Chronodisruption and Ambulatory Circadian Monitoring in Cancer Patients: Beyond the Body Clock.

PURPOSE OF REVIEW: Circadian rhythms impose daily rhythms a remarkable variety of metabolic and physiological functions, such as cell proliferation, inflammation, and DNA damage response. Accumulating epidemiological and genetic evidence indicates that circadian rhythms' disruption may be linked to cancer. The integration of circadian biology into cancer research may offer new options for increasing cancer treatment effectiveness and would encompass the prevention, diagnosis, and treatment of this disease. RECENT FINDINGS: In recent years, there has been a significant development and use of multi-modal sensors to monitor physical activity, sleep, and circadian rhythms, allowing, for the very first time, scaling accurate sleep monitoring to epidemiological research linking sleep patterns to disease, and wellness applications providing new potential applications. This review highlights the role of circadian clock in tumorigenesis, cancer hallmarks and introduces the state-of-the-art in sleep-monitoring technologies, discussing the eventual application of insights in clinical settings and cancer research.

Membrane lipids and maximum lifespan in clownfish.

The longevity-homeoviscous adaptation (LHA) theory of ageing states that lipid composition of cell membranes is linked to metabolic rate and lifespan, which has been widely shown in mammals and birds but not sufficiently in fish. In this study, two species of the genus Amphiprion (Amphiprion percula and Amphiprion clarkii, with estimated maximum lifespan potentials [MLSP] of 30 and 9-16 years, respectively) and the damselfish Chromis viridis (estimated MLSP of 1-2 years) were chosen to test the LHA theory of ageing in a potential model of exceptional longevity. Brain, livers and samples of skeletal muscle were collected for lipid analyses and integral part in the computation of membrane peroxidation indexes (PIn) from phospholipid (PL) fractions and PL fatty acid composition. When only the two Amphiprion species were compared, results pointed to the existence of a negative correlation between membrane PIn value and maximum lifespan, well in line with the predictions from the LHA theory of ageing. Nevertheless, contradictory data were obtained when the two Amphiprion species were compared to the shorter-lived C. viridis. These results along with those obtained in previous studies on fish denote that the magnitude (and sometimes the direction) of the differences observed in membrane lipid composition and peroxidation index with MLSP cannot explain alone the diversity in longevity found among fishes.

Membrane peroxidation index and maximum lifespan are negatively correlated in fish of the genus Nothobranchius.

The lipid composition of cell membranes is linked to metabolic rate and lifespan in mammals and birds but very little information is available for fish. In this study, three fish species of the short-lived annual genus Nothobranchius with different maximum lifespan potential (MLSP) and the longer-lived outgroup species Aphyosemion australe were studied to test whether they conform to the predictions of the longevity-homeoviscous adaptation (LHA) theory of ageing. Lipid analyses were performed in whole-fish samples and the peroxidation index (PIn) for every phospholipid (PL) class and for the whole membrane was calculated. Total PL content was significantly lower in A. australe and N. korthausae, the two species with the highest MLSP, and a negative correlation between membrane total PIn and fish MLSP was found, meaning that the longer-lived fish species have more saturated membranes and, therefore, a lower susceptibility to oxidative damage, as the LHA theory posits.

Analysis of the coding sequences of clownfish reveals molecular convergence in the evolution of lifespan.

BACKGROUND: Standard evolutionary theories of aging postulate that reduced extrinsic mortality leads to evolution of longevity. Clownfishes of the genus Amphiprion live in a symbiotic relationship with sea anemones that provide protection from predators. We performed a survey and identified at least two species with a lifespan of over 20 years. Given their small size and ease of captive reproduction, clownfish lend themselves as experimental models of exceptional longevity. To identify genetic correlates of exceptional longevity, we sequenced the transcriptomes of Amphiprion percula and A. clarkii and performed a scan for positively-selected genes (PSGs). RESULTS: The PSGs that we identified in the last common clownfish ancestor were compared with PSGs detected in long-lived mole rats and short-lived killifishes revealing convergent evolution in processes such as mitochondrial biogenesis. Among individual genes, the Mitochondrial Transcription Termination Factor 1 (MTERF1), was positively-selected in all three clades, whereas the Glutathione S-Transferase Kappa 1 (GSTK1) was under positive selection in two independent clades. For the latter, homology modelling strongly suggested that positive selection targeted enzymatically important residues. CONCLUSIONS: These results indicate that specific pathways were recruited in independent lineages evolving an exceptionally extended or shortened lifespan and point to mito-nuclear balance as a key factor.

Age-related changes in mitochondrial membrane composition of Nothobranchius furzeri.: comparison with a longer-living Nothobranchius species.

Membrane compositions, particularly of mitochondria, could be critical factors in the mechanisms of growth and aging, especially during phases of high oxidative stress that result in molecular damage. Changes affecting lipid class or fatty acid (FA) compositions could affect phospholipid (PL) properties and alter mitochondrial function. In the present study, mitochondrial membrane PL compositions were analysed throughout the life-cycle of Nothobranchius furzeri, a species with explosive growth and one of the shortest-lived vertebrates. Mitochondrial PLs showed several changes with age. Proportions of total PLs and PC were reduced while an increase in PS, CL and PE was observed, mainly between the 2.5 and 5 months of fish age, the time during which animals doubled their weight. FA compositions of individual PLs in mitochondria were also significantly affected with age suggesting the existence of increasing damage to mitochondrial lipids during the life-cycle of N. furzeri that could be one of the main contributors to degraded mitochondrial function associated with aging. The peroxidation index values from N. furzeri mitochondrial PLs were significantly lower than those reported in N. rachovii, a species with a twofold longer life span than N. furzeri, which seems to contradict the membrane pacemaker theory of animal metabolism.

BpWrapper: BioPerl-based sequence and tree utilities for rapid prototyping of bioinformatics pipelines.

BACKGROUND: Automated bioinformatics workflows are more robust, easier to maintain, and results more reproducible when built with command-line utilities than with custom-coded scripts. Command-line utilities further benefit by relieving bioinformatics developers to learn the use of, or to interact directly with, biological software libraries. There is however a lack of command-line utilities that leverage popular Open Source biological software toolkits such as BioPerl ( http://bioperl.org ) to make many of the well-designed, robust, and routinely used biological classes available for a wider base of end users. RESULTS: Designed as standard utilities for UNIX-family operating systems, BpWrapper makes functionality of some of the most popular BioPerl modules readily accessible on the command line to novice as well as to experienced bioinformatics practitioners. The initial release of BpWrapper includes four utilities with concise command-line user interfaces, bioseq, bioaln, biotree, and biopop, specialized for manipulation of molecular sequences, sequence alignments, phylogenetic trees, and DNA polymorphisms, respectively. Over a hundred methods are currently available as command-line options and new methods are easily incorporated. Performance of BpWrapper utilities lags that of precompiled utilities while equivalent to that of other utilities based on BioPerl. BpWrapper has been tested on BioPerl Release 1.6, Perl versions 5.10.1 to 5.25.10, and operating systems including Apple macOS, Microsoft Windows, and GNU/Linux. Release code is available from the Comprehensive Perl Archive Network (CPAN) at https://metacpan.org/pod/Bio::BPWrapper . Source code is available on GitHub at https://github.com/bioperl/p5-bpwrapper . CONCLUSIONS: BpWrapper improves on existing sequence utilities by following the design principles of Unix text utilities such including a concise user interface, extensive command-line options, and standard input/output for serialized operations. Further, dozens of novel methods for manipulation of sequences, alignments, and phylogenetic trees, unavailable in existing utilities (e.g., EMBOSS, Newick Utilities, and FAST), are provided. Bioinformaticians should find BpWrapper useful for rapid prototyping of workflows on the command-line without creating custom scripts for comparative genomics and other bioinformatics applications.

Changes in mitochondrial membrane composition and oxidative status during rapid growth, maturation and aging in zebrafish, Danio rerio.

Considering membranes and membrane components as possible pacemakers of the main processes taking place inside mitochondria, changes in phospholipids or fatty acids could play a central role linking different mechanisms involved in cumulative damage to cell molecules and dysfunction during periods of high stress, such as rapid growth and aging. Changes affecting either lipid class or fatty acid compositions could affect phospholipid and membrane properties and alter mitochondrial function and cell viability. In the present study, mitochondrial oxidative status and mitochondrial membrane phospholipid compositions were analyzed throughout the life-cycle of zebrafish. TBARS content significantly increased in 18-month-old fish while aconitase activity decreased in 24-month-old fish, which have been related with oxidative damage to molecules. Mitochondria-specific superoxide dismutase decreased in 24-month-old animals although this change was not statistically significant. Age affected both mitochondrial phospholipid content and the peroxidation index of most phospholipid classes suggesting that oxidative damage to mitochondrial lipids was occurring.

BorreliaBase: a phylogeny-centered browser of Borrelia genomes.

BACKGROUND: The bacterial genus Borrelia (phylum Spirochaetes) consists of two groups of pathogens represented respectively by B. burgdorferi, the agent of Lyme borreliosis, and B. hermsii, the agent of tick-borne relapsing fever. The number of publicly available Borrelia genomic sequences is growing rapidly with the discovery and sequencing of Borrelia strains worldwide. There is however a lack of dedicated online databases to facilitate comparative analyses of Borrelia genomes. DESCRIPTION: We have developed BorreliaBase, an online database for comparative browsing of Borrelia genomes. The database is currently populated with sequences from 35 genomes of eight Lyme-borreliosis (LB) group Borrelia species and 7 Relapsing-fever (RF) group Borrelia species. Distinct from genome repositories and aggregator databases, BorreliaBase serves manually curated comparative-genomic data including genome-based phylogeny, genome synteny, and sequence alignments of orthologous genes and intergenic spacers. CONCLUSIONS: With a genome phylogeny at its center, BorreliaBase allows online identification of hypervariable lipoprotein genes, potential regulatory elements, and recombination footprints by providing evolution-based expectations of sequence variability at each genomic locus. The phylo-centric design of BorreliaBase (http://borreliabase.org) is a novel model for interactive browsing and comparative analysis of bacterial genomes online.

Successful treatment of dumping syndrome with diazoxide in an infant with hypoplastic left heart syndrome.

Summary: Dumping syndrome is a rare but potentially serious condition that causes inappropriate postprandial hyperinsulinemia leading to hypoglycemia in children following gastrointestinal surgeries. While dietary modifications are often the first line of treatment, severe cases may require pharmacological intervention to prevent severe hypoglycemia. We present a case of successful treatment of dumping syndrome with diazoxide. A 2-month-old infant with left hypoplastic heart syndrome who underwent single ventricle palliation pathway and developed feeding intolerance that required Nissen fundoplication. Postprandial hypoglycemia was detected following the procedure, with glucose level down to 12 mg/dL, and the diagnosis of dumping syndrome was established. The patient was successfully managed with diazoxide, which effectively resolved postprandial hypoglycemia without any major adverse events. The patient was eventfully weaned off the medication at the age of 5 months. This case highlights the potential role of diazoxide in the management of pediatric patients with postprandial hyperinsulinemic hypoglycemia secondary to dumping syndrome. Learning points: Dumping syndrome is a possible complication of gastrointestinal surgeries and should be suspected in children with abnormal glucose levels. Postprandial hyperglycemia should be monitored closely for significant subsequent hypoglycemia. Diazoxide might be considered as part of the treatment plan for dumping syndrome.

Human gelatin thrombin matrix with rifampin for the treatment of prosthetic vascular graft infections.

We aim to describe and report on a novel graft preservation technique using a human gelatin thrombin matrix with rifampin for the treatment of vascular graft infections. Eight patients with vascular graft infections were included, one with bilateral infections, for a total of nine cases from January 2016 through June 2021. All the patients underwent wound exploration and placement of human gelatin thrombin matrix with rifampin. No deaths or allergic reactions had been reported at the 30-day follow-up, with only one major amputation. The graft and limb salvage rates were 77.8% at the 1-year follow-up. The mean time to a major amputation was 122 days, and the mean time to graft excision was 30 days.

Inter- and intra-specific pan-genomes of Borrelia burgdorferi sensu lato: genome stability and adaptive radiation.

BACKGROUND: Lyme disease is caused by spirochete bacteria from the Borrelia burgdorferi sensu lato (B. burgdorferi s.l.) species complex. To reconstruct the evolution of B. burgdorferi s.l. and identify the genomic basis of its human virulence, we compared the genomes of 23 B. burgdorferi s.l. isolates from Europe and the United States, including B. burgdorferi sensu stricto (B. burgdorferi s.s., 14 isolates), B. afzelii (2), B. garinii (2), B. "bavariensis" (1), B. spielmanii (1), B. valaisiana (1), B. bissettii (1), and B. "finlandensis" (1). RESULTS: Robust B. burgdorferi s.s. and B. burgdorferi s.l. phylogenies were obtained using genome-wide single-nucleotide polymorphisms, despite recombination. Phylogeny-based pan-genome analysis showed that the rate of gene acquisition was higher between species than within species, suggesting adaptive speciation. Strong positive natural selection drives the sequence evolution of lipoproteins, including chromosomally-encoded genes 0102 and 0404, cp26-encoded ospC and b08, and lp54-encoded dbpA, a07, a22, a33, a53, a65. Computer simulations predicted rapid adaptive radiation of genomic groups as population size increases. CONCLUSIONS: Intra- and inter-specific pan-genome sizes of B. burgdorferi s.l. expand linearly with phylogenetic diversity. Yet gene-acquisition rates in B. burgdorferi s.l. are among the lowest in bacterial pathogens, resulting in high genome stability and few lineage-specific genes. Genome adaptation of B. burgdorferi s.l. is driven predominantly by copy-number and sequence variations of lipoprotein genes. New genomic groups are likely to emerge if the current trend of B. burgdorferi s.l. population expansion continues.

Predisposing factors for acute kidney injury in Hispanic patients treated with diuretics for decompensated heart failure.

OBJECTIVE: In patients with congestive heart failure (CHF), use of loop diuretic therapy may result in acute kidney insufficiency (AKI). We assessed the factors that contributed to the development of AKI in patients with CHF treated with loop diuretics in a sample of patients who attended the Cardiovascular Center of Puerto Rico and the Caribbean (CCPRC). METHODS: Medical records of 236 patients admitted between: January 1, 2008 to December 31, 2008 with the diagnosis of CHF were reviewed. Diagnosis of CHF based on symptoms and signs was confirmed by echocardiography. Twenty six (26) patients with significant valvular disease and four (4) patients who did not receive diuretics during hospitalization were excluded. Hospital course was observed until diuretic therapy was discontinued or patient was discharged. AKI was defined as a 25% increase in serum creatinine level after the start of diuretic therapy. The study sample was categorized in two groups: patients who developed AKI and those who did not. Variables associated with AKI (p<0.05) in the bivariate logistic regression models were included in the multivariate logistic regression models. RESULTS: In the multivariate logistic regression model, only a greater dose of diuretic therapy (>80 mg/dl) and history of diabetes mellitus were significantly (p<0.05) associated with AKI. CONCLUSION: Analysis of data shows that increased doses of diuretic therapy and history of diabetes mellitus were significantly associated with AKI in patients with CHF. This study highlights the importance of monitoring the doses of diuretic therapy during hospitalization, in this group of patients.

Contribution of Python-based BERT software for landslide monitoring using Electrical Resistivity Tomography datasets. A case study in Tghat-Fez (Morocco).

The electrical resistivity tomography (ERT) technique was conducted for the geophysical survey of a landslide on the southern slope of Jbel Tghat, north of the city of Fez, Morocco. Nine electrical resistivity tomography profiles were implemented to: (a) characterize the geometry of the dipping zone; (b) characterize their internal structures; and (c) highlight the faulting zone between the marly deposits and the conglomerate formation. The measured data sets were processed using EarthImager™ 2D (Advanced Geosciences, Inc), and BERT (Boundless Electrical Resistivity Tomography) software packages that offer a simple workflow from data import to inversion and visualization, while offering full control over inversion parameters. Moreover, BERT software is a Python-based open-source inversion software package. Both ERT processing software allows obtaining 2D subsurface electrical models associated with the distribution of the subsurface apparent electrical resistivity property, in Ohm.m units. Those 2D subsurface electrical models are retrieved using the same inversion parameters to determine the distribution of geoelectric layers and their defining parameters (e.g., electrical resistivity, thickness, and depth), giving access to certain characteristics exclusive to one of the two processing techniques, comparing the inversion findings to better understand the process's limits, as well as evaluating the capabilities of the two inversion methods.

Nomography: A renewed pedagogical tool to sciences and engineering high-education studies.

Nomography is defined as a branch of mathematics in which methods of graphical representation of functional dependencies are studied. The resulting graphs are called nomograms, alignment charts, or abacs. Along the past century, this science branch experienced extensive development and use in many contexts to support scientists and engineers with accurate and fast calculations of complex formulas to a practical precision. However, nomography declined by the end of the twentieth century with the development and popularisation of more capable and powerful personal computers and handheld calculators. Despite this context, nomography remains attractive due to its potential for rapid and accurate graphical calculations contributing to a better understanding of complex formulas. Thus, this work defines the alignment charts and their capabilities to justify their importance as graphical tools in sciences and engineering studies. Also, PyNomo software is introduced to build vector-based and scalable nomograms. Then, this work emphasizes the importance of including nomography as a valuable and renewed computational tool, in conjunction with PyNomo software, in an academic context. In line with that, several nomograms, which have been obtained with PyNomo software, are examined to grasp the true importance of this science branch and its capabilities in an educational context.

PyNomo software dataset for sciences and engineering nomogram construction.

This article examines different python-based codes to be run under PyNomo nomographer software to represent alignment charts or nomograms for formulas commonly used in sciences and engineering studies. PyNomo nomographer supports nine basic types of nomograms based on the format of the mathematical equation. The examined PyNomo codes cover the construction of the following types of nomogram: type 1, type 2, type 7, type 8, type 9, and type 10. Each PyNomo script includes some background and the underlying mathematics for the nomogram construction and how to implement each code into PyNomo software. Potential users can use these PyNomo codes, as template scripts, to customize and construct their own nomograms for a variety of technical applications. That is especially true since a considerable number of science and engineering equations fall into one of these covered nomogram types depending on the equation form involved.

Electrical resistivity tomography (ERT) and geochemical analysis dataset to delimit subsurface affected areas by livestock pig slurry ponds.

The electrical resistivity tomography (ERT) technique was employed with the support of geochemical analyses to delimit the affected surface area by slurry pig ponds. Data were taken in three selected slurry ponds located in Fuente Álamo municipality, Murcia region (SE Spain), to obtain electrical resistivity value-based 2D sections and 3D blocks. All ERT-based survey data were obtained in September 2020 using a SuperSting R8 resistivity meter from Advanced Geosciences Inc. and using the dipole-dipole array consisting of a total of twenty-eight electrodes. The soil samples were taken from drilling core sampling by boreholes at each slurry pond, and physical-chemical analyses of soil samples were obtained using standard laboratory testing methods. Electrical resistivity values and physical-chemical analysis data obtained from soil samples were contrasted, whose comparison showed a correlation between profiles-based electrical resistivity, laboratory-based electrical conductivity (EC) data, and nitrate (N-NO3-) content from soil samples. The statistical analysis was run by SPSS Statistics v.23 software (IBM, Neconductivity York, NY, USA) to establish the non-parametric Spearman correlation. The dataset establishes a reliable methodology and provides insight and information to delimit the affected subsurface area by pig slurry. Data contained within this publication are presented concurrently with Capa-Camacho et al. 2022 [1].

Endovascular management of malperfusion in acute type B aortic dissections.

PURPOSE: To examine the feasibility, efficacy, and midterm results of endovascular stent-graft management of acute type B aortic dissection complicated by renal, visceral, or lower limb malperfusion. METHODS: A retrospective review was conducted to identify all patients with acute type B dissection treated endovascularly at a single center between 1998 and 2009. Of the 85 patients identified, 23 (27%) consecutive patients (20 men; mean age 60.9 ± 11.6 years) presented with clinical and imaging evidence of end-organ malperfusion: 7 (30%) renal, 6 (26%) lower limb, 4 (17%) renal and lower limb, 3 (13%) visceral, and single cases of renal/visceral, renal/lower limb/spinal cord, and renal/visceral/spinal cord/lower limb. RESULTS: All patients had stent-graft coverage of the proximal entry tear; 5 (22%) patients required additional branch vessel stenting, and 2 (9%) had femorofemoral bypass graft. Successful correction of malperfusion was achieved in 21 (91%) patients. In 1 patient, ischemia in the lower limb was resolved but not in the left kidney; the other patient had an ischemic but viable lower limb and did not require any additional intervention. Thirty-day mortality was 9% (2/23 patients). The incidences of postoperative stroke and paraplegia were 17% (4/23) and 9% (2/23), respectively. The 21 survivors were followed for 17.2 ± 15 months; during this period, 1 patient died, 1 was lost to follow-up, and 5 patients underwent additional open or endovascular procedures. CONCLUSION: Endovascular coverage of the proximal entry tear in acute type B dissections complicated by end-organ malperfusion resulted in correction of malperfusion in the majority of patients. It is a reasonable first line of treatment, but its superiority must be assessed in comparison with other techniques, such as fenestration.

Enhancing Electrical Contact with a Commercial Polymer for Electrical Resistivity Tomography on Archaeological Sites: A Case Study.

This communication reports an improvement of the quality of the electrical data obtained from the application of electrical resistivity tomography method on archaeological studies. The electrical contact between ground and electrode enhances significantly by using carbomer-based gel during the electrical resistivity tomography measurements. Not only does the gel promote the conservation of the building surface under investigation, but it also virtually eliminates the necessity of conventional spike electrodes, which in many archaeological studies are inadequate or not permitted. Results evidenced an enhancement in the quality of the electrical data obtained in the order of thousands of units compared with those without using the carbomer-based gel. The potential and capabilities of this affordable gel make it appropriate to be applied to other geoelectrical studies beyond archaeological investigations. Moreover, it might solve corrosion issues on conventional spike electrodes, and electrical multicore cables usually provoked for added saltwater attempting to improve the electrical contact.

Assessing Chronotypes by Ambulatory Circadian Monitoring.

In order to develop objective indexes for chronotype identification by means of direct measurement of circadian rhythms, 159 undergraduate students were recruited as volunteers and instructed to wear ambulatory circadian monitoring (ACM) sensors that continuously gathered information on the individual's environmental light and temperature exposure, wrist temperature, body position, activity, and the integrated TAP (temperature, activity, and position) variable for 7 consecutive days under regular free-living conditions. Among all the proposed indexes, the night phase marker (NPM) of the TAP variable was the best suited to discriminate among chronotypes, due to its relationship with the Munich ChronoType Questionnaire (ß = 0.531; p < 0.001). The NPM of TAP allowed subjects to be classified as early- (E-type, 20%), neither- (N-type, 60%), and late-types (L-type, 20%), each of which had its own characteristics. In terms of light exposure, while all subjects had short exposure times to bright light (>100 lux), with a daily average of 93.84 ± 5.72 min, the earlier chronotypes were exposed to brighter days and darker nights compared to the later chronotypes. Furthermore, the earlier chronotypes were associated with higher stability and day-night contrast, along with an earlier phase, which could be the cause or consequence of the light exposure habits. Overall, these data support the use of ACM for chronotype identification and for evaluation under free living conditions, using objective markers.

Occurrence of Cranial Neoplasms in Pediatric Patients with Noonan Syndrome Receiving Growth Hormone: Is Screening with Brain MRI prior to Initiation of Growth Hormone Indicated?

Noonan syndrome (NS) is associated with short stature. Growth hormone treatment has been FDA approved for use in these patients. Children with NS are at a higher risk of developing benign and malignant proliferative disorders, primary brain tumors being one of them. Since growth hormone therapy can worsen the tumor burden, screening with a brain MRI prior to growth hormone initiation in NS patients is strongly recommended. Here we present two NS patients who developed different primary brain tumors while being on growth hormone therapy.