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Nov 2025 DOI 10.14302/issn.3070-5657.je-24-5272
Passan ShrutiCorresponding author
Ovarian Hyperstimulation Syndrome (OHSS) is a significant complication that can occur during fertility treatments, particularly in the context of assisted reproduction technologies (ART) such as In-vitro fertilization (IVF). It is characterized by enlarged ovaries and the accumulation of fluid in the abdomen and sometimes the chest, which can lead to various degrees of discomfort and, in severe cases, life-threatening complications. The incidence of clinically significant OHSS is 2-3%, however, milder forms of OHSS might develop in up to 20-30% of all IVF patients.
Feb 2024 DOI 10.14302/issn.2574-4518.jsdr-24-4949
Nussbaum LACorresponding author
Background Insomnia and other sleep disorders represent a major cause of disability and impaired productivity. We evaluated the impact of peripheral somatosensory stimulation (PSS) on sleep quality in 12 patients with varying degrees of insomnia. Methods Twelve adult patients underwent daily PSS therapy for a 4-week period and were evaluated using the Insomnia Severity Index at baseline (prior to initiation of therapy) and then at the conclusion of the treatments. All data were obtained through a self-reported 7-question survey evaluating overall severity of insomnia symptoms and the impact of sleep patterns on satisfaction with sleep, daily functioning, and overall quality of life. Changes from baseline insomnia scores were analyzed using cumulative link mixed models (CLMMs). Results Seven men and five women completed one month of PSS therapy. Mean age was 55.1 (range 29 to 80 years). No adverse events were described by the patients. The average total change from baseline score was -10.3 points (baseline: 16.5 vs. week 4: 6.2). Patients had statistically significant improvements for every individual survey question by week 4. The median composite score was improved from baseline, with an overall median score of 2 (IQR: 1.25 – 2.75, min-max: 1-4) at baseline compared to 0.5 (IQR: 0 – 0.25, min-max: 0-2) by week 4 (MD = -1 95% CI: , p < 0.001), signaling typically moderate insomnia at baseline vs. typically minimal to no symptoms by week 4. The predicted probability of obtaining the best outcome (score=0) was 9% at baseline vs. 53% by week 4. The overall cumulative odds ratio was 11.9 (p < 0.001), suggesting that on average, the odds of moving from one score to a lower (improved) score at week 4 compared to the baseline are approximately 12 times higher than moving to a neutral or worse score. Conclusions PSS stimulation appeared to have a significantly favorable effect on sleep quality in this group of patients. Symptoms related to ability to fall asleep, remain asleep, and overall quality of sleep were all improved with PSS therapy. We suggest that further investigation into the potential usefulness of PSS therapy in patients with sleep disorders is warranted.
Sep 2023
Suzuki HiroyukiCorresponding author
Objectives The number of cases of cyanoacrylate closure (CAC) system for varicose veins has been increasing worldwide. However, as this is a new treatment method, the potential adverse effects and other details remain unclear. In particular, the cause of inflammation in embolized veins is still under debate. Methods We performed a drug-induced lymphocyte stimulation test (DLST) on a patient with allergic-like symptoms after CAC. Results The DLST was strongly positive in this case, and the patient underwent total removal of the CAC-filled vein due to difficulty controlling the symptoms with medication. After that the state was recovered and no medication was continued. Conclusion We encountered a case that a delayed allergy by CA after CAC treatment developed in, eventually leading to the total removal of the CA-filled vein. It was suggested that with doubting allergic-like symptom after CAC, DLST for CA could show not only the diagnosis of the delayed allergy to CA, but also the later treatment policy with stimulation index (S.I.) in the positive cases.
Aug 2023 DOI 10.14302/issn.2688-5328.ijp-23-4624
James AndersonCorresponding author
Periauricular Vagus Nerve Stimulation (pVNS) has been proven safe and effective in reducing chronic pain and related comorbidities in numerous clinical studies. This multicenter, interventional study used a non-randomized, interrupted time-series analysis to test the efficacy of an 8-week treatment protocol using the Stivax neurostimulator device. Subjects (n=33, 15 F, 18 M, age 40-77) were recruited at 3 clinic sites in California and Colorado. All subjects had long-term chronic pain and had failed other treatments. Subjects were treated with the Stivax device 3 times (2 weeks on, 1 week off). Subjective assessments of pain (Visual Analog Scale), disability (Oswestry Disability Index), depression (PHQ-9), and activity (IPAQ-E) were collected at baseline and weekly. Objective blood levels of pain-related cytokines collected at the end of weeks 2 and 8. Most subjects reported reduced pain, disability, and depression, with increased activity levels. At the end of week 8, subjects reported an average reduction in pain by 38.5% (3 subjects reported no pain), depression by 43.6% (2 subjects reported no depression), disability by 38.6% (2 subjects reported no disability), and an average 26.1% increase in activity level (5 subjects doubled their activity level). Levels of the pain-related cytokines IL-1ꞵ, IL-2, IL-3, IL-7, IL-10, IL-15, IL-17α, IL-21, TNF-α, IFN-γ, and FLT3-ligand showed improvement at week 8. pVNS is believed to “reset” central sensitization underlying chronic pain and other central sensitization syndromes, engaging the body’s pain modulation systems. Our results indicate that pVNS can clinically significantly improve chronic pain and associated morbidities without adverse effects.
Dec 2022 DOI 10.14302/issn.2766-8681.jcsr-22-4400
Hayashi TomoyaCorresponding author
Tactile information plays an important role in human manipulation of objects; however, prosthetic limb placement or teleoperation requires the manipulation of alternative bodies in the absence of tactile sensations. To provide an alternative to tactile sensation, this study proposes and assesses a continuous feedback scheme with temporally coded vibration. This scheme was designed to provide discrete intended tactile information in response to changing object-controlled situations by repetitively presenting time-coded vibration patterns. The effects of the proposed scheme on an object with acatch-and-hold task in virtual reality were confirmed. Compared to the control feedback scheme that provides vibration only when the balance of the virtual grip force and object position is changed, the proposed feedback scheme has a better effect in terms of the success rate of holding on to the object with an appropriate holding force during the task. The effect is larger, especially in the invisible task condition, suggesting that the increased amount of information with coded vibration patterns can be used without any special training, especially without visual information. Considering the existing studies that show the effect of a feedback scheme in response to motion events, the continuous feedback scheme proposed in this study may be more suitable for movements that require sequential coordination and passive responses than stimulation methods based on motion events. This feedback scheme has potential applications not only in tele-technology but also in healthcare, such as rehabilitation.
Jun 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2784
Cesar Pinto Leal-Junior ErnestoCorresponding author
Laboratory of Phototherapy and Innovative Technologies in Health, Nove de Julho University – UNINOVE, Sao Paulo, Brazil.
The aim of this clinical study was to determine the efficacy of bilateral alternating somatosensory stimulation for the management of stress and anxiety during and after the Trier Social Stress Test (TSST), a laboratory procedure for reliably inducing stress in human subjects. For this, a randomized, placebo-controlled, triple-blinded clinical trial of 80 qualified subjects was conducted. Subjects were randomized into two groups, a treatment group (n=40) and a control (placebo) group (n=40). Metrics of emotional stress assessed were a subjective rating of the level of emotional stress and salivary cortisol levels, both obtained at 3 timepoints: before treatment (baseline), immediately following completion of the TSST, and after 20 minutes of rest following completion of the TSST. Results showed that the treatment group had a statistically greater decrease in the subjective rating of stress relative to the control group both immediately following the TSST and 20 minutes after the TSST. Salivary cortisol levels in the treatment group were also lower than the control group at those same time points. These results suggest that bilateral alternating somatosensory stimulation may be effective in reducing subjective levels of stress and anxiety. It also may actively attenuate stress-related cortisol levels, which may reflect a mechanism for reducing cortisol-induced inflammation back to baseline after exposure to stressful situations.
Mar 2019 DOI 10.14302/issn.2576-2818.jfb-19-2637
Formigli LeonardoCorresponding author
CE-FER-MAD (Centre de Fertilité de Madagascar) Antananarivo, Madagascar
This preliminary study explores misoprostol as a preventive strategy for ovarian hyperstimulation syndrome. It outlines rationale, dosing considerations, and early safety signals, and calls for controlled trials to establish efficacy and risk–benefit.
Mar 2019 DOI 10.14302/issn.2379-7835.ijn-19-2639
McCarthy OliviaCorresponding author
Diabetes Research Group, Medical School, Swansea University, Swansea, UK
Nine healthy individuals with a mean ± SD BMI of 22.0 ± 0.7 kg/m² and age of 20 ± 0.2 years, participated in this single-blind randomised, crossover trial investigating the impact of ingesting two different honeys (1) Tropical Forest Honey (TFH) and (2) Manuka Honey; strength 12+ (MAN) on circulating levels of plasma interferon gamma following ex-vivo lipopolysaccharide (LPS) stimulation. Blood samples were prepared into duplicate aliquots of whole blood (800 μl) and 100 μg/l of LPS was added to samples to give a final volume of 1 ml. Levels of IFN-γ in plasma fractions were measured via commercially available sandwich ELISA and all comparisons were made with paired data using the Wilcoxon Signed Rank test taking a significance level of 5%. Whilst significant intra-and-interpersonal variation was observed, IFN-γ concentrations remained statistically unchanged 48 hours after the ingestion of either honey (p=0.15). Thus, in this instance the type of honey did not influence the IFN-γ response to plasma samples spiked with LPS.
Mar 2019 DOI 10.14302/issn.2470-5020.jnrt-19-2630
P. Schwarm FrankCorresponding author
Department of Neurosurgery, Justus-Liebig University Giessen, Giessen, Germany
Patients suffering treatment resistant Parkinson´s disease (PD) are potential candidates for deep brain stimulation (DBS). Commonly most implanted electrodes have a cylindrical shape with quadripolar electrode contacts and generate a symmetrical stimulation field around the lead. To reduce side effects through activation of neighboring fibers a new electrode design with segmented contacts was developed and enables a better adaption of the field of stimulation as well as a multi-target stimulation to improve therapeutic benefits. We report about a 51-year-old male patient with a 15-year history of treatment-refractory PD, who was implanted with bilateral segmented electrodes in the subthalamic nucleus (STN) with St. Jude Medical Infinity™ DBS System (Abbott/St. Jude Medical, Saint Paul, Minnesota, USA). Despite a clear mood-enhancing effect, stimulation with ring electrodes caused motor side effects including rigor and speech disorder. With segmented electrodes an effective and gentle stimulation was achieved. The stimulation of the anterior segments in the central position of the electrode in the STN showed no side-effects and allowed a reduction of initial symptoms in an low stimulation amplitude. Despite precise preoperatively planning and intraoperative trial stimulation, side effects of STN stimulation are very common. The application of segmented electrodes permits more options to reduce side effects rather than using ring electrodes. Studies with larger sample sizes are needed to establish the optional DBS electrode.
Sep 2018 DOI 10.14302/issn.2470-5020.jnrt-18-2185
Yilmaz AtillaCorresponding author
Hatay Mustafa Kemal University Medicine Faculty Neurosurgery Department, Hatay, Turkey.
Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) provides efficient treatment for the alleviation of motor signs in patients with Parkinson's disease (PD), but more studies about gait and functionality are needed. We aimed to understand whether short-term DBS treatment will can relieve the symptoms of PD patients, specifically we examined its effect on motor-cognitive-complication parameters, fine motor skills and daily living activity (DLA) of these patients. Method: Ten patients from Mustafa Kemal University Neurosurgery Department were recruited. The assessments were made twice, first time preoperatively, which was within one week prior to the surgery, second time postoperatively, which was 55-65 days post treatment. The motor scores, DLA scores, mental scores and complication scores were measured with Unified Parkinson's Disease Rating Scale (UPDRS), fine motor skills measured with The nine-hole peg test (9-HPT), balance measured with Berg Balance Scale (BBS) and falling risk measured with Timed Up and Go Test (TUG). Results: 10 patients (5 female, 5 male) aged between 40-60 (mean=49.44±6.69 years) were included in the study. Duration of the disease’s mean was 5.60 years. We found significant difference between pre-op and post-op results in UPDRS DLA, UPDRS motor, UPDRS complication, UPDRS total score and TUG tests (Table 2). There was no significant difference between preop-postop assessment in UPDRS mental, BBS and 9-HPT results (p>0.05). Discussion: Balance, walk and fine motor impairment occurs almost always in Parkinson’s disease and resulting in difficulties with daily living activities. We found that DBS has positive effect on PD complications, balance and walking abilities. PD patients that have falling risk and multiple motor symptoms may have benefit from DBS.
Feb 2018 DOI 10.14302/issn.2576-6694.jbbs-18-1887
S. Hageman NathanCorresponding author
David Geffen School of Medicine at UCLA, Los Angeles, CA Corresponding Author
The application of bilateral alternating stimulation in tactile (BLAST) form technology, a non-invasive, somatosensory-based method, has been shown to modulate the electrical activity of brain networks that mediate the stress response, resulting in a stress-reducing effect in individuals with high reported levels of anxiety, such as post-traumatic stress disorder (PTSD). In this study, we examined archival data from a heterogeneous group of users (n = 1109) of BLAST technology via Touchpoints, a novel BLAST-based treatment modality, all of whom had high self-reported levels of stress and anxiety. Ratings of levels of emotional stress and bodily distress on a scale of 0 (no stress/distress) to 10 (worst stress/distress of one's life) before and after the application of Touchpoints for 30 seconds were entered into an app. Results showed a statistically significant reduction in the levels of both emotional stress and bodily distress, 62.26% and 50.502%, respectively, after 30 seconds of BLAST technology was applied. This demonstrates a clear benefit of BLAST on the stress response, reducing both emotional stress and disturbing body sensations. Recent work examining EEG changes after BLAST technology is applied suggests that BLAST may reduce sympathetic activation by reducing the electrical activity of key areas of the salience network. Further work will more precisely characterize the effects of BLAST, its potential clinical uses, and the mechanisms of actions behind it’s apparent stress-reducing effects.
Nov 2017 DOI 10.14302/issn.2576-2818.jfb-17-1812
Wang Wei-HuaCorresponding author
Houston Fertility Laboratory, Houston TX, USA
The number of patients with poor ovarian response (POR) for in vitro fertilization (IVF) varies from 9 to 25%, especially high in patients of advanced maternal age. Although various stimulation protocols have been developed to improve clinical outcomes in patients with POR, a typical and effective protocol remains improvement. Some physicians prefer a mild stimulation protocol, while others like hyper stimulation protocol to obtain more eggs. This study was designed to compare the efficiency of a mild stimulation protocol with hyper stimulation protocol in patients with POR, particularly focused on live birth rate after IVF. Data were collected from 30 poor responders (over 39 years old). Patients were assigned to 2 protocols at the start of ovarian stimulation: Patients in group A were treated with a hyper stimulation (GnRH-antagonist) protocol and patients in group B were treated with a mild stimulation protocol. The ovarian stimulation characteristics, gonadotropin doses, number of eggs collected, number of high quality embryos, clinical pregnancy rates and live birth rates were compared between two groups.Although number of eggs, number of high quality embryos, clinical pregnancy rates were significantly higher in group A than in group B, miscarriage rate was also higher in group A than group B, which eventually resulted in a similar live birth rate (6.7%) in both groups. However, dosages of gonadotropins were smaller and stimulation days were shorter in group B than in group A. When poorly responding patients were treated for IVF, similar live birth rates were observed with mild stimulation protocol and hyper-stimulation protocol. After considering the higher dosages of gonadotropins and longer stimulation days in patients with hyper-stimulation protocol, it is suggested that poor responders may benefit with the mild stimulation protocol for IVF.
May 2017 DOI 10.14302/issn.2576-2818.jfb-17-1435
Wiesak TeresaCorresponding author
Abington Reproductive Medicine, Toll Center for Reproductive Science, Abington, PA, USA;
The objective of this study was to investigate whether percentage of mature oocytes retrieved from ovaries stimulated with long agonist or multi-dose antagonist protocols affect the implantation, clinical pregnancy and live birth of ICSI (Intracytoplasmic sperm injection) cycles. The 654 cycles of agonist (long lupron) and 610 cycles of multi-dose flexible antagonist (antagon) were analyzed after stratification according to the percentage of the mature oocytes retrieved. The clinical pregnancy of the groups with less than 30 % mature oocytes retrieved, both antagonist and agonist protocol was statistically lower (at least p< 0.05) compared to the groups with more than 30% mature oocytes retrieved. In the agonist protocol, the implantation and live births for this group were significantly (p<0.009) lower than in the group with ≥70% mature oocytes retrieved. The live births in groups with more mature oocytes retrieved (30-69% and ≥70 %) of the antagonist protocol were lower (22.2% vs. 35.9% and 23.9% vs. 41.5%, p<0.0001, respectively) compare to the agonist protocol. The results of our study showed that a very low percentage of mature oocytes retrieved impacts the clinical outcome of antagonist and long agonist protocols.
Mar 2017 DOI 10.14302/issn.2474-7785.jarh-16-1348
Srisuwan PatsriCorresponding author
Outpatient and Family Medicine Department, Phramongkutklao Hospital, Bangkok, Thailand;
Background and Objective: Cognitive stimulation training was effective in reducing risk of cognitive decline and dementia in patients with mild cognitive impairment. The present study aimed to explore factors that contribute to regular participation and practice cognitive stimulation training for elderly patients with mild cognitive impairment. Materials and Methods: Data were collected through individual face-to-face interviews with 25 elderly subjects with mild cognitive impairment, and analyzed using interpretive description method. Results: Five core themes emerged from the analysis of data: (i) program with four subthemes of “interesting session, ” “effective teaching materials,” “suitable duration and frequency” and “small group activities;” (ii) group facilitators with three subthemes of “good explanation,” “always facilitate” and “friendly personality;” (iii) homework assignments with two subthemes of “suitable content” and “can adapt in daily living;” (iv) family members with two subthemes of “supporting” and “sharing;” (v) before and after class notification. Conclusion: Increasing awareness of holistic factors including in clinic and at home should be emphasized in planning cognitive stimulation training. Having an effective program and facilitators and collaboration from family member were the keys of successful training.
Mar 2016 DOI 10.14302/issn.2470-5020.jnrt-15-800
Huang LiliCorresponding author
Dept. Biological Psychology, Donders Center for Cognition, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen.
Although clinical trials in refractory epilepsy are currently carried out, the field of deep brain stimulation (DBS) in epilepsy is still at its initial stage. Little is known about where, when and how to stimulate and what would be the short and long consequences. Animal studies might provide clinicians with new ideas regarding targets for DBS. Here an overview is given regarding old and new targets in rodent models of temporal lobe epilepsy. The evidence from animal models showed that stimulation of the subiculum – either in responsive or scheduled manner - is anticonvulsant in different seizure and epilepsy models, indicating that the subiculum might be a promising candidate for DBS targets. For the rest, the antiepileptic effects of low frequency stimulation were established mostly in kindling models. The presence of a critical time window in which stimulation was effective following after discharges on kindling acquisition, demonstrates that timing of DBS is an important factor for the anticonvulsant effects of DBS.
May 2026 DOI 10.14302/issn.2641-4538.jphi-26-6161
J GonzalezCorresponding author
Objectives Motor fluctuations and non-motor disorders not manageable by first-line treatments in advanced Parkinson's disease require continuous dopaminergic stimulation strategies such as subcutaneous infusions of apomorphine (APO) or foslevodopa/foscarbidopa (FLD/FCD). A Budget Impact Analysis (BIA) was performed to estimate the cost difference between both treatments assuming equivalent clinical efficacy and safety. Material and methods The efficacy results of pivotal clinical trials at 12 and 52 weeks of treatment and the safety profile of APO vs FLD/FCD were compared, based on latest scientific publications and other available clinical data. A comparative BIA was performed, based on estimated annual drug treatment costs at Spanish published prices. Results The efficacy of APO (16 h/day) and FLD/FCD (24 h/day) in reduction of OFF hours (2.47 vs 2.75, 12 weeks; 3.66 vs 3.50, 52 weeks; respectively) and increase of ON hours without disabling dyskinesias (2.77 vs 2.72, 12 weeks; 3.31 vs 3.80, 52 weeks; respectively) could be considered clinically equivalent, as well as their safety profiles. However, a significant discrepancy is observed in the costs of the aforementioned alternatives. Considering published prices and the average dose reported in the literature, in Spain the annual cost of APO would be €13,980 compared to €55,198 for FLD/FCD. Consequently, the financial resources required for the treatment of FLD/FCD would enable the treatment of approximately three to four patients with APO. The BIA indicated the potential for annual savings in more than €2,500 million, considering a total target population of over 60,000 patients per year. Finally, an univariant sensitivity analysis was performed, considering a scenario in which the hospital acquisition cost of FLD/FCD decreased between 20%-30% (€44,159- €38,638/year). In this scenario, the total annual savings range between €1,875-€1,532 million per year. Conclusions Overall APO is more efficient than FLD/FCD, as it provides similar clinical efficacy at a lower treatment cost. The selection of an appropriate treatment option is to be determined by clinical criteria and patient characteristics, but cost evaluation should be considered to select the most cost-effective therapeutic option.
Apr 2026 DOI 10.14302/issn.2640-6403.jtrr-26-6077
Kalmeta MargaretCorresponding author
Delayed wound healing in diabetes is characterized by impaired angiogenesis, persistent inflammation, extracellular matrix dysregulation, and peripheral neuropathy. A preclinical study was conducted using a diabetic mouse delayed wound model to evaluate the surrounding tissue of a wound, (its periwound) and its tissue responses following treatment with the NerveStim™ Neuropathy System, a combination topical gel and neuromuscular electrical stimulation platform. Periwound tissue was harvested at Day 14 and analyzed using NanoString gene expression profiling. Treated animals demonstrated visibly increased periwound tissue thickness compared to untreated controls. Differential expression analysis identified 76 significantly upregulated and 17 downregulated genes. Upregulated pathways included angiogenesis (Vegfa, Fgf2, Pdgfb, Nos3), neurotrophic signaling (Ngf, Bdnf, Scn9a, Trpv1), macrophage polarization (Arg1, Mrc1, Il10), and extracellular matrix remodeling (Col1a1, Col3a1, Mmp9, Timp1). Downregulation of select pro-inflammatory mediators (Nos2, Mif) was observed. These coordinated transcriptional changes are consistent with activation of reparative immune, neurovascular, and matrix remodeling pathways in diabetic periwound tissue.
Oct 2025 DOI 10.14302/issn.2474-7785.jarh-25-5784
Marks RayCorresponding author
This mini review examines the potential efficacy of applying electromagnetic field therapy for purposes of reducing osteoarthritis pain and other related disease features such as frailty, muscle sarcopenia, obesity, bone loss and fragility, and cartilage derangements and degradation in the older adult. Based on selected English language literature published largely on PUBMED between January 2000 and October 2025, papers describing the impact and potential synthetic and disease modifying impact of electromagnetic stimuli are explored. These data reveal a high degree of promise in fostering joint tissue reparative efficacy trends post electromagnetic stimulation. Its usage may allay the extent of the disease and its degree of disablement, while facilitating function.
Sep 2025 DOI 10.14302/issn.2379-8572.joa-25-5687
A Shaw NigelCorresponding author
Depending upon the species, the brainstem auditory evoked potential (BAEP) consists of four or five major high frequency components. According to longstanding doctrine, each wave represents the sequential activation of successively higher nuclei and tracts from the 8th (auditory) nerve to the midbrain (inferior colliculus). Although this conceptual framework has acquired the status of near dogma, surprisingly little evidence exists in support. In the present analysis, a new interpretation of the electrogenesis of the BAEP is proposed which is simpler although it retains skeletal elements of the older explanation. The revised model is mostly derived from two distinct sources. In the first, the timing of the BAEP waves is compared with that of cortical activity for a range of mammals including humans, monkeys, cats, rats and guinea pigs. It is demonstrated that for each of these, the conduction time of the acoustic signal to the cortex from the putative midbrain component (wave IV or V) is so unrealistically long that it implies that the entire waveform must arise in the peripheral pathways of the auditory system. In the second, a retrospective analysis is made of click repetition rates on the BAEP using extradural electrodes. It was shown that at high rates of stimulation (about 100/sec), the behavior of the waveform is almost totally at variance with the expectations of the conventional model. The essence of the revised conception is that all BAEP waves are just variations of the compound action potential of the 8th nerve, albeit generated or regenerated via separate routes and different methods. Such an explanation would thereby account for their near uniform sharp morphology as well as creating the impression of a composite neuronal response. More specifically, in the case of a four component BAEP, wave I is assumed to be generated by the normal air conduction route in an identical manner to the conventional explanation. In contrast, wave ll is assumed to be generated via bone conduction in the temporal skull thereby bypassing the transduction process in the middle ear. Wave lll is assumed to be generated by the first echo of the bone-conducted sound wave. Likewise, the second rebound within the temporal bone serves as the stimulation to evoke wave lV. As the energy of the auditory stimulus gradually dissipates, it may still continue to generate a train of lower amplitude potentials. It is concluded that the BAEP may contain little or no brainstem or midbrain activity and therefore the term BAEP may be a misnomer. A more appropriate epithet might therefore be the auditory nerve evoked potential or ANEP.
Sep 2025 DOI 10.14302/issn.2643-2811.jmbr-25-5688
Dahlmann NicolausCorresponding author
Obesity is associated with functional limitations in muscle performance. The true effect of obesity on skeletal muscle mass, including any interactions with aging effects, remains to be elucidated. The present study investigated the impact of obesity on the stimulation of muscle growth, based on a new model of body composition. A dataset of 44 men and 64 women was analysed. Body weight (Wt), body height (Ht), hand circumference (HdC) and waist circumference (WC) were measured. Processed by the Dahlmann-Body-Analysis (DBA) system, a new model of body composition, the increase of skeletal muscle mass (ΔSMM) compared to the individual reference weight was calculated. Muscle mass data derived by the DBA model are compared with DXA-derived predictive equations of studies representing different countries and ethnicities estimating the appendicular skeletal muscle mass. Means of these groups are tested by ANOVA. Age ranged from 18 to 72 years. All subjects had a BMI ≥ 29.7 (kg/m²). The mean values of ΔSMM as an estimate of muscle mass gain calculated by the DBA-system were 11.8 ±3.6 kg for men and 8.9 ±2.6 kg for women, respectively, demonstrating a linear, significantly rising relationship with BMI (ß > 0, p<0.001). The study population did not show a decrease in muscle mass with age in either men or women up to an age of 65 years. The results suggest that the present model has satisfactory prediction qualities to detect an increase in skeletal muscle mass associated with a growing burden of body fat.
Apr 2020 DOI 10.14302/issn.2832-4048.jsm-20-3211
Papaconstantinou JohnCorresponding author
The Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston Texas 77555-0643
Aging mammalian skeletal muscle satellite cells (MuSCs) undergo a decline of stem cell/progenitor cell proliferative and regenerative capacity, and the development of a physiological milieu characteristic of a state of chronic sterile inflammation. p38αMAPK and ERK1/2 are two major signaling pathways that regulate the age-associated decline of MuSC proliferative capacity. In this review we propose the following mechanism that links the p38αMAPK pathway to the decline of self-renewal and regenerative capacity of aged MuSCs: a) the HS-FGF-2-FGFR1-p38αMAPK-Axis, a tightly linked homeostatic signaling complex, is in synchrony with the autoinhibition of FGFR1; b) autoinhibition contributes to the Axis’ regulation of the homeostasis of P-p38αMAPK activity in juvenile MuSC; c) this combination of protein-protein interactions is characteristic of a juvenile cytoplasmic milieu of beneficial P-p38αMAPK activity and d) includes Sprouty1 inhibition that supports the stimulation of FGF-2 --> miR-29a; e) the miR29a dismantles the basement membrane in preparation for the initiation of replication; f) an age-associated impaired, dysregulated, over-sulfated heparan sulfate ligand (HS)-FGF-2 fails to activate FGFR1 in aged MuSCs; g) this uncouples its regulation of p38αMAPK and ERK1/2 pathways and results in desensitization of FGFR1; h) desensitization of FGFR1 and Sprouty1 interaction in aged MuSC uncouples their regulation of P-p38αMAPK in the aged MuSCs; i) this enables a state of chronic sterile inflammation to promote and sustain an increased level of P-p38αMAPK activity; and, j) the increased activity of P-p38αMAPK in aged MuSC stimulates the production of cell cycle inhibitors, miR-1 and miR-133, thereby attenuating the expression of the cell cycle regulators, SP1 and cyclin D1, resulting in a G1/S arrest; j) the increased level of p38αMAPK activity promotes the apoptosis of the aged activated MuSCs. This mechanism involves the synergistic interactions of HS-FGF2-FGFR-1, Sprouty (spry1), miR-1, miR-133 and miR-29a that unify the extracellular niche and intracellular milieu for the juvenile vs age-associated regulation of proliferative capacity of the MuSC. Our hypothesis unifies these interactions with the role of the extracellular niche and intracellular milieu in the stimulation of juvenile proliferation vs age-associated decline of skeletal muscle satellite cell self-renewal and regenerative proliferation. Word Count = 344
Mar 2019 DOI 10.14302/issn.2642-9241.jrd-19-2689
A. S. Sardenberg RodrigoCorresponding author
Chief of Thoracic Surgery, Hospital Paulistano, Americas Serviços Médicos São Paulo, Brazil
Background The aim of this study is to evaluate the outcomes of patients submitted to diaphragmatic pacing, and the impact on quality of life of patients who chronically depend on mechanical ventilation, as well as the effectiveness of phrenic stimulation to eliminate the need for mechanical ventilation. Methods From 2010- 2014, 10 patients completely dependent on mechanical ventilation were operated upon, with the implantation of phrenic pacing device. The diagnoses were quadriplegia and congenital central hypoventilation syndrome (CCHS). All patients underwent bilateral approach to the phrenic nerves, by video-assisted thoracic surgery or mini-thoracotomy. Results All patientsstarted pacing 30-40 days post-operatively. The mean age of patients was 12.1 years (2-27 years range) with a median of ten years. Six patients (54.5%) were as old as ten years, and three (27.2%) were older than 20 years. Younger patients had CCHS and older ones were quadriplegic. All patients with CCHS (n = 4) were nine years old or younger while only two quadriplegic patients were in this age group. Conclusions Diaphragmatic pacing can provide improvement in the quality of life of patients who depend on mechanical ventilation, allowing freedom to conduct daily activities, lower respiratory infections, and tracheostomy decannulation.
Mar 2018 DOI 10.14302/issn.2575-1212.jvhc-18-2013
A Halawa AmalCorresponding author
Department of Forensic Medicine and Toxicology, Faulty of Veterinary Medicine, Mansoura University, Mansoura, Egypt
Lipopolysaccharide (LPS) is a component of the outer membrane of gram negative bacteria. LPS challenging allows switching transcription of proinflammatory cytokines on via over stimulation of Toll-like receptors (TLRs) signaling pathway with subsequent pathogenic inflammatory response. We investigated the possible reproductive toxicity of LPS in male Wister albino rats. Oxidative stress markers, antioxidant status and caspase-3 activity were analyzed in testicular tissues of rats exposed to either saline or LPS (4 mg/kg BW, ip; 0.18 of the LD50). The samples were collected at 6 h and 72 h after injection of LPS. A significant reduction in testicular reduced glutathione (GSH), glutathione-S-transferase (GST) and superoxide dismutase (SOD) was observed at 72 h compared to control group. Total antioxidant capacity was decreased at 6 h with additional significant reduction at 72 h. Catalase activity was reduced significantly at both 6 and 72 h. Malondialdehyde (MDA) was increased (P ≤ 0.05) in LPS injected rats without variation between 6 and 72 h. A significant increase in nitric oxide (NO) was observed at 72 h after injection. A time-dependent increase in LPS-treated groups was observed in the concentration of caspase-3.Histopathological analysis revealed degenerative changes and necrosis of seminiferous tubules after 6 h with further accumulation of eosinophilic edematous transudate in its lumen after 72 h. In conclusion, by increasing time of exposure, LPS induced lipid peroxidation, oxidative stress, reduced testicular antioxidant capacity and encouraged testicular apoptosis which could be possible mechanisms for impairment of testicular function.
Sep 2017 DOI 10.14302/issn.2832-4048.jsm-17-1621
A. Koryak YuriCorresponding author
SSC of the Russian Federation − Institute of Biomedical Problems of the RAS
The effects of long-term space flight on human triceps surae (TS) muscle function and electromechanical delay (EMD) have been investigated. Voluntary and electrically evoked contractions of the TS were obtained from 7 male cosmonauts 30 days before and 3 days after landing. For all cosmonauts the isometric maximal voluntary contraction was reduced by 41.7 % (p < 0.01), whereas the electrically evoked maximal tetanic contraction force (Po) was found to decrease by 25.6 % (p < 0.05). Force deficit increased by 50 % (p < 0.001). This suggests that most of the force loss is due to a reduction in motor drive (motor control). The decrease in Po was associated with a significant increase of the corresponding maximal rates of tension development (43.7 %). The twitch tension (Pt) was not significantly changed and the Pt/Po ratio was increased by 46.7 % (p < 0.05) after space mission. The twitch time-to-peak tension of the TS increased by 7.7 %, but half-relaxation time decreased by 20.6 %. Force-velocity properties of the TS calculated according to a relative scale of voluntary contraction development significantly decreased. The calculations of the same properties of electrically evoked contraction development did not differ substantially from the initial physiological state. Total reaction time (TRT), pre-motor time (PMR) and motor time or EMD were determined. In response to a supramaximal single electrical pulses applied to the tibial nerve, the latent period between the M-wave and Рt beginning was determined. The voluntary contraction EMD increased by 34.1 %; but PMR and TRT decreased by 19.0 and 14.1 %, respectively. The EMD of electrically evoked contraction did not significantly change. Thus, the comparison of the mechanical alterations recorded during voluntary contractions and in contractions evoked by electrical stimulation of the motor nerve, suggests that weightlessness not only modifies the peripheral processes associated with contractions, but also changes central and/or neural command of the contraction.
Aug 2017 DOI 10.14302/issn.2576-2818.jfb-14-553
Bernardini LCorresponding author
Lunicare Medical Center-SISMER Satellite, Sarzana, Italy
All independent experimental data on epithelial and glandular cells lines of human endometrium support the evidence for a rapid production of eicosanoids from the LH/hCG receptors when exposed to the hCG hormone. Prostaglandins rapidly act on the surrounding endometrial stromal cells throughout the adenylyl cyclase enzyme leading to very large amounts of cAMP and angiogenic factors (VEGF) production. The cAMP is the most important intracellular second messenger and along with progesterone accomplishes the full process of decidualization and acquisition of receptivity after estrogenic priming of the endometrium. The status of uterine receptivity lasts few days only and timing for successful embryo-signal transduction system activation by the endometrium is probably short. In absence of in vivo embryonic signals it is impossible to predict, on individual bases, how the intensity of all the complex interlinked molecular changes of decidualization might ever be in case of exposure to native hCG. In other terms, amount of prostaglandins and cAMP produced in response to variably glycosylated hCG are all, in vivo, not measurable variables and should be viewed as a “wave” of biochemical chain reactions. Embryonic hCG is secreted in form of multiple isomers having an unpredictable variable level of glycosylation and control of this variable remains elusive. During cycles of ovarian stimulation many drugs (FSH, LH, HCG) interact with different G-protein coupled receptors (GPCRs) making it possible to alter the prostaglandins-mediated decidualization process ready to be elicited only by hCG of pregnancy. Since the molecules (cAMP and progesterone) controlling endometrial stromal cells differentiation into decidual cells are critical for successful implantation and placenta formation, the evidence of fast eicosanoids production associated with endometrial LH/hCG receptors exposure to hCG and the potential by human endometrium to produce, in response, very large amounts of cAMP has biological and clinical relevance.
Aug 2017
Nevzat UzunerCorresponding author
Objectives Increased neurovascular (NV) reactivity has been shown in patients with relapsing-remitting multiple sclerosis (RRMS) during the acute exacerbation period. However, the NV reactivity after several attacks is not known. We, therefore, have investigated the patients by transcranial Doppler (TCD) using simple visual stimulation after the repeated attack periods. Patients and Methods Thirty patients (22 females and eight males, mean age 40 years) with RRMS were examined at least two times. The average TCD examination interval was 26.7 months (range 4-120 months). Mean attack number was 3.8 (range 2-8 times), average disease duration was 57 months (range 4-124 months), and average Expanded Disability Status Scale (EDSS) value was 2.5 (range 1-5.5). We performed transcranial Doppler recordings from the P2-segments of both posterior cerebral arteries simultaneously during simple visual stimulation. The NV reactivity was defined as a relative increase of the blood flow velocities during visual stimulation. Results The NV reactivity to simple visual stimulation was significantly lower in the second test on both sides (31.5±9.2% and 29.2±7.2%; right and left side, respectively) from those of the first test (38.3±11.9% and 36.0±11.9%; right and left side, respectively) (p<0.001). Conclusion The present study is the first study examining neurovascular reactivity in patients with RRMS during repeated attacks using the transcranial Doppler to our best knowledge. Our results suggest patients with RRMS after repeated exacerbation periods have less reactive neurovascular units in the occipital cortex. The possible explanation might be the repeated demyelination, and insufficient remyelination with longer disease duration may lead glial dysfunction resulting neurovascular unit impairment. If so, functional TCD may be useful for the determining of the disease progression. However, the exact cut-off point is not known.
Jun 2017 DOI 10.14302/issn.2471-2175.jdrt-17-1481
Prakash Sasankoti Mohan RaviCorresponding author
Oral Medicine and Radiology, Subharti Dental College, India.
Background: Studies have unveiled lower levels of serum vitamin D in autoimmune diseases and the role of vitamin D in inhibition of helper T cells proliferation, stimulation of regulatory T cells, diminishing of B-lymphocyte differentiation and inhibition of immunoglobulin secretion has been discussed in the literature. Oral lichen planus (OLP) is an autoimmune mucocutaneous disorder in which cell mediated immunity plays an important part and so it may also be related to serum vitamin D levels. Aim: To estimate serum vitamin D in oral lichen planus patients of North India, compare it to the controls and to evaluate various factors influencing vitamin D level in OLP cases such as sun exposure, gender, psychosocial factors, meteorological influences, religion and diet. Methods and Material: Venous blood samples of 102 clinically diagnosed oral lichen planus patients and 102 age and sex matched controls were obtained for the study and serum vitamin D levels were estimated using Vitek Immunodiagnostic Assay System, an automated bench-top immuno-analyzer, based on the Enzyme Linked Fluorescent Assay. The data was analyzed using chi-squared test and t-test. Results: Mean vitamin D in OLP cases and controls was 20.40 ng/ml and 32.67 ng/ml respectively. Vitamin D3 deficiency was more in OLP cases (70.6%) as compared to controls (34.3%) and insufficiency was more in controls (35.3%) as compared to OLP cases (16.7%). These differences were statistically significant. Conclusion: Although vitamin D deficiency was found more in OLP cases pointing towards the possible co-relation of vitamin D and OLP, yet insufficiency was seen more commonly in controls which revealed that this important vitamin was lacking in North Indian population.
Jun 2016 DOI 10.14302/issn.2572-5424.jgm-16-1028
H Baslow MorrisCorresponding author
Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY, 10962, USA.
N-acetylaspartylglutamate (NAAG) is the highest concentration dipeptide present in brain. It is found primarily in neurons but its function is unclear. NAAG is synthesized by neurons from N-acetylaspartate and glutamate (Glu), maintained at mM concentrations and is released non-synaptically to extracellular fluid (ECF). NAAG is a non-excitatory form of Glu, and is targeted to the metabotropic group II Glu receptor 3 (mGluR3) on the surface of astrocytes. After docking with the receptor, Glu is released by the action of NAAG peptidase. Previously, it was shown for the first time that an NAAG-peptidase inhibitor reduced global cerebral blood flow (CBF) in mouse brain but did not affect their physical performance. Recently, it has been demonstrated that there are two separate systems involved in neurovascular coupling by astrocytes, one is a rapid focal phasic response providing energy for stimulation-induced neuronal activity, and the other a slower global tonic response providing energy for ongoing metabolic activities. Many neurovascular coupling mechanisms are known that regulate phasic changes in CBF, but how the brain accomplishes tonic control is unknown. In this paper we bring together two separate lines of inquiry, the decades’ long search for the function of NAAG, and the more recent search for the mechanism of tonic neurovascular control. Herein, we present evidence that NAAG is the neurovascular coupling agent that regulates tonic changes in CBF via the astrocyte mGluR3-NAAG peptidase connection.
Mar 2016 DOI 10.14302/issn.2470-0436.jos-15-739
P. Sarthy VijayCorresponding author
Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, IL 606111.
Ciliary neurotrophic factor (CNTF) is a well-tested, neuroprotective agent that has been shown to retard photoreceptor degeneration in several animal models of retinitis pigmentosa. The molecular mechanisms underlying CNTF-mediated neuroprotection are currently not understood. CNTF could act directly on photoreceptors or it could act indirectly by stimulating Müller glial cells to produce photoreceptor neuroprotective agents. To better characterize CNTF action on Müller cells, we have studied signaling pathways activated by CNTF using an established retinal Müller cell line, rMC-1. RNA was isolated from CNTF-treated cultures, and suppressor of signal transducer and activator of transcription (SOCS3) and Glial fibrillary acidic protein (GFAP) transcript levels were assessed by quantitative real-time PCR. Immunoblotting was used to examine activation ofmitogen activated protein kinase (ERK1/2/MAPK) and phosphoinositide 3-kinase (PI3-K)/Aktpathways in response to CNTF. Additionally, the level of5' AMP-activated protein kinase (AMPK), an enzyme that plays a key role in cellular energy homeostasis levels, was determined by immunoblotting. CNTF treatment resulted strong upregulation of SOCS3 and GFAP transcripts that were blocked by expression of a dominant-negative STAT3 mutant. CNTF treatment also resulted in transient activation of ERK1/2/MAPK but not PI3K/Akt signaling pathway. There was no change in activation of AMPK. We conclude that CNTF treatment leads to stimulation of JAK-STAT and MAPK signaling pathways but not the PI3K/AKT pathway, associated with cell death, in Müller cells.
Dec 2015 DOI 10.14302/issn.2324-7339.jcrhap-13-264
J. R WernikCorresponding author
Facultad de Medicina, UDELAR, Montevideo, Uruguay;
Phytochemicals (PHT) are a large group of biologically active plant chemicals that may have positive effects on human health such as immune system stimulation, down regulation of inflammatory responses, radical scavenging activities, cell repair function, and antibacterial and antiviral activity. In this proof of principle 6 months study, the effects of supplementing a PHT mix, Phyto V7, to HIV-1 seropositive individuals and AIDS patients were examined. Individuals with CD4+ T-cells below 350 counts/mm3were assigned to one of the following treatments: CG1 - no treatment, CG2 - only highly active antiretroviral treatment (HAART), TG1 - only Phyto V7, and TG2- both Phyto V7 and HAART. After 3 months of treatment there were approximately (-)1%, 1%, 2% and 4% increase in the mean weight of the CG1, CG2, TG1 and TG2 groups, respectively. The tendency for the body mass index (BMI) was similar. The CD4+ counts increased by 13%, 39%, 53% and 35%, respectively. Similar trends were noted after 6 months with 2%, 79%, 53% and 69% increases in the CD4+ counts, respectively. There was a significant reduction in viremia only in groups receiving HAART. Overall better results were obtained in the group of patients receiving both HAART and Phyto V7, in which the mean weight increased by 5.7% and the CD4+ T-cell counts increased by 69% after 6 months. This study indicates that providing Phyto V7 to HIV-1 seropositive individuals and AIDS patients, receiving or not receiving HAART, improves their physical wellbeing and CD4+ counts, enabling them to cope better with the viral infection.
Oct 2015 DOI 10.14302/issn.2470-0436.jos-14-571
SHIBA TakuyaCorresponding author
Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan.
Purpose: To describe a new functional magnetic resonance imaging (fMRI) method for measuring the influence of regular astigmatism, both against-the-rule (ATR) and with-the-rule (WTR), on the human visual cortex. Setting: Department of Ophthalmology, Jikei University School of Medicine, Tokyo, Japan. Design: Experimental study. Methods: Images were acquired in two healthy volunteers using a 1.5 T scanner equipped for echo planar imaging. Horizontal and vertical sine wave grating flickering at a frequency of 8 Hz were simultaneously presented during the 20-second stimulation period. During the control period , subjects fixated on a control target. Stimulations were performed under three different conditions that included with hard contact lenses that were equal to emmetropia without astigmatism (condition 1); with hard contact lenses and cylindrical glasses of +6.00D at 0°, imitating WTR (condition 2); and with hard contact lenses and cylindrical glasses of +6. 00 D at 90°, imitating ATR (condition 3). Raw data were processed using in-house software with the significance of activation determined by Statistical Parametric Mapping (SPM 99). Results: Although higher activation was found in the primary visual cortex for condition 1 versus conditions 2 and 3, activation in the dorsal pathway was higher in conditions 2 and 3 compared to condition 1. Dorsal pathway activation was also higher in condition 3 versus condition 2. Conclusions: Study findings showed the potential influence of ATR and WTR on the human visual cortex , with fMRI able to detect the influence of regular astigmatism on the visual cortex. Our current results suggest that fMRI may be useful in exploring the influence of astigmatism on vision.
May 2015 DOI 10.14302/issn.2372-6601.jhor-14-493
Prunier1 ECorresponding author
In autologous hematopoietic stem cell transplantation patients for whom granulocyte-colony stimulating factor fails to mobilize a sufficient number of peripheral blood stem cells, plerixafor proposes an option for successful rescue mobilization. This paper evaluates the efficacy of plerixafor to mobilize peripheral blood stem cells (PBSCs) in patients who failed previous mobilization with G-CSF alone, by retrospectively analysing the PBSC results from lymphoma and myeloma (MM) patients between 2006 and 2011. Patients were classified according to the CD34+ cells/kg yield collected by apheresis: < 2 x 106 CD34+ cells/kg was considered collection failure, whereas ≥ 5 x 106 CD34+ cells/kg was considered good mobilization. 797 patients underwent one or more apheresis. The first mobilization success rate was 82%; 140 patients proved to be poor mobilizers. Suboptimal first mobilization was significantly associated with age >50 years (p=0.005) and the absence of chemotherapy in prior PBSCs stimulation (p=0.04). 149 rescue protocols were used in the 140 poor mobilizers, and 71 patients received plerixafor. In univariate analysis the remobilization rate without plerixafor was 42% and increased to 65% when plerixafor was added. In multivariate analysis, plerixafor administration reduced the PBSC remobilization failure risk by a half (OR=0.47). The median value of CD34+ cells/kg in transplants increased from 1.43 (range, 014.03) without plerixafor to 3.85 (range, 0–18.25; p=1 x 10-4) with plerixafor. There were more good mobilizers after plerixafor use (35% with plerixafor versus 15% without plerixafor; p=0.005). Plerixafor efficacy was similar for lymphoma (60% remobilization) and MM (80%; p=0.12). These data show that plerixafor was effective in poor mobilizers and that it synergized with G-CSF to improve the quantity of collected PBSCs. Plerixafor also increased transplant feasibility by 23%. While the clinical results of this study are promising, economic data were not taken into account and there is a need for real work concerning the cost-effectiveness of this treatment. We propose a subsequent study in which the economic efficacy of plerixafor’s use is evaluated based on the financial aspects of the treatments received by the cohort evaluated in this paper.