Influence of Domain Size and Support Composition on the Reducibility of SiO2 and TiO2 Supported Tungsten Oxide Clusters.

Supported tungsten oxides are widely used in a variety of catalytic reactions. Depending on the support, the cluster size, oxidation state, reducibility and speciation of the tungsten oxides can widely differ. When promoted with a platinum group metal, the resulting spillover of hydrogen may facilitate the reduction of supported tungsten oxide species, depending on the support. High resolution scanning transmission electron microscopy imaging showed nanometer scale WO x clusters were synthesized on SiO2 whereas highly dispersed species were formed on TiO2. Results from H2-temperature-programmed reduction showed the presence of Pd lowered the initial reduction temperature of SiO2-supported WO x species but interestingly did not affect that of TiO2-supported WO x . X-ray photoelectron and absorption spectroscopies showed the W atoms in SiO2-supported WO x species reduce from a +6 oxidation state to primarily +5 after thermal treatment in 5% H2, while the fraction of W in the +5 oxidation state was relatively unaffected by reduction treatment of TiO2-supported WO x . The unusual behavior of TiO2-supported WO x was explained by quantum chemical calculations that reveal the lack of change in the oxidation state of W is attributed to charge delocalization on the surface atoms of the titania support, which does not occur on silica. Moreover, modeling results at <600 K in the presence of H2 suggest the formation of Brønsted acid sites, and the absence of Lewis acid sites, on larger aggregates of WO x on silica and all cluster sizes on titania. These results provide experimental and theoretical insights into the nature of supported tungsten oxide clusters under conditions relevant to various catalytic reactions.

Discovery of a potent, selective, and tumor-suppressing antibody antagonist of adenosine A2A receptor.

New immune checkpoints are emerging in a bid to improve response rates to immunotherapeutic drugs. The adenosine A2A receptor (A2AR) has been proposed as a target for immunotherapeutic development due to its participation in immunosuppression of the tumor microenvironment. Blockade of A2AR could restore tumor immunity and, consequently, improve patient outcomes. Here, we describe the discovery of a potent, selective, and tumor-suppressing antibody antagonist of human A2AR (hA2AR) by phage display. We constructed and screened four single-chain variable fragment (scFv) libraries-two synthetic and two immunized-against hA2AR and antagonist-stabilized hA2AR. After biopanning and ELISA screening, scFv hits were reformatted to human IgG and triaged in a series of cellular binding and functional assays to identify a lead candidate. Lead candidate TB206-001 displayed nanomolar binding of hA2AR-overexpressing HEK293 cells; cross-reactivity with mouse and cynomolgus A2AR but not human A1, A2B, or A3 receptors; functional antagonism of hA2AR in hA2AR-overexpressing HEK293 cells and peripheral blood mononuclear cells (PBMCs); and tumor-suppressing activity in colon tumor-bearing HuCD34-NCG mice. Given its therapeutic properties, TB206-001 is a good candidate for incorporation into next-generation bispecific immunotherapeutics.

The Importance of Recovery in Resistance Training Microcycle Construction.

Systemic resistance training aims to enhance performance by balancing stress, fatigue and recovery. While fatigue is expected, insufficient recovery may temporarily impair performance. The aim of this review was to examine evidence regarding manipulation of resistance training variables on subsequent effects on recovery and performance. PubMed, Medline, SPORTDiscus, Scopus and CINAHL were searched. Only studies that investigated recovery between resistance training sessions were selected, with a total of 24 articles included for review. Training to failure may lengthen recovery times, potentially impairing performance; however, it may be suitable if implemented strategically ensuring adequate recovery between sessions of similar exercises or muscle groups. Higher volumes may increase recovery demands, especially when paired with training to failure, however, with wide variation in individual responses, it is suggested to start with lower volume, monitor recovery, and gradually increase training volume if appropriate. Exercises emphasising the lower body, multi-joint movements, greater muscle recruitment, eccentric contractions, and/or the lengthened position may require longer recovery times. Adjusting volume and frequency of these exercises can affect recovery demands depending on the goals and training logistics. Daily undulating programming may maximise performance on priority sessions while maintaining purposeful and productive easy days. For example, active recovery in the form of training opposing muscle groups, light aerobic cardio, or low-volume power-type training may improve recovery and potentially elicit a post activation potentiation priming effect compared to passive recovery. However, it is possible that training cessation may be adequate for allowing sufficient recovery prior to sessions of importance.

The curse of the firstborn: Effects of dam primiparity on developmental programming in ruminant offspring.

The first parity, or first pregnancy, of ruminant females has negative effects on offspring during fetal, perinatal, and pre-weaning periods which ultimately lead to diminished pre-weaning productivity. Offspring born to primiparous ruminant females can have decreased fetal and pre-weaning growth, resulting in lower body weights at birth and weaning in cattle, sheep, and goats. Moreover, mortality is greater during both neonatal and pre-weaning periods. Insults during these critical developmental windows likely also have long-term consequences on first-parity offspring through developmental programming, but less research has been done to investigate effects in the post-weaning period. Many potential physiological, metabolic, and behavioral mechanisms exist for the outcomes of dam primiparity. Although competition for nutrient partitioning between maternal and fetal growth or lactation is often cited as a major contributor, we hypothesize that the most important mechanism causing most first-parity outcomes is the relative physiological inexperience of reproductive tissues such as the uterus and mammary gland during the first pregnancy and lactation, or a "first use theory" of tissues. More research is necessary to explore these areas, as well as if primiparous dams respond differently to stressors than multiparous dams, and if stress during the first parity affects subsequent parities.

Effects of late gestational nutrient restriction on uterine artery blood flow, placental size, and cotyledonary mRNA expression in primiparous beef females.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to parturition. Doppler ultrasonography of both uterine arteries was conducted pre-treatment and every 21 d from days 181 to 265 of gestation. Expelled placentas were collected, and ipsilateral cotyledonary tissue was sampled to assess relative messenger ribonucleic acid (mRNA) expression. Placentas were separated into ipsilateral and contralateral sides, dissected (cotyledonary vs. intercotyledonary), and dried. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Uterine blood flow included day and nutritional plane × day as repeated measures. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Maternal heart rate was less (P < 0.001) for NR dams than CON after nutritional planes began. Nutritional plane did not affect (P ≥ 0.20) uterine artery hemodynamics, but all variables were affected (P ≤ 0.04) by day. Contralateral cotyledonary and placental weight were less (P ≤ 0.04) and contralateral intercotyledonary weight and number of cotyledons tended to be less (P ≤ 0.10) for NR dams than CON, but ipsilateral and whole placental weights were not affected (P ≥ 0.13). Ipsilateral placental weight as a percentage of total placental weight was greater (P = 0.03) for NR dams than CON. Whole placental cotyledonary: intercotyledonary weight was less (P = 0.01) for NR dams than CON. Placental efficiency was not affected (P = 0.89) by nutritional plane. Cotyledonary relative mRNA expression of GLUT3 and SNAT2 was greater (P ≤ 0.05) and relative expression of GLUT1, GLUT4, and NOS3 tended to be greater (P ≤ 0.07) for NR dams than CON. Nutritional plane did not affect (P ≥ 0.13) relative mRNA expression of GLUT5, 4F2hc, CAT1, LAT1, LAT2, VEGFA, FLT1, KDR, GUCY1B3, and PAG2. Despite less contralateral placental growth, beef heifers experiencing late gestational nutrient restriction maintained uterine artery blood flow and total placental mass and had 4 nutrient transporters and 1 angiogenic factor upregulated in cotyledons, all of which likely contributed to conserving fetal growth.

Nutrient requirements increase substantially during late gestation in the beef female to support fetal, uteroplacental, and mammary growth, and in the still-growing heifer, nutrients are also needed for maternal tissue growth. During pregnancy, the placenta serves as the interface for the metabolism and transport of nutrients, gases, and wastes between maternal and fetal circulations. Inadequate gestational nutrition can result in placental insufficiency and intrauterine growth restriction of the offspring, resulting in postnatal consequences. How late gestational undernutrition in beef heifers impacts the factors involved in placental nutrient transport capacity is poorly understood. We observed that late gestational nutrient restriction in heifers decreased maternal heart rate, but total uterine artery blood flow was not affected. Additionally, total placental mass was maintained, while cotyledonary expression of 4 nutrient transporters and an angiogenic factor were upregulated in placentas of nutrient restricted dams, which collectively allowed for similar calf birth weights as adequately-fed dams.

Late gestational nutrient restriction in primiparous beef females: Performance and metabolic status of lactating dams and pre-weaning calves.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation in Calan gates until day 149 of lactation, which limited calves to milk only. From day 150 of lactation until weaning at day 243, dams and calves were group-fed in drylots. Dam BW and metabolic status were determined every 21 d, and BCS and backfat (BF) were determined every 42 d of lactation until weaning. Pre-weaning calf BW, size, and metabolic status were determined every 21 d. Data were analyzed with nutritional plane, calving date, and calf sex (when P < 0.25) as fixed effects. Circulating metabolites included day and nutritional plane × day as repeated measures. We previously reported that post-calving, NR dams were 64 kg and 2.0 BCS less than CON, but calf BW and size at birth were not affected. During the first 147 d of lactation, NR dams gained more (P < 0.01) BW than CON and increased (P < 0.01) BCS, while CON decreased (P ≤ 0.01) BCS and BF. Previously, NR dams had lower (P < 0.01) circulating triglycerides on day 1 of lactation, tended to have lower (P = 0.08) triglycerides on day 21, and had lower (P ≤ 0.04) non-esterified fatty acids (NEFA) on days 21 and 243 than CON. Maternal glucose and urea N were not affected (P ≥ 0.73). At weaning, NR dams weighed 17 kg less (P = 0.15), were 0.67 BCS lower (P < 0.01), and tended to have less (P = 0.06) BF. Calves born to NR dams weighed less (P = 0.02) than CON by day 42 of age and were 13% smaller (P < 0.01) at weaning. Calf girth measures diverged (P ≤ 0.05) by day 21 of age, and skeletal size measures were less (P ≤ 0.08) for calves born to NR dams at most timepoints after day 63 of age. Calves born to NR dams tended to have lower (P = 0.09) circulating urea N pre-weaning than CON, but glucose, triglycerides, and NEFA were not affected (P ≥ 0.16). In summary, first-parity beef females that were nutrient restricted during late gestation experienced compensatory growth and gained body condition during lactation but were still thinner at weaning. Nutrient restriction reduced pre-weaning calf growth, likely due to decreased milk production.

Nutrient requirements increase substantially during late gestation in the beef female; however, poor forage nutrient availability can result in undernutrition. For heifers, the added nutrient requirements needed to continue growing during their first pregnancy and lactation pose an even greater challenge. It is plausible that lingering effects of late gestational nutrient restriction may exist for the dam and calf pre-weaning. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation recovered quickly metabolically and experienced compensatory growth, but still had less body condition at weaning than controls. Late gestational nutrient restriction did not affect calf size at birth but resulted in calf body weight and size measures diverging early in life. Ultimately, nutrient restriction resulted in a 13% decrease in weaning weight, which was likely due to decreased milk production (in a companion paper). Despite this, metabolic status of calves born to nutrient restricted dams was not greatly altered. In summary, first-parity beef females that were nutrient restricted during late gestation prioritized partitioning nutrients to maternal growth and energy reserves over milk production during lactation, but dams were thinner at weaning, and pre-weaning calf growth was slowed.

Nutrient restriction during late gestation reduces milk yield and mammary blood flow in lactating primiparous beef females.

Fall-calving primiparous beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of estimated metabolizable energy and metabolizable protein requirements from day 160 of gestation to calving. Post-calving, all dams were individually-fed tall fescue hay supplemented to meet estimated nutrient requirements for maintenance, growth, and lactation until day 149 of lactation. Four-hour milk yields were collected on days 21, 42, 63, 84, 105, and 147 of lactation, and milk nutrient composition was determined. Doppler ultrasonography of both pudendoepigastric arterial trunks was conducted every 21 d from days 24 to 108 of lactation. Total mammary blood flow was calculated, and hemodynamics from both sides were averaged. Data were analyzed as repeated measures with nutritional plane, day of lactation, their interaction, calving date, and calf sex (if P < 0.25) as fixed effects. We previously reported that post-calving, NR dams weighed 64 kg less and were 2.0 BCS lower than CON, but calf birth weight was not affected. Milk weight and volume were 15% less (P = 0.04) for NR dams than CON. Milk protein concentration was lower (P = 0.008) for NR dams than CON, but triglyceride and lactose concentrations were not affected (P ≥ 0.20) by nutritional plane. Milk urea N concentration of NR dams tended to be greater (P = 0.07) on day 42 but was lower (P = 0.01) on day 147 of lactation than CON. Total milk protein, triglyceride, and lactose yields were less (P ≤ 0.05) for NR dams than CON. Total milk urea N yield was less (P ≤ 0.03) for NR dams than CON on days 21, 63, and 147 of lactation. Maternal heart rate was greater (P = 0.008), but pudendoepigastric arterial trunk peak systolic velocity, resistance index, and cross-sectional area were less (P ≤ 0.04) and pulsatility index tended to be less (P = 0.06) for NR dams than CON. Mammary blood flow was 19% less (P = 0.004) for NR dams than CON, but mammary blood flow relative to milk weight or dam BW was not affected (P ≥ 0.14) by nutritional plane. Most milk yield, milk nutrient composition, and mammary blood flow variables were affected (P ≤ 0.04) by day of lactation. In summary, first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had decreased milk nutrient yield and a similar reduction in mammary blood flow.

Mammary development in preparation for lactation is largely complete at the time of calving, and final prepartum mammary growth and differentiation are occurring for the first time in heifers. Nutrient requirements increase substantially during late gestation, resulting in competition for nutrient use among maternal growth, fetal growth, and mammary growth in primiparous beef females. Undernutrition during late gestation can occur due to poor forage nutrient availability or drought, potentially impacting mammary gland development and subsequent milk production. We report that first-parity beef females that were nutrient restricted during late gestation and then fed to meet estimated nutrient requirements during lactation had 15% lower milk yield, reduced milk protein concentration, and less total milk protein, triglycerides, lactose, and urea N available for their calves than controls. Additionally, previously nutrient restricted dams had 19% less total mammary blood flow, and the major arteries supplying the mammary gland were smaller.

Engineering CD276/B7-H3-targeted antibody-drug conjugates with enhanced cancer-eradicating capability.

CD276/B7-H3 represents a promising target for cancer therapy based on widespread overexpression in both cancer cells and tumor-associated stroma. In previous preclinical studies, CD276 antibody-drug conjugates (ADCs) exploiting a talirine-type pyrrolobenzodiazepine (PBD) payload showed potent activity against various solid tumors but with a narrow therapeutic index and dosing regimen higher than that tolerated in clinical trials using other antibody-talirine conjugates. Here, we describe the development of a modified talirine PBD-based fully human CD276 ADC, called m276-SL-PBD, that is cross-species (human/mouse) reactive and can eradicate large 500-1,000-mm3 triple-negative breast cancer xenografts at doses 10- to 40-fold lower than the maximum tolerated dose. By combining CD276 targeting with judicious genetic and chemical ADC engineering, improved ADC purification, and payload sensitivity screening, these studies demonstrate that the therapeutic index of ADCs can be substantially increased, providing an advanced ADC development platform for potent and selective targeting of multiple solid tumor types.

Maternal nutrient restriction during late gestation reduces vigor and alters blood chemistry and hematology in neonatal beef calves.

Fall-calving primiparous beef females [body weight: 451 ±â€…28 (SD) kg; body condition score: 5.4 ±â€…0.7] were individually-fed either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to parturition. Calves were reared naturally by their dams and monitored for latency times from birth to first sternal recumbency, attempt to stand, and stand; vigor scores were assigned at 2, 5, 10, and 20 min of age. Rectal temperatures and jugular blood were obtained at 0 (pre-suckling), 6, 12, 24, and 48 h of age, and blood chemistry, hematology, cortisol, and insulin were determined. Data were analyzed with fixed effects of late gestational nutritional plane (single data point) or nutritional plane, hour, and their interaction (data over time, repeated measures). Calving date was a fixed effect; calf sex was included when P < 0.25. We previously reported that late gestational nutritional plane did not affect gestation length or calf size at birth, but calving assistance and fetal malpresentation occurred more often in NR. Nutritional plane did not affect (P = 0.65) duration of parturition, but calves born to NR dams had slower times to attempt to stand (P = 0.09), slower times to stand (P = 0.02), and poorer 20 min vigor scores (P = 0.05). Serum immunoglobulin G and A concentrations at 48 h were greater (P ≤ 0.03) for NR calves. Rectal temperature of NR calves was less (P = 0.02) at 0 h, but greater (P = 0.04) at 24 h compared with CON. Circulating glucose, non-esterified fatty acids, triglycerides, cortisol, and insulin were not affected by nutritional plane (P ≥ 0.18). Total protein and globulin from 6 to 48 h were greater (P ≤ 0.02) in NR calves. Calves from NR dams had greater (P ≤ 0.08) gamma-glutamyl transferase at 6, 12, and 48 h. Serum aspartate aminotransferase was greater (P ≤ 0.07) from 0 to 24 h and creatine kinase was greater (P ≤ 0.04) from 6 to 24 h in NR calves. At 0 h, potassium was greater (P = 0.03) in NR calves. Calves born to CON had greater chloride (P = 0.08; main effect), sodium (P ≤ 0.09) from 0 to 48 h, and anion gap (P = 0.02) at 6 h. Hematocrit from 6 to 24 h and red blood cells and hemoglobin at 6 and 12 h were greater (P ≤ 0.09) in CON calves. These data indicate that nutrient restriction during late gestation resulted in less vigorous calves with more indicators of trauma in early life.

Early life after birth is challenging for beef calves, but a successful transition from the uterus to the outside environment is necessary for calves to survive and thrive pre-weaning. Despite this, limited research has investigated how maternal undernutrition during pregnancy affects the vigor and metabolism of beef calves during early life. Beef females in their first pregnancy were fed to meet their energy and protein requirements, or were fed 70% of these requirements, during late pregnancy. Their calves were monitored closely, and data were collected intensively during early life. Calves born to nutrient restricted females were less vigorous at birth, taking longer to attempt to stand and stand successfully for the first time, and having lower vigor scores at 20 min of age. These calves also showed more signs of calving trauma and stress (elevated aspartate aminotransferase, creatine kinase, and creatinine) and had less red blood cells, but they had successful transfer of passive immunity and minimally affected energy metabolism. Overall, the effects of nutrient restriction observed may have decreased neonatal calf health and survival in a normal production environment, but not through reduced passive transfer.

Alpaca single B cell interrogation and heavy-chain-only antibody discovery on an optofluidic platform.

In vivo VHH discovery approaches have been limited by the lack of methodologies for camelid B cell interrogation. Here, we report a novel application of the Beacon® optofluidic platform to the discovery of heavy-chain-only antibodies by screening alpaca B cells. Methods for alpaca B cell enrichment, culture, IgG2/3 detection, and sequencing were developed and used to discover target-specific VHH from an alpaca immunized with prostate-specific membrane antigen (PSMA) or a second target. PSMA-specific hits were expressed as VHH-Fc and characterized using label-free techniques. Anti-PSMA IgG2/3 titer plateaued on day 153, when on-Beacon IgG2/3 secretion and target binding rates peaked. Of 13 recombinantly expressed VHH-Fc, all but one bound with nanomolar affinity, and five were successfully humanized. Repertoire sequencing uncovered additional variants within the clonal lineages of the validated hits. The establishment of this workflow extends the powerful Beacon technology to enable rapid VHH discovery directly from natural camelid immune repertoires.

Late gestational nutrient restriction in primiparous beef females: nutrient partitioning among the dam, fetus, and colostrum during gestation.

Fall-calving primiparous crossbred beef females [body weight (BW): 451 ±â€…28 (SD) kg; body condition score (BCS): 5.4 ±â€…0.7] were allocated by fetal sex and expected calving date to receive either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to calving. Heifers were individually-fed chopped poor quality hay and supplemented to meet targeted nutritional planes based on estimated hay intakes. Dam BW, BCS, backfat, and metabolic status were determined pre-treatment, every 21 d (BW and metabolic status) or 42 d (BCS and backfat) during gestation, and post-calving. At birth, calf BW and size were measured, and total colostrum from the most full rear quarter was collected pre-suckling. Data were analyzed with nutritional plane, treatment initiation date, and calf sex (when P < 0.25) as fixed effects. Gestational metabolites included day and nutritional plane × day as repeated measures. During late gestation, CON dams gained (P < 0.01) maternal (non-gravid) BW and maintained (P ≥ 0.17) BCS and backfat, while NR dams lost (P < 0.01) maternal BW, BCS, and backfat. Circulating glucose, urea N, and triglycerides were less (P ≤ 0.05) in NR dams than CON at most late gestational timepoints after treatment initiation. Circulating non-esterified fatty acids were greater (P < 0.01) in NR dams than CON. Post-calving, NR dams weighed 63.6 kg less (P < 0.01) and were 2.0 BCS less (P < 0.01) than CON. At 1 h post-calving, NR dams had less (P = 0.01) plasma glucose and tended to have less (P = 0.08) plasma triglycerides than CON. Nutrient restriction did not affect (P ≥ 0.27) gestation length, calf birth weight, or calf size at birth. Colostrum yield was 40% less (P = 0.04) in NR dams than CON. Protein and immunoglobulin concentrations were greater (P ≤ 0.04), but free glucose and urea N concentrations were less (P ≤ 0.03), in colostrum of NR dams than CON. Colostrum total lactose, free glucose, and urea N were less (P ≤ 0.03) in NR dams than CON, but total protein, triglycerides, and immunoglobulins were not affected (P ≥ 0.55). In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth. During undernutrition, fetal and colostral nutrient demands were largely compensated for by catabolism of maternal tissue stores.

Nutrient requirements increase substantially during late gestation in the beef female. Even in well-managed herds, it is possible for females to be nutrient restricted during this time due to challenges of poor forage quality or availability and environmental stress. For heifers, the added nutrient requirements needed to continue growing pose an even greater challenge during their first pregnancy. However, little is known about how late gestational undernutrition impacts nutrient partitioning between maternal growth, the developing offspring, and colostrum production in beef heifers. Our data show that late gestational nutrient restriction in heifers slowed the expected maternal growth and instead maternal tissue stores were catabolized. Less nutrients were available in the maternal circulation, yet calf weight and size at birth were not affected. Late gestational nutrient restriction resulted in less colostrum produced by the dam and less lactose available to the offspring, but the total protein, fat, and immunoglobulins available in colostrum were not altered. In summary, beef heifers experiencing late gestational nutrient restriction prioritized partitioning nutrients to fetal growth and colostrum production over maternal growth and maintenance of body condition.

Evaluation of peripartum supplementation of methionine hydroxy analogue on beef cow-calf performance.

The objective was to evaluate the effects of peripartum supplementation of a methionine hydroxy analogue (MHA) to primiparous, spring-calving beef females on dam and progeny performance. Angus heifers (n = 60) were blocked by expected parturition date, stratified by body weight (BW) and body condition score (BCS), and randomized to 1 of 15 pens. Pens were randomly assigned to 1 of 3 dietary treatments: a basal diet supplemented with 0 (M0), 15 (M15), or 30 (M30) g/animal/d of MHA (provided as MFP feed supplement, Novus International Inc., St. Charles, MO). Diets were fed from 45 ±â€…13 (SD) d pre-calving through 81 ±â€…13 d postpartum (DPP), after which all cow-calf pairs were managed as a single group on pasture until weaning (199 ±â€…13 DPP). Dam BW, BCS, and blood samples were taken at 6 predetermined timepoints. Progeny data were collected at birth, 2 intermediate timepoints, and at weaning. Milk samples were collected for composition analysis at 7 ±â€…2 DPP and at 55 ±â€…5 DPP. Serial progesterone samples were analyzed to establish resumption of cyclicity, and ultrasonography was performed at 55 ±â€…5 DPP to evaluate ovarian function. Cows were bred via artificial insemination at 82 ±â€…13 DPP and subsequently exposed to bulls for a 55-d breeding season. Pen was the experimental unit, and preplanned orthogonal contrasts were tested (linear effect and M0 vs. M15 + M30). Dam BW and BCS were not affected by treatment (P ≥ 0.29) throughout the study. Week 1 milk fat concentration increased linearly (P = 0.05) and total solids tended to increase linearly (P = 0.07) as MHA increased; however, no other milk components were affected (P ≥ 0.16). Treatment did not affect (P ≥ 0.16) dam reproductive parameters or progeny growth from birth until weaning. Post-calving, circulating methionine equivalents tended to linearly increase (P = 0.10) with increasing MHA supplementation. At breeding, plasma urea N linearly decreased (P = 0.03) with increased supplementation of MHA, and plasma non-esterified fatty acids were less (P = 0.04) in MHA-supplemented dams compared with dams receiving no MHA. Maternal circulating glucose, glutathione peroxidase, and thiobarbituric acid-reactive substances were not affected (P ≥ 0.15) by treatment at any point. These data indicate that peripartum supplementation of MHA may increase milk fat composition shortly after calving, but MHA supplementation did not improve progeny growth or dam reproductive performance in the current study.

Implementing a velocity-based approach to resistance training: the reproducibility and sensitivity of different velocity monitoring technologies.

This study examined the reproducibility of GymAware, PUSH2 and Vmaxpro velocity monitoring devices during resistance training (RT). The sensitivity of these devices to detect the smallest changes in velocity that correspond to true changes in RT performance was also investigated. Fifty-one resistance-trained men and women performed an incremental loading (1RM) test, and two repetitions to failure tests with different loads, 72 h apart. During all repetitions, mean velocity (MV) and peak velocity (PV) were simultaneously recorded by two devices of each brand. Overall, GymAware was the most reliable and sensitive device for detecting the smallest changes in RT performance, regardless of the velocity metric used. Vmaxpro can be considered as an equivalent, cheaper alternative to GymAware for RT monitoring and prescription, but only if the MV metric is used. Caution should be exercised when using PUSH2 in practice due to their comparatively higher, unacceptable measurement error and generally low sensitivity to detect changes in RT performance. Collectively, these findings support the use of MV and PV from GymAware and MV from Vmaxpro devices for RT monitoring and prescription due to their low magnitudes of error; thus, allowing for the detection of meaningful changes in neuromuscular status and functional performance during RT.

Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.

BACKGROUND: Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI). METHODS: The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEV1 (ppFEV1) of 70% or more, or those aged 18 years or older with ppFEV1 of 60% or more, if they had been taking ETI and either (or both) mucoactive therapies (≥3% hypertonic saline or dornase alfa) for at least 90 days before screening. Participants on both hypertonic saline and dornase alfa were randomly assigned to one of the two trials, and those on a single therapy were assigned to the applicable trial. All participants were then randomly assigned 1:1 to continue or discontinue therapy for 6 weeks using permuted blocks of varying size, stratified by baseline ppFEV1 (week 0; ≥90% or <90%), single or concurrent use of hypertonic saline and dornase alfa, previous SIMPLIFY study participation (yes or no), and age (≥18 or <18 years). For participants randomly assigned to continue their therapy during a given trial, this therapy was instructed to be taken at least once daily according to each participant's pre-existing, clinically prescribed regimen. Hypertonic saline concentration was required to be at least 3%. The primary objective for each trial was to determine whether discontinuing was non-inferior to continuing, measured by the 6-week change in ppFEV1 in the per-protocol population. We established a non-inferiority margin of -3% for the difference between groups in the 6-week change in ppFEV1. Safety outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04378153. FINDINGS: From Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEV1 of 96·9%. Discontinuing treatment was non-inferior to continuing treatment with respect to the absolute 6-week change in ppFEV1 in both the hypertonic saline trial (-0·19% [95% CI -0·85 to 0·48] in the discontinuation group [n=133] vs 0·14% [-0·51 to 0·78] in the continuation group [n=140]; between-group difference -0·32% [-1·25 to 0·60]) and dornase alfa trial (0·18% [-0·38 to 0·74] in the discontinuation group [n=199] vs -0·16% [-0·73 to 0·41] in the continuation group [n=193]; between-group difference 0·35% [-0·45 to 1·14]), with consistent results in the intention-to-treat populations. In the hypertonic saline trial, 64 (35%) of 184 in the discontinuation group versus 44 (24%) of 186 participants in the continuation group and, in the dornase alfa trial, 89 (37%) of 240 in the discontinuation group versus 55 (23%) of 237 in the continuation group had at least one adverse event. INTERPRETATION: In individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

Range of Motion Predicts Performance in National-Level New Zealand Male Powerlifters.

ABSTRACT: Spence, AJ, Helms, ER, Sousa, CA, and McGuigan, MR. Range of motion predicts performance in National-level New Zealand male powerlifters. J Strength Cond Res 37(1): 123-128, 2023-Previous research established that male powerlifters have less range of motion (ROM) in several movements about the shoulder and hip compared with sedentary male subjects. It is unclear if these differences in ROM are related to strength, training type, and years of training experience or if individuals with less ROM have a better propensity to gain strength. The purpose of this study was to compare strength and ROM in male powerlifters and recreationally strength-trained male subjects and to determine if ROM would be an effective predictor of strength in these groups. Twelve powerlifters and 12 recreationally strength-trained control subjects completed 1 repetition maximum (1RM) squat and bench press testing. In a subsequent session, active ROM was measured, and velocity data were collected during submaximal squat repetitions. There was no significant difference (p > 0.05) between the groups for age, height, body mass, training experience, and training frequency. Powerlifters had significantly greater (p ≤ 0.05) training duration and absolute squat and bench press 1RM. Powerlifters had significantly less shoulder extension and horizontal abduction, and hip flexion, extension, and adduction than recreationally strength-trained men. Significant negative relationships were found between 2-lift Wilks score (body mass relative strength) and shoulder extension and horizontal abduction, as well as hip flexion and extension. In powerlifters, significant negative relationships were found between competition Wilks score, shoulder extension, and hip flexion. Because these relationships correspond to the bottom position of the squat and bench press, it may be best to ensure that shoulder extension and hip flexion remain sufficient to achieve competition depth.

Effects of spring- versus fall-calving on perinatal nutrient availability and neonatal vigor in beef cattle.

To determine the effect of calving season on perinatal nutrient availability and neonatal beef calf vigor, data were collected from 4 spring- (average calving date: February 14; n = 203 total) and 4 fall- (average calving date: September 20; n = 179 total) calving experiments. Time to stand was determined as minutes from birth to standing for 5 s. After birth, calf weight and size (length, heart and abdominal girth, and cannon circumference) were recorded. Jugular blood samples and rectal temperatures were obtained at 0, 6, 12, and 24 h postnatally in 6 experiments and at 48 h postnatally in Exp. 2 to 8. Data were analyzed with fixed effects of season (single point) or season, hour, and their interaction (over time, using repeated measures). Experiment was a random effect; calf sex was included when P ≤ 0.25. Within calving season, correlations were determined between calf size, vigor, and 48-h serum total protein. Fall-born calves tended to have lighter (P = 0.09) birth weight and faster (P = 0.05) time to stand than spring-born calves. Season did not affect (P ≥ 0.18) gestation length, other calf size measures, or 48-h serum total protein. Fall-born calves had greater (P ≤ 0.003) rectal temperature at 0, 24, and 48 h postnatal. Spring-born calves had greater (P ≤ 0.009) circulating glucose at 0 h, serum non-esterified fatty acids at 0 and 6 h, and plasma triglycerides at 0, 6, 12, and 48 h. Fall-born calves had greater (P ≤ 0.03) sodium from 6 to 48 h and magnesium from 0 to 24 h of age. Phosphorus was greater (P ≤ 0.02) at 6 and 12 h of age in spring-born calves. Spring-born calves had greater (P ≤ 0.04) aspartate aminotransferase at 12 and 24 h and creatine kinase at 0 and 12 h of age. Fall-born calves had greater (P ≤ 0.03) albumin, calcium, and chloride, had lower (P ≤ 0.03) bicarbonate and direct bilirubin, and tended to have greater (P = 0.10) anion gap (all main effects of calving season). Calf birth weight had a weak positive relationship (P ≤ 0.03) with 48-h serum total protein and time to stand in fall-born, but not spring-born, calves. Overall, fetal growth was restricted and neonatal dehydration was increased by warm conditions for fall-born calves, but vigor and metabolism were negatively affected by cold conditions in spring-born calves. These data suggest that calving season influences perinatal nutrient availability, which may impact the transition of beef calves to postnatal life.

Psychosocial determinants of adherence to public health and social measures (PHSMs) in 18 African Union Member States during the early phase of the COVID-19 pandemic: results of a cross-sectional survey.

OBJECTIVE: The objective of this study was to gain a better understanding of the psychosocial and sociodemographic factors that affected adherence to COVID-19 public health and social measures (PHSMs), and to identify the factors that most strongly related to whether citizens followed public health guidance. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: Nationally representative telephone surveys were conducted from 4-17 August 2020 in 18 African Union Member States. A total of 21 600 adults (mean age=32.7 years, SD=11.4) were interviewed (1200 in each country). OUTCOME MEASURES: Information including sociodemographics, adherence to PHSMs and psychosocial variables was collected. Logistic regression models examined the association between PHSM adherence (eg, physical distancing, gathering restrictions) and sociodemographic and psychosocial characteristics (eg, risk perception, trust). Factors affecting adherence were ranked using the Shapley regression decomposition method. RESULTS: Adherence to PHSMs was high, with better adherence to personal than community PHSMs (65.5% vs 30.2%, p<0.05). Psychosocial measures were significantly associated with personal and community PHSMs (p<0.05). Women and older adults demonstrated better adherence to personal PHSMs (adjusted OR (aOR): women=1.43, age=1.01, p<0.05) and community PHSMs (aOR: women=1.57, age=1.01, p<0.05). Secondary education was associated with better adherence only to personal PHSMs (aOR=1.22, p<0.05). Rural residence and access to running water were associated with better adherence to community PHSMs (aOR=1.12 and 1.18, respectively, p<0.05). The factors that most affected adherence to personal PHSMs were: self-efficacy; trust in hospitals/health centres; knowledge about face masks; trust in the president; and gender. For community PHSMs they were: gender; trust in the president; access to running water; trust in hospitals/health centres; and risk perception. CONCLUSIONS: Psychosocial factors, particularly trust in authorities and institutions, played a critical role in PHSM adherence. Adherence to community PHSMs was lower than personal PHSMs since they can impose significant burdens, particularly on the socially vulnerable.

Agreement Between Kinovea Video Analysis and The Open Barbell System for Resistance Training Movement Outcomes.

The purpose of this study was to examine the agreement between Kinovea video analysis software and the previously validated Open Barbell System (OBS) for assessing average concentric and eccentric velocity, eccentric duration, peak concentric velocity, height of peak concentric velocity, and concentric and eccentric range of motion. Sixteen resistance-trained males performed 11 repetitions at various intensities (between 60-100% of one-repetition maximum) on both the back squat and the bench press. For each repetition, all outcome measures were assessed with Kinovea and the OBS. Agreement between devices for each outcome measure was analyzed with paired t-tests, intraclass correlation coefficients with 95% confidence intervals, Bland-Altman plots, and folded empirical cumulative distribution plots (Mountain plots). All outcome variables were found to be statistically different (i.e. they did not agree) between the two devices (p < 0.001), except for average eccentric velocity (p = 0.315), as determined by the paired t-tests. Mountain plots had long tails for every outcome measure and Bland-Altman plots showed large limits of agreement for all outcome measures except concentric range of motion and the height of peak concentric velocity, demonstrating low agreement between devices. Based upon these findings and the previous validation of the OBS, these devices should not be used interchangeably.