Contralateral Site Research Articles

Activity specific areal bone mineral density is reduced in athletes with stress fracture and requires profound recovery time: A study of lumbar stress fracture in elite cricket fast bowlers

ObjectivesThe aims of this study were to determine whether lumbar areal bone mineral density differed between cricket fast bowlers with and without lumbar stress fracture, and whether bone mineral density trajectories differed between groups during rehabilitation. DesignCross-sectional and cohort. Methods29 elite male fast bowlers received a post-season anteroposterior lumbar dual-energy X-ray absorptiometry scan and a lumbar magnetic resonance imaging scan to determine stress fracture status. Participants were invited for three additional scans across the 59 weeks post baseline or diagnosis of injury. Bone mineral density was measured at L1 – L4 and ipsilateral and contralateral L3 and L4 sites. Independent-sample t-tests determined baseline differences in bone mineral density and multilevel models were used to examine differences in bone mineral density trajectories over time between injured and uninjured participants. Results17 participants with lumbar stress fracture had lower baseline bone mineral density at L1 – L4 (7.6 %, p = 0.034) and contralateral sites (8.8–10.4 %, p = 0.038–0.058) than uninjured participants. Bone mineral density at all sites decreased 1.9–3.0 % by 20–24 weeks before increasing to above baseline levels by 52 weeks post injury. ConclusionsInjured fast bowlers had lower lumbar bone mineral density at diagnosis that decreased following injury and did not return to baseline until up to a year post-diagnosis. Localised maladaptation of bone mineral density may contribute to lumbar stress fracture. Bone mineral density loss following injury may increase risk of recurrence, therefore fast bowlers require careful management when returning to play.

Bacterial invasion into the epidermis of rats with sodium lauryl sulphate-irritated skin increases damage and induces incontinence-associated dermatitis.

Incontinence-associated dermatitis (IAD) is caused by prolonged exposure to urine/liquid stool. It is a common and often painful skin condition in older incontinent adults because of poor prevention. Patients with urinary infections are at risk of developing IAD, and to guide the development of novel prevention strategies, we aimed to develop an animal model of IAD by urine and bacteria. First, contralateral sites on the dorsal skin of Sprague-Dawley rats were compromised by sodium lauryl sulphate (SLS), simulating frequent cleansing with soap/water. Filter discs were then placed inside ring-shaped chambers on foam dressings, inoculated with or without Pseudomonas aeruginosa, covered with agarose gels immersed in cultured filtrated urine, and secured in place with an occlusive dressing for 3 days. Untreated and SLS-compromised sites served as controls. The IAD was developed at bacteria-inoculated sites, characterised by severe IAD-like redness that persisted for up to 3 days post-exposure and higher disruption of the skin barrier function compared with non-inoculated sites. Pathological changes included epidermal thickening, partial skin loss, inflammatory cell infiltration, accumulation of red blood cells, and invasion of bacteria into the epidermis. This novel, clinically relevant IAD rat model can serve for future prevention developments.

The influence of the reference electrode location on the M−wave characteristics in the quadriceps

IntroductionIn the compound muscle action potential (M wave) recorded using the belly-tendon configuration, the contribution of the tendon electrode is assumed to be negligible compared to the belly electrode. We tested this assumption by placing the reference electrode at a distant (contralateral) site, which allowed separate recording of the belly and tendon contributions. MethodsM waves were recorded at multiple selected sites over the right quadriceps heads and lower leg using two different locations for the reference electrode: the ipsilateral (right) and contralateral (left) patellar tendon. The general parameters of the M wave (amplitude, area, duration, latency, and frequency) were measured. Results(1) The tendon potential had a small amplitude (<30%) compared to the belly potential; (2) Changing the reference electrode from the ipsilateral to the contralateral patella produced moderate changes in the M wave recorded over the innervation zone, these changes affecting significantly the amplitude of the M−wave second phase (p = 0.006); (3) Using the contralateral reference system allowed recording of short-latency components occurring immediately after the stimulus artefact, which had the same latency and amplitude (p = 0.18 and 0.25, respectively) at all recording sites over the leg. ConclusionsThe potential recorded at the “tendon” site after femoral nerve stimulation is small (compared to the belly potential), but not negligible, and makes a significant contribution to the second phase of belly-tendon M wave. Adopting a distant (contralateral) reference allowed recording of far-field components that may aid in the understanding of the electrical formation of the M wave.

Coverage of Midline Back Wounds with Perforator-Based Pedicled Fasciocutaneous Flaps

Background: The number of patients with midline back wounds is increasing. Midline back wounds may cause skin and soft tissue defects, resulting in cavity formation and bone or orthopedic metallic hardware exposure. These complexities complicate coverage of the wounds. This study aimed to determine whether a perforator-based pedicled (island) flap was useful for the coverage of midline back wounds.Methods: After debridement of the wound, flaps were designed, dissected and inset into the midline wounds. The donor site was closed primarily. If the wound was too large to be covered with a unilateral flap, another flap at the contralateral site was used. Immediate and early postoperative position changes were made.Results: Between May 2011 and November 2019, 13 patients with skin and soft tissue defects of the midline back underwent coverage with perforator-based pedicled fasciocutaneous flaps. All flaps survived. Though flap tip necrosis and/or wound dehiscence occurred in five patients, total flap necrosis was not observed. Immediate postoperative position change was possible, allowing the patient to avoid flap ischemia.Conclusion: The perforator-based pedicled fasciocutaneous flap can be a useful option for covering midline back wounds with skin and soft tissue defects.

Temporal and spatial changes in bone mineral content and mechanical properties during breast-cancer bone metastases

Cancer cells favour migration and metastasis to bone tissue for 70–80 % of advanced breast cancer patients and it has been proposed that bone tissue provides attractive physical properties that facilitate tumour invasion, resulting in osteolytic and or osteoblastic metastasis. However, it is not yet known how specific bone tissue composition is associated with tumour invasion. In particular, how compositional and nano-mechanical properties of bone tissue evolve during metastasis, and where in the bone they arise, may affect the overall aggressiveness of tumour invasion, but this is not well understood. The objective of this study is to develop an advanced understanding of temporal and spatial changes in nano-mechanical properties and composition of bone tissue during metastasis. Primary mammary tumours were induced by inoculation of immune-competent BALB/c mice with 4T1 breast cancer cells in the mammary fat pad local to the right femur. Microcomputed tomography and nanoindentation were conducted to quantify cortical and trabecular bone matrix mineralisation and nano-mechanical properties. Analysis was performed in proximal and distal femur regions (spatial analysis) of tumour-adjacent (ipsilateral) and contralateral femurs after 3 weeks and 6 weeks of tumour and metastasis development (temporal analysis). By 3 weeks post-inoculation there was no significant difference in bone volume fraction or nano-mechanical properties of bone tissue between the metastatic femora and healthy controls. However, early osteolysis was indicated by trabecular thinning in the distal and proximal trabecular compartment of tumour-bearing femora. Moreover, cortical thickness was significantly increased in the distal region, and the mean mineral density was significantly higher in cortical and trabecular bone tissue in both proximal and distal regions, of ipsilateral (tumour-bearing) femurs compared to healthy controls. By 6 weeks post-inoculation, overt osteolytic lesions were identified in all ipsilateral metastatic femora, but also in two of four contralateral femora of tumour-bearing mice. Bone volume fraction, cortical area, cortical and trabecular thickness were all significantly decreased in metastatic femora (both ipsilateral and contralateral). Trabecular bone tissue stiffness in the proximal femur decreased in the ipsilateral femurs compared to contralateral and control sites. Temporal and spatial analysis of bone nano-mechanical properties and mineralisation during breast cancer invasion reveals changes in bone tissue composition prior to and following overt metastatic osteolysis, local and distant from the primary tumour site. These changes may alter the mechanical environment of both the bone and tumour cells, and thereby play a role in perpetuating the cancer vicious cycle during breast cancer metastasis to bone tissue.

Immediate implant placement with socket shield technique in the maxilla: a prospective case series evaluation at 1-year follow-up

BackgroundThe aims of this case series were to investigate the clinical, radiographic, implant success, complication incidence, esthetic, and patient-reported outcomes of 10 immediately placed implants associated with the socket shield technique at 12 months post-loading and to assess the ridge width changes that occurred at 8 months following implant placement.MethodsA total of 10 patients received 10 socket shield immediate implants (MegaGen AnyRidge). At 8 months postimplantation, casts were made to assess the ridge width changes by measuring the ridge width at the implant sites and comparing them with the corresponding measurements at the contralateral tooth site. At 12 months post-loading, clinical indices, marginal bone loss, pink esthetic score, and patient-assessed outcomes were evaluated. The mean, standard deviation and median were calculated for all continuous variables.ResultsAll implants demonstrated a 100% success rate, while 2 implants presented with external shield exposure that was managed successfully. The mean marginal bone loss was 0.08 ± 0.14 mm mesially and 0.21 ± 0.23 mm distally. Esthetic evaluation yielded an average modified pink esthetic score of 8.65. A mean gain of 0.17 mm in the facial-palatal ridge width was recorded at 8 months postimplantation.ConclusionsThe socket shield technique enhanced the functional and esthetic results by preserving the alveolar bone and peri-implant soft tissues. However, this is a sensitive technique and still needs more robust evidence before it can be recommended for everyday clinical practice.

Systematic Review on Multilevel Analysis of Radiation Effects on Bone Microarchitecture.

Introduction Modern radiation therapy has become an effective method to treat and monitor tumour growth in cancer patients. It has proved to be a successful way to minimise mortality rates. However, the adverse effects of radiation have been historical evidence in the clinical environment involving diminishing the quality and density of bone and causing fragility fracture to the bone in the long run. This systematic review was aimed at identifying and evaluating the effects of irradiation on morphology and mechanical properties of murine model bone in previous publications. Methods A systematic literature review was undertaken following the Preferred Reporting Items for Systemic Reviews and Meta-analysis (PRISMA) guidelines. A comprehensive literature search was performed using Scopus, Web of Science, and Science Direct databases (English only studies published between 2015 and 2020). The selected studies were evaluated according to three criteria: (1) criteria for study sample selection; (2) criteria for methodological procedures; and (3) criteria for detection and evaluation. Results The initial search strategy identified 1408 related studies, 8 of were included based on inclusion and exclusion criteria. This review revealed an association between bone destruction and the magnitude of time and dose postirradiation. We agreed that the effect of radiation on bone morphology and strength primarily is a later stage event but noticeable in both low (1 Gy) and high dose (30 Gy) radiation. Trabecular and cortical bone microstructures were significantly altered at irradiation and contralateral sites. Besides, the mechanical strength was significantly impacted in both shorter and longer periods. Conclusion Overall, the radiotherapy altered bone microstructures and substantially decreases bone mechanical properties. The alteration was related to quantity and the activity of the osteoblast and osteoclast. Early detection of those most at risk for radiation-induced bone alterations could lead to better prophylactic intervention decisions.

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Comparative evaluation of healing in extraction sockets with &amp; without manuka honey: A randomized clinical control trial

The aim of this study was to compare the healing of extraction sockets with Manuka honey vs. without manuka honey attending outpatient clinic Department of Oral & Maxillofacial Surgery, Jaipur Dental College. Thirty subjects were randomized into two groups i.e., group A in which Manuka Honey is placed in the extraction socket & a group B, which is a control group. Main outcome measure was to compare the amount of time required for haemostasis, pain according to VAS scale on 1st, 3rd & 7th day, presence of swelling on 1st, 3rd & 7th day, any other post-operative discomfort such as difficulty in speech, any kind of discharge, and presence of any signs of alveolar osteitis. Through the study we concluded that sockets in which the Manuka Honey was placed had better healing and less signs of inflammation was observed as compared to the contra-lateral site.

Assessing the Effect of Smokeless Tobacco Consumption on Oral Microbiome in Healthy and Oral Cancer Patients.

Oral cancer is a globally widespread cancer that features among the three most prevalent cancers in India. The risk of oral cancer is elevated by factors such as tobacco consumption, betel-quid chewing, excessive alcohol consumption, unhygienic oral condition, sustained viral infections, and also due to dysbiosis in microbiome composition of the oral cavity. Here, we performed an oral microbiome study of healthy and oral cancer patients to decipher the microbial dysbiosis due to the consumption of smokeless-tobacco-based products and also revealed the tobacco-associated microbiome. The analysis of 196 oral microbiome samples from three different oral sites of 32 healthy and 34 oral squamous cell carcinoma (OSCC) patients indicated health status, site of sampling, and smokeless tobacco consumption as significant covariates associated with oral microbiome composition. Significant similarity in oral microbiome composition of smokeless-tobacco-consuming healthy samples and OSCC samples inferred the possible role of smokeless tobacco consumption in increasing inflammation-associated species in oral microbiome. Significantly higher abundance of Streptococcus was found to adequately discriminate smokeless-tobacco-non-consuming healthy samples from smokeless-tobacco-consuming healthy samples and contralateral healthy site of OSCC samples from the tumor site of OSCC samples. Comparative analysis of oral microbiome from another OSCC cohort also confirmed Streptococcus as a potential marker for healthy oral microbiome. Gram-negative microbial genera such as Prevotella, Capnocytophaga, and Fusobacterium were found to be differentially abundant in OSCC-associated microbiomes and can be considered as potential microbiome marker genera for oral cancer. Association with lipopolysaccharide (LPS) biosynthesis pathway further confirms the differential abundance of Gram-negative marker genera in OSCC microbiomes.

Functional Aplasia of the Contralateral A1 Segment Influences Clinical Outcome in Patients with Occlusion of the Distal Internal Carotid Artery.

Background: The importance of an A1 aplasia remains unclear in stroke patients. In this work, we analyze the impact of an A1 aplasia contralateral to an acute occlusion of the distal internal carotid artery (ICA) on clinical outcomes. Methods: We conducted a retrospective study of consecutive stroke patients treated with mechanical thrombectomy at 12 tertiary care centers between January 2015 and February 2021 due to an occlusion of the distal ICA. Functional A1 aplasia was defined as the absence of A1 or hypoplastic A1 (>50% reduction to the contralateral site). Functional independence was measured by the modified Rankin Scale (mRS ≤ 2). Results: In total, 81 out of 1068 (8%) patients had functional A1 aplasia contralateral to distal ICA occlusion. Patients with functional contralateral A1 aplasia were more severely affected on admission (median NIHSS 18, IQR 15–23 vs. 17, IQR 13–21; aOR: 0.672, 95% CI: 0.448–1.007, p = 0.054) and post-interventional ischemic damage was larger (median ASPECTS 5, IQR 1–7, vs. 6, IQR 3–8; aOR: 1.817, 95% CI: 1.184–2.789, p = 0.006). Infarction occurred more often within the ipsilateral ACA territory (20/76, 26% vs. 110/961, 11%; aOR: 2.482, 95% CI: 1.389–4.437, p = 0.002) and both ACA territories (8/76, 11% vs. 5/961, 1%; aOR: 17.968, 95% CI: 4.979–64.847, p ≤ 0.001). Functional contralateral A1 aplasia was associated with a lower rate of functional independence at discharge (6/81, 8% vs. 194/965, 20%; aOR: 2.579, 95% CI: 1.086–6.122, p = 0.032) and after 90 days (5/55, 9% vs. 170/723, 24%; aOR: 2.664, 95% CI: 1.031–6.883, p = 0.043). Conclusions: A functional A1 aplasia contralateral to a distal ICA occlusion is associated with a poorer clinical outcome.

Effectiveness of maturity of Rubus occidentalis on hyperalgesia induced by acidic saline injection in rats

BackgroundRubus occidentalis, also known as black raspberry, contains several bioactive components that vary depending on the maturity of the fruit. The goal of this study was to evaluate the efficacy of immature Rubus occidentalis extract(iROE) on acid-induced hyperalgesia, investigate the mechanism involved, and compare the antihyperalgesic effect of immature and mature ROEs.MethodsIn adult male Sprague-Dawley rats, chronic muscle pain was induced via two injections of acidic saline into one gastrocnemius muscle. To evaluate the dose response, the rats were injected intraperitoneally with 0.9% saline or iROE (10, 30, 100, or 300 mg/kg) following hyperalgesia development. To evaluate the mechanism underlying iROE-induced analgesia, the rats were injected intraperitoneally with saline, yohimbine 2 mg/kg, dexmedetomidine 50 μg/kg, prazosin 1 mg/kg, atropine 5 mg/kg, mecamylamine 1 mg/kg, or naloxone 5 mg/kg 24 h after hyperalgesia development, followed by iROE 300 mg/kg administration. To compare immature versus mature ROE, the rats were injected with mature ROE 300 mg/kg and immature ROE 300 mg/kg after hyperalgesia development. For all experiments, the mechanical withdrawal threshold(MWT) was evaluated using von Frey filaments before the first acidic saline injection, 24 h after the second injection, and at various time points after drug administration. Data were analysed using multivariate analysis of variance(MANOVA) and the linear mixed-effects model(LMEM). We compared the MWT at each time point using analysis of variance with the Bonferroni correction.ResultsThe iROE 300 mg/kg injection resulted in a significant increase in MWT compared with the control, iROE 30 mg/kg, and iROE 100 mg/kg injections at ipsilateral and contralateral sites. The iROE injection together with yohimbine, mecamylamine, or naloxone significantly decreased the MWT compared with iROE alone, whereas ROE together with dexmedetomidine significantly increased the MWT. According to MANOVA, the effects of immature and mature ROEs were not significantly different; however, the LMEM presented a significant difference between the two groups.ConclusionsImmature R. occidentalis showed antihyperalgesic activity against acid-induced chronic muscle pain, which may be mediated by the α2-adrenergic, nicotinic cholinergic, and opioid receptors. The iROE displayed superior tendency regarding analgesic effect compared to mature ROE.

Phenotypic and functional characterization of synovial fluid-derived fibroblast-like synoviocytes in rheumatoid arthritis

Fibroblast-like synoviocytes (FLS) play an important pathological role in persistent inflammatory joint diseases such as rheumatoid arthritis (RA). These cells have primarily been characterized in the RA synovial membrane. Here we aim to phenotypically and functionally characterize cultured synovial fluid-derived FLS (sfRA-FLS). Paired peripheral blood mononuclear cells (PBMC) and sfRA-FLS from patients with RA were obtained and monocultures of sfRA-FLS and autologous co-cultures of sfRA-FLS and PBMC were established. The in situ activated sfRA-FLS were CD34-, CD45-, Podoplanin+, Thymocyte differentiation antigen-1+. SfRA-FLS expressed uniform levels of NFкB-related pathway proteins and secreted several pro-inflammatory cytokines dominated by IL-6 and MCP-1. In a co-culture model with autologous PBMC, the ICAM-1 and HLA-DR expression on sfRA-FLS and secretion of IL-1β, IL-6, and MCP-1 increased. In vivo, human sfRA-FLS were cartilage invasive both at ipsilateral and contralateral implantation site. We conclude that, sfRA-FLS closely resemble the pathological sublining layer FLS subset in terms of surface protein expression, cytokine production and leukocyte cross-talk potential. Further, sfRA-FLS are comparable to tissue-derived FLS in their capabilities to invade cartilage at implantation sites but also spread tissue destruction to a distant site. Collectively, sfRA-FLS can serve as a an easy-to-obtain source of pathological sublining FLS in RA.

Spatial and temporal profile of high-frequency oscillations in posttraumatic epileptogenesis

We studied the role of temporal and spatial changes in high-frequency oscillation (HFO, 80–500 Hz) generation in epileptogenesis following traumatic brain injury (TBI).Experiments were conducted on adult male Sprague Dawley rats. For the TBI group, fluid percussion injury (FPI) on the left sensorimotor area was performed to induce posttraumatic epileptogenesis. For the sham control group, only the craniotomy was performed. After TBI, 8 bipolar micro-electrodes were implanted bilaterally in the prefrontal cortex, perilesional area and homotopic contralateral site, striatum, and hippocampus. Long-term video/local field potential (LFP) recordings were performed for up to 21 weeks to identify and characterize seizures and capture HFOs. The electrode tip locations and the volume of post TBI brain lesions were further estimated by ex-vivo MRI scans. HFOs were detected during slow-wave sleep and categorized as ripple (80–200 Hz) and fast ripple (FR, 250–500 Hz) events. HFO rates and the HFO peak frequencies were compared in the 8 recording locations and across 8-weeks following TBI.Data from 48 rats (8 sham controls and 40 TBI rats) were analyzed. Within the TBI group, 22 rats (55%) developed recurrent spontaneous seizures (E+ group), at an average of 62.2 (+17.1) days, while 18 rats (45%) did not (E- group). We observed that the HFOs in the E+ group had a higher mean peak frequency than the E- group and the sham group (P < 0.05). Furthermore, the FR rate of the E+ group showed a significant increase compared to the E-group (P < 0.01) and sham control group (P < 0.01), specifically in the perilesional area, homotopic contralateral site, bilateral hippocampus, and to a lesser degree bilateral striatum. When compared across time, the increased FR rate in the E+ group occurred immediately after the insult and remained stable across the duration of the experiment. In addition, lesion size was not statistically different in the E+ and E- group and was not correlated with HFO rates.Our results suggest that TBI results in the formation of a widespread epileptogenic network. FR rates serve as a biomarker of network formation and predict the future development of epilepsy, however FR are not a temporally specific biomarker of TBI sequelae responsible for epileptogenesis. These results suggest that in patients, future risk of post-TBI epilepsy can be predicted early using FR.

Impact of 0.12% Chlorhexidine Gluconate Mouthwash on Peri-Implant Mucositis and Gingivitis After Nonsurgical Treatment: A Multilevel Analysis.

This study investigated the impact of 0.12% chlorhexidine gluconate mouthwash on dental implants with periimplant mucositis and contralateral teeth with gingivitis at 6 months of follow-up after nonsurgical treatment. This was a secondary analysis of data from a previous controlled, randomized, double-blinded clinical trial of 30 patients diagnosed with peri-implant mucositis and gingivitis in contralateral teeth, at 6 months following treatment. Patients were randomly assigned into a test group (basic periodontal therapy + 0.12% chlorhexidine mouthwash) or a control group (basic periodontal therapy + placebo). Therapy consisted of an adaptation of the full-mouth scaling and root planing protocol. The clinical parameters of visible Plaque Index, Gingival Bleeding Index, probing depth, bleeding on probing, keratinized mucosa width, and gingival and peri-implant phenotype were evaluated at baseline and at 1, 3, and 6 months posttherapy. Data were analyzed using Poisson multilevel regression analysis with a significance level of .05. The study analyzed 47 implants and contralateral teeth (376 sites) in the test group and 49 implants and contralateral teeth (392 sites) in the control group. No differences were found between the groups at the patient level. At the site level, the teeth and implants presented statistical differences in bleeding on probing, probing depth, and keratinized mucosa width at 3 months for both treatment groups. However, no difference was observed in bleeding on probing in the test group (P = .484) at 6 months, whereas the control group demonstrated increased bleeding on probing (indicating more inflammation) at implant sites than at teeth sites (P = .039). Additionally, implant sites with a thin peri-implant phenotype (P < .001) and located posteriorly (P = .002) presented greater inflammation. Use of a 0.12% chlorhexidine mouthwash for 14 days was beneficial for implant sites with peri-implant mucositis, compared to contralateral teeth sites with gingivitis, as indicated by the reduced percentage of teeth with bleeding on probing.

Soft and Hard Tissue Changes Subsequent to Spontaneous Healing of the Extraction Sockets Using Cone-Beam Computed Tomography: A Cross-Sectional Study.

This study sought to compare the thickness of hard and soft tissues between edentulous and contralateral tooth sites. This split-mouth study evaluated 153 partially edentulous patients. The measurements were made on cone-beam computed tomography (CBCT) scans. The soft tissue thickness was measured at the cementoenamel junctional (CEJ) level, and at 2, 4, and 6mm apical to the CEJ in the facial and palatal aspects. The bone thickness of the opposite quadrant was also recorded at 2, 4, and 6mm apical to the CEJ. The Mann-Whitney U test and the Spearman's rank correlation coefficient were applied for further statistical analyses. At the edentulous sites, significant soft tissue loss was noted at the CEJ level (p < 0.0001) and a considerable gain was noted at 2, 4, and 6mm apical to the CEJ (p = 0.004, p < 0.0001, p ≤ 0.0001, respectively). A significant hard tissue loss was noted at 2mm apical to the CEJ but a significant hard tissue gain was observed at the edentulous sites (p < 0.0001). The soft tissue gain at 6mm apical to the CEJ was significantly associated with an increase in buccolingual diameter (p = 0.004) while the hard tissue loss at 2mm apical to the CEJ was significantly correlated with a reduction in buccolingual diameter (p = 0.020). Different amounts of tissue thickness alterations occurred in different levels of socket.

High-frequency electrical stimulation of cutaneous nociceptors differentially affects pain perception elicited by homotopic and heterotopic electrical stimuli.

Animal studies have shown that high-frequency electrical stimulation (HFS) of peripheral C-fiber nociceptors induces both homosynaptic and heterosynaptic long-term potentiation (LTP) within spinal nociceptive pathways. In humans, when HFS is applied onto the skin to activate nociceptors, single electrical stimuli are perceived more intense at the HFS site compared with a control site, a finding that was interpreted as a perceptual correlate of homosynaptic LTP. The present study aimed to investigate if after HFS the pain elicited by electrical stimuli delivered at the skin next to the HFS site is perceived as more intense compared with the pain at a control site (contralateral arm). To test this, HFS was applied to one of the two ventral forearms of 24 healthy participants. Before and after HFS, single electrical stimuli were delivered through the HFS electrode, through an identical electrode next to the HFS electrode and an identical electrode at the contralateral arm. After HFS, the pain elicited by the single electrical stimuli was reduced at all three sites, with the largest reduction at the HFS site. Nevertheless, electrical stimuli delivered to the skin next to the HFS site were perceived as more intense than control stimuli. This result indicates that higher pain ratings to electrical stimuli after HFS at the HFS site cannot solely be interpreted as a perceptual correlate of homosynaptic changes. Furthermore, we show for the first time, in humans, that HFS can reduce pain elicited by single electrical stimuli delivered through the same electrode.NEW & NOTEWORTHY High-frequency electrical stimulation (HFS) of cutaneous nociceptors can reduce pain perception to single electrical stimuli delivered through the same electrode. Moreover, single electrical stimuli delivered to the skin next to the site at which HFS was applied are perceived as more intense compared with that at the contralateral control site, indicating the presence of heterosynaptic effects for electrical stimuli.

Microbiome of Unilateral Chronic Rhinosinusitis: A Controlled Paired Analysis.

The sinonasal microbiota in human upper airway may play an important role in chronic rhinosinusitis (CRS). Thus, this study aimed to investigate the human upper airway microbiome in patients with unilateral CRS, and compare the sinonasal microbiome of the unilateral diseased site with that of a contralateral healthy site. Thirty samples, 15 each from the diseased and healthy sites, were collected from the middle meatus and/or anterior ethmoid region of 15 patients with unilateral CRS during endoscopic sinus surgery. DNA extraction and bacterial microbiome analysis via 16S rRNA gene sequencing were then performed. Corynebacterium showed the highest relative abundance, followed by Staphylococcus in samples from both the diseased and healthy sites. Further, the relative abundances of Staphylococcus and Pseudomonas were significantly lower in samples from diseased sites than in those from healthy sites. Conversely, anaerobes, including Fusobacterium, Bacteroides, and Propionibacterium, were abundantly present in samples from both sites, more so in samples from diseased sites. However, the sites showed no significant difference with respect to richness or diversity (p > 0.05). Our results indicate that CRS might be a polymicrobial infection, and also suggest that Corynebacterium and Staphylococcus may exist as commensals on the sinus mucosal surface in the upper respiratory tract.

RNase A Inhibits Formation of Neutrophil Extracellular Traps in Subarachnoid Hemorrhage.

Background: Subarachnoid hemorrhage (SAH) caused by rupture of an intracranial aneurysm, is a life-threatening emergency that is associated with substantial morbidity and mortality. Emerging evidence suggests involvement of the innate immune response in secondary brain injury, and a potential role of neutrophil extracellular traps (NETs) for SAH-associated neuroinflammation. In this study, we investigated the spatiotemporal patterns of NETs in SAH and the potential role of the RNase A (the bovine equivalent to human RNase 1) application on NET burden.Methods: A total number of n=81 male C57Bl/6 mice were operated utilizing a filament perforation model to induce SAH, and Sham operation was performed for the corresponding control groups. To confirm the bleeding and exclude stroke and intracerebral hemorrhage, the animals received MRI after 24h. Mice were treated with intravenous injection of RNase A (42μg/kg body weight) or saline solution for the control groups, respectively. Quadruple-immunofluorescence (IF) staining for cell nuclei (DAPI), F-actin (phalloidin), citrullinated H3, and neurons (NeuN) was analyzed by confocal imaging and used to quantify NET abundance in the subarachnoid space (SAS) and brain parenchyma. To quantify NETs in human SAH patients, cerebrospinal spinal fluid (CSF) and blood samples from day 1, 2, 7, and 14 after bleeding onset were analyzed for double-stranded DNA (dsDNA) via Sytox Green.Results: Neutrophil extracellular traps are released upon subarachnoid hemorrhage in the SAS on the ipsilateral bleeding site 24h after ictus. Over time, NETs showed progressive increase in the parenchyma on both ipsi- and contralateral site, peaking on day 14 in periventricular localization. In CSF and blood samples of patients with aneurysmal SAH, NETs also increased gradually over time with a peak on day 7. RNase application significantly reduced NET accumulation in basal, cortical, and periventricular areas.Conclusion: Neutrophil extracellular trap formation following SAH originates in the ipsilateral SAS of the bleeding site and spreads gradually over time to basal, cortical, and periventricular areas in the parenchyma within 14days. Intravenous RNase application abrogates NET burden significantly in the brain parenchyma, underpinning a potential role in modulation of the innate immune activation after SAH.

Rarities in rare: illuminating the microvascular and dermal status in juvenile localised scleroderma. A case series.

To assess the (structural and functional) characteristics of the microvascular and dermal status in juvenile localised scleroderma (jLoS), using novel non-invasive standardised research tools commonly used in adult systemic sclerosis (SSc). Ten consecutive patients with a confirmed jLoS diagnosis were studied cross-sectionally in this two-centre case series. For each patient, the most prominent lesion (i.e., "target lesion") was chosen for further examination of the centre, edge and contralateral unaffected site. High-frequency ultrasonography was used to determine dermal thickness, durometer for skin hardness, and laser speckle contrast analysis (LASCA) for a dynamical evaluation of the microcirculation. The structure of the microcirculation was evaluated at the nailfolds of the 2nd-5th finger bilaterally, using nailfold videocapillaroscopy (NVC). 6 linear and 4 plaque subtype jLoS lesions were included. Dermal thickness was thinner at the centre of the "target lesions" vs. the edges (p<0.001) and control sites (p<0.001). Skin hardness was harder at the centre of the "target lesions" vs. the edges (p=0.012) and control sites (p=0.003). A higher perfusion was found in the centre of the "target lesion" (124.87±66.40 PU) vs. the edges (87.27±46.40 PU; p<0.001) and control sites (67.85±37.49; p<0.001). Of note, all patients had a "non-scleroderma" pattern on NVC. This case series suggests the supportive value of both microcirculatory and dermal assessments of skin lesions using novel non-invasive research tools, adopted from adult SSc, for (j)LoS.