Airborne Infection Risks from Covid-19 in Meat Processing Plants and Different Solutions to Mitigate the Risks

Meat processing plants are linked to the rapid spread of COVID-19 cases. A related literature review shows a lack of proper ventilation standards for the meat processing plants for workers’ health and safety. Ventilation rates in these plants are considered adequate if the meat products are unadulterated. Thus, the air distribution and ventilation rate experiments were conducted in three meat processing plants. These measured ventilation rates were either compared to ASHRAE Std. 62.1 (2019) for a similar space or the design values provided by the plant’s administration. The measured values were low in common spaces, such as the cafeteria and locker rooms. In addition, the total airflow rates from the diffusers also characterize the air distribution. A modified Wells-Riley model was used to calculate the COVID-19 airborne infection risk for two selected spaces to compare different engineering solutions, such as installing portable air cleaners, using ultraviolet lights in the upper room and in-duct, better filtration systems, and enhanced ventilation rates. Infection risks in a single space were used to rank these solutions. However, a worker during a whole shift moved from different spaces for different time durations. Therefore, six case studies were simulated to compare the differences between schedules, ventilation rates, and shedder strength. In two baseline studies, based on regular shifts and existing ventilation conditions, the airborne infection risks were about 42 % and 8 % for high and low shedders, correspondingly. Study II and Study II-L comprised a hypothetical staggered schedule with the existing ventilation conditions, and the relative reductions of infection risks were 23% and 28%, respectively, when compared to the corresponding baselines. Study III and Study III-L used the staggered schedule and enhanced ventilation and found the relative reductions of infection probability were about 43% and 49% respectively. Therefore, administrations should recognize the mentioned engineering solutions and use a staggered schedule to mitigate the infection risks in the meat processing plants. Advisor: Josephine La

The vascular-endothelial protein tyrosine phosphatase: a novel therapeutic target in the tumour vasculature

Background: The microvasculature of solid tumours is characterized by profound structural and functional abnormality, which mediates several deleterious aspects of tumour behavior. As such, the development of therapeutic strategies to mitigate vascular dysfunction within tumours is an important goal. The Vascular Endothelial Protein Tyrosine Phosphatase (VE-PTP) attenuates the activity of the endothelial cell (EC) Tie-2 receptor tyrosine kinase, a key mediator of vessel maturation. In this study, I aimed to determine the effects of pharmacological VE-PTP inhibition on EC Tie-2 receptor activation and the resultant impact on breast cancer angiogenesis, progression, metastasis and treatment. Methods: AKB-9778 is a first-in-class VE-PTP inhibitor. I examined its effects on ECs in vitro and on embryonic angiogenesis in vivo using zebrafish assays. The impact of AKB-9778 therapy on the solid tumour vasculature was studied using orthotopic models of primary murine mammary carcinoma as well as both spontaneous and experimental models of metastasis. Finally, I used endothelial nitric oxide synthase (eNOS) deficient mice to establish the causal role of eNOS in mediating the effects of VE-PTP inhibition. Results: AKB-9778 induced ligand-independent Tie-2 activation in ECs and impaired embryonic zebrafish angiogenesis. In mouse models of breast cancer, AKB-9778 (i) delayed the early phase of tumour growth by enforcing vascular maturity; (ii) slowed progression of micrometastases by preventing extravasation of tumour cells into distant organs (prolonging survival); and (iii) stabilized established primary tumour vessels, enhancing tumour blood perfusion and radiation response. The effects of AKB-9778 on tumour vessels were mediated in part by eNOS activation. Conclusions: The results demonstrate that pharmacological VE-PTP inhibition can normalize the structure and function of tumour vessels through Tie-2 activation. This vascular normalization delays tumour growth and metastasis, and enhances response to concomitant cytotoxic treatments

The vascular-endothelial protein tyrosine phosphatase: a novel therapeutic target in the tumour vasculature

Background: The microvasculature of solid tumours is characterized by profound structural and functional abnormality, which mediates several deleterious aspects of tumour behavior. As such, the development of therapeutic strategies to mitigate vascular dysfunction within tumours is an important goal. The Vascular Endothelial Protein Tyrosine Phosphatase (VE-PTP) attenuates the activity of the endothelial cell (EC) Tie-2 receptor tyrosine kinase, a key mediator of vessel maturation. In this study, I aimed to determine the effects of pharmacological VE-PTP inhibition on EC Tie-2 receptor activation and the resultant impact on breast cancer angiogenesis, progression, metastasis and treatment. Methods: AKB-9778 is a first-in-class VE-PTP inhibitor. I examined its effects on ECs in vitro and on embryonic angiogenesis in vivo using zebrafish assays. The impact of AKB-9778 therapy on the solid tumour vasculature was studied using orthotopic models of primary murine mammary carcinoma as well as both spontaneous and experimental models of metastasis. Finally, I used endothelial nitric oxide synthase (eNOS) deficient mice to establish the causal role of eNOS in mediating the effects of VE-PTP inhibition. Results: AKB-9778 induced ligand-independent Tie-2 activation in ECs and impaired embryonic zebrafish angiogenesis. In mouse models of breast cancer, AKB-9778 (i) delayed the early phase of tumour growth by enforcing vascular maturity; (ii) slowed progression of micrometastases by preventing extravasation of tumour cells into distant organs (prolonging survival); and (iii) stabilized established primary tumour vessels, enhancing tumour blood perfusion and radiation response. The effects of AKB-9778 on tumour vessels were mediated in part by eNOS activation. Conclusions: The results demonstrate that pharmacological VE-PTP inhibition can normalize the structure and function of tumour vessels through Tie-2 activation. This vascular normalization delays tumour growth and metastasis, and enhances response to concomitant cytotoxic treatments

A Novel Locus for Leber Congenital Amaurosis (LCA4) with Anterior Keratoconus Mapping to Chromosome 17p13

5 páginas, 3 figuras, 2 tablas.-- et al.[Purpose]: A two-generation consanguineous Pakistani family with autosomal recessive Leber congenital amaurosis (LCA, MIM 204,000) and keratoconus was identified. All affected individuals have bilateral keratoconus and congenital pigmentary retinopathy. The goal of this study was to link the disease phenotype in this family. methods. Genomic DNA was amplified across the polymorphic microsatellite poly-CA regions identified by markers. Polymerase chain reaction (PCR) products were separated by nondenaturing polyacrylamide gel electrophoresis. Alleles were assigned to individuals, which allowed calculation of LOD scores using the Cyrillic and MLINK software program. The retinal guanylate cyclase (RETGC-1, GDB symbol GUC2D) and pigment epithelium-derived factor (PEDF) genes were analyzed by heteroduplex analysis and direct sequencing for mutations in diseased individuals. [Results]: Based on a whole genome linkage analysis the first locus for this combined phenotype has been mapped to chromosome 17p13. Linkage analysis gave a two point LOD score of 3.21 for marker D17S829. Surrounding this marker is a region of homozygosity of 15.77 cM, between the markers D17S1866 and D17S960; however, the crossover for the marker D17S1529 refines the region to 10.77 cM within which the disease gene is predicted to lie. Mutation screening of the nearby RETGC-1 gene, which has been shown to be associated with LCA1, revealed no mutations in the affected individuals of this family. Similarly, another prime candidate in the region PEDF was also screened for mutations. The factor has been shown to be involved in the photoreceptor differentiation and neuronal survival. No mutations were found in this gene either. Furthermore, RETGC-1 was physically excluded from the critical disease region based on the existing physical map. [Conclusions]: It is therefore suggested that this combined phenotype maps to a new locus and is due to an as yet uncharacterized gene within the 17p13 chromosomal region.Supported by The Wellcome Trust and Medical Research Council UK.Peer reviewe

Menstrual hygiene practice between rural and urban high school adolescent girls in Bangladesh

Background: Menstruation is a natural, normal biological process experienced by all adolescent girls and women. Urinary tract infection, reproductive tract infection and complication during pregnancy are the impact of poor menstrual hygiene practices. The aim of this study is to compare the menstrual hygiene practice between rural and urban high school adolescent girls in Bangladesh.Methods: A descriptive comparative study design was used. Cluster sampling technique was used to select 120 study participants. The data were collected through self-reported questionnaire by structured questionnaires. In descriptive statistics; frequency, percentage, mean, standard deviation and in inferential statistics; chi-square-test, t-test was used to compare the menstrual hygiene practice between rural and urban. Data was analyzed using SPSS version 23.Results: There was significant difference between rural and urban girls regarding mean age at menarche (5.50, p = 0.000). There was a statistically significant difference between rural and urban girls using of sanitary pad (30.54, p = 0.000) and reusable cloth (38.92, p = 0.000).Conclusions: This study found that menstrual hygiene practice (MHP) was more among the urban high school adolescent girls than in the rural high school adolescent girls. The result provides baseline information regarding menstrual hygiene practice (MHP) among rural participants that’s why need more emphasize on health promotion and counseling program regarding menstrual hygiene practice (MHP) among rural and primary level health sectors in Bangladesh

Autosomal dominant retinitis pigmentosa with apparent incomplete penetrance: a clinical, electrophysiological, psychophysical, and molecular genetic study

7 páginas, 7 figuras, 4 tablas.-- Licence Creative Commons, attribution, Non-commercial licence.-- et al.Twenty five symptomatic individuals and six asymptomatic obligate gene carriers from four families with autosomal dominant retinitis pigmentosa (adRP) showing apparent incomplete penetrance have been studied. Symptomatic individuals from three families showed early onset of night blindness, non-recordable rod electroretinograms, and marked elevation of both rod and cone thresholds in all subjects tested. In the fourth family, there was more variation in the age of onset of night blindness and some symptomatic individuals showed well preserved rod and cone function in some retinal areas. All asymptomatic individuals tested had evidence of mild abnormalities of rod and cone function, indicating that these families show marked variation in expressivity rather than true non-penetrance of the adRP gene. No mutations of the rhodopsin or RDS genes were found in these families and the precise genetic mutation(s) remain to be identified.This study was supported by the Medical Research Council (UK), The Weilcome Trust, British Retinitis Pigmentosa Society, and the National Retinitis Pigmentosa Society, Fighting Blindness, USA.Peer reviewe

CDK4/6 inhibition in breast cancer: current practice and future directions

The cyclin D/cyclin-dependent kinases 4 and 6 (CDK4/6)-retinoblastoma protein (RB) pathway plays a key role in the proliferation of both normal breast epithelium and breast cancer cells. A strong rationale for inhibiting CDK4/6 in breast cancers has been present for many years. However, potent and selective CDK4/6 inhibitors have only recently become available. These agents prevent phosphorylation of the RB tumor suppressor, thereby invoking cancer cell cycle arrest in G1. CDK4/6 inhibitors have transited rapidly from preclinical studies to the clinical arena, and three have already been approved for the treatment of advanced, estrogen receptor (ER)-positive breast cancer patients on account of striking clinical trial results demonstrating substantial improvements in progression-free survival. ER-positive breast cancers harbor several molecular features that would predict their sensitivity to CDK4/6 inhibitors. As physicians gain experience with using these agents in the clinic, new questions arise: are CDK4/6 inhibitors likely to be useful for patients with other subtypes of breast cancer? Are there other agents that could be effectively combined with CDK4/6 inhibitors, beyond endocrine therapy? Is there a rationale for combining CDK4/6 inhibitors with novel immune-based therapies? In this review, we describe not only the clinical data available to date, but also the biology of the CDK4/6 pathway and discuss answers to these questions. In particular, we highlight that CDK4 and CDK6 govern much more than the cancer cell cycle, and that their optimal use in the clinic depends on a deeper understanding of the less well characterized effects of these enzymes

Perforated Appendiceal Mucinous Cystadenoma Mimicking Ruptured Appendicitis With Abscess Formation: CT Imaging Features

AbstractWe describe the imaging features of a perforated appendiceal mucinous cystadenoma in a 72-year-old woman presenting with right lower quadrant abdominal pain, mimicking ruptured appendicitis with abscess formation. Computed tomography revealed a rim-enhanced cystic lesion at the proximal appendiceal orifice, connecting with the swollen and dilated distal part of the appendix. Disruption of the appendiceal walls and peri-appendiceal fatty infiltrations were also noted. Under the impression of ruptured appendicitis with abscess formation, the patient underwent exploratory laparotomy and appendectomy. The pathologic diagnosis was perforated appendiceal mucinous cystadenoma associated with superinfection, complicated by secondary appendicitis. The patient was uneventfully discharged on the 7th hospital day. Although primary neoplasms of the appendix are uncommon, they should be considered as a predisposing factor in elderly patients manifesting with appendicitis

Retinal pigment epithelium degeneration caused by aggregation of PRPF31 and the role of HSP70 family of proteins

Background Mutations in pre-mRNA splicing factor PRPF31 can lead to retinitis pigmentosa (RP). Although the exact disease mechanism remains unknown, it has been hypothesized that haploinsufficiency might be involved in the pathophysiology of the disease. Methods In this study, we have analyzed a mouse model containing the p.A216P mutation in Prpf31 gene. Results We found that mutant Prpf31 protein produces cytoplasmic aggregates in the retinal pigment epithelium and decreasing the protein levels of this splicing factor in the nucleus. Additionally, normal protein was recruited in insoluble aggregates when the mutant protein was overexpressed in vitro. In response to protein aggregation, Hspa4l is overexpressed. This member of the HSP70 family of chaperones might contribute to the correct folding and solubilization of the mutant protein, allowing its translocation to the nucleus. Conclusions Our data suggests that a mechanism haploinsufficiency and dominant-negative is involved in retinal degeneration due to mutations in PRPF31. HSP70 over-expression might be a new therapeutic target for the treatment of retinal degeneration due to PRPF31 mutations.This project has been financed through a) The ISCIII (Miguel Servet-I, 2015), co-financed by the European Regional Development Fund (ERDF), No CP15/00071. b) The European Union’s Horizon 2020 research and innovation program, under grant agreement No 634479. c) Regional Ministry of Economy, Innovation and Science of the Junta de Andalucía, No P09-CTS-04967.info:eu-repo/semantics/publishedVersio