Contrast-Induced Encephalopathy and the Blood-Brain Barrier.

BACKGROUND: Contrast-induced encephalopathy (CIE) is an adverse event associated with diagnostic and therapeutic endovascular procedures. Decades of animal and human research support a mechanistic role for pathological blood-brain barrier dysfunction (BBBd). Here, we describe an institutional case series and review the literature supporting a mechanistic role for BBBd in CIE. METHODS: A literature review was conducted by searching MEDLINE, Web of Science, Embase, CINAHL and Cochrane databases from inception to January 31, 2022. We searched our institutional neurovascular database for cases of CIE following endovascular treatment of cerebrovascular disease during a 6-month period. Informed consent was obtained in all cases. RESULTS: Review of the literature revealed risk factors for BBBd and CIE, including microvascular disease, pathological neuroinflammation, severe procedural hypertension, iodinated contrast load and altered cerebral blood flow dynamics. In our institutional series, 6 of 52 (11.5%) of patients undergoing therapeutic neuroendovascular procedures developed CIE during the study period. Four patients were treated for ischemic stroke and two patients for recurrent cerebral aneurysms. Mechanical stenting or thrombectomy were utilized in all cases. CONCLUSION: In this institutional case series and literature review of animal and human data, we identified numerous shared risk factors for CIE and BBBd, including microvascular disease, increased procedure length, large contrast volumes, severe intraoperative hypertension and use of mechanical devices that may induce iatrogenic endothelial injury.

Enhancing photodynamic therapy efficacy through silica nanoparticle-mediated delivery of temoporfin for targeted in vitro breast cancer treatment.

Photodynamic therapy (PDT), an approach to cancer treatment, relies fundamentally on two key elements: a light source and a photosensitizing agent. A primary challenge in PDT is the efficient delivery of photosensitizers to the target tissue, hindered by the body's reticuloendothelial system (RES). Silica nanoparticles (SiNPs), known for their unique properties, emerge as ideal carriers in this context. In this study, SiNPs are utilized to encapsulate Temoporfin, a photosensitizer, aiming to enhance its delivery and reduce toxicity, particularly for treating MCF-7 cancer cells in vitro. The synthesized SiNPs were meticulously characterized by their size and shape using Transmission Electron Microscopy (TEM). The study also involved evaluating the cytotoxicity of both encapsulated and naked Temoporfin across various concentrations. The objective was to determine the ideal concentration and exposure duration using red laser light (intensity approximately 110 mW/cm2) to effectively eradicate MCF-7 cells. The findings revealed that Temoporfin, when encapsulated in SiNPs, demonstrated significantly greater effectiveness compared to its naked form, with notable improvements in concentration efficiency (50 %) and exposure time efficiency (76.6 %). This research not only confirms the superior effectiveness of encapsulated Temoporfin in eliminating cancer cells but also highlights the potential of SiNPs as an efficient drug delivery system in photodynamic therapy. This sets the groundwork for more advanced strategies in cancer treatment.

Memantine inhibits cortical spreading depolarization and improves neurovascular function following repetitive traumatic brain injury.

Cortical spreading depolarization (CSD) is a promising target for neuroprotective therapy in traumatic brain injury (TBI). We explored the effect of NMDA receptor antagonism on electrically triggered CSDs in healthy and brain-injured animals. Rats received either one moderate or four daily repetitive mild closed head impacts (rmTBI). Ninety-three animals underwent craniectomy with electrocorticographic (ECoG) and local blood flow monitoring. In brain-injured animals, ketamine or memantine inhibited CSDs in 44 to 88% and 50 to 67% of cases, respectively. Near-DC/AC-ECoG amplitude was reduced by 44 to 75% and 52 to 67%, and duration by 39 to 87% and 61 to 78%, respectively. Daily memantine significantly reduced spreading depression and oligemia following CSD. Animals (N = 31) were randomized to either memantine (10 mg/kg) or saline with daily neurobehavioral testing. Memantine-treated animals had higher neurological scores. We demonstrate that memantine improved neurovascular function following CSD in sham and brain-injured animals. Memantine also prevented neurological decline in a blinded, preclinical randomized rmTBI trial.

pUL21 regulation of pUs3 kinase activity influences the nature of nuclear envelope deformation by the HSV-2 nuclear egress complex.

It is well established that the herpesvirus nuclear egress complex (NEC) has an intrinsic ability to deform membranes. During viral infection, the membrane-deformation activity of the NEC must be precisely regulated to ensure efficient nuclear egress of capsids. One viral protein known to regulate herpes simplex virus type 2 (HSV-2) NEC activity is the tegument protein pUL21. Cells infected with an HSV-2 mutant lacking pUL21 (ΔUL21) produced a slower migrating species of the viral serine/threonine kinase pUs3 that was shown to be a hyperphosphorylated form of the enzyme. Investigation of the pUs3 substrate profile in ΔUL21-infected cells revealed a prominent band with a molecular weight consistent with that of the NEC components pUL31 and pUL34. Phosphatase sensitivity and retarded mobility in phos-tag SDS-PAGE confirmed that both pUL31 and pUL34 were hyperphosphorylated by pUs3 in the absence of pUL21. To gain insight into the consequences of increased phosphorylation of NEC components, the architecture of the nuclear envelope in cells producing the HSV-2 NEC in the presence or absence of pUs3 was examined. In cells with robust NEC production, invaginations of the inner nuclear membrane were observed that contained budded vesicles of uniform size. By contrast, nuclear envelope deformations protruding outwards from the nucleus, were observed when pUs3 was included in transfections with the HSV-2 NEC. Finally, when pUL21 was included in transfections with the HSV-2 NEC and pUs3, decreased phosphorylation of NEC components was observed in comparison to transfections lacking pUL21. These results demonstrate that pUL21 influences the phosphorylation status of pUs3 and the HSV-2 NEC and that this has consequences for the architecture of the nuclear envelope.

Correction: Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine.

Correction for 'Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine' by Judith M. Curran et al., Lab Chip, 2010, 10, 1662-1670.

Toxic effects of arsenic on semen and hormonal profile and their amelioration with vitamin E in Teddy goat bucks.

The present environmental study has been planned to investigate the toxic effects of arsenic on reproductive functions of Teddy bucks as well as to examine whether these toxic effects are ameliorated by vitamin E. Sixteen adult Teddy bucks were divided randomly into four equal groups A, B, C and D with following treatment: A (control), B (sodium arsenite 5 mg kg-1 BW day-1 ), C (vit E 200 mg kg-1 BW day-1  + Arsenic 5 mg kg-1 BW day-1 ) and D (vit E 200 mg kg-1 BW day-1 ). This treatment was continued for 84 days. Semen quality parameters were evaluated weekly. Male testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH) and cortisol levels were measured through enzyme-linked immunosorbent assay (ELISA) after every 2 weeks. The data were subjected to two-way analysis of variance followed by Duncan test for multiple comparisons. Semen evaluation parameters were reduced significantly (P < 0.05) in arsenic-treated animals. The serum hormonal profile of testosterone, LH and FSH was reduced significantly (P < 0.05) in arsenic group, while the serum level of cortisol was increased. Vitamin E alleviated the toxic effects of arsenic on semen and hormonal parameters. It may be concluded from this study that sodium arsenite causes major toxicity changes in semen and hormonal profile in Teddy goat bucks and vitamin E has ameliorative effects on these toxic changes.

Review on the screening of semen by hypo-osmotic swelling test.

The hypo-osmotic swelling test (HOST) is widely used as a valuable test for determining sperm quality by evaluating the membrane integrity of spermatozoa of various domestic animals including cattle, horses and swine. The HOST has also been used as an indicator of the fertilising capacity of spermatozoa. This test is based on the swelling ability when functional spermatozoa submitted to hypo-osmotic solutions. This test is commonly used as an important parameter for the evaluation of semen due to its strong correlation with semen evaluation parameters. The objective of this review was to analyse its significance in semen evaluation, swelling of spermatozoa under various osmolarities and variations in swelling percentage under different seasons.

Factors Associated with Healthcare Utilization Among Arab Immigrants and Iraqi Refugees.

Arab migrants-both immigrants and refugees-are exposed to pre- and post- migration stressors increasing their risk for health problems. Little is known, however, about rates of, or factors associated with, healthcare utilization among these two groups. A sample of 590 participants were interviewed approximately 1 year post-migration to the United States. Factors associated with healthcare utilization, including active and passive coping strategies, were examined using logistic regressions. Compared to national healthcare utilization data, immigrants had significantly lower, and refugees had significantly higher rates of healthcare utilization. Being a refugee, being married, and having health insurance were significantly associated with medical service utilization. Among refugees, less use of psychological services was associated with the use of medications and having problem-focused (active) strategies for dealing with stress. Healthcare utilization was significantly higher among refugees, who also reported a greater need for services than did immigrants.

Severe cystic periventricular leukomalacia in a premature infant with capnocytophaga sepsis.

Capnocytophaga is an opportunistic gram-negative anaerobic bacillus found in the oropharyngeal cavity of mammals and is associated with periodontal disease in humans. Sepsis, osteomyelitis, lung abscess, endocarditis, and meningitis have been reported in humans following animal bites. Perinatal infection with Capnocytophaga is infrequent and is generally considered to have a low risk of morbidity to the mother and fetus. We report a case of neonatal Capnocytophaga sepsis associated with the development of severe cystic periventricular leukomalacia.

Living conditions in Iraq: 10 years after the US-led invasion.

In the early 1980s, Iraq was a middle-income and rapidly developing country with a well-developed health system. A few decades later - after wars, sanctions and a violent sectarian upsurge - child and maternal health indicators have deteriorated, its poverty headcount index is at 22.9% and diseases such as cholera have remerged. Today Iraq is beset by chronic political deadlock and a complexity of economic challenges; accordingly, all aspects of life are suffering, including health. Irrespective of the monumental investment to improve components of the health system, via national and international efforts, the health status of the population can only advance through resounding and synergistic effort in other aspects of life affecting health: the social determinants of health.

Factors associated with the development of chronic pain after surgery for breast cancer: a prospective cohort from a tertiary center in the United States.

Chronic pain has been shown to affect up to 60% of patients undergoing surgery for breast cancer. Besides younger age, other risk factors for the development of chronic pain have not been consistent in previous studies. The objective of the current investigation was to detect the prevalence and risk factors for the development of chronic pain after breast cancer surgery by examining a patient population from a tertiary cancer center in the United States. The study was a prospective observational cohort study. Subjects were evaluated at least 6 months after the surgical procedure. Subjects responded to the modified short form Brief pain inventory and the short form McGill pain questionnaire to identify and characterize pain. Demographic, surgery, cancer treatment, and perioperative characteristics were recorded. Propensity matching regression analysis were used to examine risk factors associated with the development of chronic pain. 300 patients were included in the study. 110 reported the presence of chronic pain. Subjects with chronic pain reported median (interquartile range [IQR]) rating of worst pain in the last 24 hours of 4 (2-5) and a median (IQR) rating on average pain in the last 24 hours of 3 (1-4) on a 0-10 numeric rating scale. Independent risk factors associated with the development of chronic pain were age, OR (95% CI) of 0.95 (0.93-0.98) and axillary lymph node dissection, 7.7 (4.3-13.9) but not radiation therapy, 1.05(0.56-1.95). After propensity matching for confounding covariates, radiation was still not associated with the development of chronic pain. Chronic pain after mastectomy continues to have a high prevalence in breast cancer patients. Younger age and axillary lymph node dissection but not radiation therapy are risk factors for the development of chronic pain. Preventive strategies to minimize the development of chronic pain are highly desirable.

Perioperative systemic magnesium to minimize postoperative pain: a meta-analysis of randomized controlled trials.

BACKGROUND: Systemic magnesium has been used to minimize postoperative pain with conflicting results by clinical studies. It remains unknown whether the administration of perioperative systemic magnesium can minimize postoperative pain. The objective of the current investigation was to evaluate the effect of systemic magnesium on postoperative pain outcomes. METHODS: A wide search was performed to identify randomized controlled trials that evaluated the effects of systemic magnesium on postoperative pain outcomes in surgical procedures performed under general anesthesia. Meta-analysis was performed using a random-effect model. Publication bias was evaluated by examining the presence of asymmetric funnel plots using Egger regression. RESULTS: Twenty randomized clinical trials with 1,257 subjects were included. The weighted mean difference (99% CI) of the combined effects favored magnesium over control for pain at rest (≤4 h, -0.74 [-1.08 to -0.48]; 24 h, -0.36 [-0.63 to -0.09]) and with movement at 24 h, -0.73 (-1.37 to -0.1). Opioid consumption was largely decreased in the systemic magnesium group compared with control, weighted mean difference (99% CI) of -10.52 (-13.50 to -7.54) mg morphine IV equivalents. Publication bias was not present in any of the analysis. Significant heterogeneity was present in some analysis, but it could be partially explained by the sole intraoperative administration of magnesium compared with the intraoperative and postoperative administration. None of the studies reported clinical toxicity related to toxic serum levels of magnesium. CONCLUSION: Systemic administration of perioperative magnesium reduces postoperative pain and opioid consumption. Magnesium administration should be considered as a strategy to mitigate postoperative pain in surgical patients.

Late-onset prosthetic valve endocarditis caused by Mycoplasma hominis, diagnosed using broad-range bacterial PCR.

We report what is believed to be the first case of late-onset prosthetic valve endocarditis caused by Mycoplasma hominis in a case of blood culture-negative endocarditis. The objective of this report is to emphasize the use of a broad-range PCR technique for bacterial 16S rRNA genes in identifying the causative pathogen, thus enabling targeted antimicrobial treatment.

Introducing dip pen nanolithography as a tool for controlling stem cell behaviour: unlocking the potential of the next generation of smart materials in regenerative medicine.

Reproducible control of stem cell populations, regardless of their original source, is required for the true potential of these cells to be realised as medical therapies, cell biology research tools and in vitro assays. To date there is a lack of consistency in successful output when these cells are used in clinical trials and even simple in vitro experiments, due to cell and material variability. The successful combination of single chemistries in nanoarray format to control stem cell, or any cellular behaviour has not been previously reported. Here we report how homogenously nanopatterned chemically modified surfaces can be used to initiate a directed cellular response, particularly mesenchymal stem cell (MSC) differentiation, in a highly reproducible manner without the need for exogenous biological factors and heavily supplemented cell media. Successful acquisition of these data should lead to the optimisation of cell selective properties of materials, further enhancing the role of nanopatterned substrates in cell biology and regenerative medicine. The successful design and comparison of homogenously molecularly nanopatterned surfaces and their direct effect on human MSC adhesion and differentiation are reported in this paper. Planar gold surfaces were patterned by dip pen nanolithography (DPN) to produce arrays of nanodots with optimised fixed diameter of 70 nanometres separated by defined spacings, ranging from 140 to 1000 nm with terminal functionalities of simple chemistries including carboxyl, amino, methyl and hydroxyl. These nanopatterned surfaces exhibited unprecedented control of initial cell interactions and subsequent control of cell phenotype and offer significant potential for the future.

Comparison of personal characteristics, tobacco use, and health states in Chaldean, Arab American, and non-Middle Eastern White adults.

This study compared and contrasted personal characteristics, tobacco use (cigarette and water pipe smoking), and health states in Chaldean, Arab American and non-Middle Eastern White adults attending an urban community service center. The average age was 39.4 (SD = 14.2). The three groups differed significantly (P < .006) on ethnicity, age, gender distribution, marital status, language spoken, education, employment, and annual income. Current cigarette smoking was highest for non-Middle Eastern White adults (35.4%) and current water pipe smoking was highest for Arab Americans (3.6%). Arab Americans were more likely to smoke both cigarettes and the narghile (4.3%). Health problems were highest among former smokers in all three ethnic groups. Being male, older, unmarried, and non-Middle Eastern White predicted current cigarette smoking; being Arab or Chaldean and having less formal education predicted current water pipe use.

Indices of hemodynamic and respiratory functions in premature infants at risk for the development of cerebral white matter injury.

OBJECTIVE: To examine potential differences in clinical risk factors, including indices of hemodynamic and respiratory functions, of premature infants developing periventricular hemorrhagic infarction (PHI) or periventricular leukomalacia (PVL). STUDY DESIGN: Indices of hemodynamic stability and respiratory function were measured prospectively during the first week of life in a cohort of 100 premature infants with respiratory distress. Maternal history was retrospectively reviewed. These data were correlated with cranial ultrasonography using one-way ANOVA, Bonferroni multiple comparisons, and Wilcoxon rank sum tests. Longitudinal analysis was performed using Generalized Estimating Equations. RESULTS: Fifty-two infants with normal cranial ultrasound studies were compared to 12 with PHI and 9 with PVL. Infants developing PHI had significantly lower birth weights, lower Apgar scores, were more often male and multiple gestations, and required more vasopressor support than infants with normal ultrasound studies. Infants with PHI had significantly worse indices of respiratory function than either normal infants or those with PVL. PVL was significantly associated with maternal chorioamnionitis, whereas PHI was not. CONCLUSION: These data suggest that there are important differences in the pathogenesis of PHI and PVL. A clear understanding of these differences is required before future preventive strategies can be formulated.

HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia.

Highly active anti-retroviral therapies, which incorporate HIV protease inhibitors, resolve many AIDS-defining illnesses. However, patients receiving protease inhibitors develop a marked lipodystrophy and hyperlipidemia. Using cultured human and rat hepatoma cells and primary hepatocytes from transgenic mice, we demonstrate that protease inhibitor treatment inhibits proteasomal degradation of nascent apolipoprotein B, the principal protein component of triglyceride and cholesterol-rich plasma lipoproteins. Unexpectedly, protease inhibitors also inhibited the secretion of apolipoprotein B. This was associated with inhibition of cholesteryl-ester synthesis and microsomal triglyceride transfer-protein activity. However, in the presence of oleic acid, which stimulates neutral-lipid biosynthesis, protease-inhibitor treatment increased secretion of apolipoprotein B-lipoproteins above controls. These findings suggest a molecular basis for protease-inhibitor-associated hyperlipidemia, a serious adverse effect of an otherwise efficacious treatment for HIV infection.

Technique for replacing the mitral valve with a pulmonary autograft: the Ross-Kabbani operation.

Replacing the mitral valve with a pulmonary autograft is an important option at the disposal of surgeons working in areas where lifelong anticoagulation is impractical. In this article we describe the technique of this operation as it has evolved through our experience with 51 patients operated on since July 1997.