Effect of theophylline on serum and milk pharmacokinetics of tylosin following intramuscular administration in lactating goats.

AIM OF THE WORK: The study was conducted to evaluate the influence of theophylline pre-treatment on serum pharmacokinetics and milk elimination of tylosin following single intramuscular (IM) administrations in lactating goats. METHODS AND RESULTS: In a cross-over study, tylosin was injected via intramuscular (IM) at a single dose of 15 mg/kg b.wt. After a one-month washout period goats received theophylline at a daily IM dose of 2 mg/kg b.wt. for seven consecutive days then tylosin was injected IM dose of 15 mg/kg b.wt. two hours after the last theophylline dosing. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12, and 24 h post-injection. Samples were left to clot and then centrifuged to yield serum. Milk samples were collected before and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, and 72 h post-injection from each goat by hand milking. Tylosin serum concentrations were determined by high-performance liquid chromatography (HPLC). Tylosin concentrations versus time were analyzed by a noncompartmental method. Tylosin Cmax significantly declined from 1.73 ± 0.10 to 1.01 ± 0.11 µg/ml, and attained Tmax values of 2 and 1 h, respectively in theophylline-pretreated goats. Moreover, theophylline pretreatment significantly shortened the elimination half-life (t1/2el) from 6.94 to 1.98 h, t1/2ka from 0.62 to 0.36 h and the mean residence time (MRT) from 8.02 to 4.31 h, also Vz/F and AUCs decreased from 11.91 to 7.70 L/kg and from 12.64 to 4.57 µg*h/ml, respectively, consequently, theophylline enhanced the clearance (Cl/F) of tylosin from the body. Similarly, tylosin milk concentrations were significantly lower in theophylline-pretreated goats than in goats that received tylosin alone and were detected up to 24 and 72 h in both groups, respectively. Moreover, the t1/2el and AUCs were significantly decreased from 14.68 ± 1.97 to 4.72 ± 0.48 h, and from 181 to 67.20 µg*h/ml, respectively. CONCLUSIONS: The withdrawal period for tylosin in goat milk is at least 72 h. Theophylline pretreatment significantly decreases serum and milk tylosin concentrations to subtherapeutic levels, which could have serious clinical consequences such as failure of therapy. This means that after administering tylosin to goats, milk from these animals should not be consumed for at least 96 h to ensure that the milk is free from residues of the antibiotic.

Impact of grazing around industrial areas on milk heavy metals contamination and reproductive ovarian hormones of she-camel with assessment of some technological processes on reduction of toxic residue concentrations.

Heavy metals are one of the most toxic chemical pollutants of the environment. Their hazards not restricted to human but extend to animal productivity and reproductively. The present study aimed to assess the impact of grazing around industrial areas on the levels of copper (Cu) and aluminum (Al) residues in milk samples collected from dromedary she-camels and studying their effects on some ovarian hormones. In addition, the study aimed to investigate methods of removal of the toxic concentrations of these heavy metals in milk by applying different technological processes. Blood and milk samples were collected from 30 dromedary she-camels, 15 grazing in non-industrial areas (group A) and 15 grazing in industrial areas (group B). Detection of the levels of these heavy metals in milk was done. Ovarian hormones investigation on the blood was performed. Different technological processes such as boiling, skimming and fermentation were applied to all contaminated samples to reduce the toxic concentrations of these heavy metals. Results revealed that all examined milk samples in both groups contained Cu, while 40% of group A and 100 % of group B contained Al residues with different concentrations. The levels of Cu and Al residues in samples of group A not exceeded the maximum residual limit (MRL) set by World Health Organization (WHO) while 60% and 100% of milk samples in group B contained Cu and Al residues exceeded MRL, respectively. Technological processes induce variant changes in the levels of these metals in milk. Heat treatment of milk in Al vats leads to leaching of Al from containers to the milk causing significant increase in Al load, while Cu level was not significantly affected. Boiling in stainless-steel containers decreased the levels of Al and Cu but in non-significant levels. Regarding skimming process, small amount of Cu and Al escaped into the skimmed milk while greater amount were recovered in the cream. Fermentation by probiotic bacteria showed that milk fermentation has non-significant effect on Cu and Al levels. Investigation of ovarian hormones (estrogen and progesterone) revealed presence of a signification reduction in the levels of these hormones in group B compared to group A. In addition, a negative correlation was found between these heavy metals and ovarian hormones concentrations in the blood. It is concluded that grazing of dromedary camels around industrial areas induce heavy metals toxicity represented by excretion of these metals in milk and significant reduction on ovarian function showed by reduction of estrogen and progesterone levels. Technological processes such as skimming decreased the levels of Al and Cu residues in milk.

A novel coupling quality index to estimate the coupling efficiency in Vibrant Soundbridge.

BACKGROUND: The objective-based methods for intraoperative monitoring have been suggested to assess the coupling and the outcomes of Vibrant Soundbridge (VSB). Although several techniques were proposed, they have not been widely adopted due to their complexity and invasiveness. PURPOSE: This study aimed to investigate the accuracy of a new coupling quality index using an intraoperative ABR threshold via AcoustiAP and its correlation with the perioperative measures. METHODS: This is a prospective study conducted at a tertiary center. The medical records were retrieved for all patients who underwent VSB implantation and had an intraoperative objective assessment for the coupling efficiency. AcoustiAP was used to evaluate the intraoperative ABR thresholds, which were assessed directly after the floating mass transducer (FMT) placement using acoustic CE-Chirp signals. The Vibrogram was used for the postoperative audiological evaluation. A new coupling quality index was calculated based on the intraoperative ABR thresholds. RESULTS: Ten patients were eligible for the present study. The ABR thresholds for good coupling ranged from 35 to 60 dBnHL. The loose coupling thresholds ranged considerably from 40 to 100 dBnHL. Overall, the median intraoperative ABR threshold at good coupling was 42.5 (40-60) dBnHL and 60 (40-100) dBnHL at loose coupling. The analysis showed that there was a significant change in the coupling quality index at the good and loose coupling points (24.3 ± 14 vs 38.8 ± 18.2, respectively, p < 0.001). At a cut-off value of 22.6 dB, the coupling quality index had a sensitivity of 70%  and specificity of 90% for discriminating good and loose coupling. CONCLUSION: This study provides evidence for the utility of intraoperative ABR measurements in predicting the coupling efficiency in patients with VSB. Our results showed that the coupling quality index had an acceptable accuracy in discriminating between good and poor coupling, which can help clinicians optimize the fitting process for individuals and may ultimately lead to improved patient outcomes.

Utility of CYP2D6 copy number variants as prognostic biomarker in localized anal squamous cell carcinoma.

BACKGROUND: Anal squamous cell carcinoma (ASCC) is an infrequent tumor whose treatment has not changed since the 1970s. The aim of this study is the identification of biomarkers allowing personalized treatments and improvement of therapeutic outcomes. METHODS: Forty-six paraffin tumor samples from ASCC patients were analyzed by whole-exome sequencing. Copy number variants (CNVs) were identified and their relation to disease-free survival (DFS) was studied and validated in an independent retrospective cohort of 101 ASCC patients from the Multidisciplinary Spanish Digestive Cancer Group (GEMCAD). GEMCAD cohort proteomics allowed assessing the biological features of these tumors. RESULTS: On the discovery cohort, the median age was 61 years old, 50% were males, stages I/II/III: 3 (7%)/16 (35%)/27 (58%), respectively, median DFS was 33 months, and overall survival was 45 months. Twenty-nine genes whose duplication was related to DFS were identified. The most representative was duplications of the CYP2D locus, including CYP2D6, CYP2D7P, and CYP2D8P genes. Patients with CYP2D6 CNV had worse DFS at 5 years than those with two CYP2D6 copies (21% vs. 84%; p < .0002, hazard ratio [HR], 5.8; 95% confidence interval [CI], 2.7-24.9). In the GEMCAD validation cohort, patients with CYP2D6 CNV also had worse DFS at 5 years (56% vs. 87%; p = .02, HR = 3.6; 95% CI, 1.1-5.7). Mitochondria and mitochondrial cell-cycle proteins were overexpressed in patients with CYP2D6 CNV. CONCLUSIONS: Tumor CYP2D6 CNV identified patients with a significantly worse DFS at 5 years among localized ASCC patients treated with 5-fluorouracil, mitomycin C, and radiotherapy. Proteomics pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets for these high-risk patients. PLAIN LANGUAGE SUMMARY: Anal squamous cell carcinoma is an infrequent tumor whose treatment has not been changed since the 1970s. However, disease-free survival in late staged tumors is between 40% and 70%. The presence of an alteration in the number of copies of CYP2D6 gene is a biomarker of worse disease-free survival. The analysis of the proteins in these high-risk patients pointed out mitochondria and mitochondrial cell-cycle genes as possible therapeutic targets. Therefore, the determination of the number of copies of CYP2D6 allows the identification of anal squamous carcinoma patients with a high-risk of relapse that could be redirected to a clinical trial. Additionally, this study may be useful to suggest new treatment strategies to increase current therapy efficacy.

Influence of conventional versus unidirectional barbed suture on leakage pressures in canine vesicourethral anastomosis: An ex-vivo study.

OBJECTIVE: To compare leakage pressures of vesicourethral anastomosis (VUA) performed with conventional and unidirectional barbed sutures in canine cadaveric tissue. STUDY DESIGN: Experimental, ex-vivo, randomized study. ANIMALS: A total of 24 male canine bladders with the urethra. METHODS: Specimens after prostatectomy were randomly divided into a unidirectional barbed suture (UBS) or a conventional suture (C) group. For the UBS group, the VUA was performed with 4-0 unidirectional barbed sutures. For the C group, the VUA was performed with 4-0 monofilament absorbable suture. The VUA was completed with two simple continuous sutures. Surgical time, leakage pressure, site of leakage, and the number of suture bites were recorded. RESULTS: The median suturing time was 12.70 minutes (range: 7.50-16.10 min) for the UBS group and 17.30 minutes (range: 14.00-21.30 min) for the C group (p < .0002). The median leakage pressure was 8.60 mmHg (range: 5.00-17.20 mmHg) for the UBS group and 11.70 mmHg (range: 6.00-18.50 mmHg) for the C group (p = .236). The median number of suture bites was 14 (range:11-27) for the UBS group and 19 (range:17-28) for the C group (p = .012). CONCLUSION: Unidirectional barbed suture does not statistically affect the acute leakage pressure of VUA in normal cadaveric specimen. It resulted in a shorter surgical time and fewer suture bite placements. CLINICAL SIGNIFICANCE: A urinary catheter will still be required when a unidirectional barbed suture is used to complete a VUA in dogs to prevent extravasation of urine in the postoperative period.

SeqEditor: an application for primer design and sequence analysis with or without GTF/GFF files.

MOTIVATION: Sequence analyses oriented to investigate specific features, patterns and functions of protein and DNA/RNA sequences usually require tools based on graphic interfaces whose main characteristic is their intuitiveness and interactivity with the user's expertise, especially when curation or primer design tasks are required. However, interface-based tools usually pose certain computational limitations when managing large sequences or complex datasets, such as genome and transcriptome assemblies. Having these requirments in mind we have developed SeqEditor an interactive software tool for nucleotide and protein sequences' analysis. RESULT: SeqEditor is a cross-platform desktop application for the analysis of nucleotide and protein sequences. It is managed through a Graphical User Interface and can work either as a graphical sequence browser or as a fasta task manager for multi-fasta files. SeqEditor has been optimized for the management of large sequences, such as contigs, scaffolds or even chromosomes, and includes a GTF/GFF viewer to visualize and manage annotation files. In turn, this allows for content mining from reference genomes and transcriptomes with similar efficiency to that of command line tools. SeqEditor also incorporates a set of tools for singleplex and multiplex PCR primer design and pooling that uses a newly optimized and validated search strategy for target and species-specific primers. All these features make SeqEditor a flexible application that can be used to analyses complex sequences, design primers in PCR assays oriented for diagnosis, and/or manage, edit and personalize reference sequence datasets. AVAILABILITYAND IMPLEMENTATION: SeqEditor was developed in Java using Eclipse Rich Client Platform and is publicly available at https://gpro.biotechvana.com/download/SeqEditor as binaries for Windows, Linux and Mac OS. The user manual and tutorials are available online at https://gpro.biotechvana.com/tool/seqeditor/manual. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The food and drug administration approved many drugs to treat diabetes mellitus, but those drugs do not have a noticeable effect on weight management. Recently, glucagon-like peptide 1 agonist known as Cotadutide serve as a potent drug in treating type 2 diabetes by reducing blood glucose levels and body weight indices. This study aimed to explore the safety and efficacy of Cotadutide as a treatment for type 2 diabetes individuals. METHODS: A comprehensive literature search was done on different databases, including PubMed, Scopus, Web of Science, and Cochrane Library to capture all relevant articles using an established search strategy. The inclusion criteria were randomized controlled trials that assessed the safety and efficacy of Cotadutide versus placebo or any anti-diabetes drugs in patients with type 2 diabetes mellitus and a BMI between 22 kg/m2 and 40 kg/m2. We conducted the analysis using Revman software version 5.4. RESULTS: We found 663 relevant articles. From which nine studies were included and subjected to qualitative analysis and eight for quantitative analysis. The pooled effect showed that Cotadutide was better than placebo in reducing body weight (kg) (Mean difference (MD) = 3.31, p < 0.00001), glycated hemoglobin (HbA1c) (MD = 0.68, p > 0.00001), glucose area under the plasma concentration curve (AUC [0-4 h]) (MD = 30.15, p < 0.00001), and fasting plasma glucose over time (mg/dl) (MD = 31.31, p < 0.00001). CONCLUSION: Cotadutide is safe and effective in reducing plasma glucose levels, HbA1c and body weight in individuals with type 2 diabetes. TRIAL REGISTRATION: The study protocol was registered on PROSPERO (CRD: CRD42021257670 ).

Pycnogenol a promising remedy for diabetic keratopathy in experimentally induced corneal alkali burns in diabetic rats.

AIM: This study aimed to investigate the efficiency of topically applied pycnogenol (PYC) in healing the standardized alkaline corneal ulcer in diabetic and normal rats. MATERIALS AND METHODS: The corneal alkali-burn injury (CA-I) model was unilaterally developed in Wistar rats by filter paper saturated with 0.01 M of NaOH and touching the eyes for 45 s. Rats were divided into four groups: Normal control (NC), normal PYC (NPYC), diabetic control (DC), and diabetic PYC (DPYC). Both NPYC and DPYC groups were daily treated with PY eye drops three times, whereas NC and DC ones were treated with ordinary saline for six successive days. RESULTS: The wound healing of corneal epithelial was improved in the NPYC group compared to the NC group. Meanwhile, it was significantly improved (P < 0.05) in the DPYC group than in the DC group. Histological examination revealed that corneal re-epithelialization was more accomplished in the DPYC group than in the DC group. In addition, the inflammatory cells were augmented in the DC group more than those in the DPYC one. CONCLUSION: The findings obtained revealed the efficiency of PYC for enhancing the corneal re-epithelialization and reducing the inflammatory reaction post alkali burn in rats, and thus it could be beneficially valuable as a treatment for the diabetic keratopathy.

Comparison of leakage pressures of vesicourethral anastomosis performed with intracorporeal suturing in a simulator and conventional suturing ex vivo in canine cadaveric tissue.

OBJECTIVE: To compare conventional and intracorporeal vesicourethral anastomosis (VUA) in canine cadaveric tissue. STUDY DESIGN: Cadaveric ex vivo study. STUDY POPULATION: Twenty-eight canine bladders with urethra. METHODS: Specimens after prostatectomy were randomly divided into intracorporeal (I) group or conventional (C) group. For the I group, VUA was performed in a simulator with laparoscopic needle holders and telescope. For the C group, the anastomosis was performed in vitro with standard instruments. The VUA was performed with 4-0 monofilament absorbable suture and was completed with two simple continuous sutures. Surgical time, leakage pressure, site of leakage, and number of suture bites were recorded. RESULTS: Fourteen samples were entered in each group. The dorsal side of the anastomosis was initially performed, followed by the ventral side. The median suturing time was 30.8 minutes (range, 19.3-39.2) for the I group and 17.3 minutes (range, 9.2-21.3) for the C group (P < .0001). The median leakage pressure was 10.9 mm Hg (range, 4.1-29.7) for the I group and 10.8 mm Hg (range, 6.2-18.5) for the C group (P = .94). The median number of stitches was 20 (range, 14-26) for the I group and 19 (range, 11-28) for the C group (P = .96). The distribution of the site of leakage was similar between groups (P = .381). CONCLUSION: Vesicourethral anastomosis can be performed with leakage pressures similar to intracorporeal and conventional suturing. CLINICAL SIGNIFICANCE: This study represents the first step toward laparoscopic radical prostatectomy in dogs.

Thoracoscopic treatment of persistent right aortic arch in dogs with and without one lung ventilation.

OBJECTIVE: To evaluate thoracoscopic treatment of persistent right aortic arch (PRAA) in dogs with and without the use of one lung ventilation (OLV). STUDY DESIGN: Retrospective cohort study. ANIMALS: Twenty-two (client-owned and shelter) dogs diagnosed with PRAA. METHODS: Medical records were reviewed retrospectively and intraoperative and immediate postoperative data were compared between dogs that underwent thoracoscopic treatment of PRAA with (OLV+) and without (OLV-) OLV. RESULTS: Ten of the 12 dogs in the OLV+ group and 7/10 dogs in the OLV- group had their left ligamentum arteriosum successfully ligated during thoracoscopy. Median surgical time, surgery complications, anesthesia complications, and rate of conversion to an open thoracotomy due to limited visualization or surgical complications were similar between the two groups. CONCLUSION: Thoracoscopic treatment of PRAA can be performed with or without OLV. Surgical time, intraoperative complications, and conversion rates were similar between dogs that underwent thoracoscopic treatment of PRAA with and without OLV. OLV may not have contributed to improved visualization in this group of dogs. CLINICAL SIGNIFICANCE (OR IMPACT): The use of OLV is safe during thoracoscopic treatment of PRAA. OLV did not appear to provide significant benefits in this case series and thoracoscopic treatment of PRAA in dogs may be performed successfully with or without the use of OLV.

Development of Semisynthetic Apoptosis-Inducing Agents Based on Natural Phenolic Acids Scaffold: Design, Synthesis and In-Vitro Biological Evaluation.

A crucial target in drug research is magnifying efficacy and decreasing toxicity. Therefore, using natural active constituents as precursors will enhance both safety and biological activities. Despite having many pharmacological activities, caffeic and ferulic acids showed limited clinical usage due to their poor bioavailability and fast elimination. Therefore, semisynthetic compounds from these two acids were prepared and screened as anticancer agents. In this study, CA and FA showed very potent anticancer activity against Caco-2 cells. Consequently, eighteen derivatives were tested against the same cell line. Four potent candidates were selected for determination of the selectivity index, where compound 10 revealed a high safety margin. Compound 10 represented a new scaffold and showed significant cytotoxic activity against Caco-2. Cell-cycle analysis and evaluation of apoptosis showed that derivatives 10, 7, 11, 15 and 14 showed the highest proportion of cells in a late apoptotic stage.

Readmissions after cholecystectomy in a tertiary UK centre: Incidence, causes and burden.

CONTEXT: Although cholecystectomy is a widely performed procedure, post-operative readmissions place a heavy burden on healthcare facilities. AIMS: This study assesses the incidence, causes and burden of 30-day readmissions after cholecystectomy in a tertiary UK centre. SETTINGS AND DESIGN: This study was conducted at a university hospital, and the study design involves retrospective cohort study. MATERIALS AND METHODS: Information was obtained from our prospectively maintained database and hospital's computerised records. STATISTICAL ANALYSIS: The encounters are expressed in numbers and percentages. The hospital stay, body mass index and age are expressed in mean, standard deviation (SD), min-max and median. Microsoft Excel® was used to calculate the means, SD, min-max and median. RESULTS: Out of the 1140 cholecystectomies performed over this time, there were 75 true readmissions and 29 revisits; thus, the actual readmission rate is 6.58%. Non-specific abdominal pain ± deranged liver function test (LFT) is the most common cause of readmissions/ revisits in (38; 36.54%) cases, followed by (18; 17.31%) wound infections and (12; 11.54%) collections/bile leaks/abscess. This cost the centre 93 scans, 30 procedures and 295 days of hospital stay. CONCLUSIONS: Non-specific abdominal pain ± deranged LFT is the most common cause of readmissions/revisits in the centre. Readmissions after a cholecystectomy are a significant encumbrance.

CROSSMAPPER: estimating cross-mapping rates and optimizing experimental design in multi-species sequencing studies.

MOTIVATION: Numerous sequencing studies, including transcriptomics of host-pathogen systems, sequencing of hybrid genomes, xenografts, mixed species systems, metagenomics and meta-transcriptomics, involve samples containing genetic material from divergent organisms. A crucial step in these studies is identifying from which organism each sequencing read originated, and the experimental design should be directed to minimize biases caused by cross-mapping of reads to incorrect source genomes. Additionally, pooling of sufficiently different genetic material into a single sequencing library could significantly reduce experimental costs but requires careful planning and assessment of the impact of cross-mapping. Having these applications in mind we designed Crossmapper, the first to our knowledge tool able to assess cross-mapping prior to sequencing, therefore allowing optimization of experimental design. RESULTS: Using any combination of reference genomes, Crossmapper performs read simulation and back-mapping of those reads to the pool of references, quantifies and reports the cross-mapping rates for each organism. Crossmapper performs these analyses with numerous user-specified parameters, including, among others, read length, read layout, coverage, mapping parameters, genomic or transcriptomic data. Additionally, it outputs the results in highly interactive and publication-ready reports. This allows the user to perform multiple comparisons at once and choose the experimental setup minimizing cross-mapping rates. Moreover, Crossmapper can be used for resource optimization in sequencing facilities by pooling different samples into one sequencing library. AVAILABILITY AND IMPLEMENTATION: Crossmapper is a command line tool implemented in Python 3.6 and available as a conda package, allowing effortless installation. The source code, detailed information and a step-by-step tutorial is available at our GitHub page https://github.com/Gabaldonlab/crossmapper. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Self-assembly of millimeter-scale magnetic particles in suspension.

Self-assembly is ubiquitous at all scales in nature. Most studies have focused on the self-assembly of micron-scale and nano-scale components. In this study, we explore the self-assembly of millimeter-scale magnetic particles in a bubble-column reactor to form 9 different structures. Two component systems (N-N and S-S particles) assemble faster than one-component systems (all particles have N-S poles) because they have more numerous bonding pathways. In addition, two-components add control to process initiation and evolution, and enable the formation of complex structures such as squares, tetrahedra and cubes. Self-assembly is collision-limited, thus, the formation time increases with the total number of bonds required to form the structure and the injected power. The dimensionless Mason number captures the interplay between hydrodynamic forces and magnetic interactions: self-assembly is most efficient at intermediate Mason numbers (the system is quasi-static at low Mason numbers with limited chances for particle interaction; on the other hand, hydrodynamic forces prevail over dipole-dipole interactions and hinder bonding at high Mason numbers). Two strategies to improve yield involve (1) the inclusion of pre-assembled nucleation templates to prevent the formation of incorrect initial structures that lead to kinetic traps, and (2) the presence of boundaries to geometrically filter unwanted configurations and to overcome kinetic traps through particle-wall collisions. Yield maximization involves system operation at an optimal Mason number, the inclusion of nucleation templates and the use of engineered boundaries (size and shape).

Comparison between long and lower medial head triceps branches in dual neurotization for shoulder function restoration in upper brachial plexus palsy.

PURPOSE: In upper brachial plexus injury (UBPI), restoring shoulder function is crucial. This study compares the transfer of long and lower medial heads of triceps branches to the axillary nerve to achieve proper restoration of function. PATIENTS AND METHODS: A retrospective comparative study was conducted between two groups of patients with (UBPI). Group I patients (10) [mean age: 19 ± 10.6 years] were managed by transferring triceps long head branch to axillary nerve while group II patients (8) [mean age: 26 ± 9.6 years] were managed by triceps lower medial head branch transfer. The mean time from injury to surgery was 6 ± 1.3 and 5 ± 1.7 months respectively. All patients were followed up for a minimum of 12 months with the assessment of VAS, DASH score, active range of motion (AROM) and strength of shoulder abduction and external rotation; in addition to shoulder endurance and strengths of donors. Postoperative, three-monthly, electrodiagnostic assessments were performed. RESULTS: Postoperatively, the mean VAS and DASH scores; in addition to endurance time, showed significant enhancement in both groups. Patients in both groups have accomplished a mean abduction (AROM) of 98° ± 27.9 and 97° ± 11.9 respectively. The mean external rotation (AROM) was 48° ± 18.4 and 47° ± 9.2 respectively. Furthermore, group II patients had less triceps morbidity in addition to earlier and enhanced electrophysiological recovery. CONCLUSIONS: Dual neurotization for shoulder function restoration in (UBPI) is capable of providing proper functional results with minimal donor morbidity. The triceps lower medial branch provides an excelling donor due to less triceps morbidity, extra length; yet, earlier and enhanced electrophysiological recovery.

Ex vivo comparison of hand-sutured versus circular stapled anastomosis in canine large intestine.

OBJECTIVE: To compare leakage pressures of colonic anastomoses performed with circular staplers to conventional hand-sewn techniques in dogs. STUDY DESIGN: Ex-vivo study. ANIMALS: Colon from 11 canine cadavers. METHODS: Thirty-two colonic anastomoses were performed. Four segments from each colon were randomly assigned to one of four techniques: hand-sewn colonic anastomoses performed with 4-0 glycomer 631 (G) and 4-0 barbed glycomer 631 (BG), and circular stapled colonic anastomoses using 4.8 mm End-to-End Anastomosis (EEA C4.8mm) and 3.5 mm End-to-End Anastomosis (EEA C3.5mm), 21 mm diameter circular staples in cadaveric canine colon. Leakage pressure was defined as the pressure at which dye-containing solution was first observed to leak from the anastomosis site. RESULTS: Leakage pressures were 49.5 mmHg (range:16-72) in group G, 45.5 mmHg (range:19-80) in group BG, 5.3 mmHg (range:0-31) in group C3.5mm, and 29.5 mmHg (range:23-50.3) in group C4.8mm. Anastomoses leaked at lower pressures when stapled rather than hand-sewn (C4.8mm-G p = .0313, C4.8mm-BG p = .0131, C3.5mm-G p = .0469, C3.5mm-BG p = .0313). Two of the C3.5mm constructs leaked immediately after saline infusion with 4/6 leaking at <5.3 mmHg. CONCLUSION: End-to-end colonic anastomoses closed with circular stapler leaked at lower pressures than hand-sutured anastomoses. Use of the EEA stapler with a staple height of 3.5 mm did not result in safe colonic anastomoses. CLINICAL SIGNIFICANCE: These results provide evidence to support hand-suturing colonic anatomoses with G and BG in dogs. The 4.8 mm staples may be considered in anatomical locations difficult to reach.

nextPARS: parallel probing of RNA structures in Illumina.

RNA molecules play important roles in virtually every cellular process. These functions are often mediated through the adoption of specific structures that enable RNAs to interact with other molecules. Thus, determining the secondary structures of RNAs is central to understanding their function and evolution. In recent years several sequencing-based approaches have been developed that allow probing structural features of thousands of RNA molecules present in a sample. Here, we describe nextPARS, a novel Illumina-based implementation of in vitro parallel probing of RNA structures. Our approach achieves comparable accuracy to previous implementations, while enabling higher throughput and sample multiplexing.

Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of Candida tropicalis blood isolates.

Candida tropicalis is one of the major candidaemia agents, associated with the highest mortality rates among Candida species, and developing resistance to azoles. Little is known about the molecular mechanisms of azole resistance, genotypic diversity, and the clinical background of C. tropicalis infections. Consequently, this study was designed to address those questions. Sixty-four C. tropicalis bloodstream isolates from 62 patients from three cities in Iran (2014-2019) were analyzed. Strain identification, antifungal susceptibility testing, and genotypic diversity analysis were performed by MALDI-TOF MS, CLSI-M27 A3/S4 protocol, and amplified fragment length polymorphism (AFLP) fingerprinting, respectively. Genes related to drug resistance (ERG11, MRR1, TAC1, UPC2, and FKS1 hotspot9s) were sequenced. The overall mortality rate was 59.6% (37/62). Strains were resistant to micafungin [minimum inhibitory concentration (MIC) ≥1 µg/ml, 2/64], itraconazole (MIC > 0.5 µg/ml, 2/64), fluconazole (FLZ; MIC ≥ 8 µg/ml, 4/64), and voriconazole (MIC ≥ 1 µg/ml, 7/64). Pan-azole and FLZ + VRZ resistance were observed in one and two isolates, respectively, while none of the patients were exposed to azoles. MRR1 (T255P, 647S), TAC1 (N164I, R47Q), and UPC2 (T241A, Q340H, T381S) mutations were exclusively identified in FLZ-resistant isolates. AFLP fingerprinting revealed five major and seven minor genotypes; genotype G4 was predominant in all centers. The increasing number of FLZ-R C. tropicalis blood isolates and acquiring FLZ-R in FLZ-naive patients limit the efficiency of FLZ, especially in developing countries. The high mortality rate warrants reaching a consensus regarding the nosocomial mode of C. tropicalis transmission.

Protective and antioxidant effects of copper-nicotinate complex against glycerol-induced nephrotoxicity in rats.

Copper-nicotinate complex (CNC) has antioxidant activities through scavenging of free radicals formed inside the body. CNC also has anti-tumor and anti-inflammatory activities. The current study was designed to determine the effect of glycerol on rat kidney function and oxidative stress as well as, the potential nephroprotective effects of CNC. Forty male Wistar rats were randomly allocated into four equal groups. The groups of rats were as follows: GI was kept under normal control conditions; GII was orally given CNC at a dose of 0.043 mg kg-1 body weight (BW), three times/week for 4 weeks; GIII was administered glycerol (topical application) at a dose of 3.15 ml kg-1 BW daily for 4 weeks; and GIV was given CNC and glycerol with the same dose and route. The results revealed that CNC improves the renal dysfunctions induced by glycerol by recovering the levels of urea and creatinine to normal, as well as through the antioxidant status manifested by the normalization of catalase, superoxide dismutase, reduced glutathione, and malondialdehyde levels. Moreover, by its effect as an anti-oxidant, CNC reduces the effect of glycerol on the kidney by decreasing the fibrosis, degenerative changes and necrotic changes in the renal tubules. In conclusion, CNC could alleviate the side effects that might be caused by glycerol.

Transcriptomic and biochemical effects of pycnogenol in ameliorating heat stress-related oxidative alterations in rats.

BACKGROUND: Heat stress is a condition that is due to extreme heat exposure. It occurs when the body cannot keep its temperature healthy in response to a hot climate and associated with oxidative stress. Testicular hyperthermia can induce apoptosis of sperm cells, affect sperm production and decrease sperm concentration, leading to sperm disorder, for this reason, we examined the protective impact of pycnogenol that it has a wide range of biological benefits, including antioxidant, anti-inflammatory and anti-cancer activities against the oxidative alterations that happen in testicular and brain tissues due to heat stress in rats. STUDY DESIGN: Forty-eight Wistar male rats, approximately around 6 weeks age were allocated randomly into four groups (12 in each) of control, HS (subjected to heat stress and supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days), and pycnogenol (rats supplemented orally with 50 mg of pycnogenol/kg b. w./day dissolved in saline for 21 days). RESULTS: Data revealed a promising role of pycnogenol as an antioxidant, natural product to successfully reverse the heat-induced oxidative alterations in testicular and brain tissues of rats through significant upregulation of superoxide dismutase-2, catalase, reduced glutathione, and anti-apoptotic gene, while downregulating pro-apoptotic, and heat shock protein70. Pycnogenol treatment also reversed the reproductive hormone level and spermatogenesis to their normal values. CONCLUSION: Pycnogenol as a natural protective supplement could recover these heat stress-induced oxidative changes in testes and hypothalamus.