Expanding chalcogen bonds in thiophenes to interactions with halogens.

Compounds containing the thiophene moiety find several applications in physics and chemistry, such as electrical conduction, which depends on specific conformations to properly exhibiting the desired properties. In turn, chalcogen bonding has found to modulate the conformation of some N-thiophen-2-ylfomamides. Since halogens participate in a kin interaction (halogen bonding) and are abundant in agrochemicals, pharmaceuticals, and materials, we have quantum-chemically explored the interaction between organic halogen and thiophene as a conformational modulator in some model compounds. Although such interaction indeed appears, as demonstrated by atoms in molecules and natural bond orbital analysis, it is inefficient to control the conformational equilibrium. An energy decomposition analysis scheme demonstrated that halomethane and thiophene tend to move away from one another due to a core component (Pauli repulsion and exchange), which is mainly due to a deformation term. Therefore, chalcogen bonds with halogens appear weaker than with other chalcogens.

Multi-Institutional Outcomes of Dorsal Onlay Buccal Mucosal Graft Urethroplasty in Patients With Postprostatectomy, Postradiation Anastomotic Stenosis.

PURPOSE: The treatment of urethral stenosis after a combination of prostatectomy and radiation therapy for prostate cancer is understudied. We evaluate the clinical and patient-related outcomes after dorsal onlay buccal mucosal graft urethroplasty (D-BMGU) in men who underwent prostatectomy and radiation therapy. MATERIALS AND METHODS: A multi-institutional, retrospective review of men with vesicourethral anastomotic stenosis or bulbomembranous urethral stricture disease after radical prostatectomy and radiation therapy from 8 institutions between 2013 to 2021 was performed. The primary outcomes were stenosis recurrence and development of de novo stress urinary incontinence. Secondary outcomes were surgical complications, changes in voiding, and patient-reported satisfaction. RESULTS: Forty-five men were treated with D-BMGU for stenosis following prostatectomy and radiation. There was a total of 7 recurrences. Median follow-up in patients without recurrence was 21 months (IQR 12-24). There were no incidents of de novo incontinence, 28 patients were incontinent pre- and postoperatively, and of the 6 patients managed with suprapubic catheter preoperatively, 4 were continent after repair. Following repair, men had significant improvement in postvoid residual, uroflow, International Prostate Symptom Score, and International Prostate Symptom Score quality-of-life domain. Overall satisfaction was +2 or better in 86.6% of men on the Global Response Assessment. CONCLUSIONS: D-BMGU is a safe, feasible, and effective technique in patients with urethral stenosis after a combination of prostatectomy and radiation therapy. Although our findings suggest this technique may result in lower rates of de novo urinary incontinence compared to conventional urethral transection and excision techniques, head-to-head comparisons are needed.

Management of the Devastated Bladder Outlet after Prostate CANCER Treatment.

PURPOSE OF REVIEW: Devastating complications of the bladder outlet resulting from prostate cancer treatments are relatively uncommon. However, the combination of the high incidence of prostate cancer and patient longevity after treatment have raised awareness of adverse outcomes deteriorating patients' quality of life. This narrative review discusses the diagnostic work-up and management options for bladder outlet obstruction resulting from prostate cancer treatments, including those that require urinary diversion. RECENT FINDINGS: The devastated bladder outlet can be a consequence of the treatment of benign conditions, but more frequently from complications of pelvic cancer treatments. Regardless of etiology, the initial treatment ladder involves endoluminal options such as dilation and direct vision internal urethrotomy, with or without intralesional injection of anti-fibrotic agents. If these conservative strategies fail, surgical reconstruction should be considered. Although surgical reconstruction provides the best prospect of durable success, reconstructive procedures are also associated with serious complications. In the worst circumstances, such as prior radiotherapy, failed reconstruction, devastated bladder outlet with end-stage bladders, or patient's severe comorbidities, reconstruction may neither be realistic nor justified. Urinary diversion with or without cystectomy may be the best option for these patients. Thorough patient counseling before treatment selection is of utmost importance. Outcomes and repercussions on quality of life vary extensively with management options. Meticulous preoperative diagnostic evaluation is paramount in selecting the right treatment strategy for each individual patient. The risk of bladder outlet obstruction, and its severest form, devastated bladder outlet, after treatment of prostate cancer is not negligible, especially following radiation. Management includes endoluminal treatment, open or robot-assisted laparoscopic reconstruction, and urinary diversion in the worst circumstances, with varying success rates.

Island hitchhikers: pathogen agents of Madeira and Azores ticks.

Ticks are blood-sucking arthropods that can transmit pathogens to their host. As insular ecosystems can enhance tick-host interactions, this study aimed to understand tick diversity, pathogen presence, and their respective associations in the Azores and Madeira archipelagos. Unfed or partially engorged ticks (n = 120) were collected from 58 cats and dogs in the Azores (n = 41 specimens) and Madeira (n = 79 specimens) from November 2018 to March 2019. Vector identification was based on morphology and molecular criteria. For pathogen sequencing, 18S gene fragment for Babesia/Hepatozoon and gltA for Rickettsia were performed. Sequence data was explored using BLAST and BLAST and phylogenetic inference tools. In the Azores, Ixodes hexagonus, I. ventalloi, and Rhipicephalus sanguineus (n = 6; 14.6%, n = 6; 14.6%, and n = 29; 70.7% respectively) were found and in Madeira I. ricinus and R. sanguineus (n = 78, 98.7%; and n = 1, 1.3%; respectively) were identified. Tick COI markers confirmed species highlighting confirmation of R. sanguineus s.s. and genotype A of I. ventalloi. In the Azores Islands, the detected Rickettsia massiliae was linked to R. sanguineus (dogs and cats) and I. hexagonus (dogs), and in Madeira Island, R. monacensis (dogs) and Hepatozoon silvestris (cats) were found associated with I. ricinus. Further, I. ventalloi presence in the Azores expands west its known range, and Hepatozoon silvestris in Madeira may suggest that I. ricinus could have a role as a potential vector. Finally, as R. massiliae and R. monacensis presence underlines public health risks, surveillance by health authorities is crucial as pathogen-tick interactions may drive disease spread, therefore monitoring remains pivotal for disease prevention.

Fluorinated benzoxazinones designed via MIA-QSAR, docking and molecular dynamics as protoporphyrinogen IX oxidase inhibitors.

BACKGROUND: Fluorine plays a significant role in agrochemical science because approximately 25% of herbicides licensed worldwide contain this element. In a pool of previously synthesized benzoxazinones, some compounds contained fluorine and demonstrated inhibitory activities against protoporphyrinogen IX oxidase (PPO). Therefore, three data sets of benzoxazinone derivatives with known inhibitory activity against PPO were employed to build a multivariate image analysis applied to a quantitative structure-activity relationships (MIA-QSAR) model to identify improved analogs with at least one fluorine substituent. RESULTS: The QSAR model was vigorously validated and demonstrated to be highly predictive (r2 = 0.85, q2 = 0.71, and r2 pred = 0.88); thus, the model can provide reliable estimations for the PPO inhibitory activity of unknown derivatives. From these compounds, a couple of N-substituted benzoxazinones that contained the -CH2CHF2 group were found with predicted pKi values larger than 8 (Ki in mol L-1) and higher lipophilicity than the most active data set compounds. In addition, we carried out a systematic investigation of the binding mode of PPO by performing computational docking followed by molecular dynamics simulations. The proposed binding mode was consistent with experimental studies, and several potential key residues were identified. CONCLUSION: Two new proposed benzoxazinones exhibited better performance than compounds of the data set, and fluorine substituents played pivotal roles in describing the biological activities. © 2024 Society of Chemical Industry.

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines.

Selective fluorination of the pyrrolidine ring in proline motifs has been found to induce significant conformational changes that impact the structure and biological roles of modified peptides and proteins. Vicinal difluorination of fluoroproline, for example, in (3S,4R)-3,4-difluoroproline, serves to mitigate the inherent conformational bias of the pyrrolidine ring by inducing stereoelectronic effects that attenuate this conformational bias. In this investigation, we present a quantumchemical analysis of the conformational equilibrium and effects that are induced in difluorinated pyrrolidines, with a particular focus on exploring the impact of gauche and anomeric effects on the conformer stabilities of different stereo- and regioisomers. Initially, we conducted a benchmark assessment comparing the optimal density functional theory method with coupled cluster with single and double excitations (CCSD) calculations and crystallographic data using the 3-fluoropyrrolidinium cation and 3-fluoropyrrolidine. Subsequently, we explored the relative energy of all favored conformations of all different stereoisomers of 2,3-, 2,4-, and 3,4-difluoropyrrolidines at the B3LYP-D3BJ/6-311++G** level. A generalized anomeric effect, arising from nN→σ*CF electron delocalization, is particularly important in modulating the energetics of the α-fluoro isomers and imparts a strong conformational bias. In contrast, the fluorine gauche effect assumes a secondary role, as it is overshadowed by steric and electrostatic interactions, referred to as Lewis interactions from a natural bond orbital perspective.

A first look at sea-lavenders genomics - can genome wide SNP information tip the scales of controversy in the Limonium vulgare species complex?

BACKGROUND: Sea-lavenders (Limonium Mill., Plumbaginaceae) are a cosmopolitan group of diploid and polyploid plants often adapted to extreme saline environments, with a mostly Tethyan distribution, occurring in the Mediterranean, Irano-Turanian, Euro-Siberian and in the New World. The halophylic Limonium vulgare polyploid complex in particular, presents a large distribution throughout extreme salt-marsh habitats and shows little morphological but high taximetric variation, frequently blurring species delimitation. In this work we pursue three main goals: assert whether SNP data from polyploid individuals has the resolution to distinguish the seven sampled species, to better understand how genetically structured Limonium vulgare is, and attempt to identify specific molecular mechanisms for the differentiation between L. maritimum and L. vulgare. For this purpose, 95 individuals were genotyped using Genotyping by Sequencing (GBS), which were assembled as two independent datasets using IPYRAD. All analyses performed downstream of assembly were fully automated. Phylogenetic inference, PCA, and admixture plots were used to infer answers to the study's main goals. RESULTS: Close to 10,000 SNPs were obtained for each dataset. Phylogenetic analyses reveal that polyploid data can be used to infer species relationships. Population structure analyses suggest a genetically structured L. vulgare. A set of 34 SNPs were found to be fully segregated between L. vulgare and L. maritimum, two of which are potentially linked to proteins that might be involved in the speciation process. CONCLUSION: Despite polyploid data analyses shortcomings, GBS generated SNPs have the resolution to discern all seven included species. Limonium vulgare revealed pronounced genetic structure along a geographical north-south cline. L. maritimum always appears as a distinct genetic entity. Segregated SNPs between L. vulgare and L. maritimum indicate salinity response and morphological trait control genes as potentially interesting to follow up for studying these species' divergence process.

Theoretical Exploitation of 1,2,3,4,5,6-Hexachloro- and 1,2,3,4,5,6-Hexafluorocyclohexane Isomers as Biologically Active Compounds.

Hexachlorocyclohexanes (HCHs) have been widely explored as biological compounds during the last century. However, most of them were banned due to their potential toxicity in humans, animals, and the environment. Revisiting HCHs to explore their biological activity while improving key features is valuable and may lead to a new class of pesticides that utilizes the biological response of HCHs without their toxic characteristics. In this sense, the fluorine atom can be a possible alternative since a large number of therapeutics and agrochemicals have been developed with this halogen in their structure. We have evaluated herein the conformational behavior of HCHs and their bioisosteric fluorinated compounds, namely, hexafluorocyclohexanes (HFHs), through quantum-chemical calculations. We also explored the potential of the HCH and HFH isomers as biological compounds by docking them inside three possible targets. It was demonstrated that HCH and HFH have similar ligand-protein interactions with three pockets: the picrotoxin and barbiturate sites of the GABAA receptor and the ryanodine receptor. The results support HFHs as possible alternatives for HCHs since the replacement of Cl with F does not forfeit the main ligand-protein interactions. Finally, we demonstrated that HFHs have a lower log P than HCHs by almost two logarithmic units. This result highlights the role of fluorine in distribution and bioaccumulation.

Outcomes of transecting versus non-transecting urethroplasty for bulbar urethral stricture: a meta-analysis.

OBJECTIVES: To assess outcomes of transecting vs non-transecting urethroplasty for bulbar urethral stricture in terms of stricture recurrence rate, sexual dysfunction, and patient-reported outcome measures (PROMs) related to lower urinary tract (LUT) function. METHODS: Electronic literature searches were conducted using PubMed, Cochrane Library, Web of Science and Embase databases. The studied population was limited to men with bulbar urethral stricture included in studies that compared outcomes after transecting and non-transecting urethroplasty. The main outcome appraised was the stricture recurrence rate. Additionally, the incidence of sexual dysfunction appraised in three domains (erectile function, penile complications, and ejaculatory function) and PROMs related to LUT function after transecting vs non-transecting urethroplasty were assessed. The pooled risk ratio (RR) respectively for stricture recurrence, erectile dysfunction and penile complications was calculated using a fixed-effect model with inverse variance method. RESULTS: In all, 694 studies were screened with 72 identified as relevant. Finally, 19 studies were suitable for analysis. The pooled difference between the transecting and non-transecting groups relating to stricture recurrence was not significant. Overall, the RR was 1.06 (95% confidence interval [CI] 0.82-1.36) and the 95% CI crossed the line of no effect (line RR = 1). Overall, the RR for erectile dysfunction was 0.73 (95% CI 0.49-1.08) and the 95% CI crossed the line of no effect (line RR = 1). Overall, the RR for penile complications was 0.47 (95% CI 0.28-0.76) and the 95% CI did not cross the line of no effect (line RR = 1). Hence, the risk of penile complications was significantly lower in the non-transecting group. CONCLUSIONS: Our analysis of available evidence indicates that both transecting and non-transecting urethroplasties, are equal in terms of the recurrence rate. On the other hand, non-transecting techniques are better in terms of sexual function, causing less penile complications.

No evidence of inbreeding depression despite a historical severe bottleneck in the endangered Bermuda petrel (Pterodroma cahow).

The Bermuda petrel Pterodroma cahow is an island endemic seabird that belongs to the Procellariiformes, one of the most endangered orders of birds. Historical records suggest a significant population size decline following human settlement in Bermuda, bringing the species to near extinction. Since the 1950s, the population has been recovering aided by the implementation of an ongoing conservation plan. However, it still faces several threats, and negative genetic effects resulting from that drastic decline are to be expected, including inbreeding and genetic drift. We studied genetic diversity and levels of inbreeding, and their effects on individual fitness and mating choice. We also tested for a genetic signature of the recent demographic bottleneck. For this, we analyzed variation in thousands of nuclear single-nucleotide polymorphisms derived from double digest restriction site-associated DNA sequencing and 1 mitochondrial gene (cytochrome oxidase I). The results revealed that the Bermuda petrel suffered a recent genetic bottleneck and shows low mitochondrial diversity compared with other petrel species. Conversely, nuclear diversity was similar to that of other endangered petrels. Inbreeding levels were not high overall, although some individuals were highly inbred. However, we found no evidence that individual inbreeding or relatedness between mates affected hatching success, or that mate choice is influenced by kinship in this very small population.

Epidemiology of Injuries in Elite Male Futsal Players.

OBJECTIVE: This study aimed to describe and characterize injuries sustained by elite male futsal players in Portugal. DESIGN: Prospective cohort study. SETTING: Top-tier Portuguese league in the 2019 to 2020 season. PARTICIPANTS: One hundred sixty-seven players from 9 elite/international-level (tier 4) futsal teams. INDEPENDENT VARIABLES: The location, type, body side, body part, mechanism of injury, severity, occurrence, days lost, training, and match exposure were collected. MAIN OUTCOME MEASURES: Injury incidence, prevalence, and burden. RESULTS: The study was conducted during an 8-month season. A total of 133 injuries were recorded, and 92 (67.6%) players sustained injuries. The overall time-loss injury incidence was 4.5 injuries per 1000 hours of exposure. Injury incidence during matches was higher than during training sessions (25.9 vs 3.0 per 1000 hours of exposure, respectively). Average time loss was 9 days, and moderate injuries were the most frequent (44%), followed by mild injuries (24%). Injury burden was 73.8 days lost per 1000 hours of total player exposure. Sprains/ligament (29%) and muscle rupture/tear/strains (32%) were the most common injuries. The groin (19%), thigh (17%), knee (19%), and ankle (15%) were the most affected body areas. Noncontact injuries were the most reported mechanism (65%), and 24% were overuse injuries. CONCLUSIONS: This study showed that elite/international-level (tier 4) male futsal players are more prone to noncontact injuries, primarily affecting the lower limbs. The incidence during match play increased by 9-fold compared with training sessions.

System for Estimation of Human Anthropometric Parameters Based on Data from Kinect v2 Depth Camera.

Anthropometric measurements of the human body are an important problem that affects many aspects of human life. However, anthropometric measurement often requires the application of an appropriate measurement procedure and the use of specialized, sometimes expensive measurement tools. Sometimes the measurement procedure is complicated, time-consuming, and requires properly trained personnel. This study aimed to develop a system for estimating human anthropometric parameters based on a three-dimensional scan of the complete body made with an inexpensive depth camera in the form of the Kinect v2 sensor. The research included 129 men aged 18 to 28. The developed system consists of a rotating platform, a depth sensor (Kinect v2), and a PC computer that was used to record 3D data, and to estimate individual anthropometric parameters. Experimental studies have shown that the precision of the proposed system for a significant part of the parameters is satisfactory. The largest error was found in the waist circumference parameter. The results obtained confirm that this method can be used in anthropometric measurements.

Theoretical and X-Ray Evidence of Electrostatic Phosphonium anti and gauche Effects.

Sulphur, not phosphorus, is the only known third-row element capable of experiencing an electrostatic gauche effect with fluorine. Some six-membered rings containing an endocyclic phosphorus atom and a ß-fluorine substituent that can interconvert to axial (gauche relative to phosphorus) and equatorial positions were then analysed. While phosphines do not establish an electrostatic attraction between fluorine and phosphorus, some oxidised forms exhibit surprising stability for the sterically disfavoured axial orientation. Because the nature of this behaviour was not obvious, since an intramolecular hydrogen bond can appear, a phosphonium derivative was further studied and its axial conformation was found to be highly stable. A preference for the gauche arrangement appears even for the acyclic and sterically hindered (2-fluoroethyl)triphenylphosphonium cation. On the other hand, (ethane-1,2-diyl)bis(phosphonium) cations are exclusively in anti conformation due to an (+/+)-electrostatic repulsion between the positively charged phosphonium groups.

What is the role of single-stage oral mucosa graft urethroplasty in the surgical management of lichen sclerosus-related stricture disease in men? A systematic review.

PURPOSE: The benefits and harms of the available types of surgical management for lichen sclerosus-related (LS) strictures remain unclear and, thus, clear and robust clinical practice recommendations cannot be given. MATERIALS AND METHODS: To assess the role of single-stage OMGU in the management of LS strictures and explore how its benefits and harms compare with the alternative management options. Medline, Embase and Cochrane controlled trial databases (CENTRAL, CDSR) were systematically searched. Randomized (RCTs) and nonrandomized studies (NRCSs) comparing single-stage OMGU with other surgical management options for LS strictures and single-arm studies on single-stage OMGU were included. Risk of bias (RoB) was assessed. RESULTS: Of the 1912 abstracts identified, 15 studies (1 NRCS and 14 single-arm studies) were included, recruiting in total 649 patients. All studies were at high RoB. In the only NRCS available, stricture-free rate (SFR) for single-stage and staged OMGU was 88% vs 60%, respectively (p = 0.05), at a mean follow-up of 66.5 months. SFR range for single-stage OMGU in single-arm studies was 65-100% (mean/median follow-up, 12-59 months). Single-stage OMGU had low complication rates and beneficial impact on LUTS and QoL. CONCLUSIONS: The present SR highlights the methodological limitations of the available literature. In the absence of adverse local tissue conditions, and taking into consideration benefit-harm balance and surgeon's skills and expertise, single-stage OMGU can be justified in patients with LS strictures.

Iodine Gauche Effect Induced by an Intramolecular Hydrogen Bond.

The gauche conformer in 1-X,2-Y-disubstituted ethanes, that is, the staggered orientation in which X and Y are in closer contact, is only favored for relatively small substituents that do not give rise to large X···Y steric repulsion. For more diffuse substituents, weakly attractive orbital interactions between antiperiplanar bonds (i.e., hyperconjugation) cannot overrule the repulsive forces between X and Y. Our quantum chemical analyses of the rotational isomerism of XCH2CH2Y (X = F, OH; Y = I) at ZORA-BP86-D3(BJ)/QZ4P reveal that indeed the anti conformer is generally favored due to a less destabilizing I···F and I···O-H steric repulsion. The only case when the gauche conformer is preferred is when the hydroxyl hydrogen is oriented toward the iodine atom in the 2-iodoethanol. This is because of the significantly stabilizing covalent component of the I···H-O intramolecular hydrogen bond. Therefore, we show that strong intramolecular interactions can overcome the steric repulsion between bulky substituents in 1,2-disubstituted ethanes and cause the gauche effect. Our quantum chemical computations have guided nuclear magnetic resonance experiments that confirm the increase in the gauche population as X goes from F to OH.

TERT Promoter Mutational Status in the Management of Cutaneous Melanoma: Comparison with Sentinel Lymph Node Biopsy.

BACKGROUND: While BRAF mutations seem important for early melanomagenesis, mutations in the TERT promoter (TERTp) are related to metastasis. Yet, in conventional melanoma management, risk stratification does not depend on molecular biomarkers that can indicate the stage of progression, but rather on clinical, pathological, sentinel lymph node (SLN), and radiologic evaluation. The aim of this work was to evaluate the frequency and prognostic impact of TERTp mutations, comparing their predictive value to those of conventional procedures in melanoma management. METHODS: Mutational analysis of a series of 91 cases was performed. The correlations between TERTp and BRAF mutational status and clinicopathological features were assessed. RESULTS: The mutation rate was 33% for TERTp and 30% for BRAF. There was 68% concordance between primary and metastatic samples for TERTp mutations and 92% for BRAF mutations. TERTp mutations are significantly associated with the presence of BRAF mutations, features of worse prognosis, and a reduced disease-free survival. Also, TERTp mutational status was similar to SLN biopsy as a predictive factor of cutaneous melanoma recurrence and metastasis. CONCLUSIONS: The predictive value of TERTp mutations may be similar to that of SLN biopsy and its integration in the management algorithm of melanoma patients should be considered.

Multi-institutional review of non-hypospadiac penile urethral stricture management and outcomes.

OBJECTIVES: Penile urethral stricture disease not associated with hypospadias is rare, and there is a wide range of commonly used surgical repair techniques for this disease. We sought to compile a multi-institutional database of patients who had surgical correction of strictures in the penile urethra not limited to the meatus, and who had no history of hypospadias, for analysis using the Trauma and Urologic Reconstructive Network of Surgeons length, urethral segment and etiology classification system. METHODS: A retrospective database from 13 institutions was compiled of patients who had undergone surgical correction of Trauma and Urologic Reconstructive Network of Surgeons length, urethral segment and etiology urethral stricture segments S2b/S2c and excluding E5, with a minimum follow-up time of 4 months. Failure was defined as cystoscopically confirmed recurrence of a stricture measuring less than 16-Fr. RESULTS: We analyzed 222 patients with a median age of 57 years and a follow-up of 49 months. The overall surgical success rate was 80.2%. On multivariate analysis, the two variables identified that were predictive of surgical success were stricture length ≤2 cm as well as use of a buccal mucosa graft as compared to use of a fasciocutaneous flap, which had success rates of 83% and 52%, respectively (P = 0.0004). No statistically significant differences were found based on incisional approach or surgical technique, nor were outcomes different based on etiology or preoperative patient demographics. CONCLUSIONS: Surgical repair of penile urethral strictures of non-hypospadiac origin have a favorable overall success rate, at 80.2%. Regardless of incisional approach or surgical technique, all operations appear to have similar outcomes other than repairs using fasciocutaneous flap, which were statistically less successful than those using buccal mucosa graft.

Impact of the COVID-19 Pandemic on Diagnosis and Management of Gynecological Cancer: A Single-Center Analysis.

Background and Objectives: The COVID-19 pandemic impacted health systems worldwide, particularly cancer care. Because the actual implications of these changes on gynecological oncology healthcare are still unclear, we aim to evaluate the impact of this pandemic on the diagnosis and management of gynecological cancer. Materials and Methods: This is a single-center retrospective observational study, including patients diagnosed with gynecological malignancies between January 2019 and December 2021. Patients were included into three groups based on the timing of cancer diagnosis: pre-pandemic (2019), pandemic with high restrictions (2020) and pandemic recovery (2021). Results: Overall, 234 patients were diagnosed with gynecological cancer during the period of study. A decrease in the number of newly diagnosed cervical cancers and other rare tumors (leiomyosarcoma, invasive hydatidiform mole) was apparent in 2020. Some aggressive histological types of endometrial and ovarian cancer were more commonly diagnosed in the pandemic recovery group (p < 0.05), although no differences were demonstrated concerning tumor staging in all gynecological cancers. The median time between the first multidisciplinary team meeting and the treatment initiation was higher after the COVID-19 pandemic in endometrial cancer (23.0 vs. 34.0 vs. 36.0 days, p < 0.05). Patients with ovarian cancer were more frequently proposed for neoadjuvant therapy in 2020 compared to the other periods (33.3% vs. 55.0% vs. 10.0% p < 0.05). A significant reduction in the laparoscopic approach was observed during 2020 in endometrial cancer (32.1% vs. 14.3% vs. 36.4%, p < 0.05). No significant differences were registered regarding median hospitalization days or intra- and post-operative complications between these periods. Conclusions: The COVID-19 pandemic had a significant impact on the diagnosis and management of most gynecological malignancies, namely, on time to first treatment, chosen oncological therapies and surgical approaches. These results suggest important clinical and healthcare implications that should be addressed in future prospective studies.

Dorsal onlay urethroplasty using buccal mucosal graft and vaginal wall graft for female urethral stricture - Outcome of two-institution study.

Introduction: Female urethral stricture is an underdiagnosed condition and a diagnostic challenge. Traditionally treatment has been urethral dilatation. Recent studies have shown promising outcomes after female urethroplasty (FU). We report our two-institutional experience with dorsal onlay substitution FU using buccal mucosal graft (BMG) and vaginal wall graft (VWG). Methods: In this retrospective study, 32 women who underwent dorsal onlay urethroplasty at two institutions in India and Portugal were included for comparison of outcomes between BMG and VWG. The need for re-intervention was defined as failure. Their assessment included American Urological Association (AUA) symptom score, peak flow rate (Qmax), urethral calibration, postvoid residual urine (PVR), voiding cystourethrogram, and cystoscopy. Other parameters such as age, need for suprapubic cystostomy, prior interventions, location, length, etiology, operating time, postoperative catheter time, complications, and follow-up were evaluated. Statistical analysis was done with two-sample t-test, Mann-Whitney test, and proportion test for equality. Results: 21 patients underwent BMG and 11 underwent VWG, respectively. The overall mean age was 49 years (range: 25-75) and follow-up was 26 months (range: 13-62). The overall change in AUA symptom score was from 22 to 6, Qmax from 4ml/s to 26mL/s, and PVR from 185ml to 17 ml with no statistical difference between the two groups. Other parameters showed no difference except operating time. The overall urethral patency rate was 94% with no statistical difference in these groups (P = 0.0773). Conclusions: Dorsal onlay substitution FU is easy to perform with low complication rate. We found no difference in outcome of FU in these groups. Early FU should be encouraged to avoid the adversities of repeated dilatations.

Using gradient Forest to predict climate response and adaptation in Cork oak.

Climate change is impacting locally adapted species such as the keystone tree species cork oak (Quercus suber L.). Quantifying the importance of environmental variables in explaining the species distribution can help build resilient populations in restoration projects and design forest management strategies. Using landscape genomics, we investigated the population structure and ecological adaptation of this tree species across the Mediterranean Basin. We applied genotyping by sequencing and derived 2,583 single nucleotide polymorphism markers genotyped from 81 individuals across 17 sites in the studied region. We implemented an approach based on the nearest neighbour haplotype 'coancestry' and uncovered a weak population structure along an east-west climatic gradient across the Mediterranean region. We identified genomic regions potentially involved in local adaptation and predicted differences in the genetic composition across the landscape under current and future climates. Variants associated with temperature and precipitation variables were detected, and we applied a nonlinear multivariate association method, gradient forest, to project these gene-environment relationships across space. The model allowed the identification of geographic areas within the western Mediterranean region most sensitive to climate change: south-western Iberia and northern Morocco. Our findings provide a preliminary assessment towards a potential management strategy for the conservation of cork oak in the Mediterranean Basin.