Sunlight-mediated inactivation of health-relevant microorganisms in water: a review of mechanisms and modeling approaches.

Health-relevant microorganisms present in natural surface waters and engineered treatment systems that are exposed to sunlight can be inactivated by a complex set of interacting mechanisms. The net impact of sunlight depends on the solar spectral irradiance, the susceptibility of the specific microorganism to each mechanism, and the water quality; inactivation rates can vary by orders of magnitude depending on the organism and environmental conditions. Natural organic matter (NOM) has a large influence, as it can attenuate radiation and thus decrease inactivation by endogenous mechanisms. Simultaneously NOM sensitizes the formation of reactive intermediates that can damage microorganisms via exogenous mechanisms. To accurately predict inactivation and design engineered systems that enhance solar inactivation, it is necessary to model these processes, although some details are not yet sufficiently well understood. In this critical review, we summarize the photo-physics, -chemistry, and -biology that underpin sunlight-mediated inactivation, as well as the targets of damage and cellular responses to sunlight exposure. Viruses that are not susceptible to exogenous inactivation are only inactivated if UVB wavelengths (280-320 nm) are present, such as in very clear, open waters or in containers that are transparent to UVB. Bacteria are susceptible to slightly longer wavelengths. Some viruses and bacteria (especially Gram-positive) are susceptible to exogenous inactivation, which can be initiated by visible as well as UV wavelengths. We review approaches to model sunlight-mediated inactivation and illustrate how the environmental conditions can dramatically shift the inactivation rate of organisms. The implications of this mechanistic understanding of solar inactivation are discussed for a range of applications, including recreational water quality, natural treatment systems, solar disinfection of drinking water (SODIS), and enhanced inactivation via the use of sensitizers and photocatalysts. Finally, priorities for future research are identified that will further our understanding of the key role that sunlight disinfection plays in natural systems and the potential to enhance this process in engineered systems

Optineurin downregulation induces endoplasmic reticulum stress, chaperone-mediated autophagy, and apoptosis in pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) shows a high level of basal autophagy. Here we investigated the role of optineurin (OPTN) in PDAC cell lines, which is a prominent member of the autophagy system. To that purpose, mining of publically available databases showed that OPTN is highly expressed in PDAC and that high levels of expression are related to reduced survival. Therefore, the role of OPTN on proliferation, migration, and colony formation was investigated by transient knockdown in Miapaca, BXPC3, and Suit2-007 human PDAC cells. Furthermore, gene expression modulation in response to OPTN knockdown was assessed by microarray. The influence on cell cycle distribution and cell death signaling cascades was followed by FACS, assays for apoptosis, RT-PCR, and western blot. Finally, autophagy and ROS induction were screened by acridine orange and DCFH-DA fluorescent staining respectively. OPTN knockdown caused significant inhibition of colony formation, increased migration and no significant effect on proliferation in Miapaca, BXPC3 and Suit2-007 cells. The microarray showed modulation of 293 genes in Miapaca versus 302 in Suit2-007 cells, of which 52 genes overlapped. Activated common pathways included the ER stress response and chaperone-mediated autophagy, which was confirmed at mRNA and protein levels. Apoptosis was activated as shown by increased levels of cleaved PARP, Annexin V binding and nuclear fragmentation. OPTN knockdown caused no increased vacuole formation as assessed by acridine orange. Also, there was only marginally increased ROS production. Combination of OPTN knockdown with the autophagy inducer erufosine or LY294002, an inhibitor of autophagy, showed additive effects, which led us to hypothesize that they address different pathways. In conclusion, OPTN knockdown was related to activation of ER stress response and chaperone-mediated autophagy, which tend to confine the damage caused by OPTN knockdown and thus question its value for PDAC therapy

Die flächenhafte Ausweisung von Bodenfeuchteregimes: Eine Methode im Rahmen des pre-processing für die Modellierung des Landschaftswasserhaushaltes

In dem Einzugsgebiet „Obere Brachtpe“ (2,6 km², Sauerland, Deutschland) wurden mit einer konventionellen Bohrstock-Kartierung (319 Bodenprofile) die verschiedenen Böden mit ihren spezifischen pedohydrologischen Eigenschaften erfasst und darauf aufbauend das Klassifikationskonzept zur Ableitung von Bodenfeuchteregime-Typen nach Zepp (1995) angewendet. Anhand dieser Informationen konnte die vorherrschende Wasserbewegungsrichtung und folglich verschiedene Abflussprozessflächen ausgewiesen werden. Um dieses Raumgliederungskonzept hinsichtlich der Frage, ob es zum pre-processing für die Modellierung des Landschaftswasserhaushalts beitragen kann, zu verfizieren, wurden zwei Niederschlags-Abfluss-Ereignisse tracerhydrologisch untersucht. Die Resultate zeigen, dass sich das Klassifikationskonzept nach Zepp (1995) zur hydrologischen Raumgliederung eines Einzugsgebietes gut eignet, es wird aber auch deutlich, dass neben den Bodeneigenschaften insbesondere die Lage der schnell reagierenden Flächen (Sättigungsflächen) innerhalb des Einzugsgebietes und deren Konnektivität mit dem Vorfluter entscheidend für den Beitrag schneller Abflusskomponenten sind. Besteht eine direkte Verbindung zwischen Sättigungsflächen und Vorfluter, so ist eine schnelle Abflussreaktion und ein hoher Anteil an Ereigniswasser zu erwarten.In the catchment “Obere Brachtpe” (2,6 km², Sauerland, Germany) the soils and their specific pedohydrological characteristics were investigated using a conventional drilling rig (319 drills). Based on the results the classification concept for deducing the soil moisture types by Zepp (1995) was applied so that the dominant flow directions and dominant runoff process areas could be detected. The question if this classification concept could be used as tool for the pre-processing within the runoff modelling was verified by the tracer hydrological investigation of two rainfall runoff-events. The results confirm that the classification concept by Zepp (1995) is an applicable tool for the spatial delineation of a catchment in hydrological response units. On the other hand it became apparent that in addition to the soil properties, the location of saturated areas within the catchment and their connectivity to the channel are especially important for the contribution of accelerated runoff components. If there exists a direct connection between the saturated areas and the channel a fast runoff reaction and a high portion of event water can be estimated

Ocular geometry in adults born extremely, very and moderately preterm with and without retinopathy of prematurity: results from the Gutenberg Prematurity Eye Study

Background/aims: To evaluate whether anterior segment anatomy and axial length are associated with prematurity and perinatal factors in adults. Methods: The Gutenberg Prematurity Eye Study examined adults born preterm and term aged 18–52 years. All participants underwent a prospective ophthalmic examination (optical biometry via a LenStar 900, Haag-Streit) in Germany. The associations between gestational age (GA), birth weight (BW) and BW percentile, retinopathy of prematurity (ROP) occurrence, ROP treatment and other perinatal factors with the main outcome measures were evaluated by univariate and multivariable linear regression analyses. Main outcome measures were corneal radius, white-to-white distance, anterior chamber depth, lens thickness and axial length. Results: The study involved 861 eyes of 438 preterm and full-term individuals (aged 28.6±8.7 years, 245 females,). After adjustment for age and gender, a steeper corneal radius was associated with lower GA (B=0.02; p<0.001) and a lower BW percentile (B=0.003; p<0.001). A smaller white-to-white distance was linked to lower GA (B=0.02; p<0.001), a lower BW percentile (B=0.004; p<0.001) and postnatal ROP occurrence (B=−0.26; p<0.001). Decreased axial length was associated with lower GA at birth (B=0.05; p=0.002) and pre-eclampsia (B=−0.34; p=0.015). ROP-treated eyes had a shallower anterior chamber depth (B=−0.63; p=0.001) and increased lens thickness (B=0.64, p<0.001). Conclusion: Our analyses in adults demonstrate that the corneal morphology is influenced by GA and BW percentile, while the anterior chamber depth and lens thickness are affected by ROP treatment, namely laser therapy and cryotherapy. The present study highlights that perinatal factors lead to lifelong sequelae of ocular shape

Visual acuity, amblyopia, and vision-related quality of life in preterm adults with and without ROP : results from the Gutenberg prematurity eye study

Objectives This study investigated the effects of prematurity and ROP on visual acuity and VRQoL in adults (18–52 years). Methods The Gutenberg Prematurity Eye Study is a retrospective cohort study with a prospective ophthalmologic examination. Preterm and full-term participants at an age from 18 to 52 years were included. Distant corrected visual acuity (DCVA) and VRQoL were assessed in participants (892 eyes of 450 individuals aged 28.6 ± 8.6 years, 251 females) grouped into full-term controls (gestational age [GA] at birth ≥37 weeks), preterm participants without ROP and GA 33–36 weeks (group 2), GA 29–32 weeks (group 3), GA ≤ 28 weeks (group 4), non-treated ROP (group 5) and treated ROP (group 6). Main outcome measures were distant corrected visual acuity (DCVA), VRQoL and prevalence of amblyopia. Results The DCVA of the better eye correlated (p < 0.001) with GA, birth weight, ROP, ROP treatment, and perinatal adverse events and was poorer in both ROP groups. Visual acuity of <20/200 in the better eye was observed in two participants (4.2%) in the ROP group and one person (6.7%) in the treated ROP group. The prevalence of amblyopia increased in the ROP groups. Compared to full-term controls, visual functioning VRQoL scores were lower in preterm individuals independent of ROP while socioemotional VRQoL scores were only lower in the treated ROP group. Conclusion Participants with postnatal ROP and its treatment showed decreased visual acuity and VRQol in adulthood, with amblyopia occurring more frequently in more preterm participants with ROP

A lower birth weight percentile is associated with central corneal thickness thinning : results from the Gutenberg Prematurity Eye Study (GPES)

Purpose: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. Marterials and Methods: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. Results: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. Conclusion: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage

Most people share genetic test results with relatives even if the findings are normal: Family communication in a diverse population.

PURPOSE: With increasing utilization of genetic testing, sharing genetic information can become part of general family health communication while providing biological relatives with important information about their own genetic risk. Importantly, little is known about motivations for and barriers to family communication of genetic information in historically underserved populations. METHODS: Using mixed methods, we explored patient experiences with family communication in a study population of English- and Spanish-speaking adults aged 18 to 49 years, enriched for participants from historically underserved backgrounds. Risk screening for hereditary cancer guided genetic testing for cancer risk genes and other medically actionable findings. RESULTS: Most participants overall (91%), including most with normal findings (89%), shared or planned to share their results with relatives. Common motivations for sharing results were to give relatives information about their genetic risk and because the participant thought the results were interesting. Reasons for not sharing were limited contact with relatives, perceptions of limited clinical utility for relatives, and concern that discussion of genetic information was stigmatized or taboo. CONCLUSION: Results demonstrate high rates of sharing genetic information, indicate motivations for sharing go beyond facilitating genetic testing for relatives, and suggest general willingness to share genetic information as part of family health communication

Evaluation of mailed results versus telephone disclosure of normal cancer genetic test results in a low-risk underserved population.

Scalable models for result disclosure are needed to ensure large-scale access to genomics services. Research evaluating alternatives to genetic counseling suggests effectiveness; however, it is unknown whether these findings are generalizable across populations. We assessed whether a letter is non-inferior to telephone genetic counseling to inform participants with no personal or family history of cancer of their normal results. Data were collected via self-report surveys before and after result disclosure (at 1 and 6 months) in a study sample enriched for individuals from underserved populations. Primary outcomes were subjective understanding of results (global and aggregated) and test-related feelings, ascertained via three subscales (uncertainty, negative emotions, and positive feelings) of the Feelings About genomiC Testing Results (FACToR) measure. Secondary outcomes related to satisfaction with communication. Non-inferiority tests compared outcomes among disclosure methods. Communication by letter was inferior in terms of global subjective understanding of results (at 1 month) and non-inferior to telephoned results (at 6 months). Letter was non-inferior to telephone for aggregated understanding (at 6 months). Letter was superior (at 1 month) to telephone on the uncertainty FACToR subscale. Letter was non-inferior to telephone on the positive-feelings FACToR subscale (at 6 months). Letter was non-inferior to telephone for satisfaction with mode of result delivery and genetic test results. Communication via letter was inferior to telephone in communicating the right amount of information. The use of written communication to relay normal results to low-risk individuals is a promising strategy that may improve the efficiency of care delivery