Moderate Elevation Research Articles

Study of Morphological Changes in the Inferior Turbinate After Le Fort I Osteotomy.

There are cases in which patients complain of nasal obstruction after Le Fort I osteotomy, but the relationship with postoperative morphological changes in the nasal cavity, including the septum and inferior turbinate, is not clear. The authors evaluated the three-dimensional relationship of the morphological changes in the inferior turbinate before and after surgery in 84 patients who underwent Le Fort I osteotomy. Three classifications were made according to superior amount of maxillary movement at the base of nasal cavity. The high elevation group (4.0 mm or more) had 31 sides, the moderate elevation group had 93 sides, and the low elevation group (less than 2.0 mm) had 44 sides. The volume of inferior turbinate was 76.9 ± 12.8% of that before surgery in the high elevation group. The high- and moderate-elevation groups had significantly higher changes than the low elevation group, and the rate of contact between inferior turbinate and nasal cavity floor was 67.7%. After Le Fort I osteotomy, the volume of inferior turbinate tissue decreased in proportion to the amount of elevation of the maxilla. Although the soft tissue volume may be reduced due to adaptation of respiratory function, the inferior nasal passage was not completely ventilated in the high elevation group. If the elevation exceeds 4.0 mm counterclockwise with maxillary movement, it is necessary to consider the concomitant inferior turbinate resection because it may lead to nasal obstruction.

Indices of iron homeostasis in asymptomatic subjects with HFE mutations and moderate ferritin elevation during iron removal treatment

We analysed iron biomarkers and their relationships in 30 subjects with HFE mutations and moderate hyperferritinaemia undergoing iron removal at our blood donation centre.Body mass index (BMI) and liver enzymes were assessed. Serum iron (SI), ferritin, transferrin saturation (TSAT), hepcidin and non-transferrin bound iron (NTBI) were measured serially.Seventeen subjects had p.C282Y/p.C282Y, nine p.C282Y/p.H63D, four p.H63D/p.H63D. Median age (p = 0.582), BMI (p = 0.500) and ferritin (p = 0.089) were comparable.At baseline, 12/17 p.C282Y/p.C282Y and 2/9 p.C282Y/p.H63D had measurable NTBI (p = 0.003). The p.C282Y/p.C282Y had higher TSAT (p < 0.001), lower hepcidin (p = 0.031) and hepcidin/ferritin ratio (p = 0.073). After treatment, iron indices were similar among groups, except TSAT (higher in p.C282Y/p.C282Y; p = 0.06).Strong relationships were observed between ferritin and TSAT (R = 0.71), NTBI and TSAT (R = 0.61), NTBI and SI (R = 0.54) in p.C282Y/p.C282Y. Hepcidin correlated weakly with ferritin in p.C282Y/p.C282Y (R = 0.37) but strongly in p.C282Y/p.H63D (R = 0.66) and p.H63D/p.H63D (R = 0.72), while relationships with TSAT were weak (R = 0.27), moderate (R = 0.55) and strong (R = 0.61), respectively.Low penetrance p.C282Y/p.C282Y phenotype displays hepcidin dysregulation and biochemical risk for iron toxicity.

Abstract 1732: Nanoparticle delivery of cancer-activated DNA enables the detection and localization of tumors in mice

Abstract The expression of synthetic biomarkers from genetic constructs represents a new paradigm of molecular diagnostic tools for early cancer detection and localization. One of the limitations of liquid biopsy approaches is the low abundance of endogenous biomarkers shed in early-stage disease. To overcome this, Earli’s platform instead uses genetic constructs to force tumors to produce cancer-activated synthetic biomarkers. Thus, technologies that deliver DNA to tumor cells in multiple tissues need to be developed. While non-viral delivery systems such as lipid nanoparticles (LNPs) have achieved clinical success for RNA, the delivery of DNA to tumor cells remains a challenge. We have engineered two classes of nanoparticles using biodegradable and ionizable cationic materials. The efficacy of these nanoparticles to deliver a DNA nanoplasmid containing a cancer-activated promoter to drive expression of a secreted embryonic alkaline phosphatase (SEAP) was evaluated in multiple cell-derived xenograft (CDX) models. The first class of nanoparticles was comprised of poly-beta-amino-ester polymers (PBAEs). Systematic screening of a library of PBAEs and optimization of PEG-lipid content produced nanoparticles approximately 80-100 nm in diameter with slightly positive zeta potential, enabling biodistribution to mouse lung tissues. Testing of initial nanoparticle compositions identified safe and effective formulations that produced 5-fold higher SEAP expression levels in lung tumor-bearing animals versus naïve mice. Further enhancements produced SEAP levels up to 250-fold higher in tumor-bearing versus control mice but resulted in significant increases in liver enzymes, suggesting tolerability issues that are currently being addressed by improving the polymer and formulation composition. The second class of nanoparticles was composed of ionizable lipids such as DLin-MC3-DMA that have been clinically validated for RNA delivery to the liver. Optimized compositions with helper lipid and PEG-lipid variants identified formulations that could successfully deliver DNA to the liver. These formulations produced 30-fold higher SEAP expression in tumor-bearing animals compared to naïve controls in an H1299 CDX model. A 7-fold difference in SEAP levels was demonstrated in an orthotopic Hep3B CDX model between tumor versus non-tumor bearing animals. Strikingly, LNP delivery of a cancer-activated Renilla luciferase construct produced tumor-specific bioluminescence, demonstrating the ability of the LNPs to localize liver tumors. LNP formulations were well tolerated, producing transient, mild to moderate elevations in liver enzymes one day after administration that subsequently resolved. These potent and safe nanoparticle delivery systems are promising agents for enabling future clinical translation of our synthetic biomarker platform. Citation Format: Badri Ananthanarayanan, Regina Nieu, Weihang Ji, Blaine McCarthy, Shengshuang Zhu, Alex Harwig, Maggie C. Louie, David Suhy. Nanoparticle delivery of cancer-activated DNA enables the detection and localization of tumors in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1732.

Pulmonary Hypertension Associated with Chronic Obstructive Pulmonary Disease

Pulmonary hypertension (PH) is likely to complicate chronic obstructive pulmonary disease (COPD) in a large proportion of patients, especially those with severe disease. Majority of patients have a mild to moderate elevation in the pulmonary artery pressure that usually does not require specific treatment. A small subset of patients, however, develops severe PH that is "out-of-proportion" to the severity of COPD. Generally considered a consequence of chronic hypoxaemia, endothelial dysfunction has now been recognised to play an important role in the pathogenesis of PH in COPD. Pulmonary vessels remodelling characterised by intimal enlargement with proliferating smooth muscle cells, medial hypertrophy, arteriolar muscularisation and endothelial cell proliferation, especially affecting the small arterioles and arteries, leads to permanent changes in the vascular structure and function. Clinical recognition of PH is difficult. Echocardiography is used for screening while right heart catheterisation is the gold standard for diagnosis. In patients who have a moderate degree of chronic hypoxaemia, long term oxygen therapy is indicated and is the only therapeutic measure so far known to retard the progress of PH. Newer therapies targeting the specific abnormalities of vasoconstrictor-vasodilator balance, arising as a consequence of endothelial dysfunction, are under investigation and may offer a management option especially in severe PH associated with COPD.

Roosting ecology of Gould's wild turkeys in southeastern Arizona

AbstractAvailability of suitable roosting sites influences distribution of wild turkeys (Meleagris gallopavo) across the landscape. In semi‐arid environments, roosts are limited to riparian corridors capable of supporting trees large enough to provide suitable roost sites. Gould's wild turkeys (M. g. mexicana) are spatially restricted to mountainous semi‐arid areas of southwestern United States and Mexico, and information on their distribution and habitat use is limited. We evaluated roost site selection and fidelity of Gould's wild turkeys relative to environmental gradients and forested land cover during 2016–2017 in southeastern Arizona, USA. We monitored 51 global positioning system (GPS)‐tagged individuals and collected 7,954 night roost locations. We quantified specific roost site characteristics at 274 unique roost locations. Gould's wild turkeys roosted in forested communities dominated by mature pine (Pinus spp.) and oak (Quercus spp.), and exhibited substantive roost site fidelity. Roost sites were selected at moderate elevations (range = 1,254–2,894 m), and were predominately on north‐facing slopes with slight incline (&lt;11°), suggesting little plasticity in selection of roost sites. Conserving habitat with topography and vegetative structure similar to those described in our study is likely to improve ongoing restoration and management of Gould's wild turkeys.

Improved Diagnostic Accuracy of Clonidine Suppression Testing Using an Age-Related Cutoff for Plasma Normetanephrine.

Moderately elevated plasma normetanephrine (NMN) levels are frequent among patients with suspected pheochromocytoma and paraganglioma (PPGL). Clonidine suppression testing (CST) is recommended to distinguish patients with from those without PPGL. We aimed at evaluating the diagnostic outcome of CST in patients with moderate NMN elevations. Data from patients participating in the PMT study (Prospective Monoamine-Producing Tumor) and the ENSAT (European Network for the Study of Adrenal Tumours) registry in 6 European reference centers were analyzed retrospectively. Eighty-nine patients with suspected PPGL and moderate NMN elevations upon screening were included. During follow-up, PPGL was confirmed in 16 and excluded in 73 cases. Plasma NMN was measured by liquid chromatography tandem mass spectrometry before and 180 minutes after oral clonidine. Receiver operating characteristic analysis was performed to identify optimal cutoffs. If published diagnostic criteria for CST (ie, NMN ≥112 ng/L and NMN suppression <40%) were applied, a sensitivity of 88% (CI, 61%-98%) and a specificity of 97% (CI, 90%-100%) were observed. An improved cutoff for plasma NMN 180 minutes after clonidine was established at 80% of the age-related upper limit of normal, resulting in a sensitivity of 94% and a specificity of 97%. False-negative CST results occurred in 2 patients with small PPGL. This study, involving one of the largest cohorts of patients with suspected PPGL and moderately elevated NMN, confirmed the diagnostic accuracy of CST. The application of an adapted cutoff further improved sensitivity.

Significance of highly sensitive C-reactive protein (HS-CRP) in Iraqi children with COVID-19

Background: The inflammatory reaction that is systemic to the infection with the virus (SARS-CoV-2) stands as the pathognomonic feature of this viral illness, and the majority of hospital admitted patients exhibit unusual biomarkers of inflammation. The protein C-reactive was also connected to severe illness in individuals with pneumonia caused by H1N1 influenza, and several researchers have described a link between COVID-19 disease severity and higher concentration of CRP. Aim of the study: The goal of the current research was to investigate the association among severity of COVID-19 in children, clinical presentation and the concentration of (HS-CRP). Methods and patients: The present research which is of cross sectional kind was practiced in Children and Maternity Teaching Hospital in Al-Diwaniyah Province, Iraq. The study included 200 children with COVDI-19 proved by positive RT-PCR results following nasopharyngeal swabs. The range of the age was from 1 month up to 15 years and the study included 110 males and 90 females. All children were investigated for the level of HS-CRP and the interpretation of levels was based on categorization into normal, moderate elevation, marked elevation and severe elevation.

Brain Trauma, Glucocorticoids and Neuroinflammation: Dangerous Liaisons for the Hippocampus.

Glucocorticoid-dependent mechanisms of inflammation-mediated distant hippocampal damage are discussed with a focus on the consequences of traumatic brain injury. The effects of glucocorticoids on specific neuronal populations in the hippocampus depend on their concentration, duration of exposure and cell type. Previous stress and elevated level of glucocorticoids prior to pro-inflammatory impact, as well as long-term though moderate elevation of glucocorticoids, may inflate pro-inflammatory effects. Glucocorticoid-mediated long-lasting neuronal circuit changes in the hippocampus after brain trauma are involved in late post-traumatic pathology development, such as epilepsy, depression and cognitive impairment. Complex and diverse actions of the hypothalamic–pituitary–adrenal axis on neuroinflammation may be essential for late post-traumatic pathology. These mechanisms are applicable to remote hippocampal damage occurring after other types of focal brain damage (stroke, epilepsy) or central nervous system diseases without obvious focal injury. Thus, the liaisons of excessive glucocorticoids/dysfunctional hypothalamic–pituitary–adrenal axis with neuroinflammation, dangerous to the hippocampus, may be crucial to distant hippocampal damage in many brain diseases. Taking into account that the hippocampus controls both the cognitive functions and the emotional state, further research on potential links between glucocorticoid signaling and inflammatory processes in the brain and respective mechanisms is vital.

Calcium‐activated Chloride Channel TMEM16A/ANO1 Does Not Mediate the Regulation of Sweating and Cutaneous Vasodilation in Humans In Vivo

The regulation of human body temperature during a heat stress is dependent on the activation of the heat loss responses of cutaneous vasodilation and eccrine sweating. While significant advancements have been made in our understanding of the mechanisms governing their regulation, new potential modifiers such as transmembrane member 16A (TMEM16A), a Ca2+‐activated Cl‐ channel also known as anoctamin 1 (ANO1), continue to be identified. In vitro and animal studies suggest a role for TMEM16A in the regulation of sweat secretion and vascular tone. For example, Ca2+ induced Cl‐current was abolished in TMEM16A deficit, but not BEST2 deficit, NCL‐SG3 human eccrine sweat gland cell lines. Further, animal models showed the activation of TMEM16A on vascular smooth muscle cells blunts vasodilation. However, direct evidence supporting a role of TMEM16 in mediating cutaneous vasodilation as well as eccrine sweating in humans in vivo remains to be established. Therefore, we evaluated the hypothesis that TMEM16A mediates the regulation of sweating and cutaneous vasodilation during a whole‐body heat stress in young adults.Twelve young (24 ± 2 years) adults (6 females) underwent a whole‐body heat stress induced by a water‐perfused suit to raise core temperature 1.1±0.1ºC above baseline resting levels. Sweat rate (ventilated capsule) and cutaneous vascular conductance (assessed as skin blood flow/mean arterial pressure and normalised to maximal conductance achieved via simultaneous local skin heating to 44°C and administration of sodium nitroprusside) were assessed at four skin sites on the forearm treated with 1) lactated Ringers (control), 2) 5 % dimethyl sulfoxide serving as a vehicle control, 3) 1 mM T16Ainh‐A01 (a TMEM16A blocker) or 4) 2 mM benzbromarone (another TMEM16A blocker). All drugs were administered continuously via intradermal microdialysis.Sweat rate increased as heating continued at all skin sites (P &lt; 0.001 for a main effect of heating stage). Neither the main effect of treatment site nor the interaction between treatment site and heating stage was significant (both P ≥ 0.318). Cutaneous vascular conductance increased in parallel to elevations in core temperature (P &lt; 0.001 for a main effect of heating stage). Although no main effect of treatment site was observed (P = 0.109), a significant interaction between heating stage and treatment site was measured (P &lt; 0.001). Post‐hoc analysis revealed that cutaneous vascular conductance at the DMSO‐treated site was higher than the control site at baseline (P = 0.047). By contrast, cutaneous vascular conductance at moderate elevations in core temperature (i.e., ≥0.4‐0.8 °C) was greater at the control site relative to the DMSO‐treated site (all P ≤ 0.013). Importantly, no differences were measured in cutaneous vascular conductance between the DMSO‐treated site and TMEM16A blocker‐treated sites (all P ≥ 0.073).Taken together, our findings demonstrate for the first time that TMEM16A does not contribute to the regulation of sweating and cutaneous vasodilation during whole‐body heating in young adults in vivo.

An Overview on Biochemical Parameters and Organ Injury in COVID-19 Patients

The Coronavirus disease (COVID-19) is considered as a respiratory disease which can cause a multi-organ injury like acute cardiac injury, kidney injury, and liver dysfunction. COVID-19 patients had The different of blood biochemical abnormalities where found in covid -19 patients which might indicate multiple organ dysfunction.&#x0D; Hence the aim of the present study is provision of overview on organ injury and changes in biochemical parameters in Covid-19 patients.&#x0D; The common laboratory abnormalities in COVID-19 patients included elevated inflammatory markers like CRP, ferritin, procalcitonin, cytokines and IL-6, IL-2, IL-7 and elevated prothrombin time and D-dimer. The cardiac injury is shown by increased concentration of CK-MB, LDH, and cTn and brain natriuretic peptide (BNP).&#x0D; In liver and kidney dysfunction mild or moderate elevation of AST, ALT, total bilirubin, ALP, GGT, hypoalbuminemia, blood urea, creatinine and electrolyte disturbances were seen.&#x0D; Hence reviewing currently available data, the present study can suggest that monitoring of the biochemical parameters may help in prediction of organ damage which further can prevent disease progression early interventions.

Reading Dickens Differently, edited by Leon Litvack and Nathalie Vanfasse

Reviewed by: Reading Dickens Differently ed. by Leon Litvack and Nathalie Vanfasse Melisa Klimaszewski (bio) Reading Dickens Differently, edited by Leon Litvack and Nathalie Vanfasse; pp. xvi + 259. Hoboken: Wiley-Blackwell, 2019, $50.95, $41.00 ebook. This collection of twelve essays aims to break new critical ground with fresh approaches to the works of Charles Dickens. The editors frame the volume as a type of care work, a nurturing endeavor embarked upon to save Dickens's works from obscurity. This framing relies upon nostalgia for a time when Dickens's writings were universally valued, relevant, and beloved—an idealization that was always questionable and that this collection does not set out to interrogate. Still, Leon Litvack and Nathalie Vanfasse's goal of presenting [End Page 132] interdisciplinary, diachronous readings to invigorate a field of study is laudable, and the broad scope of this volume ensures that most Victorianists will encounter some essays of interest. Reading Dickens Differently is presented in three sections: "Reconfiguring," "Reincorporating," and "Resetting Dickens." The first section, "Reconfiguring," is biographical and dominated by a lengthy piece from Litvack that presents newly published information about the key role the Dean of Westminster, Arthur Penrhyn Stanley, played in prodding Dickens's family to request a burial at the Abbey. Those interested in archival documents and granular detail about Dickens's funeral will find this section's emphasis on Dickens's burial compelling. It is less clear how the piece is "challenging a canonical view of the author" or leading to new insights beyond correcting some misunderstandings about how Dickens ended up buried in the Abbey against his own wishes (3). David Paroissien examines Thomas Babington Macaulay's influence on Dickens and the relevance of Macaulay's mode of historiography to Barnaby Rudge (1841). Lillian Nayder's piece on Dickens's relationship with his brother Fred in relation to fraternal dynamics and doubling in A Tale of Two Cities (1859) offers a more focused contribution to biographical studies. Similarly, Neil Davie's carefully historicized contribution on Dickens's acquaintances at London's Cold Bath Fields Prison, his views on prison reform, and Urania Cottage offers broadly relevant argumentation. The section as a whole, however, is not as methodologically innovative as the editors claim, which continues to hold true for most of the pieces in the volume's second section, "Reincorporating." A focus on the body—physical sensations and embodiments that cross boundaries between the imagined and the material—offers great potential for methodological innovation. Georges Letissier demonstrates how "somatic reading" can lead to new understandings of some of Dickens's descriptive techniques (95). In Dombey and Son (1846–48), for instance, "fleeting visual images force themselves in unrelenting, serial succession to the point of erasing the focaliser's consciousness" (99). Letissier draws parallels between fictional characters' hallucinatory states and the act of reading itself, urging those who read to engage in metacritical reflection on their own practice. Michael Hollington and Jeremy Tambling examine Dickens in relation to D. H. Lawrence and John Ruskin, respectively. Hollington outlines the trajectory of Lawrence's admiration for Dickens, which shifts to satirical targeting even as Lawrence's writing continues to exhibit stylistic similarities to Dickens's works. Tambling presents a dense web of linkages between Dickens, Ruskin, and J. M. W. Turner, identifying "Turneresque" (127) moments in Dickens's writing and noting that, although Ruskin's evaluations of Dickens were sometimes harsh, Ruskin "wants and needs" both Turner and Dickens in his thinking (145). Chris Louttit contributes the strongest piece in this section with a long-overdue critical assessment of posthumous illustrations of Dickens's works. Contravening early critics who maligned the original illustrations, Louttit not only offers astute analysis of the Household Edition illustrations but also ponders what a new digital resource, a Dickens Visual Archive, might offer. Imagining such a resource is exciting and stimulating in a manner that indeed leads to reading Dickens differently. As a unit, however, the pieces in this section struggle to cohere and to connect clearly to the volume's claim that it reincorporates Dickens, which exposes the collection's most glaring absence: race. [End Page 133] Particularly in a section addressing embodiment and corporeal concerns...

Applying non-parametric Bayesian networks to estimate maximum daily river discharge: potential and challenges

Abstract. Non-parametric Bayesian networks (NPBNs) are graphical tools for statistical inference widely used for reliability analysis and risk assessment and present several advantages, such as the embedded uncertainty quantification and limited computational time for the inference process. However, their implementation in hydrological studies is still scarce. Hence, to increase our understanding of their applicability and extend their use in hydrology, we explore the potential of NPBNs to reproduce catchment-scale hydrological dynamics. Long-term data from 240 river catchments with contrasting climates across the United States from the Catchment Attributes and Meteorology for Large-sample Studies (CAMELS) data set will be used as actual means to test the utility of NPBNs as descriptive models and to evaluate them as predictive models for maximum daily river discharge in any given month. We analyse the performance of three networks, one unsaturated (hereafter UN-1), one saturated (hereafter SN-1), both defined only by hydro-meteorological variables and their bivariate correlations, and one saturated network (hereafter SN-C), consisting of the SN-1 network and including physical catchments' attributes. The results indicate that the UN-1 network is suitable for catchments with a positive dependence between precipitation and discharge, while the SN-1 network can also reproduce discharge in catchments with negative dependence. The latter can reproduce statistical characteristics of discharge (tested via the Kolmogorov–Smirnov statistic) and have a Nash–Sutcliffe efficiency (NSE) ≥0.5 in ∼40 % of the catchments analysed, receiving precipitation mainly in winter and located in energy-limited regions at low to moderate elevation. Further, the SN-C network, based on similarity of the catchments, can reproduce discharge statistics in ∼10 % of the catchments analysed. We show that once a NPBN is defined, it is straightforward to infer discharge and to extend the network itself with additional variables, i.e. going from the SN-1 network to the SN-C network. However, the results also suggest considerable challenges in defining a suitable NPBN, particularly for predictions in ungauged basins. These are mainly due to the discrepancies in the timescale of the different physical processes generating discharge, the presence of a “memory” in the system, and the Gaussian-copula assumption used for modelling multivariate dependence.

Elevation Regimes Modulated the Responses of Canopy Structure of Coastal Mangrove Forests to Hurricane Damage

Mangrove forests have unique ecosystem functions and services, yet the coastal mangroves in tropics are often disturbed by tropical cyclones. Hurricane Maria swept Puerto Rico and nearby Caribbean islands in September 2017 and caused tremendous damage to the coastal mangrove systems. Understanding the vulnerability and resistance of mangrove forests to disturbances is pivotal for future restoration and conservation. In this study, we used LiDAR point clouds to derive the canopy height of five major mangrove forests, including true mangroves and mangrove associates, along the coast of Puerto Rico before and after the hurricanes, which allowed us to detect the spatial variations of canopy height reduction. We then spatially regressed the pre-hurricane canopy height and the canopy height reduction on biophysical factors such as the elevation, the distance to rivers/canals within and nearby, the distance to coast, tree density, and canopy unevenness. The analyses resulted in the following findings. The pre-hurricane canopy height increased with elevation when elevation was low and moderate but decreased with elevation when elevation was high. The canopy height reduction increased quadratically with the pre-hurricane canopy height, but decreased with elevation for the four sites dominated by true mangroves. The site of Palma del Mar dominated by Pterocarpus, a mangrove associate, experienced the strongest wind, and the canopy height reduction increased with elevation. The canopy height reduction decreased with the distance to rivers/canals only for sites with low to moderate mean elevation of 0.36–0.39 m. In addition to the hurricane winds, the rainfall during hurricanes is an important factor causing canopy damage by inundating the aerial roots. In summary, the pre-hurricane canopy structures, physical environment, and external forces brought by hurricanes interplayed to affect the vulnerability of coastal mangroves to major hurricanes.

The effect of ethanol on potato growth and production at moderate elevation

Indonesia's current potato cultivation areas are mainly in the highlands (1 000 m above sea level – a.s.l.). However, there are obstacles to potato cultivation in the highlands, including erosion, declining land productivity, limited area, and high production costs (i.e. labour wages, fertilisers, and pesticides). This study was aimed at analysing the effects of both an ethanol application and moderate altitudes on the potato production and quality. This study was conducted at the Horticulture Seed Station in the Ulu Ere subdistrict, Bantaeng Regency, South Sulawesi, Indonesia. A split randomised plot design with two factors was used. The main plots were set at two elevation levels: 500 and 700 m a.s.l. The split plots were subjected to the addition of four ethanol concentration levels: 0, 10, 20, and 30%. The results showed that the ethanol application did not significantly affect the potato growth at the moderate elevation, except for the tuber diameter. Moreover, the 20% ethanol concentration produced better results than the 0% ethanol concentration. The application of 10% ethanol at an altitude of 700 m a.s.l. and 30% ethanol at an altitude of 500 m a.s.l. resulted in the best growth and yield among the studied treatments.

Fontan-associated liver disease.

Fontan-associated liver disease.

The relationship of presurgical Personality Assessment Inventory scales to BMI following bariatric surgery.

Notwithstanding the efficacy of bariatric surgery in reducing the negative sequelae of obesity, psychological factors may play a significant role in long-term weight maintenance following surgery. Previous research on these factors has shown mixed outcomes, indicating the need for further study in samples undergoing bariatric surgery. This study evaluated archival data for 194 patients from a single-payer system for a 60-month period following bariatric surgery to examine how presurgical scores on the Personality Assessment Inventory predict body mass index (BMI) over time. Follow-up data was available on 97% of these patients at 12 months and 62% of these patients at 60 months. Hierarchical linear modeling was used to predict BMI based on demographic and psychopathology factors using linear and nonlinear coefficients while controlling for initial BMI. Results showed that Personality Assessment Inventory scales assessing anxiety-related disorders, mania, and alcohol problems showed a relationship to BMI outcomes over time. Contrary to expectations, moderate elevations on anxiety-related disorders and mania were associated with a greater initial linear trend for BMI decrease, with a steeper slope for weight regain after approximately 3 years. Patients endorsing any scores above the minimum on the alcohol problems scale showed poorer BMI outcomes. This study extends previous research on psychological factors and weight outcomes over time among patients undergoing bariatric surgery. In contrast to a focus on clinical elevations when using broadband measures of psychopathology, these results suggest a more nuanced pattern of weight loss and subsequent regain associated with certain subclinical elevations. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Relation between Serum Creatine Phosphokinase Levels and Acute Kidney Injury among ST-Segment Elevation Myocardial Infarction Patients.

Background: Among patients with rhabdomyolysis, the leakage of intracellular skeletal muscle content such as creatine phosphokinase (CPK) into the bloodstream has been associated with an increased risk of acute kidney injury (AKI). We evaluated the possible relationship between serum CPK levels and AKI occurrence among patients with myocyte injury secondary to ST-elevation myocardial infarction (STEMI). Methods: We retrospectively included 2794 patients with STEMI. Patients were stratified according to peak serum CPK levels into mild (<1000 U/L, n = 1603), moderate (1000–5000 U/L, n = 1111), and severe (>5000 U/L, n = 80) categories. The occurrence of AKI was defined by the KDIGO criteria as an increase in serum creatinine (sCR) ≥0.3 mg/dL within 48 h following PCI. The predictive value of CPK for the risk of AKI occurrence was assessed using multivariate logistic regression models. Results: The overall occurrence of AKI was 10.4%. Incidence of AKI showed a gradual increase between patients with mild, moderate, and severe serum CPK level elevations (7.8% vs. 11% vs. 26% respectively; p < 0.001). In multivariate logistic regression models, both moderate or higher (OR 1.6, 95% CI 1.1–2.2; p = 0.01) and severe (OR 2.8 95% CI 1.4–5.6; p = 0.004) serum CPK level elevations were independently associated with AKI. Conclusions: Among STEMI patients, elevated CPK levels were associated with AKI. This association is presumably independent; however, it remains unclear whether it is due to direct toxic (myoglobin-related) or hemodynamic effects (poor left ventricular function). Further studies are required to reveal the underlying mechanism.

The combined DNA and RNA synthetic capabilities of archaeal DNA primase facilitate primer hand-off to the replicative DNA polymerase

Replicative DNA polymerases cannot initiate DNA synthesis de novo and rely on dedicated RNA polymerases, primases, to generate a short primer. This primer is then extended by the DNA polymerase. In diverse archaeal species, the primase has long been known to have the ability to synthesize both RNA and DNA. However, the relevance of these dual nucleic acid synthetic modes for productive primer synthesis has remained enigmatic. In the current work, we reveal that the ability of primase to polymerize DNA serves dual roles in promoting the hand-off of the primer to the replicative DNA polymerase holoenzyme. First, it creates a 5′-RNA-DNA-3′ hybrid primer which serves as an optimal substrate for elongation by the replicative DNA polymerase. Second, it promotes primer release by primase. Furthermore, modeling and experimental data indicate that primase incorporates a deoxyribonucleotide stochastically during elongation and that this switches the primase into a dedicated DNA synthetic mode polymerase.

The regulation of mitochondrial NO synthase activity under nitroglycerine application in rat heart and liver mitochondria

Nitroglycerine (NG) affords cardioprotection via NO formation, but the impact of NG application on reactive nitrogen species (RNS) metabolism remains little studied yet. Mitochondrial NO synthase (mtNOS) is an important endogenous source of RNS. Our aim was to study the effect of NG application on mtNOS activity and RNS production in rat heart and liver mitochondria. Different regulation of mtNOS activity in the heart and liver under NG treatment was found. While in heart mitochondria it increased dose-dependently, in liver mitochondria only moderate elevation and bell-shaped dose dependence of mtNOS activity on NG was observed. Nitrite and nitrate, which are the end products of L-arginine transformation by NOS, showed similar dose dependence on NG. To find an explanation for the observed dependences, we studied the effects of NG administration on the activity of arginase which competes with NOS for physiological substrate, Larginine. A strong reciprocal dependence between mtNOS and arginase activities was found. As we observed, the arginase activity increased under NG application. However, while in heart mitochondria high mtNOS activity agreed with moderate arginase activation, in liver mitochondria high arginase activity coincided with suppression of mtNOS activity at high doses of NG. Low arginase and high mtNOS activities observed in heart mitochondria were consistent with high NO2 − and NO3 − production and low hydroperoxide (H2O2) formation, whereas high arginase activity in liver mitochondria was accompanied by the reduction of NO2− /NO3− formation and simultaneous elevation of H2O2 production. A linear correlation between the arginase activity and hydroperoxide formation was found. We came to the conclusion that under NG administration arginase activation resulted in reciprocal regulation of RNS and ROS production in mitochondria, dependent on the proportion of mtNOS to arginase activity. Suppression of RNS metabolism could be the cause of ROS overproduction caused by high arginase and low mtNOS activity.

Secretory pathway Ca2+-ATPase SPCA2 regulates mitochondrial respiration and DNA damage response through store-independent calcium entry

A complex interplay between the extracellular space, cytoplasm and individual organelles modulates Ca2+ signaling to impact all aspects of cell fate and function. In recent years, the molecular machinery linking endoplasmic reticulum stores to plasma membrane Ca2+ entry has been defined. However, the mechanism and pathophysiological relevance of store-independent modes of Ca2+ entry remain poorly understood. Here, we describe how the secretory pathway Ca2+-ATPase SPCA2 promotes cell cycle progression and survival by activating store-independent Ca2+ entry through plasma membrane Orai1 channels in mammary epithelial cells. Silencing SPCA2 expression or briefly removing extracellular Ca2+ increased mitochondrial ROS production, DNA damage and activation of the ATM/ATR-p53 axis leading to G0/G1 phase cell cycle arrest and apoptosis. Consistent with these findings, SPCA2 knockdown confers redox stress and chemosensitivity to DNA damaging agents. Unexpectedly, SPCA2-mediated Ca2+ entry into mitochondria is required for optimal cellular respiration and the generation of mitochondrial membrane potential. In hormone receptor positive (ER+/PR+) breast cancer subtypes, SPCA2 levels are high and correlate with poor survival prognosis. We suggest that elevated SPCA2 expression could drive pro-survival and chemotherapy resistance in cancer cells, and drugs that target store-independent Ca2+ entry pathways may have therapeutic potential in treating cancer.