Relationship between out-of-facility deliveries and distance and travel time to delivery facilities in Hokkaido, Japan: An ecological study.

AIM: This study aimed to investigate the relationship between the distance and travel time from each municipality to the nearest delivery facilities in the other municipalities and the frequency of out-of-facility deliveries in Hokkaido. METHODS: Vital statistics from 2016 to 2020 were used. For municipalities without delivery facilities, the distance and travel time from the town office of each municipality to the nearest delivery facility was measured using Google maps. Negative binomial regression with an offset term was used to calculate the relative risks (RRs) and 95% confidence intervals (CIs) of out-of-facility delivery for distance (<30, 30-59, ≥60 km), and travel time by car (<30, 30-59, and ≥60 min) from the town office to the nearest delivery facility compared with the presence of delivery facilities. RESULTS: The overall rate of out-of-facility deliveries in Hokkaido was 2.1‰; in municipalities with delivery facilities, 1.8‰, and in municipalities without delivery facilities, 3.1‰. The adjusted RRs (95% CIs) for out-of-facility deliveries were significantly higher in municipalities with less than 30 km and travel time of less than 30 min to delivery facilities, 2.63 (1.34-5.17) and 2.76 (1.36-5.58), respectively, compared to municipalities with delivery facilities. However, the adjusted RR of out-of-facility delivery for municipalities ≥30 km was higher, although the difference was not significant. CONCLUSIONS: Even in municipalities with a distance to delivery facilities of less than 30 km or travel time of less than 30 min, we should keep in mind the occurrence of out-of-facility deliveries.

Paternal occupational exposures and infant congenital heart defects in the Japan Environment and Children's Study

BACKGROUND@#Few prospective studies have investigated the association between paternal occupational exposures and risk of infant congenital heart defects (CHDs). We investigated the associations between paternal occupational exposures, frequency of use, and concurrent or sequential exposure to a mixture of compounds and the risk of infant CHDs.@*METHODS@#Our study examined 28,866 participants in the Japan Environment and Children's Study. Logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) associated with paternal occupational exposures during the 3 months until pregnancy was noticed after adjustment for potential confounding factors of the infant CHDs. CHD diagnosis was ascertained from medical record.@*RESULTS@#In total, 175 were diagnosed with infant CHDs. The number of fathers who were exposed to the following substances at least once a month were: 11,533 for photo copying machine/laser printer, 10,326 for permanent marker, 8,226 for soluble paint/inkjet printer, 6,188 for kerosene/petroleum/benzene/gasoline, 4,173 for organic solvents, 3,433 for chlorine bleach/germicide, 2,962 for engine oil, 2,931 for insecticide, 2,460 for medical sterilizing disinfectant, 1,786 for welding fumes, 1,614 for dyestuffs, 1,247 for any products containing lead-like solder, 986 for herbicide, 919 for radiation/radioactive substances/isotopes, 837 for lead-free solder, 341 for microbes, 319 for formalin/formaldehyde, 301 for agricultural chemical not listed above or unidentified, 196 for general anesthetic for surgery at hospital, 171 for anti-cancer drug, 147 for chromium/arsenic/cadmium, 88 for mercury and 833 for other chemical substances. Paternal occupational exposure regularly to photo copying machine or laser printer and soluble paint/inkjet printer were associated with higher risks of infant CHDs: the adjusted ORs (95%CIs) were 1.38 (1.00-1.91) and 1.60 (1.08-2.37), respectively. The higher risks were also observed for occasional exposure to engine oil, any products containing lead-like solder lead-free solder, and microbes; the adjusted ORs (95%CIs) were 1.68 (1.02-2.77), 2.03 (1.06-3.88), 3.45 (1.85-6.43), and 4.51, (1.63-12.49), respectively.@*CONCLUSIONS@#Periconceptional paternal occupational exposure was associated with a higher risk of infant CHDs. Further studies using biomarkers of the association between paternal occupational exposure and infant CHDs are warranted.

Prolyl Isomerase Pin1 Expression in the Spinal Motor Neurons of Patients With Sporadic Amyotrophic Lateral Sclerosis

Background@#and Purpose Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease. Selective deficiency of edited adenosine deaminase acting on RNA 2 (ADAR2), a key molecule in the acquisition of Ca 2+ resistance in motor neurons, has been reported in sporadic ALS (sALS) spinal motor neurons. Since ADAR2 activity is positively regulated by prolyl isomerase Protein never in mitosis gene A interacting-1 (Pin1), a known phosphorylation-dependent peptidyl-prolyl cis/trans isomerase, we investigated Pin1 expression in spinal motor neurons in sALS. @*Methods@#Specimens of the spinal cord were obtained from the lumbar region in eight sALS patients and age-matched five controls after postmortem examinations. The specimens were double stained with anti-Pin1 and anti-TAR DNA-binding protein of 43 kDa (TDP-43) antibodies, and examined under a fluorescence microscope. @*Results@#This study analyzed 254 and 422 spinal motor neurons from 8 sALS patients and 5 control subjects, respectively. The frequency of motor neurons with high cytoplasmic Pin1 expression from the spinal cord did not differ significantly between sALS specimens without cytoplasmic TDP-43 inclusions and control specimens. However, in sALS specimens, neurons for which the Pin1 immunoluminescence intensity in the cytoplasm was at least twice that in the background were more common in specimens with cytoplasmic TDP-43 inclusions (p<0.05 in χ 2 test). @*Conclusions@#In sALS, neurons with higher expression levels of Pin1 levels had more TDP-43 inclusions. Despite the feedback mechanism between Pin1 and ADAR2 being unclear, since Pin1 positively regulates ADAR2, our results suggest that higher Pin1 expression levels in motor neurons with TDP-43 pathology from sALS patients represent a compensatory mechanism.

Effective vaccine allocation strategies, balancing economy with infection control against COVID-19 in Japan

Due to COVID-19, many countries including Japan have implemented a suspension of economic activities for infection control. It has contributed to reduce the transmission of COVID-19 but caused severe economic losses. Today, several promising vaccines have been developed and are already being distributed in some countries. Therefore, we evaluated various vaccine and intensive countermeasure strategies with constraint of economic loss using SEIR model to obtain knowledge of how to balance economy with infection control in Japan. Our main result is that the vaccination strategy that prioritizes younger generation outperformed the other strategies in terms of deaths. On the other hand, when we focused on strategies that prioritize older generation, as Japan has decided to do, the optimal vaccination strategy was determined by the basic reproduction number and acceptable economic loss. The strategy vaccinating the young next to the old age group was the best when acceptable economic loss was high, or the basic reproduction number was low. Alternatively, the strategy vaccinating the middle next to the old age group was superior to the others with a moderate acceptable economic loss and the high basic reproduction number setting.

Impaired Nucleoporins Are Present in Sporadic Amyotrophic Lateral Sclerosis Motor Neurons that Exhibit Mislocalization of the 43-kDa TAR DNA-Binding Protein

BACKGROUND AND PURPOSE: Disruption of nucleoporins has been reported in the motor neurons of patients with sporadic amyotrophic lateral sclerosis (sALS). However, the precise changes in the morphology of nucleoporins associated with the pathology of the 43-kDa TAR DNA-binding protein (TDP-43) in the disease process remain unknown. We investigated the expression of nucleoporins that constitute the nuclear pore complex (NPC) in spinal motor neurons that exhibit sALS in relation to TDP-43 pathology, which is a reliable neuropathological hallmark of sALS. METHODS: Paraffin-embedded sections of the lumbar spinal cord were obtained for immunofluorescence analysis from seven control subjects and six sALS patients. Anti-TDP-43 antibody, anti-nucleoporin p62 (NUP62) antibody, and anti-karyopherin beta 1 (KPNB1) antibody were applied as primary antibodies, and then visualized using appropriate secondary antibodies. The sections were then examined under a fluorescence microscope. RESULTS: NUP62 and KPNB1 immunoreactivity appeared as a smooth round rim bordering the nuclear margin in normal spinal motor neurons that exhibited nuclear TDP-43 immunoreactivity. sALS spinal motor neurons with apparent TDP-43 mislocalization demonstrated irregular, disrupted nuclear staining for NUP62 or KPNB1. Some atrophic sALS spinal motor neurons with TDP-43 mislocalization presented no NUP62 immunoreactivity. CONCLUSIONS: Our findings suggest a close relationship between NPC alterations and TDP-43 pathology in the degenerative process of the motor neurons of sALS patients.

Dembo polymerase chain reaction technique for detection of bovine abortion, diarrhea, and respiratory disease complex infectious agents in potential vectors and reservoirs

Bovine abortion, diarrhea, and respiratory disease complexes, caused by infectious agents, result in high and significant economic losses for the cattle industry. These pathogens are likely transmitted by various vectors and reservoirs including insects, birds, and rodents. However, experimental data supporting this possibility are scarce. We collected 117 samples and screened them for 44 bovine abortive, diarrheal, and respiratory disease complex pathogens by using Dembo polymerase chain reaction (PCR), which is based on TaqMan real-time PCR. Fifty-seven samples were positive for at least one pathogen, including bovine viral diarrhea virus, bovine enterovirus, Salmonella enterica ser. Dublin, Salmonella enterica ser. Typhimurium, and Neospora caninum; some samples were positive for multiple pathogens. Bovine viral diarrhea virus and bovine enterovirus were the most frequently detected pathogens, especially in flies, suggesting an important role of flies in the transmission of these viruses. Additionally, we detected the N. caninum genome from a cockroach sample for the first time. Our data suggest that insects (particularly flies), birds, and rodents are potential vectors and reservoirs of abortion, diarrhea, and respiratory infectious agents, and that they may transmit more than one pathogen at the same time.

Discrimination of hie and hiesho using toe blood pressure in young women / 中西医结合学报

<p><b>OBJECTIVE</b>In Western medicine, hie (cold sensation) is thought as a subjective complaint. Consequently, despite women's complaints of health problems due to hie, such as distress and decreased quality of life, it is not diagnosed as a disease or given active treatment. However, hie sometimes requires emergency treatment or is a symptom of other disorders. Thus, diagnosing hie and eliminating distress due to hie are clinically significant. This research aimed to discriminate between hie and hiesho (cold disorder) and quantify hie by using objective assessments in addition to subjective assessments.</p><p><b>METHODS</b>A questionnaire was administered to 159 healthy young women without any underlying disease that could cause hie, followed by assessment of vascular function. These data were examined through exploratory factor analysis, exploratory cluster analysis, and multivariate logistic analysis. Two- and three-group comparisons were made using the Mann-Whitney test and Kruskal-Wallis test, respectively, followed by multiple comparisons using Scheffé's method.</p><p><b>RESULTS</b>The hie (including hiesho) and normal groups comprised 81 (51%) and 78 (49%) subjects, respectively. The questionnaire was a low reliability screening method for determining the severity of hie symptoms. As an index of discrimination of hie and hiesho, we determined the toe-brachial index (TBI) to be 0.81 and toe systolic blood pressure (SBP) to be 87.73 mmHg with a linear function (TBI=0.007 5× toe SBP+0.152, adjusted R=0.829, F=388.79, P<0.001).</p><p><b>CONCLUSION</b>Toe SBP and TBI were suggested to be capable of discriminating and quantifying symptoms when used in combination with a questionnaire.</p>

Evaluation of Preparation Quality for Allopurinol Ointment and Liquid / 医薬品情報学

<b>Objective: </b>It is important to ensure the quality of preparation in hospital pharmacies.  Therefore, we evaluated the quantitative method of preparation and the stability of allopurinol for external use in a new dosage form.<br><b>Methods: </b>The new dosage form utilized two kinds of ointment, white petrolatum and hirudoid soft ointment, and liquid.  Allopurinol was extracted from these preparations by the liquid-liquid partition method, and assayed by high performance liquid chromatography.  A stability test was conducted for six months in the case of the ointments and one month in the case of the liquid.<br><b>Results: </b>Good linearity was obtained, in the range of 30˜670 μg/mL (<i>r</i>²≥0.999).  The recovery of allopurinol added to the two kinds of ointment was 97.7-102.0%, and the relative standard deviation was less than 3.0%.  It was observed that the quantity remained relatively constant for one month, and increased after three months.<br><b>Conclusion: </b>A quantitative method for the preparation of allopurinol in ointment, using white petrolatum and hirudoid soft ointment, was evaluated.  The results confirmed that allopurinol was stable for one month in ointment and liquid.