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Background: Since its discovery in late 2019, COVID-19 has claimed approximately three million lives worldwide, causing a significant economic burden and strain on health care delivery and services. Therefore, the COVID-19 vaccine may offer the potential to promote global recovery. Objective: To determine the acceptability of the COVID-19 vaccine among Nigerian doctors and the factors influencing the acceptance.Methods: Using a cross-sectionaldesign, an anonymous online survey was administered to medical doctors across the six geopolitical zones in Nigeria between 13 January and 31 January 2021, using the health belief model (HBM). Results: Out of 830 respondents, 38.8% were willing to take the COVID-19 vaccine, 36.0% were unsure, while the remaining 26.5% refused to take the vaccine.Following adjustments, males were more likely to take the vaccine (OR = 3.357; 95% CI 2.009-5.610; p = 0.0001), whereas increasing age, higher perceived viral virulence and perceived viral infectivity were observed to be significantly associated with less likelihood of accepting the vaccine. Respondents who believed in the efficacy of ivermectin were much less likely to receive the vaccine (OR = 0.217; 95% CI 0.108-0.436; p=0.001). Concerns on vaccination safety were themain barriersto vaccine acceptability. Hypothetically addressing these concerns increased vaccine acceptance rates by approximately a third (34.6%) (p < 0.001). Conclusion: The proposed nationwide distribution of the COVID-19 vaccine may be met withpoor vaccine acceptability among Nigerian medical practitioners. Measures specifically addressing vaccine safety concerns should be provided to allay fears and enhance the acceptability of the vaccine.

Although there have been major improvements in oral health, with remarkable advances in the prevention and management of oral diseases, globally, inequalities persist between urban and rural communities. These inequalities exist in the distribution of oral health services, accessibility, utilization, treatment outcomes, oral health knowledge and practices, health insurance coverage, oral health- related quality of life, and prevalence of oral diseases, among others. People living in rural areas are likely to be poorer, be less health literate, have more caries, have fewer teeth, have no health insurance coverage, and have less money to spend on dental care than persons living in urban areas. Rural areas are often associated with lower education levels, which in turn have been found to be related to lower levels of health literacy and poor use of health care services. These factors have an impact on oral health care, service delivery, and research. Hence, unmet dental care remains one of the most urgent health care needs in these communities. We highlight some of the conceptual issues relating to urban-rural inequalities in oral health, especially in the African and Middle East Region (AMER). Actions to reduce oral health inequalities and ameliorate rural-urban disparity are necessary both within the health sector and the wider policy environment. Recommended actions include population-specific oral health promotion programs, measures aimed at increasing access to oral health services in rural areas, integration of oral health into existing primary health care services, and support for research aimed at informing policy on the social determinants of health. Concerted efforts must be made by all stakeholders (governments, health care workforce, organizations, and communities) to reduce disparities and improve oral health outcomes in underserved populations. [ABSTRACT FROM AUTHOR]

Background: The objective was to study whether a Kiswahili version of the OIDP (Oral Impacts on Daily Performance) inventory was valid and reliable for use in a population of older adults in urban and rural areas of Tanzania; and to assess the area specific prevalence, intensity and perceived causes of OIDP. Method: A cross-sectional survey was conducted in Pwani region and in Dar es Salaam in 2004/2005. A two-stage stratified cluster sample design was utilized. Information became available for 511 urban and 520 rural subjects (mean age 62.9 years) who were interviewed and participated in a full mouth clinical examination in their own homes. Results: The Kiswahili version of the weighted OIDP inventory preserved the overall concept of the original English version. Cronbach's alpha was 0.83 and 0.90 in urban and rural areas, respectively, and the OIDP inventory varied systematically in the expected direction with self-reported oral health measures. The respective prevalence of oral impacts was 51.2% and 62.1% in urban and rural areas. Problems with eating was the performance reported most frequently (42.5% in urban, 55.1% in rural) followed by cleaning teeth (18.2% in urban, 30.6% in rural). More than half of the urban and rural residents with impacts had very little, little and moderate impact intensity. The most frequently reported causes of impacts were toothache and loose teeth. Conclusion: The Kiswahili OIDP inventory had acceptable psychometric properties among non-institutionalized adults 50 years and above in Tanzania. The impacts affecting their performances were relatively common but not very severe. [ABSTRACT FROM AUTHOR]

Background: Cough is one of the cardinal features of Pulmonary Tuberculosis (PTB). However, even in communities with high prevalenceof TB, lung diseases other than TB appear to account for this symptom. Objective: To estimate the prevalence of sputum smear positivity among patients with TB who presented with complaints of chronic cough to the Directly Observed Therapy Short Course (DOTS) clinic at the University of Maiduguri Teaching Hospital, North Eastern Nigeria. Methodology: A cross sectional study was conducted at the University of Maiduguri Teaching Hospital (UMTH) Borno state, Northeastern Nigeria between September 2014 and January 2017. All patients (new or previously treated) who presented to the DOTS clinic of the UMTH with complaints of chronic cough and had screening for pulmonary TB using sputum smear microscopy were reviewed. Data were entered into a computer database and analyzed with SPSS version 20.0 statistical software. Results: The minimum and the maximum ages were 1 year and 85 years, respectively, and the mean age was 36.0 (SD=14.0) years. The mean age did not differ among the male and female patients (i.e.37.3 ± 14.4 vs 34.1 ± 13.2, p=0.78). The overall prevalence of sputum smear positivity for TB was 26.5%. Although majority of patients who were sputum smear positive for TB fell within the age groups 30-39 and 20-29 thus accounting for 42.6% and 28.7% respectively, however, there was no significant association between age of those with chronic cough and sputum smear positivity TB (p=0.80). Among those who were sputum smear positive, 24.3% were new cases and 2.2% were previously treated. Conclusions: This study showed a high prevalence of sputum smear positivity among suspected TB patients with complaints of chronic cough. This could be explained by the fact that the DOTS strategy has improved the case detection of PTB in this community. All patients with chronic cough should be evaluated for PTB.

We report a case of a 7-year-old unimmunized child who presented with a 2 week history of nasal quality speech, hoarseness of the voice, regurgitation of feeds, and unstable gait. He had a previous history of fever, severe sore throat and bloody nasal discharge. A throat swab was negative for Corynebacterium diphtheria; however, he had received antibiotics at a primary care clinic prior to presentation. A clinical diagnosis of diphtheria with neurologic complication was made and the child was started on oral erythromycin, nasogastric tube feeding and daily physiotherapy, following which he improved. We did not prescribe diphtheria anti-toxin because of its unavailability. [ABSTRACT FROM AUTHOR]

The introduction of highly active antiretroviral therapy (HAART) has transformed HIV infection from hopeless to manageable health condition comparable to non-infectious diseases such as asthma and diabetes mellitus. This modest achievement has reduced morbidity and mortality and increased longevity and quality of life among HIV infected persons. Although reports from developing countries such as Nigeria, shows that youth within the reproductive are most affected by the scourge of HIV/AIDS. Older patients with features that may be indicative of HIV infection are often overlooked in favour of other differential diagnosis. Objective: To document HIV positive sero-status among client aged 50 years and above that necessitated HIV test as part of their clinical evaluation after voluntary counseling and testing at a tertiary health facility. Method: Record of 1674 adults participants that presented for care between January 2009 - December 2013, were retrieved for this study. Results: The HIV-seropositive status among the participants was 370 (22.1%). It showed a female preponderance of 136 (26.0%) than 234 (20.0%) in males. The peak annual prevalence was observed in the year 2010, steady decline was observed thereafter. Overall, older participants between 60-70 years had higher HIV-seropositivity status. This study shows one out of four males and five females with index of suspicion either based on clinical presentation or risky sexual behavior are positive for HIV infection. Conclusion: This report underscores the need to explore other risk factors that may be peculiar to older segment of the society and introduce HIV intervention strategies for the older populations. Delivery of HIV intervention measures and services to this segment of the population is expedient. Measures and interventions should take into consideration the peculiarities, specific vulnerabilities and HIV-related challenges faced by this group of clients

Background: Toxoplasma gondii infection is one of the commonest opportunistic infections in HIV-infected patients, with the fatal consequences of toxoplasmic encephalitis particularly in advanced disease. However, data regarding T. gondii infection in the setting of HIV/AIDS are scant in Nigeria. Objective: To determine the seroprevalence of T. gondii amongst HIV-infected patients as well as to determine the correlation between anti-T. gondii IgG titre and the CD4+ cell count/HIV-1 RNA viral load. Method: A cross sectional study in which a total of 190 subjects were involved i.e. 110 newly diagnosed HAART naïve HIV-positive patients and 80 apparently healthy HIV-negative age- and sex-matched controls that were selected by simple random sampling method. Results: The age range of the study population was 20-64 years. The mean ages of male subjects for both HIV-positives and controls were 37.52 ±8.20 years and 35.79 ±12.31years, respectively, (p= 0.462). On the other hand, the mean ages of female subjects for both HIV-positives and controls were 29.90 ±6.98 years and 32.30 ±10.29 years, respectively, (p=0.149). Twenty one subjects (19.1%) among HIV-positives and 1 (1.25%) HIV-negative tested positive for anti-T. gondii IgG, respectively, (p= 0.000). The prevalence rate ratio of anti-T. gondii IgG of HIV positives compared to HIV negatives was 15.28. Significant proportion of anti-T.gondii positive subjects presented with AIDS defining illnesses compared with their anti-T.gondii negative counterparts. Conclusion: The study has shown that anti-T. gondii IgG is about 15 times more prevalent among HIV positive patients compared to controls. Routine screening for T. gondii IgG anti-body is therefore recommended for all HIV-infected subjects at the facility as well as commencement of chemoprophylaxis against Toxoplasmic encephalitis in HIV-infected patients with CD4+ cell count of 100 cells/ml

Background: Both HIV and HBV infections are endemic in Nigeria and patients with dual HIV/HBV-coinfections are increasingly being recognized because of shared modes of transmission as well as synergy in pathogenesis. Reports have indicated that HBV will contribute significantly to morbidity and mortality among HIV-infected population over the coming years because of increasing access to highly active antiretroviral therapy (HAART). Objective: To determine the prevalence of hepatitis B virus surface antigenaemia among HIV-infected patients and its relationship to CD4+ cell count. Method: A cross-sectional observational study in which 100 newly diagnosed HIV-infected adults comprising 59 (59%) females and 41 (41%) males were selected for the study by systematic random sampling. Results: The age range of the study population was 15-65 years. The mean ages for male and female subjects were 39.37 ± 10.52 and 31.32 ± 7.52 years, respectively. The prevalence of HBsAg among the study subjects was 21%. The mean CD4+ cell count of HBsAg positive subjects was significantly lower than that of HBsAg negative ones i.e. 105.43 cells/µl vs. 161.35cells/µl (p = 0.033). Conclusion: The HIV-HBV confection prevalence of 21% is fairly high and the significantly low mean CD4+ cell count among these subjects suggest that this group of patients are more immunocompromised and may perhaps have increased risk of liver-related morbidity and mortality than their HIV-monoinfected counterparts. Screening for serological markers of chronic HBV infection in all newly diagnosed HIV-positive patients is therefore recommended before commencement of HAART as it also guides the choice of ART regimen, as well as intensification of HBV immunization programmes in all newborns and persons at risk of contracting HBV infection.

Abstract Background The oral health education programs which have been organised and delivered in Tanzania were not based on a thorough understanding of behaviours which influence oral health. Therefore, evaluation of these programs became difficult. This study aimed at investigating the oral health related behaviours and their determinants among Tanzanian adults. Methods A national pathfinder cross sectional survey was conducted in 2006 involving 1759 respondents from the six geographic zones of mainland Tanzania. Frequency distributions, Chi square and multiple logistic regression analyses were performed using SPSS version 13.0. Results The rates of abstinence from alcohol for the past 30 days and life time smoking were 61.6% and 16.7% respectively, with males being more likely to smoke (OR 9.2, CI 6.3 -12.9, p < 0.001) and drink alcohol (OR 1.5, CI 1.2 -1.8, p < 0.001). Multiple regression analysis revealed that; having dental pain (OR 0.7, CI 0.5-0.8; p < 0.001) and being minimally educated (OR 0.48, CI 0.4-0.6; p < 0.001) reduced the likelihood of having a high sugar score. Whereas being male (OR 1.5, CI 1.2- 1.8; p < 0.001), urban (OR 1.9, CI 1.5 -2.3; p < 0.001), and young (OR 1.5, CI 1.2 -1.8; p < 0.001) increased the likelihood of having a high sugar score. Urban residents were less likely to take alcohol (OR 0.7, CI 0.6-0.9; p < 0.01), or smoke cigarette (OR = 0.7, CI = 0.6-0.9); less likely to be those who do not use fruits (OR 0.3, CI 0.2-0.4; p < 0.001); dental clinic (OR 0.5, CI 0.4-0.7; p < 0.001); factory made tooth brushes (OR 0.1, CI 0.08-0.17; p < 0.001) and toothpaste (OR 0.1, CI 0.1-0.2; p < 0.001) than their rural counterparts. More rural (13.2%) than urban (4.6%) residents used charcoal. Conclusion The findings of this study demonstrated social demographic disparities in relation to oral health related behaviors, while dental pain was associated with low consumption of sugar and high likelihood to take alcohol.

Abstract Background Need perceptions for dental care play a key role as to whether people in general will seek dental care. The aim was to assess the prevalence of perceived need of problem based dental care, dental check-ups and any type of dental care. Guided by the conceptual model of Wilson and Cleary, the relationship of perceived need for dental care with socio-demographic characteristics, clinically defined dental problems and self-reported oral health outcomes was investigated. Partial prosthetic treatment need was estimated using a socio-dental approach. Method A cross-sectional survey was conducted in Pwani region and in Dar es Salaam in 2004/2005. Information from interviews and clinical examination became available for 511 urban and 520 rural adults (mean age 62.9 yr). Results 51.7% (95% CI 46.2, 57.0) urban and 62.5 % (95% CI 53.1, 70.9) rural inhabitants confirmed need for dental check-up, 42.9% (95% CI 36.9, 48.9) urban and 52.7% (95% CI 44.5, 60.6) rural subjects confirmed need for problem oriented care and 38.4% (95% CI 32.4, 44.6) urban versus 49.6% (95% CI 41.8, 57.4) rural residents reported need for any type of dental care. Binary and ordinal multiple logistic regression analyses revealed that adults who reported bad oral health and broken teeth were more likely to perceive need for dental care across the three outcome measures than their counterparts. Socio-demographic factors and clinically defined problems had less impact. Based on a normative and an integrated socio-dental approach respectively 39.5% and 4.7% were in need for partial dentures. Conclusion About half of the participants confirmed need for problem oriented care, dental check-ups and any type of dental care. Need perceptions were influenced by perceived oral health, clinically assessed oral problems and socio-demographic characteristics. Need estimates for partial denture was higher when based on clinical examination alone compared to an integrative socio-dental approach.

Abstract Background Focusing 50 year olds and above, this study assessed the frequency, extent and correlates of tooth loss due to various reasons. Frequency and correlates of posterior occluding support was also investigated. Method A cross-sectional household survey was conducted in Pwani region and in Dar es Salaam in 2004/2005. One thousand and thirty-one subjects, mean age 62.9 years participated in a clinical examination and completed interviews. Results The prevalence of tooth loss due to any reason was 83.5 %, due to caries 63.4% and due to other reasons than caries, 32.5%. A total of 74.9% had reduced number of posterior occluding units. Compared to subjects having less than 5 teeth lost due to caries, those with 5 or more lost teeth were more likely to be females, having decayed teeth, confirming dental attendance and to be among the least poor residents. Compared to subjects who had lost less than 5 teeth due to reasons other than caries, those who had lost 5 or more teeth were more likely to be of higher age, having mobile teeth, being males, being very poor and to disconfirm dental attendance when having problems. Predictors of prevalence of tooth loss (1 or more lost tooth) due to various reasons and reduced number of occluding units followed similar patterns of relationships. Conclusion The results are consistent with prevalence and extent of tooth loss due to caries and due to reasons other than caries being differently related to disease- and socio- behavioral risk indicators. Caries was the principle cause of tooth loss and molar teeth were the teeth most commonly lost.

The COVID-19 pandemic challenged health systems globally. Reverse transcription polymerase chain reaction (RT-PCR) is the gold standard for detecting the presence of SARS-CoV-2 in clinical samples. Rapid diagnostic test (RDT) kits for COVID-19 have been widely used in Nigeria. This has greatly improved test turnover rates and significantly decreased the high technical demands of RT-PCR. However, there is currently no nationally representative evaluation of the performance characteristics and reliability of these kits. This study assessed the sensitivity, specificity, and predictive values of ten RDT kits used for COVID-19 testing in Nigeria. This large multi-centred cross-sectional study was conducted across the 6 geo-political zones of Nigeria over four months. Ten antigen (Ag) and antibody (Ab) RDT kits were evaluated, and the results were compared with RT-PCR. One thousand, three hundred and ten (1,310) consenting adults comprising 767 (58.5%) males and 543 (41.5%) females participated in the study. The highest proportion, 757 (57.7%), were in the 20-39 years' age group. In terms of diagnostic performance, Lumira Dx (61.4, 95% CI: 52.4-69.9) had the highest sensitivity while MP SARS and Panbio (98.5, 95% CI: 96.6-99.5) had the highest specificity. For predictive values, Panbio (90.7, 95% CI: 79.7-96.9) and Lumira Dx (81.2, 95% CI: 75.9-85.7) recorded the highest PPV and NPV respectively. Ag-RDTs had better performance characteristics compared with Ab-RDTs; however, the sensitivities of all RDTs in this study were generally low. The relatively high specificity of Ag-RDTs makes them useful for the diagnosis of infection in COVID-19 suspected cases where positive RDT may not require confirmation by molecular testing. There is therefore the need to develop RDTs in-country that will take into consideration the unique environmental factors, interactions with other infectious agents, and strains of the virus circulating locally. This may enhance the precision of rapid and accurate diagnosis of COVID-19 in Nigeria., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Omonkhua et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Echinococcus multilocularis is a cestode that causes human alveolar echinococcosis, a lethal zoonotic disease distributed in the northern hemisphere. The life cycle of this parasite is maintained in nature by voles as intermediate hosts and foxes as definitive hosts in Hokkaido, Japan. Although dogs are also susceptible to the parasite, the infection has been considered typically asymptomatic. We report the detection of E. multilocularis eggs in the diarrheal feces of a dog with chronic gastrointestinal signs, which disappeared after anthelmintic treatment. The mitochondrial genome sequence constructed by sequencing of the overlapping PCRs using DNA from the eggs was identical to the most predominant haplotype previously reported in red foxes in Hokkaido. This case highlights that Echinococcus infection should be considered as a differential diagnosis for diarrheal dogs in the disease endemic areas. Further efforts are needed to accumulate parasite genotypes in domestic dogs as well as humans to assess the risk of human infection from dogs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kida, Hayashi, Yokoyama, Nagata, Sasaoka, Sasaki, Morishita, Nakamura, Kouguchi, Yagi, Nakao, Takiguchi and Nonaka.)

Background: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet., Methods: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters., Findings: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2., Interpretation: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues., Funding: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato)., Competing Interests: Declaration of interests Yuki Yamamoto and Tetsuharu Nagamoto are founders and shareholders of HiLung, Inc. Yuki Yamamoto is a co-inventor of patents (PCT/JP2016/057254; "Method for inducing differentiation of alveolar epithelial cells", PCT/JP2016/059786, "Method of producing airway epithelial cells"). Jumpei Ito has consulting fees and honoraria for lectures from Takeda Pharmaceutical Co. Ltd. Kei Sato has consulting fees from Moderna Japan Co., Ltd. and Takeda Pharmaceutical Co. Ltd. and honoraria for lectures from Gilead Sciences, Inc., Moderna Japan Co., Ltd., and Shionogi & Co., Ltd. The other authors declare that no competing interests exist., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Olfactory perception depends not only on olfactory inputs but also on semantic context. Although multi-voxel activity patterns of the piriform cortex, a part of the primary olfactory cortex, have been shown to represent odor perception, it remains unclear whether semantic contexts modulate odor representation in this region. Here, we investigated whether multi-voxel activity patterns in the piriform cortex change when semantic context modulates odor perception and, if so, whether the modulated areas communicate with brain regions involved in semantic and memory processing beyond the piriform cortex. We also explored regional differences within the piriform cortex, which are influenced by olfactory input and semantic context. We used 2 × 2 combinations of word labels and odorants that were perceived as congruent and measured piriform activity with a 1-mm isotropic resolution using 7T MRI. We found that identical odorants labeled with different words were perceived differently. This labeling effect was observed in multi-voxel activity patterns in the piriform cortex, as the searchlight decoding analysis distinguished identical odors with different labels for half of the examined stimulus pairs. Significant functional connectivity was observed between parts of the piriform cortex that were modulated by labels and regions associated with semantic and memory processing. While the piriform multi-voxel patterns evoked by different olfactory inputs were also distinguishable, the decoding accuracy was significant for only one stimulus pair, preventing definitive conclusions regarding the locational differences between areas influenced by word labels and olfactory inputs. These results suggest that multi-voxel patterns of piriform activity can be modulated by semantic context, possibly due to communication between the piriform cortex and the semantic and memory regions., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has led to concerns that ancestral SARS-CoV-2-based vaccines may not be effective against newly emerging Omicron subvariants. The concept of "imprinted immunity" suggests that individuals vaccinated with ancestral virus-based vaccines may not develop effective immunity against newly emerging Omicron subvariants, such as BQ.1.1 and XBB.1. In this study, we investigated this possibility using hamsters. Although natural infection induced effective antiviral immunity, breakthrough infections in hamsters with BQ.1.1 and XBB.1 Omicron subvariants after receiving the 3-dose mRNA-lipid nanoparticle vaccine resulted in only faintly induced humoral immunity, supporting the possibility of imprinted immunity., Competing Interests: Potential conflicts of interest. SF has an honorarium for a lecture from ROYAL CANIN JAPON, Inc. NN has consulting fees from Fasmac Co., Ltd. HS has royalties from Shionogi & Co., Ltd., honoraria for lectures from Tenshi College, and is a coinventor of a patent (JP 7236065 B1, “Pharmaceutical composition containing triazine derivative”). JI has consulting fees and honoraria for lectures from Takeda Pharmaceutical Co. Ltd. KS has consulting fees from Moderna Japan Co., Ltd. and Takeda Pharmaceutical Co. Ltd. and honoraria for lectures from Gilead Sciences, Inc., Moderna Japan Co., Ltd., and Shionogi & Co., Ltd. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Diffusion-weighted magnetic resonance imaging (dMRI) is the only available method to measure the tissue properties of white matter tracts in living human brains and has opened avenues for neuroscientific and clinical studies on human white matter. However, dMRI using conventional simultaneous multi-slice (SMS) single-shot echo planar imaging (ssEPI) still presents challenges in the analyses of some specific white matter tracts, such as the optic nerve, which are heavily affected by susceptibility-induced artifacts. In this study, we evaluated dMRI data acquired by using SMS readout-segmented EPI (rsEPI), which aims to reduce susceptibility-induced artifacts by dividing the acquisition space into multiple segments along the readout direction to reduce echo spacing. To this end, we acquired dMRI data from 11 healthy volunteers by using SMS ssEPI and SMS rsEPI, and then compared the dMRI data of the human optic nerve between the SMS ssEPI and SMS rsEPI datasets by visual inspection of the datasets and statistical comparisons of fractional anisotropy (FA) values. In comparison with the SMS ssEPI data, the SMS rsEPI data showed smaller susceptibility-induced distortion and exhibited a significantly higher FA along the optic nerve. In summary, this study demonstrates that despite its prolonged acquisition time, SMS rsEPI is a promising approach for measuring the tissue properties of the optic nerve in living humans and will be useful for future neuroscientific and clinical investigations of this pathway., Competing Interests: Declaration of Competing Interest WL and HK are employed by Siemens Healthcare. Siemens Healthcare did not have any additional role in the study design, data collection and analysis. Other three authors have declared that no competing interests exist., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions., (© 2023. The Author(s).)

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022., (© 2023. The Author(s).)

The initial decrease in the blood oxygenation level-dependent (BOLD) signal reflects primary neuronal activity more than the later hemodynamic positive peak responses. Moreover, ultra-high field BOLD has high sensitivity for the initial de-oxygenation signal. However, it is not fully understood how much information about task events and cognitive processes the initial decrease in the BOLD signal contains. Multivoxel pattern analysis (MVPA) of the BOLD signal has enabled the quantification of information contained in the activity patterns, but it has mainly relied on the positive peak responses. Here, we applied a signal-based functional inter-individual alignment algorithm (i.e., hyper-alignment) to a 7T-BOLD timeseries scanned while participants conducted a facial expression discrimination task. We found that the MVPA decoding accuracy in the bilateral amygdala 2 s after the face onset was significantly beyond chance. Furthermore, we confirmed that the voxels contributing to the decoding accuracy at 2 s displayed a decreasing hemodynamics response. These results demonstrated that the initial decrease in 7T-BOLD signals contains finer information about task events and cognitive processes than thought previously., Competing Interests: Declaration of Competing Interest The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Cryopyrin-associated periodic syndrome (CAPS) is a rare inherited autoinflammatory disease caused by gain-of-function mutations in the NLRP3 gene, with a genotype-phenotype correlation. The clinical presentation of each mutation has been previously studied. However, very few studies have reported on the clinical characteristics and treatment effectiveness across different generations within a family with the same mutation. A detailed investigation of family members of patients with CAPS may help in the appropriate diagnosis and treatment of undiagnosed CAPS. Herein, we report a 2-year-old boy (proband), his father, and his grandmother who presented with several symptoms of CAPS, such as persistently positive inflammatory reactions and hearing impairment. All three patients had the same pathogenic mutation in the NLRP3 gene (c.1049C > T (p.Thr350Met) heterozygous mutation) and were diagnosed with CAPS. With canakinumab treatment, the laboratory data of all three patients improved, the proband and father's skin rash disappeared, and his grandmother's arthropathy improved. The proband's hearing also showed slight improvement but not in his father or grandmother. Among the various non-specific symptoms associated with CAPS, chronic ocular hyperaemia is a finding that can be easily identified by non-ophthalmologists. Diagnosis of CAPS should be considered when eye symptoms are present in a combination of hyperinflammatory response, arthropathy, or skin symptoms. Thorough family history records, physical examinations, and close collaboration between paediatricians and adult rheumatologists are important for prompt diagnosis and appropriate treatment of inherited autoinflammatory diseases., (© Japan College of Rheumatology 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hydroxyurea (HU) alone has the potential to prevent one out of every three deaths due to sickle cell disease (SCD) and almost all forms of disabilities caused by SCD. However, in Tanzania, only one out of every six registered SCD patients in the SPARCO-Tanzania Sickle Cell Cohort use HU. We conducted studies to understand factors influencing utilization of HU in Tanzania and discovered that among the reason for low utilization of HU include HU is classified as anticancer medication, only hematologists are supposed to prescribe HU, limited HU prescription to only National and Specialized hospitals, a special permit is required to access HU using National Health Insurance Fund (NHIF) scheme and limited importation and absence of local manufacturing of HU limit availability of this important drug in Tanzania. Therefore, with this brief, the government should allow prescription of HU to the district hospitals level, should allow all clinicians with a minimum of a Bachelor of Medicine to prescribe HU, and accessibility of HU through NHIF should be friendly., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Kilonzi M et al.)

Canines serve as the definitive host of Echinococcus multilocularis. This study evaluated the sensitivity of the Mini-FLOTAC technique (MF) for the detection of E. multilocularis eggs in definitive hosts. First, we investigated the effects of heat inactivation and preservative conditions on the detection rate of eggs obtained from experimentally infected dogs. The sensitivity of MF was compared with that of eight other techniques: the centrifugal flotation with sucrose or zinc sulfate, MGL, AMS III, and a combination of MF and flotation/sedimentation techniques. Finally, we compared the sensitivity of MF and the centrifugal flotation with sucrose for the feces of E. multilocularis-infected foxes. The detection rate reached a plateau level with a specific gravity (s.g.) 1.22 for fresh eggs, but the highest rates were obtained with s.g. greater than 1.32 for heat-inactivated eggs. There was no significant difference in the detection rate among the preservative conditions. MF showed significantly higher EPG than the other techniques. Moreover, it showed higher diagnostic sensitivity for the fox feces than the centrifugal flotation technique. These results suggest that heat inactivation may alter s.g. of E. multilocularis eggs and that MF with zinc sulfate (s.g. = 1.32) would be effective for detecting heat-inactivated E. multilocularis eggs., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Olfaction could prove to be an early marker of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. To use olfaction for disease diagnosis, elucidating the standard olfactory functions in healthy humans is necessary. However, the olfactory function in the human brain is less frequently assessed because of methodological difficulties associated with olfactory-related cerebral areas. Using ultra-high fields (UHF), functional magnetic resonance imaging (fMRI) with high spatial resolution and sensitivity may allow for the measurement of activation in the cerebral areas. This study aimed to apply 7-Tesla fMRI to assess olfactory function in the human brain by exposing individuals to four different odorants for 8 s. We found that olfactory stimulation mainly activated the piriform and orbitofrontal cortex in addition to the amygdala. Among these regions, univariate fMRI analysis indicated that subjective odor intensity significantly correlated with the averaged fMRI signals in the piriform cortex but not with subjective hedonic tone in any region. In contrast, multivariate fMRI analysis showed that subjective hedonic tone could be discriminated from the fMRI response patterns in the posterior orbitofrontal cortex. Thus, the piriform cortex is mainly associated with subjective odor intensity, whereas the posterior orbitofrontal cortex are involved in the discrimination of the subjective hedonic tone of the odorant. UHF-fMRI may be useful for assessing olfactory function in the human brain., Competing Interests: Declaration of Competing Interest YD is employed by Daikin Industries, Ltd. UC, HB, and IK have no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Central poststroke pain (CPSP) develops after a stroke around the somatosensory pathway. CPSP is hypothesized to be caused by maladaptive reorganization between various brain regions. The treatment for CPSP has not been established; however, repetitive transcranial magnetic stimulation (rTMS) to the primary motor cortex has a clinical effect. To verify the functional reorganization hypothesis for CPSP development and rTMS therapeutic mechanism, we longitudinally pursued the structural and functional changes of the brain by using two male CPSP model monkeys (Macaca fuscata) developed by unilateral hemorrhage in the ventral posterolateral nucleus of the thalamus. Application of rTMS to the ipsilesional primary motor cortex relieved the induced pain of the model monkeys. A tractography analysis revealed a decrease in the structural connectivity in the ipsilesional thalamocortical tract, and rTMS had no effect on the structural connectivity. A region of interest analysis using resting-state functional magnetic resonance imaging revealed inappropriately strengthened functional connectivity between the ipsilesional mediodorsal nucleus of the thalamus and the amygdala, which are regions associated with emotion and memory, suggesting that this may be the cause of CPSP development. Moreover, rTMS normalizes this strengthened connectivity, which may be a possible therapeutic mechanism of rTMS for CPSP.

Cerebral artery segmentation plays an important role in the direct visualization of the human brain to obtain vascular system information. On ultra-high field magnetic resonance imaging, cerebral arteries appearing hyperintense on T1 weighted (T1w) images could be segmented from brain tissues such as gray and white matter. In this study, we propose an automated method to segment the cerebral arteries using multi-contrast images including T1w images of a magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence at 7 T. The proposed method, termed MP2rase-CA (MP2rage based RApid SEgmentation Cerebral Artery), employed a seed-based region-growing strategy and Frangi filtering as well as our brain tissue segmentation (MP2rase Brain Tissue). Time-of-flight (TOF) magnetic resonance angiography (MRA) images were obtained as a reference to evaluate the MP2rase-CA. We successfully performed vessel segmentations, from T1w MP2RAGE images, which mostly overlapped with the segmentations of large cerebral arteries from the TOF-MRA. We also investigated the effect of the large cerebral arteries on spatial transformation of anatomical images to standard coordinate space using vessel segmentation by MP2rase-CA. As a result, the T1w image without the cerebral arteries by MP2rase-CA showed better agreement with the standard atlas compared with the T1w image containing the arteries. In addition, voxel-based morphology showed significant differences between T1w images with and without cerebral arteries in brain areas nearby large arteries. Thus, because MP2rase-CA using MP2RAGE images can obtain brain tissue anatomical information as well as relatively large cerebral artery information without need for additional structure acquisition, it is useful and time saving for functional and structural studies., Competing Interests: Declaration of Competing Interest HK was employed by Siemens Healthcare K.K. Siemens Healthcare K.K. did not have any additional role in the study design, data collection and analysis. UC and IK have no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The perceptual system gives priority to threat-relevant signals with survival value. In addition to the processing initiated by sensory inputs of threat signals, prioritization of threat signals may also include processes related to threat anticipation. These neural mechanisms remain largely unknown. Using ultra-high-field 7 tesla (7T) fMRI, we show that anticipatory processing takes place in the early stages of visual processing, specifically in the pulvinar and V1. When anticipation of a threat-relevant fearful face target triggered false perception of not-presented target, there was enhanced activity in the pulvinar as well as in the V1 superficial-cortical-depth (layers 1-3). The anticipatory activity was absent in the LGN or higher visual cortical areas (V2-V4). The effect in V1 was specific to the perception of fearful face targets and did not generalize to happy face targets. A preliminary analysis showed that the connectivity between the pulvinar and V1 superficial-cortical-depth was enhanced during false perception of threat, indicating that the pulvinar and V1 may interact in preparation of anticipated threat. The anticipatory processing supported by the pulvinar and V1 may play an important role in non-sensory-input-driven anxiety states., (Copyright © 2019 Koizumi et al.)