Feasibility of Integrating Leprosy Post-Exposure Prophylaxis with Single-Dose Rifampicin (LPEP) into Routine Leprosy Control Program in Bukedi and Teso Regions in Uganda

Background: World Health Organization recommends the implementation of contact tracing and Leprosy Post Exposure prophylaxis (LPEP) to interrupt the chain of transmission. To accelerate the uptake of this recommendation, a cross-sectional study among contacts of leprosy patients was conducted to investigate the feasibility of integrating leprosy systematic contact tracing and post-exposure prophylaxis (PEP) into the routine leprosy control program. Methods: This was a mixed methods cross-sectional study. The study was implemented in Kumi, Ngora, Serere, Soroti, Budaka and Kibuku Districts. Results: The 45 enrolled index patients (97.8% of the registered) identified a total of 135 contacts, of which 134 (99·2%) consented and were screened. Among them, one new leprosy patient was identified and started on treatment with multidrug therapy (MDT). All the eligible contacts, received the prophylactic treatment with Single Dose Rifampicin (SDR). Overall, SDR was administered to 133(98.5% of the listed contacts) with no adverse event reported. Factors associated with successful contact investigation and management included: Involvement of index patients, health care workers during the contact screening and SDR A administration, counselling of the index patients and contacts by the health care works, LPEP being administered as Directly observed Therapy (DOT) among others. Results Interpretation: The integration of leprosy post-exposure prophylaxis with administration of SDR and contact tracing is feasible, generally accepted by the patient, their contacts and health workers and can be integrated into the National Leprosy control programmes with minimal additional efforts once contact tracing has been established. Therefore, we recommend integration of administration of SDR in to the routine leprosy control program.

Exploring Dry-out Behaviour and Explosion Resistance of Microsilica-gel Bonded No-cement Castables

Cement-free castables have attracted significant attention due to their superior thermal-mechanical properties and rapid dry-out in comparison to cement-bonded refractory castables.However,drying industrial-scale specimens can pose more challenges than lab-scale samples.In this study,the dry-out behavior and explosion resistance of microsilica-gel bonded nocement castables(NCCs)were investigated on both lab-and industrial-scale specimens,employing various drying agents.First,the fast dry-out mechanism was assessed using thermogravimetric analysis(TGA),differential scanning calorimetry(DSC),and scanning electron microscopy(SEM)on lab-scale small samples.Then,the drying behavior of industrial-scale large samples(300 mm×300 mm×300 mm cubes,approximately 80 kg)was studied using a unique macro-thermo-balance(macro-TGA).The results showed that EMSIL-DRY^(®)reduced the temperature level for maximum dewatering rate and effectively prevented explosions during heat-up,compared to other polymer fibres.The use of a specialty drying agent(EMSIL-DRY^(®))significantly improved the explosion resistance,as demonstrated by the production of a perfect 400 kg block fired to 850℃at a rate of 50℃·h^(-1).This research contributes to the understanding and application of cement-free castables in industrial settings.

Post competency training in standardized training of resident physicians and integrated postgraduates

We focus on the importance and necessity of post-competency-based training in medical education alongside its current challenges and opportunities.Integrating post competency training into standardized educational frameworks is increasingly recognized as a critical component of preparing residents and postgraduates for real-world clinical practice.Post competency training represents a commitment to excellence in medical education,striving to produce competent,skilled practitioners to meet the challenges of modern healthcare.

Spectrum of delayed post-hypoxic leukoencephalopathy syndrome:A systematic review

BACKGROUND Delayed post hypoxic leukoencephalopathy syndrome(DPHLS),also known as Grinker’s myelinopathy,is a rare but significant neurological condition that manifests days to weeks after a hypoxic event.Characterized by delayed onset of neurological and cognitive deficits,DPHLS presents substantial diagnostic and therapeutic challenges.AIM To consolidate current knowledge on pathophysiology,clinical features,diagnostic approaches,and management strategies for DPHLS,providing a comprehensive overview and highlighting gaps for future research.METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes guidelines,we systematically searched PubMed,ScienceDirect and Hinari databases using terms related to delayed post-hypoxic leukoencephalopathy.Inclusion criteria were original research articles,case reports,and case series involving human subjects with detailed clinical,neuroimaging,or pathological data on DPHLS.Data were extracted on study characteristics,participant demographics,clinical features,neuroimaging findings,pathological findings,treatment,and outcomes.The quality assessment was performed using the Joanna Briggs Institute critical appraisal checklist.RESULTS A total of 73 cases were reviewed.Common comorbidities included schizoaffective disorder,bipolar disorder,hypertension,and substance use disorder.The primary causes of hypoxia were benzodiazepine overdose,opioid overdose,polysubstance overdose,and carbon monoxide(CO)poisoning.Symptoms frequently include decreased level of consciousness,psychomotor agitation,cognitive decline,parkinsonism,and encephalopathy.Neuroimaging commonly revealed diffuse T2 hyperintensities in cerebral white matter,sometimes involving the basal ganglia and the globus pallidus.Magnetic resonance spectroscopy often showed decreased N-acetylaspartate,elevated choline,choline-to-creatinine ratio,and normal or elevated lactate.Treatment is often supportive,including amantadine,an antioxidant cocktail,and steroids.Hyperbaric oxygen therapy may be beneficial in those with CO poisoning.Parkinsonism was often treated with levodopa.Most of the patients had substantial recovery over the course of months and many cases had some residual neurocognitive deficits.CONCLUSION DPHLS remains a complex and multifaceted condition with various etiologies and clinical manifestations.Early recognition and appropriate management are crucial to improving patient outcomes.Future research should focus on standardizing diagnostic criteria,using advanced imaging techniques,and exploring therapeutic interventions to improve understanding and treatment of DPHLS.Conducting prospective cohort studies and developing biomarkers for early diagnosis and monitoring will be essential to advance patient care.

Compressive properties of glue-laminated timber circular post modified by basalt fiber reinforced polymer

Glued timber structure is one of the main forms of modern wood architecture,which has gradually developed towards mid-and high-rise buildings.Glue-laminated timber(GLT)is comprised of several laminates of parallel-to-grain dimension lumber that are bonded together with durable,moisture resistant structural adhesives.GLT can be used in horizontal applications as a beam and in vertical applications as a post.So,its compressive performance has a significant impact on structural safety.Fiber reinforced polymers(FRPs)were commonly used to improve the bearing capacity of GLT components,and the structural and process parameters largely determined the reinforcement effect.This study was aimed at investigating the influence of structural and process parameters on the axial compression performance of GLT components.Three wrapping methods(middle-part,end-part and full wrapping)and three lengths(0.6,0.8,and 1.0 m)of wood post specimens were designed in this work and the axial compression performance and ductility of GLT post specimens modified by basalt fiber reinforced polymer(BFRP)were studied.The results showed that the effect of different BFRP wrapping methods on the compressive strength and elastic modulus of laminated wood was not statistically significant(P>0.05).The compressive bearing capacity of unreinforced GLT posts decreased with the increase of aspect ratio.The GLT posts with middle-part and end-part wrapping still followed this pattern,while the compressive bearing capacity of GLT posts with full wrapping showed a pattern of first decreasing and then increasing.For GLT with low aspect ratios(4.0 or 5.3),there was no correlation between the wrapping method and the compressive bearing capacity,while the compressive bearing capacity of GLT with a high aspect ratio(6.7)for middle-part,end-part and full wrapping increased by 3.5%,7.5%and 9.7%,respectively.Compared to the unreinforced group,the ultimate axial compressive strength and modulus of elasticity(MOE)of the 6-E series specimens reinforced at both ends decreased by 2.58%and 6.70%,respectively.The ultimate axial compressive strength of the 8-E specimens reinforced at both ends increased by 8.62%and the MOE decreased by 1.91%.The compressive strength of the 10-E specimens reinforced at both ends increased by 7.51%and the MOE increased by 8.14%.The failure modes of GLT with different aspects were consistent under the same BFRP wrapping,while the failure modes of GLT with the same aspect ratio were different for different BFRP wrapping methods.The ductility performance of GLT with different aspects ratio was improved by the BFRP wrapping.

Postoperative Complications in the General Surgery Department of the Cs Ref of Commune I of the District of Bamako Mali

Postoperative complications represent important indicators for the quality of surgical care. The objectives of this work were to study post-operative complications in the general surgery department of the Cs ref of commune I in Mali, to determine the frequency of post-operative complications, to identify the factors of occurrence, to describe the clinical aspects, diagnostic and therapeutic in order to assess the additional cost linked to post-operative complications. This study was prospective, carried out in the general surgery department on 300 cases of surgical interventions. It covered all patients aged at least 15 years, operated on and hospitalized or not, and who presented complications during the 30 days postoperatively. Patients under the age of 15 were not included (our general surgery department is not a pediatric surgery department). We collected 300 patients among whom 199 (66.33%) were men and 101 (33.66%) women, i.e. a sex ratio = 1.9. The average age was 38 years with extremes of 15 and 87 years. The main initial diagnoses were: acute appendicitis, peritonitis, occlusions, wall hernias, hemorrhoids, uterine prolapse, uterine myomas, ovarian cysts and acute cholecystitis. Emergencies represented 43% (N = 129) of interventions with 6.98% post-operative complications (POC). Postoperative complications were dominated by surgical site infections, 75% of cases (N = 20), wall hemorrhage 5% (N = 1), testicular necrosis 5% (N = 1) and testicular calcification 5% (N = 1), wire rejection 5% (N = 1) and death 5% (N = 1). The management of postoperative complications was surgical in 95% and medical in 100%. Their occurrence extended the hospital stay by 3.65 days and increased the average cost of care by 60541.85 CFA francs. The mortality index lowered by efficient management of complications (IMAGE) calculated in relation to deaths was 95% of cases. Anemia, ASA score ≥ III, Alteimeir II and IV classes, duration of surgery and post-operative hospitalization were factors contributing to post-operative complications.

Non-steroidal anti-inflammatory drugs in postoperative hand fracture management:Do they positively or negatively impact recovery?

This editorial explores the impact of non-steroidal anti-inflammatory drugs(NSAIDs)on postoperative recovery in hand fracture patients,amidst shifting pain management strategies away from opioids due to their adverse effects.With hand fractures being significantly common and postoperative pain management crucial for recovery,the potential of NSAIDs offers a non-addictive pain control alternative.However,the controversy over NSAIDs'effects on bone healing—stemming from their Cyclooxygenase-2 inhibition and associated risks of fracture non-union or delayed union—necessitates further investigation.Despite a comprehensive literature search,the study finds a lack of specific research on NSAIDs in postoperative hand fracture management,highlighting an urgent need for future studies to balance their benefits against possible risks.

Development of a Post Quantum Encryption Key Generation Algorithm Using Electromagnetic Wave Propagation Theory

In today’s rapid widespread of digital technologies into all live aspects to enhance efficiency and productivity on the one hand and on the other hand ensure customer engagement, personal data counterfeiting has become a major concern for businesses and end-users. One solution to ensure data security is encryption, where keys are central. There is therefore a need to find robusts key generation implementation that is effective, inexpensive and non-invasive for protecting and preventing data counterfeiting. In this paper, we use the theory of electromagnetic wave propagation to generate encryption keys.

Advances in Research of Post Embolism Syndrome after Transarterial Chemoembolization(TACE)for Hepatocellular Carcinoma

This article reviews the concept and clinical manifestations of post embolism syndrome after transarterial chemoembolization(TACE),and the prevention or timely intervention of post embolism syndrome in advance is expected to reduce its incidence and degree in clinical treatment,and to improve the quality of treatment of Hepatocellular Carcinoma Carcinoma(HCC).

Comparison of the Clinical Effect of Prefabricated Fiber Post and Plastic Fiber Post in Oral Repair

Objective:To observe and analyze the clinical effect of prefabricated fiber posts and plastic fiber posts in oral repair.Methods:A total of 128 patients admitted to our hospital from January 2023 to June 2024 underwent oral prosthesis treatment,of which the control group(n=64)was treated with prefabricated fiber posts and the observation group(n=64)with plastic fiber posts.The efficacy,retention rate,and complication rate of the two groups were compared.Results:The total effective rate of the observation group was 96.88%,which was significantly higher than that of the control group(84.38%)(P<0.05).The restoration retention rate in the observation group was 95.31%,which was significantly higher than that in the control group(85.94%)(P<0.05).The incidence of postoperative complications in the observation group was 4.69%,which was significantly lower than that in the control group(15.63%)(P<0.05).Conclusion:For patients with oral prostheses,the use of plastic fiber posts for treatment shows better clinical effects,effectively improving the retention rate of the prosthesis and reducing the incidence of complications.Thus,it is worthy of popularization and application.

Research Progress in the Treatment of Poststroke Depression with Traditional Chinese Medicine

In recent years,the incidence rate of stroke has increased year by year.Post stroke depres‐sion is one of its main complications,which seriously affects the recovery of physiological functions and quality of life of stroke patients.Traditional Chinese medicine has signifi‐cant therapeutic effects in treating this disease.This article provides a classification and review of traditional Chinese medicine treatment methods for post-stroke depression,and looks forward to the current problems.

Discussion on the Integration of“Post,Course,Competition,Certificate”:Taking the Internet of Things Application Technology Courses in Higher Vocational Colleges as an Example

This article explores the development of the Internet of Things(IoT)application technology course in higher vocational colleges under the background of“post,course,competition,certificate.”It first emphasizes the importance of IoT talent training and course construction in higher vocational colleges and deeply analyzes the core concept of“post,course,competition,certificate”integration.In view of the problems faced in the course construction of IoT application technology in higher vocational colleges and the practical experience of Tianjin Vocational College of Mechanics and Electricity,the implementation strategy of the course construction of IoT application technology in higher vocational colleges is elaborated in detail based on the integrated concept of“post,course,competition,certificate.”

The Model of“Post,Course,Competition,Certificate”Integrated Education for Electronic Information Engineering Technology Major in Higher Vocational Colleges

The core education function of higher vocational colleges is to train technical talents with high quality,so as to meet the needs of talents in the development stage of our society.Under the guidance of talent training,higher vocational colleges need to pay attention to establishing an all-round and three-dimensional education model,and promote innovation of higher vocational education on the basis of this.It is also a way to promote the innovation of higher vocational education to vigorously promote the construction of“post,course,competition,certificate”mode in the construction of education mode.Through the construction of“post,course,competition,certificate”mode,the education mode of higher vocational colleges is gradually improved,so as to strengthen the effectiveness of talent training in higher vocational colleges.Therefore,in this paper,the author puts forward some suggestions to promote the construction of the integrated education mode of the electronic information engineering technology major in higher vocational colleges,so as to help improve the talent training level of higher vocational colleges.

Effects of Pearl Yangxin Anshen Decoction on HAMD and PTSD-SS Scores, Cytokines and Related Metabolites in Patients with Post-Traumatic Stress Disorder

Objective: This paper aims to observe the Pearl Yangxin Anshen Decoction to influence the score of HAMD and PTSD-SS, the changes of the cytokines and the related metabolic product in patients with PTSD. Methods: From June 2015 to May 2016, in the traditional Chinese medicine clinics of Hainan Province People’s Hospital, there were 50 patients with PTSD, the age were from 30 to 60, they were randomly divided into treatment group (25 cases) and control group (25 cases), then compared the scores of HAMD and PTSD-SS between the two groups, searched the changes of cytokines and the related metabolic product. Results: In the treatment group: before and after treatment the scores of PTSD-SS were 65.64 ± 7.02, 28.32 ± 4.18, and the scores of HAMD were 29.28 ± 1.97, 11.72 ± 2.13;In the control group: before and after treatment the scores of PTSD-SS were 63.24 ± 6.16, 31.40 ± 4.29, the scores of HAMD were 30.24 ± 2.05, 13.08 ± 2.30. After 3 months patients in treatment group the scores of PTSD-SS and HAMD were lower than the control group (t = 2.570, P = 0.013, t = -2.1640, P = 0.035). In the control group: before and after 3 months treatment the IL-2 levels respectively were 79.84 ± 26.46 pg/ml, 56.18 ± 22.67 pg/ml, the IL-6 levels respectively were 110.83 ± 47.65 pg/ml, 59.67 ± 44.68 pg/ml, the IL-8 levels respectively were 73.11 ± 78.51 pg/ml, 55.83 ± 81.94 pg/ml, the NE levels respectively were 420.04 ± 674.75 pg/ml, 185.31 ± 417.91 pg/ml, the MDA levels respectively were 112.35 ± 62.87 ng/ml, 60.42.33 ± 53.64 ng/ml, the NO levels were 126.6 ± 47.4 μmol/L, 78.6 ± 45.7 μmol/L, the VIP levels were 396.6 ± 144.4 pg/ml, 122.4 ± 111.5 pg/ml. In the treatment group: before and after 3 months treatment the IL-2 levels respectively were 86.00 ± 32.29 pg/ml, 53.84 ± 27.01 pg/ml, the IL-6 levels respectively were 108.21 ± 44.60 pg/ml, 42.46 ± 42.16 pg/ml, the IL-8 levels respectively were 81.48 ± 94.19 pg/ml, 54.07 ± 84.15 pg/ml, the NE levels respectively were 392.93 ± 592.84 pg/ml, 243.85 ± 588.45 pg/ml, the MDA levels respectively were 117.58 ± 63.37 ng/ml, 45.91 ± 38.94 ng/ml, the NO levels respectively were 135.9 ± 46.4 μmol/L, 72.6 ± 46.6 μmol/L, the VIP levels respectively were 414.0 ± 140.1 pg/ml, 185.8 ± 105.3 pg/ml. In the two groups as the extension of treatment time, the content of IL-2, IL-8, IL-6, NE, MDA, NO, and VIP were gradually reduced, and the level of reduction of the treatment group patients was higher than the control group, the change of ACTH and SOD levels just the opposite. Conclusion: The Pearl Yangxin Anshen Decoction could improve the symptoms of psychological anxiety, depression and other psychological problems in patients with PTSD, and influence the change of cytokines and related metabolites product.

Post-Traumatic Stress Disorder among Defence and Security Forces in Northern Benin (2023)

Introduction: Post-traumatic stress disorder (PTSD) is defined as “actual exposure to death or the threat of death, serious injury or sexual violence”, either directly or indirectly, resulting in a symptomatic procession of repetition, avoidance, neurovegetative hyperactivity and individualized symptoms, with or without negative cognitive and mood changes. It therefore goes without saying that the defence and security forces constitute a high-risk population in need of attention. Objective: To study post-traumatic stress disorder in defence and security forces in the city of Parakou in 2023. Methods: Descriptive cross-sectional study conducted from December 2022 to July 2023. The study population consisted of active military, republican police and firefighters in the city of Parakou in 2023. Non-proportional stratified sampling was used, given the inaccessibility of the source population size for national security reasons. Post-traumatic stress disorder was assessed using the “post-traumatic stress disorder checklist-5 (PCLS-5) scale. Results: A total of 305 subjects participated in the survey. Males dominated 90.2%. The most represented corps was the Republican Police (41.6%), most of whom were non-commissioned officers (46.6%). The majority count between 11 and 20 years of service (48.9%), with 2 to 5 missions completed (67.5%). The calculated prevalence of post-traumatic stress disorder was 11.8%, based on the post-traumatic stress disorder checklist-5 (PCL-5). Of the 36 respondents with post-traumatic stress disorder, 20 (55.6%) had experienced an armed attack, 25 (69.4%) had witnessed a violent death, 18 (50.0%) had witnessed the agony of a colleague, 15 (41.7%) had been exposed to a fire or explosion, while 26 (72.2%) had been traumatized by physical and/or verbal aggression. 5 (13.9%) had consulted a specialist psychiatrist, while 6 (16.7%) were on medication and 26 (72.2%) used sport as a means of maintaining physical and mental health. Respectively 22 (61.1%) and 21 (58.3%) had definite symptoms of anxiety and depression. Multivariate analysis revealed a significant association between post-traumatic stress disorder and the following variables: total number of children ≤ 2 (p = 0.015), comorbidities such as arterial hypertension (p = 0.007), history of hepatitis (p = 0.017), work accidents (p = 0.016), alcohol dependence (p = 0.004), domestic violence (p = 0.004), psychological violence (p = 0.017) and anxiety disorders (p Conclusion: Defence and security personnel can also be prey to post-traumatic stress disorder (PTSD), which needs to be systematically taken into account when they are subjected to trauma in the course of their duties. Mental health should be an integral part of the periodic medical check-up objectives for defence and security forces throughout the country.

Correlation Study of Neurotransmitter and Immune Levels in Pre-Hospital Emergency Nurses with Post-Traumatic Stress Disorder

Objective: To investigate the occurrence of PTSD in pre-hospital emergency nurses and its related factors, and to compare the differences of neurotransmitter and immune-related factors between pre-hospital emergency nurses who experienced traumatic events and those who did not develop PTSD and healthy people. How: Post-traumatic Stress Disorder Self-Rating Scale (PCL-C) tests were performed on pre-hospital emergency nurses in PTSD group, non-PTSD group and healthy control group, and the plasma monoamine neurotransmitters and serum cytokines were determined by double-antibody sandwich ABC-ELISA assay using enzyme-linked adsorption kit provided by Shanghai Xitang Biotechnology Co., Ltd. Results: 1) There were statistically significant differences in PCL-C scores between PTSD group, non-PTSD group and healthy group (p α between PTSD group, non-PTSD group and healthy group (p Conclusion: Pre-hospital emergency nurses should have early psychological intervention and guidance to reduce the occurrence of PTSD in emergency and emergency nurses.

Evaluation of Clinical Characteristics and Plasma Cortisol Concentrations in Individuals with COVID-19 and Post-COVID Syndrome

COVID-19 generates systematic alterations in humans both in active stages of infection and over time, called post-COVID syndrome. Cortisol is a hormone that is overexpressed in inflammation and cellular stress processes. Its main function is to return to physiological homeostasis, so its evaluation together with other clinical parameters can allow us to determine the degree of systemic affectation by COVID-19. Objective: To evaluate changes in clinical parameters and plasma cortisol concentrations in patients with active COVID-19 and post-COVID syndrome. Material and Methods: Healthy patients, in stages of mild infection, critical and with post-COVID syndrome, were recruited, obtaining, through clinical diagnoses and interviews, their main clinical characteristics, in addition to plasma, in which cortisol concentrations were determined using competitive ELISA. Results: The critical stage group had higher frequencies of comorbidities, clinical symptoms, as well as more altered laboratory parameters compared to the other subgroups. In the post-COVID syndrome group after the initial infection, most laboratory parameters recovered, however, several clinical symptoms remained latent over time. The determination of cortisol showed an increase in its concentration, being higher in patients in critical stage and with post-COVID syndrome. Conclusion: COVID-19 disease generates clinical alterations that trigger an increase in plasma cortisol. These alterations increase as the stages of infection become more severe and some of them remain altered in patients with post-COVID syndrome.

Body Contour in the Post-Bariatric Male Patient

Background: Obesity is currently considered a public health problem. Bariatric procedures have become an important part of obesity management and, consequently, the number of male patients seeking post-bariatric reconstructive procedures have increased. Therefore, the clinical approach and understanding of the body contour of this population have become more relevant. The goal of post-bariatric reconstruction is to enhance the male silhouette through removal of skin and adipose tissue excess, and abdominal rectus diastasis repair. Material and Methods: We conducted a retrospective study at the Plastic and Reconstructive Surgery Department of the National Medical Center “20 de Noviembre”. All male patients referred to our department to start a post-bariatric reconstruction protocol from January 2018 to December 2022 were included in this study. Results: In total, 15 patients who underwent corporal contouring procedures were included;median age was 49.2 years with minimum of 33 years, and a maximum of 57 years. Median Body mass index was 28.4 kg/m2 with minimum of 22 kg/m2 and maximum of 38 kg/m2. All patients were treated 18 months after their bariatric surgery. All patients underwent an abdominoplasty as a body contouring procedure. 4 (26.7%) patients presented complications related to the surgery. Conclusion: We described a comprehensive and systematic approach to massive weight loss for male patients, suggesting an abdominal marking based on the patient’s clinical features and the expected results avoiding feminization of the abdominal body contour.

Principles and Techniques of Post-Traumatic Rhinoplasty: A Review of the Literature

Post-traumatic rhinoplasty is the surgical treatment of the complex functional and aesthetic sequelae of nasal trauma. Correcting a post-traumatic nose is a challenging task, requiring the surgeon to employ a range of techniques and grafts to adequately address the deformities observed. The results of our research show that restoring pre-traumatic form and function remains complex, although many guidelines have been established to refine and optimize the management of the after-effects of nasal trauma. But it is achievable with the right techniques. The objective of our review is to highlight the various post-traumatic nasal sequelae, describe the fundamental principles in the field of post-traumatic rhinoplasty and provide the surgeon with the various existing surgical techniques and strategies so that he or she can make an appropriate choice for the patient.

Systematic Analysis of Post-Translational Modifications for Increased Longevity of Biotherapeutic Proteins

Protein-based therapeutics (PPTs) are drugs used to treat a variety of different conditions in the human body by alleviating enzymatic deficiencies, augmenting other proteins and drugs, modulating signal pathways, and more. However, many PPTs struggle from a short half-life due to degradation caused by irreversible protein aggregation in the bloodstream. Currently, the most researched strategies for improving the efficiency and longevity of PPTs are post-translational modifications (PTMs). The goal of our research was to determine which type of PTM increases longevity the most for each of three commonly-used therapeutic proteins by comparing the docking scores (DS) and binding free energies (BFE) from protein aggregation and reception simulations. DS and BFE values were used to create a quantitative index that outputs a relative number from −1 to 1 to show reduced performance, no change, or increased performance. Results showed that methylation was the most beneficial for insulin (p < 0.1) and human growth hormone (p < 0.0001), and both phosphorylation and methylation were somewhat optimal for erythropoietin (p < 0.1 and p < 0.0001, respectively). Acetylation consistently provided the worst benefits with the most negative indices, while methylation had the most positive indices throughout. However, PTM efficacy varied between PPTs, supporting previous studies regarding how each PTM can confer different benefits based on the unique structures of recipient proteins.