Nurturing Hope: Reproductive Outcomes with Sinosomatics Following Unsuccessful IVF Attempts.

INTRODUCTION: For women who have experienced failed attempts at in vitro fertilization (IVF) and face medical issues leading to infertility, the renewed effort to seek fertility treatment, coupled with decreasing likelihood of success, can exert substantial emotional and physical strains. Consequently, many couples opt to discontinue treatment before attaining pregnancy. The objective of this study was to evaluate the reproductive outcomes in patients with unsuccessful prior IVF attempts who received a complementary treatment designed to alleviate emotional distress and burden. PATIENTS AND METHODS: A retrospective analysis of data from infertile patients who initiated the complementary intervention at a private clinic between January 2014 and December 2016 was conducted. Information on diagnosis, history of infertility, prior assisted reproductive technologies treatments, mode of conception, and pregnancy outcomes were retrieved. RESULTS: The data of 133 patients with a history of one or more unsuccessful IVF treatments were analyzed. Patients had an average age of 36.7 years (± 4.4 SD) and had been experiencing infertility for an average of 4.6 years (± 2.7 SD). The two main causes of their infertility were endometriosis (36.1%, 48 patients) and diminished egg quality (31.6%, 42 patients). By May 2020, a significant proportion of the patients, 81.2% (108 patients), had achieved pregnancy, leading to 94 live births, which represents a 70.7% success rate. These pregnancies mostly resulted from natural-cycle IVF (35.1%), donor cycles (23.4%), and conventional IVF (21.3%). The dropout rate was comparatively low at 23.3%. The median time from the start of complementary treatment to delivery was 18 months, with a range of 12 to 28 months. CONCLUSIONS: This study highlights the potential value of complementary treatment approaches in conjunction with standard medical care for women who have experienced unsuccessful IVF treatments in the past and thus face a reduced chance of motherhood. The reported 71% live birth rate is notably high, indicating that the inclusion of complementary treatments may provide women with past IVF failures a tangible opportunity for achieving successful pregnancy and childbirth. However, these findings need to be confirmed through randomized controlled studies.

Traumatic Events, Posttraumatic Stress Disorder, and Central Sensitization in Chronic Pain Patients of a German University Outpatient Pain Clinic.

OBJECTIVE: Posttraumatic stress disorder (PTSD) and traumatic life events are often coupled to chronic pain, possibly linked by central sensitization. We wanted to assess the prevalence of traumatic events and PTSD in chronic pain patients of a German university hospital outpatient pain clinic. Moreover, we evaluated the extent of indicators and co-occurring traits of central sensitization in comorbid patients. METHODS: We retrospectively divided 914 chronic pain patients into four groups depending on their trauma severity: no trauma, accidental trauma, interpersonal trauma, and PTSD. We collected electronic pain drawings focusing on pain area and widespreadness, as well as information about pain intensity, sleep impairment, disability, stress, anxiety, depression, and somatization. Differences between groups were calculated using Kruskal-Wallis with post-hoc Mann-Whitney tests. RESULTS: Of 914 patients, 231 (25%) had no trauma, 210 (23%) had accidental traumas, 283 (31%) had interpersonal traumas, 99 (11%) had PTSD, and 91 (10%) could not be classified. We observed statistically significant differences between groups in pain area and widespreadness, as well as maximal pain, sleep impairment, disability, stress, anxiety, depression, and somatization. The severity of symptoms increased with trauma severity. CONCLUSIONS: Traumatic life events and PTSD are frequent in chronic pain patients. The increased pain area and widespreadness, as well as the increased negative impact on co-occurring traits of sensory sensitivity (anxiety, depression, somatization), are compatible with central sensitization in comorbid patients. Therefore, a heightened awareness of the comorbidity between traumatic experiences and chronic pain is recommended.

Do Chest Compresses with Mustard or Ginger Affect Warmth Regulation in Healthy Adults? A Randomized Controlled Trial.

Background: Chest compresses with mustard (MU) or ginger (GI) are a complementary treatment option for respiratory tract infections. However, little is known about their specific thermogenic qualities. This study examines the short-term effects of MU, GI, and chest compresses with warm water only (WA) on measurable and self-perceived body warmth in healthy adults. Methods: This was a single-center, randomized controlled trial with cross-over design (WA versus MU versus GI). 18 participants (23.7 ± 3.4 years; 66.7% female) received MU, GI, and WA in a random order on three different days with a mean washout period of 13.9 days. Chest compresses were applied to the thoracic back for a maximum of 20 minutes. The primary outcome measure was skin temperature of the posterior trunk (measured by infrared thermography) immediately following removal of the compresses (t1). Secondary outcome measures included skin temperature of the posterior trunk 10 minutes later (t2) and several parameters of self-perceived warmth at t1 and t2 (assessed with the Herdecke Warmth Perception Questionnaire). Results: Skin temperature of the posterior trunk was significantly higher with MU compared to WA and GI at t1 (p < 0.001 for both, primary outcome measure) and t2 (WA versus MU: p=0.04, MU versus GI: p < 0.01). Self-perceived warmth of the posterior trunk was higher with MU and GI compared to WA at t1 (1.40 ≥ d ≥ 1.79) and remained higher with GI at t2 (WA versus GI: d = 0.74). The overall warmth perception increased significantly with GI (d = 0.69), tended to increase with MU (d = 0.54), and did not change with WA (d = 0.36) between t0 and t1. Conclusions: Different effects on warmth regulation were observed when ginger and mustard were applied as chest compresses. Both substances induced self-perceived warming of the posterior trunk, but measurable skin temperature increased only with MU. Further research is needed to examine the duration of these thermogenic effects and how chest compresses with ginger or mustard might be incorporated into practice to influence clinical outcomes in respiratory tract infections.

The Central Inflammatory Network: A Hypothalamic fMRI Study of Experimental Endotoxemia in Humans.

INTRODUCTION: Inflammation is a mechanism of the immune system that is part of the reaction to pathogens or injury. The central nervous system closely regulates inflammation via neuroendocrine or direct neuroimmune mechanisms, but our current knowledge of the underlying circuitry is limited. Therefore, we aimed to identify hypothalamic centres involved in sensing or modulating inflammation and to study their association with known large-scale brain networks. METHODS: Using high-resolution functional magnetic resonance imaging (fMRI), we recorded brain activity in healthy male subjects undergoing experimental inflammation from intravenous endotoxin. Four fMRI runs covered key phases of the developing inflammation: pre-inflammatory baseline, onset of endotoxemia, onset of pro-inflammatory cytokinemia, and peak of pro-inflammatory cytokinemia. Using masked independent component analysis, we identified functionally homogeneous subregions of the hypothalamus, which were further tested for changes in functional connectivity during inflammation and for temporal correlation with tumour necrosis factor and adrenocorticotropic hormone serum levels. We then studied the connection of these inflammation-associated hypothalamic subregions with known large-scale brain networks. RESULTS: Our results show that there are at least 6 hypothalamic subregions associated with inflammation in humans including the paraventricular nucleus, supraoptic nucleus, dorsomedial hypothalamus, bed nucleus of the stria terminalis, lateral hypothalamic area, and supramammillary nucleus. They are functionally embedded in at least 3 different large-scale brain networks, namely a medial frontoparietal network, an occipital-pericentral network, and a midcingulo-insular network. CONCLUSION: Measuring how the hypothalamus detects or modulates systemic inflammation is a first step to understand central nervous immunomodulation.

The Immediate Effect of Sinapis nigra and Zingiber officinale as Thermogenic Substances during Footbaths: A Randomized Controlled Crossover Trial.

OBJECTIVE: Warm footbaths infused with Sinapis nigra (mustard, or MU) or Zingiber officinale (ginger, or GI) are used for various thermoregulatory conditions, but little is known about how they are perceived by individuals, both short- and long-term. We analyzed the immediate and long-term effects of MU and GI on warmth and stimulus perception in healthy adults. METHODS: Seventeen individuals (mean age 22.1±2.4 years; 11 female) received three footbaths (mean temperature was 40 ± 0.2°C, administered between 1:30 and 6:30 p.m.) in a randomized order with a crossover design: 1. with warm water only (WA), 2. with warm water and MU, and 3. with warm water and GI. Warmth and stimulus perception at the feet were assessed at the 1st, 5th, 10th, 15th, and 20th minute of the footbaths, in the late evening (EVE), and the following morning (MG). We further assessed well-being (at EVE and MG) and sleep quality (at MG). The primary outcome measure was the warmth perception at the feet at the 10th minute of the footbath. RESULTS: At the 10th minute of the footbath, warmth perception at the feet was significantly higher with MU and GI compared to WA. The immediate thermogenic effects pointed to a quick increase in warmth and stimulus perception with MU, a slower increase with GI, and a gradual decrease with WA. Regarding the long-term effects, warmth and stimulus perception were still higher after GI compared to WA at EVE and MG. No differences were seen for general well-being and sleep quality. CONCLUSION: Thermogenic substances can significantly alter the dynamics of warmth and stimulus perception when added to footbaths. The different profiles in the application of GI and MU could be relevant for a more differentiated and specific use of both substances in different therapeutic indications.

Increasing Warmth in Oncological Patients: A Randomized Controlled Cross-Over Pilot Trial Examining the Efficacy of Mustard and Ginger Footbaths.

OBJECTIVE: To analyze the thermogenic effects of footbaths with medicinal powders in oncological patients (ON) and healthy controls (HC). INTERVENTION AND OUTCOMES: Thirty-six participants (23 ON, 13 HC; 24 females; 49.9 ± 13.3 years) received 3 footbaths in a random order with cross-over design: warm water only (WA), warm water plus mustard (MU, Sinapis nigra), and warm water plus ginger (GI, Zingiber officinale). Warmth perception of the feet (Herdecke Warmth Perception Questionnaire, HeWEF) at the follow-up (10 minutes after completion of footbaths, t2) was assessed as the primary outcome measure. Secondary outcome measures included overall warmth as well as self-reported warmth (HeWEF) and measured skin temperature (high resolution thermography) of the face, hands and feet at baseline (t0), post immersion (t1), and follow-up (t2). RESULTS: With respect to the warmth perception of the feet, GI and MU differed significantly from WA (P's < .05) with the highest effect sizes at t1 (WA vs GI, d = 0.92, WA vs MU, d = 0.73). At t2, perceived warmth tended to be higher with GI compared to WA (d = 0.46). No differences were detected between ON and HC for self-reported warmth. With respect to skin temperatures, face and feet skin temperatures of ON were colder (at t0 and t1, 0.42 ≥ d ≥ 0.68) and tended to have diametrical response patterns than HC (ON vs HC: colder vs warmer after MU). CONCLUSION: Among adult oncological patients and healthy controls, footbaths with mustard and ginger increased warmth perception of the feet longer than with warm water only. The potential impact of regularly administered thermogenic footbaths over extended periods merits further investigation for the recovery of cancer-related sense of cold.

Lateralization and Bodily Patterns of Segmental Signs and Spontaneous Pain in Acute Visceral Disease: Observational Study.

BACKGROUND: The differential diagnosis of acute visceral diseases is a challenging clinical problem. Older literature suggests that patients with acute visceral problems show segmental signs such as hyperalgesia, skin resistance, or muscular defense as manifestations of referred visceral pain in somatic or visceral tissues with overlapping segmental innervation. According to these sources, the lateralization and segmental distribution of such signs may be used for differential diagnosis. Segmental signs and symptoms may be accompanied by spontaneous (visceral) pain, which, however, shows a nonsegmental distribution. OBJECTIVE: This study aimed to investigate the lateralization (ie, localization on one side of the body, in preference to the other) and segmental distribution (ie, surface ratio of the affected segments) of spontaneous pain and (referred) segmental signs in acute visceral diseases using digital pain drawing technology. METHODS: We recruited 208 emergency room patients that were presenting for acute medical problems considered by triage as related to internal organ disease. All patients underwent a structured 10-minute bodily examination to test for various segmental signs and spontaneous visceral pain. They were further asked their segmental symptoms such as nausea, meteorism, and urinary retention. We collected spontaneous pain and segmental signs as digital drawings and segmental symptoms as binary values on a tablet PC. After the final diagnosis, patients were divided into groups according to the organ affected. Using statistical image analysis, we calculated mean distributions of pain and segmental signs for the heart, lungs, stomach, liver/gallbladder, and kidneys/ureters, analyzing the segmental distribution of these signs and the lateralization. RESULTS: Of the 208 recruited patients, 110 (52.9%) were later diagnosed with a single-organ problem. These recruited patients had a mean age of 57.3 (SD 17.2) years, and 40.9% (85/208) were female. Of these 110 patients, 85 (77.3%) reported spontaneous visceral pain. Of the 110, 81 (73.6%) had at least 1 segmental sign, and the most frequent signs were hyperalgesia (46/81, 57%), and muscle resistance (39/81, 48%). While pain was distributed along the body midline, segmental signs for the heart, stomach, and liver/gallbladder appeared mostly ipsilateral to the affected organ. An unexpectedly high number of patients (37/110, 33.6%) further showed ipsilateral mydriasis. CONCLUSIONS: This study underlines the usefulness of including digitally recorded segmental signs in bodily examinations of patients with acute medical problems.

Warm Footbaths with Sinapis nigra or Zingiber officinale Enhance Self-Reported Vitality in Healthy Adults More than Footbaths with Warm Water Only: A Randomized, Controlled Trial.

OBJECTIVES: To examine the effects of warm footbaths with thermogenic medicinal powders on vitality and heart rate variability in healthy adults. Intervention and Outcome. Seventeen healthy young adults (22.1 ± 2.4 years, 11 females) received three footbaths (WA: warm water only; GI: warm water and ginger; MU: warm water and mustard) in randomized order with a crossover design. We assessed vitality with the Basler Befindlichkeit questionnaire (BBS) and heart rate variability (HRV) before (t0), immediately after (t1), and 10 minutes following footbaths (t2). The primary outcome measure was self-reported vitality, measured via the BBS, at t1. RESULTS: The primary outcome measure, self-reported vitality, was higher after GI and tended to be higher after MU compared to WA with medium effect sizes (GI vs. WA, mean difference -2.47 (95% CI -5.28 to 0.34), p adj=0.048, d adj = 0.74), MU vs. WA, -2.35 (-5.32 to 0.61), p adj=0.30, d adj = 0.50). At t2, the standard deviation of beat-to-beat intervals (SDNN) of HRV increased, and the stress index tended to decrease after all three footbath conditions with small to medium effect sizes (0.42-0.66). CONCLUSION: There is preliminary evidence that footbaths with thermogenic agents GI and MU may increase self-reported vitality during a short-time period with a more pronounced effect with GI. After a short follow-up, all three conditions tended to shift the autonomic balance towards relaxation. Future research should investigate these effects in clinical samples with a larger, more diverse sample size.

Flotation Restricted Environmental Stimulation Therapy for Chronic Pain: A Randomized Clinical Trial.

Importance: Flotation restricted environmental stimulation therapy (REST) is an emerging therapeutic intervention that, to our knowledge, has never been directly compared with an indistinguishable placebo in patients with chronic pain. Objective: To determine whether 5 flotation-REST sessions alleviate chronic pain. Design, Setting, and Participants: This single-blind, randomized clinical trial compared flotation-REST as an intervention for the treatment of chronic pain with indistinguishable placebo and wait-list control conditions at Hannover Medical School, Hannover, Germany. Men and women aged 18 to 75 years who had been diagnosed with chronic pain disorder with psychological and somatic factors (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, German Modification, code F45.41) by physicians at the study center were randomly assigned to 1 of the 3 groups. Data were collected from June 26, 2018, to June 18, 2020. Interventions: Patients in the intervention and placebo groups underwent 5 treatment sessions lasting 60 to 90 minutes, each session separated by 4 days. The placebo treatment was delivered in the same floating tank but controlled for effortless floating and environmental stimulus restriction. Patients in the wait-list control group did not receive any additional treatment but were asked to continue any ongoing treatments at the time of enrollment. Main Outcomes and Measures: The primary outcome was a change in pain intensity 1 week after the last treatment session. The assessment was repeated at 12 and 24 weeks. Secondary outcomes included pain-related disability, pain area, pain widespreadness (number of body regions affected by pain), anxiety, depression, and quality of life, as well as several other short-term outcomes. Results: A total of 99 patients (mean [SD] age, 51.7 [12.3] years; 80 women [81%]) were included in the study. No differences were found among the groups in the primary outcomes (mean [SD] change in maximum pain: -7.6 [19.7] for the intervention group, -5.8 [12.7] for the placebo group, and 0.4 [14.0] for the wait-list control group; mean [SD] change in mean pain: -2.1 [19.4] for the intervention group,-4.2 [16.2] for the placebo group, and 2.0 [12.6] for the wait-list control group). Long-term secondary outcomes did not show significant differences. In the short term, patients in the intervention group showed significant improvements in pain intensity (-17.0 [17.1]; P < .001), relaxation (23.9 [22.6]; P < .001), anxiety (-10.1 [8.4]; P < .001), pain area (-3.6% [7.4%]; P < .001), and widespreadness (-2.0 [3.0]; P < .001), and similar changes where observed in the placebo group. Conclusions and Relevance: Patients with chronic pain experienced no long-term benefits from the 5 flotation-REST interventions. Clinically relevant short-term changes in pain in the placebo group suggest that improvements may not be caused by environmental stimulus restriction or effortless floating as previously thought. Trial Registration: ClinicalTrials.gov Identifier: NCT03584750.

Medullary and Hypothalamic Functional Magnetic Imaging During Acute Hypoxia in Tracing Human Peripheral Chemoreflex Responses.

[Figure: see text].

Combination of acupuncture and medical training therapy on tension type headache: Results of a randomised controlled pilot study.

OBJECTIVES: The aim of this study was to compare the effects of acupuncture and medical training therapy alone and in combination with those of usual care on the pain sensation of patients with frequent episodic and chronic tension-type headache. DESIGN: This was a prospective single-centre randomised controlled trial with four balanced treatment arms. The allocation was carried out by pre-generated randomisation lists in the ratio 1:1:1:1 with different permutation block sizes. SETTING: The study was undertaken in the outpatient clinic of Rehabilitation Medicine of the Hannover Medical School.Participants and interventions: Ninety-six adult patients with tension-type headache were included and randomised into usual care (n = 24), acupuncture (n = 24), medical training (n = 24), and combination of acupuncture and medical training (n = 24). One patient was excluded from analysis because of withdrawing her/his consent, leaving 95 patients for intention to treat analysis. Each therapy arm consisted of 6 weeks of treatment with 12 interventions. Follow-up was at 3 and 6 months. MAIN OUTCOME MEASURES: Pain intensity (average, maximum and minimum), frequency of headache, responder rate (50% frequency reduction), duration of headache and use of headache medication.Clinical results: The combination of acupuncture and medical training therapy significantly reduced mean pain intensity compared to usual care (mean = -38%, standard deviation = 25%, p = 0.012). Comparable reductions were observed for maximal pain intensity (-25%, standard deviation = 20%, 0.014) and for minimal pain intensity (-35%, standard deviation = 31%, 0.03). In contrast, neither acupuncture nor medical training therapy differed significantly from usual care. No between-group differences were found in headache frequency, mean duration of headache episodes, and pain medication intake. At 3 months, the majority of all patients showed a reduction of at least 50% in headache frequency. At 6 months, significantly higher responder rates were found in all intervention groups compared to usual care. CONCLUSIONS: In contrast to monotherapy, only the combination of acupuncture and medical training therapy was significantly superior in reduction of pain intensity compared to usual care.Trial registration: Registered on 11 February 2019. German Clinical Trials Register, DRKS00016723.

A picture is worth a thousand words: linking fibromyalgia pain widespreadness from digital pain drawings with pain catastrophizing and brain cross-network connectivity.

ABSTRACT: Pain catastrophizing is prominent in chronic pain conditions such as fibromyalgia and has been proposed to contribute to the development of pain widespreadness. However, the brain mechanisms responsible for this association are unknown. We hypothesized that increased resting salience network (SLN) connectivity to nodes of the default mode network (DMN), representing previously reported pain-linked cross-network enmeshment, would be associated with increased pain catastrophizing and widespreadness across body sites. We applied functional magnetic resonance imaging (fMRI) and digital pain drawings (free-hand drawing over a body outline, analyzed using conventional software for multivoxel fMRI analysis) to investigate precisely quantified measures of pain widespreadness and the associations between pain catastrophizing (Pain Catastrophizing Scale), resting brain network connectivity (Dual-regression Independent Component Analysis, 6-minute multiband accelerated fMRI), and pain widespreadness in fibromyalgia patients (N = 79). Fibromyalgia patients reported pain in multiple body areas (most frequently the spinal region, from the lower back to the neck), with moderately high pain widespreadness (mean ± SD: 26.1 ± 24.1% of total body area), and high pain catastrophizing scale scores (27.0 ± 21.9, scale range: 0-52), which were positively correlated (r = 0.26, P = 0.02). A whole-brain regression analysis focused on SLN connectivity indicated that pain widespreadness was also positively associated with SLN connectivity to the posterior cingulate cortex, a key node of the DMN. Moreover, we found that SLN-posterior cingulate cortex connectivity statistically mediated the association between pain catastrophizing and pain widespreadness (P = 0.01). In conclusion, we identified a putative brain mechanism underpinning the association between greater pain catastrophizing and a larger spatial extent of body pain in fibromyalgia, implicating a role for brain SLN-DMN cross-network enmeshment in mediating this association.

Therapeutic Sensations: A New Unifying Concept.

Physical sensations of tingling, warmth, dull pain, and heaviness are a common phenomenon in mind-body interventions, such as acupuncture, hypnotherapy, osteopathy, qigong, meditation, and progressive muscle relaxation. Even though there are striking parallels between sensations produced by many different interventions, no attempt has yet been made to understand them from a unifying perspective that combines information from different therapies and practices. Therefore, this narrative systematic review introduces the concept of therapeutic sensations and summarizes studies of their sensory quality, bodily topography, and the meaning that patients attach to them. Furthermore, it highlights the essential role of therapeutic sensations in the development of vital energy concepts, such as qi, prana, pneuma, and orgone, in various traditional medicine systems, body-oriented psychotherapy, and so-called energy medicine. Finally, the assessment of therapeutic sensations may help to gain a deeper understanding of such concepts, finding a common language between scientists, patients and practitioners, and bridging the wide gap between materialistic and vitalistic views.

Deciphering the neural signature of human cardiovascular regulation.

Cardiovascular regulation is integral to life. Animal studies have identified both neural and endocrine pathways, by which the central nervous system adjusts cardiac output and peripheral vascular resistance to changing physiological demands. The outflow of these pathways is coordinated by various central nervous regions based on afferent information from baroreceptors, chemoreceptors, nociceptors, and circulating hormones, and is modulated by physiologic and behavioural state. In humans, however, knowledge on central cardiovascular regulation below the cortical level is scarce. Here, we show using functional MRI (fMRI) that at least three hypothalamic subsystems are involved in cardiovascular regulation in humans. The rhythmic behaviour of these systems corresponds to high and low frequency oscillations typically seen in blood pressure and heart rate variability.

Stand up too fast and you know what happens next. You will feel faint as the blood rushes away from your head. Gravity pulls the blood into your legs, and your blood pressure drops. To correct this imbalance, the brain sends nerve impulses telling the heart to beat faster and the outer blood vessels to tighten. This is the autonomic nervous system at work. It is how the brain adjusts cardiac output, and quietly controls other internal organs in the body. It involves two key regions of the brain, the hypothalamus and the brainstem, and stimulates smooth muscles and glands around the body. The cardiovascular system also responds to the demands of exercise, with the heart supplying fresh blood laden with oxygen and the blood clearing out waste materials as it flows around the body. Perhaps surprisingly, blood pressure and heart rate fluctuate even at rest. The heart beats faster when breathing in and slower when breathing out. People's blood pressure, the force that keeps blood moving through arteries, also oscillates in so-called Mayer waves that last about 10 seconds. Much of the current understanding of the inner workings of the cardiovascular system ­ and how it is regulated by the brain ­ stems from animal experiments. This is because few attempts have been made to simultaneously measure how a person's brain and cardiovascular system work with enough detail to see how brain waves and cardiac oscillations might interact. To achieve this, Manuel et al. have now measured the brain activity, pulse and blood pressure of twenty-two healthy people while they were lying down in an MRI machine. This revealed that three distinct parts of the hypothalamus regulate cardiovascular output in humans. These 'subsystems' communicate with each other and with the lower brainstem, which sits beneath the hypothalamus. Manuel et al. also observed that the rhythmic activity of these subsystems runs in sync with oscillations typically seen in heart rate and blood pressure. With this work, Manuel et al. have shown that it is feasible to measure different systems of cardiovascular control in humans. In time, with further experiments using this new approach, the understanding of chronic high blood pressure and heart failure may improve.

Human subsystems of medial temporal lobes extend locally to amygdala nuclei and globally to an allostatic-interoceptive system.

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network and amygdala nuclei as parts of the salience network, with both networks collectively forming a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. Capitalizing on resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: N â€‹= â€‹101, 60, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level, MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems are characterized by consistent involvement of amygdala, hippocampus, and entorhinal cortex, but variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connect to salience, thalamic-brainstem, and default mode networks - the major cortical and subcortical components of the allostatic-interoceptive system. These findings provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system.

Figure Correction: Digital Pain Drawings Can Improve Doctors' Understanding of Acute Pain Patients: Survey and Pain Drawing Analysis.

[This corrects the article DOI: 10.2196/11412.].

From Paper to Digital Applications of the Pain Drawing: Systematic Review of Methodological Milestones.

BACKGROUND: In a pain drawing (PD), the patient shades or marks painful areas on an illustration of the human body. This simple yet powerful tool captures essential aspects of the subjective pain experience, such as localization, intensity, and distribution of pain, and enables the extraction of meaningful information, such as pain area, widespreadness, and segmental pattern. Starting as a simple pen-on-paper tool, PDs are now sophisticated digital health applications paving the way for many new and exciting basic translational and clinical applications. OBJECTIVE: Grasping the full potential of digital PDs and laying the groundwork for future medical PD apps requires an understanding of the methodological developments that have shaped our current understanding of uses and design. This review presents methodological milestones in the development of both pen-on-paper and digital PDs, thereby offering insight into future possibilities created by the transition from paper to digital. METHODS: We conducted a systematic literature search covering PD acquisition, conception of PDs, PD analysis, and PD visualization. RESULTS: The literature search yielded 435 potentially relevant papers, from which 53 methodological milestones were identified. These milestones include, for example, the grid method to quantify pain area, the pain-frequency maps, and the use of artificial neural networks to facilitate diagnosis. CONCLUSIONS: Digital technologies have had a significant influence on the evolution of PDs, whereas their versatility is leading to ever new applications in the field of medical apps and beyond. In this process, however, there is a clear need for better standardization and a re-evaluation of methodological and technical limitations that no longer apply today.

Novel Approach to Elucidate Human Baroreflex Regulation at the Brainstem Level: Pharmacological Testing During fMRI.

Introduction: Brainstem nuclei govern the arterial baroreflex, which is crucial for heart rate and blood pressure control. Yet, brainstem function is difficult to explore in living humans and is therefore mostly studied using animal models or postmortem human anatomy studies. We developed a methodology to identify brainstem nuclei involved in baroreflex cardiovascular control in humans by combining pharmacological baroreflex testing with functional magnetic resonance imaging. Materials and Methods: In 11 healthy men, we applied eight repeated intravenous phenylephrine bolus doses of 25 and 75 µg followed by a saline flush using a remote-controlled injector during multiband functional magnetic resonance imaging (fMRI) acquisition of the whole brain including the brainstem. Continuous finger arterial blood pressure, respiration, and electrocardiogram (ECG) were monitored. fMRI data were preprocessed with a brainstem-specific pipeline and analyzed with a general linear model (GLM) to identify brainstem nuclei involved in central integration of the baroreceptor input. Results: Phenylephrine elicited a pressor response followed by a baroreflex-mediated lengthening of the RR interval (25 µg: 197 ± 15 ms; 75 µg: 221 ± 33 ms). By combining fMRI responses during both phenylephrine doses, we identified significant signal changes in the nucleus tractus solitarii (t = 5.97), caudal ventrolateral medulla (t = 4.59), rostral ventrolateral medulla (t = 7.11), nucleus ambiguus (t = 5.6), nucleus raphe obscurus (t = 6.45), and several other brainstem nuclei [p < 0.0005 family-wise error (few)-corr.]. Conclusion: Pharmacological baroreflex testing during fMRI allows characterizing central baroreflex regulation at the level of the brainstem in humans. Baroreflex-mediated activation and deactivation patterns are consistent with previous investigations in animal models. The methodology has the potential to elucidate human physiology and mechanisms of autonomic cardiovascular disease.