MiR-143-3p regulates chondrogenic differentiation of synovium derived mesenchymal stem cells under mechanical stress through the BMPR2-Smad signalling pathway by targeting BMPR2.

BACKGROUND: Mesenchymal stem cells (MSCs) derived from the synovium, known as synovium mesenchymal stem cells (SMSCs), exhibit significant potential for articular cartilage regeneration owing to their capacity for chondrogenic differentiation. However, the microRNAs (miRNAs) governing this process and the associated mechanisms remain unclear. While mechanical stress positively influences chondrogenesis in MSCs, the miRNA-mediated response of SMSCs to mechanical stimuli is not well understood. OBJECTIVE: This study explores the miRNA-driven mechano-transduction in SMSCs chondrogenesis under mechanical stress. METHODS: The surface phenotype of SMSCs was analysed by flow cytometry. Chondrogenesis capacities of SMSCs were examined by Alcian blue staining. High throughput sequencing was used to screen mechano-sensitive miRNAs of SMSCs. The RNA expression level of COL2A1, ACAN, SOX9, BMPR2 and miR-143-3p of SMSCs were tested by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between miR-143-3p and TLR4 was confirmed by luciferase reporter assays. The protein expression levels of related genes were assessed by western blot. RESULTS: High-throughput sequencing revealed a notable reduction in miR-143-3p levels in mechanically stressed SMSCs. Gain- or loss-of-function strategies introduced by lentivirus demonstrated that miR-143-3p overexpression hindered chondrogenic differentiation, whereas its knockdown promoted this process. Bioinformatics scrutiny and luciferase reporter assays pinpointed a potential binding site for miR-143-3p within the 3'-UTR of bone morphogenetic protein receptor type 2 (BMPR2). MiR-143-3p overexpression decreased BMPR2 expression and phosphorylated Smad1, 5 and 8 levels, while its inhibition activated BMPR2-Smad pathway. CONCLUSION: This study elucidated that miR-143-3p negatively regulates SMSCs chondrogenic differentiation through the BMPR2-Smad pathway under mechanical tensile stress. The direct targeting of BMPR2 by miR-143-3p established a novel dimension to our understanding of mechano-transduction mechanism during SMSC chondrogenesis. This understanding is crucial for advancing strategies in articular cartilage regeneration.

Digital intraoperative evaluation of restorative space and nontemplate-guided tooth preparation when replacing failed anterior restorations: A dental technique.

Assessing the correlation between the current restorative space and the target restorative space is important in determining whether additional tooth preparation is required when replacing failed prostheses. However, existing techniques are not always accurate or efficient. This article describes a digital workflow for the accurate chairside evaluation of the current restorative space and nontemplate-guided tooth preparation. Reference data was obtained from an initial scan of the existing restoration with an intraoral scanner. After removing the existing restoration, a second scan of the tooth was made and compared with the reference data to evaluate the current restorative space. Subsequently, the abutment tooth was prepared and rescanned, with the restorative space being re-evaluated until it met the requirements. This workflow enables the immediate and accurate evaluation of the restorative space, facilitating accurate chairside tooth preparation without the need for silicone indices or other templates, thereby saving time and cost.

Altered electrophysiology mechanism related to inhibitory control in adults with insomnia.

Background: Insomnia disorder (ID), one of the most common psychophysiological disorders, can cause a serious burden on the individual's work and academic performance. Cognitive dysfunction often exists in patients with insomnia, which negatively affects their living quality. Inhibitory control (IC), as a vital cognitive function, allows individuals to suppress attention, behavior, or thoughts that are irrelevant to the task, so as to effectively adapt to the current goal. The earlier studies on the inhibitory control of insomnia patients predominantly used subjective scales for evaluation and that can have drawbacks because they don't provide an objective assessment. Methods: In order to investigate the inhibitory control function of insomniacs, this research subdivides inhibitory control into response inhibition and conflict inhibition. The response inhibition and conflict inhibition capacities of insomniacs were evaluated using the two-choice oddball task and the color-word stroop task, and accordingly the association between insomnia disorder and inhibitory control capacity as well as its cognitive neural mechanism was able to be examined. Results: Behavioral results finding, insomniacs conducted the two-choice oddball test and the color-word stroop task with lower accuracy and slower reaction times when compared to healthy sleepers. ERP results finding, when performing the two-choice oddball task, the P3 amplitude of the insomniacs was significantly lower than that of healthy sleepers while there was no significant difference between the two groups' N2 amplitudes. At the same time, when completing the color-word stroop task, the insomniacs' N450 amplitude was significantly lower than that of healthy sleepers. Discussion: The above findings suggest that in response inhibition tasks, insomniacs may have weaker motor inhibition abilities, and similarly perform weaker conflict monitoring abilities in conflict inhibition tasks, which indicates that insomniacs' inhibitory control is impaired compared to that of healthy sleepers. This study thus relates to the finding at the electrophysiological level that there is a certain correlation between insomnia and a decline in inhibitory control ability, which may suggest that improving inhibitory control function in patients with insomnia is a clinically significant and worthwhile area of adjuvant treatment.

A digital chairside repair protocol for removable partial dentures with polyetheretherketone frameworks.

Polyetheretherketone (PEEK) has become popular for removable partial denture (RPD) frameworks but reports on their clinical follow-up and repair are lacking. Two defective PEEK-framework RPDs were repaired with computer-aided design and manufacturing technology, saving costs and time and simplifying the treatment process.

Ethylenediamine pretreatment simultaneously improved carbohydrate hydrolysis and lignin valorization.

Lignocellulosic biomass (LCB) is the promising feedstock for value-added products, which would contribute to the bioeconomy and sustainable development. The efficient pretreatment is still required in the biorefinery of LCB. To make a simultaneous utilization of carbohydrates and lignin, a novel easy-recycled ethylenediamine (EDA) pretreatment was designed and evaluated in the present study. The results highlighted that this pretreatment yielded 96% glucose and 70% xylose in enzymatic hydrolysis. It simultaneously promoted the depolymerization of lignin into small molecules and functionalized the yielded lignin with Schiff base and amide structures. These animated-lignins showed a pH-responsive behavior and the excellent flocculation capacity by reducing more than 90% turbidity of kaolin suspensions. Therefore, easy-recycled EDA pretreatment hold the promise to simultaneously enhance the enzymatic hydrolysis of carbohydrates and endowed the new functionality of lignin toward downstream valorization, which improved the process feasibility and potentially enable the sustainability of LCB utilization.

Clinical finite element analysis of mandibular displacement model treated with Twin-block appliance.

INTRODUCTION: The mechanical distribution of the mandible is an important factor that affects functional orthosis during Twin-block (TB) appliance correction. Changes in the mandible before and after TB appliance correction are also key factors in maintaining the therapeutic effect. Finite element analysis, a powerful numerical, analytical tool, is widely used to predict the stress and strain distribution of the craniofacial bone that orthodontics generates. METHODS: The sample was a 14-year-old male patient with Class II malocclusion during growth. A cone-beam computed tomography scan was undertaken at pretreatment and posttreatment. In the Finite element analysis of the pretreatment model, the remote displacement model of the mandible was established with the sella point as the center. A mandibular model under TB appliance loading was established. Its mandibular displacement and von Mises stress were compared before and after loading. Three-dimensional registration was conducted on the pretreatment and posttreatment models to measure the sagittal displacement of the centrosome. RESULTS: The force on the mandible occurred mainly in the condyle neck and medial mandible after the TB appliance moved the mandible. After displacement, the posterior upper margin of the condyle was farther away from the articular fossa. Three-dimensional registration results showed that new bone had formed behind and above the condyle after TB appliance treatment. CONCLUSION: The TB appliance provides additional advantages in treating skeletal Class II malocclusions by helping to reduce the burden on the temporomandibular joint and promoting the adaptive reconstruction of the mandible.

Effect of N6-methyladenosine methylation-related gene signature for predicting the prognosis of hepatocellular carcinoma patients.

Background and aims: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death in humans. Increasing evidence indicates that an imbalance in N6-methyladenosine (m6A) methylation is linked to the occurrence and development of cancer. We then developed a prognostic model as an independent risk factor with which predict the prognosis of HCC. Methods: We obtained the gene expression and clinical data of HCC patients from the TCGA databases. The prognostic value of m6A methylation-related genes in patients who had HCC were subjected to comprehensive bioinformatics analysis. We use Risk Score = ∑ i = 1 n Coe f i × X i to construct the risk scoring formula. We collected pathological specimens from 68 patients who had HCC, and conducted immunohistochemical staining experiments on the specimens. Results: There was a significant correlation between candidate m6A methylation-related genes (YTHDF2, METTL14 and ZC3H13) overall survival of HCC patients. Among the 68 HCC patient specimens that underwent immunohistochemical staining, all cancer tissues were positive for METTL14, YTHDF2, and ZC3H13 staining in contrast to the adjacent tissues. We conducted a Kaplan-Meier survival analysis. The results showed that patients who had low METTL14 expression had a longer survival time than those of patients who had high METTL14 expression. Also, patients with low YTHDF2 expression had a longer survival time than patients with high YTHDF2 expression. Finally, patients with high ZC3H13 expression lived longer than those with low ZC3H13 expression. This result is consistent with the bioinformatics analysis conclusion above. Conclusions: Generally, the prognostic model that was based on m6A methylation-related genes in this study can effectively predict the prognosis of HCC patients.

The effect of repetitive transcranial magnetic stimulation on electroencephalography microstates of patients with heroin-addiction.

The effects of transcranial magnetic stimulation in treating substance use disorders are gaining attention; however, most existing studies used subjective measures to examine the treatment effects. Objective electroencephalography (EEG)-based microstate analysis is important for measuring the efficacy of transcranial magnetic stimulation in patients with heroin addiction. We investigated dynamic brain activity changes in individuals with heroin addiction after transcranial magnetic stimulation using microstate indicators. Thirty-two patients received intermittent theta-burst stimulation (iTBS) over the left dorsolateral prefrontal cortex. Resting-state EEG data were collected pre-intervention and 10 days post-intervention. The feature values of the significantly different microstate classes were computed using a K-means clustering algorithm. Four EEG microstate classes (A-D) were noted. There were significant increases in the duration, occurrence, and contribution of microstate class A after the iTBS intervention. K-means classification accuracy reached 81.5%. The EEG microstate is an effective improvement indicator in patients with heroin addiction treated with iTBS. Microstates were examined using machine learning; this method effectively classified the pre- and post-intervention cohorts among patients with heroin addiction and healthy individuals. Using EEG microstate to measure heroin addiction and further exploring the effect of iTBS in patients with heroin addiction merit clinical investigation.

Wnt/ß-catenin signaling pathway is activated in the progress of mandibular condylar cartilage degeneration and subchondral bone loss induced by overloaded functional orthopedic force (OFOF).

Objective: To explore the role of Wnt/ß-catenin signaling pathway in the pathogenesis and progression of temporomandibular joint osteoarthritis (TMJ OA) caused by overloaded force. Materials and methods: We generated a rat model of forward mandibular extension device to induce TMJ OA by overloaded force. Condylar cartilage samples were collected at 2wk, 4wk, and 8wk after appliances were installed. Changes of the condylar cartilage and subchondral bone were evaluated by hematoxylin and eosin (HE), Safranin O and Fast Green staining (SO&FG), micro-CT, tartrate resistant acid phosphatase (TRAP) staining. The expression levels of ß-catenin, COL-2, MMP3 and sclerostin (SOST) were detected by immunohistochemistry (IHC) and PCR. Results: HE, SO&FG, micro-CT, OARSI and Mankin scores showed that the condyle cartilage layer was significantly thinner and proteoglycan loss in the overloded group. TRAP staining exhibited that the number of positive osteoclasts increased and OPG level decreased in the overload group. IHC, PCR showed that the expression of COL2 and SOST decreased, while MMP3 and ß-catenin increased in the overload group. Conclusion: Wnt/ß-catenin signaling pathway is activated in the progress of mandibular condylar cartilage degeneration and subchondral bone loss induced by overloaded functional orthopedic force (OFOF).

Emerging Modification Technologies of Lignin-based Activated Carbon toward Advanced Applications.

Lignin-based activated carbon (LAC) is a promising high-quality functional material due to high surface area, abundant porous structure, and various functional groups. Modification is the most important step to functionalize LAC by altering its porous and chemical properties. This Review summarizes the state-of-the-art modification technologies of LAC toward advanced applications. Promising modification approaches are reviewed to display their effects on the preparation of LAC. The multiscale changes in the porosity and the surface chemistry of LAC are fully discussed. Advanced applications are then introduced to show the potential of LAC for supercapacitor electrode, catalyst support, hydrogen storage, and carbon dioxide capture. Finally, the mechanistic structure-function relationships of LAC are elaborated. These results highlight that modification technologies play a special role in altering the properties and defining the functionalities of LAC, which could be a promising porous carbon material toward industrial applications.

Excessive mechanical stress induced temporomandibular joint osteoarthritis via osteoclasts-mediated osteogenic differentiation of BMSCs.

BACKGROUND: Bone homeostasis is a dynamic process maintained by osteoblasts and osteoclasts, which may be regulated by excessive mechanical stress (EMS). OBJECTIVES: Our study aimed to explore the relationship between osteogenic differentiation of BMSCs and EMS-activated osteoclast differentiation of RAW 264.7 cells in order to optimise orthodontic treatment. METHODS: We established the model of EMS in vivo and in vitro. In vivo, HE, Safranin-O staining, micro-CT, and immunofluorescence double-labelling were utilised to assess the changes in condylar, the distributions of osteoblasts, osteoclasts and MAPKs. In vitro, the effects of EMS-activated osteoclast differentiation exerting on osteogenic differentiation of BMSCs were observed by Western Blot, qRT-PCR and Alizarin Red staining. Furthermore, the role of MAPKs in this progress was explored by using inhibitors of MAPKs and co-culture supernatants. RESULTS: In vivo, EMS led to the degradation of condylar cartilage and destruction of subchondral bone, diagnosed as temporomandibular joint osteoarthritis (TMJ OA). Osteoclasts and osteoblasts were both enriched in subchondral bone, but osteoclast predominated. The expressions of p-JNK, p-ERK1/2, and p-p38 were all activated in vitro and in vivo, which were localised mainly in the Trap+ area in subchondral bone. Interestingly, only the inactivation of p-ERK1/2 in osteoclasts significantly inhibited the osteogenic differentiation of BMSCs in vitro. This revealed that p-ERK1/2 played a key role in the osteoclasts-induced osteogenic differentiation of BMSCs. CONCLUSION: Our results proved that EMS led to TMJ OA, in which upregulated p-ERK1/2 in osteoclasts was mechanosensitive and facilitated the osteogenic differentiation of BMSCs.

Characterizing Brand Knowledge and Identification as Predictors of Consumer-Based Brand Equity: Mediating Role of Employee-Based Brand Equity.

Branding has been a key factor for the software houses, mainly customers' expectations for a predicted product and real-time experience. The identity and knowledge of brands set a certain set of expectations in the mind of the consumers and the organization's employees. This study mainly investigates the effects of brand identity and brand knowledge on the employee-based brand equity (EBBE) and consumer-based brand equity (CBBE). Further, it examined the mediating role of EBBE among these variables. To complete this empirical study, a quantitative survey was conducted using a 30-item survey method to collect data from 243 respondents from China's software houses. The participants were selected based on purposive sampling. Results show that brand identity and brand knowledge are the main constituents of EBBE, which significantly predicts the CBBE. The study highlights the importance of employees in building overall brand equity. Training and brand promotion activities would help the organizations build a brand identity that positively contributes to the EBBE. Further, brand identity and brand knowledge are needed to improve the human capital, engagement of employees, and their emotional affiliations with the organizations, ultimately making the brand equity of employees stronger.

Five-month-old infants attribute inferences based on general knowledge to agents.

To make sense of others' actions, we generally consider what information is available to them. This information may come from different sources, including perception and inference. Like adults, young infants track what information agents can obtain through perception: If an agent directly observes an event, for example, young infants expect the agent to have information about it. However, no investigation has yet examined whether young infants also track what information agents can obtain through inference, by bringing to bear relevant general knowledge. Building on the finding that by 4 months of age most infants have acquired the physical rule that wide objects can fit into wide containers but not narrow containers, we asked whether 5-month-olds would expect an agent who was searching for a wide toy hidden in her absence to reach for a wide box as opposed to a narrow box. Infants looked significantly longer when the agent selected the narrow box, suggesting that they expected her (a) to share the physical knowledge that wide objects can fit only into wide containers and (b) to infer that the wide toy must be hidden in the wide box. Three additional conditions supported this interpretation. Together, these results cast doubt on two-system accounts of early psychological reasoning, which claim that infants' early-developing system is too inflexible and encapsulated to integrate inputs from other cognitive processes, such as physical reasoning. Instead, the results support one-system accounts and provide new evidence that young infants' burgeoning psychological-reasoning system is qualitatively similar to that of older children and adults.

Novel Insights Into the Role of N6-Methyladenosine RNA Modification in Bone Pathophysiology.

Thus far, there are more than known 150 modifications to RNA, in which common internal modifications of mRNA include N6-methyladenosine (m6A), N1-methyladenosine, and 5-methylcytosine. Among them, m6A RNA modification is one of the highest abundance modifications in eukaryotes, regulating mechanisms controlling gene expression at the post-transcription level. As an invertible and dynamic epigenetic marker, m6A base modification influences almost all vital biological processes, cellular components, and molecular functions. Once the m6A modification process is abnormal, a series of diseases-including cancer, neurological diseases, and growth disorders-will be caused. Besides, several base modification activities also have been created by noncoding RNAs (ncRNAs), for instance, microRNAs, and circular RNAs, long ncRNAs, which were dynamically regulated during bone and cartilage pathophysiology processes. Therefore, it has now been clear that dynamic modification on coding RNAs and ncRNAs represents a completely new way to modulate genetic information. In this review, we highlight up-to-date progress and applications of m6A RNA modification in bone and cartilage pathophysiology, and we discuss the pathological roles and underlying molecular mechanism of m6A modifications in osteoarthritis and osteoporosis and osteosarcoma pathogenesis.

Maternal Reminiscing and Autobiographical Memory Features of Mother-Child Dyads in a Cross-Cultural Context.

Maternal reminiscing styles and mother-child memory features were examined in a cross-cultural context. Fifty-five Chinese (Guangzhou, China) and 48 Australian (Melbourne, Australia) mother-child dyads (child age: 3-6 years) independently retrieved autobiographical memories and jointly discussed past events. Australian mothers used greater elaborative and supportive reminiscing and provided more specific memories than Chinese mothers. Australian children provided greater memory elaboration than Chinese children, but they did not differ in memory specificity. Maternal reminiscing styles and cultural group were independently predictive of child memory elaboration but not specificity. Nonetheless, moderation analyses showed that the two maternal reminiscing styles (elaborative and supportive) interacted to predict child memory specificity. These findings indicate the importance of culture and types of reminiscing on memory development.

Effects of neoadjuvant chemotherapy on respiratory function in patients with breast cancer.

OBJECTIVE: To evaluate changes in chest X-rays, pulmonary function tests (PFTs) and quality of life in female breast cancer patients who had been treated with four cycles of neoadjuvant chemotherapy consisting of a regimen of cyclophosphamide, epirubicin and 5-fluorouracil (CEF regimen), and to determine the correlation between pulmonary function parameters and declined quality of life. METHODS: Twenty-nine eligible female patients diagnosed with breast cancer at the first visit who were 20-60 years old, were classified as the American Society of Anesthesiologists (ASA) I-II and patients whose body mass index (BMI) <30 kg/m2 were recruited and subjected to chest X-ray examinations, PFTs and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30) questionnaire before and after receiving 4 cycles of the CEF regimen. RESULTS: In this study, chest X-rays showed no abnormal changes after chemotherapy, but significant decreases in carbon monoxide diffusing capacity (DLCO) and percentage of the DLCO predicted value (DLCO%) (P<0.001). A significant increase in maximal ventilatory volume (MVV) (P=0.004) was observed, and most patients experienced dyspnea (P=0.031) and fatigue (P<0.001). However, there was no significant correlation between the changes in these PFTs parameters and the results of the EORTC QLQ-C30 (P>0.05). CONCLUSIONS: Neoadjuvant chemotherapy can reduce lung diffusion function and quality of life in females with breast cancer.

Toddlers and infants expect individuals to refrain from helping an ingroup victim's aggressor.

Adults and older children are more likely to punish a wrongdoer for a moral transgression when the victim belongs to their group. Building on these results, in violation-of-expectation experiments (n = 198), we examined whether 2.5-year-old toddlers (Exps. 1 and 2) and 1-year-old infants (Exps. 3 and 4) would selectively expect an individual in a minimal group to engage in third-party punishment (TPP) for harm to an ingroup victim. We focused on an indirect form of TPP, the withholding of help. To start, children saw a wrongdoer steal a toy from a victim while a bystander watched. Next, the wrongdoer needed assistance with a task, and the bystander either helped or hindered her. The group memberships of the wrongdoer and the victim were varied relative to that of the bystander and were marked with either novel labels (Exps. 1 and 2) or novel outfits (Exps. 3 and 4). When the victim belonged to the same group as the bystander, children expected TPP: At both ages, they detected a violation when the bystander chose to help the wrongdoer. Across experiments, this effect held whether the wrongdoer belonged to the same group as the bystander and the victim or to a different group; it was eliminated when the victim belonged to a different group than the bystander, when groups were not marked, and when either no theft occurred or the wrongdoer was unaware of the theft. Toddlers and infants thus expect individuals to refrain from helping an ingroup victim's aggressor, providing further evidence for an early-emerging expectation of ingroup support.

[Influence of dexamethasone on the incidence of postoperative nausea and vomiting in breast cancer patients with neoadjuvant chemotherapy].

OBJECTIVE: To evaluate the influence of dexamethasone on the incidence of postoperative nausea and vomiting (PONV) in patients undergoing modified radical mastectomy with neoadjuvant chemotherapy. METHODS: In a prospective trial, 280 female (18-60 years) breast cancer patients undergoing modified radical mastectomy with neoadjuvent chemotherapy were randomized to two groups: one with dexamethasone (Group D) and one without dexamethasone (Group C, n=140). In each group, anesthesia was maintained with volatile anesthesia or total intravenous anesthesia (TIVA): TIVA (propofol) without dexamethasone (Subgroup CP); volatile anesthesia (sevoflurane) without dexamethasone (Subgroup CS); TIVA with 10 mg dexamethasone intravenously before anesthetic induction (Subgroup DP); volatile anesthesia with 10 mg dexamethasone intravenously before anesthetic induction (Subgroup DS). A standard general anesthetic technique was used. All the patients received 8 mg of ondansetron intravenously 30 minutes before the end of surgical procedures. The incidence of PONV during the 24-hour postoperative period was recorded. A Logistic regression analysis was conducted to examine relevant factors for PONV. The tested factors were: age, body mass index (BMI), duration of surgery, postoperative pain, history of motion sickness/PONV, with or without dexamethasone and anesthetic regimen. RESULTS: There was a significant lower incidence of PONV in the patients who received dexamethasone than in those who received placebo during the 24-hour postoperative period (11.4% vs. 20.7%, P=0.034). In the early postoperative period (0-2 h) dexamethasone reduced the incidence of PONV ( 1.4%vs.6.4%, P=0.031), but in the late postoperative period (2-24 h) the difference of the incidence was insignificantly (10.7% vs. 17.9%, P=0.088). No differences were found between TIVA and volatile anesthesia in the 24-hour postoperative period. Dexamethasone was effective to prevent PONV(OR=0.447, P=0.030), and history of PONV or motion sickness was the risk factor of PONV (OR=15.730, P<0.001). CONCLUSION: Dexamethasone prevents PONV effectively in patients undergoing modified radical mastectomy with neoadjuvant chemotherapy, and TIVA cannot decrease the incidence of PONV in the 24-hour postoperative period in those patients.

Subclinical peripheral neuropathy in patients with multiple myeloma before chemotherapy is correlated with decreased fingertip innervation density.

PURPOSE: The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy. PATIENTS AND METHODS: QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy. RESULTS: Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold. CONCLUSION: Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density.