Diosmin nanocrystal gel alleviates imiquimod-induced psoriasis in rats via modulating TLR7,8/NF-κB/micro RNA-31, AKT/mTOR/P70S6K milieu, and Tregs/Th17 balance.

Diosmin is a flavonoid with promising anti-inflammatory and antioxidant properties. However, it has difficult physicochemical characteristics since its solubility demands a pH level of 12, which has an impact on the drug's bioavailability. The aim of this work is the development and characterization of diosmin nanocrystals using anti-solvent precipitation technique to be used for topical treatment of psoriasis. Results revealed that diosmin nanocrystals stabilized with hydroxypropyl methylcellulose (HPMC E15) in ratio (diosmin:polymer; 1:1) reached the desired particle size (276.9 ± 16.49 nm); provided promising colloidal properties and possessed high drug release profile. Additionally, in-vivo assessment was carried out to evaluate and compare the activities of diosmin nanocrystal gel using three different doses and diosmin powder gel in alleviating imiquimod-induced psoriasis in rats and investigating their possible anti-inflammatory mechanisms. Herein, 125 mg of 5% imiquimod cream (IMQ) was applied topically for 5 consecutive days on the shaved backs of rats to induce psoriasis. Diosmin nanocrystal gel especially in the highest dose used offered the best anti-inflammatory effect. This was confirmed by causing the most statistically significant reduction in the psoriasis area severity index (PASI) score and the serum inflammatory cytokines levels. Furthermore, it was capable of maintaining the balance between T helper (Th17) and T regulatory (Treg) cells. Moreover, it tackled TLR7/8/NF-κB, miRNA-31, AKT/mTOR/P70S6K and elevated the TNFAIP3/A20 (a negative regulator of NF-κB) expression in psoriatic skin tissues. This highlights the role of diosmin nanocrystal gel in tackling imiquimod-induced psoriasis in rats, and thus it could be a novel promising therapy for psoriasis.

A randomised trial comparing transurethral to percutaneous cystolithotripsy in boys.

OBJECTIVE: To compare the efficacy and morbidity of transurethral cystolithotripsy (TUCL) and percutaneous CL (PCCL) in the management of bladder stones in male children. PATIENTS AND METHODS: A total of 100 boys, aged <14 years with a single bladder or urethral stone of <30 mm, were randomised into two equal groups. Initial diagnostic urethro-cystoscopy and push back of urethral stones were done for patients in both groups. Patients in Group A had TUCL, while those in Group B had PCCL through a 20-F sheath using a 12-F nephroscope. The two groups were compared regarding preoperative criteria, intraoperative details, and postoperative outcomes. RESULTS: The patients in this study had a median (range) age of 36 (4-144) months and stone size of 10 (5-26) mm. There was no statistically significant difference between the two groups for preoperative criteria. The assigned procedure was successful in 48 (96%) patients in Group A and 49 (98%) in Group B (P = 1). Complications were encountered in 11 (22%) patients in Group A and five (10%) in Group B (P = 0.171). The median (range) operative time was 21.5 (4-90) min in Group A and 13 (5-70) min in Group B (P < 0.001). In all, 47 (94%) stones needed disintegration in Group A vs 22 (44%) in Group B (P < 0.001). CONCLUSION: Both techniques have comparable success and complications rates. However, PCCL has a shorter operative time and less need for stone disintegration.

Guidelines on Asset Management of Offshore Facilities for Monitoring, Sustainable Maintenance, and Safety Practices.

Recent activities in the oil and gas industry have shown an increasing need for monitoring engagements, such as in shipping, logistics, exploration, drilling, or production. Hence, there is a need to have asset management of these offshore assets (or facilities). Much of the offshore infrastructure is currently approaching or past its operational life expectancy. The study presents an overview on asset management of offshore facilities towards monitoring, safe practices, maintenance, and sustainability. This study outlines the major considerations and the steps to take when evaluating asset life extensions for an aging offshore structure (or asset). The design and construction of offshore structures require some materials that are used to make the structural units, such as offshore platform rigs, ships, and boats. Maintaining existing assets in the field and developing new platforms that are capable of extracting future oil and gas resources are the two key issues facing the offshore sector. This paper also discusses fault diagnosis using sensors in the offshore facilities. The ocean environment is constantly corrosive, and the production activities demand extremely high levels of safety and reliability. Due to the limited space and remote location of most offshore operations, producing cost-effective, efficient, and long-lasting equipment necessitates a high level of competence. This paper presents the guidelines on asset monitoring, sustainable maintenance, and safety practices for offshore structures. In this study, the management of offshore structures were also presented with some discussions on fault monitoring using sensors. It also proposes sustainable asset management approaches as guidelines that are advised, with policy implications.

Human and animal fertility studies in cystinosis reveal signs of obstructive azoospermia, an altered blood-testis barrier and a subtherapeutic effect of cysteamine in testis.

Cystinosis is an inherited metabolic disorder caused by autosomal recessive mutations in the CTNS gene leading to lysosomal cystine accumulation. The disease primarily affects the kidneys followed by extra-renal organ involvement later in life. Azoospermia is one of the unclarified complications which are not improved by cysteamine, which is the only available disease-modifying treatment. We aimed at unraveling the origin of azoospermia in cysteamine-treated cystinosis by confirming or excluding an obstructive factor, and investigating the effect of cysteamine on fertility in the Ctns-/- mouse model compared with wild type. Azoospermia was present in the vast majority of infantile type cystinosis patients. While spermatogenesis was intact, an enlarged caput epididymis and reduced levels of seminal markers for obstruction neutral α-glucosidase (NAG) and extracellular matrix protein 1 (ECM1) pointed towards an epididymal obstruction. Histopathological examination in human and mouse testis revealed a disturbed blood-testis barrier characterized by an altered zonula occludens-1 (ZO-1) protein expression. Animal studies ruled out a negative effect of cysteamine on fertility, but showed that cystine accumulation in the testis is irresponsive to regular cysteamine treatment. We conclude that the azoospermia in infantile cystinosis is due to an obstruction related to epididymal dysfunction, irrespective of the severity of an evolving primary hypogonadism. Regular cysteamine treatment does not affect fertility but has subtherapeutic effects on cystine accumulation in testis.

Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase.

Benzimidazole is an interesting scaffold constituting a main core in many anticancer agents against variable cell lines as Carbendazim (I) and Nocodazole (II). Accordingly, eighteen compounds of 2-((1H-benzoimidazol-2-yl)thio)-1-(aryl/heteroaryl)ethan-1-ones, in their sulfate salt and free forms, were designed and investigated as anticancer agents. In vitro preliminary screening of selected compounds by the National Cancer Institute (NCI) on a panel of 60 cell lines revealed renal cancer cell line (A498) as the most vulnerable cell line; accordingly, IC50 values against A498 cell line were determined for compounds with the best results. The best inhibitory activity was for compound 4a with (IC50 = 6.97 µM) compared to sunitinib as a reference drug (IC50 = 6.99 µM). Compound 4a was further subjected to cell cycle analysis that indicated the decrease in cell population in the G2/M phase when compared to the untreated control cells. In addition, it showed significant increase in the late apoptosis in Annexin-V FTIC study compared to the control cells. An enzymatic inhibitory study on compound 4a against c-Met and MAP kinases revealed its better activity against c-Met kinase with (IC50 = 0.27 µM) compared to sunitinib (IC50 = 0.18 µM). Molecular docking study was conducted to reveal the interactions of compound 4a in the active site of c-Met kinase. Computational ADME study was performed to insure that compound 4a has proper pharmacokinetic and drug-likeness properties.

Tumor-associated carbonic anhydrase isoform IX and XII inhibitory properties of certain isatin-bearing sulfonamides endowed with in vitro antitumor activity towards colon cancer.

Three series of indolinone-based sulfonamides (3a-f, 6a-f and 9a-f) were in vitro evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the investigated sulfonamides displayed single- or double-digit nanomolar inhibitory activities towards both hCA IX (KIs: 6.2-64.8 nM) and XII (KIs: 7.1-55.6 nM) isoforms. All sulfonamides (3a-f, 6a-f and 9a-f) were in vitro examined for their potential anticancer activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines. Sulfonamide 9e was found to be the most potent counterpart against HCT-116 (IC50 = 3.67 ±â€¯0.33 µM). Sulfonamide 9e displayed good selectivity profile for inhibition of the tumor-associated isoforms (CAs IX & XII) over the off-target cytosolic CAs I and II. 9e was screened for cell cycle disturbance and apoptosis induction in HCT-116 cells. It was found to persuade cell cycle arrest at G2-M stage as well as alter the Sub-G1 phase. Also, 9e induced the intrinsic apoptotic mitochondrial pathway in HCT-116 cells via down-regulation of the anti-apoptotic protein Bcl-2 level with concurrent boosting the pro-apoptotic Bax, caspase-9, caspase-3, cytochrome C and p53 levels.

Experience of a Tertiary-Level Urology Center in the Clinical Urological Events of Rare and Very Rare Incidence. III. Psychourological Events: 1. Psychic Anuria.

INTRODUCTION: Psychic anuria is an old term, referring to a very rare psycho-urological event that has scarcely been studied so far. MATERIALS AND METHODS: A retrospective study of the patients with psychic anuria presented to Assiut Urology and Nephrology Hospital during the period July 1991-June 2016 was done. Psychic anuria was defined, and the demographic and clinical characteristics including the methods of diagnosis and management were studied. RESULTS: Of more than 3,800 cases of anuria, 9 female patients (0.24%) experienced psychic anuria in the age range of 17-43 years. Cardinal clinical findings included anuria for 36-72 h with absence of organic causes and normal renal function tests. Psychosocial risk factors were reported in the 9 cases. Anuria was documented by reliable history (56%) or observable urine collection (44%). Diagnosis was done by exclusion, where the investigations revealed no organic causes. Seven cases responded to the placebo intervention and 2 cases were self-limiting and resolved spontaneously. CONCLUSIONS: Psychic anuria is an extremely rare urological emergency that presents, mainly, in young adult females with unknown mechanisms. Renal vasoconstriction following psychosocial stressors is suggested. It is diagnosed by exclusion and resolves spontaneously or responds to placebo intervention as a mental distraction technique.

Is Tamsulosin Effective after Shock Wave Lithotripsy for Pediatric Renal Stones? A Randomized, Controlled Study.

PURPOSE: We assessed the effect of tamsulosin as an adjunctive therapy after shock wave lithotripsy for pediatric single renal pelvic stones. MATERIALS AND METHODS: A total of 120 children with a unilateral single renal pelvic stone were included in a prospective randomized, controlled study. All children were randomized to 2 equal groups. Group 1 received tamsulosin (0.01 mg/kg once daily) as adjunctive therapy after shock wave lithotripsy in addition to paracetamol while group 2 received paracetamol only. Stone clearance was defined as no renal stone fragments or fragments less than 3 mm and no pelvicalyceal system dilatation. RESULTS: Our study included 69 boys and 51 girls with a median age of 3.5 years and a median stone size of 1.2 cm. There was no statistically significant difference between groups 1 and 2 in stone or patient criteria. Of the children 99 (82.5%) achieved stone clearance after the first session, including 50 in group 1 and 49 in group 2. All children in each group were cleared of stones after the second session. The overall complication rate was 14.2%. There was no statistically significant difference between single session stone clearance rates (p = 0.81) and complications rates (p = 0.432) in either group. On multivariate analysis using logistic regression smaller stone size (p = 0.016) and radiopaque stones (p = 0.019) were the only predictors of stone clearance at a single shock wave lithotripsy session. Tamsulosin therapy did not affect stone clearance (p = 0.649). CONCLUSIONS: Tamsulosin does not seem to improve renal stone clearance. Smaller and radiopaque renal stones have more chance of clearance after shock wave lithotripsy for pediatric single renal pelvic stones.

Untargeted Identification of Wood Type-Specific Markers in Particulate Matter from Wood Combustion.

Residential wood combustion emissions are one of the major global sources of particulate and gaseous organic pollutants. However, the detailed chemical compositions of these emissions are poorly characterized due to their highly complex molecular compositions, nonideal combustion conditions, and sample preparation steps. In this study, the particulate organic emissions from a masonry heater using three types of wood logs, namely, beech, birch, and spruce, were chemically characterized using thermal desorption in situ derivatization coupled to a GCxGC-ToF/MS system. Untargeted data analyses were performed using the comprehensive measurements. Univariate and multivariate chemometric tools, such as analysis of variance (ANOVA), principal component analysis (PCA), and ANOVA simultaneous component analysis (ASCA), were used to reduce the data to highly significant and wood type-specific features. This study reveals substances not previously considered in the literature as meaningful markers for differentiation among wood types.

Two new mini-slings compared with transobturator tension-free vaginal tape for treatment of stress urinary incontinence: A 1-year follow-up randomized controlled trial.

AIM: The aim of this study was to compare the outcome of two single-incision mini-slings (the Contasure-Needleless [C-NDL] and the endopelvic free anchorage) with the standard midurethral transobturator tension-free vaginal tape (TVT-O) procedure. METHODS: A double blind randomized controlled study was conducted at Ain Shams University Maternity Hospital from August 2014 until July 2015. A total of 209 patients were randomized into three groups. The first group underwent the TVT-O procedure, the second group underwent the endopelvic free anchorage procedure and the third group underwent the C-NDL procedure. Patients were followed up for 12 months in terms of subjective cure, objective cure, and complications rate. RESULTS: After 12 months of follow-up, there were no differences among the three groups in terms of objective cure rate, subjective cure rate, patient satisfaction, or incidence of complications (de novo urge, hemorrhage, infection, and mesh erosion). The C-NDL was associated with a shorter operative time (P < 0.001) and less blood loss (P = 0.021) than the standard TVT-O. CONCLUSION: The new single-incision mini-slings showed similar efficacy and patient acceptance to that of the standard TVT-O for up to 12 months postoperatively with no difference in the complications rate. The C-NDL is associated with shorter operative time and less blood loss.

The composition of cigarette smoke determines inflammatory cell recruitment to the lung in COPD mouse models.

COPD (chronic obstructive pulmonary disease) is caused by exposure to toxic gases and particles, most often CS (cigarette smoke), leading to emphysema, chronic bronchitis, mucus production and a subsequent decline in lung function. The disease pathogenesis is related to an abnormal CS-induced inflammatory response of the lungs. Similar to active (mainstream) smoking, second hand (sidestream) smoke exposure severely affects respiratory health. These processes can be studied in vivo in models of CS exposure of mice. We compared the acute inflammatory response of female C57BL/6 mice exposed to two concentrations [250 and 500 mg/m3 TPM (total particulate matter)] of sidestream and mainstream CS for 3 days and interpreted the biological effects based on physico-chemical differences in the gas and particulate phase composition of CS. BAL (bronchoalveolar lavage fluid) was obtained to perform differential cell counts and to measure cytokine release. Lung tissue was used to determine mRNA and protein expression of proinflammatory genes and to assess tissue inflammation. A strong acute inflammatory response characterized by neutrophilic influx, increased cytokine secretion [KC (keratinocyte chemoattractant), TNF-α (tumour necrosis factor α), MIP-2 (macrophage inflammatory protein 2), MIP-1α and MCP-1 (monocyte chemoattractant protein-1)], pro-inflammatory gene expression [KC, MIP-2 and MMP12 (matrix metalloproteinase 12)] and up-regulated GM-CSF (granulocyte macrophage colony-stimulating factor) production was observed in the mainstream model. After sidestream exposure there was a dampened inflammatory reaction consisting only of macrophages and diminished GM-CSF levels, most likely caused by elevated CO concentrations. These results demonstrate that the composition of CS determines the dynamics of inflammatory cell recruitment in COPD mouse models. Different initial inflammatory processes might contribute to COPD pathogenesis in significantly varying ways, thereby determining the outcome of the studies.

Combined on-demand sildenafil citrate and tramadol hydrochloride is an effective and safe treatment for premature ejaculation: A randomized placebo-controlled double-blind clinical trial.

Background: Premature ejaculation (PE) is a common sexual dysfunction that harms both sex partners. Aim: To evaluate the safety, efficacy and impact on sexual satisfaction scores of the combined use of tramadol HCl and sildenafil citrate for the treatment of PE. Methods: One hundred and sixty otherwise healthy males complaining of PE (primary/secondary) were enrolled in this randomized, double-blind, placebo-controlled study. Only 155 patients (age range 22-48 years) completed the study. Of them, 81 patients had primary PE, and 74 had secondary PE. The comparative groups included the placebo group (n = 34), sildenafil citrate 50 mg group (n = 39), tramadol HCl 100 mg group (n = 40), and the combination therapy group (n = 42). The treatment duration for all groups was 10 weeks. Outcomes: This combination is safe and effective. Results: Five patients discontinued the study, all from the placebo group, due to a lack of improvement over the treatment course. No significant differences were reported between groups before treatment as regards Intravaginal ejaculatory Latency Time (p = 0.8), satisfaction score (p = 0.7), age (p = 0.9), or duration of marriage (p = 0.9). There was a significant improvement in IELT after treatment with a placebo (p = 0.0001), associated with an insignificant improvement in satisfaction score (p = 1.0). In the other three groups, there was a significant improvement in IELT after treatment (p = 0.0001 for all), which coincided with a significant improvement in satisfaction scores in all three groups (p = 0.0001 for all). Clinical Implications: We recommend this combination in the treatment of premature ejaculation. Strengths: It is a prospective randomized double-blind placebo-controlled clinical trial. Limitations: Limited number of participants. Conclusion: Combined therapy of PE, whether primary or secondary, with sildenafil citrate 50 mg and tramadol HCl 100 mg is safe and effective; and its therapeutic effect is superior to the utilization of either agent alone.

IVUS-guided versus OCT-guided PCI among patients presenting with acute coronary syndrome.

BACKGROUND: Intravascular imaging modalities such as intravascular ultrasound (IVUS) and, more recently, optical coherence tomography (OCT) improved the visualization of coronary anatomy and plaque pathology. We aimed to compare the procedural and short-term outcomes between IVUS-guided and OCT-guided percutaneous coronary interventions (PCIs) in patients with acute coronary syndrome (ACS). METHODS: In the present retrospective study, we reviewed the data of 50 patients who had IVUS-guided PCI and 50 patients who had OCT-guided PCI for ACS between January 2020 and June 2021. Intravascular imaging was done before and after stenting. Both groups were compared in terms of minimal luminal area (MLA), stent dimensions, final minimal stent area (MSA) and stent expansion as well as negative angiographic outcomes. Patients were followed for six months to record major adverse cardiac events (MACE). RESULTS: The patients' mean age was 57 ± 13 years with male predominance (78%). The radiation time and dose were significantly higher among IVUS group. Pre-stenting MLA was significantly higher in IVUS group (2.63 mm vs. 2.22 mm in OCT, P = 0.013). Stent expansion was significantly higher among OCT group (97% vs. 93% in IVUS group, P = 0.001) with no significant difference between both groups regarding MSA [mm2] (8.88 ± 2.87 in IVUS vs. 8.1 ± 2.76 in OCT, P = 0.169). No significant difference between both groups was noted regarding contrast volume, edge dissection, tissue prolapse, and no reflow. The rates of six-month MACE were significantly higher in the IVUS group. CONCLUSIONS: OCT-guided PCI in ACS is safe and is associated with similar MSA to that of IVUS-guided PCI. Future randomized trials are needed to confirm these findings.

Medium- and time-related effects on hypothermic storage of rat testicular cells.

OBJECTIVE: Testicular samples obtained for fertility preservation often need to be transported between clinics. This study aimed to mimic this short-term hypothermic storage (4-8 °C) and explore the impact of these conditions and the transport medium composition on prepubertal rat testicular tissue samples. METHODS: Testicular tissue samples obtained from seven days post-partum rats were transferred to six compositionally different basal culture media and a balanced salt solution, which had been kept at 4-8 °C prior to transfer. The samples were preserved for either 12 or 24 hours in these hypothermic conditions. The potential effects of the short-term storage were evaluated by assessing the morphology, measuring the testosterone levels by radioimmunoassay and analysing 96 genes with TaqMan Low-Density Arrays. Summarizing results: Levels of gene expression related to energy, apoptosis and angiogenesis pathways were altered after hypothermic storage for 12 and especially 24 hours. We observed only minor differences in gene expression profiles for germ and testicular somatic cells, and no differences in tissue morphology and testosterone production levels. CONCLUSIONS: Short-term hypothermic storage of testicular tissue with a maximum duration of 24 hours does not affect the overall expression profile of testicular cell-specific genes; however, in a minor way, it affects the expression of specific cellular genes.

Endometrial Progesterone and Estrogen Receptors in Relation to Hormonal Levels in Women with Unexplained Recurrent Miscarriage.

OBJECTIVE: Recurrent miscarriage has been linked to hormonal disturbance due to dysregulation of its receptors rather than to the availability of the hormone. We aimed to investigate endometrial expression of progesterone and estrogen receptors in relation to serum and endometrial hormonal levels in unexplained recurrent miscarriage. METHODS: The present case control study included 20 cases with unexplained recurrent miscarriage and 20 parous women as controls. Ovulation was confirmed using an ovulation kit and 10 to 12 days after detecting the urinary luteinizing hormone surge, all women were subjected to a blood sample and to an endometrial biopsy. Progesterone and estrogen levels were measured in serum and in endometrial tissue and receptor concentrations were in the endometrial sample. RESULTS: Women with recurrent miscarriage showed significantly lower concentration of receptors in both the cytoplasm and the nucleus of endometrial tissue compared with controls. The nuclear/cytoplasm ratio of progesterone receptor was significantly higher in cases compared with controls, implicating that recurrent miscarriage is probably linked to nongenomic activity of the hormone; this was also significant for estrogen receptor. Serum progesterone and estrogen hormonal levels were comparable between groups while both hormones were significantly reduced in the endometrium of recurrent miscarriage cases. Receptors significantly correlated with endometrial hormonal level but not to serum level. CONCLUSION: Recurrent miscarriage might be linked to reduced endometrial progesterone and estrogen receptors and appears to be more related to nongenomic activity of progesterone. Endometrial receptors expression correlates to tissue hormonal level rather than to serum hormonal level.

Preemptive living donor kidney transplantation: Access, fate, and review of the status in Egypt.

BACKGROUND: Preemptive living donor kidney transplantation (PLDKT) is recommended as the optimal treatment for end-stage renal disease. AIM: To assess the rate of PLDKT among patients who accessed KT in our center and review the status of PLDKT in Egypt. METHODS: We performed a retrospective review of the patients who accessed KT in our center from November 2015 to November 2022. In addition, the PLDKT status in Egypt was reviewed relative to the literature. RESULTS: Of the 304 patients who accessed KT, 32 patients (10.5%) had preemptive access to KT (PAKT). The means of age and estimated glomerular filtration rate were 31.7 ± 13 years and 12.8 ± 3.5 mL/min/1.73 m2, respectively. Fifty-nine patients had KT, including 3 PLDKTs only (5.1% of total KTs and 9.4% of PAKT). Twenty-nine patients (90.6%) failed to receive PLDKT due to donor unavailability (25%), exclusion (28.6%), regression from donation (3.6%), and patient regression on starting dialysis (39.3%). In multivariate analysis, known primary kidney disease (P = 0.002), patient age (P = 0.031) and sex (P = 0.001) were independent predictors of achievement of KT in our center. However, PAKT was not significantly (P = 0.065) associated with the achievement of KT. Review of the literature revealed lower rates of PLDKT in Egypt than those in the literature. CONCLUSION: Patient age, sex, and primary kidney disease are independent predictors of achieving living donor KT. Despite its non-significant effect, PAKT may enhance the low rates of PLDKT. The main causes of non-achievement of PLDKT were patient regression on starting regular dialysis and donor unavailability or exclusion.

Reasons and effects of the decline of willing related potential living kidney donors.

BACKGROUND: Although the availability of related living donors (LDs) provides a better chance for receiving kidney transplantation (KT), the evaluation protocols for LD selection remain a safeguard for the LD's safety. These protocols are variable from one center to another, resulting in variable rates of decline of the potential LDs (PLDs). The decline of willing PLDs may occur at any stage of evaluation, starting from the initial contact and counseling to the day of operation. AIM: To identify the causes of the decline of PLDs, the predictors of PLD candidacy, and the effect on achieving LDKT. METHODS: A retrospective study was performed on the willing PLDs who attended our outpatient clinic for kidney donation to their related potential recipients between October 2015 and December 2022. The variables influencing their candidacy rate and the fate of their potential recipients were studied. Two groups of PLDs were compared: Candidate PLDs after a completed evaluation vs non-candidate PLDs with a complete or incomplete evaluation. A multivariate logistic regression was performed to assess the factors contributing to the achievement of PLD candidacy. RESULTS: Of 321 willing PLDs, 257 PLDs (80.1%) accessed the evaluation to variable extents for 212 potential recipients, with a mean age (range) of 40.5 ± 10.4 (18-65) years, including 169 females (65.8%). The remaining 64 PLDs (19.9%) did not access the evaluation. Only 58 PLDs (18.1%) succeeded in donating, but 199 PDLs (62.0%) were declined; exclusion occurred in 144 PLDs (56.0%) for immunological causes (37.5%), medical causes (54.9%), combined causes (9.7%), and financial causes (2.1%). Regression and release occurred in 55 PLDs (17.1%). The potential recipients with candidate PLDs were not significantly different from those with non-candidate PLDs, except in age (P = 0.041), rates of completed evaluation, and exclusion of PLDs (P < 0.001). There were no factors that independently influenced the rate of PLD candidacy. Most patients who failed to have KT after the decline of their PLDs remained on hemodialysis for 6 mo to 6 years. CONCLUSION: The rate of decline of willing related PLDs was high due to medical or immunological contraindications, release, or regression of PLDs. It reduced the chances of high percentages of potential recipients in LDKT.

Assessment of donor specific IgG Anti-HLA subclasses before and after kidney transplantation in Upper Egypt: A Single Center Study.

Donor specific antibodies (DSAs) are known as the leading cause of antibody mediated rejection (AMR), graft loss in kidney transplant (KT) recipients. DSAs characteristics, as immunoglobulin (Ig) classes, subclasses, and strength, are important to assess the immunological risk, early prediction of AMR, and therefor proper management. This longitudinal, case control study included 32 KT recipients at Assiut University Urology Hospital and 10 age and sex matched normal subjects as the control group. Total IgG, its subclasses and anti-human leukocyte antigen (anti-HLA) panel reactive antibody (PRA) were detected pre-transplantation (pre-TX), at 6-12- and 24-36-months post-TX. Rejection occurred in 4 recipients, 3 of them had high total IgG, IgG1 and/or IgG3. IgG2 and IgG4 were normal in all recipients. There were preformed anti-DSAs antibodies in 3/32 recipients (9.4%). Of these, two recipients became negative with no rejection occurred. The third recipient had high post-TX mean fluorescence intensity (MFI) and AMR occurred. The pre-TX PRA was negative in 29/32 recipients (90.6%). The PRA was negative in 8/29 recipients (27.6%) and the remaining 21/29 recipients (72.4%) developed de novo DSAs post-TX (MFI < 3000->10000). Rejection occurred with both low and high MFI. In 11 recipients, anti-HLA class I and II were not different between pre-TX, 3-6- and 24-36 months post-TX with no rejection occurred. The frequency and median levels of total IgG, IgG1 and IgG3 were increased in all recipients 24-36 months post-TX when compared with their levels pre-TX and 6-12 months post-TX in the 11 recipients and with the control group. The graft survival time significantly decreased in recipients with positive post-TX class I PRA. In conclusion, preformed DSAs may persist post-TX or turn negative. De novo DSAs developed post-TX even in non-sensitized recipients. Serum total IgG, IgG1 and IgG3 frequency increase 2-3 years post-TX.

Systems toxicology of complex wood combustion aerosol reveals gaseous carbonyl compounds as critical constituents.

Epidemiological studies identified air pollution as one of the prime causes for human morbidity and mortality, due to harmful effects mainly on the cardiovascular and respiratory systems. Damage to the lung leads to several severe diseases such as fibrosis, chronic obstructive pulmonary disease and cancer. Noxious environmental aerosols are comprised of a gas and particulate phase representing highly complex chemical mixtures composed of myriads of compounds. Although some critical pollutants, foremost particulate matter (PM), could be linked to adverse health effects, a comprehensive understanding of relevant biological mechanisms and detrimental aerosol constituents is still lacking. Here, we employed a systems toxicology approach focusing on wood combustion, an important source for air pollution, and demonstrate a key role of the gas phase, specifically carbonyls, in driving adverse effects. Transcriptional profiling and biochemical analysis of human lung cells exposed at the air-liquid-interface determined DNA damage and stress response, as well as perturbation of cellular metabolism, as major key events. Connectivity mapping revealed a high similarity of gene expression signatures induced by wood smoke and agents prompting DNA-protein crosslinks (DPCs). Indeed, various gaseous aldehydes were detected in wood smoke, which promote DPCs, initiate similar genomic responses and are responsible for DNA damage provoked by wood smoke. Hence, systems toxicology enables the discovery of critical constituents of complex mixtures i.e. aerosols and highlights the role of carbonyls on top of particulate matter as an important health hazard.

Differentiation of Human-Induced Pluripotent Stem Cells (hiPSCs) into Human Primordial Germ Cell-like Cells (hPGCLCs) In Vitro.

In humans, germ cells are specified in the extraembryonic yolk sac, at proximity of allantois, around the second week of gestation. Derivation of human germ cell-like cells (hPGCLCs) from human pluripotent cells in vitro is of a great importance for research purposes, such as disease modeling, or studying the early human germ cell development and the effect of environmental factors on this development. As it is not possible to access human embryos at early developmental stages, a two-step protocol has been proposed by Sasaki and colleagues to differentiate hPGCLCs in vitro from human pluripotent stem cells. Here, we report a detailed protocol for in vitro hPGCLCs differentiation from induced pluripotent stem cells (iPSCs).