Persistent influence of precession on northern ice sheet variability since the early Pleistocene.

Prior to ~1 million years ago (Ma), variations in global ice volume were dominated by changes in obliquity; however, the role of precession remains unresolved. Using a record of North Atlantic ice rafting spanning the past 1.7 million years, we find that the onset of ice rafting within a given glacial cycle (reflecting ice sheet expansion) consistently occurred during times of decreasing obliquity whereas mass ice wasting (ablation) events were consistently tied to minima in precession. Furthermore, our results suggest that the ubiquitous association between precession-driven mass wasting events and glacial termination is a distinct feature of the mid to late Pleistocene. Before then (increasing), obliquity alone was sufficient to end a glacial cycle, before losing its dominant grip on deglaciation with the southward extension of Northern Hemisphere ice sheets since ~1 Ma.

Therapeutic Effect of Sirolimus for Lymphangioleiomyomatosis Remaining in the Abdominopelvic Region After Lung Transplantation: A Case Report.

PURPOSE: Sirolimus (SRL) is used to treat pulmonary lymphangioleiomyomatosis (P-LAM). There is limited evidence that SRL has systemic efficacy for the patients with extrapulmonary lymphangioleiomyomatosis (E-LAM) remaining after lung transplantation (LT) for P-LAM. This report examines the efficacy of SRL treatment for the patient with E-LAM remaining after an LT for P-LAM. CASE SUMMARY: The course of the patient's recovery from an LT for P-LAM was complicated by lymphedema in the left femoral region that was caused by two E-LAM lesions remaining in the left pelvic cavity and in the retroperitoneal area. After the LT was performed, the patient started SRL treatment to reduce the E-LAM lesions. The daily SRL dose, selected based on the standard SRL dose for P-LAM, was initiated at 1 mg/d and was maintained at 2 mg/d. The remaining E-LAM lesions and lymphedema in the left femoral region improved in approximately 9 months after the LT with the administration of both SRL and the standard immunosuppressive therapy used by Okayama University Hospital, including tacrolimus, mycophenolate mofetil, and prednisolone. The SRL and tacrolimus trough concentrations in whole blood were maintained within the therapeutic window for the next 1.5 years after initiation of SRL treatment. The patient experienced no severe adverse events that required discontinuation of the SRL treatment during this time. CONCLUSION: The patients with remaining E-LAM lesions may receive SRL treatment to improve the quality of life after LT for P-LAM as effective therapy in cases where the patient's recovery is complicated by E-LAM lesions.

Does Regular Post-exercise Cold Application Attenuate Trained Muscle Adaptation?

This study examined the effects of regular post-exercise cold application on muscular and vascular adaptations induced by moderate-intensity resistance training. 14 male subjects participated in resistance training: 5 sets of 8 wrist-flexion exercises at workload of 70-80% of the single repetition maximum, 3 times a week for 6 weeks. 7 subjects immersed their experimental forearms in cold water (10±1°C) for 20 min after wrist-flexion exercises (cooled group), and the other 7 served as control subjects (noncooled group). Measurements were taken before and after the training period; wrist-flexor thickness, brachial-artery diameter, maximal muscle strength, and local muscle endurance were measured in upper extremities. Wrist-flexor thicknesses of the experimental arms increased after training in both groups, but the extent of each increase was significantly less in the cooled group compared with the noncooled group. Maximal muscle strength and brachial-artery diameter did not increase in the cooled group, while they increased in the noncooled group. Local muscle endurance increased in both groups, but the increase in the cooled group tended to be lower compared to the noncooled group. Regular post-exercise cold application to muscles might attenuate muscular and vascular adaptations to resistance training.

Nanocoating for biomolecule delivery using layer-by-layer self-assembly.

Since its introduction in the early 1990s, layer-by-layer (LbL) self-assembly of films has been widely used in the fields of nanoelectronics, optics, sensors, surface coatings, and controlled drug delivery. The growth of this industry is propelled by the ease of film manufacture, low cost, mild assembly conditions, precise control of coating thickness, and versatility of coating materials. Despite the wealth of research on LbL for biomolecule delivery, clinical translation has been limited and slow. This review provides an overview of methods and mechanisms of loading biomolecules within LbL films and achieving controlled release. In particular, this review highlights recent advances in the development of LbL coatings for the delivery of different types of biomolecules including proteins, polypeptides, DNA, particles and viruses. To address the need for co-delivery of multiple types of biomolecules at different timing, we also review recent advances in incorporating compartmentalization into LbL assembly. Existing obstacles to clinical translation of LbL technologies and enabling technologies for future directions are also discussed.

Gingival condition and tooth-brushing behavior after alcohol consumption.

BACKGROUND AND OBJECTIVE: Various studies have reported the relationship between alcohol consumption and gingival condition. However, they focus on the direct effects of alcohol consumption or alcohol sensitivity on gingival condition, and it is unclear how oral health behaviors relate these relationships. The aims of this study were to assess the inter-relationships between gingival condition, tooth-brushing behavior after drinking alcohol and alcohol sensitivity in university students who drink more than once per week on average. MATERIAL AND METHODS: A total of 808 students (541 males, 267 females) that habitually consume alcohol were analyzed. The disease activity of gingival condition was assessed as the percentage of bleeding on probing (%BOP). Additional information regarding alcohol sensitivity and oral health behaviors, including tooth-brushing behavior after drinking, were also collected. RESULTS: Thirteen percent of the current participants reported neglecting tooth-brushing after drinking, and their alcohol consumption was higher than those who did not neglect tooth-brushing. Logistic regression analysis showed that high %BOP (%BOP ≥ 20) was associated with male (OR = 1.53; 95% CI, 1.01-2.33), neglect of tooth-brushing after drinking (OR = 2.60; 95% CI, 1.20-5.61) and debris index (OR = 8.38; 95% CI, 4.24-16.60) in participants with low alcohol sensitivity. In participants with high alcohol sensitivity, high %BOP was associated with debris index (OR = 7.60; 95% CI, 3.12-18.51), but not with any oral health behaviors. CONCLUSIONS: The study revealed that alcohol consumption was indirectly related to gingival disease activity through the neglect of tooth-brushing after drinking alcohol in university students with low alcohol sensitivity.

Relationship between xerostomia and gingival condition in young adults.

BACKGROUND AND OBJECTIVE: Xerostomia is a subjective symptom of dryness in the mouth. Although a correlation between xerostomia and oral conditions in the elderly has been reported, there are few such studies in the young adults. The aim of this study was to examine the relationship of xerostomia with the gingival condition in university students. MATERIAL AND METHODS: A total of 2077 students (1202 male subjects and 875 female subjects), 18-24 years of age, were examined. The disease activity and severity of the gingival condition were assessed as the percentage of teeth with bleeding on probing (%BOP) and the presence of teeth with probing pocket depth of ≥ 4 mm, respectively. Additional information on xerostomia, oral health behaviors, coffee/tea intake and nasal congestion was collected via a questionnaire. Path analysis was used to test pathways from xerostomia to the gingival condition. RESULTS: One-hundred and eighty-three (8.8%) students responded that their mouths frequently or always felt dry. Xerostomia was related to %BOP and dental plaque formation, but was not related to the presence of probing pocket depth ≥ 4 mm. In the structural model, xerostomia was related to dental plaque formation (p < 0.01), and a lower level of dental plaque formation was associated with a lower %BOP. Xerostomia was associated with coffee/tea intake (p < 0.01) and nasal congestion (p < 0.001). CONCLUSION: Xerostomia was indirectly related to gingival disease activity through the accumulation of dental plaque. Nasal congestion and coffee/tea intake also affected xerostomia. These findings suggest that xerostomia should be considered in screening for gingivitis risk in young adults.

Tofogliflozin, a sodium/glucose cotransporter 2 inhibitor, attenuates body weight gain and fat accumulation in diabetic and obese animal models.

OBJECTIVE: Tofogliflozin, a highly selective inhibitor of sodium/glucose cotransporter 2 (SGLT2), induces urinary glucose excretion (UGE), improves hyperglycemia and reduces body weight in patients with Type 2 diabetes (T2D). The mechanisms of tofogliflozin on body weight reduction were investigated in detail with obese and diabetic animal models. METHODS: Diet-induced obese (DIO) rats and KKAy mice (a mouse model of diabetes with obesity) were fed diets containing tofogliflozin. Body weight, body composition, biochemical parameters and metabolic parameters were evaluated. RESULTS: In DIO rats tofogliflozin was administered for 9 weeks, UGE was induced and body weight gain was attenuated. Body fat mass decreased without significant change in bone mass or lean body mass. Food consumption (FC) increased without change in energy expenditure, and deduced total calorie balance (deduced total calorie balance=FC-UGE-energy expenditure) decreased. Respiratory quotient (RQ) and plasma triglyceride (TG) level decreased, and plasma total ketone body (TKB) level increased. Moreover, plasma leptin level, adipocyte cell size and proportion of CD68-positive cells in mesenteric adipose tissue decreased. In KKAy mice, tofogliflozin was administered for 3 or 5 weeks, plasma glucose level and body weight gain decreased together with a reduction in liver weight and TG content without a reduction in body water content. Combination therapy with tofogliflozin and pioglitazone suppressed pioglitazone-induced body weight gain and reduced glycated hemoglobin level more effectively than monotherapy with either pioglitazone or tofogliflozin alone. CONCLUSION: Body weight reduction with tofogliflozin is mainly due to calorie loss with increased UGE. In addition, tofogliflozin also induces a metabolic shift from carbohydrate oxidation to fatty acid oxidation, which may lead to prevention of fat accumulation and inflammation in adipose tissue and liver. Tofogliflozin may have the potential to prevent obesity, hepatic steatosis and improve insulin resistance as well as hyperglycemia.

Effects of rain on energy metabolism while running in a cold environment.

Environmental factors tend to influence the performance of individuals who exercise for extended periods. The present study aimed to determine energy metabolism while running in cold, wet conditions using a climatic chamber that can precisely simulate rainy conditions. 7 healthy men (age, 23.3±2.9 (SD) y; height, 168.6±7.5 cm; weight, 65.9±8.1 kg; V. O2max, 52.0±5.7 mL·kg - 1·min - 1) ran on a treadmill at 70% ˙VO2max intensity for 30 min in a climatic chamber at an ambient temperature of 5°C in the presence (RAIN) or absence (CON) of 40 mm/h of precipitation. Expired air, esophageal temperature, heart rate, mean skin temperature, rating of perceived exertion and blood samples were measured. Esophageal temperature and mean skin temperature were significantly lower (P<0.05) in RAIN than in CON all. Minute ventilation, oxygen consumption and levels of plasma lactate and norepinephrine were significantly higher (P<0.05) in RAIN than in CON. In conclusion, the higher oxygen consumption and plasma lactate in RAIN indicated that energy demand increases when running in cold conditions.

Activations of mitogen-activated protein kinases and regulation of their downstream molecules after rat lung transplantation from donors after cardiac death.

OBJECTIVES: Accepting organs donated after cardiac death (DCD) is an effective approach to the donor shortage. However, lung transplantations from DCD donors show severe rapid pulmonary graft dysfunction (PGD) followed by warm ischemia-reperfusion injury (IRI). This study sought to clarify the molecular mediators in warm IRI, including activation of mitogen-activated protein kinase (MAPK) and the downstream cascades. METHODS: We performed single left lung transplantation using organs from male Sprague-Dawley rats after 0 (CIT group), 30 (30WIT group), or 180 (180WIT group) minutes of warm ischemia time. Pulmonary graft functions were estimated by blood gas analysis. At 1 hour after reperfusion, the phosphorylation status of MAPKs (ERK, p38, and JNK) and the gene expression levels of transcription factors (Egr-1 and ATF-3) and immune mediators (MCP-1, MIP-2, PAI-1, ICAM-1, TNF-α, IL-1ß, IL-6, and COX-2) in the grafts were examined using Western blotting and real-time polymerase chain reaction assays. RESULTS: Severe PGD was observed in the 180WIT group compared with transplanted lungs in the other groups, which exhibited good pulmonary graft function. ERK and JNK activations, as well as mRNA levels of transcription factors (Egr-1 and ATF3) significantly increased with greater warm ischemic times. The pattern of JNK activation correlated with the severity of PGD. MCP-1, ICAM-1, IL-1ß, IL-6, and COX-2 were also up-regulated among the 180WIT group, although MIP-2 and PAI-1 showed no significant differences among the groups. CONCLUSIONS: We suggest that the ERK and JNK pathways may play important roles to induce the injury caused by prolonged warm ischemia followed by reperfusion in the setting of lung transplantation from DCD donors.

Less maintenance immunosuppression in lung transplantation following hematopoietic stem cell transplantation from the same living donor.

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.

A multiple shock tube and chemical kinetic modeling study of diethyl ether pyrolysis and oxidation.

The pyrolysis and oxidation of diethyl ether (DEE) has been studied at pressures from 1 to 4 atm and temperatures of 900-1900 K behind reflected shock waves. A variety of spectroscopic diagnostics have been used, including time-resolved infrared absorption at 3.39 mum and time-resolved ultraviolet emission at 431 nm and absorption at 306.7 nm. In addition, a single-pulse shock tube was used to measure reactant, intermediate, and product species profiles by GC samplings at different reaction times varying from 1.2 to 1.8 ms. A detailed chemical kinetic model comprising 751 reactions involving 148 species was assembled and tested against the experiments with generally good agreement. In the early stages of reaction the unimolecular decomposition and hydrogen atom abstraction of DEE and the decomposition of the ethoxy radical have the largest influence. In separate experiments at 1.9 atm and 1340 K, it is shown that DEE inhibits the reactivity of an equimolar mixture of hydrogen and oxygen (1% of each).

[Treatment strategy and outcomes of invading apical lung cancer].

Invading apical lung cancers are generally the non-small-cell lung cancers (NSCLCs) which involve the apex of the chest wall. These tumors should be classified into 2 types based on the main location of tumor because of the difference of involved surrounding structures ; (1) the superior sulcus tumor origi nally termed Pancoast tumor which involves posterior region of the apex and (2) the anterior apical tumor which involves anterior region of the apex. Previously, these NSCLCs were considered to be inoperable showing a dismal prognosis. With the development of combined modality therapies for locally advanced NSCLCs, the prognosis of invading apical NSCLCs has been improved, especially since intro duction of the neoadjuvant chemoradiotherapy. Surgical resection for invading apical NSCLCs is 1 of challenging procedures for thoracic surgeons. The point is the anatomical complication of the small apex surrounding vital structures. Several approaches have been developed such as the posterior Paul-son's approach or anterior Masaoka's approach. In particular, the approach from anterior chest has been modified or devised to achieve safe and complete resection of tumors invading anterior structures like subclavian vessels. In this article, we reviewed our 13 cases of invading apical NSCLCs, especially from the view point of surgical approach. Thoracic surgeons should understand the properties of each approach and master them for complete resection avoiding serious complications.

[Second chondrosarcoma of the rib four years after the initial operation; report of a case].

Chondrosarcoma of rib origin is rare accounting for about 2% of all chondrosarcomas. A 63-year-old female with an anterior chest wall tumor was referred to our institution for surgical treatment of a 2nd chondrosarcoma in the right 2nd rib 4 years after the initial surgery for its primary lesion. Computed tomography (CT) showed a low density mass, 36 mm in diameter, arising from the 2nd rib. An extended excision of the chest wall including the tumor was performed followed by the reconstruction of the chest wall with double Marlex Mesh. As she had already undergone the reconstruction of the chest wall for its primary lesion, this reconstruction was her 2nd one. Nevertheless, her respiratory condition was well preserved with no significant chest deformity. Wide excision and reconstruction could be performed for the 2nd arising chondrosarcoma of the rib even after the initial lesion was already widely removed and reconstructed.

Effects of petrissage massage on fatigue and exercise performance following intensive cycle pedalling.

OBJECTIVE: Petrissage is assumed to influence circulation as well as interstitial drainage of both superficial and deep tissues. To study its effect it was applied between consecutive bouts of supramaximal exercise performed by the lower leg muscles. METHODS: Subjects were 11 healthy female students actively engaged in sports. Exercise bouts of ergometer cycling at loads determined individually (0.075 kp x body weight (kg)) for 5 s repeated eight times at intervals of 20 s had to be performed twice on an experimental day with 35 min intermittent bed rest. Each subject was investigated on two occasions with a minimum interval of 1 week, once without (control, CO) and once with 10 min petrissage (massage, MA) of the exercising lower leg during the bed rest phase. Effects of exercise bouts on blood lactate, muscle stiffness and perceived lower limb fatigue and their recovery before and after the second exercise bout were determined. RESULTS: For the first exercise bouts total power did not differ between MA and CO. Courses of blood lactate did not differ between MA and CO. However, recovery from measured muscle stiffness (p<0.05) and perceived lower limb fatigue (p<0.05) were more pronounced and total power during the second exercise bout was enhanced (p<0.01) in MA as compared with CO subjects. CONCLUSION: Petrissage improved cycle ergometer pedalling performance independent of blood lactate but in correlation with improved recovery from muscle stiffness and perceived lower limb fatigue.

Measuring tooth mobility with a no-contact vibration device.

BACKGROUND AND OBJECTIVE: Mechanical parameters obtained from the frequency response at tooth vibration informs of various periodontal tissue conditions. An electromagnetic vibration device was investigated for measuring tooth mobility using mechanical parameters obtained from the frequency response characteristics of an experimental tooth model. This electromagnetic vibration device was able to assess the overall condition of periodontal tissue associated with the alteration of each parameter. In this study, reliability and effects of bottom thicknesses of simulated periodontal ligament relative to mechanical parameters were analysed. MATERIAL AND METHODS: Measurement of tooth vibration was performed by an electromagnetic vibration device on experimental tooth models with different bottom thicknesses of simulated periodontal ligament. Using an electromagnetic vibration device, the mechanical parameters resonant frequency, elastic modulus and coefficient of viscosity were calculated from the frequency response characteristics derived from tooth vibration by an electromagnetic force. Variation of those parameters was investigated under four different experimental conditions and the implications of the results were discussed. RESULTS: An electromagnetic vibration device clearly detected three mechanical parameters in all experimental conditions. The resonant frequency and the elastic modulus decreased with increasing bottom thickness. However, no significant difference in the coefficient of viscosity was observed among the experimental conditions. CONCLUSION: Assessment of tooth mobility using mechanical parameters of an electromagnetic vibration device reproduced fine details of various simulated periodontal ligament conditions. Variation in the parameters resonant frequency, elastic modulus and coefficient of viscosity might be useful in evaluating changes of components in periodontal tissues.

[Cytomegalovirus infection in lung transplantation; current status, detection, prophylactic treatment].

The control of the postoperative infectious disease is one of the important elements in transplantation. Among them, the control of the cytomegalovirus (CMV) infection may be said the most important in the management of the transplant recipient who is under the immunosuppression. This time, we review the status of the pre-transplant CMV infection in the donors and recipients of both brain-death and living-related lung transplantation that we performed, and report our prophylactic treatment for CMV infection and its results. The CMV positive rate of the recipients and donors of the lung transplantation that we experienced in Okayama University was 87%. We experienced 4 cases that developed CMV infection after lung transplantation. However, there is no case that died of a CMV-related infectious disease after lung transplantation to date. By the CMV mismatch transplant, it seemed that the frequency of the postoperative CMV disease was high in comparison with the transplant of recipient CMV (+). But, the control of the CMV infection after lung transplantation is thought to be possible if we give a proper prophylactic treatment even in CMV mismatch transplantation.

[Phrenic nerve paralysis following lung transplantation].

Phrenic nerve paralysis is a well-documented complication of cardiac operation, but there is less commonly reported after lung transplantation. A retrospective study of 49 lung transplantation was done at Okayama University Hospital. Phrenic nerve paralysis (unilateral in 3 patients and bilateral in 1) was found in 4 patients (8.2%). All of these paralyses were transiently recovered. The average length of ventilation, intensive care unit stay and hospitalization for recipients with phrenic nerve paralysis was not significantly longer than the other (no diaphragmatic paralysis) recipients, but there was a tendency to be longer. Diaphragmatic paralysis is most likely related to difficulty in detecting the phrenic nerve caused by adhesions, injury due to dissection, thermal injury by electrocartery, or local topical hypothermia using ice-slush. Therefore, it is important to take care of avoiding the injury of the nerve during the operation.

[Living-donor lobar lung transplantation for infectious lung diseases].

The rate of infection among lung transplant recipients is several times higher than that among recipients of other organs and is most likely related to the exposure of the allograft to the external environment. Meticulous peri-operative management is mandatory in performing living-donor lobar lung transplantation for patients with infectious lung diseases. All 5 patients with end-stage infectious lung diseases are currently alive for 17-104 months after receiving living-donor lobar lung transplantation at Okayama University Hospital.

[Extensive traumatic pneumomediastinum. without injuries of organs in the thorax: report of a case].

A 57-year-old man was accidentally hit by concrete blocks weighing 3 tons on his right side, and was admitted to a hospital. The radiologic findings taken immediately after trauma demonstrated pneumo-mediastinum, subcutaneous emphysema with multiple rib fractures and right clavicle fracture. At computed tomography (CT) scan 16 hours after trauma, pneumomediastinum and subcutaneous emphysema turned out to be worsened with an increased bilateral pleural effusion. An emergency thoracotomy revealed no abnormalities of trachea or esophagus, and neither bronchoscopy or esophagogastroscopy, showed injuries anywhere inside. The chest cavities and mediastinum were washed well with 3 liters of saline solution. The patient had a good course after surgery without any complications, and was discharged at the 18th hospital day. Mediastinal drainage by an emergency operation should always be a choice to a patient having a progressively worsening pneumomediastinum which might cause tachycardia, low blood pressure, and severe dyspnea due to compression of blood vessels and trachea.