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Challenges in developing a split drive targeting dsx for the genetic control of the invasive malaria vector Anopheles stephensi
No full textBackgroundAnopheles stephensi is a competent malaria vector mainly present in southern Asia and the Arabian Peninsula. Since 2012, it has invaded several countries of eastern Africa, creating an emerging risk of urban transmission. Urgent efforts are required to develop novel and more efficient strategies for targeted vector control. CRISPR/Cas9-based homing gene drives have been proposed as attractive alternative strategies. Gene drives have the potential to spread a desired trait through a population at higher rates than via normal Mendelian inheritance, even in the presence of a fitness cost. Several target genes have been suggested and tested in different mosquito vector species such as Anopheles gambiae and Aedes aegypti. Several promising suppression drives have been developed in An. gambiae that target the sex determination gene doublesex (dsx).MethodsIn this study, a geographically confineable gene drive system targeting dsx was developed (dsxgRNA). Here, a transgenic line which expresses Cas9 under the control of the endogenous zpg promoter was generated. Separately a transgenic line which expresses a gRNA targeting the female specific exon of dsx was inserted into that same target site. The reproductive fitness of males and females heterozygous and homozygous for this element was determined. A series of experimental crosses was performed to combine the two elements and assess the homing rate of the dsx element in a split drive system.ResultsThe drive was able to home in a super-Mendelian rate comparable to those obtained by an autonomous drive in this species. Although inheritance rates as high as 99.8% were observed, potentially providing very potent gene drive, dominant effects on male and female fertility were observed, which would be sufficient to hinder spread of such a drive. Molecular analysis indicated that the gRNA expressing insertion disrupted normal splicing of dsx.ConclusionsThese results should be considered when proposing the viability of dsx as a target gene for a population suppression gene drives in Anopheles stephensi. Although high homing rates were observed, the fitness defects found in both males and females carrying the transgene would likely prohibit this drive from functioning in the field
Whole genome sequencing revealed high occurrence of antimicrobial resistance genes in bacteria isolated from poultry manure
No full textBackground: Global demand for food has driven expansion and intensification of livestock production, particularly in developing nations where antibiotic use is often routine. Waste from poultry production, including manure, is commonly utilized as fertilizers in agroecosystems, risking environmental contamination with potentially zoonotic bacteria and antimicrobial resistance genes (ARGs). Methods: Here, 33 bacterial isolates were recovered from broiler ( n = 17) and layer ( n = 16) chicken manure by aerobic culture using Luria Bertani agar. Antimicrobial susceptibility testing (AST) was performed using disc diffusion method. MALDI-ToF and 16S rRNA sequencing were used to identify and compare a subset of antibiotic-resistant isolates ( n = 13). Comparison of whole genome sequence assemblies and phenotypic assays were used to assess capacity for biofilm formation, heavy metal tolerance and virulence. Results: AST by disc diffusion revealed all isolates were resistant to a minimum of three antibiotics, with resistance to ampicillin, co-trimoxazole, fluoroquinolones, tetracyclines, streptomycin, rifampicin and/or chloramphenicol detected. Stutzerimonas sp. and Acinetobacter sp. were the common genera observed in this study. Genome sequencing of each selected isolate revealed carriage of multiple ARGs capable of conferring resistance to many antimicrobials commonly employed in poultry production and human medicine, including tetracyclines, quinolones, macrolides, sulfonamide and cephalosporins. Conclusions: The high occurrence of ARGs in studied bacterial isolates confirms that poultry manure could act as a source of genetic material that could be transferred to commensal microbiota and opportunistic pathogens of humans. Understanding the complex resistome interplay between humans, animals, and the environment requires a One Health approach, with implications for agricultural settings and public health. (c) 2025 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights are reserved, including those for text and data mining, AI training, and similar technologies
Successful conservative management of urinary tract rupture in dogs and cats: 52 cases (2003-2024)
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Clinical findings, treatment, and outcomes in cats with naturally occurring hypoadrenocorticism: 41 cases
Get PDFBackground: Hypoadrenocorticism in cats is uncommonly reported. Most reports consist of cats with hyponatremia, hyperkalemia, or both. Hypothesis/Objectives: To describe clinical findings, treatment response, and outcome in cats diagnosed with hypoadrenocorticism, including cats with abnormal and normal serum sodium and potassium concentrations. Animals: Forty-one cats with hypoadrenocorticism; 36 with and 5 without abnormal serum sodium and potassium concentrations. Methods: Multicenter retrospective observational study. Data for the entire cohort were assessed using descriptive statistics and differences between cats with and without abnormal serum sodium and potassium concentrations were evaluated. Results: Median age was 5.7 years (range, 0.2-13.8). Twenty-three (56%) cats were male and 18 (44%) were female. Cats with hyponatremia, hyperkalemia, or both were less likely to have a history of vomiting (P = .01) but more likely to be hypothermic (P = .03), dehydrated (P = .04) or weak (P = .04) on examination, compared with nonhyponatremic and nonhyperkalemic cats. Frequency of hypercalcemia was 31.7%. Exocrine pancreatic insufficiency (EPI) was diagnosed in 4/7 cats tested; all 4 had concurrent cobalamin deficiency. Thirty-five (85.4%) cats survived to discharge. In 2 cats, hypoadrenocorticism occurred secondary to lymphoma. Median survival time (MST) for all-cause mortality was 2035 days (95% confidence interval [CI], 294-4380 days); MST for disease-specific mortality was not reached. Conclusions and Clinical Importance: Approximately one-third of cats with hypoadrenocorticism had hypercalcemia. In some cases, hyponatremia and hyperkalemia were not observed. Cats with nonneoplastic associated hypoadrenocorticism that survive initial hospitalization can have a favorable long-term prognosis. Testing for EPI may be warranted in cats with hypoadrenocorticism
Holocord syringomyelia in 18 dogs
Get PDFHolocord syringomyelia (HSM) is characterized by a continuous spinal cord cavitation along its entire length and is currently poorly documented in dogs. This retrospective multicentric case series investigates the clinical and MRI findings in 18 dogs with HSM. The median age at presentation was 82 months (range 9-108 months) and French Bulldogs were overrepresented (50%). Signs of myelopathy attributed to HSM were detected in 12 dogs (67%), spinal pain/paresthesia/allodynia in eight (44%), and four dogs (22%) had no HSM-associated signs. The most common neuroanatomical localization was C1-C5 spinal cord segments. On MRI, the cranial limit of HSM was at C1 vertebra in seven (39%) and at C2 in 11 dogs (61%). The caudal limit extended to L3 in four dogs (22%), L4 or L5 in six dogs (33%) each, and L6 in two dogs (11%). The conus medullaris terminated at L5 in one dog (6%), L6 in 11 (61%), and L7 in six dogs (33%). Seventeen dogs (94%) exhibited MRI features of Chiari-like and/or other intracranial/cranio-cervical junction malformations. One dog (6%) was treated surgically, 11 (61%) medically, and six (33%) received no treatment. Over a median follow-up of 12 months (range 2-65 months) in 16 dogs, one dog (6%) improved, nine (56%) deteriorated, four (25%) were static, and two (13%) remained free of HSM-associated signs. This is the first study to describe canine HSM, highlighting a possible breed predisposition in French Bulldogs. The frequent occurrence of myelopathy and disease progression underscores the need for further research into the underlying etiopathogenesis, natural disease evolution, and response to therapeutic interventions
Clinical outcomes and complications of tracheal resection and anastomosis in small animals: a 13-year multicentric retrospective study
No full textObjectives To report clinical presentation, short-term outcome and complications of tracheal resection and anastomosis in dogs and cats. Materials and Methods Clinical records of pets treated with tracheal resection and anastomosis in seven UK-based veterinary referral centres were retrospectively reviewed (2009 to 2022). Results Twenty client-owned pets (eight dogs; 12 cats) were included. Clinical signs comprised dyspnoea (n?=?15), stridor (n?=?5), subcutaneous emphysema (n?=?3), pneumothorax and pneumomediastinum (n?=?1), coughing (n?=?3), regurgitation (n?=?1) and exercise intolerance (n?=?1). Indication for surgery was traumatic tracheal rupture (n?=?5), tracheal avulsion (n?=?7), neoplasia (n?=?5) and stenosis (n?=?3). Complications occurred in 15 patients (75%). Non-anastomotic complications occurred in nine patients and consisted of cough (n?=?5), self-resolving laryngeal paralysis (n?=?1), surgical site infection (n?=?1) and septic shock (n?=?2). Anastomotic complications occurred in seven patients and consisted of anastomotic dehiscence (n?=?1), tracheal stenosis (n?=?4) and fatal respiratory failure (n?=?2). Revision surgery was performed in two dogs due to anastomotic dehiscence and stenosis, and tracheal stenting was performed in one cat due to stenosis. Sixteen patients survived to hospital discharge and 14 survived to latest follow-up (median: 119?days; range: 14 to 1744). Outcome was scored as excellent in five, good in seven, fair in two and poor in six patients. Clinical Significance Tracheal resection and anastomosis is the surgical technique of choice to reconstruct tracheal defects. Although more than half of the patients recovered well, high morbidity and mortality rates were documented. This may be due to the severe comorbidities affecting most tracheal resection and anastomosis patients, as well as the client's decision against further treatment when facing serious post-operative complications
Computed tomographic appearance of gastropexy sites in dogs
No full textObjectives: To describe the computed tomography appearance of gastropexy sites and report their anatomical and suspected functional abnormalities. Materials and methods: Medical records of dogs with prior gastropexy undergoing abdominal computed tomography between December 2010 and June 2021 were reviewed from two veterinary hospitals. Dogs were categorised into two groups based on gastric anatomic distortion: anatomic (10) or non-anatomic (12). Results: A total of 22 dogs were included, with time since gastropexy ranging from 16 to 1552 days (median: 311 days). Computed tomography findings showed a median attenuation of 38.5 HU (range: 6 to 57) of the gastropexy site, as well as focal slight thickening of the gastric wall and adjacent muscle in all dogs. Neovascularisation at the gastropexy site was found in approximately 65% of the animals, while marked gastric dilatation was noted in 32%, and a gravel sign was observed in 73%. The anatomic group had broader pedicles and a greater distance from the xiphisternum and midline compared to the non-anatomic group. Median gastric angles were significantly smaller in the gastropexy groups (Anatomic: 85.5 degrees; Non-anatomic: 52 degrees) compared to a control group (132 degrees). Clinical significance: The current study identified specific computed tomography imaging features of gastropexy sites contributing to a better understanding of the range of appearance and degree of detected anatomic distortion following gastropexy. It also identified signs of suspected gastric functional abnormalities in all gastropexy patients regardless of the degree of anatomic distortion