Menopause and the changes it brings to a woman's life necessitate a comprehensive approach to face and experience the transition. This paper aims at synthesizing results from qualitative studies of ...menopausal experiences among Chinese and other women of similar ethnicity and culture. A comprehensive search strategy of multiple databases along with bibliographic hand searches was employed to identify qualitative studies published in English peer-reviewed journals between 2008 and 2022 focused on the menopausal experiences (peri and post-menopause) of Chinese and other women of similar ethnic backgrounds. Twelve studies met the inclusion criteria. The final sample consisted of 238 women aged between 40 to 60 years who had experienced menopausal symptoms. This qualitative systematic literature review adopted Noblit and Hare's seven-stage theoretical meta-ethnographic approach to construct an inductive and interpretive form of synthesis and subsequent analysis. A comprehensive approach that considers women's physiological and psychological well-being and major attempts to change cultural beliefs and norms about women's sexual health may be effective in aiding menopausal women during their transition. Additionally, appropriate guidelines and management should be in place to enable women to address menopause difficulties effectively with the assistance of healthcare experts and the support of their families and community.
In a resource-constrained setting like Bangladesh, effective patient-provider communication is critical to the delivery of maternal healthcare services. Using communication accommodation theory, this ...study tried to understand how providers perceive, engage, and accommodate patients' needs in maternity wards. This qualitative exploratory study used a semi-structured interview guide to conduct in-depth face-to-face interviews of ten healthcare providers in two government-funded public health facilities in Bangladesh. The interview data were analyzed using MAXQDA 2020 software. The thematic analyses revealed that nurses and midwives faced conceivable neglect from patients and their attendees due to possible service and facility constraints, indicating their low status and control within the service operation. Despite efforts to address patients' emotional and psychological concerns, providers appear to avoid (divergence strategy) confronting patients and their irate visitors. Unimodal convergence emerged when providers accepted patients' arguments about the systematic inadequacy of service facilities. Providers have employed interpretability tactics to communicate medical opinions and applied nonverbal cues where necessary. A lack of open communication between healthcare providers and patients necessitated various forms of accommodation. Integrated strategies addressing service restrictions and initiatives fostering patient understanding and cooperation may improve patient-provider communication.
Huntington's disease (HD), a neurodegenerative disease characterized by progressive dementia, psychiatric problems, and chorea, is known to be caused by CAG repeat expansions in the HD gene HTT. ...However, the mechanism of this pathology is not fully understood. The translesion DNA polymerase θ (Polθ) carries a large insertion sequence in its catalytic domain, which has been shown to allow DNA loop-outs in the primer strand. As a result of high levels of oxidative DNA damage in neural cells and Polθ's subsequent involvement in base excision repair of oxidative DNA damage, we hypothesized that Polθ contributes to CAG repeat expansion while repairing oxidative damage within HTT. Here, we performed Polθ-catalyzed in vitro DNA synthesis using various CAG•CTG repeat DNA substrates that are similar to base excision repair intermediates. We show that Polθ efficiently extends (CAG)n•(CTG)n hairpin primers, resulting in hairpin retention and repeat expansion. Polθ also triggers repeat expansions to pass the threshold for HD when the DNA template contains 35 repeats upward. Strikingly, Polθ depleted of the catalytic insertion fails to induce repeat expansions regardless of primers and templates used, indicating that the insertion sequence is responsible for Polθ's error-causing activity. In addition, the level of chromatin-bound Polθ in HD cells is significantly higher than in non-HD cells and exactly correlates with the degree of CAG repeat expansion, implying Polθ's involvement in triplet repeat instability. Therefore, we have identified Polθ as a potent factor that promotes CAG•CTG repeat expansions in HD and other neurodegenerative disorders.
The Turkey Lakes Watershed (TLW) study is a federal, interdepartmental study established in 1979 to investigate the effects of acid rain on terrestrial and aquatic ecosystems. The 10.5 km2 watershed, ...located in the Eastern Temperate Mixed Forest on the Canadian Shield, has been the site of multidisciplinary studies on biogeochemical and ecological processes conducted across plot to catchment scales. The whole‐ecosystem investigative approach was adopted from the outset and has allowed research to evolve from its original (and continuing) acidification focus to include investigations on the effects of climate change, forest harvesting and other forest ecosystem perturbations. The extensive scientific and support infrastructure allows for collection of a comprehensive data record essential for understanding long‐term environmental trends. Data include atmospheric deposition, meteorology, stream hydrology and chemistry, soil, pore and ground water properties, understory and overstory vegetation, lake and outflow physical and chemical properties, and aquatic macroinvertebrate and fish community composition and abundance. These data have contributed to over 400 published research papers and graduate theses. The watershed has also figured prominently in many continent‐wide comparisons advancing fundamental watershed theory. The knowledge gained at TLW has influenced pollutant emission and natural resource management policies provincially, nationally and internationally.
How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3' flap nuclease ...that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3' nuclease, excises flaps at the immediate 3' end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth.
New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development ...due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries—two synthetic and two immunized—against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.
Congenital hyperinsulinism (HI) is a genetic disorder in which pancreatic beta cell insulin secretion is excessive and results in hypoglycemia that can cause brain damage or death without treatment. ...Most patients with loss-of-function mutations in ABCC8 and KCNJ11, the genes encoding the beta cell ATP sensitive potassium channel (KATP), are unresponsive to diazoxide, the only FDA approved medical therapy, and require a pancreatectomy. The glucagon-like peptide 1 receptor (GLP-1R) antagonist exendin-(9-39) is an effective therapeutic agent to inhibit insulin secretion in both congenital and acquired hyperinsulinism. Previously, we identified a highly potent antagonist antibody, TB-001-003, which was derived from our synthetic antibody libraries that were designed to target G protein-coupled receptors. Here, we designed a combinatorial variant antibody library to optimize the activity of TB-001-003 against GLP-1R and performed phage-display on cells overexpressing GLP-1R. One antagonist, TB-222-023, is more potent than exendin-(9-39), also known as Avexitide. TB-222-023 effectively decreased insulin secretion in primary isolated pancreatic islets from a mouse model of hyperinsulinism, Sur1-/- mice, and in islets from an infant with HI as well as increased plasma glucose and decreased the insulin to glucose ratio in Sur1-/- mice. These findings demonstrate that targeting GLP-1R with an antibody antagonist is an effective and innovative strategy for treatment of hyperinsulinism.
Purpose - The purpose of this paper is to explore Chinese adolescents' engagement in social comparison of material possessions using qualitative inquiries.Design methodology approach - In total, 64 ...Chinese adolescents aged 13-17 were face-to-face interviewed. They were asked whether they engaged in social comparison of possessions with direct and vicarious role models such as media celebrities. Characteristics of role models and products involved in social comparison were inquired.Findings - The research found that adolescents in Hong Kong frequently engaged in upward social comparison with friends and classmates. The products involved in social comparison were branded public goods that can be used to communicate ideal social self-image. There was a strong link between social comparison and peer communication about consumption. Adolescents less often engaged in social comparison with media celebrities. This can be attributed to lack of resources, understanding of product sponsorship, and difficulties in identifying with the media celebrities. Role models of the same sex and similar age were often used for social comparison. Social comparison is used mainly for self-enhancement, rather than self-evaluation.Research limitations implications - The study was from a convenient sample of adolescents in Hong Kong, a Chinese city with high advancement in terms of economic and advertising development when compared with most other Chinese cities.Originality value - This is the first qualitative study on Chinese adolescents' engagement in social comparison of material possessions.
CTG•CAG repeat expansions cause at least twelve inherited neurological diseases. Expansions require the presence, not the absence, of the mismatch repair protein MutSβ (Msh2-Msh3 heterodimer). To ...evaluate properties of MutSβ that drive expansions, previous studies have tested under-expression, ATPase function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems. Additionally, some variants destabilize MutSβ, potentially masking the effects of biochemical alterations of the variations. Here, human Msh3 was mutated to selectively inactivate MutSβ. Msh3-/- cells are severely defective for CTG•CAG repeat expansions but show full activity on contractions. Msh3-/- cells provide a single, isogenic system to add back Msh3 and test key biochemical features of MutSβ on expansions. Msh3 overexpression led to high expansion activity and elevated levels of MutSβ complex, indicating that MutSβ abundance drives expansions. An ATPase-defective Msh3 expressed at normal levels was as defective in expansions as Msh3-/- cells, indicating that Msh3 ATPase function is critical for expansions. Expression of two Msh3 polymorphic variants at normal levels showed no detectable change in expansions, suggesting these polymorphisms primarily affect Msh3 protein stability, not activity. In summary, CTG•CAG expansions are limited by the abundance of MutSβ and rely heavily on Msh3 ATPase function.
Stress has become a mass phenomenon in the modern workplace. The use of information and communication technologies is beginning to receive greater attention in the context of occupational stress. An ...exploratory qualitative study was conducted to examine both stressors and benefits resulting from technologies among practitioners in the advertising, public relations, and journalism industry in Hong Kong and Austria. Results suggest that technologies allow instant availability, which facilitates communication processes as well as information exchange. Notably, modern technologies enable employees to organize their work with greater temporal and spatial flexibility, thus creating an opportunity for better balancing work and private life. However, evolving technologies have come with a cost; the pressure to be constantly available via technologies constitutes a major source of stress, increasing the risk of experiencing prolonged work stress and its adverse consequences on employee health and well-being, such as a burnout. Furthermore, findings suggest that availability pressure may be attributed to an inner obligation rather than to an organizational expectation. Hence, making employees aware of their connectivity behaviour may help to diminish the experience of technology-induced work stress and improve and maintain employees' health and well-being in the long term. Practical implications, limitations, and future research directions are provided.
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