Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results.
We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation ...in noncritically ill patients with COVID-19.
Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit–level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group.
Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent.
Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID FREEDOM COVID Anticoagulation Strategy; NCT04512079)
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Gonadal sex differentiation in teleost fish shows greater plasticity as compared to other vertebrates, as it can be influenced by a variety of factors such as exogenous sex steroids. Exogenous ...estrogens, such as 17β-estradiol (E2), can induce feminization when administered during early embryonic development. However, the mechanisms underlying the E2-induced feminization are not fully understood, especially in Neotropical species. Therefore, the aim of this study was to evaluate the effects of E2 administration on the phenotypic sex characteristics, histological assessment of the gonads, and the expression of selected genes in Astyanax altiparanae exposed to dietary E2 prior to gonadal differentiation. At 4 days post-hatch (dph), groups of 30–40 undifferentiated larvae were fed with a diet containing varying amounts of E2 for 28 days, and fish were sampled at 90 dph. Previous studies revealed that ovary formation in A. altiparanae occurred at 58 dph, whereas the first sign of testis formation was found at 73 dph. In relation to the control, E2 exposure increased the proportion of phenotypic females in 120% and 148.4% for 4 and 6 mg E2/Kg, respectively. However, histological analysis revealed that treatments did not affect gonadal sex ratio between males and females, but induced intersex (testis-ova) in the group treated with 6 mg E2/Kg food. Treatment with E2 also altered gonadal transcript levels of a selected number of genes implicated in sexual differentiation. Males overexpressed dmrt1, sox9 and amh following E2 treatment as compared to control. Females showed increased mRNA levels of dmrt1 and sox9, which might be related to the down-regulation of cyp19a1a after E2 exposure. In summary, E2 exposure during early gonadal development affected male secondary characteristics without changing the gonadal sex ratio, and altered expression of genes implicated in sexual differentiation.
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•17β-estradiol (E2) exposure during early gonadal development affected male secondary characteristics of A. altiparanae;•E2 treatment did not change gonadal sex ratio, induced testis-ova and altered genes related to sex differentiation;•Altered expression could be considered a compensatory mechanism, or a mechanism of gonadal resilience;
C-phycocyanin is a highly valuable phycobiliprotein from
Arthrospira platensis
. However, its extraction, purification and conservation currently limit its commercial use. We review here the most ...common techniques and less conventional methods. Simple incubation in phosphate buffer at neutral pH can give high yields (> 100 mg/g) and even high protein purity (> 0.7) if the parameters (buffer concentration, temperature, incubation time,
Arthrospira platensis.
state etc.) are chosen correctly. This method is preferable to incubation in distilled water or acid solutions. Some mechanical, physical or thermal treatments can improve the extraction yield and accelerate the release of C-phycocyanin. Ultrasound-assisted extraction has been widely studied and probes generally give higher extraction yields than baths (> 100 mg/g) in less than 30 min. This technique can be coupled with others, such as freeze–thaw methods, to improve protein release. Indeed, freeze–thaw cycles are an efficient destructuring technique that can be used alone or as a pretreatment. Bead mills or pulsed electric fields can also be used to extract C-phycocyanin, but there is room for improvement in the choice of operating parameters. For purification of the extracted pigments, salting out or aqueous two-phase extraction can be used to increase phycocyanin grade. More advanced purification methods, mostly based on chromatography, can provide addition improvement. C-phycocyanin stability is dependent principally on pH and temperature, and is higher between pH 5 and pH 7 and at temperatures below 40 °C, but the use of various preservatives or conditioning can increases its lifetime.
Different methods were used to extract C-phycocyanin from
Arthrospira platensis
, alone or in synergy (freezing, incubation, ultrasounds, deep eutectic solvents). Freezing or Freeze-drying spirulina ...allows a highly facilitated rupture of the cell membranes. Incubation in water allows then a quick release of C-PC and other phycobiliproteins at 45 °C (2 h) while it takes less than 8 h at 35 °C and 25–30 h at ambient temperature. In addition to microscopic observation, the evolution of solutes concentration with incubation time confirms that hydrosoluble pigments are first preferentially released relatively to chlorophyll which requires deeper collapse of the spirulina cells. Use of ultrasounds allows an extraction of the spirulina content in 15 min of treatment with a high C-PC extraction yield (> 200 mg/g) and good protein purity (around 0.7). Ethyl acetate, ethanol and a mixture of these solvents give good extraction yields of chlorophyll (around 21 mg/g). C-PC extraction yield is yet then decreased due to a denaturation of the hydrated pigment. Fructose can be used to prevent denaturation by both organic solvent and freezing/freeze-drying. The use of deep-eutectic solvents is not recommended here as no better yield or selectivity are achieved compared to extraction in buffered water.
One thousand five hundred cachara or tiger shovelnose catfish Pseudoplatystoma fasciatum, obtained from induced reproduction, were used to determine the onset of ovarian differentiation and ...development and to record the main characteristics of this process. Samples were collected from 0 to 240 days post‐fertilization (dpf) and the results classified into stages I–XII. Ovarian formation was histologically detected for the first time when juveniles measured mean ± s.d. 51·5 ± 8·3 mm total length (LT) at 39–45 dpf (stages I–V), with intense somatic cell proliferation originating in the ovarian cavity. Both LT and age of fish had a positive correlation (P < 0·001) with ovarian differentiation, but LT showed a greater correlation (r2 = 0·95) than age (r2 = 0·85), especially during the initial stages of development. From stages VI to VII, the ovarian cavity was enlarged and undifferentiated oogonia were present. At stage VIII, small projections formed in the ovarian stroma towards the ventral region of the gonad (future ovarian lamellae) and the basal membrane and differentiated oogonia nests could be seen. At stages IX and X, the germ cells entered meiosis and folliculogenesis was completed by stages XI and XII, which can be considered late in comparison to other Siluriformes. This study has demonstrated that ovarian differentiation in P. fasciatum begins with an intense proliferation of squamous epithelial cells (somatic cells) during the early stages of development and that sex inversion protocols could, thus, be applied successfully before this period. Furthermore, the results have demonstrated that both size and age can influence gonad differentiation and development in this species.
Background: In this review we survey medical treatments and research strategies, and we discuss why they have failed to cure degenerative disc diseases or even slow down the degenerative process.
...Objective: We seek to stimulate discussion with respect to changing the medical paradigm associated with treatments and research applied to degenerative disc diseases.
Method Proposal: We summarize a Biological Transformation therapy for curing chronic inflammations and degenerative disc diseases, as was previously described in the book Biological Transformations controlled by the Mind Volume 1.
Preliminary Studies: A single-patient case study is presented that documents complete recovery from an advanced lumbar bilateral discopathy and long-term hypertrophic chronic rhinitis by application of the method proposed.
Conclusion: Biological transformations controlled by the mind can be applied by men and women in order to improve their quality of life and cure degenerative disc diseases and chronic inflammations illnesses.
Marine reserves, areas protected from exploitative anthropogenic processes, are being widely implemented to conserve biodiversity and initiate species recovery. Evidence supports the effectiveness of ...marine reserves in improving biological attributes such as biodiversity, density, biomass, and body-size for sedentary species or those with r-selected life histories. However, there is limited long-term time series- based information determining the effectiveness of these protected areas for elasmobranchs. Marine reserve effectiveness is commonly evaluated spatially by examining differences in species’ biological parameters inside and outside of protective boundaries, which can often mask the occurrence of slow population declines. We used a temporal fishery-independent standardized longline survey at Glover’s Reef Marine Reserve, Belize, to monitor long-term population trends in the commercially important Caribbean reef shark Carcharhinus perezi for more than a decade. Linear models were performed to examine whether the factors habitat, year, or their interaction had a significant impact on C. perezi catch per unit effort (CPUE) and on catch demographic composition. Only the factor ‘habitat’ had a significant influence on CPUE, with the forereef catch significantly higher than in the lagoon. Our results support that the population of Caribbean reef shark at Glover’s Reef Marine Reserve appears stable with no significant decline in CPUE or decrease in mean total length detected. This is evidence that marine reserves can be an effective conservation tool for reef-associated shark species.
Condensed abstract:
We randomized 3398 patients hospitalized with COVID-19 not yet requiring intensive care unit (ICU) management to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin or ...therapeutic-dose apixaban at 76 centers in 10 countries. The 30-day primary composite outcome of all-cause mortality, requirement for ICU level-of-care, systemic thromboembolism, or ischemic stroke was not significantly reduced in the combined therapeutic-dose anticoagulation groups compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation or died. The benefits of therapeutic-dose anticoagulation were most strongly evident in higher-risk patients.
We report on sub-40 fs pulse generation from a Yb:Sc 2 SiO 5 laser pumped by a spatially single-mode fiber-coupled laser diode at 976 nm. A maximum output power of 545 mW was obtained at 1062.6 nm in ...the continuous-wave regime, corresponding to a slope efficiency of 64% and a laser threshold of 143 mW. A continuous wavelength tuning across 80 nm (1030 -1110 nm) was also achieved. Implementing a SESAM for starting and stabilizing the mode-locked operation, the Yb:Sc 2 SiO 5 laser delivered soliton pulses as short as 38 fs at 1069.5 nm with an average output power of 76 mW at a pulse repetition rate of ∼79.8 MHz. The maximum output power was scaled to 216 mW for slightly longer pulses of 42 fs, which corresponded to a peak power of 56.6 kW and an optical efficiency of 22.7%. To the best of our knowledge, these results represent the shortest pulses ever achieved with any Yb 3+ -doped rare-earth oxyorthosilicate crystal.
No gold standard exists for histopathological diagnosis of a prosthetic joint infection (PJI). The historical criterion considers the presence of neutrophil infiltration upon examination of ...periprosthetic tissue. Morawietz et al. proposed a classification of periprosthetic membranes (Morawietz et al., Clin Pathol 59:591-597, 2006, https://doi.org/10.1136/jcp.2005.027458) and a more recently described classification with a new cutoff value of 23 neutrophils in 10 high-power fields (Morawietz et al., Histopathology 54:847-853, 2009. https://doi.org/10.1111/j.1365-2559.2009.03313.x). We performed a multicenter prospective study, which compared both methods for the diagnosis of PJI. All suspicions of PJI (
= 264) between December 2010 and March 2012 in seven centers were prospectively included. Five perioperative specimens were collected per patient for cultures, and one was collected for histology. Diagnosis of PJI was made according to the Infectious Diseases Society of America (IDSA) guidelines. Histopathological analysis classified the patients according to the threshold of 23 neutrophils and according to the classification of Morawietz. Performances of both methods were compared by using clinical and/or bacteriological criteria as the gold standard. Among 264 patients with suspected PJI, a diagnosis of infection was confirmed in 215 and unconfirmed in 49 patients. Histopathological analysis was available for 150 confirmed PJI and 40 unconfirmed PJI cases. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 78.7%, 90.0%, 96.7%, 52.9%, and 81.1%, respectively, for the Morawietz classification, and 82.0%, 90.0%, 96.9%, 57.1%, and 83.7%, respectively, for the 23-neutrophil threshold. The new algorithm using a threshold of 23 neutrophils can be proposed as a new gold standard for the histopathological diagnosis of PJI.
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