An elevated serum urate concentration is associated with kidney damage. Men’s uric acid levels are usually higher than women’s. However, postmenopausal women have a higher risk of gout than men, and comorbidities are also higher than in men. This study examined the sex differences in the relationship between hyperuricemia and renal progression in early chronic kidney disease (CKD) and non-CKD, and further examined the incidence of CKD in non-CKD populations among patients over 50 years of age. We analyzed 1856 women and 1852 men participating in the epidemiology and risk factors surveillance of the CKD database. Women showed a significantly higher risk of renal progression and CKD than men within the hyperuricemia group. After adjusting covariates, women, but not men resulted in an hazard ratio (HR) for developing renal progression (HR = 1.12; 95% CI 1.01–1.24 in women and HR = 1.03; 95% CI 0.93–1.13 in men) and CKD (HR = 1.11; 95% CI 1.01–1.22 in women and HR = 0.95; 95% CI 0.85–1.05 in men) for each 1 mg/dL increase in serum urate levels. The association between serum urate levels and renal progression was stronger in women. Given the prevalence and impact of kidney disease, factors that impede optimal renal function management in women and men must be identified to provide tailored treatment recommendations.
The TRPV4 (transient receptor potential vanilloid 4) ion channel, a member of the vanilloid subfamily of the transient receptor potential channels, is activated by membrane stretch, by non-noxious warm temperatures, and by a range of chemical activators. In the present study we examined the role of phosphorylation in modulating the activation of TRPV4. We expressed TRPV4 in HEK293 cells and activated the channel by cell swelling in a hypotonic solution. TRPV4 channel activation and serine phosphorylation were enhanced by exposure to the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate or by application of bradykinin, which activates PKC via a G-protein-coupled mechanism. The enhancement was inhibited by the PKC inhibitors staurosporine, bisindolylmaleimide I, and rottlerin or by mutation of the serine/threonine residues Ser(162), Thr(175), and Ser(189). The adenylate cyclase activator forskolin also enhanced activation of TRPV4, and the enhancement was antagonized by the selective cyclic AMP-dependent protein kinase (PKA) inhibitor H89 or by mutation of serine residue Ser(824). Sensitization of TRPV4 by both PKC and PKA depended on the scaffolding protein AKAP79, because channel activation and phosphorylation were enhanced by co-transfection of AKAP79 and were antagonized by removal of AKAP79 using small interfering RNA. We conclude that the serine/threonine kinases PKC and PKA enhance activation of the TRPV4 ion channel by phosphorylation at specific sites and that phosphorylation depends on assembly of PKC and PKA by AKAP79 into a signaling complex with TRPV4.
Diabetes mellitus (DM) is an important risk factor in patients with end-stage renal disease (ESRD). DM is associated with the development of cardiovascular diseases, such as atrial fibrillation (AF), due to poor glycemic control. However, few studies have focused on the risk of developing ESRD among DM patients with and without AF. This study evaluated ESRD risk among DM patients with and without AF in Taiwan. Data were retrieved from one million patients randomly sampled from Taiwan’s National Health Insurance Research Database, including 6,105 DM patients with AF propensity score–matched with 6,105 DM patients without AF. Both groups were followed until death, any dialysis treatment, or December 31, 2013, whichever occurred first. AF was diagnosed by a qualified physician according to the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM), using the diagnostic code 427.31. Patients aged <20 years or diagnosed with ESRD before the index date were excluded. A Cox proportional hazard regression model was used to calculate the relative ESRD risk. Among DM patients, those with AF have more comorbidities than those without AF. We also found a 1.18-fold (95% confidence interval [CI]: 1.01–1.46) increase in ESRD risk among patients with AF compared with those without AF. In addition, DM patients with hypertension, chronic kidney disease (CKD), or higher Charlson Comorbidity Index scores also have significantly increased ESRD risks than those without these complications. A 1.39-fold (95% CI: 1.04–1.86) increase in risk was observed for patients with AF among the non-CKD group. Our findings suggest that patients with DM should be closely monitored for irregular or rapid heart rates.
Allergen-specific immunotherapy (ASIT) has the potential to modify allergic diseases, and it is also considered a potential therapy for allergic asthma. House dust mite (HDM) allergens, a common source of airborne allergen in human diseases, have been developed as an immunotherapy for patients with allergic asthma via the subcutaneous and sublingual routes. Oral immunotherapy with repeated allergen ingestion is emerging as another potential modality of ASIT. The aim of this study was to evaluate the therapeutic efficacy of the oral ingestion of HDM extracts in a murine model of allergic asthma.BABL/c mice were sensitized twice by intraperitoneal injection of HDM extracts and Al(OH)3 on day 1 and day 8. Then, the mice received challenge to induce airway inflammation by intratracheal instillation of HDM extracts on days 29-31. The treatment group received immunotherapy with oral HDM extracts ingestion before the challenge. All the mice were sacrificed on day 32 for bronchoalveolar inflammatory cytokines, mediastinal lymph node T cells, lung histology, and serum HDM-specific immunoglobulins analyses.Upon HDM sensitization and following challenge, a robust Th2 cell response and eosinophilic airway inflammation were observed in mice of the positive control group. The mice treated with HDM extracts ingestion had decreased eosinophilic airway inflammation, suppressed HDM-specific Th2 cell responses in the mediastinal lymph nodes, and attenuated serum HDM-specific IgE levels.Oral immunotherapy with HDM extracts ingestion was demonstrated to have a partial therapeutic effect in the murine model of allergic asthma. This study may serve as the basis for the further development of oral immunotherapy with HDM extracts in allergic asthma.
Abstract Background: The colonization and diversification of early microbes in the infant digestive tract are crucial to the health and pathophysiology of all neonates. Fundamentally, whether the gut is sterile at birth is the key question in understanding human microbial colonization. Although the gut of an infant at birth has long been believed sterile, this paradigm has been challenged. Objectives: To confirm or reject the fist-pass meconium is sterile. Methods: The first-pass meconium of healthy term infants was collected and examined by the bacterial inoculation and identification, and molecular analysis. Results were correlated with their delivery modes. First-pass meconium was immediately collected from 60 full-term newborns. Fresh meconium was examined by the bacterial inoculation and identification. DNA was extracted from the meconium samples for real-time polymerase chain reaction. The comparisons of fecal bacterial counts by the mode of delivery were calculated by using unpaired Student’s t test. Differences in the detection rate of bacteria were calculated by Fisher’s exact probability test (Statistical Package for the Social Sciences [SPSS], version 10). P < 0.05 was considered statistically significant. Results: In the vaginally born (VB) group, 46.34% of meconium samples had detectable microbes, which were associated with vaginosis and existed in the urine and stool. In the cesarean-section born (CB) group, although microbes could not be isolated by the traditional bacterial culture methods, the bacterial counts and bacterial DNAs were detected by molecular technology. Conclusion: Meconium is not sterile. Bacteria were present in the first-pass meconium of term, healthy, VB and CB infants.
Background: This study evaluated early childhood comorbidities of cerebral palsy (CP) in low birth weight (LBW) children and assessed the impact of maternal bio-psychosocial factors on CP risk in preterm infants of varying birth weights (BWs). Methods: Data from 15,181 preterm infants (2009–2013) and 151,810 controls were analyzed using Taiwan’s National Health Insurance Research Database. CP prevalence and LBW-associated comorbidities were examined, and odds ratios (ORs) were calculated. Results: This study confirmed increasing prematurity and LBW rates in Taiwan, with LBW infants showing higher CP prevalence. Significant maternal risk factors included age extremes (<20 and >40 years). LBW infants exhibited higher risks for respiratory, circulatory, nervous system, and psycho-developmental comorbidities compared with controls, with the lowest BW having even higher ORs. Maternal factors such as family income, the number of hospital admissions, and length of hospital stay were remarkably correlated with BW and subsequent complications. Each additional gestational week crucially reduced the risk of complications in premature infants. Conclusions: LBW infants are at a higher risk for CP and various comorbidities, with maternal bio-psychosocial factors playing a critical role. Addressing these factors in prenatal care and interventions is essential to improve outcomes for premature infants.
We compared our clinical experience with currently available reference oxygen saturation level (SpO(2)) values from the American Academy of Pediatrics/American Heart Association (AAP/AHA) neonatal resuscitation program guidelines.We enrolled 145 healthy full-term neonates; infants showing respiratory distress and those with serious congenital anomalies were excluded. SpO(2) values at every 1 minute until 10 minutes after birth were measured and recorded. Infants were classified into the cesarean section (CS) and normal spontaneous delivery (NSD) groups for evaluating differences. The 10(th) percentiles of SpO(2) at each minute were used as the lower limits of normal oxygen saturation, and these were compared with the lowest target values recommended in the AAP/AHA guidelines.Overall, 130 vigorous full-term neonates (median gestational age: 38 5/7 weeks; body weight at birth: 2405-3960 g) were analyzed. The median SpO(2) were 67% and 89% at the 1(st) and 4(th) minute, respectively. On average, SpO(2) values reached >90% at the 5(th) minute. No statistical differences were noted in the SpO(2) values between the CS and NSD groups after 5 minutes; however, a trend of higher SpO(2) was observed in the NSD group. We noted a gradually increasing trend for SpO(2) values over time, similar to that noted in the AAP/AHA guidelines. However, SpO(2) values at the 10(th) percentiles of each minute within the first 5 minutes in our study were equal to or significantly lower than those in the AAP/AHA guidelines; moreover, at the 10(th) minute, SpO(2) values at the 10(th) percentiles were significantly higher than those in the guidelines.The delivery modes did not affect the SpO(2) values of full-term healthy neonates. Discrepancies in SpO(2) changes in full-term neonates not requiring resuscitation between this study and the AAP/AHA guidelines were significant. SpO(2) ranges for each time point within the first 10 minutes after birth should therefore be reevaluated locally.
Two important events highlight the crucial role of Tungs' Taichung MetroHarbor Hospital in providing critical care medical services in Taiwan: Chiu (), a little girl who had been severely beaten by her father, was forced to travel to our hospital for treatment after being turned away by other Taipei City Hospitals. Chin Liang-Feng (), a 26-year-old male from the Army Aviation and Special Forces Command, jumped from a C-130 aircraft flying at an altitude of approximately 396 m on May 17, 2018, at the annual Han Kuang drill rehearsal. His parachute failed to open completely, and after falling to the ground, he lost consciousness and was paralyzed. While staying in our hospital, he regained consciousness and has since recovered dramatically from critical injuries. These headline news stories drew the entire nation's attention to the philanthropic support and high-quality medical care provided by our hospital. To effectively utilize the ever-expanding diagnostic and therapeutic technologies and techniques developed by the research–industrial complex to care for a wide spectrum of patients, health-care providers must overcome various challenges associated with clinical practice. Tungs'MedicalJournal is a conduit for publishing these priceless experiences and substantial findings and results. In nephrology, end-stage renal disease (ESRD) is a major public health issue in Taiwan. Patients with ESRD require hemodialysis, peritoneal dialysis, and kidney transplants to enjoy an improved quality of life. Although kidney transplants provide good outcomes for patients with ESRD, the survival rate of transplant recipients remains lower than that of the general population. Chen et al.[1] discovered that delayed graft function and age were the prognostic factors associated with the survival of patients with ESRD in their cohort. Liu et al.[2] suggested that measuring grip strength using the "Timed Up and Go" test during initial screening can be a reliable indicator of weak muscle strength and mobility among elderly patients with ESRD that are on hemodialysis. Pruritus is an annoying problem, especially in patients with ESRD. Wu et al.[3] investigated patients on hemodialysis with and without uremic pruritus and found that patients' serum biochemistry, such as C-reactive protein (CRP) level, is related to uremic pruritus. Therefore, they encourage all health-care professionals to regularly assess these factors, along with itching status, to provide early and proper treatment. Chen[4] reviewed hyperuricemia through an introduction of the mechanisms underpinning the overproduction of uric acid, the disease course of gout, and the risks associated with cardiovascular diseases, metabolic syndrome, chronic kidney disease, urolithiasis, diabetes mellitus, thyroid dysfunction, and psoriasis. In cardiology, Hsu et al.[5] reported on a young patient with intermittent chest pain whose characteristic electrocardiographic T-wave changes and clinical manifestations led to the diagnosis of Wellens syndrome. After an urgent coronary angiography, the patient was found to have left anterior descending coronary artery stenosis. Early identification and emergent intervention saved his life. Guillain–Barré syndrome (GBS) is a life-threatening, acute, and immune-mediated demyelinating peripheral neuropathy. GBS typically manifests progressive ascending weakness and sensory loss from distal to proximal muscles. Hu et al.[6] reported a 14-year-old boy presenting with right lower limb weakness and sensory loss which were relieved by intravenous immunoglobulin treatment. His upper gastrointestinal endoscopy showed a typical pattern of gastritis and Helicobacterpylori infection. His weakness and sensory loss did not recur after a complete therapeutic course targeting H. pylori with a triple therapy of lansoprazole, amoxicillin, and clarithromycin. No one can live without respiration, but too much air in the mediastinum may cause agony. Spontaneous pneumomediastinum is an uncommon disorder that primarily affects young adult males. Its prognosis varies from very benign to fatal. Huang et al.[7] characterized spontaneous pneumomediastinum and found that chest pain and dyspnea were the most common clinical presentations. The clinical course of spontaneous pneumomediastinum is generally very benign and the disease is self-limiting. Therefore, unnecessary aggressive therapy and invasive diagnostic procedures should be limited. Interestingly, the air in the biliary tract (pneumobilia) is relatively rare and suggests abnormal communication between the biliary and gastrointestinal tracts. Wu et al.[8] reported a 6-month-old female infant that presented with intermittent bilious vomiting. Her abdominal plain film imagery showed typical features of pneumobilia. These were attributed to a previous intestinal operation with a gas leak, which led to the X-ray findings. In neurology, while strokes are not rare, especially in the elderly, cerebral venous thrombosis as the initial presentation of hematological malignancy is very unusual. Chen et al.[9] presented a 49-year-old woman complaining of progressive headaches for 3 weeks. Brain imaging studies revealed edema in the right thalamus and bilateral caudate nuclei, and acute thrombosis in the straight and right transverse sinuses. Initial laboratory investigations revealed several negative findings excluding anemia. Her headache resolved after anticoagulation therapy; however, acute quadriparesis and coma occurred after warfarin treatment was stopped. Magnetic resonance imaging showed acute thrombosis of the basilar artery with brainstem infarction, which may have been associated with acute leukemia. Therefore, malignancies should be ruled out if patients are found to have cerebral venous thrombosis. In conclusion, 10 additional papers consist of one editorial, one review, four research articles, two imaging cases, and two case reports. We sincerely thank all authors for their contributions and willingness to share insightful overviews and valuable experiences toward making proper diagnoses and developing and implementing appropriate therapeutic plans. Medical care and research, like the two wings of a great eagle, can help free patients from suffering through proper diagnoses and appropriate therapies. Moreover, the editorial board would like to invite our readers to publish the most influential and scientifically sound papers to help our journal become recognized as a high-impact journal of scholarly general and specialized medical care and research.
Patients with coxsackievirus A2 (CVA2) infection mostly present with herpangina and rarely have central nervous system complications.1 However, in 2012, a Hong Kong study reported that a naturally occurring recombinant CVA2 caused an outbreak of severe respiratory symptoms, leading to two deaths.2 In the current study, we report an outbreak of CVA2-infection-related acute flaccid paralysis (AFP) in Taiwan. Sequencing and analysis of the viruses isolated from fecal samples revealed that the currently prevalent CVA2 strain is highly similar to the Hong Kong recombinant.
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