Climate-land-use interactions shape tropical mountain biodiversity and ecosystem functions.

Agriculture and the exploitation of natural resources have transformed tropical mountain ecosystems across the world, and the consequences of these transformations for biodiversity and ecosystem functioning are largely unknown1-3. Conclusions that are derived from studies in non-mountainous areas are not suitable for predicting the effects of land-use changes on tropical mountains because the climatic environment rapidly changes with elevation, which may mitigate or amplify the effects of land use4,5. It is of key importance to understand how the interplay of climate and land use constrains biodiversity and ecosystem functions to determine the consequences of global change for mountain ecosystems. Here we show that the interacting effects of climate and land use reshape elevational trends in biodiversity and ecosystem functions on Africa's largest mountain, Mount Kilimanjaro (Tanzania). We find that increasing land-use intensity causes larger losses of plant and animal species richness in the arid lowlands than in humid submontane and montane zones. Increases in land-use intensity are associated with significant changes in the composition of plant, animal and microorganism communities; stronger modifications of plant and animal communities occur in arid and humid ecosystems, respectively. Temperature, precipitation and land use jointly modulate soil properties, nutrient turnover, greenhouse gas emissions, plant biomass and productivity, as well as animal interactions. Our data suggest that the response of ecosystem functions to land-use intensity depends strongly on climate; more-severe changes in ecosystem functioning occur in the arid lowlands and the cold montane zone. Interactions between climate and land use explained-on average-54% of the variation in species richness, species composition and ecosystem functions, whereas only 30% of variation was related to single drivers. Our study reveals that climate can modulate the effects of land use on biodiversity and ecosystem functioning, and points to a lowered resistance of ecosystems in climatically challenging environments to ongoing land-use changes in tropical mountainous regions.

Patient selection for urgent endoscopic retrograde cholangio-pancreatography by endoscopic ultrasound in predicted severe acute biliary pancreatitis (APEC-2): a multicentre prospective study.

OBJECTIVE: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings. DESIGN: A multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013-2017) applying the same study design. RESULTS: Overall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17-23) after hospital presentation and at a median of 29 hours (IQR 23-41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92). CONCLUSION: In patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group. TRIAL REGISTRATION NUMBER: ISRCTN15545919.

The big four of plant taxonomy - a comparison of global checklists of vascular plant names.

Taxonomic checklists used to verify published plant names and identify synonyms are a cornerstone of biological research. Four global authoritative checklists for vascular plants exist: Leipzig Catalogue of Vascular Plants, World Checklist of Vascular Plants, World Flora Online (successor of The Plant List, TPL), and WorldPlants. We compared these four checklists in terms of size and differences across taxa. We matched taxon names of these checklists and TPL against each other, identified differences across checklists, and evaluated the consistency of accepted names linked to individual taxon names. We assessed geographic and phylogenetic patterns of variance. All checklists differed strongly compared with TPL and provided identical information on c. 60% of plant names. Geographically, differences in checklists increased from low to high latitudes. Phylogenetically, we detected strong variability across families. A comparison of name-matching performance on taxon names submitted to the functional trait database TRY, and a check of completeness of accepted names evaluated against an independent, expert-curated checklist of the family Meliaceae, showed a similar performance across checklists. This study raises awareness on the differences in data and approach across these checklists potentially impacting analyses. We propose ideas on the way forward exploring synergies and harmonizing the four global checklists.

Air- and Water-Stable Heteroleptic Copper (I) Complexes Bearing Bis(indazol-1-yl)methane Ligands: Synthesis, Characterisation, and Computational Studies.

A series of four novel heteroleptic Cu(I) complexes, bearing bis(1H-indazol-1-yl)methane analogues as N,N ligands and DPEPhos as the P,P ligand, were synthesised in high yields under mild conditions and characterised by spectroscopic and spectrometric techniques. In addition, the position of the carboxymethyl substituent in the complexes and its effect on the electrochemical and photophysical behaviour was evaluated. As expected, the homoleptic copper (I) complexes with the N,N ligands showed air instability. In contrast, the obtained heteroleptic complexes were air- and water-stable in solid and solution. All complexes displayed green-yellow luminescence in CH2Cl2 at room temperature due to ligand-centred (LC) phosphorescence in the case of the Cu(I) complex with an unsubstituted N,N ligand and metal-to-ligand charge transfer (MLCT) phosphorescence for the carboxymethyl-substituted complexes. Interestingly, proper substitution of the bis(1H-indazol-1-yl)methane ligand enabled the achievement of a remarkable luminescent yield (2.5%) in solution, showcasing the great potential of this novel class of copper(I) complexes for potential applications in luminescent devices and/or photocatalysis.

Heart Disease Screening and False Hypoxemia in the Neonate.

BACKGROUND: Screening for congenital heart diseases by pulse oximetry is used for the initial assessment of the neonate. Variants of hemoglobin F can compromise light absorbance, inducing erroneous results. CASE REPORT: Two infants screened for congenital heart disease showed an asymptomatic low peripheral oxygen saturation. Arterial blood gases analysis revealed a normal arterial pressure of oxygen and oxygen saturation. More likely and/or severe causes of hypoxemia were ruled out. This "artifact" with SpO2-SaO2 dissociation, and after exclusion of other common etiologies of hypoxemia, raised the clinical suspicion of hemoglobinopathy. Hemoglobin molecular and genetic studies identified specific mutations in gamma chains from hemoglobin F, named hemoglobin F Sardinia. CONCLUSION: Hemoglobin F variants may result in low peripheral oxygen saturation readings by pulse oximetry, explaining the discordance in the clinical appearance and low peripheral oxygen saturation readings.

Refractive surgery after deep anterior lamellar keratoplasty: a review of the literature.

PURPOSE: The main objective of this work is to present an updated review of the different surgical procedures for the correction of residual refractive errors following deep anterior lamellar keratoplasty (DALK) surgery. METHODS: A review of the literature was conducted using PubMed, Web of Science, and Scopus databases. The search was conducted in January 2022 and was limited to articles published in peer-reviewed journals. The information extracted from each publication included sample size, mean follow-up time, pre- and post-operative uncorrected (UDVA) and corrected distance visual acuity (CDVA), pre- and post-operative refraction and spherical equivalent (SE), safety and efficacy indexes and complications. RESULTS: Residual ametropias, mainly high astigmatism and myopia, and the resulting anisometropia are likely to occur following DALK. They become a limiting factor and may lead to unsatisfactory visual restoration, therefore affecting patients' quality of vision and life. Alternative surgical interventions may be required to treat this residual ametropia, such as corneal refractive surgery or intraocular lens implantation. A total of 47 relevant articles were studied in detail. Different refractive surgery techniques have been shown to be effective and safe for the correction of ametropia following the DALK procedure and to improve the patient's quality of vision, although more research is needed to confirm long-term results. CONCLUSION: The final refractive technique will depend on different factors, such as the amount of ametropia, the condition of the cornea or the patient's individual needs, economics, and occupational demands.

MAEBL Contributes to Plasmodium Sporozoite Adhesiveness.

The sole currently approved malaria vaccine targets the circumsporozoite protein-the protein that densely coats the surface of sporozoites, the parasite stage deposited in the skin of the mammalian host by infected mosquitoes. However, this vaccine only confers moderate protection against clinical diseases in children, impelling a continuous search for novel candidates. In this work, we studied the importance of the membrane-associated erythrocyte binding-like protein (MAEBL) for infection by Plasmodium sporozoites. Using transgenic parasites and live imaging in mice, we show that the absence of MAEBL reduces Plasmodium berghei hemolymph sporozoite infectivity to mice. Moreover, we found that maebl knockout (maebl-) sporozoites display reduced adhesion, including to cultured hepatocytes, which could contribute to the defects in multiple biological processes, such as in gliding motility, hepatocyte wounding, and invasion. The maebl- defective phenotypes in mosquito salivary gland and liver infection were reverted by genetic complementation. Using a parasite line expressing a C-terminal myc-tagged MAEBL, we found that MAEBL levels peak in midgut and hemolymph parasites but drop after sporozoite entry into the salivary glands, where the labeling was found to be heterogeneous among sporozoites. MAEBL was found associated, not only with micronemes, but also with the surface of mature sporozoites. Overall, our data provide further insight into the role of MAEBL in sporozoite infectivity and may contribute to the design of future immune interventions.

Vegetational succession assessment in a fragment of the Brazilian Atlantic Forest.

Vegetational succession assessment is an important step for better management practices, providing relevant quantitative and qualitative information. With the advancements of remote sensing algorithms and access to data, land use and land cover (LULC) monitoring has become increasingly feasible and important for the evaluation of changes in the landscape at different spatial and temporal scales. This study aims to analyze the vegetation succession achieved by a project funded by the Brazilian Environmental Ministry (Ministério do Meio Ambiente, in Portuguese) intended to recover degraded areas. A 2014 and a 2019 LULC map was generated using high-resolution (10 cm) images. Given the great challenge of classifying high-resolution images, three classification algorithms were compared. The techniques to regenerate degraded areas were efficient to increase arboreal vegetation area by more than 30% between 2014 and 2019. Land cover and land use change monitoring is of paramount importance to strengthen sustainable practices, especially in the highly threatened Atlantic Forest biome. This study also shows that funding opportunities are essential for projects that make such actions possible, including the present research and the analysis of environmental regeneration.

Femto-LASIK after Deep Anterior Lamellar Keratoplasty to Correct Residual Astigmatism: A Long-Term Case Series Study.

Purpose: To evaluate the long-term outcomes of femtosecond laser-assisted in situ keratomileusis (Femto-LASIK) to correct residual astigmatism after deep anterior lamellar keratoplasty (DALK). Methods: This retrospective case series study included 10 eyes that underwent Femto-LASIK after a DALK. The refractive error, uncorrected (UDVA) and corrected (CDVA) distance visual acuities, thinnest corneal thickness (TCT), and central corneal thickness (CCT) were registered. The postoperative follow-up ranged between 36 and 60 months. Results: All surgeries were uneventful, with no intra- or postoperative complications. The mean UDVA (Snellen scale) rose from 0.13 ± 0.05 to 0.47 ± 0.15 six months after Femto-LASIK (p < 0.001). All cases experienced a significant improvement in UDVA. None of the eyes lost lines of CDVA, and seven eyes (70%) improved the CDVA compared to preoperative values. The refractive cylinder changed from a preoperative value of −3.88 ± 1.00 D to −0.93 ± 0.39 six months after Femto-LASIK (p < 0.0001). In eight eyes (80%), the UDVA and refractive outcomes remained stable at postoperative follow-up visits. In contrast, one eye experienced a refractive regression over the follow-up. TCT and CCT were stable at the different postoperative follow-up visits. Conclusions: Our findings suggest that Femto-LASIK might safely and effectively corrects residual astigmatism after DALK. Despite these encouraging results, further long-term studies, including a larger number of cases, are required to confirm the safety of the procedure. The refractive stability in eyes with prior RK might be lower than for other DALK indications.

Urgent endoscopic retrograde cholangiopancreatography with sphincterotomy versus conservative treatment in predicted severe acute gallstone pancreatitis (APEC): a multicentre randomised controlled trial.

BACKGROUND: It remains unclear whether urgent endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy improves the outcome of patients with gallstone pancreatitis without concomitant cholangitis. We did a randomised trial to compare urgent ERCP with sphincterotomy versus conservative treatment in patients with predicted severe acute gallstone pancreatitis. METHODS: In this multicentre, parallel-group, assessor-masked, randomised controlled superiority trial, patients with predicted severe (Acute Physiology and Chronic Health Evaluation II score ≥8, Imrie score ≥3, or C-reactive protein concentration >150 mg/L) gallstone pancreatitis without cholangitis were assessed for eligibility in 26 hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module with randomly varying block sizes to urgent ERCP with sphincterotomy (within 24 h after hospital presentation) or conservative treatment. The primary endpoint was a composite of mortality or major complications (new-onset persistent organ failure, cholangitis, bacteraemia, pneumonia, pancreatic necrosis, or pancreatic insufficiency) within 6 months of randomisation. Analysis was by intention to treat. This trial is registered with the ISRCTN registry, ISRCTN97372133. FINDINGS: Between Feb 28, 2013, and March 1, 2017, 232 patients were randomly assigned to urgent ERCP with sphincterotomy (n=118) or conservative treatment (n=114). One patient from each group was excluded from the final analysis because of cholangitis (urgent ERCP group) and chronic pancreatitis (conservative treatment group) at admission. The primary endpoint occurred in 45 (38%) of 117 patients in the urgent ERCP group and in 50 (44%) of 113 patients in the conservative treatment group (risk ratio [RR] 0·87, 95% CI 0·64-1·18; p=0·37). No relevant differences in the individual components of the primary endpoint were recorded between groups, apart from the occurrence of cholangitis (two [2%] of 117 in the urgent ERCP group vs 11 [10%] of 113 in the conservative treatment group; RR 0·18, 95% CI 0·04-0·78; p=0·010). Adverse events were reported in 87 (74%) of 118 patients in the urgent ERCP group versus 91 (80%) of 114 patients in the conservative treatment group. INTERPRETATION: In patients with predicted severe gallstone pancreatitis but without cholangitis, urgent ERCP with sphincterotomy did not reduce the composite endpoint of major complications or mortality, compared with conservative treatment. Our findings support a conservative strategy in patients with predicted severe acute gallstone pancreatitis with an ERCP indicated only in patients with cholangitis or persistent cholestasis. FUNDING: The Netherlands Organization for Health Research and Development, Fonds NutsOhra, and the Dutch Patient Organization for Pancreatic Diseases.

A role for hepcidin in the anemia caused by Trypanosoma brucei infection.

Trypanosomiasis is a parasitic disease affecting both humans and animals in the form of Human African Trypanosomiasis and Nagana disease, respectively. Anemia is one of the most common symptoms of trypanosomiasis, and if left unchecked can cause severe complications and even death. Several factors have been associated with the development of this anemia, including dysregulation of iron homeostasis, but little is known about the molecular mechanisms involved. Here, using murine models, we study the involvement of hepcidin, the key regulator of iron metabolism and an important player in the development of anemia of inflammation. Our data show two stages for the progression of anemia, to which hepcidin contributes a first stage when anemia develops, with a likely cytokine-mediated stimulation of hepcidin and subsequent limitation in iron availability and erythropoiesis, and a second stage of recovery, where the increase in hepcidin then declines due to the reduced inflammatory signal and increased production of erythroid regulators by the kidney, spleen and bone marrow, thus leading to an increase in iron release and availability, and enhanced erythropoiesis. In agreement with this, in hepcidin knockout mice, anemia is much milder and its recovery is complete, in contrast to wild-type animals which have not fully recovered from anemia after 21 days. Besides all other factors known to be involved in the development of anemia during trypanosomiasis, hepcidin clearly makes an important contribution to both its development and recovery.

Impact of contact lens wear on NLRP3 gene expression: Implications for ocular frailty in middle-aged adults.

The inflammatory process plays a crucial role in frailty syndrome, which can appear in middle age and is associated with a poor health outcome. Consequently, gerontologists recommend screening inflammatory biomarkers in middle-aged adults to detect frailty and, therefore, prevent chronic diseases and mortality. External factors could be a risk factor for frailty because they can generate and extend the inflammatory process. For these reasons, we analysed the effect of long-term contact lens wear on mRNA level of genes linked to inflammation (IL-6, NLRP3, NK1R, CD73, MUC16 and TRPV1 genes) in conjunctival cells of middle-aged individuals, by quantitative PCR. Middle-aged contact lens wearers presented a significant increase of NLRP3 and MUC16 mRNA level as well as a decrease of CD73 mRNA level, in comparison with non-contact lens wearers. Additionally, we checked for a potential correlation between these transcript levels and clinical changes of the participants' ocular surface. Unlike molecular analysis, clinical examination fails to detect inflammation in contact lens wearers. These data suggest that long-term contact lens wear could trigger an inflammatory response in middle age orchestrated by NLRP3 inflammasome and modulated by CD73 and MUC16 proteins. Further studies are needed to confirm our gene expression findings at the protein level as well as to investigate the potential role of long-term CL wear in the onset of ocular frailty.

What is the impact of post-radical prostatectomy urinary incontinence on everyday quality of life? Linking Pad usage and International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) for a COMBined definition (PICOMB definition).

AIMS: To identify the definition for urinary continence (UC) after radical prostatectomy (RP) which reflects best patients' perception of quality of life (QoL). METHODS: Continence was prospectively assessed in 634 patients, 12 months after RP using the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF) and the number of pads employed in a 24-hour period (pad usage). We used the one-way ANOVA technique with posthoc pairwise comparisons according to Scheffé's method (homogeneous subsets) for assessing the degree of QoL deficit related to urinary incontinence (UI). RESULTS: The continence prevalence is 64.4%, 74.1%, 88.3%, and 35.8% using "0 pads," "1 safety pad," "1 pad," and "ICIQ score 0" definitions, respectively. Pad usage is moderately strongly associated with ICIQ 1, 2, and 3 (ρ = 0.744, 0.677, and 0.711, respectively; p < 0.001). Concordance between classical UC definitions is acceptable between "0 pads-ICIQ score 0" (K = 0.466), but poor for "1 safety pad" and "1 pad" (K = 0.326 and 0.137, respectively). Patients with "0 pad usage" have better QoL related to urine leakage than patients with "1 safety pad" or "1 pad" (1.41 vs. 2.44 and 3.11, respectively; p < 0.05). There were no significant differences found regarding QoL between patients with ICIQ score 0 and ICIQ score 2 (1.01 vs. 1.63; p = 0.63). CONCLUSIONS: Pad usage and the ICIQ-SF's answers provide useful information. We propose a combined definition (0 pads and ICIQ score ≤2) as it is the definition with the least impact on daily QoL.

Climate implications on forest above- and belowground carbon allocation patterns along a tropical elevation gradient on Mt. Kilimanjaro (Tanzania).

Tropical forests represent the largest store of terrestrial biomass carbon (C) on earth and contribute over-proportionally to global terrestrial net primary productivity (NPP). How climate change is affecting NPP and C allocation to tree components in forests is not well understood. This is true for tropical forests, but particularly for African tropical forests. Studying forest ecosystems along elevation and related temperature and moisture gradients is one possible approach to address this question. However, the inclusion of belowground productivity data in such studies is scarce. On Mt. Kilimanjaro (Tanzania), we studied aboveground (wood increment, litter fall) and belowground (fine and coarse root) NPP along three elevation transects (c. 1800-3900 m a.s.l.) across four tropical montane forest types to derive C allocation to the major tree components. Total NPP declined continuously with elevation from 8.5 to 2.8 Mg C ha-1 year-1 due to significant decline in aboveground NPP, while fine root productivity (sequential coring approach) remained unvaried with around 2 Mg C ha-1 year-1, indicating a marked shift in C allocation to belowground components with elevation. The C and N fluxes to the soil via root litter were far more important than leaf litter inputs in the subalpine Erica forest. Thus, the shift of C allocation to belowground organs with elevation at Mt. Kilimanjaro and other tropical forests suggests increasing nitrogen limitation of aboveground tree growth at higher elevations. Our results show that studying fine root productivity is crucial to understand climate effects on the carbon cycle in tropical forests.

Surface charge modulation of rifampicin-loaded PLA nanoparticles to improve antibiotic delivery in Staphylococcus aureus biofilms.

BACKGROUND: After the golden age of antibiotic discovery, bacterial infections still represent a major challenge for public health worldwide. The biofilm mode of growth is mostly responsible for chronic infections that current therapeutics fail to cure and it is well-established that novel strategies must be investigated. Particulate drug delivery systems are considered as a promising strategy to face issues related to antibiotic treatments in a biofilm context. Particularly, poly-lactic acid (PLA) nanoparticles present a great interest due to their ability to migrate into biofilms thanks to their submicronic size. However, questions still remain unresolved about their mode of action in biofilms depending on their surface properties. In the current study, we have investigated the impact of their surface charge, firstly on their behavior within a bacterial biofilm, and secondly on the antibiotic delivery and the treatment efficacy. RESULTS: Rifampicin-loaded PLA nanoparticles were synthetized by nanoprecipitation and characterized. A high and superficial loading of rifampicin, confirmed by an in silico simulation, enabled to deliver effective antibiotic doses with a two-phase release, appropriate for biofilm-associated treatments. These nanoparticles were functionalized with poly-L-lysine, a cationic peptide, by surface coating inducing charge reversal without altering the other physicochemical properties of these particles. Positively charged nanoparticles were able to interact stronger than negative ones with Staphylococcus aureus, under planktonic and biofilm modes of growth, leading to a slowed particle migration in the biofilm thickness and to an improved retention of these cationic particles in biofilms. While rifampicin was totally ineffective in biofilms after washing, the increased retention capacity of poly-L-lysine-coated rifampicin-loaded PLA nanoparticles has been associated with a better antibiotic efficacy than uncoated negatively charged ones. CONCLUSIONS: Correlating the carrier retention capacity in biofilms with the treatment efficacy, positively charged rifampicin-loaded PLA nanoparticles are therefore proposed as an adapted and promising approach to improve antibiotic delivery in S. aureus biofilms.

Orofacial evaluation of individuals with temporomandibular disorder after LED therapy associated or not of occlusal splint: a randomized double-blind controlled clinical study.

This study compared the effects of LED therapy associated with occlusal splint (OS) on the signs and symptoms of temporomandibular disorder (TMD). In this randomized, double-blind clinical trial, 70 TMD patients were randomly divided into six groups. The volunteers received the following treatments: Group 1 (G1) was the control and received only conventional therapy with OS; Group 2 (G2) was the placebo and received treatment with OS and therapy with LED (device turned off); Group 3 (G3) LED therapy (infrared,) once a week; Group 4 (G4) LED therapy (infrared) twice a week; Group 5 (G5) OS associated with LED (infrared) therapy (once a week); Group 6 (G6) received OS therapy plus infrared LED (two sessions per week). The patients were evaluated before, after, and 30 days after treatment. The pain intensity in masticatory system was recorded at each interval. The evaluation of the electromyographic signals (EMG) of the muscles (masseter and temporal) and blood lactate was performed before and after treatment. The associated groups presented better clinical results in relation to the control. The associated groups showed significant differences (p < 0.05) from control in the analysis of pain intensity and in decrease of the RMS value (EMG analysis). In the intragroup analysis, the volunteers in G6 exhibited a significant reduction (p < 0.05) in blood lactate. In conclusion, the association of LED therapy and OS presented superior results in relation to the isolated therapies, especially the protocol with two weekly sessions.

Heart Rate Variability and Erectile Function in Younger Men: A Pilot Study.

Erectile dysfunction (ED) in younger men is an increasing concern. In middle aged and older men, ED was related to lower resting heart rate variability (HRV), but research in younger men is lacking. The present study examined, in a nonclinical sample of 105 men between 18 and 39 years, the association of ED with several parameters of resting HRV. Scores of the 5-item version of the International Index of Erectile Function (IIEF-5) below 22 were considered as indicating ED. Eighteen men (17.1%) reported ED (mild in 16, mild to moderate in 2). Welch's tests revealed that ED was associated with lower low-frequency power (LF), lower high-frequency power (HF), lower standard deviation of interbeat intervals, and lower standard deviation of the heart rate, which is influenced by both sympathetic and parasympathetic activity. After removing outliers, ED was unrelated to HF. In younger men, erections might be facilitated by a combination of higher parasympathetic tone and relatively higher sympathetic tone in the heart, as indicated by LF and greater standard deviation of the heart rate, a largely overlooked parameter in HRV research.

Platinum-drugs Ototoxicity in Pediatric Patients With Brain Tumors: A 10-Year Review.

PURPOSE: Platinum-derived chemotherapy is one of the cornerstones in the treatment of central nervous system tumors in children. We aimed to assess the incidence of hearing loss in children after the exposure to platinum drugs. MATERIAL AND METHODS: Retrospective study of prospectively collected data on children consecutively diagnosed with brain tumors and treated with platinum derivatives at a tertiary referral hospital between January 2006 and December 2015. We analyzed multiples variables, such as: age at diagnosis, tumor location, hydrocephalus, platinum drug type, radiotherapy, and follow-up time. The final sample size was 51 patients. RESULTS: The median age at diagnosis was 6 years. The median overall follow-up time was 75 months. The incidence of ototoxicity was 23.5%. Rates of hearing loss with carboplatinum were lower than with cisplatinum. A statistically significant association occurred between the presence of hydrocephalus, radiotherapy exposure, infratentorial tumor location, and ototoxicity after treatment with platinum derivatives. CONCLUSIONS: Childhood central nervous system tumors nowadays exhibit improved cure and survival rates. However, the ototoxicity resulting from the chemotherapy treatment may accompany patients for the rest of their lives. This study reveals that this occurrence is not negligible, and the association of radiotherapy and the presence of hydrocephalus can be potentiating factors.

USP7 inhibition alters homologous recombination repair and targets CLL cells independently of ATM/p53 functional status.

The role of deubiquitylase ubiquitin-specific protease 7 (USP7) in the regulation of the p53-dependent DNA damage response (DDR) pathway is well established. Whereas previous studies have mostly focused on the mechanisms underlying how USP7 directly controls p53 stability, we recently showed that USP7 modulates the stability of the DNA damage responsive E3 ubiquitin ligase RAD18. This suggests that targeting USP7 may have therapeutic potential even in tumors with defective p53 or ibrutinib resistance. To test this hypothesis, we studied the effect of USP7 inhibition in chronic lymphocytic leukemia (CLL) where the ataxia telangiectasia mutated (ATM)-p53 pathway is inactivated with relatively high frequency, leading to treatment resistance and poor clinical outcome. We demonstrate that USP7 is upregulated in CLL cells, and its loss or inhibition disrupts homologous recombination repair (HRR). Consequently, USP7 inhibition induces significant tumor-cell killing independently of ATM and p53 through the accumulation of genotoxic levels of DNA damage. Moreover, USP7 inhibition sensitized p53-defective, chemotherapy-resistant CLL cells to clinically achievable doses of HRR-inducing chemotherapeutic agents in vitro and in vivo in a murine xenograft model. Together, these results identify USP7 as a promising therapeutic target for the treatment of hematological malignancies with DDR defects, where ATM/p53-dependent apoptosis is compromised.

Leaf traits mediate changes in invertebrate herbivory along broad environmental gradients on Mt. Kilimanjaro, Tanzania.

Temperature, primary productivity, plant functional traits, and herbivore abundances are considered key predictors of leaf herbivory but their direct and indirect contributions to community-level herbivory are not well understood along broad climatic gradients. Here, we determined elevational herbivory patterns and used a path analytical approach to disentangle the direct and indirect effects of climate, land use, net primary productivity (NPP), herbivore abundance, and plant functional traits on community-level invertebrate herbivory along the extensive elevational and land use gradients at Mt. Kilimanjaro, Tanzania. We recorded standing leaf herbivory caused by leaf chewers, leaf miners and leaf gallers on 55 study sites distributed in natural and anthropogenic habitats along a 3,060 m elevation gradient. We related the total community-level herbivory to climate (temperature and precipitation), NPP, plant functional traits (specific leaf area, leaf carbon-to-nitrogen [CN] ratio and leaf nitrogen-to-phosphorus [NP] ratio) and herbivore abundances. Leaf herbivory ranged from 5% to 11% along the elevation gradient. Total leaf herbivory showed unimodal pattern in natural habitats but a strongly contrasting bimodal pattern in anthropogenic habitats. We also detected some variation in the patterns of leaf herbivory along environmental gradients across feeding guilds with leaf chewers being responsible for a disproportionally large part of herbivory. Path analyses indicated that the variation in leaf herbivory was mainly driven by changes in leaf CN and NP ratios which were closely linked to changes in NPP in natural habitats. Similarly, patterns of leaf herbivory in anthropogenic habitats were best explained by variation in leaf CN ratios and a negative effect of land use. Our study elucidates the strong role of leaf nutrient stoichiometry and its linkages to climate and NPP for explaining the variation in leaf herbivory along broad climatic gradients. Furthermore, the study suggests that climatic changes and nutrient inputs in the course of land use change may alter leaf herbivory and consequently energy and nutrient fluxes in terrestrial habitats.