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Purpose: To investigate the feasibility and initial results of superior (SRA) and middle (MRA) rectal artery embolization for patients with symptomatic hemorrhoidal disease., Materials and Methods: Prospective, single-center cohort that included ten consecutive patients (Goligher classification was II in 70% and III in 30%.) who underwent SRA and MRA embolization using a combination of microspheres and metallic coils, who completed a follow-up period of 12 months. Technical success was defined as embolization of SRA and MRA whenever MRA dominance was observed. Clinical success was defined as an improvement of the hemorrhoid severity score (HSS) and quality of life (QoL) scores without recurrence, with the need for additional treatment. Procedure-related adverse events (AEs) were recorded and defined according to CIRSE classification as minor or major complications., Results: Technical success was achieved in all patients. SRA was embolized in 100% of patients and MRA in 80%. The improvement in HSS and QoL scores was 88% and 88% (p < 0.05), respectively, without clinical recurrence in the 12-month follow-up. One patient had a major complication (level D), a rectal ischemia and perforation of the rectosigmoid leading to perforative acute abdomen with sepsis that required surgical treatment (Hartmann's procedure)., Conclusion: Embolization of both SRA-MRA using a combination of microspheres and metallic coils was feasible and significantly improved HSS and QoL scores. One major complication was observed and therefore it is essential to further investigate the safety boundaries of this technique., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interest. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent for publication: Consent for publication was obtained for every individual person’s data included in the study. Informed consent: Informed consent was obtained from all individual participants included in the study., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Introduction: Spinal cord stimulation (SCS) represents an established interventional pain therapeutic; however, the SCS effects of SCS waveforms on motor neuron recruitment of the lower limbs of chronic pain patients remain largely unknown., Methods: We investigated these effects by performing isometric ankle-dorsal flexions at varying force levels under four SCS conditions: SCS Off (1 week), burst SCS (40 Hz), SCS Off (acute), and tonic SCS (130 Hz). Muscle activity was recorded via high-density surface electromyography (64-electrode grid) on the tibialis anterior muscle. Motor unit action (MUs) potentials were analyzed for recruitment and de-recruitment thresholds, discharge rate, inter-spike interval, and common synaptic input., Results: In this prospective study, we included nine patients (five females; four males; mean age 59 years) with chronic pain treated with thoracic (Th7-Th8) epidural spinal stimulation. A total of 97 MUs were found for 15% maximal voluntary torque (MVT) and 83 for 30%MVT, an average of 10.8 ± 3.7 for 15%MVT and 10.4 ± 3.5 for 30%MVT. While a few subject-specific variations were observed, our study suggests that the different SCS frequencies applied do not significantly influence motor unit discharge characteristics in the TA muscle among the participants (p values at 15%MVT were 0.586 (Chi 2  = 1.933), 0.737 (Chi 2  = 1.267), 0.706 (Chi 2  = 1.4) and 0.586 (Chi 2  = 1.933), respectively. The p values of the Friedman test at 30%MVT were 0.896 (Chi 2  = 0.6), 0.583 (Chi 2  = 1.95), 0.896 (Chi 2  = 0.6) and 0.256 (Chi 2  = 4.05). No significant difference was found for the different stimulation types for the delta (0-5 Hz), alpha (5-12 Hz), and beta (15-30 Hz) bands at both force levels., Conclusions: In summary, we did not observe any changes in motor unit oscillatory activity at any low and high bandwidths, indicating that SCS using different waveforms (tonic/burst) does not significantly influence motor neuron recruitment for non-motor individuals with chronic pain., (© 2024. The Author(s).)

Host condition is key in understanding disease dynamics. In an urban population of Rattus norvegicus, we aimed to assess whether infection of Leptospira interrogans and helminths was associated with patterns of host hematological and hormone-biochemical stress-related conditions. Rat kidney imprints and urine were used to identify and quantify L. interrogans, and feces samples for helminth eggs and corticosterone metabolites. Blood samples were taken for complete blood counts and specific biochemicals in rats' sera. Principal Component Analyses were performed to check whether rats would be grouped according to health profiles. We obtained hematological and hormone-biochemical data from 95 and 61 rats, respectively. Hematological PCA revealed distinct rat groups: typical (T), eosinophil deficient (Eos-D), eosinophil- and monocyte- deficient (EM-D) and monocyte deficient with high immature neutrophils (Mon-D). No association between L. interrogans or helminths and rat health profiles was observed, except with Trichiuridae, which mean intensity was significantly higher when all deficient groups were pooled together compared to the T-group. The poorest condition group was found in areas with fewer rat burrows than the T-group, indicating EM-D had a reduced ability to occupy "good" quality habitats. In natural populations, hematological profiles may reflect host's overall condition, instead of responses to specific infections., Competing Interests: Author Disclosure Statement No competing financial interests exist.

Objective: Surface electromyography (sEMG) can sense the motor commands transmitted to the muscles. This work presents a deep learning method that can decode the electrophysiological activity of the forearm muscles into the movements of the human hand., Methods: We have recorded the kinematics and kinetics of the hand during a wide range of grasps and individual digit movements that cover 22 degrees of freedom of the hand at slow (0.5 Hz) and comfortable (1.5 Hz) movement speeds in 13 healthy participants. The input of the model consists of 320 non-invasive EMG sensors placed on the extrinsic hand muscles., Results: Our network achieves accurate continuous estimation of both kinematics and kinetics, surpassing the performance of comparable networks reported in the literature. By examining the latent space of the network, we find evidence that it mapped EMG activity into the anatomy of the hand at the individual digit level. In contrast to what is observed from the low-pass filtered EMG and linear decoding approaches, we found that the full-bandwidth EMG (monopolar unfiltered) signals during synergistic and individual digit movements contain distinct neural embeddings that encode each movement of the human hand. These manifolds consistently represent the anatomy of the hand and are generalized across participants. Moreover, we found a task-specific distribution of the embeddings without any presence of correlated activations during multi- and individual-digit tasks., Conclusion/significance: The proposed method could advance the control of assistive hand devices by providing a robust and intuitive interface between muscle signals and hand movements.

We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a-d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro, mechanistic studies demonstrated target activity for PfHDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c, 7c, and 8c, identified as the most active in phenotypic assays and PfHDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of PfHDAC1, with an IC 50 value of 0.74 µM in the phenotypic screening on Pf3D7 and 0.8 µM against multidrug-resistant PfDd2 parasites. Despite its potent inhibition of PfHDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with PfHDAC1 and that this compound series could bind as well as in HsHDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs., (© 2023. The Author(s).)

Dogs with visceral leishmaniasis play a key role in the transmission cycle of Leishmania infantum to humans in the urban environment. There is a consensus regarding the importance of developing a vaccine to control this disease. Despite many efforts to develop a protective vaccine against CVL, the ones currently available, Leish-tec ® and LetiFend ® , have limited effectiveness. This is due, in part, to the complexity of the immune response of the naturally infected dogs against the parasite and the complexity of the parasite transmission cycle. Thus, strategies, such as the development of a transmission-blocking vaccines (TBVs) already being applied to other vector-borne diseases like malaria and dengue, would be an attractive alternative to control leishmaniasis. TBVs induce the production of antibodies in the vertebrate host, which can inhibit parasite development in the vector and/or interfere with aspects of vector biology, leading to an interruption of parasite transmission. To date, there are few TBV studies for CVL and other leishmaniasis forms. However, the few studies that exist show promising results, thus justifying the further development of this approach.

Introduction: Chronic refractory pain of various origin occurs in 30-45% of pain patients, and a considerable proportion remains resistant to pharmacological and behavioral therapies, requiring adjunctive neurostimulation therapies. Chronic pain is known to stimulate sympathetic outflow, yet the impact of burst motor cortex stimulation (burstMCS) on objectifiable autonomic cardiovascular parameters in chronic pain remains largely unknown., Methods: In three patients with chronic pain (2 facial pain/1 post-stroke pain), we compared pain intensity using a visual analog scale (VAS 1-10) and parameters of autonomic cardiovascular modulation at supine rest, during parasympathetic challenge with six cycles per minute of metronomic deep breathing, and during sympathetic challenge (active standing) at baseline and after 4 months of burstMCS compared to age-/gender-matched healthy controls., Results: While two out of three patients were responsive after 4 months of adjunctive burstMCS (defined as pain reduction of > 30%), no differences were found in any of the three patients regarding the R-R intervals of adjacent QRS complexes (RRI, 642 vs. 676 ms) and blood pressure (BP, 139/88 vs. 141/90 mmHg). Under resting conditions, parameters of parasympathetic tone [normalized units of high-frequency oscillations of RRI (RRI-HFnu power) 0.24 vs. 0.38, root-mean-square differences of successive RRI (RRI-RMSSD) 7.7 vs. 14.7 ms], total autonomic cardiac modulation [RRI total power 129.3 vs. 406.2 ms 2 , standard deviation of RRI (RRI-SD) 11.6 vs. 18.5 ms, coefficient of variation of RRI (RRI-CV) 1.9 vs. 3.7%], and baroreceptor reflex sensitivity (BRS, 1.9 vs. 2.3 ms/mmHg) increased, and parameters of sympathetic tone [normalized units of low-frequency oscillations of RRI (RRI-LFnu power) 0.76 vs. 0.62] and sympatho-vagal balance [ratio of RR-LF to RRI-HF power (RRI-LF/HF ratio) 3.4 vs. 1.9] decreased after 4 months of burstMCS. Low-frequency oscillations of systolic blood pressure (SBP-LF power), a parameter of sympathetic cardiovascular modulation, increased slightly (17.6 vs. 20.4 mmHg 2 ). During parasympathetic stimulation, the expiratory-inspiratory ratio (E/I ratio) increased slightly, while upon sympathetic stimulation, the ratio between the shortest RRI around the 15th heartbeat and the longest RRI around the 30th heartbeat after standing up (RRI 30/15 ratio) remained unchanged., Conclusion: Four months of adjunctive burstMCS was associated with an increase in parameters reflecting both total and parasympathetic autonomic modulation and baroreceptor reflex sensitivity. In contrast, sympathetic tone declined in our three patients, suggesting stimulation-associated improvement not only in subjectively perceived VAS pain scores, but also in objectifiable parameters of autonomic cardiovascular modulation., (© 2023. The Author(s).)

The aim of this study is to evaluate if single nucleotide polymorphisms (SNPs) in WNT6 and WNT10A are associated with the risk of dental pulp calcification in orthodontic patients. This cross-sectional study followed the "Strengthening the Reporting of Genetic Association Studies" (STREGA) guidelines. Panoramic radiographs (pre- and post-orthodontic treatment) and genomic DNA from 132 orthodontic patients were studied. Dental pulp calcification (pulp stones and/or pulp space narrowing) was recorded in upper and lower first molars. The SNPs in WNT6 and WNT10A (rs7349332, rs3806557, rs10177996, and rs6754599) were assessed through genotyping analysis using DNA extracted from buccal epithelial cells. The association between pulp calcification and SNPs were analyzed using allelic and genotypic distributions and haplotype frequencies (p<0.05). Prevalence of dental pulp calcification was 42.4% in the 490 studied molars. In the genotypic analysis, the SNPs in WNT10A showed a statistically significant value for molar calcification (p = 0.027 for rs1017799), upper molar calcification (p = 0.040 for rs1017799) (recessive model), and molar calcification (p = 0.046 for rs3806557) (recessive model). In the allelic distribution, the allele C of the SNP rs10177996 in WNT10A was associated with molar calcifications (p = 0.042) and with upper first molar calcification (p = 0.035). Nine combinations of haplotypes showed statistically significant value (p<0.05). The findings of this study indicates that SNPs in WNT10A and WNT6 are associated with dental pulp calcification in molars after orthodontic treatment and may be considered as biomarkers for dental pulp calcification., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ramirez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mental fatigue (MF) does not only affect cognitive but also physical performance. This study aimed to explore the effects of MF on muscle endurance, rate of perceived exertion (RPE), and motor units' activity. Ten healthy males participated in a randomised crossover study. The subjects attended two identical experimental sessions separated by 3 days with the only difference of a cognitive task (incongruent Stroop task [ST]) and a control condition (watching a documentary). Perceived MF and motivation were measured for each session at baseline and after each cognitive task. Four contractions at 20% of maximal voluntary contraction (MVIC) were performed at baseline, after each cognitive and after muscle endurance task while measuring motor units by high-density surface electromyography. Muscle endurance until failure at 50% of MVIC was measured after each cognitive task and the RPE was measured right after failure. ST significantly increased MF (p = 0.001) reduced the motivation (p = 0.008) for the subsequent physical task and also impaired physical performance (p = 0.044). However, estimates of common synaptic inputs and motor unit discharge rates as well as RPE were not affected by MF (p > 0.11). In conclusion, MF impairs muscle endurance and motivation for the physical task but not the neural drive to the muscle at any frequency bands. Although it is physiologically possible for mentally fatigued subjects to generate an optimal neuromuscular function, the altered motivation seems to limit physical performance. Preliminarily, our results suggest that the corticospinal pathways are not affected by MF., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Despite available, advanced pharmacological and behavioral therapies, refractory chronic facial pain of different origins still poses a therapeutic challenge. In circumstances where there is insufficient responsiveness to pharmacological/behavioral therapies, deep brain stimulation should be considered as a potential effective treatment option. We performed an individual participant data (IPD) meta-analysis including searches on PubMed, Embase, and the Cochrane Library (2000-2022). The primary endpoint was the change in pain intensity (visual analogue scale; VAS) at a defined time-point of ≤3 months post-DBS. In addition, correlation and regression analyses were performed to identify predictive markers (age, duration of pain, frequency, amplitude, intensity, contact configuration, and the DBS target). A total of seven trials consisting of 54 screened patients met the inclusion criteria. DBS significantly reduced the pain levels after 3 months without being related to a specific DBS target, age, contact configuration, stimulation intensity, frequency, amplitude, or chronic pain duration. Adverse events were an infection or lead fracture (19%), stimulation-induced side effects (7%), and three deaths (unrelated to DBS-from cancer progression or a second stroke). Although comparable long-term data are lacking, the current published data indicate that DBS (thalamic and PVG/PAG) effectively suppresses facial pain in the short-term. However, the low-quality evidence, reporting bias, and placebo effects must be considered in future randomized-controlled DBS trials for facial pain.

Several studies have identified socioeconomic and environmental risk factors for infectious disease, but the relationship between these and knowledge, attitudes, and practices (KAP), and more importantly their web of effects on individual infection risk, have not previously been evaluated. We conducted a cross-sectional KAP survey in an urban disadvantaged community in Salvador, Brazil, leveraging on simultaneously collected fine-scale environmental and epidemiological data on leptospirosis transmission. Residents' knowledge influenced their attitudes which influenced their practices. However, different KAP variables were driven by different socioeconomic and environmental factors; and while improved KAP variables reduced risk, there were additional effects of socioeconomic and environmental factors on risk. For example, males and those of lower socioeconomic status were at greater risk, but once we controlled for KAP, male gender and lower socioeconomic status themselves were not direct drivers of seropositivity. Employment was linked to better knowledge and a less contaminated environment, and hence lower risk, but being employed was independently associated with a higher, not lower risk of leptospirosis transmission, suggesting travel to work as a high risk activity. Our results show how such complex webs of influence can be disentangled. They indicate that public health messaging and interventions should take into account this complexity and prioritize factors that limit exposure and support appropriate prevention practices., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Palma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study aims to evaluate the effects of exercise training on intramuscular lipid content and genes related to insulin pathway in patients with systemic autoimmune myopathies (SAMs)., Patients and Methods: Between January 2016 and May 2019, a total of seven patients with dermatomyositis (DM; 3 males, 4 females; mean age: 49.8±2.3 years; range, 43 to 54 years), six with immune mediated necrotizing myopathy (IMNM; 3 males, 3 females; mean age: 58.5±10.6 years; range, 46 to 74 years), and 10 control individuals (CTRL group; 4 males, 6 females; mean age: 48.7±3.9 years; range, 41 to 56 years) were included. The muscle biopsy before and after the intervention was performed to evaluate the intramuscular lipid content. Patients underwent a combined exercise training program for 12 weeks. Skeletal muscle gene expression was analyzed and the DM versus CTRL group, DM pre- and post-, and IMNM pre- and post-intervention were compared., Results: The DM group had a higher intramuscular lipid content in type II muscle fibers compared to the CTRL group. After the intervention, there was a reduction of lipid content in type I and II fibers in DM and IMNM group. The CTRL group showed a significantly higher expression of genes related to insulin and lipid oxidation pathways ( AMPKβ2, AS160, INSR, PGC1-α, PI3K , and RAB14 ) compared to the DM group. After exercise training, there was an increase gene expression related to insulin pathway and lipid oxidation in DM group ( AMPKβ2, AS160, INSR, PGC1-α, PI3K , and RAB14 ) and in IMNM group ( AKT2, AMPKβ2, RAB10, RAB14 , and PGC1-α )., Conclusion: Exercise training attenuated the amount of fat in type I and II muscle fibers in patients with DM and IMNM and increased gene expression related to insulin pathways and lipid oxidation in DM and IMNM. These results suggest that exercise training can improve the quality and metabolic functions of skeletal muscle in these diseases., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish League Against Rheumatism.)

Competing Interests: Declaration of interests We declare no competing interests.

The human hand possesses a large number of degrees of freedom. Hand dexterity is encoded by the discharge times of spinal motor units (MUs). Most of our knowledge on the neural control of movement is based on the discharge times of MUs during isometric contractions. Here we designed a noninvasive framework to study spinal motor neurons during dynamic hand movements with the aim to understand the neural control of MUs during sinusoidal hand digit flexion and extension at different rates of force development. The framework included 320 high-density surface EMG electrodes placed on the forearm muscles, with markerless 3D hand kinematics extracted with deep learning, and a realistic virtual hand that displayed the motor tasks. The movements included flexion and extension of individual hand digits at two different speeds (0.5 Hz and 1.5 Hz) for 40 seconds. We found on average 4.7±1.7 MUs across participants and tasks. Most MUs showed a biphasic pattern closely mirroring the flexion and extension kinematics. Indeed, a factor analysis method (non-negative matrix factorization) was able to learn the two components (flexion/extension) with high accuracy at the individual MU level ( R=0.87±0.12). Although most MUs were highly correlated with either flexion or extension movements, there was a smaller proportion of MUs that was not task-modulated and controlled by a different neural module (7.1% of all MUs with ). This work shows a noninvasive visually guided framework to study motor neurons controlling the movement of the hand in human participants during dynamic hand digit movements.