Is it possible to improve the bovine immune response to mastitis using immunogenetics?

Mastitis is a major problem for cows all over the world. For decades selection against mastitis has been performed through direct and indirect selection. Favorable outcomes of reduced mastitis incidence include: Economic gains, reduced use of antibiotics as well as improved animal welfare. Lately, new immunogenetic methods have emerged and the era of genomic selection has arrived. The innate and adaptive immune response, the bovine MHC and epigenetics are all of great relevance in this endeavor to improve immune response (IR) in cattle. Regarding breed differences in IR, few studies have been carried out on this subject and several factors need to be examined. The High Immune Response (HIR) technology is a patented method developed by the University of Guelph, it identifies so called high immune responders in the population. Another technique is Genome-wide association studies (GWAS), this method can be used to find the location of immune-related traits on the bovine genome. A few different GWAS will be accounted for. For example, GWAS searching for genome associations with natural antibodies (NAb) as well as for associations with antibody-mediated IR (AMIR) and cell-mediated IR (CMIR). Genomic selection (GS) is another modern technique in which estimated breeding values (EBV) are calculated based on single nucleotide polymorphisms (SNPs). This method requires a genotyped and phenotyped reference population and animals need only to be genotyped for the indicator markers to be assigned an EBV. This has reaped great success in increasing genetic gain as well as in decreasing generation intervals. Can these emerging methods surpass the results of the previously favored ones? The advantages as well as disadvantages are discussed. The disadvantages with the previous methods of selection for breeding are due to the time required and high expenses. Advantages with the emerging ones are faster results and shorter generation intervals. However, does the long-term genetic gain of GS actually surpass the traditional methods? Also, when manipulating the immune system, balance between responses must be considered. Otherwise, adverse effects like autoimmunity might appear. Sources of bias to the studies presented are also briefly mentioned. In conclusion, the area is still far too new to draw any major conclusions. However, it is a promising subject and further studies are of interest. The purpose of this literature study is to bring clarity to the question of whether it is possible to improve the bovine immune response to mastitis using immunogenetics

Kineziterapijos taikymas nudegimų traumos ūmiuoju ir chirurginio gydymo laikotarpiais: literatūros apžvalga

People recovering from burn injury experience a wide range of challenges throughout their recovery. Currently, the survival is not the only important issue in the treatment of burns. As the advancement and amelioration in burn treatment have improved significantly, the patients’ recovery and abilities to return to their pre-burn functional status are of equal importance as well. The results of recent scientific literature review (Kazis et al.) demonstrate that 28% of burn survivors never return to any form of employment and only 37% of burn survivors regain the fullness of previous employment. Physical therapy is a critical, though painful, component of burn rehabilitation therapy and includes a variety of physiotherapy treatment methods such as exercise therapy, cardiopulmonary training, joint mobilization, positioning, splint adjustment, etc. The application of physiotherapy after burn injury was found to improve physical capacity, muscle strength, body composition, and quality of life. The use of early physiotherapy is also recommended in patients treated in the intensive care unit

Burn survivors' pulmonary and muscular impairment, exercise tolerance and return-to-work following medical-vocational rehabilitation : A long-term follow-up

Objective: To follow up the long-term outcome in return-to-work (RTW) rate in burn-injury patients, and to determine the degree of impairment in pulmonary and muscular function and exercise tolerance. Design: A prospective, longitudinal follow-up study without a control group. Patients: Twenty-five burn-injury patients referred for medical-vocational rehabilitation. Methods: Return-to-work rate was followed after completed medical-vocational rehabilitation. Pulmonary function was evaluated with spirometry, diffusing capacity and radio spirometry. Exercise capacity was determined using a bicycle ergometer. Muscle functions evaluated in the arms and legs were: isokinetic torque, isometric strength, endurance and muscular strength utilization. Results: Return-to-work rate was 87%. During bicycle exercise tests the patients, on average, reached their expected workloads. The dominating lung function abnormality observed on lung scintigraphy was delayed wash-out time of inhaled radioactive xenon gas, suggesting airway obstruction. All tests of shoulder-flexor and knee-extensor muscle function showed large minimum-maximum differences. Mean isometric endurance of shoulder flexors was lower than mean of references, and isokinetic knee extensor torques were slightly lower. Conclusion: High return-to-work rates can be achieved after burn injury requiring hospital-ward care. Despite measurable impairments in muscle strength/endurance and pulmonary function in a substantial proportion of these patients, overall normal bicycle exercise capacity was observed except for a few cases

Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma—A Retrospective Analysis of A Swedish Cohort

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant RT were analyzed in patients referred to Karolinska University Hospital. Data were collected from 113 patients’ hospital records and MCPyV analyses were made in 54 patients (48%). We found a significantly better overall survival (OS) for women compared to men and a significant difference in OS in patients receiving adjuvant RT. Furthermore, we found that men with virus negative MCC have an increased risk for earlier death (HR 3.6). This indicates that MCPyV positive and negative MCC act as two different diseases, and it might be due to different mechanism in the immune response between male and female patients. This could have significance in tailoring treatment and follow-up in MCC patients in the future

Sex Differences in Overall Survival and the Effect of Radiotherapy in Merkel Cell Carcinoma—A Retrospective Analysis of A Swedish Cohort

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer where Merkel cell Polyomavirus (MCPyV) contributes to the pathogenesis. In an adjuvant setting, radiotherapy (RT) is believed to give a survival benefit. The prognostic impact of sex related to MCPyV-status and adjuvant RT were analyzed in patients referred to Karolinska University Hospital. Data were collected from 113 patients’ hospital records and MCPyV analyses were made in 54 patients (48%). We found a significantly better overall survival (OS) for women compared to men and a significant difference in OS in patients receiving adjuvant RT. Furthermore, we found that men with virus negative MCC have an increased risk for earlier death (HR 3.6). This indicates that MCPyV positive and negative MCC act as two different diseases, and it might be due to different mechanism in the immune response between male and female patients. This could have significance in tailoring treatment and follow-up in MCC patients in the future

<i>MiR-375</i> Regulation of LDHB Plays Distinct Roles in Polyomavirus-Positive and -Negative Merkel Cell Carcinoma

MicroRNA-375 (miR-375) is deregulated in multiple tumor types and regulates important targets involved in tumorigenesis and metastasis. This miRNA is highly expressed in Merkel cell carcinoma (MCC) compared to normal skin and other non-MCC skin cancers, and its expression is high in Merkel cell polyomavirus (MCPyV)-positive (MCPyV+) and low in MCPyV-negative (MCPyV&#8722;) MCC tumors. In this study, we characterized the function and target of miR-375 in MCPyV+ and MCPyV&#8722; MCC cell lines. Ectopic expression of miR-375 in MCPyV&#8722; MCC cells resulted in decreased cell proliferation and migration, as well as increased cell apoptosis and cell cycle arrest. However, in MCPyV+ MCC cells, inhibition of miR-375 expression reduced cell growth and induced apoptosis. Additionally, the expression of lactate dehydrogenase B (LDHB), a known target of miR-375, was inversely correlated with miR-375. Silencing of LDHB reduced cell growth in MCPyV&#8722; cell lines, while its silencing in MCPyV+ cell lines rescued the cell growth effect mediated by miR-375 inhibition. Together, our results suggest dual roles of miR-375 and LDHB in MCPyV and non-MCPyV-associated MCCs. We propose that LDHB could be a therapeutic target in MCC and different strategies should be applied in virus- and non-virus-associated MCCs