Comparison of Pre- and Posttreatment Airway Volume in Patients with Temporomandibular Joint Disorders Treated with Ultra-Low Frequency Transcutaneous Electrical Nerve Stimulation Using Cone Beam Computed Tomography.

Introduction Temporomandibular joint disorders (TMD) present with a multitude of symptoms that can range from headaches to shoulder pain. Patients frequently present with pain in the ear, dizziness, and vertigo. It is noted that some patients who report TMDs also have a history of sleep disturbances, which is noted in cone beam computed tomography (CBCT) as a reduction in the oropharyngeal airway volume. Objective To evaluate the airway volume in pre- and posttreatment of TMD with the use of neuromuscular orthotics made with ultra-low frequency transcutaneous electrical nerve stimulation (ULF-TENS). Methods A total of 15 patients were evaluated for TMDs using the related criteria. Those included were treated with ULF-TENS with evaluation of the airway volume both pre- and posttreatment using CBCT and the Dolphin 3D volume analysis software. Results While the symptoms were shown to be significantly reduced in patients who were treated with this particular modality, the airway volume varied in those who reported a reduction after a period of 3 months and those that reported after a period of 6 months. Conclusion Posttreatment evaluation of the airway should be done after a period of 6 months for a more objective evaluation. A multidisciplinary evaluation of the patient is required in such cases.

Evaluation of presence of nasal deviation in patients presenting with obstructive sleep apnea using cone beam computed tomography.

OBJECTIVE: Evaluation of the presence of nasal septal deviation in patients presenting with obstructive sleep apnea (OSA) using Cone-Beam Computed Tomography (CBCT). METHOD: Patients diagnosed with OSA using polysomnography were further evaluated radiographically for the presence of nasal septal deviation, maxillary sinus septa, and oropharyngeal airway volume using CBCT. RESULTS: Nasal deviation was present in all the patients and was classified according to Negus et al classification, further categorized with Apnea-hypopnea index (AHI) score, maxillary sinus septa in those patients were classified according to Al Faraj et al, and the oropharyngeal airway volume was found to be an average of 10,086.37 ± 3966.116 mm2 airway volume. CONCLUSION: All the patients in the study had nasal septal deviation, hence it can be considered as a radiographic marker in suspecting OSA.

Implementation and outcomes of a comprehensive emergency care curriculum at a low-resource referral hospital in Liberia: A novel approach to application of the WHO Basic Emergency Care toolkit.

BACKGROUND: Emergency care is vital in low- and middle-income countries (LMICs) but many frontline healthcare workers in low-resource settings have no formal training in emergency care. To address this gap, the World Health Organization (WHO) developed Basic Emergency Care (BEC): Approach to the acutely ill and injured, a multi-day, open-source course for healthcare workers in low-resource settings. Building on the BEC foundation, this study uses an implementation science (IS) lens to develop, implement, and evaluate a comprehensive emergency care curriculum in a single emergency facility in Liberia. METHODS: A six-month emergency care curriculum consisting of BEC content, standardized WHO clinical documentation forms, African Federation of Emergency Medicine (AFEM) didactics, and clinical mentorship by visiting emergency medicine (EM) faculty was designed and implemented using IS frameworks at Redemption Hospital, a low-resource public referral hospital in Monrovia, the capital of Liberia. Healthcare worker performance on validated knowledge-based exams during pre- and post-intervention testing, post-course surveys, and patient outcomes were used to evaluate the program. RESULTS: Nine visiting EM physicians provided 1400 hours of clinical mentorship and 560 hours of didactic training to fifty-six Redemption Hospital staff over six-months. Median test scores improved 20.0% (p<0.001) among the forty-three healthcare workers who took both the pre- and post-intervention tests. Participants reported increased confidence in caring for medical and trauma patients and comfort performing emergency care tasks on post-course surveys. Emergency unit (EU)/Isolation unit (IU) mortality decreased during the six-month implementation period, albeit non-significantly. Course satisfaction was high across multiple domains. DISCUSSION: This study builds on prior research supporting WHO efforts to improve emergency care globally. BEC implementation over a six-month timeframe using IS principles is an effective alternative strategy for facilities in resource-constrained environments wishing to strengthen emergency care delivery.

Mechanistic and Etiological Similarities in Diabetes Mellitus and Alzheimer's Disease: Antidiabetic Drugs as Optimistic Therapeutics in Alzheimer's Disease.

BACKGROUND: Diabetes mellitus and Alzheimer's disease are two common diseases that majorly affect the elderly population. Patients in both cases are increasing day by day. They are considered two independent diseases, but recent evidence suggests that they have a lot in common. OBJECTIVE: In this review, we focused on the connection between Alzheimer's disease and diabetes and highlighted the importance of antidiabetic drugs against Alzheimer's disease. METHODS: Common pathways such as obesity, vascular diseases, oxidative stress, mitochondrial dysfunction, mutation of the ApoE4 gene, and Sirtuin gene were found to manipulate both diseases. Antidiabetic drugs are found to have promising effects on Alzheimer's disease, acting by reducing insulin resistance, neuronal protection, and reducing amyloid-beta plaques. Some anti-diabetic drugs have shown promising results in vivo and in vitro studies. RESULTS: No review present focuses on the structural features of the antidiabetic molecules against Alzheimer's disease, their crosslinking pathophysiology, the role of natural bioactive molecules, in silico advancements followed by preclinical and clinical studies, and current advancements. Hence, we concentrated on the factors mentioned in the objectives. CONCLUSION: Alzheimer's disease can be considered a form of 'type-3 diabetes,' and repurposing the anti-diabetic drug will open up new paths of research in the field of Alzheimer's disease drug discovery.

Comparison of Pre- and Posttreatment Airway Volume in Patients with Temporomandibular Joint Disorders Treated with Ultra-Low Frequency Transcutaneous Electrical Nerve Stimulation Using Cone Beam Computed Tomography

Abstract Introduction Temporomandibular joint disorders (TMD) present with a multitude of symptoms that can range from headaches to shoulder pain. Patients frequently present with pain in the ear, dizziness, and vertigo. It is noted that some patients who report TMDs also have a history of sleep disturbances, which is noted in cone beam computed tomography (CBCT) as a reduction in the oropharyngeal airway volume. Objective To evaluate the airway volume in pre- and posttreatment of TMD with the use of neuromuscular orthotics made with ultra-low frequency transcutaneous electrical nerve stimulation (ULF-TENS). Methods A total of 15 patients were evaluated for TMDs using the related criteria. Those included were treated with ULF-TENS with evaluation of the airway volume both pre- and posttreatment using CBCT and the Dolphin 3D volume analysis software. Results While the symptoms were shown to be significantly reduced in patients who were treated with this particular modality, the airway volume varied in those who reported a reduction after a period of 3 months and those that reported after a period of 6 months. Conclusion Posttreatment evaluation of the airway should be done after a period of 6 months for a more objective evaluation. A multidisciplinary evaluation of the patient is required in such cases.

Structure-Activity Relationship Insight of Naturally Occurring Bioactive Molecules and Their Derivatives Against Non-Small Cell Lung Cancer: A Comprehensive Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a deadly disease that affects millions globally and its treatment includes surgery, chemotherapy, and radiotherapy. Chemotherapy and radiotherapy have many disadvantages, which include potential harmful side effects. Due to the widespread use of drugs in lung cancer, drug treatment becomes challenging due to multidrug resistance and adverse reactions. According to the recent findings, natural products (NPs) and their derivatives are being used to inhibit and suppress cancer cells. OBJECTIVE: Our objective is to highlight the importance of phytochemicals for treating NSCLC by focusing on the structural features essential for the desired activity with fewer side effects compared to synthetic molecules. METHODS: This review incorporated data from the most recent literature, including in vitro, in vivo, nanoformulation-based recent advancements, and clinical trials, as well as the structure-activity relationship (SAR), described for a variety of possible natural bioactive molecules in the treatment of NSCLC. RESULTS: The analysis of data from recent in vitro, in vivo studies and ongoing clinical trials are highlighted. The SAR studies of potential NPs signify the presence of several common structural features that can be used to guide future drug design and development. CONCLUSION: The role of NPs in the battle against NSCLC can be effective, as evidenced by their structural diversity and affinity toward various molecular targets. The main purpose of the review is to gather information about NPs used in the treatment of NSCLC.

Emergency department antimicrobial use in a low-resource setting: results from a retrospective observational study at a referral hospital in Liberia.

OBJECTIVE: Data on antimicrobial use in low-income and middle-income countries (LMICs) remain limited. In Liberia, the absence of local data impedes surveillance and may lead to suboptimal treatment, injudicious use and resistance against antimicrobials. This study aims to examine antimicrobial prescribing patterns for patients in the emergency department (ED) of a large Liberian public hospital. Secondarily, this prescribing was compared with WHO prescribing indicators. DESIGN: Retrospective observational study. SETTING: An adult ED of a large public hospital in Monrovia, Liberia. PARTICIPANTS: A total of 1082 adult patients (>18 years of age) were recorded in the ED, from 1 January to 30 June 2019. MAIN OUTCOME MEASURES: Number, type and name of antimicrobials ordered per patient were presented as number and percentages, with comparison to known WHO prescribing indicators. Pearson χ2 tests were used to assess patient variables and trends in medication use. RESULTS: Of the total patients, 44.0% (n=476) were female and the mean age was 40.2 years (SD=17.4). An average of 2.78 (SD=2.02) medicines were prescribed per patient encounter. At least one antimicrobial was ordered for 64.5% encounters (n=713) and two or more antimicrobials for 35.7% (n=386). All antimicrobial orders in our sample used the generic name. Ceftriaxone, metronidazole and ampicillin were the most common and accounted for 61.2% (n=743) of antimicrobial prescriptions. The majority (99.9%, n=1211) of antimicrobials prescribed were from the WHO Essential Drugs List. CONCLUSION: This study is one of the first on ED-specific antimicrobial use in LMICs. We revealed a high rate of antimicrobial prescription, regardless of patient demographic or diagnosis. While empiric antimicrobial use is justified in certain acute clinical scenarios, the high rate from this setting warrants further investigation. The results of this study underscore the importance of ED surveillance to develop targeted antimicrobial stewardship interventions and improve patient care.

The controversial therapeutic journey of chloroquine and hydroxychloroquine in the battle against SARS-CoV-2: A comprehensive review.

Recently, the pandemic outbreak of a novel coronavirus, officially termed as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), indicated by a pulmonary infection in humans, has become one of the most significant challenges for public health. In the current fight against coronavirus disease-2019, the medical and health authorities across the world focused on quick diagnosis and isolation of patients; meanwhile, researchers worldwide are exploring the possibility of developing vaccines and novel therapeutic options to combat this deadly disease. Recently, based on various small clinical observations, uncontrolled case studies and previously reported antiviral activity against SARS-CoV-1 chloroquine (CQ) and hydroxychloroquine (HCQ) have attracted exceptional consideration as possible therapeutic agents against SARS-CoV-2. However, there are reports on little to no effect of CQ or HCQ against SARS-CoV-2, and many reports have raised concerns about their cardiac toxicity. Here, in this review, we examine the chemistry, molecular mechanism, and pharmacology, including the current scenario and future prospects of CQ or HCQ in the treatment of SARS-CoV-2.

Crosstalk Between Covid-19 and Associated Neurological Disorders: A Review.

COVID-19 is a global pandemic, primarily affecting the pulmonary system but its effects on other systems are not certain. Coronavirus, the causative organism, binds with angiotensinconverting enzyme 2 (ACE2) receptors in the lungs and produces pneumonia-like symptoms. Other than lungs, ACE2 receptors are also seen in the endothelium of blood vessels. Therefore, viruses can bind to the ACE2 that is present in the endothelium of brain blood vessels and thus can invade BBB, leading to neuronal damage. It is also believed that olfactory cells rich in ACE2 receptors may act as the main route of viral spread into various parts of the brain. The reported neurological effects of SARS-CoV-2 include cerebrovascular diseases, ageusia and anosmia, Guillain Barre Syndrome, and viral encephalitis. The extent of neurological involvement in SARS-CoV-2 infection warrants the necessity of further research to systematically classify neurological complications associated with SARS-CoV-2 infection, its diagnosis, and treatment. As ACE2 receptors are present in various other organs, it is obligatory to study the effect of coronavirus on other organs also. Since the long-lasting effects of the COVID-19 are unclear, more studies should be conducted to confirm the effect of the virus on the central nervous system. This review highlights the reported neurological manifestations of SARS-CoV-2 and its mechanism.

Effect of deprogramming splint and occlusal equilibration on condylar position of TMD patients - A CBCT assessment.

Objective: Assessment of clinical symptoms and condylar position of TMD patients using CBCT imaging with deprogramming splint therapy and occlusal equilibration. The hypothesis tested was the alleviation of symptoms of TMD with possible changes in condylar position occurs with this treatment.Methods: The condylar position of 12 TMD patients was observed from CBCT images, and clinically, symptom severity score, mouth opening, and range of motion were compared pre- and post-treatment.Results: All patients reported a statistically significant decrease in the symptom severity score and increase in mouth opening and range of motion (p < .05). A significant decrease was only achieved in the left anterior joint space (p < .05).Conclusion: Deprogramming splint therapy and occlusal equilibration benefitted patients with a reduction in clinical symptoms, and minor changes in condylar position were observed.

Neurodegenerative Pathways in Alzheimer's Disease: A Review.

Alzheimer's disease (AD) is a complex neurodegenerative disease that leads to insidious deterioration of brain functions and is considered the sixth leading cause of death in the world. Alzheimer's patients suffer from memory loss, cognitive deficit and behavioral changes; thus, they eventually follow a low-quality life. AD is considered as a multifactorial disorder involving different neuropathological mechanisms. Recent research has identified more than 20 pathological factors that are promoting disease progression. Three significant hypotheses are said to be the root cause of disease pathology, which include acetylcholine deficit, the formation of amyloid-beta senile plaques and tau protein hyperphosphorylation. Apart from these crucial factors, pathological factors such as apolipoprotein E (APOE), glycogen synthase kinase 3ß, notch signaling pathway, Wnt signaling pathway, etc., are considered to play a role in the advancement of AD and therefore could be used as targets for drug discovery and development. As of today, there is no complete cure or effective disease altering therapies for AD. The current therapy is assuring only symptomatic relief from the disease, and progressive loss of efficacy for these symptomatic treatments warrants the discovery of newer drugs by exploring these novel drug targets. A comprehensive understanding of these therapeutic targets and their neuropathological role in AD is necessary to identify novel molecules for the treatment of AD rationally.

Performance of Abbott ID-Now rapid nucleic amplification test for laboratory identification of COVID-19 in asymptomatic emergency department patients.

OBJECTIVE: We sought to evaluate the test characteristics of Abbott ID-Now as a screening tool compared to polymerase chain reaction (PCR) testing for identification of COVID in an asymptomatic emergency department population. METHODS: We performed a prospective study enrolling a convenience sample of asymptomatic patients presenting to a single academic emergency department (ED) who received simultaneous testing with ID-Now and PCR per standardized ED protocols. Sensitivity, specificity, and positive and negative predictive value (PPV, NPV) of ID-Now were calculated compared to PCR. Stratified analysis by cycle threshold (Ct) values was also performed, defined as high viral load (Ct < 33) and low viral load (Ct ≥ 33). RESULTS: A total of 3121 patients were enrolled, of whom 2895 had valid results for ID-Now and PCR. COVID prevalence was 2.6%. ID-Now had a sensitivity of 85.1% (95% CI 75.9% to 92.7%) and a specificity of 99.7% (99.5% to 99.9%). PPV and NPV were high at 87.5% (83.1% to 96.1%) and 99.6% (99.3% to 99.8%). Stratified analysis by low and high Ct values demonstrated reduction in sensitivity in patients with low viral loads: 91.7% (81.6% to 97.2%) in low Ct value patients versus 58.3% (27.7% to 84.8%) in high Ct value patients. CONCLUSIONS: ID-Now had excellent performance in asymptomatic ED patients with a low rate of false positives. Cycle threshold analysis suggests a relationship between viral load and ID-Now sensitivity. Given its speed and performance in this population, ID-Now should be considered an excellent tool to support clinical decision-making in ED populations.

SGLT2 inhibitors, an accomplished development in field of medicinal chemistry: an extensive review.

Diabetes is a chronic progressive metabolic disease caused by insulin deficiency or insulin resistance. In spite of the availability of several antihyperglycaemics, there is a need for the development of safer antidiabetic drugs due to their undesirable effects. Sodium-glucose cotransporter-2 inhibitors are a class of antidiabetics, which hinder the reabsorption of glucose in the kidneys, causing excretion of glucose via urine. Sodium-glucose cotransporter-2 inhibitors are a well-tolerated class with no significant adverse effects and are found to be favorable in certain conditions, which may be rudimentary to cardiovascular and renal diseases. The current advancements in their design and development, their mechanism of action, structure-activity relationship, synthesis and in silico development along with their auxiliary roles have been extensively reviewed.

Alcohol use among conflict-affected persons in Ukraine: risk factors, coping and access to mental health services.

BACKGROUND: There are approximately 1.5 million internally displaced persons (IDPs) in Ukraine as a result of the conflict in eastern Ukraine. Exposure to violence, forced displacement and increased mental disorders are potential risk-factors for alcohol use disorder (AUD). The aim of this study was to estimate the prevalence of and risk factors for AUD among Ukrainian IDPs and investigate the relationship between AUD, mental health service utilization and coping behaviours. METHODS: A nation-wide cross-sectional survey of 2203 IDPs was conducted. Data were collected on AUD [using alcohol use disorder identification test (AUDIT)], mental health disorders, utilization of health services and coping behaviours. Multivariable logistic regression was used to identify risk factors for AUD, and to estimate the odds ratios for the association between alcohol use and utilization of health services and coping behaviours. RESULTS: Of 2203 IDPs surveyed, 8.4% of men and 0.7% of women screened positive for AUD (AUDIT >7). Among current drinkers, AUD was present in 14.9% of men and 1.8% of women. Age, cumulative trauma exposure and anxiety were significantly associated with AUD in multivariable analysis. Alcohol users were 43% less likely to access health services for mental health compared with non-users. AUD was associated with more negative coping behaviours. CONCLUSIONS: AUD is present within the male Ukrainian IDP population. Alcohol use was significantly associated with lower utilization of mental health services and more negative coping behaviours. AUD screening and low-intensity treatment services should be expanded for IDPs in Ukraine, particularly if integrated into mental health and psychosocial support programmes.

Comparison of Epidemiology of the Injuries and Outcomes in Two First-Level Trauma Centers in Colombia Using the Pan-American Trauma Registry System.

INTRODUCTION: The aim of this study was to compare the epidemiology of traumatic injuries and mortality outcomes between two tertiary-care trauma centers in Colombia using data from Pan-American Trauma Registry (PATR). METHODS: January 1-December 31, 2012, data from the Hospital Universitario del Valle (HUV, public) and Fundacion Valle del Lili (FVL, private) in Cali, Colombia, were considered. Differences in demographic and clinical information were compared using descriptive statistics. Propensity score matching was used to match patients on age, gender, and ISS. Within matched cohorts, multivariable logistic regression models were used to assess for differences in in-hospital mortality, further adjusting for insurance type, employment, heart rate, presence of hypotension (SBP < 90), and GCS score. RESULTS: HUV (8539; 78% male) and FVL (10,456; 60% male) had a combined total of 18,995 trauma cases in 2012 with comparable mean ages of 29.7 years. There were significant differences in insurance status, injury severity, and mechanism of injury between patients at HUV and FLV. On risk-adjusted logistic regression analyses with propensity score matched cohorts, the odds of death in HUV was higher compared to patients presenting at FVL hospital (OR [95% CI]:4.93 [3.37-7.21], p < 0.001). CONCLUSION: The study established the utility of the PATR and revealed important trends in patient demographics, injury epidemiology, and mortality outcomes, which can be used to target trauma initiatives throughout the region. It underscores the profound importance that differences in case mix play in the risk of trauma-related mortality, further emphasizing the need to monitor and evaluate unique aspects of trauma in LMIC. LEVEL OF EVIDENCE: III.

Cost-effectiveness of CRAG-LFA screening for cryptococcal meningitis among people living with HIV in Uganda.

BACKGROUND: Cryptococcal meningitis (CM) constitutes a significant source of mortality in resource-limited regions. Cryptococcal antigen (CRAG) can be detected in the blood before onset of meningitis. We sought to determine the cost-effectiveness of implementing CRAG screening using the recently developed CRAG lateral flow assay in Uganda compared to current practice without screening. METHODS: A decision-analytic model was constructed to compare two strategies for cryptococcal prevention among people living with HIV with CD4 < 100 in Uganda: No cryptococcal screening vs. CRAG screening with WHO-recommended preemptive treatment for CRAG-positive patients. The model was constructed to reflect primary HIV clinics in Uganda, with a cohort of HIV-infected patients with CD4 < 100 cells/uL. Primary outcomes were expected costs, DALYs, and incremental cost-effectiveness ratios (ICERs). We evaluated varying levels of programmatic implementation in secondary analysis. RESULTS: CRAG screening was considered highly cost-effective and was associated with an ICER of $6.14 per DALY averted compared to no screening (95% uncertainty range: $-20.32 to $36.47). Overall, implementation of CRAG screening was projected to cost $1.52 more per person, and was projected to result in a 40% relative reduction in cryptococcal-associated mortality. In probabilistic sensitivity analysis, CRAG screening was cost-effective in 100% of scenarios and cost saving (ie cheaper and more effective than no screening) in 30% of scenarios. Secondary analysis projected a total cost of $651,454 for 100% implementation of screening nationally, while averting 1228 deaths compared to no screening. CONCLUSION: CRAG screening for PLWH with low CD4 represents excellent value for money with the potential to prevent cryptococcal morbidity and mortality in Uganda.

Remodeling of dendrites and spines in the C1q knockout model of genetic epilepsy.

PURPOSE: To determine whether developmental synaptic pruning defects in epileptic C1q-knockout (KO) mice are accompanied by postsynaptic abnormalities in dendrites and/or spines. METHODS: Immunofluorescence staining was performed on biocytin-filled layer Vb pyramidal neurons in sensorimotor cortex. Basal dendritic arbors and their spines were reconstructed with NEUROLUCIDA software, and their morphologic characteristics were quantitated in Neuroexplorer. KEY FINDINGS: Seven to nine completely filled pyramidal neurons were analyzed from the wild-type (WT) and C1q KO groups. Compared to WT controls, KO mice showed significant structural modifications in their basal dendrites including (1) higher density of dendritic spines (0.60 ± 0.03/µm vs. 0.49 ± 0.03/µm dendritic length in WT, p < 0.05); (2) remarkably increased occurrence of thin spines (0.26 ± 0.02/µm vs. 0.14 ± 0.02/µm dendritic length in control, p < 0.01); (3) longer dendritic length (2,680 ± 159 µm vs. 2,119 ± 108 µm in control); and (4) increased branching (22.6 ± 1.9 vs. 16.2 ± 1.3 in WT at 80 µm from soma center, p < 0.05; 12.4 ± 1.4 vs. 8.2 ± 0.6 in WT at 120 µm from soma center, respectively, p < 0.05). Dual immunolabeling demonstrated the expression of putative glutamate receptor 2 (GluR2) on some thin spines. These dendritic alterations are likely postsynaptic structural consequences of failure of synaptic pruning in the C1q KO mice. SIGNIFICANCE: Failure to prune excessive excitatory synapses in C1q KO mice is a likely mechanism underlying abnormalities in postsynaptic dendrites, including increased branching and alterations in spine type and density. It is also possible that seizure activity contributes to these abnormalities. These structural abnormalities, together with increased numbers of excitatory synapses, likely contribute to epileptogenesis in C1q KO mice.