Notes

Submit partum dyspnoea: look beyond the bronchi.
And, like all scientific endeavors, progress in genome to phenome research will be enhanced by improvements in science education and communication both within and among working groups.Alternative electron pathways contribute to regulation of photosynthetic light reactions to adjust to metabolic demands in dynamic environments. The chloroplast NADH dehydrogenase-like (NDH) complex mediates the cyclic electron transport pathway around photosystem I (PSI) in different cyanobacteria, algae and plant species, but it is not fully conserved in all photosynthetic organisms. In order to assess how this complex's physiological role changed during plant evolution, we isolated Physcomitrella patens lines knocked out of the NDHM gene that encodes for a subunit fundamental for the activity of the complex. ndhm knock-out (KO) mosses indicated high PSI acceptor side limitation upon abrupt changes in illumination. In P. patens, pseudo-cyclic electron transport mediated by Flavodiiron proteins (FLVs) was also shown to prevent PSI overreduction in plants exposed to light fluctuations. flva ndhm double KO mosses had altered photosynthetic performance and growth defects under fluctuating light compared to wild-type and single KO mutants. The results evidenced that while NDH contribution to electron transport is minor compared to FLV, NDH still participates in modulating photosynthetic activity, and it is critical to avoid PSI photoinhibition, especially when FLVs are inactive. The functional overlap between NDH- and FLV-dependent electron transport supports PSI activity and prevents its photoinhibition under light variations.Retrochiasmatic craniopharyngiomas are difficult to treat due to their close proximity to critical neurovascular structures. Several surgical approaches with distinct advantages and limitations have been described to access these tumors, including extended transnasal endoscopic approach (ETEA), subtemporal, translamina terminalis, and transpetrosal approach.1-3 We present a 51-yr-old male with a large retrochiasmatic craniopharyngioma extending into the third ventricle, causing obstructive hydrocephalus. Preoperative magnetic resonance imaging (MRI) showed a tumor cyst abutting the fornices expanding the space between two internal cerebral veins (ICV). After surgical consent, we decided to take advantage of this corridor to approach the tumor in its long axis. Surgical goal was to achieve cyst decompression with "safe maximal" resection of the solid component at last to preserve the pituitary function. Though the long axis of the tumor could be approached using ETEA, we preferred this approach in view of cyst decompression early in the surgery while completely avoiding risks such as cerebrospinal fluid (CSF) rhinorrhea, internal carotid artery (ICA) injury, and sinonasal complications. We utilized a 3-dimensional 4 K exoscope, which provides an excellent ergonomic position, and a high-resolution immersive view compared to a microscope or endoscope. Cyst decompression and near-total resection of the solid component was achieved. Postoperatively, his headaches improved and he was neurologically intact with intact neuroendocrine function. Approach-related risks may include but not limited to hemorrhage due to the rupture of venous sinuses or ICV, stalk or hypothalamus injury, and memory disturbances due to forniceal injury. To conclude, the transcallosal, interforniceal approach to retrochiasmatic craniopharyngiomas may provide a safe surgical corridor in select cases. Patient consented to the proposed procedure. All radiological images have been anonymized. IRB/ethics committee approval was not required.Ancient biomolecule analyses are proving increasingly useful in the study of evolutionary patterns, including extinct organisms. Proteomic sequencing techniques complement genomic approaches, having the potential to examine lineages further back in time than achievable using ancient DNA, given the less stringent preservation requirements. In this study, we demonstrate the ability to use collagen sequence analyses via proteomics to provide species delimitation as a foundation for informing evolutionary patterns. We uncover biogeographic information of an enigmatic and recently extinct lineage of Nesophontes across their range on the Caribbean islands. First, evolutionary relationships reconstructed from collagen sequences reaffirm the affinity of Nesophontes and Solenodon as sister taxa within Solenodonota. This relationship helps lay the foundation for testing geographical isolation hypotheses across islands within the Greater Antilles, including movement from Cuba towards Hispaniola. Second, our results are consistent with Cuba having just two species of Nesophontes (N. micrus and N. major) that exhibit intrapopulation morphological variation. Finally, analysis of the recently described species from the Cayman Islands (N. hemicingulus) indicates that it is a closer relative to the Cuban species, N. major rather than N. micrus as previously speculated. Our proteomic sequencing improves our understanding of the origin, evolution, and distribution of this extinct mammal lineage, particularly with respect to approximate timing of speciation. Such knowledge is vital for this biodiversity hotspot, where the magnitude of recent extinctions may obscure true estimates of species richness in the past.Background This article explores the multifaceted perceptions among householders about the care, efficacy and disposal of long-lasting insecticide-treated nets (LLINs), especially those regarding the end of the useful life of LLINs, and their implications for malaria control. Methods We used a cross-sectional qualitative design. Data were gathered in the Shai-Osudoku District in the Greater Accra Region of Ghana using focus group discussions and in-depth interviews. A thematic analysis technique was applied to analyse the data. Results Four findings emerged. First, participants were familiar with LLINs and the issues concerning the end of their useful life. However, the application of this knowledge was deficient. Second, characteristics of effectiveness (e.g. torn beyond repair) other than the age of a net determined the end of the useful life of LLINs. Third, social desirability and other social practices had positive and negative influences on perceptions about LLIN use and the end of their useful life. Fourth, repurposing of LLINs signified the end of their useful life. Conclusions Policies and strategies to position LLIN use as the leading resource for malaria control need to be innovative to accommodate the perceptions and practices of targeted households.Endometriosis is an estrogen-dependent chronic inflammatory disease and is associated etiologically with environmental endocrine disruptor (EED) exposure. 4-nonylphenol (NP), a widely found EED, has weak estrogenic activity and modulates plasmacytoid dendritic cell (pDC) function in vitro and in vivo. We aimed to elucidate the immunomodulatory effect of NP on the development of endometriosis, particularly focusing on pDCs. This study established a surgically induced endometriosis murine model (C57BL/6) under conditions of NP treatment that are relevant to the level and route of human exposure. Multi-parametric flow cytometry was used for analysis of infiltrated immune cell subsets in lesions. The results showed that NP exposure significantly promoted endometriotic lesion growth, survival and angiogenesis development of lesions as well as pDC accumulation in the lesions in mice. Adoptive transfer of NP-conditioned pDCs into mice significantly enhanced lesion development and local pDC infiltration, whereas NP-conditioned conventional dendritic cells (cDCs) did not affect lesion growth. In-vitro functional analysis showed that NP-conditioned pDCs in lesions expressed high levels of CD36, a scavenger receptor, and NP-conditioned splenic pDCs secreted an enhanced level of IL-10 in response to apoptotic cell recognition in a CD36-dependent manner. Furthermore, we observed that local treatment with blocking antibodies against IL-10 and CD36 on the day of surgery significantly inhibited lesion development. NP exposure also altered the estrous cycle in mice. The results suggest that chronic and low-dose exposure to NP enhances endometriotic lesion growth by altering pDC homeostasis and function. This study has important implications for understanding the environment-innate immunity interaction in human endometriosis.Background We evaluated the validity of clinical diagnosis compared with laboratory diagnosis of dengue in a retrospective sample of patients in São José do Rio Preto, Brazil. L-Mimosine Methods Our sample included 148 299 clinically (56.3%) or laboratory-diagnosed (43.7%) dengue cases. We compared the sensitivity, specificity, positive and negative predictive value (PPV and NPV) of dengue patients' demographic and clinical characteristics with laboratory-based diagnosis. We used logistic regressions to estimate the correlation between clinical and laboratory diagnosis of dengue and a full set of dengue signs and symptoms. Results We found substantial variability in sensitivity and specificity of signs and symptoms ranging from 0.8-81.1 and 21.5-99.6, respectively. Thrombocytopenia exhibited the highest PPV (92.0) and lowest NPV (42.2) and was the only symptom showing agreement with laboratory-confirmed dengue (φ = 0.38). The presence of exanthema and thrombocytopenia led to a greater likelihood of concordant clinical and laboratory diagnoses (exanthema OR 4.23; 95% CI 2.09 to 8.57; thrombocytopenia OR 4.02; 95% CI 1.32 to 12.27). Conclusions We found substantial variation in sensitivity, specificity, PPV and NPV of dengue signs and symptoms. For accuracy, clinical and laboratory diagnosis of dengue should be performed concurrently. When laboratory tests are not available, we suggest focusing on the clinical manifestations most associated with dengue.Background Neoadjuvant FOLFIRINOX and chemoradiation have been utilized to downstage borderline and locally advanced pancreatic ductal adenocarcinoma (PDAC). Whether neoadjuvant therapy-induced tumor immune response contributes to the improved survival is unknown. Therefore, we evaluated whether neoadjuvant therapy induces an immune response towards PDAC. Methods Clinicopathologic variables were collected for surgically resected PDACs at the Massachusetts General Hospital (1998-2016). Neoadjuvant regimens included FOLFIRINOX with/without chemoradiation, proton chemoradiation (25Gy), photon chemoradiation (50.4Gy) or no neoadjuvant therapy. HLA class I and II expression, and immune cell infiltration (CD4+, FoxP3+, CD8+, Granzyme B+ cells and M2 macrophages) were analyzed immunohistochemically and correlated with clinicopathologic variables. The antitumor immune response was compared among neoadjuvant therapy regimens. All statistical tests were two-sided. Results Two hundred forty-eight PDAC patients were included. Median age was 64y; 50.0% were female. HLA-A defects were less frequent in the FOLFIRINOX cohort (p=.006). HLA class II expression was lowest in photon and highest in proton patients (p=.02). The FOLFIRINOX cohort exhibited the densest CD8+ cell infiltration (p less then .001). FOLFIRINOX and proton patients had the highest CD4+ and lowest T regulatory (FoxP3+) cell density, respectively. M2 macrophage density was statistically significantly higher in the treatment-naïve group (p less then .001), in which dense M2 macrophage infiltration was an independent predictor of poor OS. Conclusions Neoadjuvant FOLFIRINOX with/without chemoradiation may induce immunologically relevant changes in the tumor microenvironment. It may reduce HLA-A defects, increase CD8+ cell density and decrease T regulatory cell and M2 macrophage density. Therefore, neoadjuvant FOLFIRINOX therapy may benefit from combinations with checkpoint inhibitors, which can enhance patients' antitumor immune response.
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