therapeutic

Background: Parapneumonic pleural effusion is a relatively common entity and continues to be a major cause of morbidity in children. However, managing this disease is still a matter of controversy between surgical and non-surgical options. With the advancement of mini-invasive surgery, video-assisted thoracoscopic surgery (VATS) has become a mainstay in the treatment of parapneumonic effusion in children. This study aimed to evaluate the clinical characteristics and pathological features of parapneumonic pleural effusion in children and to explore the feasibility and safety of the thoracoscopic approach in the pediatric population.Methods: The clinical data of all patients who underwent VATS for parapneumonic effusion between 2007 and 2021 were analyzed retrospectively. Factors that were documented included demographic criteria, clinical manifestations, preoperative examinations, therapeutic procedures, intraoperative findings, postoperative complications, and outcomes.Results: Totally, 35 patients with a mean age of 5.14 ± 3.9 years were operated on thoracoscopically. The mean duration of evolution before VATS was 9 days ± 4. All children were hospitalized in a Pediatric Continuing Care Unit. Antibiotic therapy was administrated in combination in all cases. Corticosteroid therapy was used in 2 patients. Thoracentesis was performed in 6 patients. Thoracostomy tube drainage was placed before surgery in 11 patients. The average duration of drainage before VATS was 6 days ± 4. VATS decortication and/or debridement was indicated as second-line in 23 patients. The average duration of the surgery was 51 minutes (20 min - 115 min). There is no conversion to open surgery and no intraoperative procedure-dependent complication. 4 children have early complications after the VATS and one patient had a late postoperative complication. There were no deaths during the hospital stay or follow-up. Conclusion: In skilled hands, VATS is safe, feasible, and effective in the management of parapneumonic pleural effusion in children with excellent outcomes.

Introduction: In an earlier study, we described and validated a VKA dose-finding algorithm (B2A), based on a novel bidirectional factor (BF). We designed a prospective study to evaluate the B2A in a daily care setting. Methods: In this open-label prospective study, we compared the outcomes of the B2A over the year 2020 with the outcomes of the previous year (2019), using regular algorithms. The outcomes were the duration of Time in the Therapeutic Range (TTR), the percentage of automated dose proposals (PAuP) and the percentage of accepted dose proposals (PAcP). The data were obtained from three anticoagulation centers in the Netherlands, in four locations. The outcomes of this study were based on a non-inferiority level.Results: The TTR over the year 2020 was at least non-inferior compared with the standard of care treatment. The percentage of automated proposals increased in all centers to approximately 96% of all dosages. Conclusion: The B2A performs non-inferior compared with the existing algorithms and in some aspects even better.

Prescriptions for psychoactive substances such as Pregabalin, Methamphetamine, Caffeine, Clonazepam and Mirtazapine (PM-CCM) are common in the treatment of a variety of disorders. Indeed, the PM-CCM has been used in different therapeutic areas, including insomnia, anxiety, seizure disorders, etc. Unfortunately, these psychoactive substances are present in the illegal street market, leading to a lot of drug abuse among some addicted users, road insecurity and suicide. Hence, it has become essential to validate and develop a rapid and effective method to analyze the PM-CCM, a modified illicit drug, for drug abuse in the forensic sciences. A simple, rapid, specific and sensitive Gas Chromatography-Mass Spectrometry(GC-MS) method has been developed for the identification of Pregabalin, Methamphetamine, Caffeine, Clonazepam and Mirtazapine (PM-CCM) in forensic exhibits. At room temperature, the sample was ultrasonicated for 5 minutes before being extracted with methanol. A highly precise auto-injector is used to inject a very small quantity of samples for analysis. Helium is used as a carrier gas with a flow rate of 1 ml/min. The separation of PM-CCM was performed on SH-RXi-5 MS, ID.25 mm, film thickness. 25 µm, length of 30 m column. The constituents of PM-CCM were identified by the mass-to-charge ratio (m/z ratio) of fragments of the parent compound by comparing them with the NIST-17 MS Library. Separation and identification of PM-CCM were achieved within a 15-minute run. The proposed method has been successfully used for the routine analysis of PM-CCM in complex illicit drug preparations and in forensic exhibits as well. The application of above discussed qualitative analysis method and screening of PM-CCM, modified illicit drug samples demonstrates the potential and applicability of the technique to the fast chemical profiling of illicit samples.  

Background: Measurement of health-related quality of life (HRQOL) in children and adolescents with type 1 diabetes mellitus (T1DM) is as important as metabolic control in the management and prevention of diabetes-related complications. Aim: To describe the self-reported HRQOL outcomes in Ghanaian children and adolescents with T1DM compared with healthy controls and perceived HRQOL by caregivers.Setting: Out-patient clinics of the Departments of Child Health, Medicine and Therapeutics, Family Medicine, and Ophthalmology, the National Diabetes Management and Research Centre (all at the Korle Bu Teaching Hospital), and the Cape Coast Teaching Hospital (CCTH).Methods: Socio-demographic and clinical characteristics of study participants were documented. Participants completed the PedsQL™ 4.0 Generic Core Scales. Data analysis was done with SPSS Version 25.0. An unpaired t-test was used in comparing the HRQOL scores between children and adolescents with T1DM and controls, and parental proxy reports. Results: Fifty children and adolescents with T1DM, 50 parents/caregivers, and 80 healthy non-diabetic controls took part in this study. There was no significant difference in mean score between the patients and the caregivers for overall HRQOL (p = 0.270). Patients reported significantly worse overall HRQOL than their controls (p = 0.001). Males with diabetes reported better HRQOL than females (p = 0.007). Conclusion: Children and adolescents with T1DM and their parents/caregivers reported lower HRQOL scores compared to healthy controls. Males reported better HRQOL than females. Potential implications: HRQOL should be routinely assessed together with proxy reports from parents to identify those who might benefit from further attention including referral to a psychologist.

This article contains modern data on the etiology, clinical presentation and treatment as well as the differential diagnosis of a rare dermatosis, Sneddon-Wilkinson disease.Clinical observation of subcorneal pustular dermatosis in a 68-year-old woman is reported. Histopathological examination played a key role in making the correct diagnosis. Treatment consisted of a physiotherapeutic approach (311 nm UVB phototherapy) in combination with systemic glucocorticosteroids (dexamethasone). This therapeutic approach (instead of dapsone therapy) can be used due to its relatively good safety profile.

mRNA drugs are synthesized using cell-free systems without complex and stringent manufacturing processes, which makes their preparation simple, efficient, and economical. Over the past few years, mRNAs encoding antibodies have been one of the research frontiers of antibody drug development. In cancer immunotherapy, mRNAs encoding immune checkpoint antibodies may be advantageous regarding antibody persistence and durability of the anti-tumor immune response of patients. In our previous study, a candidate antibody—AET2010—targeting the novel immune checkpoint TIGIT was reported. Its anti-tumor activity was also investigated using adoptive transfer of NK-92MI cells in a xenograft mouse model, but the limitations of the model did not facilitate precise evaluation. In the present study, we further investigated the therapeutic potential of AET2010 for cancer in TIGIT-humanized BALB/c mice. Next, we explored the design, synthesis, and optimization of mRNAs encoding AET2010 and ultimately obtained a candidate mRNA (mRNA-BU) with favorable in vitro and in vivo expression levels of active AET2010. Particularly, lipid-nanoparticle-encapsulated mRNA-BU delivered to mice produced AET2010 with significantly higher peak concentration and expression duration than an equivalent dose of original AET2010. This study provides a sound basis for developing novel drugs targeting TIGIT.

There is an urgent need for predictive preclinical models to enhance the success rate of clinical trial outcomes. One of the main reasons for drug attrition is the lack of translational models, methods using human cells are particularly in the spotlight of regulatory bodies as they offer an alternative to in vivo studies and have the potential to improve the translational of preclinical trials. Organs-on-Chips (OoCs) are sensible candidates to reduce the cost and the ethical burden of animal models while accelerating and de-risking drug development. The innovation of such systems is based on both the increased relevance of the cells used and the ability to build precise, yet physiologically relevant, complex architectures. The use of microfluidic technologies with human induced pluripotent stem cells (hiPSCs) opens new routes to create relevant in vitro approaches as they will soon be able to reproduce clinical characteristics of donors or specific populations. The adoption of OoC models by pharmaceutical industries, and in fine by regulatory agencies, still requires: (i) establishing standardized, reproducible, robust, and replicable cell culture protocols with specific validation and characterization criteria, (ii) evidence that the technology predicts human responses, thus allowing to contribute efficiently and reliably to clinical trials success of novel therapeutics, and (iii) evidence that the models refine and reduce animal testing without compromising with the quality and the pertinence of the data generated.

Introduction: Infection and the accompanying inflammation of the upper and lower respiratory tract, influenza and COVID-19, are among the deadliest diseases in human life in the world. Due to the high emergence of bacterial resistance to antibiotics, we strive to find alternatives to contribute to the treatment by using a new formulation of a mixture of six essential oils in the form of a drop called Respira drops for a therapeutic approach to the upper or lower parts of the respiratory system infection, either by inhalation or sniffing, or by touching it with the body in the form of a skin patch on the head, neck, or chest. The present study suggested that natural essential oils may act as a prophylactic and therapeutic agent in respiratory tract hypoxia, inflammation, and bacterial and viral infection (influenza and COVID-19).Case presentation: A 62-year-old Yemeni man was suffering from acute pneumonia and had used antibiotics his condition improved, but he was suffering from difficulty breathing and stayed on the use of oxygen at home for more than three months, and his SpO2 ranged between 75 to 85 and he also suffered from an abdominal hernia, and he went for a procedure Surgery, and when the SpO2 was measured at 86, the surgery was not completed as a result, so he used Respira drops by inhalation and by steam for twenty-four hours and the next day he went to the hospital and the SpO2 was measured 96 and the operation was performed and he continued using Respira for two weeks three times per day and his condition improved completely.Conclusion: The present case study shows the excellent therapeutic response for Respira drops as inhalation and smiling three times per day increased SpO2 levels which reflect the anti-inflammatory, antimicrobial and anti-viral effects (influenza and COVID-19).

This article investigates the viability of SARS-CoV-2 and its dependence on pH levels, specifically focusing on the difference between the pH stability intervals for the coronavirus and human blood. Human blood typically maintains a pH range of around 7.35 to 7.45, while SARS-CoV-2 exhibits stability within the pH range of 6.0 to 6.5. The study aims to elucidate the critical role of hemoglobin in maintaining pH balance and explores its implications for viral susceptibility. The findings emphasize the importance of reinforcing the alkalinity of the medium as a means to weaken the virus. The research contributes to the understanding of pH-dependent mechanisms in viral infections and provides valuable insights for the development of potential therapeutic strategies.

Monkeypox is a sylvatic zoonotic sickness that initially affected tropical rainforest areas in the west and vital Africa earlier than spreading to other places. Its miles carried with the aid of the Monkeypox virus member of orthopoxvirus circle of relatives. The clinical features of the infection resembles to smallpox. The primary animal to human transmission is the cause of most people of human Monkeypox ailments. Severe rodent species and non-human primates function hosts for the virus. Transmission can manifest with infected people, animals or objects into contact with bodily fluids, sores on the skin or inner mucosal surfaces just like the mouth or throat, or breathing droplets. The incubation length for Monkeypox usually lasts 6 to 13 days, even though it could last as long as 21 days. The ailment is often self-proscribing, with signs and symptoms generally clearing up on their own inside 14 to 21 days. Signs can range from moderate to extreme, and lesions may be itchy or painful. Due to the discontinuation of recurring smallpox vaccination which supplied some pass- safety in past, populations have become more liable to Monkey pox. The outbreak of Monkeypox virus due to the fact that may additionally, 2022 has created a worldwide risk of the virus. In the present review, Monkeypox epidemiology, severity, therapeutics, vaccination and its transmission to non-endemic countries has been considered. Special care and guidelines may help in the containing in the spread of the infections to the non endemic countries.

Genistein is an isoflavone glycoside that provides a variety of health advantages. The possibility of cancer chemopreventive drugs derived from natural sources, such as polyphenols, may constitute a novel, cost-effective strategy to reduce the rising burden of cancer throughout the world. A soy-rich diet was linked to cancer prevention in several epidemiological studies, which was explained by the presence of the phenolic component genistein in soy-based foods. Inhibiting metastasis and changing apoptosis, the cell cycle, and angiogenesis are the key ways that genistin fights various cancers. It acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. This study critically evaluates the literature that is currently available on the therapeutic benefits of genistin for various cancers.

Objective: To evaluate the surgical management of myomas at the Teaching Hospital of Angré according to the FIGO (International Federation of Gynecology and Obstetrics) classification.Patients and methods: This was a cross-sectional study at the Teaching Hospital of Angre from January 1, 2020, to December 31, 2022. Patients whose operative indication was clearly identified were included in the study. Incomplete files were not included. The variables studied were anthropometric parameters, clinical characteristics of myomas, and surgery. Due to the large size and multifocal location of uterine myomas, the therapeutic option remained surgery by laparotomy.Results: Most patients were over 35 years old (71.5%) and nulliparous (52.8%). The first indication for surgery was menometrorrhagia (88.6%), followed by the desire for motherhood (37.8%) and dysmenorrhoea (20.2%) for myomas most often FIGO type 4 (p = 0.0031). Myomectomy under cervical-isthmic tourniquet was the most common procedure for FIGO type 4 myomas (66.1%; p = 0.0543). Hysterectomy was most frequently performed for FIGO type 7 myomas (43.9%; p = 0.0543). For myomectomy, the first complication was anaemia (3.5%) followed by uterine suture haemorrhage (1.7%) (p = 0.5139).Conclusion: Our surgical practice at the Teaching Hospital of Angre is in accordance with FIGO recommendations. However, an effort should be made to promote the minimally invasive surgical approach (laparoscopic, hysteroscopic, transvaginal ablation) for small fibroids (≤ 5 cm) or FIGO type 0 to 3, which is not very frequent in our current practice.

Cancer is a major public health issue and the main cause of death worldwide. Despite improvements in diagnostic techniques and treatment methods, cancer still seriously affects the quality of life of patients, which cause serious social and economic burdens. Therefore, there is an urgent need to identify potential biomarkers to improve diagnosis, treatment, and prognosis of cancer. BTG2 is a cell proliferation suppressor gene that serves as a tumor suppressor gene in the occurrence and development of various tumors. Many studies have shown that BTG2 can serve as a prognostic marker in various tumors. So, fully tap the potentials of BTG2 as a tumor prognostic marker will bring more possibilities to provide a new method or new diagnostic and therapeutic tool for treating cancer.

The well-documented therapeutic potential of group singing for patients living with Alzheimer’s disease (PLAD) has been hindered by COVID-19 restrictions, exacerbating loneliness and cognitive decline among seniors in residential and long-term care centers (CHSLDs). Addressing this challenge, the multidisciplinary study aims to develop a patient-oriented virtual reality (XR) interaction system facilitating group singing for mental health support during confinement and enhancing the understanding of the links between Alzheimer’s disease, social interaction, and singing. The researchers also propose to establish an early AD detection system using voice, facial, and non-invasive biometric measurements and validate the efficacy of selected intervention practices. The methodology involves co-designing an intelligent environment with caregivers to support PLAD mental health through online group singing, addressing existing constraints in CHSLDs. The researchers will engage volunteers in remote singing interactions and validate the impact of voice stimulation for PLADs using a control group. The primary expected outcome is the development of an “Intelligent Learning Health Environment,” fostering interactions while adapting to individual PLAD situations and incrementally accumulating knowledge on AD signs. This environment will facilitate the transfer of knowledge and technologies to promote non-verbal interactions via singing, enabling intervention at the first symptoms. Additionally, the research will contribute to transforming CHSLDs’ living environments, informed by neuroscience insights, and potentially extend the “collaborative self-care” approach to support seniors in aging safely and healthily at home.

Immune cytopenias occur when the body produces antibodies that target specific hematopoietic cells, inducing extravascular antibody-mediated phagocytosis by monocyte-macrophages in the spleen and/or liver through activation of Fcγ Receptors (FcγRs). Immune cytopenias include Immune Thrombocytopenia (ITP), Autoimmune Hemolytic Anemia (AIHA), Hemolytic Transfusion Reactions (HTR), Hemolytic Disease of the Fetus and Newborn (HDFN), and Autoimmune Neutropenia (AIN). Thus, novel therapeutics that inhibit phagocytosis would be useful, especially for short-term use while other therapies are being evaluated. In our earlier studies, we successfully identified two small-molecule drugs able to inhibit in vitro phagocytosis with a low IC50 concentration and negligible toxicity. These drugs, known as KB-151 and KB-208, have the potential to be utilized as lead compounds for further studies, once their mechanism of action is more clearly understood. In this regard, we have developed preliminary results that suggest that these small molecules may bind to the Fc receptors on monocyte macrophages and block the subsequent attachment of antibody-opsonized red blood cells to prevent phagocytosis.

The 2019 COVID-19 pandemic caused by SARS-CoV-2 has resulted in many fatalities worldwide. Despite various types of supportive care, mortality rates for patients with comorbidities remain high. To explore alternative treatment options, interferons (IFNs) have emerged as promising therapeutic drugs for SARS-CoV-2. This review aims to investigate the potential of IFNs as a drug with details on their mechanisms of action, and available data on their use with ongoing clinical trials, results, potential limitations, and challenges.  Recently published research articles, which are systematically searched through online databases, have been selected and found that IFNs have colossal potential in treating SARS-CoV-2 infection by modulating the host’s immune response and inhibiting viral replication and decreasing the severity of disease and hospitalization (p = 0.03, ± 0.05) and (p = 0.04, ± 0.05) respectively. However, due to less available data, more controlled and randomized trials are needed to confirm the efficacy and safety of IFN therapy.  The optimal dosing and duration of IFN therapy also remain to be determined. Although further research is needed the wait for ongoing clinical trial results under investigation is also important for a better understanding of IFN therapy.

Objective: Assessment of heart rate variability (HRV) is a non-invasive and reliable method to evaluate autonomic disorders after cerebral ischemia. The present study was conducted to investigate the therapeutic potential of IC87201 in reducing post-stroke cardiac dysfunction. Materials and methods: Cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO) method in 15 anesthetized adult male rats in three MCAO, MCAO+ DXM, and MCAO+ IC87201 groups, for one hour. Electrocardiogram was recorded before, and 48 hours after ischemia and drug administration, and HRV parameters were calculated from R-R intervals. In the treatment groups, IC87201 and Dextromethorphan hydrobromide monohydrate (DXM) were injected after an ischemic period. Results: After brain ischemia, the R-R interval decreased and consequently heart rate increased. The R-R intervals were used to extract the HRV frequency and time domains, including normalized low frequency (LF), high frequency (HF), LF/HF ratio, and standard deviation of R-R interval (SDRR). Normalized LF and LF/HF ratio enhanced 48 hours after ischemia, while normalized HF and SDRR significantly reduced compared to the pre-ischemic state. All HRV parameters had returned to their pre-ischemic level 48 hours after IC87201 and DXM administration, except SDRR, which recovered only in the IC87201 administered group. Conclusion: Based on our findings, it can be concluded that cerebral ischemia significantly worsens HRV parameters as a result of sympathetic overactivity. These changes were reversed by administering DXM and IC87201, but IC87201 has generally been more effective in lowering lesions. As a result, IC87201 can be introduced as an effective substance for the treatment of post-ischemic cardiac side effects.

Calciphylaxis (CP) or uremic calcific arterial disease (CUA) is a rare, potentially fatal calcific vasculopathy characterized by calcific and thrombotic occlusion of the vessels of the subcutaneous and dermis leading to extremely painful necrotic lesions. It mainly affects patients with end-stage kidney disease (ESKD) and under long time dialysis. The only therapeutic option is represented by intravenous sodium thiosulfate. Currently, clear guidelines are lacking. We have had a good therapeutic response with doses of sodium thiosulfate in association with multidisciplinary management of the patient (vulnologist, dermatologist, nephrologist, dietitian, and cardiologist). There is limited literature on the use of DOAC therapy as a successful alternative to warfarin in patients on dialysis with calciphylaxis. The left atrial appendage closure could represent an important alternative to dicumarolics in patients with atrial fibrillation with calciphylaxis. A new perspective for the treatment of this disease is SNF472 a selective inhibitor of vascular calcification.

Background and aim: Preclinical in vitro and in vivo experiments suggest that radiation-induced tumour cell death can be enhanced 10- to 40-fold when combined with focused-ultrasound (FUS)-stimulated microbubbles (MB). The acoustic exposure of MB in the tumour volume causes vasculature perturbation, activation of the acid sphingomyelinase (ASMase) ceramide pathway, and resultant endothelial cell apoptosis. When the tumour is subsequently treated with radiation, there is increased endothelial cell death and anoxic tumour killing. Here we describe a first-in-human experience treating patients with magnetic resonance (MR)-guided FUS-stimulated MB (MRgFUS+MB) radiation enhancement.Case presentation: A head and neck cancer patient with recurrent disease underwent radiotherapy for 5 separate sites of locoregional disease followed by systemic therapy. The first consisted of a course of 45 Gy in 5 fractions alone, the second of 30 Gy in 5 fractions with hyperthermia, and the three others of 20-30 Gy in 5 fractions along with MRgFUS+MB treatment. The treatment methodology used an MR-coupled FUS-device operating at 500 KHz and 540 kPa peak negative pressure with an insonification time of 750 ms spread over 5 minutes to stimulate intravenously administered MB within tumour target. All sites treated with stimulated MB had a complete radiological response, and subsequently, the patient’s other cutaneous metastatic disease disappeared. The patient has been under surveillance for over two years without active treatment or disease progression.Discussion: MRgFUS+MB was well-tolerated with no reported treatment-related adverse events, which can be attributed to the capability of FUS to selectively stimulate MB within the tumour volume while sparing the surrounding normal tissue. Sustained local control at all target sites aligns with earlier preclinical findings suggesting the radiation enhancement potential of FUS+MB.Conclusion: MRgFUS+MB represents a novel and promising therapy for enhancing radiation efficacy and improving therapeutic index with potential improvements in disease control.

Cardiovascular diseases (CVD) are considered as “lifestyle” diseases and so far “No unified procedure” or medicines are effective in the management of this group of diseases. Researchers and clinicians have indicated that no safe therapeutic window is available in therapeutics at present. Recent research showed that gut microbiota are effective in managing lifestyle diseases therefore we introduced the influence of gut microbiota in the prognosis of the CVDs. Faecal transplant therapy(FMT) has been anticipated to treat many diseases similar to recurrent bacterial Clostridioides difficile infection which has been used worldwide. Recently, FMT was tried on an animal model to treat CVDs, and recent human trials that were tried to manage CVDs in humans by FMT showed encouraging results. The mechanism of action of transplanted bacteria to manage CVDs in the human population is also discussed. In-depth knowledge on the pros and cons of FMT will pave the way to standardize the procedure once the lacuna existing at present in treating CVDs, is paved, this technology will be useful for the masses.