Application of the bacteriophage Mu-driven system for the integration/amplification of target genes in the chromosomes of engineered Gram-negative bacteria—mini review

The advantages of phage Mu transposition-based systems for the chromosomal editing of plasmid-less strains are reviewed. The cis and trans requirements for Mu phage-mediated transposition, which include the L/R ends of the Mu DNA, the transposition factors MuA and MuB, and the cis/trans functioning of the E element as an enhancer, are presented. Mini-Mu(LR)/(LER) units are Mu derivatives that lack most of the Mu genes but contain the L/R ends or a properly arranged E element in cis to the L/R ends. The dual-component system, which consists of an integrative plasmid with a mini-Mu and an easily eliminated helper plasmid encoding inducible transposition factors, is described in detail as a tool for the integration/amplification of recombinant DNAs. This chromosomal editing method is based on replicative transposition through the formation of a cointegrate that can be resolved in a recombination-dependent manner. (E-plus)- or (E-minus)-helpers that differ in the presence of the trans-acting E element are used to achieve the proper mini-Mu transposition intensity. The systems that have been developed for the construction of stably maintained mini-Mu multi-integrant strains of Escherichia coli and Methylophilus methylotrophus are described. A novel integration/amplification/fixation strategy is proposed for consecutive independent replicative transpositions of different mini-Mu(LER) units with “excisable” E elements in methylotrophic cells

Efficacy and safety of baricitinib or ravulizumab in adult patients with severe COVID-19 (TACTIC-R): a randomised, parallel-arm, open-label, phase 4 trial

Background From early in the COVID-19 pandemic, evidence suggested a role for cytokine dysregulation and complement activation in severe disease. In the TACTIC-R trial, we evaluated the efficacy and safety of baricitinib, an inhibitor of Janus kinase 1 (JAK1) and JAK2, and ravulizumab, a monoclonal inhibitor of complement C5 activation, as an adjunct to standard of care for the treatment of adult patients hospitalised with COVID-19. Methods TACTIC-R was a phase 4, randomised, parallel-arm, open-label platform trial that was undertaken in the UK with urgent public health designation to assess the potential of repurposing immunosuppressants for the treatment of severe COVID-19, stratified by a risk score. Adult participants (aged ≥18 years) were enrolled from 22 hospitals across the UK. Patients with a risk score indicating a 40% risk of admission to an intensive care unit or death were randomly assigned 1:1:1 to standard of care alone, standard of care with baricitinib, or standard of care with ravulizumab. The composite primary outcome was the time from randomisation to incidence (up to and including day 14) of the first event of death, invasive mechanical ventilation, extracorporeal membrane oxygenation, cardiovascular organ support, or renal failure. The primary interim analysis was triggered when 125 patient datasets were available up to day 14 in each study group and we included in the analysis all participants who were randomly assigned. The trial was registered on ClinicalTrials.gov (NCT04390464). Findings Between May 8, 2020, and May 7, 2021, 417 participants were recruited and randomly assigned to standard of care alone (145 patients), baricitinib (137 patients), or ravulizumab (135 patients). Only 54 (39%) of 137 patients in the baricitinib group received the maximum 14-day course, whereas 132 (98%) of 135 patients in the ravulizumab group received the intended dose. The trial was stopped after the primary interim analysis on grounds of futility. The estimated hazard ratio (HR) for reaching the composite primary endpoint was 1·11 (95% CI 0·62–1·99) for patients on baricitinib compared with standard of care alone, and 1·53 (0·88–2·67) for ravulizumab compared with standard of care alone. 45 serious adverse events (21 deaths) were reported in the standard-of-care group, 57 (24 deaths) in the baricitinib group, and 60 (18 deaths) in the ravulizumab group. Interpretation Neither baricitinib nor ravulizumab, as administered in this study, was effective in reducing disease severity in patients selected for severe COVID-19. Safety was similar between treatments and standard of care. The short period of dosing with baricitinib might explain the discrepancy between our findings and those of other trials. The therapeutic potential of targeting complement C5 activation product C5a, rather than the cleavage of C5, warrants further evaluation

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

A comparison of HIV/AIDS-related knowledge, attitudes and risk perceptions between final year medical and pharmacy students: A cross sectional study

Background: Awareness about HIV/AIDS in future healthcare professionals is necessary to control growing epidemics of the above diseases. Objective: To evaluate and compare the knowledge, attitude and risk perceptions towards HIV/AIDS between the final year pharmacy and medical students at University Sains Malaysia. Materials and Method: In a cross sectional study, validated questionnaires were served to (130) pharmacy and (160) medical students in their final year of study. The data were analyzed to find differences at a p-value <0.05. Results: About 83% pharmacy and 65% medical students responded in this study. Though 36.1% pharmacy students showed confidence on their professional education, lesser number (9.2%) of pharmacy students' demonstrated willingness to assist HIV patients. The majority (58.1%) of medical students were doubtful regarding their competency, 55.2% were wiling to assist, while 50.5% were confident on their professional education. About 72% of medical students feared of acquiring HIV in professional life compared 29.6% (p=0.000) pharmacy students. Student groups were having lower awareness levels about PEP (post exposure prophylaxis), 18.5% by pharmacy and 48.6% by medical students (p=0.000). About 40% of both groups demonstrated lack of unawareness for the use of antivirals to treat HIV/AIDS. Pharmacy students showed lesser awareness about opportunistic infections (18.5%). Low agreement on competency to treat and counsel HIV/AIDS patients were reflected, 12.9% and 29.6% for pharmacy and medical students, respectively. The confidence on the education provided was lower in pharmacy (36.1%) and medical students (49.1%). Conclusion: Significant misconceptions, negative attitudes and risk perceptions were indicated by the pharmacy and medical students and should be addressed with educational and practical progra

Preparation, characterization, and in vitro evaluation of aceclofenac PVP-solid dispersions

The objective of the present investigation was to study the effect of polyvinylpyrrolidone (PVP) on in vitro dissolution of aceclofenac from solid dispersions. Aceclofenac binary solid dispersions (SD) with different drug loadings were prepared using the melting or fusion method. In vitro dissolution of pure drug, physical mixtures, and solid dispersions were carried out. Solid dispersion of aceclofenac with PVP showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1N HCl, pH 1.2 and phosphate buffer, pH 7.4. Solid dispersions in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. The amorphous nature of the drug in solid dispersion was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in solid dispersion compared to the pure drug. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in solid dispersions in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation, and solubilizing effect of the carrier from the solid dispersions of aceclofenac. In conclusion, dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP. © Taylor & Francis Group, LLC

Students’ perception of the safety and value of a herbal vs. a conventional medicine for treating insomnia

University students suffer from variable sleep patterns including insomnia;[1] furthermore, the highest incidence of herbal use appears to be among college graduates.[2] Our objective was to test the perception of safety and value of herbal against conventional medicine for the treatment of insomnia in a non-pharmacy student population. We used an experimental design and bespoke vignettes that relayed the same effectiveness information to test our hypothesis that students would give higher ratings of safety and value to herbal product compared to conventional medicine. We tested another hypothesis that the addition of side-effect information would lower people’s perception of the safety and value of the herbal product to a greater extent than it would with the conventional medicine

Complementary and Alternative Medicine Use Among Patients with Diabetes Mellitus

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Pengaruh Edukasi Media Whatsapp Tentang Gizi Laktasi, Involusi Uteri, Dan Lochea Terhadap Pengetahuan, Sikap Dan Perilaku Ibu Nifas

The abnormal period of nifas causes problems such as the sub-involution of utero and bleeding, when it is not handled quickly can result in maternal mortality. Education is one of the upbringing to improve the knowledge, attitudes and behaviors of mother Nifas. The aim of this research is to know the effect of WhatsApp education on lactation, uteri, and Lochea on the knowledge, attitudes and behavior of puerperium in the working area of Sitti Khadijah I Muhammadiyah Makassar ". Research design that is quasi experiment with one group pre-Test and post-Test design. The research was conducted in Rsia Sitti Khadijah I Muhammadiyah Makassar in January S/d february year 2020. Sample of 39 respondents. Sampling technique using purposive sampling, intervention is given through WhatsApp media about lactation, utero and Lochea for 14 days with 2 times the provision of materials in a day and completed the division of the research material conducting group monitoring if the material is accessed then the name of the respondent is in the field "read by" but if it has not been accessed the name of the respondent is in the field Data was analyzed using Mc Nemar test. Result: Most of the respondents were 20-35 years old as much as 84.6%, the majority of the education of respondents was the college as much as 41.0%, respondents MOSTLY worked as IRT, which was 56.4%, most of the family income was 3-5 million per month as many as 69.2% and most respondents had a total of 2-4 children as much as 43.6%. There was a significant increase in the knowledge of 84.6% and an attitude of 79.5% after the intervention with P-value 0.000. While on the behavioral consumption of proteins, Vit A and vit C respectively at 35.9%, 41% and 59% after administration of the intervention with P value &lt; 0.05. There is an increase in the knowledge, attitudes and behaviors of puerperium mothers in the work area of RSIA Sitti Khadijah I Muhammadiyah Branch of Makassar. And expected to be Pregnant and mother Nifas to make use of social media owned especially Whatsapp and Dipleaseto further researchers in order to develop this research using other social media. &nbsp; Keywords: Education, Social Media Whatsapp, Nutrition, Puerperium The abnormal period of nifas causes problems such as the sub-involution of utero and bleeding, when it is not handled quickly can result in maternal mortality. Education is one of the upbringing to improve the knowledge, attitudes and behaviors of mother Nifas. The aim of this research is to know the effect of WhatsApp education on lactation, uteri, and Lochea on the knowledge, attitudes and behavior of puerperium in the working area of Sitti Khadijah I Muhammadiyah Makassar ". Research design that is quasi experiment with one group pre-Test and post-Test design. The research was conducted in Rsia Sitti Khadijah I Muhammadiyah Makassar in January S/d february year 2020. Sample of 39 respondents. Sampling technique using purposive sampling, intervention is given through WhatsApp media about lactation, utero and Lochea for 14 days with 2 times the provision of materials in a day and completed the division of the research material conducting group monitoring if the material is accessed then the name of the respondent is in the field "read by" but if it has not been accessed the name of the respondent is in the field Data was analyzed using Mc Nemar test. Result: Most of the respondents were 20-35 years old as much as 84.6%, the majority of the education of respondents was the college as much as 41.0%, respondents MOSTLY worked as IRT, which was 56.4%, most of the family income was 3-5 million per month as many as 69.2% and most respondents had a total of 2-4 children as much as 43.6%. There was a significant increase in the knowledge of 84.6% and an attitude of 79.5% after the intervention with P-value 0.000. While on the behavioral consumption of proteins, Vit A and vit C respectively at 35.9%, 41% and 59% after administration of the intervention with P value &lt; 0.05. There is an increase in the knowledge, attitudes and behaviors of puerperium mothers in the work area of RSIA Sitti Khadijah I Muhammadiyah Branch of Makassar. And expected to be Pregnant and mother Nifas to make use of social media owned especially Whatsapp and Dipleaseto further researchers in order to develop this research using other social media. &nbsp; Keywords: Education, Social Media Whatsapp, Nutrition, Puerperium &nbsp; ABSTRAK &nbsp; Masa nifas yang abnormal menyebabkan masalah seperti sub-involusi uteri dan perdarahan, apabila tidak tertangani dengan cepat dapat berakibat pada kematian ibu. Edukasi merupakan salah satu asuhan untuk meningkatkan pengetahuan, sikap dan perilaku ibu nifas. Tujuan penelitian ini adalah untuk Mengetahui efek edukasi whatsapp tentang gizi laktasi, involusi uteri, dan lochea terhadap pengetahuan, sikap dan perilaku ibu nifas di wilayah kerja RSIA Sitti Khadijah I Muhammadiyah Makassar”. Desain Penelitian yaitu quasi experiment dengan one group pre-test dan post-test design. Penelitian dilaksanakan di RSIA Sitti Khadijah I Muhammadiyah Makassar pada bulan Januari s/d Februari tahun 2020. Sampel sebanyak 39 responden. Tekhnik pengambilan sampel menggunakan purposive sampling, intervensi diberikan melalui media whatsapp tentang gizi laktasi, involusi uteri dan lochea selama 14 hari dengan 2 kali pemberian materi dalam sehari dan selesai pembagian materi peneliti melakukan pemantauan group jika materi telah diakses maka nama responden berada pada kolom “Dibaca Oleh” namun jika belum diakses nama responden berada pada kolom “Tersampaikan Ke”. Data dianalisis menggunakan uji Mc Nemar. Sebagian besar responden berumur 20-35 tahun yaitu sebanyak 84.6%, mayoritas pendidikan responden yaitu perguruan tinggi sebanyak 41.0%, responden sebagian besar bekerja sebagai IRT yaitu sebanyak 56.4%, Sebagian besar responden pendapatan keluarganya 3-5 juta perbulan sebanyak 69.2% dan sebagian besar responden memiliki jumlah anak 2-4 yaitu sebanyak 43.6%. Terjadi peningkatan yang signifikan terhadap pengetahuan sebesar 84.6% dan sikap sebesar 79.5% setelah pemberian intervensi dengan p-value 0.000. sedangkan pada perilaku konsumsi protein, VIT A dan VIT C masing-masing sebesar 35.9%, 41% dan 59% setelah pemberian intervensi dengan p value &lt; 0.05. Terdapat peningkatan pengetahuan, sikap dan perilaku ibu nifas di wilayah kerja RSIA Sitti Khadijah I Cabang Muhammadiyah Makassar. Dan diharapkan ibu hamil maupun ibu nifas agar memanfaatkan media sosial yang dimiliki khususnya Whatsapp serta diharapkan peneliti selanjutnya agar bisa mengembangkan penelitian ini dengan menggunakan media sosial yang lainnya. &nbsp; Kata Kunci : Edukasi, Media Sosial Whatsapp, Gizi, Ibu Nifa

Doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan polymeric nanoformulation: uptake by cells and organs

Ummarah Kanwal,1,2 Nadeem Irfan Bukhari,2 Nosheen Fatima Rana,3 Mehreen Rehman,1 Khalid Hussain,2 Nasir Abbas,2 Arshad Mehmood,4 Abida Raza1 1NILOP Nanomedicine Research Laboratories, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Pakistan; 2University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, Pakistan; 3Department of Biomedical Engineering and Sciences, School of Mechanical and Manufacturing Engineering, National University of Sciences and Technology, Islamabad, Pakistan; 4Material Division, National Institute of Lasers and Optronics, Pakistan Institute of Engineering and Applied Sciences Islamabad, Islamabad, Pakistan Purpose: This study was aimed to develop doxorubicin-loaded quaternary ammonium palmitoyl glycol chitosan (DOX&ndash;GCPQ) nanoformulation that could enable DOX delivery and noninvasive monitoring of drug accumulation and biodistribution at tumor site utilizing self-florescent property of doxorubicin.Materials and methods: DOX&ndash;GCPQ amphiphilic polymeric nanoformulations were prepared and optimized using artificial neural network (ANN) and characterized for surface morphology by atomic force microscopy, particle size with polydispersity index (PDI), and zeta potential by dynamic light scattering. Fourier transformed infrared (FTIR) and X-ray diffractometer studies were performed to examine drug polymer interaction. The ANN-optimized nanoformulation was investigated for in vitro release, cellular, tumor, and tissue uptake.Results: The optimized DOX&ndash;GCPQ nanoformulation was anionic spherical micelles with the hydrodynamic particle size of 97.8&plusmn;1.5&nbsp;nm, the PDI of &lt;0.3, the zeta potential of 28&plusmn;2&nbsp;mV, and the encapsulation efficiency of 80%&plusmn;1.5%. Nanoformulation demonstrated a sustained release pattern over 48&nbsp;h, assuming Weibull model. Fluorescence microscopy revealed higher uptake of DOX&ndash;GCPQ in human rhabdomyosarcoma (RD) cells as compared to free DOX. In vitro cytotoxicity assay indicated a significant cytotoxicity of DOX&ndash;GCPQ against RD cells as compared to DOX and blank GCPQ (P&lt;0.05). DOX&ndash;GCPQ exhibited low IC50 (1.7&plusmn;0.404&nbsp;&micro;mol) when compared to that of DOX (3.0&plusmn;0.968&nbsp;&micro;mol). In skin tumor xenografts, optical imaging revealed significantly lower DOX&ndash;GCPQ in heart and liver (P&lt;0.05) and accumulated mainly in tumor (P&lt;0.05) as compared to other tissues.Conclusion: The features of nanoformulation, ie, small particle size, sustained drug release, and enhanced cellular uptake, potential to target tumor passively coupled with the possibility of monitoring of tumor localization by optical imaging may make DOX&ndash;GCPQ an efficient nanotheranostic system. Keywords: quaternary ammonium palmitoyl glycol chitosan, doxorubicin, artificial neural network, optical imaging, biodistribution, nanotheranosti