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Hypothyroidism is a prevalent thyroid condition in which the thyroid gland fails to secrete an adequate amount of thyroid hormone into the bloodstream. This condition may develop due to genetic or acquired factors. The most frequent cause of acquired hypothyroidism is chronic autoimmune thyroiditis, also known as Hashimoto's disease. Acquired hypothyroidism is diagnosed when patients present with overt hypothyroidism (also known as clinical hypothyroidism), as they exhibit increased TSH and decreased T3 and T4 serum levels. This article examines the prevalence of psychiatric disorders among patients diagnosed with acquired hypothyroidism with or without Levothyroxine treatment. We discuss the available evidence indicating that acquired hypothyroidism may be a risk factor for psychiatric disorders, and the effectiveness of thyroid treatment in relieving psychiatric symptoms. Additionally, we provide critical details on thyroid hormone cutoff values reported in the literature, their potential clinical importance, and their correlation with psychiatric symptoms. Finally, we examined the various mechanisms by which acquired hypothyroidism can lead to depression. The high rate of comorbidity between hypothyroidism and psychiatric disorders deserves special attention, indicating the importance of consistent monitoring and timely identification of psychiatric symptoms to prevent disease exacerbation and facilitate therapeutic management. On the other hand, several mechanisms underlie the strong association between depression and acquired hypothyroidism. Deeper research into these mechanisms will allow knowledge of the pathophysiology of depression in patients with acquired hypothyroidism and will provide clues to design more precise therapeutic strategies for these patients.

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Species of the genus Ultratenuipalpus bear a broad subquadrate propodosoma with many large, flattened, lanceolate to ovate dorsal setae. They also bear some plesiomorphic character states, such as the presence of three pairs of ventral ps setae. Here, we describe Ultratenuipalpus parameekeri Castro, Ochoa & Feres sp. nov. based on adult females, males, and immatures, collected on ferns from Brazil. We also re-describe Ultratenuipalpus meekeri (De Leon), the type species of the genus, based on types and newly collected material from Mexico, and include additional novel data (e.g., dorsal and ventral ornamentation, leg chaetotaxy, and setal measurements) in a standardized form. We include highly detailed images obtained using LT-SEM, accompanied by DNA barcodes, for both species. The ontogenetic additions of leg chaetotaxy are presented and discussed.

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Background & Aims: Two recently developed composite models, the alpha-fetoprotein (AFP) score and Metroticket 2.0, could be used to select patients with hepatocellular carcinoma (HCC) who are candidates for liver transplantation (LT). The aim of this study was to compare the predictive performance of both models and to evaluate the net risk reclassification of post-LT recurrence between them using each model's original thresholds. Methods: This multicenter cohort study included 2,444 adult patients who underwent LT for HCC in 47 centers from Europe and Latin America. A competing risk regression analysis estimating sub-distribution hazard ratios (SHRs) and 95% CIs for recurrence was used (Fine and Gray method). Harrell's adapted c-statistics were estimated. The net reclassification index for recurrence was compared based on each model's original thresholds. Results: During a median follow-up of 3.8 years, there were 310 recurrences and 496 competing events (20.3%). Both models predicted recurrence, HCC survival and survival better than Milan criteria (p <0.0001). At last tumor reassessment before LT, c-statistics did not significantly differ between the two composite models, either as original or threshold versions, for recurrence (0.72 vs. 0.68; p = 0.06), HCC survival, and overall survival after LT. We observed predictive gaps and overlaps between the model's thresholds, and no significant gain on reclassification. Patients meeting both models ("within-ALL") at last tumor reassessment presented the lowest 5-year cumulative incidence of HCC recurrence (7.7%; 95% CI 5.1-11.5) and higher 5-year post-LT survival (70.0%; 95% CI 64.9-74.6). Conclusions: In this multicenter cohort, Metroticket 2.0 and the AFP score demonstrated a similar ability to predict HCC recurrence post-LT. The combination of these composite models might be a promising clinical approach. Impact and implications: Composite models were recently proposed for the selection of liver transplant (LT) candidates among individuals with hepatocellular carcinoma (HCC). We found that both the AFP score and Metroticket 2.0 predicted post-LT HCC recurrence and survival better than Milan criteria; the Metroticket 2.0 did not result in better reclassification for transplant selection compared to the AFP score, with predictive gaps and overlaps between the two models; patients who met low-risk thresholds for both models had the lowest 5-year recurrence rate. We propose prospectively testing the combination of both models, to further optimize the LT selection process for candidates with HCC.

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Cryptococcosis is a severe life-threatening disease and a major cause of mortality in people with advanced AIDS and CD4 ≤ 100 cells/µL. Considering the knowledge gap regarding the benefits of routine application of antigenemia tests in HIV-infected patients with 100−200 CD4 cells/µL for the prevention of cryptococcal meningitis (CM), we aimed to evaluate the prevalence of positive antigenemia through lateral flow assay (LFA) and associated factors in HIV-infected patients with CD4 < 200 cells/µL. Our findings of 3.49% of positive LFA (LFA+) patients with CD4 < 100 cells/µL and 2.24% with CD4 between 100−200 cells/µL have been included in a Bayesian analysis with 12 other studies containing similar samples worldwide. This analysis showed a proportion of 3.6% LFA+ patients (95% credible interval-Ci [2.5−5.7%]) with CD4 < 100 cells/µL and 1.1% (95%Ci [0.5−4.3%]) with CD4 between 100−200 cells/µL, without statistical difference between these groups. The difference between mortality rates in LFA+ and negative LFA groups was e = 0.05013. Cryptococcoma and CM were observed in the LFA+ group with 100−200 and <100 CD4 cells/µL, respectively. Considering the benefits of antifungal therapy for LFA+ patients, our data reinforced the recommendation to apply LFA as a routine test in patients with 100−200 CD4 cells/µL aiming to expand cost-effectiveness studies in this group.

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Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

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Hemophagocytic Lymphohistiocytosis (HLH) is a rare, highly aggressive syndrome involving dysregulated immune response. Most cases are secondary to underlying diseases including infections, autoimmune disorders and malignancies. The burden of disease of histoplasmosis and leishmaniosis associated with advanced HIV is still significant in low-and-middle income countries (LMIC). We present a case of histoplasmosis and leishmaniasis associated HLH in a man with an AIDS diagnosis.

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Background: The cardiovascular system is directly influenced by the autonomic nervous system (ANS); its changes affect heart rate variability (HRV) and are sensitive indicators of physiological changes. Autonomic dysfunction (AD) is manifested in up to 60% of patients with cirrhosis. Therefore, we aim to analyze the indexes of HRV pre- and post-surgery of children submitted for liver transplantation (LT). Methods: HRV, in children of both genders from 6 months of age to 10 years, that attended at the pediatric surgery clinic in the queue for LT at the Children's Institute were analyzed. To access HRV we analyzed indexes such as standard deviation of the RR intervals (SDNN), root-mean-square of the successive normal sinus RR interval difference (RMSSD), low frequency (LF), high frequency (HF), and LF/HF. Results: The analysis of the behavior of cardiac autonomic modulation, in the period prior to LT and after surgery, showed an increase in HRV linear parameters SDNN, TINN (triangular interpolation of NN interval histogram), HFms2. In the time domain, there was also an increase in the HFms2 index. Conclusions: The analysis of the period preceding LT and two months after surgery showed an increase in the HRV linear parameters representing a global HRV improvement. In the time domain, there was also an increase in the HFms2 index, parasympathetic tone of the HRV.

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INTRODUCTION AND OBJECTIVES: Fatty liver disease (FLD) may develop in liver transplant recipients. We investigated the recipient and donor risk factors for FLD development after liver transplantation (LT). METHODS: A total of 108 liver transplant recipients (54 men [50.0%]; median age, 52 [20-68] years) treated from 2011-2020 was enrolled. Three recipients died at < 3 months as a result of infection or blood flow impairment, and were excluded from the long-term FLD study. On evaluation of 88 prospective living donors, fatty liver was observed in 21. The prevalence and risk factors for FLD and survival were evaluated. RESULTS: After LT, 28 of 105 recipients (26.7%) developed FLD. FLD was more common in patients with a high body mass index (BMI) and dyslipidemia (both p < 0.01), primary nonalcoholic steatohepatitis (p = 0.02), after living-donor LT (p = 0.03) and everolimus (EVL) use (p = 0.08). Factors predictive of FLD included EVL use and a high BMI (hazard ratios = 3.00 and 1.34; p = 0.05 and p < 0.01, respectively). Sixteen donors lost 6.5 kg (range: 2.0-16.0 kg) of body weight prior to LT. However, there were no cases of primary non-function, which did not affect the FLD prevalence. Development of FLD did not have a negative impact on LT outcome; the 5-year survival rate was 92.6%. CONCLUSIONS: Recipient factors were more important than donor factors for FLD onset after LT.

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The eastern oyster, Crassostrea virginica, provides critical ecosystem services and supports valuable fishery and aquaculture industries in northern Gulf of Mexico (nGoM) subtropical estuaries where it is grown subtidally. Its upper critical thermal limit is not well defined, especially when combined with extreme salinities. The cumulative mortalities of the progenies of wild C. virginica from four nGoM estuaries differing in mean annual salinity, acclimated to low (4.0), moderate (20.0), and high (36.0) salinities at 28.9 °C (84 °F) and exposed to increasing target temperatures of 33.3 °C (92 °F), 35.6 °C (96 °F) or 37.8 °C (100 °F), were measured over a three-week period. Oysters of all stocks were the most sensitive to increasing temperatures at low salinity, dying quicker (i.e., lower median lethal time, LT50) than at the moderate and high salinities and resulting in high cumulative mortalities at all target temperatures. Oysters of all stocks at moderate salinity died the slowest with high cumulative mortalities only at the two highest temperatures. The F1 oysters from the more southern and hypersaline Upper Laguna Madre estuary were generally more tolerant to prolonged higher temperatures (higher LT50) than stocks originating from lower salinity estuaries, most notably at the highest salinity. Using the measured temperatures oysters were exposed to, 3-day median lethal Celsius degrees (LD50) were estimated for each stock at each salinity. The lowest 3-day LD50 (35.1-36.0 °C) for all stocks was calculated at a salinity of 4.0, while the highest 3-day LD50 (40.1-44.0 °C) was calculated at a salinity of 20.0.

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INTRODUCTION AND OBJECTIVES: Renal dysfunction before liver transplantation (LT) is associated with higher post-LT mortality. We aimed to study if this association still persisted in the contemporary transplant era. MATERIALS AND METHODS: We retrospectively reviewed data on 2871 primary LT performed at our center from 1998 to 2018. All patients were listed for LT alone and were not considered to be simultaneous liver-kidney (SLK) transplant candidates. SLK recipients and those with previous LT were excluded. Patients were grouped into 4 eras: era-1 (1998-2002, n = 488), era-2 (2003-2007, n = 889), era-3 (2008-2012, n = 703) and era-4 (2013-2018, n = 791). Pre-LT renal dysfunction was defined as creatinine (Cr) >1.5 mg/dl or on dialysis at LT. The effect of pre-LT renal dysfunction on post-LT patient survival in each era was examined using Kaplan Meier estimates and univariate and multivariate Cox proportional hazard analyses. RESULTS: Pre-LT renal dysfunction was present in 594 (20%) recipients. Compared to patients in era-1, patients in era-4 had higher Cr, lower eGFR and were more likely to be on dialysis at LT (P < 0.001). Pre-LT renal dysfunction was associated with worse 1, 3 and 5-year survival in era-1 and era-2 (P < 0.005) but not in era-3 or era-4 (P = 0.13 and P = 0.08, respectively). Multivariate analysis demonstrated the lack of independent effect of pre-LT renal dysfunction on post-LT mortality in era-3 and era-4. A separate analysis using eGFR <60 mL/min/1.73 m2 at LT to define renal dysfunction showed similar results. CONCLUSIONS: Pre-LT renal dysfunction had less impact on post-LT survival in the contemporary transplant era.

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The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker which has been investigated as a prognostic indicator in post-therapeutic recurrence and survival of patients with HCC. Our aim was to review all studies that assessed the prognostic value of pre-treatment NLR in predicting patient survival, cancer recurrence, and graft survival in patients undergoing various therapies for HCC. We searched the database of PubMed and Google Scholar to review all studies that have the word "NLR" and the word "HCC." We included all studies that assessed pre-treatment NLR as a prognostic factor in predicting outcomes in HCC patients. We excluded studies that assessed the correlation between post-treatment NLR or dynamic changes in NLR after treatment and HCC outcomes in an effort to minimize the confounding effect of each treatment on NLR. We reviewed 123 studies that studied the correlation between pre-treatment NLR and patient survival, 72 studies that evaluated the correlation between pre-treatment NLR and tumor recurrence, 21 studies that evaluated the correlation between NLR and tumor behavior, and 4 studies that assessed the correlation between NLR and graft survival. We found a remarkable heterogeneity between the methods of the studies, which is likely responsible for the differences in outcomes. The majority of the studies suggested a correlation between higher levels of pre-treatment NLR and poor outcomes. We concluded that NLR is a reliable and inexpensive biomarker and should be incorporated into other prognostic models to help determine outcomes following HCC treatment.

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Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.

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We investigate theoretically, through of first-principles calculations, the effect of the application of large in-plane uniaxial stress on single-layer of MoS2, MoSe2, and MoSSe alloys. For stress applied along the zigzag direction, we predict an anomalous behavior near the point fracture. This behavior is characterized by the reorientation of the MoS2structure along the applied stress from zigzag to armchair due to the formation of transient square-lattice regions in the crystal, with an apparent (although not real) crystal rotation of 30 degrees. After reorientation, a large plastic deformation √3-1 remains after the stress is removed. This behavior is also observed in MoSe2and in MoSSe alloys. This phenomenon is observed both in stress-constrained geometry optimizations and in ab initio molecular dynamics simulations at finite temperature and applied stress.

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Maize (Zea mays L.) is one of the most important commodities, and Brazil is the second-largest maize exporter country in the world. In April 2019, the period of the second crop maize (safrinha), it was observed black decayed lesions on roots and wilting of some maize plants, causing a "sudden death" in a commercial area in the west of Paraná state, Brazil (Figure 1A-C). Symptomatic root and stalk were collected, and tissues surface disinfected with 70% ethanol for 30 s, 1.5% NaOCl for 1 min and rinsed three times in sterile distilled water, slices of necrotic tissues were transferred to potato dextrose agar (PDA) medium and grown for 7 days at 27 ± 1ºC with a photoperiod of 12 h. Pure cultures were obtained through monosporic isolation. The fungal morphology is alike Gaeumannomyces radicicola, which is a synonym of Phialophora radicicola var. radicicola, Harpophora radicicola, P. zeicola, H. zeicola and G. graminis var. maydis (Hernández-Restrepo et al. 2016). Colonies on PDA showed flat, white to light gray at first (Fig. 1D), turning gray to black with age (Fig. 1E). Colony diameter approximately 5.2 cm on PDA in the dark after 7 days at 27ºC. Conidiophores with slightly thickened wall, mostly branched, varying in dimensions, with a range of 57.5-166.5 (avg. 128.7 µm) × 2.9-5.9 (avg. 4.2 µm) n = 25 (Fig. 1H-J). The conidia showed lunate-shaped with rounded ends, produced successively at the apex of phialide, 3.3-9.7 (avg. 6.6 µm) × 1.5-3.6 µm (avg. 2.5 µm), n = 100 (Fig. 1G-J). Morphological characteristics were comparable to the description of this specie (Cain 1952; Gams 2000; McKeen 1952). The total genomic DNA of a representative isolate, LEMIDPRZm 19-01 was extracted and the partial large subunit (28S nrDNA; LSU), internal transcribed spacer nrDNA including the intervening 5.8S nrDNA (ITS), and part of the largest subunit of the RNA polymerase II gene (RPB1) were amplified and sequenced, as following by Hernández-Restrepo et al. (2016) and Klaubauf et al. (2014). The primers to LSU - NL1 (O'Donnel, 1993) and LR5 (Vilgalys; Hester, 1990); ITS - ITS5 and ITS4 (White et al., 1990); and RPB1 - RPB1F and RPB1R (Klaubauf et al., 2014) were used in this study. The gene sequences of LSU (MT123866), ITS (MT114427), and RPB1 (MT123867) were deposited in GenBank and showed 99.67%, 99.75%, and 100% identity with type material G. radicicola CBS 296.53 (KM484962, KM484845, and KM485061). A multi-locus phylogenetic analysis based on Bayesian Inference showed the isolate LEMIDPRZm 19-01 in the G. radicicola clade (Fig. 2). To confirm pathogenicity, ex vivo assays were performed with mycelial PDA discs of 5 mm from a 7-day-old culture using detached roots (adapted method by Degani et al., 2019), on wounded and unwounded stalk and leaves, each treatment consisted of five replications. PDA discs without fungal were used in negative tissue controls. Pathogenicity tests were also conducted in vivo, two experiments performed: i) the stalk tissue was inoculated by sterilized toothpick grown on PDA with fungal mycelium and the leaves inoculated as ex vivo assay, and toothpick without fungal mycelium was used to stalk negative control, whereas PDA discs without fungal were used in the tested leaves; ii) 6 mycelial PDA discs/500 mL were placed on potato dextrose broth (PDB) media and it remained in agitation for 10 days to obtain a mycelial suspension. Subsequently, the mycelial was crushed to soil infestation, and 50 mL from this suspension were dropped in each 2 L maize pot with soil sterilization 10 days after emergence. Maize pots with soil sterilization without mycelium fungal were used as negative controls. Four replications (maize pots), for each treatment, were used in both tests. Experiments were repeated twice. In the ex vivo assay, all inoculated tissues with and without wounds showed necrotic lesions (Fig. 1K-N). In the first in vivo assay, stalk rot symptoms, including wilting of the inoculated plants causing premature plant death, were observed within 6 days (Fig. 1O-Q). In the second in vivo assay, inoculated plants had inferior growth than compared with plant control. Sixty days after inoculation, the plants were removed from the pots and it was observed a roots degeneration with symptoms of necrosis (Fig. 1R-U). No symptoms were detected in the control treatments and the pathogen was re-isolated from symptomatic tissues confirming Koch's postulate for all assays. So far, to our knowledge, the pathogen distribution was reported solely in the west area of Paraná state, but it may become a potential threat to Brazilian maize production. Further monitoring is necessary to better understand the epidemiology of this pathogen to address a strategy for disease control. The pathogen has already been detected in Canada, South Africa, and China. To our knowledge, this is the first report of G. radicicola in Brazil, as well as in South America.

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The metastable phase of solid4He and the possible role of point defects in its destabilization are investigated by the introduction of a trial function of the shadow class with an explicit symmetrical kernel. This is a trial function that ensures the possible exchange of atoms and the delocalization of atoms and defects in a very effective manner. We show that the formation energy for vacancies is equal to zero at a pressure Pc=20±2 atm, which is in excellent agreement with the experimental observation. The pressure at which a self-interstitial also has a formation energy equal to zero, is in agreement with the density where vacancies have the same property. Formation energies of a3He interstitial or a substitutional impurity were estimated. Other properties of interest for systems made from4He atoms are estimated and compared with results from the literature whenever available.

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Enterotoxigenic Escherichia coli (ETEC) represents one of the most important etiological agents of diarrhea in developing countries and characteristically produces at least one of two enterotoxins: heat-labile toxin (LT) and heat-stable toxin (ST). It has been previously shown that the production and release of LT by human-derived ETEC strains are variable. Although the natural genetic polymorphisms of regulatory sequences of LT-encoding (eltAB) genes may explain the variable production of LT, the knowledge of the transcriptional and posttranscriptional aspects affecting LT expression among ETEC strains is not clear. To further understand the factors affecting LT expression, we evaluated the impact of the natural polymorphism in noncoding regulatory sequences of eltAB among clinically derived ETEC strains. Sequence analyses of seven clinically derived strains and the reference strain H10407 revealed polymorphic sites at both the promoter and upstream regions of the eltAB operon. Operon fusion assays with GFP revealed that specific nucleotide changes in the Pribnow box reduce eltAB transcription. Nonetheless, the total amounts of LT produced by the tested ETEC strains did not strictly correspond to the detected LT-specific mRNA levels. Indeed, the stability of LT varied according to the tested strain, indicating the presence of posttranscriptional mechanisms affecting LT expression. Taken together, our results indicate that the production of LT is a strain-specific process and involves transcriptional and posttranscriptional mechanisms that regulate the final amount of toxin produced and released by specific strains.

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Aedes albopictus (Skuse 1894) is prevalent in the urban/peri-urban Port Blair, posing a public health threat, during past outbreaks of chikungunya (2006) and dengue (2010). Despite its vector potential, information on the biology is scanty. Therefore, impact of temperature on survival of immature stages, under laboratory conditions, was studied on F1 population of Andamans. Ae. albopictus larvae were exposed to static temperatures viz. 37°C, 39°C, 41°C, 43°C and 45°C, and the lethal time to cause 50% (LT50) and 90% mortality (LT90) was computed. To assess adaptive thermotolerance, larvae exposed (37°C and 39°C) were re-exposed to higher temperatures (43°C and 45°C). All larvae survived at 37°C and 39°C for the entire exposure period of 420 min, while variable mortality was observed at 41°C, 43°C and 45°C. Larvae re-exposed to 43°C and 45°C showed an increase in thermotolerance with respect to non-adapted larvae. The results are discussed in the context of survival, development and distribution.

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In species with complex life cycles, early developmental stages are often less thermally tolerant than adults, suggesting that they are key to predicting organismal response to environmental warming. Here we document the optimal and lethal temperatures of larval sea urchins, and we use those to calculate the warming tolerance and the thermal safety margin of early larval stages of seven tropical species. Larvae of Echinometra viridis, Echinometra lucunter, Lytechinus williamsi, Eucidaris tribuloides, Tripneustes ventricosus, Clypeaster rosaceus, and Clypeaster subdepressus were reared at 26, 28, 30, 32, and 34 °C for 6 days. The temperatures at which statistically significant reductions in larval performance are evident are generally the same temperatures at which statistically significant reductions in larval survival were detected, showing that the optimal temperature is very close to the lethal temperature. The two Echinometra species had significantly higher thermal tolerance than the other species, with some surviving culture temperatures of 34 °C and showing minimal impacts on growth and survival at 32 °C. In the other species, larval growth and survival were depressed at and above 30 or 32 °C. Overall, these larvae have lower warming tolerances (1 to 5 °C) and smaller thermal safety margins (-3 to 3 °C) than adults. Survival differences among treatments were evident by the first sampling on day 2, and survival at the highest temperatures increased when embryos were exposed to warming after spending the first 24 hours at ambient temperature. This suggests that the first days of development are more sensitive to thermal stress than are later larval stages.

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INTRODUCTION: The usual supplementation for hypothyroidism is based on monotherapy with levothyroxine. However, some patients persist with symptoms attributable to the deficit of thyroid hormone. It has been suggested that the a combined treatment with liothyronine and levothyroxine would provide a greater benefit. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews including twelve primary studies overall, all of which were randomized trials. We concluded that the addition of liothyronine to the treatment of hypothyroidism has minimal or no effect on fatigue and quality of life. It probably does not improve mood, pain or function cognitive, and it would not reduce body weight.

INTRODUCCIÓN: La suplementación habitual del hipotiroidismo se basa en la monoterapia con levotiroxina, sin embargo, algunos pacientes persisten con síntomas atribuibles al déficit de hormona tiroidea. Debido a esto se ha planteado que el uso de un tratamiento combinado con liotironina y levotiroxina otorgaría un mayor beneficio. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el cribado de múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas que en conjunto incluyeron 12 estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que la adición de liotironina al tratamiento del hipotiroidismo tiene un efecto mínimo o nulo sobre fatiga y calidad de vida. Probablemente tampoco mejora estado de ánimo, dolor ni función cognitiva, y no reduciría el peso corporal.

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Although positive effects on growth and reproduction of Antarctic vascular plants have been reported under warmer temperatures, it could also increase the vulnerability of these plants to freezing. Thus, we assessed in situ whether warming decreases the freezing resistance of Colobanthus quitensis and Deschampsia antarctica, and we compared the level and mechanism of freezing resistance of these species in the field with previous reports conducted in lab conditions. We assessed the freezing resistance of C. quitensis and D. antarctica by determining their low temperature damage (LT50), ice nucleation temperature (NT) and freezing point (FP) in three sites of the King George Island. Plants were exposed during two growing seasons to a passive increase in the air temperature (+W). +W increased by 1K the mean air temperatures, but had smaller effects on freezing temperatures. Leaf temperature of both species was on average 1.7K warmer inside +W. Overall, warming decreased the freezing resistance of Antarctic species. The LT50 increased on average 2K for C. quitensis and 2.8K for D. antarctica. In contrast, NT and FP decreased on average c. 1K in leaves of warmed plants of both species. Our results showed an averaged LT50 of -15.3°C for C. quitensis, and of -22.8°C for D. antarctica, with freezing tolerance being the freezing resistance mechanism for both species. These results were partially consistent with previous reports, and likely explanations for such discrepancies were related with methodological differences among studies. Our work is the first study reporting the level and mechanisms of freezing resistance of Antarctic vascular plants measured in situ, and we demonstrated that although both plant species exhibited a great ability to cope with freezing temperatures during the growing season, their vulnerability to suffer freezing damage under a warming scenario increase although the magnitude of this response varied across sites and species. Hence, freezing damage should be considered when predicting changes in plant responses of C. quitensis and D. antarctica under future climate conditions of the Antarctic Peninsula.