Improving soil carbon estimates of Philippine mangroves using localized organic matter to organic carbon equations.

BACKGROUND: Southeast Asian (SEA) mangroves are globally recognized as blue carbon hotspots. Methodologies that measure mangrove soil carbon stock (SCS) are either accurate but costly (i.e., elemental analyzers), or economical but less accurate (i.e., loss-on-ignition [LOI]). Most SEA countries estimate SCS by measuring soil organic matter (OM) through the LOI method then converting it into organic carbon (OC) using a conventional conversion equation (%Corg = 0.415 * % LOI + 2.89, R2 = 0.59, n = 78) developed from Palau mangroves. The local site conditions in Palau does not reflect the wide range of environmental settings and disturbances in the Philippines. Consequently, the conventional conversion equation possibly compounds the inaccuracies of converting OM to OC causing over- or under-estimated SCS. Here, we generated a localized OM-OC conversion equation and tested its accuracy in computing SCS against the conventional equation. The localized equation was generated by plotting % OC (from elemental analyzer) against the % OM (from LOI). The study was conducted in different mangrove stands (natural, restored, and mangrove-recolonized fishponds) in Oriental Mindoro and Sorsogon, Philippines from the West and North Philippine Sea biogeographic regions, respectively. The OM:OC ratios were also statistically tested based on (a) stand types, (b) among natural stands, and (c) across different ages of the restored and recolonized stands. Increasing the accuracy of OM-OC conversion equations will improve SCS estimates that will yield reasonable C emission reduction targets for the country's commitments on Nationally Determined Contributions (NDC) under the Paris Agreement. RESULTS: The localized conversion equation is %OC = 0.36 * % LOI + 2.40 (R2 = 0.67; n = 458). The SOM:OC ratios showed significant differences based on stand types (x2 = 19.24; P = 6.63 × 10-05), among natural stands (F = 23.22; p = 1.17 × 10-08), and among ages of restored (F = 5.14; P = 0.03) and recolonized stands (F = 3.4; P = 0.02). SCS estimates using the localized (5%) and stand-specific equations (7%) were similar with the values derived from an elemental analyzer. In contrast, the conventional equation overestimates SCS by 20%. CONCLUSIONS: The calculated SCS improves as the conversion equation becomes more reflective of localized site conditions. Both localized and stand-specific conversion equations yielded more accurate SCS compared to the conventional equation. While our study explored only two out of the six marine biogeographic regions in the Philippines, we proved that having a localized conversion equation leads to improved SCS measurements. Using our proposed equations will make more realistic SCS targets (and therefore GHG reductions) in designing mangrove restoration programs to achieve the country's NDC commitments.

The asymmetric opening of HIV-1 Env by a potent CD4 mimetic enables anti-coreceptor binding site antibodies to mediate ADCC.

HIV-1 envelope glycoproteins (Env) from primary HIV-1 isolates typically adopt a pretriggered "closed" conformation that resists to CD4-induced (CD4i) non-neutralizing antibodies (nnAbs) mediating antibody-dependent cellular cytotoxicity (ADCC). CD4-mimetic compounds (CD4mcs) "open-up" Env allowing binding of CD4i nnAbs, thereby sensitizing HIV-1-infected cells to ADCC. Two families of CD4i nnAbs, the anti-cluster A and anti-coreceptor binding site (CoRBS) Abs, are required to mediate ADCC in combination with the indane CD4mc BNM-III-170. Recently, new indoline CD4mcs with improved potency and breadth have been described. Here, we show that the lead indoline CD4mc, CJF-III-288, sensitizes HIV-1-infected cells to ADCC mediated by anti-CoRBS Abs alone, contributing to improved ADCC activity. Structural and conformational analyses reveal that CJF-III-288, in combination with anti-CoRBS Abs, potently stabilizes an asymmetric "open" State-3 Env conformation, This Env conformation orients the anti-CoRBS Ab to improve ADCC activity and therapeutic potential.

Lesser Omental Infarction: Clinical Insights and Diagnostic Challenges in a Rare Case of Acute Abdominal Pain.

Intraperitoneal focal fat infarction (IFFI) is a rare condition characterized by infarction of fatty tissue within the abdominal cavity. Lesser omental infarction, a relatively rare type of IFFI, occurs when there is an infarction of fat within the lesser omentum. Patients typically present with acute abdominal pain that can mimic more serious conditions. This case report highlights the clinical presentation, diagnostic challenges, and management strategies for patients presenting to the emergency department with lesser omental infarction. A 63-year-old female presented to the emergency department with a chief complaint of epigastric abdominal pain that had been persisting for approximately a week and a half. The pain, which initially seemed like a sore muscle, became increasingly sharp and intermittent, with tenderness upon palpation of the epigastric area. Computed tomography (CT) imaging revealed an omental infarct in the lesser sac with focal inflammation in the fat of the lesser omentum. Through conservative management with analgesics and anti-inflammatory medication, the patient experienced resolution of her symptoms within a few days and had a follow-up with the gastrointestinal team several weeks later. Lesser omental infarction typically results from compromised blood flow due to torsion or thrombosis, leading to ischemia and necrosis of the fatty tissue. CT imaging is crucial for its diagnosis and reveals fat-density lesions with surrounding inflammatory changes. Conservative management is typically effective, though in rare cases, surgical intervention may be necessary when significant vital signs and electrolyte derangements occur.

Cheminformatics-Guided Exploration of Synthetic Marine Natural Product-Inspired Brominated Indole-3-Glyoxylamides and Their Potentials for Drug Discovery.

Marine natural products (MNPs) continue to be tested primarily in cellular toxicity assays, both mammalian and microbial, despite most being inactive at concentrations relevant to drug discovery. These MNPs become missed opportunities and represent a wasteful use of precious bioresources. The use of cheminformatics aligned with published bioactivity data can provide insights to direct the choice of bioassays for the evaluation of new MNPs. Cheminformatics analysis of MNPs found in MarinLit (n = 39,730) up to the end of 2023 highlighted indol-3-yl-glyoxylamides (IGAs, n = 24) as a group of MNPs with no reported bioactivities. However, a recent review of synthetic IGAs highlighted these scaffolds as privileged structures with several compounds under clinical evaluation. Herein, we report the synthesis of a library of 32 MNP-inspired brominated IGAs (25-56) using a simple one-pot, multistep method affording access to these diverse chemical scaffolds. Directed by a meta-analysis of the biological activities reported for marine indole alkaloids (MIAs) and synthetic IGAs, the brominated IGAs 25-56 were examined for their potential bioactivities against the Parkinson's Disease amyloid protein alpha synuclein (α-syn), antiplasmodial activities against chloroquine-resistant (3D7) and sensitive (Dd2) parasite strains of Plasmodium falciparum, and inhibition of mammalian (chymotrypsin and elastase) and viral (SARS-CoV-2 3CLpro) proteases. All of the synthetic IGAs tested exhibited binding affinity to the amyloid protein α-syn, while some showed inhibitory activities against P. falciparum, and the proteases, SARS-CoV-2 3CLpro, and chymotrypsin. The cellular safety of the IGAs was examined against cancerous and non-cancerous human cell lines, with all of the compounds tested inactive, thereby validating cheminformatics and meta-analyses results. The findings presented herein expand our knowledge of marine IGA bioactive chemical space and advocate expanding the scope of biological assays routinely used to investigate NP bioactivities, specifically those more suitable for non-toxic compounds. By integrating cheminformatics tools and functional assays into NP biological testing workflows, we can aim to enhance the potential of NPs and their scaffolds for future drug discovery and development.

Myoglobin saturation as an intracellular indicator for transfusion need in oncology patients.

OBJECTIVES: This study aims to demonstrate the potential of myoglobin saturation as an indicator of oxygen delivery adequacy to help determine the need for red cell transfusion. BACKGROUND: Modern blood management approaches have been established to optimise use of red blood cells for transfusions in patients with anaemia. However, most approaches make recommendations to transfuse based on haemoglobin or haematocrit levels and do not directly address adequacy of oxygen delivery. Intracellular oxygen determined by myoglobin saturation directly measures oxygen delivery at the tissue level. METHODS/MATERIALS: A custom built spectrometer system with an optical fibre probe was used in this pilot study to measure muscle cell myoglobin saturation noninvasively from the first digital interosseous muscles in patients undergoing planned red blood cell transfusion. Patients were recruited from both the in-patient and out-patient oncology service at a major university medical centre. Measurements were made immediately before, immediately after, and 24 h following transfusion. Clinical data and tissue oxygen values from the Somanetics INVOS system were also collected. RESULTS: Myoglobin saturation, and thus cellular oxygen increased in some, but not all patients receiving a transfusion, and was most pronounced in patients who initially had low myoglobin saturation compared with the group as a whole. CONCLUSION: Clinical decisions to transfuse based on haemoglobin or haematocrit thresholds alone are likely insufficient to optimise use of red blood cell transfusions. The combination of haemoglobin or haematocrit with myoglobin saturation may optimally determine who will benefit physiologically from a transfusion.

Challenges and Successes in Introducing Coronary CT Angiography in an Emergency Medicine-Run Observation Unit.

This study was designed to analyze the departmental changes in transitioning the Emergency Department (ED)-run Observation Medicine Unit's routine noninvasive cardiac evaluation from the traditional standard-of-care procedures to coronary computed tomography angiography (CCTA).  While the routine use of CCTA for the evaluation of chest pain has been deemed feasible and safe, provider confidence appears apprehensive, and ordering patterns appear reluctant to change.  We conducted a retrospective analysis of data from two risk-matched cohorts of ED patients who presented with symptoms suggestive of acute coronary syndrome (ACS) but without ischemic electrocardiogram (ECG) changes or positive troponin. Endpoints included length of stay, major adverse cardiovascular event (MACE) rates at 28 days, recidivism rate, and downstream findings on coronary catheterization.  The adoption of CCTA led to a significant reduction in the length of stay for patients in the ED-run Observation Medicine Unit. Provider and nursing education initiatives were crucial in overcoming initial resistance and improving the implementation of CCTA. Post-education, there was a marked increase in the volume of CCTA performed and a decrease in the length of stay, enhancing overall departmental throughput.  The results suggest that CCTA offers a reliable and efficient diagnostic alternative to traditional noninvasive tests, with high diagnostic accuracy contributing to faster decision-making and reduced need for invasive procedures. Continuous education for providers and nursing staff was essential to ensure adherence to the new protocol and improve clinical outcomes.  Transitioning to CCTA for routine noninvasive cardiac evaluation in the ED-run Observation Medicine Unit demonstrated significant efficiency and diagnostic accuracy benefits. Successful implementation requires targeted educational efforts to ensure competency and confidence among healthcare providers. The findings support the integration of CCTA into standard clinical practice for the evaluation of chest pain in the emergency setting, with future research needed to validate these results in broader patient populations and assess long-term outcomes.

Development of an in vivo syngeneic mouse transplant model of invasive intestinal adenocarcinoma driven by endogenous expression of Pik3caH1047R and Apc loss.

Preclinical models that replicate patient tumours as closely as possible are crucial for translational cancer research. While in vitro cancer models have many advantages in assessing tumour response therapy, in vivo systems are essential to enable evaluation of the role of the tumour cell extrinsic factors, such as the tumour microenvironment and host immune system. The requirement for a functional immune system is particularly important given the current focus on immunotherapies. Therefore, we set out to generate an immunocompetent, transplantable model of colorectal cancer suitable for in vivo assessment of immune-based therapeutic approaches. Intestinal tumours from a genetically engineered mouse model, driven by expression of a Pik3ca mutation and loss of Apc, were transplanted into wild type C57BL/6 host mice and subsequently passaged to form a novel syngeneic transplant model of colorectal cancer. Our work confirms the potential to develop a panel of mouse syngeneic grafts, akin to human PDX panels, from different genetically engineered, or carcinogen-induced, mouse models. Such panels would allow the in vivo testing of new pharmaceutical and immunotherapeutic treatment approaches across a range of tumours with a variety of genetic driver mutations.

Characterization of Arabidopsis aldolases AtFBA4, AtFBA5, and their inhibition by morin and interaction with calmodulin.

Fructose bisphosphate aldolases (FBAs) catalyze the reversible cleavage of fructose 1,6-bisphosphate into dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. We analyzed two previously uncharacterized cytosolic Arabidopsis FBAs, AtFBA4 and AtFBA5. Based on a recent report, we examined the interaction of AtFBA4 with calmodulin (CaM)-like protein 11 (AtCML11). AtFBA4 did not bind AtCML11; however, we found that CaM bound AtFBA5 in a Ca2+-dependent manner with high specificity and affinity (KD ~ 190 nm) and enhanced its stability. AtFBA4 and AtFBA5 exhibited Michaelis-Menten kinetics with Km and Vmax values of 180 µm and 4.9 U·mg-1 for AtFBA4, and 6.0 µm and 0.30 U·mg-1 for AtFBA5, respectively. The flavonoid morin inhibited both isozymes. Our study suggests that Ca2+ signaling and flavanols may influence plant glycolysis/gluconeogenesis.

Formulating cancer worries: How doctors establish medical expertise and authority to facilitate patients' care choices.

Video recordings of oncology interviews reveal how doctors rely on worry to establish medical expertise, facilitate treatment decision-making, and construct worry parameters to help patients understand whether there is a reasonable need for worry or not. Doctors express worry as frequently as cancer patients during oncology interviews, but they face a dilemma: how to provide care for cancer patients without directly stating they are worried about them? Plausible explanations are offered for why doctors do not state personal worries. Conversation analytic methods were employed to identify how doctors rely on worry to achieve distinct social actions. Four worry formulations are examined: (1) variations of "we worry" (and at times, non-specific and second person "you"), (2) hypothetical worry scenarios, (3) dismissing worry and offering assurance, and (4) doctors claiming they are not worried, bothered, or alarmed. Doctors align with and speak for the professionals and institutions they represent, expressing collective worries and claiming the legitimate right to worry (or not). Doctors also avoid abandoning patients to their own decision-making, yet do not formulate worry to coerce deference or dictate patients' choices. In all cases patients agreed and displayed minimal resistance to doctors' worry formulations. These findings contribute to ongoing work across institutional settings where participants have been shown to construct objective, legitimate claims meriting worries about diverse problems. Work is underway to examine when and how patients explicitly raise and doctors respond to cancer worries. Clinical implications are raised for how doctors can use worry to legitimize best treatment options, help patients minimize their worries, rely on hypothetical scenarios allowing patients to compare how other patients managed their cancer, and not dismiss the importance of minimizing the need to worry as a resource for offering reassurance.

Direct activation of PI3K in osteoblasts and osteocytes strengthens murine bone through sex-specific actions on cortical surfaces.

Intracellular phosphoinositide 3-kinase (PI3K) signaling is activated by multiple bone-active receptors. Genetic mutations activating PI3K signaling are associated with clinical syndromes of tissue overgrowth in multiple organs, often including the skeleton. While one formation is increased by removing the PI3K inhibitor (phosphatase and TENsin homolog deleted on chromosome 10 (PTEN)), the effect of direct PI3K activation in the osteoblast lineage has not been reported. We introduced a known gain-of-function mutation in Pik3ca, the gene encoding the p110α catalytic subunit of PI3K, in osteocytes and late osteoblasts using the dentin matrix protein-1 Cre (Dmp1Cre) mouse and assessed the skeletal phenotype. Femur shape was grossly normal, but cortical thickness was significantly greater in both male and female Dmp1Cre.Pik3caH1047R mice, leading to almost doubled bone strength at 12 wk of age. Both sexes had smaller marrow areas from 6 wk of age. Female mice also exhibited greater cross-sectional area, which continued to increase until 24 wk of age, resulting in a further increase in bone strength. Although both male and female mice had increased endocortical mineralizing surface, only female mice had increased periosteal mineralizing surface. The bone formed in the Dmp1Cre.Pik3caH1047R mice showed no increase in intracortical remodeling nor any defect in cortical bone consolidation. In contrast, on both endocortical and periosteal surfaces, there was more lamellar bone formation, including highly organized osteocyte networks extending along the entire surface at a greater thickness than in control mice. In conclusion, direct activation of PI3Kα in cells targeted by Dmp1Cre leads to high cortical bone mass and strength with abundant lamellar cortical bone in female and male mice with no increase in intracortical remodeling. This differs from the effect of PTEN deletion in the same cells, suggesting that activating PI3Kα in osteoblasts and osteocytes may be a more suitable target to promote formation of lamellar bone.

Patients with genetic activation of enzymes called phosphoinositide-3 kinase (PI3K) have tissue overgrowth syndromes, where parts of the body become enlarged, sometimes including the skeleton. There are 2 types of mutations that cause this: one that directly activates the PI3K enzyme, and one that removes the normal brake on PI3K signaling (called PTEN). We tested the effect of directly activating a PI3K enzyme specifically in osteoblasts (the cells that form bone) and osteocytes (osteoblasts that make a network inside the bone tissue itself). We found that mice with these mutations had very strong bones with an outer shell that was thicker than usual. In both male and female mice, it became thicker on the inside of the shell, but in female mice it also became thicker on the outside, making the bones even stronger over time. The new bone was well-organized, which likely helped make the increase in bone strength so profound. This is very different to previous studies of mice with the other type of mutation in their bone-forming cells; they had a shell with many large holes (pores). This indicates that directly stimulating PI3K enzyme is more beneficial for bone than removing the PTEN brake.

Atrial Septal Defect (ASD) Repair Unveiling an Unusual Conduction Conundrum: A Wenckebach Case Report.

Atrial septal defects are a common congenital malformation that can lead to an elevated risk for stroke due to the bypass of the lungs by deep vein thrombosis, as well as the expected repercussions of pulmonary hypertension if left untreated. Surgical intervention is definitive; however, recent advancements in treatment options, such as percutaneous intervention, represent a safer and equally effective way to treat this congenital complication. While safer, percutaneous interventions can also lead to adverse events that may force patients to present to the emergency department. Here, we present a unique case of a patient with congenital atrial septal defect status post-percutaneous intervention who developed a new-onset second-degree AV block, Mobitz type 1 Wenckebach rhythm.

Incorporating verbal and nonverbal aspects to enhance a model of patient communication in cancer care: A grounded theory study.

PURPOSE: High-quality communication is essential to patient-centered care. Existing communication models and research tends to focus on what is said verbally with little attention to nonverbal aspects of communication. In sensitive and emotionally intensive healthcare encounters, such as in cancer care, provider and patient nonverbal behavior may be particularly important for communicating with empathy. Therefore, the aim of this study was to develop a conceptual model of communication that accounts for nonverbal behavior. METHODS: We followed a systematic grounded theory design that involved semi-structured interviews with 23 providers, including nurse practitioners, physicians, surgeons, and physician's assistants. Using constant comparative analysis, we analyzed transcripts and developed a grounded theory model of communication accounting for nonverbal behavior. RESULTS: The major themes included building rapport, gauging how patients will take bad news, ensuring patients' understanding of their conditions, staying honest but hopeful, centering but guiding patient through cancer care, conveying empathy while managing heightened emotions, and ensuring patient understanding. Throughout the process, providers synthesize both verbal and nonverbal information and apply what they learn to future encounters. CONCLUSIONS: The results extend existing models of patient-centered communication and invite communication intervention and research that incorporates nonverbal behavior. The model contributes an understanding of the full process of communication in clinical encounters.

Targeting a STING agonist to perivascular macrophages in prostate tumors delays resistance to androgen deprivation therapy.

BACKGROUND: Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival. ADT is known to stimulate the accumulation of immunosuppressive cells like protumoral tumor-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T cells in prostate tumors, as well as hypofunctional T cells. Protumoral TAMs have been shown to accumulate around tumor blood vessels during chemotherapy and radiotherapy in other forms of cancer, where they drive tumor relapse. Our aim was to see whether such perivascular (PV) TAMs also accumulate in ADT-treated prostate tumors prior to CRPC, and, if so, whether selectively inducing them to express a potent immunostimulant, interferon beta (IFNß), would stimulate antitumor immunity and delay CRPC. METHODS: We used multiplex immunofluorescence to assess the effects of ADT on the distribution and activation status of TAMs, CD8+T cells, CD4+T cells and NK cells in mouse and/or human prostate tumors. We then used antibody-coated, lipid nanoparticles (LNPs) to selectively target a STING agonist, 2'3'-cGAMP (cGAMP), to PV TAMs in mouse prostate tumors during ADT. RESULTS: TAMs accumulated at high density around blood vessels in response to ADT and expressed markers of a protumoral phenotype including folate receptor-beta (FR-ß), MRC1 (CD206), CD169 and VISTA. Additionally, higher numbers of inactive (PD-1-) CD8+T cells and reduced numbers of active (CD69+) NK cells were present in these PV tumor areas. LNPs coated with an antibody to FR-ß selectively delivered cGAMP to PV TAMs in ADT-treated tumors, where they activated STING and upregulated the expression of IFNß. This resulted in a marked increase in the density of active CD8+T cells (along with CD4+T cells and NK cells) in PV tumor areas, and significantly delayed the onset of CRPC. Antibody depletion of CD8+T cells during LNP administration demonstrated the essential role of these cells in delay in CRPC induced by LNPs. CONCLUSION: Together, our data indicate that targeting a STING agonist to PV TAMs could be used to extend the treatment window for ADT in prostate cancer.

Mechanistic insights into phosphoactivation of SLAC1 in guard cell signaling.

Stomata in leaves regulate gas (carbon dioxide and water vapor) exchange and water transpiration between plants and the atmosphere. SLow Anion Channel 1 (SLAC1) mediates anion efflux from guard cells and plays a crucial role in controlling stomatal aperture. It serves as a central hub for multiple signaling pathways in response to environmental stimuli, with its activity regulated through phosphorylation via various plant protein kinases. However, the molecular mechanism underlying SLAC1 phosphoactivation has remained elusive. Through a combination of protein sequence analyses, AlphaFold-based modeling and electrophysiological studies, we unveiled that the highly conserved motifs on the N- and C-terminal segments of SLAC1 form a cytosolic regulatory domain (CRD) that interacts with the transmembrane domain(TMD), thereby maintaining the channel in an autoinhibited state. Mutations in these conserved motifs destabilize the CRD, releasing autoinhibition in SLAC1 and enabling its transition into an activated state. Our further studies demonstrated that SLAC1 activation undergoes an autoinhibition-release process and subsequent structural changes in the pore helices. These findings provide mechanistic insights into the activation mechanism of SLAC1 and shed light on understanding how SLAC1 controls stomatal closure in response to environmental stimuli.

Obstruction from endometriosis causing hydronephrosis and complex renal pelvis rupture: A case report.

Endometriosis presents a diagnostic conundrum due to its diverse clinical manifestations, ranging from asymptomatic to acute obstructive uropathy. This is a case of a 30-year-old woman with a history of endometriosis and rapidly progressing left flank pain culminating in rupture of the renal pelvis in her left kidney. Initial investigations revealed left-sided hydronephrosis without evidence of nephrolithiasis. Subsequent imaging showed active extravasation indicative of urinary obstruction attributable to endometriosis. Placement of a left nephrostomy tube alleviated her symptoms, and follow-up imaging revealed a distal ureteral stricture. A stent was subsequently placed, which resolved the obstruction and obviated the need for extensive surgical intervention. In this case, the patient's history of endometriosis prompted consideration of its role in urinary obstruction, despite the absence of typical symptoms, and underscores the importance of considering endometriosis as a potential cause of acute urinary obstruction, particularly in patients with a history of the disease. Physicians in the emergency department should maintain a high index of suspicion for endometriosis-related complications to facilitate timely intervention and prevent adverse outcomes. Awareness of the variable presentations of endometriosis is paramount for ensuring comprehensive patient care and optimal outcomes.

Pulmonary responses following cardiac rehabilitation and the relationship with functional outcomes in children and young adults with heart disease.

Introduction: Patients with congenital heart disease (CHD) often have pulmonary abnormalities and exercise intolerance following cardiac surgery. Cardiac rehabilitation (CR) improves exercise capacity in patients with CHD, but minimal study has been performed to see if resting and dynamic pulmonary performance improves following CR in those with prior cardiac surgery. Methods: This was a retrospective cohort study of all patients who completed ≥12 weeks of CR from 2018 through 2022. Demographic, cardiopulmonary exercise test (CPET), spirometry, 6-minute walk, functional strength measures, and outcomes data were collected. Data are presented as median[IQR]. A Student's t-test was used for comparisons between groups and serial measurements were measured with a paired t-test. A p < 0.05 was considered significant. Results: There were a total of 37 patients [age 16.7 (14.2-20.1) years; 46% male] included. Patients with prior surgery (n = 26) were more likely to have abnormal spirometry data than those without heart disease (n = 11) (forced vital capacity [FVC] 76.7 [69.1-84.3]% vs. 96.4 [88.1-104.7]%, p = 0.002), but neither group experienced a significant change in spirometry. On CPET, peak oxygen consumption increased but there was no change in other pulmonary measures during exercise. Percent predicted FVC correlated with hand grip strength (r = 0.57, p = 0.0003) and percent predicted oxygen consumption (r = 0.43, p = 0.009). The number of prior sternotomies showed negative associations with both percent predicted FVC (r = -0.43, p = 0.04) and FEV1 (r = -0.47, p = 0.02). Discussion: Youth and young adults with a prior history of cardiac surgery have resting and dynamic pulmonary abnormalities that do not improve following CR. Multiple sternotomies are associated with worse pulmonary function.

Intergenerational toxicity of 17α-ethinylestradiol (EE2): Effects of parental exposure on early larval development and transcriptomic profiles in the Sydney rock oyster, Saccostrea glomerata.

This study exposed adult Sydney rock oysters, of either sex or both, to the synthetic estrogen 17α-ethinylestradiol (EE2) at 50 ng/L for 21 days, followed by an examination of developmental endpoints and transcriptomic responses in unexposed larvae. Reduced survival was observed at 1 day post-fertilisation (dpf) in larvae from bi-parental exposure (FTMT). Motile larvae at 2 dpf were fewer from maternal (FTMC), paternal (FCMT), and FTMT exposures. Additionally, shell length at 7 dpf decreased in larvae from FTMC and FTMT parents. RNA sequencing (RNA-seq) revealed 1064 differentially expressed genes (DEGs) in 1-dpf larvae from FTMT parents, while fewer DEGs were detected in larvae from FTMC and FCMT parents, with 258 and 7, respectively. GO and KEGG analyses showed significant enrichment of DEGs in diverse terms and pathways, with limited overlap among treatment groups. IPA results indicated potential inhibition of pathways regulating energy production, larval development, transcription, and detoxification of reactive oxygen species in FTMT larvae. qRT-PCR validation confirmed significant downregulation of selected DEGs involved in these pathways and relevant biological processes, as identified in the RNA-seq dataset. Overall, our results suggest that the intergenerational toxicity of EE2 is primarily maternally transmitted, with bi-parental exposure amplifying these effects.

Perforated Peptic Ulcer: A Case Report of a Dreaded Complication of an Insidious Disease.

Perforated peptic ulcers, though relatively rare, represent critical surgical emergencies with potentially life-threatening consequences. Their significance lies not only in their acute presentation but also in the diagnostic challenges they pose, particularly in patients with complex medical histories. Here we present a case of a 71-year-old female with a complex medical history, including insulin-dependent type 2 diabetes mellitus, hypertension, hyperlipidemia, hypothyroidism, dementia, diverticulitis, and chronic back pain, who initially were unresponsive and cyanotic. Despite challenges in diagnosis due to her medical complexity and opioid use, she was ultimately diagnosed with a perforated duodenal ulcer. Tragically, despite immediate surgical intervention, she succumbed to her illness, highlighting the complexities involved in managing perforated peptic ulcers, especially in patients with multiple chronic medical conditions. Peptic ulcer disease (PUD) can often remain asymptomatic, leading to delayed diagnosis and potentially life-threatening complications like perforation. Mortality rates associated with perforated peptic ulcers vary widely, ranging from 1.3% to 20%, with risk factors including nonsteroidal anti-inflammatory drug (NSAID) use, Helicobacter pylori infection, smoking, and corticosteroid use. Diagnosis necessitates a high index of suspicion, thorough clinical examination, and imaging modalities such as computed tomography (CT) scans with oral contrast. Treatment strategies range from nonoperative management with intravenous (IV) histamine H2-receptor blockers or proton pump inhibitors (PPIs) to surgical intervention, depending on the patient's hemodynamic stability. However, the case presented underscores the challenges in timely diagnosis and intervention, particularly in patients with complex medical histories, where symptoms may be masked or attributed to other comorbidities. Recent studies indicate a demographic shift toward older age and a higher prevalence among females, emphasizing the importance of increased awareness and vigilance among healthcare providers. Early recognition of symptoms, prompt investigation, and interdisciplinary collaboration are crucial in optimizing outcomes for patients presenting with perforated peptic ulcers, especially in the context of their underlying medical conditions.

Minimization and complete loss of general transcription factor proteins in the intracellular parasite Encephalitozoon cuniculi.

Genome compaction is a common evolutionary feature of parasites. The unicellular, obligate intracellular parasite Encephalitozoon cuniculi has one of smallest known eukaryotic genomes, and is nearly four times smaller than its distant fungi relative, the budding yeast Saccharomyces cerevisiae. Comparison of the proteins encoded by compacted genomes to those encoded by larger genomes can reveal the most highly conserved features of the encoded proteins. In this study, we identified the proteins comprising the RNA polymerases and their corresponding general transcription factors by using several bioinformatic approaches to compare the transcription machinery of E. cuniculi and S. cerevisiae. Surprisingly, our analyses revealed an overall reduction in the size of the proteins comprising transcription machinery of E. cuniculi, which includes the loss of entire regions or functional domains from proteins, as well as the loss of entire proteins and complexes. Unexpectedly, we found that the E. cuniculi ortholog of Rpc37 (a RNA Polymerase III subunit) more closely resembles the H. sapiens ortholog of Rpc37 than the S. cerevisiae ortholog of Rpc37, in both size and structure. Overall, our findings provide new insight into the minimal core eukaryotic transcription machinery and help define the most critical features of Pol components and general transcription factors.