Anosmia, characterized by the loss of smell, is associated not only with dysfunction in the peripheral olfactory system but also with changes in several brain regions involved in olfactory processing. Specifically, the orbitofrontal cortex is recognized for its pivotal role in integrating olfactory information, engaging in bidirectional communication with the primary olfactory regions, including the olfactory cortex, amygdala, and entorhinal cortex. However, little is known about alterations in structural connections among these brain regions in patients with anosmia. In this study, highresolution T1-weighted images were obtained from participants. Utilizing the volumes of key brain regions implicated in olfactory function, we employed a structural covariance approach to investigate brain reorganization patterns in patients with anosmia (n=22) compared to healthy individuals (n=30). Our structural covariance analysis demonstrated diminished connectivity between the amygdala and entorhinal cortex, components of the primary olfactory network, in patients with anosmia compared to healthy individuals (z=-2.22, FDR-corrected p=0.039). Conversely, connectivity between the orbitofrontal cortex—a major region in the extended olfactory network—and amygdala was found to be enhanced in the anosmia group compared to healthy individuals (z=2.32, FDR-corrected p=0.039). However, the structural connections between the orbitofrontal cortex and entorhinal cortex did not differ significantly between the groups (z=0.04, FDR-corrected p=0.968). These findings suggest a potential structural reorganization, particularly of higher-order cortical regions, possibly as a compensatory effort to interpret the limited olfactory information available in individuals with olfactory loss.

Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferronicorrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.

The worldwide incidence of precocious puberty, which is associated with negative health outcomes, is increasing. Several studies have suggested that environmental factors contribute to the development of precocious puberty alongside genetic factors. Some epidemiological studies have provided limited evidence suggesting an association between exposure to air pollution and changes in pubertal development. This systematic review aimed to summarize existing evidence on the association between air pollution exposure and precocious puberty. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, we searched two databases (PubMed and Web of Science) until August 2023. The included studies assessed the association between air pollutant exposure and the risk of precocious puberty, early menarche, or pubertal development. Two authors independently performed study selection and data extraction. A meta-analysis and analysis of the risk of bias were infeasible due to the limited number of studies and the heterogeneity among them. The literature search resulted in 184 studies, from which we included six studies with sample sizes ranging from 437 to 4,074 participants. The studies reported heterogeneous outcomes. Four studies found that increased exposure to air pollution was related to earlier pubertal onset. One study was inconclusive, and another suggested that air pollutant exposure may delay the onset of thelarche. Most studies suggest that exposure to air pollutants accelerates pubertal development; however, the results from the available studies are inconsistent. More extensive and well-designed longitudinal studies are required for a comprehensive understanding of the association between air pollution and precocious puberty.

Anoctamin 2 (ANO2 or TMEM16B), a calcium-activated chloride channel (CaCC), performs diverse roles in neurons throughout the central nervous system. In hippocampal neurons, ANO2 narrows action potential width and reduces postsynaptic depolarization with high sensitivity to Ca2+ at relatively fast kinetics. In other brain regions, including the thalamus, ANO2 mediates activity-dependent spike frequency adaptations with low sensitivity to Ca2+ at relatively slow kinetics. How this same channel can respond to a wide range of Ca2+ levels remains unclear. We hypothesized that splice variants of ANO2 may contribute to its distinct Ca2+ sensitivity, and thus its diverse neuronal functions. We identified two ANO2 isoforms expressed in mouse brains and examined their electrophysiological properties: isoform 1 (encoded by splice variants with exons 1a, 2, 4, and 14) was expressed in the hippocampus, while isoform 2 (encoded by splice variants with exons 1a, 2, and 4) was broadly expressed throughout the brain, including in the cortex and thalamus, and had a slower calcium-dependent activation current than isoform 1. Computational modeling revealed that the secondary structure of the first intracellular loop of isoform 1 forms an entrance cavity to the calcium-binding site from the cytosol that is relatively larger than that in isoform 2. This difference provides structural evidence that isoform 2 is involved in accommodating spike frequency, while isoform 1 is involved in shaping the duration of an action potential and decreasing postsynaptic depolarization. Our study highlights the roles and molecular mechanisms of specific ANO2 splice variants in modulating neuronal functions.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (β=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (β=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

Monoclonal antibodies are pure antibodies that react to a specific epitope. Plasmapheresis is a treatment that separates and eliminates disease-causing substances before replacing the blood with plasma. Plasmapheresis has insufficient evidence for treating new-onset refractory status epilepticus (NORSE). Sequential plasmaphereses gradually improved a female cryptogenic NORSE patient who did not benefit from monoclonal antibody treatment.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.

It is well known that sex hormones are potential modulators of brain functions and women experience dynamic hormonal changes during the menstrual cycle. Previous animal studies have reported that the variations in sex hormones over the menstrual cycle may affect cognitive function, emotion, and behavior by altering structures and functional connectivity of the brain. Considering the prevalence of certain neuropsychiatric disorders such as mood and anxiety disorders is relatively high in women, as compared with men, fluctuations of sex hormones over the menstrual cycle may influence the human brain and potentially underlie sex differences in clinical features of several neuropsychiatric disorders. There is, however, little evidence regarding the exact mechanisms underlying the effects of sex hormones on the human brain. In this review, we focused on studies to examine structural and functional changes over the menstrual cycles in women and aimed to provide an up-to-date overview of neuroimaging studies regarding the effects of sex hormonal fluctuations on the brain and behaviors.

Stress activates the hypothalamic-pituitary-adrenal system, and induces the release of glucocorticoids, stress hormones, into circulation. Many studies have shown that stress affects feeding behavior, however, the underlying circuitry and molecular mechanisms are not fully understood. The balance between orexigenic (simulating appetite) and anorexigenic (loss of appetite) signals reciprocally modulate feeding behavior. It is suggested that proopiomelanocortin (POMC) and neuropeptide Y (NPY) neurons in the arcuate nucleus (ARC) of the hypothalamus are the first-order neurons that respond to the circulating signals of hunger and satiety. Here, we examined a chronic restraint stress model and observed an increase in food intake, which was not correlated with anhedonia. We investigated whether stress affects the properties of POMC and NPY neurons and found that chronic restraint stress reduced the excitatory inputs onto POMC neurons and increased the action potential threshold. Therefore, our study suggests that chronic stress modulates the intrinsic excitability and excitatory inputs in POMC neurons, leading to changes in feeding behavior.

Objective: To elucidate whether clinical features and the weighted genetic risk score (wGRS) were associated with the presence of lupus nephritis (LN). Methods: We retrospectively divided patients with systemic lupus erythematosus (SLE, n=1,078) into biopsy-proven LN (n=507) and non-LN groups (non-LN, n=571). Baseline clinical features, serologic markers, and the wGRS were collected. The wGRS was calculated from 112 non-human leukocyte antigen (non-HLA) loci and HLA-DRβ1 amino acid haplotypes for SLE. Associations among clinical features, wGRS, and the presence of LN were identified. Results: In the multivariate analysis, patients with LN were younger at diagnosis (odds ratio [OR]=0.97, p＜0.001), had more pleuritis (OR=2.44, p＜0.001) and pericarditis (OR=1.62, p=0.029), had a higher detection rate of anti-double stranded deoxyribonucleic acid (anti-dsDNA antibodies, OR=2.22, p＜0.001), anti-Smith antibodies (anti-Sm antibodies, OR=1.70, p=0.002), low level of complement (OR=1.37, p=0.043) and absence of antiphospholipid antibodies (aPL antibodies, OR=1.60, p=0.002), and had higher wGRS (OR=1.16, p=0.012). Mediation analysis suggested that anti-Sm antibodies and low complement could be mediators in the relationship between high wGRS and the presence of LN. Conclusion Onset age, pleuritis, pericarditis, several serologic markers, and wGRS were associated with the presence of LN. Anti-Sm antibodies and low complement appeared to mediate the indirect relationship between wGRS and the presence of LN.