Catatonia:A deep dive into its unfathomable depths

This editorial addresses catatonia,a complex neuropsychiatric syndrome characterised by a spectrum of psychomotor disturbances.The editorial seeks to clarify the ambiguous aspects of catatonia,integrating recent research findings,including global studies and diagnostic advancements.It discusses catatonia’s clinical manifestations,prevalence,and associated psychiatric and medical conditions,with particular emphasis on its frequent co-occurrence with schizophrenia and mood disorders.The prevalence of catatonia,which varies across psychiatric populations,is illustrated by a significant study conducted in Nelson Mandela Bay,South Africa.This study provides valuable insights into the effectiveness of the Bush-Francis Screening Instrument compared to the Diagnostic and Statistical Manual 5 criteria in diagnosing catatonia.The editorial evaluates treatment approaches,primarily focusing on benzodiazepines and electroconvulsive therapy,and discusses emerging therapeutic strategies.It underscores the importance of robust diagnostic frameworks and early intervention in managing catatonia,as recommended by the latest evidence-based consensus guideline.Furthermore,it suggests future research directions,particularly in exploring the neurobiological and genetic factors of catatonia,to enhance our understanding and improve treatment outcomes.This editorial succinctly aims to demystify catatonia and provide valuable insights for clinicians and researchers in mental health care.

Tree: Reducing the use of restrictive practices on psychiatric wards through virtual reality immersive technology training

BACKGROUND Restrictive practices(RPs)are defined by measures linked to physical and chemical restraints to reduce the movement or control behaviours during any emergency.Seclusion is an equal part of RPs intended to isolate and reduce the sensory stimulation to safeguard the patient and those within the vicinity.Using interventions by way of virtual reality(VR)could assist with reducing the need for RPs as it could help reduce anxiety or agitation by way of placing users into realistic and immersive environments.This could also aid staff to and change current RPs.AIM To assess the feasibility and effectiveness of using a VR platform to provide reduction in RP training.METHODS A randomised controlled feasibility study,accompanied by evaluations at 1 month and 6 months,was conducted within inpatient psychiatric wards at Southern Health National Health Service Foundation Trust,United Kingdom.Virti VR scenarios were used on VR headsets to provide training on reducing RPs in 3 inpatient psychiatric wards.Outcome measures included general self-efficacy scale,generalised anxiety disorder assessment 7(GAD-7),Burnout Assessment Tool 12,the Everyday Discrimination Scale,and the Compassionate Engagement and Action Scale.RESULTS Findings revealed statistically significant differences between the VR and treatment as usual groups,in the Everyday Discrimination Scale items Q8 and Q9:P=0.023 and P=0.040 respectively,indicating higher levels of perceived discrimination in the VR group.There were no significant differences between groups in terms of general self-efficacy,generalised anxiety disorder assessment 9,and Burnout Assessment Tool 12 scores.A significant difference was observed within the VR group for compassionate engagement from others(P=0.005)over time.Most respondents recorded System Usability Scale scores above 70,with an average score of 71.79.There was a significant reduction in rates of RPs in the VR group vs treatment as usual group with a fluctuating variability observed in the VR group likely due to external factors not captured in the study.CONCLUSION Ongoing advancement of VR technology enables the possibility of creating scenarios and simulations tailored to healthcare environments that empower staff by providing more comprehensive and effective training for handling situations.

Impact of lockdown relaxation and implementation of the facecovering policy on mental health: A United Kingdom COVID-19 study

BACKGROUND Pandemic mitigation policies,such as lockdown,are known to impact on mental health of individuals.Compulsory face covering under relaxed lockdown restrictions gives assurance of less transmission of airborne infection and has the potential to improve mental health of individuals affected by restrictions.AIM To examine the association of the lockdown relaxation and the implementation of the face covering policy on the mental health of the general population and subgroups in the United Kingdom using interrupted time series model.METHODS Using a web-based cross-sectional survey of 28890 United Kingdom adults carried out during May 1,2020 to July 31,2020,changes in mental health status using generalised anxiety disorder(GAD-7),and impact of events scale-revised(IES-R)scales are examined,at the dates of the first lockdown relaxation(July 4,2020)and the subsequent introduction of face covering(July 24,2020)in United Kingdom.A sharp regression discontinuity design is used to check discontinuities in mental health outcomes at policy-change dates.RESULTS Average GAD-7 scores of participants were 5.6,5.6 and 4.3 during the lockdown period,the lockdown relaxation phase and the phase of compulsory face covering,respectively,with lower scores indicating lower anxiety levels.Corresponding scores for IES-R were 17.3,16.8 and 13.4,with lower scores indicating less distress.Easing lockdown measures and subsequent introduction of face covering,on average,reduced GAD-7 by 0.513(95%CI:0.913-0.112)and 1.148(95%CI:1.800-0.496),respectively.Corresponding reductions in IES-R were 2.620(95%CI:4.279-0.961)and 3.449(95%CI:5.725-1.172).These imply that both lockdown relaxation and compulsory face-covering have a positive association with mental health scores(GAD-7 and IES-R).CONCLUSION The differential impact of lockdown and relaxation on the mental health of population sub-groups is evident in this study with future implications for policy.Introduction of face covering in public places had a stronger positive association with mental health than lockdown relaxation.

Survey of the management of borderline ovarian tumors in the United Kingdom

Borderline ovarian tumors （BOTs） represent approxi-mately 10% of ovarian neoplasms and are a heteroge-neous group of tumors with variable biological behav-iour. The majority present with disease confned to the ovary and have an excellent prognosis after surgical removal. A small proportion subsequently has recur-rent disease or progression to invasive cancer. Tumor recurrence can occur up to 20 years after surgical resection. There are no robust clinical, histological or molecular markers that distinguish high risk cases and no satisfactory treatment for patients with progressive disease. This results in great variability in management in different centres. We conducted a national survey on the management of borderline ovarian tumors in cancer centres representing different regions in the United Kingdom. In this article we review the literature for the current concepts in diagnosis, treatment and follow up of BOTs and we report the results of the survey of current practice in the United Kingdom. On that basis we provide recommendations for the management of patients with BOTs.

Effects of cumulative COVID-19 cases on mental health:Evidence from multi-country survey

BACKGROUND Depression and anxiety were both ranked among the top 25 leading causes of global burden of diseases in 2019 prior to the coronavirus disease 2019(COVID-19)pandemic.The pandemic affected,and in many cases threatened,the health and lives of millions of people across the globe and within the first year,global prevalence of anxiety and depression increased by 25%with the greatest influx in places highly affected by COVID-19.AIM To explore the psychological impact of the pandemic and resultant restrictions in different countries using an opportunistic sample and online questionnaire in different phases of the pandemic.METHODS A repeated,cross-sectional online international survey of adults,16 years and above,was carried out in 10 countries(United Kingdom,India,Canada,Bangladesh,Ukraine,Hong Kong,Pakistan,Egypt,Bahrain,Saudi Arabia).The online questionnaire was based on published approaches to understand the psychological impact of COVID-19 and the resultant restrictions.Five standardised measures were included to explore levels of depression[patient health questionnaire(PHQ-9)],anxiety[generalized anxiety disorder(GAD)assessment],impact of trauma[the impact of events scale-revised(IES-R)],loneliness(a brief loneliness scale),and social support(The Multidimensional Scale of Perceived Social support).RESULTS There were two rounds of the online survey in 10 countries with 42866 participants in Round 1 and 92260 in Round 2.The largest number of participants recruited from the United Kingdom(112985 overall).The majority of participants reported receiving no support from mental health services throughout the pandemic.This study found that the daily cumulative COVID-19 cases had a statistically significant effect on PHQ-9,GAD-7,and IES-R scores.These scores significantly increased in the second round of surveys with the ordinary least squares regression results with regression discontinuity design specification(to control lockdown effects)confirming these results.The study findings imply that participants’mental health worsened with high cumulative COVID-19 cases.CONCLUSION Whist we are still living through the impact of COVID-19,this paper focuses on its impact on mental health,discusses the possible consequences and future implications.This study revealed that daily cumulative COVID-19 cases have a significant impact on depression,anxiety,and trauma.Increasing cumulative cases influenced and impacted education,employment,socialization and finances,to name but a few.Building a database of global evidence will allow for future planning of pandemics,particularly the impact on mental health of populations considering the cultural differences.

Evaluation of a culturally adapted cognitive behavior therapy-based,third-wave therapy manual

BACKGROUND Recommendations for psychotherapy have evolved over the years,with cognitive behavioral therapy(CBT)taking precedence since its inception within clinical guidelines in the United Kingdom and United States.The use of CBT for severe mental illness is now more common globally.AIM To investigate the feasibility and acceptability of a culturally adapted,CBT-based,third-wave therapy manual using the Comprehend,Cope,and Connect approach with individuals from a diverse population presenting to primary and secondary healthcare services.METHODS A pilot study was used to assess the feasibility and acceptability of the manualised intervention.Outcome measures were evaluated at baseline,post-intervention and 12 wk-follow up.32 participants with mental health conditions aged 20-53 years were recruited.Assessments were completed at three time points,using Clinical Outcomes in Routine Evaluation(CORE),Hospital Anxiety and Depression Scale(HADS),Bradford Somatic Inventory and World Health Organization Disability Assessment Schedule 2.0(WHODAS).The Patient Experience Questionnaire was completed post-treatment.RESULTS Repeated measures of analysis of variance associated with HADS depression,F(2,36)=12.81,P<0.001,partialη^(2)=0.42 and HADS anxiety scores,F(2,26)=9.93,P<0.001,partialη^(2)=0.36;CORE total score and WHODAS both showed significant effect F(1.25,18.72)=14.98,P<0.001,partialη^(2)=0.5.and F(1.29,14.18)=6.73,P<0.001,partialη^(2)=0.38 respectively.CONCLUSION These results indicate the effectiveness and acceptability of the culturally adapted,CBT-based,third-wave therapy manual intervention among minoritized groups with moderate effect sizes.Satisfaction levels and acceptability were highly rated.The viability and cost-effectiveness of this approach should be explored further to support universal implementation across healthcare systems.

Exploratory systematic review and meta-analysis on period poverty

BACKGROUNDPeriod poverty is a global health and social issue that needs to be addressed.It has been reported that many females compromise their education,employment,and social commitments during their menstruation days due to a number of reasons,including lack of access to toilets or menstrual products.AIM To provide a comprehensive understanding on period poverty,including outcomes associated with menstruation.METHODS All observational and randomised clinical trials reporting menstruation challenges,menstrual poverty and menstrual products were included.Our search strategy included multiple electronic databases of PubMed,Web of Science,ScienceDirect,ProQuest and EMBASE.Studies published in a peer review journal in English between the 30th of April 1980 and the 30th of April 2022 were included.The Newcastle-Ottawa Scale was used to assess the risk of bias of the systematic included studies.Pooled odds ratios(ORs)together with 95%confidence intervals(CIs)are reported overall and for sub-groups.RESULTS A total of 80 studies were systematically selected,where 38 were included in the meta-analysis.Of the 38 studies,28 focused on children and young girls(i.e.,10-24 years old)and 10 included participants with a wider age range of 15-49 years.The prevalence of using disposable sanitary pads was 45%(95%CI:0.35-0.58).The prevalence of menstrual education pre-menarche was 68%(95%CI:0.56-0.82).The prevalence of good menstrual hygiene management(MHM)was 39%(95%CI:0.25-0.61).Women in rural areas(OR=0.30,95%CI:0.13-0.69)were 0.70 times less likely to have good MHM practices than those living in urban areas.CONCLUSION There was a lack of evidence,especially from low-and middle-income countries.Further research to better understand the scope and prevalence of period poverty should be considered.This will enable the development of improved policies to increase access to menstrual products and medical support where necessary.

Current strategies for reproductive management of gilts and sows in North America

Many advances in genetic selection, nutrition, housing and disease control have been incorporated into modern pork production since the 1950s resulting in highly prolific females and practices and technologies, which significantly increased efficiency of reproduction in the breeding herd. The objective of this manuscript is to review the literature and current industry practices employed for reproductive management. In particular the authors focus on assisted reproduction technologies and their application for enhanced productivity. Modern maternal line genotypes have lower appetites and exceptional lean growth potential compared to females of 20 yr ago. Thus, nutrient requirements and management techniques and technologies, which affect gilt development and sow longevity, require continuous updating. Failure to detect estrus accurately has the greatest impact on farrowing rate and litter size. Yet, even accurate estrus detection will not compensate for the variability in the interval between onset of estrus and actual time of ovulation. However, administration of GnRH analogs in weaned sows and in gilts after withdrawal of altrenogest do overcome this variability and thereby synchronize ovulation, which makes fixed-time AI practical. Seasonal infertility, mediated by temperature and photoperiod, is a persistent problem. Training workers in the art of stockmanship is of increasing importance as consumers become more interested in humane animal care. Altrenogest, is used to synchronize the estrous cycle of gilts, to prolong gestation for 2-3 d to synchronize farrowing and to postpone post-weaning estrus. P.G. 600~ is used for induction of estrus in pre-pubertal gilts and as a treatment to overcome seasonal anestrous. Sperm cell numbers/dose of semen is significantly less for post cervical AI than for cervical AI. Real-time ultrasonography is used to determine pregnancy during wk 3-5. PGF2a effectively induces farrowing when administered within two d of normal gestation length. Ovulation synchronization, single fixed-time AI and induced parturition may lead to farrowing synchronization, which facilitates supervision and reduces stillbirths and piglet mortality. Attendance and assistance at farrowing is important especially to ensure adequate colostrum consumption by piglets immediately after birth. New performance terminologies are presented.

Staging colorectal cancer with the TNM 7^(th):The presumption of innocence when applying the M category

One of the main changes of the current TNM-7 is the elimination of the category MX,since it has been a source of ambiguity and misinterpretation,especially by pathologists.Therefore the ultimate staging would be better performed by the patient's clinician who can classify the disease M0(no distant metastasis) or M1(presence of distant metastasis),having access to the completeness of data resulting from clinical examination,imaging workup and pathology report.However this important change doesn't take into account the diagnostic value and the challenge of small indeterminate visceral lesions encountered,in particular,during radiological staging of patients with colorectal cancer.In this article the diagnosis of these lesions with multiple imaging modalities,their frequency,significance and relevance to staging and disease management are described in a multidisciplinary way.In particular the interplay between clinical,radiological and pathological staging,which are usually conducted independently,is discussed.The integrated approach shows that there are both advantages and disadvantages to abandoning the MX category.To avoid ambiguity arising both by applying and interpreting MX category for stage assigning,its abandoning seems reasonable.The recognition of the importance of small lesion characterization raises the need for applying a separate category;therefore a proposal for their categorization is put forward.By using the proposed categorization the lack of consideration for indeterminate visceral lesions with the current staging system will be overcome,also optimizing tailored follow-up.

Associated mortality risk of atypical antipsychotic medication in individuals with dementia

BACKGROUND Antipsychotic medications such as risperidone,olanzapine and aripiprazole are used to treat psychological and behavioural symptoms among dementia patients.Current evidence indicate prescription rates for antipsychotics vary and wider consensus to evaluate clinical epidemiological outcomes is limited.AIM To investigate the potential impact of atypical antipsychotics on the mortality of patients with dementia.METHODS A retrospective clinical cohort study was developed to review United Kingdom Clinical Record Interactive Search system based data between January 1,2013 to December 31,2017.A descriptive statistical method was used to analyse the data.Mini Mental State Examination(MMSE)scores were used to assess the severity and stage of disease progression.A cox proportional hazards model was developed to evaluate the relationship between survival following diagnosis and other variables.RESULTS A total of 1692 patients were identified using natural language processing of which,587 were prescribed olanzapine,quetiapine or risperidone(common group)whilst 893(control group)were not prescribed any antipsychotics.Patients prescribed olanzapine showed an increased risk of death[hazard ratio(HR)=1.32;95%confidence interval(CI):1.08-1.60;P<0.01],as did those with risperidone(HR=1.35;95%CI:1.18-1.54;P<0.001).Patients prescribed quetiapine showed no significant association(HR=1.09;95%CI:0.90-1.34;P=0.38).Factors associated with a lower risk of death were:High MMSE score at diagnosis(HR=0.72;95%CI:0.62-0.83;P<0.001),identifying as female(HR=0.73;95%CI:0.64-0.82;P<0.001),and being of a White-British ethnic group(HR=0.82;95%CI:0.72-0.94;P<0.01).CONCLUSION A significant mortality risk was identified among those prescribed olanzapine and risperidone which contradicts previous findings although the study designs used were different.Comprehensive research should be conducted to better assess clinical epidemiological outcomes associated with diagnosis and therapies to improve clinical management of these patients.

Robotic rectal cancer surgery:Results from a European multicentre case series of 240 resections and comparative analysis between cases performed with the da Vinci Si and Xi systems

Introduction:Robotic systems are designed to address the limitations of laparoscopic surgery,leading to a growing interest in robotic rectal surgery.However,certain technical limitations associated with the previous systems(da Vinci S&Si)have arguably slowed down its wholesale adoption.The latest robotic platform,the da Vinci Xi,addresses these limitations.This study aims to examine the short-term surgical outcomes of 240 single-docking fully-robotic rectal cancer resections and compare the outcomes of cases performed with the da Vinci Xi vs Si systems.Materials and methods:All consecutive patients receiving robotic rectal cancer resections from three centres between 2013 and 2018 were identified from prospectively collated databases.The baseline characteristics and short-term surgical outcomes are presented and the da Vinci Xi vs Si system outcomes are analysed.Results:A total of 240 patients were identified(124 Si,116 Xi).Median operation-time and length-of-stay were 260 minutes and 6 days respectively.Conversion and 30-day mortality rates were 0.The da Vinci Si vs Xi system analysis shows that operation-time was lower in the Si group(230 vs 300 min,p=0.000)but length-of-stay,lymph node yield and circumferential resection margin favoured the Xi group(7 vs 5 days,p=0.010;17 vs 21,p=0.000;92.7%vs 99.1%,p=0.020).Conclusion:Single-docking fully-robotic rectal cancer surgery is safe,feasible and can lead to good shortterm outcomes,making it a good alternative to laparoscopic rectal cancer surgery.The new systems technological advances may result in better short-term outcomes but further larger scale observational studies are required if we are to reach such a conclusion.

Mental health impact of the Middle East respiratory syndrome,SARS,and COVID-19:A comparative systematic review and metaanalysis

BACKGROUND Over the last few decades,3 pathogenic pandemics have impacted the global population;severe acute respiratory syndrome coronavirus(SARS-CoV),Middle East respiratory syndrome coronavirus(MERS-CoV)and SARS-CoV-2.The global disease burden has attributed to millions of deaths and morbidities,with the majority being attributed to SARS-CoV-2.As such,the evaluation of the mental health(MH)impact across healthcare professionals(HCPs),patients and the general public would be an important facet to evaluate to better understand short,medium and long-term exposures.AIM To identify and report:(1)MH conditions commonly observed across all 3 pandemics;(2)Impact of MH outcomes across HCPs,patients and the general public associated with all 3 pandemics;and(3)The prevalence of the MH impact and clinical epidemiological significance.METHODS A systematic methodology was developed and published on PROSPERO(CRD42021228697).The databases PubMed,EMBASE,ScienceDirect and the Cochrane Central Register of Controlled Trials were used as part of the data extraction process,and publications from January 1,1990 to August 1,2021 were searched.MeSH terms and keywords used included Mood disorders,PTSD,Anxiety,Depression,Psychological stress,Psychosis,Bipolar,Mental Health,Unipolar,Self-harm,BAME,Psychiatry disorders and Psychological distress.The terms were expanded with a‘snowballing’method.Cox-regression and the Monte-Carlo simulation method was used in addition to I2 and Egger’s tests to determine heterogeneity and publication bias.RESULTS In comparison to MERS and SARS-CoV,it is evident SAR-CoV-2 has an ongoing MH impact,with emphasis on depression,anxiety and post-traumatic stress disorder.CONCLUSION It was evident MH studies during MERS and SARS-CoV was limited in comparison to SARS-CoV-2,with much emphasis on reporting symptoms of depression,anxiety,stress and sleep disturbances.The lack of comprehensive studies conducted during previous pandemics have introduced limitations to the“know-how”for clinicians and researchers to better support patients and deliver care with limited healthcare resources.

Is there still a role for sucralfate in the treatment of gastritis?

The endoscopic diagnosis of gastritis is usually made when a patient develops symptoms and undergoes an upper gastrointestinal endoscopy.There are often obvious aetiological causes such as smoking,alcohol Helicobacter pylori infection or drug treatment.Lifestyle changes can sometimes improve symptoms but often patients will be treated with a proton pump inhibitor.The stomach mucosa produces a protective mucous to prevent damage cause by gastric acid and exogenous agents can disrupt this layer.Repair of this protective layer can be enhanced by reduction in gastric acid secretion using H2 receptor antagonist or proton pump inhibitors or by cytoprotective drugs such as misoprostol,sucralfate,aluminium ions or bismuth subsalts.Sucralfate is a complex polymer which at a low pH changes its chemical configuration and binds to serum protein to form a protective layer protecting the mucosa against further injury.Cytoprotective drugs were the first line treatment for peptic disease including gastritis for many years but since the launch of cimetidine in 1976 and the subsequent launch of omeprazole in 1988,their use has slowly declined.First line treatment for patients with symptomatic gastritis after removal of potential causative factors is likely to be a proton pump inhibitor in 2019.This is despite the fact that there is some evidence that sucralfate is superior than a H2 receptor antagonist in the endoscopic healing rates in patients with gastritis.The logical treatment choice in patients with resistance symptoms is a combination of a proton pump inhibitor and sucralfate but evidence is lacking.Until such evidence is available In the meantime,we would suggest that there is a role for sucralfate in the treatment of intransigent gastritis and that mucosal protection should be considered even ahead of acid suppression given its favourable safety and toxicity profile.

Rapid commentary:Ethical implications for clinical trialists and patients associated with COVID-19 research

Pandemics disrupt clinical trials worldwide,with lasting effects on research.It can severely impact clinical trialists ability to conduct safe and ethically uncompromised trials.Hence,the mounting pressure results in ethically and morally distressing decisions faced by clinical trial professionals during pandemic situations.Whilst clinical trialists attempt to think about preparedness and responses during a pandemic,the need to have an ethical framework that has real-world applicability is imperative.Pandemics are a challenging time for all,however,the safety and access to support for clinical trialists and patients within clinical trials should be at the forefront for their organisations and the government.

Mental health impact on Black,Asian and Minority Ethnic populations with preterm birth:A systematic review and meta-analysis

BACKGROUND Preterm birth(PTB)is one of the main causes of neonatal deaths globally,with approximately 15million infants are born preterm.Women from the Black,Asian,and Minority Ethnic(BAME)populations maybe at higher risk of PTB,therefore,the mental health impact on mothers experiencing a PTB is particularly important,within the BAME populations.AIM To determine the prevalence of mental health conditions among BAME women with PTB as well as the methods of mental health assessments used to characterise the mental health outcomes.METHODS A systematic methodology was developed and published as a protocol in PROSPERO(CRD420-20210863).Multiple databases were used to extract relevant data.I2 and Egger's tests were used to detect the heterogeneity and publication bias.A trim and fill method was used to demonstrate the influence of publication bias and the credibility of conclusions.RESULTS Thirty-nine studies met the eligibility criteria from a possible 3526.The prevalence rates of depression among PTB-BAME mothers were significantly higher than full-term mothers with a standardized mean difference of 1.5 and a 95%confidence interval(CI)29%-74%.The subgroup analysis indicated depressive symptoms to be time sensitive.Women within the very PTB category demonstrated a significantly higher prevalence of depression than those categorised as non-very PTB.The prevalence rates of anxiety and stress among PTB-BAME mothers were significantly higher than in full-term mothers(odds ratio of 88%and 60%with a CI of 42%-149%and 24%-106%,respectively).CONCLUSION BAME women with PTB suffer with mental health conditions.Many studies did not report on specific mental health outcomes for BAME populations.Therefore,the impact of PTB is not accurately represented in this population,and thus could negatively influence the quality of maternity services they receive.

Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer

Inframe insertions of three or more base pairs in exon 20 of the epidermal growth factor receptor(EGFR)gene were among the first EGFR mutations to be identified as oncogenic drivers in non-small cell lung cancer(NSCLC).However,unlike the classical EGFR L858R point mutation or exon 19 deletions,which represent the majority of EGFR mutations in NSCLC,low frequency EGFR exon 20 insertion mutations are associated with de novo resistance to targeted EGFR inhibitors and correlate with a poor patient prognosis.Here,we review the developments over the last 5 years in which pre-clinical studies,including elucidation of the crystal structure of an EGFR exon 20 insertion mutant kinase,have revealed a unique mechanism of kinase activation and steric conformation that define the lack of response of these EGFR mutations to clinically approved EGFR inhibitors.The recent development of several novel small molecule compounds that selectively inhibit EGFR exon 20 insertions holds promise for future therapeutic options that will be effective for patients with this molecular subtype of NSCLC.

Phosphorus utilization response of pigs and broiler chickens to diets supplemented with antimicrobials and phytase

Three experiments were conducted to evaluate the phosphorus(P) utilization responses of pigs and broiler chickens to dietary supplementation with antimicrobials and phytase and to determine if P digestibility response to phytase is affected by supplementation with antimicrobials. Experiment 1 used 4 diets(a basal negative control formulated to contain 0.41% total P and 0.71% calcium [Ca] without added antimicrobials, basal negative control with added carbadox, basal negative control with added tylosin, or basal negative control with added virginiamycin) and six 18-kg barrows in individual metabolism crates per diet. There was no effect of antimicrobials on P and Ca digestibility or retention. Carbadox supplementation increased(P < 0.05) digestibility and retention of gross energy(GE) and supplementation with tylosin increased(P < 0.05) N retention relative to the basal negative control diet. Experiment 2 used eight 19-kg barrows in individual metabolism crates per treatment and 9 dietary treatments arranged in a 3×3 factorial of antimicrobials(none, tylosin, or virginiamycin) and phytase(0, 500, or 1,500 FTU/kg).Phytase addition to the diets linearly increased(P< 0.05) apparent total tract digestibility or retention of P, Ca, nitrogen(N) and GE. Supplementation with antimicrobials did not affect apparent total tract digestibility or retention of P, Ca, N or GE. There were linear effects(P < 0.01) of phytase on Ca utilization in diets that were not supplemented with antimicrobials but only tendencies(P < 0,10) in diets supplemented with tylosin or virginiamycin. Phytase linearly improved(P < 0.05) N utilization in diets supplemented with tylosin or virginiamycin but not in diets without added antimicrobials. Experiment 3 was a broiler chicken experiment with the same experimental design as Exp. 2 but feeding 8 birds per cage and 10 replicate cages per diet. Antimicrobial supplementation improved(P < 0.05) feed efficiency and adding tylosin improved(P < 0.05) tibia ash but did not affect nutrient utilization, Dietary phytase improved(P < 0.01) growth performance, tibia ash and apparent ileal digestibility and retention of P regardless of antimicrobial supplementation. Overall, phytase supplementation improved growth performance and nutrient digestibility and retention, regardless of supplementation of diets with antimicrobials. Supplementation of diets with antimicrobials did not affect P digestibility or retention because of a lack of interaction between antimicrobials and phytase, there was no evidence that P digestibility response to phytase is affected by supplementation with antimicrobials.

Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars

New anti-tubercular drugs and drug targets are urgently needed to reduce the time for treatment and also to identify agents that will be effective against Mycobacterium tuberculosis persisting intracellularly.Mycobacteria have a unique cell wall.Deletion of the gene for arylamine N-acetyltransferase(NAT)decreases mycobacterial cell wall lipids,particularly the distinctive mycolates,and also increases antibiotic susceptibility and killing within macrophage of Mycobacterium bovis BCG.The nat gene and its associated gene cluster are almost identical in sequence in M.bovis BCG and M.tuberculosis.The gene cluster is essential for intracellular survival of mycobacteria.We have therefore used pure NAT protein for high-throughput screening to identify several classes of small molecules that inhibit NAT activity.Here,we characterize one class of such molecules—triazoles—in relation to its effects on the target enzyme and on both M.bovis BCG and M.tuberculosis.The most potent triazole mimics the effects of deletion of the nat gene on growth,lipid disruption and intracellular survival.We also present the structure-activity relationship between NAT inhibition and effects on mycobacterial growth,and use ligand-protein analysis to give further insight into the structure-activity relationships.We conclude that screening a chemical library with NAT protein yields compounds that have high potential as anti-tubercular agents and that the inhibitors will allow further exploration of the biochemical pathway in which NAT is involved.