Predictive Value of Various Atypical Cells for the Detection of Human Papillomavirus in Cervical Smears.

It is thought that numerous genotypes of human papillomavirus (HPV) are associated with various atypical cells, such as multinucleated cells, koilocytes, binucleated cells, parakeratotic cells, and giant cells, in the cervix. We previously showed the specificity of HPV genotypes for koilocytes and multinucleated cells. Therefore, in this study, we analyzed the association among HPV genotypes and binucleated cells, parakeratotic cells, and giant cells in Papanicolaou (Pap) smears. We detected HPV genotypes and atypical cells in 651 cases of liquid-based cytology with an abnormal Pap smear. The HPV genotypes associated with atypical cells were evaluated using stepwise logistic regression with backward elimination and a likelihood ratio test for model construction. Polymerase chain reaction was used to determine the HPV genotypes in whole liquid-based cytology samples and microdissected cell samples from Pap smear slides. Binucleated cells were significantly associated with HPV genotype 42. Moreover, parakeratotic cells were significantly associated with certain HPV genotypes, such as HPV40. However, it was difficult to detect specific HPV genotypes by the manual microdissection-polymerase chain reaction method despite the presence of binucleated cells and parakeratotic cells. Thus, the presence of binucleated cells, parakeratotic cells, and giant cells in Pap smears may not be predictive of cervical lesions above low-grade squamous intraepithelial lesions or infection with highly carcinogenic HPV genotypes.

Cytological features of human papillomavirus-infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2.

In reflex cytology, the presence of prominent nucleoli in immature metaplastic squamous cells (IM) may be underdiagnosed due to variations in interpretation. The aim of this study is to identify human papillomaviruses (HPVs) that infect IM clusters in cervical intraepithelial neoplasia 2 (CIN2) on Papanicolaou (Pap) smears to determine the cytological features of lesion-derived cells. Thirty-two patients with a simultaneous diagnosis of CIN2 on biopsy and high-grade squamous intraepithelial lesions (HSIL) on cytology as well as with IM clusters on HSIL smears were included. CIN2 tissues and HSIL and IM clusters on Pap smears were isolated by manual microdissection, and HPV types were identified by PCR-based genotyping. The nuclear area within the IM clusters was also measured. The median nuclear area of HPV-negative IM clusters was 48 µm2 , with a coefficient of variation (CV) of 0.20; those of HPV-positive clusters were 66 µm2 and 0.34, respectively. The cut-off values of the nuclear area and CV for HPV positivity were 62 µm2 and 0.25, respectively. IM clusters composed of cells with a nuclear area of more than twice that of neutrophils or cells with a wide variation in nuclear sizes are likely to be neoplastic cells caused by HPV.

Coronary microembolization sheep model by adjusting the number of microspheres based on coronary blood flow.

BACKGROUND: A heart failure (HF) model using coronary microembolization in large animals is indispensable for medical research. However, the heterogeneity of myocardial response to microembolization is a limitation. We hypothesized that adjusting the number of injected microspheres according to coronary blood flow could stabilize the severity of HF. This study aimed to evaluate the effect of microsphere injection based on the left coronary artery blood flow in an animal model. METHODS: Microembolization was induced by injecting different numbers of microspheres (polystyrene, diameter: 90 µm) into the left descending coronary artery of the two groups of sheep (400 and 600 times coronary blood flow [ml/min]). Hemodynamic parameters, the pressure-volume loop of the left ventricle, and echocardiography findings were examined at 0.5, 1.5, 3.5, and 6.5 h after microembolization. RESULTS: End-diastolic pressure and normalized heart rate increased over time, and were significantly higher in 600 × coronary blood flow group than those in 400 × coronary blood flow group (p = 0.04 and p < 0.01, respectively). The maximum rate of left-ventricular pressure rise and normalized stroke volume decreased over time, and were significantly lower in 600 × coronary blood flow group than those in 400 × coronary blood flow group (p < 0.01 and p < 0.01, respectively). The number of microspheres per coronary blood flow was significantly correlated with the decrease in stroke volume and the maximum rate of left ventricular pressure rise in 6.5 h (r = 0.74, p = 0.01 and r = 0.71, p = 0.02, respectively). CONCLUSIONS: Adjusting the number of injected microspheres based on the coronary blood flow enabled the creation of HF models with different degrees of severity.

Feasibility study of an artificial placenta system consisting of a loop circuit configuration extracorporeal membrane oxygenation with a bridge circuit in the form of the umbilical arterial-venous connection.

We developed a new artificial placenta (AP) system consisting of a loop circuit configuration extracorporeal membrane oxygenation (ECMO) with a bridge circuit designed to be applied to the fetus in the form of an umbilical arterial-venous connection. We aimed to evaluate the feasibility of the AP system by performing a hydrodynamic simulation using a mechanical mock circulation system and fetal animal experiment. The effect of the working condition of the AP system on the fetal hemodynamics was evaluated by hydrodynamic simulation using a mechanical mock circulation system, assuming the weight of the fetus to be 2 kg. The AP system was introduced to two fetal goats at a gestational age of 135 days. The general conditions of the experimental animals were evaluated. The mock simulation showed that in an AP system with ECMO in the form of an umbilical arterial-venous connection in series, it could be difficult to maintain fetal hemodynamics when high ECMO flow was applied. The developed AP system could have high ECMO flow with less umbilical blood flow; however, the possibility of excessive load on the fetal right-sided heart should be noted. In the animal experiment, kid 1 (1.9 kg) was maintained on the AP system for 12 days and allowed to grow to term. In kid 2 (1.6 kg), the AP system could not be established because of the occlusion of the system by a thrombus. The developed AP system was feasible under both in vitro and in vivo conditions. Improvements in the AP system and management of the general fetal conditions are essential.

Traditional Chinese medicine Jia Wei Gui Pi Tang improves behavioural and psychological symptoms of dementia and favourable positive emotions in patients.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. METHODS: Here, we performed a multicentre, randomised, observer-blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). RESULTS: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI-NH scores differed significantly between the two groups (one-way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI-NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t-test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t-test, P = 0.001), whereas there was no statistically significant change in the control group. CONCLUSION: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions.

Effects of the menstrual cycle on cytological false-negatives in women with persistent cervical intraepithelial neoplasia.

OBJECTIVES: False-negatives on cytology may be observed during follow-ups for patients with persistent cervical intraepithelial neoplasia (CIN); however, the underlying reasons are unknown, and the relationship between the intra-individual variability of false-negatives and the menstrual cycle phase has not been elucidated. Therefore, this study aimed to determine whether the menstrual cycle influences cytological results to maximise the accuracy of such tests. METHODS: A total of 154 liquid-based cytological (LBC) samples were obtained during follow-ups for 26 patients with CIN, and the relationship between cytological results and the menstrual cycle, which was classified into six phases, was analysed. RESULTS: All LBC smears were satisfactory, and 20 of 154 (13.0%) specimens were negative for intraepithelial lesions or malignancy (NILM). A statistically significant association was observed between the cytological results and the phase of the menstrual cycle, χ2 (2) = 19.322, P < 0.01. The association was moderately strong (Cramer's V = 0.354). The value of adjusted residuals showed a statistically significant increase in the NILM percentage as a cytological result during the early secretory phase (P < 0.01) and a statistically significant decrease in NILM during the menstrual and proliferative phases (P < 0.01). CONCLUSIONS: The present study revealed that false-negative cytological results were found to more likely to occur during the early secretory phase. More careful and precise microscopic observation of Pap smears collected at the early secretory phase may contribute to a reduction in the occurrence of false-negatives and improve cytological sensitivity.

Ocean currents and herbivory drive macroalgae-to-coral community shift under climate warming.

Coral and macroalgal communities are threatened by global stressors. However, recently reported community shifts from temperate macroalgae to tropical corals offer conservation potential for corals at the expense of macroalgae under climate warming. Although such community shifts are expanding geographically, our understanding of the driving processes is still limited. Here, we reconstruct long-term climate-driven range shifts in 45 species of macroalgae, corals, and herbivorous fishes from over 60 years of records (mainly 1950-2015), stretching across 3,000 km of the Japanese archipelago from tropical to subarctic zones. Based on a revised coastal version of climate velocity trajectories, we found that prediction models combining the effects of climate and ocean currents consistently explained observed community shifts significantly better than those relying on climate alone. Corals and herbivorous fishes performed better at exploiting opportunities offered by this interaction. The contrasting range dynamics for these taxa suggest that ocean warming is promoting macroalgal-to-coral shifts both directly by increased competition from the expansion of tropical corals into the contracting temperate macroalgae, and indirectly via deforestation by the expansion of tropical herbivorous fish. Beyond individual species' effects, our results provide evidence on the important role that the interaction between climate warming and external forces conditioning the dispersal of organisms, such as ocean currents, can have in shaping community-level responses, with concomitant changes to ecosystem structure and functioning. Furthermore, we found that community shifts from macroalgae to corals might accelerate with future climate warming, highlighting the complexity of managing these evolving communities under future climate change.

Koilocytic changes are not elicited by human papillomavirus genotypes with higher oncogenic potential.

Koilocytes are considered a common cytopathological effect in patients with human papillomavirus (HPV) infection. Thus, we aimed to elucidate whether koilocytes are common to all HPV infections. Liquid-based cytology samples from 651 patients with abnormal Papanicolaou (Pap) test results were used to analyze the presence of koilocytes and HPV genotype. HPV genotype was determined in complete liquid cytology samples and microdissected cell samples from Pap smear slides using the uniplex E6/E7 polymerase chain reaction method, which can detect 39 mucosal HPV genotypes. Koilocytes were found in 29.3% (191) of all patients. Logistical regression analysis of diverse HPV genotypes revealed that infections with low-risk HPV types (HPV-6b, HPV-40, HPV-42, HPV-61, HPV-74, HPV-89, and HPV-90), probably high-risk HPV types (HPV-53 and HPV-66), and high-risk types (HPV-39 and HPV-56) were significantly associated with the presence of koilocytes. However, HPV-16, HPV-18, and HPV-52, which have higher oncogenic potential, were not found to be associated with koilocytes. These results were confirmed by HPV genotyping using microdissected koilocytes in 27 patients.Most common high-risk types belonging to α-9 and α-7 genotypes appear to rarely induce koilocytic changes. Therefore, koilocytes may provide additional useful information for predicting the risk of progression to high-grade lesions.

Dramatic Performance by a Professional Actor for the Treatment of Patients with Behavioral and Psychological Symptoms of Dementia.

Behavioral and psychological symptoms of dementia (BPSD) challenge caregivers, leading to caregiver burden and subsequent nursing home or inpatient placement in a psychiatric hospital for dementia. Favorable positive emotions should be an important goal for the treatment of negative emotions of BPSD. Arts are one of the most profound areas to stimulate favorable emotions. We have asked a professional actor, who was not involved in the daily care and regular rehabilitations, to give a dramatic performance by reading selected stories as if the patients with BPSD felt to be in the audiences of a theater. We wondered whether a dramatic performance by the actor might be a way to respond to the complex needs of inpatients with BPSD, especially focused on favorable emotions. New inpatients (Alzheimer's disease, vascular dementia, or dementia with Lewy bodies) were randomly assigned to a control group (n = 20) and a dramatic performance group (n = 14) in Sendai Tomizawa Hospital, a psychiatric hospital for dementia, in Japan. Dramatic performances were performed for one and half hours once per week for 3 months. Neuropsychiatric Inventory for BPSD decreased in both groups and delightful emotional index (DEI) for favorable emotions increased in the intervention group but not in the control group after 3 months. At 3 months, there was an increase of DEI in intervention group compared with control group. We conclude that dramatic performance may be one of the appropriate interventions in patients with BPSD, as it appears to help in their favorable emotional state.

Antipsychotic drug use and favourable natures of emotional functions in patients with dementia.

AIM: To characterise the effects of antipsychotics on brain functions of patients with behavioural psychological symptoms of dementia (BPSD). METHODS: Studies were performed during 6 weeks of intervention with either a nonantipsychotic drug (group A, n = 38) or an antipsychotic drug (group B, n = 10). RESULTS: Neuropsychiatric Inventory scores were significantly decreased in both groups. Scores on the Mini-Mental State Examination did not change with intervention. By contrast, favourable natures of emotional functions, scored using the Delightful Emotional Index of 10 items, were significantly lower in the antipsychotic drug treatment group B relative to scores in the nonantipsychotic drug treatment group A. CONCLUSIONS: Antipsychotics reduce favourite emotions as well as BPSD, and this should be considered in prescribing medications for patients with dementia.

Multiple Spontaneous Iliac and Femoral Arteriovenous Fistulas.

An arteriovenous fistula (AVF) in a limb involves an abnormal connection between a limb artery and vein. It can be due to trauma or iatrogenic injury. Traumatic AVFs can be caused by penetrating or gunshot injuries to the limb, whereas iatrogenic causes include catheter intervention to the groins or open surgery of the inguinal space. By contrast, the occurrence of multiple spontaneous AVFs is rare. We report a case of endovascular therapy for multiple spontaneous AVFs between the iliac artery and the vein, common femoral artery and the vein, superficial artery and the saphenous vein, and deep femoral artery and the vein.

Foot pressure analysis of gait pattern in older Japanese females requiring different personal care support levels.

[Purpose] This study evaluated gait parameters and foot pressure in two regions of the feet among older females with different personal care support needs to analyze factors that contribute to higher support requirements. [Subjects and Methods] Thirty-two older females were divided into support-need and care-need level groups. Gait parameters (speed, cadence, step length, step width, gait angle, toe angle, double support phase, swing phase, and stance phase) and foot pressure during a 5-m walk were measured and analyzed in the two groups. [Results] The percentage of the double support phase on both feet and the right stance phase were significantly higher in the care-need level group, while that of the right swing phase was significantly lower than that of the support-need level group. Additionally, the phase showing peak pressure on the left rear foot was significantly delayed and the left forefoot pressure in the terminal stance was significantly lower in the care-need level group than in the support-need level group. [Conclusion] These findings show that the temporal duration parameters and foot pressure on a particular side were significantly different between the two groups and suggest that these differences were associated with a higher care level.

Improving the interpretability of climate landscape metrics: An ecological risk analysis of Japan's Marine Protected Areas.

Conservation efforts strive to protect significant swaths of terrestrial, freshwater and marine ecosystems from a range of threats. As climate change becomes an increasing concern, these efforts must take into account how resilient-protected spaces will be in the face of future drivers of change such as warming temperatures. Climate landscape metrics, which signal the spatial magnitude and direction of climate change, support a convenient initial assessment of potential threats to and opportunities within ecosystems to inform conservation and policy efforts where biological data are not available. However, inference of risk from purely physical climatic changes is difficult unless set in a meaningful ecological context. Here, we aim to establish this context using historical climatic variability, as a proxy for local adaptation by resident biota, to identify areas where current local climate conditions will remain extant and future regional climate analogues will emerge. This information is then related to the processes governing species' climate-driven range edge dynamics, differentiating changes in local climate conditions as promoters of species range contractions from those in neighbouring locations facilitating range expansions. We applied this approach to assess the future climatic stability and connectivity of Japanese waters and its network of marine protected areas (MPAs). We find 88% of Japanese waters transitioning to climates outside their historical variability bounds by 2035, resulting in large reductions in the amount of available climatic space potentially promoting widespread range contractions and expansions. Areas of high connectivity, where shifting climates converge, are present along sections of the coast facilitated by the strong latitudinal gradient of the Japanese archipelago and its ocean current system. While these areas overlap significantly with areas currently under significant anthropogenic pressures, they also include much of the MPA network that may provide stepping-stone protection for species that must shift their distribution because of climate change.

Popliteal Artery Pseudoaneurysm Caused by Osteochondroma.

A 16-year-old boy developed pulsating pain and dysesthesia in his right knee. Computed tomography showed a large aneurysm in the right upper popliteal artery and a spiked bone tumor arising from the right distal femoral shaft. Pseudoaneurysm due to osteochondroma was suspected, and the patient underwent emergency surgery. A 2-mm pinhole was detected in the arterial wall behind the tumor. After resection of the tumor, the damaged arterial wall was removed, and the defect was repaired using a saphenous vein patch. We suggest that patch repair is preferable to direct closure or end-to-end anastomosis to prevent recurrent pseudoaneurysm at a later time, even if the defect is small.

Endovascular Treatment for Proximal Anastomotic Pseudoaneurysm after Total Arch Replacement in Behcet's Disease.

A 17-year-old patient underwent total arch replacement for aortic arch aneurysm due to vascular Behcet's disease (BD). Follow-up computed tomography, performed 6 months after the operation, demonstrated pseudoaneurysm formation at the proximal anastomotic site. We performed endovascular treatment and used a short stent graft that was originally designed for abdominal aortic aneurysm. To avoid the occlusion of the coronary or brachiocephalic artery (BCA) due to stent graft migration, we used right ventricular rapid pacing and BCA ballooning. Thus, we believe that endovascular treatment can be used for anastomotic complications in the ascending aorta after open surgery for connective tissue disorders including BD.

[Impact of Patent False Lumen at the Descending Aorta after Total Aortic Replacement for Acute type A Aortic Dissection].

OBJECTIVE: Acute type A aortic dissection remains one of the most challenging diseases facing cardiovascular surgeons. It is associated with high mortality and morbidity. However, prevention of disease process progression in the residual dissected aorta is an important aspect of the patient's long-term outcome. The aim of this study was to examine the impact of patent false lumen at the descending aorta after total arch replacement for acute type A aortic dissection. METHODS: Between December 1994 and August 2014, a total of 145 patients underwent total arch replacement for acute type A aortic dissection. The hospital mortality was 5.5%.Of these 145 patients, 33 had patent false lumen at the descending aorta after surgery, and 94 had thrombosed false lumen. The perioperative variables and late results were statistically analyzed. RESULTS: The incidence of residual thoracic patent false lumen was 26.0%.No significant difference was observed in the cumulative survival rate between groups. The patent false lumen group was associated with significant higher risk of the descending aortic event than the thrombosed group. By multivariate analysis, younger age and non-resection of the primary tear were significant prospective factors for the patent false lumen at the descending aorta. CONCLUSIONS: The patent false lumen at the descending aorta was associated with the late aortic critical events after total arch replacement for aortic dissection.

Inhibition of growth in a rabbit VX2 thigh tumor model with intraarterial infusion of carbon dioxide-saturated solution.

PURPOSE: To evaluate the efficacy of intraarterial infusion of CO2-saturated solution in rabbit VX2 thigh tumors. MATERIALS AND METHODS: Fourteen Japanese white rabbits had VX2 tumors implanted in the right femoral muscle 3 weeks before intraarterial infusion. Rabbits were divided into control and CO2 groups (n = 7 each). Fifty milliliters of solution (saline solution and CO2-saturated solution for the control and CO2 groups, respectively) was administered via a 24-gauge catheter in the ipsilateral iliac artery close to the feeding artery of the VX2 tumor. All rabbits were killed for tumor harvest on day 3 after the procedure. Tumor volume was evaluated with in vivo direct caliper measurement and contrast-enhanced computed tomography (CT). Tumor apoptotic changes were examined by DNA fragmentation assay and immunoblot analysis. The tumor growth ratio and apoptotic cell rate were analyzed. RESULTS: Body weight was equally increased in both groups, but the mean tumor growth ratio was significantly decreased in the CO2 group compared with the control group (-9.5% ± 7.9 vs 27.2% ± 6.6 and 4.1% ± 4.4 vs 35.7% ± 4.5 measured by calipers and contrast-enhanced CT, respectively; P < .01). Apoptotic activity in the CO2 group was higher than in the control group (number of apoptotic cells per area, 215.0 ± 58.7 vs 21.8 ± 5.4; adjusted relative density of cleaved caspase-3, 0.23 ± 0.07 vs 0.04 ± 0.01; P < .01). CONCLUSIONS: Intraarterial infusion of CO2-saturated solution inhibits rabbit VX2 thigh tumor growth by activation of apoptotic cell death through cleaved caspase-3 upregulation.

Utility of 320-detector row CT for diagnosis and therapeutic strategy for paraclinoid and intracavernous aneurysms.

BACKGROUND: The aim of this study was (1) to assess the diagnostic accuracy of 320-detector row computed tomography (CT) for paraclinoid and intracavernous aneurysms, and (2) to investigate whether this method provides sufficient information for surgery. METHODS: A total of 14 patients with 16 unruptured proximal ICA aneurysms underwent three-dimensional CT angiography (3D-CTA) fusion imaging, which was created by superimposing 3D-CT venography data and/or 3D-bone data onto 3D-CTA data using 320-detector row CT, magnetic resonance imaging (MRI), and 3D digital subtraction angiography (DSA). The images of each modality were assessed using intraoperative findings as the reference standard. RESULTS: All aneurysms were clearly visualized on 320-detector row CT. Bone subtraction and arterio-venous discrimination were accurate. On 3D-CTA fusion images, 11 aneurysms were diagnosed as "extracavernous" and five as "intracavernous". No discordance in aneurysm location between the 3D-CTA fusion images and the intraoperative findings was found. In contrast, discordance between MRI and intraoperative findings were found in five of the 16 cases (31%), which was significantly more frequent than with 3D-CTA (p = 0.043). The findings DSA, which was performed in nine patients, were also in excellent agreement with the intraoperative findings. However, 3D-CTA fusion imaging provided more comprehensive information, including venous and osseous structures, than 3D-DSA. The 320-detector row CTA after surgery demonstrated a clear relationship between the clip and aneurysmal neck with notably few artifacts, which suggested the utility of this modality for postoperative assessment. CONCLUSIONS: The 320-detector row CT provided high accuracy for the diagnosis of paraclinoid and intracavernous aneurysms. This technique also provided comprehensive depiction of the aneurysms and surrounding structures. Therefore, this modality might be useful for the diagnosis of the paraclinoid and intracavernous aneurysms and for developing a surgical treatment plan.

Emotional function in dementia patients.

Behavioural and psychological symptoms of dementia, which can be considered as hyperreactivity of the emotional functioning of dementia, can be alleviated or aggravated by the behavioural and psychological symptoms of the caregiver. Comfortable stimulations of emotional function through sensory stimulations are effective methods for alleviating behavioural and psychological symptoms of dementia. Although cognitive function deteriorates with age, emotional function is often retained even in advanced years. Thus, it is recommended that care in patients with dementia be focused mainly on the stimulation of emotional function (e.g. sympathy and empathy, which are human traits), rather than relying solely on the stimulation of cognitive function.