Exploring Trypanosoma cruzi transmission dynamics in an acute Chagas disease outbreak using next-generation sequencing.

BACKGROUND: Chagas disease (CD), caused by Trypanosoma cruzi, poses a major global public health challenge. Although vector-borne transmission is the primary mode of infection, oral transmission is increasingly concerning. METHODS: This study utilized long-amplicon-based sequencing (long-ABS), focusing on the 18S rRNA gene, to explore T. cruzi's genetic diversity and transmission dynamics during an acute CD outbreak in Colombia, an area without domestic infestation. RESULTS: Analyzing samples from five patients and five T. cruzi-positive marsupial samples, we identified coinfections between T. cruzi and Trypanosoma rangeli, mixed T. cruzi DTUs, suggesting possible links between human and marsupial T. cruzi infections. Coexistence of TcI, TcIV and T. rangeli suggests marsupial secretions as the possible source of T. cruzi transmission. Our investigation revealed diversity loss in DTUs TcIV and T. rangeli in humans after infection and in marsupial samples after culture. CONCLUSION: These findings provide significant insights into T. cruzi dynamics, crucial for implementing control and prevention strategies.

Is chronic pain caused by central sensitization? A review and critical point of view.

Chronic pain causes disability and loss of health worldwide. Yet, a mechanistic explanation for it is still missing. Frequently, neural phenomena, and among them, Central Sensitization (CS), is presented as causing chronic pain. This narrative review explores the evidence substantiating the relationship between CS and chronic pain: four expert researchers were divided in two independent teams that reviewed the available evidence. Three criteria were established for a study to demonstrate a causal relationship: (1) confirm presence of CS, (2) study chronic pain, and (3) test sufficiency or necessity of CS over chronic pain symptoms. No study met those criteria, failing to demonstrate that CS can cause chronic pain. Also, no evidence reporting the occurrence of CS in humans was found. Worryingly, pain assessments are often confounded with CS measures in the literature, omitting that the latter is a neurophysiological and not a perceptual phenomenon. Future research should avoid this misconception to directly interrogate what is the causal contribution of CS to chronic pain to better comprehend this problematic condition.

Synaptic imbalance and increased inhibition impair motor function in SMA.

Movement is executed through the balanced action of excitatory and inhibitory neurotransmission in motor circuits of the spinal cord. Short-term perturbations in one of the two types of transmission are counteracted by homeostatic changes of the opposing type. Prolonged failure to balance excitatory and inhibitory drive results in dysfunction at the single neuron, as well as neuronal network levels. However, whether dysfunction in one or both types of neurotransmission leads to pathogenicity in neurodegenerative diseases characterized by select synaptic deficits is not known. Here, we used mouse genetics, functional assays, morphological methods, and viral-mediated approaches to uncover the pathogenic contribution of unbalanced excitation-inhibition neurotransmission in a mouse model of spinal muscular atrophy (SMA). We show that vulnerable motor circuits in the SMA spinal cord fail to respond homeostatically to the reduction of excitatory drive and instead increase inhibition. This imposes an excessive burden on motor neurons and further restricts their recruitment to activate muscle contraction. Importantly, genetic or pharmacological reduction of inhibitory synaptic drive improves neuronal function and provides behavioural benefit in SMA mice. Our findings identify the lack of excitation-inhibition homeostasis as a major maladaptive mechanism in SMA, by which the combined effects of reduced excitation and increased inhibition diminish the capacity of premotor commands to recruit motor neurons and elicit muscle contractions.

Chromoblastomycosis: A Potential Mimic of Squamous Cell Carcinoma in Transplant Recipients.

Chromoblastomycosis (CBM), also known as chromomycosis is a chronic, granulomatous fungal infection of the skin and subcutaneous tissue. It usually occurs by the traumatic inoculation of various dematiaceous fungi and is more common in the developing world. This condition is rare in North America and the developed world. Herein, we present a case of a 75-year-old man who received a bilateral lung transplant 4 months prior and presented for evaluation of a painful, erythematous papule on the elbow which was diagnosed as CBM. This case highlights that immunosuppression used in patients who undergo solid organ transplantation not only increases the risk of opportunistic infections like CBM but can also be confused for cutaneous squamous cell carcinoma as both these entities share many overlapping clinical and histopathologic features and may be a potential source of misdiagnosis.

Socioeconomic and environmental factors associated with dengue fever incidence in Guatemala: Rising temperatures increase dengue risk.

Dengue fever is a mosquito-borne illness that infects 390 million people annually. Dengue outbreaks in Guatemala have been occurring more often and at increased rates since the first dengue outbreak in Guatemala in the 1970s. This study will examine environmental and socioeconomic factors associated with dengue in Guatemala at the municipality (county) level. Socioeconomic factors included population density, Mayan population, economic activity, and attending school. Environmental factors included average minimum annual temperature and annual precipitation. The relationship between environmental and socioeconomic variables and dengue fever incidence was initially evaluated through univariate zero-inflated negative binomial models, and then again through three zero-inflated multivariate negative binomial regression models. For all three models, elevation was considered a predictor of zero-inflation. In the combined model, there was a positive relationship between minimum temperature, economic activity and dengue fever incidence, and a negative relationship between population density, Mayan population and dengue fever. Predicted rates of dengue fever incidence and adjusted confidence intervals were calculated after increasing minimum yearly temperature by 1°C and 2°C. The three municipalities with the highest minimum yearly temperature (El Estor, Iztapa, and Panzós) and the municipality of Guatemala, all had an increase in the magnitude of the risk of dengue fever incidence following 1°C and 2°C increase in temperature. This research suggests that these socioeconomic and environmental factors are associated with risk of dengue in Guatemala. The predicted rates of dengue fever also highlight the potential effect that climate change in the form of increasing temperature can have on dengue in Guatemala.

Xanthogranulomatous Pyelonephritis in Peritoneal Dialysis.

Introduction: Xanthogranulomatous pyelonephritis (XGP) is a rare illness that consists of a destructive chronic inflammatory process of the renal parenchyma associated with recurrent infection and obstructions of the urinary tract. Peritoneal dialysis (PD) is a form of renal replacement therapy used in advanced kidney disease. PD patients demonstrate a systemic inflammatory state, secondary to the increase in uremic toxins, decreased filtration of proinflammatory cytokines, as well as constant exposure to bioincompatible dialysis solutions or a foreign body reaction from the catheter, among other factors, as peritoneal infections. Case Presentation: We present the clinical case of a 74-year-old woman, with a history of recurrent urinary tract infections associated with nephrolithiasis and stage 5D chronic kidney disease, on a PD program. The patient presented a non-specific 3-month state of progressive asthenia, with increased inflammatory parameters in the analytical controls. After presenting multiple negative urine cultures and peritoneal fluid cultures, she was hospitalized to study the constitutional syndrome. The imaging test revealed bilateral staghorn lithiasis with severe dilatation of the right renal pelvis and great cortical thinning. Given the suspicion of XGP, it was decided to perform right renal nephrectomy, which was confirmed after the anatomopathological study. Prior to the intervention, she was transferred to hemodialysis. Over the following months, significant clinical and analytical improvement was observed. Conclusion: The systemic inflammatory state and the risk of infections in PD can mask the diagnosis of XGP in PD patients. There are no reported cases of XGP in patients in PD.

Induction immunosuppression strategies and outcomes post-lung transplant: A single center experience.

PURPOSE: Currently 80% of lung transplant centers use induction immunosuppression. However, there is a lack of standardization of induction protocols within and across lung transplant centers. This study explores the association of two different induction immunosuppression strategies used at our center [single dose rabbit antithymocyte globulin (rATG) vs. alemtuzumab] compared to no induction with immunologic and clinical outcomes after lung transplantation. METHODS: A total of 174 consecutive lung transplant recipients (LTR) between 2016 and 2019 were included in the analysis. Twenty nine LTR (16.7%) received no induction, 22 LTR (12.6%) received alemtuzumab, 123 LTR (70.6%) received a single dose of rATG; 1.5 mg/kg within 24 h of transplant for induction. All LTR had a negative flow cytometry crossmatch on the day of the transplant. All LTR were assessed for de novo HLA donor-specific antibodies (DSA) development and clinical outcomes, including the risk of acute cellular rejection (ACR), antibody-mediated rejection (AMR), chronic lung allograft dysfunction (CLAD), and overall survival post-transplant. RESULTS: The median lung allocation score (LAS) was significantly higher in LTR that did not receive Induction immunosuppression (76; range = 35.3-94.3) compared to induction with rATG (41.6; range = 31.6-91) and alemtuzumab (51; range = 33.1-88.2) (p < 0.001). De novo HLA DSA were detected in 50/174 (28.7%) LTR within 12 months post-transplant. They were detected in 13/29 (44.8%) LTR without induction immunosuppression compared to 28/123 (22.8%) and 9/22 (40.9%) LTR with rATG and alemtuzumab induction, respectively (p = 0.02). The percent freedom from ACR rates between LTR who received alemtuzumab induction was significantly higher compared to LTR who received rATG or no induction at 1 (p = 0.02), 2 (p = 0.01) and 3 (p = 0.05) years post-transplant. In addition, the overall 1-year survival rates were significantly higher in LTR who received rATG or alemtuzumab induction compared to LTR without induction immunosuppression (p = 0.02). CONCLUSION: Induction immunosuppression strategies utilizing rATG or Alemtuzumab have unique and contrasting benefits in LTR. Combination of alemtuzumab induction and a lower dose of maintenance immunosuppression may reduce the incidence of ACR in LTR. Single-dose rATG or alemtuzumab induction immunosuppression may also improve the 1 year overall LTR survival compared to no induction.

Evaluation of Different Types of Stimuli in an Event-Related Potential-Based Brain-Computer Interface Speller under Rapid Serial Visual Presentation.

Rapid serial visual presentation (RSVP) is currently a suitable gaze-independent paradigm for controlling visual brain-computer interfaces (BCIs) based on event-related potentials (ERPs), especially for users with limited eye movement control. However, unlike gaze-dependent paradigms, gaze-independent ones have received less attention concerning the specific choice of visual stimuli that are used. In gaze-dependent BCIs, images of faces-particularly those tinted red-have been shown to be effective stimuli. This study aims to evaluate whether the colour of faces used as visual stimuli influences ERP-BCI performance under RSVP. Fifteen participants tested four conditions that varied only in the visual stimulus used: grey letters (GL), red famous faces with letters (RFF), green famous faces with letters (GFF), and blue famous faces with letters (BFF). The results indicated significant accuracy differences only between the GL and GFF conditions, unlike prior gaze-dependent studies. Additionally, GL achieved higher comfort ratings compared with other face-related conditions. This study highlights that the choice of stimulus type impacts both performance and user comfort, suggesting implications for future ERP-BCI designs for users requiring gaze-independent systems.

Recent Advances on the Chemistry of Transition Metal Complexes with Monoanionic Bidentate Silyl Ligands.

The chemistry of transition-metal (TM) complexes with monoanionic bidentate (κ2-L,Si) silyl ligands has considerably grown in recent years. This work summarizes the advances in the chemistry of TM-(κ2-L,Si) complexes (L=N-heterocycle, phosphine, N-heterocyclic carbene, thioether, ester, silylether or tetrylene). The most common synthetic method has been the oxidative addition of the Si-H bond to the metal center assisted by the coordination of L. The metal silicon bond distances in TM-(κ2-L,Si) complexes are in the range of metal-silyl bond distances. TM-(κ2-L,Si) complexes have proven to be effective catalysts for hydrosilylation and/or hydrogenation of unsaturated molecules among other processes.

Temporal Dynamics of Adverse Effects across Five Sessions of Transcranial Direct Current Stimulation.

(1) Background: Transcranial direct current stimulation (tDCS) is a safe intervention, only producing mild and transient adverse effects (AEs). However, there is no detailed analysis of the pattern of adverse effects in an application transferable to the clinic. Therefore, our objective is to describe the AEs produced by tDCS and its temporal evolution. (2) Methods: A total of 33 young volunteers were randomized into a tDCS or sham group. Participants performed a hand dexterity task while receiving the tDCS or sham intervention (20 min and 1 mA), for five consecutive days. AEs were assessed daily after each intervention and classified as somatosensory, pain, or other effects. (3) Results: The number of AEs was generally increased by tDCS intervention. Specifically, tDCS led to more frequent somatosensory discomfort, characterized by sensations like itching and tingling, alongside painful sensations such as burning, compared to the sham intervention. Additionally, certain adverse events, including neck and arm pain, as well as dizziness and blurry vision, were exclusive to the tDCS group. Interestingly, tDCS produced similar AEs across the days; meanwhile, the somatosensory AEs in the sham group showed a trend to decrease. (4) Conclusions: tDCS produces mild and temporary somatosensory and pain AEs during and across sessions. The different evolution of the AEs between the tDCS and sham protocol could unmask the blinding protocol most used in tDCS studies. Potential solutions for improving blinding protocols for future studies are discussed.

Kca3.1-Related Cellular Signalling Involved in Cancer Proliferation.

Anomalous expression of potassium channels in cancer tissues is associated with several cancer hallmarks that support deregulated proliferation and tumor progression. Ion channels seem to influence cell proliferation; however, the crucial molecular mechanisms involved remain elusive. Some results show how extracellular mitogenic signals modulate ion channel activity through intracellular secondary messengers. It is relevant because we are beginning to understand how potassium channels can affect the proliferative capacity of cells, either in normal mitogen-dependent proliferation or in mitogen-unresponsive proliferation. Calciumdependent potassium channels have been implicated in cell cycle signaling in many cancerous cell lines. In particular, the so-called intermediate conductance KCa3.1 (IKCa) is reported to play a significant role in uncontrolled cell cycle signaling, among other malignant processes driven by cancer hallmarks. In addition to these features, this channel can be subjected to specific pharmacological regulation, making it a promising cornerstone for understanding the signaling behavior of several types of cancer and as a target for chemotherapeutic approaches. This review is dedicated to the connection of KCa3.1 activity, in canonical and non-canonical ways, to the cell cycle signaling, including the cooperation with calcium channels to generate calcium signals and its role as a mediator of proliferative signals.

Transcranial magnetic stimulation therapy for central post-stroke pain: systematic review and meta-analysis.

Introduction: Although rare, central post-stroke pain remains one of the most refractory forms of neuropathic pain. It has been reported that repetitive transcranial magnetic stimulation (rTMS) may be effective in these cases of pain. Aim: The aim of this study was to investigate the efficacy of rTMS in patients with central post-stroke pain (CPSP). Methods: We included randomized controlled trials or Controlled Trials published until October 3rd, 2022, which studied the effect of rTMS compared to placebo in CPSP. We included studies of adult patients (>18 years) with a clinical diagnosis of stroke, in which the intervention consisted of the application of rTMS to treat CSP. Results: Nine studies were included in the qualitative analysis; 6 studies (4 RCT and 2 non-RCT), with 180 participants, were included in the quantitative analysis. A significant reduction in CPSP was found in favor of rTMS compared with sham, with a large effect size (SMD: -1.45; 95% CI: -1.87; -1.03; p < 0.001; I2: 58%). Conclusion: The findings of the present systematic review with meta-analysis suggest that there is low quality evidence for the effectiveness of rTMS in reducing CPSP. Systematic review registration: Identifier (CRD42022365655).

Microfracture-coagulation for the real robotic liver parenchymal transection.

The use of the robotic approach in liver surgery is exponentially increasing. Although technically the robot introduces several innovative features, the instruments linked with the traditional laparoscopic approach for the liver parenchymal transection are not available, which may result in multiple technical variants that may bias the comparative analysis between the different series worldwide. A real robotic approach, minimally efficient for the liver parenchymal transection, with no requirement of external tool, available for the already existing platforms, and applicable to any type of liver resection, counting on the selective use of the plugged bipolar forceps and the monopolar scissors, or "microfracture-coagulation" (MFC) transection method, is described in detail. The relevant aspects of the technique, its indications and methodological basis are discussed.

Modulation of central synapse remodeling after remote peripheral injuries by the CCL2-CCR2 axis and microglia.

Microglia-mediated synaptic plasticity after CNS injury varies depending on injury severity, but the mechanisms that adjust synaptic plasticity according to injury differences are largely unknown. This study investigates differential actions of microglia on essential spinal motor synaptic circuits following different kinds of nerve injuries. Following nerve transection, microglia and C-C chemokine receptor type 2 signaling permanently remove Ia axons and synapses from the ventral horn, degrading proprioceptive feedback during motor actions and abolishing stretch reflexes. However, Ia synapses and reflexes recover after milder injuries (nerve crush). These different outcomes are related to the length of microglia activation, being longer after nerve cuts, with slower motor-axon regeneration and extended expression of colony-stimulating factor type 1 in injured motoneurons. Prolonged microglia activation induces CCL2 expression, and Ia synapses recover after ccl2 is deleted from microglia. Thus, microglia Ia synapse removal requires the induction of specific microglia phenotypes modulated by nerve regeneration efficiencies. However, synapse preservation was not sufficient to restore the stretch-reflex function.

Air-stepping in the neonatal mouse: a powerful tool for analyzing early stages of rhythmic limb movement development.

There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study l-3,4-dihydroxyphenylalanine (l-DOPA)-induced air-stepping in mice at postnatal day (P)7 and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion but without constraints imposed by weight bearing, postural adjustments, or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of l-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation, we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10 but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages, indicating maturation of flexion-extension cycles as the animal starts to walk. EMG recordings of TA and LG show alternation but with more focused activation particularly in the LG from P7 to P10. We discuss similarities to neonatal rat l-DOPA-induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and pave the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry.NEW & NOTEWORTHY We present novel methods to study neonatal air-stepping in newborn mice. These methods allow analyses at the onset of limb coordination during the period in which altricial species like rats, mice, and humans "learn" to walk. The methods will be useful to test a large variety of mutations that serve as models of motor disease in newborns or that are used to probe for specific circuit mechanisms that generate coordinated limb motor output.

Statistical analysis plan for the multicenter, open, randomized controlled clinical trial to assess the efficacy and safety of intravenous tirofiban vs aspirin in acute ischemic stroke due to tandem lesion, undergoing recanalization therapy by endovascular treatment (ATILA trial).

RATIONALE: In-stent reocclusion after endovascular therapy has a negative impact on outcomes in acute ischemic stroke (AIS) due to tandem lesions (TL). Optimal antiplatelet therapy approach in these patients to avoid in-stent reocclusion is yet to be elucidated. AIMS: To assess efficacy and safety of intravenous tirofiban versus intravenous aspirin in patients undergoing MT plus carotid stenting in the setting of AIS due to TL. SAMPLE SIZE ESTIMATES: Two hundred forty patients will be enrolled, 120 in every treatment arm. METHODS AND DESIGN: A multicenter, prospective, randomized, controlled (aspirin group), assessor-blinded clinical trial will be conducted. Patients fulfilling the inclusion criteria will be randomized at MT onset to the experimental or control group (1:1). Intravenous aspirin will be administered at a 500-mg single dose and tirofiban at a 500-mcg bolus followed by a 200-mcg/h infusion during the first 24 h. All patients will be followed for up to 3 months. STUDY OUTCOMES: Primary efficacy outcome will be the proportion of patients with carotid in-stent thrombosis within the first 24 h after MT. Primary safety outcome will be the rate of symptomatic intracranial hemorrhage. DISCUSSION: This will be the first clinical trial to assess the best antiplatelet therapy to avoid in-stent thrombosis after MT in patients with TL. TRIAL REGISTRATION: The trial is registered as NCT05225961. February, 7th, 2022.