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Host-pathogen specificity can arise from certain selective environments mediated by both the host and pathogen. Therefore, understanding the degree to which host species identity is correlated with pathogen genotype can help reveal historical host-pathogen dynamics. One animal disease of particular concern is chytridiomycosis, typically caused by the global panzootic lineage of the amphibian chytrid fungus (Batrachochytrium dendrobatidis, Bd), termed Bd-GPL. This pathogen lineage has caused devastating declines in amphibian communities around the world. However, the site of origin for the common ancestor of modern Bd-GPL and the fine-scale transmission dynamics of this lineage have remained a mystery. This is especially the case in North America where Bd-GPL is widespread, but disease outbreaks occur sporadically. Herein, we use Bd genetic data collected throughout the United States from amphibian skin swabs and cultured isolate samples to investigate Bd genetic patterns. We highlight two case studies in Pennsylvania and Nevada where Bd-GPL genotypes are strongly correlated with host species identity. Specifically, in some localities bullfrogs (Rana catesbeiana) are infected with Bd-GPL lineages that are distinct from those infecting other sympatric amphibian species. Overall, we reveal a previously unknown association of Bd genotype with host species and identify the eastern United States as a Bd diversity hotspot and potential site of origin for Bd-GPL.

PurposeThe phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision.MethodsIn dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking.ResultsIn light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil.ConclusionsThe sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.

The advancement of underrepresented minority and women PhD students to elite postdoctoral and faculty positions in the STEM fields continues to lag that of majority males, despite decades of efforts to mitigate bias and increase opportunities for students from diverse backgrounds. In 2015, the National Science Foundation Alliance for Graduate Education and the Professoriate (NSF AGEP) California Alliance (Berkeley, Caltech, Stanford, UCLA) conducted a wide-ranging survey of graduate students across the mathematical, physical, engineering, and computer sciences in order to identify levers to improve the success of PhD students, and, in time, improve diversity in STEM leadership positions, especially the professoriate. The survey data were interpreted via path analysis, a method that identifies significant relationships, both direct and indirect, among various factors and outcomes of interest. We investigated two important outcomes: publication rates, which largely determine a new PhD students competitiveness in the academic marketplace, and subjective well-being. Women and minority students who perceived that they were well-prepared for their graduate courses and accepted by their colleagues (faculty and fellow students), and who experienced well-articulated and structured PhD programs, were most likely to publish at rates comparable to their male majority peers. Women PhD students experienced significantly higher levels of distress than their male peers, both majority and minority, while both women and minority student distress levels were mitigated by clearly-articulated expectations, perceiving that they were well-prepared for graduate level courses, and feeling accepted by their colleagues. It is unclear whether higher levels of distress in women students is related directly to their experiences in their STEM PhD programs. The findings suggest that mitigating factors that negatively affect diversity should not, in principle, require the investment of large resources, but rather requires attention to the local culture and structure of individual STEM PhD programs.

BACKGROUND:Heatwaves have been linked to increased risk of mortality and morbidity and are projected to increase in frequency and intensity due to climate change. The current study uses emergency department (ED) data from Australia, Botswana, Netherlands, Pakistan, and the United States of America to evaluate the impact of heatwaves on ED attendances, admissions and mortality. METHODS:Routinely collected time series data were obtained from 18 hospitals. Two separate thresholds (≥4 and ≥7) of the acclimatisation excess heat index (EHIaccl) were used to define "hot days". Analyses included descriptive statistics, independent samples T-tests to determine differences in case mix between hot days and other days, and threshold regression to determine which temperature thresholds correspond to large increases in ED attendances. FINDINGS:In all regions, increases in temperature that did not coincide with time to acclimatise resulted in increases in ED attendances, and the EHIaccl performed in a similar manner. During hot days in California and The Netherlands, significantly more children ended up in the ED, while in Pakistan more elderly people attended. Hot days were associated with more patient admissions in the ages 5-11 in California, 65-74 in Karachi, and 75-84 in The Hague. During hot days in The Hague, patients with psychiatric symptoms were more likely to die. The current study did not identify a threshold temperature associated with particularly large increases in ED demand. INTERPRETATION:The association between heat and ED demand differs between regions. A limitation of the current study is that it does not consider delayed effects or influences of other environmental factors. Given the association between heat and ED use, hospitals and governmental authorities should recognise the demands that heat can place on local health care systems. These demands differ substantially between regions, with Pakistan being the most heavily affected within our study sample.

Major power outages have risen over the last two decades, largely due to more extreme weather conditions. However, there is a lack of knowledge on the distribution of power outages and its relationship to social vulnerability and co-occurring hazards. We examined the associations between localized outages and social vulnerability factors (demographic characteristics), controlling for environmental factors (weather), in Washington State between 2018–2021. We additionally analyzed the validity of PowerOutage.us data compared to federal datasets. The population included 27 counties served by 14 electric utilities. We developed a continuous measure of daily outage burden using PowerOutage.us data and operationalized social vulnerability using four factors: poverty level, unemployment, disability, and limited English proficiency. We applied zero-altered lognormal generalized additive mixed-effects models to characterize the relationship between social vulnerability and daily power outage burden, controlling for daily minimum temperature, maximum wind speed, and precipitation, from 2018 to 2021 in Washington State. We found that social vulnerability factors have non-linear relationships with outages. Wind and precipitation are consistent drivers of outage occurrence and duration. There are seasonal effects that vary by county-utility area. Both PowerOutage.us and federal datasets have missing and inaccurate outage data. This is the first study evaluating differential exposure to localized outages as related to social vulnerability that has accounted for weather and temporal correlation. There is a lack of transparency into power outage distribution for those most vulnerable to climate impacts, despite known contributions by electric utilities to climate change. For effective public health surveillance of power outages and transparency, outage data should be made available at finer spatial resolution and temporal scales and/or utilities should be required to report differential exposure to power outages for socially vulnerable populations. [ABSTRACT FROM AUTHOR]

Epilepsy is one of the most common neurological disorders in children. Diagnosing epilepsy in children can be very challenging, especially as it often coexists with neurodevelopmental conditions like autism and ADHD. Functional brain networks obtained from neuroimaging and electrophysiological data in wakefulness and sleep have been shown to contain signatures of neurological disorders, and can potentially support the diagnosis and management of co-occurring neurodevelopmental conditions. In this work, we use electroencephalography (EEG) recordings from children, in restful wakefulness and sleep, to extract functional connectivity networks in different frequency bands. We explore the relationship of these networks with epilepsy diagnosis and with measures of neurodevelopmental traits, obtained from questionnaires used as screening tools for autism and ADHD. We explore differences in network markers between children with and without epilepsy in wake and sleep, and quantify the correlation between such markers and measures of neurodevelopmental traits. Our findings highlight the importance of considering the interplay between epilepsy and neurodevelopmental traits when exploring network markers of epilepsy. [ABSTRACT FROM AUTHOR]

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

Two independent surveys of PhD students in STEM fields at the University of California, Berkeley, indicate that underrepresented minorities (URMs) publish at significantly lower rates than non-URM males, placing the former at a significant disadvantage as they compete for postdoctoral and faculty positions. Differences as a function of gender reveal a similar, though less consistent, pattern. A conspicuous exception is Berkeley's College of Chemistry, where publication rates are tightly clustered as a function of ethnicity and gender, and where PhD students experience a highly structured program that includes early and systematic involvement in research, as well as clear expectations for publishing. Social science research supports the hypothesis that this more structured environment hastens the successful induction of diverse groups into the high-performance STEM academic track.

Purpose: Due to the increase in life expectancy and high-energy traumas, anterior column acetabular fractures (ACFs) are also increasing. While open reduction and internal fixation (ORIF) is still the standard surgical procedure, minimally invasive, percutaneous fixation of osteoporotic acetabulum fractures (AF) are growing in popularity. The aim of this biomechanical study was to evaluate the biomechanical competence following antegrade fixation with a standard screw versus a cannulated compression headless screw. Methods: Eight anatomical osteoporotic composite pelvises were given an anterior column fracture. Two groups of eight specimens each (n = 8) for fixation with either a 6.5 mm cannulated compression headless screw in group Anterior Acetabulum Canulated Compression Headless Screw (AACCH), or with a 6.5 mm partially threaded cannulated screw in group Anterior Acetabulum Standard Screw (AASS) where compared. Each specimen was biomechanically loaded cyclically at a rate of 2 Hz with monotonically increasing compressive load until failure. Motions were assessed by means of optical motion tracking. Results: Initial construct stiffness trended higher in group AACCH at 152.4 ± 23.1 N/mm compared to group AASS at 118.5 ± 34.3 N/mm, p = 0.051. Numbers of cycles and corresponding peak load at failure, were significantly higher in group AACCH at 6734 ± 1669 cycles and 873.4 ± 166.9 N versus group AASS at 4440 ± 2063 cycles and 644.0 ± 206.3 N, p = 0.041. Failure modes were breakout of the screws around the proximal entry point. Conclusion: From a biomechanical perspective, group AACCH was associated with superior biomechanical competence compared to standard partially threaded cannulated screws and could therefore be considered as valid alternative for fixation of anterior acetabulum fractures. [ABSTRACT FROM AUTHOR]

Background: Low social participation is a potentially modifiable risk factor for cognitive deterioration in the general population and related to lower quality of life (QoL). We aimed to find out whether social participation is linked to cognitive deterioration and QoL for people with borderline intellectual functioning and mild intellectual disability. Method: We used data from the National Child Development Study, consisting of people born during one week in 1958, to compare midlife social participation in people with mild intellectual disability, borderline intellectual functioning, and without intellectual impairment. We defined social participation as 1. confiding/emotional support from the closest person and social network contact frequency at age 44, and 2. confiding relationships with anyone at age 50. We then assessed the extent to which social participation mediated the association between childhood intellectual functioning and cognition and QoL at age 50. Results: 14,094 participants completed cognitive tests at age 11. People with borderline intellectual functioning and mild intellectual disability had more social contact with relatives and confiding/emotional support from their closest person, but fewer social contacts with friends and confiding relationships with anyone than those without intellectual disability. Having a confiding relationship partially mediated the association at age 50 between IQ and cognition (6.4%) and QoL (27.4%) for people with borderline intellectual functioning. Conclusion: We found adults with intellectual disability have positive family relationships but fewer other relationships. Even at the age of 50, confiding relationships may protect cognition for people with borderline intellectual functioning and are important for QoL. [ABSTRACT FROM AUTHOR]

White matter (WM) changes occur throughout the lifespan at a different rate for each developmental period. We aggregated 10879 structural MRIs and 6186 diffusion-weighted MRIs from participants between 2 weeks to 100 years of age. Age-related changes in gray matter and WM partial volumes and microstructural WM properties, both brain-wide and on 29 reconstructed tracts, were investigated as a function of biological sex and hemisphere, when appropriate. We investigated the curve fit that would best explain age-related differences by fitting linear, cubic, quadratic, and exponential models to macro and microstructural WM properties. Following the first steep increase in WM volume during infancy and childhood, the rate of development slows down in adulthood and decreases with aging. Similarly, microstructural properties of WM, particularly fractional anisotropy (FA) and mean diffusivity (MD), follow independent rates of change across the lifespan. The overall increase in FA and decrease in MD are modulated by demographic factors, such as the participant's age, and show different hemispheric asymmetries in some association tracts reconstructed via probabilistic tractography. All changes in WM macro and microstructure seem to follow nonlinear trajectories, which also differ based on the considered metric. Exponential changes occurred for the WM volume and FA and MD values in the first five years of life. Collectively, these results provide novel insight into how changes in different metrics of WM occur when a lifespan approach is considered. [ABSTRACT FROM AUTHOR]

Prerequisites are embedded in most STEM curricula. However, the assumption that the content presented in these courses will improve learning in later courses has not been verified. Because a direct comparison of performance between students with and without required prerequisites is logistically difficult to arrange in a randomized fashion, we developed a novel familiarity scale, and used this to determine whether concepts introduced in a prerequisite course improved student learning in a later course (in two biology disciplines). Exam questions in the latter courses were classified into three categories, based on the degree to which the tested concept had been taught in the prerequisite course. If content familiarity mattered, it would be expected that exam scores on topics covered in the prerequisite would be higher than scores on novel topics. We found this to be partially true for "Very Familiar" questions (concepts covered in depth in the prerequisite). However, scores for concepts only briefly discussed in the prerequisite ("Familiar") were indistinguishable from performance on topics that were "Not Familiar" (concepts only taught in the later course). These results imply that merely "covering" topics in a prerequisite course does not result in improved future performance, and that some topics may be able to removed from a course thereby freeing up class time. Our results may therefore support the implementation of student-centered teaching methods such as active learning, as the time-intensive nature of active learning has been cited as a barrier to its adoption. In addition, we propose that our familiarity system could be broadly utilized to aid in the assessment of the effectiveness of prerequisites.

To investigate the underlying causes of chemoresistance in malignant pleural mesothelioma, we have studied mesothelioma cell lines as 3D spheroids, which acquire increased chemoresistance compared to 2D monolayers. We asked whether the gene expression of 3D spheroids would reveal mechanisms of resistance. To address this, we measured gene expression of three mesothelioma cell lines, M28, REN and VAMT, grown as 2D monolayers and 3D spheroids. A total of 209 genes were differentially expressed in common by the three cell lines in 3D (138 upregulated and 71 downregulated), although a clear resistance pathway was not apparent. We then compared the list of 3D genes with two publicly available datasets of gene expression of 56 pleural mesotheliomas compared to normal tissues. Interestingly, only three genes were increased in both 3D spheroids and human tumors: argininosuccinate synthase 1 (ASS1), annexin A4 (ANXA4) and major vault protein (MVP); of these, ASS1 was the only consistently upregulated of the three genes by qRT-PCR. To measure ASS1 protein expression, we stained 2 sets of tissue microarrays (TMA): one with 88 pleural mesothelioma samples and the other with additional 88 pleural mesotheliomas paired with matched normal tissues. Of the 176 tumors represented on the two TMAs, ASS1 was expressed in 87 (50%; staining greater than 1 up to 3+). For the paired samples, ASS1 expression in mesothelioma was significantly greater than in the normal tissues. Reduction of ASS1 expression by siRNA significantly sensitized mesothelioma spheroids to the pro-apoptotic effects of bortezomib and of cisplatin plus pemetrexed. Although mesothelioma is considered by many to be an ASS1-deficient tumor, our results show that ASS1 is elevated at the mRNA and protein levels in mesothelioma 3D spheroids and in human pleural mesotheliomas. We also have uncovered a survival role for ASS1, which may be amenable to targeting to undermine mesothelioma multicellular resistance.

Dietary ecology of extant great apes is known to respond to environmental conditions such as climate and food availability, but also to vary depending on social status and life history characteristics. Bonobos (Pan paniscus) live under comparatively steady ecological conditions in the evergreen rainforests of the Congo Basin. Bonobos are an ideal species for investigating influences of sociodemographic and physiological factors, such as female reproductive status, on diet. We investigate the long term dietary pattern in wild but fully habituated bonobos by stable isotope analysis in hair and integrating a variety of long-term sociodemographic information obtained through observations. We analyzed carbon and nitrogen stable isotopes in 432 hair sections obtained from 101 non-invasively collected hair samples. These samples represented the dietary behavior of 23 adult bonobos from 2008 through 2010. By including isotope and crude protein data from plants we could establish an isotope baseline and interpret the results of several general linear mixed models using the predictors climate, sex, social rank, reproductive state of females, adult age and age of infants. We found that low canopy foliage is a useful isotopic tracer for tropical rainforest settings, and consumption of terrestrial herbs best explains the temporal isotope patterns we found in carbon isotope values of bonobo hair. Only the diet of male bonobos was affected by social rank, with lower nitrogen isotope values in low-ranking young males. Female isotope values mainly differed between different stages of reproduction (cycling, pregnancy, lactation). These isotopic differences appear to be related to changes in dietary preference during pregnancy (high protein diet) and lactation (high energy diet), which allow to compensate for different nutritional needs during maternal investment.

ObjectivesWe sought to examine healthcare workers (HCWs) utilisation of formal and informal psychological support resources in the workplace during the first and third waves of the COVID-19 pandemic in Ireland.MethodsA convergent mixed methods approach was undertaken. Four hundred and thirty HCWs in the Mid West and South of Ireland responded to an online survey in terms of their use of psychological support resources during Wave 1 (April/May 2020) of COVID-19. Thirty-nine HCWs undertook in depth interviews at Wave 3 (January/February 2021), and a further quantitative survey was distributed and completed by 278 HCWs at this time. Quantitative data arising at Wave 1 and Wave 3, were synthesised with Qualitative data collected at Wave 3. A Pillar Integration Process (PIP) was utilised in the analysis of the quantitative and qualitative data.ResultsFive pillars were identified from the integration of results. These were: a) the primacy of peer support, b) the importance of psychologically informed management, c) a need to develop the organisational well-being ethos, d) support for all HCWs, and e) HCWs ideas for developing the well-being path. These pillars encapsulated a strong emphasis on collegial support, an emphasis on the need to support managers, a questioning of the current supports provided within the healthcare organisations and critical reflections on what HCWs viewed as most helpful for their future support needs.ConclusionsHCWs who utilised supportive resources indicated 'in house' supports, primarily collegial resources, were the most frequently used and perceived as most helpful. While formal psychological supports were important, the mechanism by which such psychological support is made available, through utilising peer support structures and moving towards psychologically informed supervisors and workplaces is likely to be more sustainable and perceived more positively by HCWs.

The discovery of human remains from the Lauricocha cave in the Central Andean highlands in the 1960's provided the first direct evidence for human presence in the high altitude Andes. The skeletons found at this site were ascribed to the Early to Middle Holocene and represented the oldest known population of Western South America, and thus were used in several studies addressing the early population history of the continent. However, later excavations at Lauricocha led to doubts regarding the antiquity of the site. Here, we provide new dating, craniometric, and genetic evidence for this iconic site. We obtained new radiocarbon dates, generated complete mitochondrial genomes and nuclear SNP data from five individuals, and re-analyzed the human remains of Lauricocha to revise the initial morphological and craniometric analysis conducted in the 1960's. We show that Lauricocha was indeed occupied in the Early to Middle Holocene but the temporal spread of dates we obtained from the human remains show that they do not qualify as a single contemporaneous population. However, the genetic results from five of the individuals fall within the spectrum of genetic diversity observed in pre-Columbian and modern Native Central American populations.

Background: Hair loss/thinning is a common side effect of tamoxifen in estrogen receptor (ER) positive breast cancer therapy. Some nutraceuticals known to promote hair growth are avoided during breast cancer therapy for fear of phytoestrogenic activity. However, not all botanical ingredients have similarities to estrogens, and in fact, no information exists as to the true interaction of these ingredients with tamoxifen. Therefore, this study sought to ascertain the effect of nutraceuticals (+/- estrogen/tamoxifen), on proliferation of breast cancer cells and the relative expression of ERα/β. Methods: Kelp, Astaxanthin, Saw Palmetto, Tocotrienols, Maca, Horsetail, Resveratrol, Curcumin and Ashwagandha were assessed on proliferation of MCF7, T47D and BT483 breast cancer cell lines +/- 17β-estradiol and tamoxifen. Each extract was analysed by high performance liquid chromatography (HPLC) prior to use. Cellular ERα and ERβ expression was assessed by qRT-PCR and western blot. Changes in the cellular localisation of ERα:ERβ and their ratio following incubation with the nutraceuticals was confirmed by immunocytochemistry. Results: Estradiol stimulated DNA synthesis in three different breast cancer cell lines: MCF7, T47D and BT483, which was inhibited by tamoxifen; this was mirrored by a specific ERa agonist in T47D and BT483 cells. Overall, nutraceuticals did not interfere with tamoxifen inhibition of estrogen; some even induced further inhibition when combined with tamoxifen. The ERα:ERβ ratio was higher at mRNA and protein level in all cell lines. However, incubation with nutraceuticals induced a shift to higher ERβ expression and a localization of ERs around the nuclear periphery. Conclusions: As ERα is the key driver of estrogen-dependent breast cancer, if nutraceuticals have a higher affinity for ERβ they may offer a protective effect, particularly if they synergize and augment the actions of tamoxifen. Since ERβ is the predominant ER in the hair follicle, further studies confirming whether nutraceuticals can shift the ratio towards ERβ in hair follicle cells would support a role for them in hair growth. Although more research is needed to assess safety and efficacy, this promising data suggests the potential of nutraceuticals as adjuvant therapy for hair loss in breast cancer patients receiving endocrine therapy. [ABSTRACT FROM AUTHOR]

PurposeThe phosphodiesterase inhibitor sildenafil is a promising treatment for neurodegenerative disease, but it can cause oxidative stress in photoreceptors ex vivo and degrade visual performance in humans. Here, we test the hypotheses that in wildtype mice sildenafil causes i) wide-spread photoreceptor oxidative stress in vivo that is linked with ii) impaired vision.MethodsIn dark or light-adapted C57BL/6 mice ± sildenafil treatment, the presence of oxidative stress was evaluated in retina laminae in vivo by QUEnch-assiSTed (QUEST) magnetic resonance imaging, in the subretinal space in vivo by QUEST optical coherence tomography, and in freshly excised retina by a dichlorofluorescein assay. Visual performance indices were also evaluated by QUEST optokinetic tracking.ResultsIn light-adapted mice, 1 hr post-sildenafil administration, oxidative stress was most evident in the superior peripheral outer retina on both in vivo and ex vivo examinations; little evidence was noted for central retina oxidative stress in vivo and ex vivo. In dark-adapted mice 1 hr after sildenafil, no evidence for outer retina oxidative stress was found in vivo. Evidence for sildenafil-induced central retina rod cGMP accumulation was suggested as a panretinally thinner, dark-like subretinal space thickness in light-adapted mice at 1 hr but not 5 hr post-sildenafil. Cone-based visual performance was impaired by 5 hr post-sildenafil and not corrected with anti-oxidants; vision was normal at 1 hr and 24 hr post-sildenafil.ConclusionsThe sildenafil-induced spatiotemporal pattern of oxidative stress in photoreceptors dominated by rods was unrelated to impairment of cone-based visual performance in wildtype mice.

Background: Unplanned readmissions (URs) after colorectal surgery (CRS) are common, expensive, and result from failure to progress in postoperative recovery. These are considered preventable, although the true extent is yet to be defined. In addition, their successful prediction remains elusive due to significant heterogeneity in this field of research. This systematic review and meta-analysis of observational studies aimed to identify the clinically relevant predictors of UR after colorectal surgery. Methods: A systematic review was conducted using indexed sources (The Cochrane Database of Systematic Reviews, MEDLINE, and Embase) to search for published studies in English between 1996 and 2022. The search strategy returned 625 studies for screening of which, 150 were duplicates, and 305 were excluded for irrelevance. An additional 150 studies were excluded based on methodology and definition criteria. Twenty studies met the inclusion criteria and for the meta-analysis. Independent meta-extraction was conducted by multiple reviewers (JD & SR) in accordance with PRISMA guidelines. The primary outcome was defined as UR within 30 days of index discharge after colorectal surgery. Data were pooled using a random-effects model. Risk of bias was assessed using the Quality in Prognosis Studies tool. Results: The reported 30-day UR rate ranged from 6% to 22.8%. Increased comorbidity was the strongest preoperative risk factor for UR (OR 1.39, 95% CI 1.28–1.51). Stoma formation was the strongest operative risk factor (OR 1.54, 95% CI 1.38–1.72). The occurrence of postoperative complications was the strongest postoperative and overall risk factor for UR (OR 3.03, 95% CI 1.21–7.61). Conclusions: Increased comorbidity, stoma formation, and postoperative complications are clinically relevant predictors of UR after CRS. These risk factors are readily identifiable before discharge and serve as clinically relevant targets for readmission risk-reducing strategies. Successful readmission prediction may facilitate the efficient allocation of healthcare resources. [ABSTRACT FROM AUTHOR]