Biophysical investigation of the iron in Aft1-1(up) and Gal-YAH1 Saccharomyces cerevisiae.
Aft1p is a major iron regulator in budding yeast Saccharomyces cerevisiae. It indirectly senses cytosolic Fe status and responds by activating or repressing iron regulon genes. Aft1p within the Aft1-1(up) strain has a single amino acid mutation which causes it to constitutively activate iron regulon genes regardless of cellular Fe status. This leads to elevated Fe uptake under both low and high Fe growth conditions. Ferredoxin Yah1p is involved in Fe/S cluster assembly, and Aft1p-targeted iron regulon genes are also upregulated in Yah1p-depleted cells. In this study Mössbauer, EPR, and UV-vis spectroscopies were used to characterize the Fe distribution in Aft1-1(up) and Yah1p-depleted cells. Aft1-1(up) cells grown in low Fe medium contained more Fe than did WT cells. A basal level of Fe in both WT and Aft1-1(up) cells was located in mitochondria, primarily in the form of Fe/S clusters and heme centers. The additional Fe in Aft1-1(up) cells was present as mononuclear HS Fe(III) species. These species are in a nonmitochondrial location, assumed here to be vacuolar. Aft1-1(up) cells grown in high Fe medium contained far more Fe than found in WT cells. The extra Fe was present as HS Fe(III) ions, probably stored in vacuoles, and as Fe(III) phosphate nanoparticles, located in mitochondria. Yah1p-deficent cells also accumulated nanoparticles in their mitochondria, but they did not contain HS Fe(III) species. Results are interpreted by a proposed model involving three homeostatic regulatory systems, including the Aft1 system, a vacuolar iron regulatory system, and a mitochondrial Fe regulatory system.


Compression stockings limit the incidence of postoperative lymphocele in kidney transplantation.
Lymphoceles account for considerable morbidity rates after kidney transplantation. As yet, there is no therapeutic strategy to prevent the formation of lymphoceles. The lower limb provides a large reservoir for lymphatic tissue. Prophylactic compression therapy limits tissue volume and edema formation and may therefore reduce postoperative lymph flow. In a non-randomized prospective study using a historical control group prior to 2006 as comparison from our center (2004-2008: total n=126), we found that lymphoceles are significantly diminished on the ipsilateral lower limb of the operative side when patients wear class II compression stockings (n=69) for four weeks after transplantation compared to patients achieving standard antithrombotic therapy by compression class I stockings (n=57) for thrombosis prophylaxis until full mobilization (33% versus 15%, p-value<0.05). Furthermore, a significantly lower percentage of patients needed surgical treatment of the lymphoceles for obstructive complications after class II compression (4% versus 18%, p-value<0.01). These findings were independent of the recipients' demographics, the duration of the surgical procedure, and the operating surgeon. Further studies are needed to demonstrate the usefulness of compressing stockings for the reduction of lymphoceles after kidney transplantation. This approach would not only reduce post-transplantation morbidity, but also provide an easy and cost-effective treatment without side-effects.


Dialectical Behavior Therapy Compared With Enhanced Usual Care for Adolescents With Repeated Suicidal and Self-Harming Behavior: Outcomes Over a One-Year Follow-Up.
We conducted a 1-year prospective follow-up study of posttreatment clinical outcomes in adolescents with recent and repetitive self-harm who had been randomly allocated to receive 19 weeks of either dialectical behavior therapy adapted for adolescents (DBT-A) or enhanced usual care (EUC) at community child and adolescent psychiatric outpatient clinics. Assessments of self-harm, suicidal ideation, depression, hopelessness, borderline symptoms, and global level of functioning were made at the end of the 19-week treatment period and at follow-up 1 year later. Altogether 75 of the 77 (97%) adolescents participated at both time points. Frequencies of hospitalizations, emergency department visits and other use of mental health care during the 1-year follow-up period were recorded. Change analyses were performed using mixed effects linear spline regression and mixed effect Poisson regression with robust variance. Over the 52-week follow-up period, DBT-A remained superior to EUC in reducing the frequency of self-harm. For other outcomes such as suicidal ideation, hopelessness, and depressive or borderline symptoms and for the global level of functioning, inter-group differences apparent at the 19-week assessment were no longer observed, mainly due to participants in the EUC group having significantly improved on these dimensions over the follow-up year, whereas DBT-A participants remained unchanged. A stronger long-term reduction in self-harm and a more rapid recovery in suicidal ideation, depression, and borderline symptoms suggest that DBT-A may be a favorable treatment alternative for adolescents with repetitive self-harming behavior. Treatment for Adolescents With Deliberate Self Harm; http://clinicaltrials.gov/; NCT00675129.


Fast off-line FPSE-HPLC-PDA determination of six NSAIDs in saliva samples.
A fast off-line FPSE-HPLC-PDA method has been reported that allows simultaneous clean up and determination of six non-steroidal anti-inflammatory drugs (NSAIDs) in saliva samples from healthy volunteers. Particularly, furprofen, indoprofen, ketoprofen, fenbufen, flurbiprofen, and ibuprofen were chromatographically resolved. Benzyl paraben was chosen as the internal standard (BzPB, IS). These target compounds were successfully extracted from human saliva using fabric phase sorptive extraction (FPSE) and then analysed in the liquid chromatographic system by means of a short analytical column (Symmetry C18, 75 × 4.6 mm, 3.5 µm) using acetonitrile (AcN) and phosphate buffer (PBS, 30 mM; pH = 2.5) as the mobile phases. The method, validated through the calculation of all analytical parameters in accordance of International Guidelines, was applied to real saliva sample analysis collected from informed volunteers. The proposed approach that included the use of sol-gel polytetrahydrofuran (sol-gel PTHF) sorbent immobilized on cellulose support and C18 stationary phase used in HPLC, showed high potential as a fast tool for future clinical and forensic applications. The herein reported results encourage potential future application of FPSE in the forensic field. Furthermore, the FPSE membrane was tested in dried saliva spot mode (DSS) in order to check its potential use as a sampling device, also for forensic applications.


[New insights into the seriousness of acute myocardial injury during COVID-19].
Retrospective data from Chinese cohorts published in the last few days have placed a strong emphasis on the possibility that acute myocardial injury represents a critical component in the development of serious complications in patients hospitalized with COVID-19. These analyses showed that 19-27% of hospitalized patients with moderate/severe COVID-19 developed acute myocardial injury, defined as an increase in troponin levels. Fifty-sixty percent of these patients died. The highest mortality rate was detected among patients with both progressively incremental troponin levels and a history of cardiovascular disease. Some pathophysiological reasons have been hypothesized regarding the frequently observed increase in troponin levels in patients hospitalized with COVID-19, but, at the moment, these data could already suggest some clinical management implications, also with the aim of prospectively collecting research data: a troponin dosage should be considered, as a prognostic indicator, in all patients with moderate/severe COVID-19 at hospital admission, periodically during hospitalization, and in the case of clinical deterioration. In those patients with increased troponin levels, serial determinations should be carried out to define the enzymatic trajectory and therefore also the degree of clinical attention that must necessarily be closer in those who turn out to have persistently high or increasing troponin levels. In order to reduce the overdiagnosis risk of acute myocardial injury in critically ill patients, detection of increased troponin levels should always be contextualized into a multi-parametric evaluation.


Increased Resting State Triple Network Functional Connectivity in Undergraduate Problematic Cannabis Users: A Preliminary EEG Coherence Study.
An increasing body of experimental data have suggested that aberrant functional interactions between large-scale networks may be the most plausible explanation of psychopathology across multiple mental disorders, including substance-related and addictive disorders. In the current research, we have investigated the association between problematic cannabis use (PCU) and triple-network electroencephalographic (EEG) functional connectivity. Twelve participants with PCU and 24 non-PCU participants were included in the study. EEG recordings were performed during resting state (RS). The exact Low-Resolution Electromagnetic Tomography software (eLORETA) was used for all EEG analyses. Compared to non-PCU, PCU participants showed an increased delta connectivity between the salience network (SN) and central executive network (CEN), specifically, between the dorsal anterior cingulate cortex and right posterior parietal cortex. The strength of delta connectivity between the SN and CEN was positively and significantly correlated with higher problematic patterns of cannabis use after controlling for age, sex, educational level, tobacco use, problematic alcohol use, and general psychopathology (rp = 0.40, p = 0.030). Taken together, our results show that individuals with PCU could be characterized by a specific dysfunctional interaction between the SN and CEN during RS, which might reflect the neurophysiological underpinnings of attentional and emotional processes of cannabis-related thoughts, memories, and craving.


[Antitumoral action of interferons and interleukins in combination with radiotherapy. Part I: immunologic basis].
During the last 2 decades, cytokines such as interferons (IFN) have been used to modulate tumor response in radiotherapy. Initially, the focus was on antiviral and radiosensitizing effects of interferons but increasingly, the function of interferons and interleukins (IL) within the immune response to tumor cells is becoming important. The cellular immune response toward tumor cells is reviewed. The role of cytokines in antigen presentation and activation of effector cells and their interactions with radiation are described. Preclinical strategies of the antitumor action of cytokines are presented and discussed based on the induction of IFN-gamma by IL-12. Recent advances in immunology have demonstrated the importance of local interactions between antigen-presenting cells (APC) and effector cells such as natural killer (NK) cells and T-lymphocytes for an effective immune reaction against tumors. Interferons stimulate such interactions, while IL-2 plays a central role in the activation of NK cells and T-lymphocytes. The interactions between APC and effector cells are suppressed by many tumors but can be stimulated by irradiation. Since systemic application of interferons is quite toxic, present strategies aim at local expression, e. g., the induction of IFN-gamma expression in Th1 cells by IL-12. The improved understanding of immunologic mechanisms has emphasized the role of the cytokine network in the interaction between tumor cells and effector cells such as NK cells and T-lymphocytes. This opens new possibilities for the application of cytokines as biological response modifiers, which may eventually help widening the therapeutic window in radiotherapy.


Field localization and enhanced Second-Harmonic Generation in silicon-based microcavities.
High-quality amorphous Silicon Nitride (a-Si(1-x)N(x):H) Fabry-Pérot microcavities can show resonant surface Second Harmonic Generation (SHG) effect. We consider two different layouts of planar microcavities with almost identical linear reflectance and show how the structure geometry can strongly affect SHG yield. In particular, a difference of more than one order of magnitude in the SHG intensity is observed when the fundamental beam is tuned at the cavity resonance frequency. We explain this finding on the basis of a theoretical model taking into account the spatial distribution of the electric fields of the pump and harmonic frequencies inside the structure. A satisfactory matching of experimental data with the theoretical model is obtained by considering the source of second-order nonlinearity as limited to surface contributions.


The impact of vaping ethanol-containing electronic cigarette liquids on roadside impairment investigations.
Legal professionals and others have suggested that vaping electronic cigarettes (e-cigs) prior to or during ethanol breath testing may produce false positives. Preliminary breath tests (PBTs) and evidentiary breath tests (EBTs) measure ethanol in exhaled breath and standardized field sobriety tests (SFSTs) are used to assess impairment. Ethanol has been identified in e-cig liquids (e-liquids). Presented are a series of experiments designed to determine the mechanics of vaping ethanol using an e-cig and the effects of vaping ethanol on the SFSTs and breath tests used by law enforcement officers (LEO). Twelve participants (five females, age: 21-32 and seven males, age: 21-55), vaped either one or ten puffs of an e-liquid (0% or 20% ethanol). LEOs assessed impairment using SFSTs (12 and 42 min), PBTs (<1, 27, 32, 37 and 57 min) and EBTs (2, 29, 34, 39 and 59 min) post-vaping. A self-assessment test was administered post-vaping (22 and 52 min). Baseline responses for all measures were collected prior to vaping. Results demonstrated that ethanol in the e-liquids was aerosolized by e-cigs and produced particles that could reach the deep lung tissue based on mean-mass diameter. Ethanol was detected by PBT <3 min after participants vaped one (0.007-0.030 g/210 L) or ten puffs (013-0.074 g/210 L) of a 20% ethanol e-liquid. Ethanol was not detected by PBT at any subsequent time point. Ethanol was not detected by the EBT under any condition. Impairment was not indicated by the SFST. Some subjective effects were reported, but few statistically significant differences between conditions were indicated. A wait period prior to ethanol breath testing is not always mandated, depending on jurisdiction, or observed in all applications, such as workplace testing. The results demonstrate that a wait period must be employed to prevent vaping-related false-positive breath ethanol results.


Multicenter evaluation of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization method for simultaneous dual-color identification of C. albicans and C. glabrata directly from blood culture bottles.
We evaluated the performance of the Candida albicans/Candida glabrata peptide nucleic acid fluorescent in situ hybridization (PNA FISH) method, a rapid two-color assay for detection of C. albicans and C. glabrata, in a multicenter study. The assay is designed for use directly from positive blood culture bottles in a FISH format. Intact, fixed cells are labeled fluorescent green (C. albicans) or fluorescent red (C. glabrata) by rRNA hybridization of fluorophore-labeled PNA probes. Results are available <3 h after cultures signal positive. An evaluation of 197 routine blood culture bottles newly positive for yeast by Gram staining was performed at five hospitals. The sensitivities of detection for C. albicans, and C. glabrata were 98.7% (78/79) and 100% (37/37), respectively, and the specificity for both components of the assay was 100% (82/82). The assay was also evaluated with 70 fungal reference strains and was challenged in the BacT/ALERT microbiological detection system with spiked blood culture bottles. These results support the use of the assay for rapid, simultaneous identification of C. albicans and C. glabrata in positive blood culture bottles. This rapid assay may aid in the selection of initial antifungal drugs, leading to improved patient outcomes.


Effects of psychiatric medications on sleep and sleep disorders.
Insomnia is a significant public health concern that has prompted substantial efforts to develop treatment and management strategies. A significant proportion of complaints of insomnia are related to psychiatric conditions such as anxiety disorders and depression, and treatments for these disorders are known to exert both direct and indirect benefits on sleep as well as some negative effects on sleep and sleep physiology. Insomnia is also a prominent symptom of a number of other psychiatric disorders, including schizophrenia and bipolar disorder. The observed impact of a variety of psychiatric medications on insomnia has prompted an empirically derived practice of treating non-psychiatric disorder-related insomnia with psychiatric medications by clinicians searching for alternatives to established medication treatments for primary insomnia. This article aims to review the evidence of the impact of psychiatric medications on sleep physiology, sleep disorders in psychiatric conditions, and on primary sleep disorders. The potential for exploiting the relevant pharmacological mechanisms of action in drug development for primary insomnia will be addressed as well.


Association between exposome score for schizophrenia and functioning in first-episode psychosis: results from the Athens first-episode psychosis research study.
Evidence suggests that environmental factors not only increase psychosis liability but also influence the prognosis and outcomes of psychotic disorders. We investigated temporal and cross-sectional associations of a weighted score of cumulative environmental liability for schizophrenia - the exposome score for schizophrenia (ES-SCZ) - with functioning in first-episode psychosis (FEP). Data were derived from the baseline and 1-month assessments of the Athens FEP Research Study that enrolled 225 individuals with FEP. The Global Assessment of Functioning (GAF) and the Personal and Social Performance Scale (PSP) were used to measure social, occupational, and psychological functioning. The ES-SCZ was calculated based on the previously validated method. ES-SCZ was associated with the total scores of GAF and PSP at baseline and 1-month assessments. These findings remained significant when accounting for several associated alternative explanatory variables, including other environmental factors (obstetric complications, migration, ethnic minority), clinical characteristics (duration of untreated psychosis, symptom severity, previous antipsychotic use), and family history of psychosis, demonstrating that the association between ES-SCZ and functioning is over and above other risk factors and cannot be explained by symptom severity alone. Functioning improved from baseline to 1-month assessment, but no significant ES-SCZ-by-time interaction was found on functioning, indicating that functioning changes were not contingent on ES-SCZ. Our findings suggest that rather than a predictor of functional improvement, ES-SCZ represents a stable severity indicator that captures poor functioning in early psychosis. Environmental risk loading for schizophrenia (ES-SCZ) can be beneficial for clinical characterization and incorporated into transdiagnostic staging models.


Biochemically functionalized probes for cell-type-specific targeting and recording in the brain.
Selective targeting and modulation of distinct cell types and neuron subtypes is central to understanding complex neural circuitry and could enable electronic treatments that target specific circuits while minimizing off-target effects. However, current brain-implantable electronics have not yet achieved cell-type specificity. We address this challenge by functionalizing flexible mesh electronic probes, which elicit minimal immune response, with antibodies or peptides to target specific cell markers. Histology studies reveal selective association of targeted neurons, astrocytes, and microglia with functionalized probe surfaces without accumulating off-target cells. In vivo chronic electrophysiology further yields recordings consistent with selective targeting of these cell types. Last, probes functionalized to target dopamine receptor 2 expressing neurons show the potential for neuron-subtype-specific targeting and electrophysiology.


Pediatric pedestrian injuries and associated hospital resource utilization in the United States, 2003.
The objective was to calculate national estimates of pedestrian-related hospitalizations and associated use of healthcare resources among children <or=19 years of age and to explore the effects of sociodemographic, hospital-related factors, and injury severity on total charges and lengths of stay (LOS) in the United States. Data from the 2003 Healthcare Cost and Utilization Project Kids' Inpatient Database were used. The sample included patients <or=19 years hospitalized with pedestrian-related injuries, from 3,438 hospitals in 36 states. National estimates of pedestrian-associated hospitalizations, rates, resource use, injury severity, and demographics were calculated. Potentially significant covariate associations were studied using hospital charges and LOS. In 2003, 9,172 pedestrian-associated hospitalizations occurred among children <or=19 years in the United States, resulting in USD 290.8 million (standard deviation [SD] = USD 23.6 million) in inpatient charges and 44,895 (SD = 2,964) days of hospitalization. Mean (SD) hospital charges and LOS were $32,059 ($74,778) days and 4.9 (10.9) days, respectively. Thirty-six percent of patients suffered a traumatic brain injury, and 21% sustained severe injury with an injury severity scale score >or=16. A traffic-related event was the cause of 92.7% of hospitalizations. Older age, higher injury severity, urban and Western hospital location, children's hospital type, and longer LOS were significantly associated with higher total hospital charges. Older age and higher injury severity were significantly associated with longer LOS. Pediatric pedestrian injuries contribute substantially to the healthcare resource burden in the United States, accounting for approximately 45,000 days of hospitalization and >USD 290 million in inpatient charges annually.


Over-expression of the human EAAT2 glutamate transporter within neurons of mouse organotypic hippocampal slice cultures leads to increased vulnerability of CA1 pyramidal cells.
Excitatory amino acid transporters (EAATs) maintain the balance between pathological and physiological conditions by limiting the extracellular concentration of glutamate within the CNS and thus preventing excitotoxic injury. The loss of EAAT2 has been associated with the development of neurological diseases such as amyotrophic lateral sclerosis. It has therefore been suggested that the over-expression of specific EAATs may provide some degree of neuroprotection. However, the inability to isolate and study the function of the different EAAT isoforms in a cell type-specific manner has made it difficult to determine the exact contribution of individual EAATs toward neuroprotection or neurodegeneration in the context of excitotoxic injury. To address this question, we transduced hippocampal slice cultures from 1-week-old C57B/6 mice with recombinant adeno-associated virus carrying an EAAT2 gene expression cassette. EAAT2 gene expression was driven in neurons with the neuron-specific enolase promoter. Using this model system, we were able to induce a significant increase in the expression of functional EAAT2. Consequently, a significant increase in CA1 neuronal damage was observed in slices over-expressing EAAT2 in neurons following an acute exposure to exogenous glutamate. These data suggest that the increased expression of EAAT2 within neurons may contribute to neurodegeneration.


[Problems of diagnosis and treatment of atypical mastoiditis].
The specific features of the diagnosis and therapy of the dry form of atypical mastoiditis are discussed. Of great diagnostic importance were local changes in the mastoid area, otoscopic signs in the posterior-superior tympanic membrane and bone compartment of the auditory meatus, hearing impairment, thermographic signs of purulent-destructive lesions in the antrum and other cells of the mastoid process, and X-ray symptoms of bone destruction of the mastoid process. It is obvious that the clinical picture and development of atypical mastoiditis are closely related to the age and reactivity of the patient, irrational use of antibiotics and physiotherapy, concomitant diseases, especially endocrine pathologies.


The gut microbiota regulates acute foreign body reaction and tissue repair after biomaterial implantation.
We hypothesized that the host microbiome may influence foreign body responses following biomaterial implantation. To test this, we implanted a variety of clinically relevant biomaterials into germ-free or antibiotic-treated mice. Surprisingly, these mice displayed less fibrous tissue deposition, reduced host cell recruitment to the implant site, and differential expression of angiogenic and inflammatory markers. These observations were reversed upon fecal microbiome reconstitution, confirming a causal role of the host microbiome. In a clinically relevant disease model, microbiome-depleted mice cleared hyaluronic acid and bone marrow mononuclear cells from ischemic hind limb tissues more slowly, resulting in an improved therapeutic response. Findings were confirmed in pigs which showed reduced fibrotic responses to a variety of implanted materials. Lastly, we profiled changes in the host microbiome following material implantation, implicating several key bacteria phyla.


DNA methylation changes in glial cells of the normal-appearing white matter in Multiple Sclerosis patients.
Multiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby limiting treatment options. We aimed to examine DNA methylation, a stable epigenetic mark of genome activity, in glial cells to capture relevant molecular changes underlying MS neuropathology. We profiled DNA methylation in nuclei of non-neuronal cells, isolated from 38 post-mortem normal-appearing white matter (NAWM) specimens of MS patients (n = 8) in comparison to white matter of control individuals (n = 14), using Infinium MethylationEPIC BeadChip. We identified 1,226 significant (genome-wide adjusted P-value < 0.05) differentially methylated positions (DMPs) between MS patients and controls. Functional annotation of the altered DMP-genes uncovered alterations of processes related to cellular motility, cytoskeleton dynamics, metabolic processes, synaptic support, neuroinflammation and signaling, such as Wnt and TGF-β pathways. A fraction of the affected genes displayed transcriptional differences in the brain of MS patients, as reported by publically available transcriptomic data. Cell type-restricted annotation of DMP-genes attributed alterations of cytoskeleton rearrangement and extracellular matrix remodelling to all glial cell types, while some processes, including ion transport, Wnt/TGF-β signaling and immune processes were more specifically linked to oligodendrocytes, astrocytes and microglial cells, respectively. Our findings strongly suggest that NAWM glial cells are highly altered, even in the absence of lesional insult, collectively exhibiting a multicellular reaction in response to diffuse inflammation.


Amphetamine withdrawal produces region-specific and time-dependent changes in connexin36 expression in rat brain.
Repeated amphetamine treatment produces a long-lasting augmentation of locomotor behavior in rats, a phenomenon known as behavioral sensitization. This process is thought to be a correlate of the addictive process in humans, and it is believed that there are drug-induced neuroadaptations that underlie these behavioral changes. One mechanism by which amphetamine can alter brain function is by affecting direct intercellular communication between neurons via gap junctions. The purpose of the present study was to examine the effect of an amphetamine treatment regimen known to produce changes in dye coupling between neurons, a functional correlate of gap junction function, on the expression of the neuronal gap junction-forming protein, connexin36. Here we report that withdrawal from an extended amphetamine regimen produces region-specific and time-dependent changes in connexin36 expression in rat nucleus accumbens and prefrontal cortex, brain regions known play roles in sensitization and addiction. This is, to our knowledge, the first demonstration of pharmacological manipulation of connexin36 in vivo.


Traumatic pericallosal artery aneurysm: a rare complication of transcallosal surgery. Case report.
Traumatic intracranial aneurysms are rare in adults but account for up to 33% of all aneurysms encountered in a pediatric population. The most common location of such lesions in children is the pericallosal or adjacent branch of the anterior cerebral artery, where a head impact exerts sudden decelerating shearing forces on the arteries tethered on the brain surface against an immobile falx cerebri, weakening the arterial wall. This action can lead to dissection of the damaged vascular layers, with resultant expansion of the affected site into a fusiform aneurysm. Pericallosal aneurysms following a penetrating intracranial injury have also been described, and the resultant lesion in some cases can be a pseudoaneurysm. The incidence of iatrogenic pericallosal artery aneurysms, however, is extremely rare. The authors describe the first reported case of a traumatic pericallosal artery aneurysm following transcallosal surgery. This 6-year-old boy underwent resection of a hypothalamic pilocytic astrocytoma, which was approached via the transcallosal corridor. A follow-up magnetic resonance image obtained within 1 year of surgery disclosed a small flow void off the right pericallosal artery, which was initially interpreted as residual tumor. Serial investigations showed the lesion enlarging over time, and subsequent angiography revealed a round 7-mm pericallosal artery aneurysm with an irregularly shaped 2- to 3-mm lumen. The aneurysm was difficult to treat with clip reconstruction or suturing of the affected segment, and an excellent outcome was ultimately achieved with resection of the lesion and autogenous arterial graft interposition. The authors also discuss the likely pathophysiology of the aneurysm and the surgical procedures undertaken to treat it.


[Effect of insulin and adrenaline on the respiration and glycolysis of the skeletal muscle of frog].
It was shown in the experiments on isolated sartorius muscles of the frog that insulin increased endogenous respiration by 10 mm3 O2 hr per gramm of wet weight. The effect of insulin and epinephrine on respiration is additive. Insulin in middle (5--50 milliunits/ml) and low, physiological, (50 microunits/ml) concentration does not induce acceleration of glycolyses. The conclusion was confirmed that the increase of the endogenous respiration by insulin cannot be accounted for by the mobilization of the substrate of glycolysis. In the presence of epinephrine, the low concentration (50 microunits/ml) of insulin induces the decrease of the content of glucose-6-phosphate. It is probably connected with the influence of insulin on the concentration level of the cAMP.


The cavernous sinus in cluster headache - a quantitative structural magnetic resonance imaging study.
Background It has been hypothesized that a constitutionally narrow cavernous sinus might predispose individuals to cluster headache. Cavernous sinus dimensions, however, have never been assessed. Methods In this case-control study, we measured the dimensions of the cavernous sinus, skull base, internal carotid and pituitary gland with high-resolution T2-weighted magnetic resonance imaging in 25 episodic, 24 chronic and 13 probable cluster headache patients, 8 chronic paroxysmal hemicrania patients and 22 headache-free controls. Dimensions were compared between groups, correcting for age, sex and transcranial diameter. Results On qualitative inspection, no relevant pathology or anatomic variants that were previously associated with cluster headache or chronic paroxysmal hemicranias were observed in the cavernous sinus or paracavernous structures. The left-to-right transcranial diameter at the temporal fossa level (mean ± SD) was larger in the headache groups (episodic cluster headache: 147.5 ± 7.3 mm, p = 0.044; chronic cluster headache: 150.2 ± 7.3 mm, p < 0.001; probable cluster headache: 146.0 ± 5.3 mm, p = 0.012; and chronic paroxysmal hemicrania: 145.2 ± 9.4 mm, p = 0.044) compared with controls (140.2 ± 8.0 mm). After adjusting for transcranial diameter and correcting for multiple comparisons, there were no differences in the dimensions of the cavernous sinus and surrounding structures between headache patients and controls. Conclusion Patients with cluster headache or chronic paroxysmal hemicrania had wider skulls than headache-free controls, but the proportional dimensions of the cavernous sinus were similar.


Musculoskeletal pain and risk for falls in older disabled women living in the community.
To determine whether musculoskeletal pain increased risk for falls in older women with disabilities. Prospective population-based cohort study. The city and county of the eastern area of Baltimore. One thousand two women aged 65 and older, participants in the Women's Health and Aging Study, representing the one-third of older women who were living at home with disabilities, followed semiannually for 3 years beginning in 1991. Pain was categorized into four groups according to severity and location. Widespread pain was defined as pain in the upper and lower extremities and in the axial skeletal region, with moderate to severe pain in at least one region (> or = 4 on a 10-point numeric rating scale, 10 = excruciating pain). Moderate to severe lower extremity pain that did not meet criteria for widespread pain was the next category. The reference category was no pain or mild pain in one site. The additional category of "other pain" was pain that did not fit into the other three groups. The occurrence of falls and fall-related injuries were assessed at each interview. Of the 940 women who participated in at least one follow-up examination, 39% fell in first year; of the survivors, 36% fell in Year 2, and 39% in Year 3. After adjusting for several major risk factors for falls, women with widespread pain had an increased likelihood of falling during follow-up (adjusted odds ratio (AOR) = 1.66, 95% confidence interval (CI) = 1.25-2.21) compared with those with no or mild pain in only one musculoskeletal site. Women who had other musculoskeletal pain but not widespread pain or lower extremity pain also had an increased risk of falls (AOR = 1.36, 95% CI = 1.02-1.82). Among women with musculoskeletal pain, risk for falls was lower in those who used daily analgesic medication. Risk for recurrent falls and self-reported fractures due to falls was also elevated in women with musculoskeletal pain, most consistently in women with widespread pain. Musculoskeletal pain, particularly widespread pain, is a substantial risk factor for falls in older women with disabilities. These findings add an important dimension to our understanding of the multifactorial processes leading to falls in older persons.


Generalization of Perceptual Learning of Degraded Speech Across Talkers.
We investigated whether perceptual learning of noise-vocoded (NV) speech is specific to a particular talker or accent. Four groups of listeners (n = 18 per group) were first trained by listening to 20 NV sentences that had been recorded by a talker with either the same native accent as the listeners or a different regional accent. They then heard 20 novel NV sentences from either the native- or nonnative-accented talker (test), in a 2 × 2 (Training Talker per Accent × Test Talker per Accent) design. Word-report scores at test for participants trained and tested with the same (native- or nonnative-accented) talker did not differ from those for participants trained with 1 talker per accent and tested on another. Learning of NV speech generalized completely between talkers. Two additional experiments confirmed this result. Thus, when listeners are trained to understand NV speech, they are not learning talker- or accent-specific features but instead are learning how to use the information available in the degraded signal. The results suggest that people with cochlear implants, who experience spectrally degraded speech, may not be too disadvantaged if they learn to understand speech through their implant by listening primarily to just 1 other talker, such as a spouse.


Compartment syndromes of the hand.
We retrospectively reviewed the records of nineteen patients who had been managed with fasciotomy because of compartment syndrome of the hand. The patients were five months to sixty-seven years old and included ten adults and nine children. Seventeen patients were followed for an average of twenty-one months (range, one to fifty-eight months), one patient was lost to follow-up after discharge, and one patient died four days postoperatively. All of the patients had a tense, swollen hand and elevated pressure in at least one interosseous compartment. Eight patients also had a compartment syndrome of the forearm. The compartment syndromes developed after intravenous injections (eleven patients); after a gunshot wound, a crush injury, or a complication related to the use of an arterial line (two patients each); and after a complication related to an arthrodesis of the wrist or a crush injury due to prolonged pressure on the upper extremity secondary to a drug overdose (one patient each). Fifteen patients had an obtunded sensorium-either because of a serious illness or injury or secondary to prolonged anesthesia-when the compartment syndrome was recognized. In thirteen of these patients, including eight children and five adults, the compartment syndrome developed because of a complication related to the intravenous or intra-arterial administration of drugs. Carpal tunnel release and decompression of the involved compartments led to a satisfactory result for thirteen of the seventeen patients who were followed. The remaining four patients (including two children who had an amputation, one child who had impaired function of the hand secondary to brain damage, and one adult who had extensive involvement of the forearm and complete loss of function of the hand) had a poor result. All four of these patients had been obtunded when the compartment syndrome developed. The treating physician should maintain a high index of suspicion for a compartment syndrome of the hand when managing seriously ill, obtunded patients-particularly children-who are receiving multiple intravenous or intra-arterial injections.


A longitudinal epidemiologic study of signs and symptoms of temporomandibular disorders from 15 to 35 years of age.
To study the development over 20 years of signs and symptoms of temporomandibular disorders (TMD) in an epidemiologic sample and to analyze possible correlations between these signs and symptoms and some other variables. The original group comprised 135 randomly selected 15-year-old subjects who were examined clinically and by means of a questionnaire for signs and symptoms of TMD. The examination was repeated after 5, 10, and 20 years by the same methods. After 20 years, when the original group had reached the age of 35 years, 124 individuals (92%) could be traced, and they were sent a questionnaire and invited for a clinical examination. The response rate was high: 114 subjects (92%) completed and returned the questionnaire, and 100 subjects (81%) attended the clinical examination. There was a substantial fluctuation of both reported symptoms and clinically recorded signs over the 20-year period, but progression to severe pain and dysfunction of the masticatory system was rare. In both the 15-year-old and 35-year-old subjects, 13% reported 1 or more frequent TMD symptoms. At age 35, only 3 subjects (3%) were classified as having severe or moderate clinical signs of dysfunction according to the Helkimo Index, fewer than in previous investigations. Women reported TMD symptoms and headache and had muscle tenderness and joint sounds more often than men. Correlations between the studied variables were mainly weak. Among the highest correlations found (rs = 0.4) were those between reported clenching and bruxing habits and TMJ sounds and jaw fatigue. In this epidemiologic sample followed from age 15 to 35 years, a substantial fluctuation of TMD signs and symptoms was found over time. Progression to severe pain and dysfunction was extremely rare.


Regulation of MHC class II expression and antigen processing in murine and human mesenchymal stromal cells by IFN-gamma, TGF-beta, and cell density.
Mesenchymal stromal cells (MSC) possess immunosuppressive properties, yet when treated with IFN-gamma they acquire APC functions. To gain insight into MSC immune plasticity, we explored signaling pathways induced by IFN-gamma required for MHC class II (MHC II)-dependent Ag presentation. IFN-gamma-induced MHC II expression in mouse MSC was enhanced by high cell density or serum deprivation and suppressed by TGF-beta. This process was regulated by the activity of the type IV CIITA promoter independently of STAT1 activation and the induction of the IFN regulatory factor 1-dependent B7H1/PD-L1 encoding gene. The absence of direct correlation with the cell cycle suggested that cellular connectivity modulates IFN-gamma responsiveness for MHC II expression in mouse MSC. TGF-beta signaling in mouse MSC involved ALK5 and ALK1 TGF-beta RI, leading to the phosphorylation of Smad2/Smad3 and Smad1/Smad5/Smad8. An opposite effect was observed in human MSC where IFN-gamma-induced MHC II expression occurred at the highest levels in low-density cultures; however, TGF-beta reduced IFN-gamma-induced MHC II expression and its signaling was similar as in mouse MSC. This suggests that the IFN-gamma-induced APC features of MSC can be modulated by TGF-beta, serum factors, and cell density in vitro, although not in the same way in mouse and human MSC, via their convergent effects on CIITA expression.


Infrastructure development for human cell therapy translation.
The common conception of a drug is that of a chemical with defined medicinal effect. However, cells used as drugs remain critical to patient care. Cell therapy's origins began with the realization that complex tissues such as blood can retain function when transplanted to the patient. More complex transplantation followed, culminating with the understanding that transplantation of some tissues such as bone marrow may act medicinally. Administration of cells with an intended therapeutic effect is a hallmark of cellular therapy. While cells have been used as drugs for decades, testing a specific therapeutic effect of cells has begun clinical testing relatively recently. Lessons learned during the establishment of blood banking (including the importance of quality control, process control, sterility, and product tracking) are key components in the assurance of the safety and potency of cell therapy preparations. As more academic medical centers and private companies move toward exploiting the full potential of cells as drugs, needs arise for the development of the infrastructure necessary to support these investigations. Careful consideration of the design of the structure used to manufacture is important in terms of the significant capital outlay involved and the facility's role in achieving regulatory compliance. This development perspective describes the regulatory environment surrounding the infrastructure support for cell therapy and practical aspects for design consideration with particular focus on those activities associated with early clinical trials.


Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein.
Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 diverse target genes. In the eye, retinol is also activated to 11-cis-retinal, the visual chromophore. We generated RBP knockout mice (RBP(-/-)) by gene targeting. These mice have several phenotypes. Although viable and fertile, they have reduced blood retinol levels and markedly impaired retinal function during the first months of life. The impairment is not due to developmental retinal defect. Given a vitamin A-sufficient diet, the RBP(-/-) mice acquire normal vision by 5 months of age even though blood retinol levels remain low. Deprived of dietary vitamin A, vision remains abnormal and blood retinol declines to undetectable levels. Another striking phenotype of the mutant mice is their abnormal retinol metabolism. The RBP(-/-) mice can acquire hepatic retinol stores, but these cannot be mobilized. Thus, their vitamin A status is extremely tenuous and dependent on a regular vitamin A intake. Unlike wild-type mice, serum retinol levels in adult RBP(-/-) animals become undetectable after only a week on a vitamin A-deficient diet and their retinal function rapidly deteriorates. Thus RBP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietary intake, but is otherwise dispensable for the delivery of retinol to tissues.


[LDL apheresis in the treatment of familial hypercholesterolemia].
Low density lipoprotein (LDL) apheresis is one of the main therapeutic models for homozygous and severe heterozygous form of the familial hypercholesterolemia patients. Anti-atherogenic, anti-thrombogenic and anti-inflammatory effects of apheresis has positive effects on prevention of cardiovascular disease by improving of the tissue perfusion. Blood LDL cholesterol levels, response to medical therapy, presence or severity of the coronary heart disease are the main determinants of the apheresis indications. Except bleeding tendency and heparin sensitivity, there are no contraindications. In parallel with low body weight, pediatric practice could be more risky; however, there is also a 3.5-year-old apheresis application without problems. The first successful plasmapherisis for the removal of LDL cholesterol in circulation was performed in 1975. Plasmapheresis, today, is only emergency treatment model in cases of life-threatening hyperchylomicronemia. New apheresis techniques have rather high selectivity for atherogenic lipoproteins containing apolipoprotein-B100. If existing apheresis technique has low effectiveness (acute decrease of LDL cholesterol <60%), primarily calculated plasma or blood treatment volumes could be increased and then technique could be switched to other one. Early identification of the affected patients and aggressive LDL apheresis treatment significantly reduce the burden of cardiovascular disease in children and adult patients with homozygous or severe heterozygous familial hypercholesterolemia.


Indoor positioning in wireless local area networks with online path-loss parameter estimation.
Location based services are gathering an even wider interest also in indoor environments and urban canyons, where satellite systems like GPS are no longer accurate. A much addressed solution for estimating the user position exploits the received signal strengths (RSS) in wireless local area networks (WLANs), which are very common nowadays. However, the performances of RSS based location systems are still unsatisfactory for many applications, due to the difficult modeling of the propagation channel, whose features are affected by severe changes. In this paper we propose a localization algorithm which takes into account the nonstationarity of the working conditions by estimating and tracking the key parameters of RSS propagation. It is based on a Sequential Monte Carlo realization of the optimal Bayesian estimation scheme, whose functioning is improved by exploiting the Rao-Blackwellization rationale. Two key statistical models for RSS characterization are deeply analyzed, by presenting effective implementations of the proposed scheme and by assessing the positioning accuracy by extensive computer experiments. Many different working conditions are analyzed by simulated data and corroborated through the validation in a real world scenario.


Sequence-dependent DNA helical rise and nucleosome stability.
Nucleosomes are the basic structural units of eukaryotic chromatin and play a key role in regulation of gene expression. After resolution of the nucleosome structure, the bipartite nature of this particle has revealed itself and has disclosed the presence, on the histone surface, of a symmetric distribution of positive charges, able to interact with their negative DNA phosphate counterpart. We analyzed helical steps in known nucleosomal DNA sequences, observing a significant relationship between their symmetric distribution and nucleosome stability. Synthetic DNA sequences able to form stable nucleosomes were used to compare distances on the left and on the right side of the nucleosomal dyad axis, where DNA phosphates and charged residues of the (H3H4)2-tetramer interact. We observed a linear relationship between coincidence of distances and nucleosome stability, i. e., the more symmetric these distances the more stable the nucleosome. Curves related to this symmetric distribution along the DNA sequence identify preferential sites for positioning of the dyad axis, which we termed palinstases. The comparison of our data with known nucleosome positions in archaeal and eukaryotic sequences shows many coincidences of location. Sequences that impair nucleosome formation and DNase I hypersensitive sites yield curves with a lower degree of symmetry. Analysis performed on DNA tracts of promoters close to the transcription start and termination sites identified peculiar patterns: in particular low affinity for nucleosome binding at the transcription start site and a high affinity exactly at the transcription termination site, suggesting a major role of nucleosomes in the termination of transcription.


A review of psychiatric co-morbidity described in genetic and immune mediated movement disorders.
Psychiatric symptoms are an increasingly recognised feature of movement disorders. Recent identification of causative genes and autoantibodies has allowed detailed analysis of aetiologically homogenous subgroups, thereby enabling determination of the spectrum of psychiatric symptoms in these disorders. This review evaluates the incidence and type of psychiatric symptoms encountered in patients with movement disorders. A broad spectrum of psychiatric symptoms was identified across all subtypes of movement disorder, with depression, generalised anxiety disorder and obsessive-compulsive disorder being most common. Psychosis, schizophrenia and attention deficit hyperactivity disorder were also identified, with the psychiatric symptoms often predating onset of the motor disorder. The high incidence of psychiatric symptoms across such a wide range of movement disorders suggests a degree of common or overlapping pathogenic mechanisms. Our review demonstrates the need for increased clinical awareness of such co-morbidities, which should facilitate early neuropsychiatric intervention and allied specialist treatment for patients.


Traditional male ideology and service system involvement among drug-involved men who perpetrate intimate partner violence: a longitudinal study.
The purpose of this study is to examine the extent to which drug-involved men who perpetrate male-to-female intimate partner violence (IPV) are engaged with various formal service systems as well as whether adherence to traditional male ideologies-thought to drive perpetration of male-to-female IPV-affects help-seeking behavior. This study also seeks to redress a gap in the research literature stemming from the general reliance on batterers intervention programs to acquire samples of IPV perpetrators. A sample of 126 men receiving methadone maintenance treatment who reported perpetrating IPV against a female partner participated in this longitudinal study. A large majority (88%) of participants reported use of additional services beyond methadone treatment (e.g., medical, employment/ vocational, etc.). Using generalized linear modeling, we found that greater endorsement of traditional male ideologies significantly predicted lower subsequent service utilization overall, except for legal services, for which there was a significant positive association. These findings suggest targeted assessment and engagement strategies may be required to involve a greater number of drug-involved men who perpetrate IPV with a wider spectrum of health and social services.


Predicting possible effects of H2S impurity on CO2 transportation and geological storage.
For CO(2) geological storage, permitting impurities, such as H(2)S, in CO(2) streams can lead to a great potential for capital and energy savings for CO(2) capture and separation, but it also increases costs and risk management for transportation and storage. To evaluate the cost-benefits, using a recently developed model (Ji, X.; Zhu, C. Geochim. Cosmochim. Acta 2012, 91, 40-59), this study predicts phase equilibria and thermodynamic properties of the system H(2)S-CO(2)-H(2)O-NaCl under transportation and storage conditions and discusses potential effects of H(2)S on transportation and storage. The prediction shows that inclusion of H(2)S in CO(2) streams may lead to two-phase flow. For H(2)S-CO(2) mixtures, at a given temperature, the bubble and dew pressures decrease with increasing H(2)S content, while the mass density increases at low pressures and decreases at high pressures. For the CO(2)-H(2)S-H(2)O system, the total gas solubility increases while the mass density of the aqueous solution with dissolved gas decreases. For the CO(2)-H(2)S-H(2)O-NaCl system, at a given temperature, pressure and NaCl concentration, the solubility of the gas mixture in aqueous phase increases with increasing H(2)S content and then decreases, while the mass density of aqueous solution decreases and may be lower than the mass density of the solution without gas dissolution.


Distinct epitopes recognized by I-Ad-restricted T-cell clones within antigenic site E on influenza virus hemagglutinin.
A total of 14 I-Ad-restricted helper T-cell clones specific for the hemagglutinin (HA) molecule of influenza virus were isolated from spleens of BALB/c or (BALB/c X C57BL/10)F1 mice immunized with the H3 subtype influenza virus A/Memphis/71 (Mem 71) and from lymph nodes of BALB/c mice primed with purified HA. The specificity of these T-cell clones was assessed in proliferation assays by reactivity with naturally occurring strains of viruses that arose by antigenic drift and contain known amino acid sequence changes in HA and with a panel of monoclonal antibody (MAb)-selected mutants of Mem 71 with single amino acid substitutions in HA. The HA genes of those mutant viruses that failed to stimulate one or more of the T-cell clones were sequenced. The clones could be allocated to at least four groups, each group having a distinct pattern of reactivity with the panel of natural field strains. The epitopes recognized by the four groups of clones were found, by reactivity with MAb-selected mutants, to be in very close proximity to one another and probably overlapping. All of the distinct epitopes recognized by the T-cell clones were adversely affected by a single amino acid substitution, either at residue 60 or at residue 63 in the HA1 polypeptide chain, within the region known from antibody-binding studies as site E. Some, but not all, of the epitopes may be influenced by the addition of a carbohydrate side chain to the HA of a particular MAb-selected mutant and certain field strains containing an Asp----Asn substitution at residue 63. Site E is therefore a major site of H-2d helper T-cell recognition on the H3 HA.


Immunological effects of bevacizumab-based treatment in metastatic colorectal cancer.
The efficacy of bevacizumab in metastatic colorectal cancer (mCRC) could be related not only to its well-known antiangiogenetic properties but also to a hypothetical effect on the immune system of the host. We enrolled mCRC patients treated with a bevacizumab-based first-line therapy. Lymphocyte and dendritic cell subsets were evaluated at baseline, 3rd and 6th cycle. The clinical efficacy was estimated as response rate and progression-free survival. Forty healthy subjects were used as reference. Fifty-one patients were enrolled. In comparison with healthy subjects, they showed a decrease of T and B cell compartments. Bevacizumab ameliorated the impairment of lymphocyte subsets, especially for T cells. Responders showed a trend toward an increase of CD3 (p = 0.07) and CD4 (p = 0.05). Among patients with a progression-free survival >1 year, only CD19 (p = 0.033) and CD20 (p = 0.013) showed a significant increase. No baseline impairment and no significant modification of dendritic cells were found. Bevacizumab-based therapy is able to increase B and T cell compartments. The expansion of T lymphocytes could imply an amelioration of dendritic cell-presenting capacity. These effects correlate with a more favourable clinical outcome and could be taken into account in clinical protocols aimed at combining antiangiogenetic-therapy with immunotherapy in mCRC.


Transsplenic Portal System Catheterization: Review of Current Indications and Techniques.
Multiple diseases of the portal system require effective portal vein access for endovascular management. While percutaneous transhepatic and transjugular approaches remain the standard methods of portal vein access, transsplenic access (TSA) has gained recognition as an effective and safe technique to access the portal system in patients with contraindications to traditional approaches. Recently, the utility of percutaneous TSA has grown, with described treatments including recanalization of chronic portal vein occlusion, placement of stents for portal vein stenosis, portal vein embolization of the liver, embolization of gastric varices, placement of complicated transjugular intrahepatic portosystemic shunts, and interventions after liver transplant. The authors provide a review of percutaneous TSA, including indications, a summary of related portal vein diseases, and the different techniques used for access and closure. In addition, an imaging-based review of technical considerations of TSA interventions is presented, with a review of potential procedural complications. With technical success rates that mirror or rival the standard methods and reported low rates of major complications, TSA can be a safe and effective option in clinical scenarios where traditional approaches are not feasible. ©RSNA, 2022.


Phospholipase C release of basic fibroblast growth factor from human bone marrow cultures as a biologically active complex with a phosphatidylinositol-anchored heparan sulfate proteoglycan.
Basic fibroblast growth factor (bFGF) is a potent mitogen for human bone marrow stromal cells and stimulates haematopoiesis in vitro. We report here that primary human bone marrow cultures contain bFGF and express heparin-like bFGF binding sites on the cell surface and in the extracellular matrix (ECM). bFGF bound predominantly to a 200-kD cell surface heparan sulfate proteoglycan (HSPG), which was also found in conditioned medium. bFGF was released from bone marrow cultures by incubation with phosphatidylinositol-specific phospholipase C (PI-PLC) and, less efficiently, by plasmin. Solubilized bFGF was found as a complex with the 200-kD HSPG. The complex was biologically active as shown by its ability to stimulate plasminogen activator production in bovine aortic endothelial cells. bFGF-HSPG complexes of bovine endothelial cells, however, were not released by PI-PLC. While only trace amounts of the bFGF-binding 200-kD HSPG were released spontaneously from bone marrow cultures, incubation with PI-PLC solubilized almost all of the 200-kD HSPG. The HSPG could be metabolically labeled with ethanolamine or palmitate, which was partially removed by treatment with PI-PLC. These findings indicate linkage of the HSPG to the cell surface via a phosphatidylinositol anchor. Plasmin released the 200-kD HSPG less efficiently than PI-PLC. We conclude that HSPGs of human bone marrow serve as a reservoir for bFGF, from which it can be released in a biologically active form via a dual mechanism; one involving a putative endogenous phospholipase, the other involving the proteolytic cascade of plasminogen activation.


Consistency of DNA ploidy between primary and recurrent gastric carcinomas.
Eleven patients with gastric carcinoma, who had undergone re-resection of the lesion due to recurrence in the remnant stomach, were the subjects of a cytophotometric DNA analytical study. The objective was to determine whether or not the DNA cytogenic profile of cancer cells would be consistent during the growth of the carcinoma. The DNA distribution patterns were grouped into types I, II, and III, according to the proportion of aneuploid cell population. Ten of 11 had the same DNA distribution patterns in the primary and recurrent lesions, while in the other one patient with type III in the primary lesion, type II was evident at the time of recurrence. The DNA cytogenic profile of cancer cells is thus a valid cell marker of a given tumor and should be applicable for determining the natural history of gastric carcinoma.


Two known therapies could be useful as adjuvant therapy in critical patients infected by COVID-19.
Pneumonia caused by coronavirus, which originated in Wuhan, China, in late 2019, has been spread around the world already becoming a pandemic. Unfortunately, there is not yet a specific vaccine or effective antiviral drug for treating COVID-19. Many of these patients deteriorate rapidly and require intubation and are mechanically ventilated, which is causing the collapse of the health system in many countries due to lack of ventilators and intensive care beds. In this document we review two simple adjuvant therapies to administer, without side effects, and low cost that could be useful for the treatment of acute severe coronavirus infection associated with acute respiratory syndrome (SARS-CoV-2). VitaminC, a potent antioxidant, has emerged as a relevant therapy due to its potential benefits when administered intravenous. The potential effect of vitaminC in reducing inflammation in the lungs could play a key role in lung injury caused by coronavirus infection. Another potential effective therapy is ozone: it has been extensively studied and used for many years and its effectiveness has been demonstrated so far in multiples studies. Nevertheless, our goal is not to make an exhaustive review of these therapies but spread the beneficial effects themselves. Obviously clinical trials are necessaries, but due to the potential benefit of these two therapies we highly recommended to add to the therapeutic arsenal.


Analysis of tumor markers in cytological fluid obtained from computed tomography-guided needle aspiration biopsies for the diagnosis of ground-glass opacity pulmonary lesions.
The purpose of this study was to assess whether analyses of tumor markers in cytological fluid can improve the performance of computed tomography (CT)-guided needle aspiration biopsy (NAB) for the diagnosis of ground-glass opacity (GGO) pulmonary lesions. Forty-two patients were prospectively enrolled for CT-guided NAB. Levels of cytokeratin 19 fragments (CYFRA 21-1) and carcinoembryonic antigen (CEA) from serum and cytological fluid were measured. The cutoff values of 3.3 ng/mL for CYFRA 21-1 and 5.0 ng/mL for CEA (threshold A) or thresholds by adding 2 standard deviations to the mean levels of markers found in patients without malignancy (threshold B) were used to identify malignancy. The sensitivity and area under the curve (AUC) of NAB alone were compared with those of NAB combined with serum or cytological tumor markers. Among the 42 patients, 30 (71.4%) had malignant and 12 (28.6%) had benign lesions. For NAB alone, the sensitivity, specificity, and AUC for diagnosing GGO were 70.0%, 100%, and 0.850, respectively. The sensitivity and AUC increased significantly for NAB with cytological CYFRA 21-1 compared with NAB alone, using both thresholds (threshold A: 86.7%, P=.026 and .933, P=.016; threshold B: 93.3%, P=.008 and .925, P=.046). Cytological fluid measurements of CYFRA 21-1 can improve the diagnostic performance of CT-guided NAB for GGO pulmonary lesions.


Remote Working during the Pandemic: A Q&A with Gillian Isaacs Russell: Questions from the Editor and Editorial Board of the BJP.
In this interview by email, Gillian Isaacs Russell, author of the influential Screen Relations: The Limits of Computer-Mediated Psychoanalysis and Psychotherapy, responds to a set of questions from the BJP. The interview focuses on the impact of remote working during the coronavirus epidemic, starting with the question of whether an effective therapeutic process can occur without physical co-presence. Isaacs Russell shares her immediate thoughts about the virtually overnight changes to our practice that came with the epidemic, and the work of the American Psychoanalytic Association's Covid-19 Advisory Team, on which she sits. Her responses are informed by recent cross-disciplinary and neuropsychological research on the digital age. She considers what happens to free association, evenly suspended attention and reverie when working by phone or online; the loss of the consulting room as a containing physical space for both clinician and patient; the relationship between place and time; and whether (and how) we can maintain a focus on transference and countertransference in the presence of the threat of death. The interview ends with her thoughts on whether we should assume that the landscape of analytic therapy will be permanently altered by Covid-19, and with her hope that general awareness of the impact of trauma on our mental health has been raised.


Flying rocks and flying clocks: disparity in fossil and molecular dates for birds.
Major disparities are recognized between molecular divergence dates and fossil ages for critical nodes in the Tree of Life, but broad patterns and underlying drivers remain elusive. We harvested 458 molecular age estimates for the stem and crown divergences of 67 avian clades to explore empirical patterns between these alternate sources of temporal information. These divergence estimates were, on average, over twice the age of the oldest fossil in these clades. Mitochondrial studies yielded older ages than nuclear studies for the vast majority of clades. Unexpectedly, disparity between molecular estimates and the fossil record was higher for divergences within major clades (crown divergences) than divergences between major clades (stem divergences). Comparisons of dates from studies classed by analytical methods revealed few significant differences. Because true divergence ages can never be known with certainty, our study does not answer the question of whether fossil gaps or molecular dating error account for a greater proportion of observed disparity. However, empirical patterns observed here suggest systemic overestimates for shallow nodes in existing molecular divergence dates for birds. We discuss underlying biases that may drive these patterns.


Rotator cuff tears: correlation between geometric tear patterns on MRI and arthroscopy and pre- and postoperative clinical findings.
Magnetic resonance imaging (MRI) is considered to be the best non-invasive procedure for the evaluation of rotator cuff (RC) tendon tears. Burkhart's classification is a geometric classification of full-thickness RC tears on MRI. To correlate MRI and arthroscopic geometric full-thickness RC tears according to the Burkhart's classification with pre- and postoperative clinical findings. Patients who underwent arthroscopic RC repair between 2006 and 2010 were retrospectively evaluated. Preoperative MRI and arthroscopic surgical reports were reviewed for tear geometry (Burkhart's) by three (1 radiologist, 2 surgeons) and two (surgeons) readers. MRIs were also evaluated for tear size and change of tear size in successive sagittal sections and for muscle mass and fatty infiltration. Clinical examinations were performed preoperatively and at least 12 months afterwards. Postoperative function questionnaires were filled in by the patients. Forty-six patients (35 men, 11 women; mean age, 57 years; range, 41-72 years) were evaluated. Tears depicted on MRIs were classified as crescent in 11 patients (24%), longitudinal in three (6.5%), massive contracted in 29 (63%), and cuff arthropathy in three (6.5%). Muscle changes were noted almost exclusively in patients with massive tears and cuff arthropathy (16/32 patients, P = 0.013). MRIs and arthroscopic geometric classifications were in close agreement. Tear type did not correlate with pre- and postoperative physical examination or with postoperative clinical questionnaires scores. Geometric RC tear characterizations on preoperative MRIs were closely associated with arthroscopic findings. Postoperative results were not affected by the geometric pattern of the tears.


An iCRISPR platform for rapid, multiplexable, and inducible genome editing in human pluripotent stem cells.
Human pluripotent stem cells (hPSCs) offer a unique platform for elucidating the genes and molecular pathways that underlie complex traits and diseases. To realize this promise, methods for rapid and controllable genetic manipulations are urgently needed. By combining two newly developed gene-editing tools, the TALEN and CRISPR/Cas systems, we have developed a genome-engineering platform in hPSCs, which we named iCRISPR. iCRISPR enabled rapid and highly efficient generation of biallelic knockout hPSCs for loss-of-function studies, as well as homozygous knockin hPSCs with specific nucleotide alterations for precise modeling of disease conditions. We further demonstrate efficient one-step generation of double- and triple-gene knockout hPSC lines, as well as stage-specific inducible gene knockout during hPSC differentiation. Thus the iCRISPR platform is uniquely suited for dissection of complex genetic interactions and pleiotropic gene functions in human disease studies and has the potential to support high-throughput genetic analysis in hPSCs.


Population structure of Lassa Mammarenavirus in West Africa.
Lassa mammarenavirus (LASV) is the etiologic agent of Lassa fever. In endemic regions in West Africa, LASV genetic diversity tends to cluster by geographic area. Seven LASV lineages are recognized, but the role of viral genetic determinants on disease presentation in humans is uncertain. We investigated the geographic structure and distribution of LASV in West Africa. We found strong spatial clustering of LASV populations, with two major east-west and north-south diversity gradients. Analysis of ancestry components indicated that known LASV lineages diverged from an ancestral population that most likely circulated in Nigeria, although alternative locations, such as Togo, cannot be excluded. Extant sequences carrying the largest contribution of this ancestral population include the prototype Pinneo strain, the Togo isolates, and a few viruses isolated in Nigeria. The LASV populations that experienced the strongest drift circulate in Mali and the Ivory Coast. By focusing on sequences form a single LASV sublineage (IIg), we identified an ancestry component possibly associated with protection from a fatal disease outcome. Although the same ancestry component tends to associate with lower viral loads in plasma, the small sample size requires that these results are treated with extreme caution.


Platelet glycoprotein IIb/IIIa complex in cultured cells. Localization in focal adhesion sites in spreading HEL cells.
A panel of mouse monoclonal antibodies (MoAbs) was raised that react with platelet glycoproteins (GP) IIb or IIIa. On immunofluorescence, the MoAbs reacted with 30% to 40% of the human erythroleukemia (HEL) cells. When the HEL cells were induced to spread on fibronectin in the presence of 12-O-tetradecanoylphorbol-13-acetate (TPA), the MoAbs reacted with the focal adhesion sites. Only some of the GPIIIa MoAbs reacted with cells other than platelets, megakaryocytes, or HEL cells, and these showed focal adhesion sites in cultured human endothelial cells, fibroblasts, and epithelial cells from normal kidney tubules. They did not react, however, with transformed fibroblasts, fibrosarcoma cells, cultured cells from hypernephromas, or cultured human amnion epithelial cells. The results suggest that the platelet-type GPIIb/IIIa complex is only expressed in cells showing an ability to define megakaryoblastic differentiation. Localization of the GPIIb/IIIa complex at the induced focal adhesion sites in HEL cells and localization of the GPIIIa-like molecules in other cells suggest their direct role in the adhesion process and in the actomyocin organization of adherent cells.


Hydrological response to climate change for Gilgel Abay River, in the Lake Tana Basin -Upper Blue Nile Basin of Ethiopia.
Climate change is likely to have severe effects on water availability in Ethiopia. The aim of the present study was to assess the impact of climate change on the Gilgel Abay River, Upper Blue Nile Basin. The Statistical Downscaling Tool (SDSM) was used to downscale the HadCM3 (Hadley centre Climate Model 3) Global Circulation Model (GCM) scenario data into finer scale resolution. The Soil and Water Assessment Tool (SWAT) was set up, calibrated, and validated. SDSM downscaled climate outputs were used as an input to the SWAT model. The climate projection analysis was done by dividing the period 2010-2100 into three time windows with each 30 years of data. The period 1990-2001 was taken as the baseline period against which comparison was made. Results showed that annual mean precipitation may decrease in the first 30-year period but increase in the following two 30-year periods. The decrease in mean monthly precipitation may be as much as about -30% during 2010-2040 but the increase may be more than +30% in 2070-2100. The impact of climate change may cause a decrease in mean monthly flow volume between -40% to -50% during 2010-2040 but may increase by more than the double during 2070-2100. Climate change appears to have negligible effect on low flow conditions of the river. Seasonal mean flow volume, however, may increase by more than the double and +30% to +40% for the Belg (small rainy season) and Kiremit (main rainy season) periods, respectively. Overall, it appears that climate change will result in an annual increase in flow volume for the Gilgel Abay River. The increase in flow is likely to have considerable importance for local small scale irrigation activities. Moreover, it will help harnessing a significant amount of water for ongoing dam projects in the Gilgel Abay River Basin.


Molecular characterization of a neuronal low-voltage-activated T-type calcium channel.
The molecular diversity of voltage-activated calcium channels was established by studies showing that channels could be distinguished by their voltage-dependence, deactivation and single-channel conductance. Low-voltage-activated channels are called 'T' type because their currents are both transient (owing to fast inactivation) and tiny (owing to small conductance). T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Here we report the identification of a neuronal T-type channel. Our cloning strategy began with an analysis of Genbank sequences defined as sharing homology with calcium channels. We sequenced an expressed sequence tag (EST), then used it to clone a full-length complementary DNA from rat brain. Northern blot analysis indicated that this gene is expressed predominantly in brain, in particular the amygdala, cerebellum and thalamus. We mapped the human gene to chromosome 17q22, and the mouse gene to chromosome 11. Functional expression of the channel was measured in Xenopus oocytes. Based on the channel's distinctive voltage dependence, slow deactivation kinetics, and 7.5-pS single-channel conductance, we conclude that this channel is a low-voltage-activated T-type calcium channel.


Brain topography beyond parcellations: Local gradients of functional maps.
Functional neuroimaging provides the unique opportunity to characterize brain regions based on their response to tasks or ongoing activity. As such, it holds the premise to capture brain spatial organization. Yet, the conceptual framework to describe this organization has remained elusive: on the one hand, parcellations build implicitly on a piecewise constant organization, i.e. flat regions separated by sharp boundaries; on the other hand, the recently popularized concept of functional gradient hints instead at a smooth structure. Noting that both views converge to a topographic scheme that pieces together local variations of functional features, we perform a quantitative assessment of local gradient-based models. Using as a driving case the prediction of functional Magnetic Resonance Imaging (fMRI) data -concretely, the prediction of task-fMRI from rest-fMRI maps across subjects- we develop a parcel-wise linear regression model based on a dictionary of reference topographies. Our method uses multiple random parcellations -as opposed to a single fixed parcellation- and aggregates estimates across these parcellations to predict functional features in left-out subjects. Our experiments demonstrate the existence of an optimal cardinality of the parcellation to capture local gradients of functional maps.


Molecular and phylogenetic approaches for assessing sources of Cryptosporidium contamination in water.
The high sequence diversity and heterogeneity observed within species or genotypes of Cryptosporidium requires phylogenetic approaches for the identification of novel sequences obtained from the environment. A long-term study on Cryptosporidium in the agriculturally-intensive South Nation River watershed in Ontario, Canada was undertaken, in which 60 sequence types were detected. Of these sequence types 33 were considered novel with no identical matches in GenBank. Detailed phylogenetic analysis identified that most sequences belonged to 17 previously described species: Cryptosporidium andersoni, Cryptosporidium baileyi, Cryptosporidium hominis, Cryptosporidium parvum, Cryptosporidium ubiquitum, Cryptosporidium meleagridis, muskrat I, muskrat II, deer mouse II, fox, vole, skunk, shrew, W12, W18, W19 and W25 genotypes. In addition, two new genotypes were identified, W27 and W28. C. andersoni and the muskrat II genotype were most frequently detected in the water samples. Species associated with livestock made up 39% of the total molecular detections, while wildlife associated species and genotypes accounted for 55% of the Cryptosporidium identified. The human pathogenic species C. hominis and C. parvum had an overall prevalence of 1.6% in the environment, indicating a small risk to humans from the Cryptosporidium present in the watershed. Phylogenetic analysis and knowledge of host-parasite relationships are fundamental in using Cryptosporidium as a source-tracking or human health risk assessment tool.


Enantioselective Synthesis of Dideoxy-tetrafluorinated Hexoses.
Carbohydrates typically have low affinities to protein binding sites, and the development of carbohydrate mimetics with improved binding is therefore of interest. Tetrafluorination of monosaccharides is one of the strategies currently under investigation for that purpose. The synthesis of the required tetrafluorinated monosaccharides is achieved by a fluorinated building block approach. The enantioselective synthesis of tetrafluorinated hexose derivatives is described here, in both pyranose and furanose forms. In particular, the optimization of the enantioselective synthesis of the previously reported 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexopyranose 3, 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexofuranose 4, and 2,3-dideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose 5 is described as is the synthesis of two novel sugar derivatives, 3,4-dideoxy-3,3,4,4-tetrafluoro-d-threo-hexopyranose 6 and 3,4-dideoxy-3,3,4,4-tetrafluoro-d-erythro-hexopyranose 7. The key step of all syntheses is a perfluoroalkyl lithium-mediated C-C bond formation, either intramolecular or intermolecular, which proceeds in good to excellent yields. NMR and X-ray crystallographic analyses of the tetrafluorinated methyl pyranoside derivatives confirm their (4)C1 conformation.


Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial.
In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone. We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6-8 weeks. Primary outcome was HIV infection in babies at 6-8 weeks in those not infected at birth. Analysis was by intention to treat. The overall rate of mother-to-child transmission at 6-8 weeks was 15.3% in 484 babies who received nevirapine and zidovudine and 20.9% in 468 babies who received nevirapine only (p=0.03). At 6-8 weeks, in babies who were HIV negative at birth, 34 (7.7%) babies who had nevirapine and zidovudine and 51 (12.1%) who received nevirapine only were infected (p=0.03)-a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups. Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.


Physical aspects of cortical folding.
The characteristically folded surface of the human brain is critical for brain function and allows for higher cognitive abilities. Recent mostly computational research advances have shown that mechanical instabilities play a crucial role during early brain development and cortical folding. However, it is difficult to investigate such mechanisms in vivo. To experimentally gain deeper insights into the physical mechanisms that underlie the development of brain shape, we use a setup of swelling polymers. We investigate the influence of cortical thickness and the stiffness ratio between cortex and subcortex on the resulting surface pattern by taking the initially smooth fetal brain geometry at week 22 into consideration. The gel specimens possess a two-layered structure accounting for gray and white matter tissue and yield complex surface morphologies that well resemble patterns in the human brain. The results are in good agreement with analytical predictions. Through the variation of cortical thickness and stiffness, it is possible to reproduce cortical malformations such as polymicrogyria and lissencephaly. The results suggest that wrinkling with subsequent transition into folding is the driving instability mechanism during brain development. In addition, the experiments provide valuable insights towards the distinction between wrinkling and creasing instabilities. Taken together, the presented swelling experiments impressively demonstrate the purely physical aspects of brain shape and constitute a valuable tool to advance our understanding of human brain development.


The role of the University of the West Indies Mona libraries in HIV/AIDS information access and dissemination.
The recommendations for controlling HIV/AIDS, whether prescriptive or descriptive, underscore the value of information: its translation into knowledge, and knowledge into behaviour. Thus, accessing, evaluating, disseminating and applying authoritative, credible and scholarly information on HIV/AIDS are critical elements in the control of this pandemic in the Web 2.0 era. The University of the West Indies (UWI) Mona libraries have embraced this information role. This article provides insights into three of the information initiatives implemented by the UWI Mona libraries in this important capacity. In this regard, it also provides ideas for other West Indian information units and enhances communication on access to information products and services, albeit incrementally, in an important area of health services for the West Indies.


Favism and hemolytic anemia in glucose-6-phosphate dehydrogenase-deficient subjects in North Sardinia.
The present paper reports the incidence from 1965 to 1979 of acute hemolytic anemia for a total of 948 cases in G-6-PD-deficient subjects due to the ingestion of fresh or dried fava beans or certain drugs and to viral infections. The highest percentage of hemolytic crises was due to fresh fava beans (94.4%). No cases of favism were observed in breast-fed babies whose mothers had eaten fava beans or from pollen inhalation. The male sex proved to be the hardest hit. Hemoglobin values were lower than or equal to 7 g/dl in about 75% of males and 50% of females. Total bilirubin values were lower than 103 mumol/l (6 mg/dl) in about 75% of males and 85% of females. Both the hemoglobin and bilirubin values were statistically significant. Mean transaminase values (SGPT) were significantly higher than those of normal controls. No correlation between favism and blood groups was found.


K+ efflux through postsynaptic NMDA receptors suppresses local astrocytic glutamate uptake.
Glutamatergic transmission prompts K+ efflux through postsynaptic NMDA receptors. The ensuing hotspot of extracellular K+ elevation depolarizes presynaptic terminal, boosting glutamate release, but whether this also affects glutamate uptake in local astroglia has remained an intriguing question. Here, we find that the pharmacological blockade, or conditional knockout, of postsynaptic NMDA receptors suppresses use-dependent increase in the amplitude and duration of the astrocytic glutamate transporter current (IGluT ), whereas blocking astrocytic K+ channels prevents the duration increase only. Glutamate spot-uncaging reveals that astrocyte depolarization, rather than extracellular K+ rises per se, is required to reduce the amplitude and duration of IGluT . Biophysical simulations confirm that local transient elevations of extracellular K+ can inhibit local glutamate uptake in fine astrocytic processes. Optical glutamate sensor imaging and a two-pathway test relate postsynaptic K+ efflux to enhanced extrasynaptic glutamate signaling. Thus, repetitive glutamatergic transmission triggers a feedback loop in which postsynaptic K+ efflux can transiently facilitate presynaptic release while reducing local glutamate uptake.


The magnitude of reciprocity in chronic pain management: experiences of dispersed ethnic populations of Muslim women.
Dispersed ethnic populations believe their health to be worse than the ethnic majority group in Sweden. Most studies in rehabilitation exclude dispersed ethnic populations who can not read or speak the national language although this group seems to be in need of rehabilitation to a larger extent than privileged majority groups. The aim of the study was to examine the experience of living with musculoskeletal pain and experience of health care among dispersed ethnic populations of Muslim women. The method used was inspired by Grounded Theory in this study. Interviews were made with five first-generation Muslim immigrant women who had come to Sweden via Iraq as refugees. Two interviews were performed with interpreters. A preliminary core category 'The magnitude of reciprocity' based on three categories emerged from the analysis: (1) Impact of pain, (2) Managing pain and (3) Facing health care. Chronic pain limited the informants physically and emotionally, as well as impacting on their everyday life. Informants managed their pain primarily through medicine and physical activity, which gave at least temporary relief. Health care providers were perceived as doing their best but experiences of bad meetings were also witnessed. The factors important in achieving a good meeting in this study appeared to be; time, dialogue, honesty and understanding. Communication skills, feelings of being taken seriously and a sense of security were additional factors. Not being properly examined, or offered optimal treatment, not being believed or understood, were all seen as signs of dismissal within health care. The limitations of this study are primarily concerned with language difficulties resulting in various shortcomings. Reciprocal recognition and support connected to the specific life experiences of women that come with forced resettlement from the Muslim world to the European diaspora is a vital part of a holistic approach to pain management.


Sexual function and associated factors in Iranian patients with chronic low back pain.
Case-control study. (i) To describe the prevalence of sexual dysfunction in chronic low back pain (CLBP) patients, (ii) to compare the range of sexual function outcomes between patients with CLBP and healthy controls and (iii) to investigate which factors are associated with sexual function within the cohort of individuals with CLBP. Low back pain (LBP) clinic of Qazvin University of Medical Sciences, Qazvin, Iran. A total of 702 patients with CLBP and 888 healthy controls participated in the study. The Female Sexual Function Index (FSFI), International Index of Erectile Function (IIEF) and Premature Ejaculation Diagnostic Tool (PEDT) were used to evaluate sexual function. In addition, quality of life, anxiety, functional status and pain intensity were assessed in patients. Univariate and multiple linear regression analyses were performed for the identification of factors associated with sexual function. The prevalence of sexual problems in female patients with CLBP was 71.1% (n=177) while the corresponding figure for healthy women was 36.8% (n=161). Erectile dysfunction was present in 59.5% of male patients and in 24.5% of healthy males. Higher sexual function in both male and female patients with CLBP were being younger, lower duration of back pain, lower BMI, higher education level, being unemployed, physically active shorter sick leave, lower level of pain intensity, lower disability, higher family income, lower levels of depressive and anxiety symptoms, and higher psychical functioning and mental functioning. CLBP patients report considerably higher prevalences of sexual problems compared with healthy controls. Sex therapy and sexual management should be added to routine care and treatment of patients with CLBP.


Electrophysiological Evidence That the Retrosplenial Cortex Displays a Strong and Specific Activation Phased with Hippocampal Theta during Paradoxical (REM) Sleep.
It is widely accepted that cortical neurons are similarly more activated during waking and paradoxical sleep (PS; aka REM) than during slow-wave sleep (SWS). However, we recently reported using Fos labeling that only a few limbic cortical structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) contain a large number of neurons activated during PS hypersomnia. Our aim in the present study was to record local field potentials and unit activity from these two structures across all vigilance states in freely moving male rats to determine whether the RSC and the ACA are electrophysiologically specifically active during basal PS episodes. We found that theta power was significantly higher during PS than during active waking (aWK) similarly in the RSC and hippocampus (HPC) but not in ACA. Phase-amplitude coupling between HPC theta and gamma oscillations strongly and specifically increased in RSC during PS compared with aWK. It did not occur in ACA. Further, 68% and 43% of the units recorded in the RSC and ACA were significantly more active during PS than during aWK and SWS, respectively. In addition, neuronal discharge of RSC but not of ACA neurons increased just after the peak of hippocampal theta wave. Our results show for the first time that RSC neurons display enhanced spiking in synchrony with theta specifically during PS. We propose that activation of RSC neurons specifically during PS may play a role in the offline consolidation of spatial memories, and in the generation of vivid perceptual scenery during dreaming.SIGNIFICANCE STATEMENT Fifty years ago, Michel Jouvet used the term paradoxical to define REM sleep because of the simultaneous occurrence of a cortical activation similar to waking accompanied by muscle atonia. However, we recently demonstrated using functional neuroanatomy that only a few limbic structures including the retrosplenial cortex (RSC) and anterior cingulate cortex (ACA) are activated during PS. In the present study, we show for the first time that the RSC and ACA contain neurons firing more during PS than in any other state. Further, RSC neurons are firing in phase with the hippocampal theta rhythm. These data indicate that the RSC is very active during PS and could play a key role in memory consolidation taking place during this state.


Statins, allies against antibiotic resistance?
Due to the ever-increasing rate of antibacterial resistance, the search for effective antibacterial agents has become imperative. Researchers have investigated the potential antimicrobial properties of various classes of nonantibiotic drugs. Statins are a group of antihyperlipidemic drugs with several cholesterol-independent effects, including anti-inflammatory, immune-modulating, antioxidant, and antibacterial effects. In vitro and in vivo studies have demonstrated the antibacterial properties of statins against various gram-positive and gram-negative bacteria. Simvastatin and atorvastatin are the most potent members of the family. Their antibacterial effect can be attributed to several direct and indirect mechanisms. Bacterial invasion, growth, and virulence are affected by statins. However, since in vitro minimum inhibitory concentrations (MICs) are significantly higher than serum concentrations at the lipid-lowering dosage, indirect mechanisms have been suggested to explain the positive clinical results, including reducing inflammation and improving immune response capacity. Further, statins have shown promising results when combined with antibiotics and other antibacterial agents, such as triazenes and silver nanoparticles. Despite this, the controversial aspects of statins have cast doubt on their efficacy as a possible solution for antibacterial resistance, and further research is required. Consequently, this review will examine in detail the current clinical and in vitro findings and controversies regarding statins' antibacterial properties and their relevance to antibacterial resistance.


Who gets genomic testing for breast cancer recurrence risk?
Our study examined whether patient characteristics, beliefs and decision-making styles were associated with uptake of genomic testing for breast cancer recurrence risk. Participants were 132 early-stage breast cancer patients eligible for the Oncotype DX genomic test. We interviewed patients in 2009-2010 and obtained information from medical charts. Half of the women eligible for genomic testing for breast cancer recurrence risk received it. The most common reason for not getting the test was that women's physicians did not offer it (80%). Test recipients were more likely to be unsure about receiving chemotherapy treatment compared to women who did not receive the test (p < 0.05). Women who received the test had less advanced disease pathologies, recalled a lower objective recurrence risk, perceived lower recurrence risk, and were slightly younger (all p < 0.05). Most women who described their decision-making style as active received the test (75%), whereas few women who described their style as passive received the test (12%) (p < 0.01). In the university clinic we studied, genomic testing appeared to be more common among patients who may benefit most from the information provided by results, but confirmation in larger studies is needed.