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Few large epidemiological studies have evaluated the association between dietary advanced glycation end products (AGEs) and cancer risk. We evaluated the relationship between dietary AGE intake and the incidence of total cancer and site-specific cancers in a population-based prospective study in Japan. Participants were 14,173 men and 16,549 women who were 35 years of age or older in 1992. Dietary intake was assessed via a validated food frequency questionnaire. Intake of the AGE N

Greenhouse gases (GHGs) play a crucial role regarding global warming. Therefore, precise and accurate observations of anthropogenic GHGs, especially carbon dioxide and methane, are of utmost importance for the estimation of their emission strengths, flux changes and long-term monitoring. Satellite observations are well suited for this task as they provide global coverage. However, like all measurements these need to be validated.The COllaborative Carbon Column Observing Network (COCCON) performs ground-based observations to retrieve column-averaged dry air mole fractions of GHGs (XGAS) with reference precision. The instrument used by the network is the EM27/SUN, a solar-viewing Fourier Transform infrared (FTIR) spectrometer. COCCON data are of high accuracy as COCCON uses species dependent airmass-independent and airmass-dependent adjustments for tying the XGAS products to TCCCON (Total Carbon Column Observing Network) and thereby to the World Meteorological Organization (WMO) reference scale. Moreover, instrument specific characteristics are measured for each COCCON spectrometer, and taken into account in the data analysis.Here we first introduce the COCCON network in general and summarize its capabilities for various challenges including satellite and model validation, long-term observation of GHGs, and local and regional GHG source emission strength estimations. By example of the COCCON Tsukuba station we highlight in detail its usefulness for the above-mentioned applications.

We demonstrate the generation of a MOF (Zn8-as) based on octa-nuclear zinc clusters from a curved ligand and Zn(ii) in DMF and H2O. Zn8-de displays gated adsorption for C2H2 and type-I adsorption for CO2, attributed to the framework flexibility.

Individuals with prodromal symptoms of Lewy body disease (LBD), such as rapid eye movement sleep behavior disorder (RBD), often showed imaging defects similar to patients. We examined dopamine transporter (DaT) single-photon-emission computed tomography (SPECT) and metaiodobenzylguanidine (MIBG) scintigraphy in 69 high-risk subjects with ≥ 2 prodromal symptoms (dysautonomia, hyposmia, and RBD) and 32 low-risk subjects without prodromal symptoms, whom were identified through a questionnaire survey of health checkup examinees. The high-risk subjects had significantly worse scores on Stroop test, line orientation test, and the Odor Stick Identification Test for Japanese than the low-risk subjects. The prevalence of abnormalities on DaT-SPECT was higher in the high-risk group than in the low-risk group (24.6% vs. 6.3%, p = 0.030). A decreased uptake on DaT-SPECT was associated with motor impairment, and MIBG scintigraphy defects were associated with hyposmia. The simultaneous evaluation of DaT-SPECT and MIBG scintigraphy may capture a wide range of individuals with prodromal LBD.

In this study, we report an efficient fabrication method for the membrane of a metal-organic framework (MOF) (Kgm-OEt) which is one kind of kagome-type MOF with a two-dimensional (2D) sheet structure having one-dimensional (1D) channels suitable for separation of H2 from other larger gases. The Kgm-OEt seed layer was created on an Al2 O3 substrate using layer-by-layer (LBL) growth, then a membrane was fabricated by secondary growth. The membrane on a 3-aminopropyltriethoxysilane (APTEs)-treated substrate obtained in this method was continuous and defect-free with the crystal orientation suitable for gas transportation, while the membrane grown on an unmodified substrate was loosely packed with unfavorable crystal orientation.

Accumulation of amyloid β peptides (Aβ) is thought to be one of the causal factors of Alzheimer's disease (AD). The aspartyl protease β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting protease for Aβ production, and therefore, BACE1 inhibition is a promising therapeutic approach for the treatment of AD. Starting with a dihydro-1,3-thiazine-based lead, Compound J, we discovered atabecestat 1 (JNJ-54861911) as a centrally efficacious BACE1 inhibitor that was advanced into the EARLY Phase 2b/3 clinical trial for the treatment of preclinical AD patients. Compound 1 demonstrated robust and dose-dependent Aβ reduction and showed sufficient safety margins in preclinical models. The potential of reactive metabolite formation was evaluated in a covalent binding study to assess its irreversible binding to human hepatocytes. Unfortunately, the EARLY trial was discontinued due to significant elevation of liver enzymes, and subsequent analysis of the clinical outcomes showed dose-related cognitive worsening.

A 63-year-old man was admitted to our hospital in March 2017 with dysphagia and right homonymous hemianopsia. We diagnosed him with esophagogastric junction cancer (adenocarcinoma) with metastases to the cerebral occipital lobe, bone, and lymph nodes. After one cycle of 5FU + cisplatin (FP), the brain metastasis was resected because of the hemiplegic symptoms he developed. Histology of the resected tissue showed no viable tumor cells. After three cycles of FP, the primary lesion and metastases were resolved. Upper gastrointestinal endoscopy revealed a scar at the primary site. This was considered a complete response (CR). In April 2018, CT revealed a mass at the cardia, which was considered as lymph node metastases with gastric wall invasion. Although two additional cycles of FP were administered for recurrent tumors, the efficacy was progressive. In August 2018, proximal gastrectomy and D1 + lymph node dissection were performed. The pathological diagnosis was gastric intramural metastases and lymph node metastases (ypN1 [2/22]). Weekly paclitaxel therapy was administered for three months after surgery. Two years have passed since the last surgery without recurrence. We report a rare case of esophagogastric junction cancer with brain, bone, and gastric intramural metastases that responded to combined modality therapy.

In order to improve oncologic outcomes in radiotherapy treatments of patients with unresectable pelvic sidewall recurrences of uterine cervical cancer, we combined high-dose-rate interstitial brachytherapy (HDR-ISBT) with newly tested hypoxic radiosensitizer Kochi oxydol-radiation therapy for unresectable carcinomas (KORTUC II), an enzyme-targeting radiosensitization treatment involving intra-tumoral injection of sodium hyaluronate mixed with hydrogen peroxide. We report on a 63-year-old patient referred to our department with an extensive pelvic sidewall recurrence of uterine cervical cancer after initial hysterectomy. The tumor size was 55 × 25 × 80 mm, with a calculated volume of 89.7 cc. Whole pelvic irradiation of 50 Gy in 25 fractions was administered, combined with weekly cisplatin injections. KORTUC II injections were given two times: at day 21 (42 Gy) and at day 24 (48 Gy). After finishing whole pelvic irradiation, HDR-ISBT of 25 Gy in 5 fractions b.i.d. over 3 days was administered. KORTUC II was also injected at the time of implantation. Dose-volume histogram (DVH) values for clinical target volume were D 90 , D 98 , and D 100 of 6.0, 5.0, and 3.5 Gy per fraction, respectively. D2cc values were 2.1, 4.1, 3.2, and 2.0 Gy per fraction for the bladder, rectum, sigmoid colon, and small bowel, respectively. No acute adverse events ≥ grade 3 were observed. Repeated grade 3 pyelonephritis occurred as a late complication at 11, 24, and 26 months after the treatment, and was successfully resolved with antibiotics. Moreover, grade 2 late toxicity was documented, including sciatic neuralgia, lower limb lymphedema, and urinary incontinence. At present, 32 months after HDR-ISBT, the patient remains free of disease, with no toxicity-related deterioration in physical condition.

Column-averaged dry-air mole fractions of carbon dioxide (XCO2) and methane (XCH4) measured by a solar viewing portable Fourier transform spectrometer (FTS, EM27/SUN) have been characterized and validated by comparison using in situ profile measurements made during the transfer flights of two aircraft campaigns: Korea-United States Air Quality Study (KORUS-AQ) and Effect of Megacities on the Transport and Transformation of Pollutants at Regional and Global Scales (EMeRGe). The aircraft flew over two Total Carbon Column Observing Network (TCCON) sites: Rikubetsu, Japan (43.46∘ N, 143.77∘ E), for the KORUS-AQ campaign and Burgos, Philippines (18.53∘ N, 120.65∘ E), for the EMeRGe campaign. The EM27/SUN was deployed at the corresponding TCCON sites during the overflights. The mole fraction profiles obtained by the aircraft over Rikubetsu differed between the ascending and the descending flights above approximately 8 km for both CO2 and CH4. Because the spatial pattern of tropopause heights based on potential vorticity values from the ERA5 reanalysis shows that the tropopause height over the Rikubetsu site was consistent with the descending profile, we used only the descending profile to compare with the EM27/SUN data. Both the XCO2 and XCH4 derived from the descending profiles over Burgos were lower than those from the ascending profiles. Output from the Weather Research and Forecasting Model indicates that higher CO2 for the ascending profile originated in central Luzon, an industrialized and densely populated region about 400 km south of the Burgos TCCON site. Air masses observed with the EM27/SUN overlap better with those from the descending aircraft profiles than those from the ascending aircraft profiles with respect to their properties such as origin and atmospheric residence times. Consequently, the descending aircraft profiles were used for the comparison with the EM27/SUN data. The EM27/SUN XCO2 and XCH4 data were derived by using the GGG2014 software without applying air-mass-independent correction factors (AICFs). The comparison of the EM27/SUN observations with the aircraft data revealed that, on average, the EM27/SUN XCO2 data were biased low by 1.22 % and the EM27/SUN XCH4 data were biased low by 1.71 %. The resulting AICFs of 0.9878 for XCO2 and 0.9829 for XCH4 were obtained for the EM27/SUN. Applying AICFs being utilized for the TCCON data (0.9898 for XCO2 and 0.9765 for XCH4) to the EM27/SUN data induces an underestimate for XCO2 and an overestimate for XCH4.

The present study aimed to survey the prevalence of prodromal symptoms of Parkinson’s disease (PD) in Japanese health checkup examinees, for identifying at-risk subjects. We conducted a questionnaire survey of annual health checkup examinees without neurological symptoms using the following self-reported questionnaires: Japanese version of the Scale for Outcomes in Parkinson’s disease for Autonomic Symptoms (SCOPA-AUT); Self-administered Odor Question (SAOQ); REM Sleep Behavior Disorder Screening Scale (RBDSQ); Beck Depression Inventory-Second Edition (BDI-II); Epworth Sleepiness Scale (ESS); and Physical Activity Scale for the Elderly (PASE). The presence of prodromal symptoms was determined using the 90th percentile threshold of each questionnaire. Subjects ≥ 50 years of age with ≥ 2 core prodromal symptoms (dysautonomia, hyposmia, and RBD), were classified as at risk. Between March 2017 and March 2018, 4,953 participants sufficiently answered the questionnaires. Among 2,726 subjects ≥ 50 years of age, 155 were classified as at risk. These subjects had worse values of BDI-II (12.0 ± 8.3 vs. 4.4 ± 3.8, p

The ortho-isomer of molecular hydrogen (o-H2) was converted to the para-isomer (p-H2) within 600 s by using Prussian blue analogs, {MII3[CrIII(CN)6]2} (MCr; M = Mn and Ni), as nuclear-spin conversi...

Here, we report the adsorptive removal of trace amounts of dimethyl sulfide (DMS) using metal–organic frameworks (MOFs). Cu2+-based MOFs with open metal sites (OMSs), [Cu3(btc)2] (HKUST-1), where btc = 1,3,5-benzenetricarboxylate, and without OMSs, [Cu2(bdc)2(dabco)] (Cu-JAST-1), where bdc = 1,4-benzenedicarboxylate and dabco = 1,4-diazabicyclo[2.2.2]octane, were investigated for the removal of DMS to compare their performance with that of Ag–Y zeolite, which is currently widely used in industry. HKUST-1 exhibited a considerably higher adsorption capacity for DMS than the other adsorbents, which was confirmed by breakthrough measurements. The adsorption state of DMS with HKUST-1 was directly revealed by single-crystal X-ray diffraction (SXRD) analysis and in situ Raman spectroscopy. In addition, it was shown that DMS can be removed by HKUST-1 even under humid conditions.

The influence of body mass or metabolic capacity on the association between alcohol consumption and lower risks of developing chronic kidney disease (CKD) is not fully elucidated. We examined whether the body mass index (BMI) affects the association between drinking alcohol and CKD. We defined CKD as an estimated glomerular filtration rate decline 2 and/or positive proteinuria (≥ 1+). Participants were 11,175 Japanese individuals aged 40–74 years without baseline CKD who underwent annual health checkups. Daily alcohol consumption at baseline was estimated using a questionnaire, and the participants were categorized as “infrequent (occasionally, rarely or never),” “light (2), moderate drinkers in the low (

In this study, we report an efficient fabrication method for the membrane of a metal-organic framework (MOF) (Kgm-OEt) which is one kind of kagomé-type MOF with a two-dimensional (2D) sheet structure having one-dimensional (1D) channels suitable for separation of H

A layered metal-organic framework (MOF) comprising extra-large nanographene sheets, HBCMOF, was successfully synthesized using a dicarboxylic acid derivative of hexa-peri-hexabenzocoronene (HBCLH2), and its structure was characterized by single-crystal X-ray diffraction analysis. The crystal structure shows that 2D layers composed of a dinuclear Zn2+ complex unit and HBCL are located on top of each other through multiple weak interlayer bonds, affording HBCMOF, having three dimensionally connected nanopores with large nanographene surfaces. The HBC-based nanographene sheets are anchored to the MOF framework via two zinc carboxylate linkages and therefore have an axial rotational freedom. The sorption isotherms of gaseous molecules such as carbon dioxide and hydrocarbons (acetylene, propane, propylene, benzene, and cyclohexane) on HBCMOF all displayed a hysteretic profile with reversible structural changes, as observed by in situ powder X-ray diffraction studies.

In this study, we report a facile ligand-assisted in situ hydrothermal approach for preparation of compact [Al(OH)(1,4-NDC)] (1,4-NDC=1,4-naphthalenedicarboxylate) MOF membranes on porous γ-Al2 O3 substrates, which also served as the Al3+ source of MOF membranes. Simultaneously, it was observed that the heating mode exerted significant influence on the final microstructure and separation performance of [Al(OH)(1,4-NDC)] membranes. Compared with the conventional hydrothermal method, the employment of microwave heating led to the formation of [Al(OH)(1,4-NDC)] membranes composed of closely packed nanorods with superior H2 /CH4 selectivity.

Gas-sensing materials are becoming increasingly important in our society, requiring high sensitivity to differentiate similar gases like N2 and O2. For the design of such materials, the driving force of electronic host-guest interaction or host-framework changes during the sorption process has commonly been considered necessary; however, this work demonstrates the use of the magnetic characteristics intrinsic to the guest molecules for distinguishing between diamagnetic N2 and CO2 gases from paramagnetic O2 gas. While the uptake of N2 and CO2 leads to an increase in TC through ferrimagnetic behavior, the uptake of O2 results in an O2 pressure-dependent continuous phase change from a ferrimagnet to an antiferromagnet, eventually leading to a novel ferrimagnet with aligned O2 spins following application of a magnetic field. This chameleonic material, the first with switchable magnetism that can discriminate between similarly sized N2 and O2 gases, provides wide scope for new gas-responsive porous magnets., Gas-sensing materials are of increasing societal importance, but the ability to differentiate between similarly sized gases remains highly challenging. Here the authors report on a porous ferrimagnet that distinguishes diamagnetic N2 and CO2 gases from paramagnetic O2 gas.

Triplet carbenes (TCs) are of great interest due to their magnetic properties and reactivity, which descend from TCs' unique electronic state. However, the reactivity and stability of TCs are usually a trade-off, and it is difficult to achieve both at the same time. In this work, we were able to enhance the thermal stability of a TC species while maintaining its reactivity by confining them in the nanospace of a metal-organic framework (MOF). We synthesized a new MOF using a TC precursor; subsequently, TCs were generated by photostimulation. The TCs generated in the MOF nanospace were detectable up to 170 K, whereas their non-MOF-confined counterparts (bare ligand) could not be detected above 100 K. In addition, the reactivity of TC generated in MOF with O2 was drastically improved compared to that of bare ligand. Our approach is generally applicable to the stabilization of highly reactive species, whose reactivity needs to be preserved.

Background and Aims Drinking habits are one of the most important modifiable lifestyle factors to prevent the development of chronic kidney disease (CKD). Previous studies showed that it was inversely associated with the risk of developing CKD, but the dose-response relationship between alcohol consumption and the development of CKD is still controversial. In the present study, we aimed to examine whether the amount of alcohol consumed at one time is associated with new onset of CKD in general population. Method Study subjects were 11,162 Japanese aged 45 to 74 years, with an estimated glomerular filtration rate ≥60 mL/min/1.73m2, no proteinuria, no past history of cardiovascular disease, COPD or liver disease. The drinking status was obtained by self-administered questionnaires. We categorized the study subjects into four groups based on the amount of alcohol consumption: 60g/time (highest). We set non-drinkers as a reference category. The primary outcome was the incidence of CKD, defined as 25% reduction of eGFR and to less than 60 mL/min/1.73 m2 and/or a dipstick urinalysis score of 1+ or greater (equivalent to ≥30 mg/dL) during the follow up period. We employed Cox proportional hazards regression models to examine the dose-response relationship between baseline alcohol consumption and the risk of CKD. Trend tests were performed using Cox proportional hazards regression models that treated alcohol consumption as a continuous linear term. Results Lowest and low intermediate groups were significantly associated with a decreased risk of CKD (hazard ratio [HR] 0.84; 95% confidence interval [CI], and 0.71–0.99; HR 0.79; 95% CI, 0.66–0.96, respectively) compared to non-drinkers. High intermediate group was associated with a decreased risk of CKD (HR 0.92; 95% CI, 0.70–1.21), and highest group was associated with an increased risk of CKD (HR 1.28; 95% CI, 0.84–1.95), but these associations did not reach statistical significance. There was no dose-response relationship between baseline alcohol consumption and risk of CKD (P-trend = 0.30). Conclusion A J-shape association was observed between self-reported alcohol intake and the incidence of CKD. Moderate alcohol consumption at one time may help reduce the risk of CKD.

PurposeKochi Oxydol-Radiation Therapy for Unresectable Carcinomas II (KORTUC II) is currently the most widely used radiosensitizer in clinical use in Japan. Its use sensitizes tumors to radiation by injecting hydrogen peroxide into the tumors to neutralize antioxidant enzymes and, simultaneously, increase intratumor oxygen tension. KORTUC II has achieved significant local effects with no notable adverse events. We report on the cases where KORTUC II was used to treat patients with locally advanced breast cancer (LABC) or recurrent breast cancer (LRBC).Methods and MaterialsThirty patients treated with KORTUC II for LABC (n = 9) or LRBC (n = 21), who were followed up for at least 3 months after treatment, were included in the study. This sensitizer is a solution consisting of 0.83% sodium hyaluronate and 0.5% hydrogen peroxide by volume. The mixture was injected intratumorally several times during the treatment period under ultrasound guidance, just before RT doses. RT was administered for local control. The irradiation dose and extent fields were determined by the attending physicians considering patient factors. Maximum tumor shrinkage (MTS) was measured by Computed Tomography. The duration of loco-regional control (LC) and progression free survival (PFS) after the completion of RT were determined using the Kaplan–Meier method.ResultsThe median irradiation dose was 60.4 Gy3.5 (43.6–76.1 Gy3.5) based on the calculation of EQD2, and median total number of sensitizer treatments was 5 (2–7). The median MTS was 97.0%. Fifteen patients (50%) were assessed to have achieved a clinical complete response. The proportion of patients with LC at 1, 2, and 3 years was 100%, 94.7%, and 75.4%. The proportion with PFS after RT at 1 and 2 years was 59.0%, and 24.1%, respectively.ConclusionsKORTUC II treatment demonstrated high rates of local tumor control for LABC and LRBC. KORTUC II is expected to be an inexpensive and extremely promising RT with an excellent radio-sensitizing effect.Trial registrationOsaka Medical College Clinical Trials Registry, trial no. 1973, date. May 10, 2010UMIN Clinical Trials Registry, trial no. UMIN000003734, date. June 10, 2010

Greenhouse gases (GHGs) play a crucial role with respect to global warming. Therefore, precise and accurate observations of anthropogenic GHGs, especially carbon dioxide (CO2) and methane (CH4), are of utmost importance for the estimation of their emission strengths, flux changes and long-term monitoring. Satellite observations are well suited for this task as they provide global coverage. However, like all measurements these need to be validated. The Total Carbon Column Observing Network (TCCON) performs ground-based observations of GHGs with reference precision using high-resolution Fourier Transform infrared (FTIR) spectrometers. TCCON data are of high accuracy as TCCON uses species dependent scaling factors derived from in-situ reference measurements to be calibrated to the World Meteorological Organization (WMO) reference scale. For several satellites measuring GHGs TCCON data are the main validation source.To further improve the global coverage of FTIR spectrometers and complement TCCON especially in remote areas, the COllaborative Carbon Column Observing Network (COCCON) was established. Until now the focus of COCCON was on the quality control of EM27/SUN spectrometers and dedicated campaigns to estimate emission strengths of CO2 and CH4 from local and regional sources, e.g. from cities, fracking areas or mining sites.Here we present a global validation of the Greenhouse Gases Observation Satellite GOSAT using multiple spectrometers from the COCCON network. The COCCON instruments are stationed in Finland, Germany, Greece, Japan, Namibia, Sweden and the USA. The sites span a range of different atmospheric and observing conditions, from subtropical to subpolar regions, including boreal forests and deserts, low and high albedo surfaces, polluted and clean areas. Overall, we find a good agreement between GOSAT and COCCON measurements.

Molecular motions taking place in the nanospace of metal–organic frameworks (MOFs) are an interesting research subject, although not yet fully investigated. In this work, we utilized in situ Raman spectroscopy in the ultralow-frequency region to investigate the libration motion (including the rotational motion of phenylene rings) of MOFs, in particular [Cu2(bdc)2(dabco)] (Cu-JAST-1), where bdc = 1,4-benzenedicarboxylate and dabco = 1,4-diazabicyclo[2.2.2]octane. The libration mode of Cu-JAST-1 was found to be significantly suppressed by the adsorption of various guest molecules, such as CO2, Ar, and N2. In addition, an appreciable correlation between the libration mode and adsorption equilibrium time was identified, which provides useful novel tools in the design of MOFs acting as molecular adsorption and separation materials.

Column-averaged dry-air mole fractions of carbon dioxide (XCO2) and methane (XCH4) measured by a solar viewing portable Fourier transform spectrometer (FTS, EM27/SUN) have been characterized and validated by comparison using in-situ profile measurements made during the transfer flights of two aircraft campaigns: Korea-United States Air Quality Study (KORUS-AQ) and Effect of Megacities on the Transport and Transformation of Pollutants on the Regional and Global Scale (EMeRGe). The aircraft flew over two Total Carbon Column Observing Network (TCCON) sites: Rikubetsu, Japan (43.46° N, 143.77° E) for the KORUS-AQ campaign and Burgos, Philippines (18.53° N, 120.65° E) for the EMeRGe campaign. The EM27/SUN was deployed at the corresponding TCCON sites during the overflights. The mole fraction profiles obtained by the aircraft over Rikubetsu differed between the ascending and the descending flights above approximately 8 km for both CO2 and CH4. Because the spatial pattern of tropopause heights based on potential vorticity values from the ERA5 reanalysis show that the tropopause height over the Rikubetsu site was consistent with the descending profile, we used only the descending profile to compare with the EM27/SUN data. Both the XCO2 and XCH4 derived from the descending profiles over Burgos were lower than those from the ascending profiles. Output from the Weather Research and Forecast Model indicate that higher CO2 for the ascending profile originated in central Luzon, an industrialized and densely populated region about 400 km south of the Burgos TCCON site. Air masses observed with the EM27/SUN overlap better with those from the descending aircraft profiles than those from the ascending aircraft profiles with respect to their properties such as origin and atmospheric residence times. Consequently, the descending aircraft profiles were used for the comparison with the EM27/SUN data. The EM27/SUN XCO2 and XCH4 data were derived by using the GGG2014 software in which air mass independent correction factors utilized for the TCCON data (0.9898 for XCO2 and 0.9765 for XCH4) were not applied. The comparison of the EM27/SUN observations with the aircraft data revealed that on average, the EM27/SUN XCO2 data were biased low by 1.22 % and the EM27/SUN XCH4 data were biased low by 1.67 %. The resulting air mass independent correction factors of 0.9878 for XCO2 and 0.9833 for XCH4 were obtained for the portable FTS.

Parkinson’s disease (PD) is a debilitating neurodegenerative disorder in which nonmotor symptoms, such as constipation and hyposmia, precede the onset of motor symptoms by 20 years. The aim of this study was to identify biomarkers at the premotor stage of PD. We assessed the differences in longitudinal changes in anthropometric and serological indices obtained from health check-up data before and after the onset of motor symptoms between male and female PD patients and healthy subjects. We enrolled 22 male and 23 female PD patients and 60 male and 60 female healthy controls. A mixed-effects model was used to estimate the trajectory of each clinical marker over the years before and after motor symptoms onset in the PD subjects, which were then compared with the trajectories of the healthy controls. The results showed a premotor blood pressure increase in female PD patients and premotor decreases in haematocrit, total cholesterol and low-density lipoprotein cholesterol in the male patients. Our results indicated that blood pressure, haematocrit and serum cholesterol levels are potential premotor markers of PD. Additionally, the changes in anthropometric and serological indices before PD motor symptoms onset were sex specific.

We aimed to investigate whether coffee, green tea, and caffeine intake are associated with liver cancer risk, using data of a prospective cohort study. This study included 30,824 participants (14,240 men and 16,584 women) aged 35 years or older in the Takayama study, which was launched on September 1, 1992. The consumption frequencies of coffee and green tea were assessed using a self-administered questionnaire. Caffeine intake was estimated from the consumption frequencies of caffeine-containing beverages and foods and their caffeine content per serving. The incidence of liver cancer was confirmed using regional population-based cancer registries. During the follow-up period of 16 years, a total of 172 participants developed liver cancer. The adjusted hazard ratios and 95% confidence intervals (CIs) in relation to coffee consumption were 0.65 (95% CI: 0.46-0.93) for less than once per day, 0.63 (95% CI: 0.39-1.02) for once per day, and 0.40 (95% CI: 0.20-0.79) for twice per day or more, compared with nondrinkers. No associations with green tea, black tea and caffeine intake were observed. The present study confirmed that coffee consumption significantly reduces liver cancer risk and raises the possibility that caffeine intake might not account for the association.