Magneto-Electric Directional Anisotropy in Polar Soft Ferromagnets of Two-Dimensional Organic-Inorganic Hybrid Perovskites.

Two-dimensional organic-inorganic hybrid perovskites (2D-OIHPs) are attracting interest due to their structural tunability and rich functional characteristics, such as ferroelectricity and ferromagnetism. Here, we report the chiral-polar ferromagnetic 2D-OIHP copper chlorides with discernable electric polarization in the inorganic layers. In these systems, the magneto-electric (ME) correlation has been clearly observed by measuring a magneto-electric directional anisotropy (MEA), in which an optical absorption coefficient changes with reversal of the light propagating direction. We have found that the MEA can be induced by a low magnetic field of about 50 mT, reflecting soft magnetic nature. The present results suggest a new paradigm for designing functional ME multiferroics, which effectively couples magnetic and electric properties.

Magnetochiral Dichroism in a Collinear Antiferromagnet with No Magnetization.

We show the directional dichroism in a collinear antiferromagnet MnTiO_{3}. The dichroism between two distinctive antiferromagnetic states with opposite signs of staggered magnetic moments can be regarded as magnetochiral dichroism in the absence of external fields. Electric-field reversal of antiferromagnetic domain causes a change in the absorption intensity of unpolarized light around 2.15 eV. The difference in optical absorption between two antiferromagnetic states is reversed for the light propagating in the opposite direction. The absorption coefficient displays a hysteretic behavior for a cycle of sweeping the external electric or magnetic field.

Anomalous Lattice Softening Near a Quantum Critical Point in a Transverse Ising Magnet.

We have investigated the elastic response of a transverse Ising magnet CoNb_{2}O_{6} by means of ultrasound velocity measurement. A huge elastic anomaly in the C_{66} mode is observed near a quantum critical point when sweeping a magnetic field perpendicular to the Ising axis. This anomaly appears to become critical only for the Faraday configuration (field parallel to the sound propagation direction) but is much less pronounced for the Voigt geometry (field perpendicular to the sound propagation direction). We propose that the relativistic spin-orbit interaction plays a crucial role in the quantum critical regime resulting in the elastic anomaly, which is enhanced by quantum fluctuations.

Short telomere subtelomeric hypomethylation is associated with telomere attrition in elderly diabetic patients 1.

Telomere shortening is well known to be associated with the aging process and aging-associated diseases, including diabetes. The telomere length and subtelomeric methylation status in peripheral leucocytes (LTL) were compared in elderly type 2 diabetes (T2D) patients and diabetes-free controls (C). The methylation status was analyzed between MspI-TRF lengths and HpaII-TRF lengths by using methylation-sensitive and -insensitive restriction enzyme isoschizomers, MspI and HpaII, respectively. The mean telomere lengths, MspI-TRF or HpaII-TRF, were not significantly different between C and T2D patients. The percentage of fractionated densitometry showed that long and middle telomeres (>9.4 kb, 4.4-9.4 kb) were unaltered but short telomeres (<4.4 kb) in T2D patients were increased compared with C group. The methylation status revealed subtelomeric hypomethylation in short telomeres of T2D patients. When some patients with T2D were treated with 3-hydroxy-3-methylglutaril coenzyme A (HMG-CoA) reductase inhibitors (statin), results seen in short telomere of T2D patients were not observed and were not different from C. This suggested that this altered subtelomeric hypomethylation may be associated with the accelerated telomere shortening in elderly diabetic patients. These results also mean that the subtelomeric hypomethylation can also be influenced by statin treatment in T2D.

Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes.

AIMS: To assess the safety and efficacy of monotherapy with once-weekly subcutaneous (s.c.) semaglutide vs sitagliptin in Japanese people with type 2 diabetes (T2D). METHODS: In this phase IIIa randomized, open-label, parallel-group, active-controlled, multicentre trial, Japanese adults with T2D treated with diet and exercise only or oral antidiabetic drug monotherapy (washed out during the run-in period) received once-weekly s.c. semaglutide (0.5 or 1.0 mg) or once-daily oral sitagliptin 100 mg. The primary endpoint was number of treatment-emergent adverse events (TEAEs) after 30 weeks. RESULTS: Overall, 308 participants were randomized and exposed to treatment, with similar baseline characteristics across the groups. In total, 2.9% of participants in both the semaglutide 0.5 mg and the sitagliptin group prematurely discontinued treatment, compared with 14.7% in the semaglutide 1.0 mg group. The majority of discontinuations in the semaglutide 0.5 and 1.0 mg groups were attributable to adverse events (AEs). More TEAEs were reported in semaglutide- vs sitagliptin-treated participants (74.8%, 71.6% and 66.0% in the semaglutide 0.5 mg, semaglutide 1.0 mg and sitagliptin groups, respectively). AEs were mainly mild to moderate. Gastrointestinal AEs, most frequently reported with semaglutide, diminished in frequency over time. The mean glycated haemoglobin (HbA1c [baseline 8.1%]) decreased by 1.9% and 2.2% with semaglutide 0.5 and 1.0 mg, respectively, vs 0.7% with sitagliptin (estimated treatment difference [ETD] vs sitagliptin -1.13%, 95% confidence interval [CI] -1.32; -0.94, and -1.44%, 95% CI -1.63; -1.24; both P < .0001). Body weight (baseline 69.3 kg) was reduced by 2.2 and 3.9 kg with semaglutide 0.5 and 1.0 mg, respectively (ETD -2.22 kg, 95% CI -3.02; -1.42 and -3.88 kg, 95% CI -4.70; -3.07; both P < .0001). CONCLUSIONS: In Japanese people with T2D, more TEAEs were reported with semaglutide than with sitagliptin; however, the semaglutide safety profile was similar to that of other glucagon-like peptide-1 receptor agonists. Semaglutide significantly reduced HbA1c and body weight compared with sitagliptin.

"Visible" 5d Orbital States in a Pleochroic Oxychloride.

Transition metal compounds sometimes exhibit attractive colors. Here, we report a new oxychloride, Ca3ReO5Cl2, that shows unusually distinct pleochroism; that is, the material exhibits different colors depending on the viewing direction. This pleochroism is a consequence of the coincidental complex crystal field splitting of the 5d orbitals of the Re6+ ion in a square-pyramidal coordination of low symmetry in the energy range of the visible spectrum. Since the relevant d-d transitions show characteristic polarization dependence according to the optical selection rule, the orbital states are "visible" in Ca3ReO5Cl2.

Spin-Orbital Correlated Dynamics in the Spinel-Type Vanadium Oxide MnV_{2}O_{4}.

We investigate the magnetic dynamics in the spinel-type vanadium oxide MnV_{2}O_{4}. Inelastic neutron scattering around 10 meV and a Heisenberg model analysis have revealed that V^{3+} spin-wave modes exist at a lower-energy region than previously reported. The scattering around 20 meV cannot be reproduced with the spin-wave analysis. We propose that this scattering could originate from the spin-orbital coupled excitation. This scattering is most likely attributable to V^{3+} spin-wave modes, entangled with the orbital hybridization between t_{2g} orbitals.

Postmortem Computed Tomography Findings Associated with Sudden Death in Alcoholics.

Forensic pathologists.frequently encounter sudden natural.death of alcoholic in which fatty liver is the only pathological finding detected at autopsy, however, characteristics of postmortem CT (PMCT) of sudden death of alcoholic have not been reported so far. In this study, we investigated radiographic measurements of PMCT of the cases diagnosed as sudden death of alcoholic (ALC), and compared them with those of other causes of death (IHD; ischemic heart disease, SV; starvation), with reference to autopsy findings. The cardio-thoracic ratio, the cross-sectional area of the inferior vena cava and the radio density of the lungs of ALC on PMCT were significantly lower than those of IHD, and tended to be midway between IHD and SV. These findings were in parallel with the total heart blood volume at autopsy and the extent of lung edema on histopathological findings. In addition, the radiodensity of the liver of ALC was significantly lower than the other groups, which was in parallel with the extent of fatty deposit in the hepatocytes on histopathology. More than 60% of ALC cases showed BMI < 18.0, and acetone was detected in blood in 87.5% of ALC cases. The lower radiodensity of the liver, and lack of signs suggestive of significant pulmonary edema and congestion in the great vessels, on PMCT, are considered to mirror terminal pathophysiology of sudden death of alcoholic, such as severe fatty liver- disease and metabolic disturbance (e.g., concomitant volume depletion with alcoholic ketoacidosis). Utilization of these findings on PMCT may serve to discern sudden death of alcoholic from other causes of death, in combination with detailed scene investigation, pathological, toxicological and biochemical analysis.

Characteristics of sudden bath-related death investigated by medical examiners in Tokyo, Japan.

BACKGROUND: Sudden bath-related deaths occur frequently in Japan, particularly among elderly people. However, the precise mechanism of bath-related death remains uncertain, and effective prevention strategies have not been established. METHODS: Cases of bath-related deaths (n = 3289) were selected from all cases handled by the Tokyo Medical Examiner's Office from 2009 to 2011 (N = 41 336). The ages and occurrence dates were examined, and major autopsy findings, including toxicological analysis, were evaluated for the autopsied cases (n = 550). RESULTS: Most cases occurred in individuals older than 60 years of age during winter. Analysis of autopsy findings revealed water inhalation signs in many cases (n = 435, 79.1%). Circulatory system diseases constituted more than half of the pathological findings regarding factors that may have contributed significantly to death (n = 300, 54.5%), and cardiac lesions were the most common pathological finding (n = 250, 45.5%). However, approximately one-third of the cases exhibited no remarkable pathological findings (n = 198, 36.0%). A quarter of all cases involved blood ethanol levels that exceeded 0.5 mg/mL (n = 140). CONCLUSIONS: The results suggested that drowning plays an important role in the final process of bath-related death. Circulatory system diseases may be the primary underlying pathology; however, there were variations in the medical histories and pathologies of cases of bath-related death. From a preventive perspective, family members should pay attention to elderly people with circulatory system diseases during bathing, particularly in winter. Additionally, the notion that ill or inebriated individuals should not take baths should be reinforced.

Epidemiology of Alcohol-related Death while Bathing in a Bathtub.

OBJECTIVES: Alcohol consumption before bathing is listed as a risk factor for sudden death in a bathtub, which occurs relatively frequently in Japan. This study aimed to clarify the epidemiology of alcohol-related deaths in bathtubs. SUBJECTS: Among all autopsy cases that were performed at the Tokyo Medical Examiner's Office between 2009 and 2010 (N = 5635), 357 cases of death in a bathtub were evaluated. Data regarding age, sex, blood ethanol level, manner and. cause .of death, alcohol consumption, and alcohol-related gastrointestinal diseases were extracted. The cases were divided into three groups according to their blood ethanol levels (no blood ethanol, low ethanol, and high ethanol), and their data were compared. RESULTS: A large majority of the cases in all groups involved persons who were 50-89 years old. The mean age of the high ethanol group (61.7 years) was significantly lower than.that of the control group (71.1 years; P < 0.01). In addition, the proportion of men was significantly higher in the low and high ethanol groups (70.1% and 75.5%, respectively), compared to that in the control group (55.9%; P < 0.05). Daily alcohol consumption was significantly more common in the low and high ethanol groups (49.5% and 87.8%, respectively), compared to that in the control group (23.2%; P < 0.01). Furthermore, alcohol-related gastrointestinal diseases were more common in the low and high ethanol groups (26.8% and 63.3%, respectively), compared to that in the control group (4.3%; P < 0.01). CONCLUSIONS: Preventive strategies for reducing alcohol-related deaths in bathtubs should target male habitual drinkers (middle-aged to seniors), especially patients who have been diagnosed with alcohol-related diseases.

Characteristics of sudden unexpected cancer deaths investigated by medical examiners in Tokyo, Japan (2009).

BACKGROUND: Annually, about 400 cases of sudden unexpected death are attributed to cancer in Tokyo, Japan. These individuals may have been undiagnosed, or their medical conditions may not have been carefully evaluated before death. We examined medical consultations, cancer diagnoses, and economic status of all cancer deaths investigated by medical examiners in 2009. METHODS: Among cases handled by the Tokyo Medical Examiner's Office in 2009 (N = 12 493), records for all cases of cancer death (n = 400) were reviewed to determine the extent of medical care provided, diagnosis before death, and economic status of the decedent. RESULTS: Most of the decedents (n = 232; 58%) had received a diagnosis of terminal/advanced cancer during a medical consultation. Most did not receive such medical consultations at home, despite their very weak physical condition. However, nearly one quarter of decedents (24%; 95/400) had not received a cancer diagnosis before death. The proportions of decedents who had been indigent, received no medical consulting, and had colon cancer were significantly higher among undiagnosed cases than among diagnosed cases. Indigent persons were the largest subgroup (n = 19; 43%) among those who had never received a medical consultation (n = 44). In addition, the proportion of those who had discontinued or received no medical consultation was higher among indigent persons than among non-indigent persons. CONCLUSIONS: The quality of medical services for cancer patients could be improved by educating general practitioners about terminal care, expanding efforts to monitor and diagnose cancer, especially among indigent patients, and increasing participation rates for colorectal cancer screening.

Child deaths from injury in the special wards of Tokyo, Japan (2006-2010): a descriptive study.

BACKGROUND: There has been increasing interest in the formal review of child deaths in Japan. In this study we examined the causes and scene information regarding child deaths from injury in Tokyo, the capital of Japan, as preparation for implementation of a full-scale review of child deaths. METHODS: Documents on deaths from injury (excluding homicides) investigated by the Tokyo Medical Examiner's Office during the period from 2006 through 2010 were reviewed. Deaths of children younger than 18 years (N = 217) were selected as the study sample. We examined the cause of and information on the death and were particularly interested in whether a case had preventable factors. RESULTS: Overall, 67% of the cases were deaths from unintentional injury. The main cause of death among children younger than 1 year was asphyxia, and the proportions of deaths from traffic accidents were higher in older age groups. Thirty percent of deaths from injury were due to suicide, and all cases of suicide were among children older than 10 years. Although analysis of preventable factors was difficult in some cases, owing to limited information on the death scene, 87% of deaths from unintentional injury, excluding those involving traffic accidents, had preventable factors. CONCLUSIONS: Most unintentional child deaths from injury appear to be preventable. Development of a system to collect detailed information on the scene at the time of death will help decrease child deaths in Japan.

Characteristics of caffeine intoxication-related death in Tokyo, Japan, between 2008 and 2013.

OBJECTIVES: Caffeine is widely available in beverages and over-the-counter products; however, in large doses, it can lead to lethal arrhythmia. This study aims to clarify the characteristics of caffeine intoxication-related deaths in Tokyo, Japan. SUBJECTS: Among the 4754 forensic autopsy cases between 2008 and 2013 in which a toxicological investigation was performed, cases in which the blood concentration of caffeine exceeded toxic levels (15 µg/ml) were selected (N = 22). We examined subjects' ages, medical histories, direct/underlying causes of death, and manner of death. We also assessed concurrent drug substance detection and identified the origin of the caffeine. RESULTS: More than 60% of the subjects were between the ages of 20 and 49 years (n = 14, 63.6%). Sixteen cases (72.7%) showed a history of psychiatric diseases such as depression and sleep disorders. The underlying cause of death for all cases except two was caffeine intoxication, and manner of death was classified as undetermined (n = 11), accidental (n = 7), suicide (n = 2), or others (n = 2). Toxicological analysis revealed the presence of ingredients common to analgesics/cold remedies in 12 cases (54.5%). The origin of the caffeine was identified in 11 cases (50.0%); the proportion of identification was significantly lower among the cases in which analgesic/cold remedy ingredients were not detected (20.0%). CONCLUSIONS: Caffeine intoxication-related deaths mainly occurred in young and middle-aged persons with common psychiatric diseases. Psychiatrists should take note of caffeine dependence while diagnosing common psychiatric symptoms. In half of the cases, the origin of the caffeine was unidentified; nevertheless, dietary sources or over-the-counter drugs containing caffeine were suspected. As it becomes easier to obtain caffeinated products, continuous monitoring of the number of deaths from caffeine intoxication, in addition to detailed investigations of the caffeine's origin, will be necessary.

Reconstruction using a free jejunal patch flap in salvage head and neck surgery after radiotherapy.

BACKGROUND: Chemoradiotherapy is a standard treatment for functional preservation in patients with advanced head and neck carcinoma. However, chemoradiotherapy increases the risk of postoperative complications. AIMS/OBJECTIVES: We report the usefulness of reconstruction using a free jejunal patch flap in treating recurrence or residual head and neck carcinoma after radiotherapy. Furthermore, we investigated the factors for the occurrence of postoperative complications in patients who underwent salvage surgery using a free flap transfer. MATERIAL AND METHODS: This study included 41 patients with head and neck carcinoma who underwent salvage surgery using a free flap transfer, including 11 patients who underwent reconstruction using a free jejunal patch flap. Prognostic analysis was performed for the development of complications. RESULTS: Ten jejunal patch flaps survived without microvascular problems. One patient underwent revision reconstructive surgery because of flap failure. However, no patient had a pharyngocutaneous fistula. Oral intake could be resumed in all patients at a median 14 days postoperatively. Multivariate logistic regression analysis indicated that the use of cutaneous flaps was significantly associated with the development of complications. CONCLUSIONS AND SIGNIFICANCE: Free jejunal patch flaps can be considered useful for head and neck reconstruction after radiotherapy for early intake resumption and complication prevention.

Multisource surveillance conducted by the Tokyo Metropolitan Government during the Tokyo 2020 Olympic and Paralympic Games.

The Tokyo 2020 Olympic and Paralympic Games (the Games) were held from 23 July to 5 September 2021 in Tokyo, Japan, after a 1-year delay due to the coronavirus disease (COVID-19) pandemic. The Tokyo Metropolitan Government was responsible for monitoring and responding to infectious disease outbreaks other than COVID-19 during the Games. A multisource surveillance system was used from 1 July to 12 September 2021 for the early detection and rapid response to infectious diseases. This included routine notifiable disease surveillance, sentinel surveillance, syndromic surveillance, cluster surveillance, ambulance transfer surveillance and the Tokyo Infectious Alert system. Daily reports were disseminated summarizing the data collected from the multisource surveillance system. No case of infectious disease under the Tokyo Metropolitan Government system required a response during the Games. The multisource surveillance was useful for providing intelligence during the Games and, if required, could contribute to the early detection and rapid response to outbreaks during other mass gatherings. The system could be improved to overcome the challenges implied by the findings of this multisource surveillance.

Intracranial vertebral artery dissection resulting in fatal subarachnoid hemorrhage: clinical and histopathological investigations from a medicolegal perspective.

OBJECT: Subarachnoid hemorrhage (SAH) due to a ruptured intracranial vertebral artery (VA) dissection sometimes results in a sudden fatal outcome. The authors analyzed the relationship between clinical features and histopathological characteristics among fatal cases to establish valuable information for clinical diagnostics and prophylaxis. METHODS: This study included 58 medicolegal autopsy cases of ruptured intracranial VA dissection among 553 fatal nontraumatic cases of SAH that occurred between January 2000 and December 2007. Their clinical features were obtained from autopsy records. Histopathological investigations were performed on cross-sections obtained from all 4-mm segments of whole bilateral intracranial VAs and prepared with H & E and elastica van Gieson staining. RESULTS: The autopsy cases included 47 males and 11 females, showing a marked predilection for males. The mean age was 46.8 +/- 7.7 years, with 78% of the patients in their 40s or 50s. Hypertension was the most frequently encountered history; it was found in 36% of cases from clinical history and in 55% of cases based on autopsy findings. Prodromal symptoms related to intracranial VA dissections were detected in 43% of patients. Headache or neck pain lasting hours to weeks was a frequent complaint. Of patients with prodromal symptoms, 44% had consulted doctors; however, in none of these was SAH or intracranial VA dissection diagnosed at a preventable stage. Autopsy revealed fusiform aneurysms with medial dissecting hematomas. Apart from ruptured intracranial VA dissection, previous intracranial VA dissection was detected in 25 cases (43%); among them, 10 showed previous dissection of the bilateral intracranial VAs. The incidence of prodromal symptoms (60%) among the patients with previous intracranial VA dissection was significantly higher than that (30%) among cases without previous dissection (chi-square test; p = 0.023). Most previous intracranial VA dissections formed a single lumen resembling nonspecific atherosclerotic lesions, with the exception of 3 cases (12%) with a double lumen. CONCLUSIONS: Intracranial VA dissection resulting in fatal SAH frequently affects middle-aged men with untreated hypertension. Related to the high frequency of prodromal symptoms, latent previous intracranial VA dissection was histopathologically detected. Furthermore, intracranial VA dissection tends to induce multiple lesions affecting both intracranial VAs recurrently. This suggests the importance of an awareness of sustained whole intracranial VA vulnerability for the prevention of recurrence. The incidence of prodromal symptoms was significantly higher among patients with previous intracranial VA dissections. Thus, earlier diagnosis of intracranial VA dissections at the unruptured stage is desirable for prophylaxis against fatal SAH.

Local application of CpG oligodeoxynucleotide enhances nontypeable Haemophilus influenzae-specific mucosal IgA responses in the middle ear.

CONCLUSIONS: Nasal vaccination with P6 protein of nontypeable Haemophilus influenzae (NTHi) and CpG oligodeoxynucleotide (ODN) may be effective for the induction of NTHi-specific protective immunity in the middle ear and middle ear application of CpG ODN may possibly be a new treatment strategy for otitis media (OM). OBJECTIVES: Owing to the increased prevalence of antibiotic-resistant bacteria in recent years, treatment for OM often fails. In the interest of developing an alternative treatment that does not require antibiotics, the efficacy of middle ear application of CpG ODN was examined. MATERIALS AND METHODS: Mice were immunized intranasally with P6 and CpG ODN, and CpG ODN was then inoculated into the middle ear. P6-specific antibody titers were determined by enzyme-linked immunosorbent assay (ELISA) and the numbers of P6-specific antibody-producing cells were determined by enzyme-linked immunospot (ELISPOT) assay. RESULTS: P6-specific IgA in ear wash and serum IgG titers were elevated after nasal immunization. The number of specific IgA-producing cells was markedly increased in the middle ear mucosa. Interestingly, middle ear application of CpG ODN enhanced IgA levels in the middle ear.

The demographic characteristics of medicolegal death among welfare recipients in Tokyo Metropolis (2008-2013).

Background The number of welfare recipients has steadily increased in Japan during recent years, although the number of homeless persons has decreased. Despite there being many reports regarding medicolegal death among homeless persons, medicolegal death among welfare recipients has not been fully investigated. Methods We identified 10,293 individuals who received welfare aid during their lifetime among the 81,867 cases that were examined by the Tokyo Medical Examiner's Office (2008-2013). We retrospectively compared the proportions of medicolegal death to total population, age, sex, family status, clinical history, and manners/causes of death among non-indigent persons (controls), homeless persons, and welfare recipients. Results A higher proportion of medicolegal death to total population was observed among the welfare recipients, compared with the controls. The welfare recipients (65.5 years) were younger than the controls (68.9 years), and the proportions of male sex and living alone were higher among the welfare recipients. Hypertension and circulatory disease were the leading clinical conditions among the welfare recipients. Death due to disease was the leading manner of death, and circulatory disease was the leading cause of death among the welfare recipients. The proportion of individuals with a long period between death and discovery (which made determining the cause of death difficult) was also higher among the welfare recipients. Conclusion Welfare recipients have a greater risk of sudden death compared with non-indigent persons. Preventive strategies should target middle-aged to elderly men who live alone, and should address their risks of circulatory diseases and solitary death.

Safety and efficacy of nasal application of CpG oligodeoxynucleotide as a mucosal adjuvant.

OBJECTIVES: Nasal vaccination is an effective regimen to prevent upper respiratory infections. An appropriate adjuvant is required for the development of a nasal vaccine. The safety and efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. METHODS: Mice were nasally administered various doses of CpG ODN weekly, a total of three times. Histologic changes in the spleen and the nasal mucosa were examined, and the alterations in cell subpopulations were analyzed by flow cytometry. In addition, the mice were nasally immunized with P6 outer membrane protein of nontypeable Haemophilus influenzae (NTHi) and CpG ODN, and P6-specific immune responses were examined. RESULTS: No inflammation or tissue damage was observed locally or systemically after nasal administration, even with a high dose of CpG ODN. A high dose of CpG ODN induced an increase in CD8+ T cells in the nasal mucosa and B cells in the spleen. When CpG ODN was coadministered with P6, P6-specific mucosal and systemic immune responses were effectively induced, since high levels of the specific IgA and IgG were detected in the nasal wash and serum, respectively. CONCLUSIONS: These findings suggest that CpG ODN is a safe and effective mucosal adjuvant. Further, nasal vaccination with P6 and CpG ODN might be an effective regimen to prevent upper respiratory infections.

Nasal vaccination with CpG oligodeoxynucleotide induces protective immunity against non-typeable Haemophilus influenzae in the nasopharynx.

OBJECTIVES: Nasal vaccination is an effective therapeutic regimen for preventing otitis media. Since cholera toxin (CT) is toxic, an alternative adjuvant is required for the development of a nasal vaccine. The efficacy of CpG oligodeoxynucleotide (ODN) as a mucosal adjuvant was examined. METHODS: Mice were immunized intranasally with P6 protein of non-typeable Haemophilus influenzae (NTHi) and adjuvant, CT, or CpG ODN, and P6-specific antibody responses were examined. The expression of P6-specific cytokine mRNA in splenic CD4 T cells was also determined. In addition, NTHi challenges were performed and the NTHi was quantified in nasal washes. RESULTS: P6-specific IgA in nasal wash and serum IgG titers were elevated significantly after nasal immunization. The IgG1/IgG2a ratio in serum from P6+CpG-immunized mice was less than that of P6+CT-immunized mice. Although IL-6 was expression similarly in both groups, IFN-gamma expression was greater in P6+CpG-immunized mice than in P6+CT-immunized mice. Enhanced clearance of NTHi from the nasopharynx was also shown equally in both groups. CONCLUSION: These results indicate that CpG ODN might be an effective mucosal adjuvant, acting by mechanisms that are different from CT. These findings suggest that nasal vaccination with P6 and CpG ODN might be an effective regimen for the induction of NTHi-specific protective immunity.