Genetic basis of sow hyperprolificacy and litter size optimization based on a genome-wide association study.

Over the last few decades, there has been a constant increase in sow litter size, the consequences of which include parturition duration extension, an increase in the percentage of stillborn and hypoxic piglets, and increased variation in piglet birth weight, which reduces their vitality. As such, it seems clear that further increasing sow fertility will generate difficulties and costs in rearing numerous litters with low birth weights. Therefore, the current study aimed to analyze the genetic background of sow hyperprolifcacy using a genome-wide association study (GWAS). The research included 144 sows in the maternal component, divided into two equal groups. The first group (control) consisted of females giving birth to the optimal number of piglets in their third and fourth litters (14-16), while the second group (cases) included those with excessive litter size (>16). The analyzed sows were genotyped using Illumina's PorcineSNP60v2 BeadChip microarray, comprising 64,232 single nucleotide polymorphisms (SNPs). Statistical analysis using R included quality control of genotyping data and GWAS analysis based on five logistic regression models (dominant, codominant, overdominant, recessive, and log-additive) with a single SNP marker as the explanatory variable. On this basis, one SNP (SIRI0000069) was identified on chromosome seven within the EFCAB11 (EF-hand calcium binding domain 11) gene that had a statistically significant effect on sow hyperprolificacy. Additionally, ten SNPs (INRA0007631, ALGA0011600, ALGA0043433, ALGA0043428, M1GA0010535 ALGA00443338, ALGA0087116, MARC0056787, ALGA0112928, and ALGA0089047) had a relationship with the analyzed feature at a level close to significance, set at 1-5. These SNPs appear important since they are located on chromosomes on which a large number of quantitative trait loci (QTLs) and SNPs associated with reproductive characteristics, including litter size, have been identified.

Identification of SNP markers for canine mammary gland tumours in females based on a genome-wide association study - preliminary results.

Introduction: The development of genetic research over recent decades has enabled the discovery of new genetic markers, such as single nucleotide polymorphisms (SNPs). This, as well as the full sequencing of the dog genome, has enabled genome-wide association studies (GWAS) to be used in the search for genetic causes of canine mammary tumours (CMTs). Material and Methods: Genotypic data containing 175,000 SNPs, which had been obtained using the Illumina CanineHD BeadChip microarray technique, were available for analysis in this study. The data concerned 118 bitches, including 36 animals with CMT, representing various breeds and age groups. Statistical analysis was performed in two steps: quality control of genotyping data and genome-wide association analysis based on dominant, recessive, overdominant, codominant, and log-additive models with the single SNP effects. Results: A total of 40 different SNPs significantly associated with CMT appearance were detected. Moreover, twelve SNPs showed statistical significance in more than one model. Of all the significant SNPs, two, namely BICF2G630136001 in the overdominant model and TIGRP2P107898_rs9044787 in the log-additive model, reached the 5-8 significance level. The other SNPs were significant to a 1-5 level. Conclusion: In the group of SNPs indicated as significant in the GWAS analysis, several transpired to be localised within genes that may play an important role in CMT.

General vs Local Anesthesia for Percutaneous Endoscopic Lumbar Discectomy (PELD): A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review. OBJECTIVES: It remains unknown whether general anesthesia (GA) or local ± epidural anesthesia (LA) results in superior outcomes with percutaneous endoscopic lumbar discectomy (PELD). The present study sought to examine the impact of anesthesia type on patient-reported outcomes (PROs) and complications with PELD. METHODS: Systematic review and meta-analysis examining PELD performed under GA or LA was conducted. Patient-reported outcomes including Visual Analog Scale (VAS)-leg/back, and Oswestry Disability Index (ODI) scores were collected. Complication, recurrent disc herniation, durotomy, and reoperation rates as well as surgical data were recorded. All outcomes were compared between pooled studies examining GA or LA. RESULTS: Sixty-eight studies consisting of 5269 patients (724 GA, 4465 LA) were included in the meta-analysis. Overall complication rate was significantly higher in the GA group (9% vs 4%, P = .003). Durotomy rates, length of stay, recurrent disc herniation and reoperation rates were similar between groups. At the first follow-up timepoint, the LA group demonstrated significant improvements in VAS back and ODI scores (P < .05) while the GA group did not (P > .05). At the final follow-up (> 6 months), the percent of patients achieving an excellent McNab score was significantly higher in the GA vs LA group (P < .001). CONCLUSIONS: Percutaneous endoscopic lumbar discectomy with LA may be associated with greater short-term improvement in VAS back pain and ODI scores. General anesthesia may be associated with more durable pain relief but a higher complication rate. Further systematic investigation is necessary to determine what short and long term benefits are associated with PELD performed under LA and GA.

An effect of large-scale deletions and duplications on transcript expression.

Since copy number variants (CNVs) have been recognized as an important source of genetic and transcriptomic variation, we aimed to characterize the impact of CNVs located within coding, intergenic, upstream, and downstream gene regions on the expression of transcripts. Regions in which deletions occurred most often were introns, while duplications in coding regions. The transcript expression was lower for deleted coding (P = 0.008) and intronic regions (P = 1.355 × 10-10), but it was not changed in the case of upstream and downstream gene regions (P = 0.085). Moreover, the expression was decreased if duplication occurred in the coding region (P = 8.318 × 10-5). Furthermore, a negative correlation (r = - 0.27) between transcript length and its expression was observed. The correlation between the percent of deleted/duplicated transcript and transcript expression level was not significant for all concerned genomic regions in five out of six animals. The exceptions were deletions in coding regions (P = 0.004) and duplications in introns (P = 0.01) in one individual. CNVs in coding (deletions, duplications) and intronic (deletions) regions are important modulators of transcripts by reducing their expression level. We hypothesize that deletions imply severe consequences by interrupting genes. The negative correlation between the size of the transcript and its expression level found in this study is consistent with the hypothesis that selection favours shorter introns and a moderate number of exons in highly expressed genes. This may explain the transcript expression reduction by duplications. We did not find the correlation between the size of deletions/duplications and transcript expression level suggesting that expression is modulated by CNVs regardless of their size.

Mesenchymal stem cells in glioblastoma therapy and progression: How one cell does it all.

Mesenchymal stem cells (MSCs) are among the most investigated and applied somatic stem cells in experimental therapies for the regeneration of damaged tissues. Moreover, as it was recently postulated, MSCs may demonstrate anti-tumor properties. Glioblastoma (GBM) is a grade IV central nervous system tumor with no available effective therapy and an inevitably fatal prognosis. Experimental studies utilizing MSCs in GBM treatment resulted in numerous controversies. Native MSCs were shown to exert anti-GBM activity by controlling angiogenesis, regulating cell cycle, and inducing apoptosis. They also were used as sensitizing factors and vehicles delivering various anti-cancer compounds. On the other hand, some experiments revealed significant risks related to MSC-based therapies for GBM, such as enhancement of tumor cell proliferation, invasion, and aggressiveness. The following review elaborates on all mentioned contradictory data and provides a realistic, current clinical perspective on MSCs' potential in GBM treatment.

Clipping of a ruptured middle cerebral artery aneurysm in a patient with coronavirus disease 2019 (COVID-19): A case report.

AIM OF THE STUDY: The aim of this study is to present our suggestions for organization, personal protective equipment (PPE) use, work flow of the operating theater, and the treatment of patients with COVID-19 and co-existing neurological disease. MATERIALS AND METHODS: We present the case of a 70-year-old male who was transferred to our Department because of subarachnoid hemorrhage with ruptured right middle cerebral artery aneurysm and SARS CoV-2 infection. The emergency clipping of the aneurysm and hematoma evacuation was performed. According to the therapeutic committee guidelines, chloroquine was started for COVID-19 treatment. RESULTS: Postoperatively, the patient is in good condition, with the Glasgow Coma Scale (GCS) score of 15, with mild, left hemiparesis, 4+/5 points on the Lovett scale, without symptoms of acute respiratory distress syndrome (ARDS). No one from the stuff was infected during the treatment. CONCLUSIONS: Managing patients with infectious diseases such as COVID-19 presents many challenges and risks for healthcare personnel. Our experience suggests that by following strict safety protocols of PPE use, donning and doffing, and reducing operation time, the surgery may be safe for both the healthcare personnel and the patient.

Reproduction Indicators Related to Litter Size and Reproduction Cycle Length Among Sows of Breeds Considered Maternal and Paternal Components Kept on Medium-Size Farms.

The present research aimed to study twelve reproductive indicators related to litter size and the farrowing interval for three maternal (Polish Large White, Polish Landrace, and Yorkshire) and three paternal (Duroc, Berkshire, Hampshire) breeds, raised on two farms in Poland and a farm in the United States. The study included 196 sows (45 Polish Large White, 37 Polish Landrace, 26 Berkshire, 33 Duroc, 40 Yorkshire, and 15 Hampshire), which altogether gave birth to 736 litters. The Kruskal-Wallis test was used to verify the influence of the breed on the reproductive traits, with a post-hoc procedure for pairwise comparisons implemented in the pgirmes of R. The adegenet, ade4, and factoextra packages of R were used to conduct multivariate analysis of the traits by means of principal component analysis. The breed significantly (p ≤ 0.05) influenced the following traits related to litter size: the total number of piglets born per litter, the number and percentage of piglets born alive per litter, the percentage of stillborn piglets per litter, the number and percentage of weaned piglets per litter; and those related to the farrowing interval: the lengths of gestation, lactation, the farrowing-to-conception interval, and the farrowing interval. The breed did not statistically significantly influence the number of stillborn piglets per litter and the length of the weaning-to-conception interval. Polish Landrace and Polish Large White sows had the highest numbers of born (for both, the mean of 14.0), born alive (12.9 and 12.7), and weaned piglets (11.5 and 10.5), which statistically significantly differed from these parameters in the other breeds. Polish Landrace sows significantly differed from all the other breeds in terms of the percentage of weaned piglets (84.1%), while Berkshire sows in terms of gestation length (118.4 days).

Transformation of a large multi-speciality hospital into a dedicated COVID-19 centre during the coronavirus pandemic.

INTRODUCTION: The article describes the process of converting a large multi-specialized hospital into one dedicated to COVID-19 patients, and present established standards of work organization in all the wards and training system of the medical and supporting staff. The several weeks pandemic of the COVID-19 disease has forced the healthcare systems of numerous countries to adjust their resources to the care of the growing number of COVID-19 patients. Managers were presented with the challenge of protecting the healthcare workers from transmission of the disease within medical institutions, and issues concerning the physical and psychological depletion of personnel. MATERIAL AND METHODS: Based on analyses of the structure and work processes in Central Clinical Hospital (CCH) reconstructive strategic plan was developed. It included: division of existing wards into observation and isolation wards; installing locks; weekly plan for supplying personal protection equipment (PPE); designating new access to the hospital and communication routes; training of medical and supporting staff. The plan was implemented from the first days of conversion of the hospital. RESULTS: The wards of the CCH were converted for observation and isolation, and each one was fitted with sanitary locks. There was a big improvement in the supply of PPE for the medical staff. Separation of the 'dirty' and 'clean' parts of the CCH were attained, and widespread intensive training not only protected personnel against infections, but also diminished unrest which was discernable at the beginning of conversion. CONCLUSIONS: The transformation efforts will ultimately be appraised at the end of the epidemic, but the data looks encouraging. Two weeks after conversion, the testing of hospital Staff was started and by the end of April, 459 tests were had been conducted, of which only 11 were positive.

Mesenchymal stem cells injected into carotid artery to target focal brain injury home to perivascular space.

Rationale: The groundbreaking discovery of mesenchymal stem cells (MSCs) with their multifaceted benefits led to their widespread application in experimental medicine, including neurology. Efficient delivery of MSCs to damaged regions of the central nervous system may be a critical factor in determining outcome. Integrin VLA-4 (α4ß1) coded by ITGA4 and ITGB1 genes is an adhesion molecule expressed by leukocytes, which is responsible for initiation of their diapedesis through cell docking to the inflamed vessel wall expressing VCAM1 receptor. This function of VLA-4 has been recapitulated in neural stem cells and glial progenitors. Thus, it was prudent to investigate this tool as a vehicle driving extravasation of MSCs. Since MSCs naturally express ITGB1 subunit, we decided to supplement them with ITGA4 only. The purpose of our current study is to investigate the eventual fate of IA delivered ITGA4 engineered and naive MSCs. Methods: mRNA-ITGA4 transfected and naive MSCs were injected to right internal carotid artery of rats with focal brain injury. Through next three days MSC presence in animals' brain was navigated by magnetic resonance imaging. Transplanted cell location relative to the brain blood vessels and host immunological reaction were analyzed post-mortem by immunohistochemistry. The chemotaxis of modified and naive MSCs was additionally examined in in vitro transwell migration assay. Results: Both naïve and ITGA4-overexpressing cells remained inside the vascular lumen over the first two days after IA infusion. On the third day, 39% of mRNA-ITGA4 modified and 51% naïve MSCs homed to perivascular space in the injury region (p=NS). The gradual decrease of both naive and mRNA-ITGA4 transfected hBM-MSCs in the rat brain was observed. mRNA-ITGA4 transfected MSCs appeared to be more vulnerable to phagocytosis than naïve cells. Moreover, in vitro study revealed that homogenate from the injured brain repels migration of MSCs, corroborating the incomplete extravasation observed in vivo. Conclusions: In summary, IA transplanted MSCs are capable of homing to the perivascular space, an integral part of neurovascular unit, which might contribute to the replacement of injured pericytes, a critical element facilitating restoration of CNS function. The mRNA-ITGA4 transfection improves cell docking to vessel but this net benefit vanishes over the next two days due to fast clearance from cerebral vessels of the majority of transplanted cells, regardless of their engineering status. The drawbacks of mRNA-ITGA4 transfection become apparent on day 3 post transplantation due to the lower survival and higher vulnerability to host immune attack.

Clinical characteristics and short-term outcomes of patients with coronavirus disease 2019: a retrospective single-center experience of a designated hospital in Poland.

INTRODUCTION: Since the first reported case of coronavirus disease 2019 (COVID­19) in Poland, the worldwide pandemic has spread throughout the country, leading to many hospital admissions. There has been an urgent need to determine clinical characteristics of Polish patients with laboratory­confirmed severe acute respiratory syndrome coronavirus 2 (SARS­CoV 2) infection in the clinical setting. OBJECTIVES: The aim of this retrospective study was to outline characteristics and short­ term outcomes of SARS­CoV­2-positive patients. PATIENTS AND METHODS: We retrospectively assessed 169 consecutive patients with laboratory­ confirmed COVID­ 19 with regard to their clinical manifestations, radiological findings, treatment, complications, and outcomes. RESULTS: Of the 169 patients, more than half was aged 65 years or older (88; 52.1%), 51.5% were male, and 78.3% had comorbidities. The majority of patients (106; 62.7%) were transferred from outbreak locations in medical facilities. The most common symptoms on admission were fever (42%), shortness of breath (35%), and fatigue (33%). Twenty seven (15.4%) patients required intensive care unit admission. Overall mortality was 26.3% (n = 46) and was significantly higher in patients transferred from other facilities (38 out of 106; 35.8%), than in patients admitted directly to the hospital (8 out of 63; 12.69%; P <0.001). Seventeen out of 29 patients admitted to the intensive care unit died (mortality, 58.6%), including 30 out of 41 patients with acute respiratory distress syndrome (73.2% mortality rate). CONCLUSIONS: Polish patients with COVID­19 have similar characteristics and risk factors for adverse outcomes to those observed in countries in which outbreaks occurred earlier. Significantly higher mortality in patients transferred from other centers warrants special attention and transfer policy should be verified.

sPECAM-1 and sVCAM-1: Role in Pathogenesis and Diagnosis of Chronic Hepatitis C and Association with Response to Antiviral Therapy.

AIM: To analyze the relationship between pretreatment clinical or histological features and the levels of soluble platelet-endothelial cell adhesion molecule-1 (sPECAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1), to determine their serum concentration in responders and nonresponders, to evaluate the behavior under antiviral therapy, to explain their relationship in response to therapy and to assess the association between these two molecules in chronic hepatitis C (CHC). METHODS: The study analyzed 65 CHC patients, including 50 patients (Group 1) with marked fibrosis treated with peginterferon plus ribavirin, 15 patients without fibrosis (Group 2) and 13 healthy volunteers (the control group, Group 3). sPECAM-1 and sVCAM-1 levels were assessed by an immunoenzymatic method (ELISA) before and after therapy. RESULTS: sVCAM-1 and sPECAM-1 serum concentrations increased significantly in CHC patients (p<001). sPECAM-1 levels corresponded to inflammatory grade (p = 0.03) and fibrosis stage (p =0.01). sVCAM-1 increased only in advanced fibrosis. After therapy, sPECAM-1 levels decreased significantly (p<001) with no difference between responders and nonre-sponders. sPECAM-1 correlated positively with inflammatory activity (p = 0.02), fibrosis stage (p<001), sVCAM-1 (r=0.56, p<001) and alanine aminotransferase activity (r = 0.30, p = 0.05). Receiver operating characteristic curve analysis showed a good discriminant power of serum sPECAM-1 concentrations for detection of liver fibrosis - stage 0 versus stage 1-3, AUC 0.81; cut-off 221.0 ng/ml and a fair discriminant power for distinguishing bridging fibrosis, AUC 0.78; cut-off 237.1 ng/ml. CONCLUSIONS: Hepatitis C virus (HCV) infection results in upregulation of sPECAM-1 and sVCAM-1. sPECAM-1 levels are related to necroinflammatory activity and may also identify patients with advanced fibrosis. The sPECAM-1 value was decreased by therapy but its measurement cannot predict therapy outcome and confirm HCV persistence. sPECAM-1 may influence VCAM-1 expression.