Predicting tingling sensations induced by autonomous sensory meridian response (ASMR) videos based on sound texture statistics: a comparison to pleasant feelings.

Sound serves as a potent medium for emotional well-being, with phenomena like the autonomous sensory meridian response (ASMR) showing a unique capacity for inducing relaxation and alleviating stress. This study aimed to understand how tingling sensations (and, for comparison, pleasant feelings) that such videos induce relate to acoustic features, using a broader range of ASMR videos as stimuli. The sound texture statistics and their timing predictive of tingling and pleasantness were identified through L1-regularized linear regression. Tingling was well-predicted (r = 0.52), predominantly by the envelope of frequencies near 5 kHz in the 1500 to 750 ms period before the response: stronger tingling was associated with a lower amplitude around the 5 kHz frequency range. This finding was further validated using an independent set of ASMR sounds. The prediction of pleasantness was more challenging (r = 0.26), requiring a longer effective time window, threefold that for tingling. These results enhance our understanding of how specific acoustic elements can induce tingling sensations, and how these elements differ from those that induce pleasant feelings. Our findings have potential applications in optimizing ASMR stimuli to improve quality of life and alleviate stress and anxiety, thus expanding the scope of ASMR stimulus production beyond traditional methods. This article is part of the theme issue 'Sensing and feeling: an integrative approach to sensory processing and emotional experience'.

Etiological and clinical profiles of patients with dysphagia: A teaching institution experience.

Background: Dysphagia can involve any structure from the mouth to the lower esophageal sphincter. The etiologies vary from benign causes to malignant lesions. There is dearth of data regarding dysphagia in our population. Methods: A total of 208 patients with complaints of dysphagia were screened for the study. After ruling out neurological/local oropharyngeal causes of dysphagia, 200 patients with suspected esophageal dysphagia (ED) were recruited in the study. Dysphagia was graded as per the dysphagia scoring system. All patients underwent upper gastro-intestinal endoscopy and were evaluated for the presence of mechanical and non-mechanical causes of ED. Results: The mean age of patients with dysphagia was 53.8 ± 15.4 years. with males and females being 82 and 118, respectively. The mean duration of the symptom was 7.2 ± 10.6 months (median 3 months). Ninety-eight patients (49%) having dysphagia were in the age group of 56-65 years. The dysphagia score was 0 among 58, and 4 among 26 subjects. Foreign body sensation was the most frequent chief complaint in 90 (45%) patients. Ninety-six (48%) and 104 (52%) patients had mechanical and non-mechanical causes of dysphagia, respectively. Among mechanical causes of dysphagia, 68 patients (70.8%) had esophageal growth and 28 (29.2%) had esophageal stricture. Sixty-seven patients had squamous cell carcinoma. Among non-mechanical causes, 50 (48.1%) had globus sensation, 24 (23.1%) had hiatus hernia, and 16 (15.4%) functional dysphagia. Conclusion: Dysphagia is a common problem with varied etiologies. The esophageal growth and globus sensation are among the predominant causes of ED. We stress that all patients of dysphagia must be meticulously investigated.

Efficacy of plantar tactile sensation and balance in patients with subacute stroke following plantar kinesio taping: a randomized, cross-over preliminary study.

BACKGROUND: Kinesio tape (KT) is known to enhance tactile sensation. In stroke rehabilitation, KT is often used alongside conventional therapy (CT) to improve balance recovery. OBJECTIVE: In this study, we aimed to evaluate the effectiveness of plantar KT in enhancing plantar tactile sensation (PTS) and balance ability in subacute stroke patients. METHODS: In this randomized crossover trial, 22 subacute stroke participants were randomly assigned to receive no taping, paretic plantar KT, or bilateral plantar KT, with a 24-h washout period between each condition. All participants underwent 30 min of CT. The primary outcome was PTS, involving tactile sensitivity in five areas on the plantar surface and the contact area with the ground of the paretic foot. The one-leg stand (OLS) time, functional reach test (FRT), and timed up-and-go test (TUG) were employed as secondary outcomes. RESULTS: Paretic plantar KT application led to significant increases in the contact area, OLS, FRT, and TUG test times. Particularly, bilateral plantar KT showed significantly greater improvement in PTS compared to paretic plantar KT. Additionally, bilateral plantar KT significantly improved OLS (p < 0.001, η2 = 0.575), FRT (p < 0.001, η2 = 781), and TUG (p < 0.001, η2 = 0.771) times compared with paretic plantar KT. CONCLUSIONS: This study demonstrated that plantar KT improved PTS and balance ability in stroke rehabilitation. The findings suggest that bilateral plantar KT as an adjunct to CT may have a beneficial effect on balance recovery in patients with subacute stroke. TRIAL REGISTRATION: Clinical trial KCT0009048.

Vests with Radiative Cooling Materials to Improve Thermal Comfort of Outdoor Workers: An Experimental Study.

This study focuses on improving human thermal comfort in a high-temperature outdoor environment using vests with a radiative cooling coating. The effects of coating thickness on the radiative cooling performance were first evaluated, and an optimal thickness of 160 µm was achieved. Then, six subjects were recruited to evaluate the thermal comfort in two scenarios: wearing the vest with radiative cooling coatings, and wearing the standard vest. Compared with the standard vest, the coated vest decreases the maximum temperature at the vest inner surface and the outer surface by 5.54 °C and 4.37 °C, respectively. The results show that thermal comfort is improved by wearing radiative cooling vests. With an increase of wet bulb globe temperature (WBGT), the improving effects tend to decline. A significant improvement in human thermal comfort is observed at a WBGT of 26 °C. Specifically, the percentage of thermal sensation vote (TSV) wearing the cooling vest in the range of 0 to 1 increases from 29.2% to 66.7% compared with that of the untreated vest. At the same time, the average value of thermal comfort vote (TCV) increases from -0.5 to 0.2.

Nanofluidic Membrane-Assisted Organic Electrochemical Transistors for Bioinspired Gustatory Sensation Based on Selective Cation Transport.

Natural organisms have evolved precise sensing systems relying on unique ion channels, which can efficiently perceive various physical/chemical stimuli based on ionic signal transmission in biological fluid environments. However, it is still a huge challenge to achieve extensive applications of the artificial counterparts as an efficient wet sensing platform due to the fluidity of the working medium. Herein, nanofluidic membranes with selective cation transport properties and solid-state organic electrochemical transistors (OECTs) with amplified signals are integrated together to mimic human gustatory sensation, achieving ionic gustatory reagent recognition and a portable configuration. Cu-HHTP nanofluidic membranes with selective cation transport through their uniform micropores are constructed first, followed by assembly with OECTs to form the designed nanofluidic membrane-assisted OECTs (nanofluidic OECTs). As a result, they can distinguish typically ionic gustatory reagents, and even ionic liquids (ILs), demonstrating enhanced gustatory perception performance under a wide concentration range (10-7-10-1 m) compared with those of conventional OECTs. The linear correlations between the response and the reagent concentration further indicate the promising potential for practical application as a next-generation sensing platform. It is suggested that nanofluidic membranes mediated intramembrane cation transport based on the steric hindrance effect, resulting in distinguishable and improved response to multiple ions.

Machine learning thermal comfort prediction models based on occupant demographic characteristics.

This study aims to investigate the predictive occupant demographic characteristics of thermal sensation (TS) and thermal satisfaction (TSa) as well as to find the most effective machine learning (ML) algorithms for predicting TS and TSa. To achieve this, a survey campaign was carried out in three mixed-mode buildings to develop TS and TSa prediction models by using six ML algorithms (Logistic Regression, Naïve Bayes, Decision Tree (DT), Random Forest (RF), K-Nearest Neighborhood (KNN) and Support Vector Machine). The prediction models were developed based on six demographic characteristics (gender, age, thermal history, education level, income, occupation). The results show that gender, age, and thermal history are significant predictors of both TS and TSa. Education level, income, and occupation were not significant predictors of TS, but were significant predictors of TSa. The study also found that RF and KNN are the most effective ML algorithms for predicting TS, while DT and RF are the most effective ML algorithms for predicting TSa. The study found that the accuracy of TS prediction models ranges from 83% to 99%, with neutral being the most correctly classified scale. The accuracy of TSa prediction models ranges from 84% to 97%, with dissatisfaction being the most common misclassification.

[Fillet flap transfer as alternative to conventional lower limb amputation]. / Filetlappentransfer als Alternative zu konventionellen Amputationen der unteren Extremität.

BACKGROUND: The fitting of a prosthesis after lower limb amputation is associated with several challenges. Skeletal stump-prosthesis interfaces and selective nerve transfer can partially overcome these but are also associated with new impairments that emphasize the necessity of innovative approaches. The concept of so-called spare part surgery with the use of fillet flaps could play an important role in this respect. OBJECTIVE: An overview of the classical prosthesis-associated discomforts, advantages and disadvantages of treatment strategies and presentation of alternative surgical concepts. MATERIAL AND METHODS: A selective literature search was carried out considering the experiences of the authors and perspectives with respect to the advantages and disadvantages of the surgical treatment options. Furthermore, a clinical case is presented. RESULTS AND CONCLUSION: The transfer of the sole of the foot as a fillet flap to the weight-bearing region of the amputation stump offers a number of benefits, such as creating a fully weight-bearing stump, prevention of neuralgia, preserved sensation and conservation of the body image. As long as the calcaneal region is not impaired, this technique can be performed in amputations below as well as above the knee. The question of whether parts of the bone should be included in the transfer must be individually evaluated for each patient. This approach enables optimization of the residual limb stump for the subsequent fitting of a prosthesis for the patient.

Parental phubbing and mobile phone addiction among Chinese adolescents: a moderated mediation model.

It has been reported that parental phubbing is a significant predictor of mobile phone addiction (MPA) among adolescents. However, the mechanisms underlying this association remain largely unclarified. On the basis of the social learning theories and ecological systems, this study assessed the mediating effect of deviant peer affiliation and the moderating effect of sensation seeking in the association between parental phubbing and MPA among Chinese adolescents. A total of 786 Chinese adolescents (mean age = 13.17 years, SD = 1.35) completed the questionnaires anonymously about parental phubbing, MPA, deviant peer affiliation and sensation seeking. After controlling for study variables, deviant peer affiliation could partially mediate the association between parental phubbing and MPA among adolescents and this indirect path could be moderated by sensation seeking. Notably, the effect of deviant peer affiliation on MPA was more pronounced in adolescents with higher sensation seeking than in those with lower sensation seeking.

Drinking contexts, coping motive, simultaneous cannabis use, and high-intensity drinking among adults in the United States.

AIMS: High-intensity drinking (HID), extreme drinking considerably above the level of heavy episodic drinking (HED), is associated with long-term health and social consequences. There is limited understanding of HID beyond young adulthood. This study aims to identify concurrent risk factors for HID, comparing age differences among all adults. METHODS: Multinomial logistic and linear regression modeling was performed using a nationally-representative sample of adults (analytic n = 7956) from the 2015 and 2020 National Alcohol Surveys. The outcomes were any HID of 8-11 drinks and 12+ drinks for men, and 8+ drinks for women, and corresponding frequencies. Concurrent risk factors included coping motive, sensation seeking, simultaneous use of alcohol and cannabis (SAC), and drinking at a bar or party. Analyses were stratified by age (18-29 vs. older) and sex. RESULTS: For younger men, sensation-seeking was significantly associated with HID (vs. no HED) at both levels and frequency of HID 8-11 drinks, while drinking to cope was only significant for 12+ drinks. For older men, drinking to cope was a consistent predictor for both HID level and its frequency, but sensation-seeking was not significant. Both coping and sensation-seeking were significantly associated with any HID for all women, while coping was significant for HID frequency for younger women. Frequent drinking at bars and parties were associated with greater odds of HID for all adults. With HED as referent, similar patterns of (though fewer significant) associations were observed. CONCLUSIONS: Younger and older adults share similar risk factors for HID, with coping more consistent for older men.

Oral Squamous Cell Carcinoma of the Right Buccal Mucosa: A Case Report.

Oral squamous cell carcinoma (OSCC) is indeed one of the most common types of oral cancer, typically affecting individuals over the age of 50. It primarily originates from the squamous epithelial cells lining the oral cavity. While it is relatively rare in individuals under 40 years old, it can still occur, albeit less frequently in that age group. Risk factors for developing OSCC include tobacco use (smoking or chewing), excessive alcohol consumption, chronic irritation (such as from poorly fitting dentures), human papillomavirus (HPV), infection, and certain dietary foods. Early detection and treatment are crucial for improving outcomes and reducing the mortality associated with this type of cancer. This report describes a case of OSCC, staged T2 N0 M0, involving the right buccal mucosa of a 51-year-old male patient. The patient reported intense pain in an ulcer on the right side of his cheek. This report focuses on the etiological factors and a brief literature review of squamous cell carcinoma.

Quantitative sensory testing in notalgia paresthetica reveals small fiber-type-specific differences in non-pruritic sensitivity: a pilot study.

Introduction: Notalgia paresthetica (NP) is a chronic condition characterized by pruritus and other unpleasant dysesthetic sensations unilaterally on the subscapular back. Its specific underlying mechanisms are largely unknown, though hypothesized to be neuropathic. Determination of possible somatosensory contributors to the condition could pave the way for novel treatments. Objectives: Given the potential involvement of non-pruritic mechanisms in NP, our objective was to broadly characterize the somatosensory function in NP-affected and unaffected skin using methods that have been standardized in pain-free controls and painful neuropathic disorders. We hypothesized that if NP is caused by neuropathic mechanisms not targeted directly to pruritoceptors in the skin, somatosensory abnormalities would not be itchspecific. Second, given the lack of symptoms on the contralateral side of the back, we hypothesized that this region would be normally sensitive. Methods: In this study, quantitative sensory testing (QST) was used to comprehensively assess the somatosensory function in 15 adult patients with NP. Standardized QST metrics were performed in the NP-affected region and compared with the contralateral asymptomatic skin and itch-free individuals using an age, gender, and site-matched reference data set. Results: There were no significant differences in sensitivity between symptomatic and asymptomatic skin, except for increased mechanical-evoked itch on the itchy side. However, reference data set comparisons revealed bilateral hyposensitivity to innocuous cold and noxious pinprick and higher temporal summation of pain in patients with NP. In addition, compared with reference data, patients with NP demonstrated decreased sensitivity to cold and pinprick, presence of paradoxical heat sensations, and increased wind-up of pain. Conclusion: These results suggest a role for Aδ fiber pathways and central sensitization in NP-associated itch. More research is needed to determine whether sensory differences extend beyond the NP-affected dermatomal level and what might cause neuropathy specifically targeting Aδ fibers.

Case Report: Recalcitrant oral lichen planus involving bilaterally buccal mucosae treated with a combination of photodynamic and photobiomodulation therapies.

Background: Managing recalcitrant oral lichen planus (OLP) can be challenging. Laser therapy has been suggested as an alternative to corticosteroids for treatment. Photodynamic therapy (PDT) is a non-invasive technique that enables the removal of lesions without surgery. Photobiomodulation therapy (PBMT) can promote healing and recovery of the lesions. Case presentation: The objective was to treat unresponsive bilateral OLP of the whole buccal mucosae with a combination of PDT and PBMT. Results: A 43-year-old Thai male presented with the severe painful reticular type of OLP of bilateral buccal mucosae involving upper and lower vestibular areas. The lesions were not remitted with either prednisolone systemic steroids or fluocinolone topical corticosteroids. After undergoing ten sessions of PDT with 10% 5-Aminolevulinic acid (5-ALA) in the form of thermoplastic gel and a 635 nm diode laser at 100 to 400 mW with an energy density of 20 to 30 J/cm 2 in continuous wave mode, combined with five interim-sessions of PBMT using a 635 nm diode laser at 200 to 300 mW with an energy density of 6 to 10 J/cm 2 in continuous wave, the patient reported relief of burning sensation beside remission of lesions without any complications. Conclusion: The wide-spreading recalcitrant OLP with burning sensation can be managed by combining PDT and PBMT.

Homozygosity for a Rare Plec Variant Suggests a Contributory Role in Congenital Insensitivity to Pain.

Congenital insensitivity to pain is a rare human condition in which affected individuals do not experience pain throughout their lives. This study aimed to identify the molecular etiology of congenital insensitivity to pain in two Thai patients. Clinical, radiographic, histopathologic, immunohistochemical, and molecular studies were performed. Patients were found to have congenital insensitivity to pain, self-mutilation, acro-osteolysis, cornea scars, reduced temperature sensation, tooth agenesis, root maldevelopment, and underdeveloped maxilla and mandible. The skin biopsies revealed fewer axons, decreased vimentin expression, and absent neurofilament expression, indicating lack of dermal nerves. Whole exome and Sanger sequencing identified a rare homozygous variant c.4039C>T; p.Arg1347Cys in the plakin domain of Plec, a cytolinker protein. This p.Arg1347Cys variant is in the spectrin repeat 9 region of the plakin domain, a region not previously found to harbor pathogenic missense variants in other plectinopathies. The substitution with a cysteine is expected to decrease the stability of the spectrin repeat 9 unit of the plakin domain. Whole mount in situ hybridization and an immunohistochemical study suggested that Plec is important for the development of maxilla and mandible, cornea, and distal phalanges. Additionally, the presence of dental anomalies in these patients further supports the potential involvement of Plec in tooth development. This is the first report showing the association between the Plec variant and congenital insensitivity to pain in humans.

Skin Comfort Sensation with Mechanical Stimulus from Electronic Skin.

The field of electronic skin has received considerable attention due to its extensive potential applications in areas including tactile sensing and health monitoring. With the development of electronic skin devices, electronic skin can be attached to the surface of human skin for long-term health monitoring, which makes comfort an essential factor that cannot be ignored in the design of electronic skin. Therefore, this paper proposes an assessment method for evaluating the comfort of electronic skin based on neurodynamic analysis. The holistic analysis framework encompasses the mechanical model of the skin, the modified Hodgkin-Huxley model for the transduction of stimuli, and the gate control theory for the modulation and perception of pain sensation. The complete process, from mechanical stimulus to the generation of pain perception, is demonstrated. Furthermore, the influence of different factors on pain perception is investigated. Sensation and comfort diagrams are provided to assess the mechanical comfort of electronic skin. The comfort assessment method proposed in this paper provides a theoretical basis when assessing the comfort of electronic skin.

KCNQ1 is an essential mediator of the sex-dependent perception of moderate cold temperatures.

Low temperatures and cooling agents like menthol induce cold sensation by activating the peripheral cold receptors TRPM8 and TRPA1, cation channels belonging to the TRP channel family, while the reduction of potassium currents provides an additional and/or synergistic mechanism of cold sensation. Despite extensive studies over the past decades to identify the molecular receptors that mediate thermosensation, cold sensation is still not fully understood and many cold-sensitive peripheral neurons do not express the well-established cold sensor TRPM8. We found that the voltage-gated potassium channel KCNQ1 (Kv7.1), which is defective in cardiac LQT1 syndrome, is, in addition to its known function in the heart, a highly relevant and sex-specific sensor of moderately cold temperatures. We found that KCNQ1 is expressed in skin and dorsal root ganglion neurons, is sensitive to menthol and cooling agents, and is highly sensitive to moderately cold temperatures, in a temperature range at which TRPM8 is not thermosensitive. C-fiber recordings from KCNQ1-/- mice displayed altered action potential firing properties. Strikingly, only male KCNQ1-/- mice showed substantial deficits in cold avoidance at moderately cold temperatures, with a strength of the phenotype similar to that observed in TRPM8-/- animals. While sex-dependent differences in thermal sensitivity have been well documented in humans and mice, KCNQ1 is the first gene reported to play a role in sex-specific temperature sensation. Moreover, we propose that KCNQ1, together with TRPM8, is a key instrumentalist that orchestrates the range and intensity of cold sensation.

Simultaneous cortical, subcortical, and brainstem mapping of sensory activation.

Nonpainful tactile sensory stimuli are processed in the cortex, subcortex, and brainstem. Recent functional magnetic resonance imaging studies have highlighted the value of whole-brain, systems-level investigation for examining sensory processing. However, whole-brain functional magnetic resonance imaging studies are uncommon, in part due to challenges with signal to noise when studying the brainstem. Furthermore, differentiation of small sensory brainstem structures such as the cuneate and gracile nuclei necessitates high-resolution imaging. To address this gap in systems-level sensory investigation, we employed a whole-brain, multi-echo functional magnetic resonance imaging acquisition at 3T with multi-echo independent component analysis denoising and brainstem-specific modeling to enable detection of activation across the entire sensory system. In healthy participants, we examined patterns of activity in response to nonpainful brushing of the right hand, left hand, and right foot (n = 10 per location), and found the expected lateralization, with distinct cortical and subcortical responses for upper and lower limb stimulation. At the brainstem level, we differentiated the adjacent cuneate and gracile nuclei, corresponding to hand and foot stimulation respectively. Our findings demonstrate that simultaneous cortical, subcortical, and brainstem mapping at 3T could be a key tool to understand the sensory system in both healthy individuals and clinical cohorts with sensory deficits.

Examination of Rumination's Mediating Role in the Relation Between Distal Personality Predictors, Cannabis Coping Motives, and Negative Cannabis-Related Consequences.

Objective: Perseverative cognitive processes, such as rumination, may indirectly influence effects of personality traits on cannabis use and related problems. Understanding relations among personality, rumination, and cannabis use motives may lead to better understanding of problematic cannabis use. The present study examined personality traits' influence on negative cannabis-related consequences via rumination and cannabis use coping motives. Methods: We tested a sequential path model across two independent samples such that the model was tested in one sample and replicated in the second sample. Participants were U.S. undergraduate students from multiple universities who reported using cannabis at least once in the prior thirty days. Results: Results partially supported hypotheses such negative urgency and distress tolerance were indirectly related to negative cannabis-related consequences via rumination and coping motives. Specifically, higher negative urgency and lower distress tolerance were related to higher rumination. Higher rumination was related to higher coping motives; which in turn was related to more negative cannabis-related consequences. Results indicate that rumination is a risk factor belying associations between personality and cannabis use to cope and negative consequences of use. Conclusions: Implementing techniques that attenuate rumination for individuals high in negative urgency or low in distress tolerance may reduce or prevent problematic cannabis and unintended outcomes.

The fear-avoidance model as an embodied prediction of threat.

The fear-avoidance model is a well-established framework in the understanding of persistent pain. It proposes a dichotomous path: either the context is interpreted as safe; there is no fear reaction and, therefore, the individual engages in active (positive) coping; or the context is interpreted as threatening, leading to a self-reinforcing vicious circle of fear and (negative) avoidance. We propose an embodied interpretation of this phenomenon employing the joint framework of predictive coding and active inference. The key idea is that multisensory integration of exteroceptive, proprioceptive, and interoceptive sensory inputs can lead to dysfunctional experiences of threat in nonthreatening situations. Threat inference can promote fear responses, maladaptive strategies (i.e., avoidance) and self-provides evidence for threat in associated or future contexts, or both. Under this treatment, the prediction of nonrealized threat becomes self-evidencing and context-invariant, and hence self-perpetuating. Safety cues are unable to attenuate the interpretation of the negative context as the dominant inference of the context is threatful and gains more precision and becomes resistant over time. Our model provides an explanation for the emergence of a dysfunctional fear response in the clinical setting despite apparent safety based on modern concepts from theoretical (computational) neuroscience.

The Effect of Delayed Photobiomodulation Therapy on Inferior Alveolar Nerve Recovery After Third Molar Removal: A Triple-Blinded Randomized Clinical Trial.

Background: Third molar removal is the primary reason for inferior alveolar nerve (IAN) damage, with 2% causing persistent neurosensory deficits. This study aimed to investigate how delayed photobiomodulation therapy affects long-lasting neurosensory disturbances. Methods: This study was conducted on patients with neurosensory disturbances lasting longer than 6 months. Patients were randomly allocated to the study and control groups, with the study group receiving a low-power diode laser (continuous wavelength of 810 nm, power of 200 mW) on 16 points (30 sec at each) for 12 sessions (2 sessions/week), while the control group received a placebo treatment by switched-off laser probe. Visual analog scale (VAS; ranging from 1 to 5), static light touch, two-point discrimination, direction discrimination, pinprick, and thermal discrimination tests were performed on each visit up to 9 months post-therapy to evaluate the recovery status. Results: Each group comprised 18 participants. The mean time since injury was 8.26 ± 2.05 and 8.38 ± 1.98 months for the control and intervention groups, respectively (p = 0.81). There was a significant improvement in the intervention group on the static light touch (p = 0.041), two-point discrimination (p = 0.028), VAS (p = 0.031), and pinprick (p = 0.014) tests on the 11th session and subsequent visits and also on direction discrimination test on the 12th session (p = 0.044) and after that. There was no significant difference in the thermal discrimination tests between the two groups (p > 0.05). Conclusion: Photobiomodulation demonstrated potential benefits in resolving persistent neurosensory deficits of the IAN, with noticeable improvements typically observed after around 35 days of treatment initiation (10 sessions).