bluuebunny/crossref_metadata_2025 huggingface dataset:
Systematic review of cognitive impairment and brain insult after mechanical ventilation
Authors: Bassi Thiago G. , Rohrs Elizabeth C. , Reynolds Steven C.
Published: March 2021

We conducted a systematic review following the PRISMA protocol primarily to identify publications that assessed any links between mechanical ventilation (MV) and either cognitive impairment or brain insult, independent of underlying medical conditions. Secondary objectives were to identify possible gaps in the literature that can be used to inform future studies and move toward a better understanding of this complex problem. The preclinical literature suggests that MV is associated with neuroinflammation, cognitive impairment, and brain insult, reporting higher neuroinflammatory markers, greater evidence of brain injury markers, and lower cognitive scores in subjects that were ventilated longer, compared to those ventilated less, and to never-ventilated subjects. The clinical literature suggests an association between MV and delirium, and that delirium in mechanically ventilated patients may be associated with greater likelihood of long-term cognitive impairment; our systematic review found no clinical study that demonstrated a causal link between MV, cognitive dysfunction, and brain insult. More studies should be designed to investigate ventilation-induced brain injury pathways as well as any causative linkage between MV, cognitive impairment, and brain insult.
Identification of pathogenic variants in cancer genes using base editing screens with editing efficiency correction
Authors: Huang Changcai , Li Guangyu , Wu Jiayu , Liang Junbo , Wang Xiaoyue
Published: March 2021

Background

Millions of nucleotide variants are identified through cancer genome sequencing and it is clinically important to identify the pathogenic variants among them. By introducing base substitutions at guide RNA target regions in the genome, CRISPR-Cas9-based base editors provide the possibility for evaluating a large number of variants in their genomic context. However, the variability in editing efficiency and the complexity of outcome mapping are two existing problems for assigning guide RNA effects to variants in base editing screens.

Results

To improve the identification of pathogenic variants, we develop a framework to combine base editing screens with sgRNA efficiency and outcome mapping. We apply the method to evaluate more than 9000 variants across all the exons ofBRCA1andBRCA2genes. Our efficiency-corrected scoring model identifies 910 loss-of-function variants forBRCA1/2, including 151 variants in the noncoding part of the genes such as the 5′ untranslated regions. Many of them are identified in cancer patients and are reported as “benign/likely benign” or “variants of uncertain significance” by clinicians. Our data suggest a need to re-evaluate their clinical significance, which may be helpful for risk assessment and treatment of breast and ovarian cancer.

Conclusions

Our results suggest that base editing screens with efficiency correction is a powerful strategy to identify pathogenic variants in a high-throughput manner. Applying this strategy to assess variants in both coding and noncoding regions of the genome could have a direct impact on the interpretation of cancer variants.
Editing GWAS: experimental approaches to dissect and exploit disease-associated genetic variation
Authors: Rao Shuquan , Yao Yao , Bauer Daniel E.
Published: March 2021

Genome-wide association studies (GWAS) have uncovered thousands of genetic variants that influence risk for human diseases and traits. Yet understanding the mechanisms by which these genetic variants, mainly noncoding, have an impact on associated diseases and traits remains a significant hurdle. In this review, we discuss emerging experimental approaches that are being applied for functional studies of causal variants and translational advances from GWAS findings to disease prevention and treatment. We highlight the use of genome editing technologies in GWAS functional studies to modify genomic sequences, with proof-of-principle examples. We discuss the challenges in interrogating causal variants, points for consideration in experimental design and interpretation of GWAS locus mechanisms, and the potential for novel therapeutic opportunities. With the accumulation of knowledge of functional genetics, therapeutic genome editing based on GWAS discoveries will become increasingly feasible.
Lack of detection of the Middle East respiratory syndrome coronavirus (MERS-CoV) nucleic acids in some Hyalomma dromedarii infesting some Camelus dromedary naturally infected with MERS-CoV
Authors: Hemida Maged Gomaa , Alhammadi Mohammed , Almathen Faisal , Alnaeem Abdelmohsen
Published: March 2021

Objective

The Middle East respiratory syndrome coronavirus (MERS-CoV) is one of the zoonotic coronaviruses [Hemida Peer J 7:e7556, 2019; Hemida et al. One Health 8:100102, 2019]. The dromedary camels remained the only known animal reservoir for this virus. Several aspects of the transmission cycle of the virus between animals, including arthropod-borne infection, is still largely unknown. The main objective of the current work was to study the possibility of MERS-CoV transmission through some arthropod vectors, particularly the hard ticks. To achieve this objective, we identified a positive MERS-CoV dromedary camel herd using the commercial available real-time PCR kits. We collected some arthropods, particularly the ticks from these positive animals as well as from the animal habitats. We tested these arthropods for the presence of MERS-CoV viral RNAs.

Results

Our results showing the absence of any detectable MERS-CoV-RNAs in these arthropods despite these animals were actively shedding the virus in their nasal secretions. Our results are confirming for the first the failure of detection of the MERS-CoV in ticks infesting dromedary camels. Failure of the detection of MERS-CoV in ticks infesting positive naturally infected MERS-CoV camels is strongly suggesting that ticks do not play roles in the transmission of the virus among the animals and close contact humans.
Mitochondrial activity regulates the differentiation of skin-derived mesenchymal stem cells into brown adipocytes to contribute to hypertension
Authors: Xi Wenda , Chen Wendong , Sun Weihong , Li Xiangxiao , Suo Zhimin , Jiang Gonghao , Gao Pingjin , Li Qun
Published: March 2021

Background

Brown adipocytes (BAs) are major components of brown adipose tissue (BAT), which is involved in blood pressure regulation. BAs are derived from multiple progenitors, including PDGFRα+ adipose-derived stem cells (ASCs). Skin-derived mesenchymal stem cells (S-MSCs) have the capacity to differentiate into adipocytes; however, their ability to differentiate into BAs remains unexplored. We aim to study the ability and regulatory mechanism of the differentiation of S-MSCs into BAs and the direct role of BAT in blood pressure regulation.

Methods

Protein expression was measured by flow cytometry or Western blotting, and gene mRNA levels were quantified by real-time quantitative PCR (RT-PCR). To induce the differentiation of S-MSCs into BAs, S-MSCs were stimulated with a brown adipogenic cocktail comprising insulin, IBMX, dexamethasone, triiodothyronine (T3), and rosiglitazone for the indicated periods. The oxygen consumption rate (OCR) was measured with an XF24 Extracellular Flux Analyzer. Mitochondrial mass was determined by flow cytometry and fluorescence staining. Hypertension was induced in WT mice by infusion of angiotensin II (Ang II), and systolic blood pressure (SBP) was measured using a tail cuff. Interscapular brown adipose tissue (iBAT)-deficient mice were generated by surgical removal of the iBAT depot, after which the animals were allowed to recover for 6 days. Aortic, iBAT, and heart tissue sections were analyzed by hematoxylin and eosin (HE) staining.

Results

We found that in vitro, S-MSCs isolated from the mouse dermis expressed the stem cell markers CD90/105 and PDGFRα and readily differentiated into BAs. Mitochondrial biogenesis and oxygen consumption were markedly increased during differentiation of S-MSCs into BAs. In vivo, iBAT was converted to white adipose tissue (WAT) in Ang II-induced hypertensive mice. We assessed the direct role of BAT in blood pressure (BP) regulation by using iBAT-deficient mice (generated by surgical removal of iBAT) and C57BL/6 (wild-type (WT)) mice and found that Ang II-induced BP elevation and vascular damage were markedly aggravated in iBAT-deficient mice compared with WT mice.

Conclusions

This study demonstrates that PDGFRα+ S-MSCs are able to differentiate into BAs and that this differentiation is regulated by mitochondrial activity. We also show that BAT plays a direct role in ameliorating Ang II-induced hypertension. The therapeutic potential of BAT for the prevention of hypertension-induced organ remodeling thus warrants further investigation.

Graphical abstract. Schematic of the in vitro differentiation of PDGFRα+ S-MSCs into BAs via a process regulated by mitochondrial activity. BAT plays a direct role in Ang II-induced hypertension and target organ remodeling
Initial inpatient management of adolescents and young adults admitted with severe malnutrition due to anorexia nervosa: protocol for a systematic review
Authors: Proulx-Cabana Stéphanie , Taddeo Danielle , Jamoulle Olivier , Frappier Jean-Yves , Tremblay-Racine Fannie , Stheneur Chantal
Published: March 2021

Background

Anorexia Nervosa (AN) is a highly prevalent disease in adolescents and young adults (AYAs). The quality of initial inpatient medical management in a patient with severe malnutrition due to AN is crucial to prevent further medical instability. This review aims to inventory evidence regarding initial refeeding and management of AYAs with AN in an inpatient setting, in order to avoid medical complications.

Methods

A systematic review will be conducted using PubMed, MEDLINE, All EBM Reviews, Embase, PsycINFO, Cochrane Database and CINAHL. The search strategy consists of terms related to anorexia, hospitalization and Pediatrics. Randomized controlled trials, case-control studies, cross-sectional and cohort studies will be included. Participants will include adolescents and adults 18–24 years old diagnosed with AN and meeting criteria for severe disease. The primary outcome will be any of the following complications: hypophosphatemia, refeeding syndrome, hypoglycemia, cardiac arrythmia, hepatic cytolysis or death. Data will be extracted and the risk of bias will be assessed by one author and reviewed by a second author. Results will be presented in a systematic narrative synthesis format. The quality of evidence for all outcomes will be evaluated using the GRADE methodology.

Discussion

This systematic review will examine current evidence on initial inpatient refeeding and help to document effectiveness of initial inpatient management in AYAs with severe AN in avoiding further medical complications.

Trial registration

This study is registered on PROSPERO under the reference number CRD42019123608.
Relationship between adiponectin, TNFα, and SHBG in prepubertal children with obesity
Authors: Ramon-Krauel Marta , Leal-Witt María Jesús , Osorio-Conles Óscar , Amat-Bou Montse , Lerin Carles , Selva David M.
Published: March 2021

Background

Sex hormone-binding globulin (SHBG) levels are low in adult subjects with obesity when compared to normal-weight individuals. Obesity is associated with higher tumor necrosis factor alpha (TNFα) plasma levels and lower adiponectin levels. Moreover, we have recently elucidated the molecular mechanisms by which TNFα and adiponectin regulate hepatic SHBG production.

Aim

The main objective of this study was to assess if the adult associations between TNFα, adiponectin, and SHBG are present in prepubertal children.

Methods

We determined several morphometric and biochemical parameters in normal-weight (n=15) and obese prepubertal (n=51) children, as well as quantified plasma SHBG, TNFα receptor 1 (TNFα-R1), and adiponectin levels.

Results

Our results showed that prepubertal children with obesity had decreased plasma SHBG levels compared to normal-weight controls (67 nmol/L vs 172 nmol/L). Importantly, SHBG plasma levels correlated significantly (P < 0.05) with TNFα (negatively, ßstd= − 0.31) and adiponectin (positively, ßstd= 0.58) suggesting an important role of these two cytokines in determining plasma SHBG levels in prepubertal children.

Conclusions

Our results suggest that plasma adiponectin levels may play a more important role than TNFα in influencing plasma SHBG levels in our prepubertal population with obesity.
Hydrochar from sugarcane industry by-products: assessment of its potential use as a soil conditioner by germination and growth of maize
Authors: Fregolente Laís G. , dos Santos João Vitor , Mazzati Felipe S. , Miguel Thaiz B. A. R. , de C. Miguel Emílio , Moreira Altair B. , Ferreira Odair P. , Bisinoti Márcia C.
Published: March 2021

Background

Hydrothermal carbonization (HTC) is a thermochemical process to convert biomass in carbon-rich materials (hydrochar). The use of sugarcane industry by-products in HTC has been evaluated, generating a hydrochar rich in nutrients, which could be used as a soil conditioner. We raised the hypothesis that the application of hydrochar in soil can improve its nutrient characteristics, bringing a better environment and favouring plant growth, expecting a development similar to that one observed in anthropogenic soils.

Results

Germination studies were performed expecting a species-dependent response, using maize and tomato seeds, whose development was assessed in two soluble fractions obtained from hydrochar aiming to evaluate different rhizosphere conditions. The results showed a better development of maize, especially in the aqueous soluble fraction, whose nutrient concentration was lower than that of the acid soluble fraction, as well as the organic composition. Maize growth in soils showed a better initial development in ultisol compared to oxisol, this being inferred by root:shoot biomass ratio and by scanning electron microscopy (SEM) images. However, the development of maize was better in anthropogenic soil compared to soils that received hydrochar.

Conclusion

The maize growth, compared with that carried out in anthropogenic soil, suggests that during the period evaluated the addition of hydrochar in soil did not have a negative effect upon maize development in its initial phase, and could have even favoured rooting in ultisol.
The effectiveness of an online grammar study scheme for Chinese undergraduate students
Authors: Windsor Ryan John
Published: March 2021

This paper outlines and describes the effectiveness of a virtual learning environment (VLE) as a grammar learning resource for first year students at a university in southern China over two academic years. The resource, named the Independent Grammar Study Scheme (IGSS), offered short grammar exercises that were completed over a 14-week period by two cohorts of year one students. The results of this study suggest that IGSS was successful in raising the grammar test scores of participants in both 2018 and 2019; that IGSS was more beneficial to students with lower English proficiency in 2018 but not in 2019; and that the VLE has been of great benefit to the university and to around one thousand students thus far.
Prognosis of hepatocellular carcinoma metastasizing to the oral cavity
Authors: Hong Jun-Hee , Lee Keonmo , Kim Jinhong , Ahn Kang-Min
Published: March 2021

Background

Oral metastasis by hepatocellular carcinoma (OMHCC) is extremely rare, and the prognosis had been reported quite poor due to simultaneous multiple organ metastases. In this study, we report clinical features and survival of 10 new cases of OMHCC and suggest the criteria for palliative surgery.

Methods

A retrospective clinical study including 10 new cases of oral OMHCC between 2006 and 2016 was performed. Clinical features and survival analysis were examined. The recorded variables were age, sex, site of oral metastases, size of oral tumor (largest diameter), and survival after oral histopathologic diagnosis.

Results

There was male (n=8) predilection of OMHCC. The mean survival time was 16.9 months. Patient age ranged from 40 to 71 years (mean 56.5). Eight mandibular and two maxillary lesions were found. One patient showed simultaneously the maxilla and the oral tongue involvement. The most often encountered symptoms were swelling (80%) followed by pain (60%), numbness (60%), bleeding (10%), and tooth mobility (10%). Four patients underwent operation due to spontaneous bleeding and swelling of the cancer. Overall (from onset of hepatocellular carcinoma) and truncated survival (from onset of OMHCC) were 71.9 and 13.1 months respectively.

Conclusion

The prognosis of OMHCC was quite poor. Oral and jaw bone examination should be included in patients with multiple metastasis of HCC. Palliative surgery might be performed in patients who reported spontaneous bleeding, severe pain, and oral dysphasia due to tumor enlargement.
The increasing expression of GPX7 related to the malignant clinical features leading to poor prognosis of glioma patients
Authors: Yao Jiawei , Chen Xin , Liu Zhendong , Zhang Ruotian , Zhang Cheng , Yang Quan , Yao Penglei , Jiang Qiuyi , Wu Jianing , Zhao Shiguang
Published: March 2021

Background

Glioma is the most common malignant brain tumor in adults. The standard treatment scheme of glioma is surgical resection combined alternative radio- and chemotherapy. However, the outcome of glioma patients was unsatisfied. Here, we aimed to explore the molecular and biological function characteristics of GPX7 in glioma.

Methods

The multidimensional data of glioma samples were downloaded from Chinese Glioma Genome Atlas (CGGA). RT-qPCR method was used to identify the expression status of GPX7. Kaplan–Meier curves and Cox regression analysis were used to explore the prognostic value of GPX7. Gene Set Enrichment Analysis (GSEA) was applied to investigate the GPX7-related functions in glioma.

Results

The results indicated that the expression of GPX7 in glioma was higher compared to that in normal brain tissue. Univariate and multivariate Cox regression analyses confirmed that the expression value of GPX7 was an independent prognostic factor in glioma. The GSEA analysis showed that GPX7 was significantly enriched in the cell cycle pathway, ECM pathway, focal adhesion pathway, and toll-like receptor pathway.

Conclusions

The GPX7 was recommended as an independent risk factor for patients diagnosed with glioma for the first time and GPX7 could be potentially used as the therapy target in future. Furthermore, we attempted to explore a potential biomarker for improving the diagnosis and prognosis of patients with glioma.
Insomnia in neurological diseases
Authors: Mayer Geert , Happe Svenja , Evers Stefan , Hermann Wiebke , Jansen Sabine , Kallweit Ulf , Muntean Maria-Lucia , Pöhlau Dieter , Riemann Dieter , Saletu Michael , Schichl Melanie , Schmitt Wolfgang J. , Sixel-Döring Friederike , Young Peter
Published: March 2021

Insomnia is defined as difficulties of initiating and maintaining sleep, early awakening and poor subjective sleep quality despite adequate opportunity and circumstances for sleep with impairment of daytime performance. These components of insomnia – namely persistent sleep difficulties despite of adequate sleep opportunity resulting in daytime dysfunction - appear secondary or co-morbid to neurological diseases. Comorbid insomnia originates from neurodegenerative, inflammatory, traumatic or ischemic changes in sleep regulating brainstem and hypothalamic nuclei with consecutive changes of neurotransmitters. Symptoms of neurological disorders (i.e motor deficits), co-morbidities (i.e. pain, depression, anxiety) and some disease-specific pharmaceuticals may cause insomnia and/or other sleep problems.

This guideline focuses on insomnias in headaches, neurodegenerative movement disorders, multiple sclerosis, traumatic brain injury, epilepsies, stroke, neuromuscular disease and dementia.

The most important new recommendations are: Cognitive behavioral therapy (CBTi) is recommended to treat acute and chronic insomnia in headache patients. Insomnia is one of the most frequent sleep complaints in neurodegenerative movement disorders. Patients may benefit from CBTi, antidepressants (trazodone, doxepin), melatonin and gaba-agonists. Insomnia is a frequent precursor of MS symptoms by up to 10 years. CBTi is recommended in patients with MS, traumatic brain injury and. Melatonin may improve insomnia symptoms in children with epilepsies. Patients with insomnia after stroke can be treated with benzodiazepine receptor agonists and sedating antidepressants. For patients with dementia suffering from insomnia trazodone, light therapy and physical exercise are recommended.
Mathematical analysis of a generalized epidemic model with nonlinear incidence function
Authors: Ogunmiloro O. M. , Kareem H.
Published: March 2021

Background

Though different forms of control measures have been deployed to curtail disease transmission, which are mostly through vaccination, treatment, isolation, etc., using mathematical models. Therefore, there is a need to consider the strict compliance or attendance of human individuals to medical awareness program through media outlets like radio, television, etc. In this work, a generalized mathematical model of two groups of infectious individuals who are compliant and non-compliant to medical awareness program is studied.

Results

A generalized Susceptible-Exposed-Infected-Recovered (SEIR) model with two groups of infectious individuals who attend or are compliant and those who do not attend or are non-compliant to medical awareness program is established. The analytical results of the model shows that the model is positive, well-posed, and epidemiologically reasonable. The two equilibria and the basic reproduction numberRrof the model is computed and analyzed and it is shown that the disease-free equilibrium is locally and globally asymptotically stable whenRr < 1 and the endemic equilibrium is globally stable whenRr > 1. Simulations are carried out by varying some parameters whenRris less and above unity. The simulations suggest that control interventions are to be implemented and medical awareness program scaled up to mitigate the spread of diseases. Furthermore, two numerical methods of Runge-Kutta and Differential Transform Method (DTM) are employed to obtain the approximate solutions of the model system equations, and it is observed that the results of the two methods agreeably compare with each other in terms of efficiency and convergence.

Conclusion

This work should be taken into consideration by health policy makers and bio-mathematicians, because existing literature only take into consideration, how diseases spread and its management without considering the impact of strict compliance to consistent awareness program to mitigate the spread of diseases, which has been considered in this work. The limitation of this work is the unavailability of data on individuals in disease endemic regions who always and who do not comply with medical awareness programs.
Reciprocal-condition-number-based borehole acoustic dispersion curve prediction
Authors: Zhao Jiajun , Wang Ruijia , Sun Qingtao , Coates Richard T.
Published: March 2021

The prediction of dispersion curves is an essential part of understanding borehole acoustic modes. Traditional dispersion curve calculation requires finding zeros of the determinant of the characteristic matrix of a borehole system. This approach is subject to interpretational ambiguity because the determinant can be scaled arbitrarily. We have developed an alternative approach based on the reciprocal condition number (RCN) of the characteristic matrix. The RCN quantifies the singularity of a matrix on a fixed scale between zero and unity; thus, it represents wave modal strengths. We find that our method and traditional methods give identical dispersion-curve locations for simple models and that our method provides more insights on the wave modal amplitudes of complicated models with multiple layers, such as those incorporating logging tools and casing strings. Finally, we determine how our method can be used as the basis of sensitivity analysis to indicate how the dispersion curves are dependent on the model parameters.
Sex differences in insulin resistance, but not peripheral neuropathy, in a diet-induced prediabetes mouse model
Authors: Elzinga Sarah E. , Savelieff Masha G. , O'Brien Phillipe D. , Mendelson Faye E. , Hayes John M. , Feldman Eva L.
Published: March 2021

Peripheral neuropathy (PN) is a common complication of prediabetes and diabetes and is an increasing problem worldwide. Existing PN treatments rely solely on glycemic control, which is effective in type 1 but not type 2 diabetes. Sex differences in response to anti-diabetic drugs further complicate the identification of effective PN therapies. Preclinical research has been primarily carried out in males, highlighting the need for increased sex consideration in PN models. We previously reported PN sex dimorphism in obese leptin-deficient ob/ob mice. This genetic model is inherently limited, however, owing to leptin's role in metabolism. Therefore, the current study goal was to examine PN and insulin resistance in male and female C57BL6/J mice fed a high-fat diet (HFD), an established murine model of human prediabetes lacking genetic mutations. HFD mice of both sexes underwent longitudinal phenotyping and exhibited expected metabolic and PN dysfunction compared to standard diet (SD)-fed animals. Hindpaw thermal latencies to heat were shorter in HFD females versus HFD males, as well as SD females versus males. Compared to HFD males, female HFD mice exhibited delayed insulin resistance, yet still developed the same trajectory of nerve conduction deficits and intraepidermal nerve fiber density loss. Subtle differences in adipokine levels were also noted by sex and obesity status. Collectively, our results indicate that although females retain early insulin sensitivity upon HFD challenge, this does not protect them from developing the same degree of PN as their male counterparts.

This article has an associated First Person interview with the first author of the paper.
Evolved changes in maternal care in high-altitude native deer mice
Authors: Robertson Cayleih E. , McClelland Grant B.
Published: March 2021

At high altitude (HA), unremitting low oxygen and persistent cold push small mammals close to their metabolic ceilings, leaving limited scope for aerobically demanding activities. However, HA breeding seasons are relatively short and endemic rodents compensate with larger litters than low altitude (LA) conspecifics. Rodent mothers are the sole source of heat and nutrition for altricial offspring and lactation is energetically costly. Thus, it is unclear how HA females balance energy allocation during the nursing period. We hypothesized that HA female rodents invest heavily in each litter to ensure postnatal survival. We measured maternal energetic output and behaviour in nursing deer mice (Peromyscus maniculatus) native to LA (400 m a.s.l.) and HA (4350 m a.s.l.) under control (24°C, 760 mmHg) and cold hypoxia conditions, simulating HA (5°C, 430 mmHg). Strikingly, resting metabolic rates of lactating HA and LA females under cold hypoxia were 70–85% of their maximum aerobic capacity. In cold hypoxia, LA mothers increased both nursing time and milk fat content, however their pups were leaner and severely growth restricted at weaning. HA mothers also increased nursing in cold hypoxia but for far less time than LA mothers. Despite receiving less care, HA pups in cold hypoxia only experienced small growth restrictions at weaning and maintained body composition. As adults, HA mice raised in cold hypoxia had increased aerobic capacity compared to controls. These data suggest that HA mothers prioritize their own maintenance costs over investing heavily in their offspring. Pups compensate for this lack of care, likely by reducing their own metabolic costs during development.
When it's hot and dry: life-history strategy influences the effects of heat waves and water limitation
Authors: Padda Sugjit S. , Glass Jordan R. , Stahlschmidt Zachary R.
Published: March 2021

The frequency, duration and co-occurrence of several environmental stressors, such as heat waves and droughts, are increasing globally. Such multiple stressors may have compounding or interactive effects on animals, resulting in either additive or non-additive costs, but animals may mitigate these costs through various strategies of resource conservation or shifts in resource allocation. Through a factorial experiment, we investigated the independent and interactive effects of a simulated heat wave and water limitation on life-history, physiological and behavioral traits. We used the variable field cricket, Gryllus lineaticeps, which exhibits a wing dimorphism that mediates two distinct life-history strategies during early adulthood. Long-winged individuals invest in flight musculature and are typically flight capable, whereas short-winged individuals lack flight musculature and capacity. A comprehensive and integrative approach with G. lineaticeps allowed us to examine whether life-history strategy influenced the costs of multiple stressors as well as the resulting cost-limiting strategies. Concurrent heat wave and water limitation resulted in largely non-additive and single-stressor costs to important traits (e.g. survival and water balance), extensive shifts in resource allocation priorities (e.g. reduced prioritization of body mass) and a limited capacity to conserve resources (e.g. heat wave reduced energy use only when water was available). Life-history strategy influenced the emergency life-history stage because wing morphology and stressor(s) interacted to influence body mass, boldness behavior and immunocompetence. Our results demonstrate that water availability and life-history strategy should be incorporated into future studies integrating important conceptual frameworks of stress across a suite of traits – from survival and life history to behavior and physiology.
Learning a non-neutral conditioned stimulus: place preference in the crab Neohelice granulata
Authors: Klappenbach Martín , Medina Candela , Freudenthal Ramiro
Published: March 2021

In the wild, being able to recognize and remember specific locations related to food sources and the associated attributes of landmarks is a cognitive trait important for survival. In the present work, we show that the crab Neohelice granulata can be trained to associate a specific environment with an appetitive reward in a conditioned place preference task. After a single training trial, when the crabs were presented with a food pellet in the target quadrant of the training arena, they were able to form a long-term memory related to the event. This memory was evident at least 24 h after training and was protein synthesis dependent. Importantly, the target area of the arena proved to be a non-neutral environment, given that animals initially avoided the target quadrant. In the present work, we introduce for the first time an associative one-trial memory paradigm including a conditioned stimulus with a clear valence performed in a crustacean.
Gastrointestinal complications in critically ill children: Experience from a resource-limited country
Authors: Ishaque Sidra , Shakir Marium , Ladak Asma , Haque Anwar Ul
Published: March 2021

Objectives: To determine the frequency and predictors of outcome of gastrointestinal complications (GIC) in critically ill children.

Methods: This descriptive study was prospectively conducted in The Pediatric Intensive Care Unit (PICU), The Aga Khan University Hospital (AKUH), Karachi, from September 2015 to January 2017. After obtaining approval from the Ethical Review Committee of AKUH and informed consent from the parents, all children (aged one month to 18 years), of either gender, admitted to the Pediatric Intensive Care Unit (PICU) during the study period were included. The frequency of the defined GIC: vomiting, high gastric residue volume (GRV), diarrhea, constipation, and gastrointestinal bleed were recorded daily for the first week of the PICU stay. The data was collected by the primary investigator on a predesigned data collection form with inclusion of variables and predictors in light of existing literature and local expertise. The questionnaire was shared with the Pediatric Critical Care Medicine faculty and a consensus was sought on the elements to be incorporated.

Results: GIC developed within the first 48 hours of admission in 78 (41%) patients. Of the patients who developed GIC, 37 (47.4%) patients developed high GRV: 31 (39.7%) patients developed constipation, 18 (23.1%) patients developed vomiting, 14 (17.9%) patients developed abdominal distension. With regards to prevalence by occurrence, 32/78 (41%) of patients presented with two GI complications, followed by 21 patients (27%) who presented with a single GIC. Only 11 patients (14%) presented with more than three complications. Median length of stay was higher in patients with GIC (8 days) than with those who did not develop GIC (4 days). The frequency of gastrointestinal complications was significantly higher in children receiving mechanical ventilation, on sedatives and relaxants and those with multiorgan dysfunction syndrome (MODS) and inotropes

Conclusion: GI complications are a frequent occurrence in the PICU and are associated with worse clinical outcomes. The use of sedative drugs and the presence of shock with MODS were amongst the important contributing factors.

doi: https://doi.org/10.12669/pjms.37.3.3493

How to cite this:Ishaque S, Shakir M, Ladak A, Anwar-Ul-Haque. Gastrointestinal complications in critically ill children: Experience from a resource-limited country. Pak J Med Sci. 2021;37(3):657-662. doi: https://doi.org/10.12669/pjms.37.3.3493

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.
Role of Concomitant Internal Limiting Membrane (ILM) Peeling during Rhegmatogenous Retinal Detachment (RRD) Surgery in Preventing Postoperative Epiretinal Membrane (ERM) Formation
Authors: Syed Asaad Mahmood , Syed Fawad Rizvi , Khan Burhan Abdul Majid , Khan Tanweer Hasan
Published: March 2021

Objective: To investigate the role of concomitant Internal Limiting Membrane (ILM) peeling during surgery for macula off Rhegmatogenous Retinal Detachment (RRD) in preventing postoperative Epiretinal Membrane (ERM) formation; and its effect on the visual acuity.

Methods: This was a prospective, quasi-experimental study conducted from August 2018 to July 2019 at LRBT Tertiary Eye Care hospital, Karachi. Fifty-six patients with macula off RRD were divided into groups A (with ILM peeling) and B (without ILM peeling) via non-probability convenience sampling. All patients underwent standard 3 ports pars plana vitrectomy with silicon oil tamponade. In Group-A, ILM was stained using 0.5% ICG. Patients were evaluated clinically and by spectral domain optical coherence tomography (SD-OCT), pre- and post-operatively. Main outcomes recorded were best corrected visual acuity (BCVA) and occurrence of ERM on SD-OCT.

Results: There were 26 patients in Group-A and 30 patients in Group-B. At six months’ follow-up, ERM had not developed in any case in Group-A compared to five patients (16.7%) in Group-B. There was no statistical difference in mean BCVA change from baseline.

Conclusion: ILM peeling during vitrectomy for RRD prevents the formation of macular ERM post-operatively. This may reduce the need of a second vitrectomy. However, visual outcomes were comparable to the non-ILM peeling vitrectomy.

doi: https://doi.org/10.12669/pjms.37.3.3576

How to cite this:Mahmood SA, Rizvi SF, Khan BAM, Khan TH. Role of Concomitant Internal Limiting Membrane (ILM) Peeling During Rhegmatogenous Retinal Detachment (RRD) Surgery in Preventing Postoperative Epiretinal Membrane (ERM) Formation. Pak J Med Sci. 2021;37(3):651-656. doi: https://doi.org/10.12669/pjms.37.3.3576

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.
Topics in Graph Theory, N K Sudev
Authors: Kottarathil Jomon
Published: March 2021

Review of the book "Topics in Graph Theory" by N K Sudev.
Performance of Aquatic Plant Species for Phytoremediation of Heavy Metals Contaminated Water
Authors: Pillai Priyadarshini
Published: March 2021

Heavy metals and organic pollutants are ubiquitous environmental pollutants affecting the quality of soil, water and air. Over the past 5 decades, many strategies have been developed for the remediation of polluted water.  Use of aquatic plants to extract, sequester and/or detoxify pollutants and is a new and powerful technique for environmental clean up. Plants are ideal agents for soil and water remediation because of their unique genetic, biochemical and physiological properties.  The aim of this work is to evaluate the potential of free floating duck weed Spirodela polyrhiza to remove heavy metals from waste water and the biochemical effect of heavy metals on Spirodela polyrhiza. Approximately 93% of total heavy metal induced – toxicity appears resulting in the reduced activities of nitrate reductase, total chlorophyll and protein content of the plant. The results recommended the use of Spirodela polyrhiza to ameliorate the wastewater contaminated with heavy metals.
On the Combined Role of Strong and Electroweak Interactions in Understanding Nuclear Binding Energy Scheme
Authors: U V S Seshavatharam , S Lakshminarayana
Published: March 2021

An attempt is made toa model the atomic nucleus as a combination of bound and free or unbound nucleons. Due to strong interaction, bound nucleons help in increasing nuclear binding energy and due to electroweak interaction, free or unbound nucleons help in decreasing nuclear binding energy. In this context, with reference to proposed 4G model of final unification and strong interaction, recently we have developed a unified nuclear binding energy scheme with four simple terms, one energy coefficient of 10.1 MeV and two small numbers 0.0016 and 0.0019. In this paper, by eliminating the number 0.0019, we try to fine tune the estimation procedure of number of free or unbound nucleons pertaining to the second term with an energy coefficient of 11.9 MeV. Interesting observation is that, Z can be considered as a characteristic representation of range of number of bound isotopes of  Z.
Radius of Robust Feasibility for Mixed-Integer Problems
Authors: Liers Frauke , Schewe Lars , Thürauf Johannes
Published: March 2021

For a mixed-integer linear problem (MIP) with uncertain constraints, the radius of robust feasibility (RRF) determines a value for the maximal size of the uncertainty set such that robust feasibility of the MIP can be guaranteed. The approaches for the RRF in the literature are restricted to continuous optimization problems. We first analyze relations between the RRF of a MIP and its continuous linear (LP) relaxation. In particular, we derive conditions under which a MIP and its LP relaxation have the same RRF. Afterward, we extend the notion of the RRF such that it can be applied to a large variety of optimization problems and uncertainty sets. In contrast to the setting commonly used in the literature, we consider for every constraint a potentially different uncertainty set that is not necessarily full-dimensional. Thus, we generalize the RRF to MIPs and to include safe variables and constraints; that is, where uncertainties do not affect certain variables or constraints. In the extended setting, we again analyze relations between the RRF for a MIP and its LP relaxation. Afterward, we present methods for computing the RRF of LPs and of MIPs with safe variables and constraints. Finally, we show that the new methodologies can be successfully applied to the instances in the MIPLIB 2017 for computing the RRF.

Summary of Contribution: Robust optimization is an important field of operations research due to its capability of protecting optimization problems from data uncertainties that are usually defined via so-called uncertainty sets. Intensive research has been conducted in developing algorithmically tractable reformulations of the usually semi-infinite robust optimization problems. However, in applications it also important to construct appropriate uncertainty sets (i.e., prohibiting too conservative, intractable, or even infeasible robust optimization problems due to the choice of the uncertainty set). In doing so, it is useful to know the maximal “size” of a given uncertainty set such that a robust feasible solution still exists. In this paper, we study one notion of “size”: the radius of robust feasibility (RRF). We contribute on the theoretical side by generalizing the RRF to MIPs as well as to include “safe” variables and constraints (i.e., where uncertainties do not affect certain variables or constraints). This allows to apply the RRF to many applications since safe variables and constraints exist in most applications. We also provide first methods for computing the RRF of LPs as well as of MIPs with safe variables and constraints. Finally, we show that the new methodologies can be successfully applied to the instances in the MIPLIB 2017 for computing the RRF.
Exact and Approximation Algorithms for the Expanding Search Problem
Authors: Hermans Ben , Leus Roel , Matuschke Jannik
Published: March 2021

Suppose a target is hidden in one of the vertices of an edge-weighted graph according to a known probability distribution. Starting from a fixed root node, an expanding search visits the vertices sequentially until it finds the target, where the next vertex can be reached from any of the previously visited vertices. That is, the time to reach the next vertex equals the shortest-path distance from the set of all previously visited vertices. The expanding search problem then asks for a sequence of the nodes, so as to minimize the expected time to finding the target. This problem has numerous applications, such as searching for hidden explosives, mining coal, and disaster relief. In this paper, we develop exact algorithms and heuristics, including a branch-and-cut procedure, a greedy algorithm with a constant-factor approximation guarantee, and a local search procedure based on a spanning-tree neighborhood. Computational experiments show that our branch-and-cut procedure outperforms existing methods for instances with nonuniform probability distributions and that both our heuristics compute near-optimal solutions with little computational effort.

Summary of Contribution: This paper studies new algorithms for the expanding search problem, which asks to search a graph for a target hidden in one of the nodes according to a known probability distribution. This problem has applications such as searching for hidden explosives, mining coal, and disaster relief. We propose several new algorithms, including a branch-and-cut procedure, a greedy algorithm, and a local search procedure; and we analyze their performance both experimentally and theoretically. Our analysis shows that the algorithms improve on the performance of existing methods and establishes the first constant-factor approximation guarantee for this problem.
Optimal Monopoly Mechanisms with Demand Uncertainty
Authors: Peck James , Rampal Jeevant
Published: March 2021

This paper analyzes a monopoly firm’s profit-maximizing mechanism in the following context. There is a continuum of consumers with a unit demand for a good. The distribution of the consumers’ valuations is given by one of two possible demand distributions/states. The consumers are uncertain about the demand state, and they update their beliefs after observing their own valuation for the good. The firm is uncertain about the demand state but infers it from the consumers’ reported valuations. The firm’s problem is to maximize profits by choosing an optimal mechanism among the class of anonymous, deterministic, direct revelation mechanisms that satisfy interim incentive compatibility and ex post individual rationality. We show that, under certain sufficient conditions, the firm’s optimal mechanism is to set the monopoly price in each demand state. Under these conditions, Segal’s optimal ex post mechanism is robust to relaxing ex post incentive compatibility to interim incentive compatibility.
FT-NIR associado a método quimiométrico para discriminar resíduos de antimicrobianos e antiparasitário no leite
Authors: Luiz Leandro Da Conceição , Bell Maria José Valenzuela , Dos Anjos Virgílio De Carvalho
Published: March 2021

Introdução: O leite é um dos alimentos mais consumidos pelos seres humanos. Proteínas, vitaminas, gordura, carboidratos e sais minerais fazem parte de sua composição e desempenham importantes funções para a nutrição humana. A prática de adulteração no leite é antiga e ainda se faz presente nos dias de hoje em diversos países, inclusive no Brasil. A fim de obter lucro maior, alguns fornecedores costumam adicionar ao leite: água, amido, citrato, ureia, soda cáustica, cloreto de sódio, sacarose, soro do leite, melamina e outros componentes. No entanto, ainda há outro problema, o da contaminação do leite por medicamentos veterinários. Estes podem causar danos à saúde do consumidor e prejuízos para a produção de seus derivados. Objetivo: O presente trabalho propõe uma metodologia que permite detectar de maneira rápida a presença de resíduos de medicamentos veterinários em leites, dentro do limite máximo de resíduos de cada droga. Métodos: Fez-se o uso da espectroscopia no infravermelho próximo por transformada de Fourier associada à análise de componentes principais. A espectroscopia no infravermelho tem sido utilizada não somente para a autenticidade de laticínios, mas para determinar sua qualidade. Resultados: Conseguiu-se detectar resíduos de penicilina, oxitetraciclina e enrofloxacino, e também do antiparasitário ivermectina nas amostras de leites. Conclusão: A metodologia detectou de maneira rápida e precisa os resíduos das drogas analisadas, mesmo em concentrações muito baixas. Assim, é uma opção a outras existentes, já utilizadas para tal objetivo.
Use of a superabsorbent dressing in the management of exudate in hard-to-heal wounds
Authors: Jones June , Hampton Sylvie
Published: March 2021

With the shift in demographics towards an ageing population with multimorbidity, the number of hard-to-heal (chronic) wounds is increasing each year. This poses a challenge for both health professionals, for whom wound management is becoming more complex, and for patients, who have to cope with exudate production, malodour and pain.

This article summarises understanding of healing in such wounds and how best to meet the challenge of exudate, which is a ubiquitous hallmark of hard-to-heal wounds. The role of superabsorbent dressings is considered, with particular reference to Kliniderm superabsorbent in the management of people with these challenging wounds.
Deep dissecting haematoma in patients with dermatoporosis: implications for home nursing
Authors: Vanzi Valentina , Toma Elena
Published: March 2021

Dermatoporosis is a chronic cutaneous insufficiency/fragility syndrome with a high prevalence in older adults. Dermatoporotic skin becomes thin and fragile and tends to tear. It may lead to deep dissecting haematomas (DDHs) as a final stage of dermatoporosis, which is a clinical emergency. Management can be challenging, as patients with lower-limb haematomas are frequently older and affected by multiple comorbidities, or are probably on medications that negatively influence wound healing. This article describes the essential role of nurses in prevention, early recognition and wound management of DDHs in patients with dermatoporosis.
What is an expedition medic?
Authors: Owens Jakki
Published: March 2021

In the third instalment of Paramedic Roles, Jakki Owens reflects on the multidisciplinary nature of expedition medicine, and details areas that can be the most far-ranging from a paramedic's natural environment.