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We investigated the safety, preliminary efficacy, and immune effects of large surface area microparticle docetaxel (LSAM-DTX) administered by direct injection after transurethral resection of bladder tumor (TURBT), and by intravesical instillation in high-risk nonmuscle-invasive bladder cancer.The trial followed an open-label 3+3 dose escalation with additional enrollment at the high dose. After TURBT, subjects received direct injection LSAM-DTX into the resection site and intravesical LSAM-DTX, followed by 6-week induction and 3-week maintenance intravesical LSAM-DTX courses. Tumor recurrence was evaluated by cytology, cystoscopy, or biopsy. Pharmacokinetic analysis of blood and multiplex immunofluorescence of tumor microenvironment occurred pre- and post-LSAM-DTX.Nineteen subjects were enrolled, 14 with prior bacillus Calmette-Guérin exposure and 16 with ≥1 prior TURBT. Direct injection and intravesical LSAM-DTX were well tolerated. In the 3 lowest dose escalation cohorts the median recurrence-free survival was 5.4 months (10 patients, median followup 8.6 months). In the high-dose and expansion cohorts median recurrence-free survival was significantly increased (pPost-TURBT direct injection and intravesical LSAM-DTX were well tolerated and demonstrated clinical response for patients with high-risk nonmuscle-invasive bladder cancer. Favorable immune cell infiltration and checkpoint receptor increases following LSAM-DTX treatment warrants investigation alone as well as in combination with immune checkpoint inhibitor therapy.

We sought to determine if absolute prostate specific antigen (PSA) value after 6 months of androgen deprivation therapy (ADT) is predictive of subsequent survival in patients with prostate adenocarcinoma.We performed a retrospective review of men receiving care within the Veterans Health Administration who initiated ADT for prostate adenocarcinoma. We used low- (≤0.2 ng/ml), intermediate- (0.2 to 4 ng/ml) and high-risk (4 ng/ml) absolute PSA values after 6-9 months of ADT, previously described in Southwest Oncology Group trial 9346. The primary endpoints were all-cause mortality and prostate cancer-specific mortality (PCSM). Kaplan-Meier survival curves for each PSA category were estimated and log-rank test was conducted. We employed Cox regression analysis adjusted for covariates and inverse propensity score weights associated with PSA categories to estimate the PSA category association with PCSM and all-cause mortality.We identified 9,170 patients in our cohort. Following ADT induction, 3,508 patients had low, 3,419 had intermediate and 2,243 had high PSA values. Two- and 5-year survival rates for low, intermediate and high PSA groups were 93.9% and 85.2% vs 88.6% and 71.2% vs 63.6% and 38.6%, respectively (p0.0001). Patients in the high and intermediate PSA categories had a 15-fold and 3-fold higher risk of PCSM compared to those with PSA0.2 ng/ml (p0.0001).Absolute PSA in hormone-sensitive prostate cancer after 6-9 months of ADT is a predictor of overall mortality and PCSM. This measure can rapidly assess the efficacy of new interventions in phase 2 clinical trials.

Reconstruction plays a valuable role in the management of lower extremity wounds for limb salvage. The goals of reconstruction are to improve function and quality of life, return to work, and pain reduction while providing a long-lasting durable reconstruction. The plastics and reconstructive surgical approach in conjunction with the orthopedic or trauma team, referred often as the "orthoplastic" approach, can yield the best outcomes for patients. The following sections discuss reconstruction principles and techniques that can be applied broadly for lower extremity wounds secondary to trauma, infection, and tumor resection.

A recently reported phase III randomized trial comparing open and minimally invasive hysterectomy showed significantly higher rates of local recurrence after minimally invasive surgery (MIS) for cervical cancer. This raised concerns regarding patterns of recurrences and survival after MIS in general. This study aims to determine the effect of MIS on all-cause mortality among patients undergoing radical nephrectomy for Stage I and II renal cell carcinoma (RCC).We utilized the National Cancer Database to identify patients diagnosed with clinical stage I-II RCCs between 2010 and 2013. Patients for whom a laparoscopic or robotic radical nephrectomy was attempted were compared to patients who underwent open radical nephrectomy (ORN). Adjusted regression models with inverse probability propensity score weighting (IPW) were utilized to identify independent predictors of receiving MIS. All-cause mortality rates were compared using IPW survival functions and log-rank tests. Adjusted Cox proportional hazard models were fitted to determine independent predictors of OS.27,642 patients were identified; 11,524 (41.7%) had MIS, while 16,118 (58.3%) had ORN. Kaplan-Meier survival curves in the IPW cohort showed significant OS advantage for patients who underwent MIS (p 0.001). Furthermore, length of hospital stays (3 vs. 4 days), 30 day readmission rates (2.4 vs. 2.87%), 30 day (0.53 vs. 0.96%) and 90 day mortality rates (1.04 vs. 1.77%) were significantly higher in the ORN group (p 0.001).MIS was associated with better OS outcomes compared to ORN for stage I and II RCC. In addition, MIS had lower post-operative readmission, 30- and 90 day mortality rates.

Background: The environmental legislation on pollutant concentrations in aqueous effluents tends to tighten and increase due to the huge efforts devoted as a response to global warming and its related negative impact on our planet. As a result, sour water must be handled and processed properly to provide a high quality of stripped water with insignificant traces of NH3 and H2S. This approach must be achieved within the minimum operating costs. This scientific research investigates the stripping configurations of sour water effluents from various industries. The research also offers an insight into different scenarios and configurations to accomplish set targets satisfying the environmental law criteria. Methods: This research introduces a range of heat integration schemes for saving energy. Further, vapor recompression “VRC” technique is opted for its ability to maximize energy savings. This research also investigates the effect of operating and design variables on the stripped water quality, such as feed temperature, feed location, reflux split, and steam flow rate. The option of adding new equipment is also addressed to maximize heat integration and enhance the efficiency of the process. Thus, several schemes and process configurations are explored to treat the industrial sour water waste streams seeking better efficiency. Those configurations differ from one another in heat integration layout and VRC utilization. The energy efficiency and economics of the proposed configurations are considered decisive factors in this research study. The case study adopted in this research is based on published data taken from several iron and steel factories in South Korea named POSCO (Pohang Iron and Steel Corporation). Results: The obtained results of the treated wastewater streams guarantee that the effluent sour water obeys the standard environmental regulations, i.e., NH3 contents range from 30 to 80 ppm and H2S concentration falls below 0.1 ppm. The obtained results of the seven different scenarios are compared to the original case study. It is found that scenario 7 is the most economical solution saving 51.54 % of the total annual cost compared to the original case study while satisfying the treated water environmental regulations with a concentration of 3.19 ppm NH3 and 0.05 ppm H2S. Scenario 7 creates its own steam, unlike the original case study where steam utility is needed extensively. However, scenario 7 consumes 15 % more electricity than the original case study, but it also still shows 56.34 % less than the overall utility cost. Conclusion: The optimum process configuration can be employed for other sour water purification systems such as those used in petroleum refiners. An ongoing research work focuses on the use of internal heat integration for more energy savings and economic improvement.

Tricarbonyl Re(i) complexes are piled in the intercellular junction and diffused inside the cells. This led to DNA fragmentations and both apoptotic and necrotic cell death.

Before and after illumination, as well as when it was coupled with the medicine Paclitaxel, the visible-light induced fac-Mn(CO)3 molecule of 8-amino showed interesting cytotoxicity against triple-negative breast cancer.

Summary Coupling polymer with low-salinity water (LSW) to promote enhanced oil recovery (EOR) in carbonate reservoirs has attracted significant interest in the petroleum industry. However, low-salinity polymer (LSP) application to improve oil extraction from such rocks remains a challenge because of the complex synergism between these two EOR agents. Thus, this paper highlights the main factors that govern the LSP displacement process in carbonate reservoirs in terms of wettability alteration and mobility control. A series of experiments including contact angle, spontaneous imbibition, injectivity, adsorption, and oil displacement tests were performed. The impact of mineral dissolution on the polymer/brine and polymer/rock surface interactions and its possible connection to the efficiency of the LSP in carbonates was also investigated using ζ potential analysis following an elaborative procedure. All experiments were executed at elevated temperature (75°C) using two polymers (SAV10) of different molecular weights (MWs) prepared at varying concentrations and salinities. Contact angle measurements showed that increasing the polymer concentration and MW and, at the same time, decreasing the solution salinity could effectively rend homogeneous oil-wet calcite surfaces strongly water-wet. Conversely, spontaneous imbibition tests using heterogonous oil-wet Indiana limestone cores showed that the polymer viscosity and its molecular size hinder the performance of the polymer to modify the wettability of the core samples at high concentration and MW because they could limit its penetration into the porous medium. On the other hand, the results obtained from polymer injectivities showed that LSP had better propagation with lower filtration effects in comparison with high-salinity polymer (HSP). However, polymer adsorption and inaccessible pore volume (IPV) increased with the decrease of salinity. Calcite mineral dissolution triggered by LSP, which is associated with an increase in pH and [Ca2+], considerably influenced the polymer viscosity. In addition, ζ potential measurements showed that the LSP altered the rock surface charge from positive toward negative and at the same time, the Ca2+ released due to mineral dissolution could modify the polymer molecule charge toward positive. This confirms that mineral dissolution impressively results in better wettability alteration performance; however, it could lead to undesirable high polymer adsorption at low salinity. These findings provide new insight into the influence of mineral dissolution on polymer performance in carbonates. Finally, forced oil displacement tests revealed that both HSP and LSP extracted approximatively the same amount of oil. The HSP could enhance the oil recovery through mobility control. By contrast, wettability alteration could take part in the improvement of oil recovery at LSP, as proved by spontaneous imbibition tests, along with mobility control. Despite possessing high wettability alteration potential, LSP could not yield very high recovery because of its low accessibility into the porous medium. Shearing of the LSP was found effective in improving oil recovery through enhancing the polymer accessibility. This will lead us to simply say that polymer accessibility into carbonates is crucial for the success of the wettability alteration and mobility control processes, which is remarkably important not only for this specific study but also for other various polymer EOR applications.

Background Diagnosis and treatment of prostate cancer is associated with anxiety, fear, and depression in up to one-third of men. Yoga improves health-related quality of life (QoL) in patients with several types of cancer, but evidence of its efficacy in enhancing QoL is lacking in prostate cancer. Methods In this randomized controlled study, 29 men newly diagnosed with localized prostate cancer were randomized to yoga for 6 weeks (n = 14) or standard-of-care (n = 15) before radical prostatectomy. The primary outcome was self-reported QoL, assessed by the Expanded Prostate Index Composite (EPIC), Functional Assessment of Cancer Therapy-Prostate (FACT-P), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT–F), Functional Assessment of Cancer Therapy-General (FACT-G) at baseline, preoperatively, and 6 weeks postoperatively. Secondary outcomes were changes in immune cell status and cytokine levels with yoga. Results The greatest benefit of yoga on QoL was seen in EPIC-sexual (mean difference, 8.5 points), FACIT-F (6.3 points), FACT-Functional wellbeing (8.6 points), FACT-physical wellbeing (5.5 points), and FACT-Social wellbeing (14.6 points). The yoga group showed increased numbers of circulating CD4+ and CD8+ T-cells, more production of interferon-gamma by natural killer cells, and increased Fc receptor III expression in natural killer cells. The yoga group also showed decreased numbers of regulatory T-cells, myeloid-derived suppressor cells, indicating antitumor activity, and reduction in inflammatory cytokine levels (granulocyte colony-stimulating factor [0.55 (0.05–1.05), p = 0.03], monocyte chemoattractant protein [0.22 (0.01–0.43), p = 0.04], and FMS-like tyrosine kinase-3 ligand [0.91 (−0.01, 1.82), p = 0.053]. Conclusions Perioperative yoga exercise improved QoL, promoted an immune response, and attenuated inflammation in men with prostate cancer. Yoga is feasible in this setting and has benefits that require further investigation. Trial registration clinicaltrials.org (NCT02620033).

There are currently fewer than ten antifungal drugs in clinical development, but new fungal strains, which are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains, compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or haemolytic properties at similar concentrations. The structures of 21 metal complexes which display high antifungal activity (MIC ≤ 1.25 µM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been evaluated for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larvae model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivo G. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.

Objectives To compare between the effectiveness and safety of two different daily doses of vaginal progesterone (400 vs. 200 mg) in the prevention of preterm labor in twin pregnancy. Methods This is a prospective single-blinded randomized controlled trial conducted on 100 primi-gravida who had twin pregnancy and attended the antenatal clinic of a University hospital. They were equally and randomly allocated into two arms each containing 50 patients. Arm 1 received 400 mg and arm 2 received 200 mg vaginal progesterone daily at bed time starting from 14 weeks of pregnancy to 36 weeks. Transvaginal ultrasound was performed for assessment of the length of cervix at 14 and 22 weeks. Results Both arms of the current study were comparable regarding the cervical length at 14 and 22 weeks, mean gestational age at delivery, incidence of pre-term delivery, birth weight of the first twin. Second twin in addition to the average weight of both twins. No statistical significance differences between two arms regarding incidence of early neonatal death. NICU, mechanical ventilation, length of admission in NICU for the first twin. Second twin as well as both twins. Conclusions Vaginal progesterone treatment with different doses was tolerable, but wasn’t effective in the prevention of preterm labor in twin pregnancy.

The current investigation aimed to maximize the productivity of “Washington Navel” orange by reducing fruit splitting %, increase fruit weight and size, quality, in addition to improve marketability. So, in the 2016/2017 and 2017/2018 seasons a field experiment was carried out on a private orchard in Kafr El-Sheik governorate, Egypt. Trees were treated with Benzyladenin (BA) at 50ppm, Sytofix (CPPU) at 10ppm, GA3 at 50ppm, and GA3 combined with BA or CPPU. Plant growth regulators (PGRs) were applied three times after the full bloom stage by 15, 30 and 45 days as foliar application. Results revealed that PGRs increased quality parameters, productivity, and chlorophyll content, as well as reduced fruit splitting % and carotene content. GA3 plus CPPU gave the highest fruit fresh weight, fruit length, fruit yield, and SSC%. However, GA3+BA registered the greatest fruit diameter, chlorophyll content, TA%, vitamin C, as well as decreased fruit splitting % and carotene content. Regarding the marketing period, GA3 plus BA obtained the highest reduction % in weight loss, decayed fruit percentage, however, recorded the greatest vitamin C and chlorophyll contents. ABA results clarified that application of PGRs tended to decrease significantly its content in peel fruit, in particular, GA3 alone or combined with BA showed the lowest content of ABA in both seasons. These results will not only help researchers to understand the roles of PGRs in navel orange fruit growth, development, and productivity but can also be applied to large-scale fruit production and prolong the marketing period.

Background: Placenta accreta spectrum is a term which describes abnormal invasion of the placenta into the uterine myometrium. The first line in diagnosis is ultrasonography and magnetic resonance imaging may complement the diagnosis. Aim: The aim of the work is to assess the accuracy of shear wave elastography in predication of placental invasion in women with placental previa.Materials and Methods: This is a prospective cohort study which was conducted in Ain Shams University on 50 women with a diagnosis of anterior placenta previa and history of previous cesarean section who were pregnant at 32 weeks or more and were planned for delivery by elective cesarean section. They were subjected to ultrasonography and elastography study and the diagnosis of placenta accreta spectrum was confirmed/ excluded intraoperatively.Results: Placental separation was normal in 36% of cases, delayed in 46 % of cases, partial in 6% of cases only whereas non separation occurred in 12% of cases. elastrgraphy had a sensitivity of 73.7%, specificity of 90.3%, positive predicting value of 82.4% and negative predictive value of 84.8% in diagnosing cases with abnormal placental invasion while sensitivity, specificity positive and negative predictive value of ultrasonography in diagnosing abnormal placental invasion was 89.5%, 96.8%, 94.4% and 93.8% respectively.Conclusion: Elastography is sensitive and specific but inferior to ultrasonography in evaluating women with suspected placenta accreta spectrum but it may be useful in diagnosis of focal invasion.

Background Patients with chronic hemolytic anemias (CHA) are at a high risk for transfusion-transmitted infections. Various studies in Egypt have shown a prevalence of hepatitis C virus (HCV) infection in 24–37% of those patients. Elimination of hepatitis C virus (HCV) in patients with CHA would prevent early progression of liver disease. In this study, we aimed to assess the efficacy, safety, and tolerability of sofosbuvir (SOF) and daclatasvir (DAC) in the special population of HCV-infected patients with CHA. In this prospective study, 21 consenting hepatitis C patients were recruited and treated using ribavirin-free SOF/DAC regimen for either 12 or 24 weeks according to categorization of patients into easy or hard-to-treat in accordance with the national protocols. Sustained virological response was assessed by RT-PCR for HCV-RNA at 12 weeks post-treatment (SVR12). Any treatment-related adverse events were noted. Results All patients were adherent to treatment with no discontinuation of therapy. SVR12 was achieved in 19 out of 21 patients (90.5%). There was a significant improvement in levels of ALT (p Conclusion The results of this study substantiate the favorable efficacy, safety, and tolerability of ribavirin-free direct-acting antivirals (DAAs) in the special population of HCV-infected patients with CHA. Micro-elimination of HCV in special patient populations allows for pragmatic delivery of care to patients with co-morbid conditions who are in most need for treatment and allows for achievement of global elimination of HCV worldwide.

Reaction between bromo tricarbonyl manganese(I) and N,N′-bis(phenyl)-1,4-diaza-1,3-butadiene ligands, bearing different electron-donating and electron-withdrawing groups R = OCH3, Cl, and NO2 in the ortho- and para-positions on the phenyl substituent, afforded [MnBr(CO)3(N–N)] complexes. The influence of the character and position of the substituent on the dark stability and carbon monoxide releasing kinetics was systematically investigated and correlated with the data of the time-dependent density functional theory calculations. The combined UV/Vis and IR data clearly revealed that the aerated solutions of [MnBr(CO)3(N–N)] in either coordinating or noncoordinating solvents are dark stable and the fluctuations observed during the incubation period especially in the case of the nitro derivatives may be attributed to the exchange of the axial bromo ligand with the coordinating solvent molecules. The free ligands and nitro complexes were non-cytotoxic to HepG2 cells under both the dark and illumination conditions. In the dark, Mn(I) compounds, incorporating o-OCH3 and o-Cl, exhibited excellent cytotoxicity with IC50 values of 18.1 and 11.8 μM, while their para-substituted analogues were inactive in the dark and active upon the irradiation at 365 nm with IC50 values of 5.7 and 6.7 μM, respectively.

Incidence of intracranial hemorrhage (ICH) among children with primary immune thrombocytopenia (ITP) varies among different studies. We published data during the period of 1997-2007 of ICH in children with primary ITP, addressing risk factors and outcome. The aim of this study is to assess changes in incidence, risk factors, and outcome of ICH in children with ITP from last decade and to report the overall 20 years' experience. We compared 2008-2018 with the decade before it. Data of children with ITP and ICH during study period and ITP control cases were analyzed. Neurosurgical intervention and outcome were also reported. A total of 4340 children with primary ITP were evaluated. Twenty-five (0.63%) ICH events were reported over 2 decades. Head trauma, hematuria, and platelet counts 10 × 109/L were the risk factors mostly associated with ICH. Overall mortality was 24%, and a further 28% had neurologic sequelae. Neurosurgical intervention was done in 12% of cases with good outcome.Conclusion: Persistent platelet counts 10 × 109/L were a significant risk factor for ICH in both time periods, while head trauma and hematuria were more reported in the period of 2008-2018 as significant risk factors for ICH. Outcome was comparable in both periods. What is Known: • ICH is a rare complication of ITP; however, early recognition of risk factors and aggressive treatment might lead to complete recovery without sequalae. Platelet counts less than 10 × 109/L are the main risk factor for ICH. Few studies reported other significant risk factors. What is New: • Hematuria and head trauma are significant risk factors for ICH in ITP, in addition to having a persistently low platelet count 10 × 109/L. (more than 90 days in chronic ITP, 45 days in persistent and 21 days in acute ITP) • Combined treatment with IVIG and HDMP followed by platelet transfusion was associated with complete recovery without sequelae in almost 50% of patients.

Objective: To compare cancer-specific mortality (CSM) and all-cause mortality (ACM) between patients with and without sarcopenia who underwent radical cystectomy for bladder cancer. Materials and methods: We performed a systematic review and meta-analysis of original articles published from October 2010 to March 2019 evaluating the effect of sarcopenia on CSM and ACM. We extracted hazard ratios (HRs) and 95% confidence intervals (CIs) for CSM and ACM from the included studies. Heterogeneity amongst studies was measured using the Q-statistic and the I2 index. Meta-analysis was performed using a random-effects model if heterogeneity was high and fixed-effects models if heterogeneity was low. Results: We identified 145 publications, of which five were included in the meta-analysis. These five studies represented 1447 patients of which 453 were classified as sarcopenic and 534 were non-sarcopenic. CSM and ACM were increased in sarcopenic vs non-sarcopenic patients (HR 1.64, 95% CI 1.30–2.08, P

The lysozyme binding affinity and the electronic properties of [ReX(CO)3(terpy-κ2N1,N2)] (X = Br− and triazolateCOOCH2CH3,CF3) were reported. The triazolate complex was prepared in a [3 + 2] cycloaddition click reaction. The bromo compound reacted with lysozyme affording adducts with Re(CO)3+ fragments, while the triazolate compound persisted. A red shift of the MLCT band of the triazolate compound in progressively less polar solvents may be due to the negative solvatochromism.

This work, contains some new compounds from benzimidazole derivatives, which are synthesized by condensation of Orthophenylene diamine and Carbon disulfide resulting in 2-Mercapto-benzimidazole which is treated by alcoholic potassium hydroxide forming potassium salt of 2-mercaptobenzimidazole which reacts with different substances (alkyl chloroacetates, chloroacetic chloride, alkyl halides) also the ethoxy carbonyl methyl thiobenzimidazole reacts with different amines. In addition to chloromethyl benzimidazole which resulted from the reaction between orthophenylene diamine and chloroacetic acid, which reacted with different amines. The synthesized compound tested as analgesics and anticancer activity the new derivatives revealed moderate, strong and very strong analgesics and moderate and strong anticancer activity.

The terpyridine ligand and the Pd(ii) and Pt(ii) benzimidazole complexes exhibited selective toxicity against Cryptococcus neoformans and Candida albicans, while displaying no cytotoxicity against healthy HEK293 cells.

Background Pleural effusions are either transudate or exudate according to the biochemical analysis of aspirated pleural fluid. Thoracentesis or blind pleural biopsy may not provide a definitive diagnosis. Cryobiopsy has more successful diagnostic results than forceps biopsies with complications (only hemorrhage) during procedures. Cryobiopsy can obtain more diagnostic biopsies due to the size of the biopsies and best property in expressions of an artifact-free sample area. Results This prospective intervention study was conducted on 51 patients who were divided randomly into two groups according to the biopsy technique: Group I (cryobiopsy group): 26 patients where patients will be subjected to thoracoscopic cryobiopsy. Group II (forceps group): 25 patients where patients will be subjected to thoracoscopic forceps biopsy. To demonstrate the efficacy and safety of taking biopsy specimens from parietal pleura in undiagnosed exudative pleural effusion. In the present study, the most common thoracoscopic finding was pleural nodules in 17 (65.4%) patients of cryobiopsy and 13 (53%) patients of forceps biopsy. The mean size in cryobiopsy was 14±4.2 mm, while in forceps biopsy, it was 5±0.6 mm. The most common pathological type of malignancy was the metastatic adenocarcinoma in 30 (58.8%) patients. The diagnostic yield of rigid medical thoracoscopy was 100% in both groups. Cryobiopsy was easily interpretable in the current study as focal and diffuse hemorrhage and crush artifact/atelectasis is less in biopsy. All procedures were generally well-tolerated by the patients in both groups, cryobiopsy was a painless procedure, while forceps biopsy was registered pain in 12 (48%) patients. Conclusions Cryobiopsies of the pleura using medical rigid thoracoscopy represent a safe and painless method to take biopsy and an effective tool to obtain larger tissue samples with a safe cellular architecture.

Introduction of the propyl-sulfonic acid group at N1 of the coordinated 2-(2-pyridyl)benzimidazole ligand (L) in [RhCl(η5-C5Me5)L](CF3SO3) gives rise to a water-soluble complex, which can bind to the model protein lysozyme via non-covalent interactions. The complex shows selective moderate toxicity against Cryptococcus neoformans (MIC = 21.6–43.3 μM) and exhibits no cytotoxicity to healthy HEK293 cells.

[Image: see text] There are currently fewer than 10 antifungal drugs in clinical development, but new fungal strains that are resistant to most current antifungals are spreading rapidly across the world. To prevent a second resistance crisis, new classes of antifungal drugs are urgently needed. Metal complexes have proven to be promising candidates for novel antibiotics, but so far, few compounds have been explored for their potential application as antifungal agents. In this work, we report the evaluation of 1039 metal-containing compounds that were screened by the Community for Open Antimicrobial Drug Discovery (CO-ADD). We show that 20.9% of all metal compounds tested have antimicrobial activity against two representative Candida and Cryptococcus strains compared with only 1.1% of the >300,000 purely organic molecules tested through CO-ADD. We identified 90 metal compounds (8.7%) that show antifungal activity while not displaying any cytotoxicity against mammalian cell lines or hemolytic properties at similar concentrations. The structures of 21 metal complexes that display high antifungal activity (MIC ≤1.25 μM) are discussed and evaluated further against a broad panel of yeasts. Most of these have not been previously tested for antifungal activity. Eleven of these metal complexes were tested for toxicity in the Galleria mellonella moth larva model, revealing that only one compound showed signs of toxicity at the highest injected concentration. Lastly, we demonstrated that the organo-Pt(II) cyclooctadiene complex Pt1 significantly reduces fungal load in an in vivoG. mellonella infection model. These findings showcase that the structural and chemical diversity of metal-based compounds can be an invaluable tool in the development of new drugs against infectious diseases.