Suicide Risk Among Medical Students Associated With Loneliness, Burnout, and Depressive Symptoms.

Medical students face elevated risks of depression and suicide due to rigorous training demands. However, comparative research between medical and non-medical students is limited, hindering understanding of specific risks. This study compared 337 students (89 medical) on suicide risk, depression, perfectionism, burnout, loneliness, and internet addiction. Medical students showed significantly higher suicide risk, depression, perfectionism, burnout, and loneliness. Regression analysis identified medical student status, depressive symptoms, and loneliness as significant predictors of suicide risk. Mediation analysis revealed loneliness and depressive symptoms mediating the relationship between medical student status and suicide risk. Strategies to address mental health risks among medical students are crucial, including early screening and interventions. However, this study's limitations include self-report measures and a predominantly non-medical student sample. Further research is needed to explore causal relationships and interventions effectively.

When a Patient Dies From Suicide: A Survey Among Mental Health Professionals in Israel.

Death of patients by suicide can have powerful impacts on mental health professionals (MHPs). The National Program for the Prevention of Suicidality and Suicide at Israel's Ministry of Health decided to invest in MHPs who have lost patients by suicide. Two hundred and two MHPs completed an online self-report survey regarding their emotional response, professional identity, and clinical practice, and the aid they felt would be supportive following a patient's suicide. Results indicated that 35% of MHP experienced at least one death of a patient by suicide. Respondents experienced difficult emotional reactions, and many felt responsible for the suicide. Nearly 50% reported that the patient's suicide affected their clinical practice. Most respondents reported the need for a support framework and information about the processes following a patient's suicide. It is important to increase awareness of the possibility of losing a patient by suicide and offer an appropriate supportive framework.

P(III) vs P(V): A P(V) Reagent for Thiophosphoramidate Linkages and Application to an Asymmetric Synthesis of a Cyclic Dinucleotide STING Agonist.

A highly stereoselective synthesis of a cyclic dinucleotide (CDN) STING agonist containing two chiral thiophosphoramidate linkages is described. These rare yet key functional groups were, for the first time, installed efficiently and with high diastereoselectivity using a specially designed P(V) reagent. By utilizing this strategy, the CDN was prepared in greater than 16-fold higher yield than the prior P(III) approach, with fewer hazardous reagents and chromatographic purifications.

Successful implementation of cognitive reappraisal: effects of habit and situational factors.

Reappraisal is an adaptive emotion regulation strategy associated with favourable mental health outcomes. It is unclear whether the adaptive outcomes of habitual reappraisal are associated with better implementation of reappraisal when faced with negative affective situations. The current study aimed to examine whether habitual reappraisal predicts the implementation of instructed reappraisal and to evaluate the potential moderating effects of situational factors, namely - emotional intensity and reappraisal affordance. To address this question, 100 participants reported their habitual reappraisal tendency and were asked to imagine themselves in different hypothetical interpersonal situations. Participants rated emotional intensity levels and reappraisal affordance for each situation, followed by instructions to implement reappraisal. Implementation success was measured by self-reported affect pre-and-post-implementation. Results indicated that habitual reappraisal was associated with greater reappraisal implementation success. While higher intensity scores predicted greater reappraisal implementation success, intensity did not moderate the association between habitual reappraisal and reappraisal implementation success. Reappraisal affordance did not predict reappraisal implementation success, nor did it moderate the association between habitual reappraisal and reappraisal implementation success. Our findings suggest that individual-centred factors play a significant role in reappraisal implementation success, while the effects of situation-centred factors demand further investigation.

The Association Between Gastrointestinal Symptoms and Transvaginal Ultrasound Findings in Women Referred for Endometriosis Evaluation: A Prospective Pilot Study.

PURPOSE: To evaluate the relationship between gastrointestinal (GI) symptoms and transvaginal ultrasound (TVUS) findings suggestive of endometriosis. MATERIALS AND METHODS: A prospective design. Women referred for a diagnostic ultrasound due to suspicion of endometriosis completed a Rome III and Pelvic Floor Distress Inventory (PFDI-20) questionnaire for clinical, GI symptoms, before undergoing TVUS. Endometriosis was diagnosed in the presence of endometriomas and/or deeply infiltrative endometriotic (DIE) lesions. Association between lesion sites and GI symptoms was evaluated by univariate and multivariate analysis. RESULTS: The study included 241 women who presented with: dysmenorrhea (89.6 %), dyspareunia (76.3 %), chronic pelvic pain (77.2 %), dyschezia (66 %), hematochezia (15.4 %), subfertility (24.5 %). GI symptoms were present in 25.3-76.8 % and 5.4-55.6 % of Rome III and PFDI-20 questionnaire responses, respectively. TVUS findings were endometriomas (23.2 %), peritoneal adhesions (46.5 %), uterosacral ligament (26.7 %), retrocervical (11.2 %), rectosigmoid (11.2 %), intestinal (4.6 %), and bladder (0.8 %) involvement, and pouch of Douglas (POD) obliteration (15.4 %). There was a high prevalence of peritoneal adhesions, uterosacral ligament involvement, and rectosigmoid and intestinal nodules on TVUS in women with GI symptoms, up to Chi2 = 9.639 (p = 0.013) on univariate and Chi2 = 8.102 (p = 0.005) on multivariate analysis. CONCLUSION: We observed an almost 10-fold increase in DIE lesions in women with GI symptoms. We suggest that the presence of GI symptoms should prompt a referral for endometriosis evaluation and performance of a dedicated TVUS before invasive gastrointestinal procedures.

TULP1 and TUB Are Required for Specific Localization of PRCD to Photoreceptor Outer Segments.

Photoreceptor disc component (PRCD) is a small protein which is exclusively localized to photoreceptor outer segments, and is involved in the formation of photoreceptor outer segment discs. Mutations in PRCD are associated with retinal degeneration in humans, mice, and dogs. The purpose of this work was to identify PRCD-binding proteins in the retina. PRCD protein-protein interactions were identified when implementing the Ras recruitment system (RRS), a cytoplasmic-based yeast two-hybrid system, on a bovine retina cDNA library. An interaction between PRCD and tubby-like protein 1 (TULP1) was identified. Co-immunoprecipitation in transfected mammalian cells confirmed that PRCD interacts with TULP1, as well as with its homolog, TUB. These interactions were mediated by TULP1 and TUB highly conserved C-terminal tubby domain. PRCD localization was altered in the retinas of TULP1- and TUB-deficient mice. These results show that TULP1 and TUB, which are involved in the vesicular trafficking of several photoreceptor proteins from the inner segment to the outer segment, are also required for PRCD exclusive localization to photoreceptor outer segment discs.

Reduction in maternal circulating ouabain impairs offspring growth and kidney development.

Ouabain, a steroid present in the circulation and in various tissues, was shown to affect the growth and viability of various cells in culture. To test for the possible influence of this steroid on growth and viability in vivo, we investigated the involvement of maternal circulating ouabain in the regulation of fetal growth and organ development. We show that intraperitoneal administration of anti-ouabain antibodies to pregnant mice resulted in a >80% decline in the circulating ouabain level. This reduction caused a significant decrease in offspring body weight, accompanied by enlargement of the offspring heart and inhibition of kidney and liver growth. Kidney growth inhibition was manifested by a decrease in the size and number of nephrons. After the reduction in maternal circulating ouabain, kidney expression of cyclin D1 was reduced and the expression of the α1 isoform of the Na(+), K(+)-ATPase was increased. In addition, the elevation of proliferation signals including ERK1/2, p-90RSK, Akt, PCNA, and Ki-67, and a reduction in apoptotic factors such as Bax, caspase-3, and TUNEL were detected. During human pregnancy, the circulating maternal ouabain level increased and the highest concentration of the steroid was found in the placenta. Furthermore, circulating ouabain levels in women with small-for-gestational age neonates were significantly lower than the levels in women with normal-for-gestational age newborns. These results support the notion that ouabain is a growth factor and suggest that a reduction in the concentration of this hormone during pregnancy may increase the risk of impaired growth and kidney development.

Longitudinal hair cortisol in bipolar disorder and a mechanism based on HPA dynamics.

Bipolar disorder (BD) is marked by fluctuating mood states over months to years, often with elevated cortisol levels. Elevated cortisol can also trigger mood episodes. Here, we combine longitudinal hair cortisol and mood measurements with mathematical modeling to provide a potential mechanistic link between cortisol and mood timescales in BD. Using 12 cm hair samples, representing a year of growth, we found enhanced year-scale cortisol fluctuations whose amplitude averaged 4-fold higher in BD (n = 26) participants than controls (n = 59). The proximal 2 cm of hair correlated with recent mood scores. Depression (n = 266) and mania (n = 273) scores from a longitudinal study of BD showed similar frequency spectra. These results suggest a mechanism for BD in which high emotional reactivity excites the slow timescales in the hypothalamic-pituitary-adrenal (HPA) axis to generate elevated months-scale cortisol fluctuations, triggering cortisol-induced mood episodes.

Genetic heterogeneity and consanguinity lead to a "double hit": homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. METHODS: The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. RESULTS: THE FAMILY WAS FOUND TO SEGREGATE NOVEL MUTATIONS OF TWO DIFFERENT GENES: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. CONCLUSIONS: This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient.

Sex Differences in the Diagnosis, Management, and Outcomes of Suspected Non-ST-Elevation Acute Coronary Syndromes Meeting Rapid Rule-Out Criteria.

(1) Background: patients who meet current rapid rule-out criteria for myocardial infarction (MI) are considered low risk, yet their management remains nebulous, especially among women. We aimed to examine sex differences in the diagnosis, management, and outcomes of patients meeting the rapid rule-out criteria. (2) Methods: by simulating application of the rapid rule-out MI criteria, we analyzed consecutively triaged men and women with suspected NSTE-ACS who had high-sensitivity cardiac troponin T (hs-cTnT) values that met criteria (n = 11,477), in particular, those who were admitted (n = 3775). (3) Results: men constituted ~55% of triaged patients who met the rule-out criteria, whether admitted or discharged. Men were more likely to be admitted (33.7% vs. 31.9%, p = 0.04), more commonly with hs-cTnT values between level of detection (LOD, 5 ng/ml) and the 99th percentile (59.4% of all admissions vs. 40.5% for women), whereas women were more likely to be admitted with values < level of blank (LOB, 3 ng/mL; 22.9% vs. 9.2% for men). Thirty-day mortality (1 man and 1 woman) and in-hospital MI (9 men vs. 1 woman) were uncommon among admitted patients, yet resource utilization during 3-4 hospitalization days was substantial for both sexes, with men undergoing coronary angiography (6.8% vs. 2.9%) and revascularization (3.4% vs. 1.1%) more commonly. Long-term survival for both men and women, whether admitted or discharged, was significantly worse for hs-cTnT values between LOD and the 99th percentile, even after adjusting for age and cardiovascular comorbidities. (4) Conclusions: reporting actual hs-cTnT values < 99th percentile allows for better risk stratification, especially for women, possibly closing the sex gap.

Suspected Non-ST-elevation acute coronary syndrome meeting rapid rule-out criteria: resource utilization, diagnostic yield, and clinical outcomes of hospital admission.

AIMS: Many patients with suspected non-ST-elevation (NSTE) acute coronary syndromes (ACS) are admitted, even those with initial high-sensitivity cardiac troponins (hs-cTn) values who meet rapid rule-out criteria for myocardial infarction (MI). We examined the clinical outcomes, resource utilization, and diagnostic yield of suspected NSTE-ACS patients, who presented with hs-cTnT values meeting these criteria but were nevertheless hospitalized. METHODS AND RESULTS: Applying the 2020 European Society of Cardiology (ESC) rapid rule-out MI criteria, we identified consecutive patients with an initial value of hs-cTnT <5 ng/L or an initial value of ≥5 ng/L but <14 ng/L (99th percentile) and a small increment in a subsequent test, who were nevertheless admitted. The majority (85.4%) of patients presented to the emergency department (ED) with suspected NSTE-ACS had an initial hs-cTnT <99th percentile. We examined 3775 admitted patients out of 11 477 patients who were triaged and met MI rule-out criteria. Only 0.32% (12 patients) of admitted patients experienced index MI or overall death within 30 days. Resource utilization in terms of ED stay, hospital stay, noninvasive and invasive tests was substantial, yet revascularization was uncommon (2.5%). Multivariate adjustment for age, gender, and baseline cardiovascular risk factors demonstrates similar survival of admitted vs. discharged patients (P = 0.88). Initial hs-cTnT even below the 99th percentile provided a prognostic stratification for long term mortality. CONCLUSION: Our findings support a policy of ED discharge of suspected NSTE-ACS patients meeting rapid MI rule-out criteria and subsequent ambulatory evaluation, sparing resource-consuming admissions. In-hospital and ensuing prognosis were better with lower initial hs-cTnT values.

A complete reconstruction of the early visual system of an adult insect.

For most model organisms in neuroscience, research into visual processing in the brain is difficult because of a lack of high-resolution maps that capture complex neuronal circuitry. The microinsect Megaphragma viggianii, because of its small size and non-trivial behavior, provides a unique opportunity for tractable whole-organism connectomics. We image its whole head using serial electron microscopy. We reconstruct its compound eye and analyze the optical properties of the ommatidia as well as the connectome of the first visual neuropil-the lamina. Compared with the fruit fly and the honeybee, Megaphragma visual system is highly simplified: it has 29 ommatidia per eye and 6 lamina neuron types. We report features that are both stereotypical among most ommatidia and specialized to some. By identifying the "barebones" circuits critical for flying insects, our results will facilitate constructing computational models of visual processing in insects.

The bacterial flagellar switch complex is getting more complex.

The mechanism of function of the bacterial flagellar switch, which determines the direction of flagellar rotation and is essential for chemotaxis, has remained an enigma for many years. Here we show that the switch complex associates with the membrane-bound respiratory protein fumarate reductase (FRD). We provide evidence that FRD binds to preparations of isolated switch complexes, forms a 1:1 complex with the switch protein FliG, and that this interaction is required for both flagellar assembly and switching the direction of flagellar rotation. We further show that fumarate, known to be a clockwise/switch factor, affects the direction of flagellar rotation through FRD. These results not only uncover a new component important for switching and flagellar assembly, but they also reveal that FRD, an enzyme known to be primarily expressed and functional under anaerobic conditions in Escherichia coli, nonetheless, has important, unexpected functions under aerobic conditions.

A novel splice site mutation of CDHR1 in a consanguineous Israeli Christian Arab family segregating autosomal recessive cone-rod dystrophy.

PURPOSE: To investigate the genetic basis for autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. METHODS: Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing, and optical coherence tomography. Genome-wide homozygosity mapping using a single nucleotide polymorphism array was performed to identify homozygous regions shared between the two affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico analysis was used to predict the effect of the mutation on splicing. RESULTS: The family included two affected individuals. Clinical findings included progressive deterioration of visual acuity, photophobia, defective color vision, loss of central visual fields, pigmentary deposits localized mainly in the peripheral retina, a thinned and atrophic macular region, retinal vessel attenuation, absent ERG cone responses, and reduced ERG rod responses. Homozygosity mapping revealed several homozygous intervals shared among the affected individuals. One, a 12Mb interval on chromosome 10, included the CDHR1 gene. Direct sequencing revealed a single base transversion, c.1485+2T>G, located in the conserved donor splice site of Intron 13. This mutation cosegregated with the disease in the family, and was not detected in 208 Israeli Christian Arab control chromosomes. In silico analysis predicted that this mutation eliminates the Intron 13 donor splice site. CONCLUSIONS: Only three distinct pathogenic mutations of CDHR1 have been reported to date in patients with autosomal recessive retinal degeneration. Here we report a novel splice site mutation of CDHR1, c.1485+2T>G, underlying autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. This report expands the spectrum of pathogenic mutations of the CDHR1 gene.

Temporal Summation Predicts De Novo Contralateral Pain After Cordotomy in Patients With Refractory Cancer Pain.

BACKGROUND: Percutaneous cervical cordotomy (PCC), which selectively interrupts ascending nociceptive pathways in the spinal cord, can mitigate severe refractory cancer pain. It has an impressive success rate, with most patients emerging pain-free. Aside from the usual complications of neurosurgical procedures, the risks of PCC include development of contralateral pain, which is less understood. OBJECTIVE: To evaluate whether sensory and pain sensitivity, as measured by quantitative sensory testing (QST), are associated with PCC clinical outcomes. METHODS: Fourteen palliative care cancer patients with severe chronic refractory pain limited mainly to one side of the body underwent comprehensive quantitative sensory testing assessment pre-PPC and post-PCC. They were also queried about maximal pain during the 24 h precordotomy (0-10 numerical pain scale). RESULTS: All 14 patients reported reduced pain postcordotomy, with 7 reporting complete resolution. Four patients reported de novo contralateral pain. Reduced sensitivity in sensory and pain thresholds to heat and mechanical stimuli was recorded on the operated side (P = .028). Sensitivity to mechanical pressure increased on the unaffected side (P = .023), whereas other sensory thresholds were unchanged. The presurgical temporal summation values predicted postoperative contralateral pain (r = 0.582, P = .037). CONCLUSION: The development of contralateral pain in patients postcordotomy for cancer pain might be due to central sensitization. Temporal summation could serve as a potential screening tool to identify those who are most likely at risk to develop contralateral pain. Analysis of PCC affords a unique opportunity to investigate how a specific lesion to the nociceptive system affects pain processes.

Hypothyroidism predicts worsened prognosis in patients undergoing percutaneous coronary intervention.

Background: The link between thyroid dysfunction and cardiovascular disease is well established. Hypothyroidism has been significantly associated with increased risk of dyslipidemia, atherosclerosis and heart failure. However, little is known regarding its effect on patients undergoing percutaneous coronary intervention (PCI). Aim: The aim of study was to examine the impact of concomitant hypothyroidism on mortality and major adverse cardiac event (MACE) in patients undergoing PCI. Methods: The Rabin Medical Center PCI registry includes all consecutive patients who have undergone PCI between 2004 and 2020. We identified patients with prior diagnosis of hypothyroidism, and compared rates of mortality and MACE (comprising death, myocardial infarction, target vessel revascularization and/or coronary bypass surgery). Results: Among 28,274 patients, 1,922 (6.8%) were found to have hypothryoidism. These patients were older (70.3 ± 10.4 vs. 66.0 ± 11.8 y.o, P < 0.001) and more likely to be women (34.2% vs. 26.1%, P < 0.001). They had a higher prevalence of atrial fibrillation (10.8% vs. 7.7%, P < 0.001), chronic renal dysfunction (25.1% vs. 18.7%, P = 0.04) and dementia (2.9% vs. 1.8%, P = 0.004). PCI was performed on ACS setting in 52-54% of patients in both groups (p = 0.569). Unadjusted 5-year rates of all-cause mortality (26.9% vs. 20.3%, P < 0.001) and MACE (40.3% vs. 29.4%, P < 0.001) were higher for hypothyroid patients. A propensity match score was able to form 672 matched pairs of HT and control patients, showing similar results. Moreover, following multivariate analysis, TSH as a continuous parameter was associated with a higher risk of mortality and MACE (HR, 1.06 per additional 1 mIU/L; CI, 1.02-1.11; P < 0.001 and HR, 1.07; CI, 1.02-1.12; P < 0.001, respectively) at 5-year follow up. Conclusion: In our study, hypothyroidism confers worse outcomes in patients undergoing PCI. Further research is needed to establish effective ways to mitigate this augmented risk.

Phospholipase C and termination of G-protein-mediated signalling in vivo.

In Drosophila photoreceptors, phospholipase C (PLC) and other signalling components form multiprotein structures through the PDZ scaffold protein INAD. Association between PLC and INAD is important for termination of responses to light; the underlying mechanism is, however, unclear. Here we report that the maintenance of large amounts of PLC in the signalling membranes by association with INAD facilitates response termination, and show that PLC functions as a GTPase-activating protein (GAP). The inactivation of the G protein by its target, the PLC, is crucial for reliable production of single-photon responses and for the high temporal and intensity resolution of the response to light.

External Validation of the IOTA Classification in Women with Ovarian Masses Suspected to Be Endometrioma.

The study aimed to perform external validation of the International Ovarian Tumor Analysis (IOTA) classification of adnexal masses as benign or malignant in women with suspected endometrioma. A retrospective study including women referred to an endometriosis tertiary referral center for dedicated transvaginal ultrasound (TVUS). Adnexal masses were evaluated using the IOTA classification simple descriptors, simple rules and expert opinion. The reference standard was definitive histology after mass removal at laparoscopy. In total, 621 women were evaluated and divided into four groups: endometrioma on TVUS and confirmed on surgery (Group 1 = 181), endometrioma on TVUS but other benign cysts on surgery (Group 2 = 9), other cysts on TVUS but endometrioma on surgery (Group 3 = 2), masses classified as other findings or suspicious for malignancy on TVUS and confirmed on surgery (Group 4 = 5 potentially malignant, 11 benign). This gave a sensitivity 98.9%, specificity 64%, positive 95.3% and negative 88.9% predictive values, positive 2.74 and negative 0.02 likelihood ratios and 94.7% overall accuracy. The surgical diagnosis for the five masses suspected to be malignant was: borderline serous tumor (2), borderline mucinous tumor (2), and endometrioid lesion with complex hyperplasia without atypia (1). The conclusions were that the IOTA classification simple descriptors, simple rules and expert opinion performs well for classifying adnexal masses suspected to be endometrioma. The most common potentially malignant masses in these women were borderline ovarian tumors.

Conserved nicotine-activated neuroprotective pathways involve mitochondrial stress.

Tobacco smoking is a risk factor for several human diseases. Conversely, smoking also reduces the prevalence of Parkinson's disease, whose hallmark is degeneration of substantia nigra dopaminergic neurons (DNs). We use C. elegans as a model to investigate whether tobacco-derived nicotine activates nicotinic acetylcholine receptors (nAChRs) to selectively protect DNs. Using this model, we demonstrate conserved functions of DN-expressed nAChRs. We find that DOP-2, a D3-receptor homolog; MCU-1, a mitochondrial calcium uniporter; PINK-1 (PTEN-induced kinase 1); and PDR-1 (Parkin) are required for nicotine-mediated protection of DNs. Together, our results support involvement of a calcium-modulated, mitochondrial stress-activated PINK1/Parkin-dependent pathway in nicotine-induced neuroprotection. This suggests that nicotine-selective protection of substantia nigra DNs is due to the confluence of two factors: first, their unique vulnerability to mitochondrial stress, which is mitigated by increased mitochondrial quality control due to PINK1 activation, and second, their specific expression of D3-receptors.

RIC3, the cholinergic anti-inflammatory pathway, and neuroinflammation.

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels having many functions including inflammation control, as part of the cholinergic anti-inflammatory pathway. Genome wide association studies implicated RIC3, a chaperone of nAChRs, in multiple sclerosis (MS), a neuroinflammatory disease. To understand the involvement of RIC3 in inflammatory diseases we examined its expression, regulation, and function in activated immune cells. Our results show that immune activation leads to dynamic changes in RIC3 expression, in a mouse model of MS and in human lymphocytes and macrophages. We also show similarities in the expression dynamics of RIC3 and CHRNA7, encoding for the α7 nAChR subunit. Homomeric α7 nAChRs were shown to mediate the anti-inflammatory effects of cholinergic agonists. Thus, similarity in expression dynamics between RIC3 and CHRNA7 is suggestive of functional concordance. Indeed, siRNA mediated silencing of RIC3 in a mouse macrophage cell line eliminates the anti-inflammatory effects of cholinergic agonists. Furthermore, we show increased average expression of RIC3 and CHRNA7 in lymphocytes from MS patients, and a strong correlation between expression levels of these two genes in MS patients but not in healthy donors. Together, our results are consistent with a role for RIC3 and for the mechanisms regulating its expression in inflammatory processes and in neuroinflammatory diseases.