Iron overload may be critical for liver dysfunction in anorexia nervosa, and the role of haematocrit-adjusted albumin in assessing nutritional status: a case report.

BACKGROUND: Anorexia nervosa (AN) is frequently associated with liver dysfunction, but the precise mechanism remains undefined. Since the nutritional marker albumin has a low correlation with changes in body weight in AN, and patients with AN often have dehydration as a complication, we also examined whether haematocrit (HCT)-adjusted serum albumin could be a better nutritional marker in AN. CASE PRESENTATION: We describe a 15-year-old girl with severe weight loss and liver damage whose liver enzymes normalized after 1.5 months of hospitalization and weight gain. We found a significant correlation between body weight (BW) and HCT-adjusted serum albumin (Spearman's rank correlation coefficient (rs) = 0.66, P = 5.28 × 10-3) and between BW and alanine aminotransferase (ALT) (rs = -0.825, P = 8.45 × 10-5). After division by HCT, correlations between serum albumin and ALT (rs = -0.835, P = 5.24 × 10-5) and between the iron-storage protein ferritin and the liver enzyme gamma-glutamyl transferase (rs = 1.0, P = 0.017) were also statistically significant. CONCLUSION: These results suggest that improvement of the nutritional status in AN could relieve liver dysfunction and facilitate iron transport. Since a decrease in the iron-transport protein transferrin presumably increases labile non-transferrin-bound iron, resulting in excess reactive oxygen species production, a defect in iron transport due to malnutrition could be one of the causes of liver injury in AN. In addition, HCT-adjusted albumin could be a better marker than its raw data to assess changes in nutritional status in AN.

Mitral valvuloplasty with left atrial appendage closure and pacemaker implantation in a dog with severe myxomatous mitral valve degeneration: a case report.

BACKGROUND: Mitral valvuloplasty (MVP) has been widely recognized as a treatment option for myxomatous mitral valve disease (MMVD). However, postoperative complications such as thromboembolism, arrhythmia, and pancreatitis in some cases have resulted in death. We treated a dog with severe MMVD complicated by impaired sinus function with MVP and pacemaker implantation. Also, due to an intrinsic procoagulant state and severe arrhythmia after the MVP, left atrial appendage (LAA) closure was performed to reduce the postoperative risk of thrombosis. CASE PRESENTATION: An 11-year-old castrated 7.5-kg male Miniature Schnauzer with a history of congestive heart failure was brought to Shiraishi Animal Hospital for MMVD surgical treatment. Echocardiography revealed an enlarged left atrium and ventricle secondary to MMVD. Sinus arrest with 2 to 3-second periods of asystole was identified by electrocardiogram. Mitral valvuloplasty was performed with cardiopulmonary bypass to treat the MMVD. After coronary reperfusion, there was no spontaneous electrical activity. Cardiac arrest continued. Based on this surgical outcome, a permanent pacemaker was implanted. In addition, LAA closure with an AtriClip was performed to prevent intra-atrial thrombus formation. Cardiac remodeling and congestion were ameliorated after surgery. Sinus rhythm was restored 5 days postoperatively; however, the patient continued pacemaker dependent. All cardiac drugs were discontinued 3 months after surgery. The owner reported no postoperative complications (i.e., thrombosis), and the patient was brought for a check-up 4 months after the operation in good health. CONCLUSIONS: For surgical MMVD cases complicated with impaired sinus function, the chances of spontaneous sinus rhythm are low, requiring pacemaker implantation. LAA closure may be considered to protect against decreased atrial function after mitral valvuloplasty and prevent intra-atrial thrombus formation.

Diurnal rhythms in testicular blood flow, testicular morphometry and reproductive hormones in Shiba goats.

CONTEXT: Testicular blood flow (TBF) is crucial for testicular function. The pattern of TBF in Shiba goats indicates seasonal variations. AIMS: This study aimed to investigate the effect of diurnal variations on TBF, testis volume (TV), testicular echogenicity, and reproductive hormones in goats over a 24-h period. METHODS: In three trials that went for three consecutive days each, 12 bucks were scanned using Triplex ultrasonography to assess the TV, pixel intensity of testicular echotexture (PIX), and Doppler indices of TBF (resistive index: RI and pulsatility index: PI) in four-time points a day (at 6.00, 12.00, 18.00, and 00.00h). Concomitantly, the changes in circulating FSH, LH, inhibin, testosterone (T), estradiol (E2), cortisol, and melatonin were assessed. KEY RESULTS: Results revealed diurnal alterations in the calculated RI of TBF and the PIX of testicular parenchyma (P <0.05). Lower RI values of the TBF were observed at 6.00h compared to other time points. There were significant diurnal alterations in the levels of FSH (P <0.05), LH (P <0.05), T (P <0.0001), E2 (P <0.0001), cortisol (P <0.0001), and melatonin (P <0.0001). FSH attained a higher concentration at 18.00h compared to 12.00h. Concentrations of LH were significantly higher at 06.00h compared to those at 18.00h. Concentrations of T were significantly higher at 6.00 compared to other time points. E2 showed higher concentrations at 6.00h and 00.00h compared to 12.00h and 18.00h. On the contrary, concentrations of cortisol were significantly higher at 12.00h and 18.00h compared to 06.00h and 00.00h. The highest concentrations of melatonin were observed at 00.00h compared to other time points, while the lowest concentrations were at 12.00h. CONCLUSIONS: Diurnal rhythm induces significant changes in TBF, testicular PIX, and circulating FSH, LH, T, E2, cortisol, and melatonin over the 24-hday. IMPLICATIONS: The outcomes of the study are reflected in the advisability of monitoring the TBF at a fixed time a day to avoid the circadian rhythm effect.

Adjunct ambrisentan therapy had clinical benefits in 5 dogs with sildenafil-refractory pulmonary hypertension.

Although sildenafil is used in dogs with severe pulmonary hypertension, they sometimes become resistant and clinical signs deteriorate over time. The objective of this study was to determine the benefits of adjunct ambrisentan therapy in dogs with sildenafil-refractory pulmonary hypertension. In 5 dogs with severe pulmonary hypertension with deteriorating clinical signs despite ongoing sildenafil treatment, adding ambrisentan improved appetite, activity, and respiratory functions. Although peak tricuspid valve regurgitation velocity, as measured by Doppler echocardiography, did not necessarily decrease after ambrisentan administration, there was improved partial pressure of arterial oxygen and the alveolar-arterial oxygen gradient, with no apparent side effects. We concluded that ambrisentan has potential as an adjunct treatment in dogs with pulmonary hypertension that are refractory to sildenafil therapy. Key clinical message: Ambrisentan improved clinical signs in dogs with sildenafil-refractory pulmonary hypertension.

Le traitement d'appoint à l'ambrisentan a eu des avantages cliniques chez cinq chiens atteints d'hypertension pulmonaire réfractaire au sildénafil. Bien que le sildénafil soit utilisé chez les chiens souffrant d'hypertension pulmonaire sévère, ils deviennent parfois résistants et les signes cliniques s'aggravent avec le temps. L'objectif de cette étude était de déterminer les avantages d'un traitement d'appoint à l'ambrisentan chez les chiens souffrant d'hypertension pulmonaire réfractaire au sildénafil. Chez cinq chiens souffrant d'hypertension pulmonaire sévère avec détérioration des signes cliniques malgré un traitement continu au sildénafil, l'ajout d'ambrisentan a amélioré l'appétit, l'activité et les fonctions respiratoires. Bien que la vitesse maximale de régurgitation de la valve tricuspide, mesurée par échocardiographie Doppler, n'ait pas nécessairement diminué après l'administration d'ambrisentan, la pression partielle d'oxygène artériel et le gradient alvéolo-artériel d'oxygène ont été améliorés, sans effets secondaires apparents. Nous avons conclu que l'ambrisentan a un potentiel en tant que traitement d'appoint chez les chiens souffrant d'hypertension pulmonaire qui sont réfractaires au traitement par le sildénafil.Message clinique clé:L'ambrisentan a amélioré les signes cliniques chez les chiens souffrant d'hypertension pulmonaire réfractaire au sildénafil.(Traduit par Dr Serge Messier).

Clinical and necropsy evaluation of endocardial fibroelastosis in a mixed-breed cat with left side heart failure.

A two-month-old, male intact, mixed-breed cat weighing 0.6 kg was presented with respiratory distress and anorexia. From the transthoracic echocardiographic, reduced fractional shortening (FS) and increased endocardial echogenicity were recognised with severe congestive heart failure (CHF). The kitten was administered an antibiotic and pimobendane under oxygen supplementation in an ICU cage. However, the respiratory condition worsened and the cat died the next day, and the subsequent necropsy and histopathology examinations confirmed endocardial fibroelastosis (EFE). There is a lack of information regarding the antemortem cardiac function evaluated by tissue Doppler imaging (TDI) in EFE cases. We report on the echocardiographic findings including the TDI in the EFE cat with a concomitant necropsy and histopathology confirmation in this paper. The echocardiographic findings showed presence of a ventricular false tendon within the left ventricle, a decrease in the left ventricular contractility (FS 11.1%, and a marked CHF). In this case, the echocardiographic findings were consistent with the human counterpart. However, these findings were like those of dilated cardiomyopathy and, hence, non-specific to EFE. As a result, veterinarians should keep in mind that endocardial fibroelastosis might be a possible reason for respiratory distress resulting from CHF with a low fractional shortening in young cats.

Association of urinary free cortisol with bone formation in patients with mild autonomous cortisol secretion.

CONTEXT: Mild autonomous cortisol secretion (ACS) is associated with an increased risk of vertebral fractures (VFx). However, the influence of this condition on bone turnover or its association with mild ACS is still controversial. OBJECTIVE: This study aimed to evaluate the impact of mild ACS on bone quality among patients living with the disease. DESIGN AND SETTING: A retrospective study was conducted using data from 55 mild ACS and 12 nonfunctioning adrenal tumour (NFT) patients who visited Chiba University Hospital, Japan, from 2006 to 2018. PATIENTS AND MAIN OUTCOME MEASURES: We analysed clinical features and bone-related factors, including bone mineral density (BMD) and VFx, performed blood tests to assess bone metabolism markers in patients with mild ACS and NFT, and assessed the associations between bone-related markers and endocrinological parameters in patients with mild ACS. RESULTS: No significant differences between mild ACS and NFT patients were observed with respect to the presence or absence of VFx and BMD. Urinary free cortisol (UFC) was higher in mild ACS patients with VFx than those without (p = .037). The T-score and young adult mean (YAM) of the BMD of the femoral neck in mild ACS patients with a body mass index <25 were positively correlated with dehydroepiandrosterone sulphate levels (ρ: 0.42, p = .017; ρ: 0.40, p = .024, respectively). Pearson's correlation analysis showed that bone-specific alkaline phosphatase was negatively correlated with UFC in the patients with mild ACS (ρ: -0.37, p = .026). CONCLUSIONS: These results suggest that urinary free cortisol may be useful for predicting bone formation in mild ACS patients.

Gonadal Hormones and Bone.

In both sexes, estrogen is one of the most essential hormones for maintaining bone integrity. Also, especially in men, androgen has beneficial effects on bone independent of estrogen. However, estrogen replacement therapy for postmenopausal women increases the risk of developing breast cancer and endometrial cancer, and androgen replacement therapy for partial androgen deficiency of the aging male increases the risk of developing prostate cancer. Various mechanisms have been proposed on the effects of gonadal hormones on bone, such as effects through cytokines including IL-6 and effects on the OPG/RANKL ratio. In addition, large amounts of new information deriving from high-throughput gene expression analysis raise the possibility of multiple other effects on bone cells. Both estrogen and androgen exert their effects via the estrogen receptor (ER) or the androgen receptor (AR), which belongs to the nuclear receptor superfamily. Compounds such as selective estrogen receptor modulators (SERMs) and selective androgen receptor modulators (SARMs) also bind ER and AR, respectively. However, SERMs and SARMs alter the ER or AR structure differently from estrogen or androgen, resulting in other downstream gene responses. As a result they can exert favorable effects on bone while suppressing the undesirable actions of estrogen and androgen. Elucidation of ER and AR ligand-specific and tissue-specific gene regulation mechanisms will also provide information on the signal transduction mechanisms of other nuclear receptors and will be valuable for the development of new therapeutic agents.

Effects of adsorbent carriers in modified ready biodegradability tests of quaternary ammonium salts.

Standard ready biodegradability tests are conducted at unrealistically high test concentration and therefore cannot properly evaluate toxic substances to microorganisms. The present study evaluated the effects of four adsorbent carriers in modified ready biodegradability tests of four quaternary ammonium salts (QASs) demonstrating microbial toxicity according to the Organization for Economic Co-operation and Development Test Guideline 301F and cautions for using carriers were found. In the tests with silica gel, the concentration of all QASs in the test solutions decreased due to adsorption. The percentages of biodegradation of octadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, and benzyldimethyloctadecylammonium chloride, which have a linear alkyl chain, were 89.9%, 80.6%, and 70.1% on day 28, respectively; benzethonium chloride, with a branched alkyl chain, did not undergo biodegradation. In the tests with activated carbon, although the concentrations of QASs greatly decreased, no QASs underwent biodegradation. In the tests with sea sand or quartz sand, QASs were not adsorbed on the carriers and were not biodegraded. Using an adsorbent carrier for toxic substances will increase biodegradation, but it has no effect on highly persistent substances with specific chemical structures, e.g., branched carbons, which is very important because ready biodegradability is not overestimated. Carriers having moderate adsorbability should be selected.

New adalimumab formulation associated with less injection site pain and improved motivation for treatment.

Objectives: We aimed to evaluate the effect of change to the existing formulation of adalimumab (ADA) on pain and treatment motivation.Methods: We classified injection pain into the following categories: overall pain, pain at needle insertion, pain during drug injection, and pain 10 min after injection; we evaluated the effect of change to the existing formulation on pain using a visual analogue scale. In addition, a faces pain scale was used to evaluate the effect of change in injection pain intensity on treatment motivation.Results: Compared with the existing ADA formulation, the new formulation was associated with lower scores of overall pain (1.6 vs. 6.7), pain at needle insertion (1.8 vs. 4.7), pain during injection (1.6 vs. 7.0), and pain 10 min after the injection (0.4 vs. 3.1). All results showed a significant difference. p < .001. Paired t-tests were used. In the survey, 68% and 80% of the patients reported injection pain with influenza vaccine and the existing formulation, respectively; however, the proportion of the patients who experienced pain with the new formulation decreased to 20%.Conclusions: The new ADA formulation may alleviate the burden on RA patients and improve the quality of adherence to treatment, thereby influencing the RA treatment outcomes.

Fracture risk assessment tool (FRAX) and for the diagnosis of osteoporosis in Japanese middle-aged and elderly women: Chiba bone survey.

Osteoporosis not only increases bone fracture risk but also affects survival in postmenopausal women. Although osteoporosis is diagnosed based on low bone mineral density (BMD) determined by dual energy X-ray absorptiometry (DXA), BMD measurement is sometimes difficult because DXA is not widely available in the community. The Fracture Risk Assessment tool (FRAX) can predict 10-year major osteoporotic fracture risk and hip fracture risk with or without femoral neck BMD. The FRAX has not been investigated adequately in community-dwelling Japanese women. We administered the FRAX tool in 13,421 Japanese women who underwent DXA-based forearm BMD measurement in Chiba Bone Survey, a population-based, multicenter, cross-sectional study of postmenopausal osteoporosis conducted in Chiba, Japan. Mean age was 57.77 ± 9.24 years. Mean forearm BMD was 87.94 ± 17.00% of young adult mean (YAM). Mean FRAX major osteoporotic fracture risk without femoral neck BMD was 7.06 ± 5.22%. BMD decreased and percentage of osteoporosis increased from age 55 onward. Age distribution of percentage of subjects with FRAX major osteoporotic fracture risk >15% was similar to that of percentage of osteoporosis subjects. We identified the cutoff value of FRAX major osteoporotic fracture risk for diagnosis of osteoporosis as 7.2%. With this cutoff, the positive likelihood ratio was over 1.0 at age 55 and above but accuracy was low. In conclusion, FRAX without femoral neck BMD reflects bone status, and may be useful to diagnose osteoporosis in Japanese women aged 55 and above, although the sensitivity was low for osteoporosis screening, especially in middle-aged women.

Needlescopic intragastric surgery facilitated by newly developed 2mm instruments.

BACKGROUND: Intragastric surgery is a percutaneous endoluminal surgery in the stomach aimed at resection of tumors located at the esophagogastric junction (EGJ). We developed needlescopic intragastric surgery performed via 2 mm, 2 mm, and 5 mm ports (PEIGS-225). MATERIAL AND METHODS: In cooperation with Niti-On Co., Ltd. we developed a series of 2 mm instruments including grasping forceps, a cannula, a laparoscope, an electrocautery, scissors, and a needle holder. OPERATIVE TECHNIQUE: Two 2 mm trocars and a 5 mm one are inserted into the gastric lumen percutaneously. Intragastric procedures are performed by the instruments brought through those three ports. The specimen is extracted via the esophageal-oral route. The defect in the gastroesophageal wall is closed by hand-suture. After the intragastric procedure, the 5 mm stab wound on the gastric wall is closed by hand-suture, while the 2 mm wounds are left untreated. PATIENTS: Between March and August 2015 PEIGS-225 was performed in five patients. RESULTS: There was no operative conversion. The mean operation time was 96 minutes. There were no perioperative complications. Pathological findings indicated that the margin was negative in all cases. CONCLUSION: Needlescopic intragasric surgery performed via the smallest access (2 mm, 2 mm, 5 mm) is enabled by the 2 mm instruments developed by us.

A general method for calculating the optimal leaf longevity from the viewpoint of carbon economy.

According to the viewpoint of the optimal strategy theory, a tree is expected to shed its leaves when they no longer contribute to maximisation of net carbon gain. Several theoretical models have been proposed in which a tree was assumed to strategically shed an old deteriorated leaf to develop a new leaf. We mathematically refined an index used in a previous theoretical model [Kikuzawa (Am Nat 138:1250-1263, 1991)] so that the index is exactly proportional to a tree's lifelong net carbon gain. We also incorporated a tree's strategy that determines the timing of leaf expansion, and examined three kinds of strategies. Specifically, we assumed that a new leaf is expanded (1) immediately after shedding of an old leaf, (2) only at the beginning of spring, or (3) immediately after shedding of an old leaf if the shedding occurs during a non-winter season and at the beginning of spring otherwise. We derived a measure of optimal leaf longevity maximising the value of an appropriate index reflecting total net carbon gain and show that use of this index yielded results that are qualitatively consistent with empirical records. The model predicted that expanding a new leaf at the beginning of spring than immediately after shedding usually yields higher carbon gain, and combined strategy of the immediate replacement and the spring flushing earned the highest gain. In addition, our numerical analyses suggested that multiple flushing seen in a few species of subtropical zones can be explained in terms of carbon economy.

Combined repeated dose and reproductive/developmental toxicity screening test of 4-methoxy-2-nitroaniline in rats.

4-Methoxy-2-nitroaniline (4M2NA) is widely used as an intermediate for the synthesis of dyes, pigments and other chemical compounds. Since 4M2NA has amino-group and nitro-group on the benzene ring, it was expected that it induced obvious hemolytic anemia. We conducted a combined repeated dose and reproductive/developmental toxicity screening test according to Organisation for Economic Co-operation and Development (OECD) Test Guideline No. 422 (OECD TG 422) to enrich the toxic information and ensure the safety of 4M2NA. 4M2NA was administered to Crl:CD(SD) male and female rats by gavage at 0, 12.5, 75 or 450 mg/kg/day for 42 to maximum of 54 days through pre-mating, mating, pregnancy and lactation periods. An extramedullary hematopoiesis and congestion in spleen, and higher reticulocyte ratio were noted in only females at 450 mg/kg/day without decreased anemic parameters in the hematological examination. Hypertrophy of centrilobular hepatocytes in both sexes was observed with increased relative liver weight at 450 mg/kg/day. Furthermore, the diffuse follicular cell hypertrophy of the thyroid was observed in females at 450 mg/kg/day. No abnormalities were detected in the reproductive indices of copulation, delivery or fetal viability. We concluded the no-observed-adverse-effect level (NOAEL) for repeated-dose toxicity was 75 mg/kg/day based on the trace evidences of hemolytic anemia, and the NOAEL for reproductive/developmental toxicity as 450 mg/kg/day based on no toxicological concerns for reproductive endpoints. The hemolytic anemia was much milder than expected. Thus, we discussed the reason of this much less hemolytic effect from the point of view of the structural characteristics of 4M2NA.

Comparison of St. Thomas II Cardioplegia and Modified Del Nido Cardioplegia in Dogs Undergoing Mitral Valve Surgery.

Myocardial protection has become an essential adjunctive procedure in veterinary cardiac surgery. Del Nido cardioplegia is a good alternative to the traditional St. Thomas II (ST) cardioplegia in open heart surgery in humans. This study aims to compare intra- and postoperative results between ST cardioplegia and modified del Nido (mDN) cardioplegia in mitral valve surgery in dogs with myxomatous mitral valve disease (MMVD). This retrospective study was conducted using clinical records of 16 MMVD dogs that underwent either ST or mDN cardioplegia. We measured cardiopulmonary bypass (CPB) time, aortic cross-clamp (ACC) time, total operation time, the number of cardioplegia doses, total amount of cardioplegia, required defibrillations, in-hospital mortality and pre- and one-month postoperative echocardiographic variables. CPB (159.4 ± 16.1 vs. 210.1 ± 34.0 min), ACC (101.4 ± 7.0 vs. 136.0 ± 24.8 min) and total operation time (262.3 ± 13.1 vs. 327.0 ± 45.4 min) were significantly shorter in the mDN group (p < 0.05). The number of cardioplegia doses (3.25 ± 0.4 vs. 6.25 ± 1.2) and total amount of cardioplegia (161.3 ± 51.5 vs. 405.0 ± 185.9 mL) in the mDN group were also significantly smaller than the ST group (p < 0.05). No difference was observed in the requirement of defibrillation, in-hospital mortality and pre- and postoperative echocardiographic variables. The utilization of mDN cardioplegia was associated with shorter operative time in mitral valve surgery in dogs.

Exploring sleep heart rate variability: linear, nonlinear, and circadian rhythm perspectives.

Background: Heart rate variability (HRV) is believed to possess the potential for disease detection. However, early identification of heart disease remains challenging, as HRV analysis in dogs primarily reflects the advanced stages of the disease. Hypothesis/objective: The aim of this study is to compare 24-h HRV with sleep HRV to assess the potential utility of sleep HRV analysis. Animals: Thirty healthy dogs with no echocardiographic abnormalities were included in the study, comprising 23 females and 7 males ranging in age from 2 months to 8 years (mean [standard deviation], 1.4 [1.6]). Methods: This study employed a cross-sectional study. 24-h HRV and sleep HRV were measured from 48-h Holter recordings. Both linear analysis, a traditional method of heart rate variability analysis, and nonlinear analysis, a novel approach, were conducted. Additionally, circadian rhythm parameters were assessed. Results: In frequency analysis of linear analysis, the parasympathetic index nHF was significantly higher during sleep compared to the mean 24-h period (mean sleep HRV [standard deviation] vs. mean 24 h [standard deviation], 95% confidence interval, p value, r-family: 0.24 [0.057] vs. 0.23 [0.045], 0.006-0.031, p = 0.005, r = 0.49). Regarding time domain analysis, the parasympathetic indices SDNN and RMSSD were also significantly higher during sleep (SDNN: 179.7 [66.9] vs. 156.6 [53.2], 14.5-31.7, p < 0.001, r = 0.71 RMSSD: 187.0 [74.0] vs. 165.4 [62.2], 13.2-30.0, p < 0.001, r = 0.70). In a geometric method of nonlinear analysis, the parasympathetic indices SD1 and SD2 showed significantly higher values during sleep (SD1: 132.4 [52.4] vs. 117.1 [44.0], 9.3-21.1, p < 0.001, r = 0.70 SD2: 215.0 [80.5] vs. 185.9 [62.0], 17.6-40.6, p < 0.001, r = 0.69). Furthermore, the circadian rhythm items of the parasympathetic indices SDNN, RMSSD, SD1, and SD2 exhibited positive peaks during sleep. Conclusion: The findings suggest that focusing on HRV during sleep can provide a more accurate representation of parasympathetic activity, as it captures the peak circadian rhythm items.

Lifestyle and osteoporosis in middle-aged and elderly women: Chiba bone survey.

Osteoporosis causes an enormous health and economic impact in Japan. We investigated the relation between lifestyle and bone fracture in middle-aged and elderly women. This was a population-based, multicenter, cross-sectional survey for postmenopausal osteoporosis in Chiba City, Japan (Chiba bone survey). This survey included 64,809 Japanese women aged > 40 years. All participants underwent anthropometric measurements including bone mineral density (BMD) and completed a structured, nurse-assisted, self-administered questionnaire also including patient lifestyle. Bone fracture during the recent 5 years was observed in 5.3%, and the fracture group had significantly higher age, BMI, and prevalence of delivery, family histories of kyphosis and hip fracture, diabetes mellitus (DM), dyslipidemia, kidney disease, exercise, fall, and osteoporosis, and had significantly lower BMD and proportion of menstruating participants. Logistic regression analysis revealed that bone fracture was closely associated with not only low bone mass but also age, fall, family histories of kyphosis and hip fracture, DM, kidney disease, menopause, and lifestyle factors of dieting, exercise, and alcohol. Women's health care focusing on lifestyle-related fracture risks such as dieting, exercise, and alcohol appears necessary to prevent bone fracture in postmenopausal osteoporosis.

A case of a dog with mandibular extraskeletal osteosarcoma after long-term puncture extirpation of the salivary gland cyst in the mandible.

Background: Extraskeletal osteosarcoma, unlike skeletal osteosarcoma, is a rare malignant mesenchymal tumor with a soft tissue primary that has been reported to occur in a variety of soft tissues. Case Description: The case is a 14-year-old, unneutered male Miniature Pinscher, weighing 6.7 kg, who had been treated medically for more than 5 years with a management strategy of puncture extirpation of a salivary gland cyst in the mandible; 1 month earlier, the fluid retention could not be removed, and after a computerized tomography scan showed no lesion in the mandible adjacent to the mass lesion, surgical resection was performed. Conclusion: Previous reports of extraskeletal osteosarcoma from the salivary glands in dogs have been rare. However, treatment of a salivary gland cyst in the mandible by long-term puncture extirpation may be a potential predisposing factor for the development of extraskeletal osteosarcoma around the mandible.

A case of doxorubicin and cyclophosphamide therapy-induced type 1 diabetes: a case report.

BACKGROUND: Patients receiving immune checkpoint inhibitors have been reported to develop autoimmune endocrine diseases, including type 1 diabetes, although few drugs have been shown to induce type 1 diabetes. Additionally, it is important to note that drugs other than immune checkpoint inhibitors could lead to the development of type 1 diabetes. CASE PRESENTATION: A 54-year-old Filipino female patient underwent surgery for left-sided breast cancer. Postoperative chemotherapy was initiated, including doxorubicin (Adriamycin) and cyclophosphamide therapy. The patient was brought to our hospital by ambulance after consciousness disturbance following three courses of doxorubicin and cyclophosphamide therapy and was hospitalized. Her blood glucose and hemoglobin A1c levels were 1661 mg/dL and 11.9%, respectively. The patient was diagnosed with diabetic ketoacidosis after arterial blood gas analysis indicated a blood pH of 7.120. Her insulin secretion was impaired, and her anti-glutamic acid decarboxylase antibody test result was significantly positive. CONCLUSIONS: The present case shows that doxorubicin and cyclophosphamide therapy may cause unexpected adverse responses, such as type 1 diabetes, though rarely, and highlights the importance of careful patient follow-up. This report is the first to present a case of type 1 diabetes that suddenly developed after doxorubicin and cyclophosphamide treatment.

Preliminary report of spinal cord injuries resulting from inappropriate microchip implantation in two puppies.

Since the revised Animal Welfare and Management Law in Japan became effective on June 1st, 2022, it became mandatory for pet dogs and cats to have microchips implanted and registered prior to be sold. Two cases of spinal cord injury as the result of inappropriate microchip implantation in puppies were referred to our facility, of which were diagnosed by cervical spinal radiography and computed tomography (CT). While adverse reactions following microchip implantation are rare, the possibility of iatrogenic spinal cord injury remains a serious complication. This is the first report of adverse reactions following microchip implantation in Japan, and it alerts the possibility of iatrogenic spinal cord injury secondary to inappropriate microchip implantation, where adequate training and extra caution is crucial especially in small light-weight animals.

Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study.

In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. PCSK9 was also reported to be associated with insulin secretion and diabetes mellitus (DM). Therefore, we aimed to examine the clinical significance of PCSK9 antibodies (PCSK9-Abs) levels. We measured blood PCSK9-Abs and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with DM (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. The primary endpoint of this study was to examine whether PCSK9-Abs can be a prognostic marker for overall mortality among the patients with diabetes. The secondary endpoint was to examine the relationship between PCSK9-Abs and clinical parameters. Although both PCSK9-Abs and PCSK9 protein levels were significantly higher in the DM group than in the HD group (p < 0.008), PCSK9-Abs and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, higher PCSK9-Ab levels were still associated with increased mortality among the patients with DM. PCSK9-Abs may be a novel prognostic marker for overall mortality in patients with diabetes, and further studies are warranted to verify its usefulness.