Evaluation of Hospital Antimicrobial Stewardship Programs: Implementation, Process, Impact, and Outcomes, Review of Systematic Reviews.

Antimicrobial Stewardship Programs (ASP) were introduced in healthcare as a public health priority to promote appropriate prescribing of antimicrobials, to reduce adverse events related to antimicrobials, as well as to control the escalating challenges of antimicrobial resistance. To deliver aimed outcome objectives, ASPs involve multiple connected implementation process measures. A systematic review was conducted to evaluate both concepts of ASPs. Guided by PRISMA frames, published systematic reviews (SR) focusing on ASPs restricted to secondary and tertiary healthcare were evaluated over the past 10 years involving all age groups. Out of 265 identified SR studies, 63 met the inclusion criteria. The majority were conducted in Europe and North America, with limited studies from other regions. In the reviewed studies, all age groups were examined, although they were conducted mainly on adults when compared to children and infants. Both process and outcomes measures of ASPs were examined equally and simultaneously through 25 different concepts, dominated by efficacy, antimicrobial resistance, and economic impact, while information technology as well as role of pharmacy and behavioral factors were equally examined. The main broad conclusions from the review were that, across the globe, ASPs demonstrated effectiveness, proved efficacy, and confirmed efficiency, while focused evaluation advocated that developed countries should target medium- and small-sized hospitals while developing countries should continue rolling ASPs across healthcare facilities. Additionally, the future of ASPs should focus on embracing evolving information technology to bridge the gaps in knowledge, skills, and attitude, as well as to enhance appropriate decision making.

Single-cell transcriptomics of the immune system in ME/CFS at baseline and following symptom provocation.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious and poorly understood disease. To understand immune dysregulation in ME/CFS, we use single-cell RNA sequencing (scRNA-seq) to examine immune cells in patient and control cohorts. Postexertional malaise (PEM), an exacerbation of symptoms following strenuous exercise, is a characteristic symptom of ME/CFS. To detect changes coincident with PEM, we applied scRNA-seq on the same cohorts following exercise. At baseline, ME/CFS patients display classical monocyte dysregulation suggestive of inappropriate differentiation and migration to tissue. We identify both diseased and more normal monocytes within patients, and the fraction of diseased cells correlates with disease severity. Comparing the transcriptome at baseline and postexercise challenge, we discover patterns indicative of improper platelet activation in patients, with minimal changes elsewhere in the immune system. Taken together, these data identify immunological defects present at baseline in patients and an additional layer of dysregulation in platelets.

Parents' experiences of being involved in medical decision-making for their child with a life-limiting condition: A systematic review with narrative synthesis.

BACKGROUND: Parental involvement in the decision-making processes about medical treatment for children with life-limiting conditions is recognised as good practice. Previous research highlighted factors affecting the decision-making process, but little is known about how parents experience their participation. AIM: To explore how parents experience their participation in the process of decision-making about treatment and future care for their children with life-limiting conditions. DESIGN: A systematically constructed review using narrative synthesis. The PRISMA guidelines were followed to report the findings. Databases Medline, EMBASE, SCOPUS, CINAHL and PsycINFO were searched up to December 2023. The study protocol was registered at PROSPERO (RN CRD42021215863). RESULTS: From the initial 2512 citations identified, 28 papers met the inclusion criteria and were included in the review. A wide range of medical decisions was identified; stopping general or life-sustaining treatment was most frequent. Narrative synthesis revealed six themes: (1) Temporal aspects affecting the experience with decision-making; (2) Losing control of the situation; (3) Transferring the power to decide to doctors; (4) To be a 'good' parent and protect the child; (5) The emotional state of parents and (6) Sources of support to alleviate the parental experience. CONCLUSIONS: Parental experiences with decision-making are complex and multifactorial. Parents' ability to effectively participate in the process is limited, as they are not empowered to do so and the circumstances in which the decisions are taking place are challenging. Healthcare professionals need to support parental involvement in an effective way instead of just formally asking them to participate.

Blood pressure normative values in preterm infants during postnatal transition.

BACKGROUND: The normative blood pressure values in preterm infants still not well defined during postnatal transition. We aimed to create normative blood pressure (BP) reference values in preterm infants <29 weeks gestational age recorded hourly during the postnatal transition. METHODS: We included only data from hemodynamically stable newborns. Only BP values measured by umbilical arterial catheter (UAC) were included. The regression model showed that only gestational age and postnatal age in hours determine the BP. RESULTS: We included 206 out of 547 admitted preterm infants. The BP increases with increasing gestational ages and overtime during the postnatal transition. We constructed 5 BP centile values for each gestational group. BP histograms show that the BP most of the time fluctuated between the 5th and 75th centile values, particularity during day one of life. CONCLUSIONS: The BP trend values gradually increase in stable preterm infants during the postnatal transition, and preterm infants who do not follow this trend might require hemodynamics assessment. IMPACT: The normative blood pressure is increasing gradually during the first 3 days after birth and is different with gestational ages. This is first normative blood pressure centile values in stable preterm infant and based on invasive blood pressure monitoring. The data enable more accurate monitoring of hemodynamics in preterm infants during postnatal transition.

Targeting of essential mycobacterial replication enzyme DnaG primase revealed Mitoxantrone and Vapreotide as novel mycobacterial growth inhibitors.

Tuberculosis (TB) is the second leading cause of mortality after COVID-19, with a global death toll of 1.6 million in 2021. The escalating situation of drug-resistant forms of TB has threatened the current TB management strategies. New therapeutics with novel mechanisms of action are urgently required to address the current global TB crisis. The essential mycobacterial primase DnaG with no structural homology to homo sapiens presents itself as a good candidate for drug targeting. In the present study, Mitoxantrone and Vapreotide, two FDA-approved drugs, were identified as potential anti-mycobacterial agents. Both Mitoxantrone and Vapreotide exhibit a strong Minimum Inhibitory Concentration (MIC) of ≤25µg/ml against both the virulent (M.tb-H37Rv) and avirulent (M.tb-H37Ra) strains of M.tb. Extending the validations further revealed the inhibitory potential drugs in ex vivo conditions. Leveraging the computational high-throughput multi-level docking procedures from the pool of ~2700 FDA-approved compounds, Mitoxantrone and Vapreotide were screened out as potential inhibitors of DnaG. Extensive 200 ns long all-atoms molecular dynamic simulation of DnaGDrugs complexes revealed that both drugs bind strongly and stabilize the DnaG during simulations. Reduced solvent exposure and confined motions of the active centre of DnaG upon complexation with drugs indicated that both drugs led to the closure of the active site of DnaG. From this study's findings, we propose Mitoxantrone and Vapreotide as potential anti-mycobacterial agents, with their novel mechanism of action against mycobacterial DnaG.

Unravelling the potential of Triflusal as an anti-TB repurposed drug by targeting replication protein DciA.

The increasing prevalence of drug-resistant Tuberculosis (TB) is imposing extreme difficulties in controlling the TB infection rate globally, making treatment critically challenging. To combat the prevailing situation, it is crucial to explore new anti-TB drugs with a novel mechanism of action and high efficacy. The Mycobacterium tuberculosis (M.tb)DciA is an essential protein involved in bacterial replication and regulates its growth. DciA interacts with DNA and provides critical help in binding other replication machinery proteins to the DNA. Moreover, the lack of any structural homology of M.tb DciA with human proteins makes it an appropriate target for drug development. In this study, FDA-approved drugs were virtually screened against M.tb DciA to identify potential inhibitors. Four drugs namely Lanreotide, Risedronate, Triflusal, and Zoledronic acid showed higher molecular docking scores. Further, molecular dynamics simulations analysis of DciA-drugs complexes reported stable interaction, more compactness, and reduced atomic motion. The anti-TB activity of drugs was further evaluated under in vitro and ex vivo conditions where Triflusal was observed to have the best possible activity with the MIC of 25 µg/ml. Our findings present novel DciA inhibitors and anti-TB activity of Triflusal. Further investigations on the use of Triflusal may lead to the discovery of a new anti-TB drug.

The views and perceptions of training in physical health care amongst mental health nurses, managers of mental health nurses and trainers: A systematically constructed narrative synthesis.

People with serious mental illness have higher morbidity and mortality rates compared with the general population. Mental health nurses are in an optimal position to address physical healthcare needs and inequalities experienced by this group. Research evidence suggests that mental health nurses may lack appropriate skills and confidence. The training needs of mental health nurses in physical health care of patients with serious mental illness and the perceived effectiveness of training that is provided to mental health nurses are explored in this review. A narrative synthesis approach (PROSPERO protocol registration ID=CRD42021230923) involved searching five electronic databases (PsycInfo, Cinahl, Embase, Medline and Web of Science) from 1990 to 2021. Study quality was assessed, and analysis and synthesis were initially deductively guided by a theoretical framework of training effectiveness prior to inductive data analysis. Eleven studies met the inclusion criteria. For studies examining perceived effectiveness of training, four themes were derived from the theoretical framework (individual trainee characteristics, work environment, learning outcomes, transfer of training to job) and further theme (service user factor) generated inductively. For studies examining training needs, three themes were derived inductively (knowledge and skills requirements, modality of training, service and healthcare factors). The study highlights the need for ongoing learning to improve practice. It also provides another perspective in terms of understanding the influence of service user factors (motivation and mental state) in designing and implementing of future training in mental health settings.

Do community-based singing interventions have an impact on people living with dementia and their carers? A mixed-methods study protocol.

INTRODUCTION: Psychosocial interventions have been shown to improve mood, relieve stress and improve quality of life for people living with dementia (PwD). To date, most evaluations of singing interventions have focused on the benefits for PwD and not their carers. This research aims to evaluate the benefits of dementia singing groups for both PwD and their carers. METHODS AND ANALYSIS: This 2-year project will observe the impact of two different singing intervention services, one combining singing alongside dance and another that includes a sociable lunch. This project will aim to recruit a total of n=150 PwD and n=150 carers across the two singing interventions. Using a mixed-methods approach, the influence of both services will be analysed via the following outcome measures: quality of life, neuropsychiatric symptoms, social isolation, loneliness, cognition, carer burden and depressive symptoms in PwD and their carers using a prestudy/poststudy design. Regression models will be used to analyse the data with time (pre/post) as the exposure variable. Semistructured interviews will be conducted with a subset of people (n=40) to further investigate the impact of singing services with a specific focus on the acceptability of the interventions, barriers to access and prolonged engagement and potential for remote delivery. Interview data will be analysed using Braun and Clarke's reflexive thematic analysis, and public advisers will assist with coding the transcripts. A social return on investment analysis will be conducted to determine the social impact of the services. ETHICS AND DISSEMINATION: This project has received ethical approval from the University of Liverpool's Ethics Committee (App ref: 12374) and Lancaster University's Ethics Committee (App ref: 3442). All participants will provide informed consent to participate. Results will be presented at national and international conferences, published in scientific journals and publicly disseminated to key stakeholders.

Patient-specific models link neurotransmitter receptor mechanisms with motor and visuospatial axes of Parkinson's disease.

Parkinson's disease involves multiple neurotransmitter systems beyond the classical dopaminergic circuit, but their influence on structural and functional alterations is not well understood. Here, we use patient-specific causal brain modeling to identify latent neurotransmitter receptor-mediated mechanisms contributing to Parkinson's disease progression. Combining the spatial distribution of 15 receptors from post-mortem autoradiography with 6 neuroimaging-derived pathological factors, we detect a diverse set of receptors influencing gray matter atrophy, functional activity dysregulation, microstructural degeneration, and dendrite and dopaminergic transporter loss. Inter-individual variability in receptor mechanisms correlates with symptom severity along two distinct axes, representing motor and psychomotor symptoms with large GABAergic and glutamatergic contributions, and cholinergically-dominant visuospatial, psychiatric and memory dysfunction. Our work demonstrates that receptor architecture helps explain multi-factorial brain re-organization, and suggests that distinct, co-existing receptor-mediated processes underlie Parkinson's disease.

Genomic landscape and gene expression profiles of feline oral squamous cell carcinoma.

Feline oral squamous cell carcinoma (FOSCC) is a cancer of the squamous cell lining in the oral cavity and represents up to 80% of all oral cancers in cats, with a poor prognosis. We have used whole exome sequencing (WES) and RNA sequencing of the tumor to discover somatic mutations and gene expression changes that may be associated with FOSCC occurrence. FOSCC offers a potential comparative model to study human head and neck squamous cell carcinoma (HNSCC) due to its similar spontaneous formation, and morphological and histological features. In this first study using WES to identify somatic mutations in feline cancer, we have identified tumor-associated gene mutations in six cats with FOSCC and found some overlap with identified recurrently mutated genes observed in HNSCC. Four samples each had mutations in TP53, a common mutation in all cancers, but each was unique. Mutations in other cellular growth control genes were also found such as KAT2B and ARID1A. Enrichment analysis of FOSCC gene expression profiles suggests a molecular similarity to human OSCC as well, including alterations in epithelial to mesenchymal transition and IL6/JAK/STAT pathways. In this preliminary study, we present exome and transcriptome results that further our understanding of FOSCC.

Potential Repurposed Drug Candidates for Tuberculosis Treatment: Progress and Update of Drugs Identified in Over a Decade.

The devastating impact of Tuberculosis (TB) has been a menace to mankind for decades. The World Health Organization (WHO) End TB Strategy aims to reduce TB mortality up to 95% and 90% of overall TB cases worldwide, by 2035. This incessant urge will be achieved with a breakthrough in either a new TB vaccine or novel drugs with higher efficacy. However, the development of novel drugs is a laborious process involving a timeline of almost 20-30 years with huge expenditure; on the other hand, repurposing previously approved drugs is a viable technique for overcoming current bottlenecks in the identification of new anti-TB agents. The present comprehensive review discusses the progress of almost all the repurposed drugs that have been identified to the present day (∼100) and are in the development or clinical testing phase against TB. We have also emphasized the efficacy of repurposed drugs in combination with already available frontline anti-TB medications along with the scope of future investigations. This study would provide the researchers a detailed overview of nearly all identified anti-TB repurposed drugs and may assist them in selecting the lead compounds for further in vivo/clinical research.

Performance Evaluation of Input Power of Diode Laser on Machined Leather Specimen in Laser Beam Cutting Process.

Numerous industries, including footwear, handicrafts, and the automobile industry, utilize leather materials. The main goal of this study was to investigate the effect of input power of the diode laser in laser cutting on vegetable chrome tanned buffalo leather to enhance the cutting process. In the present investigation, carbonization, kerf width, and material removal rate (MRR) were taken as performance measures. The diode-based laser beam machining was designed and fabricated with 2.5 W, 5.5 W, and 20 W diode laser to cut vegetable chrome tanned leather. The high-intensity 20 W diode laser produced lower carbonization, lower kerf width, and higher material removal rate compared with the 2.5 W and 5.5 W diodes. This improved performance was due to the adjustable features associated with this diode laser actuation in the form of circular shape with adjustable diameter. A high power with a lower spot size under pulsed mode can produce higher power density. Since a higher power density can establish less interaction time, it produces lower carbonization. Due to the ability of the 20 W diode laser driver to control the beam shape and size, it could produce a lower kerf width and higher MRR. The optimal parameters for cutting chrome vegetable tanned cow leather were a standoff distance of 18 mm, feed rate of 200 mm/min, and duty cycle of 70%.

Retrospective study of more than 5 million emergency admissions to hospitals in England: Epidemiology and outcomes for people with dementia.

INTRODUCTION: People living with dementia (PwD) admitted in emergency to an acute hospital may be at higher risk of inappropriate care and poorer outcomes including longer hospitalisations and higher risk of emergency re-admission or death. Since 2009 numerous national and local initiatives in England have sought to improve hospital care for PwD. We compared outcomes of emergency admissions for cohorts of patients aged 65+ with and without dementia at three points in time. METHODS: We analysed emergency admissions (EAs) from the Hospital Episodes Statistics datasets for England 2010/11, 2012/13 and 2016/17. Dementia upon admission was based on a diagnosis in the patient's hospital records within the last five years. Outcomes were length of hospital stays (LoS), long stays (> = 15 days), emergency re-admissions (ERAs) and death in hospital or within 30 days post-discharge. A wide range of covariates were taken into account, including patient demographics, pre-existing health and reasons for admission. Hierarchical multivariable regression analysis, applied separately for males and females, estimated group differences adjusted for covariates. RESULTS: We included 178 acute hospitals and 5,580,106 EAs, of which 356,992 (13.9%) were male PwD and 561,349 (18.6%) female PwD. Uncontrolled differences in outcomes between the patient groups were substantial but were considerably reduced after control for covariates. Covariate-adjusted differences in LoS were similar at all time-points and in 2016/17 were 17% (95%CI 15%-18%) and 12% (10%-14%) longer for male and female PwD respectively compared to patients without dementia. Adjusted excess risk of an ERA for PwD reduced over time to 17% (15%-18%) for males and 17% (16%-19%) for females, but principally due to increased ERA rates amongst patients without dementia. Adjusted overall mortality was 30% to 40% higher for PwD of both sexes throughout the time-period; however, adjusted in-hospital rates of mortality differed only slightly between the patient groups, whereas PwD had around double the risk of dying within 30 days of being discharged. CONCLUSION: Over the six-year period, covariate-adjusted hospital LoS, ERA rates and in-hospital mortality rates for PwD were only slightly elevated compared to similar patients without dementia and remaining differences potentially reflect uncontrolled confounding. PwD however, were around twice as likely to die shortly after discharge, the reasons for which require further investigation. Despite being widely used for service evaluation, LoS, ERA and mortality may lack sensitivity to changes in hospital care and support to PwD.

Design, Analysis, and 3D Printing of a Patient-Specific Polyetheretherketone Implant for the Reconstruction of Zygomatic Deformities.

The reconstruction of craniomaxillofacial deformities, especially zygomatic bone repair, can be exigent due to the complex anatomical structure and the sensitivity of the crucial organs involved. The need to reconstruct the zygomatic bone in the most precise way is of crucial importance for enhancing the patient outcomes and health care-related quality of life (HRQL). Autogenous bone grafts, despite being the gold standard, do not match bone forms, have limited donor sites and bone volume, and can induce substantial surgical site morbidity, which may lead to adverse outcomes. The goal of this study is to provide an integrated approach that includes various processes, from patient scanning to implant manufacture, for the restoration of zygomatic bone abnormalities utilizing Polyetheretherketone (PEEK) material, while retaining adequate aesthetic and facial symmetry. This study takes an integrated approach, including computer-aided implant design using the mirror reconstruction technique, investigating the biomechanical behavior of the implant under loading conditions, and carrying out a fitting accuracy analysis of the PEEK implant fabricated using state-of-the-art additive manufacturing technology. The findings of the biomechanical analysis results reveal the largest stress of approximately 0.89 MPa, which is relatively low in contrast to the material's yield strength and tensile strength. A high degree of sturdiness in the implant design is provided by the maximum value of strain and deformation, which is also relatively low at roughly 2.2 × 10-4 and 14 µm. This emphasizes the implant's capability for load resistance and safety under heavy loading. The 3D-printed PEEK implant observed a maximum deviation of 0.4810 mm in the outside direction, suggesting that the aesthetic result or the fitting precision is adequate. The 3D-printed PEEK implant has the potential to supplant the zygoma bone in cases of severe zygomatic reconstructive deformities, while improving the fit, stability, and strength of the implant.

Design and in silico analysis of mRNA vaccine construct against Salmonella.

Salmonella infections are continuously growing. Causative serovars have gained enhanced drug resistance and virulence. Current vaccines have fallen short of providing sufficient protection. mRNA vaccines have come up with huge success against SARS-CoV-2; Pfizer-BioNTech and Moderna vaccines have resulted in >90% efficacy with efficient translocation, expression, and presentation of antigen to the host immune system. Herein, based on the same approach a mRNA vaccine construct has been designed and analyzed against Salmonella by joining regions of genes of outer membrane proteins C and F of S. Typhi through a flexible linker. Construct was flanked by regulatory regions that have previously shown better expression and translocation of encoded protein. GC content of the construct was improved to attain structural and thermodynamic stability and smooth translation. Sites of strong binding miRNAs were removed through codon optimization. Protein encoded by this construct is structurally plausible, highly antigenic, non-allergen to humans, and does not cross-react to the human proteome. It is enriched in potent, highly antigenic, and conserved linear and conformational epitopes. Most conserved conformational epitopes of core protein lie on extended beta hairpins exposed to the cellular exterior. Stability and thermodynamic attributes of the final construct were found highly comparable to the Pfizer-BioNTech vaccine construct. Both contain a stable stem-loop structure downstream of the start codon and do not offer destabilizing secondary structures upstream of the start codon. Given structural and thermodynamic stability, effective immune response, and epitope composition the construct is expected to provide broad-spectrum protection against clinically important Salmonella serovars.Communicated by Ramaswamy H. Sarma.

Computational analysis of RNA methyltransferase Rv3366 as a potential drug target for combating drug-resistant Mycobacterium tuberculosis.

Mycobacterium tuberculosis (M.tb) remains a formidable global health threat. The increasing drug resistance among M.tb clinical isolates is exacerbating the current tuberculosis (TB) burden. In this study we focused on identifying novel repurposed drugs that could be further investigated as potential anti-TB drugs. We utilized M.tb RNA methyltransferase Rv3366 (spoU) as a potential drug target due to its imperative activity in RNA modification and no structural homology with human proteins. Using computational modeling approaches the structure of Rv3366 was determined followed by high throughput virtual screening of Food and Drug Administration (FDA) approved drugs to screen potential binders of Rv3366. Molecular dynamics (MD) simulations were performed to assess the drug-protein binding interactions, complex stability and rigidity. Through this multi-step structure-based drug repurposing workflow two promising inhibitors of Rv3366 were identified, namely, Levodopa and Droxidopa. This study highlights the significance of targeting M.tb RNA methyltransferases to combat drug-resistant M.tb. and proposes Levodopa and Droxidopa as promising inhibitors of Rv3366 for future pre-clinical investigations.

Nanotubes Formation in P. aeruginosa.

The present study discusses a biofilm-positive P. aeruginosa isolate that survives at pH levels ranging from 4.0 to 9.0. The biofilm consortia were colonized with different phenotypes i.e., planktonic, slow-growing and metabolically inactive small colony variants (SCVs). The lower base of the consortia was occupied by SCVs. These cells were strongly attached to solid surfaces and interconnected through a network of nanotubes. Nanotubes were observed at the stationary phase of biofilm indwellers and were more prominent after applying weight to the consortia. The scanning electron micrographs indicated that the nanotubes are polar appendages with intraspecies connectivity. The micrographs indicated variations in physical dimensions (length, width, and height) and a considerable reduction in volume due to weight pressure. A total of 35 cells were randomly selected. The mean volume of cells before the application of weight was 0.288 µm3, which was reduced to 0.144 µm3 after the application of weight. It was observed that a single cell may produce as many as six nanotubes, connected simultaneously to six neighbouring cells in different directions. The in-depth analysis confirmed that these structures were the intra-species connecting tools as no free nanotubes were found. Furthermore, after the application of weight, cells incapable of producing nanotubes were wiped out and the surface was covered by nanotube producers. This suggests that the nanotubes give a selective advantage to the cells to resist harsh environmental conditions and weight pressure. After the removal of weight and proper supply of nutrients, these phenotypes reverted to normal planktonic lifestyles. It is concluded that the nanotubes are not merely the phenomenon of dying cells; rather they are a connectivity tool which helps connected cells to tolerate and resist environmental stress.

The Use of the Transfemoral Transcaval Liver Biopsy Technique for Biopsies of Hepatic Masses.

The purpose of this study was to investigate the safety and effectiveness of the transfemoral transcaval (TFTC) liver biopsy technique in patients with hepatic masses with relative contraindications to percutaneous biopsy and/or mass location abutting the inferior vena cava. The medical records of 16 patients (56% men; age range, 21-88 years) who underwent TFTC biopsy of hepatic masses (ranging in diameter from 2.1 to 13.2 cm) from September 2015 to August 2021 were reviewed. Histopathologic diagnoses were made in 15 of 17 (88%) procedures. Two adverse events were noted: worsened preexisting hemobilia requiring embolization in 1 patient, and a decrease in hematocrit level in another patient, requiring only observation. In conclusion, this report showed that the TFTC technique is a relatively safe and effective method for sampling hepatic masses in select cases.

Effect of Vegetable Waste on Growth Performance and Hematology of Broiler Chicks.

Vegetable waste (spinach, potato, and cauliflower) is a rich and natural source of nutrients, potentially good for supplying minerals, essential amino acids, and antioxidants to the birds. Relatively, its cost very low, easily to accessible, easily process & pose little risk of illness. The aim of present study was to evaluate the effect of vegetable waste (VW) as feed supplement on growth performance and hematology of broiler chicks. For this purpose, a total of 200 (4 days old) vaccinated chicks were acquired from a commercial hatchery Multan which was acclimated for three weeks (21 days) on basal starter feed after that 25-day-old chicks with uniform body weight were allocated according to a CRD (completely randomized design) into four dietary treatments with three replicates of each contained 15 chicks in 12 pens. In dietary treatments, chicks were feed with basal feed (BF) and supplemented feed with vegetable waste (VW) of spinach, potato, and cauliflower. For this purpose, the dietary treatments included control treatment (T 1) (100% BF+0% VW) and other dietary treatments (T 2) (75% BF+25% VW), (T 3) (50% BF+50% VW), and (T 4) (25% BF+75% VW). The body weight, feed intake, food conversion ratio (FCR), and mortality were checked on weekly and daily basis. For hematology analysis, after the 1st experimental week (25-day-old chicks) and the last 5th experimental week (56-day-old chicks), the samples of blood were gathered from the wing's veins of two birds from each treatment in random way. At the end of five weeks (35 days), birds with uniform average body weight were selected per treatment with three replicates (2 bird/replicate) and then were manually slaughtered according to the Halal method to analyze the weight of internal body organs of broilers by physical and statistical analysis (ANOVA). There was no significant effect (P > 0.05) on feed intake and FCR among all the dietary treatments. But in average, body weight and BWG were higher in treatment (T 2) (P < 0.01) than all other dietary treatments (T 3) and (T 4) and control treatment (T 1). The blood constituents in this study showed that broilers in control treatment (T 1) and other dietary treatments (T 2), (T 3), and (T 4) fed on different doses were significantly (P < 0.01) different from each other. The week 5 (W 5) shows higher values of blood constituents (P < 0.01) than week 1 (W 1). The carcass yield of the chicks fed on different doses showed that they were significantly different (P < 0.01) among the dietary treatments. The VW inclusion 0%, 25%, 50%, and 75% had positive effect on blood constituents and carcass yield of the broiler chicks; they were significantly (P < 0.01) different among the treatments.

Delayed puberty, gonadotropin abnormalities and subfertility in male Padi2/Padi4 double knockout mice.

BACKGROUND: Peptidylarginine deiminase enzymes (PADs) convert arginine residues to citrulline in a process called citrullination or deimination. Recently, two PADs, PAD2 and PAD4, have been linked to hormone signaling in vitro and the goal of this study was to test for links between PAD2/PAD4 and hormone signaling in vivo. METHODS: Preliminary analysis of Padi2 and Padi4 single knockout (SKO) mice did not find any overt reproductive defects and we predicted that this was likely due to genetic compensation. To test this hypothesis, we created a Padi2/Padi4 double knockout (DKO) mouse model and tested these mice along with wild-type FVB/NJ (WT) and both strains of SKO mice for a range of reproductive defects. RESULTS: Controlled breeding trials found that male DKO mice appeared to take longer to have their first litter than WT controls. This tendency was maintained when these mice were mated to either DKO or WT females. Additionally, unsexed 2-day old DKO pups and male DKO weanlings both weighed significantly less than their WT counterparts, took significantly longer than WT males to reach puberty, and had consistently lower serum testosterone levels. Furthermore, 90-day old adult DKO males had smaller testes than WT males with increased rates of germ cell apoptosis. CONCLUSIONS: The Padi2/Padi4 DKO mouse model provides a new tool for investigating PAD function and outcomes from our studies provide the first in vivo evidence linking PADs with hormone signaling.