New Insights on Chronic Illness: Pathogenesis, Prevalence, Prevention, and Systemic Therapies

Background: The subject of the study was the effect of a multicomponent program (Mobility Routine) on muscular and fascial stiffness, flexibility, subjective well-being, and body perception. Methods: The assumption was that high physical stress affects myofascial structures and joint range of motion. The assessment of myofascial stiffness employed a Shear Wave Elastography. The joint flexibility, pressure pain threshold, and subjective experiences with regard to tension, pain, and general discomfort were documented. Results: In the CT group, a greater increase in stiffness was measured in fewer measurement areas compared to the MR group. MR demonstrated superior gains in flexibility compared to CT. Both groups experienced significant reductions in pain, tension, and discomfort. In conclusion, repetitive motion patterns akin to CT lead to increased myofascial stiffness, whereas MR yields more balanced stiffness development, compensates for asymmetries, and improves body awareness. Conclusions: Hence, this study highlights the advantages of mobility training over Crosstrainer exercises and provides valuable insights for the recommendation of training regimens aiming at the enhancement of musculoskeletal functionality and overall well-being. Full article

From a cohort of 2018 evaluable consecutive cases issued from the European Clinical Trial Database, we describe the complete clinical symptomatic presentation of electrohypersensitivity (EHS) and multiple chemical sensitivity (MCS) and their association in the framework of a unique, sensitivity-related environmental neurologic syndrome. Eligibility criteria are those of the Atlanta consensus meeting for MCS, and those of WHO for EHS. There were 1428 EHS, 85 MCS and 505 EHS/MCS evaluable cases, so EHS was associated with MCS in 25%. Women appeared to be much more susceptible to EHS and/or to MCS than men, with no statistical significance between the EHS and MCS groups (p = 0.07), but the combined group revealed a more significant female sex ratio of 80.4% (p < 0.0001). All symptoms except emotional behavior were significantly more frequent in EHS patients than in healthy controls (p < 0.0001). We found no pathognomonic symptoms to establish the diagnosis of both disorders or to distinguish EHS from MCS. The three groups of patients were found to share identical symptoms, while several symptoms were found to be more significantly frequent in EHS/MCS than in EHS (p < 0.0001). From these data, we suggest that EHS and MCS are new brain disorders, generated via a common etiopathogenic mechanism. Full article

In diabetes, possibly the most significant site of microvascular damage is the kidney. Due to diabetes and/or other co-morbidities, such as hypertension and age-related nephron loss, a significant number of people with diabetes suffer from kidney diseases. Improved diabetic care can reduce the prevalence of diabetic nephropathy (DN); however, innovative treatment approaches are still required. MicroRNA-21 (miR-21) is one of the most studied multipotent microRNAs (miRNAs), and it has been linked to renal fibrosis and exhibits significantly altered expression in DN. Targeting miR-21 offers an advantage in DN. Currently, miR-21 is being pharmacologically silenced through various methods, all of which are in early development. In this review, we summarize the role of miR-21 in the molecular pathogenesis of DN and several therapeutic strategies to use miR-21 as a therapeutic target in DN. The existing experimental interventions offer a way to rectify the lower miRNA levels as well as to reduce the higher levels. Synthetic miRNAs also referred to as miR-mimics, can compensate for abnormally low miRNA levels. Furthermore, strategies like oligonucleotides can be used to alter the miRNA levels. It is reasonable to target miR-21 for improved results because it directly contributes to the pathological processes of kidney diseases, including DN. Full article

(1) Background: Constipation is one of the most serious adverse effects of potassium-lowering agents and decreases patients’ quality of life. Sodium zirconium cyclosilicate (SZC) is a recently innovated potassium binder intended for patients with hyperkalemia. The impact of SZC on the worsening of constipation, as compared with conventional potassium binders, remains unknown. (2) Methods: Patients with hyperkalemia who continued SZC for over 3 months between July 2020 and May 2022 were included in this retrospective study. Patients who received other conventional potassium binders during the same period were included as a control group. Trends in the doses of anti-constipation agents during the 3-month therapeutic period were compared between the two groups as a surrogate for worsening constipation. (3) Results: A total of 50 patients (median age 74 years, 31 male) were included, consisting of 22 patients with SZC and 28 patients with other conventional potassium binders. All patients had hyperkalemia and chronic kidney disease at baseline. During the 3-month therapeutic period, serum potassium levels decreased significantly in both groups (p < 0.05 for both). The number of anti-constipation remained unchanged in the SZC group but tended to increase in the control group (p = 0.56 and p = 0.090, respectively). The total dose change in all anti-constipations was significantly lower in the SZC group than in the control group (p = 0.037). (4) Conclusions: Conventional potassium binders have a tendency to worsen constipation, whereas SZC may have the potential to improve hyperkalemia without worsening constipation. SZC may be recommended, particularly in elderly patients with ongoing or high-risk constipation. Full article

The cardiac variant of Fabry disease (FD) has high rates of missed diagnosis and misdiagnosis due to the lack of systemic symptoms. Here, we report a case of a 68-year-old female with delayed-onset FD presenting as concentric left ventricular hypertrophy (LVH) with right bundle branch block, atrial fibrillation, and diastolic dysfunction, which was first presented with coronary artery spasm. Early cardiac-specific signs are crucial for diagnosing this disease due to the lack of extracardiac indications and the late onset of symptoms. This case raises a new red flag that patients with unexplained LVH and its atypical electrocardiographic (ECG) manifestations accompanied by diastolic dysfunction should be considered for FD. We also recommend further refinement of examinations associated with Fabry disease, which will contribute to the early diagnosis and treatment of the disease. Full article

Background: The purpose of this study is to clarify the changes in peripheral blood eosinophil (PBE) counts and eosinophilic granulomatosis with polyangiitis (EGPA) onset in patients with asthma who were treated with dupilumab in clinical practice. Methods: The primary outcome of this study is to determine the onset of EGPA in patients whose PBE counts continued to rise within 6 months of dupilumab initiation (rising group) and in patients whose PBE counts peaked and subsequently declined within 6 months (peaked and declined group). As a secondary outcome, the incidence of developing EGPA in patients with PBE counts greater than 1500 cells/μL at 3 or 6 months after dupilumab administration is investigated. Results: A total of 37 individual were enrolled (male/female = 14/23, median age = 57.0 years old). The development of EGPA was significantly more frequent in the rising group compared with the peaked and declined group (p = 0.042, effect size = 0.455, moderate association). Patients with PBE counts greater than 1500 cells/μL showed a significantly higher risk of developing EGPA (p = 0.017, effect size = 0.678, strong association). Conclusions: Physicians should check for the onset of EGPA by monitoring the elevation of eosinophils within 6 months after dupilumab administration, especially in patients with PBE counts greater than 1500 cells/μL at 3 months. Full article

Chronic obstructive pulmonary disease (COPD) is a complex and serious disease that is characterized by dyspnea, fatigue, decreased exercise tolerance, peripheral muscle dysfunction, and mood disorders. These manifestations are successfully treated with pulmonary rehabilitation, a comprehensive intervention and holistic approach designed to improve the physical and psychological condition of people with COPD. Exercise is a big component of pulmonary rehabilitation programs, but the efficacy of non-traditional forms of exercise as used in alternative medicine is poorly understood. Here, we aim to address this gap in knowledge and summarize the clinical evidence for the use of traditional exercise regimens in the pulmonary rehabilitation of COPD patients. Full article

Introduction: One of the most prevalent conditions affecting the vaginal organs is the human papilloma virus (HPV). Human papillomavirus (HPV) knowledge and attitudes have been the subject of numerous studies in Saudi Arabia. However, there are only a few studies that have examined university students’ attitudes and knowledge of the human papillomavirus and the vaccine that is associated with it. Aim: To predict the level of knowledge and attitudes regarding HPV and its related vaccine among undergraduate nursing students. Methodology: This was descriptive cross-sectional research. After being selected from Princess Nourah bint Abdulrahman University’s College of Nursing, 307 nursing students agreed to take part and completed an online survey that was self-administered. Results: The majority of the participants (73.5%) had a low level of knowledge of HPV with a mean score of 2.77 ± 1.78. In addition, more than half of the participating nursing students (57%) had a moderate attitude toward HPV vaccination with a mean score of 51.18 ± 11.16. The study results also verified that there was a highly significant correlation between the nursing students’ demographics and their knowledge and attitudes toward HPV (p < 0.001). According to the SEM, nursing students’ knowledge regarding HPV accounted for 48% of the variance in students’ attitudes. Conclusion: Nursing students’ knowledge regarding HPV vaccination is an important predictor of students’ attitudes regarding HPV. Full article

Asthma imposes a significant social burden on children, their families, and society at large. As a chronic health condition, effective management could greatly benefit from consistent adherence to guidelines. Despite this, minimal effort has been exerted to examine the impact of asthma management guidelines and adherence to treatment on children with asthma and the mothers caring for them. This study was designed to evaluate the influence of asthma management guidelines on the knowledge and treatment adherence among children with asthma and their mothers. A quasi-experimental design was utilized, and the study was conducted at two large hospitals in Jordan: Princess Rahma Hospital and King Hussein Medical Center. A purposive sample of children aged 6–12 years (n = 100) who were accompanied by their mothers (n = 100) were recruited for this study. Data were collected using a structured questionnaire and an observation checklist before and after the implementation of guidelines. Statistical analyses were performed using SPSS. The results revealed a statistically significant improvement in knowledge related to asthma among children and their mothers (p < 0.001). Additionally, a statistically significant difference was observed in the children’s adherence to their treatment regimen before and after the implementation of asthma management guidelines (p < 0.001). Moreover, the improvements in knowledge and practice related to asthma were sustained in the follow-up assessments. In conclusion, the guidelines had a beneficial effect on the children’s adherence to their treatment regimen both before and after their implementation. Thus, asthma patients should adhere to conventional guidelines at various health services to manage their condition effectively. Full article

Rheumatoid arthritis (RA) increases the risk of cardiovascular disease. This study aimed to evaluate the clinical outcomes of elderly patients with and without RA who underwent percutaneous coronary intervention (PCI). The Korean National Health Insurance Service claims database was used to extract data on 74,623 patients (14,074 with RA and 60,549 without RA) aged ≥ 65 years who were diagnosed with acute coronary syndrome and underwent PCI between 2008 and 2019. The primary outcome was survival of elderly patients with and without RA. The secondary outcome was survival in the RA subgroup. During a 10-year follow-up, the all-cause mortality survival rate was lower in patients with RA than that in patients without (53.7% vs. 58.3%, respectively, log-rank: p < 0.001). In the all-cause mortality RA subgroup, patients with elderly-onset RA had poor survival outcomes, whereas patients with young-onset RA had good survival outcomes compared with that in patients without RA (48.1% vs. 73.7% vs. 58.3%, respectively, log-rank: p < 0.001). Elderly patients with RA who underwent PCI had an increased mortality risk, particularly those with elderly rather than young-onset RA. Full article

Background: Handgrip strength (HGS) and the appendicular lean mass index (ALMI) are important determinants of sarcopenia. Muscle quality (MQ) is a measure of muscle strength relative to muscle mass. We examined trends in handgrip strength, the appendicular lean mass index, and analyzed their relationship with age, anthropometry, and body composition in a sample of participants in the United States (US). Methods: This cross-sectional study analyzed data from 14,741 US males (49.7%) and females (50.3%) 6–80 years old who responded to the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014. Dual X-ray absorptiometry was used to measure appendicular skeletal muscle mass. HGS was evaluated using the Takei Digital Grip Strength Dynamometer. Smoothed normative curves for HGS and the ALMI were constructed using a generalized additive model. Multiple regression analyses were used to examine associations of HGS and the ALMI with age, nutrition-related factors, physical activity, and body composition. Results: Mean HGS and the ALMI declined with advancing age. While mean HGS increased with the ALMI, it decreased with the fat mass index. HGS increased in males with an increase in body mass index, energy intake, the ALMI, and vitamins; however, HGS in females increased with albumin, but it had a negative association with the fat mass index and age, but not with increasing adiposity. Conclusions: HGS and the ALMI change with age: HGS increases with age, then stabilizes and declines; the ALMI increases with age, then stabilizes. In addition, we provide evidence for the effect of anthropometry, nutrition, physical activity, and body composition on HGS and the ALMI in US population. Full article

Interoceptive awareness, the conscious perception of internal bodily states, is a key construct of mind-body interaction. Decreases in interoceptive awareness, as measured by the Multidimensional Assessment of Interoceptive Awareness (MAIA), are found in chronic pain patients. In this study, we explored whether a specific aspect of interoceptive awareness is a risk for the onset and chronicity of pain. A longitudinal cohort study was conducted in 2018 and 2020 among a sample of full-time workers in an industrial manufacturing company in Japan. Participants completed a questionnaire on pain intensity, MAIA, exercise habits, kinesiophobia, psychological distress and work stress. Principal component analyses using the MAIA identified two principal components: self-control and emotional stability. Low emotional stability was associated with the prevalence of moderate to severe pain in 2020 among people with mild or no pain in 2018 (p < 0.01). Lack of exercise habits were associated with the prevalence of moderate to severe pain in 2020 among people with pain in 2018 (p < 0.01). Furthermore, exercise habits were associated with reduction in kinesiophobia among people with moderate to severe pain in 2018 (p = 0.047). Overall, these findings indicate that low emotional stability may be a risk for the onset of moderate to severe pain; lack of exercise habits may sustain kinesiophobia and be a risk for the chronicity of pain. Full article

Decompensated liver cirrhosis is often complicated by refractory ascites, and intractable ascites are a predictor of poor prognosis in patients with liver cirrhosis. The treatment of ascites in patients with cirrhosis is based on the use of aldosterone blockers and loop diuretics, and occasionally vasopressin receptor antagonists are also used. Recent reports suggest that sodium–glucose cotransporter 2 (SGLT2) inhibitors may be a new treatment for refractory ascites with a different mechanism with respect to conventional agents. The main mechanisms of ascites reduction with SGLT2 inhibitors appear to be natriuresis and osmotic diuresis. However, other mechanisms, including improvements in glucose metabolism and nutritional status, hepatoprotection by ketone bodies and adiponectin, amelioration of the sympathetic nervous system, and inhibition of the renin–angiotensin–aldosterone system, may also contribute to the reduction of ascites. This literature review describes previously reported cases in which SGLT2 inhibitors were used to effectively treat ascites caused by liver cirrhosis. The discussion of the mechanisms involved is expected to contribute to establishing SGLT2 therapy for ascites in the future. Full article

Background: The aim of our study is to compare the efficacy of PRP, steroids, and autologous blood injection in patients with chronic lateral epicondylitis. Method: A total of 120 patients comprised our study. Three groups of 40 patients each received only one of the following: PRP, steroids, or autologous blood injections. Thereafter, VAS (visual analog scale), DASH (Disabilities of the Arm, Shoulder, and Hand), and Nirschl scores of those treated were evaluated in the second week, the fourth week, the third month, and the sixth month. Results: The baseline evaluation revealed no significant change in VAS, DASH, and Nirschl scores among the three groups (p > 0.050). At the second week evaluation, patients treated with steroids showed significant improvement compared to patients treated with PRP and autologous blood (p < 0.001). The fourth-week evaluation revealed the VAS, DASH, and Nirschl scores of the patients treated with steroids to have improved more significantly than those of patients treated with PRP and autologous blood (p < 0.001). The third month, when the results of all three groups were compared, revealed similar results (p > 0.050). The sixth-month evaluation, when the results of all three groups were compared, revealed the autologous blood and PRP applications provided significantly better results than the group treated with steroids (p < 0.001). Conclusion: We concluded that steroid administration is effective in the short term, while PRP and autologous blood applications are more effective than steroid administration in the long term. Full article

Head and neck cancers are among the deadliest cancers, ranked sixth globally in rates of high mortality and poor patient prognoses. The prevalence of head and neck squamous cell carcinoma (HNSCC) is associated with smoking and excessive alcohol consumption. Despite several advances in diagnostic and interventional methods, the morbidity of subjects with HNSCC has remained unchanged over the last 30 years. Epigenetic alterations, such as DNA hypermethylation, are commonly associated with several cancers, including HNSCC. Thus, epigenetic changes are considered promising therapeutic targets for chemoprevention. Here, we investigated the effect of EGCG on DNA hypermethylation and the growth of HNSCC. First, we assessed the expression levels of global DNA methylation in HNSCC cells (FaDu and SCC-1) and observed enhanced methylation levels compared with normal human bronchial epithelial cells (NHBE). Treatment of EGCG to HNSCC cells significantly inhibited global DNA hypermethylation by up to 70–80% after 6 days. Inhibition of DNA hypermethylation in HNSCC cells was confirmed by the conversion of 5-methylcytosine (5-mc) into 5-hydroxy methylcytosine (5hmC). DNA methyltransferases regulate DNA methylation. Next, we checked the effect of EGCG on the expression levels of DNA methyltransferases (DNMTs) and DNMT activity. Treatment of EGCG to HNSCC cells significantly reduced DNMT activity to 60% in SCC-1 and 80% in FaDu cells. The protein levels of DNMT3a and DNMT3b were downregulated in both cell lines after EGCG treatment. EGCG treatment to HNSCC cells reactivated tumor suppressors and caused decreased cell proliferation. Our in vivo study demonstrated that administration of EGCG (0.5%, w/w) as a supplement within an AIN76A diet resulted in inhibition of tumor growth in FaDu xenografts in nude mice (80%; p < 0.01) compared with non-EGCG-treated controls. The growth inhibitory effect of dietary EGCG on the HNSCC xenograft tumors was associated with the inhibition of DNMTs and reactivation of silenced tumor suppressors. Together, our study provides evidence that EGCG acts as a DNA demethylating agent and can reactivate epigenetically silenced tumor suppressors to inhibit the growth of HNSCC cells. Full article

Objective: Preoperative localization in patients with primary or secondary hyperparathyroidism before radiofrequency ablation (RFA) is crucial. There is currently a lack of consensus regarding imaging protocol. Evaluating the diagnostic performance of ultrasound, four-dimensional computed tomography (4D-CT), and technetium 99m-sestamibi single-photon-emission-computed tomography/computed tomography (SPECT/CT) is necessary for RFA of hyperparathyroidism. Methods: This retrospective study recruited patients with primary or secondary hyperparathyroidism who underwent ultrasound, 4D-CT, and SPECT/CT before RFA at a single institution. The sensitivity, accuracy, and receiver operating characteristic curve analysis were used to evaluate the diagnostic performance of the imaging modalities. Results: A total of 33 patients underwent RFA for hyperparathyroidism (8 patients with primary hyperparathyroidism, 25 patients with secondary hyperparathyroidism). Ultrasound had the highest sensitivity (0.953) and accuracy (0.943), while 4D-CT had higher sensitivity and accuracy than SPECT/CT (sensitivity/accuracy, 4D-CT vs. SPECT/CT: 0.929/0.920 vs. 0.741/0.716). Combined ultrasound with 4D-CT and the three combined modalities achieved equivalent, and the highest, diagnostic performance (sensitivity 1.000, accuracy 0.989). The lesion length and volume were important predictors of the diagnostic performance of 4D-CT and SPECT/CT (area under curve of length in 4D-CT/volume in 4D-CT/length in SPECT/volume in SPECT: 0.895/0.834/0.767/0.761). Conclusion: Combined ultrasound with 4D-CT provides optimal preoperative localization prior to RFA in patients with primary or secondary hyperparathyroidism. The length and volume of parathyroid lesions are determinative of the diagnostic performance of 4D-CT and SPECT/CT. Full article

Background: Kivach Clinic has developed a special medical spa program to prevent aging-related conditions in metabolic, cardio-vascular, and neurological states. Spa programs modify diet, physical activity, and lymphatic drainage, as it deteriorates with aging. We investigated its influence on the blood markers of biological age of patients during their stay to objectify the potential of spa treatment for influencing the risk of age-related events. Methods: The artificial deep learning model Aging.ai 3.0 was based on blood parameters. The change in the biological age of 43 patients was assessed after their 14-day spa treatment at Kivach Clinic. Results: Biological age decreased in 29 patients (median decrease: 8 years, mean: 8.83 years), increased in 10 patients (median increase: 3 years, mean: 5.33 years) and remained unchanged in 4 patients. Overall mean values for the entire patient group were as follows: median value was −3 years, and mean was −4.79 ± 1.2 years (p-value = 0.00025, t-test). Conclusions: The capability of specially selected medical spa treatment to reduce human biological age (assessed by Aging.AI 3.0) has been established. Full article

Even though clinically small ‘early’ cancers represent many millions of cells biologically, when removed surgically, these often never recur or regrow, nor reduce the individual’s lifespan. However, some early cancers remain quiescent and indolent; while others grow and metastasize, threatening life. Distinguishing between these different clinical behaviours using clinical/pathological criteria is currently problematic. It is reported that many suspicious lesions and early cancers are being removed surgically that would not threaten the patient’s life. This has been termed ‘overdiagnosis’, especially in the sphere of cancer screening. Although a controversial and emotive topic, it poses clinical and public health policy challenges. The diagnostic differentiation between ‘non-lethal’ and ‘lethal’ tumor forms is generally impossible. One perspective gathering evidential support is that a dynamic balance exists between the immune response and malignant processes governing ‘lethality’, where many more cancers are produced than become clinically significant due to the immune system preventing their progression. Higher medical screening “diagnosis” rates may reflect lead-time effects, with more ‘non-progressing’ cancers detected when an early immune-cancer interaction is occurring. We present a model for this immune-cancer interaction and review ‘excess’ or ‘overdiagnosis’ claims that accompany increasingly sensitive diagnostic and screening technologies. We consider that immune tools should be incorporated into future research, with potential for immune system modulation for some early cancers. Full article

Aim: To assess changes in blood pressure (BP) and arterial stiffness among 84 rotating shift and 25 dayworkers (control subjects) at two industrial plants during a 4-year follow-up, and to assess changes in outcome variables among shift workers at the two plants after a reduction in the number of night shifts during the last year of follow-up in one of the plants. Methods: We collected demographic data using a questionnaire, examined systolic and diastolic blood pressure (sBP, dBP), central systolic and diastolic aorta pressure (cSP, cDP), augmentation pressure (AP), central pulse pressure (cPP), and pulse wave velocity (PWV). We registered sleep quality. The last 4–14 months of follow-up one plant implemented a 12-week shift plan reducing the total number of night shifts and consecutive night shifts from 16.8 to 14 and from 7.2 to 4. To assess differences in change of outcomes between study groups we applied linear mixed models. Results: The dayworkers were older, more hypertensive, reported less sleep disturbance, and smoked/snuffed less than the shift workers did. The adjusted annual increase in PWV was 0.34 m/s (95%CI, 0.22, 0.46) among shift workers and 0.09 m/s (95%CI, −0.05, 0.23) in dayworkers, yielding a significant difference of change of 0.25 m/s (95%CI, 0.06, 0.43). No significant differences were found between the two groups of shift workers in any cardiovascular disease (CVD) outcome during the last year of follow-up. Conclusions: Shift work in industry is associated with arterial stiffness, reflecting an increased risk of future CVD. No significant changes in arterial stiffness were identified as a consequence of a small reduction in the number of night shifts and consecutive night shifts. Full article

Background: Based on the high prevalence and occult-onset of osteoporosis, the development of novel early screening tools was imminent. Therefore, this study attempted to construct a nomogram clinical prediction model for predicting osteoporosis. Methods: Asymptomatic elderly residents in the training (n = 438) and validation groups (n = 146) were recruited. BMD examinations were performed and clinical data were collected for the participants. Logistic regression analyses were performed. A logistic nomogram clinical prediction model and an online dynamic nomogram clinical prediction model were constructed. The nomogram model was validated by means of ROC curves, calibration curves, DCA curves, and clinical impact curves. Results: The nomogram clinical prediction model constructed based on gender, education level, and body weight was well generalized and had moderate predictive value (AUC > 0.7), better calibration, and better clinical benefit. An online dynamic nomogram was constructed. Conclusions: The nomogram clinical prediction model was easy to generalize, and could help family physicians and primary community healthcare institutions to better screen for osteoporosis in the general elderly population and achieve early detection and diagnosis of the disease. Full article

Cyclophosphamide (CPM) is a classical alkylating agent used in different cancer chemotherapy regimens and is restricted due to severe adverse effects, including hepatotoxicity. Natural or plant-derived antioxidants such as capsaicin were utilized in this study to examine the hepatoprotective benefits against cyclophosphamide-induced hepatotoxicity. The rats were divided into five groups: a normal control group, a toxic group (CPM), an intraperitoneal injection of a single dose of 200 mg/kg b.w. on the fourth day, a pretreated group with two doses of CPS (10 mg and 20 mg/kg b.w.) orally for six consecutive days, and an intraperitoneal administration of 200 mg/kg b.w. on the fourth day of treatment. The fifth group was administered with the highest dose of CPS (20 mg/kg b.w.) orally for six consecutive days. After 24 h of administration of CPS, the rats were anesthetized, blood was collected, and the serum enzyme toxicity was evaluated. After the blood sampling and euthanasia of all the animals, the liver was isolated for further toxicity and histopathological examination. The results revealed that serum liver markers (AST, ALT, ALP, BLI) significantly increased after CPM administration, but were subsequently restored after CPS treatment with both doses. In addition, lipid peroxidation (MDA), inflammatory cytokines (IL-1β, TNF-α), and apoptotic markers (Caspase-3) increased, and antioxidant enzymes (GSH, CAT, SOD) were significantly decreased after CPM administration, and it was re-established by CPS treatment. However, CPS effectively protected against the CPM-induced histopathological architects of liver tissues. In conclusion, CPS attenuates CPM-induced hepatotoxicity via modulating oxidative stress, apoptotic signals, and cytokine pathway. Therefore, CPS could play a significant role as a supplement during the chemotherapy of patients. Full article

Magnesium (Mg) contributes to DNA stability, protein synthesis and cardiac excitability, while Mg deficiency leads to increased cardiovascular mortality, diabetes, hyperparathyroidism and risk of fractures. In kidney transplant patients, calcineurin inhibitors (CNIs) downregulating Mg channel TRPM6 in the distal collecting tubule induce early hypomagnesemia (HypoMg), which is associated with a faster decline in allograft function. A new formulation, sucrosomial Mg (SucrMg), for oral supplements encapsulates Mg oxide in a phospholipid membrane covered by a sucrester matrix, enhancing gastric and intestinal Mg absorption. This study has evaluated Mg bioavailability, effectiveness and tolerance of SucrMg compared to the conventional preparation of Mg pidolate (PidMg). The association of blood Mg with risk of post-transplant dysglycemia and hyperparathyroidism has also been investigated. Forty hypomagnesemic adult single, double or combined kidney–pancreas or kidney–liver transplant recipients within 2 years from transplantation were recruited. In total, 16 patients received PidMg and 27 received SucrMg. Blood Mg was measured at baseline (T0), after 15 days (T1) and after 6 months (T2) of treatment. PTH, fasting glucose and calcium were measured at baseline and after 6 months of treatment. The tolerance was evaluated at the ambulatory visits. SucrMg compared to PidMg was more efficient at increasing Mg bioavailability at T1: p < 0.0001 vs. p = 0.72 ns, respectively, with a ∆% increase of 12.4% vs. 5.4%, p = 0.04. Both preparations increased blood Mg at T2, p < 0.0001 and p = 0.002, respectively. SucrMg was better tolerated. No difference was observed for fasting plasma glucose, PTH and calcium. On one hand, our study is the first among transplant patients to evaluate the efficacy of SucrMg in the correction of HypoMg, which might justify the limited number of patients enrolled and the short observation time; on the other hand, our results could serve as a useful working hypothesis for further studies with a larger number of transplant patients and an extended study duration to confirm the benefits observed with SucrMg. Full article

Background: Pneumoconiosis has considerable comorbidities, most notably pulmonary and cardiovascular diseases. However, the relationship between pneumoconiosis and chronic kidney disease (CKD) is largely unknown. The present study aimed to use a retrospective cohort study design to further clarify the association between pneumoconiosis and subsequent CKD risk. Methods: This is a nationwide, population-based, retrospective cohort study that used data from Taiwan’s National Health Insurance Database. Between 2008 and 2018, 17,952 newly diagnosed patients were included in the pneumoconiosis cohort, while 71,808 individuals without pneumoconiosis were included in the comparison cohort, with a propensity score matching for age, gender, and date of pneumoconiosis diagnosis. The development of CKD was monitored until the end of 2019. The risk was assessed using Cox proportional hazard regression models. Results: After controlling for age, gender, and comorbidity, the overall incidence of CKD was 1.69-fold higher in the pneumoconiosis cohort than in the comparison cohort (19.71 vs. 11.76 per 1000 person-years, respectively, p < 0.001), with an adjusted hazard ratio of 1.83 (95% confidence interval: 1.73–1.93). Stratified analyses by age group, gender, and presence of comorbidity revealed that the adjusted hazard ratios of CKD associated with pneumoconiosis remained significant (8/9). Furthermore, pneumoconiosis and tri-high (hypertension, hyperglycemia, and hyperlipidemia) interact positively with CKD development (p < 0.001). Conclusion: Patients with pneumoconiosis had a significantly higher risk of developing CKD than those without. Pneumoconiosis combined with hypertension, hyperglycemia, or hyperlipidemia would increase the risk even further. More studies are required to understand the possible pathophysiological mechanisms. Full article

Diabetes prevalence is growing worldwide, especially in some populations. Though migrations seem to contribute to the presence in host countries of a significant number of patients with diabetes and its comorbidities, very little is known about the health conditions of undocumented migrants. We retrospectively studied 838 patients with type 2 diabetes mellitus (T2DM), 425 Italians followed by the diabetes clinic of a university hospital, and 413 undocumented migrants receiving assistance from a non-governmental organization. We analyzed their demographic and clinical data together with the medications they were on. The prevalence of the use of specific classes of drugs was compared between undocumented migrants and Italians by fitting a Poisson regression model, and the results were reported as prevalence rate ratios (PRRs) with a 95% confidence interval. Undocumented migrants with T2DM received fewer medications for cardiovascular (CV) conditions (PRR: 0.68, 0.60 to 0.76) than Italians, after correcting for confounding factors. Only sulfonylureas were more frequently used in undocumented migrants. The causes of these differences are not completely clear, but social, cultural, and economic factors can have an important role. More efforts are needed to provide appropriate treatment of diabetes and its CV comorbidities to undocumented migrants. Full article

Chronic kidney disease (CKD) is a known risk factor for cardiovascular disease, including acute myocardial infarction. However, whether this risk is only associated with severe kidney disease or is also related to mildly impaired kidney function is still under debate. The incidence rate and risk factors of incident acute myocardial infarction (AMI) in patients with CKD are sparse. Potential differences in risk factor profiles between CKD patients with incident AMI and CKD patients with a prior AMI have not been sufficiently investigated. Furthermore, important factors such as albuminuria and socio-economic factors are often not included. The primary aim of this study was to establish the incidence rate of AMI after CKD debut. Secondly, to evaluate the importance of different CKD stages and the risk of having an AMI. Finally, to identify individuals at risk for AMI after CKD debut adjusted for prevalent AMI. Based on data from the kidney disease cohort of Southern Denmark (KidDiCo), including 66,486 CKD patients, we established incidence rates and characteristics of incident AMI among patients within a 5-year follow-up period after CKD debut. A Cox regression was performed to compute the cause-specific hazard ratios for the different risk factors. The incidence rate for CKD stage G3–5 patients suffering acute myocardial infarction is 2.5 cases/1000 people/year. In patients without a previous myocardial infarction, the risk of suffering a myocardial infarction after CKD debut was only significant in CKD stage G4 (HR = 1.402; (95% CI: 1.08–1.81); p-value = 0.010) and stage G5 (HR = 1.491; (95% CI: 1.01–2.19); p-value = 0.042). This was not the case in patients who had suffered an acute myocardial infarction prior to their CKD debut. In this group, a previous myocardial infarction was the most critical risk factor for an additional myocardial infarction after CKD debut (HR = 2.615; (95% CI: 2.241–3.05); p-value < 0.001). Irrespective of a previous myocardial infarction, age, male sex, hypertension, and a low educational level were significant risk factors associated with an acute myocardial infarction after CKD debut. The incidence rate of AMI in patients with CKD stage G3–5 was 2.5 cases/1000 people/year. Risk factors associated with incident AMI in CKD stage G3–5 patients were CKD stage, age, and hypertension. Female sex and higher educational levels were associated with a lower risk for AMI. Prior AMI was the most significant risk factor in patients with and without previous AMI before fulfilling CKD stage G3–5 criteria. Only age, sex, and a medium-long educational level were significant risk factors in this group. Full article

A large amount of recent literature has focused on impaired iron homeostasis in the pathophysiology of schizophrenia. Specifically, microarray analysis has illustrated associations between the transferrin locus and schizophrenia. To elaborate on the effects of transferrin on schizophrenia and its psychiatric phenotypes, our study aimed to investigate whether transferrin gene polymorphism was correlated with cognitive deficits and clinical symptoms in schizophrenia. We recruited 564 patients with chronic schizophrenia and 422 healthy controls (HCs) in a Han Chinese population, collected phenotypic data, and genotyped the rs3811655 polymorphism of the transferrin gene. Our results showed that the rs3811655 polymorphism was related to cognitive performance in both patients and HCs, as well as negative symptoms in patients (all p < 0.05), and patients carrying at least one G-allele showed worsened cognition/severe negative symptoms (all p < 0.05). Further analyses also found that the rs3811655 polymorphism in combination with cognition may exert small but significant contributions to the negative (β = −0.10, t = −2.48, p < 0.05) or total psychiatric symptoms (β = −0.08, t = −1.92, p < 0.05) in patients. Our findings indicated that the rs3811655 polymorphism may be implicated in the cognitive deficits of schizophrenia and HCs as well as psychiatric symptoms in patients, which suggested the possible iron regulatory mechanism in the pathology of schizophrenia. Full article