Emotional Regulation as a Transdiagnostic Process of Emotional Disorders in Therapy: A Systematic Review and Meta-Analysis.

CONTEXT: Several studies have shown that emotional regulation (ER) is a transdiagnostic construct of emotional disorders. Therefore, if therapy improves ER, it would improve psychological distress. OBJECTIVE: This review assesses and compares the changes in ER due to psychological treatment in different therapies. METHODS: A systematic review and meta-analysis of RCTs published in the databases PubMed, PsycINFO and Web of Science was performed. It was registered in PROSPERO under the number CRD42023387317. Two independent experts in the field reviewed the articles. RESULTS: A total of 18 articles met the criteria for inclusion in the review. Analysis of these studies suggests that in unified protocol (UP), cognitive behaviour therapy, dialectical behaviour therapy (DBT) and mindfulness, there is evidence to support that a moderate effect occurs during treatment. Furthermore, in mindfulness and DBT, the effect was moderate in the follow-up period, while in UP, it was high. LIMITATIONS: Given the heterogeneity of the applied interventions and the methodological limitations found in the reviewed trials, the results should be interpreted with caution. CONCLUSIONS: UP, cognitive behaviour therapy, DBT and mindfulness can improve ER after therapy, while UP, DBT and mindfulness in the follow-up period. Other therapies, such as SKY or Flotation REST, require more research.

INTRODUCCIÓN: Varios estudios han demostrado que la regulación emocional es un constructo transdiagnóstico de los trastornos emocionales. Por lo tanto, si la terapia mejora la regulación emocional, también mejorará el malestar psicológico. OBJETIVO: Evaluar y comparar el cambio en la regulación emocional debido al tratamiento psicológico en diferentes terapias. MÉTODO: Se realizó una revisión sistemática y metaanálisis de ECA publicados en las bases de datos PubMed, PsycINFO y Web of Science. Se registró en PROSPERO con el número CRD42023387317. Dos expertos independientes en la materia revisaron los artículos. RESULTADOS: Un total de 18 artículos cumplieron los criterios de inclusión en la revisión. El análisis de estos estudios sugiere que en el Protocolo Unificado, la Terapia Cognitivo Conductual, la Terapia Dialéctica Conductual y terapias basadas en mindfulness existen evidencias que apoyan que se produce un efecto moderado durante el tratamiento. Además, en las terapias basadas en mindfulness y en la Terapia Dialéctica Conductual, el efecto se moduló en el periodo de seguimiento, mientras que en el Protocolo Unificado fue mayor. LIMITACIONES: Dada la heterogeneidad de las intervenciones aplicadas y las limitaciones metodológicas encontradas en los ensayos revisados, los resultados podrán interpretarse con cautela. CONCLUSIONES: UP, CBT, DBT y mindfulness pueden mejorar la ER tras la terapia, mientras que UP, DBT y mindfulness pueden mejorar la recuperación tras un tiempo de seguimiento. Otras terapias, como SKY o Flotation REST, requieren más investigación.

Double Hit of Hydroxichloroquine and Amiodarone Induced Renal Phospholipidosis in a Patient with Monoclonal Gammopathy and Sclerodermiform Syndrome: A Case Report and Review of the Literature.

Phospholipidosis is a rare disorder which consists of an excessive intracellular accumulation of phospholipids and the appearance of zebra bodies or lamellar bodies when looking at them using electron microscopy. This disease is associated with certain genetic diseases or is secondary to drugs or toxins. Drug-induced phospholipidosis encompasses many types of pharmaceuticals, most notably chloroquine, amiodarone or ciprofloxacin. Clinically and histologically, renal involvement can be highly variable, with the diagnosis not being made until the zebra bodies are seen under an electron microscope. These findings may require genetic testing to discount Fabry disease, as its histological findings are indistinguishable. Most of the chemicals responsible are cationic amphiphilic drugs, and several mechanisms have been hypothesized for the formation of zebra bodies and their pathogenic significance. However, the relationship between drug toxicity and phospholipid accumulation, zebra bodies and organ dysfunction remains enigmatic, as do the renal consequences of drug withdrawal. We present, to our knowledge, the first case report of acute renal injury with a monoclonal gammopathy of renal significance, lesions, and sclerodermiform syndrome, with zebra bodies that were associated with the initiation of a hydroxychloroquine and amiodarone treatment, as an example of drug-induced-phospholipidosis.

Video assisted retroperitoneal debridement for infected pancreatic necrosis: A two port approach for difficult access.

INTRODUCTION AND IMPORTANCE: The incidence of acute pancreatitis varies globally, and its rates are increasing. Timely intervention in cases of infected necrosis is crucial to effective management. The landscape of acute pancreatitis management has undergone transformation through adopting a "step-up" strategy, accentuating the shift towards minimally invasive techniques. CASE PRESENTATION: A 63-year-old patient with acute pancreatitis and infected pancreatic necrosis underwent a challenging yet successful treatment using video-assisted retroperitoneal debridement employing a two-port approach facilitated access for an intricate area. The procedure, performed 45 days after admission, effectively reduced peripancreatic collections, demonstrating the efficacy of this approach in managing complex cases of infected pancreatic necrosis. CLINICAL DISCUSSION: The management of acute pancreatitis has evolved towards a comprehensive strategy involving early hydration, nutritional support, effective pain management, and interventions. Infected pancreatic necrosis poses a serious complication, with minimally invasive techniques such as video-assisted retroperitoneal debridement (VARD) emerging as preferred options. The efficacy and safety of VARD in complex cases are highlighted, although challenges persist, especially in extensive necrosis. CONCLUSION: The VARD procedure, a key component of the step-up approach, exhibits a remarkable safety profile, substantially reducing postoperative complications and mortality compared to open surgical counterparts. However, challenges persist in managing cases of infected Walled-Off Necrosis with deep extension, necessitating carefully considering a minimal-access approach. We report our experience using the VARD in a two-port approach.

Liquid biopsy for molecular characterization of diffuse large B-cell lymphoma and early assessment of minimal residual disease.

Circulating tumour DNA (ctDNA) allows genotyping and minimal residual disease (MRD) detection in lymphomas. Using a next-generation sequencing (NGS) approach (EuroClonality-NDC), we evaluated the clinical and prognostic value of ctDNA in a series of R-CHOP-treated diffuse large B-cell lymphoma (DLBCL) patients at baseline (n = 68) and after two cycles (n = 59), monitored by metabolic imaging (positron emission tomography combined with computed tomography [PET/CT]). A molecular marker was identified in 61/68 (90%) ctDNA samples at diagnosis. Pretreatment high ctDNA levels significantly correlated with elevated lactate dehydrogenase, advanced stage, high-risk International Prognostic Index and a trend to shorter 2-year progression-free survival (PFS). Valuable NGS data after two cycles of treatment were obtained in 44 cases, and 38 achieved major molecular response (MMR; 2.5-log drop in ctDNA). PFS curves displayed statistically significant differences among those achieving MMR versus those not achieving MMR (2-year PFS of 76% vs. 0%, p < 0.001). Similarly, more than 66% reduction in ΔSUVmax by PET/CT identified two subgroups with different prognosis (2-year PFS of 83% vs. 38%; p < 0.001). Combining both approaches MMR and ΔSUVmax reduction, a better stratification was observed (2-year PFS of 84% vs. 17% vs. 0%, p < 0.001). EuroClonality-NDC panel allows the detection of a molecular marker in the ctDNA in 90% of DLBCL. ctDNA reduction at two cycles and its combination with interim PET results improve patient prognosis stratification.

pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells and mouse model.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

Dietary intake of Perfluorooctanesulfonic acid (PFOS) and glucose homeostasis parameters in a non-diabetic senior population.

BACKGROUND: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food. OBJECTIVE: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study. METHODS: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI. RESULTS: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [ß-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m2(0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up. DISCUSSION: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up.

Development and validation of a clinical decision support system to prevent anticoagulant duplications.

BACKGROUND AND OBJECTIVE: Unintended duplicate prescriptions of anticoagulants increase the risk of serious adverse events. Clinical Decision Support Systems (CDSSs) can help prevent such medication errors; however, sophisticated algorithms are needed to avoid alert fatigue. This article describes the steps taken in our hospital to develop a CDSS to prevent anticoagulant duplication (AD). METHODS: The project was composed of three phases. In phase I, the status quo was established. In phase II, a clinical pharmacist developed an algorithm to detect ADs using daily data exports. In phase III, the algorithm was integrated into the hospital's electronic health record system. Alerts were reviewed by clinical pharmacists before being sent to the prescribing physician. We conducted a retrospective analysis of all three phases to assess the impact of the interventions on the occurrence and duration of ADs. Phase III was analyzed in more detail regarding the acceptance rate, sensitivity, and specificity of the alerts. RESULTS: We identified 91 ADs in 1581 patients receiving two or more anticoagulants during phase I, 70 ADs in 1692 patients in phase II, and 57 ADs in 1575 patients in phase III. Mean durations of ADs were 1.8, 1.4, and 1.1 calendar days during phases I, II, and III, respectively. In comparison to the baseline in phase I, the relative risk reduction of AD in patients treated with at least two different anticoagulants during phase III was 42% (RR: 0.58, CI: 0.42-0.81). A total of 429 alerts were generated during phase III, many of which were self-limiting, and 186 alerts were sent to the respective prescribing physician. The acceptance rate was high at 97%. We calculated a sensitivity of 87.4% and a specificity of 87.9%. CONCLUSION: The stepwise development of a CDSS for the detection of AD markedly reduced the frequency and duration of medication errors in our hospital, thereby improving patient safety.

Perception of photovoltaic energy consumption in the Spanish primary sector. An environmentally profitable alternative.

Agriculture and livestock farming are activities that depend on energy consumption. Photovoltaic self-consumption systems can reduce the production costs of these actors, especially in periods of high-energy price volatility. This work aimed to determine the degree of implementation of photovoltaic self-consumption systems, their relationship with the economic impact of the energy crisis, and the perception of producers to use renewable energy sources in the Spanish agricultural system as it is one of the most important at European level. For this purpose, a survey of the Spanish agricultural and livestock system, involving 396 primary producers, was carried out between December 2022 and March 2023. The results suggest that self-consumption systems are in place in 49.1% of all farms and that these have had a positive effect in alleviating the rising energy costs suffered by the Spanish primary sector. In summary, Spanish primary producers generally have a favorable perception of the use of renewable energies on their farms, especially photovoltaic. However, the cluster analysis shows the fact that there are two types of producers, active and passive, from an environmental point of view. The characterization of this type of producers can help the Spanish Administration to improve the efficiency of its energy strategy, and can be a source of inspiration for the governments of other countries.

Description and clinical relevance of the variable conformation of canine spinal arachnoid diverticula.

The conformation of spinal arachnoid diverticula (SAD) and their clinical implications are poorly characterized in dogs. This retrospective cross-sectional study describes different SAD conformations in dogs and aims to identify if there is an association between SAD conformation and clinical features, localization, syringomyelia (SM) presence, concurrent vertebral condition, treatment option, and short as well as long-term outcome. Sixty-two dogs were included (12 cervical and 50 thoracolumbar SAD). All dogs with a cervical SAD had a cranial tethered conformation and were not included in the statistical analysis. Half of the dogs with a thoracolumbar SAD were cranial tethered, and the other half were caudal tethered. SM associated with SAD had a moderate prevalence in the cervical region (58.3%) and a high prevalence in the thoracolumbar region (82%). All dogs with the presence of SM and caudal tethered SAD had a cranial positioned SM, and all dogs with SM and a cranial tethered SAD had a caudal positioned SM. The SM absolute length and SM length/L2 ratio were significantly higher (P = .018, respectively) in the caudal tethered SAD compared with the cranial tethered SAD. The short-term outcome was statistically different (P = .045) between caudal and cranial tethered thoracolumbar SAD, but not the long-term outcome (P = .062). Multivariable logistic regression identified thoracolumbar caudal tethered SAD conformation had a better short-term outcome (P = 0.017, OR: 0.043, CI: 0.003-0.563), independently of SM length measurements. SAD conformation in dogs can influence SM formation. A possible link between short-term outcome and SAD conformation was found, but further research is warranted.

Increased threat of urban arboviral diseases from Aedes aegypti mosquitoes in Colombia.

Objectives: Our study targets the potential of the local urban mosquito Aedes aegypti to experimentally transmit chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and Zika virus (ZIKV). Methods: We collected eggs and adults of Ae. aegypti in Medellín, Colombia (from February to March 2020) for mosquito experimental infections with DENV, CHIKV, YFV and ZIKV and viral detection using the BioMark Dynamic arrays system. Results: We show that Ae. aegypti from Medellín was more prone to become infected, to disseminate and transmit CHIKV and ZIKV than DENV and YFV. Conclusions: Thus, in Colombia, chikungunya is the most serious threat to public health based on our vector competence data.

Daratumumab and Nelarabine Treatment as Salvage Therapy for T-Lymphoblastic Lymphoma: A Case Report.

T-cell lymphoblastic lymphoma is an uncommon lymphoid neoplasm in adults, although more frequent in children and teenagers, that often affects the mediastinum and bone marrow, requiring intensive chemotherapy protocols. Its prognosis is poor if a cure is not achieved with first-line treatments. We present a case report of a 19-year-old man diagnosed with this type of lymphoma due to significant respiratory distress and a mediastinal mass. He received treatment according to the hyper-CVAD regimen, with a complete metabolic response. However, seven months later a new mediastinal growth was observed, leading to salvage treatment with a combination of nelarabine and daratumumab. We observed not only refractoriness, but also leukemization, which prompted consideration of hematopoietic stem cell transplantation. Based on this case, we conducted a review of pharmacological treatment options for refractory or relapsed lymphoblastic lymphoma, as well as the role of radiotherapy in managing mediastinal disease. This case report highlights the limited evidence available regarding later-line treatments, with unusual reports regarding employing our combination of daratumumab and nelarabine, and emphasizes the importance of achieving cures in the first line of treatment.

Deconstructing neutrophil to lymphocyte ratio (NLR) in early breast cancer: lack of prognostic utility and biological correlates across tumor subtypes.

PURPOSE: The prognostic utility and biological correlates of neutrophil to lymphocyte ratio (NLR), a potential biomarker of the balance between immune response and the inflammatory status, are still uncertain in breast cancer (BC). METHODS: We analysed a cohort of 959 women with early breast cancer, mostly treated with neoadjuvant or adjuvant chemotherapy. Clinical and pathological data, survival, NLR (continuous and categorical) and stromal tumor infiltrating lymphocytes (sTIL) were evaluated. RESULTS: NLR was only weakly associated with Ki67, while no association was found for grade, histology, immunohistochemical subtype or stage. Lymphocyte infiltration of the tumor did not correlate with NLR (Rho: 0.05, p = 0.30). These results were similar in the whole group and across the different BC subtypes, with no differences in triple negative BC. Relapse free interval (RFI), breast cancer specific survival (BCSS) and overall survival (OS) changed according to pre-treatment NLR neither in the univariate nor in the multivariate Cox models (RFI: HR 0.948, p = 0.61; BCSS: HR 0.920, p = 0.57; OS: HR 0.96, p = 0.59). CONCLUSION: These results question the utility of NLR as a prognostic biomarker in early breast cancer and suggest the lack of correlation of NLR with tumor microenvironment immune response.

Homicidio por combinación de métodos de asfixia / Homicide by combination of methods of asphyxiation

Introducción el homicidio por combinación de métodos de asfixia se observa mayoritariamente en las personas de edad avanzada o con algún impedimento físico capaz de contrarrestar la agresión. Material y métodos se realizó un estudio observacional retrospectivo sobre 634 autopsias, cinco cumplían las características de homicidios por combinación de métodos de asfixia. Resultados dos hombres y 3 mujeres, con edad promedio de 69 años, con estudios toxicológicos negativos, víctimas de un solo agresor, presentaron lesiones cutáneas periorificiales (bucales y nasales), hemorragias musculares en el tórax, fracturas costales, lesiones contusas en la cabeza, interpretadas como de sometimiento. Discusión en la combinación de métodos de asfixia, los hallazgos que deben ser vistos en conjunto son: traumatismos craneoencefálicos para someter a la víctima, lesiones cutáneas en el cuello, la cara, la cara interna de los labios, fracturas costales y lesiones por contrapresión en la espalda, los glúteos o los codos. Contextualizados en conjunto pueden explicar la dinámica de esta modalidad homicida. (AU)

Introduction Homicide by combination of suffocation methods is observed mainly in elderly people or with some physical impediment capable of counteracting the aggression. Material and methods A retrospective observational study was carried out on 634 autopsies. Five met the characteristics of homicides by combination of asphyxiation methods. Results Two men and three women, average age 69 years, with negative toxicological studies, victims of a single aggressor, presented peri orificial skin lesions (mouth and nose), muscle hemorrhages in the thorax, rib fractures, blunt injuries to the head interpreted as like submission. Discussion In the combination of asphyxia methods the findings that must be seen together: Head injuries to subdue the victim, skin lesions on the neck, face, inner face of the lips, rib fractures, and counter-pressure injuries to the back, buttocks, or elbows. Contextualized together, can explain the dynamics of this homicidal modality. (AU)

Intensive Calcium Monitoring Following Parathyroidectomy: Prevention of Hungry Bone Syndrome in Children.

Cite this article as: García Díaz FJ, Martin LB, Gómez Gila AL, Navarro Moreno C. Intensive calcium monitoring following parathyroidectomy: Prevention of hungry bone syndrome in children. Turk Arch Pediatr. 2024;59(1):109-111.

Multimodal Mobile Robotic Dataset for a Typical Mediterranean Greenhouse: The GREENBOT Dataset.

This paper presents an innovative dataset designed explicitly for challenging agricultural environments, such as greenhouses, where precise location is crucial, but GNNS accuracy may be compromised by construction elements and the crop. The dataset was collected using a mobile platform equipped with a set of sensors typically used in mobile robots as it was moved through all the corridors of a typical Mediterranean greenhouse featuring tomato crops. This dataset presents a unique opportunity for constructing detailed 3D models of plants in such indoor-like spaces, with potential applications such as robotized spraying. For the first time, to the authors' knowledge, a dataset suitable to test simultaneous localization and mapping (SLAM) methods is presented in a greenhouse environment, which poses unique challenges. The suitability of the dataset for this purpose is assessed by presenting SLAM results with state-of-the-art algorithms. The dataset is available online.

Virome analyses of Amblyomma cajennense and Rhipicephalus microplus ticks collected in Colombia.

Tick-borne viruses (TBV) have gained public health relevance in recent years due to the recognition of human-associated fatal cases and the increase in tick-borne disease and transmission. However, many tick species have not been studied for their potential to transmit pathogenic viruses, especially those found in Latin America. To gain better understanding of the tick virome, we conducted targeted amplification using broadly-reactive consensus-degenerate pan-viral targeting viruses from the genera Flavivirus, Bandavirus, Uukuvirus, and Orthonairovirus genus. Additionally, we conducted unbiased metagenomic analyses to investigate the presence of viral RNA sequences in Amblyomma cajennense, A. patinoi and Rhipicephalus microplus ticks collected from a horse slaughter plant in Medellín, Colombia. While no viral products were detected by PCR, results of the metagenomic analyses revealed the presence of viral genomes belonging to the genera Phlebovirus, Bandavirus, and Uukuvirus, including Lihan Tick Virus (LTV), which was previously reported in Rhipicephalus microplus from Colombia. Overall, the results emphasized the enormous utility of the next-generation sequencing in identifying virus genetic diversity presents in ticks and other species of vectors and reservoirs.

Low-Cost Optical Sensors for Soil Composition Monitoring.

Studying soil composition is vital for agricultural and edaphology disciplines. Presently, colorimetry serves as a prevalent method for the on-site visual examination of soil characteristics. However, this technique necessitates the laboratory-based analysis of extracted soil fragments by skilled personnel, leading to substantial time and resource consumption. Contrastingly, sensor techniques effectively gather environmental data, though they mostly lack in situ studies. Despite this, sensors offer substantial on-site data generation potential in a non-invasive manner and can be included in wireless sensor networks. Therefore, the aim of the paper is to develop a low-cost red, green, and blue (RGB)-based sensor system capable of detecting changes in the composition of the soil. The proposed sensor system was found to be effective when the sample materials, including salt, sand, and nitro phosphate, were determined under eight different RGB lights. Statistical analyses showed that each material could be classified with significant differences based on specific light variations. The results from a discriminant analysis documented the 100% prediction accuracy of the system. In order to use the minimum number of colors, all the possible color combinations were evaluated. Consequently, a combination of six colors for salt and nitro phosphate successfully classified the materials, whereas all the eight colors were found to be effective for classifying sand samples. The proposed low-cost RGB sensor system provides an economically viable and easily accessible solution for soil classification.

Synergistic enhancement of the mouse Pramex1 and Pramel1 in repressing retinoic acid (RA) signaling during gametogenesis.

BACKGROUND: PRAME constitutes one of the largest multi-copy gene families in Eutherians, encoding cancer-testis antigens (CTAs) with leucine-rich repeats (LRR) domains, highly expressed in cancer cells and gametogenic germ cells. This study aims to elucidate genetic interactions between two members, Pramex1 and Pramel1, in the mouse Prame family during gametogenesis using a gene knockout approach. RESULT: Single-gene knockout (sKO) of either Pramex1 or Pramel1 resulted in approximately 7% of abnormal seminiferous tubules, characterized by a Sertoli-cell only (SCO) phenotype, impacting sperm count and fecundity significantly. Remarkably, sKO female mice displayed normal reproductive functions. In contrast, Pramex1/Pramel1 double knockout (dKO) mice exhibited reduced fecundity in both sexes. In dKO females, ovarian primary follicle count decreased by 50% compared to sKO and WT mice, correlating with a 50% fecundity decrease. This suggested compensatory roles during oogenesis in Pramex1 or Pramel1 sKO females. Conversely, dKO males showed an 18% frequency of SCO tubules, increased apoptotic germ cells, and decreased undifferentiated spermatogonia compared to sKO and WT testes. Western blot analysis with PRAMEX1- or PRAMEL1-specific antibodies on sKO testes revealed compensatory upregulation of each protein (30-50%) in response to the other gene's deletion. Double KO males exhibited more severe defects in sperm count and litter size, surpassing Pramex1 and Pramel1 sKO accumulative effects, indicating a synergistic enhancement interaction during spermatogenesis. Additional experiments administering trans-retinoic acid (RA) and its inhibitor (WIN18,446) in sKO, dKO, and WT mice suggested that PRAMEX1 and PRAMEL1 synergistically repress the RA signaling pathway during spermatogenesis. CONCLUSION: Data from sKO and dKO mice unveil a synergistic interaction via the RA signaling pathway between Pramex1 and Pramel1 genes during gametogenesis. This discovery sets the stage for investigating interactions among other members within the Prame family, advancing our understanding of multi-copy gene families involved in germ cell formation and function.

Effect of Different Karyophilic Peptides on Physical Characteristics and In Vitro Transfection Efficiency of Chitosan-Plasmid Nanoparticles as Nonviral Gene Delivery Systems.

A strategy to increase the transfection efficiency of chitosan-based nanoparticles for gene therapy is by adding nuclear localization signals through karyophilic peptides. Here, the effect of the length and sequence of these peptides and their interaction with different plasmids on the physical characteristics and biological functionality of nanoparticles is reported. The karyophilic peptides (P1 or P2) were used to assemble nanoparticles by complex coacervation with pEGFP-N1, pQBI25 or pSelect-Zeo-HSV1-tk plasmids, and chitosan. Size, polydispersity index, zeta potential, and morphology, as well as in vitro nucleus internalization and transfection capability of nanoparticles were determined. The P2 nanoparticles resulted smaller compared to the ones without peptides or P1 for the three plasmids. In general, the addition of either P1 or P2 did not have a significant impact on the polydispersity index and the zeta potential. P1 and P2 nanoparticles were localized in the nucleus after 30 min of exposure to HeLa cells. Nevertheless, the presence of P2 in pEGFP-N1 and pQBI25 nanoparticles raised their capability to transfect and express the green fluorescent protein. Thus, karyophilic peptides are an efficient tool for the optimization of nonviral vectors for gene delivery; however, the sequence and length of peptides have an impact on characteristics and functionality of nanoparticles.

Post-COVID-19 Condition in Military Personnel.

INTRODUCTION: During the COVID-19 pandemic, a significant number of individuals experienced persistent symptoms, collectively termed post-COVID-19 condition (PCC) by the World Health Organization. While civilian prevalence has been extensively studied, little is known about PCC in military personnel. This article highlights the need for increased awareness, documentation, and research on PCC within the military context, utilizing the Defense Health Agency database. MATERIALS AND METHODS: A keyword search of the PubMed, CINAHL, and Web of Science databases was performed utilizing the keywords: military, post-COVID conditions, long COVID-19, and post-COVID19 syndrome. A five-stage integrative review framework was used to analyze 40 reports and research articles published from 2019 to 2023 to assess the current state of PCC research, including epidemiology, severe acute respiratory syndrome coronavirus 2 variants, pathophysiology, and prevalence in military personnel. RESULTS: Our review revealed a notable gap in research on PCC within the military population, with only a few mentions in the literature. A key finding was the association between immunization status, symptom severity, and ethnicity in PCC development. CONCLUSION: To comprehensively address PCC in military personnel, it is imperative to foster both awareness and documentation. Creating a centralized Defense Health Agency-DoD repository for active duty service members with PCC diagnoses offers a valuable opportunity to conduct trend analysis, identify missed cases, and better understand the individual and military readiness implications of this condition. Additionally, to address the educational needs of clinicians, it is essential to develop continuing medical education and continuing nursing education programs focusing on PCC signs, symptoms, and their impact on readiness. Furthermore, randomized controlled trials and longitudinal experimental clinical trials are essential for monitoring service members over time, providing valuable insights into the course of PCC and potential interventions. These research endeavors collectively contribute to improving the health, readiness, and care of military personnel affected by PCC.