Effect of different lung recruitment strategies and airway device on oscillatory mechanics in children under general anaesthesia.

BACKGROUND: Atelectasis has been reported in 68 to 100% of children undergoing general anaesthesia, a phenomenon that persists into the recovery period. Children receiving recruitment manoeuvres have less atelectasis and fewer episodes of oxygen desaturation during emergence. The optimal type of recruitment manoeuvre is unclear and may be influenced by the airway device chosen. OBJECTIVE: We aimed to investigate the different effects on lung mechanics as assessed by the forced oscillation technique (FOT) utilising different recruitment strategies: repeated inflations vs. one sustained inflation and different airway devices, a supraglottic airway device vs. a cuffed tracheal tube. DESIGN: Pragmatic enrolment with randomisation to the recruitment strategy. SETTING: We conducted this single-centre trial between February 2020 and March 2022. PARTICIPANTS: Seventy healthy patients (53 boys) aged between 2 and 16 years undergoing general anaesthesia were included. INTERVENTIONS: Forced oscillations (5 Hz) were superimposed on the ventilator waveform using a customised system connected to the anaesthesia machine. Pressure and flow were measured at the inlet of the airway device and used to compute respiratory system resistance and reactance. Measurements were taken before and after recruitment, and again at the end of surgery. MAIN OUTCOME MEASURES: The primary endpoint measured is the change in respiratory reactance. RESULTS: Statistical analysis (linear model with recruitment strategy and airway device as factors) did not show any significant difference in resistance and reactance between before and after recruitment. Baseline reactance was the strongest predictor for a change in reactance after recruitment: prerecruitment Xrs decreased by mean (standard error) of 0.25 (0.068) cmH 2 O s l -1 per  1 cmH 2 O -1  s l -1 increase in baseline Xrs ( P  < 0.001). After correcting for baseline reactance, the change in reactance after recruitment was significantly lower for sustained inflation compared with repeated inflation by mean (standard error) 0.25 (0.101) cmH 2 O ( P  = 0.0166). CONCLUSION: Although there was no significant difference between airway devices, this study demonstrated more effective recruitment via repeated inflations than sustained inflation in anaesthetised children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001434189.

Differential impact of COVID-19 on mental health and burnout.

BACKGROUND: There may be differential impact of the COVID-19 pandemic on mental health and burnout rates of healthcare professionals (HCPs) performing different roles. AIMS: To examine mental health and burnout rates, and possible drivers for any disparities between professional roles. METHODS: In this cohort study, online surveys were distributed to HCPs in July-September 2020 (baseline) and re-sent 4 months later (follow-up; December 2020) assessing for probable major depressive disorder (MDD), generalized anxiety disorder (GAD), insomnia, mental well-being and burnout (emotional exhaustion and depersonalization). Separate logistic regression models (at both phases) compared the risk of outcomes between roles: healthcare assistants (HCAs), nurses and midwives (nurses), allied health professionals (AHPs) and doctors (reference group). Separate linear regression models were also developed relating the change in scores to professional role. RESULTS: At baseline (n = 1537), nurses had a 1.9-fold and 2.5-fold increased risk of MDD and insomnia, respectively. AHPs had a 1.7-fold and 1.4-fold increased risk of MDD and emotional exhaustion, respectively. At follow-up (n = 736), the disproportionate risk between doctors and others worsened: nurses and HCAs were at 3.7-fold and 3.6-fold increased risk of insomnia, respectively. Nurses also had a significantly increased risk of MDD, GAD, poor mental well-being and burnout. Nurses also had significantly worsened anxiety, mental well-being and burnout scores over time, relative to doctors. CONCLUSIONS: Nurses and AHPs had excess risk of adverse mental health and burnout during the pandemic, and this difference worsened over time (in nurses especially). Our findings support adoption of targeted strategies accounting for different HCP roles.

Predicting obstructive sleep apnoea and perioperative respiratory adverse events in children: role of upper airway collapsibility measurements.

BACKGROUND: Obstructive sleep apnoea (OSA) and perioperative respiratory adverse events are significant risks for anaesthesia in children undergoing adenotonsillectomy. Upper airway collapse is a crucial feature of OSA that contributes to respiratory adverse events. A measure of upper airway collapsibility to identify undiagnosed OSA can help guide perioperative management. We investigated the utility of pharyngeal closing pressure (PCLOSE) for predicting OSA and respiratory adverse events. METHODS: Children scheduled for elective adenotonsillectomy underwent in-laboratory polysomnography 2-12 weeks before surgery. PCLOSE measurements were obtained while the child was anaesthetised and breathing spontaneously just before surgery. Logistic regression was used to assess the predictive performance of PCLOSE for detecting OSA and perioperative respiratory adverse events after adjusting for potential covariates. RESULTS: In 52 children (age, mean [standard deviation] 5.7 [1.8] yr; 20 [38%] females), airway collapse during PCLOSE was observed in 42 (81%). Of these, 19 of 42 (45%) patients did not have OSA, 15 (36%) had mild OSA, and eight (19%) had moderate-to-severe OSA. All 10 children with no evidence of airway collapse during the PCLOSE measurements did not have OSA. PCLOSE predicted moderate-to-severe OSA (odds ratio [OR] 1.71; 95% confidence interval [CI]: 1.2-2.8; P=0.011). All children with moderate-to-severe OSA could be identified at a PCLOSE threshold of -4.0 cm H2O (100% sensitivity), and most with no or mild OSA were ruled out (64.7% specificity; receiver operating characteristic/area under the curve=0.857). However, there was no significant association between respiratory adverse events and PCLOSE (OR 1.0; 95% CI: 0.8-1.1; P=0.641). CONCLUSIONS: Measurement of PCLOSE after induction of anaesthesia can reliably identify moderate or severe OSA but not perioperative respiratory adverse events in children before adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ANZCTR ACTRN 12617001503314.

Pseudoprolines as stereoelectronically tunable proline isosteres.

The cyclic structure of proline (Pro) confers unique conformational properties on this natural amino acid that influences polypeptide structure and function. Pseudoprolines are a family of Pro isosteres that incorporate a heteroatom, most prominently oxygen or sulfur but also silicon and selenium, to replace the Cß or Cγ carbon atom of the pyrrolidine ring. These readily synthetically accessible structural motifs can facilitate facile molecular editing in a fashion that allows modulation of the amide bond topology of dipeptide elements and influence over ring pucker. While the properties of pseudoprolines have been exploited most prominently in the design of oligopeptide analogues, they have potential application in the design and optimization of small molecules. In this Digest, we summarize the physicochemical properties of pseudoprolines and illustrate their potential in drug discovery by surveying examples of applications in the design of bioactive molecules.

Temporal dysregulation of genes in lamb testis cell during sheeppox virus infection.

The present study was aimed to elucidate the host-virus interactions using RNA-Seq analysis at 1 h and 8 h of post-infection of sheeppox virus (SPPV) in lamb testis cell. The differentially expressed genes (DEGs) and the underlying mechanisms linked to the host immune responses were obtained. The protein-protein interaction (PPI) network analysis and ingenuity pathway analysis (IPA) illustrated the interaction between the DEGs and their involvement in cell signalling responses. Highly connected hubs viz. AURKA, CHEK1, CCNB2, CDC6 and MAPK14 were identified through PPI network analysis. IPA analysis showed that IL-6- and ERK5-mediated signalling pathways were highly enriched at both time points. The TP53 gene was identified to be the leading upstream regulator that directly responded to SPPV infection, resulting in downregulation at both time points. The study provides an overview of how the lamb testis genes and their underlying mechanisms link to growth and immune response during SPPV infection.

Outcomes of brief versions of Dialectical Behaviour Therapy for diagnostically heterogeneous groups in a routine care setting.

INTRODUCTION: Brief versions of Dialectical Behaviour Therapy (DBT) may enhance patient outcomes in diverse service settings. This study examined the effectiveness of two DBT-informed treatments for diagnostically heterogeneous groups in routine practice: 5-day group training in DBT skills (DBT-5) and a 12-week DBT program (DBT-12). METHODS: : Depression, anxiety, stress, borderline symptoms, self-esteem, and general mental wellbeing were measured at pre-and post-treatment in a sample of inpatients and outpatients (N=395). Rates of clinically significant change on these measures were calculated and effect sizes benchmarked against prior DBT outcome studies. Readmission rates were used to measure treatment response maintenance. RESULTS: : Scores on all measures improved significantly from pre- to post-treatment. DBT-5 and DBT-12 yielded similar effect sizes compared to prior DBT outcome studies. At least 43.5% of patients were classified as recovered or improved regarding borderline symptoms at the end of both DBT-5 and DBT-12. Readmission rates were also low (5%-6.8%). CONCLUSIONS: Brief DBT-informed treatments may offer a fast reduction in symptoms and quicker return to functioning.

Essential oil combinations against Clostridium perfringens and Clostridium septicum - the causative agents of gas gangrene.

AIMS: The inhibitory and bactericidal effect of a wide range of essential oils, and their selected combinations against two pathogens (Clostridium perfringens and Clostridium septicum), the causative pathogens of gas gangrenous infections were investigated. Fractional inhibitory indices were also calculated to determine the interactions. METHODS AND RESULTS: The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) assays were used to determine the efficacy of the essential oils. Santalum austrocaledonicum demonstrated the highest activity inhibiting both Clostridial pathogens at the lowest concentration of 0·02 mg ml-1 . Santalum austrocaledonicum combined with Cymbopogon martinii had the strongest inhibition against C. perfringens (MIC 0·02 mg ml-1 ) and C. septicum (MIC 0·01 mg ml-1 ). Selected combinations demonstrated synergy (ΣFIC ≤ 0·50) in combination against both pathogens tested. Antagonism was also observed in many combinations. CONCLUSIONS: Selected essential oils, when studied either individually or in combination, have high inhibitory and bactericidal effects against both Clostridial strains. Nine combinations have proven to be synergistic with 23 combinations additive; 96 indifferent and 77 having an antagonistic effect against the pathogenic strains. Some combinations demonstrated extreme antagonism and as such, careful consideration needs to be given to essential oil selection against these pathogens. SIGNIFICANT IMPACT OF THE STUDY: Very few essential oils have been antimicrobially screened (MIC and MBC) against Clostridial strains and furthermore, the efficacies in combination are not known.

High-value alcohols and higher-oxidation-state compounds by catalytic Z-selective cross-metathesis.

Olefin metathesis catalysts provide access to molecules that are indispensable to physicians and researchers in the life sciences. A persisting problem, however, is the dearth of chemical transformations that directly generate acyclic Z allylic alcohols, including products that contain a hindered neighbouring substituent or reactive functional units such as a phenol, an aldehyde, or a carboxylic acid. Here we present an electronically modified ruthenium-disulfide catalyst that is effective in generating such high-value compounds by cross-metathesis. The ruthenium complex is prepared from a commercially available precursor and an easily generated air-stable zinc catechothiolate. Transformations typically proceed with 5.0 mole per cent of the complex and an inexpensive reaction partner in 4-8 hours under ambient conditions; products are obtained in up to 80 per cent yield and 98:2 Z:E diastereoselectivity. The use of this catalyst is demonstrated in the synthesis of the naturally occurring anti-tumour agent neopeltolide and in a single-step stereoselective gram-scale conversion of a renewable feedstock (oleic acid) to an anti-fungal agent. In this conversion, the new catalyst promotes cross-metathesis more efficiently than the commonly used dichloro-ruthenium complexes, indicating that its utility may extend beyond Z-selective processes.

Prior administration of chocolate improves the palatability of bitter drugs: The Choc-with-Med study.

AIM: The paediatric population has a low adherence and acceptance rate of unpalatable medicines. This study aimed to determine whether eating chocolate immediately prior to drug administration would help to mask the bitter taste of a drug. The difference in taste masking efficacy between white, milk and dark chocolate was a secondary measure outcome. METHODS: A controlled repeated measures crossover taste trial was conducted using a taste panel of 29 young healthy adults who met the criteria to differentiate intensity in bitterness taste. Participants separately tasted solutions of quinine, flucloxacillin and clindamycin using the swill and spit method, singularly and following blinded prior administration of white, milk or dark chocolate. Drug solutions administered without prior chocolate served as controls. Bitterness score for each tasting was recorded using a 5-point scale. RESULTS: Regardless of chocolate type, mean taste scores with prior chocolate for quinine (range 2.00-2.34), clindamycin (3.72-3.83) and flucloxacillin (3.38-3.45) were all lower than mean scores for respective drugs without chocolate (3.24, 4.75 and 4.28, respectively; P < 0.0001 for all comparisons). Dark chocolate was most efficacious for masking the bitter taste of quinine, but the differences in taste masking efficacy between dark, milk and white chocolates were not statistically significant for flucloxacillin and clindamycin. CONCLUSIONS: Prior administration of chocolate results in lower perceived bitterness compared to control tastings of quinine, flucloxacillin and clindamycin solutions; however, there is no clear difference in this effect between the dark, milk and white chocolates used in this study.

Morphology of the entering and exiting nerve as a differentiating feature of benign from malignant peripheral nerve sheath tumours of the brachial plexus.

OBJECTIVE: To identify if morphology of the entering and exiting nerve involved by a nerve sheath tumour in the brachial plexus can help differentiate between benign (B) and malignant (M) peripheral nerve sheath tumours (PNSTs). MATERIALS AND METHODS: Retrospective review of 85 patients with histologically confirmed primary PNSTs of the brachial plexus over a 12.5-year period. Clinical data and all available MRI studies were independently evaluated by 2 consultant musculoskeletal radiologists blinded to the final histopathological diagnosis assessing for maximal lesion dimension, visibility and morphology of the entering and exiting nerve, and other well-documented features of PNSTs. RESULTS: The study included 47 males and 38 females with mean age 46.7 years (range, 8-81 years). There were 73 BPNSTs and 12 MPNSTs. The entering nerve was not identified in 5 (7%), was normal in 17 (23%), was tapered in 38 (52%) and showed lobular enlargement in 13 (18%) BPNSTs compared with 0 (0%), 0 (0%), 2 (17%) and 10 (83%) MPNSTs respectively. The exiting nerve was not identified in 5 (7%), was normal in 20 (27%), was tapered in 42 (58%) and showed lobular enlargement in 6 (8%) BPNSTs compared with 4 (33%), 0 (0%), 2 (17%) and 6 (50%) MPNSTs respectively. Increasing tumour size, entering and exiting nerve morphology and suspected MRI diagnosis were statistically significant differentiators between BPNST and MPNST (p < 0.001). IOC for nerve status was poor to fair but improved to good if normal/tapered appearance were considered together with improved specificity of 81-91% for BPNST and sensitivity of 75-83%. CONCLUSIONS: Morphology of the adjacent nerve is a useful additional MRI feature for distinguishing BPNST from MPNST of the brachial plexus.

Placental Swab in Supporting Diagnosis of Vertical Transmission in SARS-CoV-2 Positive Mothers.

Aims To review the evidence regarding the possibility of fetal vertical transmission in COVID-19 positive pregnant mothers by diagnosing through placental swabs. Methods The search terms 'pregnant COVID-19 positive mothers', 'fetal vertical transmission' and 'placental swabs' were used. 20 papers were selected. Results 183 COVID-19 positive pregnant women were identified whose 184 placentas and 185 neonates were also analysed by RT-PCR or immunohistochemistry and/or in situ hybridization for the presence of SARS-CoV-2 (one case of monochorionic diamniotic twins and one case of dichorionic diamniotic twins). 183 liveborn neonates were successfully delivered primarily via caesarean section (99%). 2 mothers did not deliver liveborn infants due to severe preeclampsia resulting in a termination of pregnancy and a miscarriage, both occurring in the second trimester. 9 neonates tested positive for SARS-CoV-2 (5%). We report no neonatal mortality after live birth and no maternal mortality. 17 placentas tested positive for SARS-CoV-2 out of a total of 184 tested (9%). Of these 17, 7 cases of SARS-CoV-2 were identified in the maternal, neonatal and placental tissue. Conclusion There is no concrete evidence of vertical transmission occurring between mother and infant. We propose further research investigating the effects of COVID-19 on pregnant women by using RT-PCR to test the mother, placenta, vaginal fluid, breast milk and infant for SARS-CoV-2 at various stages of transmission.

Plasmodium falciparum Cyclic GMP-Dependent Protein Kinase Interacts with a Subunit of the Parasite Proteasome.

Malaria is caused by the protozoan parasite Plasmodium, which undergoes a complex life cycle in a human host and a mosquito vector. The parasite's cyclic GMP (cGMP)-dependent protein kinase (PKG) is essential at multiple steps of the life cycle. Phosphoproteomic studies in Plasmodium falciparum erythrocytic stages and Plasmodium berghei ookinetes have identified proteolysis as a major biological pathway dependent on PKG activity. To further understand PKG's mechanism of action, we screened a yeast two-hybrid library for P. falciparum proteins that interact with P. falciparum PKG (PfPKG) and tested peptide libraries to identify its phosphorylation site preferences. Our data suggest that PfPKG has a distinct phosphorylation site and that PfPKG directly phosphorylates parasite RPT1, one of six AAA+ ATPases present in the 19S regulatory particle of the proteasome. PfPKG and RPT1 interact in vitro, and the interacting fragment of RPT1 carries a PfPKG consensus phosphorylation site; a peptide carrying this consensus site competes with the RPT1 fragment for binding to PfPKG and is efficiently phosphorylated by PfPKG. These data suggest that PfPKG's phosphorylation of RPT1 could contribute to its regulation of parasite proteolysis. We demonstrate that proteolysis plays an important role in a biological process known to require Plasmodium PKG: invasion by sporozoites of hepatocytes. A small-molecule inhibitor of proteasomal activity blocks sporozoite invasion in an additive manner when combined with a Plasmodium PKG-specific inhibitor. Mining the previously described parasite PKG-dependent phosphoproteomes using the consensus phosphorylation motif identified additional proteins that are likely to be direct substrates of the enzyme.

In vitro potentiation of carbapenems with tannic acid against carbapenemase-producing enterobacteriaceae: exploring natural products as potential carbapenemase inhibitors.

AIMS: We hypothesized and confirmed that tannic acid (TA) reverses carbapenem resistance by inhibiting carbapenemases in class A and B carbapenemase-producing Enterobacteriaceae. METHODS AND RESULTS: Minimum inhibitory concentrations of carbapenems in the presence and absence of TA and other efflux pump inhibitors, TA-carbapenemases inhibition assays and computational studies showed that TA had the greatest effect on metallo-ß-lactamases (MBLs) followed by class A serine-ß-lactamases (SBLs). TA completely reversed the MICs of MBL producers from between 32 and ≥512 mg l-1 to susceptible values (<4 mg l-1 ) while substantially reducing the MICs of SBLs from between 16 and >512 mg l-1 to <4 to 16 mg l-1 . Tolerable cytotoxic effect was observed for the concentrations tested (8-1024 mg l-1 ). TA inhibited enzymes with a marked difference of ≈50% inhibition (IC50 ) for NDM-1 (270 µmol l-1 ) and KPC-2 (15  µmol l-1 ). CONCLUSION: TA inhibited both MBLs and SBLs by targeting their hydrophobic sites. Moreover, TA had a stronger binding affinity for MBLs than SBLs as the MBLs, specifically VIM-1 (-43·7220 ± 0·4513 kcal mol-1 ) and NDM-1(-44·2329 ± 0·3806 kcal mol-1 ), interact with a larger number of their catalytic active-site residues than that of OXA-48 (-22·5275 ±  0·1300 kcal mol-1 ) and KPC-2 (-22·1164 ± 0·0111 kcal mol-1 ). SIGNIFICANCE AND IMPACT OF THE STUDY: Tannic acid or its analogues could be developed into carbapenemase-inhibiting adjuvants to restore carbapenem activity in CRE infections, save many lives and reduce healthcare associated costs.

Antineoplastic influence of nimesulide in chemically induced hepatocellular carcinoma by inhibition of DNA synthesis.

Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150 mg/kg) intraperitoneally. Duration of the in vivo study was 12 weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [3H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE2 effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).

Catalytic Arylhydroxylation of Dehydroalanine in Continuous Flow for Simple Access to Unnatural Amino Acids.

This report discloses the first example of catalytic arylhydroxylation of dehydroalanine with aryldiazonium salts. Aryldiazonium salts, which are generated from aniline precursors under partially aqueous conditions in continuous flow, efficiently reacted with dehydroalanine in the presence of 10-15 mol % ferrocene to furnish α-hydroxyarylalanine derivatives (up to 82 % yield). The reactions proceeded with regioselectivity, broad functional group tolerance, and without polymerization of the dehydroalanine. Furthermore, the products were used to access α-unnatural amino acids, important targets with application in drug development.

Effect of mesalazine on recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease: a meta-analysis with trial sequential analysis of randomized controlled trials.

AIM: he aim was to investigate the effect of mesalazine on the recurrence of diverticulitis in patients with symptomatic uncomplicated diverticular disease (SUDD). METHODS: We performed a systematic review and conducted a search of electronic information sources to identify all randomized controlled trials (RCTs) investigating the effect of mesalazine on the recurrence of diverticulitis in patients with SUDD. We used the Cochrane tool to assess the quality of included studies. Random effects models were applied to calculate pooled outcome data. Trial sequential analysis was performed to assess the possibility of type I or II errors and to compute the information size required for conclusive meta-analysis. RESULTS: We identified six RCTs which enrolled a total of 1918 patients. There was no difference in the recurrence of diverticulitis between the mesalazine and placebo groups (OR 1.20, 95% CI 0.96-1.50, P = 0.11). A low level of heterogeneity among the studies existed (I2  = 9%, P = 0.36). When the mesalazine dose was ≤ 2 g/day, there was no difference in recurrence rate between the two groups (OR 1.10, 95% CI 0.79-1.54, P = 0.58). When the mesalazine dose was > 2 g/day, the risk of recurrence was higher in the mesalazine group (OR 1.28, 95% CI 1.02-1.62, P = 0.04). The information size was calculated as 2461 patients. Trial sequential analysis showed that the meta-analysis was conclusive and the risk of type II error was minimal. CONCLUSIONS: Mesalazine does not prevent the recurrence of diverticulitis in patients with SUDD. Further studies are required to investigate the role of mesalazine as an adjunct to other medical agents in the prevention of diverticulitis in patients with SUDD.

A large-scale study of a poultry trading network in Bangladesh: implications for control and surveillance of avian influenza viruses.

BACKGROUND: Since its first report in 2007, avian influenza (AI) has been endemic in Bangladesh. While live poultry marketing is widespread throughout the country and known to influence AI dissemination and persistence, trading patterns have not been described. The aim of this study is to assess poultry trading practices and features of the poultry trading networks which could promote AI spread, and their potential implications for disease control and surveillance. Data on poultry trading practices was collected from 849 poultry traders during a cross-sectional survey in 138 live bird markets (LBMs) across 17 different districts of Bangladesh. The quantity and origins of traded poultry were assessed for each poultry type in surveyed LBMs. The network of contacts between farms and LBMs resulting from commercial movements of live poultry was constructed to assess its connectivity and to identify the key premises influencing it. RESULTS: Poultry trading practices varied according to the size of the LBMs and to the type of poultry traded. Industrial broiler chickens, the most commonly traded poultry, were generally sold in LBMs close to their production areas, whereas ducks and backyard chickens were moved over longer distances, and their transport involved several intermediates. The poultry trading network composed of 445 nodes (73.2% were LBMs) was highly connected and disassortative. However, the removal of only 5.6% of the nodes (25 LBMs with the highest betweenness scores), reduced the network's connectedness, and the maximum size of output and input domains by more than 50%. CONCLUSIONS: Poultry types need to be discriminated in order to understand the way in which poultry trading networks are shaped, and the level of risk of disease spread that these networks may promote. Knowledge of the network structure could be used to target control and surveillance interventions to a small number of LBMs.

The methodological quality of guidelines for hospital-acquired pneumonia and ventilator-associated pneumonia: A systematic review.

WHAT IS KNOWN AND OBJECTIVES: Clinical practice guidelines serve as a framework for physicians to make decisions and to support best practice for optimizing patient care. However, if the guidelines do not address all the important components of optimal care sufficiently, the quality and validity of the guidelines can be reduced. The objectives of this study were to systematically review current guidelines for hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), evaluate their methodological quality and highlight the similarities and differences in their recommendations for empirical antibiotic and antibiotic de-escalation strategies. METHODS: This review is reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic databases including MEDLINE, CINAHL, PubMed and EMBASE were searched up to September 2017 for relevant guidelines. Other databases such as NICE, Scottish Intercollegiate Guidelines Network (SIGN) and the websites of professional societies were also searched for relevant guidelines. The quality and reporting of included guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) instrument. RESULTS AND DISCUSSION: Six guidelines were eligible for inclusion in our review. Among 6 domains of AGREE-II, "clarity of presentation" scored the highest (80.6%), whereas "applicability" scored the lowest (11.8%). All the guidelines supported the antibiotic de-escalation strategy, whereas the majority of the guidelines (5 of 6) recommended that empirical antibiotic therapy should be implemented in accordance with local microbiological data. All the guidelines suggested that for early-onset HAP/VAP, therapy should start with a narrow spectrum empirical antibiotic such as penicillin or cephalosporins, whereas for late-onset HAP/VAP, the guidelines recommended the use of a broader spectrum empirical antibiotic such as the penicillin extended spectrum carbapenems and glycopeptides. WHAT IS NEW AND CONCLUSIONS: Expert guidelines promote the judicious use of antibiotics and prevent antibiotic overuse. The quality and validity of available HAP/VAP guidelines would be enhanced by improving their adherence to accepted best practice for the management of HAP and VAP.

Allele-specific polymerase chain reaction for the detection of single nucleotide polymorphism in amlodipine-induced gingival enlargement.

WHAT IS KNOWN AND OBJECTIVE: Studies indicate that there is an increased serum concentration of amlodipine (a calcium channel blocker used to treat hypertension and angina) in patients having mutant multidrug resistance 1 (MDR1) gene. Hence, genetic factors may play a very significant role in amlodipine-induced complications including gingival enlargement. CASE DESCRIPTION: Three patients with amlodipine-induced gingival enlargement showed improvement following drug substitution of amlodipine with enalapril (an angiotensin-converting enzyme inhibitor) and non-invasive periodontal therapy. Using allele-specific polymerase chain reaction, single nucleotide polymorphism of MDR1 gene of heterozygous mutant type (CT genotype) was identified in all three cases. WHAT IS NEW AND CONCLUSION: Drug-induced complications can potentially be a result of genetic factors, in combination with various local and systemic factors. Identifying genetic polymorphisms early might help predict adverse reactions and determine prognosis.