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1.
Commun Biol ; 7(1): 687, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38839829

ABSTRACT

Understanding the factors influencing mosquitoes' fecundity and longevity is important for designing better and more sustainable vector control strategies, as these parameters can impact their vectorial capacity. Here, we address how mating affects midgut growth in Aedes aegypti, what role Juvenile Hormone (JH) plays in this process, and how it impacts the mosquito's immune response and microbiota. Our findings reveal that mating and JH induce midgut growth. Additionally, the establishment of a native bacterial population in the midgut due to JH-dependent suppression of the immune response has important reproductive outcomes. Specific downregulation of AMPs with an increase in bacteria abundance in the gut results in increased egg counts and longer lifespans. Overall, these findings provide evidence of a cross-talk between JH response, gut epithelial tissue, cell cycle regulation, and the mechanisms governing the trade-offs between nutrition, immunity, and reproduction at the cellular level in the mosquito gut.


Subject(s)
Aedes , Fertility , Gastrointestinal Microbiome , Juvenile Hormones , Animals , Aedes/microbiology , Aedes/growth & development , Aedes/physiology , Juvenile Hormones/metabolism , Female , Genetic Fitness
2.
Aging Cell ; 23(5): e14110, 2024 May.
Article in English | MEDLINE | ID: mdl-38380477

ABSTRACT

Aging increases reactive oxygen species (ROS) which can impair vascular function and contribute to brain injury. However, aging can also promote resilience to acute oxidative stress. Therefore, we tested the hypothesis that advanced age protects smooth muscle cells (SMCs) and endothelial cells (ECs) of posterior cerebral arteries (PCAs; diameter, ∼80 µm) during exposure to H2O2. PCAs from young (4-6 months) and old (20-26 months) male and female C57BL/6 mice were isolated and pressurized (~70 mm Hg) to evaluate cell death, mitochondrial membrane potential (ΔΨm), ROS production, and [Ca2+]i in response to H2O2 (200 µM, 50 min). SMC death and ΔΨm depolarization were greater in PCAs from males vs. females. Aging increased ROS in PCAs from both sexes but increased SMC resilience to death only in males. Inhibiting TRPV4 channels with HC-067047 (1 µM) or Src kinases with SU6656 (10 µM) reduced Ca2+ entry and SMC death to H2O2 most effectively in PCAs from young males. Activating TRPV4 channels with GSK1016790A (50 nM) evoked greater Ca2+ influx in SMCs and ECs of PCAs from young vs. old mice but did not induce cell death. However, when combined with H2O2, TRPV4 activation exacerbated EC death. Activating Src kinases with spermidine (100 µM) increased Ca2+ influx in PCAs from males vs. females with minimal cell death. We conclude that in males, chronic oxidative stress during aging increases the resilience of cerebral arteries, which contrasts with inherent protection in females. Findings implicate TRP channels and Src kinases as targets to limit vascular damage to acute oxidative injury.


Subject(s)
Aging , Apoptosis , Cerebral Arteries , Mice, Inbred C57BL , Oxidative Stress , Animals , Female , Male , Mice , Apoptosis/drug effects , Cerebral Arteries/metabolism , Cerebral Arteries/drug effects , Aging/metabolism , Aging/physiology , Mitochondria/metabolism , Reactive Oxygen Species/metabolism , Membrane Potential, Mitochondrial/drug effects , Hydrogen Peroxide/pharmacology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/drug effects , Calcium/metabolism
3.
Psychiatry Res ; 327: 115377, 2023 09.
Article in English | MEDLINE | ID: mdl-37562153

ABSTRACT

Community treatment orders (CTOs) have been associated with reduced crime/victimization-risk. Australia's ratification of the U.N. Convention on the Rights of Persons with Disabilities (CRPD) enabled patient-rights-advocacy to limit CTO-assignment to persons lacking decision-making-capacity. This effort was accompanied by a 15% reduction in CTO-utilization. Has this change affected crime/victimization-involvements of patients with schizophrenia-diagnoses? In Victoria Australia, the study considers crime/victimization-involvement among three patient-groups recruited with the same sampling-algorithm in the decade before (2000-2009, N = 14,711) and after (2010-2019, N = 10,702) CRPD-ratification. Each group is its own-control. Each group's positive-outcome across decades would be "no increase" in crime/victimization-involvement or in the ratio of the group's incident-rates to the State's. Following CRPD-ratification, first-hospitalized-patients with at least one CTO-assignment doubled their involvement in major crime-perpetrations (from 13% to 27%), non-CTO-hospitalized-patients almost doubled (from 10% to 18%), and 11% of outpatients were involved when none were before. Overall, a third (34%) were victimized-by-major-crime up from 28%, with 25% of outpatients experiencing victimization when none had before. Increases were most evident in major-crimes, led by assaults/abductions. Capacity-constraints on compulsory-treatment are associated with increases in crime/victimization-involvement, a transfer of responsibility for patients with schizophrenia-diagnoses from the mental-health-system to the criminal-justice-system, validation of dangerousness stereotypes, and growing negative family impact.


Subject(s)
Crime Victims , Mental Disorders , Schizophrenia , Humans , Mental Disorders/therapy , Commitment of Mentally Ill , Crime , Schizophrenia/therapy , Civil Rights , Victoria
4.
Antioxidants (Basel) ; 12(7)2023 Jul 16.
Article in English | MEDLINE | ID: mdl-37507971

ABSTRACT

High fat, western-style diets increase vascular oxidative stress. We hypothesized that smooth muscle cells and endothelial cells adapt during the consumption of high fat diets to become more resilient to acute oxidative stress. Male C57Bl/6J mice were fed a western-style diet high in fat and processed carbohydrates (WD), a high fat diet that induces obesity (DIO), or their respective control (CD) and standard (SD) diets for 16 weeks. Posterior cerebral arteries (PCAs) were isolated and pressurized for study. During acute exposure to H2O2 (200 µM), smooth muscle cell and endothelial cell death were reduced in PCAs from WD, but not DIO mice. WD selectively attenuated mitochondrial membrane potential depolarization and vessel wall Ca2+ influx during H2O2 exposure. Selective inhibition of transient receptor potential (TRP) V4 or TRPC3 channels reduced smooth muscle cell and endothelial cell death in concert with the vessel wall [Ca2+]i response to H2O2 for PCAs from CD mice and eliminated differences between CD and WD. Inhibiting Src kinases reduced smooth muscle cell death along with [Ca2+]i response to H2O2 only in PCAs from CD mice and eliminated differences between diets. However, Src kinase inhibition did not alter endothelial cell death. These findings indicate that consuming a WD, but not high fat alone, leads to adaptations that limit Ca2+ influx and vascular cell death during exposure to acute oxidative stress.

5.
Skelet Muscle ; 13(1): 3, 2023 02 14.
Article in English | MEDLINE | ID: mdl-36788624

ABSTRACT

BACKGROUND: Acute injury to skeletal muscle damages myofibers and fragment capillaries, impairing contractile function and local perfusion. Myofibers and microvessels regenerate from satellite cells and from surviving microvessel fragments, respectively, to restore intact muscle. Established models of injury have used myotoxins and physical trauma to demonstrate the concurrence of myogenesis and angiogenesis during regeneration. In these models, efferocytosis removes cellular debris while basal laminae persist to provide guidance during myofiber and microvessel regeneration. It is unknown whether the spatiotemporal coupling between myofiber and microvascular regeneration persists when muscle tissue is completely removed and local guidance cues are lost. METHODS: To test whether complete removal of skeletal muscle tissue affects the spatiotemporal relationship between myogenesis and angiogenesis during regeneration, subthreshold volumetric muscle loss was created with a biopsy punch (diameter, 2 mm) through the center of the gluteus maximus (GM) in adult mice. Regeneration into the void was evaluated through 21 days post-injury (dpi). Microvascular perfusion was evaluated in vivo by injecting fluorescent dextran into the circulation during intravital imaging. Confocal imaging and histological analyses of whole-mount GM preparations and tissue cross-sections assessed the growth of microvessels and myofibers into the wound. RESULTS: A provisional matrix filled with PDGFRα+ and CD45+ cells spanned the wound within 1 dpi. Regenerating microvessels advanced from the edges of the wound into the matrix by 7 dpi. Nascent microvascular networks formed by 10 dpi with blood-perfused networks spanning the wound by 14 dpi. In striking contrast, the wound remained devoid of myofibers at 7 and 10 dpi. Myogenesis into the wound was apparent by 14 dpi and traversed the wound by 21 dpi. Regenerated myofibers and microvessels were disorganized compared to the uninjured muscle. CONCLUSIONS: Following punch biopsy of adult skeletal muscle, regenerating microvessels span the wound and become perfused with blood prior to myofiber regeneration. The loss of residual guidance cues with complete tissue removal disrupts the spatiotemporal correspondence between microvascular and myofiber regeneration. We conclude that angiogenesis precedes myogenesis during regeneration following subthreshold volumetric muscle loss.


Subject(s)
Muscle, Skeletal , Regeneration , Animals , Mice , Muscle, Skeletal/pathology , Microvessels , Biopsy , Muscle Development
6.
Schizophr Bull Open ; 4(1): sgac071, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36756191

ABSTRACT

Background: Provision of involuntary care is an abridgment of civil rights and a source of controversy. Its circumstances require continued monitoring. This study asks 4 questions: Whether, in an era, focused on allowing patients with capacity to refuse community-treatment-order (CTO)-assignments, CTO use decreased. And whether CTOs fulfilled 3 statute mandates: Were CTO-assigned patients in greater need of treatment than other psychiatric inpatients? Was CTO assignment a less-restrictive alternative to psychiatric hospitalization? and Did CTO assignment provide needed treatment at internationally recommended levels with consequences for patient outcomes? Method: All 214 388 Victoria, Australia mental health admissions between 2000- 2017 were reviewed. Two cohort samples were drawn and followed through 2019-ie, all 7826 hospitalized patients who were first placed on CTOs from 2010 to 2017 and 13 896 hospitalized patients without CTO placement. Logistic Regression was used to specify determinants of CTO assignment from the psychiatric inpatient population. OLS Regression with propensity score control to evaluate study questions. Results: In the 2010-2017 decade, initial CTO assignments decreased by 3.5%, and initial hospitalizations increased by 5.9% compared to the 2000-2009 period. At hospital admission and discharge, based on Health of the Nations Score ratings, the CTO-cohort's need for treatment exceeded that of non-CTO patients. CTO patients had 3.75 fewer days in average inpatient episode duration than other inpatients, when adjusted for CTO-assignment determinants, the ratio of patients to community case managers, and patient housing status. CTO patients needing rehospitalization spent 112.68 more days in the community than re-hospitalized non-CTO patients. Patient to case-manager ratios falling above recommended levels and the patient marginal housing status contributed to longer hospital stays and reduced community tenure. Conclusions: Victoria relied less on CTOs as an LRA, consequently, experiencing increased initial hospitalizations. CTO patients were in greater need of treatment than non-CTO patients, yet, with required oversite had shorter hospitalizations and more time out of hospital prior to rehospitalization than the less severely ill non-CTO group. Patient LRA outcomes were adversely affected by higher than recommended community patient to case-manager ratios limiting needed treatment provision to hospital.

7.
Schizophr Bull Open ; 4(1): sgac077, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36820204

ABSTRACT

Background: Assignment to a community treatment order (CTO) has been associated with reduced mortality risk. In Victoria Australia civil-rights enhancements involving capacity to refuse involuntary treatment have contributed to a 15% reduction between 2010 and 2019 in CTO assignments among first hospitalized patients with Schizophrenia diagnoses. Has this change impacted patient mortality risk? Study Design: This study considered mortality-risk between 2010 and 2019 for 3 patient groups with schizophrenia diagnoses: All 4848 hospitalized patients who were assigned to a CTO for the first time in the period; 3988 matched and randomly selected patients, who were first hospitalized in the decade, without CTO assignment; and 1675 never hospitalized or CTO-assigned outpatients. Deaths of Schizophrenic patients in each group were evaluated against expected deaths given standardized mortality ratios for Victoria. Logistic regression was used to evaluate mortality risk for each treatment group while taking account of race, demographics, differential access to initial diagnoses of life-threatening physical illness, mental health service resources, and indicators of social disadvantage. Study Results: A total of 78% of the 777 deaths of schizophrenia patients in all 3 groups were premature. The 2 hospitalized groups did not differ in mortality risk. Among Victoria's 2010-2019 outpatients (inclusive of treatment refusers with a recorded service contact), 16.2% had a Schizophrenia diagnosis-up from 0.2% in 2000-2009, the prior decade. Outpatients with Schizophrenia were at 48% greater risk of death than individuals in the hospitalized groups, taking all the afore mentioned risk factors into account. Conclusions: Reductions in CTO utilization associated with potential treatment refusals of involuntary community-treatment supervision, seem to have increased mortality risk for this vulnerable population. The line between civil-rights protection and abandonment has been blurred.

8.
BMC Psychiatry ; 22(1): 787, 2022 12 13.
Article in English | MEDLINE | ID: mdl-36514026

ABSTRACT

BACKGROUND: Despite broad interest of the Syrian refugee plight in the academic and media circles, there are still limited studies analyzing the lived experiences of torture survivors under the Syrian regime. This qualitative study interviewed torture survivors to examine the form and function of the Syrian regime's security apparatus, and the personal aftermath of survivors. METHODS: Thirteen in-depth interviews were conducted in Arabic with Syrian refugees who endured torture. Study participants were at least 19 years of age, resided as refugees in Jordan, and voluntarily agreed to participate in the study. Participation was anonymous and no incentives were provided. Only oral consent was required. Audio-recorded interviews were transcribed and translated to English, and then analyzed for repetitive themes utilizing the narrative approach. RESULTS: Major themes were observed across three experience-phases: pre-captivity, during captivity, and post-captivity. The pre-captivity phase included two sub-themes: the Syrian regime's initial detection and arrest system, and the intelligence system. The captivity phase was also divided into two sub-themes: environmental conditions in detention facilities, and torture methods including physical and psychological torture. Some of the environmental conditions in detention facilities included lack of sanitation, crowding, starvation, and withholding of medical care. Torture methods encompassed beatings, electric shocks, nail-pulling, hanging, drowning, suffocation, rape, and the witnessing of killing, sexual assault, or torture of others. The post-captivity phase included their release from captivity, escaping Syria, and post-displacement conditions and activism. CONCLUSIONS: The Syrian regime employs a vast security apparatus to track, detain, interrogate, torture, and subjugate its civilian population. A systematic mechanism commences even before captivity and continues for years after release, with negative implications on the well-being of survivors, their families, and the Syrian people as a collective community. The Syrian war saw a shift toward mass detention, torture as a form of social punishment, subjugation, and indeterminate imprisonment. Intervention agencies, host countries, and policymakers must be informed of survivors' experiences to better address their needs. Moreover, the international community must advocate for a firm stance against torture, demand justice, and prosecute all parties engaged in perpetuating such extreme forms of suffering and trauma.


Subject(s)
Refugees , Stress Disorders, Post-Traumatic , Torture , Humans , Refugees/psychology , Stress Disorders, Post-Traumatic/psychology , Survivors/psychology , Syria , Torture/psychology
9.
Acta Physiol (Oxf) ; 235(2): e13819, 2022 06.
Article in English | MEDLINE | ID: mdl-35380737

ABSTRACT

AIM: Brain injury produces reactive oxygen species (ROS). However, little is known of how acute oxidative stress affects cell survival in the cerebral vascular supply. We hypothesized that endothelial cells (ECs) are more resilient to H2 O2 and protect vascular smooth muscle cells (SMCs) during acute oxidative stress. METHODS: Mouse posterior cerebral arteries (PCAs; diameter, ~80 µm) were exposed to H2 O2 (200 µM, 50 min, 37°C). Nuclear staining identified dead and live cells of intact and endothelium-disrupted vessels. SMC [Ca2+ ]i was assessed with Fura-2 fluorescence, and superoxide production was assessed by dihydroethidium and MitoSOX fluorescence. RESULTS: In response to H2 O2 : SMC death (21%) exceeded EC death (5%) and increased following endothelial disruption (to 48%) with a corresponding increase in SMC Ca2+ entry through transient receptor potential (TRP) channels. Whereas pharmacological inhibition of TRPV4 channels prevented SMC death and reduced Ca2+ entry for intact vessels, both remained elevated following endothelial disruption. In contrast, pharmacological inhibition or genetic deletion of TRPC3 prevented SMC death and attenuated Ca2+ entry for both intact and endothelium-disrupted vessels. Inhibiting gap junctions increased EC death (to 22%) while SMC death and [Ca2+ ]i responses were attenuated by inhibiting nitric oxide synthesis or scavenging superoxide/peroxynitrite. Inhibiting NADPH oxidases also prevented SMC Ca2+ entry and death. H2 O2 increased mitochondrial ROS production while scavenging mitochondria-derived superoxide prevented SMC death but not Ca2+ entry. CONCLUSIONS: During acute exposure of cerebral arteries to acute oxidative stress, ECs are more resilient than SMCs and the endothelium may protect SMCs by reducing Ca2+ entry through TRPC3 channels.


Subject(s)
Endothelial Cells , Endothelium, Vascular , Animals , Cell Death , Cerebral Arteries/metabolism , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Mice , Myocytes, Smooth Muscle/metabolism , Reactive Oxygen Species/metabolism , Superoxides/metabolism , TRPV Cation Channels/metabolism
10.
Psychiatr Q ; 93(1): 55-79, 2022 03.
Article in English | MEDLINE | ID: mdl-33404994

ABSTRACT

Outpatient civil commitment (OCC) requires the provision of needed-treatment, as a less restrictive alternative (LRA) to psychiatric-hospitalization in order to protect against imminent-threats to health and safety associated with severe mental illness (SMI). OCC-reviews aggregating all studies report inconsistent outcomes and interpret such as intervention failure. This review, considering those studies whose outcome criteria are consistent with the provisions of OCC-law, seeks to determine OCC-effectiveness in meeting its legislated objectives. This review incorporated studies from previous systematic-reviews, used their search methodology, and added investigations through August 2020. Selected OCC-studies evaluated samples of all eligible patients in a jurisdiction. Their outcome-measures were threats to health or safety or the receipt of needed-treatment exclusive of post-OCC-assignment- hospitalization, the latter being the OCC-default for providing needed-treatment in the absence of an LRA and dependent on bed-availability. A study's evidence-quality was evaluated with the Berkeley Evidence Ranking and the New Castle Ottawa systems. Thirty-nine OCC-outcome-studies in six-outcome-areas directly addressed OCC-statute objectives: 21 considered imminent threats to health and safety, 10 compliance with providing needed-treatment, and 8 conformity to the LRA-standard. With the top evidence-rank equal to one, the studies M = 2.55. OCC-assignment was associated with reducing mortality-risk, increasing access to acute-medical-care, and reducing risks of violence and victimization. It enabled reaching these objectives as a LRA to hospitalization and facilitated the use of community-services by individuals refusing such assistance when outside of OCC-supervision. OCC's appears to enable recovery by reducing potentially life-altering health and safety risks associated with SMI.


Subject(s)
Crime Victims , Mental Disorders , Commitment of Mentally Ill , Hospitalization , Humans , Mental Disorders/therapy , Violence
11.
J Physiol ; 600(1): 41-60, 2022 01.
Article in English | MEDLINE | ID: mdl-34761825

ABSTRACT

Injury to skeletal muscle disrupts myofibres and their microvascular supply. While the regeneration of myofibres is well described, little is known of how the microcirculation is affected by skeletal muscle injury or its recovery during regeneration. Nevertheless, the microvasculature must also recover to restore skeletal muscle function. We aimed to define the nature of microvascular damage and time course of repair during muscle injury and regeneration induced by the myotoxin BaCl2 . To test the hypothesis that microvascular disruption occurred secondary to myofibre injury, isolated microvessels were exposed to BaCl2 or the myotoxin was injected into the gluteus maximus (GM) muscle of mice. In isolated microvessels, BaCl2 depolarized smooth muscle cells (SMCs) and endothelial cells while increasing intracellular calcium in SMCs but did not elicit death of either cell type. At 1 day post-injury (dpi) of the GM, capillary fragmentation coincided with myofibre degeneration while arteriolar and venular networks remained intact; neutrophil depletion before injury did not prevent capillary damage. Perfused capillary networks reformed by 5 dpi in association with more terminal arterioles and were dilated through 10 dpi. With no change in microvascular area or branch point number in regenerating capillary networks, fewer capillaries aligned with myofibres and were no longer organized into microvascular units. By 21 dpi, capillary orientation and microvascular unit organization were no longer different from uninjured GM. We conclude that following their disruption secondary to myofibre damage, capillaries regenerate as disorganized networks that remodel into microvascular units as regenerated myofibres mature. KEY POINTS: Skeletal muscle regenerates after injury; however, the nature of microvascular damage and repair is poorly understood. Here, the myotoxin BaCl2 , a standard experimental method of acute skeletal muscle injury, was used to investigate the response of the microcirculation to local injury of intact muscle. Intramuscular injection of BaCl2 induced capillary fragmentation with myofibre degeneration; arteriolar and venular networks remained intact. Direct exposure to BaCl2 did not kill microvascular endothelial cells or smooth muscle cells. Dilated capillary networks reformed by 5 days post-injury (dpi) in association with more terminal arterioles. Capillary orientation remained disorganized through 10 dpi. Capillaries realigned with myofibres and reorganized into microvascular units by 21 dpi, which coincides with the recovery of vasomotor control and maturation of nascent myofibres. Skeletal muscle injury disrupts its capillary supply secondary to myofibre degeneration. Reorganization of regenerating microvascular networks accompanies the recovery of blood flow regulation.


Subject(s)
Capillaries , Endothelial Cells , Animals , Mice , Mice, Inbred C57BL , Microvessels , Muscle, Skeletal , Regeneration
12.
Gen Psychiatr ; 35(6): e100858, 2022.
Article in English | MEDLINE | ID: mdl-36654668

ABSTRACT

Background: The conclusion that people with severe mental illness require involuntary care to protect their health (including threats due to physical-non-psychiatric-illness) is challenged by findings indicating that they often lack access to general healthcare and the assertion that they would access such care voluntarily if available and effective. Victoria, Australia's single-payer healthcare system provides accessible medical treatment; therefore, it is an excellent context in which to test these challenges. Aims: This study replicates a previous investigation in considering whether, in Australia's easy-access single-payer healthcare system, patients placed on community treatment orders, specifically involuntary community treatment, are more likely to access acute medical care addressing potentially life-threatening physical illnesses than voluntary patients with and without severe mental illness. Methods: Replicating methods used in 2000-2010, for the years 2010-2017, this study compared the acute medical care access of three new cohorts: 7826 hospitalised patients with severe mental illness who received a post-hospitalisation, community treatment order; 13 896 patients with severe mental illness released from the hospital without a community treatment order and 12 101 outpatients who were never psychiatrically hospitalised (individuals with less morbidity risk who were not considered to have severe mental illness) during periods when they were under versus outside community mental health supervision. Logistic regression was used to determine the influence of community-based community mental health supervision and the type of community mental health supervision (community treatment order vs non-community treatment order) on the likelihood of receiving an initial diagnosis of a life-threatening physical illness requiring acute care. Results: Validating their shared elevated morbidity risk, 43.7% and 46.7%, respectively, of each hospitalised cohort (community treatment order and non-community treatment order patients) accessed an initial acute-care diagnosis for a life-threatening condition vs 26.3% of outpatients. Outside community mental health supervision, the likelihood that a community treatment order patient would receive a diagnosis of physical illness was 36% lower than non-community treatment order patients-1.30 times that of outpatients. Under community mental health supervision, their likelihood was two times greater than that of non-community treatment order patients and 6.6 times that of outpatients. Each community treatment order episode was associated with a 14.6% increase in the likelihood of a community treatment order patient receiving a diagnosis. The results replicate those found in an independent 2000-2010 cohort comparison. Conclusions: Community mental health supervision, notably community treatment order supervision, in two independent investigations over two decades appeared to facilitate access to physical healthcare in acute care settings for patients with severe mental illness who were refusing treatment-a group that has been subject to excess morbidity and mortality.

13.
Microcirculation ; 28(8): e12733, 2021 11.
Article in English | MEDLINE | ID: mdl-34633728

ABSTRACT

OBJECTIVE: We sought to define how sensory neurotransmitters substance P and calcitonin gene-related peptide (CGRP) affect membrane potential of vascular smooth muscle and endothelium. METHODS: Microelectrodes recorded membrane potential of smooth muscle from pressurized mouse mesenteric arteries (diameter, ~150 µm) and in endothelial tubes. RESULTS: Resting potential was similar (~ -45 mV) for each cell layer. Substance P hyperpolarized smooth muscle and endothelium ~ -15 mV; smooth muscle hyperpolarization was abolished by endothelial disruption or NO synthase inhibition. Blocking KCa channels (apamin + charybdotoxin) attenuated hyperpolarization in both cell types. CGRP hyperpolarized endothelium and smooth muscle ~ -30 mV; smooth muscle hyperpolarization was independent of endothelium. Blocking KCa channels prevented hyperpolarization to CGRP in endothelium but not smooth muscle. Inhibiting KATP channels with glibenclamide or genetic deletion of KIR 6.1 attenuated hyperpolarization in smooth muscle but not endothelium. Pinacidil (KATP channel agonist) hyperpolarized smooth muscle more than endothelium (~ -35 vs. ~ -20 mV). CONCLUSIONS: Calcitonin gene-related peptide elicits greater hyperpolarization than substance P. Substance P hyperpolarizes both cell layers through KCa channels and involves endothelium-derived NO in smooth muscle. Endothelial hyperpolarization to CGRP requires KCa channels, while KATP channels mediate hyperpolarization in smooth muscle. Differential K+ channel activation in smooth muscle and endothelium through sensory neurotransmission may selectively tune mesenteric blood flow.


Subject(s)
Calcitonin Gene-Related Peptide , Substance P , Animals , Calcitonin Gene-Related Peptide/metabolism , Calcitonin Gene-Related Peptide/pharmacology , Endothelium , Endothelium, Vascular/physiology , Mesenteric Arteries/metabolism , Mice , Muscle, Smooth, Vascular/physiology , Substance P/metabolism , Substance P/pharmacology
14.
Am J Physiol Cell Physiol ; 320(6): C1099-C1111, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33852364

ABSTRACT

During embryogenesis, blood vessels and nerves develop with similar branching structure in response to shared signaling pathways guiding network growth. With both systems integral to physiological homeostasis, dual targeting of blood vessels and nerves to promote neurovascular regeneration following injury is an emerging therapeutic approach in biomedical engineering. A limitation to this strategy is that the nature of cross talk between emergent vessels and nerves during regeneration in an adult is poorly understood. Following peripheral nerve transection, intraneural vascular cells infiltrate the site of injury to provide a migratory pathway for mobilized Schwann cells of regenerating axons. As Schwann cells demyelinate, they secrete vascular endothelial growth factor, which promotes angiogenesis. Recent advances point to concomitant restoration of neurovascular architecture and function through simultaneous targeting of growth factors and guidance cues shared by both systems during regeneration. In the context of traumatic injury associated with volumetric muscle loss, we consider the nature of biomaterials used to engineer three-dimensional scaffolds, functionalization of scaffolds with molecular signals that guide and promote neurovascular growth, and seeding scaffolds with progenitor cells. Physiological success is defined by each tissue component of the bioconstruct (nerve, vessel, muscle) becoming integrated with that of the host. Advances in microfabrication, cell culture techniques, and progenitor cell biology hold great promise for engineering bioconstructs able to restore organ function after volumetric muscle loss.


Subject(s)
Biocompatible Materials/pharmacology , Muscle, Skeletal/drug effects , Muscular Diseases/drug therapy , Nerve Regeneration/drug effects , Animals , Humans , Muscle, Skeletal/metabolism , Muscular Diseases/metabolism , Peripheral Nerves/drug effects , Peripheral Nerves/metabolism , Schwann Cells/drug effects , Schwann Cells/metabolism , Signal Transduction/drug effects , Stem Cells/drug effects , Stem Cells/metabolism , Vascular Endothelial Growth Factor A/metabolism
15.
Adm Policy Ment Health ; 48(6): 942-961, 2021 11.
Article in English | MEDLINE | ID: mdl-33534072

ABSTRACT

Outpatient civil commitment (OCC) requires people with severe mental illness (SMI) to receive needed-treatment addressing imminent-threats to health and safety. When available, such treatment is required to be provided in the community as a less restrictive alternative (LRA) to psychiatric-hospitalization. Variance in hospital-utilization outcomes following OCC-assignment has been interpreted as OCC-failure. This review seeks to specify factors accounting for this outcome-variation and to determine whether OCC is used effectively. Twenty-five studies, sited in seven meta-analyses and subsequently published investigations, assessing post-OCC-assignment hospital utilization outcomes were reviewed. Studies were grouped by structural pre-determinants of hospital-utilization and OCC-implementation-i.e. deinstitutionalization (bed-availability), availability of a less restrictive alternative to hospitalization, and illness severity. Design quality at study completion was ranked on causal-certainty. In OCC-follow-up-studies, deinstitutionalization associated hospital-bed-cuts, when not taken into account, ensured lower hospital-bed-day utilization. OCC-assignment coupled with aggressive case-management was associated with reduced-hospitalization. With limited community-service, hospitalizations increased as the default option for providing needed-treatment. Follow-up studies showed less hospitalization while on OCC-assignment and more outside of it. Studies using fixed-follow-up periods usually found increased-utilization as patients spent less time under OCC-supervision than outside it. Comparison-group-studies reporting no between-group differences bring more severely ill OCC-patients to equivalent use as less disturbed patients, a success. Mean evidence-rank for causal-certainty 2.96, range 2-4, of 5 with no study ranked 1, the highest rank. Diverse mental health systems yield diverse OCC hospital-utilization outcomes, each fulfilling the law's legal mandate to provide needed-treatment protecting health and safety.


Subject(s)
Commitment of Mentally Ill , Mental Disorders , Day Care, Medical , Hospitalization , Hospitals , Humans , Mental Disorders/therapy
16.
Front Psychol ; 12: 537131, 2021.
Article in English | MEDLINE | ID: mdl-33603695

ABSTRACT

OBJECTIVE: Violent conflict forced millions of Syrians to flee their homes to host countries. This study examines Syrian refugee women's experiences from the war's outset through their journey to Jordan. It addresses the toll this journey had on their lives. METHODS: Twenty-four in-depth interviews were completed with Syrian refugee women who currently reside in urban areas of Jordan. Researchers translated, transcribed, and analyzed the interviews using group narrative methodology. RESULTS: The Syrian women had unique nostalgic memories of times before the war. They experienced atrocities during the war that forced their decision to escape Syria. Their journey narratives testify of internal displacement, personal and collective traumatic journeys via legal and illegal routes. Almost all the women were placed in refugee camps during their transitions to host country residency. In Jordan, they faced diverse hurdles of displacement and extremely different realities compared to the ones they had in Syria. Despite how very different but difficult each of their journeys were, every single woman longed to return home to Syria. CONCLUSIONS: This study presents a new understanding of the role and process of the journeys undertaken and highlights the concept of "return" as the defining element for Syrian refugee women. Regardless of the hardships women endured to escape their homeland to find safety, "return" marks an ending to their horror journey and the beginning of a new journey of hope for a better future.

17.
Am J Physiol Heart Circ Physiol ; 320(4): H1625-H1633, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33606587

ABSTRACT

Reactive oxygen species (ROS) are implicated in cardiovascular and neurologic disorders including atherosclerosis, heart attack, stroke, and traumatic brain injury. Although oxidative stress can lead to apoptosis of vascular cells, such findings are largely based upon isolated vascular smooth muscle cells (SMCs) and endothelial cells (ECs) studied in culture. Studying intact resistance arteries, we have focused on understanding how SMCs and ECs in the blood vessel wall respond to acute oxidative stress induced by hydrogen peroxide, a ubiquitous, membrane-permeant ROS. We find that apoptosis induced by H2O2 is far greater in SMCs compared to ECs. For both cell types, apoptosis is associated with a rise in intracellular calcium concentration ([Ca2+]i) during H2O2 exposure. Consistent with their greater death, the rise in [Ca2+]i for SMCs exceeds that in ECs. Finding that disruption of the endothelium increases SMC death, we address how myoendothelial coupling and paracrine signaling attenuate apoptosis. Remarkably, conditions associated with chronic oxidative stress (advanced age, Western-style diet) protect SMCs during H2O2 exposure, as does female sex. In light of intracellular Ca2+ handling, we consider how glycolytic versus oxidative pathways for ATP production and changes in mitochondrial structure and function impact cellular resilience to H2O2-induced apoptosis. Gaining new insight into protective signaling within and between SMCs and ECs of the arterial wall can be applied to promote vascular cell survival (and recovery of blood flow) in tissues subjected to acute oxidative stress as occurs during reperfusion following myocardial infarction and thrombotic stroke.


Subject(s)
Apoptosis/drug effects , Endothelial Cells/drug effects , Endothelium, Vascular/drug effects , Hydrogen Peroxide/toxicity , Mitochondria/drug effects , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Oxidative Stress/drug effects , Animals , Calcium Signaling , Cell Communication/drug effects , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/pathology , Endothelial Cells/metabolism , Endothelial Cells/pathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/pathology , Energy Metabolism/drug effects , Female , Humans , Male , Mitochondria/metabolism , Mitochondria/pathology , Muscle, Smooth, Vascular/metabolism , Muscle, Smooth, Vascular/pathology , Myocytes, Smooth Muscle/metabolism , Myocytes, Smooth Muscle/pathology , Reactive Oxygen Species/metabolism , Sex Factors
18.
J Interpers Violence ; 36(1-2): NP960-NP983, 2021 01.
Article in English | MEDLINE | ID: mdl-29294964

ABSTRACT

This study of rape crisis counselors considers whether increased exposure to victims' trauma is associated with increased supervision-believed necessary to combat trauma contagion-and whether such supervision will reduce the negative impact of such exposure. One hundred six women counselors in seven of nine rape crisis centers in Israel completed anonymous questionnaires documenting their work and trauma exposure. Trauma exposure was defined by counselors' number of victim-contact hours per week and their assessment of the trauma severity they experienced. Supervision was measured by the number of hours received. Counselors trauma outcome indicators included sexual intimacy, secondary traumatization (evidenced in posttraumatic stress disorder [PTSD]-type symptomology), and vicarious traumatization (expressed as a disturbance in cognitive schemes that undermine the self and others). Hypotheses were evaluated in fully recursive path analyses via ordinary least squares (OLS) regression. Participants' mean age was 43.4 years; 58% were married, 26% single, 13% divorced, and 3% widowed; 81% had a college degree or more; 18.9% reported being exposed to victims-trauma at a minimal level, 54.7% moderate and 26.4% extreme; and 43.4% were abused at some time in their lives. Job exposure to victims' trauma was significantly associated with increases in supervision time (ß = .33, p = .002). Supervision time fully mediated the relationship between duration of exposure to victims' trauma and counselors' secondary traumatization reports such that increased supervision was associated with degrading sexual intimacy (ß = .22; p = .032) and increased Secondary Trauma Scale scores (ß = .44; p = .004) after taking into account counselors' education level, history of abuse, anger management in intimate relationship, and posttraumatic growth scores. The study results raise concern about counselors' mental health in that the supervision effect exacerbated the trauma contagion impacts. The study suggests a need for documenting the nature of the supervision and considering different types of supervision methods.


Subject(s)
Counselors , Rape , Adult , Counseling , Crisis Intervention , Female , Humans , Israel
19.
Article in English | MEDLINE | ID: mdl-33198333

ABSTRACT

This research examines Syrian refugee mothers' accounts of the physical and mental health of their children being affected by war traumas and displacement challenges. Open-ended audio-recorded interviews were conducted in Arabic with 23 mothers residing in Jordan. Using a narrative approach in the data collection and analysis, five major themes were identified: (1) children were exposed to diverse war traumatic experiences in Syria; (2) the escape journey and refugee camps threatened children's lives; (3) displacement and family stressors exposed children to poverty, hostility from local peers, educational and recreational challenges, child labor, and domestic violence (these three major themes were considered as trauma related variables); (4) children were not only directly affected physically and mentally by their own traumatic experiences and displacement stressors, but these experiences were mediated and magnified by familial interrelated processes, evidenced in intergenerational transmission of trauma, harsh parenting style, parental control, and parentification; and (5) adverse consequences of both trauma related variables and family processes directly and indirectly traumatized children and adversely impacted their physical and mental health. We examined the themes that emerged from the data in view of three theoretical frameworks and the impact of trauma in the family system on child development. To conclude, humanitarian organizations that provide services and interventions to refugees need to take into account familial processes and not only individual factors affecting refugee children's physical and mental health. Further implications on policies and trauma research are discussed.


Subject(s)
Child Health , Mental Health , Refugees , Child , Child Health/statistics & numerical data , Family Characteristics , Female , Humans , Jordan , Mental Health/statistics & numerical data , Refugees/psychology , Syria
20.
J Affect Disord ; 276: 839-847, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32738669

ABSTRACT

BACKGROUND: Bearing witness to Syrian refugee atrocities may result in aid-workers' vicarious traumatization (VT). This study examined work stressors and organizational support and their associations with vicarious posttraumatic growth (VPTG) and intimate relationships. It also examined the potential mediating effects of differentiation of the self and finding meaning in trauma-work. METHODS: Aid-workers (N = 317) from organizations in Jordan were surveyed. Univariate statistics and structural equation modeling (SEM) were utilized to test hypothesized relationships. RESULTS: Increased VT was associated with increased VPTG, decreased intimacy and decreased differentiation. Increased needs addressed by NGOs was associated with increased VPTG, differentiation, and finding meaning. Increased trauma-exposure was associated with increased finding meaning. Increased co-workers support was associated with increased intimacy and finding meaning. Higher differentiation was associated with decreased VPTG, and increased intimacy. Whereas, increased finding meaning was associated with increased VPTG and intimacy. Differentiation partially mediated the associations between VT, and both VPTG and intimacy, and between needs at work and VPTG. Differentiation fully mediated the association between needs at work and intimacy. Finding meaning fully mediated the associations between extent of trauma-exposure, and both VPTG and intimacy, and between co-workers support and VPTG; needs at work and intimacy. It partially mediated the associations between needs at work and VPTG; co-workers support and intimacy. LIMITATIONS: The study is cross-sectional and generalization is limited to aid-workers who provide services to Syrian refugees in Jordan. CONCLUSIONS: Organizational support is crucial in mitigating the negative impacts of trauma-work, and in enabling a nurturing space for potential growth.


Subject(s)
Compassion Fatigue , Posttraumatic Growth, Psychological , Refugees , Cross-Sectional Studies , Humans , Interpersonal Relations
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