Construction and application of fetal loss risk model in systemic lupus erythematosus patients with mild disease severity.

BACKGROUND: This dynamic nomogram model was developed to predict the probability of fetal loss in pregnant patients with systemic lupus erythematosus (SLE) with mild disease severity before conception. METHODS: An analysis was conducted on 314 pregnancy records of patients with SLE who were hospitalized between January 2015 and January 2022 at Shenzhen People's Hospital, and the Longhua Branch of Shenzhen People's Hospital. Data from the Longhua Branch of the Shenzhen People's Hospital were utilized as an independent external validation cohort. The nomogram, a widely used statistical visualization tool to predict disease onset, progression, prognosis, and survival, was created after feature selection using multivariate logistic regression analysis. To evaluate the model prediction performance, we employed the receiver operating characteristic curve, calibration curve, and decision curve analysis. RESULTS: Lupus nephritis, complement 3, immunoglobulin G, serum albumin, C-reactive protein, and hydroxychloroquine were all included in the nomogram model. The model demonstrated good calibration and discriminatory power, with an area under the curve of 0.867 (95% confidence interval: 0.787-0.947). According to decision curve analysis, the nomogram model exhibited clinical importance when the probability of fetal loss in patients with SLE ranged between 10 and 70%. The predictive ability of the model was demonstrated through external validation. CONCLUSION: The predictive nomogram approach may facilitate precise management of pregnant patients with SLE with mild disease severity before conception.

The Launch of Massachusetts Community Health Worker Certification: Findings From the Massachusetts Community Health Worker Workforce Surveys.

OBJECTIVES: The launch of state certification for community health workers (CHWs) in Massachusetts in 2018 aimed to promote and champion this critical workforce. However, concerns exist about unintentional adverse effects of certification. Given this, we conducted 2 cross-sectional surveys to evaluate this certification policy. METHODS: We conducted surveys of CHW employers and CHWs in 3 sample frames: community health centers and federally qualified health centers, acute-care hospitals, and community-based organizations. We administered the surveys in 2016 (before certification launch) and 2021 (after certification launch) to answer the following questions: Was certification associated with positive outcomes among CHWs after its launch? Did harmful shifts occur among the CHW workforce and employers after certification launch? Was certification associated with disparities among CHWs after its launch? RESULTS: Certification was associated with higher pay among certified (vs noncertified) CHWs, better perceptions of CHWs among certified (vs noncertified) CHWs, and better integration of certified (vs noncertified) CHWs into care teams. We found no adverse shifts in CHW workforce by sociodemographic variables or in CHW employer characteristics (most notably CHW employer hiring requirements) after certification launch. After certification launch, certified and uncertified CHWs had similar demographic and educational characteristics. However, certified CHWs more often worked in large, clinical organizations while uncertified CHWs most often worked in medium-sized community-based organizations. CONCLUSIONS: Our evaluation of Massachusetts CHW certification suggests that CHW certification was not associated with workforce disparities and was associated with positive outcomes. Our study fills a notable gap in the research literature and can guide CHW research agendas, certification efforts in Massachusetts and other states, and program efforts to champion this critical, grassroots workforce.

Desmopressin in combination with anticholinergic agents in the treatment of nocturnal enuresis: a systematic review and meta-analysis.

Background: The desmopressin combined with anticholinergic agents for the treatment of nocturnal enuresis (NE) remains controversial. This meta-analysis assesses the efficacy and safety of desmopressin compared with desmopressin plus anticholinergic agents for the treatment of NE. Methods: We searched MEDLINE, Embase, and Cochrane Controlled Trials Register databases for RCTs published for the treatment of NE. Systematic review was carried out using the Preferred Reporting Items for Systematic Reviews and Meta-analyses. This meta-analysis used RevMan v.5.1.0 to analyze data. Results: Eight studies involving 600 patients (293 in the combination group and 307 in the desmopressin group) contained meaningful data. The results were as follows: after one month of treatment, compared with the desmopressin monotherapy group, the combination group was significantly better in treating NE in FR (full responders, P = 0.003), FR + PR (partial responders) (P < 0.0001), and the mean number of wet nights (P = 0.004); also, the combination group had a better effect in FR (P < 0.00001), FR + PR (P = 0.02) and the mean number of wet nights (P = 0.04) after 3 months' treatment. For side effects, combination therapy does not cause more adverse events in treating NE (P = 0.42). Conclusions: This study elucidates that desmopressin combined with the anticholinergic agent was demonstrated to be more effective in treating NE than desmopressin monotherapy, and the anticholinergic agent does not increase the risk of adverse events (AEs).

Clinical value of miR-23a-3p expression in early diagnosis of diabetic kidney disease.

INTRODUCTION: The objective was to observe the expression of miR-23a-3p in the serum of patients with type 2 diabetic nephropathy (T2DN) and to explore its clinical significance. MATERIALS AND METHODS: 112 patients with type 2 diabetes were divided into a simple diabetes mellitus (NON) group, T2DN microalbuminuria (MIC) group, and T2DN macroalbuminuria (MAC) group, according to the urinary protein-creatinine ratio (uACR). Clinical data were collected, miR-23a-3p levels in serum were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and clinical parameters were measured by an automatic biochemical analyser; the influencing factors of diabetic kidney disease (DKD) and the correlation between miR-23a-3p expression and clinical parameters were analysed. RESULTS: The expression of miR-23a-3p in the serum of the DKD group was lower than that of the normal control (CON) and NON groups. Correlation analysis showed that miR-23a-3p was positively correlated with urinary albumin (Albu), glycosylated haemoglobin (HbA1c), total cholesterol (CHOL), glycated albumin (GA-L), serum creatinine (Scr), fasting blood glucose (GLU), and uric acid (UA), negatively correlated with uACR and high-density lipoprotein cholesterol (HDL-C), but not correlated with urinary creatinine (CREA). The area under the receiver operating characteristic (ROC) curve (AUC) of miR-23a-3p for the diagnosis of DKD was 0.686 [95% confidence interval (CI): 0.599-0.773], with a sensitivity of 64.5% and a specificity of 71.2%; the AUC for differentiating NON from DKD was 0.700 (95% CI: 0.598-0.802), with a sensitivity of 61.8% and a specificity of 77.8%. Multivariate logistic regression analysis showed that serum miR-23a-3p levels were not associated with the development of DKD after adjusting for other levels of influence and were not significant for the differentiation of NON and DKD. CONCLUSION: Serum miR-23a-3p levels are decreased in T2DN patients, and this change becomes more significant with the severity of the disease, which may be a marker for the early diagnosis and progression of T2DN.

Mendelian Randomization Analysis Reveals Causal Associations of Polyunsaturated Fatty Acids with Sepsis and Mortality Risk.

INTRODUCTION: Despite numerous observational studies reporting a positive correlation between polyunsaturated fatty acids (PUFAs) and the risk of sepsis and mortality, the causation of such an association has yet to be firmly established. Thus, our study aimed to undertake the Mendelian randomization (MR) approach to scrutinize the potential causalities of PUFAs with sepsis and mortality risk. METHODS: We conducted the MR investigation using genome-wide association study (GWAS) summary statistics of PUFAs [including omega-3 fatty acids (omega-3), omega-6 fatty acids (omega-6), the ratio of omega-6 to omega-3 fatty acids (omega-6:3), docosahexaenoic acid (DHA), linoleic acid (LA)], sepsis, and sepsis mortality. We utilized the GWAS summary data from the UK Biobank. To establish reliable causality, we employed the inverse-variance weighted (IVW) method as the primary analytical approach, together with four additional MR methods. In addition, we performed heterogeneity and horizontal pleiotropy assessments using Cochrane's Q test and MR-Egger intercept test, respectively. Finally, we performed a series of sensitivity analyses to enhance the precision and veracity of our findings. RESULTS: The IVW method showed that genetically predicted omega-3 [odd ratio (OR) 0.914, 95% confidence interval (CI) 0.845-0.987, P = 0.023] and DHA (OR 0.893, 95% CI 0.815-0.979, P = 0.015) were suggestively linked to a decreased risk of sepsis. Furthermore, genetically predicted DHA (OR 0.819, 95% CI 0.681-0.986, P = 0.035) was suggestively associated with a reduced risk of sepsis-related death. Conversely, the omega-6:3 ratio (OR 1.177, 95% CI 1.011-1.371, P = 0.036) was suggestively linked to an increased risk of sepsis-induced mortality. On the basis of the MR-Egger intercept assessment, it appears that our MR examination was not influenced by any horizontal pleiotropy (all P > 0.05). Moreover, the reliability of the estimated causal association was confirmed by the sensitivity analyses. CONCLUSION: Our study supported the casual effect between PUFAs and susceptibility to sepsis and sepsis-related death. Our findings underline the importance of specific PUFAs levels, particularly for individuals with a genetic susceptibility to sepsis. Further research is needed to confirm these findings and investigate the underlying mechanisms.

Evaluating the impact of community health worker certification in Massachusetts: Design, methods, and anticipated results of the Massachusetts community health worker workforce survey.

Background: Professional certification of community health workers (CHWs) is a debated topic. Although intended to promote CHWs, certification may have unintended impacts given the grassroots nature of the workforce. As such, both intended effects and unintended adverse effects should be carefully evaluated. However, there is a lack of published literature describing such effective evaluations with a robust methodology. In this methods paper, we describe a key component of evaluating CHW certification in Massachusetts-the Massachusetts CHW Workforce Survey. Methods: Design of the surveys was informed by a program theory framework that delineated both positive and negative potential impacts of Massachusetts CHW certification on CHWs and CHW employers. Using this framework, we developed measures of interest and preliminary CHW and CHW employer surveys. To validate and refine the surveys, we conducted cognitive interviews with CHWs and CHW employers. We then finalized survey tools with input from state and national stakeholders, CHWs, and CHW employers. Our sample consisted of three frames based on where CHWs are most likely to be employed in Massachusetts: acute care hospitals, community-based organizations, and ambulatory care health centers, primarily community health centers and federally qualified health centers. We then undertook extensive outreach efforts to determine whether each organization employed CHWs and to obtain CHW and CHW employer contact information. Our statistical analysis of the data utilized inverse probability score weighting accounting for organizational, site, and individual response. Anticipated results: Wave one of the survey was administered in 2016 prior to launch of Massachusetts CHW certification and wave two in 2021. We report descriptive statistics of the three sample frames and response rates of each survey for each wave. Further, we describe select anticipated results related to certification, including outcomes of the program theory framework. Conclusions: The Massachusetts CHW Workforce Survey is the culmination of 5 years of effort to evaluate the impact of CHW certification in Massachusetts. Our comprehensive description of our methodology addresses an important gap in CHW research literature. The rigorous design, administration, and analysis of our surveys ensure our findings are robust, valid, and replicable, which can be leveraged by others evaluating the CHW workforce.

Construction and clinical practice of an enteral nutrition nursing quality control system for critically ill patients.

Critically ill patients are prone to a series of complications during early enteral nutrition (EEN), including gastrointestinal complications, infectious complications, metabolic complications, and mechanical complications, with an incidence of 30.5-65.7%, which attributes to prolonged hospitalization and increased mortality. Therefore, this retrospective study aimed to construct a quality control system of enteral nutrition nursing for critically ill patients as well as apply this system in clinical practice to evaluate its effect. Delphi method was utilized for this purpose, and we compared the incidence of enteral nutrition complications between patients using quality control system and using routine enteral nutrition. The mastery of enteral nutrition related knowledge by nursing staff was also compared before and after the implementation of a quality control system. Our data showed that, after applying the system to patients with critical illness in the nursing clinic, the incidence of enteral nutrition gastrointestinal complications, infectious complications, metabolic complications, and mechanical complications was significantly decreased from 11.51%, 1.96%, 3.41% and 5.88% to 1.86%, 0.52%, 1.71% and 0.97% (P<0.005), respectively. Furthermore, the awareness of enteral nutrition theory by ICU nurses was also significantly improved, and the questionnaire score was increased from 70.22±8.78 to 95.25±4.18 (t=18.792, P<0.001). Hence, the enteral nutrition nursing quality control system we developed could effectively guide nursing staff to implement enteral nutrition, reduce the occurrence of enteral nutrition complications in patients with critical illness and ensure the safety of patients, suggesting the clinical application value of our system.

Single-cell RNA-sequencing reveals the dynamic process and novel markers in porcine spermatogenesis.

BACKGROUND: Spermatogenesis is the process by which male gametes are formed from spermatogonial stem cells and it is essential for the reliable transmission of genetic information between generations. To date, the dynamic transcriptional changes of defined populations of male germ cells in pigs have not been reported. RESULTS: To characterize the atlas of porcine spermatogenesis, we profiled the transcriptomes of ~ 16,966 testicular cells from a 150-day-old pig testis through single-cell RNA-sequencing (scRNA-seq). The scRNA-seq analysis identified spermatogonia, spermatocytes, spermatids and three somatic cell types in porcine testes. The functional enrichment analysis demonstrated that these cell types played diverse roles in porcine spermatogenesis. The accuracy of the defined porcine germ cell types was further validated by comparing the data from scRNA-seq with those from bulk RNA-seq. Since we delineated four distinct spermatogonial subsets, we further identified CD99 and PODXL2 as novel cell surface markers for undifferentiated and differentiating spermatogonia, respectively. CONCLUSIONS: The present study has for the first time analyzed the transcriptome of male germ cells and somatic cells in porcine testes through scRNA-seq. Four subsets of spermatogonia were identified and two novel cell surface markers were discovered, which would be helpful for studies on spermatogonial differentiation in pigs. The datasets offer valuable information on porcine spermatogenesis, and pave the way for identification of key molecular markers involved in development of male germ cells.

Stage-specific embryonic antigen 4 is a membrane marker for enrichment of porcine spermatogonial stem cells.

BACKGROUND: Spermatogonial stem cells (SSCs), as tissue-specific stem cells, are capable of both self-renewal and differentiation and supporting the continual and robust spermatogenesis for male fertility. As a rare sub-fraction of undifferentiated spermatogonia, SSCs share most molecular markers with the progenitor spermatogonia. Thus, the heterogeneity of the progenitor cells often obscures the characteristics of stem cells. Distinguishing SSCs from the progenitors is of paramount importance to understand the regulatory mechanisms governing their actions. OBJECTIVES: The present study was designed to reveal that SSEA4 can be a marker for putative porcine SSCs that distinguished it from the progenitors and to build a sorting program for efficient enrichment of porcine SSCs. METHODS: To explore expression of SSEA4 within the undifferentiated spermatogonial population, we performed co-immunofluorescent staining for SSEA4 and common molecular markers (VASA, DBA, PLZF, c-KIT, and SOX9) in the 7-, 90-, and 150-day-old porcine testicular tissues. SSEA4-positive cells were isolated from the 90-day-old porcine testes by flow cytometry. Immunofluorescent, RNA-sequencing, and transplantation analysis were used to reveal that SSEA4-positive fraction holds the stem cell capacity. RESULTS: We found that SSEA4 was expressed in a rare sub-fraction of porcine undifferentiated spermatogonia, and RNA-sequencing analysis revealed that the genes for stem cell maintenance and SSC-specific markers (ID4 and PAX7) were up-regulated in the SSEA4-sorted fraction, compared with undifferentiated spermatogonia. In addition, germ cell transplantation assay demonstrated that SSEA4-positive spermatogonia colonized in the recipient testicular tubules. Sorting of the undifferentiated spermatogonia with anti-SSEA4 antibody resulted in a 2.5-fold enrichment of SSCs compared with the germ cell gate group, and 21-fold enrichment of SSCs compared with the SSEA4-negative spermatogonia group. CONCLUSIONS: Our findings revealed that SSEA4 is a new surface marker for porcine undifferentiated spermatogonia. This finding helps to elucidate the characteristics of porcine SSCs and facilitates the culture and manipulation of SSCs.

Establishment of cell lines with porcine spermatogonial stem cell properties.

BACKGROUND: Spermatogonial stem cells (SSCs) are capable of both self-renewal and differentiation to mature functional spermatozoa, being the only adult stem cells in the males that can transmit genetic information to the next generation. Porcine SSCs hold great value in transgenic pig production and in establishment of porcine models for regenerative medicine. However, studies and applications of porcine SSCs have been greatly hampered by the low number of SSCs in the testis as well as the lack of an ideal stable long-term culture system to propagate porcine SSCs perpetually. RESULTS: In the present study, by lentiviral transduction of plasmids expressing the simian virus 40 (SV40) large T antigen into porcine primary SSCs, we developed two immortalized cell lines with porcine SSC attributes. The established cell lines, with the expression of porcine SSC and germ cell markers UCHL1, PLZF, THY1, VASA and DAZL, could respond to retinoic acid (RA), and could colonize the recipient mouse testis without tumor formation after transplantation. The cell lines displayed infinite proliferation potential, and have now been cultured for more than 7 months and passaged for over 35 times without morphological abnormalities. CONCLUSIONS: We have for the first time established porcine SSC lines that could provide abundant cell sources for mechanistic studies on porcine SSC self-renewal and differentiation, thereby facilitating development of an optimal long-term culture system for porcine primary SSCs and their application to animal husbandry and medicine.

Comparison of Patient Experience between a Practice for Homeless Patients and Other Practices Engaged in a Patient-Centered Medical Home Initiative.

Despite its increasing popularity, little is known about the patient-centered medical home (PCMH) model in primary care settings serving homeless populations. Our objective was to understand how patient experience differs between a PCMH demonstration practice designed for homeless people in Massachusetts and other practices participating in the same statewide initiative. The study population included 194 homeless patients and 1,868 patients from comparison practices. Patient experience was compared on key measures of patient-centeredness, while applying case-mix adjustment to control for sociodemographic and clinical factors. The practice for homeless patients scored higher than the comparison group on self-management support and behavioral health integration, while being equivalent on three other measures. Potential areas for improvement include measures related to communication, front desk staff, and timely appointments. We discuss possible explanations for the observed pattern of results in the context of the unique challenges faced by a practice designed to serve individuals experiencing homelessness.