Initial Respiratory System Involvement in Juvenile Idiopathic Arthritis with Systemic Onset Is a Marker of Interstitial Lung Disease: The Results of Retrospective Cohort Study Analysis.

Background: Pulmonary involvement in systemic juvenile idiopathic arthritis (SJIA) is a rare but dangerous complication. The main risk factors are already known, such as macrophage activation syndrome, a refractory course of systemic juvenile arthritis, infusion reaction to interleukin 1 and/or interleukin 6 blockers, trisomy 21, and eosinophilia. However, information about respiratory system involvement (RSI) at the onset of SJIA is scarce. Our study aimed to evaluate the specific features of children with SJIA with RSI and their outcomes. Methods: In a single-center retrospective cohort study, we compared the information from the medical records of 200 children with SJIA according to ILAR criteria or SJIA-like disease (probable/possible SJIA) with and without signs of RSI (dyspnea, shortness of breath, pleurisy, acute respiratory distress syndrome, and interstitial lung disease (ILD)) at the disease onset and evaluated their outcomes (remission, development of chronic ILD, clubbing, and pulmonary arterial hypertension). Results: A quarter (25%) of the SJIA patients had signs of the RSI at onset and they more often had rash; hepato- and splenomegaly; heart (pericarditis, myocarditis), central nervous system, and kidney involvement; hemorrhagic syndrome; macrophage activation syndrome (MAS, 44.4% vs. 9.0%, p = 0.0000001); and, rarely, arthritis with fewer active joints, compared to patients without RSI. Five patients (10% from the group having RSI at the onset of SJIA and 2.5% from the whole SJIA cohort) developed fibrosing ILD. All of them had a severe relapsed/chronic course of MAS; 80% of them had a tocilizumab infusion reaction and further switched to canakinumab. Unfortunately, one patient with Down's syndrome had gone. Conclusion: Patients with any signs of RSI at the onset of the SJIA are required to be closely monitored due to the high risk of the following fibrosing ILD development. They required prompt control of MAS, monitoring eosinophilia, and routine checks of night oxygen saturation for the prevention/early detection of chronic ILD.

Microwave radiation and thermal effects on the bioenergetics of isolated mitochondria.

AIMS: This study proposes to investigate the effects of microwave radiation and its thermal effects, compared to thermal effects alone, on the bioenergetics of mitochondria isolated from mouse liver. METHODS: The main parameters investigated in this study are mitochondrial respiration (coupled states: S3 and S4; uncoupled state), using a high-resolution respirometer, and swelling, using a spectrophotometer. RESULTS: Mitochondria irradiated at 2.45 GHz microwave with doses 0.085, 0.113 and 0.141 kJ/g, presented a decrease in S3 and uncoupled state, but an increase in S4. Conversely, mitochondria thermally treated at 40, 44 and 50 °C presented an increasing in S3 and S4, while uncoupled state was unaltered. Mitochondrial swelling increases as a function of the dose or temperature, indicating membrane damages in both cases. CONCLUSION: Microwave radiation and thermal effect alone indicated different bioenergetics mitochondria response. These results imply that the effects due to microwave in medical treatment are not exclusively due to the increase in temperature, but a combination of electromagnetic and thermal effects.

Multifunctional calcium-based nanocarriers for synergistic treatment of triple-negative breast cancer.

Targeted breast cancer therapies hold the potential to improve the efficiency of drug delivery to the pathology site without impacting the viability and function of healthy cells. Herein, we developed multifunctional nanocarriers that target simultaneously several downstream signaling processes in triple negative breast cancer cells. The system comprises pH sensitive CaCO3 nanoparticles (NPs) as carriers of the anticancer drug doxorubicin (DOX). The NPs were coated in a layer-by-layer (LbL) fashion using poly-l-lysine and hyaluronic acid to target receptors overexpressed in breast cancer (e.g. CD44, RHAMM). Spheroids of the triple-negative Hs578T cell line were used as a 3D model to assess the therapeutic potential of this system. Our results showed that the NPs act via a synergistic mechanism that combines Ca2+ overload causing cell calcification and DNA damage by DOX. The LbL coating was crucial for the protection of the healthy cells, i.e. it provides NPs with targeting capacity. The overall data suggests that the LbL-coated NPs loaded with DOX hold great potential for the treatment of breast cancer.

Symbionts out of sync: Decoupled physiological responses are widespread and ecologically important in lichen associations.

A core vulnerability in symbioses is the need for coordination between the symbiotic partners, which are often assumed to be closely physiologically integrated. We critically re-examine this assumed integration between symbionts in lichen symbioses, recovering a long overlooked yet fundamental physiological asymmetry in carbon balance. We examine the physiological, ecological, and transcriptional basis of this asymmetry in the lichen Evernia mesomorpha. This carbon balance asymmetry depends on hydration source and aligns with climatic range limits. Differences in gene expression across the E. mesomorpha symbiosis suggest that the physiologies of the primary lichen symbionts are decoupled. Furthermore, we use gas exchange data to show that asymmetries in carbon balance are widespread and common across evolutionarily disparate lichen associations. Using carbon balance asymmetry as an example, we provide evidence for the wide-ranging importance of physiological asymmetries in symbioses.

Hidden Threat: Incidental Finding of Pancreatic Body Solid Pseudopapillary Tumor During Bariatric Evaluation With an Open Central Pancreatectomy Resolution.

Incidentalomas, or tumors found incidentally, are very common. However, pancreatic tumors are usually not found as incidentalomas. To date, these tumors represent a diagnostic and therapeutic challenge, since the risks and benefits associated with surgeries that can be performed to remove these tumors must be evaluated due to perioperative complications. It is vitally important to always carry out a correct approach that includes a histopathological study to allow timely identification of tumors that require surgical management or other preoperative treatment, such as chemotherapy or radiotherapy. The majority of these tumors are benign cystic tumors; however, there are cases, like the one presented here, where the tumor turns out to be a solid pseudopapillary tumor (SPT) that requires a different diagnostic and surgical approach. Also, in this case, the importance of evaluating the patient's general health status is highlighted to determine whether or not the required surgery can be performed at that moment or if any prior intervention is required. This case report talks about a patient in whom an incidental pancreatic tumor was found and how its management was carried out from diagnosis to the postoperative period.

Studying of psycholinguistic features of doctors' professional communication under war conditions.

OBJECTIVE: Aim: Studying of psycholinguistic features of doctors' communication competence in Ukraine under war conditions. PATIENTS AND METHODS: Materials and Methods: Bibliosemantic method; method of system analysis, comparison and generalization; empirical methods - direct observation of the doctors' and patients' living language, typology of empirical data according to socio-demographic indicators. RESULTS: Results: Within the study, 286 dialogues were collected. With voluntary consent, they were recorded in video and audio formats in compliance with ethical, bioethical, and legal norms. Next, initial typology of dialogues, their lexical and semantic analysis with identification of typical positive and negative communicative strategies were carried out. With the help of the ≪Textanz≫ specialized computer software, 48 dialogues were subjected to the content analysis procedure for two separate ≪Doctors≫ and ≪Patients≫ samples. CONCLUSION: Conclusions: The results of the analysis of ≪Doctor-Patient≫ dialogues enabled identifying and describing psycholinguistic markers of typical physiological, mental, social, and spiritual states of individuals seeking medical help under martial law. Thus, the markers of positive emotional states (optimism, confidence, empathy, etc.) and affective, negative emotional processes (anxiety, fear, anger, aggression, sadness, depression, etc.) were identified.

Diminished Immune Cell Adhesion in Hypoimmune ICAM-1 Knockout Pluripotent Stem Cells.

Hypoimmune gene edited human pluripotent stem cells (hPSCs) are a promising platform for developing reparative cellular therapies that evade immune rejection. Existing first-generation hypoimmune strategies have used CRISPR/Cas9 editing to modulate genes associated with adaptive (e.g., T cell) immune responses, but have largely not addressed the innate immune cells (e.g., monocytes, neutrophils) that mediate inflammation and rejection processes occurring early after graft transplantation. We identified the adhesion molecule ICAM-1 as a novel hypoimmune target that plays multiple critical roles in both adaptive and innate immune responses post-transplantation. In a series of studies, we found that ICAM-1 blocking or knock-out (KO) in hPSC-derived cardiovascular therapies imparted significantly diminished binding of multiple immune cell types. ICAM-1 KO resulted in diminished T cell proliferation responses in vitro and in longer in vivo retention/protection of KO grafts following immune cell encounter in NeoThy humanized mice. The ICAM-1 KO edit was also introduced into existing first-generation hypoimmune hPSCs and prevented immune cell binding, thereby enhancing the overall hypoimmune capacity of the cells. This novel hypoimmune editing strategy has the potential to improve the long-term efficacy and safety profiles of regenerative therapies for cardiovascular pathologies and a number of other diseases.

Uncovering a Rare Case of Hepatic Round Ligament Epigastric Hernia.

Abdominal wall hernias are one of the most common surgical diseases present in both males and females nowadays. However, with only a few cases reported in the literature, hepatic round ligament hernias are a rare clinical manifestation. This case shows how a common symptom such as epigastric pain can be associated with this rare condition. In general, abdominal computed tomography (CT) images are the choice of study to evaluate complications and the involvement of different intestinal sections. Some laboratory tests can be performed to suspect intestinal ischemia secondary to strangulated hernias. Primary repair utilizing mesh is the preferred surgical treatment. This procedure can be performed through laparoscopic or open technique, depending on the surgeon's skills and patient preference.

Tackling the Unyielding Challenge of Necrotic Unresectable Hepatocellular Carcinoma: A Liver Necrosectomy Approach for Intratumoral Hemorrhage and Abscess Resolution.

Hepatocellular carcinoma (HCC) is one of the most common causes of gastrointestinal and hepatobiliary cancer worldwide. Chronic liver disease and cirrhosis persist as the most common risk factors, typically linked to instances of alcohol abuse or viral infections, notably hepatitis B and hepatitis C infection. Diagnosis can be made using patient history and image studies as there is no need for pathological confirmation. The only curative treatment is surgical resection, and in cases where the tumor is unresectable, as the one presented in this case, and when there are no contraindications, the only option is an orthotopic liver transplantation. This malignancy is not only associated with high mortality but also high morbidity associated with severe complications, such as hemorrhage, necrosis, and infection of the tumor. The significant relevance of this case lies in its capacity to illustrate that despite remaining in non-surgical management for months when an acute complication presented, it was timely identified and surgically treated. The emergence of complications, such as necrosis accompanied by abscess formation and intratumoral hemorrhage, represents an indication for prompt surgical management.

Tailoring the efficiency of porphyrin molecular frameworks for the electroactivation of molecular N2.

The combination of compositional versatility and topological diversity for the integration of electroactive species into high-porosity molecular architectures is perhaps one of the main appeals of metal-organic frameworks (MOFs) in the field of electrocatalysis. This premise has attracted much interest in recent years, and the results generated have also revealed one of the main limitations of molecular materials in this context: low stability under electrocatalytic conditions. Using zirconium MOFs as a starting point, in this work, we use this stability as a variable to discriminate between the most suitable electrocatalytic reaction and specific topologies within this family. Our results revealed that the PCN-224 family is particularly suitable for the electroreduction of molecular nitrogen for the formation of ammonia with faradaic efficiencies above 30% in the presence of Ni2+ sites, an activity that improves most of the catalysts described. We also introduce the fluorination of porphyrin at the meso position as a good alternative to improve both the activity and stability of this material under electrocatalytic conditions.

Stakeholder-engaged development of a rapid test for detection of acute HIV infection.

Background/Objective: The utilization of rapid HIV tests has been effective at reducing transmission rates in high-risk populations by allowing individuals to receive diagnosis in as little as one minute and begin treatment. However, no current rapid tests can detect HIV immediately after infection in the acute HIV infection (AHI) phase, when the virus is at its most infectious, and instead require a waiting period of up to 90 days after exposure. Rapid HIV tests to detect AHI are currently under development. Investigation of stakeholder perspectives and context-specific needs are critical to ensure successful translation of novel AHI tests. The objectives of this study were to 1) understand context-specific factors such as barriers to HIV testing in Indiana, a state with one of 48 prioritized counties for HIV elimination; 2) assess the acceptability of a novel rapid AHI test, and 3) identify key implementation considerations for such a device, including ideal end-users. Methods: Semi-structured in-depth interviews were conducted with staff (n = 14) and clients (n = 5) of Indiana-based organizations that conduct HIV testing, including syringe service programs. Utilizing human-centered design frameworks, interview guides were developed and tailored to each participant group to understand their experiences with HIV testing, perspectives on a novel rapid AHI test in development, and preferences for self-testing versus testing by a community health worker (CHW) or a peer recovery coach. Thematic analysis was conducted to identify major themes, including barriers to HIV testing and perceived benefits and concerns of the proposed AHI test. Results: Overall acceptability for a novel AHI rapid test was high with a greater preference for CHW/Peerled testing. While self-testing was not a preferred modality, it was still seen as a potential tool to reach and address key barriers among high-risk individuals. Key considerations for implementation emphasized accuracy, cost-effectiveness, ease of use, ensuring access to counseling, education, and navigation to care while maintaining a human element to self-testing. Conclusion: Stakeholder engagement is meaningfully informing the design, development, and implementation of rapid AHI testing in order to facilitate adoption among populations at high-risk for HIV.

Pathological Thoracic Vertebral Fractures Secondary to Achromobacter denitrificans: A Case Report.

Vertebral fractures remain a diagnostic challenge nowadays. The first and most common diagnosis needed to be ruled out is osteoporosis. Other diagnoses to rule out involve pathological fractures. Pathological fractures are a group of pathologies that result in a spine fracture as part of an underlying disease process that affects the spine. This group includes Paget's disease, tumors, osteomyelitis, and vertebral compression fractures. Fractures secondary to vertebral osteomyelitis are presented as collapsed vertebral bodies secondary to bone destruction and the formation of lytic lesions. Clinical presentation includes severe back pain refractory to analgesic therapy, persistent unexplained fever, and leukocytosis without any other obvious focus of infection. In cases like the one presented here, early biopsy and culture should be performed on every patient that fits these criteria. However, as it presents unspecific symptoms most of the time, it is not suspected, and therefore it is associated with high morbidity and mortality.

Exploring Gastric Perforation as an Uncommon yet Critical Complication of Gastrointestinal Stromal Tumors.

Hollow viscus perforation poses a significant diagnostic and therapeutic dilemma for the majority of clinicians. It is vitally important that in cases of gastrointestinal perforation, the tissue that was perforated is always evaluated, since a malignant tumor can cause this complication as a presentation form. Here, we present the case of a patient whose first manifestation of a malignant gastric tumor was its perforation and the presence of septic shock secondary to this. This case exemplifies the importance of innovative thinking in facilitating a comprehensive diagnostic and therapeutic strategy, leading to the timely identification and management of a malignant tumor by the oncology team; such interventions not only enhance patient outcomes but also mitigate morbidity and mortality rates.

From Gut to Heart: A Case Report of Infectious Endocarditis Stemming From Cholecystitis-Induced Enterococcus faecium Bacteremia.

Systemic infections are not always going to present as we expect. The study of bacteremia and febrile syndrome represents one of the most important diagnostic challenges nowadays. This case demonstrates the importance of a multidisciplinary approach and finding a common point that explains all the patient's symptoms, no matter how disconnected they may seem. Here, we present the case of a patient where multiple treatments were performed to manage recurrent infective endocarditis due to Enterococcus faecium but the cause of this persistence was never found despite surgical management. With only a few cases reported in literature involving this pathogen, it is of great importance to emphasize how searching for a natural reservoir, such as the gallbladder, for this pathogen helped solve the diagnostic mystery that this patient represented. Here, we present how the culture of biological materials, such as the aortic valve replacement, as well as blood cultures, made it possible to identify the etiological agent associated with the pathology and, in turn, find the cause of recurrent bacteremia.

Enhancing immigrant families' mental health through the promotion of structural and community-based support.

Immigrant communities in the United States are diverse and have many assets. Yet, they often experience stressors that can undermine the mental health of residents. To fully promote mental health and well-being among immigrant communities, it is important to emphasize population-level policies and practices that may serve to mitigate stress and prevent mental health disorders. In this paper, we describe the stressors and stress experienced by immigrant families, using Sunset Park, Brooklyn as an example. We discuss ways to build structures and policies in support of equitable environments that promote mental health at the population level and enable families and their children to thrive.

Comparative efficacy of buparvaquone and imidocarb in inhibiting the in vitro growth of Babesia bovis.

Introduction: B. bovis is an apicomplexan parasite responsible for bovine babesiosis, a tick-borne disease with a worldwide impact. The disease remains inefficiently controlled, and few effective drugs, including imidocarb dipropionate (ID), are currently available in endemic areas. The objective of this study was to evaluate whether buparvaquone (BPQ), a drug currently used to treat cattle infected with the Babesia-related Theileria spp. parasites, could be active against Babesia parasites. Herein, we compared the effect of ID and BPQ on B. bovis growth in vitro erythrocyte culture. Methods: We compared the effect of ID and BPQ on the culture-adapted Texas T2Bo strain of B. bovis. In vitro cultured parasites were incubated with ID and BPQ at two starting parasitemia levels (PPE), 0.2% and 1%. In vitro cultured parasites were treated with ID or BPQ at concentrations ranging from 10 to 300 nM, during 4 consecutive days. Parasitemia levels were daily evaluated using microscopic examination. Data was compared using the independent Student's t-test. Results and discussion: Both ID and BPQ significantly inhibited (p < 0.05) the growth of B. bovis, regardless of the initial parasitemia used. At 1% parasitemia, BPQ had lower calculated inhibitory concentration 50 (IC50: 50.01) values than ID (IC50: 117.3). No parasites were found in wells with 0.2% starting parasitemia, treated previously with 50 nM of BPQ or ID, after 2 days of culture without drugs. At 1% parasitemia, no parasite survival was detected at 150 nM of BPQ or 300 nM of ID, suggesting that both drugs acted as babesiacidals. Conclusion: Overall, the data suggests that BPQ is effective against B. bovis and shows a residual effect that seems superior to ID, which is currently the first-line drug for treating bovine babesiosis globally.

Pluronic P123/DMSO Lyotropic Liquid Crystal for Incorporating Bioactive Substances for Topical Application.

Lyotropic liquid crystals (LLCs) have attracted considerably growing interest in drug delivery applications over the last years. The structure of LLC matrices is complementary to cell membranes and provides an efficient, controlled, and selective release of drugs. In this work, a complex of experimental methods was used to characterize binary LLCs Pluronic P123/DMSO and triple LLC systems Pluronic P123/DMSO/Ibuprofen, which are interesting as transdermal drug delivery systems. Liquid crystalline, thermal, and rheological properties of LLCs were studied. Concentration and temperature areas of the lyomesophase existence were found, and phase transition enthalpies were evaluated. Intermolecular interactions among the components were studied by infrared (IR) spectroscopy. In vitro studies of Ibuprofen (Ibu) release from various LLCs allow differentiation of its release depending on the polymer content. Atomic force microscopy and contact angle methods were used to characterize the surface morphology of the hydrophobic membrane, which was used as a stratum corneum model, and also evaluate the adhesion work of the LLCs. A complex analysis of the results provided by these experimental methods allowed revealing correlations between the phase behavior and rheological characteristics of the LLCs and release kinetics of ibuprofen. The proposed biocompatible systems have considerable potential for a transdermal delivery of bioactive substances.

Infectious Disease Preparedness for Homeless Populations: Recommendations from a Community-Academic Partnership.

BACKGROUND: People experiencing homelessness are at increased risk of infectious disease transmission due to congregate living conditions, barriers to healthcare, and excess burden of underlying chronic disease. OBJECTIVES: We are a multisectoral community-academic partnership working to address the intersecting crises of homelessness and health disparities in Tippecanoe County, Indiana. We offer key recommendations for infectious disease preparedness and risk mitigation for homeless populations based on our ongoing community-based participatory research and lessons learned through COVID-19 response and Monkeypox preparations. LESSONS LEARNED: Infectious disease preparedness and response in homeless populations requires strong local partnerships; ongoing training and support for staff and volunteers of homeless shelters and service agencies; tailored outreach, education, and communication with people experiencing homelessness; and standardized processes for creating, disseminating, enforcing, and evaluating public health policies in homeless shelters. Consistency and open communication are key to a successful community-academic partnership. CONCLUSIONS: Community-academic partnerships are critical to effective infectious disease preparedness in homeless populations. The lessons learned from community-based participatory research with homeless communities and multisectoral partners on the frontline can improve future outbreak and pandemic response for people experiencing homelessness and other vulnerable communities in the United States.

Conduction velocity, G-ratio, and extracellular water as microstructural characteristics of autism spectrum disorder.

The neuronal differences contributing to the etiology of autism spectrum disorder (ASD) are still not well defined. Previous studies have suggested that myelin and axons are disrupted during development in ASD. By combining structural and diffusion MRI techniques, myelin and axons can be assessed using extracellular water, aggregate g-ratio, and a new approach to calculating axonal conduction velocity termed aggregate conduction velocity, which is related to the capacity of the axon to carry information. In this study, several innovative cellular microstructural methods, as measured from magnetic resonance imaging (MRI), are combined to characterize differences between ASD and typically developing adolescent participants in a large cohort. We first examine the relationship between each metric, including microstructural measurements of axonal and intracellular diffusion and the T1w/T2w ratio. We then demonstrate the sensitivity of these metrics by characterizing differences between ASD and neurotypical participants, finding widespread increases in extracellular water in the cortex and decreases in aggregate g-ratio and aggregate conduction velocity throughout the cortex, subcortex, and white matter skeleton. We finally provide evidence that these microstructural differences are associated with higher scores on the Social Communication Questionnaire (SCQ) a commonly used diagnostic tool to assess ASD. This study is the first to reveal that ASD involves MRI-measurable in vivo differences of myelin and axonal development with implications for neuronal and behavioral function. We also introduce a novel formulation for calculating aggregate conduction velocity, that is highly sensitive to these changes. We conclude that ASD may be characterized by otherwise intact structural connectivity but that functional connectivity may be attenuated by network properties affecting neural transmission speed. This effect may explain the putative reliance on local connectivity in contrast to more distal connectivity observed in ASD.

Cerebral rScO2 Measured by Near-Infrared Spectroscopy (NIRS) During Therapeutic Hypothermia in Neonates with Hypoxic-Ischemic Encephalopathy: A Systematic Review.

INTRODUCTION: Perinatal asphyxia, a leading cause of neonatal mortality and neurological sequelae, necessitates early detection of pathophysiological neurologic changes during hypoxic-ischaemic encephalopathy (HIE). This study aimed to review published data on rScO2 monitoring during hypothermia treatment in neonates with perinatal asphyxia to predict short- and long-term neurological injury. METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Study identification was performed through a search between November and December 2021 in the electronic databases PubMed, Embase, Lilacs, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL). The main outcome was short-term (Changes in brain magnetic resonating imaging) and long-term (In neurodevelopment) neurological injury. The study protocol was registered in PROSPERO (International Prospective Register of Systematic Reviews) with CRD42023395438. RESULTS: 380 articles were collected from databases in the initial search. Finally, 15 articles were selected for extraction and analysis of the information. An increase in rScO2 measured by NIRS (Near-infrared spectroscopy) at different moments of treatment predicts neurological injury. However, there exists a wide variability in the methods and outcomes of the studies. CONCLUSION: High rScO2 values were found to predict negative outcomes, with substantial discord among studies. NIRS is proposed as a real-time bedside tool for predicting brain injury in neonates with moderate to severe HIE.