Silicon Analogues of Cyclopropyl Radical Derived from a Highly Stable Cyclic Disilene Compound Featuring a Si-Br Bond.

A halogen-substituted cyclic disilene compound, bromocyclotrisilene, Si3Br(Eind)3 (3a), bearing fused-ring bulky Eind (a: R1 = R2 = Et) groups, has been synthesized as an extraordinarily air-stable compound by the reduction of 1,2-dibromodisilene, (Eind)BrSi═SiBr(Eind) (2a), or tribromosilane, (Eind)SiBr3 (1a), with the Mg or Li metal. The X-ray diffraction analysis of 3a showed that the disilene moiety has an almost planar, but slightly trans-bent structure. Even though 3a is quite air-stable both in solutions and in the solid state, its Si-Br bond is reactive under reducing conditions. The further treatment of 3a with the Li metal leads to the formation of room-temperature thermally stable silicon homologues of the cyclopropyl radical, i.e., the cyclotrisilanyl radicals (6a) [6a(syn) and 6a(anti)], via intramolecular C-H bond activation in a transient silicon homologue of the cyclopropenyl radical, i.e., the cyclotrisilenyl radical, [Si3(Eind)3]• (5a). The formation mechanism of 6a from 5a is discussed based on the theoretical calculations. The unique structural and electronic properties of these Si3 three-membered ring species incorporating the Eind groups have been experimentally and theoretically investigated.

Effects of different doses of caffeine on cognitive performance in healthy physically active individuals.

PURPOSE: Caffeine is a potent central nervous system stimulant that increases the activity of the prefrontal cortex and can improve various cognitive skills. An improvement in these cognitive skills can lead to further benefits in athletic performance. Therefore, it is necessary to clarify the dose-response of caffeine on cognitive performance. This study aimed to determine the effects of different doses of caffeine on sport-related cognitive aspects. METHODS: Twenty-nine healthy physically active young adults were recruited. All participants completed three trials under the following conditions: (a) placebo, (b) 3 mg/kg, or (c) 6 mg/kg body mass of caffeine. In each trial, different cognitive abilities were evaluated with the following battery of tests: reaction time (Dynavision™ D2), anticipation (Bassin Anticipation Timer), sustained attention (Go/No-Go and Eriksen Flanker Test) and memory tests. Moreover, the side effects and the perceived sensation index were recorded 24 h after each test. RESULTS: Reaction time only improved following 6 mg/kg of caffeine intake (Physical reaction time: -0.04 s, 95% CI -0.08 to -0.01 s, P = 0.036, d = 0.5; Motor reaction time: -0.04 s, 95% CI -0.07 to -0.01 s, P = 0.008, d = 0.6) compared to the placebo condition. Anticipation, sustained attention, and memory were not affected after either caffeine dose intake (all P > 0.05). In addition, the 6 mg/kg dose of caffeine augmented the occurrence of the side effects of increased activeness (P = 0.046) and nervousness (P = 0.001). CONCLUSION: Acute intake of 6 mg/kg caffeine is effective in improving reaction time despite increasing the occurrence of side effects in healthy physically active young adults. STUDY REGISTRATION: This study has been registered in ClinicalTrials whose ID is: NCT05995314 (2023-08-08).

Electrochemical sensor for glutathione reductase based on screen-printed electrodes coated with 3,5-dinitrobenzoic acid-modified carbon nanotubes.

The preparation of a hybrid nanomaterial is reported by covalently attaching 3,5-dinitrobenzoic acid groups to the surface of oxidized multi-walled carbon nanotubes using 1,6-diaminohexane as cross-linking agent. This nanomaterial, modified with the redox mediator, was used as transduction element to construct an amperometric sensor for the efficient indirect determination of glutathione reductase at a low working potential of - 0.05 V, through the oxidation of unconsumed nicotinamide adenine dinucleotide phosphate (NADPH) in the enzymatic reaction. The sensor exhibited an excellent linear response in the range 1.6 to 174 µU/µL, with high reproducibility and selectivity. The developed device was successfully validated in real samples, accurately determining the active enzyme in diluted human serum, making it a promising alternative for the determination of glutathione reductase and other related NADPH-dependent enzymes with relevance in clinical analysis.

General and Substantive Accountability in Nursing Home Services: Assessing Messages from the Demand Side and the Supply Side.

This study examines the extent to which general and substantive accountability is integrated into the language used by key actors involved in nursing home services. Particularly, we investigate the messages used by the supply side, which includes public and private organizations involved in residential care for older adults, and the demand side, which comprises organizations representing service beneficiaries. Moreover, we explore the alignment between the messages used by both sides of the accountability relationship. In the context of Spanish nursing homes, we analyzed a corpus of tweets by organizations from both sides of the accountability relationship, from one year before the outbreak of COVID-19 restrictions to after their implementation. Using text analysis techniques, we found that messages related to general and substantive accountability had a low priority before and after the outbreak. Public organizations were slightly more likely to employ general accountability terms than private organizations. This is particularly in non-crisis situations, although less frequently than organizations representing beneficiaries. Our analysis demonstrates a lack of convergence between the messaging on the supply and demand sides, indicating a communication breakdown between the two sides in the accountability relationship.

Lysophosphatidylinositol Promotes Chemotaxis and Cytokine Synthesis in Mast Cells with Differential Participation of GPR55 and CB2 Receptors.

Mast cells (MCs) are the main participants in the control of immune reactions associated with inflammation, allergies, defense against pathogens, and tumor growth. Bioactive lipids are lipophilic compounds able to modulate MC activation. Here, we explored some of the effects of the bioactive lipid lysophosphatidylinositol (LPI) on MCs. Utilizing murine bone marrow-derived mast cells (BMMCs), we found that LPI did not cause degranulation, but slightly increased FcεRI-dependent ß-hexosaminidase release. However, LPI induced strong chemotaxis together with changes in LIM kinase (LIMK) and cofilin phosphorylation. LPI also promoted modifications to actin cytoskeleton dynamics that were detected by an increase in cell size and interruptions in the continuity of the cortical actin ring. The chemotaxis and cortical actin ring changes were dependent on GPR55 receptor activation, since the specific agonist O1602 mimicked the effects of LPI and the selective antagonist ML193 prevented them. The LPI and O1602-dependent stimulation of BMMC also led to VEGF, TNF, IL-1α, and IL-1ß mRNA accumulation, but, in contrast with chemotaxis-related processes, the effects on cytokine transcription were dependent on GPR55 and cannabinoid (CB) 2 receptors, since they were sensitive to ML193 and to the specific CB2 receptor antagonist AM630. Remarkably, GPR55-dependent BMMC chemotaxis was observed towards conditioned media from distinct mouse and human cancer cells. Our data suggest that LPI induces the chemotaxis of MCs and leads to cytokine production in MC in vitro with the differential participation of GPR55 and CB2 receptors. These effects could play a significant role in the recruitment of MCs to tumors and the production of MC-derived pro-angiogenic factors in the tumor microenvironment.

Eagle's syndrome as a cause of oropharyngeal dysphagia.

Eagle's syndrome is a little known entity defined as the elongation of the stylohyoid process and/or calcification of the stylohyoid ligament. It is a rare pathology that due to its presentation and possible complications should be taken into consideration in the differential diagnosis of oropharyngeal dysphagia. We present the case of a patient with Eagle's syndrome as well as essential aspects in the diagnosis and treatment of this entity.

Endoscopic rescue of a fistulizing biliary plastic stent.

55-year-old male with a history of cholecystectomy complicated by perforation of the common bile duct, contained with placement of a plastic biliary stent. He presented several subsequent episodes of recurrent cholangitis secondary to biliary lithiasis and residual benign stenosis of the common bile duct, resolved with the implantation of plastic biliary prostheses. Finally, given the recurrent episodes of cholangitis, it was agreed to perform a hepaticojejunostomy. During the operation, the last implanted stent was not detected, which was identified by CT scan of the abdomen, causing a fistulous tract between the duodenum and the ascending colon. The stent was removed endoscopically, without complications, and the fistulous tract was resolved.

Determination of essential biomarkers in lung cancer: a real-world data study in Spain with demographic, clinical, epidemiological and pathological characteristics.

BACKGROUND: The survival of patients with lung cancer has substantially increased in the last decade by about 15%. This increase is, basically, due to targeted therapies available for advanced stages and the emergence of immunotherapy itself. This work aims to study the situation of biomarker testing in Spain. PATIENTS AND METHODS: The Thoracic Tumours Registry (TTR) is an observational, prospective, registry-based study that included patients diagnosed with lung cancer and other thoracic tumours, from September 2016 to 2020. This TTR study was sponsored by the Spanish Lung Cancer Group (GECP) Foundation, an independent, scientific, multidisciplinary oncology society that coordinates more than 550 experts and 182 hospitals across the Spanish territory. RESULTS: Nine thousand two hundred thirty-nine patients diagnosed with stage IV non-small cell lung cancer (NSCLC) between 2106 and 2020 were analysed. 7,467 (80.8%) were non-squamous and 1,772 (19.2%) were squamous. Tumour marker testing was performed in 85.0% of patients with non-squamous tumours vs 56.3% in those with squamous tumours (p-value < 0.001). The global testing of EGFR, ALK, and ROS1 was 78.9, 64.7, 35.6% respectively, in non-squamous histology. PDL1 was determined globally in the same period (46.9%), although if we focus on the last 3 years it exceeds 85%. There has been a significant increase in the last few years of all determinations and there are even close to 10% of molecular determinations that do not yet have targeted drug approval but will have it in the near future. 4,115 cases had a positive result (44.5%) for either EGFR, ALK, KRAS, BRAF, ROS1, or high PDL1. CONCLUSIONS: Despite the lack of a national project and standard protocol in Spain that regulates the determination of biomarkers, the situation is similar to other European countries. Given the growing number of different determinations and their high positivity, national strategies are urgently needed to implement next-generation sequencing (NGS) in an integrated and cost-effective way in lung cancer.

Alcohol and early mortality (before 65 years) in the 'Seguimiento Universidad de Navarra' (SUN) cohort: does any level reduce mortality?

The aim of this study was to assess the association between alcohol intake and premature mortality (younger than 65 years) and to explore the effect of potential alcohol underreporting by heavy drinkers. We followed-up 20 272 university graduates. Four categories of alcohol intake were considered (abstainer, light, moderate and heavy consumption). Repeated measurements of alcohol intake and updated information on confounders were used in time-dependent Cox models. Potential underreporting of alcohol intake by some heavy drinkers (likely misclassified as light or moderate drinkers) was explicitly addressed in an attempt to correct potential underreporting by using indirect information. During 12·3 years of median follow-up (interquartile range: 6·8-15·0), 226 participants died before their 65th birthday. A higher risk of early mortality was found for the highest category of alcohol intake (≥50 g/d) in comparison with abstention (multivariable-adjusted hazard ratio (HR) = 2·82, 95 % CI 1·38, 5·79). In analyses of alcohol as a continuous variable, the multivariable-adjusted HR was 1·17 (95 % CI 1·08, 1·26), for each 10 g/d of alcohol. This harmful linear association was present both in uncorrected models and in models corrected for potential underreporting. No significant inverse association between light or moderate alcohol intake and premature mortality was observed, even after correcting for potential misclassification. Alcohol intake exhibited a harmful linear dose-response association with premature mortality (<65 years) in this young and highly educated Mediterranean cohort. Our attempts to correct for potential misclassification did not substantially change these results.

Mast Cells Localize in Hypoxic Zones of Tumors and Secrete CCL-2 under Hypoxia through Activation of L-Type Calcium Channels.

Hypoxia is a condition that together with low pH, high amounts of reactive oxygen species (ROS), and increased adenosine levels characterize tumor microenvironment. Mast cells (MCs) are part of tumor microenvironment, but the effect of hypoxia on the production of MC-derived cytokines has not been fully described. Using the hypoxia marker pimonidazole in vivo, we found that MCs were largely located in the low-oxygen areas within B16-F1 mice melanoma tumors. In vitro, hypoxia promoted ROS production, a ROS-dependent increase of intracellular calcium, and the production of MCP 1 (CCL-2) in murine bone marrow-derived MCs. Hypoxia-induced CCL-2 production was sensitive to the antioxidant trolox and to nifedipine, a blocker of L-type voltage-dependent Ca2+ channels (LVDCCs). Simultaneously with CCL-2 production, hypoxia caused the ROS-dependent glutathionylation and membrane translocation of the α1c subunit of Cav1.2 LVDCCs. Relationship between ROS production, calcium rise, and CCL-2 synthesis was also observed when cells were treated with H2O2 In vivo, high CCL-2 production was detected on hypoxic zones of melanoma tumors (where tryptase-positive MCs were also found). Pimonidazole and CCL-2 positive staining diminished when B16-F1 cell-inoculated animals were treated with trolox, nifedipine, or the adenosine receptor 2A antagonist KW6002. Our results show that MCs are located preferentially in hypoxic zones of melanoma tumors, hypoxia-induced CCL-2 production in MCs requires calcium rise mediated by glutathionylation and membrane translocation of LVDCCs, and this mechanism of CCL-2 synthesis seems to operate in other cells inside melanoma tumors, with the participation of the adenosine receptor 2A.

Electrochemical aptasensor based on anisotropically modified (Janus-type) gold nanoparticles for determination of C-reactive protein.

Novel Janus nanoparticles based on Au colloids anisotropically modified with polyamidoamine dendrons were prepared though a masking/toposelective modification approach. These nanomaterials were further functionalized with horseradish peroxidase on the dendritic face and provided on the opposite metal surface with a ssDNA aptamer for C-reactive protein (CRP). The resulting nanoparticles were employed as biorecognition/signaling elements to construct an amperometric aptasensor with sandwich-type architecture for the specific detection of this cardiac biomarker. To do this, screen-printed carbon electrodes modified with electrodeposited Au nanoparticles and functionalized with anti-CRP aptamers were used as transduction interface. The aptasensor was employed for the amperometric detection of CRP (working potential: - 200 mV vs pseudo-Ag/AgCl) in the broad range from 10 pg·mL-1 to 1.0 ng·mL-1 with a detection limit of 3.1 pg·mL-1. This electroanalytical device also showed good specificity, reproducibility (RSD = 9.8%, n = 10), and stability and was useful to quantify CRP in reconstituted human serum samples, with a RSD of 13.3%.

The Applicability of Shear Wave Elastography to Assess Myotendinous Stiffness of Lower Limbs during an Incremental Isometric Strength Test.

The aim of the study was to describe the applicability of shear wave elastography to assess muscular and tendinous stiffness of the lower limbs during an incremental isometric strength test and to differentiate the stiffness evolution between superficial and deep muscle regions. Dominant rectus femoris and patellar tendons of 30 physically active people (28.3 ± 9.2 years, 173.2 ± 7.7 cm, 76.2 ± 12.6 kg) were measured in different isometric strength conditions (relaxed muscle, and at 10%, 20%, 30%, 40%, 50% and 60% of maximal voluntary contraction (MVC)). The percentage of success was >85% at all muscle contraction intensities for rectus femoris muscles but only in a relaxed condition for patellar tendons. Rectus femoris stiffness significantly increased compared to the relaxed condition from 30% to 60% MVC (p ≤ 0.011) in superficial muscle regions, and from 10% to 60% MVC (p ≤ 0.002) in deep muscle regions. Deep muscle regions showed higher stiffness values than superficial muscle regions at 30% MVC (51.46 ± 38.17 vs. 31.83 ± 17.05 kPa; p = 0.019), 40% MVC (75.21 ± 42.27 vs. 51.25 ± 28.90 kPa; p = 0.018), 50% MCV (85.34 ± 45.05 vs. 61.16 ± 37.03 kPa; p = 0.034) and 60% MVC (109.29 ± 40.04 vs. 76.67 ± 36.07 kPa; p = 0.002). Rectus femoris stiffness increased during the incremental isometric contraction test, and inter-region differences were found at 30% MVC.

Therapeutic approach of esophageal bezoar due to enteral feed.

Enteral feed bezoars are a rare and difficult to treat complication of enteral feeding. In our case, we report the case of a young man with prolonged admission at the intensive care unit; who requires enteral nutrition. This doesn't run properly after a week; which is why we performed an endoscopy with the finding of an esophageal bezoar that didn't respond to endoscopic treatment at first; being finallay resolved with a second endoscopic therapy after treatment with solvent substances.

Disconnected pancreatic duct syndrome. Endoscopic approach.

Disconnected pancreatic duct syndrome (DPCS) is due to disruption of the main pancreatic duct (PC) or its secondary branches, a complication present in 30-80% of acute necrotizing pancreatitis. The secretion of pancreatic enzymes by isolated functioning pancreatic tissue can facilitate the recurrence of encapsulated necrotic collections, so its endoscopic management remains a controversial issue in daily practice. We present a case of disconnected pancreatic duct syndrome resolved after placement of a pancreatic stent.

TLR4 Receptor Induces 2-AG-Dependent Tolerance to Lipopolysaccharide and Trafficking of CB2 Receptor in Mast Cells.

Mast cells (MCs) contribute to the control of local inflammatory reactions and become hyporesponsive after prolonged TLR4 activation by bacterial LPS. The molecular mechanisms involved in endotoxin tolerance (ET) induction in MCs are not fully understood. In this study, we demonstrate that the endocannabinoid 2-arachidonoylglycerol (2-AG) and its receptor, cannabinoid receptor 2 (CB2), play a role in the establishment of ET in bone marrow-derived MCs from C57BL/6J mice. We found that CB2 antagonism prevented the development of ET and that bone marrow-derived MCs produce 2-AG in a TLR4-dependent fashion. Exogenous 2-AG induced ET similarly to LPS, blocking the phosphorylation of IKK and the p65 subunit of NF-κB and inducing the synthesis of molecular markers of ET. LPS caused CB2 receptor trafficking in Rab11-, Rab7-, and Lamp2-positive vesicles, indicating recycling and degradation of the receptor. 2-AG also prevented LPS-induced TNF secretion in vivo, in a MC-dependent model of endotoxemia, demonstrating that TLR4 engagement leads to 2-AG secretion, which contributes to the negative control of MCs activation. Our study uncovers a functional role for the endocannabinoid system in the inhibition of MC-dependent innate immune responses in vivo.

Objective Assessment of Regional Stiffness in Vastus Lateralis with Different Measurement Methods: A Reliability Study.

The objective of this study was to evaluate the reliability of four methods of assessing vastus lateralis (VL) stiffness, and to describe the influence of structural characteristics on them. The stiffness of the dominant lower-limb's VL was evaluated in 53 healthy participants (28.4 ± 9.1 years) with shear wave elastography (SWE), strain elastography (SE), myotonometry and tensiomyography (TMG). The SWE, SE and myotonometry were performed at 50%, and TMG was assessed at 30%, of the length from the upper pole of the patella to the greater trochanter. The thickness of the VL, adipose tissue and superficial connective tissue was also measured with ultrasound. Three repeated measurements were acquired to assess reliability, using intraclass correlation coefficients (ICC). Pearson's correlation coefficients were calculated to determine the relationships between methodologic assessments and between structural characteristics and stiffness assessments of the VL. Myotonometry (ICC = 0.93; 95%-CI = 0.89,0.96) and TMG (ICC = 0.89; 95%-CI = 0.82,0.94) showed excellent inter-day reliability whereas with SWE (ICC = 0.62; 95%-CI = 0.41,0.77) and SE (ICC = 0.71; 95%-CI = 0.57,0.81) reliability was moderate. Significant correlations were found between myotonometry and VL thickness (r = 0.361; p = 0.008), adipose tissue thickness (r = -0.459; p = 0.001) and superficial connective tissue thickness (r = 0.340; p = 0.013). Myotonometry and TMG showed the best reliability values, although myotonometry stiffness values were influenced by the structural variables of the supra-adjacent tissue.

Influence of Badminton Practice on Age-Related Changes in Patellar and Achilles Tendons.

Regular sport practice could prevent age-related changes in tendinous tissues. The purpose of the study was to investigate the effect of regular badminton practice on patellar and Achilles tendon mechanical properties in senior competitive badminton players (>35 years old) and to compare the results with physically active people matched by age. One hundred ninety-two badminton players and 193 physically active people were divided by age into four groups, between 35 and 44 (U45), between 45 and 54 (U55), between 55 and 64 (U65), and over 65 (O65) years old. A LogiqS8 transducer in elastography mode and a MyotonPRO myotonometer were used to assess patellar and Achilles mechanical properties. Achilles tendon stiffness was higher in the control group than the badminton players for the U45, U55, and O65 age groups (p < .01). Also, the elastography index was higher in the control group than the badminton players for the U45, U55, U65, and O65 age groups (p < .05). In conclusion, regular badminton practice could prevent the decline in mechanical properties of the patellar and Achilles tendons.

Institutional arthroplasty registry: what is the minimum acceptable dataset to be included in your hospital? Recommendations from a single-country national consensus using the Delphi method.

PURPOSE: Institutional arthroplasty registries are very popular nowadays; however, very few efforts have been made in order to standardize the information to be collected, thus limiting the possibility of inter-institutional data interpretation. This manuscript reports the results of a single-country consensus designed to define the minimum standardized dataset to be recorded within an institutional arthroplasty registry. METHODS: A national consensus was carried out among all members of the Colombian Society of Hip and Knee Surgeons using the Delphi method. Eleven questions and answers comprising every potential domain of an institutional registry of hip and knee arthroplasty were defined. According to the methodology, anonymous voting and multiple discussion rounds were performed. Three levels of agreement were defined: Strong consensus: equal to or greater than 80%, weak consensus between 70 and 79.9%, and no consensus below 70%. RESULTS: All of the questions reached consensus level. The minimum dataset was defined to include demographic and clinical information, intraoperative and implant details, follow-up and early complications, implant survival, and functional outcome scores, as well as the validation model to assess information quality within the database. Currently, this dataset is being implemented voluntarily by the members of our national society. DISCUSSION: A national consensus is a feasible method to build homogeneous arthroplasty registries. We recommend such an exercise since it establishes the basis to compare and add data between institutions and the joint analysis of said information in a national registry.

Is gastroparesis that is often detected in patients with alcoholic chronic liver disease a manifestation of an autonomic dysfunction syndrome? A preliminary study.

BACKGROUND: the autonomic dysfunction defines the neuropathy of the autonomic nervous system. The prevalence of the gastric dysmotility and its relationship with the autonomic dysfunction in patients with alcohol chronic liver disease is not well known. METHODS: thirty-six patients with alcohol chronic liver disease and 25 healthy controls were evaluated, in order to detect an autonomic dysfunction through different cardiovascular reflexes and gastric emptying tests. RESULTS: ninety-four per cent of the patients showed an impaired R index (variations in heart rate during six deep inspirations-expirations per minute) and/or S/S-HR (variations in heart rate when standing from a supine position). Seventy-five per cent of the patients showed gastroparesis (T1/2: gastric half-emptying time was delayed). There was a correlation between the R index and T1/2 (r = -0.49; p < 0.01). CONCLUSIONS: we suggest that gastroparesis detected in alcoholic chronic liver disease is another clinical manifestation of the autonomic parasympathetic dysfunction.

Mutant Huntingtin affects toll-like receptor 4 intracellular trafficking and cytokine production in mast cells.

BACKGROUND: Huntington's disease (HD) is caused by the expression of a mutated variant of Huntingtin (mHtt), which results in the complex pathology characterized by a defective function of the nervous system and altered inflammatory responses. While the neuronal effects of mHtt expression have been extensively studied, its effects on the physiology of immune cells have not been fully described. Mast cells (MCs) are unique tissue-resident immune cells whose activation has been linked to protective responses against parasites and bacteria, but also to deleterious inflammatory allergic reactions and, recently, to neurodegenerative diseases. METHODS: Bone marrow-derived mast cells (BMMCs) were obtained from wild-type (WT-) and mHtt-expressing (R6/1) mice to evaluate the main activation parameters triggered by the high-affinity IgE receptor (FcεRI) and the Toll-like receptor (TLR) 4. Degranulation was assessed by measuring the secretion of ß-hexosaminidase, MAP kinase activation was detected by Western blot, and cytokine production was determined by RT-PCR and ELISA. TLR-4 receptor and Htt vesicular trafficking was analyzed by confocal microscopy. In vivo, MC-deficient mice (c-KitWsh/Wsh) were intraperitonally reconstituted with WT or R6/1 BMMCs and the TLR4-induced production of the tumor necrosis factor (TNF) was determined by ELISA. A survival curve of mice treated with a sub-lethal dose of bacterial lipopolysaccharide (LPS) was constructed. RESULTS: R6/1 BMMCs showed normal ß-hexosaminidase release levels in response to FcεRI, but lower cytokine production upon LPS stimulus. Impaired TLR4-induced TNF production was associated to the lack of intracellular dynamin-dependent TLR-4 receptor trafficking to perinuclear regions in BMMCs, a diminished ERK1/2 and ELK-1 phosphorylation, and a decrease in c-fos and TNF mRNA accumulation. R6/1 BMMCs also failed to produce TLR4-induced anti-inflammatory cytokines (like IL-10 and TGF-ß). The detected defects were also observed in vivo, in a MCs-dependent model of endotoxemia. R6/1 and c-KitWsh/Wsh mice reconstituted with R6/1 BMMCs showed a decreased TLR4-induced TNF production and lower survival rates to LPS challenge than WT mice. CONCLUSIONS: Our data show that mHtt expression causes an impaired production of pro- and anti-inflammatory mediators triggered by TLR-4 receptor in MCs in vitro and in vivo, which could contribute to the aberrant immunophenotype observed in HD.