Exfoliation of titanium nitride using a non-thermal plasma process.

In this study, we present a novel approach for the exfoliation of titanium nitride (TiN) powders utilizing a rapid, facile, and environmentally friendly non-thermal plasma method. This method involves the use of an electric arc and nitrogen as the ambient gas at room temperature to generate ionized particles. These ionized species interact with the ceramic crystal of TiN, resulting in a pronounced structural expansion. The exfoliated TiN products were comprehensively characterized using transmission electron microscopy, X-ray diffraction, and Raman spectroscopy. Remarkably, the cubic crystal structure of TiN was effectively retained, while the (200) crystal plane d-spacing increased from 2.08 to 3.09 Å, accompanied by a reduction in crystallite size and alterations in Raman vibrational modes. Collectively, these findings provide compelling evidence for the successful exfoliation of TiN structures using our innovative non-thermal plasma method, opening up exciting possibilities for advanced material applications.

Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.

BACKGROUND: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. METHODS AND RESULTS: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. CONCLUSIONS: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.

Pharmacological potential of 4-dimethylamino chalcone against acute and neuropathic pain in mice.

OBJECTIVES: This work investigated the acute antinociceptive effect of a synthetic chalcone, 4-dimethylamino chalcone (DMAC), as well as its effects on vincristine-induced peripheral neuropathy (VIPN) in mice. METHODS: The inhibitory activity of myeloperoxidase was assessed by measuring HOCl formation. Formalin and hot plate tests were used to study the acute antinociceptive effect of DMAC. VIPN was induced through the administration of vincristine sulphate (0.1 mg/kg, i.p., 14 days). Then, DMSO, DMAC (10 or 30 mg/kg; i.p.), or pregabalin (10 mg/kg, i.p.) were administered for 14 consecutive days. Thermal hyperalgesia and mechanical allodynia were evaluated before and after VIPN induction and on days 1, 3, 7, and 14 of treatment. Neurodegeneration and neuroinflammation were assessed through immunohistochemistry for NF200, iNOS, and arginase-1 within the sciatic nerve. KEY FINDINGS: DMAC inhibited myeloperoxidase activity in vitro and presented an acute antinociceptive effect in both formalin and hot plate tests, with the involvement of muscarinic and opioid receptors. Treatment with 30 mg/kg of DMAC significantly attenuated thermal hyperalgesia and mechanical allodynia and prevented macrophage proinflammatory polarisation in VIPN mice. CONCLUSIONS: Our results show that DMAC, acting through different mechanisms, effectively attenuates VIPN.

Multiple variation of right renal and gonadal vascularization: report of two cases.

We present two cases of multiple anatomical variations of the renal and gonadal vessels. The first case presented duplication of the renal vein and the presence of an accessory renal artery. However, the most interesting fact, in this case, was that the right gonadal vein emptied into the inferior right renal vein instead of ending in the inferior vena cava as would typically be the case. In the second case, we also found an accessory renal artery and the right gonadal vein emptied at the exact junction between the right renal vein and the inferior vena cava. Clinicians and surgeons should be familiar with anatomical variations to provide an accurate diagnosis during preoperative studies and to avoid surprises in abdominal surgical procedures.

Este estudo apresenta dois casos de variação anatômica múltipla de vasos renais e gonadais. O primeiro caso apresentou uma duplicação da veia renal e a presença de uma artéria renal acessória. Porém, o fato mais interessante nesse caso foi a veia gonadal direita desembocar na veia renal direita inferior em vez de terminar na veia cava inferior, como seria o normal. No segundo caso, além de também encontrarmos uma artéria renal acessória, a veia gonadal direita desembocava no exato ponto de junção entre a veia renal direita e a veia cava inferior. Clínicos e cirurgiões devem estar familiarizados com a presença de possíveis variações dos vasos renais e gonadais, sendo um conhecimento imprescindível para obter um diagnóstico mais preciso e para evitar surpresas em procedimentos cirúrgicos abdominais.

The Fbn1 gene variant governs passive ascending aortic mechanics in the mgΔlpn mouse model of Marfan syndrome when superimposed to perlecan haploinsufficiency.

Introduction: Ascending thoracic aortic aneurysms arise from pathological tissue remodeling that leads to abnormal wall dilation and increases the risk of fatal dissection/rupture. Large variability in disease manifestations across family members who carry a causative genetic variant for thoracic aortic aneurysms suggests that genetic modifiers may exacerbate clinical outcomes. Decreased perlecan expression in the aorta of mgΔlpn mice with severe Marfan syndrome phenotype advocates for exploring perlecan-encoding Hspg2 as a candidate modifier gene. Methods: To determine the effect of concurrent Hspg2 and Fbn1 mutations on the progression of thoracic aortopathy, we characterized the microstructure and passive mechanical response of the ascending thoracic aorta in female mice of four genetic backgrounds: wild-type, heterozygous with a mutation in the Fbn1 gene (mgΔlpn), heterozygous with a mutation in the Hspg2 gene (Hspg2+/-), and double mutants carrying both the Fbn1 and Hspg2 variants (dMut). Results: Elastic fiber fragmentation and medial disarray progress from the internal elastic lamina outward as the ascending thoracic aorta dilates in mgΔlpn and dMut mice. Concurrent increase in total collagen content relative to elastin reduces energy storage capacity and cyclic distensibility of aortic tissues from mice that carry the Fbn1 variant. Inherent circumferential tissue stiffening strongly correlates with the severity of aortic dilatation in mgΔlpn and dMut mice. Perlecan haploinsufficiency superimposed to the mgΔlpn mutation curbs the viability of dMut mice, increases the occurrence of aortic enlargement, and reduces the axial stretch in aortic tissues. Discussion: Overall, our findings show that dMut mice are more vulnerable than mgΔlpn mice without an Hspg2 mutation, yet later endpoints and additional structural and functional readouts are needed to identify causative mechanisms.

Concentration of lipids, cholesterol, and fatty acid profile in chicken breast meat affected by wooden breast myopathy frozen for up to 12 mo.

The aim of this study was to examine the effects of frozen storage for 12 mo on the concentrations of lipids and cholesterol and fatty acid profile of wooden chicken breast meat. A total of 120 samples of chicken breasts were selected, according to the degree of "wooden breast" myopathy ["severe," "moderate," and "normal" (absence of myopathy)], from male chickens slaughtered at 42 d of age, from Cobb 500 strain. Part of the samples (n = 20/grade of severity) were evaluated on the day of collection and the remainder were packaged, frozen and stored at -18°C for up to 12 mo. At the beginning (collection day) and at the end of the proposed freezing period (12 mo), analyses of lipid, cholesterol, and fatty acid profile were carried out. Percentage of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids were evaluated. Meats affected by wooden breast myopathy had lower levels of PUFA that exert beneficial effects on health, such as DHA, EPA and ARA, and this profile is impaired by prolonged storage (12 mo), which results in important nutritional losses for the consumer.

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression.

Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.

Capsaicin and 1,25-Dihydroxyvitamin D3 Glycoside: Effects on the Reproductive Performance of Hyper-Prolific Sows.

This study evaluated the effect of a natural source of vitamin D3 [1,25-(OH)2D3] and capsaicin (CAP) in the dietary supplementation of sows in the final phase (85-114 days) of gestation (Gest) and lactation (Lact) on the reproductive performance of the sows and health of piglets through two experiments (Exp I and II). In Exp I, 120 sows were subjected to four treatments: T1-control (without [1,25-(OH)2D3] and supplemental CAP); T2-3.5 µg 1,25-(OH)2D3/Gest/day and 7.0 µg Vit 1,25-(OH)2D3/Lact/day; T3-7.0 µg CAP/Gest/day and 14.0 µg CAP/Lact/day; T4-1.75 µg Vit 1,25-(OH)2D3 + 3.5 µg CAP/Gest/day and 3.5 µg 1,25-(OH)2D3 + 7.0 µg CAP/Lact/day. In Exp II, 200 sows were randomly blocked, factorial 2 × 2 (without or with Vit 1,25-(OH)2D3 and without or with CAP): T1-control (without Vit 1,25-(OH)2D3 and CAP); T2-3.5 µg Vit 1,25-(OH)2D3/Gest/day and 7.0 µg Vit 1,25-(OH)2D3/Lact/day; T3-7.0 µg CAP/Gest/day and 14.0 µg CAP/Lact/day; T4-3.5 µg Vit 1,25-(OH)2D3 + 7 µg CAP/Gest/day; and 7.0 µg Vit 1,25-(OH)2D3 + 14.0 µg CAP/Lact/day. The duration of delivery (3:48 vs. 4:57 h) and the percentage of stillbirths (5.37% vs. 7.61%) were improved (p < 0.05) in the group that received Vit 1,25-(OH)2D3 (Exp II) compared to the control group. Moreover, the dystocia rate decreased (p < 0.05) in Exp II, which received Vit 1,25-(OH)2D3 (4.21 vs. 27.63%), and in Exp I, which received the combination of Vit 1,25-(OH)2D3 + CAP (12 vs. 40%) compared to the respective control groups. Colostrum production was greater (p < 0.05) in sows that received Vit 1,25-(OH)2D3 supplementation compared to the control group, consequently resulting in higher colostrum intake (p < 0.05) of the piglets (330 vs. 258 g/piglet). The additives reduced the incidence of diarrhea (p < 0.05) in piglets (Exp I and II). Thus, the use of additives improved the reproductive performance of sows and contributed to litter growth.

Physical, chemical, and microbiological evaluation of sausages produced with chicken meat affected by deep pectoral myopathy.

The purpose of the present study was to characterize the chemical composition, lipid oxidation, and physical characteristics of fresh sausages produced with meat from the pectoralis major muscle affected by deep pectoral myopathy. For the characterization of myopathy, samples were collected from broiler chickens slaughtered between 42- and 46-days old in a slaughterhouse in the state of São Paulo. The experiment consisted of samples from pectoralis major muscle of birds affected or not by DPM (normal-absence of myopathy and DPM category 3-progressive degeneration of the pectoralis minor with a greenish appearance). After classification of the samples, a part of raw products with the pectoralis minor removed, was submitted to microbiological and physical analyses for the characterization of DPM. Afterward, only the pectoralis major muscle was used to manufacture fresh sausages and 2 groups were established. The evaluated parameters were: color, pH, water-holding capacity (WHC), cooking loss (CL), shear force (SF), water activity (Aw), and chemical composition. Meat pH was higher (P < 0.05) in meats with DPM, however, WHC values were lower (71.92%), which made CL value increase (25.31%). In addition, the coloring increased and the technological characteristics of raw breasts were less favorable with the presence of DPM. All fresh sausages' color (except a* higher control group), pH, and Aw values were higher in DPM group. No effect on SF values was observed between fresh sausages. In chemical composition, only protein content increased in fresh sausages with DPM. Microbiological analyses did not indicate bacterial contamination of raw samples and fresh sausages. Data obtained in the present study suggest fresh sausages produced with breasts affected by DPM are a viable alternative and may confer more favorable qualitative characteristics to sausages than the raw marketed meat.

Developing Amphetamine Certified Reference Materials: From Batch and Continuous-Flow Synthesis to Certification Protocol.

Certified reference materials (CRM) of amphetamine derivatives were produced through a simple, rapid and efficient synthesis in both batch and continuous-flow conditions, accompanied by the development of a comprehensive certification protocol for this class of substances. Our chemistry enabled the synthesis of MDA, MDMA, PMA and PMMA in two steps from safrole and estragole with overall yields of 38-61 % in 48 hours under batch conditions and 61-65 % in 65 minutes under continuous-flow conditions, followed by the development of a certification protocol for these materials through identity checking, homogeneity, stability, and characterization studies. Furthermore, as result of this work, a very pure CRM of MDA.HCl with 99.1±1.4 g/100 g of certified characterization value was produced. Considering the importance of supplying amphetamine calibrants for public security efforts in Forensic Chemistry, the potential therapeutical applications, and responding to the rising demand for the synthesis of CRM, this work presents a pioneering approach for the production of amphetamine and related compounds.

The Effects of NAM on the Symmetry of the Face and Maxillary Arch in Babies With Unilateral Cleft.

The study aimed to evaluate the effect of nasoalveolar molding (NAM) therapy through reverse engineering, or its absence, to obtain symmetry of the face and maxillary arch. Twenty-six babies with unilateral cleft lip and palate received treatment with NAM, and 12 babies with unilateral cleft lip and palate without presurgical orthopedics (control group). Patients were molded and photographed in 2-stages: the first month of life (T1/pre) and after the use of NAM/before the cheiloplasty (T2/post). In the digital models, the analyses performed were arch perimeter, arch length, and labial frenulum angle. The photographs allowed us to analyze nasal width, mouth width, columella angle, and nostril area. The results demonstrated that there was an increase in arch perimeter and arch length in control and NAM groups in the T2 period in comparison to T1. Labial frenulum angle was reduced in the NAM group compared to the NAM-T1 and control-T2 periods. Treatment with NAM yielded a reduction in nasal width in the period of T2 compared with T1. Columella angle was enhanced after NAM use in T2 and, was different from control group. The nostril area was reduced in the NAM group in T2 compared with control group. Nasoalveolar molding therapy reduced the labial frenulum angle, contributing to a reduction in the extension of the cleft. The NAM protocol improved facial symmetry, mainly through nasal effects, whereas the absence of orthopedic therapy yielded a commitment to the face and maxillary arch symmetry.

Hitting the Road: Haplotype Diversity of Fire Ants Nesting on Disturbed Atlantic Forest Habitats.

Ants of the genus Solenopsis are globally distributed, presenting high diversity and many generalist species. In South America, the dominant species is Solenopsis saevissima (Smith, 1855), commonly found nesting in grassy fields surrounding humanized areas. In spite of being so common, there has been no research evaluating the effect of human disturbances on the mitochondrial DNA (mtDNA) haplotype diversity in this species. In this context, we here characterized the mtDNA haplotype diversity in S. saevissima nests by highway roadsides, dust roads, and forest borders of Atlantic Forest, based on partial sequences of cytochrome c oxidase subunit I (COI). Based on the facts that the species is a rapid colonizer of disturbed habitats, we specifically probed how the genetic diversity of native S. saevissima is impacted by highways and roads infrastructure expanding around the rainforest. Species diagnosis was established both by morphological characters and obtained mtDNA COI sequences. Overall, the species exhibited high haplotypes and nucleotide diversity, particularly around forest borders; though all haplotypes seemed closely related across the different habitats. We identified seven mitochondrial haplotypes (H1 to H7), where haplotype H1 was exclusively found in highway roadside nests, and H7 on dust roads; the remaining haplotypes were recorded from all habitats. Haplotype H1 was geographically isolated to the south of the Atlantic Forest, supporting previous suggestions that it acts as a biogeographical barrier. The pattern is suggestive of a recent species expansion, probably resulting from extensive habitat fragmentation. Taken together, our data demonstrates fire ant haplotypes prevailing in some anthropized habitats, characterizing how a native species lining the remnants of the Brazilian Atlantic Forest might be a concern for environmental conservation.

Effect of freezing on the quality of breast meat from broilers affected by wooden breast myopathy.

The objective of the present study was to characterize possible variations in the quality of wooden chicken breast meat during freezing for 12 mo, in order to prove whether the shelf life recommended by the industry allows the storage of that type of meat without compromising its consumption. Three hundred samples of male Cobb 500 broilers slaughtered at 42 d of age were used. Part of the samples (n = 20 normal-control group; n = 20 moderate degree; n = 20 severe degree) were analyzed on the day of collection (beginning), previously kept under refrigeration (4°C). The other samples were stored (-18°C) for up to 12 mo. At the end of each proposed freezing period (3, 6, 9, and 12 mo), physical and chemical analyses were performed (per period: n = 20 normal-control group; n = 20 moderate degree; n = 20 severe degree). Color (L*, a*, and b*), pH, water-holding capacity, cooking losses, tenderness, lipid oxidation, chemical composition, cholesterol concentration, mineral profile, and collagen concentration were evaluated. The physicochemical quality of wooden chicken breast meat is significantly altered during frozen storage for 12 mo, being of inferior quality when compared to normal chicken breast meat, which can negatively affect consumer acceptance. However, it should be noted that even after 12 mo of freezing, the meats did not show oxidative rancidity.

Long-Term Outcomes of Sternal-Sparing Versus Sternotomy Approaches for Mitral Valve Repair: Meta-Analysis of Reconstructed Time-to-Event Data.

OBJECTIVE: Since there are concerns about the durability of mitral valve repair (MVRp) with minimally invasive techniques in patients with mitral regurgitation (MR), we aimed to evaluate the long-term outcomes of these sternal-sparing approaches when compared with conventional approaches with sternotomy in patients undergoing MVRp. METHODS: We performed a systematic review according to a preestablished protocol and performed a pooled analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies with longer follow-up comparing sternal-sparing versus sternotomy approaches for MVRp. Our outcomes of interest were survival, freedom from recurrent MR, and freedom from reoperation. RESULTS: Eleven studies met our eligibility criteria comprising 7,596 patients with follow-up (sternal sparing, n = 4,246; sternotomy, n = 3,350). Patients who underwent sternal-sparing MVRp had a significantly lower risk of mortality over time compared with patients who underwent MVRp with sternotomy (hazard ratio [HR] = 0.29, 95% confidence interval [CI]: 0.23 to 0.36, P < 0.001) in the overall analysis. However, we found no statistically significant difference between the groups in the sensitivity analysis with adjusted populations (HR = 0.85, 95% CI: 0.63 to 1.15, P = 0.301). Regarding the outcomes freedom from recurrent MR and freedom from reoperation, we found no statistically significant differences between the groups in the follow-up in both overall and sensitivity analyses. CONCLUSIONS: In comparison with MVRp with sternotomy approaches, sternal-sparing MVRp was not associated with worse outcomes in terms of survival, recurrent MR, and reoperations over time.

Plasmodium falciparum Chloroquine-pfcrt Resistant Haplotypes in Brazilian Endemic Areas Four Decades after CQ Withdrawn.

(1) Background: Malaria is a public health problem worldwide. Despite global efforts to control it, antimalarial drug resistance remains a great challenge. In 2009, our team identified, for the first time in Brazil, chloroquine (CQ)-susceptible Plasmodium falciparum parasites in isolates from the Brazilian Amazon. The present study extends those observations to include survey samples from 2010 to 2018 from the Amazonas and Acre states for the purpose of tracking pfcrt molecular changes in P. falciparum parasites. (2) Objective: to investigate SNPs in the P. falciparum gene associated with chemoresistance to CQ (pfcrt). (3) Methods: Sixty-six P. falciparum samples from the Amazonas and Acre states were collected from 2010 to 2018 in patients diagnosed at the Reference Research Center for Treatment and Diagnosis of Malaria (CPD-Mal/Fiocruz), FMT-HVD and Acre Health Units. These samples were subjected to PCR and DNA Sanger sequencing to identify mutations in pfcrt (C72S, M74I, N75E, and K76T). (4) Results: Of the 66 P. falciparum samples genotyped for pfcrt, 94% carried CQ-resistant genotypes and only 4 showed a CQ pfcrt sensitive-wild type genotype, i.e., 1 from Barcelos and 3 from Manaus. (5) Conclusion: CQ-resistant P. falciparum populations are fixed, and thus, CQ cannot be reintroduced in malaria falciparum therapy.

Staphylococcus aureus and CA-MRSA Carriage among Brazilian Indians Living in Peri-Urban Areas and Remote Communities.

The emergence of Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections among indigenous populations has been reported. Usually, indigenous communities live in extreme poverty and are at risk of acquiring infections. In Brazil, healthcare inequality is observed in this population. To date, there are no reports of CA-MRSA infections, and no active search for asymptomatic S. aureus carriage has been conducted among Brazilian Indians. The aim of this study was to investigate the prevalence of colonization with S. aureus and CA-MRSA among Brazilian Indians. We screened 400 Indians (from near urban areas and remote hamlets) for S. aureus and CA-MRSA colonization. The isolates were submitted to clonal profiling by pulsed-field gel electrophoresis (PFGE), and selected isolates were submitted to multilocus sequence typing (MLST). Among 931 specimens (nasal and oral) from different indigenous individuals in remote hamlets, S. aureus was cultured in 190 (47.6%). Furthermore, CA-MRSA was found in three isolates (0.7%), all SCCmec type IV. PFGE analysis identified 21 clusters among the S. aureus isolates, and MLST analysis showed a predominance of sequence type 5 among these isolates. Our study revealed a higher prevalence of S. aureus carriage among Shanenawa ethnicity individuals (41.1%). Therefore, ethnicity appears to be associated with the prevalence of S. aureus in these populations.

Heme: The Lord of the Iron Ring.

Heme is an iron-protoporphyrin complex with an essential physiologic function for all cells, especially for those in which heme is a key prosthetic group of proteins such as hemoglobin, myoglobin, and cytochromes of the mitochondria. However, it is also known that heme can participate in pro-oxidant and pro-inflammatory responses, leading to cytotoxicity in various tissues and organs such as the kidney, brain, heart, liver, and in immune cells. Indeed, heme, released as a result of tissue damage, can stimulate local and remote inflammatory reactions. These can initiate innate immune responses that, if left uncontrolled, can compound primary injuries and promote organ failure. In contrast, a cadre of heme receptors are arrayed on the plasma membrane that is designed either for heme import into the cell, or for the purpose of activating specific signaling pathways. Thus, free heme can serve either as a deleterious molecule, or one that can traffic and initiate highly specific cellular responses that are teleologically important for survival. Herein, we review heme metabolism and signaling pathways, including heme synthesis, degradation, and scavenging. We will focus on trauma and inflammatory diseases, including traumatic brain injury, trauma-related sepsis, cancer, and cardiovascular diseases where current work suggests that heme may be most important.

Frequency of pleural effusion in dengue patients by severity, age and imaging modality: a systematic review and meta-analysis.

BACKGROUND: Identification of pleural effusion (PE) in dengue infection is an objective measure of plasma leakage and may predict disease progression. However, no studies have systematically assessed the frequency of PE in patients with dengue, and whether this differs across age and imaging modality. METHODS: We searched Pubmed, Embase Web of Science and Lilacs (period 1900-2021) for studies reporting on PE in dengue patients (hospitalized and outpatient). We defined PE as fluid in the thoracic cavity detected by any imaging test. The study was registered in PROSPERO (CRD42021228862). Complicated dengue was defined as hemorrhagic fever, dengue shock syndrome or severe dengue. RESULTS: The search identified 2,157 studies of which 85 studies were eligible for inclusion. The studies (n = 31 children, n = 10 adults, n = 44 mixed age) involved 12,800 patients (30% complicated dengue). The overall frequency of PE was 33% [95%CI: 29 to 37%] and the rate of PE increased significantly with disease severity (P = 0.001) such that in complicated vs. uncomplicated dengue the frequencies were 48% and 17% (P < 0.001). When assessing all studies, PE occurred significantly more often in children compared to adults (43% vs. 13%, P = 0.002) and lung ultrasound more frequently detected PE than conventional chest X-ray (P = 0.023). CONCLUSIONS: We found that 1/3 of dengue patients presented with PE and the frequency increased with severity and younger age. Importantly, lung ultrasound demonstrated the highest rate of detection. Our findings suggest that PE is a relatively common finding in dengue and that bedside imaging tools, such as lung ultrasound, potentially may enhance detection.

Extracellular matrix and vascular dynamics in the kidney of a murine model for Marfan syndrome.

Fibrillin-1 is a pivotal structural component of the kidney's glomerulus and peritubular tissue. Mutations in the fibrillin-1 gene result in Marfan syndrome (MFS), an autosomal dominant disease of the connective tissue. Although the kidney is not considered a classically affected organ in MFS, several case reports describe glomerular disease in patients. Therefore, this study aimed to characterize the kidney in the mgΔlpn-mouse model of MFS. Affected animals presented a significant reduction of glomerulus, glomerulus-capillary, and urinary space, and a significant reduction of fibrillin-1 and fibronectin in the glomerulus. Transmission electron microscopy and 3D-ultrastructure analysis revealed decreased amounts of microfibrils which also appeared fragmented in the MFS mice. Increased collagen fibers types I and III, MMP-9, and α-actin were also observed in affected animals, suggesting a tissue-remodeling process in the kidney. Video microscopy analysis showed an increase of microvessel distribution coupled with reduction of blood-flow velocity, while ultrasound flow analysis revealed significantly lower blood flow in the kidney artery and vein of the MFS mice. The structural and hemodynamic changes of the kidney indicate the presence of kidney remodeling and vascular resistance in this MFS model. Both processes are associated with hypertension which is expected to worsen the cardiovascular phenotype in MFS.

The value of private properties for the conservation of biodiversity in the Brazilian Cerrado.

Areas set aside for conservation within private lands may be key to enhancing biodiversity-friendly landscapes. This conservation strategy should be especially effective in highly threatened regions that are poorly protected by public lands, such as the Brazilian Cerrado. Brazil's Native Vegetation Protection Law has included set-aside areas within private properties, but their relevance to conservation has not been evaluated. We assess whether private lands are contributing to biodiversity in the Cerrado, a global biodiversity conservation priority and major region for food production, where land use conflicts are often at odds with conservation objectives. We determined that private protected areas accommodate up to 14.5% of threatened vertebrate species ranges, which increases to 25% when considering the distribution of remaining native habitat. Moreover, the spatial spread of private protected areas benefits a large number of species. Ecological restoration of private protected lands would improve the benefits of this protection system, especially in the Southeastern Cerrado, where a large economic hub meets a threat hotspot.