Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

A latent profile analysis of resilience and their relation to differences in sleep quality in patients with lung cancer.

PURPOSE: Sleep problems are a significant issue in patients with lung cancer, and resilience is a closely related factor. However, few studies have identified subgroups of resilience and their relationship with sleep quality. This study aimed to investigate whether there are different profiles of resilience in patients with lung cancer, to determine the sociodemographic characteristics of each subgroup, and to determine the relationship between resilience and sleep quality in different subgroups. METHODS: A total of 303 patients with lung cancer from four tertiary hospitals in China completed the General Sociodemographic sheet, the Connor-Davidson Resilience Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis was applied to explore the latent profiles of resilience. Multivariate logistic regression was used to analyze the sociodemographic variables in each profile, and ANOVA was used to explore the relationships between resilience profiles and sleep quality. RESULTS: The following three latent profiles were identified: the "high-resilience group" (30.2%), the "moderate-resilience group" (46.0%), and the "low-resilience group" (23.8%). Gender, place of residence, and average monthly household income significantly influenced the distribution of resilience in patients with lung cancer. CONCLUSION: The resilience patterns of patients with lung cancer varied. It is suggested that health care providers screen out various types of patients with multiple levels of resilience and pay more attention to female, rural, and poor patients. Additionally, individual differences in resilience may provide an actionable means for addressing sleep problems.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

Association of Aortic Arch Calcification with Acute Ischemic Stroke Subtypes and Endovascular Thrombectomy Outcomes.

PURPOSE: To analyze the aortic arch calcification (AAC) on computed tomography (CT) scans, with the goal of predicting the subtypes of patients with ischemic stroke and endovascular thrombectomy (EVT) outcomes. MATERIALS AND METHODS: Automated analysis was used to quantify AAC on CT scans. From January 2020 to March 2021, 119 patients diagnosed with ischemic stroke were analyzed, and the feasibility of EVT was assessed; 43 underwent the procedure. RESULTS: AAC was present in 117 (98.3%) of 119 patients. There was a significant difference (P <.001) in AAC severity among all patients with ischemic stroke according to the Trial of ORG 10172 in Acute Stroke Treatment classification. In patients who underwent EVT, AAC severity was significantly related to the thrombolysis in cerebral infarction grade, thrombectomy procedure time, and modified Rankin scale at discharge (P =.002, P =.035 and P =.015, respectively). Multivariate logistic regression analysis also showed that severe AAC (volume, ≥1,000 mm3) (adjusted odds ratio [OR], 12.1; adjusted 95% confidence interval [CI]), 2.1-36.4; P =.001) and intracranial atherosclerotic disease (adjusted OR, 9.5; adjusted 95% CI, 2.3-33.7; P =.001) were both independently associated with poor thrombolysis reperfusion rate. CONCLUSIONS: A high proportion of patients with ischemic stroke have AAC, the severity of which is a potential imaging marker of ischemic stroke subtypes and the outcome of EVT.

The effect of serum uric acid, bilirubin, and albumin levels on antioxidant status in HIV-negative immunocompetent cryptococcal meningitis patients with post-infectious inflammatory response syndrome.

Oxidative imbalances have been observed in various neurological diseases. Despite the microbiological control in cryptococcal meningitis (CM), a proportion of previously healthy patients experience a clinical deterioration known as post-infectious inflammatory response syndrome (PIIRS). However, the antioxidant status in PIIRS remains unclear. In this study, we found that the serum antioxidant status of HIV-negative immunocompetent CM patients during PIIRS episodes was lower than that of healthy controls. There was a relationship between baseline serum indirect bilirubin levels and the development of PIIRS, and serum uric acid levels may indicate the severity of the disease during PIIRS episodes. Oxidative stress may play a role in the development of PIIRS.

This retrospective study on the serum antioxidant status in HIV-negative immunocompetent CM patients suggested that during PIIRS episodes, the serum antioxidant status in CM patients may be lower. CM patients with high baseline serum Ibil levels were more likely to develop PIIRS.

Clinical characteristics, treatment, and outcome of low-risk non-HIV-associated cryptococcal meningitis: A retrospective cohort study.

Although non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM) is a severe disease, there are still some non-HIV CM patients with a low risk of therapeutic failure. Recognizing clinical characteristics of low-risk non-HIV-associated CM may enable clinicians to treat non-HIV-associated CM more reasonably. According to the definition of low-risk non-HIV-associated CM in the 2010 Infectious Diseases Society of America guideline, a total of 220 non-HIV CM patients were divided into two groups (Group 1: 35 low-risk patients and Group 2: 185 non-low-risk patients). Clinical characteristics, treatment, and outcome were compared between the two groups. Compared with non-low-risk patients, low-risk patients had a lower rate of headache (82.9% vs. 95.7%, P = .012), cerebrospinal fluid (CSF) opening pressure (OP) at baseline (CSF OP < 250-mm H2O, 60.0% vs. 32.4%, P = .001), and baseline CSF cryptococcal count (median, 0 vs. 2376, P < .001), higher baseline CSF white blood cell (median, 130 vs. 90, P = .029) and CSF protein (median, 0.87 vs. 0.73, P = .011). Multivariate analysis showed that baseline CSF OP <250-mm H2O (OR: 2.545, 95% CI 1.168, 5.545, P = .019) was independently associated with low-risk for non-HIV-associated CM. The lengths of AMB-d-based induction therapy of low-risk patients (median, 20 days) were shorter (P < .001) than that of non-low-risk patients (median, 38 days). The successful outcome rate of low-risk patients was higher than non-low-risk patients (97.1% vs. 54.6%, P < .001). We demonstrated that non-HIV-associated CM patients with baseline CSF OP < 250-mm H2O were prone to the low-risk status.

This was a retrospective cohort study to find the features of low-risk non-human immunodeficiency virus (HIV)-associated cryptococcal meningitis (CM). We found that non-HIV-associated CM patients with baseline cerebrospinal fluid opening pressure <250-mm H2O were prone to low-risk status.

Panax notoginseng: derived exosome-like nanoparticles attenuate ischemia reperfusion injury via altering microglia polarization.

Cerebral ischemia/reperfusion (CI/R) injury is a clinical conundrum during the treatment of ischemic stroke. Cell-derived exosomes (CDE) were proved to be therapeutically effective for CI/R injury. However, production of CDE is time and effort consuming. Increasing studies reported that plants can also generate exosome-like nanoparticles (ELN) which are therapeutically effective and have higher yield compared with CDE. In this study, a commonly used Chinese herb Panax notoginseng (PN), whose active ingredients were well-documented in the treatment of CI/R injury, was chosen as a source of ELNs. It was found that Panax notoginseng derived exosome like nanoparticles (PDN) could enter the brain without modification and ameliorate cerebral infarct volume, improve behavior outcome and maintained the integrity of BBB. PDNs attenuated CI/R injury by altering the phenotype of microglia from "pro-inflammation" M1 type to "anti-inflammation" M2 type. Also, we found that lipids from PDNs were the major therapeutic effective component. As a mechanism of action, PDN was proved to exert therapeutic effect via activating pI3k/Akt pathway.

Genetic and Environmental Correlation Analysis of Serum Creatinine Levels in Chinese Twins.

Almost all creatinine is excreted by the kidney in individuals. Serum creatinine concentration, a widely used renal function index in clinical practice, can be affected by both genetic and environmental factors, as evidenced by current research exploring the relationship between these factors and kidney function. However, few studies have explored the heritability of serum creatinine in Asian populations. Therefore, we explored the genetic and environmental factors that affect the serum creatinine level in Asian populations. Participants in this study came from the Qingdao Twin Registry in China, and 374 pairs of twins were included, of which 139 pairs were dizygotic twins, whose ages ranged from 40 to 80 years old, and the serum creatinine level ranged from 10 to 126 µmol/L. Structural equation models were constructed using Mx software to calculate heritability, with adjusted covariates being age, sex, and body mass index. The results of heritability analysis showed that ACE was the best fit model. Serum creatinine level is influenced by genetic and environmental factors. The result of heritability was 35.44%, and the influence of shared environmental factors accounted for 52.13%. This study provided the relevant basis for future research on genetic and environmental factors affecting serum creatinine levels in Asian populations.

Family resilience of patients requiring long-term care: A meta-synthesis of qualitative studies.

BACKGROUND: Long-term care of patients with chronic illnesses is an important global public health issue, compromising the well-being of family members and the family functioning. Previous studies have examined the interactive experiences and processes of various systems in the families coping with long-term care stress; however, these studies have not been systematically reviewed and integrated. AIMS: This review aimed to synthesise the existing qualitative evidence on the experiences and processes of family resilience operate in families providing long-term care for patients with chronic illnesses and to provide suggestions for the development of interventions in future studies. MATERIALS & METHODS: We searched databases including PubMed, CINAHL, EMBASE, Web of Science, ProQuest and CNKI from their inception to March 2022. We used the JBI Critical Appraisal Tool for qualitative studies to evaluate the quality of the included studies was evaluated according to. We followed The Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) statement. The results were integrated using the thematic and content analysis method. RESULTS: Fourteen studies from eight countries covering 11 diseases reported on the experiences and coping processes of long-term care families. Based on McCubbin's Resiliency Model of Family Stress, Adjustment and Adaptation (FAAR), five analytical themes were synthesised: stressors (risk factors), family belief system, internal family coping strategies, external support and resilient adaptation indicators; the relationships between themes and subthemes were illustrated. DISCUSSION: This review synthesized qualitative evidence on the experiences and processes of family resilience operate in families providing long-term care. The results of this study found that the cognition and belief of family members regarding dilemmas have a two-way effect and act on the adaptation process of family members. In family adaptation, spirituality, hope, internal and external support are extremely important. In 14 studies, caregivers were from different countries with intercultural differences, but due to less reports on this content, it is difficult to compare the differences or impact that culture or ethnicity may have. CONCLUSIONS: Family resilience plays an important role in coping with stressors associated with the long-term care of a loved one through family belief systems, internal support systems and external support systems. The development of family resilience-based interventions for long-term care families should consider the family as a whole and further construct a multidisciplinary, multilevel and multi-type social support network to enhance family resilience.

Validation of the Chinese version of the Walsh Family Resilience Questionnaire.

The Walsh Family Resilience Questionnaire (WFRQ) is one of the most widely used and strong theory-based measurement tools of family resilience. This study aimed to develop and psychometrically test the Chinese version of the WFRQ (WFRQ-C). The WFRQ was translated following Brislin's translation model. Psychometric testing, combining classical theory test and item response theory, was conducted with a sample of 800 community adult residents. The Connor-Davidson resilience scale-10 (CD-RISC-10), Self-reported Family Happiness Scale (SFHS-1), and Family APGAR (Adaption, Partnership, Growth, Affection, Resolve) Scale (Family APGAR-5) were applied for convergent validity. Six items were deleted at the item analysis level. The minimum average partial test and a parallel analysis supported a three-factor structure, which was validated by confirmatory factor analysis. The three factors were named "Family belief system," "Organization, communication and problem solving," and "Utilization of external resources." The WFRQ-C was significantly correlated with CD-RISC-10, SFHS-1, and Family APGAR-5, with r values ranged from 0.51 to 0.56. The Cronbach's α was 0.97 for the scale and 0.93, 0.95, and 0.72 for the three factors, respectively. The ICCs of 0.96 for the whole scale, and 0.95, 0.75, and 0.95 for the three factors, respectively. The mean score for the WFRQ-C was 97.00 ± 17.94, of which per capita monthly income and education level were predictors. The 26-item WFRQ-C is a stable, concise, and validated tool to measure family resilience. It is applicable for Chinese community adults in nonspecific stressful settings and has potential utility in the health care domain.

El Cuestionario de resiliencia familiar de Walsh (Walsh Family Resilience Questionnaire, WFRQ) es uno de los instrumentos teóricos de medición de la resiliencia familiar más utilizados y sólidos. Este estudio tuvo como finalidad desarrollar y evaluar psicométricamente la versión china del WFRQ (WFRQ-C). El WFRQ se tradujo siguiendo el modelo de traducción de Brislin. Se realizó una evaluación psicométrica combinando la teoría clásica de los tests y una teoría de respuesta al ítem con una muestra de 800 residentes adultos de la comunidad. Se aplicó la Escala de resiliencia de Connor y Davidson-10 (CD-RISC-10), la Escala de felicidad familiar autoinformada (SFHS-1) y la Escala del APGAR familiar (Family APGAR-5) -adaptación, asociación, crecimiento, afecto, determinación- para la validez convergente. Se borraron seis ítems a nivel del análisis de los ítems. La evaluación parcial de promedio mínimo y un análisis paralelo respaldaron una estructura de tres factores, que fue validada por el análisis factorial confirmatorio. Se denominó a los tres factores "sistema de creencias familiares", "organización, comunicación y resolución de problemas" y "utilización de recursos externos". El WFRQ-C estuvo correlacionado significativamente con la CD-RISC-10, la SFHS-1 y el APGAR-5 familiar, con valores r que oscilaron entre 0.51 y 0.56. El alfa de Cronbach fue de 0.97 para la escala, y de 0.93, 0.95 y 0.72 para los 3 factores, respectivamente. Los coeficientes de correlación intraclase fueron de 0.96 para la escala completa, y de 0.95, 0.75 y 0.95 para los 3 factores, respectivamente. El puntaje promedio para el WFRQ-C fue de 97.00±17.94, que fue pronosticado por los ingresos mensuales por persona y el nivel de educación. El WFRQ-C de 26 ítems es un instrumento estable, conciso y validado para medir la resiliencia familiar. Puede aplicarse en adultos de la comunidad china en entornos estresantes no específicos y posiblemente en el ámbito de la asistencia sanitaria.

MARS1 mutations linked to familial trigeminal neuralgia via the integrated stress response.

BACKGROUND: While new genetic analysis methods are widely used in the clinic, few researchers have focused on trigeminal neuralgia (TN) with familial clustering (≥ 2 TN patients in one kindred family). Previous literature suggests that familial trigeminal neuralgia (FTN) may be associated with inherited genetic factors. To date, few next-generation sequencing studies have been reported for FTN. This study investigated the pathogenic mechanism of FTN by using whole-exome sequencing (WES) technology, which may enhance our understanding of human TN pathophysiology.  METHOD: We performed WES for 7 probands from families of FTN. Sanger sequencing was performed for two control groups (FTN family members group and nonfamilial TN subject group) to potentially identify new FTN-related gene mutations. In families where FTN probands carried potentially pathogenic gene mutations, the ribonucleic acid (RNA) of FTN probands and related family members, as well as nonfamilial TN patients were analysed by RNA sequencing (RNA-seq) to confirm differential gene expression. RESULTS: Seven probands were derived from 3 Chinese families. WES and Sanger sequencing identified MARS1 mutation c.2398C > A p.(Pro800Thr) in Family 1. MARS1 mutation was confirmed in 14/26 [53.8%] members of Family 1 in FTN family member group, while none of nonfamilial TN subjects had this MARS1 mutation. RNA-seq showed that 3 probands in Family 1 had higher expression of Fosl1 (Fos-like antigen 1) and NFE2 (Nuclear factor, erythroid 2) than 3 subjects in the nonfamilial TN subject group. Fosl1 and NFE2 are genes related to integrated stress response (ISR). CONCLUSION: MARS1 mutations may cause chronic activation of ISR, contribute to ISR pathophysiological changes in FTN, and cause/accelerate peripheral nerve degeneration. The findings of this study can enrich our knowledge of the role of molecular genetics in TN in humans.

Dyadic transmission of depression in the elderly people with disabilities to caregiver burden: Multiple mediating roles of caring ability and resilience. / å¤±èƒ½è€äººæŠ‘éƒå¯¹ç §é¡¾è€ è´Ÿæ‹ çš„äºŒå ƒä¼ é€’ï¼šç §æŠ¤èƒ½åŠ›å’Œå¿ƒç†å¼¹æ€§çš„å¤šé‡ä¸­ä»‹ä½œç”¨.

OBJECTIVES: The interaction between elderly people with disabilities and their caregivers and the improvement of caregiver burden is important for elderly people with disabilities and their caregivers. This study aims to explore the multiple mediating roles of caregiver's caring ability and resilience in depression in the elderly people with disabilities on caregiver burden. METHODS: A total of 246 elderly people with disabilities at home and their family caregivers from 5 regions were investigated by questionnaires, including the General Information Questionnaire, the Patient Health Questionnaire, the Family Caregiver Task Inventory, the Resilience Scale, and the Caregiver Burden Interview. A multiple mediation model was constructed and tested. RESULTS: Univariate analysis showed that the caregiver burden of disabled elderly men is higher than that of women; the lower the level of self-care of disabled elderly individuals, the greater the burden on their caregivers (both P<0.05). Correlation analysis showed that depression of the disabled elderly people was positively correlated with the caregiver burden (P<0.01). Caregiver's caring ability was positively correlated with caregiver's resilience (P<0.01), and both were negatively correlated with caregiver burden (both P<0.01). The multiple mediating effects of caregiver caring capacity and resilience between depression of the disabled elderly people and caregiver burden were significant, with the mediating effects of caregiver caring capacity and resilience accounting for 68.9% and 26.2% of the total effect, respectively. CONCLUSIONS: Depression in the elderly people with disabilities can indirectly affect caregiver burden through the caregiver's caring ability and resilience. Families of older people with disabilities need to focus on both the elderly and their caregivers. It is possible to reduce the caregiver burden and improve the physical and mental health of the dyads by empowering the caregiver's caring ability and resilience.

Continuous high-frequency deep brain stimulation of the anterior insula modulates autism-like behavior in a valproic acid-induced rat model.

BACKGROUND: Until now, the treatment of patients with autism spectrum disorder (ASD) remain a difficult problem. The insula is involved in empathy and sensorimotor integration, which are often impaired in individuals with ASD. Deep brain stimulation, modulating neuronal activity in specific brain circuits, has recently been considered as a promising intervention for neuropsychiatric disorders. Valproic acid (VPA) is a potential teratogenic agent, and prenatal exposure can cause autism-like symptoms including repetitive behaviors and defective sociability. Herein, we investigated the effects of continuous high-frequency deep brain stimulation in the anterior insula of rats exposed to VPA and explored cognitive functions, behavior, and molecular proteins connected to autism spectrum disorder. METHODS: VPA-exposed offspring were bilaterally implanted with electrodes in the anterior insula (Day 0) with a recovery period of 1 week. (Day 0-7). High-frequency deep brain stimulation was applied from days 11 to 29. Three behavioral tests, including three-chamber social interaction test, were performed on days 7, 13, 18, 25 and 36, and several rats were used for analysis of immediate early genes and proteomic after deep brain stimulation intervention. Meanwhile, animals were subjected to a 20 day spatial learning and cognitive rigidity test using IntelliCage on day 11. RESULTS: Deep brain stimulation improved the sociability and social novelty preference at day 18 prior to those at day 13, and the improvement has reached the upper limit compared to day 25. As for repetitive/stereotypic-like behavior, self- grooming time were reduced at day 18 and reached the upper limit, and the numbers of burried marbles were reduced at day 13 prior to those at day 18 and day 25. The improvements of sociability and social novelty preference were persistent after the stimulation had ceased. Spatial learning ability and cognitive rigidity were unaffected. We identified 35 proteins in the anterior insula, some of which were intimately linked to autism, and their expression levels were reversed upon administration of deep brain stimulation. CONCLUSIONS: Autism-like behavior was ameliorated and autism-related proteins were reversed in the insula by deep brain stimulation intervention, these findings reveal that the insula may be a potential target for DBS in the treatment of autism, which provide a theoretical basis for its clinical application., although future studies are still warranted.

Amphotericin B plus fluorocytosine combined with voriconazole for the treatment of non-HIV and non-transplant-associated cryptococcal meningitis: a retrospective study.

BACKGROUND: Our previous study explored Amphotericin B (AMB) plus 5-flucytosine (5-FC) combined with fluconazole (FLU) therapy in the induction period, which seemed to be better than the previous AMB + 5-FC antifungal therapy in non-HIV and non-transplant-associated CM. However, based on our clinical finding, the outcomes of some CM patients who received AMB plus 5-FC combined with FLU antifungal therapy were still poor. Therefore, we need to explore new antifungal methods in non-HIV and non-transplant-associated CM during the induction period. METHODS: Clinical data from 148 patients admitted to the Third Affiliated Hospital of Sun Yat Sen University from January 2011 to December 2020 were collected. These patients were stratified based on antifungal treatment methods in the induction period (group I with AMB + 5-FC + VOR, group II with AMB + 5-FC + FLU, group III with AMB + 5-FC). RESULTS: The first hospitalization time of Group I (median: 25 days, IQR: 20-34.5) was significantly shorter than that of Group II (median: 43 days, IQR: 29-62) (p < 0.001) and Group III (median: 50.5 days, IQR: 43-77.5) (p < 0.001). After 2 weeks of follow-up, Group I (26/49) had more patients reaching CSF clearance (p = 0.004) than Group II (18/71) and Group III (7/28). In multivariable analysis, Group II (OR: 3.35, 95%CI 1.43-7.82, p = 0.005) and Group III (OR: 3.8, 95%CI 1.23-11.81, p = 0.021) were associated with higher risk about CSF clearance failure at 2 weeks follow-up than Group I. After 10 weeks of follow-up, the incidence of hypokalemia in Group I was significantly lower than that in Group II (p = 0.003) and Group III (p = 0.004), and the incidence of gastrointestinal discomfort in Group I was significantly lower than that in Group II (p = 0.004). CONCLUSION: AMB plus 5-FC combined with VOR may rapidly improve clinical manifestation, decrease CSF OP and clear the cryptococci in CSF during the early phase, substantially shorten the hospitalization time, and reduce the incidences of hypokalemia and gastrointestinal discomfort.

A latent class analysis of resilience and its relationship with depressive symptoms in the parents of children with cancer.

PURPOSE: Depressive symptoms are among the most common afflictions that plague the parents of children with cancer. Given that resilience is an important factor that inhibits the development and progression of depressive symptoms, it can be harnessed as a potential solution for this psychological issue. This study aimed to identify the latent classes of resilience in the parents of children with cancer and explore the relationships of these classes with depressive symptoms. METHODS: The study was conducted in three tertiary hospitals in mainland China. The parents of children (0-19 years old) with cancer were invited to participate in the study. We used standardised self-report questionnaires to collect data. A latent class analysis was performed to identify the classes of resilience in the parents of children with cancer. RESULTS: The study recruited 258 participants. Four classes of resilience were identified, namely, good adaptation and optimism (24.9%), high strength and low control (12.1%), moderate resilience (37.3%), and maladaptation and low tenacity (25.6%). The mothers (OR = 3.48, P = 0.003) and parents with more than one child (OR = 2.73, P = 0.023) were more likely to belong to the maladaptation and low tenacity class. The depressive symptoms experienced by the participants differed significantly between the four classes of resilience (F = 30.80, P < 0.001). CONCLUSION: Targeted interventions should be developed and implemented based on the characteristics of each class of resilience to maximise the effectiveness of interventions and thereby promote parental well-being.

Targeting therapy and tumor microenvironment remodeling of triple-negative breast cancer by ginsenoside Rg3 based liposomes.

The chemotherapy effect of docetaxel (DTX) against triple-negative breast cancer (TNBC) remains mediocre and limited when encapsulated in conventional cholesterol liposomes, mainly ascribed to poor penetration and immunosuppressive tumor microenvironment (TME) caused by tumor stroma cells, especially cancer-associated fibroblasts (CAFs). Many studies have attempted to address these problems but trapped into the common dilemma of excessively complicated formulation strategies at the expense of druggability as well as clinical translational feasibility. To better address the discrepancy, ginsenoside Rg3 was utilized to substitute cholesterol to develop a multifunctional DTX-loaded Rg3 liposome (Rg3-Lp/DTX). The obtained Rg3-Lp/DTX was proved to be preferentially uptake by 4T1 cells and accumulate more at tumor site via the interaction between the glycosyl moiety of Rg3 exposed on liposome surface and glucose transporter1 (Glut1) overexpressed on tumor cells. After reaching tumor site, Rg3 was shown to reverse the activated CAFs to the resting stage and attenuate the dense stroma barrier by suppressing secretion of TGF-ß from tumor cells and regulating TGF-ß/Smad signaling. Therefore, reduced levels of CAFs and collagens were found in TME after incorporation of Rg3, inducing enhanced penetration of Rg3-Lp/DTX in the tumor and reversed immune system which can detect and neutralize tumor cells. Compared with wooden cholesterol liposomes, the smart and versatile Rg3-Lp/DTX could significantly improve the anti-tumor effect of DTX, providing a promising approach for TNBC therapy with excellent therapeutic efficacy and simple preparation process.

Dyadic interventions in older people with chronic diseases: An integrative review.

This integrative review aims to explore the current state of dyadic interventions in older people with chronic diseases and to review how these interventions are developed and conducted. 'Older people' and 'dyadic intervention' were searched in six databases to include studies published before August 2021. The constant comparison method was used for data synthesis, combined with the Joanna Briggs Institute (JBI)1 and mixed methods appraisal tool (MMAT)2 to assess the quality of the literature. Nineteen studies were included and could be divided into four types in which caregivers could be seen as subordinators, directors, cooperators and collaborators. Dyadic interaction could be observed in all studies, including dyad coled, patient-led, and caregiver-led interactions. The outcome indicators included patient-, caregiver-, dyad-, and family-related indicators. It is important not only to include the dyad but also to consider the dyadic interactions. In the future, dyadic intervention can be guided by matching dyadic theories. NO PATIENT OR PUBLIC CONTRIBUTION: This study is an integrative review; the study population was not directly contacted. Data from included studies were analysed and interpreted.

Obstetricians' perspectives on trial of labor after cesarean (TOLAC) under the two-child policy in China: a cross-sectional study.

BACKGROUND: As the birth policy has been adjusted from one-child-one-couple to universal two-child-one-couple in China, there is an increasing number of women undergoing a second pregnancy after a previous cesarean section (CS). Undertaking an elective repeat CS (ERCS) has been taken for granted and has thus become a major contributor to the increasing CS rate in China. Promoting trial of labor after CS (TOLAC) can reduce the CS rate without compromising delivery outcomes. This study aimed to investigate Chinese obstetricians' perspectives regarding TOLAC, and the factors associated with their decision-making regarding recommending TOLAC to pregnant women with a history of CS under the two-child policy. METHODS: A cross-sectional survey was carried out between May and July 2018. Binary logistic regression was used to determine the factors associated with the obstetricians' intention to recommend TOLAC to pregnant women with a history of CS. The independent variables included sociodemographic factors and perceptions regarding TOLAC (selection criteria for TOLAC, basis underlying the selection criteria for TOLAC, and perceived challenges regarding promoting TOLAC). RESULTS: A total of 426 obstetricians were surveyed, with a response rate of ≥83%. The results showed that 31.0% of the obstetricians had no intention to recommend TOLAC to pregnant women with a history of CS. Their decisions were associated with the perceived lack of confidence regarding undergoing TOLAC among pregnant women with a history of CS and their families (odds ratio [OR] = 2.31; 95% CI: 1.38-1.38); obstetricians' uncertainty about the safety of TOLAC for pregnant women with a history of CS (OR = 0.49; 95% CI: 0.27-0.96), and worries about medical lawsuits due to adverse delivery outcomes (OR = 0.14; 95% CI: 0.07-0.31). The main reported challenges regarding performing TOLAC were lack of clear guidelines for predicting or avoiding the risks associated with TOLAC (83.4%), obstetricians' uncertainty about the safety of TOLAC for women with a history of CS (81.2%), pregnant women's unwillingness to accept the risks associated with TOLAC (81.0%) or demand for ERCS (80.7%), and the perceived lack of confidence (77.5%) or understanding (69.7%) regarding undergoing TOLAC among pregnant women and their families. CONCLUSION: A proportion of Chinese obstetricians did not intend to recommend TOLAC to pregnant women with a history of CS. This phenomenon was closely associated with obstetricians' concerns about TOLAC safety and perceived attitudes of the pregnant women and their families regarding TOLAC. Effective measures are needed to help obstetricians predict and reduce the risks associated with TOLAC, clearly specify the indications for TOLAC, improve labor management, and popularize TOLAC in China. Additionally, public health education on TOLAC is necessary to improve the understanding of TOLAC among pregnant women with a history of CS and their families, and to improve their interactions with their obstetricians regarding shared decision making.

Contextualization of Psychological First Aid: An Integrative Literature Review.

PURPOSE: Contextualization of psychological first aid (PFA) in different cultural, political, and socioeconomic contexts and in different population groups is essential. This review analyzes the efforts that have been made to contextualize PFA in different parts of the world for different disasters and emergencies. DESIGN: Integrative literature review. METHODS: The major databases that were searched for related literature published until August 2019 included JBI, MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), BIOSIS, ISI Web of Knowledge, Scopus, EBSCOhost, and PsycINFO. A total of 17 studies published in peer-reviewed journals were included. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model, and the 6W3H tool was applied to synthesize the results. FINDINGS: PFA has been adapted to various disasters and populations in different countries and regions. The organizations that administer PFA range from community level to national level. Professional or "outside helpers" who enter disaster-affected locations include psychologists, fire fighters, social workers, and nurses. "Inside helpers," who live and work in the disaster-affected areas, include HR staff, teachers, and peer emergency personnel. Only a few studies have reported the exact number of first responders who administered PFA. Some studies revised PFA as group based, and a few reported the classification of groups of victims. Notably, all adaptations adhered to the basic principles of PFA, and the time at which PFA was administered ranged from a few days to months after an incident. PFA was conducted on site in all studies. The selection of the location depended on the type of disaster and local situation with due consideration of safety. Only a few studies specified the rationale for revising the PFA. None of these 17 studies reported the cost, cost-benefit, or cost-effectiveness of PFA. CONCLUSIONS: Population-focused, context-specific, and group-based PFA is emerging worldwide. Nurses are actively playing a role in providing PFA. Research gaps exist in differentiating between the roles played by "outside" and "inside" responders, considering vulnerable age groups other than children, incorporating the major PFA concepts such as resilience, and evaluating the cost-effectiveness of PFA. CLINICAL RELEVANCE: It is imperative that nurses and other emergency staff consider the intersection of age, gender, cultural, political, social economic, and spiritual contexts when developing a context appropriate PFA.