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1.
J Am Vet Med Assoc ; : 1-10, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38906171

ABSTRACT

OBJECTIVE: To determine the rate of nodal metastasis in dogs with thyroid cancer and evaluate whether immunohistochemistry (IHC) identifies additional metastases beyond evaluation with H&E. ANIMALS: 70 prospectively enrolled client-owned dogs with thyroid cancer managed with thyroidectomy. METHODS: Dogs underwent thyroidectomy with concurrent elective bilateral medial retropharyngeal (MRP) ± deep cervical lymphadenectomy. Thyroid tumors and associated lymph nodes were reviewed by a single board-certified pathologist. Immunohistochemistry was used for all primary tumors (thyroid transcription factor-1 and calcitonin) to support a diagnosis of follicular or medullary carcinoma. Lymph nodes without evidence of metastasis after H&E review were labeled with the antibody associated with the wider uptake in the primary tumor. RESULTS: 77 thyroid cancers were resected from the 70 dogs enrolled, including 61 (79.2%) follicular, 8 (10.7%) medullary, and 7 (9.3%) mixed follicular/medullary carcinomas, with 1 (1.3%) carcinosarcoma. Twelve dogs had evidence of nodal metastasis following H&E review. Occult micrometastasis was identified in 1 dog following nodal IHC, resulting in documented metastasis in 13 of 70 (18.6%) dogs. Metastasis was more common with medullary (5/8) and follicular/medullary carcinoma (3/7) than follicular carcinoma (5/61). All MRP metastases were ipsilateral (7/77 [9.1%]), without contralateral MRP metastases (0/62). Fourteen of 41 (34.1%) deep cervical lymph nodes were metastatic. CLINICAL RELEVANCE: Nodal metastasis was uncommon for follicular carcinoma but was seen in > 50% of dogs with thyroid cancer involving a medullary component. Routine nodal IHC appears to be low yield for thyroid carcinoma. Extirpation of ipsilateral MRP and identifiable deep cervical lymph nodes is recommended with thyroidectomy until detailed preoperative risk stratification becomes available.

3.
Metabolomics ; 20(2): 36, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38446263

ABSTRACT

INTRODUCTION: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging. OBJECTIVE: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality. METHODS: We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact. RESULTS: Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased. CONCLUSION: Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.


Subject(s)
Mitochondrial Diseases , Sepsis , Shock, Septic , Humans , Amino Acids , N-Formylmethionine , Metabolomics , Methionine , Lactic Acid , Racemethionine
4.
Vet Comp Oncol ; 22(2): 239-244, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38488259

ABSTRACT

Thyroid follicular tumours may take up iodide via the sodium-iodide symporter. Knowledge of iodide uptake could then allow treatment with I-131 in dogs with high-risk tumours. The objective of this study was to determine the relationship between clinically detectable iodide uptake (as determined by scintigraphy and/or thyroxine concentrations) and sodium iodide symporter immunohistochemical labelling on histologically fixed thyroid tumours. Nineteen dogs were identified who were diagnosed with thyroid carcinoma and underwent surgery from November 2017 to July 2021. All had recorded thyroid hormone concentrations and were hyperthyroid and/or underwent preoperative nuclear imaging using planar scintigraphy (technetium-99m or I-123), or I-124 PET-CT. All dogs subsequently underwent surgery to remove the thyroid mass. Twenty-two tumours were submitted for histopathologic analysis immediately following surgery, which confirmed a diagnosis of thyroid carcinoma for each tumour. Images and/or thyroid hormone concentrations were reviewed for the included cases, and tumours were sorted into an avid/functional group (group 1) and a non-avid/functional group (group 2). The tumour tissues were re-examined histologically using sodium iodide symporter (NIS) immunohistochemistry (IHC). Group 1 contained 15 avid/functional tumours. Twelve of these tumours had membranous NIS IHC labelling. Group 2 contained 7 non-avid tumours. One of these tumours had membranous NIS IHC labelling. This resulted in an overall sensitivity and specificity for identification of avid/functional tumours with membranous NIS of 80.0% and 85.7%, respectively. NIS IHC may predict ion trapping in canine follicular thyroid tumours. Further studies using iodide-based imaging are warranted to better determine the clinical utility of this diagnostic modality.


Subject(s)
Dog Diseases , Symporters , Thyroid Neoplasms , Animals , Dogs , Symporters/metabolism , Thyroid Neoplasms/veterinary , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/pathology , Dog Diseases/metabolism , Dog Diseases/diagnosis , Male , Female , Iodine Radioisotopes , Immunohistochemistry/veterinary , Iodides/metabolism
5.
Cell ; 187(3): 659-675.e18, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38215760

ABSTRACT

The electron transport chain (ETC) of mitochondria, bacteria, and archaea couples electron flow to proton pumping and is adapted to diverse oxygen environments. Remarkably, in mice, neurological disease due to ETC complex I dysfunction is rescued by hypoxia through unknown mechanisms. Here, we show that hypoxia rescue and hyperoxia sensitivity of complex I deficiency are evolutionarily conserved to C. elegans and are specific to mutants that compromise the electron-conducting matrix arm. We show that hypoxia rescue does not involve the hypoxia-inducible factor pathway or attenuation of reactive oxygen species. To discover the mechanism, we use C. elegans genetic screens to identify suppressor mutations in the complex I accessory subunit NDUFA6/nuo-3 that phenocopy hypoxia rescue. We show that NDUFA6/nuo-3(G60D) or hypoxia directly restores complex I forward activity, with downstream rescue of ETC flux and, in some cases, complex I levels. Additional screens identify residues within the ubiquinone binding pocket as being required for the rescue by NDUFA6/nuo-3(G60D) or hypoxia. This reveals oxygen-sensitive coupling between an accessory subunit and the quinone binding pocket of complex I that can restore forward activity in the same manner as hypoxia.


Subject(s)
Caenorhabditis elegans , Electron Transport Complex I , Hypoxia , Animals , Mice , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Electron Transport Complex I/metabolism , Hypoxia/genetics , Hypoxia/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Oxygen/metabolism
6.
Vet Surg ; 53(3): 524-534, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37753557

ABSTRACT

OBJECTIVES: To categorize the fascial planes and the intersections of these fascial planes in the hindlimb of the dog to facilitate preoperative planning for superficial cancers. STUDY DESIGN: Qualitative anatomical study. SAMPLE POPULATION: Four male and five female mixed breed dogs, weighing ~15-35 kg. METHODS: Skin and subcutaneous fat were removed, and fascial planes were explored to determine borders and quality. Fascia was categorized as type I (discrete sheets), type II (adhered to thin muscles), type III (adhered to thick muscles), or type IV (associated with periosteum). Digital modification of specimen photographs was performed to map tissues. RESULTS: Differences in dogs were noted due to either size or sex but were sufficiently minor to allow mapping. Fasciae of the hindlimb were predominantly type II or III, with type I fascia primarily at the lateral gluteal region, fascia lata, and lateral crus. Type IV fascia was seen at the iliac wing, ischium, patella, tibial tuberosity, medial tibia, distal crus, and pes. Fascia for surgical use was thin or absent at the ischiorectal fossa, femoral triangle, extensor mechanism, medial and distal crus, and pes. Intersections and tissues at the ventral perineum may also pose challenges for maintenance of a deep margin. CONCLUSION: Fascial types and integrity of the hindlimb varied with location, with the perineum, cranial stifle, and distal limb presenting the greatest challenges. CLINICAL SIGNIFICANCE: These images may be used to guide both therapeutic decision-making and intraoperative excision of superficial tumors of the hindlimb and pelvis.


Subject(s)
Lower Extremity , Tibia , Male , Dogs , Female , Animals , Stifle , Pelvis , Fascia Lata
7.
J Am Vet Med Assoc ; 261(12): 1-9, 2023 12 01.
Article in English | MEDLINE | ID: mdl-37734721

ABSTRACT

OBJECTIVE: To conduct a retrospective multi-institutional study reporting short- and long-term outcomes of adrenalectomy in patients presenting with acute hemorrhage secondary to spontaneous adrenal rupture. ANIMALS: 59 dogs and 3 cats. METHODS: Medical records of dogs and cats undergoing adrenalectomy between 2000 and 2021 for ruptured adrenal masses were reviewed. Data collected included clinical presentation, preoperative diagnostics, surgical report, anesthesia and hospitalization findings, histopathology, adjuvant treatments, and long-term outcome (recurrence, metastasis, and survival). RESULTS: Median time from hospital admission to surgery was 3 days, with 34% of surgeries being performed emergently (within 1 day of presentation). Need for intraoperative blood transfusion was significantly associated with emergent surgery and presence of active intraoperative hemorrhage. The short-term (≤ 14 days) complication and mortality rates were 42% and 21%, respectively. Negative prognostic factors for short-term survival included emergent surgery, intraoperative hypotension, and performing additional surgical procedures. Diagnoses included adrenocortical neoplasia (malignant [41%], benign [12%], and undetermined [5%]), pheochromocytoma (38%), a single case of adrenal fibrosis and hemorrhage (2%), and a single case of hemangiosarcoma (2%). Local recurrence and metastasis of adrenocortical carcinoma were confirmed in 1 and 3 cases, respectively. Overall median survival time was 574 days and 900 days when short-term mortality was censored. No significant relationship was found between histopathological diagnosis and survival. CLINICAL RELEVANCE: Adrenalectomy for ruptured adrenal gland masses was associated with similar short- and long-term outcomes as compared with previously reported nonruptured cases. If hemodynamic stability can be achieved, delaying surgery and limiting additional procedures appear indicated to optimize short-term survival.


Subject(s)
Adrenal Cortex Neoplasms , Adrenal Gland Neoplasms , Cat Diseases , Dog Diseases , Hemorrhage , Laparoscopy , Animals , Cats , Dogs , Humans , Adrenal Cortex Neoplasms/complications , Adrenal Cortex Neoplasms/surgery , Adrenal Cortex Neoplasms/veterinary , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/veterinary , Adrenalectomy/veterinary , Adrenalectomy/adverse effects , Adrenalectomy/methods , Cat Diseases/surgery , Dog Diseases/pathology , Hemorrhage/veterinary , Laparoscopy/veterinary , Retrospective Studies , Rupture, Spontaneous/veterinary , Treatment Outcome
8.
Vet Comp Oncol ; 21(4): 673-684, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37652746

ABSTRACT

Adrenalectomies for canine adrenal tumours are associated with peri-operative morbidity and mortality. Objectives of this study included assessing the prognostic value of tumour- or surgery-related variables in predicting peri-operative mortality and overall survival in dogs undergoing adrenalectomies for primary adrenal tumours as well as pre-treatment with phenoxybenzamine on survival to discharge with pheochromocytomas specifically. A multi-institutional retrospective cohort study was performed across nine institutions. Electronic medical record searches identified 302 dogs which met the inclusion criteria. Data collected included dog-related, tumour-related, treatment-related, surgery-related, and outcome variables. Univariate and multivariable logistic regression and cox proportional hazards models were used to identify variables associated with death prior to discharge and tumour-related survival. Overall, 87% of dogs survived to discharge with a tumour-related survival time of 3.96 years. Post-operative complications were reported in 25%. Increased surgical time (p = 0.002) and pre-surgical medical treatment other than phenoxybenzamine (p = 0.024) were significantly associated with increased peri-operative mortality while ureteronephrectomy (p = 0.021), post-operative pancreatitis (p = 0.025), and post-operative aspiration pneumonia (p < 0.001) were significantly associated with decreased overall survival. Phenoxybenzamine pretreatment had no effect on peri-operative mortality. Thirty-seven of 45 (82%) dogs with pheochromocytomas not pretreated survived to discharge, and 50 of 59 (85%) dogs with pheochromocytomas pretreated with phenoxybenzamine survived to discharge (p = 0.730). This study provides information on risk factors for death prior to discharge and tumour-related survival that may help guide clinical management and owner expectations. In addition, the study findings challenge the previously reported benefit of phenoxybenzamine for pretreatment of dogs undergoing adrenalectomies for pheochromocytomas.


Subject(s)
Adrenal Gland Neoplasms , Dog Diseases , Pheochromocytoma , Animals , Dogs , Adrenal Gland Neoplasms/surgery , Adrenal Gland Neoplasms/veterinary , Adrenalectomy/veterinary , Dog Diseases/drug therapy , Patient Discharge , Phenoxybenzamine/therapeutic use , Pheochromocytoma/surgery , Pheochromocytoma/veterinary , Pheochromocytoma/pathology , Retrospective Studies , Risk Factors
9.
Nat Metab ; 5(5): 765-776, 2023 05.
Article in English | MEDLINE | ID: mdl-37198474

ABSTRACT

Glucose is vital for life, serving as both a source of energy and carbon building block for growth. When glucose is limiting, alternative nutrients must be harnessed. To identify mechanisms by which cells can tolerate complete loss of glucose, we performed nutrient-sensitized genome-wide genetic screens and a PRISM growth assay across 482 cancer cell lines. We report that catabolism of uridine from the medium enables the growth of cells in the complete absence of glucose. While previous studies have shown that uridine can be salvaged to support pyrimidine synthesis in the setting of mitochondrial oxidative phosphorylation deficiency1, our work demonstrates that the ribose moiety of uridine or RNA can be salvaged to fulfil energy requirements via a pathway based on: (1) the phosphorylytic cleavage of uridine by uridine phosphorylase UPP1/UPP2 into uracil and ribose-1-phosphate (R1P), (2) the conversion of uridine-derived R1P into fructose-6-P and glyceraldehyde-3-P by the non-oxidative branch of the pentose phosphate pathway and (3) their glycolytic utilization to fuel ATP production, biosynthesis and gluconeogenesis. Capacity for glycolysis from uridine-derived ribose appears widespread, and we confirm its activity in cancer lineages, primary macrophages and mice in vivo. An interesting property of this pathway is that R1P enters downstream of the initial, highly regulated steps of glucose transport and upper glycolysis. We anticipate that 'uridine bypass' of upper glycolysis could be important in the context of disease and even exploited for therapeutic purposes.


Subject(s)
Ribose , Uridine , Ribose/metabolism , Uridine/metabolism , RNA/metabolism , Glycolysis , Humans , Cell Line, Tumor , Oxidative Phosphorylation , Culture Media , Glucose , K562 Cells , Cell Proliferation , Pentose Phosphate Pathway
11.
Nature ; 613(7944): 550-557, 2023 01.
Article in English | MEDLINE | ID: mdl-36599986

ABSTRACT

Animals display substantial inter-species variation in the rate of embryonic development despite a broad conservation of the overall sequence of developmental events. Differences in biochemical reaction rates, including the rates of protein production and degradation, are thought to be responsible for species-specific rates of development1-3. However, the cause of differential biochemical reaction rates between species remains unknown. Here, using pluripotent stem cells, we have established an in vitro system that recapitulates the twofold difference in developmental rate between mouse and human embryos. This system provides a quantitative measure of developmental speed as revealed by the period of the segmentation clock, a molecular oscillator associated with the rhythmic production of vertebral precursors. Using this system, we show that mass-specific metabolic rates scale with the developmental rate and are therefore higher in mouse cells than in human cells. Reducing these metabolic rates by inhibiting the electron transport chain slowed down the segmentation clock by impairing the cellular NAD+/NADH redox balance and, further downstream, lowering the global rate of protein synthesis. Conversely, increasing the NAD+/NADH ratio in human cells by overexpression of the Lactobacillus brevis NADH oxidase LbNOX increased the translation rate and accelerated the segmentation clock. These findings represent a starting point for the manipulation of developmental rate, with multiple translational applications including accelerating the differentiation of human pluripotent stem cells for disease modelling and cell-based therapies.


Subject(s)
Embryo, Mammalian , Embryonic Development , Animals , Humans , Mice , Cell Differentiation , Embryonic Development/physiology , NAD/metabolism , Oxidation-Reduction , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/metabolism , Species Specificity , In Vitro Techniques , Electron Transport , Biological Clocks , Time Factors , Embryo, Mammalian/cytology , Embryo, Mammalian/embryology , Embryo, Mammalian/metabolism , Levilactobacillus brevis
12.
Vet Surg ; 52(2): 276-283, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36420619

ABSTRACT

OBJECTIVE: To describe the technique and outcomes of the closure of maxillary lip defects using a buccal transposition flap and to identify potential routes of vascular supply to the flap. ANIMALS: Five dogs treated clinically and 1 cadaveric dog head. STUDY DESIGN: Short case series and cadaveric study. METHODS: A left maxillary labial defect and a buccal transposition flap were created on a cadaver head. Iodinated contrast was injected into the left common carotid artery and computed tomography was performed to assess the vascular supply. Medical records were reviewed for all dogs that underwent tumor excision with maxillary lip resection, reconstructed with a buccal transposition flap. RESULTS: The buccal transposition flap was perfused by branches of the angularis oris artery and superior labial artery. Five dogs were included in this study. All flaps survived. Three dogs developed postoperative complications, including oronasal fistula (n = 2) and partial flap dehiscence (n = 1). The cosmetic and functional outcomes were considered satisfactory in all cases. CONCLUSION: Buccal transposition flaps for the closure of large maxillary lip defects provided adequate functional and cosmetic outcomes. The buccal transposition flap had vascular contributions from the angularis oris artery and the superior labial artery.


Subject(s)
Dog Diseases , Plastic Surgery Procedures , Dogs , Animals , Plastic Surgery Procedures/veterinary , Lip/surgery , Surgical Flaps/veterinary , Cadaver , Carotid Artery, Common/surgery , Dog Diseases/surgery
13.
Can Vet J ; 63(9): 929-934, 2022 09.
Article in English | MEDLINE | ID: mdl-36060485

ABSTRACT

Objective: To report intraoperative and immediate postoperative complications associated with removal of metastatic iliosacral lymph nodes in dogs with apocrine gland anal sac adenocarcinoma. Animals: There were 136 client-owned dogs in the study. Procedure: Retrospective multi-institutional study. The database of collaborating institutions was searched for dogs with metastatic apocrine gland anal sac adenocarcinoma that underwent lymphadenectomy for removal of one or more iliosacral lymph nodes. Information of signalment, hematological abnormalities, abdominal computed tomography or ultrasound findings, number and size of enlarged lymph nodes, intraoperative and postoperative complications, treatment and outcome were collected. Results: The overall complication rate associated with metastatic iliosacral lymphadenectomy was 26.1%. The only intraoperative complication recorded was hemorrhage and was reported in 24 (17.6%) surgeries, 11 (45.8%) of which received a blood transfusion. Postoperative complications were reported in 10.4% of surgeries, and included edema formation (n = 4, 2.6%), unilateral or bilateral paraparesis (n = 4, 2.6%), hypotension (n = 3, 2.0%), surgical site infection (n = 2, 1.3%), abdominal incision dehiscence (n = 1, 0.6%), urinary incontinence (n = 1, 0.6%), and death (n = 1, 0.6%). The size of the iliosacral lymph nodes was significantly associated with a greater risk of complications, hemorrhage, and the need of transfusion during lymphadenectomy for metastatic apocrine gland anal sac adenocarcinoma. Conclusion: Complications associated with iliosacral lymphadenectomy for metastatic apocrine gland anal sac adenocarcinoma are relatively common and mostly relate to hemorrhage. These complications are significantly associated with the size of the extirpated metastatic lymph nodes. Clinical relevance: This retrospective study provides information for the clinician regarding the potential surgical complications for extirpation of metastatic iliosacral lymph nodes. These complications, although not common, can be severe and should be discussed with owners before surgery.


Objectif: Rapporter les complications peropératoires et postopératoires immédiates associées à l'ablation des ganglions lymphatiques ilio-sacrés métastatiques chez les chiens atteints d'un adénocarcinome des glandes apocrines des sacs anaux. Animaux: Il y avait 136 chiens appartenant à des clients dans l'étude. Procédure: Étude multi-institutionnelle rétrospective. La base de données des institutions collaboratrices a été recherchée pour les chiens atteints d'un adénocarcinome métastatique des glandes apocrines des sacs anaux qui ont subi une lymphadénectomie pour l'ablation d'un ou plusieurs ganglions lymphatiques ilio-sacrés. Des informations sur le signalement, les anomalies hématologiques, les résultats de la tomodensitométrie abdominale ou de l'échographie, le nombre et la taille des ganglions élargis, les complications peropératoires et postopératoires, le traitement et les résultats ont été recueillis. Résultats: Le taux global de complications associées à la lymphadénectomie ilio-sacrée métastatique était de 26,1 %. La seule complication peropératoire enregistrée était une hémorragie et a été rapportée dans 24 (17,6 %) chirurgies, dont 11 (45,8 %) ont reçu une transfusion sanguine. Des complications postopératoires ont été signalées dans 10,4 % des interventions chirurgicales et comprenaient la formation d'oedème (n = 4, 2,6 %), la paraparésie unilatérale ou bilatérale (n = 4, 2,6 %), l'hypotension (n = 3, 2,0 %), l'infection du site opératoire (n = 2, 1,3 %), la déhiscence de l'incision abdominale (n = 1, 0,6 %), l'incontinence urinaire (n = 1, 0,6 %) et le décès (n = 1, 0,6 %). La taille des ganglions ilio-sacrés était significativement associée à un risque accru de complications, d'hémorragie et à la nécessité d'une transfusion lors d'une lymphadénectomie pour un adénocarcinome métastatique des glandes apocrines des sacs anaux. Conclusion: Les complications associées à la lymphadénectomie ilio-sacrée pour l'adénocarcinome métastatique des glandes apocrines des sacs anaux sont relativement fréquentes et concernent principalement l'hémorragie. Ces complications sont significativement associées à la taille des ganglions lymphatiques métastatiques retirés. Pertinence clinique: Cette étude rétrospective fournit des informations au clinicien concernant les complications chirurgicales potentielles pour le retrait des ganglions lymphatiques ilio-sacrés métastatiques. Ces complications, bien que rares, peuvent être graves et doivent être discutées avec les propriétaires avant la chirurgie.(Traduit par Dr Serge Messier).


Subject(s)
Adenocarcinoma , Anal Gland Neoplasms , Anal Sacs , Bone Neoplasms , Dog Diseases , Adenocarcinoma/pathology , Adenocarcinoma/veterinary , Anal Gland Neoplasms/drug therapy , Anal Gland Neoplasms/pathology , Anal Gland Neoplasms/surgery , Anal Sacs/pathology , Animals , Apocrine Glands/pathology , Bone Neoplasms/veterinary , Dog Diseases/pathology , Dog Diseases/surgery , Dogs , Lymph Node Excision/veterinary , Retrospective Studies
14.
J Biol Chem ; 298(8): 102210, 2022 08.
Article in English | MEDLINE | ID: mdl-35780837

ABSTRACT

Microaerophilic pathogens such as Giardia lamblia, Entamoeba histolytica, and Trichomonas vaginalis have robust oxygen consumption systems to detoxify oxygen and maintain intracellular redox balance. This oxygen consumption results from H2O-forming NADH oxidase (NOX) activity of two distinct flavin-containing systems: H2O-forming NOXes and multicomponent flavodiiron proteins (FDPs). Neither system is membrane bound, and both recycle NADH into oxidized NAD+ while simultaneously removing O2 from the local environment. However, little is known about the specific contributions of these systems in T. vaginalis. In this study, we use bioinformatics and biochemical analyses to show that T. vaginalis lacks a NOX-like enzyme and instead harbors three paralogous genes (FDPF1-3), each encoding a natural fusion product between the N-terminal FDP, central rubredoxin (Rb), and C-terminal NADH:Rb oxidoreductase domains. Unlike a "stand-alone" FDP that lacks Rb and oxidoreductase domains, this natural fusion protein with fully populated flavin redox centers directly accepts reducing equivalents of NADH to catalyze the four-electron reduction of oxygen to water within a single polypeptide with an extremely high turnover. Furthermore, using single-particle cryo-EM, we present structural insights into the spatial organization of the FDP core within this multidomain fusion protein. Together, these results contribute to our understanding of systems that allow protozoan parasites to maintain optimal redox balance and survive transient exposure to oxic conditions.


Subject(s)
Rubredoxins , Trichomonas vaginalis , Flavins/metabolism , NAD/metabolism , NADH, NADPH Oxidoreductases/metabolism , Oxidation-Reduction , Oxidoreductases/metabolism , Oxygen/metabolism , Rubredoxins/genetics , Rubredoxins/metabolism , Trichomonas vaginalis/genetics , Trichomonas vaginalis/metabolism , Water/metabolism
15.
Vet Comp Oncol ; 20(3): 669-678, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35420253

ABSTRACT

The aim of this study was to determine the outcome of dogs with soft tissue sarcoma (STS) within the region of the ischiatic tuberosity (ITSTS) treated surgically. This was a multi-institutional retrospective study. Fifty-two dogs met the inclusion criteria, which were: histologically confirmed STS in the region of the IT treated with surgical resection between March 1st, 2009 and March 1st, 2021 with a minimum follow-up time of 6 months. Data collected included patient signalment, preoperative diagnostics, surgical intent/method, surgical complications, histopathology, margins, outcome and cause of death. Statistical analyses were performed to determine significant factors in the treatment and prognosis of ITSTS. Overall survival time (OST) and disease progression were negatively associated with tumour grade, while recurrence was positively associated with grade and incomplete margins. Of the 52 included dogs, there were 24 grade I, 20 grade II and 7 grade III tumours. Forty dogs had reported histopathologic margins of which 26 were reported to be complete and 14 were incomplete. OST and progression-free survival was not reached for tumours graded as I or II and was 255 and 268 days respectively, for grade III. Median time to recurrence was not reached for tumours excised with complete margins and was 398 days for those with incomplete margins. The surgical complication rate was 25%. ITSTS was not found to be a unique clinical entity in dogs as tumour behavior, treatment recommendations, and prognosis were similar to STS in other locations, with overall outcome and prognosis influenced by histologic grade and margins. While surgical complications were common, none resulted in significant morbidity or mortality.


Subject(s)
Dog Diseases , Sarcoma , Soft Tissue Neoplasms , Surgical Oncology , Animals , Dog Diseases/pathology , Dogs , Margins of Excision , Neoplasm Recurrence, Local/veterinary , Retrospective Studies , Sarcoma/surgery , Sarcoma/veterinary , Societies, Veterinary , Soft Tissue Neoplasms/surgery , Soft Tissue Neoplasms/veterinary , Treatment Outcome
16.
Vet Comp Oncol ; 20(3): 664-668, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35411711

ABSTRACT

The axillary lymph center drains a large area; however, axillary lymphadenectomy is rarely reported in series detailing lymph node extirpation in dogs. No surgical technique has yet been described for axillary and superficial axillary lymphadenectomy. This study describes a technique for excision of nodes in the axillary lymph center of the dog. Two male neutered and two male intact cadavers weighing between 6.3 and 36.1 kg were used. With cadavers in dorsal recumbency and the shoulder extended, an incision was made in the caudal axillary region. Blunt dissection was used to separate the pectoralis profundus and latissimus dorsi muscles and loose connective tissue was dissected until the axillary lymph node was identified caudal to the brachial vein. The axillary lymphatic trunk was followed caudad from the axillary lymph node to identify the accessory axillary lymph node, deep to the lateral border of the pectoralis profundus muscle, for subsequent extirpation. Axillary lymph nodes were successfully removed in all axillae, and accessory axillary lymph nodes were located in 6/7 axillae and could not be visualized within the axillary lymphatic trunk in the remaining axilla. The described surgical technique allowed consistent identification of the axillary lymph node and the lymphatic trunk associated with the accessory axillary lymph node. This technique description provides a guide for surgeons to facilitate axillary and accessory axillary lymphadenectomy in the dog. While anatomic variation must be considered, the use of the axillary lymphatic trunk as a landmark may simplify identification of the small and inconsistent accessory axillary lymph node.


Subject(s)
Dog Diseases , Animals , Axilla/surgery , Cadaver , Dog Diseases/pathology , Dog Diseases/surgery , Dogs , Lymph Node Excision/methods , Lymph Node Excision/veterinary , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis/pathology , Male , Sentinel Lymph Node Biopsy/veterinary
17.
J Am Vet Med Assoc ; 260(11): 1369-1376, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35429376

ABSTRACT

OBJECTIVE: To describe veterinary house officers' perceptions of dimensions of well-being during postgraduate training and to identify potential areas for targeted intervention. SAMPLE: 303 house officers. PROCEDURES: A 62-item questionnaire was generated by use of an online platform and sent to house officers at participating institutions in October 2020. Responses were analyzed for trends and associations between selected variables. RESULTS: 239 residents, 45 rotating interns, and 19 specialty interns responded to the survey. The majority of house officers felt that their training program negatively interfered with their exercise habits, diet, and social engagement. House officers reported engaging in exercise significantly less during times of clinical responsibility, averaging 1.6 exercise sessions/wk (SD ± 0.8) on clinical duty and 2.4 exercise sessions/wk (SD ± 0.9) when not on clinical duty (P < 0.001). Ninety-four percent of respondents reported experiencing some degree of anxiety regarding their physical health, and 95% of house officers reported feeling some degree of anxiety regarding their current financial situation. Overall, 47% reported that their work-life balance was unsustainable for > 1 year; there was no association between specialty and sustainability of work-life balance. Most house officers were satisfied with their current training program, level of clinical responsibility, and mentorship. CLINICAL RELEVANCE: Veterinary house officers demonstrated a poor balance between the demands of postgraduate training and maintenance of personal health. Thoughtful interventions are needed to support the well-being of veterinary house officers.


Subject(s)
Physical Conditioning, Animal , Animals , Attitude of Health Personnel , Health Personnel , Humans , Surveys and Questionnaires
18.
Vet Surg ; 51(4): 611-619, 2022 May.
Article in English | MEDLINE | ID: mdl-35257394

ABSTRACT

OBJECTIVE: To describe the clinical characteristics, perioperative protocols, and outcomes in dogs diagnosed with ventricular fibrillation (VF) while undergoing pericardiectomy. STUDY DESIGN: Retrospective, multi-institutional study. ANIMALS: Sixteen client-owned dogs. METHODS: Cases were accrued through a listserve request posted to 3 subspecialty veterinary societies. Dogs were included if they developed VF during a pericardiectomy performed through an open or thoracoscopic approach. Data collected included signalment, history and physical examination, surgical approach, histopathology, treatment, and outcome. RESULTS: Indications for pericardiectomy included idiopathic chylothorax (n = 7), neoplasia (4), idiopathic pericardial effusion (4), and foreign body granuloma (1). Surgical approaches included thoracoscopy (12), intercostal thoracotomy (3) and median sternotomy (1). Electrosurgical devices were used to complete at least part of the pericardiectomy in 15 of 16 dogs. Ventricular fibrillation appeared to be initiated during electrosurgical use in 8/15 dogs. However, in 5/15 dogs it was not obviously associated with electrosurgical use. In 3/16 dogs the timing of initiation of VF was unclear. In 7/16 dogs, cardiac arrhythmias were noted prior to the development of VF. Fourteen of 16 dogs died from intraoperative VF. CONCLUSION: In most dogs ventricular fibrillation was a fatal complication of pericardiectomy. Ventricular fibrillation might be associated with the use of electrosurgical devices and cardiac manipulation during pericardiectomy although a causal link could not be established from the data in this study. CLINICAL SIGNIFICANCE: Surgeons must be aware of the risk of VF during pericardial surgery. Electrosurgery might need to be used judiciously during pericardiectomy, particularly in dogs exhibiting cardiac arrythmias.


Subject(s)
Dog Diseases , Pericardiectomy , Animals , Arrhythmias, Cardiac/complications , Arrhythmias, Cardiac/veterinary , Dog Diseases/etiology , Dog Diseases/surgery , Dogs , Pericardiectomy/adverse effects , Pericardiectomy/methods , Pericardiectomy/veterinary , Retrospective Studies , Ventricular Fibrillation/complications , Ventricular Fibrillation/veterinary
19.
Vet Surg ; 51(1): 68-78, 2022 Jan.
Article in English | MEDLINE | ID: mdl-33476413

ABSTRACT

OBJECTIVE: To provide qualitative fascial categories and classify the intersections of various fascial planes of the trunk of the dog to facilitate preoperative planning for superficial cancers. STUDY DESIGN: Qualitative anatomical study. SAMPLE POPULATION: Two male and three female mixed breed canine cadavers weighing approximately 15 to 35 kg. METHODS: The skin and subcutaneous fat were excised. Fascial planes were incised and elevated to allow exploration of their quality and borders. Fascia was categorized as type I (discrete sheets), type II (tightly adhered to thin muscles), type III (tightly adhered to thick muscles), or type IV (associated with periosteum). Photographs of specimens were digitally modified with overlays to map tissue types. RESULTS: Differences between cadavers were largely associated with muscle mass or sex, with only minor anatomical differences and enough subjective similarity among specimens to allow mapping. The fasciae of the neck and trunk were predominantly type I or type II, with type III fascia at the shoulder and type IV fascia at the scapular spine, 13th rib, dorsal spinous processes, and the wing of the ilium. CONCLUSION: The superficial fasciae of the canine trunk were consistent among the dogs evaluated and can be classified as four broad fascial types. The population used was small, and individual variation should be considered when using these images in a clinical setting. CLINICAL SIGNIFICANCE: The images and categorization of fascia and transitions between fascial layers detailed here provide a visual and written reference for surgeons to facilitate preoperative planning and excision of superficial cancers.


Subject(s)
Dog Diseases , Fascia , Neoplasms , Animals , Cadaver , Dog Diseases/surgery , Dogs , Female , Male , Muscles , Neck , Neoplasms/surgery , Neoplasms/veterinary , Torso
20.
Vet Surg ; 51(1): 79-87, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34292615

ABSTRACT

OBJECTIVE: To detail the qualitative fascial categories and fascial intersections of the forelimb of the dog to facilitate preoperative planning for superficial cancers. STUDY DESIGN: Qualitative anatomical study. SAMPLE POPULATION: Three male and four female mixed breed canine cadavers weighing approximately 20-35 kg. METHODS: The skin and subcutaneous fat were excised. Fascial planes were incised and elevated to allow exploration of their quality and borders. Fascia was categorized as type I (discrete sheets), type II (tightly adhered to thin muscles), type III (tightly adhered to thick muscles), or type IV (associated with periosteum). Photographs of specimens were digitally modified with overlays to map tissue types. RESULTS: Differences between the cadavers used were largely based on muscle mass and sex, with minimal other subjective differences affecting fascial mapping. The fasciae of the forelimb were largely type II or type III, with type I fascia at the antebrachium and type IV fascia at the olecranon, scapular spine, and accessory carpal bone. Fascial integrity was often questionable or lacking distal to the distal quarter of the antebrachium. CONCLUSION: The fascial types and integrity of the forelimb varied with anatomic location with thin or absent fascia for surgical use at the elbow, carpus, and manus. CLINICAL SIGNIFICANCE: This study provides information for preoperative planning and excision of superficial tumors of the forelimb. Knowledge of the potential limitations of fascia to provide a deep margin may influence selection of treatment modalities.


Subject(s)
Dog Diseases , Fascia , Neoplasms , Animals , Cadaver , Dog Diseases/surgery , Dogs , Female , Forelimb/surgery , Male , Muscles , Neoplasms/surgery , Neoplasms/veterinary
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