Initial gastrointestinal endocrine cells (GIECs) likely appear at the proximal and distal sites of abdominal intestines and may take a close topographical relation with neural elements in the gut. We examined immunohistochemically-stained sections from 10 fetuses at approximately 8–18 weeks of gestational age (36–155 mm of crown-rump length). Irrespective of whether physiological herniation was present (early 5 specimens) or absent (the other 5), the duodenum and jejunum had well-developed mucosa with villi containing abundant flask-like chromogranin-positive cells. In the earlier 5 specimens, the rectum, standing up to a level of the umbilicus, had a lumen and villi with a few positive cells, but the colon carried neither the lumen or chromogranin-positive cells. The initial GIECs seemed to appear in the basal payer of the epithelium at the distal and proximal foci depending on double pathways of neural crest cell migration. Less number of the colic chromograninpositive cells, more than 5-times difference in density relative to small intestine, was seen in the larger 5 specimens. The appearance of GIECs was delayed at the anal transitional zone (a border area between the columnar and squamous epithelia).The reactivity of neuronal nitric oxide synthase was restricted in the myenteric plexus, whereas clusters of slender calretininpositive cells existed in the lamina propria or core of villi in the duodenum and colon. Relatively small, round or oval positive cells were also seen in the basal layer of the columnar epithelium. Therefore, calretinin-positive cells might exist closely to GIECs in the developing villi.

Neck epaxial muscles, which are differentiated for suspending the head, occupy a large space posterior to the cervical lordosis. Limited information exists regarding developmental process that determines the muscle fiber direction and bony attachment of neck epaxial muscles. We examined histological sections of 28 human fetuses aged approximately 7–18 weeks (crown-rump length, 20–150 mm). In place of the underdeveloped lordosis, the transverse process of cervical vertebrae was shifted anteriorly at the cervicothoracic junction. The semispinalis and longissimus were distinguished by the direction of muscle fibers connecting between the surface aponeurosis and transverse process. The semispinalis capitis and splenius capitis had a bulky anterior margin without bony attachments. The obliquus capitis inferior continued to both the rectus capitis posterior major and the semispinalis cervicis, but the obliquus capitis superior was consistently independent. Muscle attachments to the scapula were quite different from the final morphology: 1) the levator and rhomboidei usually extended inferiorly along the developing scapula beyond the inferior angle and 2) the splenius capitis or semispinalis cervicis rarely issued an aberrant bundle attaching to the scapula. The scaleni, rhomboidei, levator scapulae, iliocostalis and longissimus were arranged in parallel from the anteromedial to the posterolateral planes and together formed a thick oblique muscle bundle originating from the cervical transverse process and running toward the upper thoracic vertebra and ribcage. The transient oblique muscle bundle seen in early fetuses seemed to provide the so-called intermediate axial muscle between the epaxial-hypaxial muscles: a concept postulated in recent molecular neurology and embryology.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

roblem: Once COVID-19 vaccines were rolled out, there was a need to monitor real-world vaccine effectiveness to accumulate evidence to inform policy and risk communication. This was especially true in Japan and the Philippines, given historical issues that affected vaccine confidence. Context: Neither country had public health surveillance that could be enhanced to evaluate vaccine effectiveness or readily available national vaccination databases. Action: Study groups were established in multiple health-care facilities in each country to assess vaccine effectiveness against both symptomatic infection and severe disease. Outcome: In Japan, multiple study reports were published in Japanese on the website of the National Institute of Infectious Diseases and presented at the national government’s advisory board. Nationwide media coverage facilitated transparency and increased the confidence of the government and the public in the vaccination programme. In the Philippines, the launch of the study was delayed so as to align the research plan with the interests of various stakeholders and to obtain institutional review board approval. Ultimately, the studies were successfully initiated and completed. Discussion: There were four main challenges in conducting our studies: finding health-care facilities for data collection; obtaining exposure (vaccination) data; identifying epidemiological biases and confounders; and informing policy and risk communication in a timely manner. Preparedness during inter-emergency/epidemic/pandemic periods to rapidly evaluate relevant interventions such as vaccination is critical and should include the following considerations: (1) the establishment and maintenance of prospective data collection platforms, ideally under public health surveillance (if not, clinical research networks or linked databases); (2) uniform and practical protocols considering biases and confounders; and (3) communication with stakeholders including institutional review boards.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

Objective: To clarify whether early mobilization is a predictive factor for ambulation recovery in elderly patients and/or patients with severe subarachnoid hemorrhage (SAH).Methods: This multicenter retrospective observational study included 471 patients with treated SAH (Group 1). We focused on SAH patients with a poor prognosis, including a subgroup of elderly SAH patients (age>65 years: n=203) (Group 2) and patients with severe SAH (World Federation of Neurological Societies [WFNS] grade IV or V: n=117) (Group 3). The chi-square test and Mann-Whitney U test were used to compare the differences between the ambulation recovery group and the non-recovery group. Multivariable logistic regression analysis modeling was used to estimate odds ratios and 95% confidence intervals of early mobilization for the ambulation-recovered group within 30 days of onset compared with the unrecovered group. Other covariates examined as possible confounders of the outcome were age, sex, location of the ruptured aneurysm, modified Fisher scale score, WFNS grade, mode of treatment (surgical vs. endovascular), duration of cerebrospinal fluid drainage, days on mechanical ventilation, intracerebral hemorrhage, symptomatic cerebral vasospasm, complications, shunt placement for hydrocephalus, and time to start mobilization.Results: Early mobilization was an independent predictive factor for gait recovery in all groups. Furthermore, location of the ruptured aneurysm (anterior circulation), absence of complications, and absence of shunt placement were independent factors for ambulation recovery in all groups.Conclusion: Early mobilization in elder or/and sever patients with SAH may be a predictive factor for ambulation recovery within 30 days of onset.

Objective: We examined sociobehavioural factors associated with SARS-CoV-2 infection and estimated COVID-19 vaccine effectiveness against symptomatic SARS-CoV-2 infection in the Philippines. Such studies are limited in low- and middle-income countries, especially in Asia and the Pacific. Methods: A case-control study was conducted in two hospitals in Manila, Philippines, from March 2022 to June 2023. Sociobehavioural factors and vaccination history were collected. PCR-positive individuals were cases, while PCR-negative individuals were controls. Adjusted odds ratios (aORs) were calculated to examine associations between sociobehavioural factors/vaccination and medically attended SARS-CoV-2 infection. Results: The analysis included 2489 individuals (574 positive cases, 23.1%; 1915 controls, 76.9%; median age [interquartile range]: 35 [27–51] years). Although education and household income were not associated with infection, being a health-care worker was (aOR: 1.45; 95% confidence interval [CI]: 1.03–2.06). The odds of infection were higher among individuals who attended gatherings of five or more people compared to those who attended smaller gatherings (aOR: 2.58; 95% CI: 1.14–5.83). Absolute vaccine effectiveness for vaccination status was not estimated due to a high risk of bias, for example, unascertained prior infection. Moderate relative vaccine effectiveness for the first booster (32%; 95% CI: -120–79) and the second booster (48%; 95% CI: -23–78) were observed (both with wide CI), albeit with a waning trend after half a year. Discussion: The higher odds of infection among health-care workers emphasize the importance of infection prevention and control measures. Moderate relative vaccine effectiveness with a waning trend reiterates the need for more efficacious vaccines against symptomatic infection caused by circulating variants and with longer duration of protection.

Objective: To clarify whether early mobilization is a predictive factor for ambulation recovery in elderly patients and/or patients with severe subarachnoid hemorrhage (SAH).Methods: This multicenter retrospective observational study included 471 patients with treated SAH (Group 1). We focused on SAH patients with a poor prognosis, including a subgroup of elderly SAH patients (age>65 years:n=203) (Group 2) and patients with severe SAH (World Federation of Neurological Societies [WFNS] grade IV or V:n=117) (Group 3). The chi-square test and Mann-Whitney U test were used to compare the differences between the ambulation recovery group and the non-recovery group. Multivariable logistic regression analysis modeling was used to estimate odds ratios and 95% confidence intervals of early mobilization for the ambulation-recovered group within 30 days of onset compared with the unrecovered group. Other covariates examined as possible confounders of the outcome were age, sex, location of the ruptured aneurysm, modified Fisher scale score, WFNS grade, mode of treatment (surgical vs. endovascular), duration of cerebrospinal fluid drainage, days on mechanical ventilation, intracerebral hemorrhage, symptomatic cerebral vasospasm, complications, shunt placement for hydrocephalus, and time to start mobilization.Results: Early mobilization was an independent predictive factor for gait recovery in all groups. Furthermore, location of the ruptured aneurysm (anterior circulation), absence of complications, and absence of shunt placement were independent factors for ambulation recovery in all groups.Conclusion: Early mobilization in elder or/and sever patients with SAH may be a predictive factor for ambulation recovery within 30 days of onset.

Tohoku University Hospital served as the research office for two projects of Kampo medicine treatment: an observational study and a randomized controlled study on Coronavirus Disease 2019 led by the Japanese Society for Oriental Medicine. We review the practical operations together with the results of a questionnaire survey conducted after the completion of the studies, and discuss issues and areas for improvement in the management of the multicenter research office. Questionnaire 1 surveyed the participants’ impressions and opinions of the implementation system and responses at the research-sharing facilities, as well as future issues. Comments on observational studies were dichotomized into “no particular problems” and “difficulties.” In the randomized controlled trial, most respondents answered, “It was difficult to understand the administrative procedures for specific clinical research.” Questionnaire 2 surveyed the status of clinical research support staff, their impressions and opinions of being entrusted with the work, and future issues. We were able to collect opinions about impressions, issues, and areas for improvement from a variety of perspectives. Looking back at the summary of the questionnaire survey and the practical experience, smooth promotion of research is expected through appropriate research planning and system construction, as well as improvement of research support skills.