bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of individualized PEEP titration guided by intratidal compliance profile analysis on regional ventilation assessed by electrical impedance tomography – a randomized controlled trial
Authors: Weber Jonas , Gutjahr Jan , Schmidt Johannes , Lozano-Zahonero Sara , Borgmann Silke , Schumann Stefan , Wirth Steffen
Published: February 2020

Background

The application of positive end-expiratory pressure (PEEP) may reduce dynamic strain during mechanical ventilation. Although numerous approaches for PEEP titration have been proposed, there is no accepted strategy for titrating optimal PEEP. By analyzing intratidal compliance profiles, PEEP may be individually titrated for patients.

Methods

After obtaining informed consent, 60 consecutive patients undergoing general anesthesia were randomly allocated to mechanical ventilation with PEEP 5 cmH2O (control group) or PEEP individually titrated, guided by an analysis of the intratidal compliance profile (intervention group). The primary endpoint was the frequency of each nonlinear intratidal compliance (CRS) profile of the respiratory system (horizontal, increasing, decreasing, and mixed). The secondary endpoints measured were respiratory mechanics, hemodynamic variables, and regional ventilation, which was assessed via electrical impedance tomography.

Results

The frequencies of the CRS profiles were comparable between the groups. Besides PEEP [control: 5.0 (0.0), intervention: 5.8 (1.1) cmH2O, p < 0.001], the respiratory and hemodynamic variables were comparable between the two groups. The compliance profile analysis showed no significant differences between the two groups. The loss of ventral and dorsal regional ventilation was higher in the control [ventral: 41.0 (16.3)%; dorsal: 25.9 (13.8)%] than in the intervention group [ventral: 29.3 (17.6)%; dorsal: 16.4 (12.7)%; p (ventral) = 0.039, p (dorsal) = 0.028].

Conclusions

Unfavorable compliance profiles indicating tidal derecruitment were found less often than in earlier studies. Individualized PEEP titration resulted in slightly higher PEEP. A slight global increase in aeration associated with this was indicated by regional gain and loss analysis. Differences in dorsal to ventral ventilation distribution were not found.

Trial registration

This clinical trial was registered at the German Register for Clinical Trials (DRKS00008924) on August 10, 2015.
Early prediction of acquiring acute kidney injury for older inpatients using most effective laboratory test results
Authors: Chen Yi-Shian , Chou Che-Yi , Chen Arbee L.P.
Published: February 2020

Background

Acute Kidney Injury (AKI) is common among inpatients. Severe AKI increases all-cause mortality especially in critically ill patients. Older patients are more at risk of AKI because of the declined renal function, increased comorbidities, aggressive medical treatments, and nephrotoxic drugs. Early prediction of AKI for older inpatients is therefore crucial.

Methods

We use 80 different laboratory tests from the electronic health records and two types of representations for each laboratory test, that is, we consider 160 (laboratory test, type) pairs one by one to do the prediction. By proposing new similarity measures and employing the classification technique of the K nearest neighbors, we are able to identify the most effective (laboratory test, type) pairs for the prediction. Furthermore, in order to know how early and accurately can AKI be predicted to make our method clinically useful, we evaluate the prediction performance of up to 5 days prior to the AKI event.

Results

We compare our method with two existing works and it shows our method outperforms the others. In addition, we implemented an existing method using our dataset, which also shows our method has a better performance. The most effective (laboratory test, type) pairs found for different prediction times are slightly different. However, Blood Urea Nitrogen (BUN) is found the most effective (laboratory test, type) pair for most prediction times.

Conclusion

Our study is first to consider the last value and the trend of the sequence for each laboratory test. In addition, we define the exclusion criteria to identify the inpatients who develop AKI during hospitalization and we set the length of the data collection window to ensure the laboratory data we collect is close to the AKI time. Furthermore, we individually select the most effective (laboratory test, type) pairs to do the prediction for different days of early prediction. In the future, we will extend this approach and develop a system for early prediction of major diseases to help better disease management for inpatients.
What about lay counselors’ experiences of task-shifting mental health interventions? Example from a family-based intervention in Kenya
Authors: Wall Jonathan T. , Kaiser Bonnie N. , Friis-Healy Elsa A. , Ayuku David , Puffer Eve S.
Published: February 2020

Background

A key focus of health systems strengthening in low- and middle-income countries is increasing reach and access through task-shifting. As such models become more common, it is critical to understand the experiences of lay providers because they are on the forefront for delivering care services. A greater understanding would improve lay provider support and help them provide high-quality care. This is especially the case for those providing mental health services, as providing psychological care may pose unique stressors. We sought to understand experiences of lay counselors, focusing on identity, motivation, self-efficacy, stress, and burnout. The goal was to understand how taking on a new provider role influences their lives beyond simply assuming a new task, which would in turn help identify actionable steps to improve interventions with task-shifting components.

Methods

Semi-structured interviews (n = 20) and focus group discussions (n = 3) were conducted with three lay counselor groups with varying levels of experience delivering a community-based family therapy intervention in Eldoret, Kenya. Thematic analysis was conducted, including intercoder reliability checks. A Stress Map was created to visualize stress profiles using free-listing and pile-sorting data collected during interviews and focus group discussions.

Results

Counselors described high intrinsic motivation to become counselors and high self-efficacy after training. They reported positive experiences in the counselor role, with new skills improving their counseling and personal lives. As challenges arose, including client engagement difficulties and balancing many responsibilities, stress and burnout increased, dampening motivation and self-efficacy. In response, counselors described coping strategies, including seeking peer and supervisor support, that restored their motivation to persevere. At case completion, they again experienced high self-efficacy and a desire to continue.

Conclusions

Findings informed suggestions for ways to incorporate support for lay providers into task-shifting interventions at initiation, during training, and throughout implementation. These include acknowledging and preparing counselors for challenges during training, increasing explicit attention to counselor stress in supervision, fostering peer support among lay providers, and ensuring a fair balance between workload and compensation. Improving and building an evidence base around practices for supporting lay providers will improve the effectiveness and sustainability of lay provider-delivered interventions.
Primary aldosteronism concurrent with subclinical Cushing’s syndrome: a case report and review of the literature
Authors:   the Chongqing Primary Aldosteronism Study (CONPASS) Group, Zhang Yingxiao , Tan Jianyu , Yang Qin , Du Zhipeng , Yang Shumin , He Wenwen , Song Ying , Hu Jinbo , Yang Yi , Li Qifu , Zhang Yao , He Yunfeng , Cheng Qingfeng
Published: February 2020

Background

The prevalence of primary aldosteronism concurrent with subclinical Cushing’s syndrome was higher than previously thought. Through analyzing a rare clinical case, we summarized the diagnosis and management of primary aldosteronism with subclinical Cushing’s syndrome.

Case presentation

A 54-year-old Chinese man of Han nationality was diagnosed as having primary aldosteronism with subclinical Cushing’s syndrome. An abdominal computed tomography scan revealed a mass in his left adrenal gland and a mass in his right adrenal gland. After finishing sequential adrenal venous sampling without adrenocorticotropic hormone, the result reminded us that the left and right nodules were responsible for hypercortisolism and aldosterone hypersecretion, respectively. Right and left adrenalectomy were performed successively. The pathological diagnosis was adrenocortical adenoma for both. Histological findings revealed that the right one had positive immunostaining for CYP11B2 and the left one had positive immunostaining for CYP11B1. The immunohistochemistry result helped us to confirm the diagnosis. Somatic KCNJ5 mutation (Leu168Arg) was found in the right tumor; there was no KCNJ5 mutation in the left adrenal tumor.

Conclusions

We suggest that patients with primary aldosteronism should have a low-dose overnight dexamethasone suppression test to screen for hypercortisolism. It can help avoid misdiagnoses and contribute to proper understanding of the adrenal vein sampling result. Making sure of the nidus of aldosterone and cortisol secretion is crucial for the therapy of patients with primary aldosteronism and subclinical Cushing’s syndrome.
Fracture saturation in paintings makes them less vulnerable to environmental variations in museums
Authors: Bratasz Łukasz , Akoglu Kiraz Goze , Kékicheff Patrick
Published: February 2020

Understanding paintings as physical systems is fundamental for advancing environmental specifications that would allow for effective management of museum environments in terms of reducing energy use and carbon emissions while maintaining high standards of collection care. The current environmental specifications were derived using the criterion of the crack initiation in undamaged, usually new, material. In reality, historical paintings exhibit complex crack patterns called craquelures. The present paper analyses painted wood which is among the category of cultural objects most vulnerable to relative humidity and temperature fluctuations and frequently found in museum collections of various kinds. Fracture toughness determined experimentally for the most brittle component of pictorial layer—the ground layer (gesso) is used as a ‘failure criterion’. Comparison of energy release rate—calculated for the model of the gesso laid on a wooden substrate using finite element analysis—with the structure toughness, allowed the fracture saturation expressed as the ratio of spacing between cracks S to gesso layer thickness t to be determined for various combinations of the gesso stiffness and geometries of structural flaws at which cracks initiate. For flat geometry of a panel painting and panel thickness of 40 mm, representing the worst-case, largest stresses in the gesso layer, the fracture saturation occurs when S/t is larger than 5, even if flaws in the gesso layer are present. The paper shows that the fracture saturation significantly changes vulnerability of paintings to climate variations—a panel painting with developed craquelure network is significantly less vulnerable to climate variations than an undamaged one.
Impact of petroleum and non-petroleum indices on financial development in Oman
Authors: Alshubiri Faris Nasif , Tawfik Omar Ikbal , Jamil Syed Ahsan
Published: February 2020

This study analyzes the impact of petroleum and non-petroleum indices on the financial development of the Sultanate of Oman from 1978 to 2017. To this end, it uses the petroleum proxy of oil rents (% of gross domestic product, GDP) and the non-petroleum proxy of industry (including construction) value added (% of GDP); agriculture, forestry, and fishing value added (% of GDP); and services value added (% of GDP) to determine the effect on financial development, measured by the amount of domestic credit extended to the private sector by banks (% of GDP). It applies an autoregressive distributed lag (ARDL) model. The long-term equation illustrates that the agriculture and industry GDPs have a negative and significant relationship with domestic credit in Oman. However, the oil and service sector GDPs promote financial development. The short-term equation illustrates that the oil, agricultural, and service sectors have positive and significant effects on domestic credit. The conclusion is that the economy of Oman is still in the first phase of economic diversification. Accordingly, the government should use oil revenues to develop various non-oil industrial sectors. This would enhance the country’s competitiveness in the global economy and positively contribute to improving the liquidity of the banking sector for stimulating credit at the macroeconomic level.
Designing social networks: joint tasks and the formation and endurance of network ties
Authors: Hasan Sharique , Koning Rembrand
Published: February 2020

Can managers influence the formation of organizational networks? In this article, we evaluate the effect of joint tasks on the creation of network ties with data from a novel field experiment with 112 aspiring entrepreneurs. During the study, we randomized individuals to a set of 15 joint tasks varying in duration (week-long teams to 20-min conversations). We then evaluated the impact of these interactions on the formation and structure of individuals’ social networks. We find strong evidence that these designed interactions led to the systematic creation of new friendship and advice relations as well as changes to the participants’ network centrality. Overall, network ties formed after a randomized interaction account for about one-third the individuals a participant knows, of their friendships, and their advice relations. Nevertheless, roughly 90% of randomized interactions never become social ties of friendship or advice. A key result from our research is that while joint tasks may serve to structure the social consideration set of possible connections, individual preferences strongly shape the structure of networks. As a consequence, there will likely remain a considerable unpredictability in the presence of specific ties even when they are designed.
Evaluation of a Bacillus thuringiensis isolate-based formulation against the pod borer, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae)
Authors: Bouslama Thameur , Chaieb Ikbal , Rhouma Ali , Laarif Asma
Published: February 2020

The present study focuses on the evaluation of the potential of a Tunisian Bacillus thuringiensis (Bt) isolate named Hr1, isolated from dead and diseased pod borer, Helicoverpa armigera Hübner (Lepidoptera: Noctuidae) larvae under laboratory and field semi-controlled conditions. The bacterial strain Hr1 showed an insecticidal activity against the pest’s neonates in comparison to the spinosad-based insecticide (Tracer 240 SC®) during bioassays under laboratory conditions. A carboxymethyl cellulose-talc (CMC-talc)-based formulation of the Bt isolate was prepared to evaluate the potential of the bacterium on tomato plants infested with H. armigera under semi-controlled field conditions with and without rain simulation. The results showed the efficacy of the formulation than the spinosad-based insecticide and the treatment with unformulated bacterium. The results also showed the persistence of Bt isolate activity even after rain-wash than the treatment with unformulated bacterium.
The clinical phenotypes and genetic characteristics of seven epilepsy patients related to heterozygous DEPDC5 variants in China
Authors: Wei Zihan , Wang Luojun , Qiao Xiaozhi , Zhang Ying , Liu Chao , Deng Yanchun
Published: February 2020

Objective

DEPDC5 together with NPRL2 and NPRL3 forms the GATOR1 which plays an important role in the the mechanistic target of rapamycin (mTOR) pathway. Deregulation of mTOR signalling has been associated to various neurological conditions, including epilepsy. Variants in the gene encoding GATOR1 complex, especially in DEPDC5, have been implicated in the pathogensis of several focal epilepsies. While there was little report on the electroencephalogram (EEG) feature of DEPDC5 related epilepsy, we decided to investigate the specific EEG pattern and the prognosis of DEPDC5 related epilepsy.

Methods

The records of 546 epilepsy patients with unknown causes who were admitted in Xijing Hospital and underwent whole exome sequencing (WES) from 2015 to 2019 were retrospectively reviewed. Finally, the clinical data of these 7 patients with DEPDC5 variants were collected in this study. We analyzed their clinical manifestations, EEG and magnetic resonance imaging (MRI).

Results

Seven DEPDC5 variants, including six novel mutations, were identified in seven individuals with focal epilepsy. Among these patients, one had family history. Four showed specific interictal EEG patterns, periodic-like sharp waves or spike waves, were found in four patients. Five out of seven patients (71.4%) were well-controlled by anti-epilepsy drugs while two patients with sleep-related hypermotor epilepsy had either drug resistance or relapse of epilepsy.

Conclusion

DEPDC5 variants were related to focal epilepsy in patients with or without family history. The EEG abnormalities of DEPDC5 related epilepsy were heterogeneous among different patients, while periodic-like sharp waves or spike waves might be the most characteristic interictal EEG pattern for DEPDC5 related epilepsies. In this study the prognosis of DEPDC5 related epilepsy was similar to other epilepsies. DEPDC5 variants may not predict the prognosis so far.
Epigenetic Conservation Is a Beacon of Function: An Analysis Using Methcon5 Software for Studying Gene Methylation
Authors: Hvitfeldt Emil , Xia Chao , Siegmund Kimberly D. , Shibata Darryl , Marjoram Paul
Published: February 2020

PURPOSE

Different epigenetic configurations allow one genome to develop into multiple cell types. Although the rules governing what epigenetic features confer gene expression are increasingly being understood, much remains uncertain. Here, we used a novel software package, Methcon5, to explore whether the principle of biologic conservation can be used to identify expressed genes. The hypothesis is that epigenetic configurations of important expressed genes will be conserved within a tissue.

MATERIALS AND METHODS

We compared the DNA methylation of approximately 850,000 CpG sites between multiple clonal crypts or glands of human colon, small intestine, and endometrium. We performed this analysis using the new software package, Methcon5, which enables detection of regions of high (or low) conservation.

RESULTS

We showed that DNA methylation is preferentially conserved at gene-associated CpG sites, particularly in gene promoters (eg, near the transcription start site) or the first exon. Furthermore, higher conservation correlated well with gene expression levels and performed better than promoter DNA methylation levels. Most conserved genes are in canonical housekeeping pathways.

CONCLUSION

This study introduces the new software package, Methcon5. In this example application, we showed that epigenetic conservation provides an alternative method for identifying functional genomic regions in human tissues.
GIP and GLP-1 Receptor Antagonism During a Meal in Healthy Individuals
Authors: Gasbjerg Lærke S , Helsted Mads M , Hartmann Bolette , Sparre-Ulrich Alexander H , Veedfald Simon , Stensen Signe , Lanng Amalie R , Bergmann Natasha C , Christensen Mikkel B , Vilsbøll Tina , Holst Jens J , Rosenkilde Mette M , Knop Filip K
Published: February 2020

Context

The actions of both endogenous incretin hormones during a meal have not previously been characterized.

Objective

Using specific receptor antagonists, we investigated the individual and combined contributions of endogenous glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) to postprandial glucose metabolism, energy expenditure, and gallbladder motility.

Design

Randomized, double-blinded, placebo-controlled, crossover design.

Setting

On four separate days, four liquid mixed meal tests (1894 kJ) over 270 minutes (min).

Patients or Other Participants

Twelve healthy male volunteers.

Interventions

Infusions of the GIP receptor antagonist GIP(3–30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9–39)NH2 (0–20 min: 1000 pmol/kg/min; 20–270 min: 450 pmol/kg/min), GIP(3–30)NH2+exendin(9–39)NH2, or placebo/saline.

Main Outcome Measure

Baseline-subtracted area under the curve (bsAUC) of C-peptide.

Results

Infusion of GIP(3–30)NH2+exendin(9–39)NH2 significantly increased plasma glucose excursions (bsAUC: 261 ± 142 mmol/L × min) during the liquid mixed meals compared with GIP(3–30)NH2 (180 ± 141 mmol/L × min; P = 0.048), exendin(9–39)NH2 (171 ± 114 mmol/L × min; P = 0.046), and placebo (116 ± 154 mmol/L × min; P = 0.015). Correspondingly, C-peptide:glucose ratios during GIP(3–30)NH2+exendin(9–39)NH2 infusion were significantly lower than during GIP(3–30)NH2 (P = 0.0057), exendin(9–39)NH2 (P = 0.0038), and placebo infusion (P = 0.014). GIP(3–30)NH2 resulted in significantly lower AUCs for glucagon than exendin(9–39)NH2 (P = 0.0417). Gallbladder ejection fraction was higher during GIP(3–30)NH2 compared with placebo (P = 0.004). For all interventions, energy expenditure and respiratory quotient were similar.

Conclusions

Endogenous GIP and GLP-1 lower postprandial plasma glucose excursions and stimulate insulin secretion but only endogenous GIP affects gallbladder motility. The two incretin hormones potentiate each other’s effects in the control of postprandial glycemia in healthy men.
The origin of animal body plans: a view from fossil evidence and the regulatory genome
Authors: Erwin Douglas H.
Published: February 2020

The origins and the early evolution of multicellular animals required the exploitation of holozoan genomic regulatory elements and the acquisition of new regulatory tools. Comparative studies of metazoans and their relatives now allow reconstruction of the evolution of the metazoan regulatory genome, but the deep conservation of many genes has led to varied hypotheses about the morphology of early animals and the extent of developmental co-option. In this Review, I assess the emerging view that the early diversification of animals involved small organisms with diverse cell types, but largely lacking complex developmental patterning, which evolved independently in different bilaterian clades during the Cambrian Explosion.
Cell invasion by intracellular parasites – the many roads to infection
Authors: Horta Maria Fátima , Andrade Luciana Oliveira , Martins-Duarte Érica Santos , Castro-Gomes Thiago
Published: February 2020

Intracellular parasites from the genera Toxoplasma, Plasmodium, Trypanosoma, Leishmania and from the phylum Microsporidia are, respectively, the causative agents of toxoplasmosis, malaria, Chagas disease, leishmaniasis and microsporidiosis, illnesses that kill millions of people around the globe. Crossing the host cell plasma membrane (PM) is an obstacle these parasites must overcome to establish themselves intracellularly and so cause diseases. The mechanisms of cell invasion are quite diverse and include (1) formation of moving junctions that drive parasites into host cells, as for the protozoans Toxoplasma gondii and Plasmodium spp., (2) subversion of endocytic pathways used by the host cell to repair PM, as for Trypanosoma cruzi and Leishmania, (3) induction of phagocytosis as for Leishmania or (4) endocytosis of parasites induced by specialized structures, such as the polar tubes present in microsporidian species. Understanding the early steps of cell entry is essential for the development of vaccines and drugs for the prevention or treatment of these diseases, and thus enormous research efforts have been made to unveil their underlying biological mechanisms. This Review will focus on these mechanisms and the factors involved, with an emphasis on the recent insights into the cell biology of invasion by these pathogens.
A DNA polymerization-independent role for mitochondrial DNA polymerase I-like protein C in African trypanosomes
Authors: Miller Jonathan C. , Delzell Stephanie B. , Concepción-Acevedo Jeniffer , Boucher Michael J. , Klingbeil Michele M.
Published: February 2020

Mitochondrial DNA of Trypanosoma brucei and related parasites is a catenated network containing thousands of minicircles and tens of maxicircles, called kinetoplast DNA (kDNA). Replication of a single nucleoid requires at least three DNA polymerase I-like proteins (i.e. POLIB, POLIC and POLID), each showing discrete localizations near the kDNA during S phase. POLIB and POLID have roles in minicircle replication but the specific role of POLIC in kDNA maintenance is less clear. Here, we use an RNA interference (RNAi)-complementation system to dissect the functions of two distinct POLIC regions, i.e. the conserved family A DNA polymerase (POLA) domain and the uncharacterized N-terminal region (UCR). While RNAi complementation with wild-type POLIC restored kDNA content and cell cycle localization of kDNA, active site point mutations in the POLA domain impaired minicircle replication similar to that of POLIB and POLID depletions. Complementation with POLA domain alone abolished the formation of POLIC foci and partially rescued the RNAi phenotype. Furthermore, we provide evidence that the UCR is crucial in cell cycle-dependent protein localization and facilitates proper distribution of progeny networks. This is the first report of a DNA polymerase that impacts on mitochondrial nucleoid distribution.

This article has an associated First Person interview with the first author of the paper.
Distinct roles of two eIF4E isoforms in the germline of Caenorhabditis elegans
Authors: Huggins Hayden P. , Subash Jacob S. , Stoffel Hamilton , Henderson Melissa A. , Hoffman Jenna L. , Buckner David S. , Sengupta Madhu S. , Boag Peter R. , Lee Myon-Hee , Keiper Brett D.
Published: February 2020

Germ cells use both positive and negative mRNA translational control to regulate gene expression that drives their differentiation into gametes. mRNA translational control is mediated by RNA-binding proteins, miRNAs and translation initiation factors. We have uncovered the discrete roles of two translation initiation factor eIF4E isoforms (IFE-1, IFE-3) that bind 7-methylguanosine (m7G) mRNA caps during Caenorhabditis elegans germline development. IFE-3 plays important roles in germline sex determination (GSD), where it promotes oocyte cell fate and is dispensable for spermatogenesis. IFE-3 is expressed throughout the germline and localizes to germ granules, but is distinct from IFE-1 and PGL-1, and facilitates oocyte growth and viability. This contrasts with the robust expression in spermatocytes of IFE-1, the isoform that resides within P granules in spermatocytes and oocytes, and promotes late spermatogenesis. Each eIF4E is localized by its cognate eIF4E-binding protein (IFE-1:PGL-1 and IFE-3:IFET-1). IFE-3 and IFET-1 regulate translation of several GSD mRNAs, but not those under control of IFE-1. Distinct mutant phenotypes, in vivo localization and differential mRNA translation suggest independent dormant and active periods for each eIF4E isoform in the germline.
Regulation of intrinsic polarity establishment by a differentiation-type MAPK pathway in S. cerevisiae
Authors: Prabhakar Aditi , Chow Jacky , Siegel Alan J. , Cullen Paul J.
Published: February 2020

All cells establish and maintain an axis of polarity that is critical for cell shape and progression through the cell cycle. A well-studied example of polarity establishment is bud emergence in the yeast Saccharomyces cerevisiae, which is controlled by the Rho GTPase Cdc42p. The prevailing view of bud emergence does not account for regulation by extrinsic cues. Here, we show that the filamentous growth mitogen activated protein kinase (fMAPK) pathway regulates bud emergence under nutrient-limiting conditions. The fMAPK pathway regulated the expression of polarity targets including the gene encoding a direct effector of Cdc42p, Gic2p. The fMAPK pathway also stimulated GTP-Cdc42p levels, which is a critical determinant of polarity establishment. The fMAPK pathway activity was spatially restricted to bud sites and active during the period of the cell cycle leading up to bud emergence. Time-lapse fluorescence microscopy showed that the fMAPK pathway stimulated the rate of bud emergence during filamentous growth. Unregulated activation of the fMAPK pathway induced multiple rounds of symmetry breaking inside the growing bud. Collectively, our findings identify a new regulatory aspect of bud emergence that sensitizes this essential cellular process to external cues.
PTPN23 binds the dynein adaptor BICD1 and is required for endocytic sorting of neurotrophin receptors
Authors: Budzinska Marta I. , Villarroel-Campos David , Golding Matthew , Weston Anne , Collinson Lucy , Snijders Ambrosius P. , Schiavo Giampietro
Published: February 2020

Signalling by target-derived neurotrophins is essential for the correct development of the nervous system and its maintenance throughout life. Several aspects concerning the lifecycle of neurotrophins and their receptors have been characterised over the years, including the formation, endocytosis and trafficking of signalling-competent ligand–receptor complexes. However, the molecular mechanisms directing the sorting of activated neurotrophin receptors are still elusive. Previously, our laboratory identified Bicaudal-D1 (BICD1), a dynein motor adaptor, as a key factor for lysosomal degradation of brain-derived neurotrophic factor (BDNF)-activated TrkB (also known as NTRK2) and p75NTR (also known as NGFR) in motor neurons. Here, using a proteomics approach, we identified protein tyrosine phosphatase, non-receptor type 23 (PTPN23), a member of the endosomal sorting complexes required for transport (ESCRT) machinery, in the BICD1 interactome. Molecular mapping revealed that PTPN23 is not a canonical BICD1 cargo; instead, PTPN23 binds the N-terminus of BICD1, which is also essential for the recruitment of cytoplasmic dynein. In line with the BICD1-knockdown phenotype, loss of PTPN23 leads to increased accumulation of BDNF-activated p75NTR and TrkB in swollen vacuole-like compartments, suggesting that neuronal PTPN23 is a novel regulator of the endocytic sorting of neurotrophin receptors.
What determines systemic blood flow in vertebrates?
Authors: Joyce William , Wang Tobias
Published: February 2020

In the 1950s, Arthur C. Guyton removed the heart from its pedestal in cardiovascular physiology by arguing that cardiac output is primarily regulated by the peripheral vasculature. This is counterintuitive, as modulating heart rate would appear to be the most obvious means of regulating cardiac output. In this Review, we visit recent and classic advances in comparative physiology in light of this concept. Although most vertebrates increase heart rate when oxygen demands rise (e.g. during activity or warming), experimental evidence suggests that this tachycardia is neither necessary nor sufficient to drive a change in cardiac output (i.e. systemic blood flow, Q̇sys) under most circumstances. Instead, Q̇sys is determined by the interplay between vascular conductance (resistance) and capacitance (which is mainly determined by the venous circulation), with a limited and variable contribution from heart function (myocardial inotropy). This pattern prevails across vertebrates; however, we also highlight the unique adaptations that have evolved in certain vertebrate groups to regulate venous return during diving bradycardia (i.e. inferior caval sphincters in diving mammals and atrial smooth muscle in turtles). Going forward, future investigation of cardiovascular responses to altered metabolic rate should pay equal consideration to the factors influencing venous return and cardiac filling as to the factors dictating cardiac function and heart rate.
Higher DNA methylation of ABO gene promoter is associated with acute myocardial infarction in a hospital-based population in Karachi
Authors: Yousuf Farzana Abubakar , Kazmi Khawar , Iqbal Junaid , Ahmed Nikhat , Iqbal Mohammad Perwaiz
Published: February 2020

Objective: To find out if there is any relationship of methylation status of ABO gene promoter with the risk of acute myocardial infarction (AMI) in a hospital-based Pakistani population in Karachi, Pakistan.

Methods: A case control study comprising of 39 adult AMI patients (both males and females; age range 30-70 years) and 39 normal healthy controls (both males and females and similar age range) nested in a large study (to see the relationship of ABO genotypes with AMI) was designed to investigate the methylation status of ABO gene promoter and its association with AMI. The study was carried out at the Aga Khan University, Karachi during July 2018 to June 2019. DNA isolated from samples of AMI patients and normal healthy controls were converted into bisulphite DNA using a kit method. Methylation specific polymerase chain reaction was carried out to determine the methylation status of ABO gene promoter in both cases and controls. Logistic regression was used to find out any association between increased methylation status of ABO gene promoter and risk of AMI.

Results: A significantly higher percentage of DNA methylation of the ABO gene promoter was observed in AMI patients as compared to normal healthy controls (82.1% vs. 35.9%; p value <0.001). This higher methylation status of ABO gene promoter was associated with AMI and the odds of AMI in this population were more than 6-fold in subjects with methylated gene promoter compared to those with unmethylated gene promoter after adjusting with age and waist circumference [AOR (95% CI) = 6.27 (1.76-22.3); p value = 0.005].

Conclusion: The ABO gene promoter’s hypermethylation appears to be increasing the risk of AMI in a hospital-based Pakistani population in Karachi, Pakistan.

doi: https://doi.org/10.12669/pjms.36.3.1406

How to cite this:Yousuf FA, Kazmi K, Iqbal J, Ahmed N, Iqbal MP. Higher DNA methylation of ABO gene promoter is associated with acute myocardial infarction in a hospital-based population in Karachi. Pak J Med Sci. 2020;36(3):505-510. doi: https://doi.org/10.12669/pjms.36.3.1406

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Anti-Mullerian hormone levels in female cancer patients of reproductive age in Indonesia: A cross-sectional study
Authors: Harzif Achmad Kemal , Wiweko Budi , Addina Putri , Iswaranti Kartika , Silvia Melisa , Mariana Ana , Mutia Kresna , Sumapraja Kanadi , Muharam R , Pratama Gita
Published: February 2020

Background: Efforts in reproductive preservation for cancer patients have become one of the important aspects of cancer management. In fact, decline in reproductive function is known to occur after exposure to anti-cancer treatments. Measuring anti-Müllerian hormone (AMH) levels is known to be the best parameter in predicting ovarian reserves, which indicates reproductive function. In total, 68% of cancer survivors of reproductive age who underwent anti-cancer treatments suffer from infertility. Meanwhile, ovarian reserves also decrease with increasing age. There is ongoing debate on whether the ovarian reserves of cancer patients could be reduced long before exposure to anti-cancer therapy. Therefore, it is important to know whether ovarian reserves in cancer patients decrease before or after anti-cancer therapy. This can help predict the reproductive function in such cases and the effectiveness of ovarian preservation efforts.

Methods: A cross-sectional study was conducted, comparing the AMH levels of 44 female cancer patients of reproductive age before cancer therapy, to 44 non-cancer patients of reproductive age (age matched). The AMH was determined from blood.The biological ages from both groups were adjusted using the Indonesian Kalkulator of Oocytes.

Results: The median age in both groups was 28 years old. The AMH levels in the blood of the cancer group were found to be significantly lower in contrast to those in the non-cancer group (1.11 [0.08-4.65] ng/ml vs. 3.99 [1.19- 8.7]; p- value <0.001). Therefore, the biological age in the cancer group was 10 years older than that of the non-cancer group, indicating that ovarian aging occurs earlier in cancer patients.

Conclusions: AMH levels of cancer patients of reproductive age were already reduced before cancer therapy, given an older biological age, in contrast to that of the non-cancer patients. Proper counseling and implementation of fertility-preserving methods is highly recommended in this group of patients.
Lipidomics reveal the protective effects of a vegetable-derived isothiocyanate against retinal degeneration
Authors: Kwa Faith A. , Dulull Nabeela K. , Roessner Ute , Dias Daniel A. , Rupasinghe Thusitha W.
Published: February 2020

Background:Age-related macular degeneration (AMD) is a leading cause of blindness in the ageing population. Without effective treatment strategies that can prevent disease progression, there is an urgent need for novel therapeutic interventions to reduce the burden of vision loss and improve patients’ quality of life. Dysfunctional innate immune responses to oxidative stress observed in AMD can be caused by the formation of oxidised lipids, whilst polyunsaturated fatty acids have shown to increase the risk of AMD and disease progression in affected individuals. Previously, our laboratory has shown that the vegetable-derived isothiocyanate, L-sulforaphane (LSF), can protect human adult pigment epithelial cells from oxidative damage by upregulating gene expression of the oxidative stress enzyme Glutathione-S-Transferase µ1. This study aims to validate the protective effects of LSF on human retinal cells under oxidative stress conditions and to reveal the key players in fatty acid and lipid metabolism that may facilitate this protection.

Methods:Thein vitrooxidative stress model of AMD was based on the exposure of an adult retinal pigment epithelium-19 cell line to 200µM hydrogen peroxide. Percentage cell proliferation following LSF treatment was measured using tetrazolium salt-based assays. Untargeted fatty acid profiling was performed by gas chromatography-mass spectrometry. Untargeted lipid profiling was performed by liquid chromatography-mass spectrometry.

Results:Under hydrogen peroxide-induced oxidative stress conditions, LSF treatment induced dose-dependent cell proliferation. The key fatty acids that were increased by LSF treatment of the retinal cells include oleic acid and eicosatrienoic acid. LSF treatment also increased levels of the lipid classes phosphatidylcholine, cholesteryl ester and oxo-phytodienoic acid but decreased levels of phosphatidylethanolamine lipids.

Conclusions:We propose that retinal cells at risk of oxidative damage and apoptosis can be pre-conditioned with LSF to regulate levels of selected fatty acids and lipids known to be implicated in the pathogenesis and progression of AMD.
SNPector: SNP inspection tool for diagnosing gene pathogenicity and drug response in a naked sequence
Authors: Habib Peter T. , Alsamman Alsamman M. , Hassanein Sameh E. , Shereif Ghada A. , Hamwieh Aladdin
Published: February 2020

Due to the ability to diagnose diseases early and evaluate the effectiveness of medicinal drugs, single nucleotide polymorphism (SNP) identification receives significant interest. Detection and diagnosis of genetic variation through skill-less computational tools would help researchers reducing the severity of such health complications and improving well-tailored therapies using discovered and previously known information. We introduce SNPector, which is a standalone SNP inspection software, which can be used to diagnose gene pathogenicity and drug reaction in naked genomic sequences. It identifies and extracts gene-related SNPs, and reports their genomic position, associated phenotype disorder, associated diseases, linkage disequilibrium, in addition to various drug reaction information. SNPector detects and verifies the existence of an SNP in a given DNA sequence without the reference based on different clinically relevant SNP databases, such as NCBI ClinVar, AWESOME, and PharmGKB, and generates highly informative visualizations of the recovered information.
Differences in total iron content at various altitudes of Amazonian Andes soil in Ecuador
Authors: Mendoza Benito , Guananga Nelly , Melendez Jesus R. , Lowy Daniel A.
Published: February 2020

Although iron is not contained by chlorophyll, it is indispensable for plants as it plays an essential role in the biosynthesis of chlorophyll. It is a component of many important plant enzyme systems, e.g. cytochrome oxidase, which is responsible for electron transport. Therefore, examining iron content of soils, particularly ionic forms of iron (Fe2+ and Fe3+) is important for fruit growers. In this article, we disclose the total iron content determined in soils (Hyperalic Alisol soil) at three altitudes of Amazonian rainforest in Ecuador. We examine how different altitudes impact the pH and total iron content in the selected study area. We found that total iron content significantly decreases (R2=0.966) at lower altitudes. For future studies, the authors recommend that along with Fe ion content one should determine calcium, microbial biomass, and microbial activity to better understand iron mobility and dynamics of iron uptake in the area.
Zones with special conditions of use of territories (problems of the establishment and implementation of the legal regime)
Authors: Galinovskaya Elena , Boltanova Elena , Volkov Gennadiy , Vyphanova Galina , Ignat'eva I. , Kichigin N. , Kovaleva E. , Mel'nik T. , Ponomarev M. , Sivakov D. , Solov'eva S.
Published: February 2020

The peculiarities of the modern spatial development necessitated the development of organizational, managerial and legal measures to reduce the risks of neighbourhood objects that have a negative impact on humans and the environment, as well as to strengthen the protection of especially dangerous or sensitive objects.
Introduction to the Land code of the Russian Federation the concept of "zones with special conditions of use of territories" is one of the promising solutions to the above tasks and is aimed at ensuring sanitary and epidemiological welfare of the population, industrial safety, safety in operating all types of transport, defence and state security, environmental protection etc.
The Handbook describes the concept and the legal nature of the zones with special conditions of use of territories as a new category, which should become a full part of fur-
the mechanism of the land law regulation. Describes the evolution of national legislation on conservation and protection zones, the analysis of the regulation of similar zones in foreign legislation. Special attention is paid to General issues of the legal regime of these zones, the specifics of their establishment and accounting.
Researched legal requirements for the adherence of all types of zones with special conditions of use.
For practitioners and specialists in the field of state and municipal administration, scientific workers and lecturers of higher and secondary professional educational institutions, students, graduates, and also for a wide range of readers.
Sports environment
Authors: Polievskiy Sergey
Published: February 2020

Discussed global environmental problems of the biosphere, ecology in the city, radiation factor, and its impact on human health, including those engaged in physical culture, sports and tourism, food as endoecological factor. Illuminated by the experience of environmental protection in various sports, including the Olympic games, legislation and international legal cooperation in the field of environmental protection sport environment, increasing the efficiency of physical training and condition under different environmental conditions.
Tutorial to be served in integrated, multidisciplinary plan, taking into account the necessity of integrated assessment of ecological positions of safety and hygiene.
Meets the requirements of Federal state educational standard of higher education of the last generation.
For students of higher education institutions.
Philosophy for economists and managers
Authors: Kanke Viktor
Published: February 2020

The tutorial is a sequential course of philosophy. The article considers the questions of philosophy of science and the history of philosophy, ontology, epistemology, ethics and aesthetics. The course is designed taking into account the achievements of analytical philosophy, phenomenology, hermeneutics, postructuralism and other major philosophical issues of the day. Uses the theory of conceptual transduction. Special attention is paid to the relationship of philosophy to Economics and management. The course is carefully calibrated in the didactic relation. Each paragraph ends with the conclusions, and test, by a reference list.
For students of higher educational institutions, primarily economists and managers. Of interest to a wide circle of readers.
Philosophy of law
Authors: Popova Anna
Published: February 2020

Textbook is universal in nature, is short and at the same time the perfection of the supply of educational material. Consistently and logically set out the philosophical and legal doctrine, the study of the relationship of legal and economic postulates in the explanation of legal reality and legal reality.
Prepared taking into account experience of teaching of philosophy of law students studying in the direction of training 40.04.01 "Law", in accordance with the requirements of Federal state educational standards of higher education of the last generation.
For students of humanitarian directions of training, graduate students in training 40.04.01 Jurisprudence, graduates, teachers of law schools and faculties, as well as anyone interested in the philosophy of law.
Agricultural entomology in the state of Acre: a historical overview and future challenges
Authors: Sutil Weidson Plauter , Santos Rodrigo Souza
Published: February 2020

In the state of Acre, Brazil, family-based agriculture is predominant and although it has less economic impact in relation to large-scale plantations, it is also subject to biological imbalances, such as the attack of pests, generating economic losses for producers. Phytosanitary knowledge in the state is still incipient and becomes an obstacle to production, often resulting in mistaken management decisions. In this context, this work aimed to present a history of research carried out in the field of Agricultural Entomology, especially in the areas of integrated management and biological control of pests of the most relevant crops grown in the Acre state. In this review, 55 scientific papers related to Agricultural Entomology were presented, 23 on new insect records and/or new insect associations with host plants, 16 on insect control using plant extracts from the Amazon region, 13 on integrated pest management and three on bioecology and population dynamics of pests in the state of Acre. Through this review, it is observed that research in the area  of Agricultural Entomology in the state of Acre is characterized by basic research (surveys, registration of new species, bioecological and dynamic population studies). However, there has been a notable advance in scientific studies aimed at integrated pest management in the state in the past ten years. Still, there is a need to concentrate efforts on research aimed at prospecting and using Amazonian biodiversity (fauna and flora), which subsidize applied programs for integrated pest management of the main crops grown in the Acre state.