Clinical practice guidelines for the diagnosis and treatment of scabies.

Scabies, caused by the Sarcoptes scabiei var hominis mite burrowing into the skin, is a highly contagious disease characterized by intense nocturnal itching. Its global impact is considerable, affecting more than 200 million individuals annually and posing significant challenges to healthcare systems worldwide. Transmission occurs primarily through direct skin-to-skin contact, contributing to its widespread prevalence and emergence as a substantial public health concern affecting large populations. This review presents consensus-based clinical practice guidelines for diagnosing and managing scabies, developed through the fuzzy Delphi method by dermatology, parasitology, pediatrics, pharmacology, and public health experts. The presence of burrows containing adult female mites, their eggs, and excreta is the diagnostic hallmark of scabies. Definitive diagnosis typically involves direct microscopic examination of skin scrapings obtained from these burrows, although dermoscopy has become a diagnostic tool in clinical practice. Treatment modalities encompass topical agents, such as permethrin, balsam of Peru, precipitated sulfur, and benzyl benzoate. In cases where topical therapy proves inadequate or in instances of crusted scabies, oral ivermectin is recommended as a systemic treatment option. This comprehensive approach addresses the diagnostic and therapeutic challenges associated with scabies, optimizing patient care, and management outcomes.

Unveiling the potential of antisense oligonucleotides: Mechanisms, therapies, and safety insights.

Antisense oligonucleotides (ASOs) are short, synthetic, single-stranded deoxynucleotide sequences composed of phosphate backbone-connected sugar rings. Designing of those strands is based on Watson-Crick hydrogen bonding mechanism. Thanks to rapidly advancing medicine and technology, evolving of the gene therapy area and ASO approaches gain attention. Considering the genetic basis of diseases, it is promising that gene therapy approaches offer more specific and effective options compared to conventional treatments. The objective of this review is to explain the mechanism of ASOs and discuss the characteristics and safety profiles of therapeutic agents in this field. Pharmacovigilance for gene therapy products is complex, requiring accurate assessment of benefit-risk balance and evaluation of adverse effects.

Microglia cells treated with synthetic vasoactive intestinal peptide or transduced with LentiVIP protect neuronal cells against degeneration.

A common pathological hallmark of neurodegenerative disorders is neuronal cell death, accompanied by neuroinflammation and oxidative stress. The vasoactive intestinal peptide (VIP) is a pleiotropic peptide that combines neuroprotective and immunomodulatory actions. The gene therapy field shows long-term promise for treating a wide range of neurodegenerative diseases (ND). In this study, we aimed to investigate the in vitro efficacy of transduction of microglia using lentiviral gene therapy vectors encoding VIP (LentiVIP). Additionally, we tested the protective effects of the secretome derived from LentiVIP-infected "immortalized human" microglia HMC3 cells, and cells treated with Synthetic VIP (SynVIP), against toxin-induced neurodegeneration. First, LentiVIP, which stably expresses VIP, was generated and purified. VIP secretion in microglial conditioned media (MG CM) for LentiVIP-infected HMC3 microglia cells was confirmed. Microglia cells were activated with lipopolysaccharide, and groups were formed as follows: 1) Control, 2) SynVIP-treated, or 3) LentiVIP-transduced. These MG CM were applied on an in vitro neurodegenerative model formed by differentiated (d)-SH-SY5Y cells. Then, cell survival analysis and apoptotic nuclear staining, besides measurement of oxidative/inflammatory parameters in CM of cells were performed. Activated MG CM reduced survival rates of both control and toxin-applied (d)-SH-SY5Y cells, whereas LentiVIP-infected MG CM and SynVIP-treated ones exhibited better survival rates. These findings were supported by apoptotic nuclear evaluations of (d)-SH-SY5Y cells, alongside oxidative/inflammatory parameters in their CM. LentiVIP seems worthy of further studies for the treatment of ND because of the potential of gene therapy to treat diseases effectively with a single injection.

Gene therapy in cancer.

Gene therapy, recently frequently investigated, is an alternative treatment method that introduces therapeutic genes into a cancer cell or tissue to cause cell death or slow down the growth of the cancer. This treatment has various strategies such as therapeutic gene activation or silencing of unwanted or defective genes; therefore a wide variety of genes and viral or nonviral vectors are being used in studies. Gene therapy strategies in cancer can be classified as inhibition of oncogene activation, activation of tumor suppressor gene, immunotherapy, suicide gene therapy and antiangiogenic gene therapy. In this review, we explain gene therapy, gene therapy strategies in cancer, approved gene medicines for cancer treatment and future of gene therapy in cancer. Today gene therapy has not yet reached the level of replacing conventional therapies. However, with a better understanding of the mechanism of cancer to determine the right treatment and target, in the future gene therapy, used as monotherapy or in combination with another existing treatment options, is likely to be used as a new medical procedure that will make cancer a controllable disease.

Additive cell protective and oxidative stress reducing effects of combined treatment with cromolyn sodium and masitinib on MPTP-induced toxicity in SH-SY5Y neuroblastoma cells.

The suppression of oxidative-stress induced neurotoxicity by antioxidants serves as a potential preventive strategy for neurodegenerative diseases. In this study, we aimed to investigate the cell protective and antioxidant effects of masitinib and cromolyn sodium against toxin-induced neurodegeneration. First, human neuroblastoma SH-SY5Y cells were differentiated into neuron-like (d)-SH-SY5Y cells. The differentiated cells were confirmed by immuno-staining with anti-PGP9.5 antibody, a neuronal marker. Cell culture groups were formed, and a neurotoxin, 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) was applied on cells followed by masitinib and/or cromolyn sodium treatments. Survival rate of cells were detected by MTT assay. Anti-inflammatory Transforming Growth Factor-ß1 (TGF-ß1) and nitric oxide (NO) levels and total oxidant and antioxidant capacities (TOC and TAC) in cell conditioned media (CM) were measured. Morphological analysis and apoptotic nuclear assessment of cells were also noted. When (d)-SH-SY5Y cells were exposed to neurotoxin, cell viability rates of these cells were found to be decreased in a concentration-dependent manner. CM of toxin applied group displayed higher levels of TOC/TAC ratios and NO levels compared to control (p < 0.01). Both masitinib and cromolyn sodium protected cells from toxin-induced cell death as revealed by ameliorated rates of viability, reversed toxin-induced elevation of TOC/TAC ratios, and decreased NO levels in their CM (p < 0.01). Combined treatment significantly reduced TOC/TAC ratios and NO levels more effectively compared to mono-treatments. Both drugs also increased TGF-ß1 levels significantly in cell CM. When these agents were tested for therapeutic effects against toxin-induced cell degeneration, better viability results were obtained by both masitinib and cromolyn sodium treatment, with significantly better amelioration provided by combined application of these drugs (p < 0.01). This study demonstrated new findings that combined treatment with cromolyn sodium, an FDA-approved drug of asthma, and masitinib, an orally administered drug with a low toxicity, exert neuroprotective and additive therapeutic effects. We propose that combination therapy of masitinib and cromolyn sodium may represent an innovative treatment in neurodegenerative diseases. Combination therapy may be more advantageous that it enables combined application of lower doses of both drugs, providing less side effects.

Medical students' knowledge and awareness levels about biologics and biosimilars: the earlier the better?

BACKGROUND: Although most studies about physician knowledge and attitude toward biosimilars have been conducted on specialists, studies addressing this issue among medical students are missing. OBJECTIVE: We aimed to evaluate the knowledge and awareness levels of biologics and biosimilars of medical students who will encounter these products soon. METHODS: In this cross-sectional study, 228 medical students were grouped as preclinical (Years 1,2,3) and clinical (Years 4,5,6). Students were given a survey including demographic (grade and gender) and questions about assessing their knowledge about biologics and biosimilars. RESULTS: Clinical students' knowledge was better than preclinical students (54% and 25%, respectively). Students did not know much about biosimilars (7-20%) and thought a biosimilar is identical to its generic product (35%). More than 90% of the students thought that a lesson about biologics should be included in the medical curriculum. CONCLUSIONS: Our study showed that medical students had inadequate knowledge about biosimilars. We suggest that to establish a positive attitude toward prescribing biosimilars, knowledge about biologics and biosimilars should be delivered to physicians early, while they are still medical students, by including this topic into the medical curriculum.

SARS-CoV-2 Mutations and their Viral Variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occur spontaneously during replication. Thousands of mutations have accumulated and continue to since the emergence of the virus. As novel mutations continue appearing at the scene, naturally, new variants are increasingly observed. Since the first occurrence of the SARS-CoV-2 infection, a wide variety of drug compounds affecting the binding sites of the virus have begun to be studied. As the drug and vaccine trials are continuing, it is of utmost importance to take into consideration the SARS-CoV-2 mutations and their respective frequencies since these data could lead the way to multi-drug combinations. The lack of effective therapeutic and preventive strategies against human coronaviruses (hCoVs) necessitates research that is of interest to the clinical applications. The reason why the mutations in glycoprotein S lead to vaccine escape is related to the location of the mutation and the affinity of the protein. At the same time, it can be said that variations should occur in areas such as the receptor-binding domain (RBD), and vaccines and antiviral drugs should be formulated by targeting more than one viral protein. In this review, a literature survey in the scope of the increasing SARS-CoV-2 mutations and the viral variations is conducted. In the light of current knowledge, the various disguises of the mutant SARS-CoV-2 forms and their apparent differences from the original strain are examined as they could possibly aid in finding the most appropriate therapeutic approaches.

Host variations in SARS-CoV-2 infection.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the zoonotic pathogen that causes the "Coronavirus Disease of 2019 (COVID-19)", and COVID-19 itself is yet to be thoroughly understood. Both the disease as well as the mechanisms by which the host interacts with the SARS-CoV-2 have not been fully enlightened. The epidemiological factors -e.g. age, sex, race-, the polymorphisms of the host proteins, the blood types and individual differences have all been in discussions about affecting the progression and the course of COVID-19 both individually and collectively, as their effects are mostly interwoven. We focused mainly on the effect of polymorphic variants of the host proteins that have been shown to take part in and/or affect the pathogenesis of COVID-19. Additionally, how the procedures of diagnosing and treating COVID-19 are affected by these variants and what possible changes can be implemented are the other questions, which are sought to be answered.

Promising Perspective to Facioscapulohumeral Muscular Dystrophy Treatment: Nutraceuticals and Phytochemicals.

Facioscapulohumeral Muscular Dystrophy (FSHD) is in the top three list of all dystrophies with an approximate 1:8000 incidence. It is not a life-threatening disease; however, the progression of the disease extends over being wheelchair bound. Despite some drug trials continuing, including DUX4 inhibition, TGF-ß inhibition and resokine which promote healthier muscle, there is not an applicable treatment option for FSHD today. Still, there is a need for new agents to heal, stop or at least slow down muscle wasting. Current FSHD studies involving nutraceuticals as vitamin C, vitamin E, coenzyme Q10, zinc, selenium, and phytochemicals as curcumin or genistein, daidzein flavonoids provide promising treatment strategies. In this review, we present the clinical and molecular nature of FSHD and focus on nutraceuticals and phytochemicals that may alleviate FSHD. In the light of the association of impaired pathophysiological FSHD pathways with nutraceuticals and phytochemicals according to the literature, we present both studied and novel approaches that can contribute to FSHD treatment.

Silencing acpP gene via antisense oligonucleotide-niosome complex in clinical Pseudomonas aeruginosa isolates.

Pseudomonas aeruginosa, an opportunistic Gram-negative pathogen, is one of the major causes of nosocomial infections. In addition to its physiological adaptation capacity, it can develop resistance to disinfectants and antibiotics through various mechanisms. Recently, new eradication methods are gaining attention. Therefore, in this study, an LNA-2'-O-methyl hybrid antisense oligonucleotide targeting the acyl carrier protein P (acpP) gene was introduced into P. aeruginosa isolates. The design was determined through sequence analysis and prediction of the secondary structure of mRNA by software. Niosomes were used for enhancing cellular uptake. The control of the binding and transfection ability of the sequence was determined fluorometrically by labeling with 6-Fam. The effects were determined with broth microdilution method and qPCR studies. Eight different formulations were prepared. Among these, one formulation has shown to have ASO complexation ability whose composition was 312 µl Span 80 + 69.5 mg Cholesterol+ 36.4 mg CTAB+1 ml Chloroform and 5 ml dH2O. Thus this formulation was determined as the delivery system for the next stages. Significant gene inhibition was detected at the six isolates. Results of this study suggested that niosomes can be used as a delivery system for cellular uptake of ASO and could eliminate bacterial growth.

Knowledge level and attitude towards complementary and alternative treatment methods among medical students: a cross-sectional survey study in Turkey.

OBJECTIVE: People often use complementary and alternative medicine (CAM) methods in Turkey, but reliability of the application of these methods is controversial. Considering the role of medical students (i.e. physician candidates) in sustainable health, their perspectives on CAM methods are important. This report explores the level of knowledge, experience, and preferences for the use of CAM methods among medical school students. MATERIAL AND METHODS: A survey about the use of CAM and interest in CAM methods was applied to 101 first-year and 87 fifth-year medical school students. The binary and multinomial logistic regression models were used for statistical analysis. RESULTS: Sixteen percent of the first-year and 9% of the fifth-year students were familiar with "The Regulation on Traditional and Complementary Medical Practices" published by the Ministry of Health of Turkey in 2014. While participants reported the most familiarity with acupuncture treatment, they were the most unfamiliar with prolotherapy among all CAM methods. Seeking advice from a licensed physician before applying CAM methods was the general agreement among the participants. Interest in learning and practicing hypnosis was the highest-rated CAM method among the participants. CONCLUSIONS: Increasing knowledge and awareness of CAM methods by including them into the medical curriculum would be essential for the correct use of CAM methods.