Serious surgical complications of canine cryptorchid castration are associated with surgical approach: a case-control study of 202 dogs.

OBJECTIVE: The purpose of this study was to compare a cohort of dogs with serious or life-threatening complications following cryptorchid castration to dogs without complications to identify potential contributing factors to the development of these complications. METHODS: Dogs that had a cryptorchid castration between 2018 and 2022 in 2 hospital networks were retrospectively reviewed in a case-control manner for reported complications. Inclusion criteria for cases and controls consisted of dogs with documented surgical procedures to address a retained testicle within the abdomen and an in-person follow-up visit at least 2 weeks postoperatively. Exclusion criteria consisted of felines, procedures limited to inguinal cryptorchid castrations, if the retained testicle had undergone malignant transformation, and medical records lacking essential patient or procedure information. RESULTS: 202 dogs were included in the study, with 38 dogs with reported complications and 164 controls. The most reported serious complication was trauma to the prostate, followed by gastrointestinal signs and urinary tract trauma. A complication was more likely if a paramedian skin incision was performed (OR, 4.01; 95% CI, 1.45 to 11.1) compared to a parapreputial incision, as well as if a paramedian abdominal incision was performed compared to a ventral midline incision (OR, 3.4; 95% CI, 1.5 to 7.4). CONCLUSIONS: The most common complication found in this case-control study was prostatic trauma and was likely associated with inadequate exposure based on the incision location. CLINICAL RELEVANCE: Parapreputial skin incision and ventral midline abdominal incision increase exposure and visualization of organs, decreasing the risk of serious complications associated with cryptorchid castration.

Tertiary lymphoid structures in tongue cancer: Association with clinicopathological parameters, preoperative S-1 chemotherapy response, and prognosis.

BACKGROUND: Tertiary lymphoid structures (TLSs) are observed in cancer-invasive sites of various organs, and show evidence of tumor-specific B and/or T cells, suggesting an active humoral antitumor response. The aim of this study was to evaluate the relationship between TLSs and prognosis in patients with tongue squamous cell carcinoma (TSCC) after preoperative S-1 chemotherapy. METHODS: Among 196 TSCC cases, 111 patients who received preoperative S-1 chemotherapy were compared to 85 patients who did not receive chemotherapy. We investigated the incidence of TLSs in both preoperative biopsy and resected specimens. RESULTS: TLSs were present in 24 (12%) biopsy specimens and 31 (16%) resected specimens. TLSs were associated with clinicopathologically advanced cases and positivity for lymphatic invasion. None of the cases with pStage 0 (i.e., noninvasive cancer) showed TLSs. In preoperative S-1 chemotherapy cases, TLSs were significantly more common in those treated with S-1 for more than 21 days and in those with treatment effects 0, Ia, and Ib. TLSs may not be a favorable prognostic factor by themselves but maybe a prognostic factor when combined with preoperative S-1 treatment. CONCLUSION: The presence of TLSs was suggested to be a factor indicating a favorable prognosis when considering the indication for preoperative S-1 chemotherapy. The synergistic effect of S-1 by activating antitumor immunity may be associated with a better prognosis in TSCC patients with TLSs.

The inhibition of malignant melanoma cell invasion of bone by the TLR7 agonist R848 is dependent upon pro-inflammatory cytokines produced by bone marrow macrophages.

Distant metastasis remarkably worsens the prognoses of malignant melanoma patients. Toll-like receptors (TLRs) recognize molecules derived from many types of pathogens and activate the innate intravital immune system. In this study, we examined the effects of R848, a TLR7 ligand, on bone invasion by malignant melanoma cells. Mice underwent transplantation with cells of a malignant melanoma cell line B16F10, and were also administered R848 every three days. Hindlimbs were obtained 13 days after transplantation and invasion of bone marrow by B16F10 cells was evaluated. ELISA was used to determine the concentrations of cytokines in mouse serum and in the culture medium from bone marrow macrophages (BMMs) in the presence or absence of R848. In addition, MTS assays were used to examine the effects of media from BMM cultures on the proliferation of B16F10 cells. The rate of infiltration by B16F10 cells and the area of invasion were significantly reduced with R848 administration. Furthermore, serum levels of IL-6, IL-12, and IFN-γ were significantly increased in mice administered R848, with the same trend observed in the culture medium of BMMs treated with R848. In addition, B16F10 cell proliferation was suppressed by the addition of medium from cultured BMMs treated with R848. Neutralization by antibodies against IL-6, IL-12, and IFN-γ abrogated the suppression of proliferation of B16F10 cells by culture medium from BMMs treated with R848. Our results suggest that R848 drives the production of IL-6, IL-12, and IFN-γ in BMMs, which reduces proliferation and bone invasion by B16F10 cells.

Characterization of myofibrillar adenosine triphosphatase activity and liberation of actin from myofibrils upon heating chicken breast meat.

Denaturation of actin and myosin in myofibrils induced by heating at 50°C was investigated to reveal the mechanism of irreversible liberation of actin from myofibrils on heating at lower temperatures than conventional cooking. Denaturation of these proteins was determined by Mg2+ -ATPase (adenosine triphosphatase) and Ca2+ -ATPase activities. When minced meat was heated for 20 min, actin was liberated accompanying denaturation of 80% of actin and 50% of myosin. Heating of the myofibrillar fraction (MFF) isolated from meat homogenate induced much slower denaturation of actin than myosin. When MFF was heated with sarcoplasmic fractions, denaturation of actin was facilitated, suggesting that sarcoplasmic fractions contain factors to facilitate actin denaturation. Inosine-5'-monophosphate, a component of sarcoplasmic fractions, was shown to have no effect on actin and myosin denaturation. These results suggest that heating meat at 50°C dissociates binding ('Bond A') between actin and myosin participating in ATPase activities, resulting in denaturation of both proteins under influence of sarcoplasmic components. Although denaturation of actin and myosin disrupted Bond A, actin was not liberated simultaneously, suggesting the presence of another bond ('Bond B', more heat-stable than Bond A) between both proteins and necessity of disruption of Bond B for actin release from myofibrils.

Down-regulation of Irf8 by Lyz2-cre/loxP accelerates osteoclast differentiation in vitro.

Interferon regulatory factor 8 (Irf8) is a transcription factor that negatively regulates osteoclast differentiation and Irf8 global knockout (Irf8 -/-) mice have been shown to have reduced bone volume resulting from increased osteoclast numbers. However, detailed analysis of the functions of Irf8 in osteoclast precursors with a monocyte/macrophage linage is difficult, because the population and properties of hematopoietic cells in Irf8 -/- mice are severely altered. Therefore, to clearly elucidate the functions of Irf8 during osteoclastogenesis, we established myeloid cell-specific Irf8 conditional knockout (Irf8 fl/fl ;Lyz2 cre/+) mice. We found that trabecular bone volume in the Irf8 fl/fl ;Lyz2 cre/+ mice was not significantly affected, while exposure to M-CSF and RANKL significantly increased TRAP activity in vitro in osteoclasts that underwent osteoclastogenesis from bone marrow-derived macrophages (BMMs) induced from bone marrow cells (BMCs) of those mice by addition of M-CSF. Our results also showed that expression of Irf8 mRNA and protein in BMMs obtained from Irf8 fl/fl ;Lyz2 cre/+ mice and cultured with M-CSF was reduced. These findings predicted that Lyz2/Lyz2-cre expression is induced when BMCs differentiate into BMMs in cultures with M-CSF. In osteoclast differentiation cultures, Lyz2 was gradually increased by M-CSF during the first 3 days of culture, then rapidly decreased by the addition of RANKL with M-CSF during the next 3 days. Furthermore, BMCs differentiated into osteoclasts while maintaining a low level of Lyz2 expression when cultured simultaneously with both M-CSF and RANKL from the initiation of culture. These findings suggest that Lyz2-cre expression is induced along with differentiation to BMMs by BMCs obtained from Irf8 fl/fl ;Lyz2 cre/+ mice and cultured with M-CSF. In addition, Irf8 was down-regulated by activation of the cre/loxP recombination system in BMMs and osteoclastogenesis was accelerated. Based on our results, we propose the existence in vivo of a new lineage of osteoclast precursors among BMCs, which differentiate into osteoclasts without up-regulation of Lyz2 expression.

Late-onset glucocorticoid-responsive circulatory collapse in preterm infants: clinical characteristics of 14 patients.

Preterm infants may develop acute systemic hypotension that responds to glucocorticoid therapy, but not to volume loading or vasopressors, during the postnatal period. This condition is termed late-onset circulatory collapse (LCC) that develops a few weeks after birth in relatively stable infants. LCC may cause periventricular leukomalacia, periventricular necrosis in the white matter. The aim of this study was to identify the clinical characteristics of LCC. We retrospectively reviewed the clinical data of infants with LCC. Among 41 infants born at < 29 weeks of gestation between 2010 and 2014, we identified 14 infants (median gestational age 25.6 weeks) with LCC. All infants were stable before the acute onset of circulatory collapse at a median age of 21 days, which is characterized by the decreased physical activity, systolic blood pressure (12 mmHg decrease), urine output (76% decrease), and serum sodium level (4 mEq/L decrease), and the increased resistance index in the cerebral and renal arteries on Doppler ultrasonography. Both left ventricular dimension and contraction were well preserved. Three infants developed hyperkalemia. The median time from the initial hydrocortisone dose to improvements was 4 h (interquartile range 3-5 h). Hydrocortisone therapy was effective, but had to be withdrawn slowly to prevent relapse. The median duration of hydrocortisone therapy was 23 days. There was no evidence of periventricular leukomalacia in any of the infants. None of the infants developed adrenal insufficiency during the follow-up period. During the acute stage of LCC, the main priority is the early initiation of glucocorticoid therapy.

Case of femoral diaphyseal stress fracture after long-term risedronate administration diagnosed by iliac bone biopsy.

Bisphosphonate excessively inhibits bone resorption and results in pathological fracture of the femur or ilium. The subject of this study was administered risedronate for 7 years; we suspected an easy fracture of the femoral diaphysis. In this study, we report the results of this patient's bone biopsy and bone morphometric analysis. A 76-year-old female patient presented with right femoral pain. Bone mineral density of the anteroposterior surface of the 2nd to 4th lumbar vertebrae (L2-L4) was decreased and levels of bone turnover markers were high. Therefore, we initiated treatment with risedronate. As she continued the medication, urinary levels of cross-linked N-terminal telopeptides of type I collagen and alkaline phosphatase (bone-type isozyme) were found to be within the normal ranges. After 7 years of administration, the patient experienced pain when she put weight on the right femur and right femoral pain while walking. Plain radiographic examination revealed polypoid stress fracture-like lesions on the right femoral diaphysis and on the slightly distal-lateral cortical bone. Similar lesions were observed on magnetic resonance imaging and bone scintigraphy. We suspected severely suppressed bone turnover. Bone biopsy was obtained after labeling with tetracycline, and bone morphometric analysis was performed. On microscopic examination, slight double tetracycline labeling was observed. The trabeculae were narrow, and the numbers of osteoblasts and osteoclasts were decreased. Further, rates of bone calcification and bone formation were slow. Hence, we diagnosed fracture as a result of low turnover osteopathy. Risedronate was withdrawn, and Vitamin D3 was administered to improve the bone turnover. At 6 months, abnormal signals on magnetic resonance imaging had decreased and her pain while walking or undergoing the stress test disappeared as well. Thus, long-term administration of bisphosphonates may lead to easy fracture, although bone turnover markers were observed to be within the normal range. During bisphosphonate administration, physicians need to monitor closely and treat their patients for any pain experienced in the femoral region while walking or undergoing a stress test.

Chemistry of renieramycins. Part 8: synthesis and cytotoxicity evaluation of renieramycin M-jorunnamycin A analogues.

Twenty-four ester analogues of renieramycin M (1m) were prepared from jorunnamycin A (3a), which was easily transformed from marine natural 1m in three steps. These analogues, along with 1m itself, cyanojorumycin (2b), and jorunnamycins A (3a) and C (3b), were evaluated in vitro for cytotoxicity by measuring IC(50) values through the 3-(4,5-dimethyltriazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay using human HCT116 colon carcinoma and MDA-MB-435 breast carcinoma cell lines. Nitrogen-containing heterocyclic ester derivatives 9a-f showed similar in vitro cytotoxicity to 1m, whereas the other derivatives were slightly less cytotoxic than 1m. 2'-Pyridinecarboxylic acid ester derivative (9c) exhibited a threefold increase in cytotoxicity relative to 1m.

Genes associated with the genesis of leiomyoma of the uterus in a commonly deleted chromosomal region at 7q22.

Uterine leiomyoma occurs in about 20-30% of women over the age of 30, and is the most frequent benign tumor in gynecology. Despite its benign status, leiomyoma of the uterus has been reported to involve chromosomal abnormalities on chromosome 7. To search for genes associated with the genesis and development of this disease, we examined microsatellite alterations on chromosome 7 in 41 uterine leiomyomas, and identified a commonly-deleted region. Allelic imbalance on chromosome 7 was detected with an incidence of 7% (3/41), with the D7S501 locus being the most frequently affected (13%). The commonly deleted region was between D7S2545 and D7S2420. We examined alterations in the expression of genes located within this region by RT-PCR. Only the LAMB1 (Laminin beta1) gene showed a variable expression. Of the 21 cases, 12 showed an increase, and 5 (24%) a decrease in the expression of LAMB1 in the leiomyomatous region. These results suggested that alteration of LAMB1 expression is associated with the genesis and development of uterine leiomyoma.