A Comprehensive Review of the Current State of Robot-assisted Laparoscopic Salvage Prostatectomy

ABSTRACT Background and Objective Salvage robot assisted radical prostatectomy (sRARP) is performed for patients with biochemical or biopsy proven, localized prostate cancer recurrences after radiation or ablative therapies. Traditionally, sRARP has been avoided by lower volume surgeons due to technical demand and high complication rates. Post-radiation sRARP outcomes studies exist but remain few in number. With increasing use of whole gland and focal ablative therapies, updates on sRARP in this setting are needed. The aim of this narrative review is to provide an overview of recently reviewed studies on the oncologic outcomes, functional outcomes, and complications after post-radiation and post-ablative sRARP. Tips and tricks are provided to guide surgeons who may perform sRARP. Materials and Methods We performed a non-systematic literature search of PubMed and MEDLINE for the most relevant articles pertaining to the outlined topics from 2010-2022 without limitation on study design. Only case reports, editorial comments, letters, and manuscripts in non-English languages were excluded. Key Content and Findings Salvage robotic radical prostatectomy is performed in cases of biochemical recurrence after radiation or ablative therapies. Oncologic outcomes after sRARP are worse compared to primary surgery (pRARP) though improvements have been made with the robotic approach when compared to open salvage prostatectomy. Higher pre-sRARP PSA levels and more advanced pathologic stage portend worse oncologic outcomes. Patients meeting low-risk, EAU-biochemical recurrence criteria have improved oncologic outcomes compared to those with high-risk BCR. While complication rates in sRARP are higher compared to pRARP, Retzius sparing approaches may reduce complication rates, particularly rectal injuries. In comparison to the traditional open approach, sRARP is associated with a lower rate of bladder neck contracture. In terms of functional outcomes, potency rates after sRARP are poor and continence rates are low, though Retzius sparing approaches demonstrate acceptable recovery of urinary continence by 1 year, post-operatively. Conclusions Advances in the robotic platform and improvement in robotic experience have resulted in acceptable complication rates after sRARP. However, oncologic and functional outcomes after sRARP in both the post-radiation and post-ablation settings are worse compared to pRARP. Thus, when engaging in shared decision making with patients regarding the initial management of localized prostate cancer, patients should be educated regarding oncologic and functional outcomes and complications in the case of biochemically recurrent prostate cancer that may require sRARP.

Leukoplakia and erythroplakia in youngers versus older individuals: a clinicopathological retrospective study.

BACKGROUND: The incidence of oral cancer has exhibited a rise within the young population. Considering that oral potentially malignant disorders (OPMDs) can precede the development of oral cancer, it is imperative to conduct studies in this particular younger population. This study aimed to evaluate the frequency and conduct a comparative analysis of the clinical-demographic characteristics of OPMDs in two distinct age groups. MATERIAL AND METHODS: A retrospective analysis was conducted with patients diagnosed with leukoplakia, erythroplakia, and leukoerythroplakia between 1965 and 2020. The individuals were categorized into two groups: those aged up to 40 years (Group Younger) and those aged 41 years and above (Group Older). RESULTS: A total of 640 lesions were subjected to analysis. Among these, patients aged up to 40 years constituted 10.63% of the sample, however, this proportion decreased significantly to 6.9% between 2010 and 2020. A predominant male representation was observed in both groups, with white lesions being the most common in both as well. However, the frequency of red or mixed lesions was significantly higher (p=0.034) in the older group, along with a higher prevalence of dysplastic lesions (26.9% versus 11.8%, p=0.01). Moreover, the older group exhibited a relatively higher percentage of smokers/ex-smokers (78.6%), compared to the younger group (61.5%, p=0.085) and alcohol consumers/ex-consumers (54.9% versus 22.7%, p=0.028). Elderly individuals exhibited an unfavorable progression (p=0.028). However, a logistic regression analysis identified as significant variables associated with malignant transformation, the presence of epithelial dysplasia, and red lesions diagnosed as erythroplakia. CONCLUSIONS: A declining frequency of OPMDs in young adults was observed over the years, whereas in older adults, these disorders exhibited an unfavorable progression.

Preeclampsia in the Context of COVID-19: Mechanisms, Pathophysiology, and Clinical Outcomes.

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the global COVID-19 pandemic, significantly impacting the health of pregnant women. Obstetric populations, already vulnerable, face increased morbidity and mortality related to COVID-19, aggravated by preexisting comorbidities. Recent studies have shed light on the potential correlation between COVID-19 and preeclampsia (PE), a leading cause of maternal and perinatal morbidity worldwide, emphasizing the significance of exploring the relationship between these two conditions. Here, we review the pathophysiological similarities that PE shares with COVID-19, with a particular focus on severe COVID-19 cases and in PE-like syndrome cases related with SARS-CoV-2 infection. We highlight cellular and molecular mechanistic inter-connectivity between these two conditions, for example, regulation of renin-angiotensin system, tight junction and barrier integrity, and the complement system. Finally, we discuss how COVID-19 pandemic dynamics, including the emergence of variants and vaccination efforts, has shaped the clinical scenario and influenced the severity and management of both COVID-19 and PE. Continued research on the mechanisms of SARS-CoV-2 infection during pregnancy and the potential risk of developing PE from previous infections is warranted to delineate the complexities of COVID-19 and PE interactions and to improve clinical management of both conditions.

Effects of antioxidant Bis-carboxyethyl germanium sesquioxide added to bovine semen cryopreservation medium on in vitro assessed morphofunctional sperm parameters.

This study investigated the impact of various Ge132 (Bis-carboxyethyl germanium sesquioxide) concentrations on frozen bovine semen. Ejaculates from three bulls were pooled and divided into six groups, each one with different Ge132 concentrations (0, 500, and 1000 µg/mL) and each group was incubated in different conditions (33°C for 30 min (D: D0, D500, and D1000), and the other was immediately cooled to 4°C (R: R0-control; R500 and R1000)). Thawed semen was evaluated for sperm characteristics by CASA and flow cytometer. Results showed better motility in the immediate cooling group without Ge132 compared with high Ge132 concentrations. Values for total motility dropped after 5 and 60 min in groups with high Ge132 levels and some control groups. Linearity increased with 1000 µg/mL Ge132, while straightness differed between moments in multiple groups. Membrane integrity was higher in a control group and certain Ge132 groups. Lower O2 - generation occurred without Ge132. After oxidative stress induction, lipid peroxidation intensity increased with arachidonic acid, but D1000 had lower peroxidation than R0. Overall, Ge132 appears to have provided protection against PLM when subjected to oxidative stress, since even at high concentrations it maintained sperm metabolism.

SCI1, a flower regulator of cell proliferation, and its partners NtCDKG2 and NtRH35 interact with the splicing machinery.

Successful plant reproduction depends on the adequate development of flower organs controlled by cell proliferation and other processes. The SCI1 gene regulates cell proliferation and affects the final size of the female reproductive organ. To unravel the molecular mechanism exerted by SCI1 in cell proliferation control, we searched for its interaction partners through semi-in vivo pulldown experiments, uncovering a cyclin-dependent kinase, NtCDKG;2. Bimolecular fluorescence complementation (BiFC) and co-localization experiments showed that SCI1 interacts with NtCDKG;2 and its cognate NtCyclin L in nucleoli and splicing speckles. The screening of a yeast two-hybrid (Y2H) cDNA library using SCI1 as bait revealed a novel DEAD-box RNA helicase (NtRH35). The interaction between the NtCDKG;2-NtCyclin L complex, and NtRH35 was also shown. Subcellular localization experiments showed that SCI1, NtRH35, and the NtCDKG;2-NtCyclin L complex associate with each other within splicing speckles. The Y2H screening of NtCDKG;2 and NtRH35 identified the conserved spliceosome components U2a', NKAP, and CACTIN. This work presents SCI1 and its interactors NtCDKG;2-NtCyclin L complex, and NtRH35 as new spliceosome-associated proteins. Our findings reveal a network of interactions and suggest that SCI1 may regulate cell proliferation through the splicing process. This study provides new valuable insights into the intricate molecular pathways governing plant development.

Influence and presumption of the vaccine against Covid-19 in South American families.

Faced with the uncertainty of whether the vaccines against Covid-19 are effective or not and faced with living or dying, it is important to know the perception and expectation of their acceptance. The main aim of the study to analyze the perception and expectation of the vaccine against Covid- 19 that South American families have in an urban area of De Pasco. Descriptive, cross-sectional study, simple random sampling of 197 families. The participants were recruited digitally through a neighborhood leadership and an online survey was applied with prior consent. The logistic regression analysis was performed in EPIDAT 4.1 with a significance level of 5%. Regarding the desire to be vaccinated, it is worth noting that a family member died from the coronavirus, hence the health personnel must continue with the preventive promotional work of vaccination in order to obtain favorable results in the entire population. The majority (100%) have a favorable perception and expectation about the vaccine against Covid- 19 ( X c 2 =132.83) and the p-value (0.00); As regards the desire to be vaccinated, it is worth noting having had a family member die from the coronavirus, hence the health personnel must continue with the preventive promotional work of vaccination in order to obtain favorable results in the entire population.

Geobotanical characteristics of plant communities with participation of rare species Alnus glutinosa (L.) Gaertn.

The article gives a geobotanical description and a floristic analysis of communities with the participation of the rare and relict species Alnus glutinosa in condition of Aktobe region. The aim of the study is to provide a geobotanical assessment of the current status of a rare, relict species of the Alnus glutinosa population, which was included in the Red Data Book of Kazakhstan. At present, the flora of the Aktobe region is not sufficiently studied. Conservation of the biodiversity of the Aktobe region flora is one of the most topical issues. In Aktobe region, due to the lack of grazing, felling of trees, using as fuel and the emergence of uncontrolled tourism and at the same time due to the lack of natural renewal of the area, these consequences lead to a quantitative reduction in the species. In this regard, it is necessary to study the species and organize protection and conservation measures. The results of the study showed that the plant Alnus glutinosa is rarely found in the flora of Kazakhstan and also the distribution areas are reduced. Of the three investigated points, plants from 24 families were identified. Plant communities of Alnus glutinosa are being studied for the first time in the Aktobe region. For the first time in the conditions of the Aktobe region, the habitat of black alder was discovered. The floral composition of plant communities of Alnus glutinosa grown in various ecological environments was revealed, the ratio of life forms and phytocenotic features were studied for the first time. In addition, alder felt mite and ground bug, damaging black alder, were identified from 3 studied populations. It has been established that the main reason for the spread of this pest is a very strong moistening of the ground on which sticky Alder grows. Results sequencing showed that the DNA sample under study belongs to the fungus Alternaria alternata.

Astragalus grahamianus extract: a novel source of bioactive compounds with antioxidant and neuroprotective activities.

The Astragalus grahamianus (AG) Royle ex. Benth is traditionally used for the treatment of various human disorders. The current research work is aimed to explore the neuroprotective anti-Parkinson effects of various fractions of Astragalus grahamianus (A. grahamianus). Fine powder of Astragalus grahamianus was extracted with 70% methanol and then fractionated with various solvents on the basis of polarity. Standard protocols were used to investigate the bioactive constituents present in the various plant fractions. In-vitro antioxidant potential of various fractions was checked using diverse free radicals. In-vivo rats model was used to determined the neuroprotective effects of methanol fraction of A. grahamianus. The results revealed that various fractions of A. grahamianus contain flavonoids, cardiac glycosides, steroids, gums, terpenes, proteins, and carbohydrates except chloroform fraction lake the presence of steroids, cardiac glycosides, gums and saponins, aqueous fraction of steroids, terpenoids, gums and saponins, n-Hexane fraction steroids, carbohydrates, alkaloids, gums and flavonoids. The highest amount of total phenolic contents was found in AGME (32.67 ± 2.3 mg GAE / g). The AGME also showed enhanced free radicals cations potential against DPPH, ABTS and H2O2, respectively. The correlation between AOA (antioxidant activity) and TPC (total phenolic contents) revealed to be substantial. Relative R2 values for ABTS, H2O2, and DPPH activity are 0.9974, 0.9845, and 0.9678, respectively. The in-vivo neuroprotective activities showed significant results. Our findings highlight significant antioxidant, and neuroprotective possessions of AGME attributed to powerful bioactive compounds.

Effect of fertilizers and growth stimulants on the yield and feed qualities of the green mass of the yellow melilot in the Akmola region.

This study is aimed at evaluating the effect of various types of fertilizers and growth stimulants on the productivity and quality of yellow melilot. Their increase is necessary to ensure a balanced mineral composition of livestock diet. Research methods include the analysis of field germination of seeds, the study of plant growth at various stages, and the analysis of the agrochemical composition of the soil and feed mass. The field experiments were conducted in the steppe zone of the Akmola region, Kazakhstan with fluctuating air temperature and low rainfall. The results show that the use of fertilizers and growth stimulants significantly increased the field germination of seeds, the content of protein, carotene, and feed units, as well as the yield of the green mass of the yellow melilot. Particularly high rates were achieved with the use of the Fulvimax N and Start Up fertilizers and the Gumato Fosfat N and K growth stimulants. The results indicate the potential of fertilizers and growth stimulants to improve agricultural production and emphasize the importance of choosing the optimal fertilizers to achieve maximum results. The study contributes to the expansion of knowledge about methods of increasing the yield and quality of feed crops, which is an important issue in agriculture.

Lavandula dentata L. essential oil: a promising antifungal and antibiofilm agent against oral Candida albicans.

Candida albicans is the main fungal species involved in oral candidiasis, and its increasing resistance to pharmacological treatment encourages the search for improved antifungal agents. Lavandula dentata L. essential oil (LD-EO) has been recognized for its antimicrobial activity, but little is known about its role against oral C. albicans. This study evaluated the antifungal and antibiofilm activities, mechanisms of action, and toxicity of LD-EO from Brazil against oral strains of C. albicans. Antifungal activity was assessed based on Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC), association study with miconazole (Checkerboard method), and sorbitol and ergosterol assays. Inhibition of biofilm formation and disruption of preformed biofilm were considered when studying the effects of the product. Additionally, the toxicity of LD-EO was evaluated by a hemolysis assay on human erythrocytes. Phytochemical analysis by gas chromatography-mass spectrometry identified eucalyptol (33.1%), camphor (18.3%), and fenchone (15.6%) as major constituents. The test substance showed mainly fungicidal activity (MIC100 = 8 µg/mL; MFC = 16 µg/mL), including against two miconazole-resistant isolates of C. albicans. The effects of LD-EO were synergistic with those of miconazole and appeared not to involve damage to the fungal cell wall or plasma membrane. Its effectiveness in inhibiting biofilm formation was higher than the effect of disrupting preformed biofilm. Finally, the product exhibited low hemolytic activity at MIC. Based on the favorable and novel results described here, LD-EO could constitute a promising therapeutic alternative for oral candidiasis, including miconazole-resistant cases.

Socioeconomic and environmental factors associated with dengue fever incidence in Guatemala: Rising temperatures increase dengue risk.

Dengue fever is a mosquito-borne illness that infects 390 million people annually. Dengue outbreaks in Guatemala have been occurring more often and at increased rates since the first dengue outbreak in Guatemala in the 1970s. This study will examine environmental and socioeconomic factors associated with dengue in Guatemala at the municipality (county) level. Socioeconomic factors included population density, Mayan population, economic activity, and attending school. Environmental factors included average minimum annual temperature and annual precipitation. The relationship between environmental and socioeconomic variables and dengue fever incidence was initially evaluated through univariate zero-inflated negative binomial models, and then again through three zero-inflated multivariate negative binomial regression models. For all three models, elevation was considered a predictor of zero-inflation. In the combined model, there was a positive relationship between minimum temperature, economic activity and dengue fever incidence, and a negative relationship between population density, Mayan population and dengue fever. Predicted rates of dengue fever incidence and adjusted confidence intervals were calculated after increasing minimum yearly temperature by 1°C and 2°C. The three municipalities with the highest minimum yearly temperature (El Estor, Iztapa, and Panzós) and the municipality of Guatemala, all had an increase in the magnitude of the risk of dengue fever incidence following 1°C and 2°C increase in temperature. This research suggests that these socioeconomic and environmental factors are associated with risk of dengue in Guatemala. The predicted rates of dengue fever also highlight the potential effect that climate change in the form of increasing temperature can have on dengue in Guatemala.

Biomedical properties, characterization of seaweeds species and antimicrobial activity.

Marine organisms produce a variety of compounds with pharmacological activities. In order to better comprehend the medicinal value of five particular seaweed orders Ulvales (Ulva intestinalis), Bryopsidales (Codium decorticatum), Ectocarpales (Iyengaria stellata), Dictyotales (Spatoglossum aspermum) and Gigartinales (Hypnea musciformis), a bioactive analysis including the screening of phytochemical components, antioxidant and antimicrobial activities was the aim of the investigation. The species include U. intestinalis was collected from Sandspit, while C. decorticatum, I. stellata, S. aspermum, and H. musciformis were gathered from Buleji. These species evaluated for their ability to inhibit human infectious gram positive pathogens Staphylococcus aureus, Staphylococcus epidermidis as well as gram negative bacteria Escherichia coli. Additionally vegetable pathogen Fusarium oxysporum, and fruit pathogens (Aspergillus niger and Aspergillus flavus) were evaluated to determine the zone of inhibition. Two organic solvents, ethanol and methanol, were used to prepare seaweed extract. The disc diffusion method was utilized to quantify the zone of inhibition and the DPPH method was employed to measure the antioxidant activity. The study unveiled various phyto-constituents in the tested seaweeds, with flavonoids, tannins, and proteins found in all selected species, while saponins, terpenoids, and carbohydrates were absent in I. stellata and S. aspermum. Notably, ethanolic extracts of I. stellata and S. aspermum demonstrated superior higher antioxidant activity, with increasing percentages of inhibition from 1 to 6 mg/ml. Furthermore, the findings indicated that the ethanolic extract of U. intestinalis displayed the highest resistance against F. oxysporum and A. flavous among other seaweeds. Meanwhile, the ethanolic extract of C. decorticatum exhibited the highest resistance against A. Niger. Additionally, the ethanolic extract of I. stellata and H. musciformis displayed the highest resistance against the gram-negative bacteria E. coli and the gram-positive bacteria S. epidermidis, whereas the methanolic extract of U. intestinalis demonstrated the highest resistance against the gram-positive bacteria S. aureus. The findings of this investigation show that a range of bioactive compounds with antioxidant properties are involved in the antimicrobial activities of disease-causing pathogens.

Association of polymorphic variants of prolactin (PRL) and beta-lactoglobulin (BLG) genes with resistance/susceptibility to mastitis in holstein cows.

The work aims to analyze the associations of polymorphic variants of the PRL and BLG genes with resistance and susceptibility to mastitis in Holstein cows. The experimental study consisted of the selection of biomaterial samples from 250 heads of Holstein cows aged 3 years divided into two groups (healthy and with a confirmed diagnosis of mastitis). The determination of animal genotypes was carried out using polymerase chain reaction and restriction fragment length polymorphism. The study of the nature of the association of polymorphic variants of the PRL and BLG gene with resistance/increased risk of mastitis established a significant deviation from the theoretically expected distribution of bBLG-HaeIII genotypes in the group of animals suffering from mastitis (the value of χ2 was 0.24). The bBLG-HaeIIIBB genotype can act as a marker of an increased risk of developing mastitis in Holstein cows; its frequency in the group of sick animals exceeds the frequency in the control group by more than 2 times (44.0 compared to 17.0%, respectively). The bBLG-HaeIIIAB genotype is significantly associated with mastitis resistance in Holstein cows; its frequency is 2 times lower than in the control group (28.0 compared to 54.0%).

Unveiling diagnostic prowess: a comparative study of exercise treadmill test and CT coronary in coronary artery disease detection in Pakistan (2021-2023).

Coronary Artery Disease (CAD) is a global health concern, with diagnostic modalities and risk factors that exhibit regional variations. This study, conducted at the Islamabad Diagnostic Center, Pakistan, aimed to provide a comprehensive assessment of CAD prevalence, severity, and associated risk factors, while also evaluating the diagnostic accuracy of Computed Tomography Coronary Test (CTT) and Exercise Treadmill Test (ETT) in a cohort of 2909 patients. Among the patients assessed via CT Coronary scans, CAD was universally observed, presenting with varying degrees of severity. Our findings indicated that 24.5% of patients had mild CAD, 28.6% exhibited mild to moderate CAD, 16.3% were diagnosed with moderate CAD, 18.4% demonstrated moderate to severe CAD, and 20.4% displayed severe CAD. This spectrum underscores the diverse nature of CAD within the study population. In addition to CTT, we conducted a detailed evaluation of ETT results in 49 patients. These results revealed that 55.1% of patients tested positive for ischemia during the exercise test, emphasizing the prevalence of cardiac stress and underlying CAD. Conversely, 32.7% of patients exhibited negative ETT results, indicating favorable cardiac tolerance during physical activity. A subset of patients yielded non-diagnostic or inconclusive results, necessitating further clinical assessment. Disease history analysis showed a dichotomy within the cohort, with 20.4% having a known medical history and 79.6% possessing an unknown disease history, highlighting the importance of comprehensive medical records in clinical practice. Hypertension, a critical cardiovascular risk factor, was identified in 87.8% of patients, underscoring its significance. Smoking history displayed notable variation, with 69.4% categorized as smokers, 14.3% as ex-smokers, and 10.2% as non-smokers. Lipid profile analysis indicated that 69.4% of patients had abnormal lipid levels. To assess the diagnostic accuracy of CTT and ETT, we calculated Positive Predictive Values (PPV) and Negative Predictive Values (NPV). CTT exhibited a PPV of approximately 5.99% and an NPV of approximately 4.40%, whereas ETT displayed a higher PPV of around 26.44% and a substantially higher NPV of about 49.24%. This study offers valuable insights into CAD prevalence, severity, and associated risk factors in a Pakistani cohort, emphasizing the importance of holistic risk assessment and tailored interventions in clinical practice. Our findings also highlight the diagnostic utility of ETT in CAD assessment.

Land use land cover and land surface temperature changes and their relationship with human modification in Islamabad Capital Territory, Pakistan.

Human activities are altering the existing patterns of Land Use Land Cover (LULC) and Land Surface Temperature (LST) on a global scale. However, long-term trends of LULC and LST are largely unknown in many remote mountain areas such as the Karakorum. . The objective of our study therefore was to evaluate the historical changes in land use and land cover (LULC) in an alpine environment located in Islamabad Capital Territory, Pakistan. We used Landsat satellite pictures (namely Landsat 5 TM and Landsat 8 OLI) from the years 1988, 2002, and 2016 and applied the Maximum Likelihood Classification (MLC) approach to categorize land use classes. Land Surface Temperatures (LST) were calculated using the thermal bands (6, 10, and 11) of Landsat series data. The correlation between the Human Modification Index (HMI) and LULC as well as LST was evaluated by utilizing data from Google Earth Engine (GEE). Over the study period, the urbanized area increased by 9.94%, whilst the agricultural and bare soil areas decreased by 3.81% and 3.94%, respectively. The findings revealed a significant change in the LULC with a decrease of 1.99% in vegetation. The highest LST class exhibited a progressive trend, with an increase from 12.27% to 48.48%. Based on the LST analysis, the built-up area shows the highest temperature, followed by the barren, agricultural, and vegetation categories. Similarly, the HMI for different LST categories indicates that higher LST categories have higher levels of human alteration compared to lower LST categories, with a strong correlation (R-value = 0.61) between HMI and LST. The findings can be utilized to promote sustainable urban management and for biodiversity conservation efforts. The work also has the potential of utilizing it to protect delicate ecosystems from human interference and to formulate strategies and regulations for sustainable urban growth, including aspects of land utilization and zoning, reduction of urban heat stress, and urban infrastructure.

SuFEx-Functionalized Quinones via Ruthenium-Catalyzed C-H Alkenylation: A Potential Building Block for Bioactivity Valorization.

Herein, we describe the Ru-catalyzed C-H alkenylation of 1,4-naphthoquinones (1,4-NQs), resulting in 1,4-naphthoquinoidal/SuFEx hybrids with moderate to good yields. This method provides a novel route for direct access to ethenesulfonyl-fluorinated quinone structures. We conducted mechanistic studies to gain an in-depth understanding of the elementary steps of the reaction. Additionally, we evaluated the prototypes against trypomastigote forms of T. cruzi, leading to the identification of compounds with potent trypanocidal activity.

Effects of concurrent training and N-acetylcysteine supplementation on cardiac remodeling and oxidative stress in middle-aged spontaneously hypertensive rats.

BACKGROUND: This study evaluated the effects of concurrent isolated training (T) or training combined with the antioxidant N-acetylcysteine (NAC) on cardiac remodeling and oxidative stress in spontaneously hypertensive rats (SHR). METHODS: Six-month-old male SHR were divided into sedentary (S, n = 12), concurrent training (T, n = 13), sedentary supplemented with NAC (SNAC, n = 13), and concurrent training with NAC supplementation (TNAC, n = 14) groups. T and TNAC rats were trained three times a week on a treadmill and ladder; NAC supplemented groups received 120 mg/kg/day NAC in rat chow for eight weeks. Myocardial antioxidant enzyme activity and lipid hydroperoxide concentration were assessed by spectrophotometry. Gene expression of NADPH oxidase subunits Nox2, Nox4, p22 phox, and p47 phox was evaluated by real time RT-PCR. Statistical analysis was performed using ANOVA and Bonferroni or Kruskal-Wallis and Dunn. RESULTS: Echocardiogram showed concentric remodeling in TNAC, characterized by increased relative wall thickness (S 0.40 ± 0.04; T 0.39 ± 0.03; SNAC 0.40 ± 0.04; TNAC 0.43 ± 0.04 *; * p < 0.05 vs T and SNAC) and diastolic posterior wall thickness (S 1.50 ± 0.12; T 1.52 ± 0.10; SNAC 1.56 ± 0.12; TNAC 1.62 ± 0.14 * mm; * p < 0.05 vs T), with improved contractile function (posterior wall shortening velocity: S 39.4 ± 5.01; T 36.4 ± 2.96; SNAC 39.7 ± 3.44; TNAC 41.6 ± 3.57 * mm/s; * p < 0.05 vs T). Myocardial lipid hydroperoxide concentration was lower in NAC treated groups (S 210 ± 48; T 182 ± 43; SNAC 159 ± 33 *; TNAC 110 ± 23 *# nmol/g tissue; * p < 0.05 vs S, # p < 0.05 vs T and SNAC). Nox 2 and p22 phox expression was higher and p47 phox lower in T than S [S 1.37 (0.66-1.66); T 0.78 (0.61-1.04) *; SNAC 1.07 (1.01-1.38); TNAC 1.06 (1.01-1.15) arbitrary units; * p < 0.05 vs S]. NADPH oxidase subunits did not differ between TNAC, SNAC, and S groups. CONCLUSION: N-acetylcysteine supplementation alone reduces oxidative stress in untreated spontaneously hypertensive rats. The combination of N-acetylcysteine and concurrent exercise further decreases oxidative stress. However, the lower oxidative stress does not translate into improved cardiac remodeling and function in untreated spontaneously hypertensive rats.

Novel lipid-interaction motifs within the C-terminal domain of Septin10 from Schistosoma mansoni.

Septins are cytoskeletal proteins and their interaction with membranes is crucial for their role in various cellular processes. Septins have polybasic regions (PB1 and PB2) which are important for lipid interaction. Earlier, we and others have highlighted the role of the septin C-terminal domain (CTD) to membrane interaction. However, detailed information on residues/group of residues important for such feature is lacking. In this study, we investigate the lipid-binding profile of Schistosoma mansoni Septin10 (SmSEPT10) using PIP strip and Langmuir monolayer adsorption assays. Our findings highlight the CTD as the primary domain responsible for lipid interaction in SmSEPT10, showing binding to phosphatidylinositol phosphates. SmSEPT10 CTD contains a conserved polybasic region (PB3) present in both animals and fungi septins, and a Lys (K367) within its putative amphipathic helix (AH) that we demonstrate as important for lipid binding. PB3 deletion or mutation of this Lys (K367A) strongly impairs lipid interaction. Remarkably, we observe that the AH within a construct lacking the final 43 amino acid residues is insufficient for lipid binding. Furthermore, we investigate the homocomplex formed by SmSEPT10 CTD in solution by cross-linking experiments, CD spectroscopy, SEC-MALS and SEC-SAXS. Taken together, our studies define the lipid-binding region in SmSEPT10 and offer insights into the molecular basis of septin-membrane binding. This information is particularly relevant for less-studied non-human septins, such as SmSEPT10.

Assessment of the chemical composition of buriti (Mauritia flexuosa Liliopsida) and cassava (Manihot esculenta Crantz) residues and their possible application in the bioproduction of coconut aroma (6 pentyl-α-pyrone).

This work aimed to define strategies to increase the bioproduction of 6 pentyl-α-pyrone (bioaroma). As first strategy, fermentations were carried out in the solid state, with agro-industrial residues: Mauritia flexuosa Liliopsida. and Manihot esculenta Crantz in isolation, conducting them with different nutrient solutions having Trichoderma harzianum as a fermenting fungus. Physicochemical characterizations, centesimal composition, lignocellulosic and mineral content and antimicrobial activity were required. Fermentations were conducted under different humidification conditions (water, nutrient solution without additives and nutrient solutions with glucose or sucrose) for 9 days. Bioaroma was quantified by gas chromatography, assisted by solid-phase microextraction. The results showed the low production of this compound in fermentations conducted with sweet cassava (around 6 ppm (w/w)). The low bioproduction with sweet cassava residues can probably be related to its starch-rich composition, homogeneous substrate, and low concentration of nutrients. Already using buriti, the absence of aroma production was detected. Probably the presence of silicon and high lignin content in buriti minimized the fungal activity, making it difficult to obtain the aroma of interest. Given the characteristics presented by the waste, a new strategy was chosen: mixing waste in a 1:1 ratio. This fermentation resulted in the production of 156.24 ppm (w/w) of aroma using the nutrient solution added with glucose. This combination, therefore, promoted more favorable environment for the process, possibly due to the presence of fermentable sugars from sweet cassava and fatty acids from the buriti peel, thus proving the possibility of an increase of around 2500% in the bioproduction of coconut aroma.

Dermatology-related quality-of-life outcomes in patients with RAS wild-type metastatic colorectal cancer treated with fluorouracil and folinic acid with or without panitumumab (Pmab) maintenance after FOLFOX + Pmab induction: a prespecified secondary analysis of the phase II randomized PanaMa (AIO KRK 0212) trial.

BACKGROUND: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction. PATIENTS AND METHODS: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany. For this prespecified secondary analysis, DRQOL outcomes were assessed using the Functional Assessment of Cancer Therapy-epidermal growth factor receptor inhibitor (FACT-EGFRI), Dermatology Life Quality Index (DLQI), and Skindex-16 questionnaires at every second cycle of therapy until disease progression/death. RESULTS: At least one DRQOL questionnaire was completed by a total of 310/377 (82%) patients who received induction therapy, and by 216/248 (87%) patients who were randomized and received maintenance therapy. Patients who experienced skin toxicity according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) during induction therapy had significantly worse DRQOL according to all three measures, compared to those who did not [i.e. Skindex-16, mean difference at cycle 2 -12.87; 95% confidence interval (CI) -20.01 to -5.73; P < 0.001]. During maintenance therapy, significantly improved recovery was observed in all DRQOL measures for patients receiving FU/FA, compared to those receiving additional Pmab (i.e. Skindex-16, mean difference at cycle 6 -16.53; 95% CI -22.68 to -10.38; P < 0.001). CONCLUSIONS: In this secondary analysis of a phase II randomized clinical trial, patient-reported DRQOL outcomes correlated with skin toxicity according to NCI-CTCAE during induction therapy. Maintenance therapy with FU/FA + Pmab was associated with deteriorated DRQOL versus FU/FA alone in patients with RAS wt mCRC.