Dysregulation of persistent inward and outward currents in spinal motoneurons of symptomatic SOD1-G93A mice.

Persistent inward currents (PICs) and persistent outward currents (POCs) regulate the excitability and firing behaviours of spinal motoneurons (MNs). Given their potential role in MN excitability dysfunction in amyotrophic lateral sclerosis (ALS), PICs have been previously studied in superoxide dismutase 1 (SOD1)-G93A mice (the standard animal model of ALS); however, conflicting results have been reported on how the net PIC changes during disease progression. Also, individual PICs and POCs have never been examined before in symptomatic ALS. To fill this gap, we measured the net and individual PIC and POC components of wild-type (WT) and SOD MNs in current clamp and voltage clamp during disease progression (assessed by neuroscores). We show that SOD MNs of symptomatic mice experience a much larger net PIC, relative to WT cells from age-matched littermates. Specifically, the Na+ and Ca2+ PICs are larger, whereas the lasting SK-mediated (SKL) POC is smaller than WT (Na+ PIC is the largest and SKL POC is the smallest components in SOD MNs). We also show that PIC dysregulation is present at symptom onset, is sustained throughout advanced disease stages and is proportional to SOD MN cell size (largest dysregulation is in the largest SOD cells, the most vulnerable in ALS). Additionally, we show that studying disease progression using neuroscores is more accurate than using SOD mouse age, which could lead to misleading statistics and age-based trends. Collectively, this study contributes novel PIC and POC data, reveals ionic mechanisms contributing to the vulnerability differential among MN types/sizes, and provides insights on the roles PIC and POC mechanisms play in MN excitability dysfunction in ALS. KEY POINTS: Individual persistent inward currents (PICs) and persistent outward currents (POCs) have never been examined before in spinal motoneurons (MNs) of symptomatic amyotrophic lateral sclerosis (ALS) mice. Thus, we contribute novel PIC and POC data to the ALS literature. Male SOD MNs of symptomatic mice have elevated net PIC, with larger Na+ and Ca2+ PICs but reduced SKL POC vs. wild-type littermates. Na+ PIC is the largest and SKL POC is the smallest current in SOD cells. The PIC/POC dysregulation is present at symptom onset. PIC dysregulation is sustained throughout advanced disease, and is proportional to SOD MN size (largest dysregulation is in the largest cells, the most vulnerable in ALS). Thus, we reveal ionic mechanisms contributing to the vulnerability differential among MN types/sizes in ALS. Studying disease progression using SOD mice neuroscores is more accurate than using age, which could distort the statistical differences between SOD and WT PIC/POC data and the trends during disease progression.

The generalized order statistics arising from three populations with the lower truncated proportional hazard rate models and its application to the sensitivity to the early disease stage.

In this paper, we present some results to make inference about the parameters of lower truncated proportional hazard rate models with the same baseline distributions based on three independent generalized order statistics samples. Then, especially by considering the results of the diagnostic tests for the non-diseased, early-diseased stage and fully diseased populations, we make inference about sensitivity to the early disease stage parameter. The maximum likelihood estimator, a generalized pivotal estimator and some Bayes estimators are obtained for different structures of prior distributions. The percentile bootstrap confidence interval, a generalized pivotal confidence interval and some Bayesian credible intervals are also presented. A Monte Carlo simulation study is used to evaluate the performances of the obtained point estimators and confidence/credible intervals and two competitors. We use two real datasets to illustrate the proposed methods.

Efficacy of rituximab and risk factors for poor prognosis in patients with childhood-onset steroid-resistant nephrotic syndrome: a multicenter study.

BACKGROUND: The efficacy of rituximab in steroid-resistant nephrotic syndrome (SRNS) is controversial. We previously reported that rituximab in combination with methylprednisolone pulse therapy (MPT) and immunosuppressants was associated with favorable outcomes. We determined risk factors for poor response following rituximab treatment, which remains unknown. METHODS: This retrospective study included 45 patients with childhood-onset SRNS treated with rituximab across four pediatric kidney facilities. Treatment effects were categorized as complete remission (CR), partial remission (PR), and no remission (NR) at one year after rituximab treatment. The primary outcome was the rate of CR, PR, and NR. Risk factors for non-CR were calculated with multivariate logistic regression. Adverse events and the relationship between disease status at one year and long-term prognosis were also evaluated. RESULTS: The rates of CR, PR, and NR at one year were 69%, 24%, and 7%, respectively. The median time from rituximab administration to CR was 90 days. The median follow-up period after rituximab administration was 7.4 years. In multivariate analysis, significant risk factors for poor response were the pathologic finding of focal segmental glomerular sclerosis and a long interval between SRNS diagnosis and rituximab administration. The rates of CR were 90.3% and 21.4% in patients receiving rituximab within and after 6 months following SRNS diagnosis, respectively (p < 0.001). Five patients developed chronic kidney disease stage G5, including 2 of the 11 patients with PR and all 3 patients with NR, whereas none of the 31 patients with CR developed chronic kidney disease stage G5. CONCLUSION: Early administration of rituximab in combination with MPT and immunosuppressants might achieve favorable outcomes in patients with SRNS.

The impact of the COVID-19 pandemic on renal cancer care.

PURPOSE: To evaluate the impact of the COVID-19 pandemic on renal cell carcinoma (RCC) care in the Netherlands. METHODS: Newly diagnosed RCCs between 2018 and 2021 were selected from the Netherlands Cancer Registry; 2020-2021 was defined as COVID period and 2018-2019 as reference period. Numbers of RCCs were evaluated using 3-week-moving averages, overall and by disease stage and age. Changes in treatment were evaluated with logistic regression analyses. To evaluate possible delays in care, time to start of treatment was assessed. The cumulative number of metastatic RCC (mRCC) over time was assessed to evaluate stage shift. RESULTS: During the 1st COVID wave (weeks 9-22, 2020), the number of new RCC diagnoses decreased with 15%. Numbers restored partially in 2020, but remained 10% lower compared to 2018/2019. The decline was mostly due to a drop in T1a/T1b RCCs and in age > 70 years. 2021 showed similar numbers of new RCC diagnoses compared to 2018/2019 without an increase due to previously missed RCCs. Treatment-related changes during the 1st COVID wave were limited and temporarily; less surgery in T1a RCCs in favor of more active surveillance, and in mRCC targeted therapy was preferred over immunotherapy. Time to start of firstline treatment was not prolonged during the 1st COVID wave. No increase in mRCC was found until the end of 2021. CONCLUSIONS: The COVID-19 pandemic resulted in fewer RCC diagnoses, especially T1a/T1b tumors. Treatment-related changes appeared to be limited, temporarily and in accordance with the adapted guidelines. The diagnostic delay could lead to more advanced RCCs in later years but there are no indications for this yet.

Exploring the impact of stage and tumor site on colorectal cancer survival: Bayesian survival modeling.

Colorectal cancer is a prevalent malignancy with global significance. This retrospective study aimed to investigate the influence of stage and tumor site on survival outcomes in 284 colorectal cancer patients diagnosed between 2001 and 2017. Patients were categorized into four groups based on tumor site (colon and rectum) and disease stage (early stage and advanced stage). Demographic characteristics, treatment modalities, and survival outcomes were recorded. Bayesian survival modeling was performed using semi-competing risks illness-death models with an accelerated failure time (AFT) approach, utilizing R 4.1 software. Results demonstrated significantly higher time ratios for disease recurrence (TR = 1.712, 95% CI 1.489-2.197), mortality without recurrence (TR = 1.933, 1.480-2.510), and mortality after recurrence (TR = 1.847, 1.147-2.178) in early-stage colon cancer compared to early-stage rectal cancer. Furthermore, patients with advanced-stage rectal cancer exhibited shorter survival times for disease recurrence than patients with early-stage colon cancer. The interaction effect between the disease site and cancer stage was not significant. These findings, derived from the optimal Bayesian log-normal model for terminal and non-terminal events, highlight the importance of early detection and effective management strategies for colon cancer. Early-stage colon cancer demonstrated improved survival rates for disease recurrence, mortality without recurrence, and mortality after recurrence compared to other stages. Early intervention and comprehensive care are crucial to enhance prognosis and minimize adverse events in colon cancer patients.

Comparisons of postural control, proprioception, muscle strength, pain and disability between individuals with acute, subacute and chronic low back pain.

PURPOSE/AIM: Postural control, proprioception and lower extremity muscle strength are affected in individuals with low back pain (LBP). However, it is yet unknown whether these variables differentiate between acute, subacute and chronic stages of LBP. The aim was to investigate if there were any differences in postural control, proprioception, lower extremity muscle strength, pain intensity and disability between individuals in the different stages of LBP. MATERIALS AND METHODS: In this cross-sectional study, 124 individuals with LBP were grouped as acute LBP (ALBP) (n = 38), subacute LBP (SLBP) (n = 30) and chronic LBP (CLBP) (n = 56) groups. Postural control was assessed via computerised technology. Lumbar proprioception, lower extremity muscle strength, pain intensity and disability were assessed using Joint Repositioning Error Test, hand-held dynamometer, Numeric Rating Scale and Oswestry Disability Index (ODI), respectively. Kruskal-Wallis Tests, ANCOVA and post hoc Mann-Whitney U-Test with Bonferroni correction were performed. RESULTS: While there were no significant differences in terms of postural control, proprioception and pain intensity (p > 0.05), significant differences were found in terms of lower extremity muscle strength and ODI scores between groups when adjusted for age (p < 0.05). Individuals with CLBP demonstrated poorer lower extremity muscle strength than those with ALBP and SLBP, and higher disability than those with ALBP (p < 0.017). CONCLUSIONS: Although postural control, proprioception and pain intensity were similar between individuals with acute, subacute and chronic LBP, muscle strength and disability seem to worsen stepwise as the pain becomes chronic. Muscle strength and disability should be taken into account while evaluating and/or managing individuals with acute and subacute stages of LBP.

Relationship between plasma SP-A expression level and disease stage in silicosis patients / 上海预防医学

ObjectiveTo investigate the relationship between plasma surfactant protein⁃A （SP⁃A） expression level and silicosis progression， and to provide early evidence for exploring whether SP⁃A can be used as a biomarker for clinical monitoring of silicosis disease progression. MethodsWe recruited 187 silicosis patients in Guangdong Province hospital for occupational disease prevention and treatment between November， 2019 and November，2020. Their peripheral venous blood samples were collected for the plasma isolation. The level of pulmonary SP⁃A was detected by enzyme-linked immunosorbent assay. ResultsThere was a statistically significant difference in the level of SP⁃A among the silicosis groups （P<0.05）， and the plasma SP-A level of the silicosis patients in stage Ⅲ was higher than that in stage Ⅰ and stage Ⅱ （P<0.05）. Smoking had effect on plasma SP⁃A levels， Age， working years and drinking had no effect on plasma SP⁃A levels. ConclusionThe expression level of SP⁃A in the plasma of silicosis patients is increased， which has a certain correlation with the disease stage， and plays a certain early warning role in the occurrence and development of silicosis， and may be a potential biomarker for the diagnosis and prognosis of silicosis.

Biological Connotation of Disease-stage-state of Hypertension in Concept of State-target Differentiation and Treatment From Perspective of Lipophagy / 中国实验方剂学杂志

Hypertension is a common chronic disease with elevated arterial pressure as the main clinical manifestation，which can cause lesions in important organs such as heart，brain and kidney. In recent years，the prevalence of hypertension has increased，and its incidence is also increasing year by year. Combining the theory of traditional Chinese medicine （TCM） with personal clinical experience，Academician TONG Xiaolin put forward the specific pathogenesis of "disease-stage-state" of hypertension based on the state-target theory. Lipophagy plays an important role in the pathogenesis of hypertension by interfering with lipid metabolism，atherosclerosis，arterial plaque formation，vascular remodeling，vascular endothelial injury and other aspects of hypertension. Through modern medical and biological research，on the one hand，it is believed that the dynamic pathological changes in lipophagy are closely related to the "stage" of hypertensive state-target differentiation and treatment，corresponding to the time points of disease occurrence and development in the three stages of hypertension. On the other hand，it is believed that lipophagy is an important microscopic manifestation of the "state" of hypertensive state-target differentiation and treatment. From the perspective of lipophagy，this paper discusses the biological connotation of the 'disease-stage-state' model of state-target differentiation and treatment of hypertension and draws on the modern medicine to understand the law of disease development，matching the macro differentiation and treatment of TCM and the micro physico-chemical indicators of modern medicine to achieve precise TCM treatment. This study provides new ideas for the early prevention and treatment of hypertension and its complications.

Nano-Brush Structure for Rapid Label-Free Differentiation of Alzheimer's Disease Stages and Direct Capture of Neuron-Derived Exosomes from Human Blood Plasma.

The measurement of the neurofilament light chain (NFL) in human blood plasma/serum is a promising liquid biopsy for Alzheimer's disease (AD) diagnosis, offering advantages over conventional neuroimaging techniques recommended in clinical guidelines. Here, a controllable nano-brush structure comprising upstanding silicon nanowires coated with indium tin oxide was employed as the sensing substrate. This nano-brush structure was modified with an NFL antibody (NFLAb) via silane coupling and then further connected as the extended gate in a field-effect transistor (EGFET). Notable signal differences emerged within a 2 min timeframe, enabling the label-free differentiation in human blood plasmas among four distinct cohorts: healthy controls, subjective cognitive decline, mild cognitive impairment, and dementia due to AD. Our study indicates that achieving a surface roughness exceeding 400 nm on the modified nano-brush structure enables the effective electrical sensing in our EGFETs. These distinct electrical responses measured via the NFLAb-modified nano-brush EGFETs can be attributed to the combined effects of the captured NFLs and NFL-specific neuron-derived exosomes (NDEs) found in dementia patients, as confirmed by electron spectroscopy for chemical analysis, atomic force microscopy, and scanning electron microscopy. Finally, the potential of quantitatively detecting NDEs on the NFLAb-modified nano-brush structure was demonstrated using spiked solutions containing NFL-specific NDEs from IMR-32 neuroblast cells, wherein concentration-dependent changes were observed in the EGFETs output signal. Our findings show that the NFLAb-modified nano-brush EGFET enables rapid, label-free differentiation between healthy individuals and patients at varying stages of AD.

Liver Metabolomics Analysis Revealing Key Metabolites Associated with Different Stages of Nonalcoholic Fatty Liver Disease in Hamsters.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is not only the top cause of liver diseases but also a hepatic-correlated metabolic syndrome. This study performed untargeted metabolomics analysis of NAFLD hamsters to identify the key metabolites to discriminate different stages of NAFLD. METHODS: Hamsters were fed a high-fat diet (HFD) to establish the NAFLD model with different stages (six weeks named as the NAFLD1 group and twelve weeks as the NAFLD2 group, respectively). Those liver samples were analyzed by untargeted metabolomics (UM) analysis to investigate metabolic changes and metabolites to discriminate different stages of NAFLD. RESULTS: The significant liver weight gain in NAFLD hamsters was observed, accompanied by significantly increased levels of serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Moreover, the levels of TG, LDL-C, ALT, and AST were significantly higher in the NAFLD2 group than in the NAFLD1 group. The UM analysis also revealed the metabolic changes; 27 differently expressed metabolites were detected between the NAFLD2 and NAFLD1 groups. More importantly, the levels of N-methylalanine, allantoin, glucose, and glutamylvaline were found to be significantly different between any two groups (control, NAFLD2 and NAFLD1). Receiver operating characteristic curve (ROC) curve results also showed that these four metabolites are able to distinguish control, NAFLD1 and NAFLD2 groups. CONCLUSION: This study indicated that the process of NAFLD in hamsters is accompanied by different metabolite changes, and these key differently expressed metabolites may be valuable diagnostic biomarkers and responses to therapeutic interventions.

Socioeconomic position and the pre-diagnostic interval among patients diagnosed with head and neck squamous cell carcinoma - a population-based study from DAHANCA.

BACKGROUND: The socioeconomic differences in survival are pronounced for patients diagnosed with head and neck cancer; disease stage at diagnosis is suggested to be a main driver of this association. This nationwide, population-based study investigates socioeconomic differences in the pre-diagnostic interval and disease stage at diagnosis. MATERIAL AND METHODS: Information on patient-reported symptoms, symptom onset and disease-specific factors was obtained from the nationwide population-based Danish Head and Neck Cancer Group (DAHANCA) database for patients diagnosed with head and neck squamous cell carcinoma between 2008 and 2019 in Denmark. Socioeconomic position (SEP) was measured by individual-level education, income and cohabitation status obtained from administrative registers. Socioeconomic differences in the interval from symptom onset to diagnosis were investigated in general linear models with 95% confidence intervals (CIs); overall and by subsite, symptom and comorbidity score. Consultation patterns prior to diagnosis were examined using methods for change-point detection. Associations with advanced-stage disease were estimated in logistic regression models. RESULTS: Patients with low, medium and high SEP had a similar interval from patient-reported symptom onset to diagnosis of 10 weeks. Although this interval varied according to primary symptom and anatomical subsite, no apparent socioeconomic differences were observed within these subgroups. Aligned with the patient-reported symptom onset, a distinct increase in consultation rates was observed at 9 weeks (95% CI [7.3; 10.7]) for patients with low SEP and 7 weeks (95% CI [4.8; 9.2]) for patients with high SEP, with overlapping CIs. Patients with low compared to high SEP had increased odds for advanced-stage glottic and oral cavity squamous cell carcinoma. For the remaining subsites the association varied according to SEP-indicator and TNM-edition. CONCLUSION: The interval from symptom onset to diagnosis and consultation patterns were similar across SEP groups. Still, socioeconomic differences in stage at diagnosis were observed for some - but not all - subsites.

Human microglial state dynamics in Alzheimer's disease progression.

Altered microglial states affect neuroinflammation, neurodegeneration, and disease but remain poorly understood. Here, we report 194,000 single-nucleus microglial transcriptomes and epigenomes across 443 human subjects and diverse Alzheimer's disease (AD) pathological phenotypes. We annotate 12 microglial transcriptional states, including AD-dysregulated homeostatic, inflammatory, and lipid-processing states. We identify 1,542 AD-differentially-expressed genes, including both microglia-state-specific and disease-stage-specific alterations. By integrating epigenomic, transcriptomic, and motif information, we infer upstream regulators of microglial cell states, gene-regulatory networks, enhancer-gene links, and transcription-factor-driven microglial state transitions. We demonstrate that ectopic expression of our predicted homeostatic-state activators induces homeostatic features in human iPSC-derived microglia-like cells, while inhibiting activators of inflammation can block inflammatory progression. Lastly, we pinpoint the expression of AD-risk genes in microglial states and differential expression of AD-risk genes and their regulators during AD progression. Overall, we provide insights underlying microglial states, including state-specific and AD-stage-specific microglial alterations at unprecedented resolution.

Healthcare resource utilization at different stages of amyotrophic lateral sclerosis: Results from a real-world survey.

People with amyotrophic lateral sclerosis (pALS) require complex, multi-disciplinary care, resulting in extensive healthcare resource utilization (HCRU). To investigate the relationship between HCRU and ALS progression, the study objectives were (i) to characterize HCRU in pALS and (ii) to establish whether this varied according to disease stage, as defined using three different methodologies: neurologist-defined early/mid/late stage, the King's clinical staging system for ALS, and the Milan Torino Staging system for ALS (MiToS). Real-world data were drawn from the Adelphi ALS Disease-Specific Programme™, a point-in-time survey of neurologists in France, Germany, Italy, Spain, the UK, and the USA conducted July 2020-March 2021. The analysis included survey responses from 142 physicians with respect to 880 pALS. With advancing ALS stage, significant differences were observed in the number of healthcare professional consultations and X-rays per person (both p < 0.05 for all staging systems), and the proportion of pALS with emergency room admissions, intensive care unit admissions, and assisted ventilation (all p < 0.05 for all staging systems). Across stages, >55% of pALS received care from a general neurologist and a general/primary care practitioner. With increasing stage, there was a significant difference in the proportion receiving care from a physical therapist, pulmonologist/respiratory care practitioner, respiratory therapist, speech/language therapist, and palliative care team, and in the proportion receiving care only from professional caregivers (all p < 0.05 for all staging systems). This study confirmed the substantial HCRU required to support pALS through all stages of ALS and highlighted an increasing need for healthcare resources as the disease progresses.

The Clinical Usefulness of Mean Corpuscular Hemoglobin Concentration in Patients with Pneumoconiosis.

Aim: We investigated the clinical usefulness of mean corpuscular hemoglobin concentration (MCHC) in patients with pneumoconiosis. Methods: We retrospectively investigated the medical records from 52 patients with pneumoconiosis, and erythrocyte parameters were analyzed in pneumoconiosis patients with different stages. Results: Here, we found that the values of MCHC were significantly lower in III stage pneumoconiosis than those with I/II stage (p = 0.024), and there was no significantly difference in MCHC between smoking pneumoconiosis patients and non-smoking pneumoconiosis patients. A negatively correlation between MCHC and disease stage was observed in patients with pneumoconiosis (r = -0.298, p = 0.032). In multiple linear regression analysis, the MCHC was found to be independently associated with advanced pneumoconiosis in patients with pneumoconiosis (p=0.011). The results of logistic regression analysis indicated that decreased MCHC was an independent risk factor of advanced pneumoconiosis in patients with pneumoconiosis (OR: 0.936, CI95%: 0.877-0.999, p = 0.046). Receiver operating characteristic curve analysis showed that the optimal cutoff value of MCHC was 330 g/L to identify advanced pneumoconiosis with the area under the curve of 0.694 (CI95%:0.550-0.839, p = 0.018). Conclusion: The decreased MCHC is associated with advanced pneumoconiosis, and MCHC may be used as a monitoring marker for follow-up of pneumoconiosis patients.

Are persons living with diagnosed HIV capable of mounting a strong inflammatory response to the new coronavirus?

BACKGROUND: The impact of COVID-19 on persons living with diagnosed HIV (PLWDH) remains incompletely understood. It's unclear whether an impaired immune system offers protection against mounting cytokine storm. METHODS: Retrospective matched cohort study of COVID-19 hospitalized individuals in New York State (NYS). Medical records were abstracted and analyzed for 853 PLWDH hospitalized with COVID-19 in NYS and 1621 HIV-negative controls. Preexisting comorbidities and inflammatory markers measured within 24 h of hospital admission were abstracted. RESULTS: PLWDH were significantly less likely to have elevated inflammatory markers compared to matched controls. Elevated WBC occurred in 23.3% of PLWDH vs 30.1% of controls (p = .0002), elevated CRP in 37.4% of PLWDH vs 43.2% of controls (p = .03), elevated ferritin in 73.4% of PLWDH vs 78.9% of controls (p = .004). There was an inverse but not statistically significant relationship between the frequency of elevated inflammatory markers and HIV disease stage, with greatest percent of PLWDH with elevated WBC, LDH, CRP, and ferritin among PLWDH with HIV disease stage 1. CONCLUSION: PLWDH had lower inflammatory marker elevation during COVID-19 infection compared to matched controls. PLWDH with low CD4 were less likely to mount a cytokine storm in the setting of impaired immune function.

Symptom aggravation after withdrawal of metal chelating agent therapy in patients with Wilson's disease.

OBJECTIVE: To study the aggravation of clinical symptoms after discontinuation of metal chelating agent therapy in Wilson's disease (WD) patients, analyze the causes of aggravation, and observe the prognosis. METHODS: 40 WD patients (cerebral type 30 cases and hepatic type 10 cases) who stopped using metal chelating agent were selected, 40 WD patients with normal therapy, and 10 normal control cases were selected. All patients underwent neurological symptom evaluation using modified Young scale, Child-Pugh liver function grading, metal metabolism, and disease typing. Magnetic sensitivity imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy imaging (MRS) were performed. According to the imaging results, WD patients were divided into metal deposition stage, fiber damage stage, and neuron necrosis stage. All patients were treated with metal chelating agent for 6 months. RESULTS: The score of modified Young scale in drug withdrawal group was lower than that in normal treatment group before drug withdrawal (p = .032). The score of modified Young scale was higher after drug withdrawal than before (p = .011). The number of Child-Pugh B-grade patients after drug withdrawal was more than that before drug withdrawal and in normal treatment group. The proportion of patients in the stage of neuronal necrosis after drug withdrawal (25%) was higher than that before drug withdrawal (10%) (p = .025). After drug withdrawal, urine copper was significantly higher than that before drug withdrawal and in the normal treatment group (p = .032, .039). After the withdrawal group resumed metal chelating agent treatment, 34.2% of neurological symptoms worsened. CONCLUSIONS: WD patients showed neurological symptoms aggravation and increased liver injury after metal chelating agent withdrawal. Increased metal deposition and new nerve injury occurred in the brain. After re-treatment, the aggravated neurological symptoms of WD patients are difficult to reverse.

Overview of, and Preparations for, Dialysis.

Chronic kidney disease (CKD) is a progressive condition which is defined by decreased kidney function evidenced by a glomerular filtration rate (GFR) less than 60 mL/min per 1.73 m2 or markers of kidney damage, or both, for at least 3 months, regardless of the underlying cause. The 5 stages of CKD are based on the estimated GFR. Patients with CKD have significantly higher rates of morbidity, mortality, hospitalization, and health care utilization. Renal replacement therapy in the form of dialysis or kidney transplant is the life-sustaining treatment for patients with kidney failure. Predialysis education helps patients make informed decisions and opt for a modality conducive with their lifestyle/values. It has also been associated with improvement in measurable outcomes such as delayed initiation of dialysis, cardiovascular complications, and mortality.

The profile of Black South African men diagnosed with prostate cancer in the Free State, South Africa.

BACKGROUND: Prostate cancer (PCa) ranks high in terms of morbidity and mortality, especially in Africa. Prostate-specific antigen (PSA) screening remains a practical method of screening for and thereby detecting PCa early, especially among African men who are more negatively affected. Modifiable risk factors for PCa are mostly behavioural and lifestyle. Understanding community-specific determinants is important when developing health promotion interventions. OBJECTIVE: This study aimed to determine the profile of African men with PCa in the Free State, South Africa. METHOD: A cross-sectional descriptive study was conducted using case record information and self-administered questionnaires among 341 African men with PCa attending the oncology and urology clinics of a tertiary hospital. RESULT: Participants' median age at diagnosis was 66 years. Only 76 (22.3%) participants had ever heard of PCa prior to being diagnosed with the disease, 36 (47.4%) of whom had ever had screening performed. The majority (n = 298, 87.4%) were symptomatic; 50% sought medical help within six months. At diagnosis, 133 (39.0%) men presented with stage T3 or T4 disease, 75 (22.0%) with metastatic disease and 84 (24.6%) with Gleason score ≥ 8. Factors associated with advanced and high-grade disease included smoking, decreased sunlight exposure and physical activity, relatively increased ingestion of dairy products and red meat. Factors associated with early stage and low-grade disease included relatively increased ingestion of fruits, vegetables and fish. CONCLUSION: Advanced and high-grade PCa disease is not uncommon among men ≥ 60 years in this study setting. Certain modifiable risk factors associated with advanced disease were established in this study. The majority had lower urinary tract symptoms (LUTS) prior to PCa diagnosis, but they were of poor health-seeking behaviour. Although there seems not to be a systematic delay in the definitive diagnosis and initiation of treatment for PCa, there is a need to improve on health education and awareness in the study setting.

Universal HIV testing and the impact of late diagnosis on disease stage among adults in urban Ethiopia.

BACKGROUND: Treatment as prevention evolved into the universal HIV test-and-treat (UTT) strategy, which entails testing to the general population and treatment to every people living with HIV. We investigated universal testing (UT) performance and its determinants in urban Ethiopia and explore magnitude of late diagnosis and its impact on disease stages. METHOD: We used data from the Ethiopia Population Based HIV Impact assessment (EPHIA), conducted in 2017/2018 which was a cross-sectional and household-based study. For current analysis, we considered self-report first diagnosis to estimate universal testing irrespective of their serostatus and also consider HIV LAg avidity vs viral load vs plasma antiretroviral drug level algorithm to categorize the late diagnosis. We finally evaluate disease stages using CD4 count and viral load. A 2-level multilevel mixed-effect logistic regression model was employed. The effects of individual-level predictors were quantified by the estimates from the fixed-effect part of the model with p-value < 0.05. RESULT: Data were collected from 18,926 adults among those 29.4% of people living in Urban Ethiopia were never tested for HIV. Never tested females was 26.4% (95% CI = 25.3; 27.5). Never tested among divorced and widowed were 19.4% (95% CI: 17.3; 21.8) and 28.3% (95% CI: 24.6; 32.2), respectively. Never tested among elderly and youth were high (28.3% among 45-54 years old) to (41.2% among 55-64 years old) to 47.8% among 15-24 years old. Overall, late HIV diagnosis among adults in urban Ethiopia was 25.9% (95% CI: 21.7, 30.2). Late diagnosis varies by region ranged from 38.1% in the Gambella to 5.8% in Benishangul Gumuz. Advanced immune suppression (CD4 count < 350 cells/µl) among newly diagnosed long-term infection were significantly higher compared to those who were recently infected which accounted 47.8% (95%CI = 33.2-52.1) and 30.9% (95%CI = 21.3-32.2), respectively. Moreover, Viral load suppression were significantly lower among those who were late diagnosed 26.1% (95%CI = 13.6-33.8) compared to those of newly infected 89.6% (95%CI = 76.2; 93.4). CONCLUSION: With the aim of UT for high risk and priority population, the low rate of HIV testing among widowed, elderly, young adolescent and women in urban Ethiopia calls for enhanced HIV testing. Moreover, the low HIV testing and high late diagnosis among the high-burden regions calls for region-specific intervention. Advanced disease stages as a result of the high proportion of late diagnosis may impact on fueling community transmission and hinder treatment outcome among PLHIV.