The cognitive impairment and risk factors of the older people living in high fluorosis areas: DKK1 need attention

Objective To evaluate cognitive impairment and risk factors of elders in high fluoride drinking water areas and investigate whether DKK1 is involved in this disorder. Methods MoCA-B and AD-8 were used to measure the cognitive functions of 272 and 172 subjects over the age of 60 came from the high and normal fluoride drinking water areas respectively, general information and peripheral blood were collected, the level of SOD, GSH and MDA were measured, mRNA level of DKK1, the concentration of blood fluoride and the polymorphism of APOE were tested. Results The blood fluoride concentration, mRNA level of DKK1 and ratio of abnormal cognitive function of subjects in high fluorine drinking water areas were higher than those in normal areas. The level of SOD of subjects in high fluorine drinking water was low compared with those in normal areas. The level of MDA and GSH had no difference between the two crowds in different fluorine drinking water areas. There were differences in cigarette smoking, education, dental status, hypertension, hyperlipidaemia and APOE results between the two crowds in different fluorine drinking water areas. The mRNA level of DKK1 and the level of cognitive function showed a positive correlation and DKK1 was one of five risk factors involved in cognitive impairment of older people living in high fluorosis areas. Conclusions The cognitive functions could be impaired in the older people living in high fluoride drinking water areas, and DKK1 may as a potential intervention point of this brain damage process need attention.

Sympathetic signaling facilitates progression of neuroendocrine prostate cancer

The progression of prostate cancer (PC) into neuroendocrine prostate cancer (NEPC) is a major challenge in treating PC. In NEPC, the PC cells undergo neuroendocrine differentiation (NED); however, the exact molecular mechanism that triggers NED is unknown. Peripheral nerves are recently shown to promote PC. However, their contribution to NEPC was not studied well. In this study, we explored whether sympathetic neurosignaling contributes to NED. We found that human prostate tumors from patients that later developed metastases and castration-resistant prostate cancer (CRPC), a stage preceding to NEPC, have high sympathetic innervations. Our work revealed that high concentrations of the sympathetic neurotransmitter norepinephrine (NE) induces NED-like changes in PC cells in vitro, evident by their characteristic cellular and molecular changes. The NE-mediated NED was effectively inhibited by the Adrβ2 blocker propranolol. Strikingly, propranolol along with castration also significantly inhibited the development and progression of NEPC in vivo in an orthotopic NEPC model. Altogether, our results indicate that the NE-Adrβ2 axis is a potential therapeutic intervention point for NEPC.

Mild Cognitive Impairment and Alzheimer Disease

Many patients who have Alzheimer disease (AD) present initially with mild cognitive impairment (MCI). This chapter reviews the clinical features of MCI and AD, the clinical evaluation of patients with these entities, and the approaches to management. MCI is defined by cognitive decline that is more than expected by aging alone but does not meet criteria for dementia because the person has the ability to perform activities of daily living. MCI is considered to be a prodrome to dementia, especially AD, given the increased risk of progression to dementia. MCI, which probably represents the earliest stages of dementia in many patients, requires clinical follow-up and is expected to become an important intervention point in future clinical trials of novel preventive therapies.

803. The Impact of Bundled Interventions to Decrease Transmission of Drug-Resistant Pseudomonas aeruginosa from Wastewater Drain Sites on a Hematologic Malignancy/Hematopoietic Stem Cell Transplant Unit

Background Wastewater drain (WWD) sites are an important reservoir for amplification, propagation and transmission of multidrug resistant organisms. We observed an increase in the incidence of carbapenem and fluoroquinolone non-susceptible (CP-NS and FQ-NS) P. aeruginosa bloodstream infections (BSI) among patients on our hematologic malignancies (HM) and hematopoietic cell transplant (HCT) unit. The incidence of CP-NS/FQ-NS P. aeruginosa BSI from 2012 through May 2021 is represented in Figure 1. We sought to determine the impact of low-cost, low-barrier interventions targeting WWD sites on the prevalence of patient and environmental P. aeruginosa colonization and incidence of BSI. Figure 1. Incidence of P. aeruginosa BSI, 2012 through May 2021 Methods Behavioral and structural interventions to limit acquisition from WWD sites were informed by an environmental analysis and rolled out in staged fashion beginning in September 2019. Pre- and post-intervention colonization surveys were performed on the unit to assess for patient and WWD site P. aeruginosa colonization. Whole genome sequencing (WGS) was performed on select isolates. A sensitivity analysis performed accounted for the unconfirmed patient isolates. BSI data was collected retrospectively. Results Characteristics of the pre- and post-intervention groups are presented in Table 1. Five of 27 (18.5%) and 1 of 26 (3.8%) patients in the pre- and post-intervention point prevalence survey, respectively, were confirmed to be colonized with P. aeruginosa (Figure 2), corresponding to a prevalence rate ratio of 0.21 (0.03,1.66). If the two indeterminate samples in the pre-intervention period were positive, the prevalence rate ratio would instead be 0.15 (0.02,1.12). The most frequent P. aeruginosa strains identified by WGS from the patients and environment were 111, 308 and 446. At least 87% of rooms were colonized with P. aeruginosa from at least one WWD site, from pre- and post-intervention periods (Table 2). Table 1. Demographic and clinical characteristics of patients in each epoch. Results are given as percent (frequency) unless otherwise noted. Chi square test was used unless otherwise noted. Figure 2. Proportion of patients colonized with P. aeruginosa Positive: Colonized with P. aeruginosa, confirmed by WGS; Unknown: Phenotype of isolate suggestive of P. aeruginosa, WGS not performed; Negative: No growth on selective agar or non-P aeruginosa identification on WGS Table 2. WWD site colonization, by phenotypic and WGS determination. Fisher’s exact test was used unless otherwise noted. Conclusion P. aeruginosa WWD colonization on our HM/HCT unit may predispose patients to colonization and BSI. The prevalence of patient colonization decreased following implementation of the interventions, despite persistent environmental colonization. We will follow the incidence of P. aeruginosa BSI to determine the long-term impact of these interventions. Disclosures All Authors: No reported disclosures

Suicide in primary care: How to screen and intervene

Suicide is significant public health concern within the United States. Research results are mixed about the effectiveness of universal screening and interventions with patients who are at-risk for suicide. Primary care is a logical intervention point to mitigate risk among patients in each of these areas. The Department of Veterans Affairs and Department of Defense have developed comprehensive guidelines for the assessment and management of suicidal patients. This approach involves specific screening tools, risk stratification by categories and interventions used by clinicians to help reduce risk levels in their patients. This article aims to provide a model, built on the principles of these guidelines, which primary care physicians can use to identify, assess and intervene with patients who are at-risk for suicide.

Racial and Language Microaggressions in the School Ecology

The growth trajectory of ethnically and linguistically diverse individuals in the United States, particularly for youth, compels the education system to have urgent awareness of how diverse aspects of culture (e.g., Spanish-speaking, Black Latina student) are implicated in outcomes in American school systems. Students spend a significant amount of time in the school ecology, and this experience plays an important role in their well-being. Diverse ethnic, racial, and linguistic students face significant challenges and are placed at considerable risk by long-observed structural inequities evidenced in society and schools. Teachers must develop the capacity to be culturally sensitive, provide culturally responsive pedagogy, and regularly self-assess for biases implicated in positive academic outcomes for students in kindergarten through Grade 12. Research and practice have suggested that racism and discrimination in the form of racial microaggressions are observed daily in schools and classrooms. This article provides an overview of racial microaggressions in the school context and their damaging effects on students. We provide specific examples of microaggressions that may be observed in the U.S. classroom environment and how schools can serve as a positive intervention point to ameliorate racism, discrimination, and racial and language microaggressions. This comprehensive approach blends theory with practice to support the continued development of cultural humility, culturally sustaining pedagogy, and an equity-responsive climate.

The Evaluation of Preventive and Control Measures on Congenital Syphilis in South China: A Time Series Modelling Study

Background: The re-emergence of congenital syphilis (CS) was witnessed since the 1990s over the globe, including China. The country, therefore, carried out the prevention and control measures in an all-around way in 2010, including large-scale syphilis screening for pregnant women, providing standard treatment and follow-up management for both infected mothers and their infants, as well as the supportive strategies from the government as the response. However, there is a lack of the published evaluation for these measures when the deadline of the final goal (CS notification rate < 15/100,000 livebirths by 2025) is approaching. This study evaluates the effectiveness of CS control measures based on the change of the notification rate from 2005 to 2020 and predicts the CS case number in the following year in Guangdong, one of the provinces which used to have the highest CS notification rate in China. Methods: The interrupted time series analysis was conducted to compare changes in slope and level of CS notification rate from 2005 to 2020 in Guangdong Province and its three regions with different economic development levels. The year 2012 was identified as the intervention point, the time when Guangdong Province officially launched a bunch of measures. The autoregressive integrated moving average model was established to predict the CS case number of Guangdong Province in 2021. Results: A total of 12,687 CS cases were reported from 2005 to 2020. The notification rate of CS had been increasing in Guangdong Province until 2012 (128.55/ 100,000 livebirths), followed by a constant downward trend. It hit the lowest point in 2020 (5.76/ 100,000 livebirths), which was lower than the national goal set for 2025 (15/100,000 livebirths). The effectiveness of preventive and control measures was proved by the significant change in slope of the notification rate which was found in both of the whole province and two less-developed regions (-18.18, 95%CI: -25.63 to -10.75, -10.49, 95%CI: -13.13 to -7.86 and − 32.89, 95%CI: -41.67 to -24.10, respectively). In the developed region where the notification rate had already been decreasing in the pre-program period, implementing these measures also aided in hastening the rate of descent. The CS case number in 2021 was predicted to be 48, which remains a low-level epidemic. Conclusions: The comprehensive preventive and control measures have assisted Guangdong Province to control CS and exceed the goal that China set for 2025 ahead of schedule. As these measures worked effectively in places with varying levels of development and produced satisfying outcomes in regions with limited resources, it could be feasible to be generalized in other Low-and-Middle-Income countries where CS is still a public health concern.

ACE2 and RAAS: Therapeutic intervention point for COVID-19

COVID-19 has caused widespread mortality and morbidity and significant economic disruption. Several potential therapeutic and/ or preventive approaches to address the pandemic are being worked out, a few effective vaccines are under clinical trials and few vaccines has been approved but still the expected result has not been achieved. Some Spiritual Leader claims it to be natural process and can be protected by chant of Mantra 'Pujya Anakarananta Nirakar niranjan shivajyoti mahamanav pita'. Renin-Angiotensin-Aldosterone System (RAAS) is no more a mere research area in cardio-pulmonary and renal physiology alone but has gained focus as an infection and therapeutic point for COVID-19. This article discusses about ACE2 receptor as a centre point of infection of SARS-CoV-2 and also suggests it as the therapeutic intervention point for COVID-19.

Genetic insights on single cross maize hybrid and its importance on maize self-sufficiency in Nepal

When the world's population rises, total crop production worldwide is not meeting rising food demand. Focus on developing high yielding single cross hybrids of maize that are resource-efficient under diverse soil and climatic conditions is utmost for countries like Nepal. With the aim of exploring genetic reasons for higher hybrid vigor of single cross hybrid of maize, global genetic importance and addressing the emerging issue of needed higher productivity in Nepal to achieve maize self-sufficiency status, comprehensive review work was performed. Research findings explored that; the Heterosis hypothesis has been widely exploited in crop breeding, resulting in a large increase in yield. The ability analysis is of special importance in cross-pollinated crops like maize as it helps in identifying potential parents that can be used for producing hybrids and synthetics. New molecular tools and techniques can complement traditional methods to allow breeders to tackle priority research areas efficiently. Nepal’s reliance on imported hybrid maize seed and grain increased each year as competitive hybrid cultivars became unavailable within the country. Recently, higher yield gap due to lower productivity, being the major concern in Nepal, single cross hybrids are intervention point. For the countries like Nepal, where achieving higher yield of maize to address self-sufficiency is the nationally prioritized issue, single cross hybrids of maize could be the best way to come up.

Pterygium—The Good, the Bad, and the Ugly

Pterygium is a multifaceted pathology that displays apparent conflicting characteristics: benign (e.g., self-limiting and superficial), bad (e.g., proliferative and potentially recurrent) and ugly (e.g., signs of preneoplastic transformation). The natural successive question is: why are we lacking reports showing that pterygium lesions become life-threatening through metastasis, especially since pterygium has considerable similarities with UV-related malignancies on the molecular level? In this review, we consider how our pathophysiological understanding of the benign pterygium pathology overlaps with ocular surface squamous neoplasia and skin cancer. The three UV-related disorders share the same initial insult (i.e., UV radiation) and responsive repair mechanisms to the ensuing (in)direct DNA damage. Their downstream apoptotic regulators and other cellular adaptations are remarkably alike. However, a complicating factor in understanding the fine line between the self-limiting nature of pterygium and the malignant transformation in other UV-related diseases is the prominent ambiguity in the pathological evaluation of pterygium biopsies. Features of preneoplastic transformation (i.e., dysplasia) are used to define normal cellular reactions (i.e., atypia and metaplasia) and vice versa. A uniform grading system could help in unraveling the true nature of this ancient disease and potentially help in identifying the earliest intervention point possible regarding the cellular switch that drives a cell’s fate towards cancer.