Proteomic analysis reveals Renibacterium salmoninarum grown under iron-limited conditions induces iron uptake mechanisms and overproduction of the 57-kDa protein.

Renibacterium salmoninarum, a slow-growing facultative intracellular pathogen, is the causative agent of bacterial kidney disease, a chronic, progressive and granulomatous infection that threatens farmed and wild salmonids worldwide. Pathogenic R. salmoninarum colonizes tissues and invades the host through cell surface-associated and secreted proteins. While correlations between iron acquisition genes and virulence have been demonstrated in vitro, these mechanisms have not undergone proteomic characterization. The present study applied a proteomic approach to elucidate the differences between the virulent Chilean R. salmoninarum H-2 strain and the type strain ATCC 33209T . Analyses were conducted under normal (control) and iron-limited conditions (DIP) emulating the host environment. Interestingly, strain H-2 apparently responded better to the iron-limited condition-for example, only this strain presented a significantly enriched iron ion homeostasis pathway. Furthermore, key virulence factors related to an iron-limited environment were more abundant in strain H-2. Importantly, the lack of iron favoured the expression of the 57-kDa protein in strain H-2, the principal virulence factor for R. salmoninarum. Our findings can be employed in the design and development of treatments targeted to iron uptake mechanisms (e.g. siderophore synthesis or haem uptake), which represents a promising therapeutic approach for treating this persistent fastidious bacterium.

Increased hippocampal, thalamus and amygdala volume in long-term lithium-treated bipolar I disorder patients compared with unmedicated patients and healthy subjects.

OBJECTIVE: Magnetic resonance imaging (MRI) studies in bipolar I disorder (BD-I) suggest that lithium is associated with increased volumes of cortico-limbic structures. However, more rigorous control of confounding factors is needed to obtain further support for this hypothesis. The aim of the present study was to assess differences in brain volumes among long-term lithium-treated BD-I patients, unmedicated BD-I patients, and healthy controls. METHODS: This was a cross-sectional study with 32 euthymic BD-I patients (16 on lithium monotherapy for a mean of 180 months, and 16 receiving no medication for at least the 2 months prior to the study) and 20 healthy controls. Patients were euthymic (Hamilton Depression Rating Scale [HDRS] <6 and Young Mania Rating Scale [YMRS] <7) and had not taken psychotropic medications other than lithium for at least 6 months. Brain images were acquired on a 1.5 Tesla MRI (Phillips, Amsterdam, The Netherlands) and segmented to generate volumetric measures of cortical and subcortical brain areas, ventricles and global brain. RESULTS: Significant differences were found in the volumes of the left amygdala (P=.0003), right amygdala (P=.030), left hippocampus (P=.022), left thalamus (P=.022), and right thalamus (P=.019) in long-term lithium-treated BD-I patients, compared to unmedicated patients and controls, after multivariable adjustment. No differences were observed in global brain volume or in ventricular size among the three groups. Likewise, there was no correlation between serum lithium levels and the increase in size in the described brain areas. CONCLUSIONS: The structural differences found among the three groups, and specifically those between long-term lithium-treated and unmedicated BD-I patients, indicate increased limbic structure volumes in lithium-treated patients.

Ocean acidification and pathogen exposure modulate the immune response of the edible mussel Mytilus chilensis.

Ocean acidification (OA) is one of the main consequences of increasing atmospheric carbon dioxide (CO2), impacting key biological processes of marine organisms such as development, growth and immune response. However, there are scarce studies on the influence of OA on marine invertebrates' ability to cope with pathogens. This study evaluated the single and combined effects of OA and bacterial infection on the transcription expression of genes related to antioxidant system, antimicrobial peptides and pattern recognition receptors in the edible mussel Mytilus chilensis. Individuals of M. chilensis were exposed during 60 days at two concentrations of pCO2 (550 and 1200 µatm) representing respectively current and future scenario of OA and were then injected with the pathogenic bacterium Vibrio anguillarum. Results evidenced an immunomodulation following the OA exposure with an up-regulation of C-type Lectin and Mytilin B and a down-regulation of Myticin A and PGRP. This immunomodulation pattern is partially counteracted after challenge with V. anguillarum with a down-regulation of the C-type lectin and Mytilin B and the up-regulation of Myticin A. In turn, these results evidence that pCO2-driven OA scenarios might triggers specific immune-related genes at early stages of infection, promoting the transcription of antimicrobial peptides and patterns recognition receptors. This study provides new evidence of how the immune response of bivalves is modulated by higher CO2 conditions in the ocean, as well one factor for the resilience of marine population upon global change scenarios.

Biomineralization changes with food supply confer juvenile scallops (Argopecten purpuratus) resistance to ocean acidification.

Future ocean acidification (OA) will affect physiological traits of marine species, with calcifying species being particularly vulnerable. As OA entails high energy demands, particularly during the rapid juvenile growth phase, food supply may play a key role in the response of marine organisms to OA. We experimentally evaluated the role of food supply in modulating physiological responses and biomineralization processes in juveniles of the Chilean scallop, Argopecten purpuratus, that were exposed to control (pH ~ 8.0) and low pH (pH ~ 7.6) conditions using three food supply treatments (high, intermediate, and low). We found that pH and food levels had additive effects on the physiological response of the juvenile scallops. Metabolic rates, shell growth, net calcification, and ingestion rates increased significantly at low pH conditions, independent of food. These physiological responses increased significantly in organisms exposed to intermediate and high levels of food supply. Hence, food supply seems to play a major role modulating organismal response by providing the energetic means to bolster the physiological response of OA stress. On the contrary, the relative expression of chitin synthase, a functional molecule for biomineralization, increased significantly in scallops exposed to low food supply and low pH, which resulted in a thicker periostracum enriched with chitin polysaccharides. Under reduced food and low pH conditions, the adaptive organismal response was to trade-off growth for the expression of biomineralization molecules and altering of the organic composition of shell periostracum, suggesting that the future performance of these calcifiers will depend on the trajectories of both OA and food supply. Thus, incorporating a suite of traits and multiple stressors in future studies of the adaptive organismal response may provide key insights on OA impacts on marine calcifiers.

Molecular evidence for a new endemic species of Acartia (Copepoda, Calanoida) from the Southeast Pacific coast.

The loss of biodiversity in marine populations is one of the consequences of the increased events of extreme environmental conditions in the oceans, which can condition the persistence of populations to future scenarios of climate change. Therefore, it is extremely necessary to explore and monitor the genetic diversity of natural populations. In the Southeast Pacific Ocean (SEPO), specifically on the coast of Chile, the presence of the copepod Acartia tonsa has been indicated solely using morphological evidence, due to the absence of genetic information. In the present work, the genetic diversity, population structure and phylogenetic position within the genus Acartia, of populations identified morphologically as A. tonsa, was evaluated by amplification of the mitochondrial cytochrome c oxidase subunit I and nuclear marker 18 s. Our results showed that the populations identified as A. tonsa correspond to a new monophyletic group endemic to SEPO (GMYC = 1.00; PTP = 0.95). The populations showed moderate to high genetic diversity with an incipient structuring between populations and biogeographic zones. Our results suggest that despite the homogenizing effect of the Humboldt Current, isolation by distance and contrasting environmental conditions at different geographic scales have an important influence on the genetic diversity of zooplankton in the SEPO region.

Inorganic Polyphosphate Affects Biofilm Assembly, Capsule Formation, and Virulence of Hypervirulent ST23 Klebsiella pneumoniae.

The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to high mortality rates and propensity to cause severe community-acquired infections in healthy individuals. The ability to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Polyphosphate kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a proteomic analysis to gain further insights into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins involved in capsule synthesis (Wzi-Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB-LpxC-PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hvKP. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

[Tetanus: an immunopreventable disease]. / Tétanos: una enfermedad inmunoprevenible.

Tetanus is an infectious disease caused by a ubiquitous bacterium Clostridium tetani, that synthesizes and releasesa potent neurotoxin under anaerobic conditions, which is responsible for the clinical manifestations. As it is found in soil contaminated with animal and human excreta, it is difficult to eradicate but it may be prevented by immunization. Immunization rate has decreased in the last years, especially during the COVID-19 pandemic. We report two cases of tetanus, attended during 2022. A 39-year-old man whose entry route was a gunshot wound and he was discharged from the intensive care unit (ICU) and a second case of an 83-year-old woman with unknown entry point, who died during her ICU stay. The cases reported highlight that it is a life-threatening disease, its diagnosis is mainly clinical and it should be in the algorithm of differential diagnoses. We emphasize about the prompt treatment administration or consultation to a specialized healthcare center. The importance of this presentation is to show the severity of the disease, whose assessment is mainly clinical and should not escape the algorithm of differential diagnoses, emphasizing that treatment should be instituted early or when in doubt consult a specialized center. In addition to this, it is important to check theimmunization rate in our country, especially during thepandemic, becauseit is a vaccine-preventable disease.

El tétanos es causado por el Clostridium tetani, una bacteria ubicua que frente a condiciones de anaerobiosis puede sintetizar y liberar sus toxinas, responsables del cuadro clínico. Dado que es una bacteria que se encuentra en el suelo y en el tracto gastrointestinal de muchas especies, se trata de una enfermedad no erradicable pero si controlable a través de la inmunización para la prevención. Las tasas de inmunización han disminuido en los últimos años, evento que se ha acentuado durante la COVID-19. Se presentan a continuación dos casos clínicos ingresados durante el año 2022. El primero es un hombre de 39 años cuya puerta de entrada fue una herida de arma de fuego conevolución favorable y el segundo caso se trata de una mujer de 83 años sin puerta de entrada clara quien falleció durante su internación en terapia intensiva. La importancia de esta presentación es mostrar la gravedad de la enfermedad, cuyavaloración es principalmente clínica y no debe escapar al algoritmo de diagnósticos diferenciales, acentuando que se debe instaurar el tratamiento de forma precoz o frente a la duda consultar con un centro especializado. Asímismo, es importante revisar las tasas de inmunización en nuestro país y los cambios que se presentaron durante la pandemia, teniendo en cuenta, como se ha expuesto previamente, se trata de una enfermedad inmunoprevenible.

Differential gene expression analysis in the scallop Argopecten purpuratus exposed to altered pH and temperature conditions in an upwelling-influenced farming area.

Increased carbon dioxide in the atmosphere and its absorption across the ocean surface will alter natural variations in pH and temperature levels, occurring in coastal upwelling ecosystems. The scallop Argopecten purpuratus, one of the most economically important species farmed in northern Chile, has been shown to be vulnerable to these environmental drivers. However, the regulatory responses at the gene-level of scallops to these climate stressors remain almost unknown. Consequently, we used an orthogonal experimental design and RNAseq approach to analyze the acute effects of variability in pH and temperature on gene expression in the muscle tissue of A. purpuratus. In respect to control conditions (pH ~ 8.0/ 14 °C), the influence of low pH (~ 7.7) and temperature (14 °C) induced the activation of several genes associated with apoptotic signaling pathways and protein localization to plasma membrane. Elevated temperature (18 °C) and pH (~8.0) conditions increased the expression of transcripts associated with the activation of muscle contraction, regulation, and sarcomere organization effects on muscle tissue. In scallops exposed to low pH and elevated temperature, the genes expressed were differentially associated with the oxidation-reduction process, signal translation, and positive regulation of GTPase activity. These results indicated that the differentially expressed genes under the experimental conditions tested are mainly related to the mitigation of cellular damage and homeostasis control. Our results add knowledge about the function of the adductor muscle in response to stressors in scallops. Furthermore, these results could help in the identification of molecular biomarkers of stress necessary to be integrated into the aquaculture programs for the mitigation of climate change.

Proteomic and toxicological analysis of the response of dinoflagellate Alexandrium catenella to changes in NaNO3 concentration.

Dinoflagellates of the genus Alexandrium cause Harmful Algal Blooms (HABs) in coastal waters worldwide, damaging marine environments, aquaculture, and human health. They synthesize potent neurotoxic alkaloids known as PSTs (i.e., Paralytic Shellfish Toxins), the etiological agents of PSP (i.e., Paralytic Shellfish Poisoning). In recent decades, the eutrophication of coastal waters with inorganic nitrogen (e.g., nitrate, nitrite, and ammonia) has increased the frequency and scale of HABs. PSTs concentrations within Alexandrium cells can increase by up to 76% after a nitrogen enrichment event; however, the mechanisms that underlie their biosynthesis in dinoflagellates remains unclear. This study combines mass spectrometry, bioinformatics, and toxicology and investigates the expression profiles of PSTs in Alexandrium catenella grown in 0.4, 0.9 and 1.3 mM NaNO3. Pathway analysis of protein expression revealed that tRNA amino acylation, glycolysis, TCA cycle and pigment biosynthesis were upregulated in 0.4 mM and downregulated in 1.3 mM NaNO3 compared to those grown in 0.9 mM NaNO3. Conversely, ATP synthesis, photosynthesis and arginine biosynthesis were downregulated in 0.4 mM and upregulated in 1.3 mM NaNO3. Additionally, the expression of proteins involved in PST biosynthesis (sxtA, sxtG, sxtV, sxtW and sxtZ) and overall PST production like STX, NEO, C1, C2, GTX1-6 and dcGTX2 was higher at lower nitrate concentrations. Therefore, increased nitrogen concentrations increase protein synthesis, photosynthesis, and energy metabolism and decrease enzyme expression in PST biosynthesis and production. This research provides new clues about how the changes in the nitrate concentration can modulate different metabolic pathways and the expression of PST biosynthesis in toxigenic dinoflagellates.

Community health worker navigation to improve allostatic load: The Integrated Population Health (IPOP) study.

Background: Social determinants of health (SDOH) and cumulative stress contribute to chronic disease development. The physiological response to repeated stressors typical of lower-income environments can be measured through allostatic load - a composite measure of cardiovascular, metabolic, and immune variables. Healthcare systems have employed patient navigation for social and medical needs to improve SDOH that has demonstrated limited impact on chronic disease outcomes. This study evaluates a novel community health worker navigation intervention developed using behavioral theories to improve access to social and medical services and provide social support for poverty stressed adults. Methods: The Integrated Population Health Study (IPOP) study is a randomized, parallel two arm study evaluating community health worker navigation in addition to an existing integrated population health program (IPOP CHW) as compared to Usual Care (population health program only, IPOP) on allostatic load and chronic disease risk factors. IPOP CHW participants receive a 10-month navigation intervention. Results: From 381 screened individuals, a total of 202 participants (age 58.15 ± 12.03 years, 74.75 % female, 79.21 % Black/African American, 17.33 % Hispanic) were enrolled and randomized to IPOP CHW (n = 100) or IPOP Only (n = 102). Conclusion: This study will evaluate whether CHW navigation, using a structured intervention based on health behavior theories, can effectively guide poverty stressed individuals to address social and medical needs to improve allostatic load-a composite of cumulative stress and physiological responses. Healthcare systems, nonprofit organizations, and governmental entities are interested in addressing SDOH to improve health, thus developing evidence-based interventions could have broad clinical and policy implications.

Clinical and pulmonary function analysis in long-COVID revealed that long-term pulmonary dysfunction is associated with vascular inflammation pathways and metabolic syndrome.

Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

Long term environmental variability modulates the epigenetics of maternal traits of kelp crabs in the coast of Chile.

The methylation of DNA is an environmentally inducible epigenetic mechanism reflecting the short-term ecological and environmental background of populations. Marine invertebrate populations, which spread along a latitudinal cline, are particularly suitable for profiling DNA methylation, due to the heterogenous environmental conditions experienced. We used the MSAP (Methylation Sensitive Amplified Polymorphism) technique to investigate the natural variation in DNA methylation of different female's tissues (muscle, gonads, and gills) and early-stage eggs from five populations of the kelp crab Taliepus dentatus, distributed along a latitudinal cline in the coast of Chile. We assessed whether, (1) the distribution of DNA methylation profiles can be associated with the temporal variability of long term (18 years) climatologies (sea surface temperature, turbidity and productivity) and (2) the epigenetic diversity of eggs is related to the population-level phenotypic variability of several maternal investment traits (egg volume, egg weight, egg lipids and fecundity). The DNA methylation of eggs correlated positively and negatively with the long term variability in productivity and sea surface temperature, respectively. Furthermore, the diversity of DNA methylation of eggs correlated positively with the population-level phenotypic variability of several maternal investment traits, suggesting a key role of epigenetic mechanisms in generating phenotypic variability at population level for this species. We provide evidence of a strong link between the temporal variability of long term climatologies with the epigenetic profiles of key early ontogenetic traits associated with the maternal investment of kelp crabs. These modulating mechanisms can hence contribute early to phenotypic variability at population levels in response to local and past environmental fluctuation.

Physical-chemical factors influencing the vertical distribution of phototrophic pico-nanoplankton in the Oxygen Minimum Zone (OMZ) off Northern Chile: The relative influence of low pH/low O2 conditions.

The vertical distribution of phytoplankton is of fundamental importance in the structure, dynamic, and biogeochemical pathways in marine ecosystems. Nevertheless, what are the main factors determining this distribution remains as an open question. Here, we evaluated the relative influence of environmental factors that might control the coexistence and vertical distribution of pico-nanoplankton associated with the OMZ off northern Chile. Our results showed that in the upper layer Synechococcus-like cells were numerically important at all sampling stations. Pico-nano eukaryotes and phototrophic nanoflagellates (PNF) also showed high abundances in the upper layer decreasing in abundance down to the upper oxycline, while only Prochlorococcus showed high abundances under oxycline and within the oxygen-depleted layer. Statistical analyses evidenced that temperature, oxygen, and carbonate chemistry parameters (pH and dissolved inorganic carbon, DIC) influenced significantly the vertical distribution of phototrophic pico-nanoplankton. Additionally, we experimentally-evaluated the combined effect of low pH/low O2 conditions on a nanophytoplankton species, the haptophyte Imantonia sp. Under control conditions (pH = 8.1; O2 = 287.5 µM, light = 169.6 µEm-2s-1), Imantonia sp. in vivo fluorescence increased over fifty times, inducing supersaturated O2 conditions (900 µM) and an increasing pH (8.5), whereas upon an experimental treatment mimicking OMZ conditions (pH = 7.5; O2 = 55.6 µM; light = 169.6 µEm-2s-1), in vivo fluorescence declined dramatically, suggesting that Imantonia sp. did not survive. Although preliminary, our study provides evidence about the role of low pH/low O2 conditions on the vertical distribution of nanophytoplankton, which deserve future attention through both fieldwork and more extended experimental experiences.

Neuropsychological aspects of bipolar disorder.

Bipolar disorder (BD) is a chronic condition with serious consequences on the health and functionality of patients who suffer from it, with a high heritability and segregation, and aprevalence of between 1% and 2%. Neuropsychological deficits have been implicated as a very important issue related to BD prognosis, so a review was conducted of these deficits, the related factors and their functional consequences. It has been determined that the presence of neuropsychological deficits can vary in patients with BD according to their mood state, with a great influence of depressive symptoms on the cognitive variability of patients with respect to the general population and differences with respect to patients in the manic phase. In euthymic patients, the most affected cognitive domains are those of memory, attention, and executive function, associated with a more severe disease, sociodemographic vulnerability factors, and stable over time. A relationship has been found between poor cognitive performance, especially executive dysfunction, and objective functional deficit. Furthermore, cognitive differences have been outlined between BD and other serious mental illnesses that are described in this review.

Approaching the Ecological Role of the Squat Lobster (Munida gregaria) and the Fuegian Sprat (Sprattus fuegensis) in the Francisco Coloane Marine Area (Magellan Strait, Chile) Using a Pelagic Food Web Model.

The structure and functioning of the food web of the Francisco Coloane Marine Area in the Magellan Strait, Chile, was quantified, with an emphasis on identifying the ecological role of the squat lobster (Munida gregaria) and the Fuegian sprat (Sprattus fuegensis). Food web indicators, the trophic level, and centrality indices were estimated using Ecopath with Ecosim. Dynamic simulations were carried out to evaluate the ecosystem impacts of biomass changes in squat lobster and Fuegian sprat. The model calculated a total ecosystem biomass of 71.7 t km-2 and a total primary production of 2450.9 t km-2 year-1. Squat lobster and Fuegian sprat were located in specific trophic levels of 2.3 and 2.7, respectively. Squat lobster reduction produced a decrease in the biomass of red cod (42-56%) and humpback whales (25-28%) and Fuegian sprat reduction a decrease in penguins (15-37%) and seabirds (11-34%). The Francisco Coloane Area is an immature ecosystem with productivity and energy flows values within those reported for productive ecosystems; the role of the squat lobster seems to be related to the structure of the food web, and the role of the Fuegian sprat seems to be related to the functioning of the ecosystem and to the energy transfer to top predators.

Structural neuroimaging and predominant polarity in patients with type 1 bipolar disorder from Antioquia.

INTRODUCTION: Predominant polarity (PP) has been proposed as a specifier of bipolar disorder (BD) due to its relationship with clinical and prognostic variables. It is possible that this is due to a different underlying neurobiology, in such a way that the changes found by structural nuclear magnetic resonance imaging (sMRI) in BD are different and specific. OBJECTIVES: To explore findings of structural neuroimaging in patients with BD type I (BD-I) according to PP. METHODS: Cross-sectional study that evaluated 77 patients with BD-I using the DIGS interview. PP was established using the operative definition of two-thirds of all affective episodes throughout life to classify PP as manic (MPP), depressive (DPP) or indeterminate (IPP). MRI was performed during the euthymia phase to measure intracranial structures. The data obtained was analysed using a linear regression model adjusted for confounding variables (drug use, alcohol use, psychoactive substance use) and were compared between the three groups finding the standardised mean difference (SMD). RESULTS: Differences with adequate effect size were found in three brain structures after adjusting for confounding variables, specifically in the right fusiform gyrus and the left lingual gyrus, which were greater in the DPP group than in the MPP group (SMD = 0.92; 95% CI = 0.34-1.49 and SMD = 0.78; 95% CI = 0.21-1.35). Likewise, in the right thalamus, it was shown to be greater in the IPP group compared to MPP group (SMD 0.89, 95% CI = 0.31-1.46). CONCLUSIONS: A reduction in the thickness of the right fusiform gyrus and the left lingual gyrus, as well as the right thalamic volume was observed in patients with BD-I with PPM, which supports the hypothesis that PP has a plausible neurobiological correlate and could have potential utility as a BD specifier.

Resting-state functional nuclear magnetic resonance imaging in patients with bipolar disorder: Beyond euthymia.

INTRODUCTION: Functional nuclear magnetic resonance imaging in the resting state (R-fMRI) allows the identification of complete functional connectivity networks and the possible neuronal correlations of psychiatric disorders. The literature on R-fMRI and bipolar disorder (BD) will be reviewed, emphasising the findings in the phases of mania, hypomania and depression. METHODS: It is a narrative review of the literature in which articles were searched in PubMed and Embase, with the key words in English "bipolar disorder" AND "resting state", without limit on the date of publication. RESULTS: The studies of BD patients in the mania and hypomania phases who underwent R-fMRI show concordant results in terms of decreased functional cerebral connectivity between the amygdala and some cortical regions, which indicates that this functional connection would have some implication in the normal affect regulation. Patients in the depressive phase show a decrease in functional brain connectivity, but as there are several anatomical structures involved and neural networks reported in the studies, it is not possible to compare them. CONCLUSIONS: There is a decrease in functional connectivity in patients with BD, but current evidence does not allow establishing specific changes in specific functional brain connectivity networks. However, there are already some findings that show correlation with the patients' symptoms.

Contrasting land-uses in two small river basins impact the colored dissolved organic matter concentration and carbonate system along a river-coastal ocean continuum.

Human activities have led to an increase in land use change, with effects on the structure and functioning of ecosystems. The impact of contrasting land uses along river basins on the concentration of colored dissolved organic matter (CDOM) reaching the coastal zone, and its relationship with the carbonate system of the adjacent coastal ocean, is poorly known. To understand the relationship between land use change, CDOM and its influence on the carbonate system, two watersheds with contrasting land uses in southern Chile were studied. The samples were collected at eight stations between river and adjacent coastal areas, during three sampling campaigns in the austral summer and spring. Chemical and biological samples were analyzed in the laboratory according to standard protocols. Landsat 8 satellite images of the study area were used for identification and supervised classification using remote sensing tools. The Yaldad River basin showed 82% of native forest and the Colu River basin around 38% of grassland (agriculture). Low total alkalinity (AT) and Dissolved Inorganic Carbon (DIC), but high CDOM proportions were typically observed in freshwater. A higher CDOM and humic-like compounds concentration was observed along the river-coastal ocean continuum in the Yaldad basin, characterized by a predominance of native forests. In contrast, nutrient concentrations, AT and DIC, were higher in the Colu area. Low CaCO3 saturation state (ΩAr < 2) and even undersaturation conditions were observed at the coastal ocean at Yaldad. A strong negative correlation between AT, DIC and ΩAr with CDOM/fDOM, suggested the influence of terrestrial material on the seawater carbon chemistry. Our results provide robust evidence that land uses in river basins can influence CDOM/fDOM proportion and its influence on the carbonate chemistry of the adjacent coastal, with potential implications for the shellfish farming activity in this region.

Proteogenomic analysis in an early onset diffuse gastric cancer patient revealed alterations in PIK3R1, TP53, SMAD4 and a potential role of the PI3K-AKT and EGFR pathways: a case report.

Background: Early-onset gastric cancers (EOGC) are poor prognosis hard-to treat malignancies that affect young individuals (<45 years old). Case Description: Herein we describe the case of a 26-year-old female EOGC patient that initially displayed stable disease after first-line CAPOX plus immunotherapy. However, patient eventually developed progressive disease and was consecutively switched to paclitaxel plus ramucirumab, and palliative irinotecan. In search for therapeutic alternatives a proteo-genomic analysis was performed in a tissue biopsy taken after the first progression. Our analyses found a total of 18 somatic mutations, including TP53 and PIK3R1, and a previously unreported germline alteration in the tumor suppressor SMAD4. Also, our proteomic analysis found 62 proteins previously documented as "enriched in stomach cancer" and AKT/mTOR and EGFR as pathways with therapeutic potential. Unfortunately, the clinical utility of AKT/mTOR inhibitors or EGFR targeted therapies could not be assessed. Conclusions: As explained above EOGC is a growing health concern that affects young individuals. Furthermore, the reported case displayed a poor response to standard therapy including checkpoint inhibitors and chemotherapy despite the presence of biomarkers that predict a favorable outcome. Future studies should adopt alternative approaches to find novel, more effective therapies.