Corridor and real-time 6-minute walk tests in healthy young adults: A randomized cross-over study.

Objective: Cardiopulmonary endurance is important for comfortably participating in activities of daily living. Exercise tests, such as the 6-minute walk test (6MWT), are commonly used to evaluate cardiopulmonary endurance. We investigated the effects of the Gait Real-Time Analysis Interactive Lab (GRAIL)- and corridor-based 6MWTs on functional performance. Methods: Thirty healthy men were randomly divided into two groups. Group A participants performed a corridor-based 6MWT, followed by a washout period (1 h). Subsequently, they performed the GRAIL-based 6MWT. Group B participants performed the tests in the reverse order of that performed by Group A participants. Results: The corridor-based 6MWT resulted in significantly higher 6MW distance and 6MW speed than the GRAIL-based 6MWT. No significant differences were observed between the two groups in any of the following secondary outcomes: systolic blood pressure, diastolic blood pressure, oxygen saturation, heart rate, dyspnea, and overall fatigue. A strong positive correlation was observed between the 6MW distance and 6MW speed. Conclusion: The corridor- and GRAIL-based 6MWT should not be used interchangeably.

Rapid detection of West Nile and Dengue viruses from mosquito saliva by loop-mediated isothermal amplification and displaced probes.

Arthropod-borne viruses are major causes of human and animal disease, especially in endemic low- and middle-income countries. Mosquito-borne pathogen surveillance is essential for risk assessment and vector control responses. Sentinel chicken serosurveillance (antibody testing) and mosquito pool screening (by RT-qPCR or virus isolation) are currently used to monitor arbovirus transmission, however substantial time lags of seroconversion and/or laborious mosquito identification and RNA extraction steps sacrifice their early warning value. As a consequence, timely vector control responses are compromised. Here, we report on development of a rapid arbovirus detection system whereby adding sucrose to reagents of loop-mediated isothermal amplification with displaced probes (DP-LAMP) elicits infectious mosquitoes to feed directly upon the reagent mix and expectorate viruses into the reagents during feeding. We demonstrate that RNA from pathogenic arboviruses (West Nile and Dengue viruses) transmitted in the infectious mosquito saliva was detectable rapidly (within 45 minutes) without RNA extraction. Sucrose stabilized viral RNA at field temperatures for at least 48 hours, important for transition of this system to practical use. After thermal treatment, the DP-LAMP could be reliably visualized by a simple optical image sensor to distinguish between positive and negative samples based on fluorescence intensity. Field application of this technology could fundamentally change conventional arbovirus surveillance methods by eliminating laborious RNA extraction steps, permitting arbovirus monitoring from additional sites, and substantially reducing time needed to detect circulating pathogens.

Does prior exposure to larvicides influence dengue virus susceptibility in Aedes aegypti (Diptera: Culicidae)?

Control of mosquito vector populations is primarily intended to reduce the transmission of pathogens they transmit. Use of chemical controls, such as larvicides, can have unforeseen consequences on adult traits if not applied properly. The consequences of under application of larvicides are little studied, specifically the impacts on pathogen infection and transmission by the vectors that survive exposure to larvicides. We compared vector susceptibility of Aedes aegypti (L.) for dengue virus, serotype 1 (DENV-1) previously exposed as larvae to an LC50 of different classes of insecticides as formulated larvicides. Larval exposure to insect growth regulators (methoprene and pyriproxyfen) significantly increased susceptibility to infection of DENV-1 in Ae. aegypti adults but did not alter disseminated infection or transmission. Larval exposure to temephos, spinosad, and Bti did not increase infection, disseminated infection, or transmission of DENV-1. Our findings describe a previously under observed phenomenon, the latent effects of select larvicides on mosquito vector susceptibility for arboviruses. These data suggest that there are unintended consequences of sublethal exposure to select larvicides that can influence susceptibility of Ae. aegypti to DENV infection, and indicates the need for further investigation of sublethal effects of insecticides on other aspects of mosquito biology, especially those parameters relevant to a mosquitoes ability to transmit arboviruses (life span, biting behavior, extrinsic incubation period).

Neutral Mechanical Alignment and Prevalence of Constitutional Varus Knees Among the Saudi Population at King Saud University Medical City.

Background Various studies have described the restoration of the neutral mechanical alignment of the lower limb in total knee replacement (TKR) as a key factor of knee implant durability. Mechanical alignment of the knee requires that the tibial and femoral cuts are perpendicular to the mechanical axis of each bone in the coronal plane. Objectives The aim of this study is to investigate mechanical knee alignment and the prevalence of constitutional varus knee among the Saudi population at a single tertiary center with no history of musculoskeletal abnormalities. Methodology This is a retrospective cross-sectional study involving patients with no musculoskeletal abnormality who had their lower limb X-ray Centigram using the universal viewer zero footprint system made between 2015 and 2021. The study took place at King Saud University Medical City. The X-rays were obtained from patients' electronic medical records retrospectively. A total of 728 knees of 370 males and 358 females were included in this study. Results The results showed that 165 male knees (44.4%) and 218 female knees (60%) had constitutional varus alignment with the hip-knee-ankle (HKA) angle of ≤3° or less. The average HKA angle was smaller in males than in females: -3.69° versus -1.98°, respectively. Conclusion We have identified variables and factors that can help surgeons detect the constitutional varus on a full leg radiograph preoperatively at the time of TKA, regardless of the osteoarthritic changes of the knee. We encourage the scientific community to look for causes and risk factors for developing constitutional varus.

Assessment of insecticide resistance of Aedes aegypti (Diptera: Culicidae) populations to insect growth regulator pyriproxyfen, in the northeast region of Brazil.

Vector control has been an essential strategy in Brazil to manage vector-borne diseases, and the use of insecticides plays an important role in this effort. Pyriproxyfen (PPF) has become a common insect growth regulator used to control juvenile stages of mosquitoes by disturbing their growth and development. This study assesses the susceptibility and resistance status of Brazilian Ae. aegypti populations that previously showed low resistance levels to PPF. Eggs of Ae. aegypti were collected from six cities located in the northeast states of Ceará (Quixadá, Icó, and Juazeiro do Norte), and Bahia (Itabuna, Brumado, and Serrinha). We used the Ae. aegypti Rockefeller strain as an experimental control and a strain known to be susceptible to insecticides. Inhibition of emergence rates by 50% of Ae. aegypti populations varied from 0.0098-0.046 µg/L. Mosquitoes from Icó, Serrinha, and Brumado showed low resistance levels [resistance ratio (RR50) = 2.33, 4.52, and 4.83, respectively], whereas moderate levels of resistance were detected in populations from Juazeiro do Norte (RR50=5.83) and Itabuna (RR50=7.88). Aedes aegypti collected from the Quixadá population showed a high resistance level to pyriproxyfen (RR50=11). The evolution of resistance in Brazilian Ae. aegypti populations to PPF can compromise vector control efforts. Continuous monitoring of insecticide resistance in Ae. aegypti is essential for making timely management decisions for effective vector control and management.

Native Wolbachia infection and larval competition stress shape fitness and West Nile virus infection in Culex quinquefasciatus mosquitoes.

Introduction: Wolbachia transinfections established in key mosquito vectors, including Aedes aegypti are typically associated with pathogen blocking-reduced susceptibility to infection with key pathogens and reduced likelihood those pathogens are transmitted to new hosts. Host-symbiont-virus interactions are less well understood in mosquitoes like Culex quinquefasciatus, which naturally harbor Wolbachia, with pathogen blocking observed in some populations but not others, potentially due to innate differences in their Wolbachia load. In nature, mosquito larvae are often subject to developmental stresses associated with larval competition, which can lead to reduced body size and differential susceptibility to arbovirus infection. Methods: In this study, we sought to understand whether competition stress and Wolbachia infection in Cx. quinquefasciatus combine to impact host fitness and susceptibility to infection with West Nile virus. We reared Wolbachia-infected and uninfected Cx. quinquefasciatus larvae under three competition stress levels, increasing larval density without increasing the amount of food supplied. We then monitored larval development and survival, measured wing length and quantified Wolbachia density in adults, and then challenged mosquitoes from each treatment group orally with West Nile virus. Results and Discussion: We observed that high competition stress extended development time, decreased the likelihood of eclosion, decreased body size, and increased susceptibility to West Nile virus (WNV) infection. We also observed that Wolbachia infection reduced WNV load under low competition stress, and significantly improved the rate of survival for larval reared under higher competition stress. Consequently, our data suggest that native Wolbachia infection in Cx. quinquefasciatus has differential consequences for host fitness and susceptibility to WNV infection depending on competition stress.

The Journey to Diagnose Spondyloarthritis in Patients From Riyadh: A Cross-Sectional Study.

Introduction  Ankylosing spondylitis, now frequently referred to as spondyloarthritis (SpA), is a chronic inflammatory disease causing axial arthritis and inflammatory lower back pain resulting in the eventual impairment of spinal mobility. Moreover, its systemic complications include stiffness and inflexibility, restriction of lung capacity and function, eye inflammation, compression spinal fractures, and heart problems. Hence, early diagnosis and intervention play a key role in preventing acute complications and improving the quality of life. Objective  We aimed to estimate the average duration of diagnosis, the average number of doctors visited, and the association between the specialty of the first physician and the length of SpA diagnosis delay. Methods A cross-sectional retrospective study was conducted from November 2019 to April 2020 with patients from King Khalid University Hospital, Riyadh, Saudi Arabia. The patients were 18 years and older and diagnosed with SpA. Call interviews were conducted and patients' medical charts were reviewed. The data were analyzed using the Statistical Package for Social Sciences statistical software, version 23 (IBM Corp., Armonk, NY). Result  The total sample was 101 patients: 59 (58.4%) males and 42 (41.6%) females. The average duration from the onset of symptoms until seeking medical advice (lag 1) and from seeking medical advice until the definite diagnosis (lag 2) was 24.74 ± 48.13 and 16.16 ± 34.62 months, respectively. The average number of doctors visited between the first medical encounter and the final diagnosis was 3.56 ± 5.3. Patients who consulted rheumatologists as the first medical encounter showed less delay in diagnosis compared to patients who sought non-rheumatologists, such as orthopedists, emergency physicians, and general physicians (11.81 ± 33.35 months vs. 26.63 ± 44.28, 26.96 ± 44.88, and 44.33 ± 65.75 months, respectively). Conclusion  Patients with SpA who were not seen by rheumatologists took a longer period till the final diagnosis than those who visited rheumatologists earlier in the course of the disease. Therefore, more studies are required to define the exact factors leading to the delay.

Brazilian Populations of Aedes aegypti Resistant to Pyriproxyfen Exhibit Lower Susceptibility to Infection with Zika Virus.

Zika virus (ZIKV) infection has caused devastating consequences in Brazil as infections were associated with neurological complications in neonates. Aedes aegypti is the primary vector of ZIKV, and the evolution of insecticide resistance (IR) in this species can compromise control efforts. Although relative levels of phenotypic IR in mosquitoes can change considerably over time, its influence on vector competence for arboviruses is unclear. Pyriproxyfen (PPF)-resistant populations of Ae. aegypti were collected from five municipalities located in Northeast of Brazil, which demonstrated different resistance levels; low (Serrinha, Brumado), moderate (Juazeiro do Norte, Itabuna), and high (Quixadá). Experimental per os infection using ZIKV were performed with individuals from these populations and with an insecticide susceptible strain (Rockefeller) to determine their relative vector competence for ZIKV. Although all populations were competent to transmit ZIKV, mosquitoes derived from populations with moderate to high levels of IR exhibited similar or lower susceptibility to ZIKV infection than those from populations with low IR or the susceptible strain. These observations suggest an association between IR and arbovirus infection, which may be attributable to genetic hitchhiking. The use of PPF to control Brazilian Ae. aegypti may be associated with an indirect benefit of reduced susceptibility to infection, but no changes in disseminated infection and transmission of ZIKV among PPF-resistant phenotypes.

Ingestion of spinosad-containing toxic sugar bait alters Aedes albopictus vector competence and vectorial capacity for dengue virus.

Dengue virus (DENV) is a highly prevalent vector-borne virus that causes life-threatening illnesses to humans worldwide. The development of a tool to control vector populations has the potential to reduce the burden of DENV. Toxic sugar bait (TSB) provides a form of vector control that takes advantage of the sugar-feeding behavior of adult mosquitoes. However, studies on the effect of ingestion of toxins in TSB on vector competence and vectorial capacity for viruses are lacking. This study evaluated vector competence for DENV serotype-1 of Aedes albopictus at 7 and 14 days post-ingestion of TSB formulated with spinosad (of bacteria origin) as an oral toxin. Our results and others were modeled to estimate effects on Ae. albopictus vectorial capacity for DENV. Ingestion of TSB caused a reduction in survival of females, but increased mosquito susceptibility to DENV infection, disseminated infection, and transmission. However, this increase in vector competence was obviated by the reduction in survival, leading to a lower predicted vectorial capacity. The findings of this study highlight the importance of evaluating the net impact of TSB ingestion on epidemiological parameters of vectorial capacity in the context of vector control efforts to reduce the risk of transmission of vector-borne viruses.

Temperature-Mediated Effects on Mayaro Virus Vector Competency of Florida Aedes aegypti Mosquito Vectors.

Mayaro virus (MAYV) is an emerging mosquito-borne arbovirus and public health concern. We evaluated the influence of temperature on Aedes aegypti responses to MAYV oral infection and transmission at two constant temperatures (20 °C and 30 °C). Infection of mosquito tissues (bodies and legs) and salivary secretions with MAYV was determined at 3, 9, 15, 21, and 27 days post ingestion. At both temperatures, we observed a trend of increase in progression of MAYV infection and replication kinetics over time, followed by a decline during later periods. Peaks of MAYV infection, titer, and dissemination from the midgut were detected at 15 and 21 days post ingestion at 30 °C and 20 °C, respectively. Mosquitoes were able to transmit MAYV as early as day 3 at 30 °C, but MAYV was not detectable in salivary secretions until day 15 at 20 °C. Low rates of MAYV in salivary secretions collected from infected mosquitoes provided evidence supporting the notion that a substantial salivary gland barrier(s) in Florida Ae. aegypti can limit the risk of MAYV transmission. Our results provide insights into the effects of temperature and time on the progression of infection and replication of MAYV in Ae. aegypti vectors.

Thymolipomatous myasthenia gravis outcomes following thymectomy: a systematic review.

OBJECTIVES: Our goal was to evaluate the effect of thymectomy on the progression of thymolipomatous myasthenia gravis. METHODS: An electronic search performed across PubMed, MEDLINE and Web of Science databases included all article types. We included 15 series comprising 36 cases that met specific criteria, including case reports or case series related to thymolipoma with a myasthenia gravis association, where thymectomy was cited as the primary intervention with postoperative reporting of the prognosis and articles written in the English language. RESULTS: Our study included 17 men (47.2%) and 19 women (52.8%). Tumour sizes varied between 34 × 18 × 7 cm and 2.8 × 2.3 × 1.9 cm; the weight of the tumours ranged between 38 and 1780 g (mean 190, standard deviation 341). The surgical approaches were a median sternotomy in 29 patients (80.6%), a thoracotomy in 1 patient (2.8%), video-assisted thoracoscopic surgery in 2 patients (5.6%) and unreported approaches in 4 (11.1%) patients. The disease was entirely resolved with complete, stable remission in 5 patients (13.9%); symptoms were improved in 19 (52.8%) and stable in 10 patients (27.7%). We identified 2 groups of patients according to their improvement post-thymectomy (improved group and group with no change). CONCLUSIONS: Although the cases were uncontrolled and did not demonstrate strong associations, they do support some hypotheses. We found a significant statistical difference between the 2 groups in terms of age, because younger patients tended to improve to a greater degree post-thymectomy. Also, we found that female patients with thymoma visible on the imaging scans were significantly associated with post-thymectomy myasthenia gravis improvement. REGISTRATION NUMBER IN PROSPERO: CRD42020173229.

Spinosyns Delivered in Sugar Meals to Aedes aegypti and Aedes albopictus (Diptera: Culicidae): Acute Toxicity and Subacute Effects on Survival, Fecundity, and Fertility.

Sugar is an essential source of nutrition for adult mosquitoes to acquire energy. Toxic sugar bait (TSB) provides a promising method for mosquito control by incorporating toxins into artificial sources of sugar (i.e., toxic baits) presented to wild populations. Spinosyns comprise a family of bacterial secondary metabolites with a unique mode of action against the insect nervous system, an appealing environmental safety profile, and potential for incorporation into sugar baits. This research evaluated acute and subacute effects of spinosad (spinosyns A and D) and spinetoram (spinosyns J and L) in sugar meals on survival, fecundity, and fertility of Aedes aegypti and Aedes albopictus. Acute toxicity of spinosyns doubled from 24 to 48 h of assessment, revealing a relatively slow and cumulative action of the formulated spinosyns. Median lethal concentrations at 48 h were lower for spinetoram than for spinosad, lower for Ae. albopictus than Ae. aegypti, and lower for males than females. When exposed to subacute LC50 concentrations of spinosad and spinetoram for 24 h, survival of males and females of both species was diminished compared with controls, fecundity of females was increased, but fertility as measured by hatch rate of eggs was decreased. The formulations may have increased the nutritive value of the sugar meals thereby boosting fecundity, while toxifying embryos, reducing fertility. The inclusion of subacute effects of spinosyns allows assessment of the broader consequences of TSB for adult mosquito control.

Evaluation of Pyriproxyfen Effects on Aedes aegypti and Predatory Mosquito Toxorhynchites rutilus (Diptera: Culicidae).

Control of mosquito vectors of pathogens remains heavily dependent on the application of conventional insecticides. Pyriproxyfen (PPF) is a novel insecticide that has been proposed for use in autodissemination techniques to control mosquito vectors. The use of PPF can inhibit adult emergence but does not inhibit larval development. This feature is favorable for controlling Aedes aegypti because PPF has the potential to work in combination with natural sources of mortality (competition, predation) during the immature stages, and other control methods, including biocontrol agents that further suppress recruitment of adult mosquitoes. However, the PPF effects on life-history traits of Ae. aegypti in comparison to predatory mosquito Toxorhynchites rutilus, a source of mortality, are not fully understood. Here, we show that larval exposure to PPF concentrations that inhibit 50-90% of adult emergence in Ae. aegypti had a negligible effect on adult emergence and lifespan of Tx. rutilus. Weights of adult Ae. aegypti and Tx. rutilus were not influenced by PPF. These findings suggest that the use of PPF to control mosquito vectors may have low effects on mosquito biocontrol agents. Our results extend and confirm earlier data showing that PPF has potential to implement with Tx. rutilus to suppress Ae. aegypti and provide an additional advantage of PPF use in autodissemination control strategies.

Impact of wearing personal protective equipment on the performance and decision making of surgeons during the COVID-19 pandemic: An observational cross-sectional study.

ABSTRACT: During the coronavirus disease 2019 (COVID-19) pandemic, the mandatory use of personal protective equipment (PPE) has resulted in a significant reduction in the infection rate among health care workers (HCWs). However, there are some ongoing concerns about the negative impact of using PPE for prolonged periods.This study examined the impact of wearing PPE on surgeons' performance and decision making during the COVID-19 pandemic.In this cross-sectional study, an anonymous online questionnaire was created and disseminated to surgeons all over the Eastern Province of Saudi Arabia. The questionnaire included the demographic data, the local hospital policies, the non-technical skills (e.g., communication, vision, and comfort) and the technical skills, and the process of decision making.From June 2020 to August 2020, 162 surgeons participated in this questionnaire. Of them, 80.2% were aged from 26 to 45 years, 70.4% have received a special training for PPE, and 59.3% of participants have operated on COVID-19 confirmed cases. A negative impact of wearing PPE was reported on their overall comfort, vision, and communication skills (92.6%, 95.1%, and 82.8%, respectively). The technical skills and decision making were not significantly affected (60.5% and 72.8%, respectively). More preference for conservative approach, damage control procedures, and/or open approach was reported.Despite its benefits, PPE is associated with a significant negative impact on the non-technical skills (including vision, communication, and comfort) as well as a non-significant negative impact on technical skills and decision making of surgeons. Extra efforts should be directed to improve PPE, especially during lengthy pandemics.

Juvenile hormone analog enhances Zika virus infection in Aedes aegypti.

In recent years, there has been a rise in the emergence of arboviruses of public health importance, including Zika, chikungunya, dengue, and yellow fever viruses. Insecticide-based mosquito control has been the primary method for mitigating transmission of arboviruses. The consequences for the application of insecticides include both lethal and sublethal effects, and associated development of insecticide resistance. However, little is known about the influence on arboviral transmission. Mosquitoes with phenotypes that exhibit insecticide resistance or experience sublethal effects may be associated with altered susceptibility to arbovirus infection and transmission. Juvenile hormone analogs (JHAs) are insecticides that prevent pupa to adult molting of mosquitoes by mimicking the action of their natural juvenile hormone. Here, we examined whether the JHA pyriproxyfen interacts with ambient temperature (20 °C and 30 °C) during juvenile stages to influence life-history traits, population growth (λ'), and Zika virus (ZIKV) infection in Aedes aegypti. Development time of females was lengthened at 20 °C and in the presence of JHA. Prevention of pupa to adult molting by JHA was differentially higher at elevated temperature than low temperature. Size of females was larger at 20 °C and smaller at 30 °C. Infection, disseminated infection, and transmission of ZIKV in females were enhanced by JHA at both 20 °C and 30 °C relative to the controls. These results demonstrate that mosquito life-history and vector competence parameters are strongly influenced by interactive effects of JHA and temperature. The JHA-induced enhancement of ZIKV infection in females should be a consideration when implementing JHA in vector control strategies.

The effects of exposure to pyriproxyfen and predation on Zika virus infection and transmission in Aedes aegypti.

Zika virus (ZIKV) is an emerging mosquito-borne pathogen that can cause global public health threats. In the absence of effective antiviral medications, prevention measures rely largely on reducing the number of adult mosquito vectors by targeting juvenile stages. Despite the importance of juvenile mosquito control measures in reducing adult population size, a full understanding of the effects of these measures in determining mosquito phenotypic traits and in mosquito-arbovirus interactions is poorly understood. Pyriproxyfen is a juvenile hormone analog that primarily blocks adult emergence, but does not cause mortality in larvae. This mechanism has the potential to work in combination with other juvenile sources of mortality in nature such as predation to affect mosquito populations. Here, we experimentally evaluated the effects of juvenile exposure to pyriproxyfen and predatory mosquito Toxorhynchites rutilus on Aedes aegypti phenotypes including susceptibility to ZIKV infection and transmission. We discovered that combined effects of pyriproxyfen and Tx. rutilus led to higher inhibition of adult emergence in Ae. aegypti than observed in pyriproxyfen or Tx. rutilus treatments alone. Adult body size was larger in treatments containing Tx. rutilus and in treatments mimicking the daily mortality of predation compared to control or pyriproxyfen treatments. Susceptibility to infection with ZIKV in Ae. aegypti was reduced in predator treatment relative to those exposed to pyriproxyfen. Disseminated infection, transmission, and titers of ZIKV in Ae. aegypti were similar in all treatments relative to controls. Our data suggest that the combination of pyriproxyfen and Tx. rutilus can inhibit adult Ae. aegypti emergence but may confer a fitness advantage in survivors and does not inhibit their vector competence for ZIKV relative to controls. Understanding the ultimate consequences of juvenile mosquito control measures on subsequent adults' ability to transmit pathogens is critical to fully understand their overall impacts.

Immune-mediated comorbidities in Saudi patients with narcolepsy.

Background: Autoimmunity has been proposed as a cause of narcolepsy. A few studies have assessed comorbid autoimmune diseases in patients with narcolepsy, with conflicting results; however, no study has assessed autoimmune diseases in Arab narcolepsy patients. This study aimed to assess the coexistence of immune-mediated conditions such as allergies, autoimmune diseases, and autoinflammatory diseases in patients with narcolepsy type 1 (with cataplexy) (NT1) and narcolepsy type 2 (without cataplexy) (NT2). Methods: Personal and family history of autoimmune/autoinflammatory and allergic disorders was collected using a questionnaire in 80 consecutive Saudi patients with narcolepsy (46 NT1 and 24 NT2), who were diagnosed according to the International Classification of Sleep Disorders, Third Edition. The control group comprised 222 adults from the general population. Results: Comorbid autoimmune/autoinflammatory diseases were reported by 21.4% of the NT1 patients, and 12.2% of the controls, with no significant difference between cases and controls in a model adjusted for confounding covariates. However, allergic disorders were significantly more prevalent among NT1 patients. Both comorbid autoimmune/autoinflammatory and allergic disorders were significantly more prevalent among NT2 patients compared to controls. No differences in demographic and clinical characteristics were detected between narcolepsy patients with and without autoimmune/autoinflammatory diseases. Conclusion: NT1 is not associated with increased comorbid autoimmune diseases in the studied sample of Saudi patients. However, autoimmune diseases are associated with NT2, and allergic disorders are associated with both NT1 and NT2. These findings suggest the existence of dysregulation in the immune system of narcolepsy patients that requires further research.