Relationship Between Clinical Outcomes and Nerve Conduction Studies Before and After Viral Infections in Healthy Individuals: Case Series.

BACKGROUND: The neurological effect of viral respiratory infections has been acknowledged in many studies. However, patients who recovered from this infection show neurological manifestations and are not being routinely transferred for electrodiagnostic evaluation. AIM: This study aimed to examine the neurological effect of viral respiratory infections on the nerve function using electrophysiology in patients fully recovered from viral respiratory infections. METHODS: To limit bias in the results, the authors decided to choose patients who recovered from one virus in all participants (coronavirus). Medical records were screened for patients who performed nerve conduction studies (NCSs) before the coronavirus pandemic. Thirty patients met our inclusion criteria, and only 10 showed up to perform NCS. Data of the NCS was compared before and after the coronavirus infection for motor and sensory NCS parameters. RESULTS: An increase in both the median and ulnar sensory nerve latencies and a decrease in the sensory nerve amplitude was observed. Also, there was a decrease in the motor conduction velocity (MCV) of the ulnar nerves and motor amplitude in the median nerve. In the lower limbs, there was a decrease in the sural nerve latency, increased MCV in the tibial nerves, and decreased MCV in the peroneal nerves. The proximal amplitudes of the tibial and peroneal nerves were increased, but the distal amplitude was increased only in the peroneal nerves and decreased in the tibial nerves. CONCLUSION: There is a significant impact of viral infections on the peripheral nerves. Large-scale prospective studies are required to investigate the pathogenesis of the neuropathy and myopathy after viral infections.

The Physiology of Cognition in Autism Spectrum Disorder: Current and Future Challenges.

Cognitive impairment is among the most challenging characteristics of autism spectrum disorder (ASD). Although ASD is one of the common neurodevelopmental disorders, we are still behind in diagnosing and treating cognitive impairment in ASD. Cognitive impairment in ASD varies, meaning it could be at the sensory perception level to cognitive processing, learning, and memory. There are no diagnostic criteria for cognitive impairment that are specific to ASD. The leading causes of cognitive impairment in ASD could be neurological, immune, and gastrointestinal dysfunction. Immune dysfunction might lead to neuroinflammation, affecting neural connectivity, glutamate/gamma-aminobutyric acid (GABA) balance, and plasticity. The gut-brain axes are essential in the developing brain. Special retinal changes have recently been detected in ASD, which need clinical investigation to find their possible role in early diagnosis. Early intervention is crucial for ASD cognitive dysfunction. Due to the heterogeneity of the disease, the clinical manifestation of ASD makes it difficult for clinicians to develop gold-standard diagnostic and therapeutic criteria. We suggest a triad for diagnosis, which includes clinical tests for immune and gastrointestinal dysfunction biomarkers, clinical examination for the retina, and an objective neurocognitive evaluation for ASD, and to develop a treatment strategy involving these three aspects. Developing clear treatment criteria for cognitive impairment for ASD would improve the quality of life of ASD people and their caregivers and would delay or prevent dementia-related disorders in ASD people.

A Disintegrin and Metalloproteinase Protein 8 (ADAM 8) in Autism Spectrum Disorder: Links to Neuroinflammation.

Background: Converging lines of evidence confirmed neuroinflammation's role in autism spectrum disorder (ASD) etiological pathway. A disintegrin and metalloproteinase 8 (ADAM8) play major roles in inflammatory and allergic processes in various diseases. Aim: This study aimed to investigate ADAM8 plasma levels in autistic children compared to healthy controls. Also, to discover the association between ADAM8, disease severity, and neuroinflammation in ASD. Methodology: This case-control study included children with ASD (n=40) and aged-matched healthy controls (n=40). The plasma levels of the ADAM 8 were determined using enzyme-linked immunosorbent assay (ELISA). The assessment of ASD severity and social and sensory behaviors were categorized as mild, moderate and severe. Correlations among ADAM8 plasma levels and ASD severity scores [Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS) and Short Sensory Profile (SSP)] were obtained by Spearman correlation coefficient (r). Results: ASD children (n=40), including severe autism (n=21) and mild-to-moderate autism (n=19), showed significantly (p ≤ 0.05) lower plasma levels of ADAM8 [4683 (2885-5229); 4663 (4060-5000); 4632 (2885-5229)], respectively, than those of healthy controls [5000 (4047-5000)] [median (IQR) pg/mL]. However, there was no significant difference between the ADAM8 levels of children with severe and mild-to-moderate autism (p = 0.71). Moreover, ADAM8 plasma levels were not significantly correlated with the severity of ASD measured by behavioral scales [CARS (r= -0.11, p=0.55), SRS (r=0.11, p= 0.95), SSP (r=-0.23, p=0.23)]. Conclusion: The low ADAM8 plasma levels in children with ASD possibly indicated that ADAM8 might be implicated in the pathogenesis of ASD but not in the severity of the disease. These results should be interpreted with caution until additional studies are carried out with larger populations to decide whether the reduction in plasma ADAM8 levels is a mere consequence of ASD or if it plays a pathogenic role in the disease.

Exploring the Potential Role of ADAM 17 and ADAM 22 in the Etiology of Autism Spectrum Disorders.

BACKGROUND: Autism spectrum disorder (ASD) encompasses a group of disorders characterized by difficulties with social interaction and repetitive behavior. The condition is supposed to originate from early shifts in brain development, while the underlying processes are unknown. Moreover, a considerable number of patients with ASD experience digestive difficulties. Metalloproteases (ADAMs) are a class of enzymes capable of cleaving membrane-bound proteins. Members of this family, ADAM17 and ADAM22, have the ability to cleave proteins like the pro-inflammatory cytokine TNF-ά and glutamate synaptic molecules, which are both engaged in neuro-inflammation and glutamate excitotoxicity as crucial etiological mechanisms in ASD. ADAM17 and ADAM22 may also have a role in ASD microbiota-gut-brain axis connections by regulating immunological and inflammatory responses in the intestinal tract. SUBJECTS AND METHODS: Using ELISA kits, the plasma levels of ADAM17 and ADAM22 were compared in 40 children with ASD and 40 typically developing children. All of the autistic participants' childhood autism rating scores (CARS), social responsiveness scales (SRS), and short sensory profiles (SSP) were evaluated as indicators of ASD severity. RESULTS: Our results showed that plasma levels of ADAM17 were significantly lower in ASD children than in control children, while ADAM22 demonstrated non-significantly lower levels. Our data also indicate that while ADAM17 correlates significantly with age, ADAM22 correlates significantly with CARS as a marker of ASD severity. CONCLUSIONS: Our interpreted data showed that alteration in ADAM17 and ADAM22 might be associated with glutamate excitotoxicity, neuroinflammation, and altered gut microbiota as etiological mechanisms of ASD and could be an indicator of the severity of the disorder.

The possible role of sodium leakage channel localization factor-1 in the pathophysiology and severity of autism spectrum disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social, stereotypical, and repetitive behaviors. Neural dysregulation was proposed as an etiological factor in ASD. The sodium leakage channel (NCA), regulated by NLF-1 (NCA localization factor-1), has a major role in maintaining the physiological excitatory function of neurons. We aimed to examine the level of NLF-1 in ASD children and correlate it with the severity of the disease. We examined the plasma levels of NLF-1 in 80 ASD and neurotypical children using ELISA. The diagnosis and severity of ASD were based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), Childhood Autism Rating Score, Social Responsiveness Scale, and Short Sensory Profile. Then, we compared the levels of NLF-1 with the severity of the disease and behavioral and sensory symptoms. Our results showed a significant decrease in the plasma levels of NLF-1 in ASD children compared to neurotypical children (p < 0.001). Additionally, NLF-1 was significantly correlated with the severity of the behavioral symptoms of ASD (p < 0.05). The low levels of NLF-1 in ASD children potentially affect the severity of their behavioral symptoms by reducing neuron excitability through NCA. These novel findings open a new venue for pharmacological and possible genetic research involving NCA in ASD children.

Electrophysiological assessment in patients with COVID-19-related peripheral neuropathies and myopathies: a systematic review.

Neurological manifestations associated with Coronavirus Disease-2019 (COVID-19) are commonly reported, but patients were not referred to perform the electrophysiological assessment. We aimed to review the existing literature on clinical studies on COVID-19 peripheral neuropathy to correlate patients' symptoms and characteristics with nerve conduction studies/electromyography (NCS/EMG) outcomes. This protocol is registered in the Open Science Framework (https://www.doi.org/10.17605/OSF.IO/ZF4PK). The systematic search included PubMed, ScienceDirect, and Google Scholar, for articles published from December 2019 to March 2022. A total of 727 articles were collected, and according to our inclusion and exclusion criteria, only 6 articles were included. Of 195 participants, only 175 underwent NCS/EMG assessment. Of these, 44 participants (25.1%) had abnormal EMG, 54 participants (30.8%) had abnormal motor NCS, and only 7 participants (4%) had abnormal sensory NCS. All cases presented with myopathy, while a limited number of cases presented with polyneuropathy. According to motor NCS and EMG, the most affected nerves were the tibial and peroneal in the lower extremities and the ulnar nerve in the upper extremities. Interestingly, the median nerve was reported to be associated with the severity and the rate of motor recovery of patients with COVID-19. COVID-19 generates a demyelinating motor neuropathy and myopathy. Clinicians are encouraged to refer patients with COVID-19 presenting with neurological symptoms to be assessed by electrophysiological methods to objectively determine the nature of their symptoms, follow their prognosis, and plan their rehabilitation.

Assessing Physiological and Psychological Factors Contributing to Stress among Medical Students: Implications for Health.

Background: Physiological responses to stress disturb internal homeostasis, leading to serious health consequences. Medical students experience high stress levels that should be managed promptly to prevent stress-related impacts on students' health and education. Aim: This study aims to identify the relationship between stress factors, general health, and academic performance. Methods: This study recruited 421 medical students of all academic years. Participants completed an online survey assessing stress levels using a validated 10-item Perceived Stress Scale. Stress was also compared with students' health and academic performance. Results: We found that 93.6% of our sample experienced moderate to severe stress, and 31% reported increased stress due to the coronavirus disease (COVID-19) pandemic. Except for internship students, stress significantly decreases as students progress each academic year (p < 0.05). Students with higher GPAs and with comorbidities are more stressed. Comorbidities were primarily reported in students in their final years of education with a 4% lower GPA than healthy students. Although we had three stress-related themes (general, academic, and pandemic), students' perceptions of stress factors were primarily academically related. Conclusions: Students experience high stress levels in their final educational years, which might increase the risk of health issues and low academic performance. It is essential to innovate stress-coping strategies specially designed for medical students and mandatorily provided by all medical colleges and to educate students on the effects of stress on their health.

Pregnancy Complications in Pandemics: Is Pregnancy-Related Anxiety a Possible Physiological Risk Factor?

BACKGROUND: Birth and pregnancy complications increased by 10.2% during the 2019 coronavirus (COVID-19) pandemic. Pregnant women are at high risk for anxiety, which might trigger physio-logical stress, leading to pregnancy complications. AIM: This study aimed to investigate factors leading to antenatal anxiety during the COVID-19 pandemic. We also aimed to discuss our find-ings with regard to the current literature about pregnancy complications. METHODS: This cross-sectional study interviewed 377 pregnant women and assessed anxiety using a validated 7-item general anxiety disorder (GAD-7) scale. Anxiety was related to physiological and demo-graphic parameters. Anxiety was subdivided into pandemic- and pregnancy-related anxiety to minimize results bias. RESULTS: Our results showed that 75.3% of pregnant women were anxious. The mean GAD-7 score was 8.28 ± 5. Linear regression analysis showed that for every increase in the number of previous pregnancies, there was a 1.3 increase in anxiety level (p < 0.001). Women with no previous miscarriages were more anxious (p < 0.001). Surprisingly, pregnant women who were previously infected with COVID-19 were 6% less stressed. Pregnant women with comorbid-ities were more stressed (p < 0.001). Low income (p < 0.001) and age (p < 0.05) were the demo-graphic factors most significantly related to increased anxiety. CONCLUSIONS: The prevalence of pregnancy-related anxiety increased threefold in Saudi Arabia due to the COVID-19 pandemic. Healthcare support should be available remotely during pandemics; pregnant women (especially those with comorbidities) should be educated about the risks of infection and complications to prevent anxiety-related complications during pregnancy.

National Profile of Caregivers' Perspectives on Autism Spectrum Disorder Screening and Care in Primary Health Care: The Need for Autism Medical Home.

Although autism spectrum disorder (ASD) is a common developmental disorder, primary healthcare providers show a deficit in providing early diagnosis. To understand parents' experience and perspective in the diagnosis and intervention process of their children, a survey was deployed through social media to parents' with at least one child diagnosed with ASD. The survey included parents experience, satisfaction and perception in the diagnosis process and services provided for their children, stigma and type of support received. A total of 223 participants were enrolled. Although 62% of ASD patients were diagnosed by three years old, most diagnoses (66%) were non-physician initiated. Additionally, 40.8% of the parents reported that the services required for their child are available in their area of residence, but only 7.9% were satisfied with these services. Parents who received psychological support (9.9%) started early intervention, and their children have a better prognosis (p ≤ 0.005). Stigmatized parents were more likely to delay intervention (p ≤ 0.005). Parents' perception is to have qualified healthcare and educational professionals experienced in ASD. Our findings suggest that a specialized family-centred medical home for ASD patients would significantly benefit ASD patients, increase parents' satisfaction, reduce parents' stress, and ease their children's transition to adolescents.

Alpha-Synuclein, cyclooxygenase-2 and prostaglandins-EP2 receptors as neuroinflammatory biomarkers of autism spectrum disorders: Use of combined ROC curves to increase their diagnostic values.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention. METHODS: In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed. RESULTS: A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported. CONCLUSIONS: The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.

Can the Three-Dimensional Heads-Up Display Improve Ergonomics, Surgical Performance, and Ophthalmology Training Compared to Conventional Microscopy?

PURPOSE: To explore ophthalmic surgeons' opinions regarding three-dimensional heads-up display (3D HUD) use and investigate musculoskeletal (MSK) complaints among ophthalmologists. METHODS: Physicians were invited to complete an online questionnaire. Musculoskeletal complaints and data of the HUD system use were correlated with demographic information. We explored surgeons' feedback on image quality, depth perception, and the educational value of 3D microscopy. RESULTS: In this study, the prevalence of self-reported MSK pain was 82.6% (n=132). The pain started after joining ophthalmology practice and significantly improves on weekends and vacations. We found that the pain intensity in non-HUD users is higher than in HUD users, but this correlation was not statistically significant. Sixty-one (84.7%) of HUD system users were satisfied with depth perception, and 27 (37.5%) reported improvement in peripheral acuity. Thirty-seven (51.4%) of the participants believed they perform surgeries better through HUD; this was why most participants (83.3%) recommended its use in surgical training. CONCLUSION: Heads-up display use provides more comfortable sitting positions for surgeons, superior depth perception, and serves as a better educational tool. We believe that adopting this technology may help improve career longevity and productivity.

Plasma Levels of Alpha and Gamma Synucleins in Autism Spectrum Disorder: An Indicator of Severity.

OBJECTIVES: The aim of this study was to correlate plasma levels of the synaptic proteins α-synuclein and γ-synuclein in autism spectrum disorder (ASD) children in order to elucidate their possible contribution to the pathogenesis of ASD and to study their association with the severity of the disorder. SUBJECTS AND METHODS: Plasma levels of α-synuclein and γ-synuclein were measured in 38 male children diagnosed with ASD and 40 healthy age-matched male children by ELISA. RESULTS: Our results showed that plasma levels of α-synuclein (18.02 ± 5.3 pg/mL) were significantly higher in ASD children than in control children (14.39 ± 2 pg/mL), and plasma levels of γ-synuclein were decreased in the ASD group (23.74 ± 7.7 pg/mL) compared to the control group (32.40 ± 6.8 pg/mL) (p < 0.0001). Our data also indicate that plasma levels of both α-synuclein and γ-synuclein are significantly associated with the severity of ASD. CONCLUSIONS: Our study showed that alteration in α-synuclein and γ-synuclein might be associated with ASD pathogenesis and could be an indicator of the severity of the disorder.

Association of Interleukin-6 and Other Cytokines with Self-Reported Pain in Prostate Cancer Patients Receiving Chemotherapy.

Background: Pain is a common and dose-limiting side effect of many potentially curative cancer chemotherapeutic agents. This chemotherapy-induced pain (CIP) affects the quality of life of cancer patients and survivors and hampers the optimal clinical management of chemotherapy in cancer patients. The underlying mechanisms remain largely unknown, but changes in levels of cytokines/chemokines may contribute to the pathophysiology of CIP. Objective: This retrospective study was aimed at examining whether plasma levels of various cytokines change in prostate cancer patients after chemotherapy treatment and whether such changes (if any) are associated with their pain intensity. Methods: Using a Luminex assay, plasma levels of 27 cytokines/chemokines were measured in 78 men: 30 patients with metastatic prostate cancer who received chemotherapy (Docetaxel, 75 mg/m2 intravenously), 29 untreated patients with nonmetastatic prostate cancer, and 19 healthy controls. Subjective pain was assessed in chemotherapy-treated cancer patients using the 11-point numeric rating scale (NRS) pain scores. Results: Chemotherapy-treated patients with pain (NRS ≥ 3) exhibited significantly increased levels of the pro-inflammatory cytokines (IL-6, IL-8) and chemokines (Eotaxin, VEGF, and IP-10) compared with untreated cancer patients or with patients without pain (NRS = 0). Of the 27 cytokines examined, only IL-6 was positively correlated with pain intensity in the chemotherapy-treated patients with pain. Conclusions: These findings suggest that the cytokines, particularly IL-6, whose levels were elevated in the chemotherapy-treated patients may be involved in the pathophysiology of CIP, and that they might be potential new targets for pain control in cancer patients receiving chemotherapy.