Evaluation of Prevention and Control Strategies for Human Noroviruses in Long-Term Care Facilities in South Carolina

Long-term care facilities (LTCF) are the most common setting for human norovirus (HuNoV) outbreaks in United States. We identified presence of prevention and control strategies for HuNoV in LTCF in South Carolina (SC) under non-outbreak conditions. A convenience sample of 26 LTCF was visited and directors were interviewed to determine facility prevention and control practices. A facility audit in one commons area and food preparation area was conducted to assess sanitary conditions. Institutional policies and procedures were collected to determine alignment with Centers for Disease Prevention and Control (CDC) recommendations and to determine readability based on Federal Plain Language Guidelines and Microsoft Word readability statistics. Findings of director interview responses showed presence of gaps in prevention and control practices. Most Directors had little knowledge of proper sanitizing and disinfecting products and reported missing written procedures for cleaning staff/visitor bathrooms. Many used the wrong products for pathogen removal after vomit/fecal events, had no written procedures for cleaning contaminated soft surfaces, did not remove other individuals during clean-up of vomit/fecal episodes, and did not clean a large area surrounding vomit/fecal episodes. Most did not assign specific staff to care for sick; not designate specific toilets for sick during an outbreak. All kitchens and commons areas in participating facilities were in good sanitary condition. However, possible environmental risk factors for HuNoV transmission in commons areas were identified. Most contained upholstered, rather than hard-surface chairs and some had carpeted floors. Quaternary ammonium-based disinfectants were used in most commons areas. Handwashing signage was not posted in some staff/visitor bathrooms, and a few staff/visitor bathrooms were accessible to residents. Inconsistencies were identified in hand hygiene, outbreak management and environmental sanitation procedures. Most facilities had procedures for hand hygiene but recommendations for handwashing events and duration varied greatly. Few had separate procedures devoted to HuNoV outbreak control. Both hand hygiene and bodily fluid clean-up procedures had low mean scores for readability. Our study results can be used for development of better quality interventions for prevention and control of HuNoV in LTCF

Role of the Bcl-2 gene family in prostate cancer progression and its implications for therapeutic intervention.

Prostate cancer (PC) is an escalating health burden in the western world. A large number of patients still present with extraprostatic (i.e., T3/T4, N0, M0/M1 or any T category and M1 disease or involved lymph nodes) and therefore incurable disease. Since the work of Huggins in 1940, there have been no major therapeutic advances and androgen ablation remains the best treatment option for extraprostatic androgen-responsive PC. Eighty to ninety percent of PC patients respond well to this form of treatment initially. After a median time of approximately 2 years, however, relapse to an androgen-independent (AI) state occurs, followed by death after a further median 6 months. Androgen ablation is rarely curative. The major molecular defect in extraprostatic and AI PC is the inability of PC cells to initiate apoptosis in response to a variety of stimuli, including different forms of androgen ablation and cytotoxic agents. The balance between cellular proliferation and cell death is regulated by multiple genes or families of genes through the cell cycle. The exact mechanisms governing this intricate and complex process are as yet not fully understood. One family of genes involved in cell survival/death control is the Bcl-2 gene family, which consists of homologous proteins that function to regulate distal and crucial commitment steps of the apoptotic pathway. The Bcl-2 family constitutes both agonists and antagonists of apoptosis that function at least in part through protein-protein interactions between various members of the family. The final outcome depends on the relative ratio of death agonists and antagonists. Bcl-2 expression has been closely associated with the AI phenotype of PC. Cytotoxic chemotherapy may be used as palliative therapy in AI PC but has not been found effective. Most chemotherapeutic cytotoxic agents induce apoptosis in cancer cells by direct and indirect action on the cell cycle. In vitro and in vivo studies have established that Bcl-2 expression confers an antiapoptotic activity against androgen withdrawal and cytotoxic chemotherapy. It thus offers a tempting potential target for therapeutic manipulations of PC

WINGS: Wellness Interventions for Nurses’ growth and selfcare study at Purdue University, US and UEL, UK

During the pandemic, a quasi-experimental study was designed to empirically test the effectiveness of SOPHIE intervention among palliative care nurses in US. Along with SOPHIE framework, the study also included Nurses’ Psychological Trauma (NPT) model (Foli, et al., 2021). Our study included N=94 nurses working in palliative care setting including long-term care, nursing homes and hospice setting. Intervention included four weekly blog writing with pre and post surveys. Findings showed significant improvement in subjective wellbeing of nurses. Narrative analysis of the four weekly blogs and post blog feedback demonstrated self-reflexivity on the part of participants. Participants shared blogs were helpful as it provided them a valuable opportunity to generate self-awareness and ability to share traumatic experiences while creating avenues for personal growth and wellbeing. Our preliminary data suggest that SOPHIE tool is an effective tool for self-reflexivity and create pathways for selfcare and wellbeing

Tissue-specific expression of a human Polymorphic Epithelial mucin (MUCI) in transgenic mice

The human MUC1 gene codes for the core protein of a mucin which is expressed by glandular epithelia and the carcinomas which develop from these tissues. The core protein is aberrantly glycosylated in cancers, and some antibodies show specificity in their reactions with the cancer-associated mucin, which also contains epitopes recognized by T-cells from breast and pancreatic cancer patients. For evaluating the potential use of mucin-reactive antibodies and mucin-based immunogens in cancer patients, a mouse model, expressing the MUC1 gene product PEM (polymorphic epithelial mucin) as a self antigen, would be extremely useful. To this end, we have developed transgenic mouse strains expressing the human MUC1 gene product in a tissue-specific manner. The TG4 mouse strain was established using a 40-kilobase fragment containing 4.5 kilobases of 5\u27 and 27 kilobases of 3\u27 flanking sequence. The TG18 strain was developed using a 10.6-kilobase SacII fragment from the 40-kilobase fragment; this fragment contained 1.6 kilobases of 5\u27 sequence and 1.9 kilobases of 3\u27 flanking sequence. Both strains showed tissue specificity of expression of the MUC1 gene, which was very similar to the profile of expression seen in human tissues. The antibody SM-3 is directed to a core protein epitope, which is selectively exposed in breast cancers and which shows a more restricted distribution on normal human tissues. It was established that the distribution of the SM-3 epitope of PEM in the tissues of the transgenic mice is similar to that seen in humans. The transgenic mouse strains described here should form the basis for the development of a preclinical model for the evaluation of PEM-based antigens and of antibodies directed to PEM in cancer therapy

Efficient Immortalization of luminal Epithelial Cells from Human Mammary gland by introduction of Simian virus 40 large Tumor antigen with a Recombinant Retrovirus

When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining with monoclonal antibodies, 14 lines showed features of luminal epithelial cells and of these, 7 resembled the common luminal epithelial cell type in the profile of keratins expressed. These cells express keratins 7, 8, 18, and 19 homogeneously and do not express keratin 14 or vimentin; a polymorphic epithelial mucin produced in vivo by luminal cells is expressed heterogeneously and the pattern of fibronectin staining is punctate. Although the cell lines have a reduced requirement for added growth factors, they do not grow in agar or produce tumors in the nude mouse. When the v-Ha-ras oncogene was introduced into two of the cell lines by using a recombinant retrovirus, most of the selected clones senesced, but one entered crisis and emerged after 3 months as a tumorigenic cell line

Trefoil factor 2 (Tff2) deficiency in murine digestive tract influences the immune system

Background & Aims: The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency. Methods: TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry. Results: On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. Expression of proteasomal subunits genes (LMP2, LMP7 and PSMB5) involved in the MHC class I presentation pathway were modulated indicating the formation of immunoproteasomes improving antigen presentation. Expression of one subunit of a transporter (TAP1) responsible for importing degraded antigens into ER was increased, similarly to the BAG2 gene that modulates chaperone activity in ER helping proper loading on MHC class I molecules. Several mouse defensin (cryptdin) genes coding important intestinal microbicidal proteins were up-regulated as a consequence of TFF2 deficiency. Normally moderate expression of TFF3 was highly increased in stomach