Changes in cerebrovascular disease-related deaths and their location during the COVID-19 pandemic in Japan.

OBJECTIVE: The COVID-19 pandemic placed an enormous strain on healthcare systems and raised concerns for delays in the management of patients with acute cerebrovascular events. In this study, we investigated cerebrovascular excess deaths in Japan. STUDY DESIGN: Vital mortality statistics from January 2012 to May 2022 were obtained from the Japanese Ministry of Health, Labour and Welfare. METHODS: Using quasi-Poisson regression models, we estimated the expected weekly number of cerebrovascular deaths in Japan from January 2020 through May 2022 by place of death. Estimates were calculated for deaths in all locations, as well as for deaths in hospitals, in geriatric health service facilities, and at home. The age subgroups of ≥75 and <75 years were also considered. Weeks with a statistically significant excess of cerebrovascular deaths were determined when the weekly number of observed deaths exceeded the upper bound of 97.5% prediction interval. RESULTS: Excess deaths were noted in June 2021 and became more pronounced from February 2022 onward. The trend was notable among those aged ≥75 years and for those who died in hospitals. With respect to the location of deaths, the excess was significant in geriatric health services facilities from April 2020 to June 2021, whereas no evidence of excess hospital deaths was observed during the same period. CONCLUSIONS: Beginning in the late 2021, excess cerebrovascular deaths coincided with the spread of the Omicron variant and may be associated with increased healthcare burden. In 2020, COVID-19 altered the geography of cerebrovascular deaths, with fewer people dying in hospitals and more dying in geriatric health service facilities and at home.

Excess deaths from COVID-19 in Japan and 47 prefectures from January through June 2021.

OBJECTIVES: In Japan, several studies have reported no excess all-cause deaths (the difference between the observed and expected number of deaths) during the coronavirus disease 2019 (COVID-19) pandemic in 2020. This study aimed to estimate the weekly excess deaths in Japan's 47 prefectures for 2021 until June 27. STUDY DESIGN: Vital statistical data on deaths were obtained from the Ministry of Health, Labour and Welfare of Japan. For this analysis, we used data from January 2012 to June 2021. METHODS: A quasi-Poisson regression was used to estimate the expected weekly number of deaths. Excess deaths were expressed as the range of differences between the observed and expected number of all-cause deaths and the 95% upper bound of the one-sided prediction interval. RESULTS: Since January 2021, excess deaths were observed for the first time in the week corresponding to April 12-18 and have continued through mid-June, with the highest excess percentage occurring in the week corresponding to May 31-June 6 (excess deaths: 1431-2587; excess percentage: 5.95-10.77%). Similarly, excess deaths were observed in consecutive weeks from April to June 2021 in 18 of 47 prefectures. CONCLUSIONS: For the first time since February 2020, when the first COVID-19 death was reported in Japan, excess deaths possibly related to COVID-19 were observed in April 2021 in Japan, during the fourth wave. This may reflect the deaths of non-infected people owing to the disruption that the pandemic has caused.

The burden of heat-related mortality attributable to recent human-induced climate change.

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

Human papillomavirus vaccine effectiveness within a cervical cancer screening programme: cohort study.

OBJECTIVE: To assess the effectiveness of an HPV vaccination programme in reducing the risk of cervical abnormalities identified at subsequent screening. DESIGN: Retrospective cohort study using administrative health data. SETTING: General population of Ferrara Province, Italy. POPULATION: Female residents born in 1986-1993 and participating in the organized cervical screening programme in 2011-2018, who were eligible for HPV vaccination in catch-up cohorts. METHODS: Logistic regression to evaluate the potential association between abnormal cervical cytology and one, two, three or at least one dose of HPV vaccine. MAIN OUTCOME MEASURES: Cervical abnormalities, as predicted by low-grade or high-grade cytology, by number of vaccine doses, stratified by age. RESULTS: The sample consisted of 7785 women (mean age 27.5 years, SD 2.3). Overall, 391 (5.0%) were vaccinated with ≥1 dose and 893 (11.5%) had abnormal cytology. Women receiving at least one vaccine dose were significantly less likely to have an abnormal cytology (adjusted odds ratio 0.52; 95% confidence interval 0.34-0.79). Similar results were observed for women receiving a single dose, for both bivalent and quadrivalent vaccines, and applying buffer periods (excluding cytological outcomes within 1 month, 6 months and 1 year of the first dose). CONCLUSIONS: In the context of an organised cervical screening programme in Italy, catch-up HPV vaccination almost halved the risk of cytological abnormalities. TWEETABLE ABSTRACT: Among Ferrara women, vaccination against human papillomavirus halved the risk of screening cervical abnormalities.

Seasonality of suicide: a multi-country multi-community observational study.

AIMS: We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations. METHODS: Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986-2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression. RESULTS: We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33-1.62) to 1.05 (95% CI: 1.01-1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05). CONCLUSIONS: Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.

Alteration in faecal bile acids, gut microbial composition and diversity after laparoscopic sleeve gastrectomy.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a well established treatment for severe obesity and type 2 diabetes. Although the gut microbiota is linked to the efficacy of LSG, the underlying mechanisms remain elusive. The effect of LSG for morbid obesity on the gut microbiota and bile acids was assessed here. METHODS: Severely obese subjects who were candidates for LSG were included and followed until 6 months after surgery. The composition and abundance of the microbiota and bile acids in faeces were assessed by 16S ribosomal RNA sequencing, quantitative PCR and liquid chromatography-mass spectrometry. RESULTS: In total, 28 patients with a mean(s.d.) BMI of 44·2(6·6) kg/m2 were enrolled. These patients had achieved excess weight loss of 53·2(19·0) per cent and showed improvement in metabolic diseases by 6 months after LSG, accompanied by an alteration in the faecal microbial community. The increase in α-diversity and abundance of specific taxa, such as Rikenellaceae and Christensenellaceae, was strongly associated with reduced faecal bile acid levels. These changes had a significant positive association with excess weight loss and metabolic alterations. However, the total number of faecal bacteria was lower in patients before (mean(s.d.) 10·26(0·36) log10 cells per g faeces) and after (10·39(0·29) log10 cells per g faeces) operation than in healthy subjects (10·83(0·27) log10 cells per g faeces). CONCLUSION: LSG is associated with a reduction in faecal bile acids and greater abundance of specific bacterial taxa and α-diversity that may contribute to the metabolic changes.

ANTECEDENTES: La gastrectomía vertical laparoscópica (laparoscopic sleeve gastrectomy, LSG) es un tratamiento bien establecido para la obesidad grave y la diabetes tipo 2. Aunque la microbiota intestinal se ha vinculado con la eficacia de LSG, los mecanismos subyacentes siguen siendo poco conocidos. En este estudio se evaluó el efecto de LSG en la obesidad mórbida sobre la microbiota del intestino y de los ácidos biliares (bile acids, BA). MÉTODOS: Tras la aprobación del Comité ético y la obtención del consentimiento informado, los sujetos con obesidad grave que eran candidatos para LSG fueron incluidos en el estudio y seguidos durante 6 meses después de la operación. Se evaluaron la composición y abundancia de la microbiota y BA en las heces mediante secuenciación del gen 16S rRNA, PCR cuantitativa y cromatografía líquida-espectrometría de masas. RESULTADOS: En total, 28 pacientes con una mediana (rango) del IMC de 43,9 kg/m2 (35,0-61,9) fueron reclutados y a los 6 meses tras una LSG, consiguieron una pérdida del exceso de peso de 47,3% (20,7-95,1) y mejoría de las enfermedades metabólicas acompañada de una alteración en la comunidad microbiana fecal. El aumento en la diversidad α y abundancia de especies taxonómicas específicas como Rikenellaceae y Christensenellaceae, se asociaba fuertemente con niveles fecales reducidos de BA. Estos cambios se asociaban de manera positiva y significativa con la pérdida del exceso de peso y las alteraciones metabólicas. Sin embargo, el número total de bacterias fecales en los pacientes fue inferior al de los sujetos sanos (10,84 log10 células/g heces (9,46-11,35)) antes de la operación (10,26 log10 células/g heces (9,44-10,91)) y después de la misma (10,42 log10 células/g heces (9,57-10,96)). CONCLUSIÓN: LSG se asoció con menos BA fecal y mayor abundancia de especies bacterianas específicas y diversidad α lo que puede contribuir a los cambios metabólicos.

Enhanced sealing strength of a hydrophobically-modified Alaska pollock gelatin-based sealant.

The aim of this study was the development of an innovative biocompatible sealant composed of Alaska pollock-derived gelatin partially modified with a dodecyl group (C12-ApGltn) and a poly(ethylene glycol)-based crosslinker, pentaerythritol poly(ethylene glycol) ether tetrasuccinimidyl glutarate. The burst strength of the developed sealants was measured using porcine aorta and rat lungs. The maximum burst strength of a C12-ApGltn-based sealant against the porcine aorta was 4-fold higher than that of an original ApGltn (Org-ApGltn)-based sealant. No significant increase in the burst strength was observed between C12-ApGltn-based sealants with 4.2 and 8.9 mol% modification ratios. From histological observation after burst strength measurement, tissue tearing was observed when a C12-ApGltn-based sealant was applied. In contrast, the Org-ApGltn-based sealant was peeled away from the aorta surface due to cohesion failure. Similar to the porcine aorta, the burst strength of C12-ApGltn-based sealants applied on a rat lung defect was 3-fold higher than that of an Org-ApGltn-based sealant. The curing time of the C12-ApGltn-based sealant measured by a simple mixing method was shorter (2.6 ± 0.1 s) than that of the Org-ApGltn-based sealant (4.1 ± 0.3 s). The swelling ratio of the C12-ApGltn-based sealant (23.7 ± 3.1) was significantly lower than that of the Org-ApGltn-based sealant (32.3 ± 1.1). The C12-ApGltn-based sealant was completely degraded within 28 days after implantation in the backs of rats without a severe inflammation reaction. However, the Org-ApGltn-based sealant disappeared within 14 days. These results indicated that hydrophobically-modified ApGltn has an effective sealing effect on moist tissues and biocompatibility in vivo.

Serum BDNF levels before and after the development of mood disorders: a case-control study in a population cohort.

Serum levels of brain-derived neurotrophic factor (BDNF) are low in major depressive disorder (MDD), and were recently shown to decrease in chronic depression, but whether this is a trait or state marker of MDD remains unclear. We investigated whether serum BDNF levels decrease before or after the developments of MDD and other mood disorders through a case-control study nested in a cohort of 1276 women aged 75-84 years in 2008. Psychiatrists using the Structured Clinical Interview for DSM-IV identified incident cases of mood disorders at follow-up surveys in 2010 and 2012: 28 of MDDs, 39 of minor depressive disorders (minDDs) and 8 of minor depressive episodes with a history of major depressive episodes (minDEs with MDE history). A total of 106 representative non-depressed controls were also identified in the 2012 follow-up. We assayed BDNF levels in preserved sera of cases and controls at baseline and at follow-up. Serum BDNF levels at baseline in cases of MDD, minDD or minDE with MDE history were no lower than those in controls. The decrease in the serum BDNF level from baseline to follow-up was greater in cases of MDD or minDE with MDE history than in controls or cases of minDD. These results show that serum BDNF levels are not a trait marker of MDD in old women but appeared to be a state marker. The different changes in BDNF levels among diagnostic groups suggest that MDD has a pathophysiologic relation to minDE with MDE history, rather than to minDD.

Kainate-induced network activity in the anterior cingulate cortex.

Anterior cingulate cortex (ACC) plays a pivotal role in higher order processing of cognition, attention and emotion. The network oscillation is considered an essential means for integration of these CNS functions. The oscillation power and coherence among related areas are often dis-regulated in several psychiatric and pathological conditions with a hemispheric asymmetric manner. Here we describe the network-based activity of field potentials recorded from the superficial layer of the mouse ACC in vitro using submerged type recordings. A short activation by kainic acid administration to the preparation induced populational activities ranging over several frequency bands including theta (3-8Hz), alpha (8-12Hz), beta (13-30Hz), low gamma (30-50Hz) and high gamma (50-80Hz). These responses were repeatable and totally abolished by tetrodotoxin, and greatly diminished by inhibitors of ionotropic and metabotropic glutamate receptors, GABAA receptor or gap-junctions. These observations suggest that the kainate-induced network activity can be a useful model of the network oscillation in the ACC circuit.

Blockade of interleukin-6 receptor enhances the anti-arthritic effect of glucocorticoids without decreasing bone mineral density in mice with collagen-induced arthritis.

In a mouse arthritis model, we investigated whether interleukin-6 receptor (IL-6R) blockade would enhance the anti-arthritic effect of glucocorticoids (GCs). DBA/1J mice were immunized with type II collagen (CII), and were treated with prednisolone (PSL) and/or anti-mouse IL-6R antibody (MR16-1). Also, the effects of IL-6 on gene expression and the nuclear translocation of glucocorticoid receptors (GRs) were examined in cultured cells treated with dexamethasone (DEX). PSL reduced the arthritis score dose-dependently in the collagen-induced arthritis (CIA) mouse model. The arthritis score in the PSL (3 mg/kg) + MR16-1 group was lower than in the PSL (3 mg/kg) group, and at the same level as in the PSL (6 mg/kg) group. Lumbar vertebra bone mineral density (BMD) was decreased significantly in CIA mice and was higher in the PSL (3 mg/kg) + MR16-1 group than in the PSL (6 mg/kg) group. In the in-vitro synovial cells, IL-6 pretreatment attenuated the inhibitory effect of DEX on cyclooxygenase (COX)-2 expression and inhibited the nuclear translocation of GR induced by DEX. In contrast, in MC3T3-E1 osteoblastic cells, IL-6 pretreatment exacerbated the decrease in expression of osteocalcin and the increase in expression of receptor activator of nuclear factor kappa-B ligand (RANKL) by DEX. We demonstrated that IL-6 signalling blockade by an anti-IL-6R antibody can augment the anti-arthritic effect of GCs and inhibit the bone loss they cause.

Comparison of recombinant human thrombomodulin and gabexate mesylate for treatment of disseminated intravascular coagulation (DIC) with sepsis following emergent gastrointestinal surgery: a retrospective study.

PURPOSE: Recombinant thrombomodulin (rTM) has been available in Japan since 2008, but there is concern about its association with postoperative hemorrhage. The efficacy and safety of rTM were examined in patients with disseminated intravascular coagulation (DIC) caused by a septic condition after gastrointestinal surgery. METHODS: Forty-two patients were emergently admitted to the intensive care unit after emergent gastrointestinal surgery in Kyushu University Hospital from May 2008 to April 2013. Of these patients, 22 had DIC (defined as an acute DIC score ≥ 4). All but three patients received treatment with gabexate mesylate (GM) (n = 9) or rTM (n = 10). The causes of sepsis were peritonitis with colorectal perforation, anastomotic leakage, and intestinal necrosis. Acute DIC score, sepsis-related organ failure assessment score, platelet count, and a variety of biochemical parameters were compared between rTM and GM recipients after treatment administration. RESULTS: There were no significant differences between the groups for any parameter except C-reactive protein levels. The CRP level tended to be lower in the rTM group than in the GM group. Acute DIC score in the rTM group resolved significantly earlier than that in the GM group. No patient stopped the administration of rTM because of postoperative bleeding. CONCLUSION: rTM may be an effective therapeutic drug for the treatment of septic patients with DIC following emergent gastrointestinal surgery.

Safe and rapid contouring of fibro-osseous lesions in the orbital area using navigation with minimally invasive cranial bone registration.

BACKGROUND: Bone contouring is currently the best treatment for fibro-osseous lesions after bone growth arrest. Navigation systems available for this surgery allow intra-operative visualisation with improved cosmetic outcomes. However, conventional navigation systems using superficial skin registration cannot prevent subtle discrepancies. METHOD: To address this problem, we used a non-invasive cranial bone registration that uses patient-specific dental templates to maintain exact registration. We created the preset goal using the mirror image of the unaffected side for unilateral lesions, and using images obtained before the onset of symptoms for bilateral lesions. This system achieved precise pre-operative simulation. A sound aid in the navigation system provided information regarding proximity to critical structures and to the preset goal. RESULTS: We used this system to contour fibro-osseous lesions in three patients. All patients achieved good facial contours and improvement in symptoms. CONCLUSIONS: This method offers a safe, rapid surgical aid in treating orbital fibro-osseous lesions.

Development and testing of an endoscopic pseudo-viewpoint alternating system.

PURPOSE: An endoscopic system is needed that presents informative images irrespective of the surgical situation and the number of degrees of freedom in endoscopic manipulation. This goal may be achieved with a virtual reality view for a region of interest from an arbitrary viewpoint. An endoscopic pseudo-viewpoint alternation system for this purpose was developed and tested. METHOD: Surgical experts and trainees from an endoscopic surgery training course at the minimally invasive surgery training center of Kyushu University were enrolled in a trial of a virtual reality system. The initial viewpoint was positioned to approximate the horizontal view often seen in laparoscopic surgery, with [Formula: see text] between the optical axis of the endoscope and the task surface. A right-to-left suturing task with right hand, based on a task from the endoscopic surgery training course, was selected for testing. We compared task outcomes with and without use of a new virtual reality-viewing system. RESULT: There was a 0.37 mm reduction in total error ([Formula: see text]) with use of the proposed system. Error reduction was composed of 0.1 mm reduction on the y-axis and 0.27 mm reduction on the x-axis. Experts benefited more than novices from use of the proposed system. Most subjects worked at a pseudo-viewpoint of around 34[Formula: see text]. DISCUSSION: Suturing performance improved with the new virtual reality endoscopic display system. Viewpoint alternation resulted in an overview that improved depth perception and allowed subjects to better aim the marker. This suggests the proposed method offers users better visualization and control in endoscopic surgery.

Preliminary study on the clinical application of augmented reality neuronavigation.

OBJECTIVE: To develop an augmented reality (AR) neuronavigation system with Web cameras and examine its clinical utility. METHODS: The utility of the system was evaluated in three patients with brain tumors. One patient had a glioblastoma and two patients had convexity meningiomas. Our navigation system comprised the open-source software 3D Slicer (Brigham and Women's Hospital, Boston, Massachusetts, USA), the infrared optical tracking sensor Polaris (Northern Digital Inc., Waterloo, Canada), and Web cameras. We prepared two different types of Web cameras: a handheld type and a headband type. Optical markers were attached to each Web camera. We used this system for skin incision planning before the operation, during craniotomy, and after dural incision. RESULTS: We were able to overlay these images in all cases. In Case 1, accuracy could not be evaluated because the tumor was not on the surface, though it was generally suitable for the outline of the external ear and the skin. In Cases 2 and 3, the augmented reality error was ∼2 to 3 mm. CONCLUSION: AR technology was examined with Web cameras in neurosurgical operations. Our results suggest that this technology is clinically useful in neurosurgical procedures, particularly for brain tumors close to the brain surface.

Effect of weather variability on the incidence of mumps in children: a time-series analysis.

The increasing international interest in the potential health effects of climate change has emphasized the importance of investigations into the relationship between weather variability and infectious diseases. However, few studies have examined the impact of weather variability on mumps in children, despite the fact that children are considered particularly vulnerable to climate change. We acquired data about cases of mumps in children aged <15 years and weather variability in Fukuoka, Japan from 2000 to 2008, and then used time-series analyses to assess how weather variability affected mumps cases, adjusting for seasonal variations, inter-annual variations, and temporal variations of two large epidemics in 2001 and 2004-2005. The weekly number of mumps cases increased by 7·5% (95% CI 4·0-11·1) for every 1°C increase in average temperature and by 1·4% (95% CI 0·5-2·4) for every 1% increase in relative humidity. The percentage increase was greatest in the 0-4 years age group and tended to decrease with increasing age. The number of mumps cases in children increased significantly with increased average temperature and relative humidity.

Intercellular adhesion molecule-1 on synovial cells attenuated interleukin-6-induced inhibition of osteoclastogenesis induced by receptor activator for nuclear factor κB ligand.

In a co-culture of osteoclast precursor cells and synovial cells, interleukin-6 (IL-6) induces osteoclast formation. In contrast, in a monoculture of osteoclast precursor cells, IL-6 directly suppresses receptor activator for nuclear factor κB ligand (RANKL)-induced differentiation of osteoclast precursor cells into osteoclasts. In the present study, we explored why the effect of IL-6 differed between the monoculture and the co-culture systems. In the monoculture, mouse osteoclast precursor cell line, RAW 264·7 (RAW) cells were cultured with soluble RANKL (sRANKL) for 24 h or 3 days. sRANKL increased both expression of osteoclastogenesis marker, tartrate-resistant acid phosphatase isoform 5b (TRAP5b) and nuclear factor of activated T cells cytoplasmic 1 (NFATc1), whereas the co-addition of IL-6 decreased them both in a dose-dependent manner. In the co-culture, RAW cells and human synovial cell line, SW982 cells were cultured with IL-6+soluble IL-6 receptor (sIL-6R) for 3 days. TRAP5b and NFATc1 expression reduced by IL-6 was increased by the addition of SW982 cells in a manner dependent upon the number of added cells. IL-6+sIL-6R treatment significantly induced RANKL production in SW982 cells, and anti-RANKL antibody inhibited IL-6+sIL-6R-induced osteoclastogenesis. SW982 cells expressed high levels of ICAM-1 originally, and ICAM-1 expression was increased significantly by IL-6+sIL-6R. Anti-ICAM-1 antibody suppressed IL-6-induced osteoclastogenesis. Finally, in the monoculture system, addition of sICAM-1 dose-dependently restored the expression of TRAP5b reduced by IL-6. Similar results were obtained when the formation of TRAP-positive multi-nuclear cells were examined using mouse bone marrow cells. In conclusion, IL-6 gave different results in the co-culture and monoculture systems because in the co-culture, ICAM-1 from the synovial cells restored osteoclastogenesis suppressed by IL-6.

Weather variability and paediatric infectious gastroenteritis.

Investigations of the relationship between weather variability and infectious gastroenteritis (IG) are becoming increasingly important in light of international interest in the potential health effects of climate change. However, few studies have examined the impact on children, despite the fact that children are considered particularly vulnerable to climate change. We acquired data about cases of IG in children aged <15 years and about weather variability in Fukuoka, Japan from 2000 to 2008 and used time-series analyses to assess how weather variability affected IG cases, adjusting for confounding factors. The temperature-IG relationship had an inverted V shape, with fewer cases at temperatures lower and higher than ~13°C. Every 1°C increase in temperature below the threshold (13°C) was associated with a 23·2% [95% confidence interval (CI) 16·6-30·2] increase, while every 1°C increase in temperature above the threshold (13°C) was associated with an 11·8% (95% CI 6·6-17·3) decrease in incidence. The increase in cases per 1% drop in relative humidity was 3·9% (95% CI 2·8-5·0). The percentage increase of IG cases was greatest in the 0-4 years age group and tended to decrease with increasing age. We found a progressive reduction in weather-related IG cases in children aged >4 years. Our results suggest that public health interventions aimed at controlling weather-related IG may be most effective when focused on young children.

Development of a colon endoscope robot that adjusts its locomotion through the use of reinforcement learning.

PURPOSE: Fibre optic colonoscopy is usually performed with manual introduction and advancement of the endoscope, but there is potential for a robot capable of locomoting autonomously from the rectum to the caecum. A prototype robot was designed and tested. METHODS: The robot colonic endoscope consists in a front body with clockwise helical fin and a rear body with anticlockwise one, both connected via a DC motor. Input voltage is adjusted automatically by the robot, through the use of reinforcement learning, determining speed and direction (forward or backward). RESULTS: Experiments were performed both in-vitro and in-vivo, showing the feasibility of the robot. The device is capable of moving in a slippery environment, and reinforcement learning algorithms such as Q-learning and SARSA can obtain better results than simply applying full tension to the robot. CONCLUSIONS: This self-propelled robotic endoscope has potential as an alternative to current fibre optic colonoscopy examination methods, especially with the addition of new sensors under development.

Risk factors for portal venous thrombosis after splenectomy in patients with cirrhosis and portal hypertension.

BACKGROUND: Portal venous thrombosis (PVT) is a potentially fatal complication following splenectomy. Its mechanisms and risk factors are poorly understood, especially in patients with cirrhosis and portal hypertension. This study investigated risk factors for PVT following splenectomy in such patients. METHODS: All consecutive patients with cirrhosis who underwent splenectomy in Kyushu University Hospital between 1998 and 2004 were included in this retrospective study. They were divided into two groups based on the presence or absence of postoperative PVT. Preoperative and operative factors were compared, and the relationships between formation of PVT and its independent variables were analysed. In some cases, portal venous flow was measured before and after splenectomy using duplex Doppler ultrasonography. RESULTS: PVT developed after surgery in 17 (24 per cent) of 70 patients studied. Multivariable analysis showed that increased splenic vein diameter and low white cell count were significant independent risk factors for PVT. Portal venous flow after splenectomy was greatly reduced in the PVT group, but not in patients without PVT. CONCLUSION: Large splenic vein diameter and low white cell count are independent risk factors for PVT after splenectomy in patients with cirrhosis and portal hypertension.

Gemcitabine synergistically enhances the effect of adenovirus gene therapy through activation of the CMV promoter in pancreatic cancer cells.

Adenovirus-mediated gene therapy shows remarkable promise as a new strategy for advanced pancreatic cancer, but satisfactory clinical results have not yet been obtained. To improve this gene therapy, we investigated the effects of gemcitabine (GEM) on transgene expression by adenoviral vectors and their biological effects. We used Ad-lacZ and adenoviral vector-expressing NK4 (Ad-NK4) as representative adenoviral vectors. These vectors express beta-galactosidase (beta-gal) and NK4 (which inhibits the invasion of cancer cells), respectively, under the control of the CMV promoter. Cells were infected with the individual adenoviruses and then treated with GEM. GEM increased beta-gal mRNA expression and beta-gal activity, and increased NK4 expression in both culture media and within infected cells, in dose-dependent manners. The increased expression of NK4 delivered by Ad-NK4 had biological effects by inhibiting the invasion of cancer cells. GEM also enhanced NK4 expression in SUIT-2 cells transfected with an NK4-expressing plasmid, suggesting that GEM enhanced CMV promoter activity. In in vivo experiments, NK4 expression within subcutaneously implanted tumors was increased in GEM-treated mice compared with control mice. These results suggest that adenovirus-mediated gene therapy with GEM may be a promising approach for treating pancreatic cancer, and that this combination therapy may decrease the risks of side effects.