Plastics in Pharmacy and Medicine

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Glucocorticoid-induced polycystic kidney disease—A threshold trait

Glucocorticoid-induced polycystic kidney disease—A threshold trait. Administration of hydrocortisone acetate (250 mg/kg) to newborn mice caused polycystic kidney disease (PKD) of varying proportions in each of 18 different inbred strains; none of the injected controls were affected. All kidneys were histologically examined and scored for degree of cyst formation using a semi-continuous (0 to 4+) grading scheme. Results suggested that this condition is a multifactorial threshold trait. For each strain, estimates of the mean and standard deviation of normally distributed liability were determined by maximum likelihood methods. Concomitant analyses showed: 1) a significant environmental effect related to drug source; 2) a variation in thresholds ranging from 0.94 (N = 46) for the B10.M strain to -0.71 (N = 297) for the C57B1/6J strain; and 3) three groups of strains with different susceptibility to PKD. These results are consistent with a multifactorial basis for susceptibility to PKD. Quantitative analysis of thresholds and liability distributions reveals that genetic, environmental and random elements all contribute to the expression and extent of the cystic trait

An economic comparison of pasture-based production systems differing in sward type and cow genotype

peer-reviewedThe objective of this study was to compare the economic performance of 2 sward types [perennial ryegrass (PRG; Lolium perenne L.) sown with or without white clover (Trifolium repens L.)] grazed by 3 cow genotypes. Physical performance data were collected from a 4-yr systems experiment based at Clonakilty Agricultural College, Clonakilty, Co. Cork, Ireland. The experiment compared 2 sward types (PRG-only swards and PRG–white clover swards), with each sward type being grazed by cows from 3 genotypes [Holstein-Friesian (HF), Jersey × HF (JEX), and Norwegian Red × JEX (3-way)]. All systems were stocked at 2.75 cows/ha with fixed fertilizer applications and concentrate supplementation. The data supplied 6 production systems (2 sward types × 3 cow genotypes). The production systems were modeled using the Moorepark Dairy Systems Model (stochastic budgetary simulation model) under 2 scenarios, one in which land area was fixed and one in which cow numbers were fixed. The analysis was completed across a range of milk prices, calf prices, and reseeding programs. The analysis showed that in the fixed-land scenario with a milk price of €0.29/L, adding white clover to PRG swards increased profitability by €305/ha. In the same fixed-land scenario, JEX cows were most profitable (€2,606/ha), followed by 3-way (€2,492/ha) and HF (€2,468/ha) cows. In the fixed-cow scenario, net profit per cow was €128 greater for PRG–white clover swards compared with PRG-only swards. In this scenario, JEX was the most profitable per cow (€877), followed by HF (€855) and 3-way (€831). The system that produced the highest net profit was JEX cows grazing PRG–white clover swards (€2,751/ha). Regardless of reseeding frequency or variations in calf value, JEX cows grazing PRG–white clover swards consistently produced the highest net profit per hectare

Milk production per cow and per hectare of spring-calving dairy cows grazing swards differing in Lolium perenne L. ploidy and Trifolium repens L. composition

peer-reviewedGrazed grass is the cheapest feed available for dairy cows in temperate regions; thus, to maximize profits, dairy farmers must optimize the use of this high-quality feed. Previous research has defined the benefits of including white clover (Trifolium repens L.) in grass swards for milk production, usually at reduced nitrogen usage and stocking rate. The aim of this study was to quantify the responses in milk production of dairy cows grazing tetraploid or diploid perennial ryegrass (Lolium perenne L.; PRG) sown with and without white clover but without reducing stocking rate or nitrogen usage. We compared 4 grazing treatments in this study: tetraploid PRG-only swards, diploid PRG-only swards, tetraploid with white clover swards, and diploid with white clover swards. Thirty cows were assigned to each treatment, and swards were rotationally grazed at a farm-level stocking rate of 2.75 cows/ha and a nitrogen fertilizer rate of 250 kg/ha annually. Sward white clover content was 23.6 and 22.6% for tetraploid with white clover swards and diploid with white clover swards, respectively. Milk production did not differ between the 2 ploidies during this 4-yr study, but cows grazing the PRG-white clover treatments had significantly greater milk yields (+596 kg/cow per year) and milk solid yields (+48 kg/cow per year) compared with cows grazing the PRG-only treatments. The PRG-white clover swards also produced 1,205 kg of DM/ha per year more herbage, which was available for conserving and buffer feeding in spring when these swards were less productive than PRG-only swards. Although white clover is generally combined with reduced nitrogen fertilizer use, this study provides evidence that including white clover in either tetraploid or diploid PRG swards, combined with high levels of nitrogen fertilizer, can effectively increase milk production per cow and per hectar

An assessment of the production, reproduction, and functional traits of Holstein-Friesian, Jersey × Holstein-Friesian, and Norwegian Red × (Jersey × Holstein-Friesian) cows in pasture-based systems

Peer-ReviewedPasture-based production systems typically require highly fertile, healthy, and robust genetics, with greater emphasis on milk solids (MSo; kg of fat + protein) production as opposed to milk yield. This study assessed milk production, production efficiency, reproductive performance, body weight (BW), body condition score, and functional traits in 3 different dairy cow genotypes: Holstein-Friesian (HF), Jersey × Holstein-Friesian (JEX), and Norwegian Red × (Jersey × Holstein- Friesian) (3-way). The 3 genotypes were rotationally grazed on 4 different grazing treatments after calving in spring and were stocked at a rate of 2.75 cows/ha. Holstein-Friesian cows produced higher daily and total milk yields compared with JEX and 3-way cows (5,718 vs. 5,476 and 5,365 kg/cow, respectively). However, JEX and 3-way cows had higher milk fat and protein contents (4.86 and 4.75%, respectively, for JEX and 3.87 and 3.88%, respectively, for 3-way) compared with HF (4.52 and 3.72%), resulting in similar MSo yield for JEX and HF (469 and 460 kg/cow) and slightly lower MSo yield for 3-way (453 kg/cow) compared with JEX. As parity increased, milk and MSo yield per cow increased. Reproductive performance was not significantly different between the 3 genotypes, which had similar 24-d submission rates, 6-wk pregnancy rates, and overall pregnancy rates over the 4-yr period. No difference in calving difficulty, incidence of mastitis, or incidence of lameness was observed among the 3 genotypes. Body weight was significantly different among all 3 genotypes, with HF being the heaviest followed by 3-way and JEX (530, 499, and 478 kg, respectively), and 3-way cows had a higher body condition score throughout lactation compared with HF and JEX cows. The differences in BW coupled with similar MSo production resulted in JEX cows having the highest production efficiency (4.58 kg of MSo/kg of metabolic BW), 3-way cows being intermediate (4.30 kg of MSo/kg of metabolic BW), and HF cows having the lowest (4.16 kg of MSo/kg of metabolic BW). In conclusion, HF herds with poor reproductive performance and low milk fat and protein contents are likely to benefit considerably from crossbreeding with Jersey, and all herds are likely to benefit in terms of production efficiency. However, where herd performance, particularly in relation to reproductive performance, is comparable with HF in the current study, crossbreeding with Jersey or Norwegian Red is unlikely to lead to significant improvements in overall herd performance

The effect of Lolium perenne L. ploidy and Trifolium repens L. inclusion on dry matter intake and production efficiencies of spring-calving grazing dairy cows

peer-reviewedThe objective of this study was to investigate the effect of perennial ryegrass (Lolium perenne L.; PRG) ploidy and white clover (Trifolium repens L.) inclusion on milk production, dry matter intake (DMI), and milk production efficiencies. Four separate grazing treatments were evaluated: tetraploid PRG only, diploid PRG only, tetraploid PRG with white clover, and diploid PRG with white clover. Individual DMI was estimated 8 times during the study (3 times in 2015, 2 times in 2016, and 3 times in 2017) using the n-alkane technique. Cows were, on average, 64, 110, and 189 d in milk during the DMI measurement period, corresponding to spring, summer, and autumn, respectively. Measures of milk production efficiency were total DMI/100 kg of body weight (BW), milk solids (kg of fat + protein; MSo)/100 kg of BW, solids-corrected milk/100 kg of BW, and MSo/kg of total DMI. Perennial ryegrass ploidy had no effect on DMI; however, a significant increase in DMI (+0.5 kg/cow per day) was observed from cows grazing PRG-white clover swards compared with PRG-only swards. Sward white clover content influenced DMI as there was no increase in DMI in spring (9% sward white cover content), whereas DMI was greater in summer and autumn for cows grazing PRG-white clover swards (+0.8 kg/cow per day) compared with PRG-only swards (14 and 23% sward white clover content, respectively). The greater DMI of cows grazing PRG-white clover swards led to increased milk (+1.3 kg/cow per day) and MSo (+0.10 kg/cow per day) yields. Cows grazing PRG-white clover swards were also more efficient for total DMI/100 kg of BW, solids-corrected milk/100 kg of BW, and MSo/100 kg of BW compared with cows grazing PRG-only swards due to their similar BW but higher milk and MSo yields. The results highlight the potential of PRG-white clover swards to increase DMI at grazing and to improve milk production efficiency in pasture-based systems

Sustained efficacy and detailed clinical follow-up of first-line ibrutinib treatment in older patients with chronic lymphocytic leukemia: extended phase 3 results from RESONATE-2.

Results of RESONATE-2 (PCYC-1115/1116) supported approval of ibrutinib for first-line treatment of chronic lymphocytic leukemia. Extended analysis of RESONATE-2 was conducted to determine long-term efficacy and safety of ibrutinib in older patients with chronic lymphocytic leukemia. A total of 269 patients aged ≥65 years with previously untreated chronic lymphocytic leukemia without del(17p) were randomized 1:1 to ibrutinib (n=136) or chlorambucil (n=133) on days 1 and 15 of a 28-day cycle for 12 cycles. Median ibrutinib treatment duration was 28.5 months. Ibrutinib significantly prolonged progression-free survival versus chlorambucil (median, not reached vs 15 months; hazard ratio, 0.12; 95% confidence interval, 0.07-0.20; P<0.0001). The 24-month progression-free survival was 89% with ibrutinib (97% and 89% in patients with del[11q] and unmutated immunoglobulin heavy chain variable region gene, respectively). Progression-free survival rates at 24 months were also similar regardless of age (<75 years [88%], ≥75 years [89%]). Overall response rate was 92% (125/136). Rate of complete response increased substantially from 7% at 12 months to 18% with extended follow up. Greater quality of life improvements occurred with ibrutinib versus chlorambucil in Functional Assessment of Chronic Illness Therapy-Fatigue (P=0.0013). The most frequent grade ≥3 adverse events were neutropenia (12%), anemia (7%), and hypertension (5%). Rate of discontinuations due to adverse events was 12%. Results demonstrated that first-line ibrutinib for elderly patients with chronic lymphocytic leukemia provides sustained response and progression-free survival benefits over chemotherapy, with depth of response improving over time without new toxicity concerns. This trial was registered at clinicaltrials.gov identifier 01722487 and 01724346

Nosocomial COVID-19 infection : examining the risk of mortality. The COPE-Nosocomial Study (COVID in Older PEople)

In the United Kingdom, authority to conduct the study was granted by the Health Research Authority (20/HRA/1898), and in Italy by the Ethics Committee of Policlinico Hospital Modena (Reference 369/2020/OSS/AOUMO). Cardiff University was the study sponsor.Peer reviewedPostprin

Study protocol; Thyroid hormone Replacement for Untreated older adults with Subclinical hypothyroidism - a randomised placebo controlled Trial (TRUST).

Subclinical hypothyroidism (SCH) is a common condition in elderly people, defined as elevated serum thyroid-stimulating hormone (TSH) with normal circulating free thyroxine (fT4). Evidence is lacking about the effect of thyroid hormone treatment. We describe the protocol of a large randomised controlled trial (RCT) of Levothyroxine treatment for SCH. Participants are community-dwelling subjects aged ≥65 years with SCH, diagnosed by elevated TSH levels (≥4.6 and ≤19.9 mU/L) on a minimum of two measures ≥ three months apart, with fT4 levels within laboratory reference range. The study is a randomised double-blind placebo-controlled parallel group trial, starting with levothyroxine 50 micrograms daily (25 micrograms in subjects &lt;50Kg body weight or known coronary heart disease) with titration of dose in the active treatment group according to TSH level, and a mock titration in the placebo group. The primary outcomes are changes in two domains (hypothyroid symptoms and fatigue / vitality) on the thyroid-related quality of life questionnaire (ThyPRO) at one year. The study has 80% power (at p = 0.025, 2-tailed) to detect a change with levothyroxine treatment of 3.0% on the hypothyroid scale and 4.1% on the fatigue / vitality scale with a total target sample size of 750 patients. Secondary outcomes include general health-related quality of life (EuroQol), fatal and non-fatal cardiovascular events, handgrip strength, executive cognitive function (Letter Digit Coding Test), basic and instrumental activities of daily living, haemoglobin, blood pressure, weight, body mass index and waist circumference. Patients are monitored for specific adverse events of interest including incident atrial fibrillation, heart failure and bone fracture. This large multicentre RCT of levothyroxine treatment of subclinical hypothyroidism is powered to detect clinically relevant change in symptoms / quality of life and is likely to be highly influential in guiding treatment of this common condition. Clinicaltrials.gov NCT01660126 ; registered 8th June 2012