Purpose
To determine the efficacy of real-time PCR for the diagnosis and prognosis of varicella-zoster virus (VZV) keratitis.
Study design
Retrospective case series.
Methods
Patients: 545 consecutive ...patients with keratitis were examined to quantify copy numbers of VZV DNA by real-time PCR. Association of copy numbers of VZV DNA to clinical signs and disease course was assessed by logistic regression analysis and Cox proportional hazard model.
Results
Of the 545 eyes, 38 (6.9%) were diagnosed as VZV keratitis. The median copy number of the VZV DNA was 10
4.19
copies; this number was significantly associated with diagnosis of VZV keratitis with the highest odds ratio of 3390 (for median copy) compared to the clinical signs. The diagnostic accuracy of the VZV DNA copy indicated good diagnostic value of area under the curve (0.92) by receiver operating characteristic analysis, and detection of unrelated VZV DNA from the cornea was very rare (0.2%). When the VZV DNA copy and clinical signs were assessed for association with the disease course of herpes zoster ophthalmicus, the disease duration was significantly prolonged in VZV keratitis cases with higher numbers of VZV DNA copies, iritis, and history of recurrences. The amount of VZV DNA led to a continuous risk of prolonged disease duration until the ocular inflammation subsided (hazard ratio 0.17, 95% CI 0.07–0.42, for median copies).
Conclusions
Higher VZV DNA copy numbers are associated with the refractoriness of VZV keratitis, and its evaluation may be a useful way to clinically diagnose and manage VZV keratitis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: The Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome is a rare disorder characterized by congenital vaginal defects and uterine traces. Because of its rarity, standardized management for ...MRKH syndrome is unavailable. This study reviewed the management of the patients with MRKH syndrome in our institution. Methods: Using medical records, we retrospectively reviewed the surgical techniques, outcomes, postoperative management methods, and outpatient follow-up of 17 patients with MRKH syndrome in Keio University Hospital. Results: Of the 14 patients who requested vaginoplasty, 12 underwent surgery with Davydov’s modified procedure after the Frank method, and it took 17 months to 34 months (median two years) for the vaginal cavity to enlarge by 5–6 cm. The Frank method is a non-surgical dilation with instrumental stretching of the vaginal vestibular mucosa. Davydov’s procedure is a surgical vaginoplasty in which the vesicoureteral space is coated by the peritoneum. Although one patient lost 3800 mL of bleeding from the plexus vein and four needed to remove the prosthesis under anesthesia about one month after surgery, all patients achieved anatomic success with a vaginal cavity length of 6 cm or more and could have sexual intercourse with their sexual partners. However, two patients interrupted their preoperative hospital visits, and three were lost to follow-up postoperatively. Two of the three patients who did not accept vaginoplasty presented myoma at uterine trace and underwent myomectomy. Another one was scheduled for surgery through psychological support. Conclusions: Davydov’s modified procedure is effective, and dilating the vaginal cavity adequately using the Frank method before surgery is needed to ensure sufficient vaginal length with less perineum. During the operation, attention is required to care for the plexus vein. Comprehensive psychological support, providing appropriate information to the patient for mental maturity, and planning surgery according to their life stages are essential for successful treatment.
Studies examining long-term longitudinal metabolomic data and their reliability in large-scale populations are limited. Therefore, we aimed to evaluate the reliability of repeated measurements of ...plasma metabolites in a prospective cohort setting and to explore intra-individual concentration changes at three time points over a 6-year period. The study participants included 2999 individuals (1317 men and 1682 women) from the Tsuruoka Metabolomics Cohort Study, who participated in all three surveys-at baseline, 3 years, and 6 years. In each survey, 94 plasma metabolites were quantified for each individual and quality control (QC) sample. The coefficients of variation of QC, intraclass correlation coefficients, and change rates of QC were calculated for each metabolite, and their reliability was classified into three categories: excellent, fair to good, and poor. Seventy-six percent (71/94) of metabolites were classified as fair to good or better. Of the 39 metabolites grouped as excellent, 29 (74%) in men and 26 (67%) in women showed significant intra-individual changes over 6 years. Overall, our study demonstrated a high degree of reliability for repeated metabolome measurements. Many highly reliable metabolites showed significant changes over the 6-year period, suggesting that repeated longitudinal metabolome measurements are useful for epidemiological studies.
Despite widespread awareness of the necessity of early intervention for children with autism spectrum disorders (ASDs), evidence is still limited, in part, due to the complex nature of ASDs. This ...exploratory study aimed to examine the change across time in young children with autism and their mothers, who received less intensive early interventions with and without applied behavior analysis (ABA) methods in community settings in Japan.
Eighteen children with autism (mean age: 45.7 months; range: 28-64 months) received ABA-based treatment (a median of 3.5 hours per week; an interquartile range of 2-5.6 hours per week) and/or eclectic treatment-as-usual (TAU) (a median of 3.1 hours per week; an interquartile range of 2-5.6 hours per week). Children's outcomes were the severity of autistic symptoms, cognitive functioning, internalizing and externalizing behavior after 6 months (a median of 192 days; an interquartile range of 178-206 days). In addition, maternal parenting stress at 6-month follow-up, and maternal depression at 1.5-year follow-up (a median of 512 days; an interquartile range of 358-545 days) were also examined.
Large individual variations were observed for a broad range of children's and mothers' outcomes. Neither ABA nor TAU hours per week were significantly associated with an improvement in core autistic symptoms. A significant improvement was observed only for internalizing problems, irrespective of the type, intensity or monthly cost of treatment received. Higher ABA cost per month (a median of 1,188 USD; an interquartile range of 538-1,888 USD) was associated with less improvement in language-social DQ (a median of 9; an interquartile range of -6.75-23.75).
To determine an optimal program for each child with ASD in areas with poor ASD resources, further controlled studies are needed that assess a broad range of predictive and outcome variables focusing on both individual characteristics and treatment components.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK, VSZLJ
SHPS-1 is a transmembrane protein predominantly expressed in macrophages. The possible role of SHPS-1 in regulation of Toll-like receptor (TLR)-dependent production of proinflammatory cytokines by ...macrophages has remained unknown, however. We now show that expression either of a mutant version of mouse SHPS-1 (SHPS-1-4F) in which the four tyrosine phosphorylation sites in the cytoplasmic region are replaced by phenylalanine or of a chimeric protein comprising the extracellular and transmembrane regions of human CD8 fused to the cytoplasmic region of SHPS-1-4F (CD8-4F) markedly promoted the production of tumor necrosis factor-α (TNF-α) or interleukin-6 (IL-6) induced by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid poly(I : C) in RAW264.7 macrophages. In contrast, expression of a mutant form of SHPS-1 that lacks most of the cytoplasmic region did not promote such responses. Expression of SHPS-1-4F promoted the LPS- or poly(I : C)-induced activation of NF-κB. LPS and poly(I : C) each induced the tyrosine phosphorylation of SHPS-1 through a Src family kinase and the association of SHPS-1 with SHP-1 and SHP-2. These results suggest that LPS or poly(I : C) induces tyrosine phosphorylation of SHPS-1 and the association of SHPS-1 with SHP-1 and SHP-2 in a manner dependent on a Src family kinase. SHPS-1 then negatively regulates TLR4- or TLR3-dependent cytokine production through inhibition of NF-κB-dependent signaling.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
A 73-year-old woman admitted to our hospital because of headache, poor appetite, malaise, weight loss, and vomiting was found to have central adrenal insufficiency and thyrotoxicosis due to silent ...thyroiditis. Polyuria developed after replacement with glucocorticoid (masked diabetes insipidus), which was controlled with nasal administration of desmopressin. Magnetic resonance imaging of the brain showed a large cystic pituitary mass (18 × 18 × 12 mm) extending suprasellarly to the optic chiasm. Transsphenoidal surgery revealed that the pituitary tumor was Rathke’s cleft cyst. Following surgery, replacement with neither glucocorticoid nor desmopressin was needed any more. Therefore, it is suggested that Rathke’s cleft cyst is responsible for the masked diabetes insipidus and the central insufficiency. Furthermore, it is speculated that thyrotoxicosis with painless thyroiditis might induce changes from subclinical adrenal insufficiency to transiently overt insufficiency.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
•Some preschool-aged children with autism spectrum disorder may benefit from low-intensity behavioral interventions for their language and social development.•A greater intensity of one-to-one ...behavioral interventions was found to be associated with greater progress in language development and communication skills.•The current study highlights the importance of implementing early interventions in the community, even at a low intensity.
Despite the need for evidence-based practice for children with autism spectrum disorders in the community, especially in areas with a scarcity of qualified experts and high financial costs, there is a lack of evidence concerning the potential benefits of early interventions which may be affordable in the real world (e.g. low-intensity behavioral or eclectic interventions). This study examined behavioral changes in preschool-aged children with autism spectrum disorders who received low-intensity behavioral interventions (a mean of 5.5 h per week) or non-behavioral eclectic interventions delivered in community settings in Japan across a 1-year period and compared outcomes between the groups. We assessed children’s developmental quotient, adaptive behavior, autism symptom/severity, and maternal stress and depression at baseline and after 1 year. Our results revealed that children receiving interventions in their communities showed improvement in language and social development. Further, the degree of improvement in children receiving low-intensity behavioral interventions was significantly greater than in children receiving non-behavioral eclectic interventions. The improvement was associated with the intensity of total, especially one-to-one interventions. On the other hand, there were no group differences in the degree of improvement in other outcome measures. Our results suggest that some preschool-aged children with autism spectrum disorder may benefit from low-intensity behavioral interventions for their language and social development. A greater intensity of one-to-one interventions was found to be associated with greater progress in language development and communication skills. The current study highlights the importance of implementing early interventions in the community, even at a low intensity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision ...prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35–74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study used an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability, functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.
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FFLJ, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, ODKLJ, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Aim
To investigate the efficacy and safety of a dipeptidyl peptidase-4 inhibitor, sitagliptin, for treating diabetes mellitus complicated by chronic liver injury.
Methods
Sitagliptin was administered ...for 13.7 ± 10.1 months to 122 patients with DM complicated by chronic liver injury (including 19 patients with liver cirrhosis), and changes in hemoglobin A1c (HbA1c) and liver enzymes (transaminases, etc.) were evaluated.
Results
HbA1c was reduced from 8.48 ± 1.43% to 7.87 ± 1.35% (P < 0.001). Among liver enzymes, alanine aminotransferase (ALT) levels improved from 75.1 ± 45.2 to 65.8 ± 35.8 IU/L (P = 0.012) and gamma-glut amyl-trans peptidase from 155.2 ± 161.1 to 133.2 ± 127.4 IU/L (P = 0.044). Among the causes of liver injury, non-alcoholic fatty liver disease and alcoholic liver disease both showed the reductions in HbA1c with no deterioration of liver enzymes. An analysis of 19 patients with liver cirrhosis also showed reductions in HbA1c with no deterioration of liver enzymes.
Conclusion
It is suggested that sitagliptin can be administered effectively and safely to patients with diabetes mellitus complicated by chronic liver injury, including liver cirrhosis.
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