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Chinese hamster ovary (CHO) is the most commonly used host cell line for therapeutic protein production. Their exposure to highly concentrated feed solution during fed-batch cultivation can cause an unphysiological osmolality increase (>300 mOsm/kg) affecting cell physiology, morphology, and proteome. In a companion article “Hyperosmolality in CHO Culture: Effects on Cellular Behavior and Morphology” we show that hyperosmolalities of up to 545 mOsm/kg force cells to ablate proliferation and gradually increase their volume, almost triplicating it. CHO cells also exhibit a significant hyperosmolality-dependent mitochondrial activity increase. To get a deeper insight into molecular mechanisms involved in these processes, we performed a comparative quantitative label-free proteome study of hyperosmolality-exposed vs. control CHO cells. Our analysis revealed key differentially expressed proteins mediating mitochondrial activation, oxidative stress amelioration, and cell cycle progression. We also discovered a previously unknown strong regulation of proteins altering cell membrane rigidity and permeability. Among others, we detected three members of septins, filamentous proteins forming diffusion barriers in the cell, to be highly upregulated in response to hyperosmolality. Taken together, our observations correlate well with the recent CHO-based fluxome and transcriptome studies and expose new unknown targets involved in response to hyperosmotic pressure in mammalian cells.

Exposure of Chinese hamster ovary cells (CHO) to highly concentrated feed solution during fed-batch cultivation is known to result in an unphysiological osmolality increase (>300 mOsm/kg), affecting cell physiology and morphology. Extending previous observation on osmotic adaptation, the present study investigates for the first time potential effects of hyperosmolality on CHO cells on both population and single-cell level. We intentionally exposed CHO cells to hyperosmolality of up to 545 mOsm/kg during fed-batch cultivation. Contrarily to an expected osmosis effect promoting cell shrinkage, hyperosmolality-exposed CHO cells showed a nearly triplicated volume accompanied by ablation of proliferation. On the molecular level, we observed a strong hyperosmolality-dependent increase in mitochondrial activity in CHO cells compared to control. The companion article “Hyperosmolality in CHO Culture: Effects on Proteome” provides a proteome-based insight into the effects of hyperosmolality on mitochondria. In contrast to mitochondrial activity, hyperosmolality-dependent proliferation arrest of CHO cells was not accompanied by DNA accumulation or caspase-3/7-mediated apoptosis. Notably, we demonstrate for the first time a formation of up to eight multiple, small nuclei in single hyperosmolality-stressed CHO cells. The here presented observations reveal unknown hyperosmolality-dependent morphological changes and support existing data on the osmotic response in mammalian cells.

Microorganisms that support higher trophic life forms are given a central place in global climate change biology. However, the impact of temperature rise on biofilms, dominant microbial life style in aquatic environments is still unclear. Here, we investigated the impact of temperature rise in the context of power plant cooling seawater system on ecological fitness of marine Bacillus. Our results showed that biofilm formation was significantly increased at 37 – 45 °C as compared to ambient seawater temperature of 30 °C. This was supported by increased production of extracellular polymeric substances (EPS) and amyloid in warmer waters. Amyloid, an important structural component in the EPS matrix of Bacillus biofilms, in turn altered the colony characteristics such as morphology, roughness and wetting behaviour facilitating fitness. We hypothesize that biofilm formation and amyloid production is a survival strategy for ecological fitness in marine Bacillus for thriving in the warmer environmental settings.

Background: Pulmonary Hypertension in mitral valvular heart disease leads to various adverse outcome following surgical treatment of this condition. In majority of the patients this Pulmonary Hypertension is reversible following surgery. The objective of this study is to assess the outcome of changes in Severe Pulmonary Hypertension after Mitral Valve Replacement during the follow up with postop Echocardiogram. Patients and methods: In all our 265 patients who underwent Mitral Valve Replacement Surgery (MVR) for Mitral valvular heart disease with pulmonary hypertension, females 111/195(56.9%) outnumbered the males in this study. 195 among 265 cases had severe PHT. MVR was done with cardiopulmonary bypass using St Jude’s medical valve. Results: Despite the high operative mortality in most series of MVR in patients with severe PHT, a striking improvement in survival was noted in the study with 5.3% mortality rate.A sudden drop of PHT is not observed in our study. The fall was found to be gradual and significant over follow up and the maximum reduction was at 1-3 months post operatively. Conclusion: It is concluded that MVR reduces PHT in a gradual way and the mortality rate is also minimum in severe PHT patients. MVR thereby is an effective invasive procedure for the management of patients with severe mitral valve disease and PHT. Keywords: Severe Pulmonary Hypertension, mitral valvular disease, mitral valve replacement, Pulmonary artery pressure, Rheumatic Heart Disease

Contemporary forest management strives to satisfy contrasting demands on forest ecosystems by promoting multiple ecosystem services. These services are affected in varied manners by alternative management actions operating at local or landscape scales, potentially leading to trade-offs and synergies. We here studied ecosystem functions and biodiversity data across ecosystem compartments in 53 mature forest plots varying in stand-level (tree species composition) and landscape-level (degree of fragmentation) characteristics. We show that more than two-thirds of the 20 trade-offs and synergies between functions and diversity variables were driven by variation in tree species composition and fragmentation. Interestingly, more fragmented landscapes had higher landscape-level forest functioning, but this came at the expense of forest biodiversity. At the same time, mixed forest stands had higher levels of biodiversity than monocultures without affecting forest functioning. Diversifying forest stands thus represents a potential management strategy that promotes both ecosystems functioning and biodiversity in fragmented landscapes.

Objective: In some adult patients diagnosed with Covid-19, abnormal lung imaging and then pulmonary fibrosis were detected in these patients after discharge. Studies on pulmonary function tests have been carried out in these patients, but not yet in pediatric patients. In our study, we performed pulmonary function tests 1 month after discharge in pediatric patients diagnosed with Covid-19. Thus, we thought that when we encountered pulmonary dysfunction in our patients, we could reduce morbidity and mortality by enabled them get involved in pulmonary rehabilitation programs. Material and Methods: In this prospective study, pediatric patients aged 5-18 years who were hospitalized and discharged with the diagnosis of Covid-19 were included. Pulmonary function tests were performed with spirometry in our patients. Results: 76 patients were screened. 34 patients were able to perform pft.When the percentage values of the patients in pulmonary function tests were compared with the test value of 100, no significant decrease was found. When the actual values measured by spirometry were compared with the predictive values that should be at the same age, weight and height, no significant decrease was found. However, in the correlation analysis, a moderately negative correlation was found between the length of hospital stay and Fef 25-75. Conclusion: The fact that the decreasing of Fef 25-75 as the hospitalization period increases due to Covid-19 may be meaningful in terms of showing us that having covid 19 worsens lung functions even in pediatric patients. More comprehensive studies are needed to understand the prognosis of these patients.

Fatigue behaviour of HIPed and stress relieved Ti6Al4V alloy specimen’s produced by SLM was analysed (Rε = -1). The HIP process caused a microstructural transformation decreasing the hardness and monotonic properties that not allowed fatigue strength increase. A bilinear behaviour in the elastic strain-fatigue life curve was observed, because of Young´s modulus decrease during the cyclic elasto-plastic tests consequence of subgrains formation. The Smith-Watson-Topper and total strain energy density models showed a good concordance between predicted and experimental fatigue lives in notched samples.

Postdoctoral positions provide critical opportunities for early career scientists to build skills, knowledge, and networks, but these positions often come with personal and professional challenges such as stress, isolation, and lack of agency. Here, we describe a peer-led postdoc program we created to maximize benefits and minimize challenges while preparing ourselves for a wide range of possible future careers. We also give recommendations for other postdocs and early career scientists seeking to build a similar program.

Long-term experiments are important in evaluating ecosystem properties and processes that are slow to develop or require proper evaluation over an appropriately variable climate. We repurpose the wealth of data accessible through the forty-year-old Long-Term Ecological Research (LTER) network with a novel moving window algorithm and meta-analysis approach to ask if aspects of study taxa or environment alter the extent of research necessary to detect consistent results, or the proportion of spurious short-term trends. We found that experimental studies focused on plants, and those conducted in dynamic abiotic environments, were characterized by longer critical temporal thresholds and more spurious trends. Further, nearly half of the studies we investigated required 10 years or longer to reach a temporal threshold, and 4 studies (of 100) required longer than 20 years. We champion long-term data and argue that long-term experiments are more necessary than ever to understand, explain, and predict long-term trends.

Background:. In January 2020 a modification is applied for pediatric ventilator associated events (Ped-VAE) surveillance by Center for Disease Control and Prevention. İn this study we investigate the potential impact of this newly criteria and determine whether the adult ventilator-associated conditions (VAC), infection-related ventilator-associated complications (İVAC) and possible ventilator-associated pneumonia (PVAP) criteria could be applied pediatric patients with ped-VAE Methods:. We analyzed data between January 2014 and December 2019 using the new ped-VAE criteria. We compared two different criteria for identifying VAE: the 2013 adult VAE criteria, and the newly ped-VAE criteria. Result: The data of 91 VAE patients were evaluated, 42.8 % were not categorized as ped-VAE and 57.2% patients were compatible with the ped-VAE , 19.2% were categorized as adult VAC, 21.1% were categorized as IVAC, and 59.6% patients were categorized as PVAP. There was no significant difference between mortality and the diagnostic ventilator surveillance types. Conclusions: Pediatric ventilator-associated event algorithm is a better tool for children than the VAE algorithm defined for adults and the new pediatric criteria are more effective in detecting ventilator assosiated complications in children. We think further studies will be needed for evaluate ped VAE criteria.

We describe six teenagers presenting with fever and severe abdominal symptoms admitted with concerns for multisystem inflammatory syndrome in children (MIS-C). Laboratory evaluation revealed elevated markers of inflammation, lymphopenia, and increased d-dimers. Imaging studies revealed multifocal airspace disease and ground-glass opacities. SARS-CoV-2 PCR and serologies were negative. All patients reported a history of vaping, prompting E-cigarette, or vaping, product use-associated lung injury (EVALI) diagnosis. MIS-C has overlapping clinical and laboratory features highlighting the added challenge of diagnosing EVALI during the COVID-19 pandemic.

The main objective of this study was to evaluate two restoration techniques, “stone rows” and “stone rows + tree planting” on soil organic carbon (SOC) sequestration and structure in terms of water stable aggregates as well as the time required to restore soil fertility. The Carbon, Aggregate and Structure Turnover (CAST) model was used to model the changes of SOC content and water stable aggregate formation under the two restoration techniques. Field experiments used for calibration of the model were conducted using a randomized block design. Soil samples were class fractionated followed by a micro-aggregate isolation procedure. The two restoration techniques contributed significantly to improving soil total carbon content. By running five year simulation of the “stone rows”, the estimated total carbon input was 27 Mg ha-1 of which 6.1 Mg ha-1 were sequestered in the soil and 20.7 Mg ha-1 were released as CO2. In “stone rows + planting”, the total SOC content after five years was estimated to be 22.96 Mg ha-1, which was broken down to 15.43 Mg ha-1 aggregated carbon and 26.60 Mg ha-1 CO2. Fifty-year simulations showed a SOC increase to 54.8 Mg ha-1 in “stone rows”, and to 86.0 Mg ha-1 in “stone rows + planting”. This means that natural grassland vegetation slowly improves soil carbon content and soil quality, but with trees behind stone rows, the result will be about 50% higher.

Background: Chronic rhinitis (CR) is currently defined as at least two nasal symptoms present for at least 1 hour per day for more than 12 weeks per year. Such definition lacks evidence-based foundation. Depending on the most troublesome symptom, CR patients are often divided into ‘runners’ and ‘blockers’, although the evidence supporting such subdivision is limited. The aim of the current study was to define CR, and to estimate its prevalence and the prevalence of the ‘runners’ and ‘blockers’ subtypes. Methods: Cross-sectional, questionnaire-based study in a random sample of participants representing the general population of the Netherlands. Results: The questionnaire was sent to 5000 residents; the response rate was 27%. CR was defined as at least 1 nasal complaint present for more than 3 weeks per year. The prevalence of CR in the general population was 40%. Participants who were excluded by the former CR definition (i.e. nasal complaints present for less than 1 hour per day, only one complaint, duration of complaints for 3-12 weeks per year) were shown to have a significantly higher VAS compared to the control group. The larger part of CR group was represented by non-allergic rhinitis (NAR): 70% vs 30%. There were 25% ‘Blockers’ and 22% ‘Runners’ in the CR group, whereas more than a half of the CR group could be classified in neither of these subgroups. Conclusion: Based on our data, we propose a new definition of CR: at least one nasal complaint present for at least 3 weeks per year.

It is well appreciated that moist tropical forests from South America have been broadly affected by climate change. However, long-term trends of seasonal forests are still largely understudied. Here, we evaluate the long-term ecological trends of seasonal Brazilian forests. We used 33 years of locally collected soil and vegetation data (837 tree species) gathered from 34 hectares of evergreen, semideciduous and deciduous forests. We expected them to be more sensitive than resilient to climate change. Across the study region, more species were extinct (315) than locally recruited (238). Locally extinct species’ niches were characterized by lower temperatures and higher precipitation. Climatic variables were the main drivers of productivity decrease, especially for larger trees. Deciduous forests were the most vulnerable for being at their ecological threshold. For encompassing a broad temporal scale, our study provided a detailed view of species responses and ecosystem function in tropical forests.

Background: ECEL1 has been represented as a causal gene of an autosomal recessive form distal arthrogryposis (DA) which affects the distal joints. The present study focused on bioinformatic analysis of a novel mutation in ECEL1, c.535A>G (p. Lys179Glu), which reported in a family with 2 affected boy and fetus through prenatal diagnosis. Material and Methods: Whole exome sequencing data analyzed followed by Molecular Dynamics (MD) simulation of native ECEL1 protein and mutant structures using GROMACS software. Results: One variant c.535A>G, p. Lys179Glu (Homozygous) on gene ECEL1 has been detected in proband which was segregated in all family members. we demonstrated remarkable constructional differences by MD simulation between wild type and novel mutant of ECEL1 gene.the reason of the lack of the Zn ion binding in mutation in the ECEL1 protein have been identified by average atomic distance and SMD analysis among the wild type and mutant Conclusion: Overall, our findings in this study we present aknowledge of the effect of the mutation on the ECEL1 protein leading towards the fatal neurodegenerative disorder in humans. This work may hopefully be supplementary to classical molecular dynamics to dissolve the mutational effects of cofactor dependent protein, since the second one is time consuming and laborious.

Freshwater ecosystems occupy <1% of the Earth’s total surface area but provide an array of ecosystem services. However, these ecosystems are threatened by multiple stressors, including overexploitation, infrastructure developments, habitat alteration, and alien species introductions. The magnitude of these threats varies in different water bodies, requiring site-based conservation actions. In this paper, we aimed at developing a priority index (CPIw) that can be used to inform conservation managers in prioritizing the selection of a waterbody for site-based fish conservation purposes. We used data on distribution, diversity, and conservation status of fishes of Uganda, which were retrieved from the Global Biodiversity Information Facility (GBIF) and International Union Conservation for Nature (IUCN) databases. In the index, we incorporated the species richness, surface area of a waterbody, species rarity, and species IUCN status. A total of 288 fish species were recorded in 81 waterbodies (7 large lakes, 37 small lakes, and 37 rivers). Of these species, 110 were only found in large lakes, followed by rivers (19) and small lakes (6). Despite the higher species richness in large lakes relative to small lakes, the latter recorded significantly higher CPIw compared with the former (t = -2.8, df = 30, p-value = 0.008, d=0.7). This observation is consistent with the expectation, given the low ecological substitutability for the species and higher levels of exposure to human-induced threats in small water bodies compared with large systems. Therefore, we suggest that in situations where resources are limiting, small water bodies need to be given much attention, although we do not suggest ignoring water bodies with low CPIw values.

Aim: To develop clinical algorithms for the assessment and management of slow progress of labour. Population: Low-risk singleton, term, pregnant women in labour. Setting: Institutional births in low- and middle-income countries. Search Strategy: We systematically reviewed the literature on normal labour progression, and guidance on clinical management of abnormally slow progression from 1 December 2015 to 1 December 2020. Case scenarios: We developed two clinical algorithms: one for abnormally slow labour progression and arrest during first and one for second stage. Conclusions: Identifying abnormal progress of labour is often challenging. These algorithms may help to reduce misdiagnosis.

Background: There is variation in the reported incidence of levator avulsion (LA). Objective: Explore incidence of LA by mode of birth, imaging modality, timing of diagnosis and laterality of avulsion. Search strategy: We searched MEDLINE, EMBASE, CINAHL, AMED and MIDIRS with no language restriction from inception to April 2019. Study eligibility criteria: A study was included if LA was assessed by an imaging modality after the first vaginal birth or if only delivered by caesarean section. Case series and reports were not included. Data collection and analysis: RevMan v5.3 was used for the meta-analyses and SW SAS and STATISTICA packages for type and timing of imaging analyses. . Results: We included 37 primary non-randomized studies from 17 countries and involving 5594 women. Incidence of LA was 1%, 15%, 21%, 38.5% and 52% following caesarean, spontaneous, vacuum, spatula and forceps births respectively, with no differences by imaging modality. OR of LA following spontaneous birth vs. caesarean was 10.69. While the OR for LA following vacuum and forceps compared to the spontaneous birth were 1.66 and 6.32 respectively. LA was more likely to occur on the right side following spontaneous birth (p = 0.02) and unilaterally vs. bilaterally following spontaneous (P < .0001) and vacuum-assisted births (P = 0.0103) only. Incidence was higher if assessment was performed in the first 4 weeks postpartum. Conclusions: Forceps significantly increases incidence and severity of LA. Ultrasound and MRI are comparable diagnostic tools but early postpartum imaging may lead to over diagnosis of LA.

Vector-borne diseases (VBDs) are embedded within complex socio-ecological systems. While research has traditionally focused on direct effects of VBDs on morbidity and mortality, it is increasingly clear that VBD impacts are much more pervasive, dynamically linked to feedbacks between environmental conditions, vector ecology, disease burden, and societal responses that drive transmission. VBDs have had profound influence on human history via mechanisms that include: (1) killing or debilitating large numbers of people, with direct demographic and population-level impacts; (2) differentially affecting populations based on prior history of disease exposure, immunity, and resistance; (3) being weaponized to promote or justify existing hierarchies of power, colonialism, racism, classism, and sexism; (4) catalyzing changes in ideas, institutions, infrastructure, technologies, and social practices in efforts to control disease outbreaks; and (5) changing human relationships with the land and environment. We use historical and archaeological evidence interpreted through an ecological lens to illustrate how four major VBDs have shaped society and culture: plague, malaria, yellow fever, and trypanosomiasis. By comparing across diseases, time periods, and geographies, this review highlights the enormous scope and variety of mechanisms by which VBDs have influenced human history from the age of early Homo sapiens to the modern context.

An 11 years-old male mixed-breed cat, with exclusively indoor life, presented 3 cough episodes after the owners tested positive by RT-PCR for SARS-CoV-2. The house is inhabited by 5 people (3 adults and 2 children), and 2 of the adults have shown mild symptoms associated with throat discomfort. The cat was vaccinated, had no history of any previous disease, and tested negative for Feline Coronavirus (FeCoV), Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV). Rectal sample collected from the cat was positive for SARS-CoV-2 by RT-PCR. Viral genome sequences recovered from human and cat samples showed an average 99.4% sequence identity. This is the first report of genome sequences of SARS-CoV-2 recovered from a cat and its owner in Latin America.

Objective: To explore and understand health-seeking behaviors of women affected by obstetric fistula in Zimbabwe and to determine reasons women stayed with their fistula. Design: A cross sectional qualitative study was conducted using in-depth interview guides. Setting: Chinhoyi Provincial Hospital, the main fistula repair center in Zimbabwe. Study population: Women who had come for fistula repair between November and December 2019 were the study population for this study. Methods: All women who had come for fistula repair during the study period, who consented to participate were purposively enrolled into the study. Those who did not consent were excluded. In-depth interviews were audio recorded and transcribed into written scripts and analyzed using NVIVO 10. Main outcome measures: Health seeking behaviors of fistula survivors and reasons for living with fistula. Results: Twenty-one of the 29 women who had come for the fistula camp, were enrolled. Mean period staying with fistula was 4.7 years (SD±12). Participants sought help from faith and spiritual healers first before medical help for fistula but all sought medical care at one time during or after delivery. Reasons cited for staying with fistula included lack of knowledge of availability of repair services, lack of resources and powerlessness in decision making. Conclusions: Barriers to access should be addressed so that women get the treatment they require. Since all participants accessed a health facility at one point, medical care could be offered for prevention and care of fistula Funding: Nil Key words: Obstetric fistula; Health seeking behavior; Zimbabwe

Background There is neither a surveillance system nor a study to reveal the HD related infection rates in Turkey. We aimed to investigate the infection rate among HD outpatients and implement CDC’s surveillance system. Methods A multicenter prospective surveillance study is performed to investigate the infection rate among HD patients. CDC National Healthcare Safety Network dialysis event (DE) protocol is adopted for definitions and reporting. Results During April 2016–April 2018, 9 centers reported data. A total of 199 DEs reported in 10035 patient-months, and the overall DE rate was 1.98 per 100 patient-months. Risk of blood culture positivity is found to be 17.6 times higher when hemodialysis was through a tunneled catheter than through an arteriovenous fistula. DE rate was significantly lower in patients educated about the care of their vascular access site. Mean body mass index was significantly higher in patients with any DE. Staphylococcus aureus was the most causative microorganism among mortal patients. Outcomes of DEs were hospitalization (73%), loss of vascular access (18.2%), and death (7.7%). Conclusions This first surveillance study in Turkey gave insight into current DE status and will guide to generate a national surveillance system for maintaining much lower DE rates.

A 50 year old male with a history of myocardial infarction 3 months prior presents to the emergency department with shortness of breath. Diagnostic workup revealed a left ventricular pseudoaneurysm of the inferolateral wall. Coronary artery disease and mitral valve regurgitation were concomitantly identified. Surgical intervention on these issues was successful. This case report highlights a rare but important complication of myocardial infarction.