We present a case report describing an unexpected anomaly encountered during a total thyroidectomy for a patient with papillary carcinoma of the left lobe of the thyroid with retrosternal extension. Intraoperatively, we discovered that the left lobe of the thyroid gland had extended posteriorly, invading the carotid space and displacing the carotid sheath anteriorly. The vagus nerve was identified as a cord-like structure abutting the anterior surface of the tumor, in close relation to the strap muscles. This case highlights the importance of careful dissection and identification of anatomical structures during thyroidectomy procedures to avoid inadvertent nerve injury. We discuss the significance of meticulous dissection-wide exposure and advocate for greater awareness and vigilance among surgeons.

Non-recurrent laryngeal nerve (NRLN) is an anatomic variation seen in about 0.52-0.7% patients, generally on right side. It exits the vagus nerve having a direct route to the larynx, unlike usual recurrent laryngeal nerve, supplying intrinsic laryngeal muscles except cricothyroid. It is sited over left side on extremely rare occasions, that is, 0.04% of the cases. Some cases of NRLN co-exists with aberrant right subclavian artery which courses behind the esophagus, also known as \'arteria lusoria\'. Here we present a case of 60-years old patient, diagnosed as goiter presented to us in june 2023 at the department of head and neck surgery at a tertiary care setup of Karachi Pakistan. Intra-operatively, non-recurrent nerve was encountered, whose association was found with arteria lusoria, observed in pre-operative CT-scan. The nerve was saved and no post-operative complications were seen in patient. The association of arteria lusoria in this case emphasize its importance in predicting NRLN via pre-operative imaging techniques which can prevent its injury intra-operatively.

(1) Background: We examined the effect of the acute administration of olive oil (EVOO), linseed oil (GLO), soybean oil (SO), and palm oil (PO) on gastric motility and appetite in rats. (2) Methods: We assessed food intake, gastric retention (GR), and gene expression in all groups. (3) Results: Both EVOO and GLO were found to enhance the rate of stomach retention, leading to a decrease in hunger. On the other hand, the reduction in food intake caused by SO was accompanied by delayed effects on stomach retention. PO caused an alteration in the mRNA expression of NPY, POMC, and CART. Although PO increased stomach retention after 180 min, it did not affect food intake. It was subsequently verified that the absence of an autonomic reaction did not nullify the influence of EVOO in reducing food consumption. Moreover, in the absence of parasympathetic responses, animals that received PO exhibited a significant decrease in food consumption, probably mediated by lower NPY expression. (4) Conclusions: This study discovered that different oils induce various effects on parameters related to food consumption. Specifically, EVOO reduces food consumption primarily through its impact on the gastrointestinal tract, making it a recommended adjunct for weight loss. Conversely, the intake of PO limits food consumption in the absence of an autonomic reaction, but it is not advised due to its contribution to the development of cardiometabolic disorders.

BACKGROUND: A recent meta-analysis revealed that vagally mediated heart rate variability (vmHRV; a biomarker of emotion regulation capacity) significantly decreases in the luteal phase of the menstrual cycle. As two follow-up studies suggest, these vmHRV decreases are driven primarily by increased luteal progesterone (P4). However, analyses also revealed significant interindividual differences in vmHRV reactivity to the cycle, which is in line with longstanding evidence for interindividual differences in mood sensitivity to the cycle. The present study begins to investigate whether these interindividual differences in vmHRV cyclicity can explain who is at higher risk of showing premenstrual emotional changes. We expected a greater degree of midluteal vmHRV decrease to be predictive of a greater premenstrual increase in negative affect.
METHODS: We conducted an observational study with a naturally cycling community sample (N = 31, M = 26.03 years). Over a span of six weeks, participants completed (a) daily ratings of negative affect and (b) counterbalanced lab visits in their ovulatory, midluteal, and perimenstrual phases. Lab visits were scheduled based on positive ovulation tests and included assessments of baseline vmHRV and salivary ovarian steroid levels.
RESULTS: In line with previous research, multilevel models suggest that most of the sample shows ovulatory-to-midluteal vmHRV decreases which, however, were not associated with premenstrual emotional changes. Interestingly, it was only the subgroup with luteal increases in vmHRV whose negative affect markedly worsened premenstrually and improved postmenstrually.
CONCLUSIONS: The present study begins to investigate cyclical changes in vmHRV as a potential biomarker of mood sensitivity to the menstrual cycle. The results demonstrate a higher level of complexity in these associations than initially expected, given that only atypical midluteal increases in vmHRV are associated with greater premenstrual negative affect. Potential underlying mechanisms are discussed, among those the possibility that luteal vmHRV increases index compensatory efforts to regulate emotion in those with greater premenstrual negative affect. However, future studies with larger and clinical samples and more granular vmHRV assessments should build on these findings and further explore associations between vmHRV cyclicity and menstrually related mood changes.

Heart failure is a major clinical problem, with treatments involving medication, devices, and emerging neuromodulation therapies such as vagus nerve stimulation (VNS). Considering the ongoing interest in using VNS to treat cardiovascular disease it is important to understand the genetic and molecular changes developing in the heart in response to this form of autonomic neuromodulation. This experimental animal (rat) study investigated the immediate transcriptional response of the ventricular myocardium to selective stimulation of vagal efferent activity using an optogenetic approach. Vagal preganglionic neurons in the dorsal motor nucleus of the vagus nerve were genetically targeted to express light-sensitive chimeric channelrhodopsin variant ChIEF, and stimulated using light. RNA sequencing of left ventricular myocardium identified 294 differentially expressed genes (DEGs, false discovery rate <0.05). Qiagen Ingenuity Pathway Analysis (IPA) highlighted 118 canonical pathways that were significantly modulated by vagal activity, of which 14 had a z-score of ≥2/≤-2, including EIF-2, IL-2, Integrin, and NFAT-regulated cardiac hypertrophy. IPA revealed the effect of efferent vagus stimulation on protein synthesis, autophagy, fibrosis, autonomic signalling, inflammation, and hypertrophy. IPA further predicted that the identified DEGs were the targets of 50 upstream regulators, including transcription factors (e.g., MYC, NRF1) and microRNAs (e.g., miR-335-3p, miR-338-3p). These data demonstrate that the vagus nerve has a major impact on myocardial expression of genes involved in regulation of key biological pathways. The transcriptional response of the ventricular myocardium induced by stimulation of vagal efferents is consistent with the beneficial effect of maintained/increased vagal activity on the heart.

Background: Evidence suggests that vagus nerve stimulation can modulate heart rate variability (HRV). However, there is a lack of mechanistic studies in healthy subjects assessing the effects of bilateral transcutaneous auricular vagus nerve stimulation (taVNS) on HRV. Our study aims to investigate how taVNS can influence the HRV response, including the influence of demographic variables in this response. Methods: Therefore, we conducted a randomized controlled study with 44 subjects, 22 allocated to active and 22 to sham taVNS. Results: Our results showed a significant difference between groups in the high-frequency (HF) metric. Active taVNS increased the HF metric significantly as compared to sham taVNS. Also, we found that age was a significant effect modifier of the relationship between taVNS and HF-HRV, as a larger increase in HF-HRV was seen in the older subjects. Importantly, there was a decrease in HF-HRV in the sham group. Conclusions: These findings suggest that younger subjects can adapt and maintain a constant level of HF-HRV regardless of the type of stimulation, but in the older subjects, only the active taVNS recipients were able to maintain and increase their HF-HRV. These results are important because they indicate that taVNS can enhance physiological regulation processes in response to external events.

The vagus nerve regulates metabolic homeostasis and mediates gut-brain communication. We hypothesized that vagus nerve dysfunction, induced by truncated vagotomy (VGX) or carotid artery occlusion (AO), would disrupt gut-brain communication and exacerbate metabolic dysregulation, neuroinflammation, and cognitive impairment. This study aimed to test the hypothesis in gerbils fed a high-fat diet. The gerbils were divided into four groups: AO with VGX (AO_VGX), AO without VGX (AO_NVGX), no AO with VGX (NAO_VGX), and no AO without VGX (NAO_NVGX). After 5 weeks on a high-fat diet, the neuronal cell death, neurological severity, hippocampal lipids and inflammation, energy/glucose metabolism, intestinal morphology, and fecal microbiome composition were assessed. AO and VGX increased the neuronal cell death and neurological severity scores associated with increased hippocampal lipid profiles and lipid peroxidation, as well as changes in the inflammatory cytokine expression and brain-derived neurotrophic factor (BDNF) levels. AO and VGX also increased the body weight, visceral fat mass, and insulin resistance and decreased the skeletal muscle mass. The intestinal morphology and microbiome composition were altered, with an increase in the abundance of Bifidobacterium and a decrease in Akkermansia and Ruminococcus. Microbial metagenome functions were also impacted, including glutamatergic synaptic activity, glycogen synthesis, and amino acid biosynthesis. Interestingly, the effects of VGX were not significantly additive with AO, suggesting that AO inhibited the vagus nerve activity, partly offsetting the effects of VGX. In conclusion, AO and VGX exacerbated the dysregulation of energy, glucose, and lipid metabolism, neuroinflammation, and memory deficits, potentially through the modulation of the gut-brain axis. Targeting the gut-brain axis by inhibiting vagus nerve suppression represents a potential therapeutic strategy for ischemic stroke.

Slow and deep breathing (SDB) is a relaxation technique that can increase vagal activity. Respiratory sinus arrhythmia (RSA) serves as an index of vagal function usually quantified by the high-frequency power of heart rate variability (HRV). However, the low breathing rate during SDB results in deviations when estimating RSA by HRV. Besides, the impact of the inspiration-expiration (I: E) ratio and guidelines ways (fixed breathing rate or intelligent guidance) on SDB is not yet clear. In our study, 30 healthy people (mean age = 26.5 years, 17 females) participated in three SDB modes, including 6 breaths per minute (bpm) with an I:E ratio of 1:1/ 1:2, and intelligent guidance mode (I:E ratio of 1:2 with guiding to gradually lower breathing rate to 6 bpm). Parameters derived from HRV, multimodal coupling analysis (MMCA), Poincaré plot, and detrended fluctuation analysis were introduced to examine the effects of SDB exercises. Besides, multiple machine learning methods were applied to classify breathing patterns (spontaneous breathing vs. SDB) after feature selection by max-relevance and min-redundancy. All vagal-activity markers, especially MMCA-derived RSA, statistically increased during SDB. Among all SDB modes, breathing at 6 bpm with a 1:1 I:E ratio activated the vagal function the most statistically, while the intelligent guidance mode had more indicators that still significantly increased after training, including SDRR and MMCA-derived RSA, etc. About the classification of breathing patterns, the Naive Bayes classifier has the highest accuracy (92.2%) with input features including LFn, CPercent, pNN50, [Formula: see text], SDRatio, [Formula: see text], and LF. Our study proposed a system that can be applied to medical devices for automatic SDB identification and real-time feedback on the training effect. We demonstrated that breathing at 6 bpm with an I:E ratio of 1:1 performed best during the training phase, while intelligent guidance mode had a more long-lasting effect.

Bioelectronic therapies modulating the vagus nerve are promising for cardiovascular, inflammatory, and mental disorders. Clinical applications are however limited by side-effects such as breathing obstruction and headache caused by non-specific stimulation. To design selective and functional stimulation, we engineered VaStim, a realistic and efficient in-silico model. We developed a protocol to personalize VaStim in-vivo using simple muscle responses, successfully reproducing experimental observations, by combining models with trials conducted on five pigs. Through optimized algorithms, VaStim simulated the complete fiber population in minutes, including often omitted unmyelinated fibers which constitute 80% of the nerve. The model suggested that all Aα-fibers across the nerve affect laryngeal muscle, while heart rate changes were caused by B-efferents in specific fascicles. It predicted that tripolar paradigms could reduce laryngeal activity by 70% compared to typically used protocols. VaStim may serve as a model for developing neuromodulation therapies by maximizing efficacy and specificity, reducing animal experimentation.

Transcutaneous auricular vagus nerve stimulation (taVNS) targets subcutaneous axons in the auricular branch of the vagus nerve at the outer ear. Its non-invasive nature makes it a potential treatment for various disorders. taVNS induces neuromodulatory effects within the nucleus of the solitary tract (NTS), and due to its widespread connectivity, the NTS acts as a gateway to elicit neuromodulation in both higher-order brain regions and other brainstem nuclei (e.g. spinal trigeminal nucleus; Sp5). Our objective was to examine stimulation parameters on single-neuron electrophysiological responses in α-chloralose-anaesthetized Sprague-Dawley rats within NTS and Sp5. taVNS was also compared to traditional cervical VNS (cVNS) on single neuronal activation. Specifically, electrophysiological extracellular recordings were evaluated for a range of frequency and intensity parameters (20-250 Hz, 0.5-1.0 mA). Neurons were classified as positive, negative or non-responders based on increased activity, decreased activity or no response during stimulation, respectively. Frequency-dependent analysis showed that 20 and 100 Hz generated the highest proportion of positive responders in NTS and Sp5 with 1.0 mA intensities eliciting the greatest magnitude of response. Comparisons between taVNS and cVNS revealed similar parameter-specific activation for caudal NTS neuronal populations; however, individual neurons showed different activation profiles. The latter suggests that cVNS and taVNS send afferent input to NTS via different neuronal pathways. This study demonstrates differential parameter-specific taVNS responses and begins an investigation of the mechanisms responsible for taVNS modulation. Understanding the neuronal pathways responsible for eliciting neuromodulatory effects will enable more tailored taVNS treatments in various clinical disorders. KEY POINTS: Transcutaneous auricular vagus nerve stimulation (taVNS) offers a non-invasive alternative to invasive cervical vagus nerve stimulation (cVNS) by activating vagal afferents in the ear to induce neuromodulation. Our study evaluated taVNS effects on neuronal firing patterns in the nucleus of the solitary tract (NTS) and spinal trigeminal nucleus (Sp5) and found that 20 and 100 Hz notably increased neuronal activity during stimulation in both nuclei. Increasing taVNS intensity not only increased the number of neurons responding in Sp5 but also increased the magnitude of response, suggesting a heightened sensitivity to taVNS compared to NTS. Comparisons between cVNS and taVNS revealed similar overall activation but different responses on individual neurons, indicating distinct neural pathways. These results show parameter-specific and nuclei-specific responses to taVNS and confirm that taVNS can elicit responses comparable to cVNS at the neuronal level, but it does so through different neuronal pathways.