Secondary Consequence Research Articles

Minimal Increments of Hydrophobic Collapse within the N-Terminus of the Neuropeptide Galanin.

The neuropeptide galanin has a 35-year history as an intriguing target in drug design owing to its implication as a potential anticonvulsant and neuronal trophic factor among many other therapeutically interesting functions including analgesia and mood alteration. In this study, we report the structural characterization of three synthetic fragments of the galanin N-terminus in buffered aqueous solution: hGal(2-12)KK, hGal(1-12)KK, and hGal(1-17)KK. High-field two-dimensional 1H-1H nuclear magnetic resonance (NMR) data were acquired for these fragments and used to derive distance restraints. We further utilized modified hydrogen bonding and dihedral restraints to reflect chemical shift patterns in the data, which revealed the signature of a weakly folded helix. Together, these sets of restraints were used to generate NMR structures of all three fragments, which depict a core of hydrophobic residues that cluster together regardless of the presence of a helical structure, and correspond to residues in the N-terminus of galanin that have been previously shown to be critical for binding its receptors. The helical structure only appears following the inclusion of Gly(1) in the sequence, and at longer sequence lengths, unlike many other peptides, the helix does not propagate. Rather, a few turns of poorly ordered helix appear to be a secondary consequence of clusters of hydrophobic sidechains that are conserved across all of the peptides in this study; the helices themselves appear ordered as a consequence of this clustering, and these clusters compare directly to those observed recently to make contacts between galanin and two of its receptor subtypes. Collapsed hydrophobic residues therefore organize and compose the functional core of human galanin and raise interesting questions about the nature of the conformational order in ligands that bind cell surface receptors.

Physical, Psychological and Social Secondary Consequences of the COVID-19 Pandemic in Turkish University Students.

This study aims to investigate the effect of the COVID‐19 pandemic on university students and their families. A total of 274 students participated in this study. A questionnaire is developed regarding the physical, psychological, and social effects of the COVID‐19 pandemic, and sent to the students via e‐mail. According to the results of the study, students who contracted COVID‐19 experienced significantly higher musculoskeletal pain (MSP) (p = 0.01). Students with increased propensity for harmful habits experienced significantly more MSP (p = 0.01). Anxiety levels of students who experienced MSP were significantly higher (p = 0.01). Students living in an inadequate home environment were significantly more prone to harmful habits (p = 0.01). The anxiety level of the students who experienced domestic unrest was high (p = 0.02). The home environment of students with economic difficulties was significantly inadequate (p = 0.01). The anxiety levels of the students whose participation in sports and art activities decreased, were high (p = 0.04). The home environment of the students who reported that they were positively affected by distance education was significantly inadequate (p = 0.03). The authors suggest that physiotherapy, nutrition and psychological assistance services should be provided to students, scholarship opportunities and extracurricular activities (art and sports activities) should be increased.

Adapting a codesign process with young people to prioritize outcomes for a systematic review of interventions to prevent self-harm and suicide.

BackgroundResearch and clinical outcomes that matter to people with lived experience can significantly differ from those outcomes studied by researchers. To inform a future Cochrane review of suicide and self‐harm prevention interventions, we aimed to work with young people with relevant lived experience to agree on priority outcomes.DesignFour participatory codesign workshops were completed across two sites (New Zealand, United Kingdom) with 28 young people in total. We iteratively adapted the methods over the course of the study.Results‘Improved coping’ and ‘safer/more accepting environment to disclose’ were the final top‐rated outcomes. ‘Reduction of self‐harm’ was considered a low priority as it could be misleading, stigmatizing and was considered a secondary consequence of other improvements. In contrast to typical research outcomes, young people emphasized the diversity of experience, the dynamic nature of improvement and holistic and asset‐based framing. Methodologically, dialogue using design materials (personas) to thematically explore outcomes was effective in overcoming the initial challenge of disparate quantitative ratings.DiscussionThe results will directly inform the development of a Cochrane review, enabling identification of whether and how outcomes of most importance to young people are measured in trials. Rather than producing discrete measurable outcomes that could be easily added to the systematic review, the young people challenged the academic conceptualization of outcomes, with implications for future evidence synthesis and intervention research, and for future codesign.Patient or Public ContributionYoung people with lived experience were codesigners of the outcomes, and their feedback informed iterative changes to the study methods.

MO066: The Role of Platelet-Derived Growth Factor in Focal Segmental Glomerulosclerosis

Abstract BACKGROUND AND AIMS Focal segmental glomerulosclerosis (FSGS) describes a primary disease of podocytes (podocytopathy) and a secondary consequence of severe or progressive glomerular damage. No specific treatment options exist for FSGS, with many patients progressing to end-stage kidney disease. While podocyte injury is considered to initiate FSGS, parietal epithelial cells (PECs) were shown to be one of the main effector cells forming FSGS. Given the involvement of platelet-derived growth factor (PDGF) in fibrotic processes, we hypothesized that PDGF signaling is involved in the formation and progression of FSGS. METHOD We analyzed the role of PDGF in FSGS development and progression using a murine Thy1.1 trangenic FSGS model, patient kidney biopsies and primary murine PECs. In a second step, we therapeutically treated mice with FSGS with a neutralizing anti-PDGF-B antibody. RESULTS The podocyte-specific Thy1.1 transgenic mice 3 weeks after anti-Thy1.1 antibody injection showed reduced kidney function due to FSGS development. In this model, compared with control mice, PECs were progressively activated (63.3-fold increase in CD44 expression), showed a significantly increased proliferation (14-fold increase in Ki67 expression), followed by glomerular extracellular matrix deposition (2.6-fold increase in collagen 4) and FSGS development. Fluorescence in situ hybridization showed that mRNA of Pdgfb and Pdgfd was elevated in podocytes and Pdgfrb was upregulated in PECs during the time course of the disease. Similarly, in human FSGS biopsies, gene expression of both ligands, PDGFB and PDGFD, was elevated in podocytes and PDGFRB was increased in PECs compared with healthy glomeruli. Stimulation of primary mouse PECs with PDGF-B and PDGF-D in vitro led to significant activation (1.37- and 1.44-fold increase in CD44 expression, respectively), proliferation (1.46- and 1.36-fold increase, respectively), migration and extracellular matrix production (1.40-fold increase in fibronectin after PDGF-D stimulation) which could be inhibited by imatinib or a neutralizing PDGF-B antibody. In mice with FSGS, both a short- and long-term treatment with PDGF-B neutralizing antibody improved kidney function and reduced FSGS, PEC proliferation and profibrotic activation. CONCLUSION PDGFR-β and its ligands PDGF-B and PDGF-D were upregulated in experimental and clinical samples with FSGS in PECs and podocytes, respectively, and the inhibition of PDGF-B reduced PEC proliferation and FSGS development. This suggests paracrine cross-talk between injured podocytes and PECs, leading to PECs activation toward a profibrotic (pro-FSGS) phenotype and FSGS development. Thus, PDGF represents a novel molecular pathway in FSGS pathogenesis and potential target for therapy.

Accessory Muscle Support of Breathing in Young Dystrophin‐deficient mdx Mice

Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder that occurs due to the absence of the structural protein dystrophin and secondary consequences. DMD is characterized by severe and progressive skeletal muscle weakness, which extends to the respiratory muscles. In young dystrophin‐deficient mdx mice, peak inspiratory pressure‐generating capacity is preserved despite diaphragm muscle weakness and reduced electromyogram (EMG) activitya. Our overarching hypothesis is that accessory muscle compensation limits ventilatory deficit in early dystrophic disease. Four‐month‐old male wild‐type (n=39) and mdx (n=41) mice were studied. Breathing was assessed in conscious mice using whole body plethysmography during normoxia and chemochallenge (10% O2/6% CO2). Thoracic oesophageal pressure and obligatory (diaphragm and external intercostal) respiratory muscle EMG activities were recorded in urethane (1.7g/kg i.p.) anaesthetised spontaneously breathing mice during baseline and sustained tracheal occlusion (maximal muscle activation). Diaphragm and scalene (accessory respiratory muscle) force output were examined ex vivo. Data were statistically compared using unpaired Student’s t test or two‐way ANOVA with Bonferroni post hoc test. Peak diaphragm force ex vivo (P < 0.0001) and baseline diaphragm EMG activity (P = 0.01) were significantly lower in mdx compared with wild‐type. Minute ventilation was equivalent in age‐matched wild‐type and mdx mice during baseline and chemochallenge (P = 0.1). Peak diaphragm (P < 0.0001) and external intercostal (P = 0.01) EMG activities during obstruction were significantly lower in mdx mice compared to wild‐type, while peak inspiratory pressure was equivalent (P = 0.4). Interestingly, peak scalene muscle force ex vivo was preserved in 4‐month‐old mdx mice (P = 0.8). Despite a decline in diaphragm muscle performance (decreased EMG activity and mechanical weakness) at baseline, ventilatory capacity is preserved in mdx mice. Furthermore, despite lower peak electrical activation of the obligatory muscles of breathing and diaphragm muscle functional deficit, peak inspiratory pressure is preserved in 4‐month‐old mdx mice, confirming our previous findings in 2‐month‐old micea. Our finding of preserved scalene muscle force suggests that compensation may be provided by accessory muscles to support ventilatory and non‐ventilatory behaviours in early dystrophic disease. Current studies are examining the EMG activity of accessory respiratory muscles (e.g. scalene, sternomastoid, cleidomastoid and trapezius) in early and advanced dystrophic disease in mdx mice.References a Burns DP, Murphy KH, Lucking EF, O'Halloran KD. Inspiratory pressure‐generating capacity is preserved during ventilatory and non‐ventilatory behaviours in young dystrophic mdx mice despite profound diaphragm muscle weakness. J. Physiol. 2019;597(3):831‐848.

Pengaruh Geotekstil Terhadap Stabilitas Timbunan Jalan

Infrastructure development, especially roads are closely related to geotechnical activities. The difference of contours at construction site forces embankment and excavation work. Embankment is an interesting thing to study more deeply because embankments have characteristics such as slopes that have safety factor and must be handled specifically. Geotextiles as an alternative to handling embankment stability are populary used for embankment construction. Many types of geotextile need to calculate and analyze in determining the type of geotextile that are suitable to the characteristics of the subgrade and embankment construction. Embankment stability analysis in this study was calculated using PLAXIS version 8.2 software and Mohr-Coulomb method as basic for calculation. Base on the result of this studie, use of geotextiles, whether woven, non-woven or geogrid, can increase the safety factor and accelerate consolidation time. There will be secondary consolidation consequence of the plastic adjustment of soil grains and geotextiles. The ideal of stress percentage for geotextile to be suitable for use is 56.957% - 37.194%.

Spectral Distribution Dynamics across Different Attentional Priority States.

Anticipatory covert spatial attention improves performance on tests of visual detection and discrimination, and shifts are accompanied by decreases and increases of α band power at electroencephalography (EEG) electrodes corresponding to the attended and unattended location, respectively. Although the increase at the unattended location is often interpreted as an active mechanism (e.g., inhibiting processing at the unattended location), most experiments cannot rule out the alternative possibility that it is a secondary consequence of selection elsewhere. To adjudicate between these accounts, we designed a Posner-style visual cueing task in which male and female human participants made orientation judgments of targets appearing at one of four locations: up, down, right, or left. Critically, trials were blocked such that within a block the locations along one meridian alternated in status between attended and unattended, and targets never appeared at the other two, making them irrelevant. Analyses of the concurrently measured EEG signal were conducted on "traditional" narrowband α (8-14 Hz), as well as on two components resulting from the decomposition of this signal: "periodic" α; and the slope of the aperiodic 1/f-like component. Although data from right-left blocks replicated the familiar pattern of lateralized asymmetry in narrowband α power, with neither α signal could we find evidence for any difference in the time course at unattended versus irrelevant locations, an outcome consistent with the secondary-consequence interpretation of attention-related dynamics in the α band. Additionally, 1/f slope was shallower at attended and unattended locations, relative to irrelevant, suggesting a tonic adjustment of physiological state.SIGNIFICANCE STATEMENT Visual spatial attention, the prioritization of one location in the visual field, is critical for guiding behavior in cluttered environments. Although influential theories posit an important role for α band oscillations in the inhibition of processing at unattended locations, we used a novel procedure to find evidence for an alternative interpretation: selection of one location may simply result in a return to physiological baseline at all others. In addition to determining one way that attention does not work (important for future progress in this field), we also discovered novel evidence for one way that it does work: by modifying the tonic physiological state (indexed by an aperiodic component of the electroencephalography (EEG)] at locations where spatial selection is likely to occur.

Maintenance of physical activity after cardiac rehabilitation (FAIR): study protocol for a feasibility trial

IntroductionTo enhance health and prevent secondary consequences for patients with cardiovascular disease (CVD), maintenance of an active lifestyle following participation in cardiac rehabilitation (CR) is important. However, levels of physical...

MANIFESTATIONS OF SARS-COV-2-INDUCED COVID-19 ON THE SKIN AND ORAL MUCOSA

Over the past centuries, it is difficult to find diseases similar in resonance to the coronа-virus infection COVID-19 caused by SARS-CoV-2. From the day of manifestation of the infection, it has become the dominant nosology, and its etiological agent has dramatically changed, in its favor, the species spectrum of anthropogenic pathological microorganisms. The review is devoted to the skin manifestations of new coronovirus infection (SARS-CoV-2), information about which is constantly updated. However, this information has not been systematized yet. The purpose of this review is to analyze the dermatological manifestations of a new coronavirus infection. On average, 12.5—20.4% of patients with confirmed COVID-19 have developed skin manifestations. The question of whether the skin symptoms are a secondary consequence of a respiratory infection or a primary infection of the skin itself remains open at the moment. The possible mechanisms of development of skin lesions and the role of diseases of complement system and blood hypercoagulation in the pathogenesis of the disease are discussed in the article. The review also provides descriptive and clinical examples of skin manifestations in COVID-19. Since COVID-19 tends to be asymptomatic within 14 days, skin manifestations can be an indicator of infection, which leads to the timely diagnosis. In addition, doctors' awareness about skin symptoms associated with COVID-19 infection plays a big role in preventing misdiagnosis of the disease. Keywords: COVID-19, SARS-CoV-2, Skin, Oral Mucosa.

Skeletal muscle abnormalities in heart failure with preserved ejection fraction.

Almost half of all heart failure (HF) disease burden is due to HF with preserved ejection fraction (HFpEF). The primary symptom in patients with HFpEF, even when well compensated, is severe exercise intolerance and is associated with their reduced quality of life. Recently, studies showed that HFpEF patients have multiple skeletal muscle (SM) abnormalities, and these are associated with decreased exercise intolerance. The SM abnormalities are likely intrinsic to the HFpEF syndrome, not a secondary consequence of an epiphenomenon. These abnormalities are decreased muscle mass, reduced type I (oxidative) muscle fibers, and reduced type I-to-type II fiber ratio as well as a reduced capillary-to-fiber ratio, abnormal fat infiltration into the thigh SM, increased levels of atrophy genes and proteins, reduction in mitochondrial content, and rapid depletion of high-energy phosphate during exercise with markedly delayed repletion of high-energy phosphate during recovery in mitochondria. In addition, patients with HFpEF have impaired nitric oxide bioavailability, particularly in the microvasculature. These SM abnormalities may be responsible for impaired diffusive oxygen transport and/or impaired SM oxygen extraction. To date, exercise training (ET) and caloric restriction are some of the interventions shown to improve outcomes in HFpEF patients. Improvements in exercise tolerance following aerobic ET are largely mediated through peripheral SM adaptations with minimal change in central hemodynamics and highlight the importance of targeting SM to improve exercise intolerance in HFpEF. Focusing on the abnormalities mentioned above may improve the clinical condition of patients with HFpEF.

COVID-19: infection and neurological complications

The issues of neurological complications after coronavirus disease 2019 (COVID-19) are highlighted, since coronaviruses affect not only the respiratory system but also other organs and systems of the body, notably they can cause neurological disorders and diseases. There is little evidence for a direct mechanism of SARS-CoV-2 virus neuroinvasiveness and neurotoxicity. Various mechanisms of coronavirus invasion into the brain are discussed - anterograde and retrograde, neuronal spread, transcriptional and hematogenous pathways. Retrograde / anterograde transport and transsynaptic transmission of the virus have been confirmed by in vitro studies, notably SARS-CoV-2 can enter the central nervous system through olfactory nerve receptor cells. Once in the olfactory bulb, the coronavirus can spread to the cortex and other brain structures, in particular the hippocampus and spinal cord. Invasion of the virus into the central nervous system is also possible by spreading along peripheral nerves, such as along the vagus nerve, which innervates the lungs and intestines. The virus invasion into the central nervous system through the blood-brain barrier is considered to be one of the most frequent routes. There are several possible mechanisms for the spread of SARS-CoV-2 across the blood-brain barrier (circulation of viral particles in the bloodstream, viral transcytosis through vascular and capillary endothelial cells, infection of leukocytes with viruses and their transmission of viruses across the blood-brain barrier ("Trojan horse")). However, there is no robust evidence of CNS infection with SARS-CoV-2. Hypoxia induced by the cytokine storm and respiratory distress lead to the impairment of brain metabolism and neurological complications development. There is an ongoing debate as to whether neurological disorders are primary neurological symptoms or secondary consequences of acute respiratory distress syndrome and inflammation. Among the large number of disorders of the nervous system, there are five main types with long-term neurological complications associated with COVID-19: 1) encephalopathy with delirium / psychosis, 2) inflammatory syndromes of the central nervous system, including encephalitis, myelitis, acute disseminated encephalomyelitis, 3) ischemic strokes (half of them with pulmonary embolism), 4) peripheral neuropathies, Guillain-Barré syndrome and brachial plexopathies, 5) other disorders of the central nervous system. Incompleteness or inconsistency of statistical data on neurological complications after infection was noted. Further study is required of all early and long-term manifestations of neurological disorders and diseases in mild and asymptomatic manifestations of infection, acute and long COVID-19 and after vaccination.

Computational analysis of Lisfranc surgical repairs.

Ligamentous Lisfranc injuries cause debilitating pain and loss of function. Even small diastasis of this normally rigid joint after injury requires surgical treatment, but outcomes remain poor. Existing literature has compared the different surgical procedures using cadaveric models, but no approach has been recommended over others. This study uses a computational biomechanical approach consistent with a cadaveric study to evaluate the different procedures' ability to stabilize the Lisfranc joint without inducing secondary consequences. A validated rigid body model for the cadaver foot with a Lisfranc injury was extended to compare the stability of four different surgical repairs-three open reduction and internal fixation procedures with different hardware (cannulated screws, endobuttons, and screws with a dorsal plate) and primary arthrodesis with screws. Forces calculated from the rigid body model for 50% partial weight bearing provided boundary conditions for a finite element model of the surgical repairs. Comparing the different surgical procedures, the open reduction and internal fixation with screws and primary arthrodesis with screws showed the most stable postoperative Lisfranc joint. However, the use of cannulated screws for fixation showed regions of high stress that may be susceptible to breakage and also resulted in higher contact forces in joints adjacent to the surgery site. Endobuttons and dorsal plates did not restore sufficient stability. Since all procedures showed different points of concern that could impact outcomes, additional surgical approaches could be needed in the future. This study offers a standard protocol for benchmarking the new procedures against those currently used.

Subacute cytokine changes after a traumatic brain injury predict chronic brain microstructural alterations on advanced diffusion imaging in the male rat

IntroductionThe process of neuroinflammation occurring after traumatic brain injury (TBI) has received significant attention as a potential prognostic indicator and interventional target to improve patients’ outcomes. Indeed, many of the secondary consequences of TBI have been attributed to neuroinflammation and peripheral inflammatory changes. However, inflammatory biomarkers in blood have not yet emerged as a clinical tool for diagnosis of TBI and predicting outcome. The controlled cortical impact model of TBI in the rodent gives reliable readouts of the dynamics of post-TBI neuroinflammation. We now extend this model to include a panel of plasma cytokine biomarkers measured at different time points post-injury, to test the hypothesis that these markers can predict brain microstructural outcome as quantified by advanced diffusion-weighted magnetic resonance imaging (MRI). MethodsFourteen 8–10-week-old male rats were randomly assigned to sham surgery (n = 6) and TBI (n = 8) treatment with a single moderate-severe controlled cortical impact. We collected blood samples for cytokine analysis at days 1, 3, 7, and 60 post-surgery, and carried out standard structural and advanced diffusion-weighted MRI at day 60. We then utilized principal component regression to build an equation predicting different aspects of microstructural changes from the plasma inflammatory marker concentrations measured at different time points. ResultsThe TBI group had elevated plasma levels of IL-1β and several neuroprotective cytokines and chemokines (IL-7, CCL3, and GM-CSF) compared to the sham group from days 3 to 60 post-injury. The plasma marker panels obtained at day 7 were significantly associated with the outcome at day 60 of the trans-hemispheric cortical map transfer process that is a frequent finding in unilateral TBI models. DiscussionThese results confirm and extend prior studies showing that day 7 post-injury is a critical temporal window for the reorganisation process following TBI. High plasma level of IL-1β and low plasma levels of the neuroprotective IL-7, CCL3, and GM-CSF of TBI animals at day 60 were associated with greater TBI pathology.

Ccd-5, a novel cdk-5 binding partner, regulates pioneer axon guidance in the ventral nerve cord of Caenorhabditis elegans.

During nervous system development, axons navigate complex environments to reach synaptic targets. Early extending axons must interact with guidance cues in the surrounding tissue, while later extending axons can interact directly with earlier "pioneering" axons, "following" their path. In Caenorhabditis elegans, the AVG neuron pioneers the right axon tract of the ventral nerve cord. We previously found that aex-3, a rab-3 guanine nucleotide exchange factor, is essential for AVG axon navigation in a nid-1 mutant background and that aex-3 might be involved in trafficking of UNC-5, a receptor for the guidance cue UNC-6/netrin. Here, we describe a new gene in this pathway: ccd-5, a putative cdk-5 binding partner. ccd-5 mutants exhibit increased navigation defects of AVG pioneer as well as interneuron and motor neuron follower axons in a nid-1 mutant background. We show that ccd-5 acts in a pathway with cdk-5, aex-3, and unc-5. Navigation defects of follower interneuron and motoneuron axons correlate with AVG pioneer axon defects. This suggests that ccd-5 mostly affects pioneer axon navigation and that follower axon defects are largely a secondary consequence of pioneer navigation defects. To determine the consequences for nervous system function, we assessed various behavioral and movement parameters. ccd-5 single mutants have no significant movement defects, and nid-1 ccd-5 double mutants are less responsive to mechanosensory stimuli compared with nid-1 single mutants. These surprisingly minor defects indicate either a high tolerance for axon guidance defects within the motor circuit and/or an ability to maintain synaptic connections among commonly misguided axons.

Promising results from a residential rehabilitation intervention focused on fatigue and the secondary psychological and physical consequences of cardiac arrest: The SCARF feasibility study

AimsThis study investigated the feasibility and potential effect of SCARF (Survivors of Cardiac ARest focused on Fatigue) a multidisciplinary residential rehabilitation intervention focused on fatigue and the secondary psychological and physical consequences of cardiac arrest (CA). MethodsThis was a prospective one-armed feasibility study. Six progression criteria were identified related to the feasibility of the intervention and viability of a future effect study in terms of: participant recruitment (1), participant retention (2,3,4), and completeness of outcomes (5,6). Data on participant/clinician satisfaction with the intervention was also collected along with self-reported outcomes: fatigue, quality of life, anxiety, depression, function and disability, and physical activity (at baseline, 12 weeks and 6 months) and physical capacity (baseline and 12 weeks). ResultsFour progression criteria were met including retention (87.5%) and completion of baseline outcomes (97.5%). Two criteria were not met: recruitment rate was 2.9 participants per month (estimated rate needed 6.1) and completion of final outcomes was 65% (estimated proportion needed 75%). Participant/clinician satisfaction with the intervention was high. Three months after the SCARF intervention small to moderate effect size changes of r = 0.18–0.46 were found for self-reported fatigue, quality of life, anxiety, depression, function and disability and for two of the physical capacity tests (d = 0.46–0.52). ConclusionSCARF was found to be a feasible intervention with high participant/clinician satisfaction, high participant retention and the possible potential to improve self-reported and physical capacity outcomes. Procedures for study recruitment and collection of final outcomes should be modified before a fully powered randomised controlled trial is conducted.

Changes in coral forest microbiomes predict the impact of marine heatwaves on habitat-forming species down to mesophotic depths

Global warming is causing the increase in intensity and frequency of heatwaves, which are often associated with mass mortality events of marine organisms from shallow and mesophotic rocky habitats, including gorgonians and other sessile organisms. We investigated the microbiome responses of the gorgonians Paramuricea clavata, Eunicella cavolini, and the red coral Corallium rubrum to the episodic temperature anomalies detected in the North Western Mediterranean, during August 2011. Although the investigated corals showed no signs of visible necrosis, the abundance of associated Bacteria and Archaea increased with increasing seawater temperature, suggesting their temperature-dependent proliferation. Coral microbiomes were highly sensitive to thermal anomaly amplitude and exhibited increased bacterial diversity to greater thermal shifts. This effect was explained by the decline of dominant bacterial members and the increase of new, rare and opportunistic taxa, including pathogens, revealing a direct effect of heatwave-induced alteration of the microbiomes and not a secondary consequence of coral necrosis.

Protein Aggregation and Self Assembly in Health and Disease

: Self-attachment of proteins leading to the formation of highly insoluble protein oligomers and aggregates has become an important focus of research owing to its diverse implications in pathophysiology and diseases. This has become a more frequent phenomenon in most neurological and neurodegenerative diseases as well as in dementia. In recent years such event of protein aggregation has linked to other disease conditions, disorders or adverse health conditions. Interestingly, aggregation of protein also plays role in development, growth or metabolism. Most often physiological proteins are initially bio-synthesised in native or nascent geometrical forms or conformations but later they undergo specific folding pattern and thereby acquire a stable configuration that is biologically relevant and active. It is highly important that these proteins remain in their biologically active configuration in order to exert their functional properties. Any alteration or change to this structural configuration can be detrimental to their specific functions and may cause pathological consequences leading to the onset of diseases or disorders. Several factors such as the action of chaperones, binding partners, physiological metal ions, pH level, temperature, ionic strength, interfacial exposure (solid-liquid, liquid-liquid, gas-liquid), mutation and post translational modification, chemical changes, interaction with small molecules such as lipids, hormones, etc. and solvent environment have been either identified or proposed as important factors in conferring the ultimate status of protein structure and configuration. Among many misfolding protein conformations, self-assembly or aggregation is the most significant. It leads to the formation of highly oligomeric self-aggregates that precipitate and interfere with many biochemical processes with serious pathological consequences. The most common implication of protein aggregation leading to the formation of deposits / plaques of various morphological types is the onset of neurological and neurodegenerative diseases that include Alzheimer’s, Parkinson’s, Huntington, ALS (Amyotrophic Lateral Sclerosis), CJD (Creutzfeldt Jakob Dementia), Prion diseases, Amyloidosis and other forms of dementia. However increasingly studies revealed that protein aggregation may also be associated with other diseases such as cancer, type 2 diabetes, renal, corneal and cardiovascular diseases. Protein aggregation diseases are now considered as part of “Proteinopathy” which refers to conditions where proteins become structurally abnormal or fail to fold into stable normal configurations. In this review, we reflect on various aspects of protein self-aggregation, potential underlying causes, mechanism, role of secondary structures, pathological consequences and possible intervention strategies as reported in published literatures.

Secondary Qualitative Analysis of Moral Injury in Obstetric and Neonatal Nurses

ObjectiveTo investigate the presence of symptoms of moral injury in obstetric and neonatal nurses. DesignA secondary qualitative analysis using an analytic expansion of three primary studies. SettingPostal mail and electronic surveys. ParticipantsI used three primary studies: participants in the first consisted of 78 labor and delivery nurses, participants in the second consisted of 75 nurse-midwives, and participants in the third consisted of 22 NICU nurses. MethodsI used Krippendorff’s content analysis method for qualitative data to reanalyze the three primary data sets. The categories I used in this analysis were the 10 symptoms of moral injury that are assessed by the Moral Injury Symptoms Scale–Health Professionals Version. ResultsWhen combining the three types of obstetric and neonatal participants, the top three most frequently cited symptoms of moral injury were moral concern, guilt, and self-condemnation. For participants in labor and delivery units and NICUs, moral concern was the most often described symptom, whereas for participants in midwifery it was guilt. None of the participants reported loss of meaning in their lives, loss of faith, or religious struggle. Participants who worked in NICUs did not describe any symptoms of shame or difficulty forgiving. ConclusionIn addition to the primary symptoms of moral injury, reported secondary consequences of moral injury can include depression, anxiety, anger, self-harm, and social problems. Interventions such as acceptance and commitment therapy are needed to help nurses address the potential for moral injury and repair its effects. Since the COVID-19 pandemic, now more than ever, moral injury needs to be recognized in obstetric and neonatal nurses and not just in the military population.

Maternal Obesity Programming of Perivascular Adipose Tissue and Associated Immune Cells: An Understudied Area With Few Answers and Many Questions.

At present, the worldwide prevalence of obesity has become alarmingly high with estimates foreshadowing a continued escalation in the future. Furthermore, there is growing evidence attributing an individual’s predisposition for developing obesity to maternal health during gestation. Currently, 60% of pregnancies in the US are to either overweight or obese mothers which in turn contributes to the persistent rise in obesity rates. While obesity itself is problematic, it conveys an increased risk for several diseases such as diabetes, inflammatory disorders, cancer and cardiovascular disease (CVD). Additionally, as we are learning more about the mechanisms underlying CVD, much attention has been brought to the role of perivascular adipose tissue (PVAT) in maintaining cardiovascular health. PVAT regulates vascular tone and for a significant number of individuals, obesity elicits PVAT disruption and dysregulation of vascular function. Obesity elicits changes in adipocyte and leukocyte populations within PVAT leading to an inflammatory state which promotes vasoconstriction thereby aiding the onset/progression of CVD. Our current understanding of obesity, PVAT and CVD has only been examined at the individual level without consideration for a maternal programming effect. It is unknown if maternal obesity affects the propensity for PVAT remodeling in the offspring, thereby enhancing the obesity/CVD link, and what role PVAT leukocytes play in this process. This perspective will focus on the maternal contribution of the interplay between obesity, PVAT disruption and CVD and will highlight the leukocyte/PVAT interaction as a novel target to stem the tide of the current obesity epidemic and its secondary health consequences.

Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside.

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality. Consequences vary from mild cognitive impairment to death and, no matter the severity of subsequent sequelae, it represents a high burden for affected patients and for the health care system. Brain trauma can cause neuronal death through mechanical forces that disrupt cell architecture, and other secondary consequences through mechanisms such as inflammation, oxidative stress, programmed cell death, and, most importantly, excitotoxicity. This review aims to provide a comprehensive understanding of the many classical and novel pathways implicated in tissue damage following TBI. We summarize the preclinical evidence of potential therapeutic interventions and describe the available clinical evaluation of novel drug targets such as vitamin B12 and ifenprodil, among others.