Improving market (cull) dairy cows carcass traits and meat quality.

Despite a high volume of market (cull) dairy cows entering the food chain every year, beef from market dairy cows is largely considered insignificant when compared with beef from beef cattle in the market and is widely thought to be used for ground beef only. Our study aimed to evaluate the effects of feeding dairy market cows on a lactating TMR diet before slaughter on carcass and beef quality traits. Forty-three Holstein market cows were randomly assigned into 2 treatments: Fed or Direct. Fed cows (n = 22) were dried off, then fed a lactating cow TMR ration for approximately 60 d whereas Direct cows (n = 21) were sent directly to slaughter. Hot carcass weight (HCW) was used to calculate the dressing percentage (DP) together with the animals' body weight recorded when animals left the farm to go to the abattoir. At 24h post-mortem, the rib fat thickness (RFT) and rib eye area (REA) were measured by a certified grader. Afterward, rib samples were collected between the 12th -10th ribs from one side of the carcass and divided into 5 ribeye steaks. The first steak was used for intramuscular fat (IMF) content analysis by NIRS. The other 4 steaks were then aged for 7, 14, 21, or 28 d. Following aging, the steaks available were assessed for tenderness using the Warner-Bratzler Shear Force protocol. Data were analyzed by mixed linear regression to compare experimental groups for continuous outcomes. HCW of the Fed cows was higher than the Direct cows, with a mean HCW of 408.3 kg and 326.1 kg, respectively (SE ± 9.0). Average DP in Fed cows was 49.1%, compared with 42.5% in Direct cows (SE ± 0.69). The average percentage of IMF in Fed cows was 8.1% and in Direct cows was 5.0% (SE ± 0.43). Fed cows had a mean REA of 68.1 cm2 and Direct cows had a mean of 57.7 cm2 (SE ± 11.9). No differences were found for RFT. The steaks aged for 14 d resulted in meat with a mean shear force (SF) of 4.19 kg in Fed cows, while Direct cows had a mean SF of 6.28 kg (SE ± 0.29) Feeding market dairy cows for 60 d before slaughter enhanced carcass weight and yield, IMF content, and tenderness. These results indicate that approximately 60 d of feeding can improve the quality of market dairy cow meat and may help improve market cow value.

The vedotin antibody-drug conjugate payload drives platform-based nonclinical safety and pharmacokinetic profiles.

Nonclinical safety and pharmacokinetic data for MMAE and 14 vedotin ADCs were evaluated to determine patterns of toxicity, consistency of pharmacokinetic results, and species differences between rats and monkeys. Most nonclinical toxicities were antigen-independent, common across ADCs, and included hematologic, lymphoid, and reproductive toxicity related to MMAE pharmacology. Hematologic toxicity was the dose-limiting or predominant toxicity for the majority of vedotin ADCs in both species. Tissue expression of the targeted antigen of an ADC rarely correlated with dose-limiting toxicity (DLT); only two ADCs had antigen-dependent skin DLTs. For two additional ADCs, antigen-dependent delivery of MMAE in the bone marrow may have exacerbated the antigen-independent hematologic DLT. The highest tolerated doses and pharmacokinetics were similar within a given species, with rats tolerating higher doses than monkeys. Studies longer than one month in duration detected the same or fewer toxicities than one-month studies and had no additional findings that affected the human risk assessment. These data support opportunities to streamline ADC toxicity assessments without compromising human starting dose selection or target organ identification.

Reversible Chemical Modification of Antibody Effector Function Mitigates Unwanted Systemic Immune Activation.

Antibody effector functions including antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) are mediated through the interaction of the antibody Fc region with Fcγ receptors present on immune cells. Several approaches have been used to modulate antibody Fc-Fcγ interactions with the goal of driving an effective antitumor immune response, including Fc point mutations and glycan modifications. However, robust antibody-Fcγ engagement and immune cell binding of Fc-enhanced antibodies in the periphery can lead to the unwanted induction of systemic cytokine release and other dose-limiting infusion-related reactions. Creating a balance between effective engagement of Fcγ receptors that can induce antitumor activity without incurring systemic immune activation is an ongoing challenge in the field of antibody and immuno-oncology therapeutics. Herein, we describe a method for the reversible chemical modulation of antibody-Fcγ interactions using simple poly(ethylene glycol) (PEG) linkers conjugated to antibody interchain disulfides with maleimide attachments. This method enables dosing of a therapeutic with muted Fcγ engagement that is restored in vivo in a time-dependent manner. The technology was applied to an effector function enhanced agonist CD40 antibody, SEA-CD40, and experiments demonstrate significant reductions in Fc-induced immune activation in vitro and in mice and nonhuman primates despite showing retained efficacy and improved pharmacokinetics compared to the parent antibody. We foresee that this simple, modular system can be rapidly applied to antibodies that suffer from systemic immune activation due to peripheral FcγR binding immediately upon infusion.

Transmission of viable Haemophilus ducreyi by Musca domestica.

Haemophilus ducreyi was historically known as the causative agent of chancroid, a sexually-transmitted disease causing painful genital ulcers endemic in many low/middle-income nations. In recent years the species has been implicated as the causative agent of nongenital cutaneous ulcers affecting children of the South Pacific Islands and West African countries. Much is still unknown about the mechanism of H. ducreyi transmission in these areas, and recent studies have identified local insect species, namely flies, as potential transmission vectors. H. ducreyi DNA has been detected on the surface and in homogenates of fly species sampled from Lihir Island, Papua New Guinea. The current study develops a model system using Musca domestica, the common house fly, as a model organism to demonstrate proof of concept that flies are a potential vector for the transmission of viable H. ducreyi. Utilizing a green fluorescent protein (GFP)-tagged strain of H. ducreyi and three separate exposure methods, we detected the transmission of viable H. ducreyi by 86.11% ± 22.53% of flies sampled. Additionally, the duration of H. ducreyi viability was found to be directly related to the bacterial concentration, and transmission of H. ducreyi was largely undetectable within one hour of initial exposure. Push testing, Gram staining, and PCR were used to confirm the identity and presence of GFP colonies as H. ducreyi. This study confirms that flies are capable of mechanically transmitting viable H. ducreyi, illuminating the importance of investigating insects as vectors of cutaneous ulcerative diseases.

Attitudes and professional values of veterinarians and veterinary students toward positive welfare states for dairy cattle.

Research that involves agricultural animal welfare has typically aimed to improve welfare by decreasing disease, distress, and pain. Positive welfare does not necessarily occur with the absence of suffering but in combination with opportunities for behaviors or affective states desired by animals. Our objectives were to describe Canadian bovine veterinarians' and veterinary students' attitudes, professional normative values, and perceived ability to promote positive welfare for dairy cows, and to explore participants' provided rationale. With an online cross-sectional survey, Canadian veterinary practitioners (n = 78) and veterinary students (n = 148) were asked, on a 7-point Likert scale, about their attitudes, perceived professional normative values, and perceived ability of veterinarians to promote positive welfare for dairy cows. We used an applied thematic analysis approach within the qualitative description methodology to analyze participants' open-ended text responses. Quantitatively, participants had very favorable attitudes (mean ± SE; 6.3 ± 0.04) and perceived favorable values (5.7 ± 0.06) in the veterinary community toward positive welfare opportunities for dairy cows. Three themes were identified to explain the professional normative values: influences from within the veterinary profession, influences from outside the veterinary profession, and personal views of participants. Participants were confident that veterinarians could suggest positive welfare opportunities for dairy cows (6.1 ± 0.06) but were uncertain that the decision to suggest these opportunities to producers was within a veterinarian's control (4.3 ± 0.11) and were not confident that implementation of positive welfare opportunities was under a veterinarian's control (2.1 ± 0.07). Three themes were identified to explain the barriers to veterinarians promoting positive welfare opportunities for dairy cows: not practical to implement, resistance to change, and concern for the animal. Participants stated that many positive welfare opportunities were impractical or expensive to implement. We conclude that positive attitudes and positive professional values exist in the veterinary community toward positive welfare for dairy cows but that much uncertainty exists regarding a veterinarian's ability to influence change to current practices.

Can 60 days of feeding lead to increased fitness for transport in cull dairy cows?

The welfare of cull cows during transport to slaughter is a current concern in the Canadian dairy industry. Cull cows sold through auction often have a high prevalence of lameness, low BCS, hock lesions, and udder engorgement. To evaluate whether drying off and feeding cull dairy cows before transport can mitigate these challenges, 45 cows designated for culling were randomly assigned to either be fed for 60 d after being dried off (fed group; n = 24) or to serve as controls by being sent directly to slaughter (direct group; n = 21). Two fed group cows were removed for health reasons before completing the feeding period. Both fed group and direct group cows were assessed for locomotion (5-point scale), BCS (5-point scale), hock lesions (3-point scale), udder engorgement (3-point scale), and BW at the time of enrollment. Fed group cows, locomotion, BCS, hock, and udder engorgement scores were assessed weekly until slaughter. Weights of the fed group cows were measured again the day before slaughter. Mixed linear regression models were used to assess continuous outcomes BCS and weight. Mixed logistic regression models were used to assess dichotomous outcomes presence of hock lesions and lameness. Fed group cows gained an average of 116.9 kg over the feeding period (SE ± 8.20). Fed group cows had an average weight at slaughter of 834.2 kg, whereas direct group cows' average weight was 767.3 kg (SE ± 26.8). The fed group cows' average BCS at the start of the trial was 2.4, and at slaughter was 3.6, with an average gain of 1.2 BCS points. At slaughter, the proportion of udders involuted in the fed group was 45.1% (10/22) and in the direct group cows, was 0% (0/21). No differences were found in locomotion or hock lesions between the fed group and direct groups. It is important to weigh potential benefits for the fed group cows with the fact that direct group cows did not endure a drying off procedure, nor were they placed at risk of potential adverse health events. However, despite these potential limitations, due to the improved BCS and udder engorgement scores, cows fed for 60 d may be better prepared for the transportation to slaughter, as well as sell for a higher price due to increased BW and body condition.

Efficacy and Durability of Intravenous Ertapenem Therapy for Recalcitrant Hidradenitis Suppurativa.

Importance: Hidradenitis suppurativa (HS) is a debilitating follicular skin disorder in which bacterial colonization is typical. Oral antibiotic efficacy can be unreliable; however, selective intravenous antibiotics, specifically ertapenem, may provide favorable clinical outcomes. Objective: To explore optimal course duration, efficacy, and patient satisfaction associated with intravenous ertapenem for HS. Design, Setting, and Participants: This retrospective review of the medical records of 98 patients with HS between 2018 and 2022 measured and evaluated patient outcomes before and after treatment with intravenous ertapenem. Participants were followed up in a telephone survey assessing patient perspectives and satisfaction. All of those included in this study received medical care from the Albert Einstein College of Medicine's Montefiore HS Center. Exposures: Patients were treated with 1 g of ertapenem that was self-administered at home through a peripheral intravenous central catheter using an elastomeric pump for 12 to 16 weeks. Antiandrogens and immunomodulatory biologic therapies initiated prior to ertapenem were maintained throughout the treatment course. Main Outcomes and Measures: The primary outcomes, encompassing clinical severity (evaluated through the HS Physician Global Assessment score [a 6-point scale ranging from clear to very severe] and a numerical rating scale for pain [an 11-point scale in which a score of 0 indicates no pain and a score of 10 indicates the worst possible pain]) and markers of inflammation (such as leukocytes, erythrocyte sedimentation rate, C-reactive protein, and interleukin-6), were measured at baseline, the midcourse of intravenous ertapenem treatment, at the end of the course, and posttherapy. Bacterial abundance was also examined at these 4 points, and patient satisfaction was assessed during follow-up. Results: A total of 98 patients (mean [SD] age, 35.8 [13.0] years; 61 [62.2%] female) with HS were treated with intravenous ertapenem. The self-reported racial distribution included 3 individuals identifying as Asian (3.1%), 59 as Black/African American (60.2%), 13 as White (13.3%), and 23 as either other or unknown (23.5%). Additionally, 24 participants (24.5%) reported Spanish/Hispanic/Latino ethnicity. The mean (SD) treatment duration spanned 13.1 (4.0) weeks, with posttherapy follow-up occurring after 7.8 (3.6) weeks. From baseline to posttherapy follow-up, significant reductions were found in the mean (SD) HS Physician Global Assessment scores (3.9 [1.0] vs 2.7 [1.2]; P < .001) and the numerical rating scale for pain (4.2 [3.3] vs 1.8 [2.7]; P < .001), C-reactive protein (5.4 [11.4] vs 2.4 [2.0] mg/dL; P < .001), interleukin-6 (25.2 [21.1] vs 13.7 [13.9]; P < .001), and leukocytes (11.34 [3.9] vs 10.0 [3.4]; P < .001). At follow-up, 76 patients (78.0%) participated in the telephone survey, where 63 (80.3%) reported medium to high satisfaction; further, 69 (90.8%) would recommend ertapenem to other patients. Conclusions and Relevance: In this retrospective review of medical records and telephone survey, treating HS with intravenous ertapenem, administered for a mean of 13 weeks, was associated with improvement in clinical and inflammatory markers, as well as heightened patient satisfaction. Nonetheless, this approach should be monitored for the emergence of antimicrobial resistance given a longer than standard treatment course.

A foundational description of Antilocapra americana pronghorn core osteohistology.

Cranial bony projections ("headgear") have diverse forms and functions, such as defense, species recognition, mate selection, and thermoregulation. Most commonly, they are associated with the artiodactyl infraorder, Pecora. All pecoran headgear-antlers, horns, ossicones, and pronghorns-are osseous protrusions of the frontal or parietal bone with an integumentary covering, although there is taxonomic, developmental, and compositional variation. However, compared with other pecorans, there is a dearth of literature addressing extant antilocaprids-Antilocapra americana. This study provides a foundational osteohistological description of A. americana pronghorn cores in order to start building a framework to better understand the complex interplay among microanatomy, development, behavior, environment, and phylogenetic history of pronghorn headgear. Osteohistological analysis of adult A. americana pronghorn cores reveal the inner medullary region is composed of trabecular bone. Based on similar studies in bovids, we propose that these trabeculae may function to reduce the effects of repeated loading incurred by intraspecific combat. The deep aspect of the outer region was found to be composed of compacted coarse cancellous bone and primary bone remodeled to dense Haversian bone, in both male and female specimens, respectively, and superficially composed of highly vascularized fibrolamellar bone. The presence of fibrolamellar bone may indicate that the bone is fast-growing, and its presence at the periosteal surface suggests protracted growth of the pronghorn core beyond sexual maturity.