Analysis of combined coiling and neuroendoscopy in the treatment of intraventricular hemorrhage due to ruptured aneurysm.
Subarachnoid hemorrhage (SAH) with intraventricular hemorrhage (IVH) is associated with poor outcomes. The aim of this study was to evaluate the effectiveness of combined coiling and neuroendoscopy to treat severe SAH with massive IVH. Between April 2008 and March 2012, 13 patients had massive IVH with a ruptured aneurysm treated at the Department of Neurosurgery, Fukuoka University, Japan. All 13 patients were treated within 2 days of onset by coiling and neuroendoscopic removal of the IVH, including the fourth ventricle. No rebleeding or acute hydrocephalus were noted. Glasgow Outcome Scale scores (GOS) at discharge were: good recovery (two patients), moderate disability (three patients), severe disease (one patient), vegetative state (four patients), and dead (three patients). A good modified Rankin Scale score (mRS) (0-2) at 6 months was observed in six patients and a poor mRS score (3-6) occurred in seven. The pre- and post-operative Graeb scores were significantly lower in the good mRS group (p = 0.020 and 0.033, respectively, Mann-Whitney U-test). GOS scores at discharge were significantly associated with mRS score at 6 months (p = 0.011, Fisher's Exact Test). Combined coiling and neuroendoscopic removal of the IVH, including the fourth ventricle, were feasible procedures and achieved preferable outcomes in approximately half of the cases.


Stochastic resonance analysis of a coupled high-speed maglev vehicle-bridge coupled system under bounded noise.
Coupled oscillations typically occur in maglev vehicle-bridge coupled systems excited by bounded noise caused by guideway irregularities. The paper employed Hamilton equations to derive the corresponding canonical transformation equations and determined the critical stable regions for two kinds of resonances using the largest Lyapunov exponents. The results show that the critical stable region between the excitation amplitude and the resonant frequency ratio is a valley shape when the system has external resonance only. When considering both internal and external resonances, the critical stable region between the excitation amplitude and resonant frequency ratio presents a small saddle shape. Energy transfers from the first to the second oscillator under with both internal and extrinsic resonance. As the guideway irregularities' coefficients increase, the maximum Lyapunov exponents of the two conditions change from negative to positive, which means that the system varies from a stable state to instability.


Description and surface topography of the cercaria of Austrobilharzia sp. (Digenea: Schistosomatidae).
The cercaria of Austrobilharzia sp. from the marine prosobranch gastropod Planaxis sulcatus in Kuwait Bay is described. The surface microtopography and pattern of the tegumentary sensory receptors are examined using scanning electron microscopy. The general microtopography of the surface of the cercaria is similar to that previously observed in cercariae of mammalian schistosomes, although differences are recorded in the types, numbers and distribution of the sensory receptors. The study identified more than 13 types of receptors comprising aciliated, uniciliated and for the first time a multiciliated receptor in a strigeid cercaria. The ciliated receptor types differ in the cilium length and structure of the surrounding collar and tegumentary base. The receptor types are site specific: (1) the aciliated and pitlike on the anterior organ-neck region and ventral sucker; (2) the uniciliated with a long flexible cilium with or without collar or a tegumentary base on the body and tail; and (3) the uniciliated with a short rigid cilium and a robust collar and tegumentary base, and the multiciliated with 6 flexible cilia and a high cylindrical collar on the anterior organ tip. The reported SEM information on the sensory receptors may contribute to elucidating their functional role and to establishing morphological characters for the phylogeny of the family Schistosomatidae.


Zero suicide implementation-effectiveness trial study protocol in outpatient behavioral health using the A-I-M suicide prevention model.
The treatment of suicidal patients often suffers owing to a lack of integrated care and standardized approaches for identifying and reducing risk. The National Strategy for Suicide Prevention endorsed the Zero Suicide (ZS) model, a multi-component, system-wide approach to identify, engage, and treat suicidal patients. The ZS model is a framework for suicide prevention in healthcare systems with the aspirational goal of eliminating suicide in healthcare. While the approach is widely endorsed, it has yet to be evaluated in a systematic manner. This trial evaluates two ZS implementation strategies statewide in specialty mental health clinics. This trial is the first large-scale implementation of the ZS model in mental health clinics using the Assess, Intervene, and Monitor for Suicide Prevention (A-I-M) clinical model. Using a hybrid effectiveness-implementation type 1 design, we are testing the effectiveness of ZS implementation in 186 mental health clinics in 95 agencies in New York State. Agencies are randomly assigned to either: "Basic Implementation" (BI; a large group didactic learning collaboratives) or "Enhanced Implementation" (EI; participatory small group learning collaboratives; enhanced consultation for site champions). Primary outcomes include suicidal behaviors, hospitalizations and Emergency Department visits; implementation outcomes include protocol adoption, protocol fidelity and barriers/facilitators to implementation. This project has the potential to have a significant public health impact by determining the effectiveness of the ZS model in mental health clinics, a setting where suicide attempts and suicides occur at a higher rate than any other healthcare setting. It will also provide guidance on the implementation level required to achieve uptake and sustainability of ZS. N/A.


Dying in the arms of Dutch governmental authorities.
Thorough investigation of deaths related to police actions or of persons placed under the 'care' of governmental authorities is anchored in the legal systems of every democratic system. The quality of this investigation should be guarded by an adequate set of control measures. Recently the Dutch Ombudsman published a report about this issue In the Netherlands no central registry of these deaths exists. The estimates based on the available data number some 400-500 deaths in custody in the past 10 years in the Netherlands of which only in 193 cases a legal postmortem was performed. We present an overview of these cases and discuss the present Dutch practice in the perspective of national and international legislation.


Pupillary adrenergic sensitivity and idiopathic headache in pediatric patients.
Electronic pupillometry before and after phenylephrine eye drops was performed in 83 headache patients divided into two groups: Group A included 59 pediatric patients aged 5 to 16 years suffering from tension headache (TH = 8), common migraine (CM = 33) and classic migraine (CLM = 18); Group B comprised 24 adult patients aged 28 to 49 years suffering from CM. Comparisons were made with a group of healthy volunteer controls, 12 children and 15 adults, not suffering from headache. In Group A, only the CLM patients had significant mydriasis after phenylephrine; pupillary responses in the TH and CM cases did not differ significantly from the healthy controls, although there was an evident tendency for increased response in the CM by comparison with the TH cases. On the other hand, in Group B (adult CM) there was a significant pupillary hyper-responsiveness to adrenergic receptor stimulation, higher than in the same clinical condition in the pediatric group. In pre-pharmacological testing conditions, a significantly higher percentage of anisocoria (p less than 0.05) and a significant reduction in mean pupil size (p less than 0.01) were only evident in adult migraineurs as compared with controls. These findings suggest that a subtle chronic sympathetic deficiency affecting the iris neuromuscular junction in some clinical forms of primary headache may be detected by pupillometry at an early age. Moreover, apart from a temporal factor responsible for a progressive sympathetic imbalance during development, there may be a more evident neural transmission disorder in migraine forms as opposed to tension forms.


Steering CAR T cell epigenetic programs by tweaking manufacturing protocol.
CAR T cell persistence remains a significant roadblock to effective clinical translation of CAR T cells for solid and brain tumors. Jung et al.1 demonstrate enrichment of resident memory phenotypes through simple changes to the CAR T cell manufacturing process.


Prevalence and diversity of rotavirus A in pigs: Evidence for a possible reservoir in human infection.
Rotavirus A (RVA) are a group of diverse viruses causing acute gastroenteritis (AGE) in humans and animals. Zoonotic transmission is an important mechanism for rotavirus evolution and strain diversity in humans, but the extent of pigs as a major reservoir for human infection is not clear. We have surveyed 153 pig farms across Taiwan with a total of 4588 porcine stool samples from three age groups from 2014 to 2017. Nursing piglets (less than one month of age) had higher detection rate for rotavirus than older age groups. Five VP7 (G) genotypes and 5 VP4 (P) genotypes were found in a total of 14 different G/P genotype combinations. In addition, porcine RVA strains had 2 NSP4 (E) genotypes and 3 VP6 (I) genotypes. A P[3]-like genotype was also discovered among strains collected in 2016 and 2017. Most of the genes from Taiwanese porcine strains clustered with each other and the lineages formed by these strains were distinct from the sequences of numerous regional variants or globally circulating porcine strains, suggesting an independent evolutionary history for Taiwanese rotavirus genotypes. The close relationship among porcine RVA strains and some unique porcine-like genotypes detected sporadically among human children in swine farms illustrates that pigs might serve as a reservoir for potential zoonotic transmission and novel genotype evolution in Taiwan's insular environment.


Effect of acute cocaine use on vasospasm and outcome in aneurysmal subarachnoid hemorrhage.
Although acute cocaine use has been correlated with aneurysmal subarachnoid hemorrhage, its effect on vasospasm and outcome is controversial. We investigated the effect of acute cocaine use on response to vasospasm treatment and neurologic outcome in patients with aneurysmal subarachnoid hemorrhage. Data from 600 patients with aneurysmal subarachnoid hemorrhage admitted to the University of Illinois Medical Center in Chicago between June 2002 and July 2007 were retrospectively analyzed. Patients who were positive for cocaine on urine toxicology or admitted to cocaine use within 72 hours of admission were compared with control patients with no history of cocaine use. Patients with unknown or remote history were excluded. Of the 600 patients with aneurysmal subarachnoid hemorrhage, 27 (5%) were excluded. Thirty-one patients (5%) acutely used cocaine before admission. Cocaine users were younger than control (45.1 vs 54.1; P ≤ .0003), and were more likely to smoke tobacco, drink alcohol, and have renal dysfunction. There was no significant difference in Hunt-Hess or Fisher grade. In univariate and multivariate analyses, there was no difference in unfavorable short-term outcome (modified Rankin scale > 3), incidence of symptomatic or radiologic vasospasm, stroke, or death. The number of interventional procedures for the treatment of vasospasm did not differ between the two groups. There is no significant difference in incidence of symptomatic vasospasm or neurologic outcome between cocaine users and nonusers. The severity of the vasospasm and the response to treatment, as indicated by the number of vasospasm interventions, did not differ between the two groups.


Postcordotomy spontaneous dysesthesias in macaques: recurrence after spinal cord transection.
Monkeys chronically attack the hypoalgesic hindlimb after thoracic contralateral anterolateral cordotomy or hemisection. This compulsive behavior could be induced by innocuous stimulation in the hypoalgesic region, and it also appeared to occur spontaneously. The postcordotomy spontaneous compulsive self-directed behavior was studied in 4 macaques after subsequent upper lumbar crush spinal transection. Despite the paraplegia and bilateral analgesia/anesthesia, this spontaneous abnormal behavior continued to be directed to the same hindlimb as before transection, but not to the opposite hindlimb. Hence, it is concluded that the recurring syndrome originated from the initial contralateral cordotomy. The rationale for the presumption of postcordotomy spontaneous dysesthesias is presented, and the experimental results are offered in refutation of alternative interpretive hypotheses. In conjunction with previous findings, these results lead to the argument that postcordotomy dysesthesias are caused by a neuropathological compensatory response to partial deafferentation of brain somatosensory neurons.


A Multimodal Intervention to Improve the Quality and Safety of Interhospital Care Transitions for Nontraumatic Intracerebral and Subarachnoid Hemorrhage.
Regionalization of care has increased interhospital transfers (IHTs) of nontraumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) to specialized centers yet exposes patients to the latent risks inherent to IHT. The researchers examined how a multimodal quality improvement intervention affected quality and safety measures for patients with ICH or SAH exposed to IHT. Pre and post analyses of timeliness, effectiveness, and communication outcome measures were performed for patients transferred to an urban, academic center with nontraumatic ICH/SAH following implementation of a multimodal intervention. Intervention components included clinical practice guideline dissemination, IHT process redesign, electronic patient arrival notification, electronic imaging exchange, and electronic health record improvements. Three months of preintervention outcomes were compared to six months of postintervention outcomes to assess impact and sustainability of the intervention; t-tests and chi-square tests were used to compare continuous and proportional outcomes, respectively. The IHT study population included 106 patients (37 preintervention, 69 postintervention). Significant improvements were observed in timeliness outcomes, including emergency department (ED) time to admission order (preintervention median: 66 minutes vs. postintervention: 33 minutes, p = 0.008), ED boarding time (preintervention median: 223 minutes vs. postintervention: 93 minutes, p = 0.001), and ED length of stay (preintervention median: 300 minutes vs. postintervention: 150 minutes, p ≤ 0.0001). Verbal communication between ED and neurocritical care clinicians prior to IHT improved from 40.0% preintervention to 90.9% postintervention. Application of scripted quality improvement interventions as part of the IHT process is feasible and effective at improving the timeliness of care and communication of critical information in patients with nontraumatic ICH/SAH.


Protein quinone complexes. Bovine plasma albumin and halogenated p-quinones.
A colloidal dispersion of chloranil in water or an aqueous solution of an amino acid shows an ESR signal characteristic of the semiquinone radical anion. The signal is broadened in the presence of bovine plasma albumin, and the available evidence supports the idea that the freedom of the free radical is restricted by a weak association with a specific site in the protein.


Minimally Invasive Techniques for Resection of Pancreatic Neuroendocrine Tumors.
Surgical resection remains the treatment of choice for primary pancreatic neuroendocrine tumors (PNETs), because it is associated with increased survival. Minimally invasive procedures are a safe modality for the surgical treatment of PNETs. In malignant PNETs, laparoscopy is not associated with a compromise in terms of oncologic resection, and provides the benefits of decreased postoperative pain, better cosmetic results, shorter hospital stay, and a shorter postoperative recovery period. Further prospective, multicenter, randomized trials are required for the analysis of these minimally invasive surgical techniques for the treatment of PNETs and their comparison with traditional open pancreatic surgery.


Subantral sinus augmentation using hydraulic lift system and alloplastic phosphosilicate putty followed by simultaneous implant placement for the rehabilitation of an atrophic posterior maxilla: A case report.
Tooth extraction is generally accompanied by bone remodeling and pneumatization of the maxillary sinus in the posterior region of the maxilla, which can result in a reduction in the height and width of the bone and compromise the placement of the implant. However, this anatomic deficiency can be restored through maxillary sinus elevation. Among the various surgical methods used, the indirect sinus floor elevation technique is relatively less invasive and less complex. Herein, we present the case of a 58-year-old partially edentulous female who underwent rehabilitation of the right maxillary molar region using the indirect sinus floor elevation technique. The hydraulic lift system was used followed by immediate implant placement. This technique incorporates the advantages of both the lateral wall and crestal approaches for sinus elevation and is associated with a lower incidence of sinus membrane perforation and minimum bone loss.


Clinical, cytological, and biochemical investigations in a case of an XX male.
Lymphocytes and fibroblasts of an XX male were investigated to evaluate the etiology of this trait. DNA extracted from lymphocytes was digested with restriction endonucleases to probe for male specific DNA. There was no indication of such DNA fragments. The X-linked steroid sulfatase showed an activity of female controls while H-Y antigen was found in concentrations comparable to male controls. Cytological examinations excluded a mosaic between 46,XX and 46,XY cells. With the "high resolution banding" technique no evidence was found for a chromosomal aberration in our patient. It is therefore concluded that a "de novo" gene mutation leading to male development is the most suitable explanation for the present case of an XX male.


In vivo whole animal body imaging reveals colonization of Chlamydia muridarum to the lower genital tract at early stages of infection.
The leading cause of sexually transmitted bacterial infection is Chlamydia trachomatis. The aim of this study is to investigate the early events in colonization of this bacterium within the murine genital tract. An in vivo animal body imaging technology was used to track fluorophore labeled C. muridarum elementary bodies (EBs) inoculated intravaginally in C57BL/6 mice during the first 24 h of infection. Ascension of viable EBs was observed (1) to be localized to the lower regions of the murine genital tract within the first 24 h post challenge and (2) was dose independent during this early exposure period. Molecular detection revealed enhanced bacterial load in lower regions of the genital tract with increasing bacterial load in the upper region beginning 12 h post inoculation. This study provides additional insight into chlamydial colonization in the murine genital tract during the first 12-24 h following inoculation.


Usefulness of microsurgery to isolation of recurrent laryngeal nerve and parathyroid during thyroidectomy operations.
The authors report their experience of the application of microsurgical techniques in total and subtotal thyroidectomy operations from January 1984-January 1997. Four hundred and eighty-six patients with thyroid diseases were operated upon with both traditional and microsurgical techniques. The comparison of results shows that microsurgical skills are effective in reducing the dangers and important complications in both laryngeal nerves and parathyroids.


Hemipelvic amputations for recalcitrant pelvic osteomyelitis.
To evaluate the outcome of recalcitrant deep pelvic infection that required a hemipelvic amputation. Retrospective cohort. Tertiary referral centre; Level I trauma. There were 20 patients with an infection of the pelvic girdle who developed life-threatening sepsis or had an intolerable existence due to putrefied tissues that prevented end of life care. All patients failed other more conservative treatments such as limited debridement and local wound care. The indication for amputation was life-threatening sepsis (eight patients), intolerable state with putrid tissue (four patients), and both sepsis/putrefaction (eight patients). A hemipelvic amputation, multidrug antibiotic treatment, and long-term suppression. Ten internal hemipelvectomies, eight external hemipelvectomies, and two hemicorporectomies were performed. Survival and recurrence of infection. Six patients died within 6 months (mean time 17 weeks, range 2-24). The 14 surviving patients had a mean follow-up time of 28 weeks (9-48). Of these, 10 patients survived with no evidence of ongoing infection, and four patients had ongoing infection requiring suppressive antibiotics. All of the six deaths were in C-hosts with an average of six comorbidities each; mean age was 62 years old. Aetiologies of the infection were vasculopathy (5), spinal cord injury (4), post fracture (3), post abdominal surgery (2), gunshot wound (2), seeding from bacteraemia (4). Cierny-Mader host class was C (11) and B systemic/local (9) with an average of four (4) comorbidities each. Mean estimated blood loss=3100 cc and operative time=157 min. There were 11 cases of minor wound problems and no flap loss. Pathogens were polymicrobial (16 total pathogens) with mean of three per patient (most common was MRSA). Multi-agent antibiotic and suppression were used in all patients. In cases with putrefied tissues, appropriate nursing care was possible. Patients requiring hemipelvectomies usually present with sepsis or an intolerable state. Despite expected complications, we found that hemipelvectomy is an effective palliative tool in selected cases. Age and vascular disease seemed to be associated with worse outcomes.


Pulmonary arterial wall stiffness and its impact on right ventricular afterload in patients with repaired tetralogy of Fallot.
Recent histologic studies involving patients with tetralogy of Fallot (TOF) have revealed a reduction in normal elastic fibers in the pulmonary trunk. Such histologic changes may significantly alter the mechanical properties of the arterial wall and may thereby augment the pulsatile afterload on the right ventricle (RV) and propagate RV dilation and dysfunction. We studied 29 patients with repaired TOF (median age, 5.9 years) and 29 age-matched controls. Pulmonary arterial hemodynamics were investigated by measuring the pulmonary input impedance during cardiac catheterization. Patients with TOF had higher characteristic impedance (p = 0.0002), lower total pulmonary vascular compliance (p < 0.0001), and enhanced wave reflection (p < 0.0001). Consistent with these changes, patients with TOF were subject to higher pulsatile load, measured by fundamental frequency impedance (p < 0.0001), which was significantly related to both reduced RV output and increased RV end-diastolic volume (p = 0.006 and 0.003, respectively). Moreover, pulmonary arterial compliance was strongly related to RV end-diastolic volume (r = -0.69, p = 0.0001). In multivariate analysis, pulmonary arterial compliance was a significant predictor of RV dilation independent of pulmonary regurgitation and pulmonary stenosis (p = 0.03). In line with known histologic changes, pulmonary arterial stiffness is increased and is significantly related to reduced RV ejection and RV enlargement in patients with repaired TOF. These results suggest that not only pulmonary valvular function (pulmonary regurgitation/pulmonary stenosis) but also pulmonary vascular pulsatile properties can be an important therapeutic target to improve prognosis in this population.


Use of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus.
Balanced progenitor activities are crucial for the development and maintenance of high turn-over organs such as the esophagus. However, the molecular mechanisms regulating these progenitor activities in the esophagus remain to be elucidated. Here, we demonstrated that Yap is required for the proliferation of esophageal progenitor cells (EPCs) in the developing murine esophagus. We found that Yap deficiency reduces EPC proliferation and stratification whereas persistent Yap activation increases cell proliferation and causes aberrant stratification of the developing esophagus. We further demonstrated that the role of YAP signaling is conserved in the developing human esophagus by utilizing 3D human pluripotent stem cell (hPSC)-derived esophageal organoid culture. Taken together, our studies combining loss/gain-of-function murine models and hPSC differentiation support a key role for YAP in the self-renewal of EPCs and stratification of the esophageal epithelium.


First report of a Canadian epidemiological study of autistic syndromes.
This report describes an epidemiological investigation of the autistic syndrome using new research diagnostic criteria (Denckla, 1986). The focus here is on the methods of screening and follow-up, and on a description of the cases identified within a circumscribed region of Nova Scotia. Autism, as defined by social deviance, language impairment and repetitive or ritualistic behaviours, has a prevalence of 10 per 10,000 and a male to female ratio of 2.5:1. These findings are discussed relative to those reported previously.


Squamous cell carcinoma of the gallbladder masquerading liver abscess with review of literature.
Squamous cell carcinoma of the gall bladder is a rare but aggressive tumor. It has a wide variety of presentations. Presentation as a liver abscess is a rare condition only 2 cases reported in the literature before. A 45-year-old male patient presented to the emergency with complaints of fever, right upper quadrant pain, and jaundice. On evaluation, an initial diagnosis of the liver abscess was made. Due to the deteriorating condition of the patient, he was taken up for surgery. Upon exploration, there were multiple deposits over the bilateral lobes of the liver, so a controlled drainage of abscess cavity was done with biopsy from the wall of the gall bladder and liver metastasis was taken which showed squamous cell carcinoma of gall bladder with liver metastasis. The patient was given gemcitabine and oxaliplatin as palliative chemotherapy. He died after 11 months of presentation. The aggressive and advanced nature of the disease at the presentation poses a formidable challenge in managing such patients but early diagnosis and surgical management can provide long term benefits.


A possible mechanism for the beneficial effect of ethanol in essential tremor.
Essential tremor is one of the most common movement disorders in elderly people. The hypothesis of a disregulation of N-methyl-D-aspartate (NMDA) pathways has been suggested. It was shown experimentally that infusion of NMDA in cerebellar nuclei down-regulates glutamate release. We assessed the effects of intranuclear administration of harmaline on the NMDA-mediated regulation of glutamate in rats using reverse dialysis. We hypothesized that ethanol, which improves essential tremor in the clinic, antagonizes the effect of harmaline upon glutamatergic transmission. We tested the interaction of ethanol and harmaline upon glycerol (a marker of membrane turn-over), lactate, and pyruvate concentrations. Harmaline increased the concentrations of glutamate and impaired the NMDA-mediated regulation of glutamate. Ethanol decreased the concentrations of glutamate during NMDA stimulation in case of pre-administration with harmaline. Concentrations of glycerol rose with harmaline. Glycerol levels markedly decreased during NMDA infusion when inhibitors of nitric oxide synthase, alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate antagonists or NMDA antagonists were administered. Harmaline increased lactate/pyruvate ratios during NMDA infusion but these ratios returned to normal values in presence of ethanol. We provide a possible mechanism for the beneficial effect of ethanol on essential tremor. The concept of glutamatergic disregulation underlying essential tremor is highlighted. Consequences for our understanding of essential tremor are discussed.


Cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy: A longitudinal cohort study.
Despite the well-known negative impacts of cancer and anticancer therapies on cognitive performance, little is known about the cognitive compensatory processes of older patients with cancer. This study was designed to investigate the cognitive compensatory processes of older, clinically fit patients with hematologic malignancies undergoing chemotherapy. We assessed 89 consecutive patients (age ≥ 65 y) without severe cognitive impairment and 89 age-, sex-, and education level-matched healthy controls. Cognitive compensatory processes were investigated by (1) comparing cognitive performance of patients and healthy controls in novel (first exposure to cognitive tasks) and non-novel (second exposure to the same cognitive tasks) contexts, and (2) assessing psychological factors that may facilitate or inhibit cognitive performance, such as motivation, psychological distress, and perceived cognitive performance. We assessed cognitive performance with the Trail-Making, Digit Span and FCSR-IR tests, psychological distress with the Hospital Anxiety and Depression Scale, and perceived cognitive performance with the FACT-Cog questionnaire. In novel and non-novel contexts, average cognitive performances of healthy controls were higher than those of patients and were associated with motivation. Cognitive performance of patients was not associated with investigated psychological factors in the novel context but was associated with motivation and psychological distress in the non-novel context. Older, clinically fit patients with hematologic malignancies undergoing chemotherapy demonstrated lower cognitive compensatory processes compared to healthy controls. Reducing distress and increasing motivation may improve cognitive compensatory processes of patients in non-novel contexts.


Rescue from tau-induced neuronal dysfunction produces insoluble tau oligomers.
Aggregation of highly phosphorylated tau is a hallmark of Alzheimer's disease and other tauopathies. Nevertheless, animal models demonstrate that tau-mediated dysfunction/toxicity may not require large tau aggregates but instead may be caused by soluble hyper-phosphorylated tau or by small tau oligomers. Challenging this widely held view, we use multiple techniques to show that insoluble tau oligomers form in conditions where tau-mediated dysfunction is rescued in vivo. This shows that tau oligomers are not necessarily always toxic. Furthermore, their formation correlates with increased tau levels, caused intriguingly, by either pharmacological or genetic inhibition of tau kinase glycogen-synthase-kinase-3beta (GSK-3β). Moreover, contrary to common belief, these tau oligomers were neither highly phosphorylated, and nor did they contain beta-pleated sheet structure. This may explain their lack of toxicity. Our study makes the novel observation that tau also forms non-toxic insoluble oligomers in vivo in addition to toxic oligomers, which have been reported by others. Whether these are inert or actively protective remains to be established. Nevertheless, this has wide implications for emerging therapeutic strategies such as those that target dissolution of tau oligomers as they may be ineffective or even counterproductive unless they act on the relevant toxic oligomeric tau species.


The Role of Sexual Abuse and Dysfunctional Attitudes in Perceived Stress and Negative Mood in Pregnant Adolescents: An Ecological Momentary Assessment Study.
Latinas have the highest rates of adolescent pregnancy in the United States. Identifying means to improve the well-being of these young women is critical. The current study examined whether a history of child sexual abuse-itself a risk factor for adolescent pregnancy-was associated with more perceived stress and negative mood over the course of pregnancy and whether dysfunctional attitudes explained these associations. This mixed methods study involved laboratory-based assessments of perceived stress, sexual abuse history, and dysfunctional attitudes, as well as Ecological Momentary Assessments (EMA) of mood states every 30 minutes during a 24-hour period once during each trimester of pregnancy. Pregnant adolescents (N = 204, 85% Latina). EMA mood states and laboratory-based retrospective self-reports of perceived stress. One in 4 pregnant adolescents had a history of sexual abuse. Sexually abused adolescents reported greater perceived stress during the first trimester relative to those without, though the groups did not differ on EMA negative mood ratings. Dysfunctional attitudes explained associations between sexual abuse and perceived stress. Sexual abuse was indirectly associated with the intercept and slope of negative mood through dysfunctional attitudes. Findings were circumscribed to sexual abuse and not other types of child abuse. Identifying sexually abused pregnant adolescents and providing support and cognitive therapy to target dysfunctional beliefs may decrease stress during the first trimester as well as negative affect throughout pregnancy.


The University of Tennessee experience with the Indigo 830e laser device for the minimally invasive treatment of benign prostatic hyperplasia: interim analysis.
Benign prostatic hyperplasia (BPH) is the most common benign tumor in men and is responsible for urinary symptoms in the majority of men older than 50 years of age. Although transurethral resection of the prostate (TURP) is the gold standard, its complications have impacted upon its utility. As a consequence, new pharmacologic and minimally invasive approaches to the management of BPH have been developed. One minimally invasive approach that employs interstitial laser coagulation by the Indigo 830e LaserOptic system heats the prostate to the point of irreversible necrosis while preserving the urethral lining, potentially resulting in fewer complications. To test the efficacy of this device we evaluated the interim results obtained in 25 patients treated for BPH. Parameters evaluated included the AUA symptom score, uroflowometry, post-void residual, and prostate size. Following treatment, patients were discharged home and the catheter was removed within 3-7 days. Patients were assessed at 1 month and at subsequent 3-month intervals following the procedure using a questionnaire, AUA symptom score, and uroflowometry. The results of the paired t-tests demonstrated a significant increase in the maximal and average flow rates from baseline. The mean baseline maximal flow rate was 8.3 ml/s and increased to 10, 12.7, 14.1, and 12.0 ml/s at 1, 3, 6, and 9 months, respectively, and the mean baseline average flow rate was 4.4 ml/s and increased to 5.3, 6.0, 6.6, and 6.2 ml/s at 1, 3, 6, and 9 months, respectively. The AUA symptom scores decreased from 20.2 to 9.8 at 9 months. There was no intraoperative complication. Six patients developed transient retention. No patient developed bladder neck contractures, urinary incontinence, impotence, or urinary tract infections. One patient developed retrograde ejaculation and one patient required retreatment by TURP. Hence, improvements in symptom scores and voiding parameters suggest that the laser interstitial coagulation prostatectomy is safe and effective for the treatment of BPH.


Gene therapy for Down syndrome.
The presence of an additional copy of HSA21 chromosome in Down syndrome (DS) individuals leads to the overexpression of 30-50% of HSA21 genes. This upregulation can, in turn, trigger a deregulation on the expression of non-HSA21 genes. Moreover, the overdose of HSA21 microRNAs (miRNAs) may result in the downregulation of its target genes. Additional complexity can also arise from epigenetic changes modulating gene expression. Thus, a myriad of transcriptional and posttranscriptional alterations participate to produce abnormal phenotypes in almost all tissues and organs of DS individuals. The study of the physiological roles of genes dysregulated in DS, as well as their characterization in murine models with gene(s) dosage imbalance, pointed out several genes, and functional noncoding elements to be particularly critical in the etiology of DS. Recent findings indicate that gene therapy strategies-based on the introduction of genetic elements by means of delivery vectors-toward the correction of phenotypic abnormalities in DS are also very promising tool to identify HSA21 and non-HSA21 gene candidates, contributing to DS phenotype. In this chapter, we focus on the impact of normalizing the expression levels of up or downregulated genes to rescue particular phenotypes of DS. Attempts toward gene-based treatment approaches in mouse models will be discussed as new opportunities to ameliorate DS alterations.


An AFM determination of the effects on surface roughness caused by cleaning of fused silica and glass substrates in the process of optical biosensor preparation.
The covalent attachment of organic films and of biological molecules to fused silica and glass substrates is important for many applications. For applications such as biosensor development, it is desired that the immobilised molecules be assembled in a uniform layer on the surface so as to provide for reproducibility and speed of surface interactions. For optimal derivatisation the surface must be appropriately cleaned to remove contamination, to create surface attachment sites such as hydroxyl groups, and to control surface roughness. The irregularity of the surface can be significant in defining the integrity and density of immobilised films. Numerous cleaning methods exist for fused silica and glass substrates and these include gas plasmas, and combinations of acids, bases and organic solvents that are allowed to react at varying temperatures. For many years, we have used a well established method based on a combination of washing with basic peroxide followed by acidic peroxide to clean and hydroxylate the surface of fused silica and glass substrates before oligonucleotide immobilisation. Atomic force microscopy (AFM) has been used to evaluate the effect of cleaning on surface roughness for various fused silica and glass samples. The results indicate that surface roughness remains substantial after use of this common cleaning routine, and can provide a surface area that is more than 10% but less than 30% larger than anticipated from geometric considerations of a planar surface.


Catfish Glycoprotein, a Highly Powerful Safe Preservative of Minced Beef Stored at 4 °C for 15 Days.
Minced beef is a very perishable food product, due to its vulnerability to microbial contamination and its fast quality deterioration. In the current study, the biological efficiency of different concentrations (0, 50 and 100 µg g-1) of the antibacterial catfish glycoprotein (CFG) was estimated as a possible improver of the storability and safety of minced beef preserved at 4 °C for 15 days. CFG (50 and 100 µg g-1) could efficiently control the changes in meat pH during 15 days storage at 4 °C to be within the normal, acceptable levels (6.4 and 6.2, respectively), equalizing the level of the control for minced beef after 6 days of storage under similar conditions. Likewise, the level of metmyoglobin in minced beef stored at the same conditions was maintained at 53.67 and 46.67% by CFG supplementation at 50 and 100 µg g-1, respectively, at the 15th day of storage, which is comparable to the 6th day in case of the control samples. However, the antioxidant effect of CFG against lipid peroxidation was less effective. The antibacterial action of CFG was most pronouncedly powerful and efficient. Supplementation of minced beef with CFG at 50 and 100 µg g-1 significantly (p < 0.05) decreased the bacterial counts at all the time inspection points as compared to the control. After 15 days of storage, the total viable bacteria, psychrotrophic bacterial count and coliforms count were reduced to 3.12, 2.65 and 0.0 log CFU g-1, respectively, in response to CFG (50 µg g-1), and 2.41, 2.04 and 0.0 log CFU g-1, respectively, in response to CFG (100 µg g-1); this compared to 5.13, 4.78 and 2.5 in the control samples after only six days cold storage. Using CFG at 50, 100 and 200 µg g-1 in rat diets did not affect their liver or kidney functions, reflecting the non-toxicity of this substance. Substantiating the antioxidant and antimicrobial potential of CFG in minced beef storage may support its use as a naturally powerful and safe food preservative, as well as a shelf-life extender.


Cyperus (Cyperus esculentus L.): A Review of Its Compositions, Medical Efficacy, Antibacterial Activity and Allelopathic Potentials.
Cyperus (Cyperus esculentus L.) is an edible perennial grass-like plant, which propagates exclusively with underground tubers. Its tubers are rich in starch (20-30%), fat (25-35%), sugar (10-20%), protein (10-15%) and dietary fiber (8-9%). In addition, the tubers also contain alkaloids, organic acids, vitamins (C and E), steroids, terpenoids and other active components. The contents of oleic acid and linoleic acid in Cyperus oil are very high, which have important medicinal value and health-promoting properties. Most of the extracts from the tubers, stems and leaves of Cyperus have allelopathic potential and antibacterial, antioxidant and insecticidal activities. In recent years, the planting area of Cyperus has increased significantly all over the world, especially in China and some other countries. This paper presents the current status of Cyperus and the recent trend in research in this area. Published reports on its nutritional contents, active ingredients, medicinal efficacy, antibacterial activity and allelopathic potential were also reviewed.


Iliofemoral complications associated with thoracic endovascular aortic repair: frequency, risk factors, and early and late outcomes.
Risk factors and outcomes after iliofemoral complications after thoracic aortic endovascular repair remain poorly characterized. This study was performed to characterize factors influencing perioperative iliofemoral complications during thoracic aortic endovascular repair. All patients undergoing transfemoral thoracic aortic endovascular repair since 2005 with adequate preoperative aortoiliac 3-dimensional imaging (n = 126) were identified. Assessment of imaging was blinded with regard to occurrence of iliofemoral complications, defined as anything other than successful transfemoral device delivery and primary closure of an arteriotomy. The complication rate was 12% (n = 15). Univariate analysis identified that female gender, preoperative ankle-brachial index, average and minimal iliac diameters, diameter difference between iliac artery and sheath size, and iliac morphology score (calculated by combining iliac tortuosity, calcification, and vessel diameter) were associated with iliofemoral complications (all P < .05). Multivariate analysis identified the (1) difference between average iliac diameter and sheath size (P = .014), (2) iliac artery morphology score (P = .033), and (3) ankle-brachial index (P = .012) as independent predictors for iliofemoral complications. Early mortality was higher in those with complications (13.3% vs 1.8%, P = .069). Four-year freedom from limb loss, claudication, or revascularization was 97.9%. Iliofemoral complications reduced late survival primarily as a result of increased mortality within the first year (P = .047). Thoracic aortic endovascular repair can be performed safely via a transfemoral approach. Alternative access in patients with high preoperative iliac artery morphology scores and device delivery size requirements over the native iliofemoral size may reduce iliofemoral complications. If early complications occur, prompt repair results in low rates of ischemic limb complications at late follow-up.


Getting personal with epigenetics: towards individual-specific epigenomic imputation with machine learning.
Epigenetic modifications are dynamic mechanisms involved in the regulation of gene expression. Unlike the DNA sequence, epigenetic patterns vary not only between individuals, but also between different cell types within an individual. Environmental factors, somatic mutations and ageing contribute to epigenetic changes that may constitute early hallmarks or causal factors of disease. Epigenetic modifications are reversible and thus promising therapeutic targets for precision medicine. However, mapping efforts to determine an individual's cell-type-specific epigenome are constrained by experimental costs and tissue accessibility. To address these challenges, we developed eDICE, an attention-based deep learning model that is trained to impute missing epigenomic tracks by conditioning on observed tracks. Using a recently published set of epigenomes from four individual donors, we show that transfer learning across individuals allows eDICE to successfully predict individual-specific epigenetic variation even in tissues that are unmapped in a given donor. These results highlight the potential of machine learning-based imputation methods to advance personalized epigenomics.


Genetic and environmental influences on behavioral and neurochemical aspects of emotionality in rats.
Three pairings of rats (two derived from divergent, selective breeding and one from divergent environmental conditions) were compared with regard to behavioral and hormonal parameters. Striking differences were observed: results obtained in our own laboratory as well as those found in a review of the literature pointed to higher emotionality (e.g., increased defecation and corticosterone secretion, etc.) in Roman low-avoidance, Wistar-Kyoto and group-housed rats, as compared to their respective counterparts, Roman high-avoidance, spontaneously hypertensive, and individually housed Wistar rats. Concomitant receptor binding studies reviewed here (3H-diazepam- and 3H-imipramine-binding sites) have revealed, however, less consistent intrapair differences.


The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats.
Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy.


Targeting and retention of Golgi membrane proteins.
Recent cloning of genes encoding membrane proteins of the Golgi complex has allowed investigation of protein targeting to this organelle. Targeting signals have been identified in three glycosyltransferases, a viral envelope protein and several proteins of the trans-Golgi network. Interestingly, the targeting signals for membrane proteins of the Golgi stacks seem to be contained in transmembrane domains. Information in the cytoplasmic tails is required for the targeting of trans-Golgi network proteins. Mechanisms involving both retention and retrieval have been invoked.


Dietary and nutritional biomarkers of lens degeneration, oxidative stress and micronutrient inadequacies in Indian cataract patients.
Habitual food and nutrient intakes of 140 Indian cataract patients and 100 age- and sex-matched controls (50-75 years), from high income group and low income groups, were assessed. Food intake was recorded by food frequency questionnaire and data were examined for linkages with blood/lens parameters of oxidative stress through a case-control study. Intake of animal foods and fried snacks was significantly higher while vegetables, green leafy vegetables, fruit, tea and micronutrient intakes were lower in patients than in controls (p<0.001). Lens oxidative stress and opacity showed a significant negative association with fruit intake (p<0.05). Multiple regression analysis indicated association of intakes of iron, beta-carotene, ascorbic acid, tannic acid and inositol pentaphosphate with plasma oxidative stress (p<0.01) and association of intakes of iron, ascorbic acid and inositol triphosphate with lens oxidative stress (p<0.01). Weighted least square regression for lens opacity revealed that intakes of ascorbic acid, folic acid and inositol pentaphosphate explained 59.7% of the total variation (p<0.01). Dietary deficiency of antioxidant micronutrients was greater for patients than controls. Deficiency of beta-carotene, ascorbic acid, folic acid, iron, phytate and polyphenols increased oxidative stress in blood and lens.


Characterization and quantification of the Chinese medical formula Zhi-Zi-Chi decoction, a systematic strategy for the attenuation and synergy of compatibility mechanism.
Zhi-Zi-Chi decoction (ZZCD), comprising of Gardenia jasminoides Ellis (GJE) and Semen sojae preparatum (SSP), is a classical Chinese medicine formula. A novel analysis strategy was set up to obtain an evaluation of ZZCD on attenuation and synergy of compatibility. High-resolution ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) was used for qualitative analysis. Variant ingredients were analyzed to compare the componential differences between ZZCD formula and single herbs. Based on our previous fingerprint studies that combined with chemometric methods, 13 remarkable chemical markers were selected and evaluated for quantitative determination by high performance liquid chromatography (HPLC) in three different ratios of ZZCD. 62 compounds in ZZCD, 55 compounds in GJE and 16 compounds in SSP were characterized. The compatibility of GJE and SSP may lead to the undetection of hepatotoxic components such as genipin and the emergence of protective components such as jasminoside A, which was not found in single herbs. Meanwhile, 13 selected chemical markers were successfully determined in three ratios of ZZCD. The compatibility may lead to the decrease of toxic ingredients and the increase of beneficial ingredients. By comparing the dissolution of chemical markers, iridoids in GJE and flavonoids in SSP had the best dissolution when the compatibility ratio was 1:1. This strategy would be a valuable reference for further study on the compatibility of traditional Chinese medicine formula.


Meta-Analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Narrowing.
Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p <0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD.


Complete Genome Sequence of Gordonia rubripertincta Bacteriophage Hexbug Suggests Potential for a New CT Subcluster.
Through the SEA-PHAGES program at Tufts University, a bacteriophage infecting Gordonia rubripertincta NRRL B-16540 was isolated and characterized. Hexbug is a lytic phage and is currently one of 44 phages belonging to cluster CT. The Hexbug genome shares >96% nucleotide identity with cluster CT phage Orla.


Synergistic breast cancer suppression efficacy of doxorubicin by combination with glycyrrhetinic acid as an angiogenesis inhibitor.
Therapeutic regimens of breast cancer treatment are increasingly inclined to adopt combination strategy based on the broad spectrum antitumor effect of doxorubicin (Dox). Currently, combination therapy comprises of conventional anti-cancer drugs and angiogenesis inhibitors have been corroborated as an effective approach in cancer treatment. We explored the ability of a natural anti-angiogenic compound glycyrrhetinic acid (GA), derived from an edible-medicinal herb licorice, to enhance the breast cancer suppression effect of Dox. The drug ratio of GA and Dox with synergistic anticancer effect against MCF-7 cells was optimized by combination index (CI) value in vitro, followed by evaluation of the improved anticancer effects and reduced side-effects of this combination in vitro and in vivo. Cell viability was measured by MTT assay. Analyses of mitochondrial membrane potential and cell apoptosis on MCF-7 cells were performed by JC-1 dye and Annexin V-FITC/PI assays. The cellular accumulation of Dox when combined with GA was evaluated. Levels of apoptosis-related proteins in MCF-7 cells were measured by Western blot analysis. Synergistic anti-angiogenic effects on HUVECs were evaluated. A breast cancer mouse model was established to investigate the anti-tumor effects in vivo. Based on the optimization by CI value, Dox and GA at 1:20 molar ratio was chosen as the optimal combination drug ratio that exhibited synergistic effect against MCF-7 breast cancer cells. In addition, the combination of GA and Dox exhibited significantly enhanced cytotoxicity, apoptosis, and loss of mitochondrial membrane potential via the upregulation of a mitochondrial-dependent apoptosis pathway against MCF-7 cells. Interestingly, the addition of GA increased the intracellular accumulation of Dox in MCF-7 cells. Moreover, VEGF-induced HUVECs proliferation, migration, and tube formation were strongly inhibited by Dox when used with GA via the significant down-regulation of VEGFR2-mediated pathway, indicating that the combination of Dox and GA could exhibit ideal synergistic anti-angiogenesis effect. Expectedly, the enhanced anti-tumor efficacy of Dox and reduced Dox-induced cardiotoxicity when used in combination with GA were evident in a mouse breast tumor model. These findings support that the combination of Dox with GA is a novel and promising therapeutic strategy for the treatment of breast cancer.


Differential effects of bifrontal and occipital nerve stimulation on pain and fatigue using transcranial direct current stimulation in fibromyalgia patients.
Fibromyalgia is a disorder characterized by widespread musculoskeletal pain frequently accompanied by other symptoms such as fatigue. Moderate improvement from pharmacological and non-pharmacological treatments have proposed non-invasive brain stimulation techniques such as transcranial direct current stimulation (tDCS) to the occipital nerve (more specifically the C2 area) or to the dorsolateral prefrontal cortex (DLPFC) as potential treatments. We aimed to explore the effectiveness of repeated sessions of tDCS (eight sessions) targeting the C2 area and DLPFC in reducing fibromyalgia symptoms, more specifically pain and fatigue. Forty-two fibromyalgia patients received either C2 tDCS, DLPFC tDCS or sham procedure (15 C2 tDCS-11 DLPFC tDCS-16 sham). All groups were treated with eight sessions (two times a week for 4 weeks). Our results show that repeated sessions of C2 tDCS significantly improved pain, but not fatigue, in fibromyalgia patients, whereas repeated sessions of DLPFC tDCS significantly improved pain as well as fatigue. This study shows that eight sessions of tDCS targeting the DLPFC have a more general relief in fibromyalgia patients than when targeting the C2 area, suggesting that stimulating different targets with eight sessions of tDCS can lead to benefits on different symptom dimensions of fibromyalgia.


Idiopathic scoliosis: identification of candidate regions on chromosome 19p13.
We performed genomic screening, statistical linkage analysis, and fine mapping of 202 families with at least 2 individuals with idiopathic scoliosis. To identify regions on chromosome 19p13 statistically linked to the phenotypic expression of idiopathic scoliosis. Idiopathic scoliosis is a common structural curvature of the spine affecting otherwise healthy children. Presently, no clear consensus exists regarding the underlying abnormality or genetic determinants of this disease. Model-independent linkage analysis of qualitative and quantitative traits related to scoliosis was used to screen genotyping data from 391 markers in 202 families (1198 individuals). Subsets of families with probands having a curve > or = 30 degrees were dichotomized based on the most likely mode of inheritance for each family (autosomal dominant or X-linked dominant). Fine mapping was performed to show linkage to candidate regions on chromosome 19. When the threshold of disease was set at a curvature of > or = 30 degrees, qualitative linkage analysis revealed significant results at 2 successive markers on chromosome 19. The data confirm a previously reported genetic locus on chromosome 19 as potentially significant in the etiology of idiopathic scoliosis.


Best evidence topic report. Differential diagnosis of narrow complex tachycardias by increasing electrocardiograph speed.
A shortcut review was carried out to establish whether increasing the paper speed during ECG recording could improve the accuracy of diagnosis of narrow complex tachycardias. Altogether 256 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated in table 2. It is concluded that increasing paper speed does indeed improve diagnostic accuracy.


Accommodation and vergence response gains to different near cues characterize specific esotropias.
To describe preliminary findings of how the profile of the use of blur, disparity, and proximal cues varies between non-strabismic groups and those with different types of esotropia. This was a case control study. A remote haploscopic photorefractor measured simultaneous convergence and accommodation to a range of targets containing all combinations of binocular disparity, blur, and proximal (looming) cues. Thirteen constant esotropes, 16 fully accommodative esotropes, and 8 convergence excess esotropes were compared with age- and refractive error-matched controls and 27 young adult emmetropic controls. All wore full refractive correction if not emmetropic. Response AC/A and CA/C ratios were also assessed. Cue use differed between the groups. Even esotropes with constant suppression and no binocular vision (BV) responded to disparity in cues. The constant esotropes with weak BV showed trends for more stable responses and better vergence and accommodation than those without any BV. The accommodative esotropes made less use of disparity cues to drive accommodation (p = 0.04) and more use of blur to drive vergence (p = 0.008) than controls. All esotropic groups failed to show the strong bias for better responses to disparity cues found in the controls, with convergence excess esotropes favoring blur cues. AC/A and CA/C ratios existed in an inverse relationship in the different groups. Accommodative lag of > 1.0 D at 33 cm was common (46%) in the pooled esotropia groups compared with 11% in typical children (p = 0.05). Esotropic children use near cues differently from matched non-esotropic children in ways characteristic to their deviations. Relatively higher weighting for blur cues was found in accommodative esotropia compared to matched controls.


Near-infrared fluorescent probe based on rhodamine derivative for detection of NADH in live cells.
A near-infrared fluorescent probe was prepared for selective detection of reduced nicotinamide adenine dinucleotide (NADH) in live cells. The probe turns off the fluorescence with a closed spironolactone switch. However, reduction of the probe by NADH turns on fluorescence at 740 nm. Theoretical calculations suggest a more planar arrangement between the rhodamine and quinoline moieties with increased π-delocalization resulting from reduction.


Experience with ultrasonographically guided vacuum-assisted resection of benign breast tumors.
To evaluate the feasibility and safety of vacuum-assisted resection of benign breast tumours using an 8 G handheld device. Over a 2-year period, 22 patients with 26 breast tumours diagnosed as benign using aspiration biopsy cytology were enrolled. The mean patient age was 38 years, and the mean maximal diameter of the tumour was 13 mm. A handheld Aloka SSD 6500 ultrasonography device with a linear-type 7.5 MHz transducer was inserted into the posterior aspect of the tumour with the patient under local anaesthesia, and the tumour was resected under ultrasonographic guidance. This method was employed successfully in all patients, and the mean operation time was 33 min. Post-procedure complications included subcutaneous bleeding in 12 cases and haematoma in one. The pathological diagnoses were fibroadenoma in 16 cases, mastopathy in six, and tubular adenoma and pseudoangiomatous stromal hyperplasia in two cases each, respectively. Follow-up ultrasonography revealed residual tumours in four cases (15.4%). Although this method is feasible and safe without severe complications, it is necessary to select appropriate patients, and to obtain informed consent regarding the possibility of recurrence or residual tumour.


Traumatic ulcerative granuloma with stromal eosinophilia: a malignant-appearing benign lesion.
Traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) is an underreported diagnosis in dermatologic literature. Rapid expansion with an ulcerative clinical appearance often provokes fear of malignancy despite its benign nature. Traumatic ulcerative granuloma with stromal eosinophilia is thought to be a reactive tissue response to trauma, but CD30+ mononuclear cells within a TUGSE lesion suggests the possibility of an underlying lymphoproliferative disorder. This case highlights the clinical and histological features of TUGSE and provides a brief review of the literature addressing this debate. Knowledge of this condition, which uncommonly presents to the practicing dermatologist, is important in providing appropriate patient care and counseling. When correctly identified, unnecessary therapies and emotional stress can be avoided.


A viral Sm-class RNA base-pairs with mRNAs and recruits microRNAs to inhibit apoptosis.
Viruses express several classes of non-coding RNAs; the functions and mechanisms by which most of these act are unknown. Herpesvirus saimiri, a γ-herpesvirus that establishes latency in the T cells of New World primates and has the ability to cause aggressive leukaemias and lymphomas in non-natural hosts, expresses seven small nuclear uracil-rich non-coding RNAs (called HSURs) in latently infected cells. These HSURs associate with Sm proteins, and share biogenesis and structural features with cellular Sm-class small nuclear RNAs. One of these HSURs (HSUR2) base-pairs with two host cellular microRNAs (miR-142-3p and miR-16) but does not affect their abundance or activity, which suggests that its interactions with them perform alternative functions. Here we show that HSUR2 also base-pairs with mRNAs in infected cells. We combined in vivo psoralen-mediated RNA-RNA crosslinking and high-throughput sequencing to identify the mRNAs targeted by HSUR2, which include mRNAs that encode retinoblastoma and factors involved in p53 signalling and apoptosis. We show that HSUR2 represses the expression of target mRNAs and that base-pairing between HSUR2 and miR-142-3p and miR-16 is essential for this repression, suggesting that HSUR2 recruits these two cellular microRNAs to its target mRNAs. Furthermore, we show that HSUR2 uses this mechanism to inhibit apoptosis. Our results uncover a role for this viral Sm-class RNA as a microRNA adaptor in the regulation of gene expression that follows precursor mRNA processing.


Deep learning application of the discrimination of bone marrow aspiration cells in patients with myelodysplastic syndromes.
Myelodysplastic syndromes (MDS) are a group of hematologic neoplasms accompanied by dysplasia of the bone marrow hematopoietic cells with cytopenia. Detecting dysplasia is important in the diagnosis of MDS, but it takes considerable time and effort. Also, since the assessment of dysplasia is subjective and difficult to quantify, a more efficient tool is needed for quality control and standardization of bone marrow aspiration smear interpretation. In this study, we developed and evaluated an algorithm to automatically discriminate hematopoietic cell lineages and detect dysplastic cells in bone marrow aspiration smears using deep learning technology. Bone marrow aspiration images were acquired from 34 patients diagnosed with MDS and from 24 normal bone marrow slides. In total, 8065 cells were classified into eight categories: normal erythrocytes, normal granulocytes, normal megakaryocytes, dysplastic erythrocytes, dysplastic granulocytes, dysplastic megakaryocytes, blasts, and others. The algorithm demonstrated acceptable performance in classifying dysplastic cells, with an AUC of 0.945-0.996 and accuracy of 0.912-0.993. The algorithm developed in this study could be used as an auxiliary tool for diagnosing patients with MDS and is expected to contribute to shortening the time required for MDS bone marrow aspiration diagnosis and standardizing visual reading.


Self-corrective behavior for turn alternation in pill bugs (Armadillidium vulgare).
Pill bugs (Armadillidium vulgare) demonstrate a behavior called turn alternation that keeps their overall direction of movement straight after obstacles in experimental settings force them to deviate from a course. For example, this behavior is seen when they alternate their path choice on successive trials of the T-maze test. However, sometimes pill bugs stop after turning and change their direction (directional change). The function of this directional change has not been investigated because such individuals are usually omitted from the data. The present paper shows that pill bugs use directional changes to prevent them from turning in the same direction on two successive turns, a behavior called turn repetition. We examined the behavior of 36 pill bugs that each completed 130 successive T-maze trials. Directional changes appeared more frequently when individuals had begun a turn repetition than when they had begun a turn alternation. Furthermore, after correcting for turn repetition, turn alternations increased. These results suggest that pill bugs have an inherent mechanism that acts to maintain turn-alternating behavior.


Determination of the 90% effective dose (ED90) of phenylephrine for hypotension during elective cesarean delivery using a continual reassessment method.
The purpose of this study was to determine, by continual reassessment, the 90% effective dose (ED90) of phenylephrine for hypotension after combined spinal-epidural anesthesia. Term pregnant women scheduled for elective cesarean delivery received combined spinal epidural anesthesia. Subjects received phenylephrine at one of 6 incremental doses ranging from 60 to 160μg (n=3 for each dose). While the first cohort received a conservative, predetermined dose of 60μg, subsequent cohorts received phenylephrine doses determined using Bayesian-based software. One of the predetermined bolus doses of phenylephrine was given in the event of both hypotension [defined as systolic blood pressure (SBP)<80% of baseline or below 100mmHg] and tachycardia [defined as heart rate >120% of baseline or >100beatsmin(-1)]. Treatment was considered successful if SBP returned to within 80% of the baseline or ≥100mmHg within 2min. Twenty-four subjects with hypotension and tachycardia were included. T6 block was achieved within 15min in 20 patients and after additional epidural chloroprocaine in the remaining four. The estimated ED90 was 100μg, with a response probability of 90.7% (95% CI 74.1-99.5%). Treatment was successful in 20 patients. Probability of success at each bolus dose (in μg) was as follows: 60, 58.9%; 80, 80.3%; 100, 90.7%; 120, 95.5%; 140, 98.3%; and 160, 99.2%. The ED90 of a phenylephrine bolus dose for hypotension in term pregnant women is approximately 100μg, based on continual reassessment.


A comparison of the effect of oleandomycin and oxytetracycline supplementation on the growth and the meat quality of Dokki-4 chicks reared in hot weather.
1000 chickens were used to investigate up to 24 weeks under high environmental temperatures the addition of different types (oxytetracycline and oleandomycin) and different levels (5 or 20 ppm) of antibiotics to the basal diet. Supplementation with 20 ppm had--with both types of antibiotics--a marked positive effect on the growth rate and various quality characteristics of the products. The effect was higher in male animals than in females.


Magnetic critical properties and basal-plane anisotropy of Sr₂IrO₄.
The anisotropic magnetic properties of Sr2IrO4 are investigated, using longitudinal and torque magnetometry. The critical scaling across T(c) of the longitudinal magnetization is that expected for the 2D XY universality class. Modeling the torque for a magnetic field in the basal plane, and taking into account all in-plane and out-of-plane magnetic couplings, we derive the effective fourfold anisotropy K4 ≈ 1 × 10(5) erg mol(-1). Although larger than for the cuprates, it is found to be too small to account for a significant departure from the isotropic 2D XY model. The in-plane torque also allows us to set an upper bound for the anisotropy of a field-induced shift of the antiferromagnetic ordering temperature.


Evaluation of erythemal UV effective irradiance from UV lamp exposure and the application in shield metal arc welding processing.
Ultraviolet radiation (UVR) exposure is known to cause potential effects such as erythema in skin. For UV-induced erythema (sunburn), the action spectrum from the Commission Internationale de l'Eclairage, International Commission on Illumination (CIE) was adopted. Erythemal UV effects from UVR lamp exposure were investigated with commercial spectroradiometry devices in this research. Three kinds of portable UV germicidal lamps with broadband UVA (BB UVA, 350-400 nm), broadband UVB (BB UVB, 280-350 nm), and narrowband UVC (NB UVC, 254 nm) wavelengths served as the UVR emission sources. An action spectrum expresses the effectiveness of radiation for assessing the hazard of UVR in the erythemal action spectrum from 250-400 nm. The UV Index (UVI) is an irradiance scale computed by multiplying the CIE erythemal irradiance integral in milliwatts per square meter by 0.04 m mW. A comprehensive approach to detecting erythemal UVR magnitude was developed to monitor the effective exposure from UV lamps. The erythemal UVR measurement was established and the exposure assessment was applied to monitor erythemal UVR magnitude from shield metal arc welding (SMAW) processing. From this study, the erythemal UVR exposures were assessed and evaluated with environmental solar simulation of the UVI exposure.


Generation of the e-wave of the electroretinogram in the frog retina.
The e-wave and a delayed-OFF increase in extracellular K+ concentration are both maximum in the distal half of the inner plexiform layer. These responses also have similar latency, time-course, intensity-dependence, surround properties, and sensitivity to tetrodotoxin. Current source-density analysis of the e-wave reveals a current sink through the proximal retina, a source at the retinal surface, and, in some cases, a weaker source in the mid-retina. These results suggest a model for e-wave generation: delayed-OFF activity in proximal neurons releases K+, which enters Muller cells in the inner plexiform layer; a current exists Muller cells primarily via their endfeet, and the return flow through extracellular space produces the e-wave.


Polyanionic Imido-P(V) Ligands: From Transition Metal Complexes to Coordination Driven Self-Assemblies.
The chemistry of the imido-anions of the main group elements has been studied for more than three decades. The imido (NR)- group is isoelectronic to the oxo (=O) group and can coordinate with metal ions through its lone pairs of electrons. The polyimido-P(V) anions are well explored as they resemble the phosphorus oxo moieties such as H3 PO4 , H2 PO4 - , HPO4 2- and PO4 3- species. These imido anions are typically generated using strong main group organometallic reagents such as n BuLi, Et2 Zn, Me3 Al and n Bu2 Mg, etc. As a result, their coordination chemistry has been restricted to reactions in anhydrous aprotic solvents for a few main group metal ions. This account presents our findings on using certain soft transition metal such Ag(I) and Pd (II) for isolating these imido-P(V) anions as their corresponding self-assembled clusters and cages. Using the various salts of Ag(I) ions in reaction with 2-pyridyl (2 Py) functionalized phosphonium salts and phosphoric triamides, we obtained the mono- and dianionic form of these imido ligands {[P(N2 Py)2 (NH2 Py)2 ]- , [P(N2 Py)2 (NH2 Py)]- , [PO(N2 Py)(NH2 Py)2 ]2- } and derived interesting examples of tri, penta, hepta and octanuclear Ag(I) clusters. Interestingly, by using the salts of Pd (II) ions, the elusive imido-phosphate trianions of the type [(RN)3 PO]3- (R=t Bu, c Hex, i Pr) were generated in a facile one pot reaction as their corresponding tri- and hexanuclear clusters of the type {Pd3 [(NR)3 PO](OAc)3 }n (n=1 or 2). These trianions acts as a cis-coordinated hexadentate ligand for a trinuclear Pd (II) cluster and serve as the polyhedral building units for constructing hitherto unknown family of neutral cages in tetrahedral {Pd3 [(Ni Pr)3 PO]4 (L)6 } and cubic {Pd3 [(Ni Pr)3 PO]8 (L)12 } structures in the presence of suitable linker ligands (L2- ). These cages show interesting host-guest chemistry and post-assembly reactions. Remarkably, by employing chiral tris(imido)phosphate trianions, enantiopure chiral cages of the type [(Pd3 X*)4 (L)6 ], ([X*]3- =RRR- or SSS-[PO(N(*CH(CH3 )Ph)3 ]3- ), were synthesized and used for the chiral-recognition and enantio-separation of small racemic guest molecules. Some of these chiral cages were also shown to exhibit polyradical framework structures. In future, these and other similar types of cages are envisioned as potential molecular vessels for performing the reactions in their confined environment. The enantiomeric cages can be probed for asymmetric catalysis and the separation of a range of small chiral molecules.


Wood-Ljungdahl pathway utilisation during in situ H2 biomethanation.
Biogas production from organic waste is a waste-to-energy technology with the potential to contribute significantly to sustainable energy production. Upgrading of biogas using in situ biomethanation with hydrogen has the potential for surplus electricity storage, and delivery of biogas with a methane content of >90%, allowing for easier integration into the natural gas grid, as well as conversion to other products. Microbial communities in biomethanation reactors undergo changes, however, these changes are largely unexplored. In the present study, metagenome-resolved protein stable isotope probing (Protein-SIP) was applied to laboratory scale batch incubations operating under anaerobic digestion, and (pre-adapted) biomethanation conditions, fed with 13C-labelled bicarbonate, in order to gain insight into the microbial activities during CO2-reduction. The strongest and most microbially diverse isotopic incorporation was observed in the pre-adapted biomethanation incubation. Furthermore, divergent incorporation of 13C-labelled bicarbonate was also observed in the Wood-Ljungdahl pathway, with the anaerobic digester incubations primarily showing labelled proteins in the peripheral pathways leading toward production of energy and biomass. The pre-adapted biomethanation incubations consumed H2 and CO2, but did not convert it to CH4, suggesting the production of acetate in these incubations, which was supported by heavy labelling of key enzymes in the Wood-Ljungdahl pathway. Twelve (ten high quality) metagenome-assembled genomes (MAGs) coding for 13C-incorporated proteins were extracted from the metagenome, eight of which contained one or more of the key genes in the Wood-Ljungdahl pathway, one of which was affiliated to Methanosarcina. Together, the findings in the present study deepen our knowledge surrounding microbial communities in biomethanation systems, and contribute to the development of better strategies for implementation of biogas upgrading and microbial management.


MicroRNA-144 inhibits the metastasis of gastric cancer by targeting MET expression.
Gastric cancer (GC) remains one of the most common types of malignant cancer, and the molecular mechanism underlying its metastasis is still largely unclear. MicroRNAs have emerged as important regulators of metastasis because of their ability to act on multiple signaling pathways. In our study, we found that miR-144 is significantly downregulated in both highly metastatic GC cell lines and tissues. Results from both gain-of-function and loss-of-function experiments demonstrate that increased miR-144 expression significantly reduced GC cell migration, whereas decreased miR-144 expression dramatically enhanced GC cell migration. The met proto-oncogene (MET), which is often amplified in human cancers and functions as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-144. Moreover, silencing of MET using small interfering RNA (siRNA) recapitulated the anti-metastatic function of miR-144, whereas restoring MET expression attenuated the function of miR-144 in GC cells. Furthermore, we found that miR-144, by targeting MET, suppresses phosphorylation of Akt. Finally, we observed an inverse correlation between the expression of miR-144 and MET mRNA in GC metastatic tissues. In summary, miR-144 suppresses GC progression by directly downregulating MET expression, which subsequently prevents activation of the pro-oncogenic Akt pathway. Reintroduction of miR-144 expression in GC cells presents an attractive therapeutic approach to block the metastasis of gastric cancer.


Protein degradation by the phosphoinositide-specific phospholipase C-alpha family from rat liver endoplasmic reticulum.
A 60-kDa protein homologous to phosphoinositide-specific phospholipase C-alpha was purified to apparent homogeneity on sodium dodecyl sulfate-polyacrylamide gel electrophoresis from the rough endoplasmic reticulum of rat liver through three sequential chromatographies on DEAE Toyopearl 650, AF-heparin Toyopearl 650M, and TSK gel G3000SW. The purified protein was monomeric, with an M(r) of 60,000. Eight types of protein were further separated from the 60-kDa protein and named ER60A-ER60H according to the order of their elution from a TSK gel DEAE-5PW column. They were essentially identical in terms of immunochemical properties and the NH2-terminal amino acid sequence. The partial amino acid sequence of ER60F showed homology to that of phosphoinositide-specific phospholipase C-alpha. ER60A-ER60H showed no phosphoinositide-specific phospholipase C activity. However, ER60A-ER60H catalyzed cleavage of themselves and the endoplasmic reticulum proteins protein disulfide-isomerase and calreticulin. Proteolytic degradation was inhibited by p-chloromercuribenzoate. These results indicate that ER60A-ER60H comprise a group of endoplasmic reticulum resident proteins and show thiol group-related proteolytic activity.


A clinico-pathological study of actinomycotic mycetomas caused by Actinomadura madurae and Actinomadura pelletierii.
Twenty seven cases of actionomycotic mycetoma caused either by Actinomadura madurae or Actinomadura pelletierii have been described. Infection by A. madurae has been more common than A. pelletierii. Left foot in A. madurae and right foot in A. pelletierii infections were involved more commonly in adult males, whereas right foot of the females was frequently affected in A. madurae infection. Large, soft, white grains in A. madurae and small, firm, red grains in A. pelletierii were consistently seen. Deep hematoxylin stained grains with scalloped margin and prominent eosinophilic club in A. madurae and such deep stained grains with smooth margin and horizontal cracks appearing as portions of a spherical mass in A. pelletierri were diagnostic. Large numbers of plasma cells and Russel bodies were also characteristic of A. madurae infection. Both the grains were stainable with Von Kossa method for calcium. Bone changes were similar in both the infections. Oral tetracycline produced soft tissue and bone resolution to almost normalcy in those who regularly consumed the drug any time from 2 to 6 years. Mild glucose intolerance, facial hyperpigmentation and urticaria were the side effects observed in a few. Two patients developed cataract following tetracycline therapy. The value of medical therapy with oral tetracycline in Actionomadura mycetomas is emphasized.


Trends and Racial Disparities in the Prevalence of Urinary Incontinence Among Men in the USA, 2001-2020.
Male urinary incontinence (UI) affects quality of life and leads to a significant burden to the health care system. However, the contemporary prevalence and recent trends in UI and its subtypes among US men remain unknown. We evaluated 20-yr trends in the prevalence of UI and its subtype in US men aged ≥20 yr. A serial, cross-sectional analysis of the US nationally representative data from the National Health and Nutrition Examination Survey among men from 2001 to 2020. Prevalence of any, stress, urgency and overflow UI were derived. The frequency of UI was assessed in four categories: less than one time per month, a few times per month, a few times per week, and every day and/or night. All analyses were conducted using sample weights, stratification, and clustering of the complex sampling design. Sociodemographic and lifestyle correlates of UI over time were identified using multivariable logistic regressions. Data on 22994 US men (mean age, 46.6 yr [standard error, 0.20]; weighted population, 848642150) were analyzed. The prevalence of any UI increased from 2001-2002 (11.5% [95% confidence interval {CI}, 10.0-13.0]) to 2017-2020 (19.3% [95% CI, 17.2-21.3]), driven by urgency (from 9.0% [95% CI, 7.5-10.4]) to 15.2% [95% CI, 13.4-16.9]) and overflow UI (from 3.3% [95% CI, 2.7-4.0] to 5.5% [95% CI, 4.5-6.4]; all p for trend < 0.01). UI affects 38.5% US men ≥60 yr of age, with increasing trends in urgency and overflow UI and a decreasing trend in stress UI (all p for trend < 0.05). Racial/ethnic disparities were noted, with patterns differed by UI subtype. Compared with non-Hispanic White, non-Hispanic Black men were more likely to report urgency UI (odds ratio [OR], 1.94 [95% CI, 1.71-2.20]). Hispanic men were more likely to report urgency UI (OR, 1.33 [95% CI, 1.14-1.56]), but less likely to report stress (OR, 0.74 [95% CI, 0.56-0.98]) and overflow (OR, 0.75 [95% CI, 0.58-0.98]) UI. Men with higher body mass index and current smokers were more likely to report any, stress, and urgency UI than their counterparts. A higher prevalence of any UI was found in men with low family poverty ratios and chronic diseases, and those who were physically inactive. From 2001 to 2020, the overall prevalence of UI increased among US men, particularly for urgency and overflow UI. In this report, we looked at the prevalence of urinary incontinence among US men in a nationally representative sample. We found that urinary incontinence increased in the past 20 yr driving by the urgency and overflow urinary incontinence.


Interaction of (n-3) and (n-6) fatty acids in desaturation and chain elongation of essential fatty acids in cultured glioma cells.
Recent research in various biological systems has revived interest in interactions between the (n-6) and (n-3) essential fatty acids. We have utilized cultured glioma cells to show that linolenic acid, 18:3(n-3), is rapidly desaturated and chain elongated; 20:5(n-3) is the major product and accumulates almost exclusively in phospholipids. We examined effects of various (n-6), (n-3), (n-9) and (n-7) fatty acids at 40 microM concentration on desaturation and chain elongation processes using [1-14C]18:3(n-3) as substrate. In general, monoenoic fatty acids were without effect. The (n-6) fatty acids (18:2, 18:3, 20:3, 20:4 and 22:4) had little effect on total product formed. There was a shift of labeled product to triacylglycerol, and in phospholipids, slightly enhanced conversion of 20:5 to 22:5 was evident. In contrast, 22:6(n-3) was inhibitory, whereas 20:3(n-3) and 20:5(n-3) had much less effect. At concentrations less than 75 microM, all acids were inhibitory. Most products were esterified to phosphatidylcholine, but phosphatidylethanolamine also contained a major portion of 20:5 and 22:5. We provide a condensed overview of how the (n-6) and (n-3) fatty acids interact to modify relative rates of desaturation and chain elongation, depending on the essential fatty acid precursor. Thus, the balance between these dietary acids can markedly influence enzymes providing crucial membrane components and substrates for biologically active oxygenated derivatives.


Increased densities of binding sites for the "peripheral-type" benzodiazepine receptor ligand [3H]PK11195 in vulnerable regions of the rat brain in thiamine deficiency encephalopathy.
Quantitative receptor autoradiography was used to evaluate the density of high-affinity binding sites for the "peripheral-type" benzodiazepine receptor (PTBR) ligand [3H]PK11195 in brain regions of the rat at different stages of pyrithiamine-induced thiamine deficiency encephalopathy, an experimental model of the Wernicke-Korsakoff syndrome (WKS). Assessment of the density of [3H]PK11195 binding sites in thiamine-deficient animals showing no neurologic signs of thiamine deficiency encephalopathy, and revealed no significant alterations compared with pair-fed control animals in any brain region studied. Densities of [3H]PK11195 binding sites were, however, significantly increased in brain regions of the rat at the symptomatic stage, where increased densities were seen in the inferior colliculus (233% increase, p < 0.001), inferior olivary nucleus (154% increase, p < 0.001) and thalamus (up to 107% increase, p < 0.001). Histologic studies of these same brain regions revealed evidence of neuronal cell loss and concomitant gliosis. Densities of [3H]PK11195 binding sites in nonvulnerable brain regions that showed no histologic evidence of neuronal loss, such as the cerebral cortex, hippocampus, and caudate-putamen, were not significantly different from those in control animals. Increased densities of binding sites for the PTBR ligand probably reflect glial proliferation and are consistent with an excitotoxic mechanism in the pathogenesis of neuronal cell loss in thiamine deficiency encephalopathy. Positron emission tomography (PET) using [11C]PK11195 could offer a potentially useful diagnostic tool in WKS in humans.


Machine-learned analysis of side-differences in odor identification performance.
A right-left dichotomy of olfactory processes has been recognized on several levels of the perception or processing of olfactory input. On a clinical level, the lateralization of components of human olfaction is contrasted by the predominantly birhinal olfactory testing. The present analyses aimed at investigation of the relation of such side-differences related with the subject's age, sex and with the cause or degree of olfactory loss. The detection of 12 different odors from a validated clinical standard test of human olfactory function was assessed separately for both nostrils in a cohort of 6016 subjects who had reported for olfactory loss associated with different etiologies. In 26.8% of all odor identification tasks, the same odor was correctly identified only when using one but not the other nostril. Beside the subjects' age, associated with reduced olfactory performance, the analysis identified additional modulators of the agreement between nostrils, quantified as Cohen's kappa. Classical hierarchical clustering and machine-learning based deep clustering resulted in a consistent cluster structure of odors. This structure could be interpreted as possibly owing to different familiarity of the odors. The observation particularly owed to olfactory loss attributed to head trauma, which may hint at a different impact on the left or right hemisphere processing of olfactory input. Thus, between-nostrils agreement in odor identification is limited and the common unilateral olfactory testing probably misses important information. Lateral differences owe to age, sex, kind of odor and etiology of olfactory loss.


Molecular evidence of Culex pipiens form molestus and hybrids pipiens/molestus in Morocco, North Africa.
Culex pipiens L. is the most widespread mosquito vector in temperate regions including North Africa. Cx. pipiens has two recognized forms or biotypes; pipiens and molestus are morphologically indistinguishable with distinct behavior and physiology that may influence their vectorial status. In our study, we prospected for the different forms of Cx. pipiens in Morocco. Cx. pipiens larvae were collected in 9 sites throughout Morocco during summer 2010 and reared until imago stage. Cx. pipiens was identified using diagnostic primers designed for the flanking region of microsatellite CQ11. We established the presence of both forms of Cx. pipiens and their hybrids in Morocco. Molecular identification provides the first evidence of the presence of Cx. pipiens form molestus in Morocco and hybrids between pipiens and molestus forms in North Africa. The epidemiological implications of our findings are discussed.


Alcohol-based hand-disinfection reduced children's absence from Swedish day care centers.
To determine if the use of alcohol-based hand-disinfection as a complement to regular hand washing at daycare centers (DCCs) can reduce the childhood rate of absenteeism. Children aged 0-6 years attending DCC were studied in a cluster randomized controlled trial during 30 weeks. Thirty matched pairs of DCCs were included in the study, where one of the DCCs was randomized to intervention and the other to control within each pair. The intervention consisted in children and staff using alcohol-based oily disinfectant gel containing 70% ethanol after regular hand washing. The main outcome was the rate of episodes of absence from DCC due to infection. A regression model was fitted at the individual level and controlling several possible confounders for illness. Absences were reported by the parents. Differences in missing absence reports between the two groups led to only evaluating those 29 DCCs (1431 children) that were able to provide complete reports. In the multivariate regression, the intervention significantly reduced the rate of absenteeism of a child by 12% compared to a child in a control DCC (IRR 95% CI: 0.799-0.965). Hand-disinfection used by children and staff significantly decreased childrens absences due to infections in Swedish DCCs.


Small bowel capsule endoscopy impacts diagnosis and management of pediatric inflammatory bowel disease: a prospective study.
Accurately classifying inflammatory bowel disease (IBD) type in pediatric patients may impact medical decision-making, direct therapy, and improve outcomes. This was a prospective cohort study evaluating classification of IBD and patient management with use of capsule endoscopy in pediatric patients with suspected or known IBD. Treating physicians completed a questionnaire before and after capsule endoscopy (CE) assessing clinical suspicion of Crohn's disease (CD) diagnosis, patient management decisions, and perceived impact of CE findings. Eighteen subjects [11F/7M, mean age 13.8 (± 2.5) years], 4 previously diagnosed with CD, 4 with ulcerative or indeterminate colitis (UC/IC), and 10 "suspected" to have IBD were included. Following CE, 2 of 4 (50%) UC/IC patients were reclassified as having small bowel CD. In the 4 subjects with known CD, 2 (50%) had CE evidence of more proximal small bowel mucosal disease than previously recognized. In the 10 subjects with "suspected" IBD, 8 (80%) had SB ulcerations leading to a definitive diagnosis of CD. Treating physicians reported CE helped diagnosing CD in 15 of 18 (83.3%) subjects and impacted medical decision-making in 13 of 18 (72.2%), leading to a change in medical management in 14 of 18 (77.8%). In "suspected" pediatric IBD, CE often leads to a definitive diagnosis of CD. CE can lead to reclassification of IBD from UC/IC to CD and previously diagnosed CD patients may have a more significant burden of small bowel disease. These data may help integrate CE in evaluating IBD patients, lead to more targeted medical management changes and improve outcomes.


Characterization of the infection of equine fibroblasts by equine infectious anemia virus.
Equine dermal fibroblasts persistently infected with equine infectious anemia virus (EIAV) show no alterations in cell morphology or growth kinetics when compared to uninfected cells. The percentage of cells immunofluorescent positive for viral proteins fluctuated, depending upon the stage of the cell cycle, while production of extracellular virus was uniform throughout the cell cycle, increasing only as the cell number increased. This was shown in log versus stationary phase cultures as well as in cultures synchronized by sterum starvation. The establishment of productive infection did not require host cell DNA synthesis. Normal levels of progeny virus were produced in cultures pretreated with mitomycin C and placed in serum-containing medium. Serum-starved cultures, however, did not support EIAV replication as well as other cultures, presumably because synthesis of provirus was inhibited.


Development of a candidate influenza vaccine based on virus-like particles displaying influenza M2e peptide into the immunodominant loop region of hepatitis B core antigen: Insertion of multiple copies of M2e increases immunogenicity and protective efficiency.
The extracellular domain of the transmembrane protein M2 (M2e) of influenza A virus is a promising target for the development of "universal" vaccines against influenza. M2e is a poor immunogen by itself; however, when M2e is linked to an appropriate carrier, such as hepatitis B virus core (HBc) particles, it becomes highly immunogenic. Insertions of target peptides into the surface-exposed major immunodominant loop region (MIR) of the HBc antigen are especially immunogenic, but such insertions often affect the protein folding and formation of recombinant virus-like particles. To facilitate an appropriate conformation of the M2e insert, we introduced flexible linkers at the junction points between the insert and flanking HBc sequences. This approach allowed the construction of recombinant HBc particles carrying 1, 2 and 4 copies of M2e in the MIR region. These particles were produced in Escherichia coli and purified to homogeneity. The immune response and protective activity of hybrid HBc particles in mice correlated with the number of inserted M2e peptides: the highest immunogenicity and complete protection of mice against the lethal challenge by influenza virus was observed with particles carrying four copies of M2e. The possibility of the simultaneous presentation of M2e peptides from several important influenza strains on a single HBc particle could also facilitate the development of a broad-specificity vaccine efficient not only against influenza A strains of human origin but also for newly emerging strains of animal origin, such as the avian influenza.