Association between glomerular filtration rate and plasma N-terminal pro-atrial natriuretic peptide concentration in dogs.

OBJECTIVES: To investigate the association between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate in dogs. MATERIALS AND METHODS: Dogs were classified into four categories by bodyweight. Dogs were divided into four groups (Groups 1 to 4) based on glomerular filtration rate estimates using plasma iohexol clearance per bodyweight category. Generalised linear models were built to explore the relationship between plasma N-terminal pro-atrial natriuretic peptide concentration and glomerular filtration rate and the effect of confounders on plasma N-terminal pro-atrial natriuretic peptide concentration. RESULTS: Fifty-three dogs were included (Group 1, 25; Group 2, seven; Group 3, five; and Group 4, 16). The medians (interquartile range) N-terminal pro-atrial natriuretic peptide concentrations for Groups 1 to 4 were 7224 pg/mL (4766 to 10,254 mg/dL), 8958 pg/mL (4935 to 11,271 mg/dL), 9280 pg/mL (9195 to 10,384 mg/dL) and 12,683 pg/mL (9133 to 19,217 mg/dL), respectively. Group 4, estimated to have the highest reduction in glomerular filtration rate, had a higher plasma N-terminal pro-atrial natriuretic peptide concentration than Groups 1 to 3. Based on the final generalised linear model, influencing factors for plasma N-terminal pro-atrial natriuretic peptide concentration were plasma iohexol clearance (-0.136; 95% confidence interval, -0.227 to -0.046) and bodyweight (-0.058; 95% confidence interval, -0.098 to -0.018). CLINICAL SIGNIFICANCE: N-terminal pro-atrial natriuretic peptide concentration is associated with the glomerular filtration rate.

Handlebody decompositions of three-manifolds and polycontinuous patterns.

We introduce the concept of a handlebody decomposition of a three-manifold, a generalization of a Heegaard splitting, or a trisection. We show that two handlebody decompositions of a closed orientable three-manifold are stably equivalent. As an application to materials science, we consider a mathematical model of polycontinuous patterns and discuss a topological study of microphase separation of a block copolymer melt.

Depression prevention in healthcare workers during the COVID-19 pandemic.

BACKGROUND: Few studies have assessed depression in healthcare workers (HCWs) in Japan owing to the coronavirus disease 2019 (COVID-19) pandemic, and no studies have proposed effective interventions to help support their mental health. AIMS: To test the hypothesis that enhancing access to mental healthcare professionals helps to improve HCWs' mental health. METHODS: This cross-sectional study assessed depressive symptoms in HCWs at three hospitals in Osaka prefecture between May and July, 2020. The survey obtained information on HCWs' mental state and related situations/perceptions. Multivariable logistic regression analysis was performed to identify factors associated with depressive symptoms. RESULTS: Of the 3291 eligible HCWs, 1269 (39%) completed the survey. Of all HCWs, 87 (7%) were physicians, and 700 (55%) were nurses. A total of 181 (14%) HCWs had moderate-to-severe symptoms of depression. Being a frontline worker was not significantly associated with depressive symptoms (odds ratio: 0.86 [95% confidence intervals: 0.54-1.37], P = 0.50). The unwillingness to consult with anyone was significantly associated with more severe depressive symptoms (1.70 [1.10-2.63], P < 0.01). HCWs who had no opportunity to confide in family/friends (1.66 [1.10-2.52], P < 0.01) or colleagues/supervisors (3.19 [2.22-4.58], P < 0.001) were significantly more likely to have depressive symptoms. CONCLUSIONS: Being a frontline HCW in a Japanese hospital treating patients with COVID-19 was not significantly associated with having depressive symptoms. The study highlights that encouraging daily communication with close persons (family, friends, colleagues and supervisors), rather than improving access to mental health professionals, might help to prevent depression in HCWs during the COVID-19 pandemic.

Evaluation of the progression of non-azotemic proteinuric chronic kidney disease in dogs.

Proteinuria is a recognized risk factor for progression of canine chronic kidney disease (CKD). However, the prognosis of non-azotemic proteinuric CKD in dogs has been studied only to a limited extent. Moreover, the degree to which proteinuria should be decreased to delay CKD progression remains unknown. The purposes of this study were (1) to identify factors associated with disease progression and (2) to investigate the degree of proteinuria, albuminuria, and blood pressure during the course of treatment associated with the progression using time-averaged urine protein:creatinine ratio (UPC) and urine albumin:creatinine ratio (UAC) in canine non-azotemic proteinuric CKD. Twenty-one dogs with non-azotemic proteinuric CKD were included in the study. High UPC and UAC were associated with CKD progression (P < .05). Time-averaged high UPC and UAC were significantly related to progression (P < .05). The cutoff values of these time-averaged parameters for predicting the progression were 4.1 and 2.0, respectively. In dogs with non-azotemic proteinuric CKD, more severe proteinuria and albuminuria were associated with progression. The present study suggests that because UPC ≥ 4.1 and UAC ≥ 2.0 during treatment were associated with a faster progression of non-azotemic proteinuric CKD, therapeutic intervention is warranted.

Correlation between alterations in blood flow of malignant lymphomas after induction chemotherapies and clinical outcomes: a pilot study utilising contrast-enhanced ultrasonography for early interim evaluation of lymphoma treatment.

AIM: To clarify the utility of contrast-enhanced ultrasonography (CEUS) for interim evaluation of response to chemotherapy in lymphoma treatment. MATERIALS AND METHODS: CEUS was performed both before (day 0) and after the treatment (7 and/or 14 days), and a time-intensity curve was obtained. The patients were divided into two groups (complete remission [CR] group and non-CR group) according to the results of conventional response evaluation, and peak enhancement (PE), time to peak enhancement, perfusion index (PI), the total area under the curve during wash-in (AUC-in), and the total AUC were compared between the groups. RESULTS: Among 27 patients with various types of lymphoma, the median change ratio of PE and PI at day 7 evaluation were significantly different between the CR group and the non-CR group (0.81 versus 1.39, p=0.017 for PE and 0.92 versus 2.09, p=0.010 for PI). The change ratio of PE < 1.09 (specificity: 86%; sensitivity, 88%) and PI < 1.65 (specificity: 86%; sensitivity: 94%) distinguished CR from non-CR. Patients who achieved a PE change ratio <1.09 or a PI change ratio <1.65 had significantly better estimated progression-free survival (p<0.001). CONCLUSION: The present study demonstrated that changes in tumour perfusion parameters evaluated with CEUS at 1 week after the treatment initiation were significantly different between lymphoma patients in CR group and non-CR group. Alterations in perfusion parameters evaluated via CEUS could impact the prognosis of lymphoma patients.

Relation of Poor Nutritional Status to Mild Cognitive Impairment in Patients with Coronary Artery Disease.

OBJECTIVES: Nutritional status affects cerebral circulation and cognitive function. More attention needs to be paid to nutritional status in coronary artery disease (CAD) patients, yet the relation between nutritional status or dietary intake (DI) and cognitive function or mild cognitive impairment (MCI) in CAD patients remain unclear. Thus, we examined the following relations: 1) that between nutritional status and cognitive function, and MCI and 2) that between DI and cognitive function, and MCI. DESIGN, SETTING, AND PARTICIPANTS: We conducted a cross-sectional study of 208 patients with CAD but without dementia. MEASUREMENTS: MCI was estimated with the Japanese version of the Montreal Cognitive Assessment (MoCA-J). Nutritional status was assessed by the Geriatric Nutritional Risk Index (GNRI), and DI was assessed by total energy intake per day. We investigated the relation between nutritional status or DI and cognitive function by Pearson correlation analysis, and that between nutritional status or DI and MCI by multivariable logistic regression analysis. RESULTS: The GNRI and DI were positively associated with the MoCA-J score (r = 0.23, p < 0.001, and r = 0.24, p < 0.001, respectively), and both were independently associated with MCI in the multivariable logistic regression analysis (odds ratio, 0.96; p = 0.045, and odds ratio, 0.998; p = 0.020, respectively). CONCLUSIONS: Poor nutritional status and low DI were found to be significantly associated with cognitive function and MCI in CAD patients. Our findings regarding nutritional status and DI might be useful for clinicians to prevent or intervene in the early cognitive decline of inpatients with CAD.

Fibroblast growth factor-23 as an early marker of CKD-mineral bone disorder in dogs: preliminary investigation.

OBJECTIVES: To examine the relationship between fibroblast growth factor-23 levels, chronic kidney disease severity and mineral metabolic disorders associated to chronic kidney disease in dogs. MATERIALS AND METHODS: Fifteen control and 75 chronic kidney disease dogs were retrospectively included. Serum fibroblast growth factor-23 concentration and other phosphate metabolite parameters were compared between controls and each International Renal Interest Society stage. Multiple regression analysis was performed to determine the predictors of fibroblast growth factor-23. RESULTS: Serum fibroblast growth factor-23 concentrations were significantly higher in dogs with IRIS stages 2, 3 and 4 chronic kidney disease than those in dogs in control group and with stage 1 and increased along with the severity of chronic kidney disease. Compared with control dogs, serum intact parathyroid hormone significantly increased from stage 2 and serum phosphorus concentrations increased in dogs with stage 4. In dogs with stage 2, fibroblast growth factor-23 levels significantly increased in those with hyperphosphatemia compared with those with normophosphatemia. While eight of 26 (30.8%) dogs with stage 2 developed hyperparathyroidism (intact parathyroid hormone>8.5 ng/L), 19 (73.1%) dogs with stage 2 had elevated fibroblast growth factor-23 levels above the reference range (>528 pg/mL). Log creatinine, log intact parathyroid hormone and log product of total calcium and phosphorus were independent predictors of log fibroblast growth factor-23. CLINICAL SIGNIFICANCE: This preliminary study suggests that canine fibroblast growth factor-23 might be involved in mineral metabolic disorders associated to chronic kidney disease in dogs, and this factor could be potentially used as an early marker for this condition.

Use of vertebral left atrial size for staging of dogs with myxomatous valve disease.

INTRODUCTION/OBJECTIVES: The American College of Veterinary Internal Medicine (ACVIM) guidelines suggest that pimobendan should be initiated in dogs which meet all criteria of stage B2 myxomatous mitral valve disease (MMVD): murmur intensity ≥ 3/6, left atrial-to-aortic ratio ≥ 1.6, normalized left ventricular internal diameter in diastole ≥ 1.7, and vertebral heart size > 10.5. Recently, a new radiographic index for left atrial enlargement, vertebral left atrial size (VLAS), was proposed. The objective of the present study was to evaluate whether VLAS is useful in staging MMVD and if it can distinguish between ACVIM stages B1 and B2. ANIMALS: Ninety-seven client-owned dogs with MMVD were evaluated and classified as ACVIM stage B1, B2, or C-D. MATERIALS AND METHODS: The echocardiographs and radiographs of all the dogs were retrospectively evaluated to obtain left atrial-to-aortic ratio, normalized left ventricular internal diameter in diastole, and VLAS values. The data were analyzed to assess the correlation between these measurements and VLAS, and the optimal cutoff value of VLAS was determined. RESULTS: A VLAS cutoff value of 2.6 provided the greatest diagnostic accuracy for identification of dogs with ACVIM stage B2 MMVD (area under the curve, 0.96; sensitivity, 95%; specificity, 84%). A VLAS ≥2.5 exhibited the highest sensitivity (sensitivity, 100%; specificity, 78%), and a VLAS ≥ 3.1 exhibited the highest specificity (sensitivity, 47%; specificity, 100%). CONCLUSIONS: VLAS is a helpful index for monitoring MMVD using radiography. A VLAS cutoff value of 2.5 could be used to identify dogs that may benefit from echocardiography to determine if they have reached ACVIM stage B2.

Accelerometer-Determined Intensity and Duration of Habitual Physical Activity and Walking Performance in Well-Functioning Middle-Aged and Older Women: A Cross-Sectional Study.

BACKGROUND: The association of physical activity (PA) intensities and duration spent in those activities with different walking tasks remains unclear. OBJECTIVES: To examine the association between the duration of PA intensities and three walking speeds (usual walking speed, maximal walking speed and zig-zag walking speed). DESIGN: Multiple linear regression analysis was used to estimate the association of age, BMI, maximum knee extension strength, light PA, moderate PA and vigorous PA with walking speeds. SETTING: University lab. PARTICIPANTS: Eighty-six older women (67 ± 7 years). MEASUREMENTS: PA was measured for 30 consecutive days using the Lifecorder-EX accelerometer. Exercise intensity was categorized as light (levels 1-3), moderate (levels 4-6) and vigorous (levels 7-9) based on the manufacturer algorithms. Usual straight walking speed (20 m), maximal straight walking speed (20 m) and zig-zag walking speed tests (10 m) were performed by each participant. RESULTS: For the usual straight walking speed model (R2 = 0.296, SEE = 0.15 m/s), the significant predictors were BMI, knee extension strength, light PA and vigorous PA. For the maximal straight walking speed model (R2 = 0.326, SEE = 0.20 m/s), only age was a significant predictor. For the zig-zag walking speed model (R2=0.417, SEE = 0.14 m/s), age and maximum knee strength were significant predictors in the model. CONCLUSIONS: Overall, the results of this study suggest that vigorous PA and maximal knee extension strength are two important factors that are associated with different walking speeds in older women.

Practical and Safe Method of Long-Term Cryopreservation for Clinical Application of Human Adipose-Derived Mesenchymal Stem Cells Without a Programmable Freezer Or Serum.

BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) have emerged as a promising modality for cellular therapy. However, techniques of ADSC cryopreservation, which can facilitate their clinical application, haven't been established yet. OBJECTIVE: To determine optimal conditions for ADSC cryopreservation. MATERIALS AND METHODS: We used three cryoprotectants [serum containing 10% dimethyl sulfoxide; CP-1TM (5% dimethyl sulfoxide, serum-free); Stem-CellBankerTM (dimethyl sulfoxide and serum-free)], two storage temperatures (-80°C, -150°C) and two cell densities (1 × 106, 7 × 106 cells/mL). Storage was up to 18 months using cryovials. We didn't use a rate-controlled freezer or liquid nitrogen storage. RESULTS: We found that CP-1TM was a suitable cryoprotectant. Storage at -150°C and higher cell density (7×106 cells/mL) kept the best viability of ADSCs, but storage at -80°C and a lower cell density (1×106 cells/mL) is acceptable for up to 9 months. We also confirmed large quantities of ADSCs, stored with CP-1 in a cryobag, were still viable after -150°C cryopreservation for 24 months. CONCLUSION: We have developed a safe, cost-effective way to cryopreserve ADSCs that could be used in the clinical setting.

Visualization of Nigrosome 1 from the Viewpoint of Anatomic Structure.

BACKGROUND AND PURPOSE: Parkinson disease is related to neurodegeneration and iron deposition in the substantia nigra pars compacta and nigrosome 1. However, visualization of nigrosome 1 via MR imaging is poor owing to the bilateral asymmetry, regardless of whether it is healthy. We focused on the magic angle and susceptibility effect and evaluated the anatomic slant structure of nigrosome 1 by tilting subjects' heads in the B0 direction. MATERIALS AND METHODS: To investigate the effectiveness of the magic angle, we tilted the volunteers' heads to the right and left in the B0 direction or not at all for evaluating correlations between the degree of head tilting and visualization of the right nigrosome 1 and left nigrosome 1 using 3D spoiled gradient-echo sequences with multiecho acquisitions. We evaluated the susceptibility of nigrosome 1 and the local field using quantitative susceptibility mapping to assess static magnetic field inhomogeneity. RESULTS: The heads tilted to the right and left showed significantly higher contrasts of nigrosome 1 and the substantia nigra pars compacta than the nontilted heads. No significant differences were observed in the visualization and susceptibility between the right nigrosome 1 and left nigrosome 1 for each head tilt. The effect of the magic angle was remarkable in the nontilted heads. This finding was supported by quantitative susceptibility mapping because the anatomic slant structure of nigrosome 1 was coherent between the axis of nigrosome 1 and the magic angle. CONCLUSIONS: The asymmetric visualization of nigrosome 1 is affected by the magic angle and susceptibility. The anatomic slant structure of nigrosome 1 causes these challenges in visualization.

A case of feline gastrointestinal eosinophilic sclerosing fibroplasia limited to the mesentery.

An entire, female, mixed-breed cat of unknown age was presented with a 6-week history of lethargy, anorexia and vomiting. There was an increase in the number of white blood cells in the blood, including neutrophils and eosinophils; moderate anaemia; ascites; and possible mesenteric peritonitis. Exploratory laparotomy revealed firm, multifocal small nodules in the mesentery. As the nodules were surgically unresectable, they were biopsied. Histologically, the nodules were composed of thin trabeculae of dense collagen fibres mixed with plump fibroblasts and numerous eosinophils, consistent with feline gastrointestinal eosinophilic sclerosing fibroplasia. Bacteria were not detected on histological examination of the nodules and cytology of the ascites. Remission of disease occurred following treatment with prednisolone and ciclosporin A for 22 days and antibiotics for 40 days. After remission, ciclosporin A was administered for 236 days and then discontinued. Eosinophilia also resolved after treatment with ciclosporin A. The cat is still alive and in good condition on day 689. This report describes what may be an atypical case of feline gastrointestinal eosinophilic sclerosing fibroplasia, lacking involvement of the gastrointestinal tract, and was apparently cured by treatment that involved ciclosporin A.

Effects of postoperative dietary intake on functional recovery of patients undergoing cardiac surgery.

BACKGROUND AND AIM: Among elderly patients undergoing cardiac surgery, malnutrition is very common and related to muscle wasting known as sarcopenia. Cardiac surgery causes a further decline of nutritional status due to reduced dietary intake (DI); however, the impact of postoperative DI on functional recovery is unclear. METHODS AND RESULTS: We enrolled 250 consecutive patients undergoing cardiac surgery. Daily DI was measured between postoperative days 3 and 7. Patients were categorized as having sufficient or insufficient DI based on whether their DI met or was less than estimated total energy requirements. Functional capacity was measured using the 6-minute walking distance (6MWD) preoperatively and at discharge. Mean postoperative DI was 22.4 ± 3.0 kcal/kg/day, and postoperative DI was insufficient in 92 patients (36.8%). The prevalence of sarcopenia was not different by postoperative DI. Although there was no significant difference in preoperative 6MWD results (P = 0.65), the sufficient DI group had longer 6MWD at discharge than the insufficient DI group (P = 0.04). In multivariate regression analysis, preoperative poor nutritional status (ß = -0.29), duration of surgery (ß = -0.18), and postoperative DI (ß = 0.40) remained statistically significant predictors for improvement of 6MWD (P < 0.0001, adjusted R2 = 0.41). CONCLUSIONS: Postoperative DI was independently associated with functional recovery, but preoperative sarcopenia was not. Regardless of preoperative nutritional status or the presence of sarcopenia, aggressive nutritional intervention in the early stage after surgery helps support functional recovery.

Retention among full-time occupational physicians in Japan.

BACKGROUND: To secure human resources for occupational medicine, it is important to analyse occupational physician retention trends and the factors associated with retention. However, little is currently known about this topic. AIMS: To identify occupational physician retention trends, to identify factors associated with this retention and to discuss the policy implications of the findings. METHODS: We analysed data from the biannual national physician census surveys conducted by the government of Japan from 2002 to 2014. In this study, those who chose 'working as an occupational physician' as their workplace/type of work from a pre-determined list in the survey questionnaire were considered full-time occupational physicians. We presented retention trends by calculating the annual retention rate for each set of two consecutive surveys. We then used logistic regression to identify factors associated with retention among occupational physicians. RESULTS: The annual retention rate of full-time occupational physicians from 2012 to 2014 was estimated as 76%, which represents a 6% improvement in retention over the study period. The odds of continuing to practise as an occupational physician were higher for occupational physicians working in cities compared with those working in towns or villages. CONCLUSIONS: Improving and facilitating smooth transitions between clinical practice and occupational medicine would help to secure human resources in occupational medicine, even if the current trend of low retention continues.

Tretinoin (0.05% cream vs. 5% peel) for photoaging and field cancerization of the forearms: randomized, evaluator-blinded, clinical trial.

BACKGROUND: Topical tretinoin cream is the gold standard treatment for skin ageing, particularly photoaging. The purpose of tretinoin peel was to obtain similar results, but in a shorter time, however, there have been few controlled trials on its effectiveness. OBJECTIVE: To compare efficacy and safety of tretinoin 0.05% cream and 5% as a peeling agent on photoaging and field cancerization of the forearms. METHODS: Clinical trial with therapeutic intervention, prospective, randomized (computer-generated randomization list), parallel, comparative (intrasubject) and evaluator-blinded (except for histology and immunohistochemistry), including 24 women (48 forearms) aged over 60 years who have not undergone hormone replacement and categorized as Fitzpatrick skin phototype II or III. The forearms of the participants were randomized for treatment with 0.05% tretinoin cream three nights a week, or 5% tretinoin peel every 2 weeks. The opinion of the participant, severity of photoaging, corneometry, profilometry, high-frequency ultrasound, histology (haematoxylin-eosin and Verhoeff stainings) and immunohistochemistry (p53, bcl-2, Ki67 and collagen I) were assessed. RESULTS: One participant dropped out. The mean photoaging score reduced 20% and the mean actinic keratosis (AK) count reduced 60% with no difference between treatments. Three efficacy parameters showed opposite effects between the tretinoin treatments (P < 0.05%): (i) thickness of the corneal layer decreased with 0.05% tretinoin and increased by 5%; (ii) dermis echogenicity increased by 0.05% and decreased by 5% and (iii) Ki67 expression increased by 0.05% and decreased by 5%. There was good tolerability for both regimens. CONCLUSION: Tretinoin as a cream 0.05% or peeling (5%) is safe and effective for the treatment of moderate photoaging and forearm field cancerization. The cream was superior in improving ultrasonographic parameters of ageing. Peeling was shown a superior performance in the stabilization of field cancerization.

The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation.

BACKGROUND: Barrier dysfunction is an important feature of atopic dermatitis (AD) in which IL-4 and IL-13, signature type 2 cytokines, are involved. Periostin, a matricellular protein induced by IL-4 or IL-13, plays a crucial role in the onset of allergic skin inflammation, including barrier dysfunction. However, it remains elusive how periostin causes barrier dysfunction downstream of the IL-13 signal. METHODS: We systematically identified periostin-dependent expression profile using DNA microarrays. We then investigated whether IL-24 downregulates filaggrin expression downstream of the IL-13 signals and whether IL-13-induced IL-24 expression and IL-24-induced downregulation of filaggrin expression are dependent on the JAK/STAT pathway. To build on the significance of in vitro findings, we investigated expression of IL-24 and activation of STAT3 in mite-treated mice and in AD patients. RESULTS: We identified IL-24 as an IL-13-induced molecule in a periostin-dependent manner. Keratinocytes are the main IL-24-producing tissue-resident cells stimulated by IL-13 in a periostin-dependent manner via STAT6. IL-24 significantly downregulated filaggrin expression via STAT3, contributing to barrier dysfunction downstream of the IL-13/periostin pathway. Wild-type mite-treated mice showed significantly enhanced expression of IL-24 and activation of STAT3 in the epidermis, which disappeared in both STAT6-deficient and periostin-deficient mice, suggesting that these events are downstream of both STAT6 and periostin. Moreover, IL-24 expression was enhanced in the epidermis of skin tissues taken from AD patients. CONCLUSIONS: The IL-13/periostin pathway induces IL-24 production in keratinocytes, playing an important role in barrier dysfunction in AD.

Standard morphology of the oral commissure and changes resulting from reconstruction for defects involving the commissure.

The aim of this study was to characterize the standard morphology of the oral commissure and to describe the changes after reconstruction in patients with through-and-through cheek defects involving the oral commissure. Indices for the morphological analyses of the commissure were derived from examinations of 50 normal Japanese volunteers. Ten patients with full-thickness cheek defects involving the commissure were then evaluated. All of these patients underwent free flap reconstruction with vermilion advancement flaps from the remaining vermilion. The morphology of the commissure with the mouth closed was classified based on the point of entrance of the vermilion into the oral cavity. In normal volunteers, the commissure pattern consisting of the entrance of the upper vermilion into the oral cavity before the lower vermilion and just prior to forming the oral commissure was considered to be the standard. However, in the reconstructed cases, there was an increase in the pattern in which the lower vermilion enters the oral cavity before the upper vermilion for the remaining commissure postoperatively, especially when the lower lip defects were greater than those of the upper lip. It is important to refer not only to the standard morphology of the commissure, but also to the changes according to the extent of resection and the method of reconstruction.