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Objectives: External validation of the 4C and NEWS2 scores for the prediction of in-hospital mortality in COVID-19 patients, and evaluation of its operational performance in two time periods: before and after the start of the vaccination program in Colombia., Methods: Retrospective cohort in three high complexity hospitals in the city of Medellín, Colombia, between June 2020 and April 2022., Results: The areas under the ROC curve (AUC) for the 4C mortality risk score and the NEWS2 were 0.75 (95% CI 0.73-0.78) and 0.68 (95% CI 0.66-0.71), respectively. For the 4C score, the AUC for the first and second periods was 0.77 (95% CI 0.74-0.80) and 0.75 (95% CI 0.71-0.78); whilst for the NEWS2 score, it was 0.68 (95% CI 0.65-0.71) and 0.69 (95% CI 0.64-0.73). The calibration for both scores was adequate, albeit with reduced performance during the second period., Conclusions: The 4C mortality risk score proved to be the more adequate predictor of in-hospital mortality in COVID-19 patients in this Latin American population. The operational performance during both time periods remained similar, which shows its utility notwithstanding major changes, including vaccination, as the pandemic evolved., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Good syndrome (GS) is a rare primary immunodeficiency in adults consisting of hypogammaglobulinemia and thymoma that affects both cellular and humoral immunity. It usually appears in patients between the 4th and 6th decade of life and affects both genders equally. Ophthalmological clinical presentation is highly variable; associations with herpetic keratitis, toxoplasmosis, and cytomegalovirus retinitis (CMVR) have been described. GS associated with CMVR is uncommon. Ophthalmologists may be the first to diagnose systemic disease and change the outcome. Only18 cases of CMVR have been described, most of them unilateral with poor visual outcomes. We discuss the clinical features of CMVR in patients with reported GS, pathogenesis, and outline a work-up for diagnosis. CMVR in an apparently healthy patient should encourage the clinician to search for human immunodeficiency virus (HIV) and non-HIV-associated immunosuppression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: To describe cytomegalovirus retinitis in a patient with Good syndrome (hypogammaglobulinemia and thymoma), ocular progression despite treatment and fatal outcome., Methods: A 71-year-old woman with unilateral panuveitis of unknown cause and a history of thymoma resection was referred to the clinic. Visual acuity was 20/100 in her right eye and light perception in her left eye. In slit-lamp examination, the right eye had inferior, fine, pigmented keratic precipitates, 2+ anterior chamber cells, cataract, and 2+ vitreous cells, with no fundus detail and normal ocular ultrasound results. Left eye presented a white cataract, chronic hypotony, and increased choroidal thickness with calcifications. Laboratory evaluations showed normal or negative results for common causes of infection and inflammation. Prednisolone acetate eye drops were started, with improvement of AC inflammation. Cataract surgery was performed, reaching visual acuity of 20/30. Two years later, visual acuity had decreased and 2+ vitritis and retinitis were found. On clinical suspicion of masquerade syndrome, a vitrectomy biopsy was performed; pathologic assessments reported no data on ocular lymphoma. Leukopenia and lymphopenia were found: immunoglobulin levels, CD4 count, and viral load revealed systemic immunosuppression. The aqueous tap was positive for cytomegalovirus. Oral valganciclovir and intravitreal ganciclovir were initiated., Results: In a patient with previous resection of thymoma and hypogammaglobulinemia, final diagnosis was Good syndrome, with cytomegalovirus retinitis being secondary to immunosuppression. Despite treatment, cytomegalovirus retinitis progressed and systemic deterioration resulted in mortal outcome., Conclusion: Good syndrome is an extremely rare disease, and association with cytomegalovirus retinitis is uncommon. To the authors' knowledge, only 14 cases exist in the literature.

Aim: A cross-sectional descriptive study to determine the frequency of ocular manifestations associated with systemic autoimmune diseases in a third-level hospital in Mexico., Methods: Records from 2014 to 2017 at the Inflammatory Eye Disease Clinic of the Asociación Para Evitar la Cegueraen México were examined by both an ophthalmologist and a rheumatologist on the same day. Diagnosis was achieved from initial ocular manifestations with later systemic assessment., Results: Out of 311 medical records, 276 were included, 75% of the patients were female. Keratoconjunctivitis sicca was the most frequent ocular manifestation (33.3%), followed by anterior uveitis (29.5%), scleritis (23.2%), and peripheral ulcerative keratitis (7.2%). The leading autoimmune diseases were spondyloarthritis (29%), rheumatoid arthritis (28.6%), primary Sjögren's syndrome (10.5%) and granulomatosis with polyangiitis (9.1%). 41.3% of systemic disease diagnoses were made after an initial ocular manifestation., Conclusions: Inflammatory eye manifestations can imply systemic autoimmune diseases. It is crucial to suspect and confirm this association and provide timely interdisciplinary management.

Background: Ocular toxoplasmosis (OT) is caused by the parasite Toxoplasma gondii. OT is the leading cause of posterior uveitis globally; it is a recurrent disease that may result in visual impairment and blindness. This systematic review and meta-analysis aim to summarize and evaluate the risk factors for recurrences, visual impairment, and blindness described in the literature worldwide., Methods and Findings: We performed a systematic literature search in PubMed, Embase, VHL, Cochrane Library, Scopus, and DANS EASY Archive. All studies reporting patients with clinically and serologically confirmed OT presenting any clinical or paraclinical factor influencing recurrences, visual impairment, and blindness were included. Studies presenting secondary data, case reports, and case series were excluded. An initial selection was made by title and abstract, and then the studies were reviewed by full text where the eligible studies were selected. Then, the risk of bias was assessed through validated tools. Data were extracted using a validated extraction format. Qualitative synthesis and quantitative analysis were done. This study was registered on PROSPERO (CRD42022327836)., Results: Seventy two studies met the inclusion criteria. Fifty-three were summarized in the qualitative synthesis in three sections: clinical and environmental factors, parasite and host factors, and treatment-related factors. Of the 72 articles, 39 were included in the meta-analysis, of which 14 were conducted in South America, 13 in Europe, four in Asia, three multinational, two in North America and Central America, respectively, and only one in Africa. A total of 4,200 patients with OT were analyzed, mean age ranged from 7.3 to 65.1 year of age, with similar distribution by sex. The frequency of recurrences in patients with OT was 49% (95% CI 40%-58%), being more frequent in the South American population than in Europeans. Additionally, visual impairment was presented in 35% (95% CI 25%-48%) and blindness in 20% (95% CI 13%-30%) of eyes, with a similar predominance in South Americans than in Europeans. On the other hand, having lesions near the macula or adjacent to the optic nerve had an OR of 4.83 (95% CI; 2.72-8.59) for blindness, similar to having more than one recurrence that had an OR of 3.18 (95% CI; 1.59-6.38). Finally, the prophylactic therapy with Trimethoprim/Sulfamethoxazole versus the placebo showed a protective factor of 83% during the first year and 87% in the second year after treatment., Conclusion: Our Systematic Review showed that clinical factors such as being older than 40 years, patients with de novo OT lesions or with less than one year after the first episode, macular area involvement, lesions greater than 1 disc diameter, congenital toxoplasmosis, and bilateral compromise had more risk of recurrences. Also, environmental and parasite factors such as precipitations, geographical region where the infection is acquired, and more virulent strains confer greater risk of recurrences. Therefore, patients with the above mentioned clinical, environmental, and parasite factors could benefit from using prophylactic therapy., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cifuentes-González et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this paper, we compare the post-operative macular microvascular parameters (vascular density and foveal avascular zone) in eyes with refractory macular hole (MH) that underwent pars plana vitrectomy and autologous retinal transplant (ART) with the fellow unoperated eye. We conducted a retrospective case control study of six consecutive patients who underwent pars plana vitrectomy and ART with at least six months of post-operative follow-up. Pre-operatively, all eyes underwent SD-OCT (Spectral Domain Optical Coherence Tomography) examination. Post-operative OCT-A analyses included vascular density (VD) and the foveal avascular zone (FAZ) area. Six patients with a mean age of 63.7 ± 14.3 years were included. The mean follow-up was 24 months (range 6-30 months). The pre-operative BCVA (best-corrected visual acuity) was 0.99 ± 0.46 logMAR and 1.02 ± 0.23 logMAR at the last post-operative visit ( p = 1.00). The mean MH diameter was 966 ± 620 µm. VD in the MH group was 28.1 ± 7.3% compared to 20.2 ± 2.9% in the fellow eyes group ( p < 0.05). The mean post-operative FAZ area in the MH group was 109.8 ± 114.6 mm 2 compared to 41.5 ± 10.4 mm 2 in the control group ( p < 0.05). In all six eyes, MH closure was obtained. The post-operative visual acuity did not improve after ART. Eyes with a closed MH showed a bigger FAZ with a higher VD compared to the fellow healthy eye.

Introduction: Females may have greater susceptibility to Alzheimer's disease (AD)-pathology. We examined the effect of sex on pathology, neurodegeneration, and memory in cognitively-unimpaired Presenilin-1 (PSEN1) E280A mutation carriers and non-carriers., Methods: We analyzed baseline data from 167 mutation carriers and 75 non-carriers (ages 30 to 53) from the Alzheimer's Prevention Initiative Autosomal Dominant AD Trial, including florbetapir- and fludeoxyglucose-PET, MRI based hippocampal volume and cognitive testing., Results: Females exhibited better delayed recall than males, controlling for age, precuneus glucose metabolism, and mutation status, although the effect was not significant among PSEN1 mutation carriers only. APOE ε4 did not modify the effect of sex on AD biomarkers and memory., Discussion: Our findings suggest that, among cognitively-unimpaired individuals at genetic risk for autosomal-dominant AD, females may have greater cognitive resilience to AD pathology and neurodegeneration than males. Further investigation of sex-specific differences in autosomal-dominant AD is key to elucidating mechanisms of AD risk and resilience., (© 2021 the Alzheimer's Association.)

Purpose: To expand the knowledge regarding the clinical presentation of Kocuria endophthalmitis., Methods: We included six cases of Kocuria endophthalmitis between January 2018 and December 2020. From all cases, we collected general demographic data, relevant medical, ophthalmological history, microbiological and antibiotic sensitivity results. All cases had a minimum follow-up of 9 months. All cases were treated with intravitreal moxifloxacin and dexamethasone and pars plana vitrectomy. Undiluted vitreous, corneal, conjunctival, and aqueous samples were cultured and analyzed with the Vitek 2 system., Results: The prevalence of Kocuria endophthalmitis was 6%. (95%CI: 2.26%-12.73%). The mean age at diagnosis was 60.5 ± 15.5 years. All patients had poor visual acuity, severe pain, and severe conjunctival hyperemia at diagnosis. Only one case had a significant improvement in visual acuity at the end of the follow-up., Conclusion: Kocuria spp are an emerging cause of endophthalmitis and should be considered as part of the differential diagnosis.

Introduction: The API AutosomalDominant AD (ADAD) Colombia Trial is a placebo-controlled clinical trial of crenezumab in 252 cognitively unimpaired 30 to 60-year-old Presenilin 1 (PSEN1) E280A kindred members, including mutation carriers randomized to active treatment or placebo and non-carriers who receive placebo., Methods: Of the 252 enrolled, we present data on a total of 242 mutation carriers and non-carriers matched by age range, excluding data on 10 participants to protect participant confidentiality, genetic status, and trial integrity., Results: We summarize demographic, clinical, cognitive, and behavioral data from 167 mutation carriers and 75 non-carriers, 30 to 53 years of age. Carriers were significantly younger than non-carriers ((mean age ± SD) 37 ± 5 vs 42 ± 6), had significantly lower Mini Mental Status Exam (MMSE) scores (28.8 ± 1.4 vs 29.2 ± 1.0), and had consistently lower memory scores., Discussion: Although PSEN1 E280A mutation carriers in the Trial are cognitively unimpaired, they have slightly lower MMSE and memory scores than non-carriers. Their demographic characteristics are representative of the local population., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

We investigated the distribution of pathogenic non-agalactiae gram-positive, catalase-negative cocci (GPCN) in a convenience sample of New York State dairy farms. Our primary objective with the clinical mastitis (CM) GPCN samples was to evaluate somatic cell count (SCC) resolution and bacteriological cure of Streptococcus dysgalactiae or Streptococcus uberis versus Lactococcus lactis or Lactococcus garvieae in cows that received an approved intramammary treatment. In phase I, we assessed the distribution of the GPCN and SCC resolution. In phase II, we evaluated the SCC resolution and bacteriological cure in CM samples from the 4 farms with the highest prevalence of L. lactis or L. garvieae in phase I. In phase I, 8,868 CM and subclinical mastitis (SCM) milk samples were received from 143 farms. The GPCN samples identified by culture were confirmed with MALDI-TOF. From the 473 MALDI-TOF-confirmed GPCN samples, 155 were S. dysgalactiae (33%); 150, S. uberis (32%); 112, L. lactis (24%); 16, L. garvieae (3%); and 40, other GPCN (8%). From these, 277 were CM samples and 127 were eligible for the evaluation of SCC resolution, which was defined as SCC ≤200,000 cells/mL in a composite sample 15 to 60 d post-diagnosis. The odds of SCC resolution in CM samples was evaluated with multivariable logistic regression, and the odds were 6.1 [95% confidence interval (CI):2.7-13.9] times higher for S. dysgalactiae or S. uberis compared with L. lactis or L. garvieae. In phase II, a total of 1,662 CM and SCM samples were evaluated with microbiological methods as in phase I, of which 211 samples were confirmed by MALDI-TOF: 39% were S. dysgalactiae (n = 61) and S. uberis (n = 21); 55%, L. lactis (n = 114) and L. garvieae (n = 2); and 6%, other GPCN (n = 13). In total, 168 CM samples were eligible for analysis and 118 were included in the final SCC resolution model. Similar statistical methods as in phase I were performed, and the odds of SCC resolution were 2.4 (95% CI: 1.1-5.5) times higher for S. dysgalactiae or S. uberis compared with L. lactis or L. garvieae. Bacteriological cure was defined as having a different or negative culture on a quarter sample taken 14 to 28 d after initial diagnosis. The odds of bacteriological cure (n = 121) were 8.0 (95% CI: 2.5-25.6) times higher for S. dysgalactiae or S. uberis compared with L. lactis or L. garvieae. Differences in SCC resolution and bacteriological cure between these groups may dictate a different management approach., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Optimization of work processes and personnel compliance becomes progressively essential to ensure high process and product quality on dairy farms with an increasingly nonfamily work force. Standard operating procedures (SOP) are important to minimize variation. In addition to having a set of protocols and SOP, regular training of employees is indispensable to reduce procedural drift. A total of 243 farm owners, employees, and veterinarians from 35 farms were invited to take 3 microlearning lessons for colostrum management and provide feedback in an embedded survey. The overall response rate was 48%, and almost all participants accessed the SOP within the course (i.e., 92, 90, and 96% in the first, second, and third course, respectively). Overall, 59% (22/37) launched the course in their leisure time and 80% stated that they were convinced to work more accurately after having taken the course. Most employees underestimated the time spent in the course (76%), accessed background information (89%), or provided feedback (55%). These observations are indicative of high engagement. Overall, 78% of employees felt more confident in correct task completion after the training., (Copyright © 2019 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The Alzheimer's Prevention Initiative (API) Autosomal Dominant Alzheimer's Disease (ADAD) trial evaluates the anti-amyloid-β antibody crenezumab in cognitively unimpaired persons who, based on genetic background and age, are at high imminent risk of clinical progression, and provides a powerful test of the amyloid hypothesis. The Neurosciences Group of Antioquia implemented a pre-screening process with the goals of decreasing screen failures and identifying participants most likely to adhere to trial requirements of the API ADAD trial in cognitively unimpaired members of Presenilin1 E280A mutation kindreds. The pre-screening failure rate was 48.2%: the primary reason was expected inability to comply with the protocol, chiefly due to work requirements. More carriers compared to non-carriers, and more males compared to females, failed pre-screening. Carriers with illiteracy or learning/comprehension difficulties failed pre-screening more than non-carriers. With the Colombian API Registry and our prescreening efforts, we randomized 169 30-60 year-old cognitively unimpaired carriers and 83 non-carriers who agreed to participate in the trial for at least 60 months. Our findings suggest multiple benefits of implementing a pre-screening process for enrolling prevention trials in ADAD., Competing Interests: Rios-Romenets, Giraldo-Chica, López, Piedrahita, Ramos, Acosta-Baena, Muñoz, Ospina, Tobón, Lopera, Langbaum, Reiman and Tariot report the funding disclosures above. S. Rios-Romenets receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. M. Giraldo-Chica receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. H. Lopez receives grant and contract support from the NIH, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. F. Piedrahita receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. C. Ramos receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. N. Acosta-Baena receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. C. Muñoz receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. P. Ospina receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. C. Tobon receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. F. Lopera receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop the API ADAD Registry and help conduct the API ADAD Trial in Colombia. One co-author, a member of the GNA team, is a relative of PSEN1 E280A families. P. Tariot receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation. J. Langbaum receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation to develop. E. Reiman receives grant and contract support from the NIA, Genentech/Roche, and an anonymous foundation. P. Tariot also reports the following (pertinent for the last two years): consulting fees from Abbott Laboratories, AbbVie, AC Immune, Acadia, Auspex, Boehringer-Ingelheim, Brain Test, Inc., California Pacific Medical Center, Chase Pharmaceuticals, Clintara, CME Inc., Glia Cure, Insys Therapeutics, Pfizer, and T3D; Consulting fees and research support from AstraZeneca, Avanir, Lilly, Lundbeck, Merck and Company, and Takeda; Research support only from Amgen, Avid, Functional Neuromodulation (f(nm)), GE, and Novartis; he is a contributor to a patent owned by the University of Rochester, “Biomarkers of Alzheimer’s disease” and owns stock options in Adamas. J. Langbaum also reports the following (pertinent for the last two years): consulting fees from Biogen and Lilly. E. Reiman also reports: he is a paid research consultant to Alkahest, Alzheon, Axovant, Biogen, Denali, Pfizer, and United Neuroscience and Zinfandel. W. Cho and M. Ward are full time employee of Genentech and are Roche equity holders.

Parkinson's disease (PD) patients show marked impairments in processing action verbs, and to a lesser extent, concrete (specially, manipulable) nouns. However, it is still unclear to what extent deficits in each of these categories are influenced by more general cognitive dysfunctions, and whether they are modulated by the words' implied motility. To examine these issues, we evaluated 49 non-demented PD patients and 49 healthy volunteers in an oral production task. The patients were divided into two groups depending on the presence or absence of mild cognitive impairment (PD-MCI and PD-nMCI, respectively). Participants named pictures of actions varying in motion content (low and high) and of objects varying in manipulability (low and high). The PD-MCI group showed deficits across all four categories. However, PD-nMCI patients exhibited a selective difficulty for high-motion action verbs. This finding corroborates and refines previous results suggesting that disturbances of action-related lexico-semantic information in PD constitute a sui generis alteration manifested early in the course of the disease's physiopathology. Moreover, it suggests that the grounding of action verbs on motor circuits could depend on fine-grained intracategorical semantic distinctions., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The objective of this study was to determine the effects of subclinical hypocalcemia on reproductive performance in dairy cows. In a prospective cohort study, 97 cows on 2 dairy farms with automatic milking systems were monitored for subclinical hypocalcemia. Animals were enrolled 7 ± 3 days prior to estimated calving date and three parity groups were defined based on the lactation that the animals were going to start: lactation = 1, lactation = 2, and lactation ≥3. Serum calcium concentration (Ca) was measured in all animals in the first 3 DIM and subclinical hypocalcemia (SCH) was defined as Ca ≤ 8.6 mg/dL; animals that presented a low Ca level during all 3 days were classified as chronic SCH (cSCH). Return to cyclicity during the voluntary waiting period was analyzed based on weekly progesterone concentrations measured in serum. Information on reproductive outcomes (i.e., number of breedings, pregnancy status, days open, etc.), were collected from on-farm software after all study cows had completed their study period. Chronic SCH was present in all parity groups with higher incidence in multiparous animals (20% of parity = 1, 32% of parity = 2; and 46% of parity ≥ 3 animals). The cSCH animals took longer to show active ovaries when compared to eucalcemic and SCH animals. In a multivariable Cox's Proportional Hazard model animals with normal Ca were 1.8 times more likely to return to cyclicity by the end of the voluntary waiting period when compared to cSCH animals. Animals with cSCH also had 0.27 odds of being pregnant at first service compared to eucalcemic cows when analyzed by multivariable logistic regression. Subclinical hypocalcemia had a negative effect on return of ovarian function during the voluntary waiting period and decreased the odds of pregnancy at first service. Those cows with cSCH had an even more pronounced impaired reproductive function than those with one subclinical measurement., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In this dataset, we present the collected data of two experiments with the application of the gamified peer assessment model into online learning environment MeuTutor to allow the comparison of the obtained results with others proposed models. MeuTutor is an intelligent tutoring system aims to monitor the learning of the students in a personalized way, ensuring quality education and improving the performance of its members (Tenório et al., 2016) [1]. The first experiment evaluated the effectiveness of the peer assessment model through metrics as final grade (result), time to correct the activities and associated costs. The second experiment evaluated the gamification influence into peer assessment model, analyzing metrics as access number (logins), number of performed activities and number of performed corrections. In this article, we present in table form for each metric: the raw data of each treatment; the summarized data; the application results of the normality test Shapiro-Wilk; the application results of the statistical tests T -Test and/or Wilcoxon. The presented data in this article are related to the article entitled "A gamified peer assessment model for on-line learning environments in a competitive context" (Tenório et al., 2016) [1].

The study objective was to compare 2 commercial dry cow mastitis products at the quarter level, with concurrent internal teat sealant application, evaluating the cure risk difference, odds of a cure, odds of a new intramammary infection (NIMI) during the dry period, and risk for a clinical mastitis (CM) case between calving and 60d in milk (DIM). A total of 590 cows (2,360 quarters) from 8 commercial dairy herds in Italy were enrolled and randomized to 1 of the 2 treatments at dry off: Cefovet A (CF; 250mg of cephazoline; Merial Italia SpA, Milan, Italy), and Cepravin (CP; 250mg of cephalonium dehydrate MSD Animal Health Srl, Segrate, Italy). Quarter milk samples were collected before dry cow therapy treatment at dry off, 2 to 9 DIM, and 10 to 17 DIM. Quarter milk samples from CM cases were collected during the first 60 DIM. Noninferiority analysis was used to evaluate the effect of treatment on the risk difference of a bacteriological cure during the dry period, the primary outcome. The odds of cure, developing a NIMI during the dry period, and the risk of a CM event within 60 DIM were evaluated with multivariable logistic regression and hazard analysis, respectively. The overall crude quarter-level prevalence of NIMI at dry off was 15.3%. The most common pathogen isolated from milk samples at dry-off was coagulase-negative staphylococci. Noninferiority analysis showed no effect of treatment on the risk difference for a cure between dry off and both postpartum samples, difference was 0.013. The least squares means from the multivariable model evaluating the odds of cure was 94% for CF and 95%for CP. We observed no effect of treatment on the odds for the presence of a NIMI at 2 to 9 DIM (least squares means: CF=0.09 and CP=0.07), nor did we note a difference in risk of experiencing a CM event between calving and 60 DIM (hazard ratio=0.8). In conclusion, no difference was observed between the 2 products evaluated when assessing the aforementioned outcomes in quarters also receiving an internal teat sealant., (Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

In a prospective cohort study, the daily bodyweight (BW) and milk production of 92 cows were recorded using automatic milking systems. The objectives were to characterize calcium serum concentration variability on days 1-3 post-partum and to evaluate the association between subclinical hypocalcemia (SHPC) and change in BW over the first 30 days in milk (DIM) in Holstein dairy cows, while controlling for concurrent disease and negative energy balance (NEB). SHPC was defined as total serum calcium concentration between 6 and 8 mg/dL, NEB was defined as non-esterified fatty acids (NEFA) > 0.7 mEq/L or β-hydroxybutyrate (BHB) ≥ 1.2 mmol/L. The peak incidence of SHPC was at 1 DIM for all groups (11%, 42% and 60% for parities 1, 2, and ≥3, respectively). All parity groups lost weight (21, 33, and 34 kg) during the first 30 DIM. Parity 1 animals with disease compared with those without disease lost the most weight (2.6 kg/day BW loss vs. <1.9 kg/day, respectively). Normocalcemic parity 2 animals with either NEB or disease lost the most weight (>5 kg/day) compared with those in the SHPC group (≤4.5 kg/day). In parity ≥ 3 animals, SHPC was an important factor for BW loss; SHPC animals lost the most weight (>3.7 kg/day) vs. normocalcemic cows (≤3.3 kg/day) regardless of NEB or disease status. Even though all animals lost weight during early lactation the effect of disease, NEB, and SHPC on BW loss was different in each parity group., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

The objectives were (1) to explain why the risk ratio (RR) is an appropriate measure of association when the outcome of interest is dichotomous (e.g., displaced abomasum or no displaced abomasum) in both cohort studies and randomized trials; and (2) to outline an applied method for estimating the RR using currently available software. Interest in the association between multiple risk factors and a yes or no outcome is very common in the dairy industry; historically, logistic regression, which reports odds ratios (OR), was the method available in common statistical packages to evaluate this kind of association. However, the OR can overestimate the magnitude of the response in cohort studies and randomized trials when the outcome frequency is large. In addition, the interpretation of odds is not intuitive; fortunately, recent advances in statistical software have allowed the estimation of the RR. Because SAS software (SAS Institute Inc., Cary, NC) is commonly used to analyze data, this technical note outlines the basic programming code that may be used to estimate the RR from raw data. Example data from a prospective cohort study was used to compare the OR and RR of developing a displaced abomasum or ketosis or metritis based on multiple predictors, their interaction, and a random effect (e.g., herd)., (Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The purpose of this study was to determine the effect of oral propylene glycol (PG) administration on ketosis resolution and milk yield in cows diagnosed with subclinical ketosis (SCK). Cows from 4 freestall dairy herds (2 in New York and 2 in Wisconsin) were each tested 6 times for SCK from 3 to 16 d in milk on Mondays, Wednesdays, and Fridays. Subclinical ketosis was defined as a β-hydroxybutyrate (BHBA) concentration of 1.2 to 2.9 mmol/L, [corrected] and clinical ketosis was defined as ≥ 3.0 mmol/L. [corrected]. Cows with SCK were randomized to the treatment group (oral PG) or control group (no PG); treatment cows were drenched with 300 mL of PG once daily from the day they tested 1.2 to 2.9 mmol/L [corrected] until the day they tested <1.2 mmol/L. [corrected]. Outcomes evaluated for all farms included time from SCK until BHBA test <1.2 mmol/L [corrected] or until BHBA test ≥ 3.0 mmol/L. [corrected]. Individual milk weights for the first 30 d of lactation were evaluated for the 3 farms monitoring daily milk. Semiparametric proportional hazards models were used to evaluate time to event outcomes; repeated-measures ANOVA was used to assess milk weights. A total of 741 of 1,717 (43.2%) eligible enrolled cows had at least one BHBA test of 1.2 to 2.9 mmol/L. [corrected]. Of these, 372 were assigned to the treatment group and 369 to the control group. Based on hazard ratios, PG-treated cows were 1.50 times more likely (95% confidence interval=1.26 to 1.79) to resolve their SCK and 0.54 times less likely (95% confidence interval=0.34 to 0.86) to develop clinical ketosis than control cows. Across the 3 herds measuring individual milk weights, treated cows produced 0.23 kg more milk per milking in the first 30 d of lactation than control cows, for a total difference of 0.69 kg/cow per day. After identification of a treatment by herd interaction, stratification by herd showed that treated cows produced more milk per milking on farm A (0.44 kg) and farm B (0.53 kg) in the first 30 d of lactation than control cows, for a total difference of 1.34 and 1.59 kg/d, respectively; milk production did not differ (0.02 kg per milking) between the 2 groups on farm D. These results show the positive effects of oral PG administration in fresh cows with SCK by helping to resolve SCK and preventing clinical ketosis. In addition, oral PG improves milk yield during early lactation in cows diagnosed with SCK., (Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

In this study the herd alarm level was defined as the proportion of sampled transition cows per herd with increased prepartum nonesterified fatty acid (NEFA), postpartum beta-hydroxybutyrate (BHBA), or NEFA concentrations that were associated with herd-level incidence of displaced abomasum (DA) or clinical ketosis (CK), pregnancy rate (PR), and milk production. The objectives were to 1) identify the herd alarm level for excessive negative energy balance and 2) describe the herd-level prevalence of this proportion. This was a prospective cohort study of 60 free-stall herds fed total mixed rations in the northeast United States. Two cohorts of approximately 15 animals were assessed for prepartum NEFA and postpartum BHBA and NEFA. The herd alarm level (i.e., the proportion of sampled animals above a certain metabolite threshold) was as follows: 15% had prepartum NEFA of 0.27 mEq/L; 15 and 20% had BHBA of 10 and 12 mg/dL, respectively; and 15% had postpartum NEFA of 0.60 and 0.70 mEq/L. The different herd alarm levels correspond to differences between the metabolites and respective herd-level effect. The herd-level effects for herds above the herd alarm level for prepartum NEFA were 3.6% increase in DA and CK incidence, 1.2% decrease in PR, and 282 kg decrease in average mature equivalent 305-d (ME 305) milk. For BHBA, the herd-level effects were a 1.8% increase in DA and CK, 0.8% decrease in PR, and 534 and 358 kg decrease in projected ME 305 milk yield for heifers and cows, respectively. For postpartum NEFA, the herd-level effects were 1.7% increase in DA and CK, 0.9% decrease in PR, and 288 and 593 kg decrease in projected ME 305 milk yield for heifers and cows, respectively. The prevalence of herds in which more than 15% of animals sampled had prepartum NEFA concentration >or=0.30 mEq/L was 75%, BHBA >or=12 mg/dL was 40%, and postpartum NEFA >or=0.70 mEq/L was 65%. This study showed that there were detrimental herd-level effects if a large enough proportion of cows had increased metabolite concentrations, and further demonstrated that a high prevalence of herds have opportunity for improvement., (Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objectives were to evaluate the effects of elevated pre- and postpartum nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA) concentrations during the transition period on reproductive performance and milk production in dairy cattle. In a prospective cohort study of 91 freestall, total mixed ration-fed herds in the northeastern United States, blood samples were collected from approximately 15 prepartum and 15 different postpartum transition animals in each herd. All samples were stratified based on pre- or postpartum status at the time of sample collection, and 2,259 and 2,290 animals were used to evaluate reproductive and milk production performance, respectively. Reproductive performance was assessed by time to conception within 70 d post-voluntary waiting period (VWP) and milk production was assessed using mature-equivalent 305-d (ME305) milk yield estimated at 120 d in milk. While controlling for body condition score (BCS), calving season, median ME305 milk production, and parity, NEFA and BHBA concentrations were evaluated with time to event analysis to investigate reproductive performance. These same predictor variables were used to determine the effects of elevated NEFA and BHBA concentrations on ME305 milk yield with herd as a random effect. Heifers and cows were grouped in the final analyses if the results between groups were similar. In all animals sampled prepartum, the risk of pregnancy within 70 d post-VWP was reduced by 19% when NEFA concentrations were >or=0.27 mEq/L. In all animals sampled postpartum, those with NEFA concentrations >or=0.72 mEq/L had a 16% decrease in risk of pregnancy and those with BHBA concentrations >or=10mg/dL had a 13% decrease in risk. In cows and heifers, ME305 milk yield was decreased by 683 kg when prepartum NEFA concentrations were >or=0.33 mEq/L. In heifers sampled postpartum, ME305 milk yield was increased by 488 kg when NEFA concentrations were >or=0.57 mEq/L and increased by 403 kg when BHBA concentrations were >or=9 mg/dL. In cows sampled postpartum, ME305 milk yield was decreased by 647 kg when NEFA concentrations were >or=0.72 mEq/L and decreased by 393 kg when BHBA concentrations were >or=10mg/dL. With the exception of milk production in heifers, this study indicates that increased concentrations of serum NEFA and BHBA had a detrimental effect on reproductive performance and milk production., (Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

The objectives of this study were to 1) establish cow-level critical thresholds for serum concentrations of nonesterified fatty acids (NEFA) and beta-hydroxybutyrate (BHBA) to predict periparturient diseases [displaced abomasa (DA), clinical ketosis (CK), metritis and retained placenta, or any of these three], and 2) investigate the magnitude of the metabolites' association with these diseases within 30 d in milk. In a prospective cohort study of 100 freestall, total mixed ration-fed herds in the northeastern United States, blood samples were collected from approximately 15 prepartum and 15 different postpartum transition animals in each herd, for a total of 2,758 samples. Serum NEFA concentrations were measured in the prepartum group, and both NEFA and BHBA were measured in the postpartum group. The critical thresholds for NEFA or BHBA were evaluated with receiver operator characteristic analysis for all diseases in both cohorts. The risk ratios (RR) of a disease outcome given NEFA or BHBA concentrations and other covariates were modeled with multivariable regression techniques, accounting for clustering of cows within herds. The NEFA critical threshold that predicted any of the 3 diseases in the prepartum cohort was 0.29mEq/L and in the postpartum cohort was 0.57mEq/L. The critical threshold for serum BHBA in the postpartum cohort was 10mg/dL, which predicted any of the 3 diseases. All RR with NEFA as a predictor of disease were >1.8; however, RR were greatest in animals sampled postpartum (e.g., RR for DA=9.7; 95% CI=4.2 to 22.4. All RR with BHBA as the predictor of disease were >2.3 (e.g., RR for DA=6.9; 95% CI=3.7 to 12.9). Although prepartum NEFA and postpartum BHBA were both significantly associated with development of clinical disease, postpartum serum NEFA concentration was most associated with the risk of developing DA, CK, metritis, or retained placenta during the first 30 d in milk., (Copyright 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Aim: The efficacy and safety of insulin aspart (IAsp), a rapid-acting human insulin analogue, were compared with regular human insulin (HI) as the bolus component of basal-bolus therapy for subjects with gestational diabetes mellitus (GDM)., Methods: In a randomized, parallel-group, open-labelled trial, 27 women with GDM (age 30.7 +/- 6.3 years, HbA(1c) < 7%) were randomized to receive IAsp (5 min before meal) or HI (30 min before meal). The trial period extended from diagnosis of GDM (18-28 weeks) to 6 weeks postpartum., Results: Both treatment groups maintained good overall glycaemic control during the study (beginning and end of study HbA(1c)< or = 6%). During the meal test, mean glucose at week 6 (IAsp 4.2 +/- 0.57 mmol/l, HI 4.8 +/- 0.86 mmol/l) was slightly lower than at week 0 (IAsp 4.9 +/- 0.59 mmol/l, HI 5.1 +/- 0.36 mmol/l). However, change from baseline values for average glucose (IAsp -1.09 +/- 0.54 mmol/l, HI -0.54 +/- 0.74 mmol/l; P = 0.003) and C-peptide (IAsp -0.50 +/- 0.67 nmol/l, HI -0.30 +/- 0.70 nmol/l; P = 0.027) were significantly lower after IAsp treatment than HI treatment. No major hypoglycaemic events were reported during the study. Cross-reacting insulin antibody binding increased slightly from baseline in both treatments groups (end of study: IAsp 2.1 +/- 5.4%, HI 6.4 +/- 13.9%), whereas antibodies specific to IAsp or HI remained relatively low (< 1% binding)., Conclusion: IAsp was more effective than HI in decreasing postprandial glucose concentrations. Duration of IAsp injection 5 min before a meal rather than 30 min prior to meals offers a more convenient therapy for subjects with GDM. Overall safety and effectiveness of IAsp were comparable to HI in pregnant women with GDM.

Objective: To determine whether some offspring of women with diabetes are intrinsically more active than others in utero and whether those who are active are able to normalize their birth weight despite maternal hyperglycemia., Research Design and Methods: We conducted a three-phase study to view the relationship between fetal movements and subsequent birth weight in women with diabetes. Phase I was designed to assess maternal perception of fetal movements in a population of 10 women with diabetes. To improve our fetal monitoring techniques, in phase II we analyzed fetal movements using the Card Guard home fetal monitoring device (CG 900P) in a population of 13 women with gestational diabetes mellitus (GDM). To apply our observations of fetal movements to a larger population, during phase III we conducted a retrospective analysis of fetal monitoring strips (HP 8041A) from 46 women with GDM to examine the relationship between fetal heart rate (FHR) accelerations and percentile birth weight, corrected for gestational age., Results: Phase I confirmed that there is little variability in fetal movements (i.e., fetal kicks did not significantly deviate from one another on a day-to-day basis). In phase II, the fetal monitoring strips illustrated that the active fetuses (defined as > or = 4 FHR accelerations in a 20-min period) were always active, and the inactive fetuses were always inactive. The mean birth weight percentile, corrected for gestational age, in the active group was 37 vs. 63% in the inactive group (P = 0.05). In phase III, the fetal monitoring strips showed an inverse correlation between the mean number of FHR accelerations and the birth weight of the fetus, corrected for gestational age. The mean birth weight percentile in the active group was 37 vs. 62% in the inactive group (P = 0.0017)., Conclusions: The fetus appears to play a role in determining its own destiny. Increased fetal activity may minimize the impact of hyperglycemia on subsequent birth weight. The inactive fetus appears to be at a higher risk for glucose-mediated macrosomia.

Background: This study was designed to determine if it was feasible to use a run-to-run algorithm to improve postprandial glucose concentrations in individuals with type 1 diabetes mellitus (T1DM)., Methods: Fourteen subjects were recruited for this 10-week study. During the initial phases of the study, the following information was derived for each subject: basal insulin infusion rates, insulin-to-carbohydrate ratios, insulin correction factors for hyperglycemia, and insulin sensitivities. During the final phases, the algorithm was used to suggest preprandial insulin doses, with a goal of bringing the postprandial glucose into a predetermined target range within 3-7 days., Results: In the single-meal phase (phase 5), 33% of the subject-meal responses were convergent in 3-4 days to a clinically acceptable range, 33% always stayed in range, and 33% had divergent responses, incorrect sensitivities, and/or other mitigating circumstances. In the three-meal phase (phase 6), 41% of the subject-meal responses were convergent in 3-4 days to a clinically acceptable range, 26% were always in range, and 33% had divergent responses, incorrect sensitivities, and/or other mitigating circumstances., Conclusions: Overall, we were able to safely demonstrate that run-to-run control can be used to manage meal-related insulin in subjects with T1DM.

Objective: To assess the short-term efficacy of insulin aspart in comparison with regular human insulin in women with gestational diabetes mellitus (GDM) during standardized meal tests., Research Design and Methods: The study included 15 women with GDM who had inadequate diabetes control with diet alone. On 3 consecutive days, breakfast meal tests were performed-the first with no exogenous insulin and the other two after the injection of either regular insulin or insulin aspart., Results: The peak insulin concentration was higher and the peak glucose and C-peptide concentrations were lower with both insulin preparations than with no exogenous insulin. Glucose areas under the curve above baseline were significantly lower with insulin aspart (180-min area, 7.1 mg. h. dl(-1); P = 0.018), but not with regular insulin (30.2 mg. h. dl(-1); P = 0.997), than with no insulin (29.4 mg. h. dl(-1))., Conclusions: This study demonstrates that effective postprandial glycemic control in women with GDM who required insulin was brought about by insulin aspart through higher insulin peak and lower demand on endogenous insulin secretion.