Cofilin Inhibitor Improves Neurological and Cognitive Functions after Intracerebral Hemorrhage by Suppressing Endoplasmic Reticulum Stress Related-Neuroinflammation.

Neuroinflammation after intracerebral hemorrhage (ICH) is a crucial factor that determines the extent of the injury. Cofilin is a cytoskeleton-associated protein that drives neuroinflammation and microglia activation. A novel cofilin inhibitor (CI) synthesized and developed in our lab has turned out to be a potential therapeutic agent for targeting cofilin-mediated neuroinflammation in an in vitro model of ICH and traumatic brain injury. The current study aims to examine the therapeutic potential of CI in a mouse collagenase model of ICH and examine the neurobehavioral outcomes and its mechanism of action. Male mice were subjected to intrastriatal collagenase injection to induce ICH, and sham mice received needle insertion. Various concentrations (25, 50, and 100 mg/kg) of CI were administered to different cohorts of the animals as a single intravenous injection 3 h following ICH and intraperitoneally every 12 h for 3 days. The animals were tested for neurobehavioral parameters for up to 7 days and sacrificed to collect brains for hematoma volume measurement, Western blotting, and immunohistochemistry. Blood was collected for cofilin, TNF-α, and IL-1ß assessments. The results indicated that 50 mg/kg CI improved neurological outcomes, reversed post-stroke cognitive impairment, accelerated hematoma resolution, mitigated cofilin rods/aggregates, and reduced microglial and astrocyte activation in mice with ICH. Microglia morphological analysis demonstrated that CI restored the homeostasis ramification pattern of microglia in mice treated with CI. CI suppressed endoplasmic reticulum stress-related neuroinflammation by inhibiting inflammasomes and cell death signaling pathways. We also showed that CI prevented synaptic loss by reviving the pre- and post-synaptic markers. Our results unveil a novel therapeutic approach to treating ICH and open a window for using CI in clinical practice.

Astrocytes in functional recovery following central nervous system injuries.

Astrocytes are increasingly recognised as partaking in complex homeostatic mechanisms critical for regulating neuronal plasticity following central nervous system (CNS) insults. Ischaemic stroke and traumatic brain injury are associated with high rates of disability and mortality. Depending on the context and type of injury, reactive astrocytes respond with diverse morphological, proliferative and functional changes collectively known as astrogliosis, which results in both pathogenic and protective effects. There is a large body of research on the negative consequences of astrogliosis following brain injuries. There is also growing interest in how astrogliosis might in some contexts be protective and help to limit the spread of the injury. However, little is known about how astrocytes contribute to the chronic functional recovery phase following traumatic and ischaemic brain insults. In this review, we explore the protective functions of astrocytes in various aspects of secondary brain injury such as oedema, inflammation and blood-brain barrier dysfunction. We also discuss the current knowledge on astrocyte contribution to tissue regeneration, including angiogenesis, neurogenesis, synaptogenesis, dendrogenesis and axogenesis. Finally, we discuss diverse astrocyte-related factors that, if selectively targeted, could form the basis of astrocyte-targeted therapeutic strategies to better address currently untreatable CNS disorders.

Neuroprotection or Sex Bias: A Protective Response to Traumatic Brain Injury in the Females

Traumatic brain injury (TBI) is a major healthcare problem and a common cause of mortality and morbidity. Clinical and preclinical research suggests sex-related differences in short- and long-term outcomes following TBI; however, males have been the main focus of TBI research. Females show a protective response against TBI. Female animals in preclinical studies and women in clinical trials have shown comparatively better outcomes against mild, moderate, or severe TBI. This reflects a favorable protective nature of the females compared to the males, primarily attributed to various protective mechanisms that provide better prognosis and recovery in the females after TBI. Understanding the sex difference in the TBI pathophysiology and the underlying mechanisms remains an elusive goal. In this review, we provide insights into various mechanisms related to the anatomical, physiological, hormonal, enzymatic, inflammatory, oxidative, genetic, or mitochondrial basis that support the protective nature of females compared to males. Furthermore, we sought to outline the evidence of multiple biomarkers that are highly potential in the investigation of TBI's prognosis, pathophysiology, and treatment and which can serve as objective measures and novel targets for individualized therapeutic interventions in TBI treatment. Implementations from this review are important for the understanding of the effect of sex on TBI outcomes and possible mechanisms behind the favorable response in females. It also emphasizes the critical need to include females as a biological variable and in sufficient numbers in future TBI studies.

The ER chaperone, BIP protects Microglia from ER stress-mediated Apoptosis in Hyperglycemia.

A major endoplasmic reticulum (ER) chaperone, binding of Immunoglobulin heavy chain protein (BIP) facilitates the assembly of newly synthesized proteins in the ER. Microglia vigorously respond to brain injuries and eliminate the damaged neuronal and apoptotic cells through phagocytosis in the central nervous system. However, the mechanism of BIP-mediated microglial function is not clear in hyperglycemia. We explored the molecular mechanism of BIP in microglial function during hyperglycemic conditions. Hyperglycemia was induced in mice by two consecutive intraperitoneal injections of streptozotocin (STZ 100/kg) and confirmed by measuring the blood glucose from day 2 to day 14. After 14 days of experimental hyperglycemia, mice were sacrificed and brains were collected for ER chaperone expression. In-vitro hyperglycemia was induced by exposing HMC3 cells to 25 mM glucose for 5 days and proteins involved in ER stress, apoptosis, and autophagy were analyzed. In hyperglycemic conditions, BIP protein expression was dramatically reduced in HMC3 cells, which led to increased apoptosis through the activation of CHOP and mitochondrial pro-apoptotic proteins (Bax, Bad, and cleaved caspase-3). The flow cytometry results indicate hyperglycemia-induced apoptosis and reactive oxygen species (ROS) production. Interestingly, the BIP inducer X restored the apoptosis in HMC3 cells by derepressing BIP expression and inhibiting ER stress. These results suggest that the ER chaperone BIP is required for the microglial function and protects from apoptosis in hyperglycemia. A better understanding of BIP's molecular mechanism and role in microglial function may contribute to developing novel therapies for microglia dysfunction-associated neurodegenerative diseases.

Cofilin Inhibitor Protects against Traumatic Brain Injury-Induced Oxidative Stress and Neuroinflammation.

Microglial activation and failure of the antioxidant defense mechanisms are major hallmarks in different brain injuries, particularly traumatic brain injury (TBI). Cofilin is a cytoskeleton-associated protein involved in actin binding and severing. In our previous studies, we identified the putative role of cofilin in mediating microglial activation and apoptosis in ischemic and hemorrhagic conditions. Others have highlighted the involvement of cofilin in ROS production and the resultant neuronal death; however, more studies are needed to delineate the role of cofilin in oxidative stress conditions. The present study aims to investigate the cellular and molecular effects of cofilin in TBI using both in vitro and in vivo models as well as the first-in-class small-molecule cofilin inhibitor (CI). An in vitro H2O2-induced oxidative stress model was used in two different types of cells, human neuroblastoma (SH-SY5Y) and microglia (HMC3), along with an in vivo controlled cortical impact model of TBI. Our results show that treatment with H2O2 increases the expression of cofilin and slingshot-1 (SSH-1), an upstream regulator of cofilin, in microglial cells, which was significantly reduced in the CI-treated group. Cofilin inhibition significantly attenuated H2O2-induced microglial activation by reducing the release of proinflammatory mediators. Furthermore, we demonstrate that CI protects against H2O2-induced ROS accumulation and neuronal cytotoxicity, activates the AKT signaling pathway by increasing its phosphorylation, and modulates mitochondrial-related apoptogenic factors. The expression of NF-E2-related factor 2 (Nrf2) and its associated antioxidant enzymes were also increased in CI-treated SY-SY5Y. In the mice model of TBI, CI significantly activated the Nrf2 and reduced the expression of oxidative/nitrosative stress markers at the protein and gene levels. Together, our data suggest that cofilin inhibition provides a neuroprotective effect in in vitro and in vivo TBI mice models by inhibiting oxidative stress and inflammatory responses, the pivotal mechanisms involved in TBI-induced brain damage.

Use of mesenchymal stem cell therapy in COVID-19 related strokes.

Coronavirus disease 2019 (COVID-19) has affected a broad demographics, eliciting a more significant effect on specific groups such as males, African Americans, and Hispanic minorities. Treatment of COVID-19 often requires antiviral drugs or monoclonal antibodies. However, immunotherapies such as mesenchymal stem cells and mesenchymal stem cells-derived exosomal vesicles should be evaluated as treatment options for COVID-19. Mesenchymal stem cell therapy offers regenerative, anti-inflammatory, and immunomodulatory properties that can speed up the recovery from COVID-19. Mesenchymal stem cell therapy can also benefit COVID-19 patients who suffer from strokes, as COVID-19 increases the risk of strokes due to increased cytokines and clotting factors. Most stroke cases that occur in COVID-19 patients are ischemic strokes. Therefore, with the help of mesenchymal stem cell therapy and mesenchymal stem cells-derived exosomes, COVID-19-induced stroke patients might benefit from dual-ended treatment. The objective of this review was to discuss COVID-19 and stroke incidence and the available treatment options.

Stroke: Molecular mechanisms and therapies: Update on recent developments.

Stroke, a neurological disease, is one of the leading causes of death worldwide, resulting in long-term disability in most survivors. Annual stroke costs in the United States alone were estimated at $46 billion recently. Stroke pathophysiology is complex, involving multiple causal factors, among which atherosclerosis, thrombus, and embolus are prevalent. The molecular mechanisms involved in the pathophysiology are essential to understanding targeted drug development. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. In addition, various modifiable and non-modifiable risk factors increase the chances of stroke manifolds. Once a patient encounters a stroke, complete restoration of motor ability and cognitive skills is often rare. Therefore, shaping therapeutic strategies is paramount for finding a viable therapeutic agent. Apart from tPA, an FDA-approved therapy that is applied in most stroke cases, many other therapeutic strategies have been met with limited success. Stroke therapies often involve a combination of multiple strategies to restore the patient's normal function. Certain drugs like Gamma-aminobutyric receptor agonists (GABA), Glutamate Receptor inhibitors, Sodium, and Calcium channel blockers, and fibrinogen-depleting agents have shown promise in stroke treatment. Recently, a drug, DM199, a recombinant (synthetic) form of a naturally occurring protein called human tissue kallikrein-1 (KLK1), has shown great potential in treating stroke with fewer side effects. Furthermore, DM199 has been found to overcome the limitations presented when using tPA and/or mechanical thrombectomy. Cell-based therapies like Neural Stem Cells, Hematopoietic stem cells (HSCs), and Human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) are also being explored as a treatment of choice for stroke. These therapeutic agents come with merits and demerits, but continuous research and efforts are being made to develop the best therapeutic strategies to minimize the damage post-stroke and restore complete neurological function in stroke patients.

Type-I diabetes aggravates post-hemorrhagic stroke cognitive impairment by augmenting oxidative stress and neuroinflammation in mice.

Diabetes Mellitus (DM) is a major comorbid condition that increases susceptibility to stroke. Intracerebral hemorrhage (ICH), a devastating type of stroke, accounts for only 13% of the total stroke cases but is associated with higher mortality. Multimorbid models of DM and ischemic stroke have been widely studied; however, fewer pieces of evidence are available on the impact of DM on the outcomes of ICH injury. In this study, we investigated the effect of DM on ICH-induced injury and cognitive impairments. Streptozotocin (STZ) induced type-I DM (T1DM) animal model was used, and experimental ICH was induced by intrastriatal injection of collagenase. Our results demonstrated that DM is associated with a significant increase in hematoma volume and deficits in post-stroke locomotor, sensorimotor, and cognitive behavior in mice. The levels of neuroinflammation, oxidative/nitrosative stress, and glial cell activation were also increased in the diabetic mice following ICH injury. This study provides a better understanding of the influence of DM comorbidity on hemorrhagic stroke outcomes and uncovers the important pathological mechanisms underlying DM-induced exacerbation of ICH injury.

Intracerebral Hemorrhage and Diabetes Mellitus: Blood-Brain Barrier Disruption, Pathophysiology and Cognitive Impairments.

There is a surge in diabetes incidence, with an estimated 463 million individuals been diagnosed worldwide. Diabetes Mellitus (DM) is a major stroke-related comorbid condition that increases the susceptibility of disabling post-stroke outcomes. Although less common, intracerebral hemorrhage (ICH) is the most dramatic subtype of stroke associated with higher mortality, particularly in the DM population. Previous studies have focused mainly on the impact of DM on ischemic stroke. Few studies have focused on the impact of DM on ICH and discussed the blood- -brain barrier disruption, brain edema, and hematoma formation. However, more recently, investigating the role of oxidative damage and Reactive Oxygen Species (ROS) production in preclinical studies involving DM-ICH animal models has gained attention. But, little is known about the correlation between neuroinflammatory processes, glial cells activation, and peripheral immune cell invasion with DM-ICH injury. DM and ICH patients experience impaired abilities in multiple cognitive domains by relatively comparable mechanisms, which could get exacerbated in the setting of comorbidities. In this review, we discuss both the pathology of DM as a comorbid condition for ICH and the potential molecular therapeutic targets for the clinical management of the ICH and its recovery.

Advance Care Planning Engagement Among Muslim Community-Dwelling Adults Living in the United States.

Advance care planning (ACP) is a cornerstone of self-determination for the type of care provided at the end of life. Despite many national efforts to improve American adults' engagement in ACP, statistics indicate low engagement. Low engagement, especially among racial and ethnic minority populations, immigrants, people with lower socioeconomic status, young adults, rural residents, or non-English speakers, is common. Advance care planning engagement among Muslims living in the United States has been minimally studied. The purpose of this study was to explore Muslims' engagement in ACP. A cross-sectional descriptive design was used. Participants were recruited from Islamic organizations through convenience and snowball sampling. Engagement in ACP was measured by the Advance Care Planning Engagement Survey. A sample of 148 Muslims (18-79 years of age) participated in the study. The average engagement scores ranged from 1.97 to 2.09, with about two-thirds in the precontemplation stage. Significant differences in engagement scores were found according to health condition and end of life experiences. Results suggest a need for further collaborative efforts by health care providers, policymakers, and researchers to mitigate the disparities in ACP engagement in the American Muslim community.

Tunable High Spatio-Spectral Purity Undulator Radiation from a Transported Laser Plasma Accelerated Electron Beam.

Undulator based synchrotron light sources and Free Electron Lasers (FELs) are valuable modern probes of matter with high temporal and spatial resolution. Laser Plasma Accelerators (LPAs), delivering GeV electron beams in few centimeters, are good candidates for future compact light sources. However the barriers set by the large energy spread, divergence and shot-to-shot fluctuations require a specific transport line, to shape the electron beam phase space for achieving ultrashort undulator synchrotron radiation suitable for users and even for achieving FEL amplification. Proof-of-principle LPA based undulator emission, with strong electron focusing or transport, does not yet exhibit the full specific radiation properties. We report on the generation of undulator radiation with an LPA beam based manipulation in a dedicated transport line with versatile properties. After evidencing the specific spatio-spectral signature, we tune the resonant wavelength within 200-300 nm by modification of the electron beam energy and the undulator field. We achieve a wavelength stability of 2.6%. We demonstrate that we can control the spatio-spectral purity and spectral brightness by reducing the energy range inside the chicane. We have also observed the second harmonic emission of the undulator.

Publisher Correction: Control of laser plasma accelerated electrons for light sources.

The original version of this Article contained an error in the last sentence of the first paragraph of the Introduction and incorrectly read 'A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-volts per centimetre acceleration gradient with undulators in the amplification regime in equation 11, nx(n-ß) x ß: n the two times and beta the two times should be bold since they are vectorsin Eq. 12, ß should be bold as well.' The correct version is 'A proper electron beam control is one of the main challenges towards the Graal of developing a compact alternative of X-ray free-electron lasers by coupling LWFA gigaelectron-volts per centimetre acceleration gradient with undulators in the amplification regime.'This has been corrected in both the PDF and HTML versions of the Article.

Control of laser plasma accelerated electrons for light sources.

With gigaelectron-volts per centimetre energy gains and femtosecond electron beams, laser wakefield acceleration (LWFA) is a promising candidate for applications, such as ultrafast electron diffraction, multistaged colliders and radiation sources (betatron, compton, undulator, free electron laser). However, for some of these applications, the beam performance, for example, energy spread, divergence and shot-to-shot fluctuations, need a drastic improvement. Here, we show that, using a dedicated transport line, we can mitigate these initial weaknesses. We demonstrate that we can manipulate the beam longitudinal and transverse phase-space of the presently available LWFA beams. Indeed, we separately correct orbit mis-steerings and minimise dispersion thanks to specially designed variable strength quadrupoles, and select the useful energy range passing through a slit in a magnetic chicane. Therefore, this matched electron beam leads to the successful observation of undulator synchrotron radiation after an 8 m transport path. These results pave the way to applications demanding in terms of beam quality.

Osteoporosis knowledge and beliefs in diabetic patients: a cross sectional study from Palestine.

BACKGROUND: Osteoporosis is a potential metabolic complication of diabetes mellitus (DM). Therefore, patients with DM should have adequate osteoporosis knowledge and beliefs in order to get engaged in osteoporosis preventive behaviors. The objective of this study was to assess osteoporosis knowledge and beliefs among diabetic patients. METHODS: This was a cross sectional study carried out at Al-Makhfiah governmental primary healthcare unit in Nablus, Palestine from September 2016 to December 2016. The tools used to assess knowledge and beliefs were Osteoporosis Health Belief Scale (OHBS) and the Osteoporosis Knowledge Test (OKT) respectively. RESULTS: Three hundred diabetic patients were interviewed regarding their knowledge and belief about osteoporosis. The study sample included 192 (64.0%) females. Mean ± standard deviation (SD) of the participants was 58.5 ± 9.3 years. Regarding co-morbidities, 229 (76.3%) had at least one co-morbidity other than DM. The majority of participants incorrectly answered 19 out of 32 questions of OKT scale. The mean OKT score was 13.5 ± 4.2 indicating poor osteoporosis - related knowledge. Females had significantly higher nutrition (p = 0.037), exercise (p = 0.043), and OKT score (p = 0.021) than males. Regarding OHBS, female participants had significantly higher belief score of susceptibility (p <  0.01) and seriousness (p <  0.01) of osteoporosis compared to males. CONCLUSIONS: Diabetic patients had poor osteoporosis knowledge and moderate perception of susceptibility and seriousness of osteoporosis. These results require implementation of awareness programs among DM patients to increase their practices regarding preventive measures of osteoporosis such as calcium intake and exercise.

Laparoscopic access overview: Is there a safest entry method? / Revisión del acceso laparoscópico: ¿hay un método de entrada más seguro?

BACKGROUND: Laparoscopy is a minimally invasive technique to access the abdominal cavity, for diagnostic or therapeutic applications. Optimizing the access technique is an important step for laparoscopic procedures. The aim of this study is to assess the outcomes of different laparoscopic access techniques and to identify the safest one. METHODS: Laparoscopic access questionnaire was forwarded via e-mail to the 60 centers who are partners in working group for laparoscopic and robotic surgery of the Italian Urological Society (SIU) and their American and European reference centers. RESULTS: The response rate was 68.33%. The total number of procedures considered was 65.636. 61.5% of surgeons use Veress needle to create pneumoperitoneum. Blind trocar technique is the most commonly used, but has the greatest number of complications. Optical trocar technique seems to be the safest, but it's the less commonly used. The 28,2% of surgeons adopt open Hasson's technique. Total intra-operative complications rate was 3.3%. Open conversion rate was 0.33%, transfusion rate was 1.13%, and total post-operative complication rate was 2.53%. CONCLUSION: Laparoscopic access is a safe technique with low complication rate. Most of complications can be managed conservatively or laparoscopically. The choice of access technique can affect the rate and type of complications and should be planned according to surgeon experience, safety of each technique and patient characteristics. All access types have perioperative complications. According with our study, optical trocar technique seems to be the safest.

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes.

PURPOSE: This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. METHODS: Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scatteredphotons at the maze entrance. The dose of the backscatteredphotons from a concrete wall was measured for various scattering angles. The dose was also calculated by the FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. RESULTS: It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscatteredphotons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. CONCLUSIONS: This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose.

Dose reduction of scattered photons from concrete walls lined with lead: Implications for improvement in design of megavoltage radiation therapy facility mazes.

PURPOSE: This study explores the possibility of using lead to cover part of the radiation therapy facility maze walls in order to absorb low energy photons and reduce the total dose at the maze entrance of radiation therapy rooms. METHODS: Experiments and Monte Carlo simulations were utilized to establish the possibility of using high-Z materials to cover the concrete walls of the maze in order to reduce the dose of the scattered photons at the maze entrance. The dose of the backscattered photons from a concrete wall was measured for various scattering angles. The dose was also calculated by the FLUKA and EGSnrc Monte Carlo codes. The FLUKA code was also used to simulate an existing radiotherapy room to study the effect of multiple scattering when adding lead to cover the concrete walls of the maze. Monoenergetic photons were used to represent the main components of the x ray spectrum up to 10 MV. RESULTS: It was observed that when the concrete wall was covered with just 2 mm of lead, the measured dose rate at all backscattering angles was reduced by 20% for photons of energy comparable to Co-60 emissions and 70% for Cs-137 emissions. The simulations with FLUKA and EGS showed that the reduction in the dose was potentially even higher when lead was added. One explanation for the reduction is the increased absorption of backscattered photons due to the photoelectric interaction in lead. The results also showed that adding 2 mm lead to the concrete walls and floor of the maze reduced the dose at the maze entrance by up to 90%. CONCLUSIONS: This novel proposal of covering part or the entire maze walls with a few millimeters of lead would have a direct implication for the design of radiation therapy facilities and would assist in upgrading the design of some mazes, especially those in facilities with limited space where the maze length cannot be extended to sufficiently reduce the dose.

Freezing transition, characteristic polynomials of random matrices, and the Riemann zeta function.

We argue that the freezing transition scenario, previously explored in the statistical mechanics of 1/f-noise random energy models, also determines the value distribution of the maximum of the modulus of the characteristic polynomials of large N×N random unitary matrices. We postulate that our results extend to the extreme values taken by the Riemann zeta function ζ(s) over sections of the critical line s=1/2+it of constant length and present the results of numerical computations in support. Our main purpose is to draw attention to possible connections between the statistical mechanics of random energy landscapes, random-matrix theory, and the theory of the Riemann zeta function.

Role of descending venography and endovenous embolization in treatment of females with lower extremity varicose veins, vulvar and posterior thigh varices.

OBJECTIVE: To evaluate the prevalence of refluxing pelvic veins among female patients with lower extremity varicose veins and the role of embolization treatment in these cases. METHODS: Of 158 female patients suffering from primary varicose veins of the lower extremities presented to the Venous Disease Clinic at Dhahran Health Center between January 2002 and December 2004, 25 patients (15.8%) were noted to have vulvar or postero-medial thigh varices or both. Those were referred for trans-jugular descending pelvic venography with or without subsequent embolization of the contributing refluxing veins. RESULTS: Venous reflux contributing to the vulvoperineal or posterior thigh varices was detected in 23 patients (92%) on catheter venography. Left ovarian venous reflux was responsible for 60% of all cases. Embolization, using multiple coils, was successful in 18 patients with positive reflux (78.3%). One patient had primary vulvar venous malformation that required additional percutaneous sclerotherapy using dehydrated ethanol. Four patients had femoro-saphenous reflux contributing to the varices and required subsequent surgical ligation excision. All treated cases showed significant improvement of their symptoms without any procedure related complications. CONCLUSION: In patients with vulvar or postero-medial thigh varicose veins, radiological study of ovarian and hypogastric venous reflux should be considered. Trans-jugular descending venography and embolization is a feasible, effective and safe diagnostic and therapeutic modality.

Suicidal incised wound of a fistula for hemodialysis access in an elderly woman: case report.

A very rare case of suicide by stab wound of a fistula for hemodialysis access in an elderly woman is reported. The incidence of suicide attempts in people undergoing hemodialysis is well known. Nevertheless, suicide means do not usually include stab wounds of the arteriovenous access. Various pattern differences between homicidal and suicidal stab wounds, characteristics of suicide in the elderly, and approaches to the investigation of such cases are briefly discussed.