Targeting Tumor-Associated Macrophages with the Immune-Activating Nanomedicine for Achieving Strong Antitumor Activity with Rapid Clearance from the Body.

Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) crucial for the detection of infections and activation of downstream signaling pathways that lead to the production of pro-inflammatory cytokines and interferons. The TLR pathway is an attractive actively studied target pathway. Because of their strong immunostimulatory activity, TLRs are thought to be a "double-edged sword" for systemic treatment, even in the cancer field. To solve this, we have developed dextran-based TAM targeting activating conjugate (D-TAC) technology, which successfully uses tumor-associated macrophages (TAMs) to deliver the TLR7 agonist DSP-0509. We used low molecular weight dextran to target CD206 high M2-type macrophages, activate them, and induce a change in phenotype to antitumor M1-type macrophages with rapid clearance from the body and astonishing antitumor activity. We also demonstrated that the antitumor effect of our best drug candidate 5DEX-0509R is dependent on the abundance of TAMs, which is consistent with their mechanism of action. We believe that 5DEX-0509R generated by D-TAC technology can be a clinically applicable immunotherapy targeting the TLR signaling pathway.

Factors contributing to subjective well-being and supporting successful aging among rural Japanese community-dwelling older adults: A cross-sectional and longitudinal study.

AIM: We aimed to identify the factors contributing to subjective well-being in community-dwelling older adults in rural Japan. This study explored the relationship among physical and mental health, socioeconomic status, and activity levels with regard to the subjective well-being of older adults. METHODS: In the Frail Elderly in the Sasayama-Tamba Area study, a cohort investigation of independent older adults in a rural Japanese community, 541 of 844 participants completed a 2-year follow-up survey. Subjective well-being was assessed as a binary based on three factors - "happiness," "satisfaction with life" and "meaning in life" - using a subset of the World Health Organization's Quality of Life questionnaire. The improvement group transitioned from not having subjective well-being during the baseline survey to having subjective well-being during the follow-up survey. Furthermore, we used multivariable log-Poisson regression models to calculate the prevalence ratios of subjective well-being. RESULTS: The cross-sectional study showed that sleep satisfaction, health services access satisfaction and having a higher-level functional capacity were positively associated with having "happiness" and "satisfaction with life." Furthermore, being aged ≥ 80 years and having financial leeway were positively associated with having "meaning in life." The longitudinal study showed that having a higher-level functional capacity was positively associated with improving "happiness" and "satisfaction with life." Being female was positively associated with improving "happiness" and "meaning in life," and health services access satisfaction and alcohol drinking were positively associated with improving "satisfaction with life" and "meaning in life," respectively. CONCLUSIONS: These findings offer promising avenues for enhancing the subjective well-being of older adults. Geriatr Gerontol Int 2024; 24: 311-319.

The Japanese version of Problem Areas in Diabetes Scale: a clinical and research tool to assess emotional functioning among people with diabetes.

Introduction: The purpose of this study was to develop the Japanese version of the Problem Areas in Diabetes (PAID) scale, a measure of emotional adjustment to diabetes that has been translated into Japanese by our group. Materials and methods: A total of 418 Japanese people with diabetes attending our outpatient clinic participated (n = 65 type 1 and n = 353 type 2). We assessed the internal reliability of the PAID, examined correlations of the PAID with conceptually related psychosocial constructs, evaluated mean differences in the PAID between diabetes treatment groups, and examined correlations of the PAID with diabetes self-care behaviours and selected treatment outcomes. Results: Results showed that the PAID had excellent reliability (Cronbach alpha = 0.934). The PAID correlated significantly with the Diabetes Treatment Satisfaction Questionnaire (r = -0.593, p < 0.0001) and the positive wellbeing (r = -0.396, p < 0.0001), negative wellbeing (r = -0.640, p < 0.0001) and energy (r = -0.444, p < 0.0001) subscales of the Wellbeing Questionnaire. Adherence to diet was negatively correlated with PAID score (r = -0.263, p < 0.0001). The frequency of recent hypoglycemia and number of chronic complications (retinopathy, nephropathy and neuropathy) were positively correlated with PAID scores. PAID was weakly correlated with HbA1c (r = 0.13, p = 0.01). Conclusions: In conclusion, the Japanese version of the PAID demonstrated good internal reliability and evidence of concurrent and discriminant validity. The PAID measures the impact of diabetes, diabetes treatment and treatment outcomes on the emotions of people with diabetes. The results provide encouraging evidence for the clinical utility of the PAID in Japanese people with diabetes.

Association Between Timed Up-and-Go Test and Future Changes in the Frailty Status in a Longitudinal Study of Japanese Community-Dwelling Older Adults.

Purpose: This study aimed to evaluate the relationship between timed up-and-go (TUG) test time and changes in frailty status in a longitudinal cohort study of rural Japanese older adults. Patients and Methods: This prospective cohort study included 545 community-dwelling older adults. Initial and 2-year follow-up surveys were conducted. We compared the number of the Japanese version of the Cardiovascular Health Study components during the follow-up period and classified the participants into three groups: the favorable change, unchanged as prefrail, and unfavorable change groups. Associations between changes in frailty status and TUG time in the first survey were examined. The predictive ability of the TUG test was determined using the receiver operating characteristic (ROC) curve. Results: The favorable change group comprised 315 individuals (57.8%), the unchanged as prefrail group 105 (19.2%), and the unfavorable change group 125 (22.9%). TUG time was associated with the favorable and unfavorable changes after adjustment for covariates (OR 0.79, 95% CI 0.68-0.92, P=0.001 and OR 1.27, 95% CI 1.09-1.49, P=0.002). The ROC curve of TUG time as a predictor of unfavorable changes showed an area under the curve of 0.59. A cut-off point of TUG was calculated as 6.3 s with 49.6% sensitivity and 66.0% specificity. Conclusion: TUG time in the first survey was significantly associated with changes in frailty status 2 years later. However, its predictive value as a stand-alone test is limited and has the potential to predict future changes in the frailty status in older adults in combination with other tests.

Evaluation of the radiofrequency identification lung marking system: a multicenter study in Japan.

BACKGROUND: The radiofrequency identification (RFID) lung marking system is a novel technique using near-field radio-communication technology. The purpose of this study was to investigate the utility and feasibility of this system in the resection of small pulmonary nodules. METHODS: We retrospectively reviewed clinical records of 182 patients who underwent sublobar resection with the RFID marking system between March 2020 and November 2021 in six tertial hospitals in Japan. Target markings were bronchoscopically made within 3 days before surgery. The contribution of the procedure to the surgery and safety was evaluated. RESULTS: Target nodule average diameter and depth from the lung surface were 10.9 ± 5.4 mm and 14.6 ± 9.9 mm, respectively. Radiologically, one third of nodules appeared as pure ground-glass nodules (GGNs) on CT. The average distance from target nodule to RFID tag was 8.9 ± 7.1 mm. All surgical procedures were completed by video-assisted thoracoscopic surgery. Planned resection was achieved in all cases without any complications. The surgeons evaluated this system as helpful in 93% (necessary: 67%, useful; 26%) of cases. Nodule radiological features (p < 0.001) and type of surgery (p = 0.0013) were associated with the degree of contribution. In most cases, identification of the RFID tag was required within 1 min despite adhesion (p = 0.27). CONCLUSION: The RFID lung marking system was found to be safe and effective during successful sublobar resection. Patients with pure GGNs are the best candidates for the system.

Phase 1/2 study evaluating the safety and efficacy of DSP-7888 dosing emulsion in myelodysplastic syndromes.

DSP-7888 is an immunotherapeutic cancer vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of DSP-7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP-7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2-4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose-limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty-seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher-risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8-10.3) months. Median OS was 10.0 (90% CI, 7.6-11.4) months in patients with a WT1-specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3-8.1) months in those without a WT1-specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP-7888 dosing emulsion.

New practical scoring system to predict post-endoscopic retrograde cholangiopancreatography pancreatitis: Development and validation.

BACKGROUND AND AIM: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most serious adverse event of ERCP. Therefore, it is important to identify high-risk patients who require prophylactic measures. The aim of this study was to develop a practical prediction model for PEP that identifies high-risk patients. METHODS: Patients who underwent ERCP at three tertiary hospitals between April 2010 and September 2012 were enrolled. The dataset was divided into a training set (two centers) and validation set (one center). Using the training set, univariable and multivariable analyses were performed to identify predictive factors for PEP. We constructed a scoring system and evaluated reproducibility using the validation set. RESULTS: A total of 2719 ERCPs were analyzed. PEP developed in 133 cases (4.9%). Risk factors (adjusted odds ratios [OR]) in the training set were a history of PEP (OR: 4.2), intact papilla (OR: 2.4), difficult cannulation (OR: 1.9), pancreatic guidewire-assisted biliary cannulation (OR: 2.2), pancreatic injection (OR: 2.1), pancreatic intraductal ultrasonography (IDUS)/sampling from the pancreatic duct (OR: 2.2), and biliary IDUS/sampling from the biliary tract (OR: 2.8). A scoring system was constructed using these seven clinical variables. The areas under the receiver-operating characteristic curve of this model were 0.799 in the training set and 0.791 in the validation set. In the high-risk group at a score of 3 or higher, the incidence of PEP was 13.4%, and all severe/fatal cases were in the high-risk group. CONCLUSIONS: This scoring system helps to predict each patient's risk and select preventive measures.

Methotrexate-associated lymphoproliferative disorder with histopathological features of histiocytic necrotizing lymphadenitis.

An 84-year-old Japanese woman suffering from rheumatoid arthritis (RA), who had been treated with methotrexate (MTX) for 15 years, was admitted to our hospital for generalised lymphadenopathy, thrombocytopenia, anaemia, elevated aminotransferases, and elevated CRP levels. Pathological findings of cervical lymph node biopsy were compatible with histiocytic necrotising lymphadenitis (HNL). Small lymphocytes positive for Epstein-Barr virus (EBV)-encoded small RNA were detected in the tissue. We suspected a MTX-associated lymphoproliferative disorder (MTX-LPD), withdrew MTX and administered leucovorin (folic acid). The patient's symptoms gradually resolved following discontinuation of MTX. We considered that this patient developed HNL as an MTX-LPD when EBV was reactivated. This is the first case of HNL associated with MTX treatment for RA, which we report here along with clinical course.

Early use of donepezil against psychosis and cognitive decline in Parkinson's disease: a randomised controlled trial for 2 years.

OBJECTIVES: Brain acetylcholine is decreased even in patients with cognitively preserved Parkinson's disease (PD). We investigated whether early and long-term use of donepezil prevents psychosis in non-demented PD patients. METHODS: A double-blinded, placebo-controlled trial was conducted. A total of 145 non-demented PD patients were randomly assigned to receive 5 mg/day donepezil (n=72) or placebo (n=73) for 96 weeks. Medications for PD were not restricted, but antipsychotic drugs were not permitted throughout the study. The primary outcome measure was survival time to psychosis that was predefined by Parkinson's Psychosis Questionnaire (PPQ) B score ≥2 or C score ≥2. Secondary outcome measures included psychosis developing within 48 weeks, total PPQ score, Mini-Mental State Examination (MMSE), Wechsler Memory Scale (WMS) and subgroup analysis by apolipoprotein ε4 genotyping. RESULTS: Kaplan-Meier curves for psychosis development were very similar between the two groups, and the Cox proportional hazard model revealed an adjusted HR of 0.87 (95%CI 0.48 to 1.60). The changes in MMSE and WMS-1 (auditory memory) were significantly better with donepezil than in placebo. In the subgroup analysis, donepezil provided an HR of 0.31 (0.11-0.86) against psychosis in 48 weeks for apolipoprotein ε4 non-carriers. CONCLUSIONS: Although donepezil provided beneficial effects on PPQ, MMSE and auditory WMS score changes in 2 years, it had no prophylactic effect on development of psychosis in PD. Apolipoprotein ε4 may suppress the antipsychotic effect of donepezil. TRIAL REGISTRATION NUMBER: UMIN000005403.

HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties.

The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a human PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, decreased PCSC marker expression, and downregulation of POU5F1/OCT4 expression. Conversely, HNF1A overexpression increased PCSC marker expression and tumorsphere formation in pancreatic cancer cells and drove pancreatic ductal adenocarcinoma (PDA) cell growth. Importantly, depletion of HNF1A in xenografts impaired tumor growth and depleted PCSC marker-positive cells in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of PCSC properties and novel oncogene in PDA.

Oxidation of squalene by singlet oxygen and free radicals results in different compositions of squalene monohydroperoxide isomers.

Oxidation of squalene (SQ) causes a decline in the nutritional value of SQ in foods, as well as an accumulation of SQ oxidation products in skin lipids which lead to adverse skin conditions. However, mechanistic insights as to how SQ is oxidized by different oxidation mechanisms have been limited, and thus effective measures towards the prevention of SQ oxidation have not been identified. In this study, we oxidized SQ by either singlet oxygen oxidation or free radical oxidation, and monitored the formation of the six SQ monohydroperoxide (SQOOH) isomers, the primary oxidation products of SQ, at the isomeric level. While singlet oxygen oxidation of SQ resulted in the formation of similar amounts of the six SQOOH isomers, free radical oxidation of SQ mainly formed two types of isomers, 2-OOH-SQ and 3-OOH-SQ. The addition of ß-carotene during singlet oxygen oxidation, and the addition of α-tocopherol during free radical oxidation lead to a dose-dependent decrease in the formation of SQOOH isomers. Such results suggest that the analysis of SQOOH at the isomeric level allows for the determination of the cause of SQ oxidation in various samples, and provides a foothold for future studies concerning the prevention of SQ oxidation.

[Successful Early Surgical Treatment for Infected Traumatic Pulmonary Pseudocyst].

Almost all traumatic pulmonary pseudocysts (TPP), such as cavitary pulmonary lesions after blunt chest trauma, resolve spontaneously. On the contrary, secondary infection of a TPP should be considered in the presence of purulent sputum or hemosputum and a persistent cavity. We report a case of an infected TPP that was successfully treated by early surgical treatment. A 25-year-old man was transferred to our hospital with a TPP, shown by computed tomography (CT) as having a thick-walled large cavity, after the acute phase of blunt chest trauma. Purulent hemosputum suggested infection of the cavity. Serial CT scans of the chest revealed a persistent cavity. The thick-walled large cavity was diagnosed as a secondary infection of the TPP, that is, a potential lung abscess. We resected the cavity before a systemic inflammatory reaction occurred.

Antioxidant Artemisia princeps Extract Enhances the Expression of Filaggrin and Loricrin via the AHR/OVOL1 Pathway.

The Japanese mugwort, Artemisia princeps (yomogi in Japanese), has anti-inflammatory and antioxidant effects. Skin care products containing Artemisia princeps extract (APE) are known to improve dry skin symptoms in atopic dermatitis. Atopic dry skin is associated with a marked reduction of skin barrier proteins, such as filaggrin (FLG) and loricrin (LOR). Recently, aryl hydrocarbon receptor (AHR), and its downstream transcription factor OVO-like 1 (OVOL1), have been shown to regulate the gene expression of FLG and LOR. The focus of this paper is to evaluate the effects of APE on the AHR/OVOL1/FLG or LOR pathway since they have remained unknown to this point. We first demonstrated that non-cytotoxic concentrations of APE significantly upregulated antioxidant enzymes, NAD(P)H dehydrogenase quinone 1 and heme oxygenase 1, in human keratinocytes. Even at these low concentrations, APE induced nuclear translocation of AHR and significantly upregulated CYP1A1 (a specific target gene for AHR activation), FLG, and LOR expression. AHR knockdown downregulated OVOL1 expression. The APE-induced upregulation of FLG and LOR was canceled in keratinocytes with AHR or OVOL1 knockdown. In conclusion, antioxidant APE is a potent phytoextract that upregulates FLG and LOR expression in an AHR/OVOL1-dependent manner and this may underpin the barrier-repairing effects of APE in treating atopic dry skin.

[CLINICAL INVESTIGATION OF 6 CASES OF TUBERCULOUS SPONDYLITIS].

[Objective] A delay in the diagnosis of tubercu- lous spondylitis can result in worsening of the condition. We investigated previously reported cases of tuberculous spondylitis, as well as cases experienced in our hospital, to identify factors that are useful in the diagnosis. [Materials and Methods] We retrospectively evaluated six cases of tuberculous spondylitis diagnosed in our hospital between October 2007 and September 2012, and an additional 23 cases that had been reported in Japan between 1994 and 2014. [Results] The median age of our six patients was 78.5 years and five were women. In all cases, the focal lesion was seen in 2-3 adjacent vertebrae; four patients had miliary tuberculosis and five had lower back pain. All patients received oral treatment for 10-12 months. Among the 23 patients previously reported, 57% were women, and a focal lesion was found in 2-3 adjacent vertebrae in 86%. In addition, 57% had miliary tuberculosis and 65% had lower back pain. A personal and family history of tuberculosis was found in 20% and 26%. [Discussion] Radiographic assessment and microbiological testing of areas other than the chest and spine are useful in the diagnosis of tuberculous spondylitis. Furthermore, lower back pain, lower extremity symptoms, and personal and family history of tuberculosis are important factors. [Conclusion] When tuberculous spondylitis is suspected, diagnosis may be possible by investigating focal lesions in areas other than the spine.

Hypothesis of Long-Term Outcome after Coronary Revascularization in Japanese Patients Compared to Multiethnic Groups in the US.

BACKGROUND: Ethnicity has a significant impact on coronary artery disease (CAD). This study investigated the long-term outcomes of Japanese patients undergoing revascularization compared with US patients belonging to multiple ethnic groups. METHODS AND RESULTS: We evaluated clinical outcomes, based on ethnicity, of patients included in the Coronary Revascularization Demonstrating Outcome (CREDO-Kyoto) and the Texas (US) Heart Institute Research Database (THIRDBase) registries. For the analysis, we included 8871 patients from the CREDO-Kyoto registry (median follow-up period [FU], 3.5 years; interquartile range [IQR], 2.6-4.3) and 6717 patients from the THIRDBase registry (FU, 5.2 years; IQR, 3.8-6.5) who underwent percutaneous coronary intervention or bypass surgery. Cox proportional hazard models were constructed to compare the adjusted long-term outcomes for each ethnic group. A total of 8871 Japanese, 5170 Caucasians, 648 African-Americans, 817 Hispanics, and 82 Asian-Americans were identified. When adjusted, Japanese patients had significantly better outcomes than US patients, classified by ethnicity (Caucasians: hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.35-1.79; Hispanics: HR, 1.53; 95% CI, 1.22-1.93; African-Americans: HR, 2.03; 95% CI, 1.62-2.56), except for Asian-Americans (HR, 0.84; 95% CI. 0.38-1.89) who had outcomes similar to Japanese patients. CONCLUSION: Our findings indicate better survival outcomes in re-vascularized Japanese CAD patients compared to major ethnic groups in the US, including Caucasian, Hispanic, and African-American CAD patients. The characteristics and outcomes of Japanese CAD patients were similar to those of Asian-Americans, despite the sample size limitations in the US dataset.

[Perioperative Management of Lung Cancer Patients with atrial fibrillation being treated by antiplatelet or anticoagulant therapy].

In an aging society, the high incidence of surgery for the patients with ischemic heart disease(IHD)or atrial fibrillation(Af) under antiplatelet or anticoagulant therapy is a great problem. Interruption of antiplatelet or anticoagulant oral agents in the perioperative period may increase the risk of coronary or cerebral events. We retrospectively reviewed the surgical outcomes for lung cancer patients with IHD or Af. We reviewed 135 patients with lung cancer(41~88 years;97 men) who had preoperative oral administration of antiplatelet or anticoagulant drugs for IHD or Af between 2005 and 2012 at 2 centers, and analyzed retrospectively the perioperative medications and complications. IHD, Af and vasospastic angina(VSA) were complicated in 94, 33 and 8 patients, respectively. Drugeluted and bare-metal stents had been placed in 18 and 19 patients. Oral agents were aspirin in 68 patients, ticlopidine in 10 patients, clopidogrel in 15 patients and warfarin in 25 patients. These agents were stopped 2 to 60 days before surgery. Perioperative heparinization was performed in 22 patients. Oral agents were restarted after confirmation of hemostasis and no need for further invasive treatment. The surgical procedures were lobectomy in 88 patients, segmentectomy in 19 and partial resection in 25. There were no hemorrhagic or thromboembolic complications in a perioperative period except 1 case of pulmonary hemorrhage and 1 case of cerebral infarction. No perioperative hospital death was documented. Short-term interruption of antiplatelet or anticoagulant drugs before lung cancer surgery and heparinization was acceptable from the view of perioperative outcomes.

Social regulations predispose people to complete vaccination for vaccine-preventable diseases.

Japan experienced measles outbreaks in both 2006 and 2007 mainly among university students. Improvement of vaccine coverage against vaccine-preventable viral infections is the prime task for preventing outbreaks of viral infections. To elucidate the promoting factors for complete vaccination against measles, rubella, mumps, and varicella-zoster viruses, we conducted a case-control study among single university students in Japan. Information on vaccinations and clinico-demographical factors were collected using a self-administered questionnaire and a photocopy of the Maternal and Child Health Handbook. Logistic regression analysis was performed to estimate odds ratios (ORs) and their 95% confidence intervals (CIs) for two-time vaccination against measles and rubella viruses as mandatory vaccinations and at least one-time vaccination against mumps and varicella-zoster viruses as optional vaccinations. A total of 1,370 (744 medical, 508 paramedical, and 118 pharmaceutical) students were invited to participate, 960 (70.1%) of whom were enrolled in the study. Students aged < 20 years had a greater propensity for measles and rubella vaccinations (OR 7.8 [95% CI, 5.1-11.8] and OR 6.1 [95% CI, 3.7-10.0], respectively) compared with those aged ≥ 20 years. Students with a history of living over-seas for 1 month or longer were more likely to complete vaccination for measles (OR 4.4 [95% CI, 1.4-13.5] compared with those without such history. This significantly high vaccination coverage was attributed to the measles-rubella catch-up campaign by the Japanese government and the immunization regulations by foreign countries. These findings suggest that social regulations would predispose people to complete vaccination.

Non-superiority of Kakkonto, a Japanese herbal medicine, to a representative multiple cold medicine with respect to anti-aggravation effects on the common cold: a randomized controlled trial.

OBJECTIVE: Kakkonto, a Japanese herbal medicine, is frequently used to treat the common cold not only with a physician's prescription, but also in self-medication situations. This study aimed to examine whether Kakkonto prevents the aggravation of cold symptoms if taken at an early stage of illness compared with a well-selected Western-style multiple cold medicine. METHODS: This study was a multicenter, active drug-controlled, randomized trial. Adults 18 to 65 years of age who felt a touch of cold symptoms and visited 15 outpatient healthcare facilities within 48 hours of symptoms onset were enrolled. The participants were randomly assigned to two groups: one treated with Kakkonto (Kakkonto Extract-A, 6 g/day) (n=209) and one treated with a Western-style multiple cold medicine (Pabron Gold-A, 3.6 g/day) (n=198) for at most four days. The primary outcome of this study was the aggravation of cold, nasal, throat or bronchial symptoms, scored as moderate or severe and lasting for at least two days within five days after entry into the study. RESULTS: Among the 410 enrollees, 340 (168 in the Kakkonto group and 172 in the Pabron group) were included in the analyses. The proportion of participants whose colds were aggravated was 22.6% in the Kakkonto group and 25.0% in the Pabron group (p=0.66). The overall severity of the cold symptoms was not significantly different between the groups. No harmful adverse events occurred in either group. CONCLUSION: Kakkonto did not significantly prevent the progression of cold symptoms, even when prescribed at an early stage of the disease.

Serological assessment of measles-rubella vaccination catch-up campaign among university students.

BACKGROUND: In Japan, 5000-300,000 persons contracted measles every year until 2001. The measles/rubella-combined (MR) vaccination at age 17-18 years (phase 4 MR vaccination: MR-IV) was launched in 2008 in Japan as a measles-rubella catch-up campaign. A serological assessment of this campaign has not been thoroughly performed. METHODS: Titers of anti-measles and anti-rubella immunoglobulin G antibodies, and past medical history including measles and rubella vaccination and infection were obtained from first-year university students in 2008 and 2009, and the immune status against measles and rubella was compared between students at the target MR-IV age (the target age group) and those 1 year older than the target age (non-target age group). RESULTS: A total of 186 students were in the target age group and 146 were in the non-target age group. The proportion of students with a history of measles and rubella infection was not significantly different between the two groups (8.8% vs. 6.3%, P = 0.41 and 11.0% vs. 9.9%, P = 0.75, respectively). A history of two or more measles and rubella vaccinations was significantly more frequent in the target age group (85.2% and 54.9%, respectively) than in the non-target age group (20.8% and 13.2%, respectively; both P < 0.001). Prevalence of seropositivity for measles and for rubella was also higher in the target age group (98.9% and 97.8%, respectively) than in the non-target age group (91.0% and 87.5%, respectively; both P < 0.001). CONCLUSIONS: The MR-IV catch-up campaign helped achieve herd immunity and will contribute to the elimination of measles and rubella.