Antiretroviral therapy (ART) has been introduced recently and has significantly impacted morbidity and mortality, but can also engender drug resistance. To identify the prevalence of HIV-1 drug resistance (HIVDR) among patients with antiretroviral therapy failure in Sichuan during the period from 2010 to 2016, we carried out a longitudinal study in Sichuan, a province with the highest HIV/AIDS prevalence in China. The data and blood samples were collected from HIV/AIDS patients who received ART for more than half a year. Overall 5,512 sequences were completed from 7,059 ART-failure patients, and 2,499 individuals were identified as drug resistant. Among those with HIVDR mutations identified, 25.37% were against non-nucleoside reverse transcriptase inhibitors (NNRTIs), and 1.60% was against nucleoside reverse transcriptase inhibitors (NRTIs). NRTI-resistant drugs were mainly lamivudine (3TC) (57.77%) and emtricitabine (FTC), while NNRTI-resistant drugs were mainly nevirapine (NVP) (91.13%) and efavirenz (EFV) (72.81%). The most common recombination subtypes of HIV-1 in sequenced samples were CRF07_BC (circulating recombinant form, CRF) (41.42%), followed by CRF01_AE (40.77%). Moreover, drug resistance rate increased with the prolongation of treatment time (χ2 = 14.758, P < 0.05). The overall prevalence of acquired drug resistance in HIV-1 infected patients in Sichuan was 5.47%, which has remained relatively stable from 2010 to 2016. HIV-1 CRF01_AE and CRF07_BC subtypes were the main epidemic strains, and the possibility of resistance was higher in CRF01_AE subtypes. The current study highlights the importance of acquired drug resistance surveillance over a long period.
Psychological distress has become a serious health risk after the Fukushima nuclear accident. Although, following the lifting of evacuation orders, the affected people have started returning home, their current status of psychological distress has not been reported yet. Here, we report the levels of psychological distress in both returnees and evacuees by using a K6 indicator. In January 2018, questionnaires were randomly distributed among 2,000 people, aged 20 to 79 years old, who were registered on the Basic Resident Register in the evacuation order areas of nine municipalities where residents have now started returning home. The total number of participants was 625. The returnees showed a significantly better psychological distress status than the evacuees. Multivariate-adjusted odds ratios (95% confidence intervals) among the returnees (reference = evacuees), estimated from a logistic analysis by using age, sex, and annual income as covariates, were 0.525 (0.325-0.846) for K6 ≥ 10 and 0.444 (0.216-0.911) for K6 ≥ 13. The prevalence of K6 ≥ 10 in the returnees when adjusted by the age and sex distribution of the whole of Japan was 16.2%, higher than the value (10.3%) at 20 to 79 years old in the whole of Japan. Psychological distress among the evacuees is an urgent problem to be resolved, and social support is still necessary for the returnees. Long term follow-up of returnees, investigations of causality between return and psychological distress and its governing factors in each of the evacuee and returnee groups are required for the implementation of effective countermeasures.
Patients with laryngopharyngeal reflux (LPR) were reported to suffer from hypogeusia that affects quality of life. Proton pump inhibitor (PPI) is a useful drug in the treatment of LPR, but its effect on hypogeusia is not known. We therefore assessed the effects of PPI or a histamine H2 receptor antagonist (H2 blocker) on hypogeusia among patients with LPR. Both PPI and H2 blocker could inhibit acid reflux. LPR was diagnosed with reflux finding score and reflux symptom index. The visual analogue scale (VAS) of taste disturbance symptoms and the gustatory tests were assessed before and 8 weeks after treatment with esomeprazole, a PPI (20 patients, aged 50.0 ± 1.7 years) or famotidine, a H2 blocker (20 patients, aged 47.1 ± 1.8 years). There were no significant differences in VAS scores and recognition thresholds for four basic tastes between the two groups before treatment. Only PPI therapy significantly decreased the VAS scores, suggesting the improvement of taste perception. Moreover, PPI therapy significantly decreased recognition thresholds for bitter taste in the anterior tongue (chorda tympani nerve area) and the thresholds in the posterior tongue (glossopharyngeal nerve area) for salty, sour, and bitter tastes. By contrast, H2-blocker therapy caused no significant changes of thresholds in the anterior tongue, but improved the threshold only for bitter in the posterior tongue, the value of which was however significantly higher than that in PPI group. In conclusion, PPI could ameliorate hypogeusia by improving bitter, salty, and sour tastes among patients with LPR.
Japan is an aging society, and the incidence of diseases related to aging, such as pneumonia, heart failure, vertebral compression fracture (VCF), is increasing. Prolonged hospital stays are becoming a serious social problem, leading to elevated medical expenses. Thus, shortening the period of hospitalization is important. This study aimed to reveal determinants associated with prolonged hospital stays for patients with VCF. Our institution is the primary hospital in a rural area in the Kanto region of Japan. Altogether, 110 patients with a VCF, aged 65 years or older, including 79 women, were divided into two groups according to the average hospital stay period of 28 days: the long-stay group (mean stay 40.0 ± 11.6 days, n = 39) and the short-stay group (mean stay 20.6 ± 4.4 days, n = 71). Notably, the short-stay group included 55 women. Multivariate logistic regression analyses in male showed no variates significantly associated with prolonged hospitalization. By contrast, multivariate logistic regression analyses in female showed requiring emergency transportation to hospital was significantly associated with prolonged hospitalization [odds ratio 7.69, 95% confidence interval 1.13-52.29, P = 0.04]. In conclusion, this study implies that patients with better levels of activities of daily living are able to walk alone sooner and are easily discharged. Furthermore, the patient requiring emergency transportation might be in a poor social living environment, such as living alone. These results may give us a good opportunity to re-consider fundamental problems surrounding the elderly.
Cyclosporine A is known to be effective in some genetic podocyte injury. However, the efficacy of cyclosporine A depends on the degree of histopathological findings, and the relationship between long-term use and renal prognosis remains unknown. Frasier syndrome is a rare genetic disorder caused by intronic mutations in WT1, and is characterized by progressive glomerulopathy, a 46,XY disorder of sex development, and an increased risk of gonadoblastoma. We report here a 16-year-old phenotypically female patient with Frasier syndrome. A renal biopsy at the age of seven years showed segmentally effaced podocyte foot processes with no evidence of glomerulosclerosis. Steroid-resistant proteinuria progressed to the nephrotic range at the age of 10 years, which responded to once-daily administration of cyclosporine A with low two-hour post-dose cyclosporine A (C2) levels; she then achieved stable partial remission in combination with renin-angiotensin system (RAS) blockade. At the age of 12 years, examinations for delayed puberty confirmed the diagnosis of Frasier syndrome. The second renal biopsy showed widespread foot process effacement and a minor lesion of segmental glomerulosclerosis without findings suggestive of cyclosporine A nephropathy. She maintained partial remission and normal renal function with the continuation of once-daily low-dose cyclosporine A. The C2 levels required for the remission were between 212 and 520 ng/ml. Cyclosporine A dosages sufficient for maintaining the C2 levels were 1.1-1.2 mg/kg per day. In conclusion, the long-lasting treatment of once-daily low-dose cyclosporine A with RAS inhibition was effective for induction and maintenance of partial remission in Frasier syndrome.
Esophageal achalasia is a disease characterized by the impaired esophageal peristalsis and non-relaxation of the lower esophageal sphincter muscle with unknown causes. Clinical manifestation of the disease is nonspecific (e.g., weight loss, vomiting, and persistent cough); namely, early diagnosis of the disease is often difficult. Delayed diagnosis of the disease is known to impair the patients’ quality of life. Identifying the diagnostic factors that could cause diagnostic delay is needed. In this study, we collected data from 38 patients with achalasia and searched for diagnostic factors associated with delayed diagnosis (i.e., ≥ 6 months from the first hospital visit to diagnosis). The enrolled patients, diagnosed with achalasia based on esophageal manometry findings, had undergone surgical myotomy. As a result, the diagnosis of achalasia was likely to be delayed when the physician who had first contacted the patient did not perform a barium swallow test (p < 0.0001) or chest CT scan (p < 0.01) in a timely fashion. Among the patients with a delayed diagnosis (n = 15), none underwent a barium swallow test or chest CT within 6 months from their first hospital visit. The estimated sensitivities of diagnostic examinations for achalasia based on the enrolled 38 patients were higher than 80% for the barium swallow test and chest CT scan, but only 50-81% for endoscopy. To avoid the delayed diagnosis of achalasia, performing a barium swallow test or chest CT scan in a timely fashion, in addition to routine endoscopy, appears to be highly important.
Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.
The La-related proteins (LARPs) are a family of RNA binding proteins that control the degradation and stabilization of RNAs. As emerging research reveals the biology of each LARP, it is evident that LARPs are dysregulated in some types of cancer. Upregulation of cell motility potentiates the metastatic potential of ovarian cancer cells; however, the roles of LARPs in cell motility remain unknown. In the present study, we investigated the roles of LARPs in the progression of ovarian cancer using SKOV3 human ovarian cancer cells and a public database that integrates microarray-based gene expression data and clinical data. To explore the involvement of LARPs in the cell motility, we performed RNA interference screening for LARP mRNAs in SKOV3 cells. The screening identified LARP4 as a potential suppressor of the formation of lamellipodia. Conversely, enforced expression of LARP4 suppressed the formation of lamellipodia. Moreover, cell migration was significantly increased in LARP4-depleted SKOV3 cells. Mechanistically, LARP4 depletion was associated with the decrease in RhoA protein expression. These results suggest that LARP4 may limit RhoA-dependent cell motility. In a mouse xenograft model with SKOV3 cells, LARP4 depletion potentiated peritoneal metastasis. Upon analysis of a public database of patients with ovarian cancer, the LARP4 mRNA-high expression group (n = 166) showed longer overall survival compared with the LARP4 mRNA-low expression group (n = 489), implying a positive correlation of LARP4 mRNA levels in ovarian cancer tissues with patient prognosis. Taken together, we propose that LARP4 could suppress motility and metastatic potential of ovarian cancer cells.