Delivery of functional Cas:DNA nucleoprotein complexes into recipient bacteria through a type IV secretion system.

CRISPR-associated (Cas) endonucleases and their derivatives are widespread tools for the targeted genetic modification of both prokaryotic and eukaryotic genomes. A critical step of all CRISPR-Cas technologies is the delivery of the Cas endonuclease to the target cell. Here, we investigate the possibility of using bacterial conjugation to translocate Cas proteins into recipient bacteria. Conjugative relaxases are translocated through a type IV secretion system into the recipient cell, covalently attached to the transferred DNA strand. We fused relaxase R388-TrwC with the endonuclease Cas12a and confirmed that it can be transported through a T4SS. The fusion protein maintained its activity upon translocation by conjugation into the recipient cell, as evidenced by the induction of the SOS signal resulting from DNA breaks produced by the endonuclease in the recipient cell, and the detection of mutations at the target position. We further show how a template DNA provided on the transferred DNA can be used to introduce specific mutations. The guide RNA can also be encoded by the transferred DNA, enabling its production in the recipient cells where it can form a complex with the Cas nuclease transferred as a protein. This self-contained setup enables to target wild-type bacterial cells. Finally, we extended this strategy to the delivery of relaxases fused to base editors. Using TrwC and MobA relaxases as drivers, we achieved precise editing of transconjugants. Thus, conjugation provides a delivery system for Cas-derived editing tools, bypassing the need to deliver and express a cas gene in the target cells.

Computational algorithm based on health and lifestyle traits to categorize lifemetabotypes in the NUTRiMDEA cohort.

Classifying individuals based on metabotypes and lifestyle phenotypes using exploratory factor analyses, cluster definition, and machine-learning algorithms is promising for precision chronic disease prevention and management. This study analyzed data from the NUTRiMDEA online cohort (baseline: n = 17332 and 62 questions) to develop a clustering tool based on 32 accessible questions using machine-learning strategies. Participants ranged from 18 to over 70 years old, with 64.1% female and 35.5% male. Five clusters were identified, combining metabolic, lifestyle, and personal data: Cluster 1 ("Westernized Millennial", n = 967) included healthy young individuals with fair lifestyle habits; Cluster 2 ("Healthy", n = 10616) consisted of healthy adults; Cluster 3 ("Mediterranean Young Adult", n = 2013) represented healthy young adults with a healthy lifestyle and showed the highest adherence to the Mediterranean diet; Cluster 4 ("Pre-morbid", n = 600) was characterized by healthy adults with declined mood; Cluster 5 ("Pro-morbid", n = 312) comprised older individuals (47% >55 years) with poorer lifestyle habits, worse health, and a lower health-related quality of life. A computational algorithm was elicited, which allowed quick cluster assignment based on responses ("lifemetabotypes"). This machine-learning approach facilitates personalized interventions and precision lifestyle recommendations, supporting online methods for targeted health maintenance and chronic disease prevention.

The Interactive Effects of Rejection and Rumination on Diurnal Cortisol among Adolescent Girls: A Preliminary Daily Diary Study.

Background: The perseverative cognition hypothesis stipulates that rumination (repetitive, passive, uncontrollable negative thinking) prolongs the experience of a stressor which impacts stress physiology. In line with this hypothesis, we proposed that in response to real-life experiences of social rejection, adolescent girls who ruminate would show a blunted diurnal cortisol slope the next day relative to girls who do not ruminate. We also examined the effects of social rejection and rumination on waking cortisol levels and the cortisol awakening response. Method: Participants were (n = 50) adolescent girls (mean age = 13.30, SD = 2.34) who varied on psychiatric risk and provided saliva samples 4 times a day for 3 days, as well as, daily diary reports of social rejection and rumination. A lagged multilevel model was utilized to examine the interactive effects of rejection and rumination on diurnal cortisol. Results: There was a significant interaction between social rejection and rumination. Specifically, rumination following social rejection was associated with a flatter diurnal cortisol slope. In the absence of rumination, social rejection was marginally associated with a steeper diurnal cortisol slope. The effects for waking cortisol levels and the cortisol awakening response were null. Conclusion: Findings support the perseverative cognition hypothesis and suggest that cognitive mechanisms such as rumination can impact stress physiology.

Lymphocytic esophagitis - A little-known cause of dysphagia.

Lymphocytic esophagitis is a little-known entity whose cause is not fully established, and which basically presents with dysphagia. It is characterized by the presence of an infiltrate mainly formed by lymphocytes and other signs of epithelial damage in the absence of other granulocytes. The lack of knowledge about this pathology as well as standardized diagnostic criteria complicates its diagnosis. We present the case of an 84-year-old male with dysphagia and pathological findings compatible with lymphocytic esophagitis, requiring several lines of treatment and even endoscopic dilation with subsequent clinical improvement.

A guide for the generation of repositories of clinical samples for research on Chagas disease.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.

Association of hTERT expression, Her2Neu, estrogen receptors, progesterone receptors, with telomere length before and at the end of treatment in breast cancer patients.

Background: Breast cancer shows significant clinical, morphologic, and molecular variation. Telomeres are nucleoprotein complexes composed of hexanucleotide repeat DNA sequence, TTAGGG, and numerous telomere-associated proteins. The maintenance of telomere length is carried out by a ribonucleoprotein called telomerase, which consists of two main components: a catalytic subunit called hTERT (human telomerase reverse transcriptase) and an RNA template called hTR (human telomerase RNA). The importance of evaluating hTERT expression lies in its potential therapeutic application, being an attractive target due to its almost non-existent expression in normal somatic cells. It is also expected that the anti-neoplastic effect would appear earlier in neoplastic cells with shorter telomeres. Additionally, a significant relationship has been observed between Her2-Neu overexpression and Her2-Neu positivity, which could suggest new combined therapies.The aim of this study was to detect the expression of hTERT, estrogen receptor (ER), progesterone receptor (PR), and HER2-Neu in neoplastic breast tissue embedded in paraffin before treatment and to investigate the relationship between them and with baseline and post-treatment telomere length, as well as with various clinicopathological parameters. Materials and methods: A cross-sectional-correlational, 21 women diagnosed with breast cancer at the Oncology Service of the High Specialty Medical Unit No. 1 of Bajio of the Mexican Institute of Social Security. The study complies with the Helsinki Declaration and was approved by the Institutional Ethical Committee of the Mexican Institute of Social Security (R-2019-1001-127). A peripheral blood sample was obtained before oncological treatment and at the end of oncological treatment for the measurement of telomere length by extracting DNA from leukocytes, was performed by the quantitative polymerase chain reaction (PCR) method described by Cawthon. Tumor samples were collected from each patient at the oncology department for immunohistochemical determination of biomarker expression (ER, PR, Her2/neu) and hTERT. Results: Of the 21 cases included in the study, the median age was 57.57 years. Eighteen cases were classified as invasive ductal carcinoma NOS (85.71%), 10 were histologic grade 2 (47.61%), 16 cases were hormone receptor positive (76.19%), 7 were Her2Neu positive (33.33%), and only 2 cases were triple negative (9.52%). Positive hTERT expression was detected in 11 cases (52.38%) and was negative in the remaining cases. A significant association was identified between hTERT-positive cases and Her2-Neu positive cases (p = 0.04). Baseline and post-treatment telomere lengths showed a significant difference using the non-parametric Wilcoxon t-test (p = 0.002). In hTERT-positive cases, there was significant telomere shortening at the end of oncological treatment (6.14 ± 1.54 vs. 4.75 ± 1.96 Kb, p = 0.007). Conclusion: Positive hTERT immunostaining cases were associated with poor prognostic factors, such as Her2-Neu overexpression and post-treatment telomere shortening. In the future, hTERT immunostaining could be used to select patients for therapies with antagonistic effects on hTERT, as well as in the selection of more appropriate chemotherapy regimens for patients who express it.

Prevalence and Diversity of Trypanosoma cruzi in Triatomine Vectors and Their Blood Meal Sources from South Central Texas, USA.

The prevalence of Trypanosoma cruzi was assessed in 117 triatomine insects from central Texas. The qPCR-based results revealed T. cruzi in 59% of the insects (62 adults and eight nymphs), with overall prevalences of T. cruzi of 0% (0/9), 64% (11/17), 58% (10/17), 73% (30/41), and 57% (19/33) for the Bastrop, Caldwell, Gonzales, Guadalupe, and Hays counties, respectively. Analyses of 18S rRNA fragments confirmed T. cuzi in 81% of these samples. Vectors were identified as Triatoma gerstaeckeri (35% of which 65% were positive for T. cruzi), T. sanguisuga (21%, 43% positive), and Paratriatoma leticularia (0.3%, 100% positive). Food sources were recovered from 29% of the insects. Raccoons were 53% of the blood meals (83% positive for T. cruzi), while the remainder came from a variety of sources, including humans (33% positive), house geckos, Eastern woodrats, plain-bellied water snakes (50% positive), hispid cotton rats (0% positive), chickens (100% positive); Asian forest turtles, bison, and pigs (0% positive). The serendipitous detection of blood meal sources at known minimum distances from the collection of the vector insect enabled us to provide several instances where the insect foraging distance was greater than 400 m. These vector foraging distances are novel information that can assist in our understanding of the landscape dynamics for the spread of the pathogen.

Renal Regional Oxygen Saturation and Acute Kidney Injury in Neonates with Perinatal Asphyxia.

OBJECTIVE: Neonates with moderate-to-severe perinatal asphyxia often develop acute kidney injury (AKI). Additionally, therapeutic hypothermia (TH) can affect renal blood flow. This study aimed to evaluate the association between renal regional oxygen saturation (rSrO2) during TH and AKI in neonates with moderate and severe perinatal asphyxia. STUDY DESIGN: This retrospective longitudinal study included neonates with moderate-to-severe asphyxia who required TH. The primary outcome was the occurrence of AKI, classified as a rate of decrease in creatinine levels of <33% at 72 hours of TH. rSrO2 was continuously monitored by near-infrared spectroscopy during the hypothermia and rewarming phases. Data analysis involved dividing the average rSrO2 levels into 12-hour periods. We analyzed the association between AKI and rSrO2 levels using univariate and multivariate logistic regression models. Furthermore, we assessed the predictive capacity of rSrO2 for AKI by analyzing the area under the receiver operating characteristic curve. RESULTS: Ninety-one patients were included in the study. On average, patients with AKI exhibit lower rSrO2 levels during TH. Specifically, rSrO2 levels within the first 12 hours and between 25 and 72 hours of TH demonstrated the highest predictive capability for AKI. Multivariate logistic regression analysis revealed that rSrO2 levels within the initial 12 hours (adjusted odds ratio [aOR] = 1.11, 95% confidence interval [CI]: 1.01-1.21) and between 61 and 72 hours (aOR = 0.85, 95% CI: 0.78-0.92) were significantly associated with AKI. CONCLUSION: An increase in rSrO2 during the first 12 hours of TH and lower rSrO2 levels between 61 and 72 hours of treatment were associated with the development of AKI in asphyxiated neonates undergoing TH. KEY POINTS: · Neonates with asphyxia often develop AKI.. · Renal saturations are affected by hypothermia and asphyxia. · Patients with AKI initially show higher rSrO2, then lower rSrO2.. · Monitoring rSrO2 identifies early AKI..

Modulatory role of Faecalibacterium on insulin resistance and coagulation in patients with post-viral long haulers depending on adiposity.

Patients with Post-viral long hauler encompass lasting symptoms and comorbid complexities, often exacerbated in individuals with excessive body weight. The aim was to study gut microbiota in 130 patients with post-viral long hauler stratified by body mass index (BMI) and the relationship between inflammation and microbiota. Significant higher values were found for anthropometric variables and markers of glucose and dyslipidemia in individuals with higher BMI, as well as elevated levels of C-reactive protein, fibrinogen, IL-6, uric acid, and D-dimer. An interactive association showed an interplay between Faecalibacterium, D-dimer levels, and insulin resistance. This investigation showed that anthropometric, biochemical, and inflammatory variables were impaired in patients with post-viral long haulers with higher BMI. In addition, gut microbiota differences were found between groups and a modification effect on Faecalibacterium abundance regarding insulin resistance and D-dimer. These findings suggest that considering adiposity and gut microbiota structure and composition may improve personalized clinical interventions in patients with chronic inflammation.

Sediment source and dose influence the larval performance of the threatened coral Orbicella faveolata.

The effects of turbidity and sedimentation stress on early life stages of corals are poorly understood, particularly in Atlantic species. Dredging operations, beach nourishment, and other coastal construction activities can increase sedimentation and turbidity in nearby coral reef habitats and have the potential to negatively affect coral larval development and metamorphosis, reducing sexual reproduction success. In this study, we investigated the performance of larvae of the threatened Caribbean coral species Orbicella faveolata exposed to suspended sediments collected from a reef site in southeast Florida recently impacted by dredging (Port of Miami), and compared it to the performance of larvae exposed to sediments collected from the offshore, natal reef of the parent colonies. In a laboratory experiment, we tested whether low and high doses of each of these sediment types affected the survival, settlement, and respiration of coral larvae compared to a no-sediment control treatment. In addition, we analyzed the sediments used in the experiments with 16S rRNA gene amplicon sequencing to assess differences in the microbial communities present in the Port versus Reef sediments, and their potential impact on coral performance. Overall, only O. faveolata larvae exposed to the high-dose Port sediment treatment had significantly lower survival rates compared to the control treatment, suggesting an initial tolerance to elevated suspended sediments. However, significantly lower settlement rates were observed in both Port treatments (low- and high-dose) compared to the control treatment one week after exposure, suggesting strong latent effects. Sediments collected near the Port also contained different microbial communities than Reef sediments, and higher relative abundances of the bacteria Desulfobacterales, which has been associated with coral disease. We hypothesize that differences in microbial communities between the two sediments may be a contributing factor in explaining the observed differences in larval performance. Together, these results suggest that the settlement success and survival of O. faveolata larvae are more readily compromised by encountering port inlet sediments compared to reef sediments, with potentially important consequences for the recruitment success of this species in affected areas.

Reciprocal and Differential Influences of Mediterranean Diet and Physical Activity on Adiposity in a Cohort of Young and Older than 40 Years Adults.

Translational research has documented the conjoint beneficial relationships between dietary and physical activity habits concerning weight maintenance. However, the precise interplay between diet and exercise impacting body composition remains unclear, challenging personalized interventions. This study aimed to explore potential interactions and effect modifications of these factors affecting the body mass index (BMI) within an online adult cohort. Data from 11,883 NUTRiMDEA cohort participants were analyzed in this cross-sectional study, categorizing individuals by age, sex, and BMI using linear regression models to assess the interactions between lifestyle factors and adiposity. Significant differences emerged in anthropometry, lifestyle, and health-related quality of life (HRQoL) across categories. The combined effect of diet and physical activity had a greater impact on BMI than physical activity or Mediterranean diet adherence alone, with lower BMI as physical activity levels increased (ß: -0.5) and adherence to the Mediterranean diet decreased, where a modification effect between them was identified (ß: -0.28). Participants with lower Mediterranean diet adherence displayed superior BMI when physical activity was low, but when activity levels were higher, their BMI aligned with those with healthier dietary habits. An interaction link between lifestyle factors and BMI was found, showing the differential effects of the Mediterranean diet and physical activity combination concerning adiposity.

In-gel protein digestion using acidic methanol produces a highly selective methylation of glutamic acid residues.

Mass-tolerant open search methods allow the high-throughput analysis of modified peptides by mass spectrometry. These techniques have paved the way to unbiased analysis of post-translational modifications in biological contexts, as well as of chemical modifications produced during the manipulation of protein samples. In this work, we have analyzed in-depth a wide variety of samples of different biological origin, including cells, extracellular vesicles, secretomes, centrosomes and tissue preparations, using Comet-ReCom, a recently improved version of the open search engine Comet-PTM. Our results demonstrate that glutamic acid residues undergo intensive methyl esterification when protein digestion is performed using in-gel techniques, but not using gel-free approaches. This effect was highly specific to Glu and was not found for other methylable residues such as Asp.

Stent Duodenal in Malignant Obstruction of the Gastric Outflow Tract in a Reference Center in Cundinamarca: Case Series / Stent duodenal en obstrucción maligna del tracto de salida gástrico en un centro de referencia de Cundinamarca: serie de casos

Abstract Objective: To describe the experience of the insertion of the duodenal stent in patients with malignant obstruction of the gastric outflow tract in a third-level reference center in Cundinamarca. Materials and methods: Observational study, case series. Patients with Malignant gastric outlet obstruction (MGOO) diagnosed between December 2019 and February 2022 underwent the insertion of a self-expanding duodenal metal stent in the Gastroenterology unit of Hospital Universitario de la Samaritana. Results: 17 patients were enrolled, 76% of whom were male, with a mean age of 69 years (standard deviation [SD]: 11 years). Histology confirmed gastric adenocarcinoma was found in 82% of the patients, and 41% reported peritoneal carcinomatosis. We achieved total technical success (100%) and clinical success (88%) (15 patients). Regarding the size of the stent used, 35% (6 patients) were 12 cm, 53% (9 patients) were 9 cm, and 12% (2 patients) were 6 cm. Fluoroscopic and endoscopic guidance was used in 88% of cases. Patient survival at follow-up was an average of 84 days (2.8 months; range: 0-414 days) and currently, 1 patient continues in post-insertion surveillance for stent at the time described in the study. Conclusion: Duodenal stent is an effective and safe palliative management alternative in patients with MGOO that improves symptoms, particularly, oral tolerance and early hospital discharge in this group of patients (with advanced terminal neoplastic disease in the palliative management phase), reducing the need for surgical management.

Resumen Objetivo: Describir la experiencia de la inserción del stent duodenal en pacientes con obstrucción maligna del tracto de salida gástrico en un centro de referencia de tercer nivel de Cundinamarca. Materiales y métodos: Estudio observacional, serie de casos. Pacientes con obstrucción maligna del tracto de salida gástrico (OTSG) diagnosticados entre diciembre de 2019 y febrero de 2022 llevados a inserción de stent metálico autoexpandible duodenal en la unidad de Gastroenterología del Hospital Universitario de la Samaritana. Resultados: 17 pacientes fueron incluidos, de los cuales el 76 % eran hombres, con una edad promedio de 69 años (desviación estándar [DE]: 11 años). Se encontró adenocarcinoma gástrico confirmado por histología en el 82 % de los pacientes, y el 41 % tenía carcinomatosis peritoneal. El éxito técnico fue del 100 % y el éxito clínico fue del 88 % (15 pacientes). En cuanto al tamaño del stent utilizado, el 35 % (6 pacientes) fue de 12 cm, el 53 % (9 pacientes) de 9 cm y el 12 % (2 pacientes) de 6 cm. Se utilizó guía fluoroscópica y endoscópica en el 88 % de los casos. La sobrevida de los pacientes en el seguimiento fue en promedio de 84 días (2,8 meses; rango: 0-414 días) y actualmente 1 paciente continúa en vigilancia posterior a la inserción de stent en el tiempo descrito del estudio. Conclusión: El stent duodenal es una alternativa de manejo paliativo efectiva y segura en los pacientes con OTSG que permite mejorar los síntomas y, en especial, la tolerancia a la vía oral y el egreso hospitalario temprano en este grupo de pacientes con una enfermedad neoplásica avanzada terminal en fase de manejo paliativo, lo que disminuye la necesidad de manejo quirúrgico.

Feasibility and reliability of a quality indicator system for an ambulatory dispensing service.

Background: For a medication dispensing service to function with quality, continuous evaluation is required, which is why it is necessary to have reliable measurement tools that make it possible. Quality indicators can serve as tools for managing quality, as they are variables that directly or indirectly measure changes in a situation and help evaluate the progress made in addressing it. This article aims to determine the feasibility and reliability of a quality indicator system for a drug dispensing service for paediatric outpatients in two Mexican hospitals. Methods: A study of the development type of health systems and services at a microlevel was conducted from October 2020 to October 2021 in the pharmaceutical service of two Mexican hospitals. To determine the feasibility of the quality indicators, a retrospective evaluation was performed, which considered the indicators that could be calculated with the available information to be feasible. To determine reliability, an inter-observer agreement study (Kappa (κ)) was performed. Results: The feasibility analysis revealed that all five reference indicators related to the structure were feasible in both hospitals. In the Infantil of the Californias hospital, all six process indicators evaluated were feasible, whilst only one was found feasible in H+ Querétaro. As for outcome indicators, only one was feasible in the Infantil of the Californias hospital. The causes of non-feasibility in both hospitals were the non-documentation of the primary data related to the stages of the process and the lack of instruments to measure patient satisfaction. The reliability of the indicators showed little variability. Conclusion: Although not all indicators were feasible, solutions were proposed so that the 15 reference indicators could be used if an organization decided to do so. The reliability of the indicators was demonstrated, evidencing the importance of the data sheet as a tool to generate valid reliable measures.This article is part of the Hospital pharmacy, rational use of medicines and patient safety in Latin America Special Issue: https://www.drugsincontext.com/special_issues/hospital-pharmacy-rational-use-of-medicines-and-patient-safety-in-latin-america/.

OnabotulinumtoxinA as a promising treatment for primary trochlear headache: A retrospective case series.

OBJECTIVES: To report the efficacy of onabotulinumtoxinA (BoNTA) injections in relieving pain in patients with primary trochlear headache (PRTH). METHODS: Examination of medical records for patients diagnosed with PRTH according to the International Classification of Headache Disorders, 3rd edition criteria and treated with BoNTA. Data were collected for variables related to pain relief, duration of effectiveness, and adverse effects. RESULTS: Six patients were included in the study. All had previously undergone standard care interventions, including infiltrations or oral treatments, yet experienced treatment failure or symptom recurrence. All patients received 20 units of BoNTA, administered in the corrugator and procerus muscles. Subsequent to the BoNTA injections, all six patients reported substantial pain relief, with five achieving complete remission of symptoms. The analgesic effect persisted for a duration of 3 months. No adverse events were reported in any of the cases. CONCLUSIONS: Our case series presents the first evidence of the potential of BoNTA as a safe and effective treatment option for PRTH. From a clinical standpoint, having a safer alternative is of paramount significance for patients with limited treatment options, such as those with PRTH. Further research is warranted to validate these findings and explore the long-term efficacy of BoNTA in PRTH management.

Primary follicular lymphoma of the duodenum as an incidental finding on upper gastrointestinal endoscopy.

Primary follicular lymphoma of the duodenum (FLD) is a rare variant of follicular lymphoma (FL), which represents only 1-4% of gastrointestinal non-hodgkin lymphomas (NHL). It usually appears in the second portion of the duodenum as micronodular lesions and the diagnosis is often incidental. Unlike other NHLs, the prognosis is excellent and the treatment ranges from "watch and wait" to rituximab-based immunochemotherapy regimens, depending on the symptoms and the presence of systemic involvement.

Association of microscopic colitis and enteropathy due to olmesartan.

We report the case of a patient with severe chronic diarrhea. He was admitted on multiple occasions for this reason, with the cause remaining undetected. After obtaining a detailed medical history and performing several studies, the patient was diagnosed with microscopic colitis and enteropathy due to Olmesartan. In the literature, both diseases appear concurrently only in a few cases. Here we highlight the importance of conducting a comprehensive medical history and maintaining high clinical suspicion to avoid delays in the diagnosis of these uncommon pathologies, as well as unnecessary tests and empirical treatments.

Quality of Recovery After Unplanned and Planned Cesarean Deliveries: A Prospective Observational Study Using the Obstetric Quality of Recovery-10 Tool.

BACKGROUND: There is a paucity of literature examining the differences between patient-reported outcome measures after planned and unplanned cesarean delivery using a validated quality of recovery tool. The Obstetric Quality of Recovery-10 (ObsQoR-10) scoring tool has been validated to quantify functional recovery after cesarean delivery. We aimed to use the ObsQoR-10 to compare the postoperative recovery characteristics of patients undergoing planned and unplanned cesarean deliveries. METHODS: We conducted a prospective single-center observational study. Patients undergoing planned and unplanned cesarean deliveries under neuraxial anesthesia were asked to complete the ObsQoR-10 questionnaire 24 hours, 48 hours, and 1 week postpartum. We collected information on total in-hospital postoperative opioid consumption and patients´ perception of readiness for discharge at 24 and 48 hours postpartum. Additionally, patient characteristics were collected to assess their correlation with our findings. RESULTS: We included 112 patients (56 in each group). No statistical differences in ObsQoR-10 scores at 24 hours, 48 hours, and 1 week postpartum were observed between the planned and unplanned cesarean deliveries. Additionally, there was no difference between the groups in patients' perception of readiness for hospital discharge at 24 and 48 hours and opioid consumption in the first 2 days after surgery. Most patients in both groups did not think they would be ready for discharge at 24 hours postpartum. Analysis of the individual components of ObsQoR-10 at 24 hours showed a difference in the responses assessing the severity of shivering (higher in unplanned cesarean deliveries) and the ability to look after personal hygiene (lower in unplanned cesarean deliveries). CONCLUSIONS: As assessed by the ObsQoR-10, no significant difference in the quality of recovery was observed between patients undergoing planned and unplanned cesarean delivery.

Immune and metabolic challenges induce changes in pain sensation and related pathways in the hypothalamus.

The hypothalamic molecular processes participate in the regulation of the neuro-immune-endocrine system, including hormone, metabolite, chemokine circulation, and corresponding physiological and behavioral responses. RNA-sequencing profiles were analyzed to understand the effect of juvenile immune and metabolic distress 100 days after virally elicited maternal immune activation during gestation in pigs. Over 1,300 genes exhibited significant additive or interacting effects of gestational immune activation, juvenile distress, and sex. One-third of these genes presented multiple effects, emphasizing the complex interplay of these factors. Key functional categories enriched among affected genes included sensory perception of pain, steroidogenesis, prolactin, neuropeptide, and inflammatory signaling. These categories underscore the intricate relationship between gestational immune activation during gestation, distress, and the response of hypothalamic pathways to insults. These effects were sex-dependent for many genes, such as Prdm12, Oprd1, Isg20, Prl, Oxt, and Vip. The prevalence of differentially expressed genes annotated to proinflammatory and cell cycle processes suggests potential implications for synaptic plasticity and neuronal survival. The gene profiles affected by immune activation, distress, and sex pointed to the action of transcription factors SHOX2, STAT1, and REST. These findings underscore the importance of considering sex and postnatal challenges when studying causes of neurodevelopmental disorders and highlight the complexity of the "two-hit" hypothesis in understanding their etiology. Our study furthers the understanding of the intricate molecular responses in the hypothalamus to gestational immune activation and subsequent distress, shedding light on the sex-specific effects and the potential long-lasting consequences on pain perception, neuroendocrine regulation, and inflammatory processes.NEW & NOTEWORTHY The interaction of infection during gestation and insults later in life influences the molecular mechanisms in the hypothalamus that participate in pain sensation. The response of the hypothalamic transcriptome varies between sexes and can also affect synapses and immune signals. The findings from this study assist in the identification of agonists or antagonists that can guide pretranslational studies to ameliorate the effects of gestational insults interacting with postnatal challenges on physiological or behavioral disorders.