A Template Analysis of Intimate Partner Violence Survivors’ Experiences of Animal Maltreatment: Implications for Safety Planning and Intervention

This study explores the intersection of intimate partner violence (IPV) and animal cruelty in an ethnically diverse sample of 103 pet-owning IPV survivors recruited from community-based domestic violence programs. Template analysis revealed five themes: (a) Animal Maltreatment by Partner as a Tactic of Coercive Power and Control, (b) Animal Maltreatment by Partner as Discipline or Punishment of Pet, (c) Animal Maltreatment by Children, (d) Emotional and Psychological Impact of Animal Maltreatment Exposure, and (e) Pets as an Obstacle to Effective Safety Planning. Results demonstrate the potential impact of animal maltreatment exposure on women and child IPV survivors’ health and safety

Pain and agitation treatment in severe dementia patients: The need for Italian Mobilization-Observation-Behavior-Intensity-Dementia (I-MOBID2) pain scale translation, adaptation and validation with psychometric testing

The 97% of dementia patients develops fluctuant neuropsychiatric symptoms often related to under-diagnosed and unrelieved pain. Up to 80% severe demented nursing home residents experiences chronic pain due to age-related comorbidities. Patients lacking self-report skills risk not to be appropriately treated for pain. Mobilization-Observation-Behavior-Intensity-Dementia (MOBID2) is the sole pain scale to consider the frequent co-occurrence of musculoskeletal and visceral pain and to unravel concealed pain through active guided movements. Accordingly, the Italian real-world setting can benefit from its translation and validation. This clinical study provides a translated, adapted and validated version of the MOBID2, the Italian I-MOBID2. The translation, adaptation and validation of the scale for non-verbal, severe demented patients was conducted according to current guidelines in a cohort of 11 patients over 65 with mini-mental state examination ≤ 12. The I-MOBID2 proves: good face and scale content validity index (0.89); reliable internal consistency (Cronbach's α = 0.751); good to excellent inter-rater (Intraclass correlation coefficient, and test-retest (ICC = 0.902) reliability. The construct validity is high (Rho = 0.748 p < 0.05 for 11 patients, Spearman rank order correlation of the overall pain intensity score with the maximum item score of I-MOBID2 Part 1; rho=0.895 p < 0.01 for 11 patients, for the overall pain intensity score with the maximum item score of I-MOBID2 Part 2) and a good rate of inter-rater and test-retest agreement was demonstrated by Cohen's K = 0.744. The average execution time is of 5.8 min, thus making I-MOBID2 a useful tool suitable also for future development in community setting with administration by caregivers

De novo mutation in SLC25A22 gene: expansion of the clinical and electroencephalographic phenotype

The SLC25A22 (Solute Carrier Family 25, Member 22) gene encodes for a mitochondrial glutamate/H+ symporter and is involved in the mitochondrial transport of metabolites across the mitochondrial membrane. We hereby report a 12-year-old girl presenting with early-onset epileptic encephalopathy, hypotonia, and global developmental delay. Whole exome sequencing identified a novel homozygous missense mutation in SLC25A22 gene (c.97A>G; p.Lys33Glu), as the likely cause of the disease. The phenotype of our patient and EEG recordings do not completely overlap with the phenotypes previously described, leading to a new and more complex form of disease associated with SLC25A22 variants, characterized by dyskinetic movements and oculogyric crisis

Value of minimum intensity projections for chest CT in COVID-19 patients

Purpose: To investigate whether minimum intensity projection (MinIP) reconstructions enable more accurate depiction of pulmonary ground-glass opacity (GGO) compared to standard transverse sections and multiplanar reformat (MPR) series in patients with suspected coronavirus disease 2019 (COVID-19). Method: In this multinational study, chest CT scans of 185 patients were retrospectively analyzed. Diagnostic accuracy, diagnostic confidence, image quality regarding the assessment of GGO, as well as subjective time-efficiency of MinIP and standard MPR series were analyzed based on the assessment of six radiologists. In addition, the suitability for COVID-19 evaluation, image quality regarding GGO and subjective time-efficiency in clinical routine was assessed by five clinicians. Results: The reference standard revealed a total of 149 CT scans with pulmonary GGO. MinIP reconstructions yielded significantly higher sensitivity (99.9 % vs 95.6 %), specificity (95.8 % vs 86.1 %) and accuracy (99.1 % vs 93.8 %) for assessing of GGO compared with standard MPR series. MinIP reconstructions achieved significantly higher ratings by radiologists concerning diagnostic confidence (medians, 5.00 vs 4.00), image quality (medians, 4.00 vs 4.00), contrast between GGO and unaffected lung parenchyma (medians, 5.00 vs 4.00) as well as subjective time-efficiency (medians, 5.00 vs 4.00) compared with MPR-series (all P <.001). Clinicians preferred MinIP reconstructions for COVID-19 assessment (medians, 5.00 vs 3.00), image quality regarding GGO (medians, 5.00 vs 3.00) and subjective time-efficiency in clinical routine (medians, 5.00 vs 3.00). Conclusions: MinIP reconstructions improve the assessment of COVID-19 in chest CT compared to standard images and may be suitable for routine application

Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety

Chronic migraine is a disabling neurovascular disorder that ranks amongst the top causes of years lived with disability worldwide. The duration and the frequency of migraine affect cognitive and affective domains, inducing worsening of memory, executive functions, orientation and causing anxiety. Population-based studies report a worrying level of resistance to treatments. Therefore, this study aims: 1) to assess efficacy of monoclonal antibodies (mAbs) directed towards the calcitonin gene-related peptide (CGRP) or its receptor (CGRP-R) for chronic migraine resistant to current preventatives; 2) to design a clinical trial protocol to evaluate the efficacy and safety of combination therapy utilizing anti-CGRP/CGRP-R together with onabotulinumtoxin A in patients suffering from resistant chronic migraine; 3) to provide a molecular rationale for combination therapy. A controlled trial is warranted as pooled analysis of real-world data from our group highlighted that combined treatment provides ≥50% reduction vs. baseline (onabotulinumtoxin A) of monthly headache days (MHDs) in up to 58.8% of patients, but there has been only sparse application of this combined therapy to date. The mAbs chosen are: erenumab, because its combination effect with onabotulinumtoxin A improved symptoms in 65% of patients; eptinezumab, due to its faster action. The results highlight that early diagnosis of migraine improves therapeutic outcomes with mAbs alone, confirming their effectiveness and the need for an adequately powered clinical trial evaluating the safety and potential superior effectiveness of eptinezumab/erenumab and onabotulinumtoxin A together

Essential versus accessory aspects of cell death: recommendations of the NCCD 2015

Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death

Is complexity leadership theory complex enough? A critical appraisal, some modifications and suggestions for further research

Scholars are increasingly seeking to develop theories that explain the underlying processes whereby leadership is enacted. This shifts attention away from the actions of ‘heroic’ individuals and towards the social contexts in which people with greater or lesser power influence each other. A number of researchers have embraced complexity theory, with its emphasis on non-linearity and unpredictability. However, some complexity scholars still depict the theory and practice of leadership in relatively non-complex terms. They continue to assume that leaders can exercise rational, extensive and purposeful influence on other actors to a greater extent than is possible. In effect, they offer a theory of complex organizations led by non-complex leaders who establish themselves by relatively non-complex means. This testifies to the enduring power of ‘heroic’ images of leader agency. Without greater care, the terminology offered by complexity leadership theory could become little more than a new mask for old theories that legitimize imbalanced power relationships in the workplace. This paper explores how these problems are evident in complexity leadership theory, suggests that communication and process perspectives help to overcome them, and outlines an agenda for further research on these issues

Gentamicin Rapidly Inhibits Mitochondrial Metabolism in High-Frequency Cochlear Outer Hair Cells

Aminoglycosides (AG), including gentamicin (GM), are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL) in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs) preferentially succumb to multiple HL pathologies while inner hair cells (IHCs) are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH) fluorescence during acute (1 h) GM treatment were compared. GM-mediated decreases in NADH fluorescence and succinate dehydrogenase activity were observed shortly after GM application. High-frequency basal turn OHCs were found to be metabolically biased to rapidly respond to alterations in their microenvironment including GM and elevated glucose exposures. These metabolic biases may predispose high-frequency OHCs to preferentially produce cell-damaging reactive oxygen species during traumatic challenge. Noise-induced and age-related HL pathologies share key characteristics with AG ototoxicity, including preferential OHC loss and reactive oxygen species production. Data from this report highlight the need to address the role of mitochondrial metabolism in regulating AG ototoxicity and the need to illuminate how fundamental differences in IHC and OHC metabolism may dictate differences in HC fate during multiple HL pathologies

Gadd45α activity is the principal effector of Shigella mitochondria-dependent epithelial cell death in vitro and ex vivo

Modulation of death is a pathogen strategy to establish residence and promote survival in host cells and tissues. Shigella spp. are human pathogens that invade colonic mucosa, where they provoke lesions caused by their ability to manipulate the host cell responses. Shigella spp. induce various types of cell death in different cell populations. However, they are equally able to protect host cells from death. Here, we have investigated on the molecular mechanisms and cell effectors governing the balance between survival and death in epithelial cells infected with Shigella. To explore these aspects, we have exploited both, the HeLa cell invasion assay and a novel ex vivo human colon organ culture model of infection that mimics natural conditions of shigellosis. Our results definitely show that Shigella induces a rapid intrinsic apoptosis of infected cells, via mitochondrial depolarization and the ensuing caspase-9 activation. Moreover, for the first time we identify the eukaryotic stress-response factor growth arrest and DNA damage 45α as a key player in the induction of the apoptotic process elicited by Shigella in epithelial cells, revealing an unexplored role of this molecule in the course of infections sustained by invasive pathogens