted to identify quantitative research papers (any language) between 1990 and 2018 from LMIC which reported on the prevalence of psychiatric morbidity in suicidal behaviour. We used meta-analytic techniques to generate pooled estimates for any psychiatric disorder and specific diagnosis based on ICD-10 criteria. A total of 112 studies (154 papers) from 26 LMIC (India: 25%; China: 15%; and Other LMIC: 60%) were identified, including 18 non-English articles. They included 30030 individuals with non-fatal suicidal behaviour and 4996 individuals who had died by suicide. Of the 15 studies (5 LMIC) that scored highly on our quality assessment, prevalence estimates for psychiatric disorders ranged between 30% and 80% in suicide deaths, and between 3% and 86% in those who engaged in non-fatal suicidal behaviour. There was substantial heterogeneity between study estimates. Fifty-eight percent (95% CI 46-71%) of those who died by suicide and 45% (95% CI 30-61%) of those who engaged in non-fatal suicidal behaviour had a psychiatric disorder. The most prevalent disorder in both fatal and non-fatal suicidal behaviour was mood disorder (25% and 21% respectively). Schizophrenia and related disorders were identified in 8% (4-12%) of those who died by suicide and 7% (3-11%) of those who engaged in non-fatal suicidal behaviour. In non-fatal suicidal behaviour, anxiety disorders, and substance misuse were identified in 19% (1-36%) and 11% (7-16%) of individuals respectively. This systematic review was limited by the low number of high-quality studies and restricting our searches to databases which mainly indexed English language journals. Conclusions: Our findings suggest a possible lower prevalence of psychiatric disorders in suicidal behaviour in LMIC. We found very few high-quality studies and high levels of heterogeneity in pooled estimates of psychiatric disorder, which could reflect differing study methods or real differences. There is a clear need for more robust evidence in order for LMIC to strike the right balance between community-based and mental health focused interventions

Critical Control Points for Profitability in the Cow-Calf Enterprise

Financial, economic, and biological data collected from cow-calf producers who participated in the Illinois and Iowa Standardized Performance Analysis (SPA) programs were used in this study. Data used were collected for the 1996 through 1999 calendar years, with each herd within year representing one observation. This resulted in a final database of 225 observations (117 from Iowa and 108 from Illinois) from commercial herds with a range in size from 20 to 373 cows. Two analyses were conducted, one utilizing financial cost of production data, the other economic cost of production data. Each observation was analyzed as the difference from the mean for that given year. The independent variable utilized in both the financial and economic models as an indicator of profit was return to unpaid labor and management per cow (RLM). Used as dependent variables were the five factors that make up total annual cow cost: feed cost, operating cost, depreciation cost, capital charge, and hired labor, all on an annual cost per cow basis. In the economic analysis, family labor was also included. Production factors evaluated as dependent variables in both models were calf weight, calf price, cull weight, cull price, weaning percentage, and calving distribution. Herd size and investment were also analyzed. All financial factors analyzed were significantly correlated to RLM (P \u3c .10) except cull weight, and cull price. All economic factors analyzed were significantly correlated to RLM (P \u3c .10) except calf weight, cull weight and cull price. Results of the financial prediction equation indicate that there are eight measurements capable of explaining over 82 percent of the farm-to-farm variation in RLM. Feed cost is the overriding factor driving RLM in both the financial and economic stepwise regression analyses. In both analyses over 50 percent of the herd-to-herd variation in RLM could be explained by feed cost. Financial feed cost is correlated (P \u3c .001) to operating cost, depreciation cost, and investment. Economic feed cost is correlated (P \u3c .001) with investment and operating cost, as well as capital charge. Operating cost, depreciation, and capital charge were all negatively correlated (P \u3c .10) to herd size, and positively correlated (P \u3c .01) to feed cost in both analyses. Operating costs were positively correlated with capital charge and investment (P \u3c .01) in both analyses. In the financial regression model, depreciation cost was the second critical factor explaining almost 9 percent of the herd-to-herd variation in RLM followed by operating cost (5 percent). Calf weight had a greater impact than calf price on RLM in both the financial and economic regression models. Calf weight was the fourth indicator of RLM in the financial model and was similar in magnitude to operating cost. Investment was not a significant variable in either regression model; however, it was highly correlated to a number of the significant cost variables including feed cost, depreciation cost, and operating cost (P \u3c .001, financial; P \u3c .10, economic). Cost factors were far more influential in driving RLM than production, reproduction, or producer controlled marketing factors. Of these cost factors, feed cost had by far the largest impact. As producers focus attention on factors that affect the profitability of the operation, feed cost is the most critical control point because it was responsible for over 50 percent of the herd-to-herd variation in profit