SPIROCH?TA HEBDOMADIS,THE CAUSATIVE AGENT OF SEVEN DAY FEVER (NANUKAYAMI) : FIRST PAPER.

A new species of spirochete which we have called Spirochæta hebdomadis has been described as the specific etiological agent of seven day fever, a disease prevailing in the autumn in Fukuoka and other parts of Japan. This spirochete is distinguishable from Spirochæta icterohæmorrhagiæ to which it presents certain similarities. Young guinea pigs are susceptible to inoculation with the blood of patients and to pure cultures of the spirochete, and those developing infection exhibit definite symptoms suggestive of those of seven day fever in man. The blood serum of convalescents from seven day fever contains specific immune bodies acting spirochetolytically and spirocheticidally against the specific spirochetes, but not against Spirochæta icterohæmorrhagiæ. The field mouse (Microtus montebelli) is the normal host of the spirochetes, which have been detected in the kidneys and urine of 3.3 per cent of the animals examined. The endemic area of prevalence of seven day fever corresponds with the region in which field mice abound.     

THE SERUM TREATMENT OF WEIL'S DISEASE (SPIROCH?TOSIS ICTEROH?MORRHAGICA)

Horses immunized with cultures of Spirochæta icterohæmorrhagiæ yield an immune serum having therapeutic properties. With rare exceptions the serum destroys completely the spirochetes contained in the circulating blood. The development of antibodies is promoted by the serum injections. The number of spirochetes in the organs is reduced by the treatment. Secondary manifestations due to the serum are slight and disappear promptly. The ultimate effects of the serum treatment on the symptoms and final outcome of the disease have still to be determined.     

Control of Fe3+ coordination by excess Cl− in alcohol solutions

We spectroscopically investigated coordination state of Fe³⁺ in methanol (MeOH) and ethanol (EtOH) solutions against Cl⁻ concentration ([Cl⁻]). In both the system, we observed characteristic absorption bands due to the FeCl₄ complex at high-[Cl⁻] region. In the MeOH system, the proportion (r) of [FeCl₄]⁻ exhibits a stationary value of 0.2–0.3 in the intermediate region of 10 mM < [Cl⁻] < 50 mM, which is interpretted in terms of [FeCl_nL_6−n]³⁻ⁿ (n = 1 and 2). In the EtOH system, r steeply increases from 0.1 at [Cl⁻] = 1.5 mM to 0.7 at [Cl⁻] = 3.5 mM, indicating direct transformation from [FeL₆]³⁺ to [FeCl₄]⁻. We further found that the coordination change significantly decreases the redox potential of Fe²⁺/Fe³⁺.

Fe³⁺ coordination in alcohol solution can be controlled by the Cl⁻ concentration ([Cl⁻]). The coordination state changes from FeL₆ (L: solvent molecule) to FeCl₄ type via FeCl_nL_6−n with increases in [Cl⁻].     

The Effect of a Web-Based Cervical Cancer Survivor’s Story on Parents' Behavior and Willingness to Consider Human Papillomavirus Vaccination for Daughters: Randomized Controlled Trial

BackgroundProviding adequate information to parents who have children eligible for human papillomavirus (HPV) vaccination is essential to overcoming vaccine hesitancy in Japan, where the government recommendation has been suspended. However, prior trials assessing the effect of brief educational tools have shown only limited effects on increasing the willingness of parents to vaccinate their daughters.ObjectiveThe aim of this trial is to assess the effect of a cervical cancer survivor’s story on the willingness of parents to get HPV vaccination for their daughters.MethodsIn this double-blinded, randomized controlled trial (RCT) implemented online, we enrolled 2175 participants aged 30-59 years in March 2020 via a webpage and provided them with a questionnaire related to the following aspects: awareness regarding HPV infection and HPV vaccination, and willingness for HPV vaccination. Participants were randomly assigned (1:1) to see a short film on a cervical cancer survivor or nothing, stratified by sex (male vs female) and willingness for HPV vaccination prior to randomization (yes vs no). The primary endpoint was the rate of parents who agreed for HPV vaccination for their daughters. The secondary endpoint was the rate of parents who agreed for HPV vaccination for their daughters and the HPV vaccination rate at 3 months. The risk ratio (RR) was used to assess the interventional effect.ResultsOf 2175 participants, 1266 (58.2%) were men and 909 (41.8%) were women. A total of 191 (8.8%) participants were willing to consider HPV vaccination prior to randomization. Only 339 (15.6%) participants were aware of the benefits of HPV vaccination. In contrast, 562 (25.8%) participants were aware of the adverse events of HPV vaccination. Although only 476 (21.9%) of the respondents displayed a willingness to vaccinate their daughters for HPV, there were 7.5% more respondents in the intervention group with this willingness immediately after watching the short film (RR 1.41, 95% CI 1.20-1.66). In a subanalysis, the willingness in males to vaccinate daughters was significantly higher in the intervention group (RR 1.50, 95% CI 1.25-1.81); however, such a difference was not observed among females (RR 1.21, 95% CI 0.88-1.66). In the follow-up survey at 3 months, 1807 (83.1%) participants responded. Of these, 149 (8.2%) responded that they had had their daughters receive vaccination during the 3 months, even though we could not see the effect of the intervention: 77 (7.9%) in the intervention group and 72 (8.7%) in the control group.ConclusionsA cervical cancer survivor’s story increases immediate willingness to consider HPV vaccination, but the effect does not last for 3 months. Furthermore, this narrative approach to parents does not increase vaccination rates in children eligible for HPV vaccination.Trial RegistrationUMIN Clinical Trials Registry UMIN000039273; https://tinyurl.com/bdzjp4yf     

Efficacy and safety of once‐weekly semaglutide in Japanese individuals with type 2 diabetes by baseline age and body mass index

Aims/IntroductionMany East Asians with type 2 diabetes are elderly and have a low body mass index (BMI), especially in ''super‐aged'' populations, such as Japan. This post‐hoc analysis assessed once‐weekly semaglutide efficacy and safety in Japanese individuals with type 2 diabetes across baseline age and BMI subgroups.Materials and MethodsData were derived from the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) Japan monotherapy and SUSTAIN Japan oral antidiabetes drug (OAD) combination trials comparing once‐weekly semaglutide with sitagliptin or OADs, respectively. Participants were grouped by baseline age (<65 and ≥65 years) and/or BMI (<25 and ≥25 kg/m²). Reductions from baseline in glycosylated hemoglobin and bodyweight (efficacy), and adverse events (safety) were assessed.ResultsIn this analysis, participants from the SUSTAIN Japan monotherapy trial (n = 308; n per subgroup; range, 8–73) and SUSTAIN Japan OAD combination trial (n = 601; n per subgroup; range, 20–168) were included. Reductions in glycosylated hemoglobin and bodyweight were numerically greater with semaglutide versus comparators across all age and BMI subgroups. Reductions from baseline in glycosylated hemoglobin ranged from –1.7 to –2.1 with semaglutide 0.5 mg, –1.8 to –2.4 with semaglutide 1.0 mg and –0.6 to –1.0 with comparators. Corresponding ranges for bodyweight (kg) were –1.0 to –2.5, –2.4 to –4.3 and 1.0 to –1.0 kg, respectively. The safety profile of semaglutide was broadly similar across BMI and age subgroups.ConclusionsIn this post‐hoc analysis with modest subgroup numbers, once‐weekly semaglutide appeared consistently more efficacious versus comparators across age and BMI subgroups in Japanese patients, with a similar safety profile.     

Transplantation of bone marrow stromal cell-derived Schwann cells promotes axonal regeneration and functional recovery after complete transection of adult rat spinal cord

The aim of this study was to evaluate whether transplantation of Schwann cells derived from bone marrow stromal cells (BMSC-SCs) promotes axonal regeneration and functional recovery in completely transected spinal cord in adult rats. Bone marrow stromal cells (BMSCs) were induced to differentiate into Schwann cells in vitro. A 4-mm segment of rat spinal cord was removed completely at the T7 level. An ultra-filtration membrane tube, filled with a mixture of Matrigel (MG) and BMSC-SCs (BMSC-SC group) or Matrigel alone (MG group), was grafted into the gap. In the BMSC-SC group, the number of neurofilament- and tyrosine hydroxylase-immunoreactive nerve fibers was significantly higher compared to the MG group, although 5-hydroxytryptamine- or calcitonin gene-related peptide-immunoreactive fibers were rarely detectable in both groups. In the BMSC-SC group, significant recovery of the hindlimb function was recognized, which was abolished by retransection of the graft 6 weeks after transplantation. These results demonstrate that transplantation of BMSC-SCs promotes axonal regeneration of lesioned spinal cord, resulting in recovery of hindlimb function in rats. Transplantation of BMSC-SCs is a potentially useful treatment for spinal cord injury.     

Increased insulin sensitivity and hypoinsulinemia in APS knockout mice

A tyrosine kinase adaptor protein containing pleckstrin homology and SH2 domains (APS) is rapidly and strongly tyrosine phosphorylated by insulin receptor kinase upon insulin stimulation. The function of APS in insulin signaling has heretofore remained unknown. APS-deficient (APS(-/-)) mice were used to investigate its function in vivo. The blood glucose-lowering effect of insulin, as assessed by the intraperitoneal insulin tolerance test, was increased in APS(-/-) mice. Plasma insulin levels during fasting and in the intraperitoneal glucose tolerance test were lower in APS(-/-) mice. APS(-/-) mice showed an increase in the whole-body glucose infusion rate as assessed by the hyperinsulinemic-euglycemic clamp test. These findings indicated that APS(-/-) mice exhibited increased sensitivity to insulin. However, overexpression of wild-type or dominant-negative APS in 3T3L1 adipocytes did not affect insulin receptor numbers, phosphorylations of insulin receptor, insulin receptor substrate-1, or Akt and mitogen-activated protein kinase. The glucose uptake and GLUT4 translocation were not affected by insulin stimulation in these cells. Nevertheless, the insulin-stimulated glucose transport in isolated adipocytes of APS(-/-) mice was increased over that of APS(+/+) mice. APS(-/-) mice also showed increased serum levels of leptin and adiponectin, which might explain the increased insulin sensitivity of adipocytes.     

Continuing Medical Education Activity in Echocardiography

Article Title: Speckle Tracking Global Strain Rate E/E’ Predicts LV Filling Pressure More Accurately Than Traditional Tissue Doppler E/E’ (Echocardiography, 2012;29:403)     

Latent class models for medical diagnostic tests in multicenter trials

Medical diagnostic tests must enjoy appropriate validity and high reliability in order to qualify as adequate assessment tools. Without a gold standard test, available medical diagnostic tests are not perfect; hence, the reliability of such tests must be evaluated precisely. Kappa coefficient statistics are often utilized to assess reliability of tests when there are two or more medical diagnostic tests. However, the statistics are imprecise for a typical case when the prevalence rate of a target disease is unknown. Although latent class models could be used to assess reliability, the models cannot estimate reliability in the case of two tests, due to unidentifiability or the lack of degrees of freedom. An alternative approach to assess reliability for the case of two tests is stratifying a two‐by‐two contingency table under the assumption that sensitivities and specificities between the two tests be equal over all strata and that prevalence rates in the strata be different from each other. Because stratification is basically a multi‐sample analysis, it should not be applied to the situation where subsamples (i.e., centers) are randomly selected from a larger population. In this article, a type of mixed‐effect model is proposed to evaluate the reliability of two tests for trials in randomly selected multiple centers. Several types of distributions for prevalence rates over subpopulations are considered. Simulation studies show that our proposed method performs nicely. Analysis of real data is also reported. Copyright © 2013 John Wiley & Sons, Ltd.