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Toxoplasma gondii is one of the world's most successful parasites, in part because of its ability to infect and persist in most warm-blooded animals. A unique characteristic of T. gondii is its ability to persist in the central nervous system (CNS) of a variety of hosts, including humans and rodents. How, what, and why T. gondii encysts in the CNS has been the topic of study for decades. In this review, we will discuss recent work on how T. gondii is able to traverse the unique barrier surrounding the CNS, what cells of the CNS play host to T. gondii, and finally, how T. gondii infection may influence global and cellular physiology of the CNS.

The inflammatory response to spinal cord injury (SCI) involves localization and activation of innate and adaptive immune cells and proteins, including the complement cascade. Complement C3 is important for the classical, alternative, and lectin pathways of complement activation, and its cleavage products C3a and C3b mediate several functions in the context of inflammation, but little is known about the potential functions of C3 on regeneration and survival of injured neurons after SCI. We report that 6 weeks after dorsal hemisection with peripheral conditioning lesion, C3 −/− mice demonstrated a 2-fold increase in sensory axon regeneration in the spinal cord in comparison to wildtype C3 +/+ mice. In vitro , addition of C3 tripled both myelin-mediated neurite outgrowth inhibition and neuron loss versus myelin alone, and ELISA experiments revealed that myelin serine proteases cleave C3 to generate active fragments. Addition of purified C3 cleavage products to cultured neurons suggested that C3b is responsible for the growth inhibitory and neurotoxic or anti-adhesion activities of C3. These data indicate that C3 reduces neurite outgrowth and neuronal viability in vitro and restricts axon regeneration in vivo , and demonstrate a novel, non-traditional role for this inflammatory protein in the central nervous system.

Toxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma -injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. In addition, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2 + ) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2 + ). By performing single neuron patch clamping on striatal TINs and neighboring uninfected MSNs, we discovered that TINs have highly aberrant electrophysiology. As approximately 90% of TINs will die by 8 weeks post-infection, this abnormal physiology suggests that injection with Toxoplasma protein—either directly or indirectly—affects neuronal health and survival. Collectively, these data offer the first insights into which neurons interact with Toxoplasma and how these interactions alter neuron physiology in vivo. Toxoplasma gondii is an intracellular parasite that infects the brain. Whereas most microbial infections of the brain result in severe illness or death, Toxoplasma gondii infections are usually asymptomatic. This is because the parasite has evolved the ability to exist within the brain by dampening the immune response. The parasite can therefore asymptomatically co-exist with its host for years – or even an entire lifetime. The strategy has proved so successful that up to one third of the world’s population is now thought to be infected with Toxoplasma gondii . While this persistence tends not to be a problem for most healthy individuals, dormant Toxoplasma gondii parasites can reactivate in individuals whose immune systems fail. This can result in life-threatening neurological disease. In pregnant women, Toxoplasma gondii parasites can also cross the placenta, which can trigger miscarriage or cause harmful disease in the newborn. To develop treatments for these cases of symptomatic disease, we need to understand how the parasite hides from the immune system in asymptomatic individuals. Mendez et al. have therefore leveraged a mouse model in which neurons injected with Toxoplasma gondii proteins ( Toxoplasma -injected neurons, or ‘TINs’) produce a green fluorescent protein. This enables the infected cells to be viewed under a microscope. Examining the mouse brains revealed that most TINs were located in two specific regions: the cortex and the striatum. The cortex is the brain’s outer layer of tissue. The striatum is a structure deep within the brain that helps regulate movement and responses to rewards. Both the cortex and the striatum contain different types of neurons. The results revealed that the proteins from the parasite were spread roughly equally among the various cell types, rather than targeting a specific subtype of neuron. Neurons close to TINs had slightly abnormal electrical activity, whereas the TINs themselves had highly abnormal activity. By eight weeks post-infection, however, the number of TINS had fallen by around 90%. This suggests that many neurons containing Toxoplasma protein are sick and dying, and that their altered electrical activity reflects this unhealthy state. Understanding how Toxoplasma parasites persist in the brain has the potential to reveal new targets for treating symptomatic infections. It could even provide new possibilities for targeting the inflammation that drives many other neurological diseases. Harnessing this potential will require finding out why Toxoplasma gondii infects specific brain regions and why most neurons that directly interact with the parasite die.

Background LCAT (lecithin-cholesterol acyltransferase) deficiency is characterized by two distinct phenotypes, familial LCAT deficiency (FLD) and Fish Eye disease (FED). This is the first systematic review evaluating the ethnic distribution of LCAT deficiency, with particular emphasis on Latin America and the discussion of three Mexican-Mestizo probands. Methods A systematic review was conducted following the PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis) Statement in Pubmed and SciELO. Articles which described subjects with LCAT deficiency syndromes and an assessment of the ethnic group to which the subject pertained, were included. Results The systematic review revealed 215 cases (154 FLD, 41 FED and 20 unclassified) pertaining to 33 ethnic/racial groups. There was no association between genetic alteration and ethnicity. The mean age of diagnosis was 42 ± 16.5 years, with fish eye disease identified later than familial LCAT deficiency (55 ± 13.8 vs. 41 ± 14.7 years respectively). The prevalence of premature coronary heart disease was significantly greater in FED vs. FLD. In Latin America, 48 cases of LCAT deficiency have been published from six countries (Argentina (1 unclassified), Brazil (38 FLD), Chile (1 FLD), Columbia (1 FLD), Ecuador (1 FLD) and Mexico (4 FLD, 1 FED and 1 unclassified). Of the Mexican probands, one showed a novel LCAT mutation. Conclusions The systematic review shows that LCAT deficiency syndromes are clinically and genetically heterogeneous. No association was confirmed between ethnicity and LCAT mutation. There was a significantly greater risk of premature coronary artery disease in fish eye disease compared to familial LCAT deficiency. In FLD, the emphasis should be in preventing both cardiovascular disease and the progression of renal disease, while in FED, cardiovascular risk management should be the priority. The LCAT mutations discussed in this article are the only ones reported in the Mexican- Amerindian population.

Multiple sclerosis (MS) is a chronic neurological disease which affects young adults at a time of maximum personal, professional and social growth. Recent guidelines on physical activity have established that exercise is an essential component of the clinical management of people with MS with mild or moderate degree of disability. The main purpose of this study was to test the feasibility and the effects of two different 40-week structured physical exercise interventions (a supervised high intensity interval training plus home exercise program and a self-applied home-based exercise program) on clinical evolution, psychological wellbeing, quality of life, fatigue, cardiorespiratory fitness, strength and balance of people with MS. Twenty-nine participants with relapsing-remitting MS (RRMS) participated in this study. All of them were fully ambulatory and with minimal disability (Expanded Disability Status Scale <3), for at least the last six months. Participants selected to be part of a combined face-to-face plus home exercise group (CFTFG; n = 8); a self-applied home-based exercise group (HG; n = 11) or a control group (CG; n = 10). A total of 23 participants completed the protocol (79.3%), of which 8 participants (100%) from the CFTFG, 7 (63.6%) from the HG and 8 (80%) from the CG. During the first 20-weeks of training, adherence from the CFTFG reached 77.5% and from the HG reached 50 %. During the second 20-weeks of training, adherence from the CFTFG reached 62.5% and from the HG reached 45.4%. After 20-weeks of training, a significant improvement in the absolute VO peak and in the 30-second sit to stand test was observed in the CFTFG (all < .05). This study confirms that offering a 40-week structured exercise programme to a group of fully ambulatory and minimally disabled persons with RRMS is feasible and safe. Any adverse event related to the trial was reported by the participants.

Background Opioid sparing anesthesia and enhanced recovery after surgery protocols are not innovative ideas. However, the utilization of pancreaticoduodenectomy is limited. With the rise in awareness of the opioid epidemic in the United States, we have created a multimodal approach to anesthesia and postoperative care to limit adverse effects of opioids and curb the use of opioids postoperatively. Methods We conducted a retrospective cohort study performed by chart review of an opioid-sparing anesthetic and enhanced recovery after surgery (ERAS) protocol initiated jointly by the anesthesiology departments and transplant surgery for pancreaticoduodenectomy from January 2017 to October 2019. Results Demographic data was found to be comparable between the control and protocol groups. Hospital length of stay, ICU length of stay, and opioid requirements significantly decreased in the protocol group. Hospital length of stay decreased from 8.92 to 5.72 days, ICU days decreased from 1.52 to 0.42 days, and narcotics for the first five hospital days were significantly decreased from 130.13 to 71.2 morphine milligram equivalents. Conclusion Proper postoperative pain management can improve patient satisfaction and decrease complication rates. Pancreaticoduodenectomy is a complicated procedure with relatively limited data regarding enhanced recovery after surgery protocols. Likewise, there is limited data regarding opioid-sparing anesthesia techniques. Our protocol produced promising hospital length of stay and reduced opioid administration during the first five hospital days without increasing 30-day readmission rates.

BackgroundFascial plane blocks are a valuable and important aspect of patient care. However, nerve blocks sometimes present with a technical difficulty that can lead to upsetting the operating room schedule, cause discomfort to the patient, or lead to inadequate block. Potential predictors of this difficulty were evaluated.MethodsIn a single-blind study, ultrasound image quality was evaluated on a grading metric, and its correlation with several factors that could potentially impact the difficulty of a procedure, including age, BMI, weight, length of surgery, IV fluids, and pre- vs postoperative block, was assessed.ResultsNo correlation was found between any of our anesthetic, patient, or surgical factors, and the resulting image quality.ConclusionThe study population was limited compared to our initial goals. We found no correlation between studied variables and image quality, but confounding factors that may affect image quality have not been ruled out.

Introduction: Maximal oxygen uptake (VO2) may be one of the most important variables in the study of the responses ofpeople with spinal cord injury (SCI) and without SCI to physical exercise. The results achieved during its assessment serve as adiagnostic and health indicator in clinical settings. Objective: this study aimed to investigatethe physiological responses in males withand without SCI performing a maximal incremental test on an asynchronous arm crank ergometer (ACr) and on a recumbent synchronoushandbike ergometer (HB). Methods: ten males with SCI and 11 able-bodied males (AB group) participated in this study. Two maximalgraded exercise tests were performed, starting at 10 watts and increasing the workload by 10 watts every minute until exhaustion.Results: the AB group achieved lower workloads and absolute VO2 values than the SCI group during the HB test (all p < 0.05). Thesubmaximal values of the relative VO2 peak and RER at workloads between 40-90 watts showed significant differences between SCI andAB on HB and ACr. Significant linear relationships between workload and relative VO2 peak were found during the HB test (p < 0.001).Conclusions: these findings demonstrate that there are different physiological responses between adults with and without SCI whenperforming maximal and submaximal arm-ergometry. Interestingly, higher VO2 peak and workloads were achieved by the SCI group. Inaddition, specific prediction equations derived from the current study can be used to calculate the relative VO2 peak in handbikers with Introducción: el consumo de oxígeno (VO2) es una de las variables más importantes en el estudio de la respuesta al ejercicio en personas con y sin lesión medular (SCI; AB). Objetivo: en este estudio se analizaron las respuestas fisiológicas en hombres adultos con y sin SCI al realizar pruebas de esfuerzo máximas en un ergómetro de brazos asincrónico (ACr) en sedestación y en un ergómetro de brazos sincrónico (HB) en posición supina. Métodos: diez hombres con SCI y 11 sin SCI participaron en este estudio. Dos pruebas de esfuerzo gradual fueron realizadas por cada participante, iniciando a 10 watts e incrementando la carga 10 watts cada minuto. Resultados: el grupo sin SCI alcanzó cargas y VO2 menores que los participantes con SCI durante el test en HB (p < 0.05). Los valores submáximos para el VO2 relativo y el RER a cargas de 40-90 watts fueron estadísticamente diferentes entre los grupos en ambos tests. Se observó una correlación lineal entre las cargas de trabajo y el VO2 relativo durante el test en HB (p < 0.001). Conclusiones: los resultados obtenidos en este estudio demuestran que existen respuestas fisiológicas diferentes entre personas con y sin SCI cuando realizan pruebas de esfuerzo con cargas máximas y submáximas. Llamativamente, el grupo SCI alcanzó mayores cargas de trabajo y VO2 que los no SCI. Finalmente, se presentan dos ecuaciones específicas para obtener el VO2 de manera indirecta en personas con y sin SCI mediante el uso de un HB.

Background/Objectives: Myotonic dystrophy type 1 (DM1) is a rare, multisystemic disorder caused by an expanded (CTG)n repeat in the DMPK gene. Although DM1 has been studied in several populations, access to molecular diagnosis and comprehensive care remains limited in many low- and middle-income countries. This study provides an updated overview of DM1 in Mexico, from diagnostic implementation to patient management, describing key clinical and genetic findings. Methods: We conducted a nationwide, 15-year prospective study at Mexico’s National Reference Center for neuromuscular diseases. A total of 853 individuals at risk were subjected to clinical and molecular evaluation using PCR, TP-PCR, and SP-PCR, encompassing symptomatic, pre-symptomatic, prenatal, and preimplantation genetic diagnosis. Socioeconomic, clinical, and molecular variables were analyzed. Results: A total of 488 individuals were confirmed as DM1 carriers, with the most prevalent phenotypes being classic (36.5%) and juvenile (28.5%). Genomic analysis revealed a correlation between CTG tract sizes and phenotypes. Intriguingly, interrupted CTG repeat tracts were identified in 2.8% of DM1 carriers, who exhibited milder clinical phenotypes and a reduced degree of somatic and intergenerational instability. Survival analysis revealed a reduction in symptom-free survival in patients with larger expansions, while interrupted CTG tracts were associated with delayed onset. Conclusions: The centralization of diagnostic services in Mexico resulted in regional disparities, impacting early diagnosis and family planning. This study highlights the clinical and molecular diversity of DM1 in a Latin American population and underscores the urgent need for decentralized diagnostic services, integrated care models, and tailored prognostic tools in underserved settings.

Abstract Toxoplasma gondii is an intracellular parasite that causes a long-term latent infection of neurons. Using a custom MATLAB-based mapping program in combination with a mouse model that allows us to permanently mark neurons injected with parasite proteins, we found that Toxoplasma-injected neurons (TINs) are heterogeneously distributed in the brain, primarily localizing to the cortex followed by the striatum. Using immunofluorescence co-localization assays, we determined that cortical TINs are commonly (>50%) excitatory neurons (FoxP2+) and that striatal TINs are often (>65%) medium spiny neurons (MSNs) (FoxP2+). As MSNs have highly characterized electrophysiology, we used ex vivo slices from infected mice to perform single neuron patch-clamping on striatal TINs and neighboring uninfected MSNs (bystander MSNs). These studies demonstrated that TINs have highly abnormal electrophysiology, while the electrophysiology of bystander MSNs was akin to that of MSNs from uninfected mice. Collectively, these data offer new neuroanatomic and electrophysiologic insights into CNS toxoplasmosis. Competing Interest Statement The authors have declared no competing interest.