The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes.
Following a comparison of nutrient total-tract ...digestibility estimates in lactating buffaloes using single-point undigestible NDF (uNDF) or acid-insoluble ash (AIA) as internal markers, the potential of fecal near-infrared spectroscopy (NIRS) to provide calibration equations for the assessment of the chemical composition of feces and nutrient total-tract digestibility estimated with internal markers was explored. Chemical analyses were performed on 147 fecal samples from lactating buffaloes reared on 5 farms in central Italy (Naples). Each farm fed a silage-based TMR to the buffaloes, and the TMR was sampled in the 2 d before the fecal collection. The TMR and individual fecal samples were collected and analyzed for DM, OM, ash, AIA, ether extract (EE), starch, fiber fractions (amylase-treated NDF without residual ash aNDFom, amylase-treated NDF inclusive of residual ash aNDF, ADF without residual ash ADFom, ADF, hemicellulose, cellulose, ADL, uNDF), N, CP and CP bound to aNDF (NDICP) and to ADF (ADICP). The uNDF content was determined through a 240-h in vitro fermentation and employed, together with AIA as markers, to estimate the total-tract apparent digestibility and total-tract digestibility of DM, OM, ash, N, CP, EE, aNDFom, aNDF, NDIP, ADFom, and ADF, ADIN, ADL, hemicellulose, cellulose, starch, NFC, and the B3 fraction of N (NB3). No correlation was found between DM and OM digestibility estimated with AIA and uNDF as internal markers. Weak correlations were detected for all the other nutients digestibilities, and strong correlations were observed for EE, ADFom, hemicellulose, NDIN, ADIN, NB3, NFC, and starch. The sample set (n = 147) was divided in a calibration set (n = 111) and a validation set (n = 36) to “train” and “validate” the fecal NIRS curve through an external validation process. An estimation usable for preliminary or initial evaluation was obtained for N, CP, and aNDF fecal content. An excellent prediction was obtained for total tract digestibility of ADIN (R2 = 0.90) when estimated with uNDF as the internal marker. The NIRS technology was not able to accurately predict all the other traits and the estimated nutrient digestibility of lactating buffalo diets from fecal spectra.
The aim of this study was to investigate the possible impact of smoking on the humoral response to the BNT162b2 mRNA COVID-19 vaccine (also known as the BioNTech-Pfizer COVID-19 vaccine).
A ...longitudinal sero-epidemiological study was conducted in sample of Italian healthcare workers (HCWs).
HCWs who were administered two doses of the BNT162b2 mRNA vaccine, 21 days apart, between December 2020 and January 2021, were invited to undergo multiple serology tests to identify SARS-CoV-2 S-RBD-specific immunoglobulin G (IgG) antibodies. Participants also responded to questions about their smoking status (i.e. current smokers vs non-smokers) in a survey.
Sixty days after the completion of the vaccination cycle, serological analyses showed a difference in vaccine-induced IgG titre between current smokers and non-smokers, with median antibody titres of 211.80 AU/mL (interquartile range IQR 149.80–465.50) and 487.50 AU/mL (IQR 308.45–791.65) P-value = 0.002, respectively. This significant difference in vaccine-induced IgG titres between current smokers and non-smokers remained after adjusting for age, sex, and previous infection with SARS-CoV-2.
This study observed that vaccine-induced antibody titres decrease faster among current smokers than non-smokers. Further research to investigate the impact of smoking on the immunological response to COVID-19 and non-COVID-19 vaccines is required.
Background
There is limited information on the influence of body mass index (BMI) on clinical outcomes in patients with venous thromboembolism (VTE).
Objectives
Investigate the influence of BMI on ...baseline characteristics, treatment patterns, and 24‐month outcomes in VTE patients.
Methods
GARFIELD‐VTE is a prospective, non‐interventional study of 10 869 patients with objectively confirmed VTE. Patients were grouped according to BMI: <18.5 (underweight; n = 214); 18.5–24.9 (normal; n = 2866); 25.0–29.9 (overweight; n = 3326); ≥30 (obese; n = 3073).
Results
Compared with patients with a normal BMI, obese patients were more frequently Caucasian (77.4% vs. 57.9%), treated in the outpatient setting (30.4% vs. 23.1%), and had previous VTE (17.5% vs. 11.7%). Active cancer was associated with lower BMI (underweight: 30.4%, normal: 13.5%, overweight: 9.4%, obese: 7.0%). At baseline, overweight and obese patients less often received parenteral therapy alone (16.7% and 14.4%) compared with those with an underweight or normal BMI (30.8% and 21.6%). Obese patients more commonly remained on anticoagulants for ≥2‐years compared to those with a normal BMI (52.3% vs. 37.7%). After 24‐months, the risk of all‐cause mortality was lower in overweight and obese patients than in those with normal BMI (adjusted hazard ratio 95% CI; 0.75 0.63–0.89 and 0.59 0.49–0.72, respectively). Underweight patients more often experienced major bleeding (2.45 1.41–4.26) and all‐cause mortality (1.90 1.43–2.53) than patients with a normal BMI. Recurrent VTE was comparable among groups.
Conclusion
Underweight VTE patients have the highest risk of mortality and major bleeding. The risk of mortality in obese VTE patients is lower than that in VTE patients with a normal BMI.
Poly (glycerol adipate) (PGA) can be produced from divinyl adipate and unprotected glycerol by an enzymatic route to generate a polymer with relatively low molar mass (12 kDa). PGA bears a pendant ...hydroxyl group which imparts a hydrophilic character to this water insoluble polymer. We have examined the effect of synthesis temperature on polymer characteristics through various techniques including FT-IR, 1H and 13C NMR, surface and thermal analysis, both to expand the data already present in the literature about this material and to understand better its properties for potential pharmaceutical applications. The use of a lipase (Novozym 435) as a catalyst suppresses cross-linking at the pendant glyceryl hydroxyl through steric hindrance at the active site, thus producing polymers with low degrees of branching (5–30%), and removes the need for any pre- or post-polymerization protection/deprotection reactions. Careful temperature control during synthesis can give polymers with reproducible molecular weights and reduced amounts of polymer branching compared to synthesis at higher temperatures. Due to the ability of the synthetic route to produce a range of structures, PGA generated by enzymatic routes may emerge as a useful biodegradable polymer platform to engineer solid dispersions or nanoparticles for healthcare applications.
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•Review and optimization of enzymic synthesis of high Mw poly(glycerol adipate).•Improved physicochemical characterization of poly(glycerol adipate).•Variation in branching with synthesis temperature (minimum branching 5% at 40 °C).•Change in physicochemical properties (Tg, contact angle) with degree of branching.
Background Atrial fibrillation (AF) is associated with high rates of morbidity and mortality. Patients with AF carry a fivefold increased risk of stroke and the risk of death from AF-related stroke ...is doubled. Current management is often inadequate, leaving patients at risk for a potentially fatal or disabling event. The purpose of the GARFIELD registry is to evaluate the management and outcomes of patients with newly diagnosed non-valvular AF at risk for stroke. Design The GARFIELD registry is an observational, multicenter, prospective study of patients with newly diagnosed AF and one or more additional risk factors for stroke. The aim is to enroll 55,000 patients at >1,000 centers in 50 countries. Enrollment will take place in five independent, sequential, prospective cohorts. An additional retrospective validation cohort of 5,000 patients with established AF and at least one additional risk factor for stroke will be conducted in parallel with cohort one. The study started in December 2009, with a planned recruitment period of 4 years and a minimum of 2-year follow-up for each patient. Summary The GARFIELD registry will provide valuable insights into the clinical management and related outcomes of AF patients throughout many regions of the world and across the spectrum of healthcare systems. By capturing data from unselected patients treated in everyday practice, the registry has the potential to identify best practices as well as deficiencies in available treatment options for specific patient populations and to describe how therapeutic strategies, patient care, and outcomes will evolve over time.
ABSTRACT Objective To estimate a value set for the calculation of Italian-specific quality-adjusted life years (QALYs), based on preferences elicited on EuroQol five-dimensional (EQ-5D) questionnaire ...health states using the time trade-off technique. Methods The revised standard Measurement and Valuation of Health protocol was followed. Twenty-five health states, divided into three groups and given to 450 subjects, were selected to obtain 300 observations per state. Subjects aged 18 to 75 years were recruited to be representative of the Italian general adult population for age, sex, and geographical distribution. To improve efficiency, face-to-face interviews were conducted by using the Computer Assisted Personal Interviewing approach. Several random effects regression models were tested to predict the full set of EQ-5D questionnaire health states. Model selection was based on logical consistency of the estimates, sign and magnitude of the regression coefficients, goodness of fit, and parsimony. Results The model that satisfied the criteria of logical consistency and was more efficient includes 10 main effect dummy variables for the EQ-5D questionnaire domain levels and the D1 interaction term, which accounts for the number of dimensions at levels 2 or 3 beyond the first. This model has an R2 of 0.389 and a mean absolute error of 0.03, which are comparable to or better than those of models used in other countries. The utility estimates after state 11111 range from 0.92 (21111) to −0.38 (33333). Italian utility estimates are higher than those estimated in the United Kingdom and Spain and used so far to assess QALYs and conduct cost-utility evaluations in Italy. Conclusions A specific value set is now available to calculate QALYs for the conduction of health economic studies targeted at the Italian health care system.
Patients with cardiovascular autonomic failure (AF) may suffer from neurogenic supine hypertension (nSH), defined as systolic blood pressure (SBP) ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, ...after 5 min of rest in the supine position, combined with neurogenic orthostatic hypotension (nOH) in approximately 50% of the cases.
nSH may be the manifestation of central or peripheral autonomic lesions.
Long-term risks are hypothesized with SH, including renal dysfunction, left ventricular hypertrophy, cerebrovascular disease and cognitive impairment. Yet, large longitudinal studies investigating long-term outcomes of nSH are lacking.
In clinical practice, nSH should be investigated in patients with nOH. Office screening should be performed measuring supine BP immediately after lying down and 5 min later, combined with BP measurement on active or passive standing. Home BP recordings performed by patients themselves may also be useful, while 24 h-Ambulatory Blood Pressure Monitoring (ABPM) may allow for detection of nocturnal hypertension and confirm the diagnosis.
Current expert recommendations suggest treatment interventions if SBP exceeds 160–180 mmHg. Non-pharmacological strategies represent the first-line treatment approach and include head-up sleeping, avoiding supine position during the daytime, and having a snack before bedtime to lower supine BP using post-prandial hypotension. Pharmacological treatments may be considered if severe nSH persists. Short-acting antihypertensive medications administered at bedtime are preferably used in order to selectively lower supine BP and reduce pressure diuresis without worsening daytime hypotension.
Highlights • DRD2 agonist inhibits NFPT cell migration and invasion. • DRD2 agonist increases cofilin phosphorylation (inactivation) in NFPT cells. • The invasiveness of pituitary tumors is promoted ...by the activation of cofilin. • Cofilin phosphorylation might be a novel biomarker for pituitary tumors invasiveness.
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Pulmonary delivery is increasingly seen as an attractive, non-invasive route for the delivery of forthcoming protein therapeutics. In this context, here we describe protein complexes ...with a new ‘complexing excipient’ - vitamin B12-targeted poly(ethylene glycol)-block-poly(glutamic acid) copolymers. These form complexes in sub-200nm size with a model protein, suitable for cellular targeting and intracellular delivery. Initially we confirmed expression of vitamin B12-internalization receptor (CD320) by Calu-3 cells of the in vitro lung epithelial model used, and demonstrated enhanced B12 receptor-mediated cellular internalization of B12-targeted complexes, relative to non-targeted counterparts or protein alone. To develop an inhalation formulation, the protein complexes were spray dried adopting a standard protocol into powders with aerodynamic diameter within the suitable range for lower airway deposition. The cellular internalization of targeted complexes from dry powders applied directly to Calu-3 model was found to be 2–3 fold higher compared to non-targeted complexes. The copolymer complexes show no complement activation, and in vivo lung tolerance studies demonstrated that repeated administration of formulated dry powders over a 3 week period in healthy BALB/c mice induced no significant toxicity or indications of lung inflammation, as assessed by cell population count and quantification of IL-1β, IL-6, and TNF-α pro-inflammatory markers. Importantly, the in vivo data appear to suggest that B12-targeted polymer complexes administered as dry powder enhance lung retention of their protein payload, relative to protein alone and non-targeted counterparts. Taken together, our data illustrate the potential developability of novel B12-targeted poly(ethylene glycol)-poly(glutamic acid) copolymers as excipients suitable to be formulated into a dry powder product for the inhalation delivery of proteins, with no significant lung toxicity, and with enhanced protein retention at their in vivo target tissue.
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