Relationship between the combination of polyunsaturated fatty acids intake and psychological distress during pregnancy: The Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study.

No studies have examined the association of the combination of n-3 polyunsaturated fatty acids (PUFAs) and n-6 PUFAs intake with psychological distress during pregnancy. To examine these associations, we divided Japanese pregnant women into 25 groups based on combining quintiles of n-3 PUFAs intake and quintiles of n-6 PUFAs intake. We conducted multivariable logistic regression analyses to assess the risk of psychological distress during pregnancy (Kessler Psychological Distress Scale ≥ 5 or 13). Compared to the third quintile of both n-3 PUFAs and n-6 PUFAs intake, the groups with unbalanced intake, high intake of both, and low intake of both were associated with a higher risk of both Kessler Psychological Distress Scale ≥ 5 and 13 in early and mid-pregnancy. Further research is needed to identify the precise combination of n-3 PUFAs and n-6 PUFAs intake associated with the lowest psychological distress during pregnancy.

Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study).

BACKGROUND: Anti-programmed cell death protein 1 (PD-1) antibody monotherapy (PD1) has led to favorable responses in advanced non-acral cutaneous melanoma among Caucasian populations; however, recent studies suggest that this therapy has limited efficacy in mucosal melanoma (MCM). Thus, advanced MCM patients are candidates for PD1 plus anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) combination therapy (PD1 + CTLA4). Data on the efficacy of immunotherapy in MCM, however, are limited. We aimed to compare the efficacies of PD1 and PD1 + CTLA4 in Japanese advanced MCM patients. PATIENTS AND METHODS: We retrospectively assessed advanced MCM patients treated with PD1 or PD1 + CTLA4 at 24 Japanese institutions. Patient baseline characteristics, clinical responses (RECIST), progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan-Meier analysis, and toxicity was assessed to estimate the efficacy and safety of PD1 and PD1 + CTLA4. RESULTS: Altogether, 329 patients with advanced MCM were included in this study. PD1 and PD1 + CTLA4 were used in 263 and 66 patients, respectively. Baseline characteristics were similar between both treatment groups, except for age (median age 71 versus 65 years; P < 0.001). No significant differences were observed between the PD1 and PD1 + CTLA4 groups with respect to objective response rate (26% versus 29%; P = 0.26) or PFS and OS (median PFS 5.9 months versus 6.8 months; P = 0.55, median OS 20.4 months versus 20.1 months; P = 0.55). Cox multivariate survival analysis revealed that PD1 + CTLA4 did not prolong PFS and OS (PFS: hazard ratio 0.83, 95% confidence interval 0.58-1.19, P = 0.30; OS: HR 0.89, 95% confidence interval 0.57-1.38, P = 0.59). The rate of ≥grade 3 immune-related adverse events was higher in the PD1 + CTLA4 group than in the PD1 group (53% versus 17%; P < 0.001). CONCLUSIONS: First-line PD1 + CTLA4 demonstrated comparable clinical efficacy to PD1 in Japanese MCM patients, but with a higher rate of immune-related adverse events.

The ideal strategy for cervical cancer screening in Japan: Result from the Fukui Cervical Cancer Screening Study.

INTRODUCTION: The aims of the Fukui Cervical Cancer Screening (FCCS) study are to determine the frequency of women with high-risk HPV (hrHPV), whether HPV16 or HPV18 (HPV16/18), in the Japanese cancer screening population for the first time and to identify the best strategy for cervical cancer screening in Japan. METHODS: This study enrolled 7584 women aged ≥25 years who were undergoing routine screening. All women underwent LBC and cobas HPV tests. Women with abnormal cytology, whether hrHPV positive or negative; women with hrHPV positivity with either normal or abnormal cytology; and women randomly selected from women with normal cytology and negative hrHPV negative were referred for colposcopy. RESULTS: The prevalences of hrHPV positivity and HPV16/18 positivity were 6.8% and 1.7%, respectively. The baseline data from the FCCS study showed that the combination of HPV tests and cytology was more sensitive than cytology with respect to the detection of intraepithelial neoplasia grade 2 or worse. However, the specificity (94.1%) of the co-testing strategy that required all women with abnormal cytology or hrHPV positivity to be referred for colposcopy was much lower than that (97.8%) of cytology. The sensitivity and specificity of the co-testing strategy that required only women with abnormal cytology or HPV16/18 positivity to undergo colposcopy were 85.5% and 97.0%, respectively. CONCLUSION: The baseline data from the FCCS study suggest that a cervical cancer screening strategy in which only women with abnormal cytology or HPV16/18 positivity undergo colposcopy offers a more balanced sensitivity and specificity than other strategies.

Immunoexpression of angiogenesis and proliferation markers in patients treated with cyclosporin A.

AIM: In the present immunohistochemical study, the expression of vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67 in the gingival tissues of renal transplant patients treated with cyclosporin A was assessed. Gingival overgrowth (GO) frequently occurs in transplant patients receiving immunosuppressive drugs such as cyclosporine and this gingival inflammation might play an important role in the pathogenesis of drug-induced GO. METHODS: Twenty-eight human gingival biopsies were taken from healthy patients with chronic periodontitis (N.=14 control group), and from renal transplant recipients treated with cyclosporin A (N.=14 test group). The retrieved specimens were immunohistochemically processed and stained for vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67. RESULTS: The levels of vascular endothelial growth factor, nitric oxide synthase 1 and 3, and Ki-67 were found to be significantly different among groups (P>0.001), with patients treated with cyclosporin A showing higher levels of all the analyzed markers compared to control group. CONCLUSION: In summary, the data from this pilot study suggests that the investigated factors have a role in the inflammation processes associated to immunosuppressive therapy. However, further studies with a larger sample population need to be conducted for an exhaustive knowledge of the mechanisms leading to GO.

Femtosecond-laser-driven photoelectron-gun for time-resolved cathodoluminescence measurement of GaN.

A rear-excitation femtosecond-laser-driven photoelectron gun (PE-gun) is developed for measuring time-resolved cathodoluminescence (TRCL) spectrum of wide bandgap materials and structures such as semiconductors and phosphors. The maximum quantum efficiency of a 20-nm-thick Au photocathode excited using a frequency-tripled Al(2)O(3):Ti laser under a rear-excitation configuration is 3.6×10(-6), which is a reasonable value for a PE-gun. When the distance between the front edge of the PE-gun and the observation point is 10 mm, the narrowest electron-beam (e-beam) diameter is 19 µm, which corresponds to one tenth of the laser-beam diameter and is comparable to the initial e-beam diameter of a typical W hair-pin filament of thermionic electron-gun. From the results of TRCL measurements on the freestanding GaN grown by the ammonothermal method and a GaN homoepitaxial film grown by metalorganic vapor phase epitaxy, overall response time for the present TRCL system is estimated to be 8 ps. The value is the same as that of time-resolved photoluminescence measurement using the same excitation laser pulses, meaning that the time-resolution is simply limited by the streak-camera, not by the PE-gun performance. The result of numerical simulation on the temporal e-beam broadening caused by the space-charge-effect suggests that the present PE-gun can be used as a pulsed e-beam source for spatio-time-resolved cathodoluminescence, when equipped in a scanning electron microscope.

Donor-derived HLA antibody production in patients undergoing SCT from HLA antibody-positive donors.

Pre-existing donor-specific HLA antibodies in patients undergoing HLA-mismatched SCT have increasingly been recognized as a risk factor for primary graft failure. However, the clinical implications of the presence of HLA antibodies in donors remain unknown. We prospectively examined 123 related donors for the presence of HLA antibodies by using a Luminex-based single antigen assay. Of these, 1/57 (1.8%) male, 6/27 (22%) parous female and 0/39 (0%) nonparous female donors were HLA antibody-positive. Then, we determined the presence of HLA antibodies in seven patients who received SCT from antibody-positive donors. Of these, four became HLA antibody-positive after SCT. The specificities of the antibodies that emerged in the patients closely resembled those of the antibodies found in the donors, indicating their production by donor-derived plasma cells. Moreover, the kinetics of the HLA antibody levels were similar in all four patients: levels started increasing within 1 week after SCT and peaked at days 10-21, followed by a gradual decrease. These results suggest that donor-derived HLA antibody production frequently occurs in patients undergoing SCT from antibody-positive donors. Further studies are warranted for clarifying the clinical significance of donor-derived HLA antibodies, including the role of these antibodies in post transplant platelet transfusion refractoriness.

Risk and prevention of graft failure in patients with preexisting donor-specific HLA antibodies undergoing unmanipulated haploidentical SCT.

A role of donor-specific HLA antibodies (DSA) in graft failure after SCT has been suggested, but the relevance of DSA in unmanipulated haploidentical SCT (haplo-SCT) remains unknown. We prospectively examined HLA antibodies using the Luminex-based single Ag assay for 79 adult patients undergoing unmanipulated haplo-SCT. Among them, 16 (20.2%) were HLA Ab-positive, including five patients with antibodies not corresponding to donor HLA Ags and 11 DSA-positive patients. Of the 11 DSA-positive patients, five received treatments to decrease DSA levels, including two, who received plasma exchange and rituximab, two who received platelet transfusions from healthy-related donors having DSA-corresponding HLA Ags and one who received bortezomib. Platelet transfusion was the most simple and effective treatment option for class I DSA. The cumulative incidence of neutrophil recovery was significantly lower in pretransplant (post-treatment) DSA-positive patients than in DSA-negative patients (61.9 vs 94.4%, P=0.026). Notably, three of five patients with high levels of DSA had graft failure. Donors should be selected on the basis of an evaluation of HLA antibodies. If haplo-SCT from donors with HLA Ags that correspond to high levels of DSA must be performed, then recipients should be treated for DSA to improve the chances of successful donor engraftment.

On site noninvasive assessment of peri-implant inflammation by optical spectroscopy.

BACKGROUND AND OBJECTIVE: Optical spectroscopy has been proposed to measure regional tissue hemodynamics in periodontal tissue. The objective of this study was to further evaluate the diagnostic potential of optical spectroscopy in peri-implant inflammation in vivo by assessing multiple inflammatory parameters (tissue oxygenation, total tissue hemoglobin, deoxyhemoglobin, oxygenated hemoglobin and tissue edema) simultaneously. MATERIAL AND METHODS: A cross-sectional study was performed in a total of 64 individuals who presented with dental implants in different stages of inflammation. In brief, visible-near-infrared spectra were obtained, processed and evaluated from healthy (n = 151), mucositis (n = 70) and peri-implantitis sites (n = 75) using a portable spectrometer. A modified Beer-Lambert unmixing model that incorporates a nonparametric scattering loss function was employed to determine the relative contribution of each inflammatory component to the overall spectrum. RESULTS: Tissue oxygenation at peri-implantitis sites was significantly decreased (p < 0.05) when compared with that at healthy sites, which was largely due to an increase in deoxyhemoglobin and a decrease in oxyhemoglobin at the peri-implantitis sites compared with the mucositis and healthy sites. In addition, the tissue hydration index derived from the optical spectra in mucositis was significantly higher than that in other groups (p < 0.05). CONCLUSION: In summary, the results of this study revealed that hemodynamic alterations can be detected around diseased peri-implant sites by optical spectroscopy, and this method may be considered an alternative and feasible approach for the monitoring and diagnosis of peri-implant diseases.

[An epithelial cyst at the frontal convexity].

We report a rare case of an epithelial cyst at the right frontal convexity. A 60-year-old woman came to our hospital suffering from dysarthria and gait disturbance. Computed tomography (CT) of the brain on admission showed a round low-density area, 6 cm in diameter, at the right frontal convexity. Midline shift and displacement of the lateral ventricle are seen. There is no contrast enhancement effect. Excision of the cyst wall and fenestration into the subarachnoid space was carried out and the patient was discharged with no neurological deficits. After 5 years, regrowth of the cyst was seen. Cyst-peritoneal shunt was performed and she was discharged uneventfully. Light microscopy showed the cyst wall consisted of a monolayer of flat epithelium and loose connective tissue. An electronmicrograph of the cyst wall showed a non-ciliated epithelial layer with microvilli and basement membrane. The epithelial cells connecting with each other through desmosome have numerous endoplasmic reticulum and mitochondria. Interdigitation of the cytoplasmic membrane was not seen. The term "epithelial cyst" seems ambiguous. We discuss the pathogenesis and the nomenclature for intracranial benign cystic lesions based on the previous literature.

Intracerebral haematomas with agenesis of the internal carotid artery and tetralogy of Fallot.

We report a rare case with tetralogy of Fallot (TOF) and agenesis of the internal carotid artery (ICA) who presented serious intracerebral haematomas. In the literature, this is the first documented case having these complications simultaneously. Extreme hypoxic insults followed by recovery were detected by O2 saturation monitor before two bleeds. Chronic brain hypoxia could make the vasculature weak, which was shown in the histological examination. A 2-year-old girl was transferred to us with a general convulsion due to intracerebral haematoma. She had been showing general cyanosis from birth due to TOF. Repeated intracerebral haemorrhages ended her life. Histological study showed dilated vascular channels in the subarachnoid space and necrotizing vasculature obstructed by fibrinous thrombi adjacent to the haematoma. Fibrosis of the vessel wall with infiltration of macrophages suggested subacute or chronic lesions rather than acute necrosis due to the multiple haemorrhages. The intracerebral haematomas and agenesis of the ICA were observed as unilateral hemispheric vascular complications of TOF. Chronic brain hypoxia could play an important role in weakening the vessel wall and erythrocytosis caused obstructing thrombi. We speculate these factors generated the intracerebral haematomas.

Acute subdural hematoma in patients who underwent aneurysm clipping--four case reports.

Four patients presented with intracranial hemorrhage mainly consisting of acute subdural hematoma (ASDH), who had all undergone aneurysm clipping 2-20 years earlier. Whether the clips had slipped or new trauma had caused the bleeding was difficult to determine, since the initial computed tomography showed that the subarachnoid hemorrhage or the intracerebral hematoma developed near the clips. Angiography in three patients showed that the clips had not slipped off. Three of four ASDHs appeared in the same side as the craniotomy used for the previous aneurysm surgery. Anti-platelet agents and ventriculoperitoneal shunting had been previously used in two patients with no causal signs of trauma. The outcomes were poor in three patients and one patient died. Weakening of the extra- or intracranial structure after aneurysm surgery might have been involved together with the postoperative anti-platelet agent and shunt treatment in the etiology of the present ASDH.

Free hand aspiration for large periventricular hemorrhage. Case report.

BACKGROUND: At present, there are several therapeutic options, including craniotomy and stereotactic aspiration, for large intracerebral hemorrhage perforating into the lateral ventricle. In the cases with Glasgow Coma Scale (GCS) scores under 6 with anisocoria, external ventricular drainage would be the first choice [2-4]. We have also performed anterior ventricular horn puncture in a standard manner. The target was the foramen of Monro, at a depth of 5.5 cm from the inner table of the skull. The point of insertion was located just anterior to the coronal suture, approximately 10 cm above the nasion, and 3 cm from the midline [1]. However, we noticed that the insertion of a catheter into the periventricular hematoma adjacent to the lateral ventricle was made easier by tilting the catheter 30 degrees laterally as in the first case (Figure 1). METHODS: In our method, inclining the catheter by 30 degrees laterally, we used a silicone tube 3.5 mm in internal diameter (Silascon ventricle drainage tube, Kaneka Medix Corp., Osaka, Japan) and then replaced it with another Silascon tube with a 2.5 mm-internal diameter. From January 1999 through December 2000, eleven patients who all had GCS scores under 6 and anisocoria preoperatively were treated by this method. The series included two patients who were undergoing hemodialysis because of renal failure, two with bleeding tendency because of liver dysfunction, and one with heart failure. RESULTS: The insertion itself caused no complications. Cerebrospinal fluid was drained smoothly after removal of hematoma because the hematoma cavity connecting with the lateral ventricle was opened. Two typical cases using this technique are shown (Figures 1 and 2). All patients recovered favorable consciousness postoperatively compared with the preoperative state but hemiparesis remained. Postsurgical follow up at 3 months revealed the outcomes evaluated by Glasgow Outcome Scale (GOS) were moderate disability in 5 patients and severe disability in 6 patients . CONCLUSION: This direct aspiration and drainage of a large intracerebral hematoma that ruptures into the lateral ventricle is superior to simple ventricular drainage in regard to the removal of the hematoma clot. This technique would be the choice especially in patients with serious complications such as cardiac disease and renal failure.

Dentatorubral-pallidoluysian atrophy (DRPLA) presenting with psychosis.

The authors report on four DRPLA patients who manifested delusions. All patients demonstrated autosomal dominant DRPLA confirmed by standard gene analysis. Patients with DRPLA can exhibit a variety of psychiatric symptoms in addition to extrapyramidal and cerebellar symptoms.

Usefulness of stable HbA(1c) for supportive marker to diagnose diabetes mellitus in Japanese subjects.

To evaluate the adequacy and usefulness of the stable glycated hemoglobin (HbA(1c)) value of 6.5% suggested by the Japan Diabetic Society in 1999 for supportive diagnostic marker of diabetes, we assessed the sensitivity and specificity of an HbA(1c) value of 6.5% in patients who were newly diagnosed by the 75 g oral glucose tolerance test (75g-OGTT). A total of 866 Japanese subjects underwent the 75g-OGTT and HbA(1c) measurement (normal range: 4.3-5.8%). They were divided into three groups [normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM)], using the WHO criteria, since no subject with impaired fasting glycemia (IFG) was observed. The cut-off value of HbA(1c) separating DM from NGT or DM from IGT on cumulative distribution curve analysis was 5.9% (sensitivity 0.76 and specificity 0.86) and 5.9% (sensitivity 0.76 and specificity 0.77), respectively. The sensitivity of an HbA(1c) of 6.5% for separation of DM from NGT or IGT by the same analysis was 0.49 and 0.49, respectively. Similarly, the specificity for separation of DM from NGT or IGT was 0.98 and 0.98, respectively. These results mean that 49% of diabetic subjects show an HbA(1c)> or =6.5%, and 51% have an HbA(1c) less than 6.5%, while only 2% of NGT and IGT subjects have an HbA(1c)> or =6.5%, and 98% have a value less than 6.5%. Therefore, the sensitivity of an HbA(1c) value of 6.5% in separating DM from NGT or IGT is low, and thus 6.5% is too high value to use when screening for diabetes. However, the specificity is very high, so an HbA(1c) of 6.5% is a useful supportive marker to diagnose diabetes.

Organized chronic subdural hematoma requiring craniotomy--five case reports.

Two child and three elderly patients underwent craniotomy for organized and/or partially calcified chronic subdural hematomas (CSHs). The characteristic feature of magnetic resonance imaging was a heterogeneous web-like structure in the hematoma cavity. Both children had undergone one side subduroperitoneal shunt for bilateral CSHs when infants. As a result, the opposite hematoma cavities persisted and developed into calcified CSHs after a couple of years. All three elderly patients with senile brain atrophy showed various systemic complications such as cerebral infarction, diabetes mellitus, leg ulceration, cirrhosis, and bleeding tendency. Craniotomy for removal of the hematoma and calcification achieved good results in all patients. Subdural space created by shunt, craniotomy, or brain atrophy and persisting for a certain period, and additional various brain damage such as microcirculatory disorder, meningitis, encephalitis, or premature delivery may be important in generating calcified or organized CSH.