Rationale
d
-Serine is an endogenous co-agonist of the
N
-methyl-
d
-aspartate (NMDA) receptor and has been suggested to improve cognitive deficits in schizophrenia.
Objectives
The present study ...investigates the effects of treatment with
d
-serine in mice on tasks that require recognition learning and working memory, two cognitive domains that are impaired in schizophrenia.
Methods
We studied the effects of various regimens of systemic administration of
d
-serine (50 mg/kg/day) on BALB/c mice performing object recognition, T-maze alternation, and open-field exploration tasks. For the object recognition task, we also contrasted the effects of
d
-serine and
d
-cycloserine and investigated whether
d
-serine could reverse alterations induced by subchronic injections of the NMDA antagonist MK-801.
d
-Serine levels after injections were measured by high-performance liquid chromatography.
Results
In the object recognition task, pre-training treatment with
d
-serine or
d
-cycloserine significantly enhanced recognition memory 24 h after training. A single administration of
d
-serine 30 min (but not 6 h) after training produced similar enhancement, suggesting an effect on memory consolidation. Daily treatment with
d
-serine enhanced both object recognition and T-maze performance over multiple days and improved short-term memory in MK-801-treated mice.
d
-Serine treatment did not alter open-field exploration. Behavioral effects were accompanied by increased levels of
d
-serine in the hippocampus of treated animals.
Conclusions
Our results show that treatment with
d
-serine can improve performance in tasks related to recognition learning and working memory, suggesting that this agent can be useful for the treatment of disorders involving declines in these cognitive domains.
This case report describes the anesthetic management of a one-year-old patient with Xia-Gibbs syndrome, which is a rare genetic condition caused by a mutation in the AHDC1 gene. The procedure ...involved calvarial vault remodeling and fronto-orbital advancement to correct a left coronal craniosynostosis. In addition, the patient had a history of seizures and latex-fruit syndrome, which necessitated careful preoperative planning and management. Despite the difficulties provided by the patient's cranial abnormalities and the paucity of literature on anesthetic experiences with the condition, the treatment was completed successfully and without complications. Insights are offered about the anesthetic approach for this syndromic pediatric patient undergoing neurosurgery with a high risk of bleeding. It is important to understand and prepare for the perioperative implications of this disease in order to achieve a safe outcome.
Fungi have a complex role in the intestinal tract, influencing health and disease, with dysbiosis contributing to obesity. Our objectives were to investigate fungal diversity in human gut microbiota ...among eutrophic, overweight, and obese. Epidemiological and nutritional information were collected from adult individuals, as well as stool samples processed for selective fungi isolation and identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (yeasts) or microculture (filamentous fungi). Further 18S rDNA sequencing was performed to confirm identification. The mean count of fungi was 241 CFU/g of feces. Differences in the population level of the filamentous fungi were observed within eutrophic and obese groups. Overall, 34 genera were identified. The predominant phylum was Ascomycota with 20 different genera, followed by Basidiomycota and Zygomycota. As for Ascomycota, the most prevalent species were
Paecilomyces
sp.,
Penicillium
sp.,
Candida
sp.,
Aspergillus
sp.,
Fonsecaea
sp., and
Geotrichum
sp. (76.39, 65.28, 59.72, 58.33, 12.50, and 9.72%, respectively). As for Basidiomycota,
Trichosporon
sp. and
Rhodotorula
sp. were the most prevalent (30.56 and 15.28%, respectively), and for Zygomycota,
Rhizopus
sp. and
Mucor
sp. were the most numerous (15.28 and 9.72%, respectively). As expected there is a mycobiota shift towards obesity, with slightly higher diversity associated to eutrophic individuals. This mycobiota shift seems also to be related to the nutritional behavior of the individuals, as observed that the macronutrients intake may be positively related to the different fungi occurrences. Other studies are needed to better understand relationships between mycobiota and obesity, which could be used in future obesity treatments.
Technosols are anthropogenic soils that may be strongly impacted by heavy metal deposition, which have not yet been described in Antarctica. In this paper, we present a chemical study of what is ...supposedly the oldest manmade soil from Antarctic Peninsula, developed in the vicinity of Trinity House and Nordenskjold Hut at Hope Bay. Chemical and morphological soil attributes indicate that a former ornithogenic site (penguin rookery) was further subjected to human disturbance, following local exploration since 1903. We detected very high amounts of heavy metals such as Cd, Cu, Pb, and Zn. For the most impacted site, pseudototal concentrations of these elements reach 47, 2,082, 19,381, and 5,225 mg kg
−1
, respectively. Enrichment factors were calculated using Zr as reference element, and high values were found for these contaminated sites, qualifying some of them as extremely polluted. Also, both the mobilizable and mobile fraction of Cd and Pb indicate the need of intervention in the affected area. These findings are all consistent with the human impacts and strong contamination. Strong positive correlation between the pseudototal concentrations of Cd, Cu, Mn, Ni, Pb, and Zn indicates a similar source of pollution. These soils may represent the oldest Technosols in Antarctic Continent.
Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease ...progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.
Ethnobotanical surveys of Cerrado native plants show that leaves of Celtis iguanaea (Jacq.) Sargent (Cannabaceae), popularly known in Brazil as "esporão de galo", are used in folk medicine for body ...pain, asthma, cramps, poor digestion, urinary infection, kidney dysfunctions, as well as a stimulant and diuretic. This work aimed at evaluating possible C. iguanaea aqueous leaf extract (CALE) cytotoxicity, genotoxicity, and antigenotoxicity using the mouse bone marrow micronucleous test. To assess CALE genotoxicity, Swiss mice were orally treated with three different extract concentrations (100, 300, and 500 mgkg-1). To evaluate its antigenotoxicity, the same doses were used simultaneously with a single i.p. dose of mitomycin C (MMC, 4mg.kg-1). The frequencies of micronucleated polychromatic erythrocytes (MNPCE) were evaluated 24 h and 48 h after administration except for the negative control (24 h). Genotoxicity was evaluated using the frequency of micronucleated polychromatic erythrocytes (MNPCE), whereas cytotoxicity was assessed by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed that CALE did not exhibit a significant reduction in the PCE/NCE ratio, neither a considerable increase in the frequency of MNPCE. Nonetheless, CALE reduced bone marrow toxicity (increased PCE/NCE ratio) and decreased the micronuclei frequency induced by MMC. We can conclude that CALE presented no cytotoxic and genotoxic effects, but showed antigenotoxic and anticytotoxic actions under the experimental conditions applied in this study.
It is unknown whether angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have a positive, neutral, or negative effect on clinical outcomes in patients with ...coronavirus disease 2019 (COVID-19).
To determine whether discontinuation compared with continuation of ACEIs or ARBs changed the number of days alive and out of the hospital through 30 days.
A randomized clinical trial of 659 patients hospitalized in Brazil with mild to moderate COVID-19 who were taking ACEIs or ARBs prior to hospitalization (enrolled: April 9-June 26, 2020; final follow-up: July 26, 2020).
Discontinuation (n = 334) or continuation (n = 325) of ACEIs or ARBs.
The primary outcome was the number of days alive and out of the hospital through 30 days. Secondary outcomes included death, cardiovascular death, and COVID-19 progression.
Among 659 patients, the median age was 55.1 years (interquartile range IQR, 46.1-65.0 years), 14.7% were aged 70 years or older, 40.4% were women, and 100% completed the trial. The median time from symptom onset to hospital admission was 6 days (IQR, 4-9 days) and 27.2% of patients had an oxygen saturation of less than 94% of room air at baseline. In terms of clinical severity, 57.1% of patients were considered mild at hospital admission and 42.9% were considered moderate. There was no significant difference in the number of days alive and out of the hospital in patients in the discontinuation group (mean, 21.9 days SD, 8 days) vs patients in the continuation group (mean, 22.9 days SD, 7.1 days) and the mean ratio was 0.95 (95% CI, 0.90-1.01). There also was no statistically significant difference in death (2.7% for the discontinuation group vs 2.8% for the continuation group; odds ratio OR, 0.97 95% CI, 0.38-2.52), cardiovascular death (0.6% vs 0.3%, respectively; OR, 1.95 95% CI, 0.19-42.12), or COVID-19 progression (38.3% vs 32.3%; OR, 1.30 95% CI, 0.95-1.80). The most common adverse events were respiratory failure requiring invasive mechanical ventilation (9.6% in the discontinuation group vs 7.7% in the continuation group), shock requiring vasopressors (8.4% vs 7.1%, respectively), acute myocardial infarction (7.5% vs 4.6%), new or worsening heart failure (4.2% vs 4.9%), and acute kidney failure requiring hemodialysis (3.3% vs 2.8%).
Among patients hospitalized with mild to moderate COVID-19 and who were taking ACEIs or ARBs before hospital admission, there was no significant difference in the mean number of days alive and out of the hospital for those assigned to discontinue vs continue these medications. These findings do not support routinely discontinuing ACEIs or ARBs among patients hospitalized with mild to moderate COVID-19 if there is an indication for treatment.
ClinicalTrials.gov Identifier: NCT04364893.
Blowflies have major medical and sanitary importance because they can be vectors of viruses, bacteria, and helminths and are also causative agents of myiasis. Also, these flies, especially those ...belonging to the genus Chrysomya, are among the first insects to arrive at carcasses and are therefore valuable in providing data for the estimation of the minimum postmortem interval (PMIₘᵢₙ). The PMIₘᵢₙ can be calculated by assessing the weight, length, or development stage of blowfly larvae. Lack of information on the variables that might affect these parameters in different fly species can generate inaccuracies in estimating the PMIₘᵢₙ. This study evaluated the effects of different types of bovine tissues (the liver, muscle, tongue, and stomach) and chicken heart on the development rates of larvae of Chrysomya albiceps Wiedemann, Chrysomya megacephala Fabricius, and Chrysomya putoria Wiedemann (Diptera: Calliphoridae). The efficiency of each rearing substrate was assessed by maggot weight gain (mg), larval development time (h), larval and pupal survival (%), and emergence interval (h). The development rates of larvae of all blowfly species studied here were directly influenced by the type of food substrate. Tissues that have high contents of protein and fat (muscle and heart) allowed the highest larval weight gain. For bovine liver, all Chrysomya species showed slower growth, by as much as 48 h, compared to the other tissues. Different rates of development are probably associated with specific energy requirements of calliphorids and the nutritional composition of each type of food.
The use of non-edible oils, waste oils, and animal fats have been investigated as a low-cost feedstock for biodiesel (fatty acid alkyl esters) synthesis. However, these alternative raw materials have ...some drawbacks due to the high content of free fatty acid (FFA). This work aimed to study the continuous enzymatic ethyl esters synthesis, in a solvent-free system, from the reaction of acid soybean oil (acid value, AV, of 0.5, 8.5, 50, and 90) and ethanol using a dual commercial immobilized lipase system (Novozym 435®, Lipozyme TL IM®, Lipozyme RM IM®). Initially, a dual lipase system was used in a single packed-bed reactor (PBR). The blend of Lipozyme TL IM and Novozym 435 had a positive synergistic effect on biodiesel synthesis: an increase of 76% in ethyl ester content was observed after 2 h using refined soybean oil. However, a reduction in the yield was observed in longer reaction times (25 h). Therefore, a continuous reaction system, operated with two different catalytic beds, was investigated. The use of two series reactors allowed high ethyl ester yield (>90%) and high acid conversion (>90%). The reaction using acid soybean oil (50 AV), and Lipozyme RM IM and Novozym 435 reached an ethyl ester content of 95% and 70% after 2 and 25 h, respectively. The results showed that using two different commercial immobilized lipases in intercalated packed-bed reactors enhanced biodiesel synthesis from acid soybean oil. The enzymatic system allows a high fatty acid conversion present in the acidic oil into ethyl ester.
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•The use of two packed-bed reactors in series ensured high levels of ethyl esters.•A synergistic effect was obtained by mixing two different immobilized lipases.•The remaining activity of Novozym 435 was raised with the increasing acidity of the oil.