Emergence of Small Interfering RNA-Based Gene Drugs for Various Diseases.

Small molecule, peptide, and protein-based drugs have been developed over decades to treat various diseases. The importance of gene therapy as an alternative to traditional drugs has increased after the discovery of gene-based drugs such as Gendicine for cancer and Neovasculgen for peripheral artery disease. Since then, the pharma sector is focusing on developing gene-based drugs for various diseases. After the discovery of the RNA interference (RNAi) mechanism, the development of siRNA-based gene therapy has been accelerated immensely. siRNA-based treatment for hereditary transthyretin-mediated amyloidosis (hATTR) using Onpattro and acute hepatic porphyria (AHP) by Givlaari and three more FDA-approved siRNA drugs has set up a milestone and further improved the confidence for the development of gene therapeutics for a spectrum of diseases. siRNA-based gene drugs have more advantages over other gene therapies and are under study to treat different types of diseases such as viral infections, cardiovascular diseases, cancer, and many more. However, there are a few bottlenecks to realizing the full potential of siRNA-based gene therapy. They include chemical instability, nontargeted biodistribution, undesirable innate immune responses, and off-target effects. This review provides a comprehensive view of siRNA-based gene drugs: challenges associated with siRNA delivery, their potential, and future prospects.

Bumblebees acquire alternative puzzle-box solutions via social learning.

The astonishing behavioural repertoires of social insects have been thought largely innate, but these insects have repeatedly demonstrated remarkable capacities for both individual and social learning. Using the bumblebee Bombus terrestris as a model, we developed a two-option puzzle box task and used open diffusion paradigms to observe the transmission of novel, nonnatural foraging behaviours through populations. Box-opening behaviour spread through colonies seeded with a demonstrator trained to perform 1 of the 2 possible behavioural variants, and the observers acquired the demonstrated variant. This preference persisted among observers even when the alternative technique was discovered. In control diffusion experiments that lacked a demonstrator, some bees spontaneously opened the puzzle boxes but were significantly less proficient than those that learned in the presence of a demonstrator. This suggested that social learning was crucial to proper acquisition of box opening. Additional open diffusion experiments where 2 behavioural variants were initially present in similar proportions ended with a single variant becoming dominant, due to stochastic processes. We discuss whether these results, which replicate those found in primates and birds, might indicate a capacity for culture in bumblebees.

The Impact of Rigid Cervical Collars on Outcome of Patients Who Underwent Posterior Cervical Laminectomy and Fusion: A Retrospective Comparative Study.

STUDY DESIGN: Retrospective cohort study. PURPOSE: This study aimed to investigate the cervical collar impact on the functional outcomes of patients after posterior cervical laminectomy and lateral mass screw fixation (PCLF) surgery. OVERVIEW OF LITERATURE: The safety and possible benefits of implementing rigid cervical collars subsequent to PCLF are insufficiently investigated. METHODS: Patients who underwent PCLF and received postoperative cervical collars from 2018 to 2020 were included in this retrospective cohort study. Their data were compared with an age- and sex-matched group of subjects who did not receive collars after PCLF during the same period. Pain intensity (using the Visual Analog Scale), Neck Disability Index, and quality of life (using 36-item Short Form Health Survey) of the patients were compared at baseline, 1, 3, 6, and 12 months postoperatively. RESULTS: A total of 36 patients who received cervical collars after surgery and 40 controls were included. At baseline and 1-month follow-up, there were no differences in pain intensity, functional status, and quality of life between the groups. However, at 3 months postoperatively, the quality of life of the subjects with no orthosis was higher than those who received cervical collars (p =0.01). At 6- and 12-month follow-up, there were no differences between the groups in pain intensity, functional status, and quality of life. CONCLUSIONS: No difference in the pain intensity and functional status of patients who used cervical collars and controls was shown in our study. Patients who did not wear cervical collars had a higher quality of life during the 3-month postoperative evaluation. Future prospective, well-controlled studies with longer follow-ups are needed to further investigate the effects of cervical orthosis on the clinical outcome of patients after PCLF.

The Impact of Rigid Cervical Collars on Outcome of Patients Who Underwent Posterior Cervical Laminectomy and Fusion: A Retrospective Comparative Study

Methods@#Patients who underwent PCLF and received postoperative cervical collars from 2018 to 2020 were included in this retrospective cohort study. Their data were compared with an age- and sex-matched group of subjects who did not receive collars after PCLF during the same period. Pain intensity (using the Visual Analog Scale), Neck Disability Index, and quality of life (using 36-item Short Form Health Survey) of the patients were compared at baseline, 1, 3, 6, and 12 months postoperatively. @*Results@#A total of 36 patients who received cervical collars after surgery and 40 controls were included. At baseline and 1-month follow-up, there were no differences in pain intensity, functional status, and quality of life between the groups. However, at 3 months postoperatively, the quality of life of the subjects with no orthosis was higher than those who received cervical collars (p =0.01). At 6- and 12-month follow-up, there were no differences between the groups in pain intensity, functional status, and quality of life. @*Conclusions@#No difference in the pain intensity and functional status of patients who used cervical collars and controls was shown in our study. Patients who did not wear cervical collars had a higher quality of life during the 3-month postoperative evaluation. Future prospective, well-controlled studies with longer follow-ups are needed to further investigate the effects of cervical orthosis on the clinical outcome of patients after PCLF.

Complement C5a and Clinical Markers as Predictors of COVID-19 Disease Severity and Mortality in a Multi-Ethnic Population.

Coronavirus disease-2019 (COVID-19) was declared as a pandemic by WHO in March 2020. SARS-CoV-2 causes a wide range of illness from asymptomatic to life-threatening. There is an essential need to identify biomarkers to predict disease severity and mortality during the earlier stages of the disease, aiding treatment and allocation of resources to improve survival. The aim of this study was to identify at the time of SARS-COV-2 infection patients at high risk of developing severe disease associated with low survival using blood parameters, including inflammation and coagulation mediators, vital signs, and pre-existing comorbidities. This cohort included 89 multi-ethnic COVID-19 patients recruited between July 14th and October 20th 2020 in Doha, Qatar. According to clinical severity, patients were grouped into severe (n=33), mild (n=33) and asymptomatic (n=23). Common routine tests such as complete blood count (CBC), glucose, electrolytes, liver and kidney function parameters and markers of inflammation, thrombosis and endothelial dysfunction including complement component split product C5a, Interleukin-6, ferritin and C-reactive protein were measured at the time COVID-19 infection was confirmed. Correlation tests suggest that C5a is a predictive marker of disease severity and mortality, in addition to 40 biological and physiological parameters that were found statistically significant between survivors and non-survivors. Survival analysis showed that high C5a levels, hypoalbuminemia, lymphopenia, elevated procalcitonin, neutrophilic leukocytosis, acute anemia along with increased acute kidney and hepatocellular injury markers were associated with a higher risk of death in COVID-19 patients. Altogether, we created a prognostic classification model, the CAL model (C5a, Albumin, and Lymphocyte count) to predict severity with significant accuracy. Stratification of patients using the CAL model could help in the identification of patients likely to develop severe symptoms in advance so that treatments can be targeted accordingly.

The correlation of antioxidant levels of breast cancer: A case controlled study.

ABSTRACT: Many free radicles are implicated to activate a number of oncogenic signaling, cause damage to deoxyribonucleic acid and tumor suppressor genes, or promote expression of proto-oncogenes. Reduced level of antioxidants and increases oxidative stress markers are associated with the development of various types of cancer.This prospective study included 60 women who were grouped into equal groups. Patients group included 30 breast cancer women and control group consisting of 30 apparently healthy women. Both groups were compared regarding the serum levels of antioxidants biomarkers (vitamin C, ceruloplasmin, glutathione) and oxidative stress biomarkers, malondialdehyde (MDA), peroxynitrite, and gamma-glutamyl transferase.In regard to the antioxidant biomarkers, there was a significant difference between the patients and the controls regarding the levels of serum ceruloplasmin and glutathione, (P values .000) for each while vitamin C showed no significant correlation (P value .053), while regarding oxidative stress biomarkers, the correlation was significant for both peroxynitrite and MDA (P value .000 and .001) respectively, and not significant for gamma-glutamyl transferase (P value 1.00).Reduced level both ceruloplasmin and glutathione is seen in patients with breast cancer while vitamin C is not associated. Elevated levels of both peroxynitrite and MDA is seen in patients with breast cancer which may be used as serum markers for the early detection of breast cancer.

Contamination and Decontamination of Autologous Bone in the Operating Room: A Systematic Review.

OBJECTIVE: To perform a systematic review of the literature to determine the rate of contamination of autologous bone fragments inadvertently dropped on the operating room floor, the microbial profile (contaminating organism), and the outcome of intraoperative decontamination techniques in terms of effectiveness and cellular toxicity. DATA SOURCES: PubMed, Medline, and Embase were searched for English literature published from 1990 through 2020 using terms such as "bone graft contamination," "dropped osteoarticular fragments," "autogenous bone decontamination," and similar interchangeable words. STUDY SELECTION: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Inclusion criteria consisted of all studies on contamination of host bone fragments, means and/or rate of autologous bone contamination in operating rooms, microbial analysis of contaminated bone autograft, outcome of decontamination, and cellular viability after decontamination. DATA EXTRACTION: All potentially eligible studies underwent a full-text review and cross-referencing after title and abstract screening. Data on authors, publication year, study type, means and rate of contamination, microbial profile, decontamination technique, and effectiveness and cellular toxicity outcomes were extracted. DATA SYNTHESIS: Analysis and synthesis of data were performed on Microsoft Excel 2016. CONCLUSION: The rate of contamination for dropped osteoarticular or osteochondral host fragment approached 40%. Staphylococcus epidermidis was the most common organism contaminating the bone graft when dropped on the operating room floor. A 5-minute bath in 10% povidone-iodine solution followed by 1-minute bulb syringe lavage with normal saline has proved successful in decontamination and maintenance of cellular viability. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Avoiding Anchoring Bias in the Times of the Pandemic!

COVID-19 has a broad spectrum of clinical presentations, including central nervous system manifestations that are not uncommon. The high pretest probability of COVID-19 in pandemic can lead to anchoring. We present a patient of COVID-19 pneumonia who presented with dyspnea and acute confusional state. His initial workup was suggestive of tuberculous meningoencephalitis with lymphocytic pleocytosis, high protein in CSF analysis, and suspicious MRI findings, which was later confirmed with a positive CSF culture. To the best of our knowledge, it is the first such case. Anchoring to the diagnosis of COVID-19 may deter clinicians from considering other concurrent diagnoses and a poor outcome consequently.

Evaluation of the Inter and Intra-Observer Reliability of the AO Classification of Intertrochanteric Fractures and the Device Choice (DHS, PFNA, and DCS) of Fixations.

BACKGROUND: ArbeitsgemeinschaftfürOsteosynthesefragen (AO) classification is the most frequently used tool to classify intertrochanteric fractures. However, there is limited evidence regarding its reliability. Therefore, this study was designed to evaluate inter-observer and intra-observer reliability of the AO-2018 intertrochanteric fracture classification. METHOD: A retrospective study was conducted in Imam Khomeini Hospital Complex, on radiography of patients who came with intertrochanteric fractures from March 21, 2018, to March 19, 2019. Four orthopedic trauma surgeons assessed 96 anteroposterior pelvic radiographs of intertrochanteric fractures and classified using an AO intertrochanteric fracture classification of 2018. The reading and review of radiography were performed in 2 separate occasions in a 1-month interval. The inter-observer and intra-observer reliability was assessed using kappa statistics. RESULT: The level of both mean inter-observer (K =0.322; 95%CI: 0.321-0.323) and intra-observer agreement (K =0.317; 95%CI: 0.314-0.320) in AO intertrochanteric fracture classification subgrouping were not satisfactory. The inter-observer (K =0.61; 95%CI: 0.608-0.611) and intra-observers' (K=0.560; 95%CI: 0.544-0.566) reliability in AO main groupings showed moderate agreement. CONCLUSION: The AO classification does not show adequate and acceptable inter-observer and intra-observer reliability and reproducibility. Therefore, it will be hard to base on the AO classification for treatment protocols.

Non-nutritive sucking habits among preschool children in southern Saudi Arabia: A cross-sectional study

Prolonged non-nutritive sucking habits have negative effects on child’s orofacial structures, physical, social and psychological wellbeing. The objectives of the present study were (1) to determine the prevalence of non-nutritive sucking habit in Saudi preschool children, (2) to assess the factors influencing the habit, (3) to determine mothers’ view on causes of non-nutritive sucking and their reasons to stop the habit and (4) to report methods used by the mothers in eliminating the habit. This cross-sectional observational study was conducted in the kindergartens in Abha and Khamis Mushayt cities. The sample included parents of 328 male and female preschool children. A pre-piloted self-administered questionnaire was used for data collection and the response rate was 85.4%. The prevalence of non-nutritive sucking habit was 46.6%; of these, pacifier sucking was 30.2% and digit sucking was 16.4%. There were significant differences with pacifier habit between mother’s educational status and sex (p=0.008 and p=0.002 respectively). The odds of pacifier habit were higher in females [OR=2.14, 95% CI (1.32, 2.52)] and mothers with higher university education [OR=1.67, 95% CI (1.03, 2.72)]. There were significant differences with digit sucking habit and mothers’ educational status (p=0.022). The odds of digit sucking habit was higher in mothers with intermediate and secondary education [OR=2.25, 95% CI (1.24, 4.07)]. Some mothers (37.90%) used non-nutritive sucking as solution to calm the crying child, while others (47.05%) wanted to stop the habit as it might affect the child’s dentition. Some mothers (37%) interrupted the habit physically, while only 10% had preferred to consult the dentist.

Cow's Milk Protein Allergy Mimicking Acrodermatitis Enteropathica.

Cow's milk protein allergy is an adverse immune reaction to one or more of the constituent proteins of milk obtained from any animal, most commonly alpha s 1-casein cow's milk. In many cases, the allergy is genetic in origin. The infants may experience symptoms within minutes after feeding (rapid onset) or commonly after 7-10 days of consuming the cow's milk (slower onset). Many children with cow's milk protein allergy develop symptoms in at least two of the following organ systems: gastrointestinal, skin and respiratory tract. Acrodermatitis Enteropathica (primary or secondary zinc deficiency) can also produce lesions in the skin and also gastro intestinal symptoms which can mimic milk protein allergy and differentiating between these two may be difficult. We are reporting a case of cow's milk protein allergy in an infant, which was initially diagnosed as Acrodermatitis Enteropathica and treated with zinc. The lesions did not subside completely even after achieving adequate zinc levels, but on stopping the cow's milk all the symptoms and signs disappeared completely and there was no recurrence on long term follow up.

Dental erosion among 12-15-year-old school boys in southern Saudi Arabia

The aim of this study was to determine the prevalence and severity of dental erosion in 12-15-year-old schoolchildren and to compare prevalence between public and private school boys. This cross-sectional study was carried out on 1000, 12-15-year-old school boys in Abha, Saudi Arabia. Dental erosion index proposed by O‘Sullivan was used for the four maxillary incisors. Data analysis included descriptive statistics, location, distribution, and extension of affected area and severity of dental erosion. The prevalence of dental erosion was 25.60% with no significant difference between private and public school students. Matt appearance of the enamel was the most prevalent type of dental erosion (63.63%). In most of the involved cases, more than half of their surfaces were diagnosed as affected by erosion (78.49%). Labial surfaces were the most affected (80.90%), while incisal surfaces were least affected (0.22%). Thus it can be concluded that dental erosion among Saudi school boys is becoming a significant problem, hence it is essential to provide adequate preventive care, and healthier dietary habits campaign for Saudi children.