Incorporation of compost and biochar enhances yield and medicinal compounds in seeds of water-stressed Trigonella foenum-graecum L. plants cultivated in saline calcareous soils.

BACKGROUND: The combination of compost and biochar (CB) plays an important role in soil restoration and mitigation strategies against drought stress in plants. In the current study, the impact of CB was determined on the characteristics of saline calcareous soil and the productivity of fenugreek (Trigonella foenum-graecum L.) plants. The field trials examined CB rates (CB0, CB10 and CB20 corresponding to 0, 10, and 20 t ha‒1, respectively) under deficit irrigation [DI0%, DI20%, and DI40% receiving 100, 80, and 60% crop evapotranspiration (ETc), respectively] conditions on growth, seed yield (SY), quality, and water productivity (WP) of fenugreek grown in saline calcareous soils. RESULTS: In general, DI negatively affected the morpho-physio-biochemical responses in plants cultivated in saline calcareous soils. However, amendments of CB10 or CB20 improved soil structure under DI conditions. This was evidenced by the decreased pH, electrical conductivity of soil extract (ECe), and bulk density but increased organic matter, macronutrient (N, P, and K) availability, water retention, and total porosity; thus, maintaining better water and nutritional status. These soil modifications improved chlorophyll, tissue water contents, cell membrane stability, photosystem II photochemical efficiency, photosynthetic performance, and nutritional homeostasis of drought-stressed plants. This was also supported by increased osmolytes, non-enzymatic, and enzymatic activities under DI conditions. Regardless of DI regimes, SY was significantly (P ≤ 0.05) improved by 40.0 and 102.5% when plants were treated with CB10 and CB20, respectively, as similarly observed for seed alkaloids (87.0, and 39.1%), trigonelline content (43.8, and 16.7%) and WP (40.9, and 104.5%) over unamended control plants. CONCLUSIONS: Overall, the application of organic amendments of CB can be a promising sustainable solution for improving saline calcareous soil properties, mitigating the negative effects of DI stress, and enhancing crop productivity in arid and semi-arid agro-climates.

Tobacco Use and Uptake of COVID-19 Vaccinations in Finland: A Population-Based Study.

INTRODUCTION: People who smoke are at higher risk of Coronavirus Disease-2019 (COVID-19) hospitalizations and deaths and might benefit greatly from high COVID-19 vaccination coverage. Studies on tobacco use and COVID-19 vaccine uptake in the general population are lacking. AIMS AND METHODS: We conducted a cohort study utilizing linked data from 42 935 participants from two national surveys in Finland (FinSote 2018 and 2020). Exposures were smoking and smokeless tobacco (snus) use. The primary outcome was the uptake of two COVID-19 vaccine doses. Secondary outcomes were the uptake of one COVID-19 vaccine dose; three COVID-19 vaccine doses; time between the first and second dose; and time between the second and third dose. We examined the association between tobacco use and COVID-19 vaccine uptake and between-dose spacing in Finland. RESULTS: People who smoke had a 7% lower risk of receiving two COVID-19 vaccine doses (95% confidence interval [CI] = 0.91; 0.96) and a 14% lower risk of receiving three doses (95% CI = 0.78; 0.94) compared to never smokers. People who smoked occasionally had a lower risk of receiving three vaccine doses. People who currently used snus had a 28% lower uptake of three doses (95% CI = 0.56; 0.93) compared to never users but we did not find evidence of an association for one or two doses. We did not find evidence of an association between tobacco use and spacing between COVID-19 vaccine doses. CONCLUSIONS: People who smoke tobacco products daily, occasionally, and use snus had a lower uptake of COVID-19 vaccines. Our findings support a growing body of literature on lower vaccination uptake among people who use tobacco products. IMPLICATIONS: People who smoke or use snus might be a crucial target group of public health efforts to increase COVID-19 vaccinations and plan future vaccination campaigns. CLINICAL TRIALS REGISTRATION NUMBER: NCT05479383.

Stereotactic radiosurgery for intracranial cavernous malformations of the deep-seated locations: systematic review and meta-analysis.

OBJECTIVE: To determine the outcomes of stereotactic radiosurgery (SRS) for deep-seated (brainstem, basal ganglia, thalamus, cerebellar peduncle) intracranial cavernous malformations (ICMs). METHODS: A systematic review and meta-analysis was performed according to PRISMA and MOOSE guidelines. The main outcomes were comparing pre- and post-SRS hemorrhage rates, using the pooled risk ratios (RR) as the measure of effect. Additionally, the study assessed lesion volume changes and radiation-injury incidence. RESULTS: Data of 850 patients across 14 studies were included in the meta-analysis. The pooled RR of all deep-seated ICMs show a decrease in hemorrhage rate after SRS compared to pre-SRS over the total follow-up period (RR =0.13), initial 2 years (RR =0.22), and after 2 years (RR =0.07). For 9 studies that reported hemorrhage rate of the brainstem only, the pooled RR shows a decrease of hemorrhage rate after SRS compared to pre-SRS over the total follow-up period (RR =0.13), initial 2 years (RR =0.19), and after 2 years (RR =0.07). Volumetric regression was achieved in 44.25% and stability in 56.1%. The pooled incidence of symptomatic and permanent radiation injury was 9% (95% CI, 7-11) and 3% (95% CI, 0-1.9%), respectively. CONCLUSION: SRS appears effective in reducing hemorrhage rates for deep-seated ICMs. The risk of symptomatic radiation injury is low. Given the high risk of surgical morbidity, SRS is a reasonable treatment option for patients with deep-seated ICMs with at least one prior hemorrhage.

To B or not to B: the application of uterine compression sutures to reduce blood loss after myomectomy.

Introduction: The aim was to assess the hemostatic impact of B-Lynch sutures following an open myomectomy for efficacy. Material and methods: In this prospective clinical research, performed in Alazhar university hospitals (Al-Hussain, Damietta, Assiut) and Minia University Maternity Hospital, 250 women scheduled for open myomectomy between January 2021 and January 2023 had multiple fibroid uteri with uterine sizes corresponding to 12-22 weeks. There were two groups of women. Group I (125) underwent standard open myomectomy surgery, whereas Group II (125) underwent normal open laparotomy surgery followed by B-Lynch sutures. Certain inclusion and exclusion criteria were applied to every patient. We recorded vital data, length of the procedure, complications (bleeding during the procedure, bleeding from multiple bites, bladder injury, fever, wound infection), complete blood count before and after surgery, need for blood transfusion, postoperative vital data, time until ambulation, passing flatus, and ability to eat and drink, as well as the amount of blood lost during and after the procedure. Results: There was no statistically significant difference between the two groups in age, parity, weight, number of fibroids, or uterine size as measured by ultrasonography. Between groups I and II, there was a significant difference in the average intraoperative blood loss (Group I lost 562.6 ml, whereas Group II lost 411.3 ml) as well as the mean blood loss following surgery (205 ±82 ml in Group I and 117 ±41 ml in Group II). No significant difference was observed in the mean length of hospital stay between groups I and II (2 ±0.3 days and 2 ±0.6 days, respectively). Conclusions: Using a B-Lynch suture can help minimize blood loss during and after an open myomectomy. Therefore, if the uterus is large and has a lot of fibroids, it is recommended to be done frequently.

Does misclassification of former tobacco smokers explain the 'smoker's paradox' in the risk of COVID-19? Insights from the Stockholm Public Health Cohort.

BACKGROUND: The association between tobacco smoking and the risk of COVID-19 and its adverse outcomes is controversial, as studies reported contrasting findings. Bias due to misclassification of the exposure in the analyses of current versus non-current smoking could be a possible explanation because former smokers may have higher background risks of the disease due to co-morbidity. The aim of the study was to investigate the extent of this potential bias by separating non-, former, and current smokers when assessing the risk or prognosis of diseases. METHODS: We analysed data from 43,400 participants in the Stockholm Public Health Cohort, Sweden, with information on smoking obtained prior to the pandemic. We estimated the risk of COVID-19, hospital admissions and death for (a) former and current smokers relative to non-smokers, (b) current smokers relative to non-current smokers, that is, including former smokers; adjusting for potential confounders (aRR). RESULTS: The aRR of a COVID-19 diagnosis was elevated for former smokers compared with non-smokers (1.07; 95% confidence interval (CI) =1.00-1.15); including hospital admission with any COVID-19 diagnosis (aRR= 1.23; 95% CI = 1.03-1.48); or with COVID-19 as the main diagnosis (aRR=1.23, 95% CI= 1.01-1.49); and death within 30 days with COVID-19 as the main or a contributory cause (aRR=1.40; 95% CI=1.00-1.95). Current smoking was negatively associated with risk of COVID-19 (aRR=0.79; 95% CI=0.68-0.91). CONCLUSIONS: Separating non-smokers from former smokers when assessing the disease risk or prognosis is essential to avoid bias. However, the negative association between current smoking and the risk of COVID-19 could not be entirely explained by misclassification.

Current tobacco use and SARS-CoV-2 infection in two Norwegian population-based cohorts.

BACKGROUND: Clear evidence of an increased risk for SARS-CoV-2 infection among smokers has not been established. We aimed to investigate associations between cigarette smoking or use of snus (snuff) and other nicotine-containing products and a positive SARS-CoV-2 test, taking test behavior into account. METHODS: Current tobacco use and testing behavior during the pandemic were recorded by adult participants from the Norwegian Mother, Father and Child Cohort Study and The Norwegian Influenza Pregnancy Cohort. SARS-CoV-2 infection status was obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) in May 2021 (n = 78,860) and antibody measurements (n = 5581). We used logistic regression models stratified by gender and adjusted for age, education, region, number of household members, and work situation. RESULTS: Snus use was more common among men (26%) than women (9%) and more prevalent than cigarette smoking. We found no clear associations between cigarette smoking or snus and a COVID-19 diagnosis among men. Associations among women were conflicting, indicating that cigarette smoke was negatively associated with a diagnosis (OR 0.51, 95% CI 0.35, 0.75), while no association was found for snus use (OR 1.07, 95% CI 0.86, 1.34). Compared with non-users of tobacco, both cigarette smokers and snus users had increased odds of being tested for SARS-CoV-2. CONCLUSIONS: Cigarette smoking, but not snus use, was negatively associated with SARS-CoV-2 infection in women. The lack of an association between snus use and SARS-CoV-2 infection in this population with prevalent snus use does not support the hypothesis of a protective effect of nicotine.

Association between AXIN1 gene polymorphism (rs9921222) of WNT signaling pathway and susceptibility to osteoporosis in Egyptian patients: a case-control study.

BACKGROUND: Osteoporosis (OP) is the most prevalent metabolic bone disease. Numerous genetic loci are strongly related to OP. AXIN1 is a significant gene that serves an important role in the WNT signaling pathway. The aim of this study was to explore the association between the AXIN1 genetic polymorphism (rs9921222) and OP susceptibility. METHODS: A total of 101 subjects were enrolled in the study (50 patients with OP and 51 healthy individuals). Genomic DNA was extracted from whole blood using the QIAamp DNA Blood Mini Kit, and the AXIN1 gene polymorphism (rs9921222) was genotyped by TaqMan allelic discrimination assays. A logistic regression analysis was used to assess the association between genotypes and OP risk. RESULTS: We found that AXIN1 rs9921222 had a significant association with the susceptibility of OP under the homozygote model (TT vs. CC: OR = 16.6, CI = 2.03-136.4, p = 0.009), (CT vs. CC: OR = 6.3, CI = 1.23-31.8, p = 0.027), recessive genetic model (TT vs.TC-CC: OR = 13.6, CI = 1.7-110.4, p = 0.015), and the dominant model (TT-TC vs. CC: OR = 9.7, CI = 2.6-36.3, p < 0.001). Allele T was significantly associated with OP risk (T vs. C: OR = 10.5, CI = 3.5-31.15, p = 0.001). There was a statistically significant difference between genotypes in mean platelet volume (p = 0.004), and platelet distribution width (p = 0.025). In addition, lumbar spine bone density, and femur neck bone density were significantly different between genotypes (p < 0.001). CONCLUSION: AXIN1 rs9921222 was associated with OP susceptibility in the Egyptian population and should be considered a potential determinant risk for OP.

Two-stage endoscopic assisted approach for large pineal region and falcotentorial meningioma: first stage paramedian supracerebellar infratentorial approach, second stage interhemispheric occipital transtentorial approach: surgical cases and anatomical study.

Resection of complex falcotentorial meningiomas, growing along the pineal region (PR), and posterior incisural space (PIS) represents a neurosurgical challenge. Here, we present our strategy for effective resection of large falcotentorial meningiomas applying a paramedian supracerebellar infratentorial and interhemispheric occipital transtentorial approach in staged surgeries. We further systematically compared the effectiveness of midline (MSIA) and paramedian (PSIA) supracerebellar infratentorial, as well as interhemispheric occipital transtentorial approaches (IOTA) to operate along the PR and PIS in 8 cadaveric specimens. The staged PSIA and IOTA enabled successful resection of both falcotentorial meningiomas with an uneventful postoperative course. In our anatomo-morphometrical study, superficial vermian veins at an average depth of 11.38 ± 1.5 mm and the superior vermian vein (SVV) at 54.13 ± 4.12 mm limited the access to the PIS during MSIA. MSIA required sacrifice of these veins and retraction of the vermian culmen of 20.88 ± 2.03 mm to obtain comparable operability indexes to PSIA and IOTA. Cerebellar and occipital lobe retraction averaged 14.31 ± 1.014 mm and 14.81 ± 1.17 mm during PSIA and IOTA respectively, which was significantly lower than during MSIA (p < 0.001). Only few minuscule veins were encountered along the access through PSIA and IOTA. The application of PSIA provided high operability scores around the pineal gland, ipsilateral colliculus and splenium, and acceptable scores on contralateral structures. The main advantage of IOTA was improving surgical maneuvers along the ipsilateral splenium. In summary, IOTA and PSIA may be advantageous in terms of brain retraction, vein sacrifice, and operability along the PR and PIS and can be effective for resection of complex falcotentorial meningiomas.

Lateral cervical approach for ventrally located upper cervical meningioma: experience of 14 cases with a narrative comparison with other surgical techniques.

BACKGROUND: Upper cervical meningioma represents a large portion of intradural extramedullary tumors that occur in the cervical spinal canal. Most of them are located ventrally or ventrolateral to the spinal cord. Reaching lesions at this location surgically is technically challenging. OBJECTIVES: The ideal approach to ventrally located upper cervical lesions continues to be controversial. The aim of this study was to discuss the advantage of the lateral cervical approach and compare it with other surgical routes. METHODS: This retrospective study was conducted on all cases of ventrally located upper cervical meningiomas (C1-C3) who have been operated on using the lateral cervical approach in a tertiary neurosurgery unit between 2006 and 2020. Demographic, clinical, surgical, and follow-up data were collected from hospital records. RESULTS: During the study period, fourteen patients (Nine females and five males, aged 42-73 years) were recruited. The follow-up period was 2-16 years. The most frequent presenting symptoms were neck pain, occipital headache, motor deficits, and sensory disturbances. Total excision was achieved in all patients. All patients who had preoperative motor deficits improved significantly postoperatively, and those who presented with sensory disturbance had partial recovery. There was neither mortality nor permanent neurological morbidity. CONCLUSION: A lateral cervical approach is a safe approach for ventrally located upper cervical lesions. In our series, it offered enough exposure for a safe dissection and total or extensive subtotal removal of the tumors. Retraction or rotation of the neuroaxis was avoided, and the incidence of complications (injury of neural or vascular structures, instability, infection) was very low.

Digoxin mitigates diethylnitrosamine-induced acute liver injury in mice via limiting production of inflammatory mediators.

The cardiotonic digoxin has been recently shown to possess an anti-inflammatory potential in numerous metabolic and inflammatory disorders. However, data about digoxin's impact in the setting of acute liver injury and sterile inflammation are still limited. Here, we investigated the potential effect of digoxin pretreatments (0.25 and 0.5 mg/kg, oral) on the severity of acute hepatotoxicity in mice challenged with a single dose of diethylnitrosamine (DN; 150 mg/kg, intraperitoneal) for 24 h. Our results indicated that digoxin pretreatments dose-dependently mitigated DN-induced rise of hepatocellular injury parameters and necroinflammation scores. Digoxin, particularly at dose of 0.5 mg/kg, boosted the number of PCNA positive hepatocytes, leading to improvement of the reparative potential in hepatocytes of DN-intoxicated livers. Digoxin's ameliorative effect on DN-hepatotoxicity coincided with (i) lowering the increased hepatic production and release of the proinflammatory mediators IL-17A, IL-1ß and TNF-α, and (ii) impeding the attraction and infiltration of monocytes to the liver, as denoted by decreasing serum MCP-1 and F4/80 immunohistochemical expression. These effects were attributed to reducing DN-induced activation of NF-κB and overexpression of CD98 in the liver. Meanwhile, DN elicited a decline in the hepatic production and release of the anti-inflammatory cytokines IL-22 and IL-6, which was intensified by digoxin, especially at a dose 0.5 mg/kg. In conclusion, digoxin conferred liver protection against DN-insult by impairing the overproduction of proinflammatory cytokines and infiltration of inflammatory cells to the liver.

Statistical models for analyzing count data: predictors of length of stay among HIV patients in Portugal using a multilevel model.

BACKGROUND: This study offers a comprehensive approach to precisely analyze the complexly distributed length of stay among HIV admissions in Portugal. OBJECTIVE: To provide an illustration of statistical techniques for analysing count data using longitudinal predictors of length of stay among HIV hospitalizations in Portugal. METHOD: Registered discharges in the Portuguese National Health Service (NHS) facilities Between January 2009 and December 2017, a total of 26,505 classified under Major Diagnostic Category (MDC) created for patients with HIV infection, with HIV/AIDS as a main or secondary cause of admission, were used to predict length of stay among HIV hospitalizations in Portugal. Several strategies were applied to select the best count fit model that includes the Poisson regression model, zero-inflated Poisson, the negative binomial regression model, and zero-inflated negative binomial regression model. A random hospital effects term has been incorporated into the negative binomial model to examine the dependence between observations within the same hospital. A multivariable analysis has been performed to assess the effect of covariates on length of stay. RESULTS: The median length of stay in our study was 11 days (interquartile range: 6-22). Statistical comparisons among the count models revealed that the random-effects negative binomial models provided the best fit with observed data. Admissions among males or admissions associated with TB infection, pneumocystis, cytomegalovirus, candidiasis, toxoplasmosis, or mycobacterium disease exhibit a highly significant increase in length of stay. Perfect trends were observed in which a higher number of diagnoses or procedures lead to significantly higher length of stay. The random-effects term included in our model and refers to unexplained factors specific to each hospital revealed obvious differences in quality among the hospitals included in our study. CONCLUSIONS: This study provides a comprehensive approach to address unique problems associated with the prediction of length of stay among HIV patients in Portugal.

Retrospective analysis of the surgical management of spontaneous supratentorial intracerebral hemorrhage: A single-center study.

BACKGROUND: Intracerebral hemorrhage (ICH) remains a devastating disease with high morbidity and mortality. The mortality rate ranges from 40% at 1 month to 54% at 1 year, and only 12%-39% achieve good outcomes and functional independence. The current management guidelines for spontaneous supratentorial ICH are still controversial. OBJECTIVE: Patients who presented with ICH and underwent craniotomy with hematoma evacuation or minimal procedures from January 2016 to May 2020 were included in the analysis. Several clinical, radiological, and surgical variables were collected to identify the variables most likely related to lower mortality and better functional outcomes. RESULTS: A total of 87 patients presented with HMC with ICH from January 2016 to May 2020. The mean age was 44.7 (42.2-47.2) years. There were 76 male (87.4%)/11 female (12.6%) patients, which reflect the population distribution in Qatar, which is mainly male predominant. Although Qatar is mainly a Middle-Eastern country, the ethnic distribution of patients was mainly of South Asian and Indian (60.9%) and Far-Eastern (20.7%) ethnicities because of diversity. The mean baseline Glasgow coma scale (GCS) was 8.2+/ - 3.7. The mean baseline functional independence measure (FIM) score was 59.4+/ - 36.7. Most hematomas were located in the basal ganglia (79.3%%). Baseline characteristics based on long-term outcomes are summarized in Table 1. The following variables were correlated with poor outcome: low GCS on postoperative day 1 (P = 0.06), low FIM score (P = 0.006), ICH location (P = 0.04), distance of the closest point to the surface (P = 0.009), and presence of uncal herniation (P = 0.04). The baseline characteristics based on mortality are outlined in Table 2. The following variables were correlated with mortality: diabetes mellitus (P = 0.02), baseline GCS (P = 0.04), GCS on postoperative day 1 (P = 0.002), unequal pupils (P = 0.05), and postoperative midline shift (P = 0.001). CONCLUSION: The preoperative clinical neurological status as well as mass effect (uncal herniation and midline shift) can be determinants of functional outcome and mortality. A deeper hematoma may result in poor functional outcome because of more surgical damage in functional brain tissues. Thus, the goal of surgery in spontaneous supratentorial ICH is to reduce mortality, but no evidence support that it can improve functional outcome. Although our findings are interesting, more prospective studies with a larger sample size are needed to confirm our results.

The selective c-Met inhibitor capmatinib offsets cisplatin-nephrotoxicity and doxorubicin-cardiotoxicity and improves their anticancer efficacies.

The incorporation of mesenchymal-epithelial transition factor (c-Met) inhibitors with conventional chemotherapeutics may increase the anticancer efficacy of chemotherapeutic agents, but bears the risk of enhancing the adverse effects. To test the hypothesis, co-administration of the novel c-Met inhibitor capmatinib with cisplatin (CIS) or doxorubicin (DOX) was investigated on nephrotoxicity and cardiotoxicity induced by these agents in mice, as well as their in vitro cytotoxicities. The results demonstrated that capmatinib in vivo offered protection against nephrotoxicity and cardiotoxicity by both CIS and DOX, respectively. The underlying mechanisms behind capmatinib protective effect were found to be i) limiting excessive generation of reactive oxygen species by decreasing the level of lipid peroxidation and nitrosative stress products; and ii) suppressing overproduction of pro-inflammatory mediators like TNF-α and IL-6 that coincided with less inflammatory cell infiltration as denoted by lower levels of serum MCP-1 and Ly6G immunostaining. Besides, capmatinib effectively improved the in vivo anticancer efficacy of both CIS and DOX against solid tumors. In vitro, capmatinib increased the apoptotic activity of DOX against cancerous cells, but did not affect that of CIS. This effect might be linked to capmatinib and DOX abilities to lower IL-12(p40) that has an inhibitory effect on IL-12(p70)/IFN-γ-mediated apoptotic activity. In conclusion, the favorable effects of capmatinib can be applied clinically to decrease the toxicity of DOX and CIS chemotherapeutic agents.

Effect of febuxostat on biochemical parameters of hyperlipidemia induced by a high-fat diet in rabbits.

Febuxostat, a highly potent xanthine oxidase inhibitor with an antioxidant effect, inhibits elevated xanthine oxidase, leading to reduction of reactive oxygen species and oxidative stress, the main causes of vascular inflammation in hyperlipidemia. The aim of this study was to test the potential antioxidant and anti-inflammatory effects of febuxostat and (or) stopping a high-fat diet on the biochemical parameters in rabbits with hyperlipidemia induced by a high-fat diet. Male New Zealand rabbits were distributed into 3 groups: a normal control group fed standard chow for 12 weeks and 2 other groups fed a high-fat diet with 1% cholesterol for 8 weeks, and then shifted to standard chow for 4 weeks. During the last 4 weeks, one high-fat diet group received 0.5% carboxymethyl cellulose, whereas the other group was treated with febuxostat (2 mg/kg per day p.o.). Febuxostat significantly lowered low-density lipoprotein cholesterol ("bad" cholesterol) compared to the untreated group (high-fat diet group). Febuxostat also displayed a potent anti-inflammatory and antioxidant activity by decreasing serum levels of lipid peroxidation index, proinflammatory cytokines, and enhancing antioxidant enzyme activity. Stopping the hyperlipidemic diet in the high-fat diet group did not show improvement. These findings indicate the antioxidant and anti-inflammatory effects of febuxostat that may be common mechanisms of the anti-hyperlipidemic effect of this drug. Stopping a hyperlipidemic diet without treatment is not sufficient once injury has occurred.

Alanine-(87)-threonine polymorphism impairs signaling and internalization of the human P2Y11 receptor, when co-expressed with the P2Y1 receptor.

The P2Y11 nucleotide receptor detects high extracellular ATP concentrations. Mutations of the human P2RY11 gene can play a role in brain autoimmune responses, and the P2Y11 receptor alanine-87-threonine (A87T) polymorphism has been suggested to affect immune-system functions. We investigated receptor functionality of the P2Y11 A87T mutant using HEK293 and 1321N1 astrocytoma cells. In HEK293 cells, the P2Y11 receptor agonist 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (BzATP) was completely inactive in evoking intracellular calcium release while the potency of ATP was reduced. ATP was also less potent in triggering cAMP generation. However, 1321N1 astrocytoma cells, which lack any endogenous P2Y1 receptors, did not display a reduction. Only when 1321N1 cells were co-transfected with P2Y11 A87T and P2Y1 receptors, the calcium responses to the P2Y11 receptor-specific agonist BzATP were reduced. It is already known that P2Y1 and P2Y11 receptors interact. We thus conclude that the physiological impact of A87T mutation of the P2Y11 receptor derives from detrimental effects on P2Y1 -P2Y11 receptor interaction. We additionally investigated alanine-87-serine and alanine-87-tyrosine P2Y11 receptor mutants. Both mutations rescue the response to BzATP in HEK293 cells, thus ruling out polarity of amino acid-87 to be the molecular basis for altered receptor characteristics. We further found that the P2Y11 A87T receptor shows complete loss of nucleotide-induced internalization in HEK293 cells. Thus, we demonstrate impaired signaling of the P2Y11 A87T-mutated receptors when co-operating with P2Y1 receptors.

The role of platelet rich plasma enriched fat graft for correction of deformities after conservative breast surgery.

BACKGROUND: Fat transfer has been widely used after breast conservative surgery (BCS) where it aims to recover shapes as a simple, inexpensive, biocompatible method but the technique is not without complications. Platelet Rich Plasma (PRP) is a promising approach to enhance fat graft survival and subsequently improve the outcome. The aim of this study was to evaluate the effect of enriching fat graft with PRP for delayed correction of deformities after conservative surgery for breast cancer regarding esthetic outcome and incidence of complications. METHODS: The current study included 50 female patients who were scheduled for delayed lipofilling for correction of deformities after conservative surgery for breast cancer. The studied patients were randomly allocated into 2 groups: Group I (G I) included 25 patients scheduled for PRP enriched lipoinjection and Group II (G II) included 25 patients scheduled for lipoinjection without PRP as a control group. RESULTS: Number of sessions of lipoinjection was significantly less in G I in comparison to G II (P = 0.024). During the 2nd session; the amounts of fat injected and harvested were significantly less in G I in comparison to G II (P = 0.049 and 0.001 respectively). Recipient site complications were significantly more evident in G II in comparison to G I (P = 0.01). Surgeon and patient satisfactions were significantly more evident in GI in comparison to G II (P = 0.005 and 0.029 respectively). CONCLUSION: The addition of PRP to fat grafts is a simple, cost-effective and safe method to improve esthetic outcome and decrease complications.

G protein-coupled estrogen receptor selective agonist, G1, improves the molecular and biochemical markers in a cisplatin mouse model of CKD.

Multiple cycles of cisplatin result in a permanent loss of kidney function with severe and life-limited chronic kidney disease (CKD) after successful cisplatin therapy. Recently, studies have showed that the activation of G-protein coupled estrogen receptor (GPER) could protect against kidney disease. This study aimed to test the potential of the G1 compound, a GPER selective agonist, to prevent CKD development after cisplatin therapy. Male C57BL/6 mice were exposed to 2 cycles of 2.5 mg/kg cisplatin in a regimen miming clinical exposure (1 injection daily for 5 days, followed by a 16-day recovery period between cycles). G1 (50 or 100 µg/kg) was administered daily for 6 weeks. G1 dose-dependently improved kidney function biomarkers (serum creatinine, creatinine clearance, and protein excretion) and histopathological changes compared to the cisplatin-treated group. Collagen 3 expression was dose-dependently decreased in G1-treated groups that was parallel to the reduction of fibrosis in Masson's trichrome-stained sections. G1 administration also increased total antioxidant capacity (TAC) and nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced the level of malondialdehyde and the proinflammatory cytokine, tumor necrosis factor-α. In addition, G1 downregulated the expression of inflammasome NLRP3 and nuclear factor kappa B p65 (NF-κB p65) in a dose-dependent manner. In conclusion, these data suggest that G1 could be a new therapeutic tool for CKD prevention post cisplatin therapy. These effects might be mediated through the activation of Nrf2 and the inhibition of NF-κB/NLRP3 signaling.

Enhancing sweet potato (Ipomoea batatas) resilience grown in cadmium-contaminated saline soil: a synergistic approach using Moringa leaf extract and effective microorganisms application.

Raising soil contamination with cadmium (Cd2+) and salinization necessitates the development of green approaches using bio-elicitors to ensure sustainable crop production and mitigate the detrimental health impacts. Two field trials were carried out to study the individual and combined effects of foliage spraying of Moringa leaf extract (MLE) and soil application of effective microorganisms (EMs) on the physio-biochemical, osmolytes, antioxidants, and performance of sweet potato grown in Cd2+-contaminated salty soil (Cd2+ = 17.42 mg kg-1 soil and soil salinity ECe = 7.42 dS m-1). Application of MLE, EMs, or MLE plus EMs significantly reduced the accumulation of Cd2+ in roots by 55.6%, 50.0%, or 68.1% and in leaves by 31.4%, 27.6%, or 38.0%, respectively, compared to the control. Co-application of MLE and EMs reduced Na+ concentration while substantially raising N, P, K+, and Ca2+ acquisition in the leaves. MLE and EMs-treated plants exhibited higher concentrations of total soluble sugar by 69.6%, free proline by 47.7%, total free amino acids by 29.0%, and protein by 125.7% compared to the control. The enzymatic (SOD, APX, GR, and CAT) and non-enzymatic (phenolic acids, GSH, and AsA) antioxidants increased in plants treated with MLE and/or EMs application. Applying MLE and/or EMs increased the leaf photosynthetic pigment contents, membrane stability, relative water content, water productivity, growth traits, and tuber yield of Cd2+ and salt-stressed sweet potato. Consequently, the integrative application of MLE and EMs achieved the best results exceeding the single treatments recommended in future application to sweet potato in saline soil contaminated with Cd2+.

Repeat Single-Session Stereotactic Radiosurgery for Cerebral Arteriovenous Malformations: A Systematic Review, Meta-Analysis, and International Stereotactic Radiosurgery Society Practice Guidelines.

BACKGROUND AND OBJECTIVES: Repeat stereotactic radiosurgery (SRS) for residual arteriovenous malformations (AVMs) can be considered as a salvage approach after failure of initial SRS. There are no published guidelines regarding patient selection, timing, or SRS parameters to guide clinical practice. This systematic review aimed to review outcomes and complications from the published literature to inform practice recommendations provided on behalf of the International Stereotactic Radiosurgery Society. METHODS: We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of MEDLINE, Scopus, Web of Science, and Embase was conducted. Fourteen studies with 925 patients met the inclusion criteria. Patients were treated between 1985 and 2022. All studies were retrospective, except for one prospective cohort. RESULTS: The median patient age at repeat SRS ranged from 32 to 60 years. Four studies (630 patients) reported detailed information on Spetzler-Martin grade at the time of repeat SRS; 12.54% of patients had Spetzler-Martin grade I AVMs (79/630 patients), 46.51% had grade II (293/630), 34.92% had grade III (220/630), 5.08% had grade IV (32/630), and 0.95% had grade V (6/630). The median prescription doses varied between 15 and 25 Gy (mean, 13.06-22.8 Gy). The pooled overall obliteration rate at the last follow-up after repeat SRS was 59% (95% CI 51%-67%) with a median follow-up between 21 and 50 months. The pooled hemorrhage incidence at the last follow-up was 5% (95% CI 4%-7%), and the pooled overall radiation-induced change incidence was 12% (95% CI 7%-20%). CONCLUSION: For an incompletely obliterated AVM, repeat radiosurgery after 3 to 5 years of follow-up from the first SRS provides a reasonable benefit to the risk profile. After repeat SRS, obliteration is achieved in the majority of patients. The risk of hemorrhage or radiation-induced change appears low, and International Stereotactic Radiosurgery Society recommendations are presented.

Long-term radiographic and endocrinological outcomes of stereotactic radiosurgery for recurrent or residual nonfunctioning pituitary adenomas.

OBJECTIVE: Stereotactic radiosurgery (SRS) is used for the treatment of residual/recurrent nonfunctional pituitary adenoma (NFPA). The aim of this study was to evaluate the factors related to long-term tumor control and delayed endocrinopathies following SRS. METHODS: This retrospective, multicenter study included patients with recurrent/residual NFPA treated with single-fraction SRS; they were then divided into two arms. The first arm included patients with at least 5 years of radiographic follow-up and all patients with local tumor progression. The second arm included patients with at least 5 years of endocrinological follow-up and all patients who developed endocrinopathy. Study endpoints were tumor control and new or worsening hypopituitarism after SRS and were analyzed using Cox regression and Kaplan-Meier methodology. RESULTS: There were 360 patients in the tumor control arm (median age 52.7 [IQR 42.9-61] years, 193 [53.6%] males) and 351 patients in the hypopituitarism arm (median age 52.5 [IQR 43-61] years, 186 [53.0%] males). The median follow-up in the tumor control evaluation group was 7.95 (IQR 5.7-10.5) years. Tumor control rates at 5, 8, 10, and 15 years were 93% (95% CI 90%-95%), 87% (95% CI 83%-91%), 86% (95% CI 82%-90%), and 69% (95% CI 59%-81%), respectively. The median follow-up in the endocrinopathy evaluation group was 8 (IQR 5.9-10.7) years. Pituitary function preservation rates at 5, 8, 10, and 15 years were 83% (95% CI 80%-87%), 81% (95% CI 77%-85%), 78% (95% CI 74%-83%), and 71% (95% CI 63%-79%), respectively. A margin dose > 15 Gy (HR 0.8, 95% CI 0.7-0.9; p < 0.001) and a delay from last resection to SRS > 1 year (HR 0.9, 95% CI 0.7-0.9; p = 0.04) were significant factors related to tumor control in multivariable analysis. A maximum dose to the pituitary stalk ≤ 10 Gy (HR 1.1, 95% CI 1.09-1.2; p < 0.001) was associated with pituitary function preservation. New visual deficits after SRS occurred in 7 (1.94%) patients in the tumor control group and 8 (2.3%) patients in the endocrinopathy group. Other new cranial nerve deficits post-SRS occurred in 4 of 160 patients with data in the tumor control group and 3 of 140 patients with data in the endocrinopathy group. CONCLUSIONS: SRS affords favorable and durable tumor control for the vast majority of NFPAs. Post-SRS hypopituitarism occurs in a minority of patients, but this risk increases with time and warrants long-term follow-up.