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Two cases of otomycosis have been reported in patients undergoing tympanomastoidectomy. The first one had chronic otitis media, hypertrophic concha and nasal septum deviation, tympanic perforation and otorrhea. The second had otalgia, pruritus, chronic otitis media and cholesteatoma. Direct examination showed mycelial septate filaments with a branch at an angle close to 45°, later identified as Aspergillus sydowii by sequencing the BenA and CaM genes. Susceptibility testing showed low MIC of amphotericin B, itraconazole, ketoconazole and ciclopirox olamine. In both cases, ketoconazole was instituted for 10 days. Otomycosis is a challenge as it is primarily recurrent in patients undergoing surgery. The clinical implication, the identification of the emerging pathogen and the determination of MIC were necessary for the knowledge of the epidemiological profile and establishment of the treatment.

The correct diagnosis of a chronic periprosthetic joint infection (PJI) is a major challenge in clinical practice, with the "gold standard" for diagnosis yet to be established. Synovial fluid analysis has been proven to be a useful tool for that purpose. Cell-free DNA (cf-DNA) levels have been shown to be increased in several conditions such as cancer, trauma, and sepsis. Therefore, this study was designed to evaluate the potential of synovial fluid cf-DNA quantification for the diagnosis of chronic periprosthetic infections following total knee arthroplasty.A prospective study with patients undergoing total knee arthroplasty revision surgery for any indication was performed. PJI diagnosis was defined according to the Second International Consensus Meeting on Musculoskeletal Infection (2018) criteria. The study cohort consisted of 26 patients classified as infected and 40 as noninfected. Synovial fluid cf-DNA direct quantification by fluorescent staining was made. Sensitivity, specificity, and receiver operating characteristic curve were calculated.The cf-DNA levels were significantly higher in patients who had PJIs (122.5 ± 57.2 versus 4.6 ± 2.8 ng/μL, P.0001). With a cutoff of 15 ng/μL, the area under the receiver operating characteristic, sensitivity, and specificity of cf-DNA were 0.978, 96.2%, and 100%, respectively.The present study has shown that cf-DNA is increased in synovial fluid of patients who have chronic PJIs. It is a promising biomarker for knee PJI diagnosis and further studies are needed to confirm its utility.

Introduction Thoracic perivascular adipose tissue (tPVAT) has a phenotype resembling brown AT. Dysfunctional tPVAT appears to be linked to vascular dysfunction. Methods We evaluated uncoupling protein 1 (UCP1) expression by Western blot, oxidative stress by measuring lipid peroxidation, the antioxidant capacity by HPLC and spectrophotometry, and mitochondrial respiration by high-resolution respirometry (HRR) in tPVAT, compared to inguinal white AT (iWAT), obtained from non-diabetic (NDM) and streptozocin-induced diabetic (STZ-DM) mice. Mitochondrial respiration was assessed by HRR using protocol 1: complex I and II oxidative phosphorylation (OXPHOS) and protocol 2: fatty acid oxidation (FAO) OXPHOS. OXPHOS capacity in tPVAT was also evaluated after UCP1 inhibition by guanosine 5'-diphosphate (GDP). Results UCP1 expression was higher in tPVAT when compared with iWAT in both NDM and STZ-DM mice. The malondialdehyde concentration was elevated in tPVAT from STZ-DM compared to NDM mice. Glutathione peroxidase and reductase activities, as well as reduced glutathione levels, were not different between tPVAT from NDM and STZ-DM mice but were lower compared to iWAT of STZ-DM mice. OXPHOS capacity of tPVAT was significantly decreased after UCP1 inhibition by GDP in protocol 1. While there were no differences in the OXPHOS capacity between NDM and STZ-DM mice in protocol 1, it was increased in STZ-DM compared to NDM mice in protocol 2. Moreover, complex II- and FAO-linked respiration were elevated in STZ-DM mice under UCP1 inhibition. Conclusions Pharmacological therapies could be targeted to modulate UCP1 activity with a significant impact in the uncoupling of mitochondrial bioenergetics in tPVAT.

The aims of the study were to assess subanesthetic esketamine as an antidepressant for major depressive disorder with psychotic features (PMDD) and to compare posttreatment symptoms among those with PMDD to a sample of nonpsychotic depression (major depressive disorder [MDD]).This study is a retrospective chart review of patients with major depression and current psychotic symptoms, treated with a single parenteral 0.5-mg/kg dose of esketamine. Depression symptoms were assessed at baseline and 24-hour posttreatment with the Montgomery-Åsberg Depression Rating Scale. Individuals with PMDD were matched in a 1:2 ratio to nonpsychotic MDD patients from a randomized, noninferiority clinical trial of esketamine.A total of 15 individuals with PMDD were included, which had higher baseline depression scores (PMDD = 40.9, MDD = 33.6, P = 0.004). A statistically significant change in depressive symptoms was found for the PMDD sample (β = -16.20 [95% confidence interval, -23.30 to -9.10], P0.001), and no difference between PMDD and MDD groups was observed in the matched-sample analysis (β = -2.2 [95% confidence interval, -9.32 to 4.58], P = 0.537). Treatment-induced dissociative symptoms were present for both groups, self-contained to within 2 hours after treatment, and no exacerbation of psychotic symptoms was found in clinical assessments.Results suggest a single 0.5-mg/kg dose of esketamine may benefit individuals with PMDD, and the symptom reduction may be comparable with esketamine's effects for MDD. Furthermore, esketamine may induce an antidepressant response in those with PMDD without complication of psychotic symptoms. Future research with controlled designs is warranted.

Dysfunction in key cellular organelles has been linked to diabetic complications. This study intended to investigate the alterations in the unfolded protein response (UPR), autophagy, and mitochondrial function, which are part of the endoplasmic reticulum (ER) stress response, in wound healing (WH) under diabetes conditions. WH mouse models were used to evaluate the UPR, autophagy, mitochondrial fusion, fission, and biogenesis as well as mitophagy in the skin of control and diabetic mice at baseline and 10 days after wounding. The autophagic flux in response to high-glucose conditions was also evaluated in keratinocyte and fibroblast cell cultures. WH was impaired in the diabetic mouse model, and we found that the UPR and autophagy pathways were activated in skin wounds of control mice and in the non-wounded skin of diabetic mice. Moreover, high-glucose conditions induced autophagy in the keratinocyte and fibroblast cell cultures. However, mitophagy did not change in the skin of diabetic mice or the wounded skin. In addition, mitochondrial fusion was activated in control but not in the skin wounds of diabetic mice, while mitochondrial biogenesis is downregulated in the skin of diabetic mice. In conclusion, the activation of the UPR, autophagy, and mitochondrial remodeling are crucial for a proper WH. These results suggest that the increase in ER stress and autophagy in the skin of diabetic mice at baseline significantly escalated to pathological levels after wounding, contributing to impaired WH in diabetes.

Supplementary Figures and Supplementary Figure legends. Supplementary Fig. 1.- CDK4 inhibition or depletion decreases mTORC1 activity in several cancer cell lines, Supplementary Fig. 2.- CDK4 effects on mTORC1 are α-ketoglutarate and E2F1-independent, Supplementary Fig. 3.- CDK4 phosphorylates FLCN, Supplementary Fig. 4.- CDK4 regulates mTORC1 activity through phosphorylating FLCN, Supplementary Fig. 5.- CDK4 inhibition or depletion increases lysosomal mass, Supplementary Fig. 6.- Hematoxylin and eosin staining and gene expression analysis of tumors from mice treated with or without LY2835219, Supplementary Fig. 7.- In vitro cell death analysis and in vivo electron microscopy analysis of tumors treated with DMSO, LY2835219, A769662 and the combination of A769662 with LY2835219

Cyclin-dependent kinase 4 (CDK4) is well-known for its role in regulating the cell cycle, however, its role in cancer metabolism, especially mTOR signaling, is undefined. In this study, we established a connection between CDK4 and lysosomes, an emerging metabolic organelle crucial for mTORC1 activation. On the one hand, CDK4 phosphorylated the tumor suppressor folliculin (FLCN), regulating mTORC1 recruitment to the lysosomal surface in response to amino acids. On the other hand, CDK4 directly regulated lysosomal function and was essential for lysosomal degradation, ultimately regulating mTORC1 activity. Pharmacologic inhibition or genetic inactivation of CDK4, other than retaining FLCN at the lysosomal surface, led to the accumulation of undigested material inside lysosomes, which impaired the autophagic flux and induced cancer cell senescence in vitro and in xenograft models. Importantly, the use of CDK4 inhibitors in therapy is known to cause senescence but not cell death. To overcome this phenomenon and based on our findings, we increased the autophagic flux in cancer cells by using an AMPK activator in combination with a CDK4 inhibitor. The cotreatment induced autophagy (AMPK activation) and impaired lysosomal function (CDK4 inhibition), resulting in cell death and tumor regression. Altogether, we uncovered a previously unknown role for CDK4 in lysosomal biology and propose a novel therapeutic strategy to target cancer cells.Significance:These findings uncover a novel function of CDK4 in lysosomal biology, which promotes cancer progression by activating mTORC1; targeting this function offers a new therapeutic strategy for cancer treatment.

Supplementary Tables. Supplementary Table 1. Target sequences for guide RNA used to create KO stable cell lines with CRISP/Cas9 technology, Supplementary Table 2. Primers used for qPCR Analysis of Transcription Factor EB (TFEB) regulated genes (human), Supplementary Table 3. Primers used for qPCR Analysis of Senescence genes (human), Supplementary Table 4. Primers used for qPCR Analysis of housekeeping genes (human), Supplementary Table 5. Primers used for FLCN mutagenesis

Supplementary Methods.

Highly competitive and aggressive ant species are efficient bodyguards that monopolize the more attractive plants bearing extrafloral nectaries. Given that herbivory often increases the quality of extrafloral nectar, we hypothesized that plants damaged by herbivory would be more prone to interact with high-quality ant bodyguards and be better defended against herbivores. We performed an experiment with Chamaecrista nictitans plants. We induced anti-herbivore responses by applying jasmonic acid to a group of plants while keeping another group unmanaged. We measured extrafloral nectar production, censused ants visiting extrafloral nectaries and, subsequently, added herbivore mimics to measure the efficiency of ant anti-herbivore defence in both conditions. Induction increased the volume of extrafloral nectar and the mass of sugar per nectary without affecting the sugar concentration or the patterns of plant attendance and defence by ants. Thus, we found no evidence that defence-induced C. nictitans plants are more prone to interact with high-quality bodyguards or to receive better anti-herbivore defence. These findings highlight that increases in extrafloral nectar production are not always rewarded with increases in the biotic defences; instead, these rewards might be dependent on the traits of the nectar induced by herbivory events and/or on the ecological context in which the interaction is embedded. Consequently, herbivory might increase the costs of this induced biotic defence to plants bearing extrafloral nectaries when the induced defence does not increase the attractiveness of the plants to ants.

U.S. national research priorities include reducing the disruption caused by sonic booms, which hindered the economic viability of supersonic aircraft in decades past. However, shock waves are unavo...

SARS-CoV-2 triggers inflammasome-dependent release of pro-inflammatory cytokine IL-1β and pyroptosis, therefore contributes to the huge inflammatory response observed in severe COVID-19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID-19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID-19 patients, and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID-19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID-19 pathogenesis.

The heterogeneity of response to SARS-CoV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome-related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stands out as a good novel candidate as severity factor for COVID-19 disease.To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B, and IL18 single nucleotide variants (SNVs) in a cohort of 945 COVID-19 patients.The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to COVID-19 severity, which could contribute to the excessive cytokine release reported in severe cases.Inflammasome genetic background contributes to individual response to SARS-CoV-2.

Two cases of otomycosis have been reported in patients undergoing tympanomastoidectomy. The first one had chronic otitis media, hypertrophic concha and nasal septum deviation, tympanic perforation and otorrhea. The second had otalgia, pruritus, chronic otitis media and cholesteatoma. Direct examination showed mycelial septate filaments with a branch at an angle close to 45°, later identified as

This study aimed to evaluate the effect of genetic variants in glutamate ionotropic receptor N-methyl- d -aspartate type subunit 2B ( GRIN2B ), glutamate ionotropic receptor α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid type subunit 1 ( GRIA1 ), and brain-derived neurotrophic factor ( BDNF ) genes on therapeutic response, remission, and total Montgomery-Åsberg Depression Rating Scale scores after treatment with ketamine or esketamine in treatment-resistant depression (TRD) patients.Participants (N = 60) are from a double-blind, randomized, noninferiority clinical trial comparing single-dose intravenous ketamine (0.5 mg/kg) to esketamine (0.25 mg/kg) for TRD. Montgomery-Åsberg Depression Rating Scale was applied at baseline, 24 hours, 72 hours, and 7 days postinfusion to assess depressive symptoms. Blood samples were collected to evaluate single nucleotide polymorphisms rs1805502 ( GRIN2B ), rs1994862 ( GRIA1 ), and rs6265 ( BDNF ).There was no association between rs1805502, rs1994862, or rs6265 polymorphisms and antidepressant response ( P = 0.909, P = 0.776, and P = 0.482, respectively), remission P = 0.790, P = 0.086, and P = 0.669), or Montgomery-Åsberg Depression Rating Scale scores at each time point ( P = 0.907, P = 0.552, and P = 0.778).We found no association between the studied single nucleotide polymorphisms (rs6265, rs1805502, and rs1994862) and ketamine's therapeutic action in TRD patients. Further studies with larger samples are needed to clarify the utility of these genes of interest as predictors for antidepressant treatment.

Objective and design: The heterogeneity of response to SARS-COV-2 infection is directly linked to the individual genetic background. Genetic variants of inflammasome related genes have been pointed as risk factors for several inflammatory sterile and infectious disease. In the group of inflammasome receptors, NLRP1 stand out as a good novel candidate as severity factor for Covid-19 disease. Methods: To address this question, we performed an association study of NLRP1, DPP9, CARD8, IL1B and IL18 single nucleotide variants (SNVs) in a cohort of 945 Covid-19 patients. Results: The NLRP1 p.Leu155His in the linker region, target of viral protease, was significantly associated to Covid-19 severity, which could contribute to the excessive cytokine release reported in severe cases.

Chemical fixation of CO2 to produce cyclic carbonates can be a green and atomic efficient process. In this work, a series of porphyrazines (Pzs) containing electron-withdrawing groups and central MII ions (where M = Mg, Zn, Cu, and Co) were synthesized and investigated as catalysts for the cycloaddition of CO2 to epoxides. Then, the efficiency of the Pzs was tested by varying cocatalyst type and concentration, epoxide, temperature, and pressure. MgIIPz bearing trifluoromethyl groups (1) showed the best conversion, producing, selectively, 78% of propylene cyclic carbonate (PCC), indicating that a harder and stronger Lewis acid is more effective for epoxide activation. Moreover, cocatalyst variation showed a notable effect on the reaction yields. Spectrophotometric titrations, MALDI-TOF mass spectra, and theoretical calculations suggest poisoning of the catalyst when tetrabutylammonium chloride (TBAC) and large amounts of tetrabutylammonium bromide (TBAB) were used in the system. The same was not observed for tetrabutylammonium iodide (TBAI), indicating that the metal-cocatalyst interaction may govern the reaction rate. In addition, two rare examples of crystalline structures were obtained, proving the distorted square pyramidal geometry with water molecule as axial ligand. This is one of the first studies reporting Pzs as catalysts for the chemical fixation of CO2, and we believe that the intricate balance between cocatalyst concentration and conversion efficiency shown here may aid future studies in the area.

Slow dynamic response sources, such as fuel cells, are frequently used with faster units, such as batteries and ultracapacitors. In this context, this article gathers the advantages of two energy management techniques to propose the droop k -sharing function. In droop control, energy management is easily implemented using the virtual resistances concept, eliminating the need for fast communication links between the sources. The k -sharing function improves the performance of microgrids with slower sources assigning a preestablished dynamic behavior using a low-pass filter, while the storage unit absorbs the fast transients. Additionally, the k -sharing function also enables the storage unit to share power at a steady state. Therefore, the main advantage of the proposed energy management algorithm is that the control loops of each power source are not coupled to each other, which is accomplished by designing the k -sharing function similarly to the droop technique, eliminating the need for high-speed links of communication and improving the microgrid speed response during fast changes of load. The effectiveness of the proposed function and the theoretical analysis are evaluated using a dc microgrid composed of an H-1000 fuel cell manufactured by Horizon Fuel Cells and three Zippy Compact 5000 25 C Li-Ion batteries in series connection.

Dissociative symptoms are common, possibly severe, side effects associated with the use of ketamine and esketamine in depression. We investigated the relationship between trait dissociation and dissociation induced by ketamine and esketamine used as augmentation therapy in treatment-resistant depression (TRD). Adults with TRD were randomly assigned to receive a single intravenous infusion, with a duration of 40 min, of either esketamine 0.25 mg/kg or ketamine 0.5 mg/kg. We assessed trait dissociation with the Dissociative Experience Scale (DES) and, to evaluate induced dissociation, the Clinician-Administered Dissociative States Scale (CADSS) was used. Thirty-two subjects received esketamine and 29 received ketamine. The groups had similar median DES scores (p = 0.26). More than 30% of the patients in both groups had DES scores ≥30 points. The median CADSS score in the esketamine group was equivalent to that in the ketamine group (p = 0.40). Every 5 points increment in the DES was associated with a 10.9% (95% CI 4.5–17.8%) increase in the CADSS, in an exponential fashion when the two groups were pooled together. Subjects with high trait dissociation had a higher risk of induced dissociation state (relative risk [RR] 1.41, 95% CI 1.11–1.78) and very high induced dissociation (RR 3.05, 95% CI 1.14–8.15). Induced dissociation was not a serious adverse effect. The findings suggest that trait dissociation is a predictor of induced dissociation by Ketamine or Esketamine in TRD subjects. Screening for trait dissociation and counseling patients with high trait dissociation on the risks of dissociation by these drugs are recommended.

Design and development of innovative material compositions and mechanisms based on shape memory alloys (SMAs) were accomplished as part of the Consortium for the Advancement of Shape Memory Alloy Research and Technology (CASMART) 2nd student design challenge. The challenge consisted of developing an expandable space habitat where the retention and deployment of such structure employs the use of SMAs. Student groups were provided with an initial set of requirements and given an option to design the material or design with the material, within six months. This paper collectively documents the evaluation, alloy selection, fabrication, testing, and implementation processes of three teams, including the tools and information used to successfully design, develop, and implement SMA material systems and habitat technologies. For the mechanism design, students used a combination of superelastic rods and shape memory springs/wires to design collapsible rings to fold and deploy the habitat. Publicly available design tools were used to size the SMA components based on the provided loading scenarios. For the material system development, compositions based on CuAlMn, NiTiFe, NiTi and NiTiSn alloys were explored and designed to satisfy the given set of requirements. Details pertinent to these designs are described in this work, along with lessons learned.

Background Main aim: To evaluate the retention rate of ustekinumab compared to vedolizumab in Crohn’s disease patients who failed anti-TNF therapy in clinical practice. Secondary aims: To compare the short-term and long-term effectiveness, and the safety of both treatments. Methods Crohn’s disease patients who had received either vedolizumab or ustekinumab after failure or intolerance to anti-TNF agents from ENEIDA registry were included. ENEIDA is a prospectively maintained database promoted by GETECCU. A total of 755 patients from 30 centres were included at time of data extraction. Clinical activity was classified based on Harvey-Bradshaw index both at short (during induction) and in the long-term. Kaplan-Meier curves, Cox regression models, inverse probability weighting and propensity matching score analyses were performed to compare both drugs and to identify predictive factors of treatment effectiveness and durability. Results 755 patients were included (195 in the vedolizumab cohort and 560 in the ustekinumab cohort). After a median of 20 months (IQR 7.4–30) of follow-up, the survival rate for ustekinumab therapy was higher than vedolizumab (Figure 1). The propensity matching score verified the differences between both therapies. The short-term proportion of patients on clinical remission, steroid-free remission and clinical response was also superior in the ustekinumab cohort (Figure 2). In the long-term, significant differences were observed 2 years after the beginning of the treatments, although no differences in clinical response and remission rates were detected in patients who achieved clinical response at week 16 between both cohorts. Vedolizumab was discontinued in 142 patients and ustekinumab in 185, mainly due to primary non-response (52% in the vedolizumab and 58% in the ustekinumab cohort) and loss of response (34% and 25%, respectively) despite the fact that 35% of the patients required intensification. The predictive factors associated to the discontinuation of the therapy are described in table 1. Adverse events were observed, overall, in 12% of the patients, without differences between both groups (Table 2). Following the discontinuation of the treatment with vedolizumab/ustekinumab, other biologic agents were prescribed in 56% of the patients, and 27% underwent surgery. Conclusion In clinical practice, a relatively high proportion of Crohn’s disease patients who received ustekinumab or vedolizumab for anti-TNF failure, maintained these drugs in the medium-long term, although ustekinumab retention rate was higher in comparison with vedolizumab.

This study sought to evaluate in vitro the effect of a dentifrice containing sodium trimetaphosphate (TMP) combined or not with low fluoride (500 ppm NaF) on dentine erosion of intrinsic origin. Human root dentine blocks were selected based on surface microhardness and randomly allocated into five groups (n = 12): negative control (0 ppm F; no TMP); F500 (500 ppm NaF); F1500 (1500 ppm NaF—positive control); TMP (1% TMP); and F + TMP (500 ppm NaF + 1% TMP). The blocks were submitted to erosion cycles (3 ×/day) for 3 days (0.01 M HCl, pH 1.5–30 s), treatment (1 min—1:3 p/p dentifrice/distilled water) and remineralization (artificial saliva/120 min). Dentine alterations were determined according to the percentage of microhardness loss (%HL), surface loss (SL) and surface analysis by scanning electron microscopy. The data were analyzed using one-way ANOVA (p

AIM To assess the effect of aesthetic crown lengthening (ACL) and lip repositioning surgery (LRS) on perception of smile attractiveness. MATERIALS AND METHODS Preoperative and 6-month postoperative smile photographs of ACL- or LRS-treated patients were evaluated by 100 raters (five gender-balanced groups of ten per procedure) of diverse background (dental students, general dentists, periodontists and laypersons with and without any aesthetic concerns about their own smile). Smile attractiveness was rated by visual analogue scale (VAS). Multivariate mixed-effect models were applied to determine the effect of procedure, rater (age, gender and group) and case (gingival display and GD) on smile attractiveness rating. RESULTS Average preoperative and postoperative VAS scores for ACL patients were 3.8 ± 2.0 and 6.2 ± 1.9, respectively. Corresponding LRS patient values were 4.8 ± 2.0 and 6.4 ± 1.9. Treatment, baseline GD and rater age were significant determinants (p

Bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory properties; however, the effects on diabetic wound healing remain poorly understood. The wound healing potential of LFcinB was investigated with in vitro, ex vivo, and in vivo models. Cell migration and proliferation were tested on keratinocytes and on porcine ears. A type 1 diabetic mouse model was also used to evaluate wound healing kinetics, bacterial diversity patterns, and the effect of LFcinB on oxidative stress, macrophage phenotype, angiogenesis, and collagen deposition. LFcinB increased keratinocyte migration in vitro (p < 0.05) and ex vivo (p < 0.001) and improved wound healing in diabetic mice (p < 0.05), though not in normoglycemic control mice. In diabetic mouse wounds, LFcinB treatment led to the eradication of Bacillus pumilus, a decrease in Staphylococcus aureus, and an increase in the Staphylococcus xylosus prevalence. LFcinB increased angiogenesis in diabetic mice (p < 0.01), but this was decreased in control mice (p < 0.05). LFcinB improved collagen deposition in both diabetic and control mice (p < 0.05). Both oxidative stress and the M1-to-M2 macrophage ratios were decreased in LFcinB-treated wounds of diabetic animals (p < 0.001 and p < 0.05, respectively) compared with saline, suggesting a downregulation of inflammation in diabetic wounds. In conclusion, LFcinB treatment demonstrated noticeable positive effects on diabetic wound healing., Graphical Abstract, Topical delivery of bovine lactoferricin (LFcinB) has antimicrobial and immunomodulatory actions and improves wound closure and changes the bacterial diversity of diabetic wounds. Hallmarks of diabetic wound healing impairments like inflammation, oxidative stress, disrupted angiogenesis, and collagen deposition improved by LFcinB indicate its therapeutic potential.

Study question What are the needs related to facing the diagnosis and treatment of in vitro fertilization with donated oocytes? Summary answer The scarcity of clinical case reports on egg donation treatments makes acceptance difficult, highlighting the importance of an educational portal focused on the topic. What is known already It is known that in vitro fertilization with donated oocytes is a solitary treatment, since the vast majority of people who undergo do not tell friends and family about it. In addition, it is a treatment that can exacerbate different feelings such as sadness, shame of friends and family, feelings of incapacity, among others. Thus, it is known that the little information combined with the difficulty of accepting this new possibility makes it difficult for patients to engage in treatment. Study design, size, duration A methodological study divided into three stages was carried out: 1) descriptive quantitative study with a total of 222 participants; 2) qualitative study with a total of 22 participants; 3) construction and validation of the educational portal with health judges. Data were collected between January 2017 and April 2020. The collection, data analysis, construction and validation of the educational portal took a period of two years. Participants/materials, setting, methods Participants women and heterosexual couples undergoing IVF treatment with donated oocytes. Quantitative research: through information from the database of the clinic under study. Qualitative research: sending an electronic questionnaire to selected participants. The construction of the educational portal: from the data collected in the qualitative research. The validation of the educational portal: the content was by seven health judges and the quality of the tool through the google lighthouse program. Main results and the role of chance The quantitative research identified the profile of patients, 37% are between 40 and 44 years old, 79% had a diagnosis of ovarian failure and in 84% and 81% of the participants received fresh eggs and did not undergo preimplantation genetic testing, respectively. Regarding qualitative studies, it was possible to confirm the feeling of lack of information and lack of knowledge about the egg donation theme, in 100% of the reports. In addition, patients commented about many different feelings experienced during treatment, in addition to the lack of contact with people who had already been through the same situation. Based on these reports, it was possible to identify the patients' needs for information/support and to develop an educational portal where it was possible to find up-to-date articles, local legislation, listen and read testimonies from patients who have gone through all stages of the process. After the construction of the educational portal, the content validation index was 1, in the categories: objectives, structure and presentation and relevance. All stages of the study were carried out so that the future patient has a good experience when accessing the site, promoting the promotion of knowledge and being a facilitator in the acceptance of knowledge. Limitations, reasons for caution The survey of cases, as well as the needs of the patient, took place within the units of the same clinic, limiting the population studied. The qualitative stage was carried out only with couples who were pregnant or had already given birth due to the delicacy of the topic. Wider implications of the findings As it is the first educational portal on egg donation in Brazil, it has potential facilitated through the promotion of knowledge to couples who need to use the technique of in vitro fertilization with donated oocytes and to all those interested in the subject. Trial registration number Não aplicável

Optic nerve sheath fenestration (ONSF) is a surgical procedure commonly performed in the Anglo-Saxon countries for the treatment of medically refractory idiopathic intracranial hypertension (IIH). We chose to compare 6 different trans-orbital surgical approaches to ONSF. We also desired to determine the number of optic nerve decompression procedures performed in France in 2019 and 2020.Four fresh frozen orbits were dissected at the University of Nice anatomy laboratory. We performed the following surgical approaches: (i) eyelid crease, (ii) lid-split, (iii) medial transconjunctival with medial rectus disinsertion, (iv) medial transconjunctival without rectus disinsertion, (v) lateral transconjunctival and (vi) lateral orbitotomy. For each surgical approach, we measured the distance between the incision and the optic nerve dura mater. We also extracted data from the French National PMSI (Programme de Médicalisation des Systèmes d' Information) database from January 2019 through December 2020 to determine the annual number of optic nerve decompression procedures.The lid crease and medial transconjunctival approaches provided the shortest distance to the optic nerve (average 21mm and 24mm, respectively) and the lowest levels of difficulty compared to the other surgical routes. A total of 23 and 45 optic nerve decompressions were performed in France in 2019 and 2020, respectively. Among them, only 2 and 7 procedures, respectively, were performed through a trans-orbital approach.Upper lid crease incision and medial transconjunctival approaches are the most direct and easiest surgical routes when performing an ONSF. We found that ONSF was rarely performed in France. We strongly recommend close cooperation between ophthalmologists, neurologists, neurosurgeons and interventional radiologists.

Doar sangue é um ato de solidariedade e capaz de salvar inúmeras vidas. A falta de sangue é um problema recorrente na sociedade, que parece ter sido agravada com o advento da pandemia da COVID-19. Instituições de saúde costumam promover campanhas periodicamente no intuito de aumentar a captação de doadores. Ações como essa são importantes para manter os estoques condizentes com a demanda populacional. Este trabalho apresenta a utilização de técnicas de machine learning para predição de fidelização de doadores de sangue. Trata-se de um trabalho em andamento com resultados preliminares promissores e que possibilitará auxiliar em políticas de captação e fidelização de doadores.

A total of 122 Patinga specimens were collected from fish farms (P1, P2 and P3), and only those from fish farm P1 were shown to be infected with Echinorhynchus gomesi. In addition, fish in this study were shown to have diets that consisted of 21 different food items, and Notodiaptomus sp. (Copepoda: Calanoida) was identified as a potential intermediate host for E. gomesi.

Significance This research deals with the development of capacity-building through marine bioresearch from a scientific standpoint, particularly through a new approach based on publication and authorship metrics. By using a 50-y dataset on the discovery of marine natural products, this study draws verifiable conclusions on capacity-building, a process that is often difficult to quantify. This is a stepping-stone toward evidence-based capacity building for bioprospecting as originally envisioned in the framework of high-level international fora, such as the Convention on Biological Diversity and, more recently, the Nagoya Protocol., The Convention on Biological Diversity, and the Nagoya Protocol in particular, provide a framework for the fair and equitable sharing of benefits arising from the utilization of biological resources and traditional knowledge, and ultimately aim to promote capacity-building in the developing world. However, measuring capacity-building is a challenging task due to its intangible nature. By compiling and analyzing a database of scientific peer-reviewed publications over a period of 50 y (1965 to 2015), we investigated capacity-building in global marine natural product discovery. We used publication and authorship metrics to assess how the capacity to become scientifically proficient, prolific, and independent has changed in bioprospecting countries. Our results show that marine bioprospecting is a dynamically growing field of research with continuously increasing numbers of participating countries, publications, and scientists. Yet despite longstanding efforts to promote equitability and scientific independence, not all countries have similarly increased their capacity to explore marine biodiversity within their national jurisdiction areas. Although developing countries show an increasing trend in the number of publications, a few developed countries still account for almost one-half of all publications in the field. Multiple lines of evidence suggest that economic capacity affects how well countries with species-rich marine ecosystems can scientifically explore those resources. Overall, the capacity-building data analyzed here provides a timely contribution to the ongoing international debate about access to and benefit-sharing of biological resources for countries exploring biodiversity within and outside their national jurisdiction areas.

The bioeconomy is a new paradigm for the sustainable development of society. Novel uses of blue bioresources and biotechnology solutions, co-created with value chain stakeholders, accelerate the bioeconomy, foster innovation, and promote novel circular business models. Bottom-up approaches sharing visions, needs, and expertise are key to the successful implementation of bioeconomy initiatives.

Morphing structures can allow significant improvements in performance by optimally changing shape across varying conditions. A critical barrier to the design of morphing structures is the challenge of determining how optimal shape changes as a function of the many operating conditions that affect optimality. Traditional engineering optimization techniques are able to determine an optimal shape only for one condition or an aggregation over operating conditions (i.e., optimizing average performance). Parametric optimization is an alternative approach that can solve a family of related optimization problems simultaneously. Herein the authors analyze the design of a structurally consistent camber morphing wing for light aircraft applications using parametric optimization techniques. The approach combines rigorous consideration of structural constraints via Class/Shape Transformation (CST) equations and use of a C1-continuous analytical representation of wing outer mold line geometry with the Predictive Parametric Pareto Genetic Algorithm (P3GA), an algorithm for nonlinear multi-parametric optimization. The system is tuned to maximize lift-to-drag ratio, a key metric for aircraft flight range. Kriging-based interpolation is applied to P3GA output to obtain an optimal solution map determining optimal shape variable values as a function of flight conditions (airspeed, angle of attack, and altitude). Solutions obtained from iterated use of traditional optimization techniques are utilized to benchmark the more novel and efficient parametric optimization accuracy. Results show that parametric optimization is useful for optimizing morphing structures across a range of operating conditions.

Objective: This study explored differences in sense of belonging between students who identify as having PTSD and those who do not and then investigated the role of safety, stigma, and campus climate for mental health in this process. Participants: Participants included 162 undergraduates enrolled at United States institutions. Methods: Data were from the 2015-2016 Healthy Minds study. Analysis included an independent samples t-test and hierarchical regression models. Results: Results suggested that students with PTSD experienced less of a sense of belonging on their campus relative to students who do not have PTSD. Our model including safety, stigma, and campus climate explained 50% of the variance in predicting sense of belonging in the PTSD group. Conclusions: Results support the importance of clinicians, staff, and faculty helping students with PTSD to feel an increased sense of safety, reducing stigma for mental health, and improving campus climate for mental health on their campuses.

To evaluate the heart rate (HR) and behaviour of children and teenagers with Cerebral Palsy (CP) when having a dental appointment. A comparative cross-sectional study was carried out with 60 participants with CP, between 2 and 14 years old (study group—SG), and 60 normotypical individuals (CG). The sample was paired according to age, gender and socioeconomic status. Behaviour was evaluated during dental prophylaxis using the Frankl Scale, and HR was measured at five moments: before the appointment, when sitting in the dental chair, during the clinical examination, during prophylaxis and immediately after prophylaxis. Mann–Whitney, Friedman and Chi-square tests were applied at a significance level of 5%. SG presented significantly higher HR (p

The fact that opioids are valuable tools for the management of pain has been known and used for thousands of years. Currently, millions of Americans are treated annually with opioids, and many of these patients are elderly. Opioids present risks to geriatric patients, some of which are unique to the population, and providers should have a good grasp of those risks. An understanding of how to select appropriate medications for the management of pain and of the myriad of alternatives available for pain management is vital to the care of older patients. This article presents a review, for primary care providers, of issues unique to opioid management in older adults.

Objective - Every parent aspires to have perfect or close-to-perfect children. This study was conducted to determine the roles and practices of parents in the growth and development of students of Isabela State University which can be used as a basis by the guidance unit in developing an enhancement program in consonance to the growth and development of students. Moreover, this study determines the significant relationship between problems encountered and roles and practices of parents in child rearing. Methodology/Technique – A descriptive–correlation research design was used with five-part questionnaire which was administered randomly to 372 parents of students. Finding - The findings reveal that parents practice different parenting types such as permissive, authoritarian, authoritative and neglectful. They differ in disciplinary measures, practices, roles in raising their children and even techniques in developing the moral character of their children. However, different parenting styles, parental controls, disciplinary measures and techniques in raising their children in the development of their moral character is very evident. They also believed that employing disciplinary measures is an effective way in disciplining their children. Thus, the roles and practices of parents in rearing their children plays a crucial role in the growth and development of their children. Type of Paper: Empirical. Keywords: Parenting Style; Roles; Practices; Child Rearing; Parental Control; Disciplinary Measures. Reference to this paper should be made as follows: Espinosa, J. F.; Leal, R. C.. 2020. Global J. Bus. Soc. Sci. Review 8(1): 60 –72. https://doi.org/10.35609/gjbssr.2020.8.1(7) JEL Classification: Y8, Y80.

Objective – This study assesses the impact of mungbean (Vigna radiata) as a source of income among San Mateo folks. More specifically, this study aims to measure the benefits of respondents derived from mungbean as a source or additional income and the creation of a database of the generated activities, employment and innovative projects from mungbean. Methodology/Technique – The respondents of the study were 100 mungbean growers that were randomly selected within San Mateo. Data was collected using a structured questionnaire and focus group discussion and was analyzed using frequency and percentage. Findings – The data analysis reveals that mungbean farming generates both income and employment. The findings also reveal that a return of investment of 132.66% per hectare can be generated in producing mungbean. Novelty –This study aims to validate the economic impact of mungbean production among the people in San Mateo, Isabela. It is also the goal of this study to analyze how the production of mungbean helps increase employment in the community. Type of Paper: Empirical. Keywords: Mungbean; Assessment; San Mateo; Productivity; Farmers. Reference to this paper should be made as follows: Yanos, M. H. A.; Leal, R. C., 2020. Mungbean (Vigna radiata) as a Source of Income among Farmers, J. Bus. Econ. Review, 5(1) 10 – 17, https://doi.org/10.35609/jber.2020.5.1(2) JEL Classification: Q12, Q14.

Objective - Local Government Units (LGUs) play a significant role in the development of their constituents. Basic services should be their main priority in order to implement these services to a high standard. Hence, this study aims to assess the level of implementation of basic services in San Mateo, Isabela, taking into account the profile of the respondents, their perception on the implementation of basic services and good governance, significant differences in their perceptions, and problems encountered in the implementation process. Methodology/Technique – The data collected was measured and analysed using the Social Sciences Statistical Package (SPSS). Finding - The results show that the respondents (which were grouped into 4) vary in their perceptions on the implementation of the basic services; however, the level of implementation was high. Moreover, the 4 dimensions of good governance recorded a very satisfactory level of implementation. These findings imply that the mechanisms used in the delivery of basic services are effective and responsive. Thus, the model used by the LGU San Mateo may be shared with other municipalities to achieve quality delivery of basic services. Type of Paper: Empirical. Keywords: Basic Services; Perceptions; Level of Implementation; Local Government Unit; Public Service. Reference to this paper should be made as follows: Leal, R.C; Sagubo, O.S; Brutas, R. M. 2020. Local Government Unit Basic Services: Implementation and Assessment, Global J. Bus. Soc. Sci. Review, 8(1): 49 – 59. https://doi.org/10.35609/gjbssr.2020.8.1(6) JEL Classification: H7, H70.

Background Ketamine and its enantiomers have recently been highlighted as one of the most effective therapeutic options in refractory depression. However, racemic ketamine and esketamine have not been directly compared. The aim of this study is to assess the efficacy and safety of esketamine compared to ketamine in patients with treatment-resistant depression (TRD). Methods This is a randomized, double-blind, active-controlled, bicentre, non-inferiority clinical trial, with two parallel groups. Participants were randomly assigned to a 40-min single intravenous infusion of ketamine 0.5 mg/kg or esketamine 0.25 mg/kg. The primary outcome was the difference in remission rates for depression 24 h following intervention using the Montgomery-Asberg Depression Rating Scale (MADRS), with a non-inferiority margin of 20%. Results 63 subjects were included and randomly assigned (29 to receive ketamine and 34 to receive esketamine). At 24 h, 24.1% of participants in the ketamine group and 29.4% of participants in the esketamine group showed remission, with a difference of 5.3% (95% CILB -13.6%), confirming non-inferiority. MADRS scores improved from 33 (SD 9.3) to 16.2 (SD 10.7) in the ketamine group and from 33 (SD 5.3) to 17.5 (SD 12.2) in the esketamine one, with a difference of -5.27% (95% CILB, -13.6). Both groups presented similar mild side effects. Conclusions Esketamine was non-inferior to ketamine for TRD 24 h following infusion. Both treatments were effective, safe, and well tolerated. Trial Registration Registered in Japan Primary Registries Network: UMIN000032355.

Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder with a higher susceptibility to occur in men. Studies suggest that this susceptibility is related to the hormonal differences observed between men and women, being a risk factor for PD. In addition, testosterone supplementation has shown controversial results in animal models of PD and parkinsonian patients. This study evaluated the effect of chronic administration of testosterone propionate (TP) on motor behavior and neurochemical parameters in the reserpine-induced rat model of parkinsonism. Male Wistar rats received 15 injections of reserpine (RES - 0.1 mg/kg) every other day and were concomitantly treated with different doses (0.1, 1.0, or 5.0 mg/kg) of daily TP for 30 days. The rats were euthanized 48 h after the 15th injection of RES or vehicle. Brains were removed and subjected to Tyrosine hydroxylase (TH) immunohistochemistry. TP at 1.0 mg/kg reduced the damages caused by reserpine in the vacuous chewing and tong protrusion behaviors and prevented dopaminergic damage in the SNpc, VTA, and Striatum. TP at 5.0 mg/kg reduced the damages caused by reserpine in the catalepsy and tong protrusion behaviors, prevented the weight loss, and prevented dopaminergic damage in the VTA. Our results suggest that chronic administration of TP has a protective effect in a rat model of parkinsonism, improving motor alterations and dopamine depletion induced by RES.