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Craniofacial and dentoalveolar abnormalities are present in all types of osteogenesis imperfecta (OI). Mouse models of the disorder are critical to understand these abnormalities and underlying OI pathogenesis. Previous studies on severely affected OI mice report a broad spectrum of craniofacial phenotypes, exhibiting some similarities to the human disorder. The Brtl/+ and G610c/+ are moderately severe and mild-type IV OI, respectively. Little is known about the aging effects on the craniofacial bones of these models and their homology to human OI. This study aimed to analyze the Brtl/+ and G610c/+ craniofacial morphometries during aging to establish suitability for further OI craniofacial bone intervention studies. We performed morphological measurements on the micro-CT-scanned heads of 3-wk-old, 3-mo-old, and 6-mo-old female Brtl/+ and G610c/+ mice. We observed that Brtl/+ skulls are shorter in length than WT ( P  < .05), whereas G610c/+ skulls are similar in length to their WT counterparts. The Brtl/+ mice exhibit alveolar bone with a porotic-like appearance that is not observed in G610c/+. As they age, Brtl/+ mice show severe bone resorption in both the maxilla and mandible ( P  < .05). By contrast, G610c/+ mice experience mandibular resorption consistently across all ages, but maxillary resorption is only evident at 6 mo ( P  < .05). Western blot shows high osteoclastic activities in the Brtl/+ maxilla. Both models exhibit delayed pre-functional eruptions of the third molars ( P  < .05), which are similar to those observed in some bisphosphonate-treated OI subjects. Our study shows that the Brtl/+ and G610c/+ mice display clear features found in type IV OI patients; both show age-related changes in the craniofacial growth phenotype. Therefore, understanding the craniofacial features of these models and how they age will allow us to select the most accurate mouse model, mouse age, and bone structure for the specific craniofacial bone treatment of differing OI groups., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Background: Globally, poor nutrition is a driver of many chronic diseases and is responsible for more deaths than any other risk factor. Accordingly, there is growing interest in the direct provision of healthy foods to patients to tackle diet-linked chronic diseases and mortality., Aim: To assess the effect of two healthy food interventions in conjunction with nutrition counseling and education on select chronic disease markers, food insecurity, diet quality, depression, and on self-efficacy for healthy eating, healthy weight, and chronic disease management., Methods: This parallel-arm quasi-randomized control trial will be conducted between January 2022 and December 2023. Seventy adult patients recruited from a single academic medical center will be randomly assigned to receive either: i) daily ready-made frozen healthy meals or ii) a weekly produce box and recipes for 15 weeks. Participants will, additionally, take part in one individual nutrition therapy session and watch videos on healthy eating, weight loss, type 2 diabetes, and hypertension. Data on weight, height, glycated hemoglobin, blood pressure, and diabetes and blood pressure medications will be collected in-person at the baseline visit and at 16 weeks from baseline and via medical chart review at six months and 12 months from enrollment. The primary outcome of the study is weight loss at 16 weeks from baseline. Pre- and post-intervention survey data will be analyzed for changes in food insecurity, diet quality, depression, as well as self-efficacy for health eating, healthy weight, and chronic disease management. Through retrospective chart review, patients who received standard of care will be matched to intervention group participants as controls based on body mass index, type 2 diabetes, and/or hypertension., Findings: By elucidating the healthy food intervention with better health outcomes, this study aims to offer evidence that can guide providers in their recommendations for healthy eating options to patients.

Bacteriophages are biocontrol agents used to manage bacterial diseases. They have long been used against plant pathogenic bacteria; however, several factors impede their use as a reliable disease management strategy. Short-lived persistence on plant surfaces under field conditions results mainly from rapid degradation by exposure to ultraviolet (UV) light. Currently, there are no effective commercial formulations that protect phages from UV. The phage ΦXp06-02-1, which lyses strains of the tomato bacterial spot pathogen Xanthomonas perforans , was mixed with different concentrations of the nanomaterial N -acetylcysteine surface-coated manganese-doped zinc sulfide (NAC-ZnS; 3.5 nm). In vitro, NAC-ZnS at 10,000 μg/ml formulated phage, when exposed to UV for 1 min, provided statistically equivalent plaque-forming unit (PFU) recovery as phages that were not exposed to UV. NAC-ZnS had no negative effect on the phage's ability to lyse bacterial cells under in vitro conditions. NAC-ZnS reduced phage degradation over time in comparison with the nontreated control, whereas N -acetylcysteine-zinc oxide (NAC-ZnO) had no effect. In fluorescent light, without UV exposure, NAC-ZnO-formulated phages were more infective than NAC-ZnS-formulated phages. The nanomaterial-phage mixture did not cause any phytotoxicity when applied to tomato plants. Following exposure to sunlight, the NAC-ZnS formulation improved phage persistence in the phyllosphere by 15 times compared with nonformulated phages. NAC-ZnO-formulated phage populations were undetectable within 32 h, whereas NAC-ZnS-formulated phage populations were detected at 10 3 PFU/g. At 4 h of sunlight exposure, NAC-ZnS-formulated phages at 1,000 μg/ml significantly reduced tomato bacterial spot disease severity by 16.4% compared with nonformulated phages. These results suggest that NAC-ZnS can be used to improve the efficacy of phages for bacterial diseases., Competing Interests: The author(s) declare no conflict of interest.

The endeavor to understand the human brain has seen more progress in the last few decades than in the previous two millennia. Still, our understanding of how the human brain relates to behavior in the real world and how this link is modulated by biological, social, and environmental factors is limited. To address this, we designed the Healthy Brain Study (HBS), an interdisciplinary, longitudinal, cohort study based on multidimensional, dynamic assessments in both the laboratory and the real world. Here, we describe the rationale and design of the currently ongoing HBS. The HBS is examining a population-based sample of 1,000 healthy participants (age 30-39) who are thoroughly studied across an entire year. Data are collected through cognitive, affective, behavioral, and physiological testing, neuroimaging, bio-sampling, questionnaires, ecological momentary assessment, and real-world assessments using wearable devices. These data will become an accessible resource for the scientific community enabling the next step in understanding the human brain and how it dynamically and individually operates in its bio-social context. An access procedure to the collected data and bio-samples is in place and published on https://www.healthybrainstudy.nl/en/data-and-methods/access. Trail registration: https://www.trialregister.nl/trial/7955., Competing Interests: The authors have declared that no competing interests exist.

Objective: RNA-binding protein with multiple splicing (RBPMS) has been shown to physically interact with Smads and enhance transforming growth factor-β (TGF-β)-mediated Smad2/3 transcriptional activity in mammalian cells. Objective of this study was to examine whether expression of RBPMS is regulated by interleukin-1β (IL)-1β and TGF-β superfamily growth factors and whether expression of RBPMS is altered during aging and experimental osteoarthritis., Methods: Expression of RBPMS protein was investigated in chondrocyte cell lines of murine (H4) and human (G6) origin using Western blot analysis. Regulation of RBPMS expression in H4 chondrocytes at mRNA level was done by reverse transcriptase-quantitative polymerase chain reaction. Furthermore, characterization of Smad signaling pathways regulating RBPMS expression was performed by blocking studies using small molecule inhibitors or by transfection studies with adenoviral vector constructs (constitutive-active ALK1 and constitutive-active ALK5). Expression of RBPMS in cartilage of different age groups of C57BL/6N mice (6 months and 20 months) and in a surgically induced osteoarthritis (OA) mouse model was analyzed using immunohistochemistry., Results: RBPMS was shown to be expressed in chondrocytes and cartilage of murine, human, and bovine origin. TGF-β inhibited RBPMS expression while BMP2 and IL-1β increased its expression. TGF-β-induced inhibition was blocked by ALK5 inhibitor. Overexpression of ca-ALK1 stimulated RBPMS expression. Moreover, RBPMS expression was found to be reduced with ageing and in OA pathogenesis., Conclusions: Expression of RBPMS in chondrocytes is regulated by TGF-β superfamily members and IL-1β, indicating a counter-regulatory mechanism. Expression of RBPMS, in cartilage and its reduction during ageing and OA might suggest its potential role in the maintenance of normal articular cartilage., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the tensile strength, elongation, and degradation of 4 monofilament absorbable suture materials that undergo degradation by hydrolysis in specimens of canine urine with various physical characteristics., Sample Population: 4 monofilament absorbable sutures (polydioxanone, poliglecaprone 25, polyglyconate, and glycomer 631)., Procedure: Voided urine was collected from 6 healthy dogs, pooled, filter-sterilized, and prepared to provide 5 media: sterile neutral (pH, 7.0), sterile acidic (pH, 6.2), sterile basic (pH, 8.8), Escherichia coli-inoculated, and Proteus mirabilis-inoculated urine. Ten strands of each suture material were immersed in each of the media for 0 to 28 days. Tensile strength and elongation of each suture material were evaluated by use of a texture analyzer on days 0, 1, 3, 7, 10, 14, 21, and 28., Results: Reduction in tensile strength was detected for all materials in all urine specimens over time. Polyglyconate and polydioxanone had superior tensile strengths in sterile neutral and E. coli-inoculated urine, and polydioxanone retained the greatest tensile strength throughout the study period. All suture materials disintegrated before day 7 in P. mirabilis-inoculated urine., Conclusions and Clinical Relevance: Polydioxanone, polyglyconate, and glycomer 631 may be acceptable for urinary bladder closure in the presence of sterile neutral and E. coli-contaminated urine. Tensile strength of poliglecaprone 25 in urine may be unacceptable by the critical healing time for bladder tissue (14 to 21 days). During bladder surgery, exposure of suture material that degrades via hydrolysis to urine containing Proteus spp should be minimized.

Objective: To confirm in vivo optimal laser energy settings previously determined in vitro for lithotripsy, to develop a technique for Ho:YAG laser lithotripsy, and to evaluate acute and chronic tissue effects of laser lithotripsy., Study Design: Prospective, randomized preclinical trial., Animals or Sample Population: Nineteen intact, adult male dogs., Methods: Via cystotomy, a single urolith was inserted into the urethra to the level of the base of the os penis to simulate obstruction. Uroliths (calcium oxalate, urate, or magnesium ammonium phosphate) were fragmented by Ho:YAG laser, in contact mode through a 320 micro optic fiber, passed through the operating channel of a 2.8 mm flexible endoscope. The time and total energy to fragmentation were recorded. Dogs were euthanatized immediately after lithotripsy (3 dogs) or at 3 days (7 dogs), and urethral lesions and any stone remnants were evaluated. Urethral integrity was also evaluated in 9 other dogs by endoscopy on day 10; these were also monitored clinically for 30 days., Results: The mean time for adequate fragmentation was 166.7 seconds (range, 47-494.5 seconds). The mean+/-SD energy used was 1418+/-851.2 J. In part 1, 2 dogs were obstructed with urolith fragments at necropsy. Eight dogs had minimal (<30 mg) or no urolith material evident within the urethra. Four dogs had gross focal or circumferential erosion, ulceration, or hemorrhage of the urethral mucosa. Lesions were not associated with the site of laser irradiation in 2 dogs. In dogs observed for 30 days, hematuria, pollakiuria, and stranguria that were observed after lithotripsy, resolved in all affected dogs by day 5. No mucosal lesions were observed by endoscopy and none of the dogs became obstructed., Conclusion: Laser lithotripsy with the Ho:YAG laser in contact mode successfully fragmented obstructive uroliths in male dogs., Clinical Relevance: Laser lithotripsy may be a clinically relevant technique for treatment of urolithiasis in male dogs; clinical studies to evaluate long-term effects on urethral mucosa and the role of repeat treatment for recurrence are indicated.

Objectives: To evaluate technique, complication rates, postoperative pain scores, and clinical outcomes in dogs after laparoscopic ovariohysterectomy (LOVH) or traditional ovariohysterectomy (OVH)., Study Design: Prospective clinical trial., Animals or Sample Population: Thirty-four intact female dogs, weighing 2.4-31 kg., Methods: LOVH (16 dogs) was performed by ligation of the uterus and ovaries with surgical wire, and then removal by an assisted laparoscopic technique. OVH was performed in 18 dogs. Subjective and objective pain scores were assigned at 0, 2, 8, and 24 hours. Surgical time, complications, and pain and incision scores were evaluated. Dogs were followed for up to 6 months., Results: The mean surgical time for LOVH (120 minutes; range, 47-175 minutes) was significantly longer than for OVH (69 minutes; range, 25-140 minutes). Significantly lower pain scores (subjective, in 2 of 10 categories; objective, in 8 of 10 categories) were identified with LOVH at 1 or more time periods. Surgical complications with LOVH were postoperative fever and anorexia (1 dog), minor splenic (3) or pedicle hemorrhage (4), intermittent vaginal hemorrhagic discharge (1), and suture reaction (3). Surgical complications with OVH were hemorrhage from an ovarian pedicle requiring reoperation (1 dog), dehiscence of the abdominal wall (1), and seroma (1). Anesthetic complications included hypotension in 8 OVH dogs and 1 LOVH dog, and hypothermia in 4 OVH and 9 LOVH dogs. The mean incision scores were lower for LOVH at all time periods., Conclusion: LOVH was performed successfully in young nonparous dogs >10 kg. Surgical time and complication rates were greater; however, LOVH postoperative pain scores were < or =OVH scores., Clinical Relevance: LOVH is a potentially safe surgical alternative to traditional OVH in dogs. Equipment cost and necessity for more than 1 surgeon may limit its usefulness in small animal practice.

Background and Objectives: To assess the effect of holmium laser energy on canine uroliths and porcine urethra., Study Design/materials and Methods: Uroliths of known composition and fresh cadaveric urethra were exposed to holmium laser energy. Urolith fragmentation times and depth of urethral lesions were determined., Results: Overall mean fragmentation time was 11.8 +/- 8.01 seconds. Magnesium ammonium phosphate (MAP) and urate uroliths had significantly shorter fragmentation times compared to other uroliths. Fragmentation time of MAP uroliths irradiated with 1.2 J/pulse was significantly longer than the fragmentation time of MAP uroliths irradiated with 0.3 J/pulse. Overall mean lesion depth for urethral specimens treated with 90 degrees contact mode irradiation was significantly greater than overall mean lesion depth for specimens treated with 30 degrees non-contact mode., Conclusions: Holmium laser energy effectively fragmented canine uroliths and caused minimal urethral damage in vitro. Dogs with urolithiasis may represent a useful animal model for developing human lithotripsy procedures., (Copyright 2003 Wiley-Liss, Inc.)

Objective: To compare clinical outcome, healing, and effect of tracheostomy in conventional incisional and carbon dioxide (CO2) laser techniques for resection of soft palates in brachycephalic dogs., Design: Prospective randomized trial., Animals: 20 adult brachycephalic dogs., Methods: Dogs were randomly allocated into 4 groups, and 1 of the following was performed: palate resection by use of a CO2 laser; incisional palate resection and closure with suture; and palate resection by use of a C02 laser or incision with tracheostomy. A clinical score for respiratory function was assigned to each dog at 0, 2, 8, 16, and 24 hours. Biopsy specimens of incision sites obtained at days 0, 3, 7, and 14 were examined. Data were analyzed to determine the effects of technique on clinical and histologic outcome., Results: Mean surgical time for laser (309 seconds) was significantly shorter than for sharp dissection (744 seconds). Surgical technique significantly affected clinical scores at 3 of the 5 postoperative time points, but differences were not clinically apparent. Tracheostomy significantly affected clinical scores at 3 of 5 postoperative time points. After tracheostomy tube removal, clinical scores were similar to those of dogs without tracheostomies. Inflammation, necrosis, and ulceration were evident in all groups at day 3; these lesions had almost resolved by day 14. Most complications were associated with tracheostomy., Conclusions and Clinical Relevance: Clinical outcomes appear to be similar with the laser and incisional techniques. Regarding surgical time and ease, laser resection of the soft palate appears advantageous. Tracheostomy is not warranted in dogs that have uncomplicated surgeries and recoveries.

A new surgical method for treating cholesteatoma in dogs is described. Although rarely reported in dogs, cholesteatomas may be more common than previously believed. Complete excision of a cholesteatoma is associated with low recurrence and good long-term prognosis. Surgical intervention, with total ear canal ablation and lateral bulla osteotomy, has been recommended in dogs with tumors of the middle ear; however, this technique often results in conductive hearing loss. Through a caudal auricular approach to the tympanic bulla, we were able to preserve the external ear canal, reconstruct the auditory ossicles, and graft the tympanic membrane. Results of brain stem auditory-evoked response tests in the dog revealed intact conduction potentials. A caudal auricular approach to the tympanic bulla is technically possible, preserves normal appearance, and may maintain, or even improve, hearing conduction of affected ears in dogs.

Objective: The purpose of this study was to determine the tumor-free interval and survival times of cats who had one (group 1) or more (group 2) surgeries, or surgery and radiation therapy (RTH) (group 3) for treatment of soft tissue fibrosarcomas (FSA)., Study Design: Retrospective study., Animals or Sample Population: 45 client-owned cats., Methods: Medical records of cats with soft tissue FSA were examined. Vaccination and feline leukemia virus (FeLV) status, age, sex, breed, tumor location, number of surgeries, completeness of excision, and histopathological grade were evaluated to correlate with tumor-free interval and survival periods., Results: Overall median tumor-free interval and survival times were 10 and 11.5 (range, 1 to 40) months. Median tumor-free interval and survival times were more than 16 months each in group 1, more than 5 and 13 months in group 2, and 4.5 and 9 months in group 3. Age, sex, breed, vaccination or FeLV status, tumor location, or histopathological grade did not affect median tumor-free interval or survival times (P > .05). Cats with complete excisions had significantly longer median tumor-free interval (> 16 versus 4 months) and survival time (> 16 versus 9 months) than those with incomplete excisions (P = .008). Radiation therapy did not seem to extend tumor-free interval and survival times (P = .013). However, most group 3 cats had incomplete surgical excisions, resulting in recurrent or progressive disease., Conclusions: Complete surgical excision of FSA in cats is possible and can be curative., Clinical Relevance: Aggressive surgical excision with wide margins appears to contribute to extended tumor-free interval and survival times in cats with soft tissue FSA. Controlled prospective studies are needed to determine the efficacy of RTH in treatment.