PET imaging of myocardial beta-adrenergic receptors with fluorocarazolol: lack of interference by endogenous catecholamines.
beta-Adrenergic receptor (beta-AR) concentration can be measured in vivo using positron emission tomography (PET) and the high-affinity antagonist [18F]-(S)-fluorocarazolol {[18F]-(S)-FCZ}. However, the influence of endogenous catecholamines on the in vivo binding properties of [18F]-(S)-FCZ should be measured to aid in selection of the model used to estimate receptor concentration based on PET data. Herein we addressed the questions "What is the influence of endogenous catecholamines on the [18F]-(S)-FCZ binding in the heart?" and "In what range are the in vivo concentrations of endogenous beta-AR ligands?" In PET studies, 3 drug regimens were used to manipulate the levels of endogenous catecholamines. The time courses of myocardial concentration of [18F]-(S)-FCZ were compared before and after drug administration. In vitro binding assays and computer simulations were performed to complement the in vivo studies. Despite the large changes of endogenous catecholamines, no significant changes were observed in the [18F]-(S)-FCZ myocardial concentration. In vitro assays showed that (S)-FCZ has an affinity for beta-receptors that is 3900 and 9500 times higher than those of norepinephrine (NE) and epinephrine (EPI), respectively. Computer simulations support the hypothesis that the binding affinities relative to ligand concentrations in vivo are sufficient to explain the apparent lack of effect of endogenous catecholamines on [18F]-(S)-FCZ myocardial concentration. Increased levels of catecholamines in the physiological range do not affect the myocardial concentration of [18F]-(S)-FCZ as measured by PET. This lack of effect suggests that the myocardial concentration of NE at the synaptic sites cannot be higher than 300 nM.


Resectoscopic surgery in women with abnormal uterine bleeding and nonatypical endometrial hyperplasia.
To evaluate the role of resectoscopic surgery in the diagnosis and treatment of women with abnormal uterine bleeding and endometrial hyperplasia without atypia. Retrospective analysis (Canadian Task Force classification II-2). University-affiliated teaching hospital. Twenty-five women with simple and seven with complex hyperplasia. Hysteroscopic endometrial ablation. In patients with simple hyperplasia, average age, parity, body mass index, and mean arterial pressure were 53.2 years, 2.4 pregnancies, 30 kg/m2, and 99.5 mm Hg, respectively; in those with complex hyperplasia corresponding figures were 48 years, 2 pregnancies, 36 kg/m2, and 100 mm Hg. Nineteen of 32 women had postmenopausal bleeding, 9 of whom were taking combined hormone replacement therapy. Two had subsequent hysterectomies, one for pain and the other for incomplete resection due to an enlarged uterus. Resection could not be completed in one morbidly obese woman. One patient died from heart disease. During the follow-up of 1 to 8 years (mean 4 yrs) all patients remained amenorrheic with no evidence of recurrent disease or progression to cancer. Resectoscopic surgery by experienced hysteroscopists may be effective therapy for endometrial hyperplasia without atypia, especially in women at high risk for medical therapy or hysterectomy. Patient surveillance is mandatory for early detection and management of recurrent disease and progression to cancer.


Atrioventricular valve repair or replacement in atriopulmonary anastomosis: surgical considerations.
Three patients who underwent a modified Fontan-Kreutzer (F-K) operation required additional procedures to correct left atrioventricular valve regurgitation. Valve replacement was performed in two additional procedures, and initial annuloplasty with a Carpentier ring was carried out in the third. All 3 survived the combined procedures and are doing well after a follow-up period ranging from five months to three years. More frequent presentation of these types of patients can be expected with broadening indications for F-K procedure to more complex lesions.


HLA frequency in candidates to transplant without compatible cord blood at the National Center of Blood Transfusion (Mexico).
Umbilical Cord Blood Units (UCBU) for transplantation, are a therapeutic possibility for patients with a wide range of oncohaematological diseases and other immunologic disorders. The search of compatible donors for bone marrow transplantation is increasingly difficult for patients of mixed ethnicity. The aim of this work was determine the HLA frequency of candidates for transplantation without compatible UCBU at the National Center of from Blood Transfusion (NCBT) - Mexico. A retrospective analysis of candidates to transplant without compatible UCBU was performed in the archives from 2003 to 2016 at the NCBT. HLA class I and II genotyping of candidates was performed by medium resolution methods: Sequence Specific Primer and/or Specific Sequence Oligonucleotide. HLA frequencies were obtained by including individuals without any particular bias to a phenotype and strict statistical and genetic analysis of populations were done. The database in www.allelefrequencies.net was used in order to identify the ethnic origin of the most frequent alleles. Three hundred and sixty-four candidates without compatible UCBU for transplantation were identified. The most frequent haplotype HLA I and II were: HLA-A*02/02, 02/24, 24/24, 02/68, 01/24 and 24/68; HLA-B*39/39, 35/51, 44/44, 44/40, 35/40 and 35/35; HLA-DRB1*04/04, 13/07, 04/13, 13/13 and 03/11. The ethnic origins of the analyzed data were represented in most cases by Amerindians, Caucasics, Orientals, Asians, Arabs and Africans. This work shows the existence of a broad genetic diversity of candidates for transplantation with UCBU, making it difficult to find compatible units considering donors only from the capital.


Use of a double-hook plate to repair a subtrochanteric femoral fracture in an immature dog.
A subtrochanteric femoral fracture in a 5-month-old Doberman Pinscher was repaired by use of a 5-hole, 3.5-mm, double-hook plate. The double-hook plate afforded rigid 3-point fixation of the short proximal metaphyseal segment without impingement of the proximal femoral physis and allowed compression of the fracture fragments by placement of an interfragmentary screw through its pendulum hole. The fracture healed without complications, and the dog had a rapid return to function. Although designed for use in performing femoral osteotomies in dogs afflicted with hip dysplasia, the double-hook plate can be used to repair fractures with short proximal or distal segments.


Biomass production and nitrogen content of C3- and C4- grasses in pure and mixed culture with different nitrogen supply.
Two C3 grasses (Hordeum vulgare L., Avena sativa L.) and two C4 grasses (Panicum miliaceum L., Panicum crus-galli L.) were cultivated in standard soil in the open air in pure cultures and in various mixed cultures at low and high nitrogen fertilization levels. After three months the dry weight, length and nitrogen content of the aboveground and below-ground parts of the plants and the shoot/root ratios were determined. Hordeum vulgare was the most successful species irrespective of the nitrogen fertilization level, and also exhibited in most cases the highest nitrogen concentrations. Panicum miliaceum, on the other hand, was the species least able to compete. The production of biomass was reduced in cultures growing under nitrogen starvation conditions, this phenomenon being more pronounced with respect to the C4 than to the C3 species. The decrease in the production of biomass at low N conditions was most drastic with Panicum crus-galli, the species with the lowest nitrogen content and thus assumed to be best adapted to nitrogen starvation conditions. In cultures growing at low nitrogen fertilization levels the shoot/root ratios of all species.shifted in favour of an increasing root proportion. The extent of this shift, however, differed from species to species.


In vitro quantitative microhardness assessment of enamel with early salivary pellicles after exposure to an eroding cola drink.
To assess the erosive effect of a cola drink on enamel incorporating early salivary pellicles, 72 groups of human enamel slabs were immersed in fresh cola, with groups differing in that slabs were (1) incubated in whole or in clarified saliva, (2) under three regimes of frequency intake (1, 5 and 10 times/day); (3) immersed with or without agitation, and (4) the pellicle was incubated for 20 min, 6 or 24 h. Quantitative assessments were done over an 8-day interval using surface microhardness testing. Results for primary enamel showed a sharp decrease from baseline (344.2+/-32.4 Vickers Units; mean +/-SD) to day 1 (268.9+/-36.8), and reached 155.2+/-68.6 on day 8. Results for permanent enamel were 350.8+/-42.2, 315.9+/-39.2, and 149.8+/-85.2. Microhardness was affected by agitation, level of intake and type of saliva, but not by the pellicle incubation interval nor the type of enamel. The joint effect of static baths and higher immersion frequency was the most important factor in decreasing hardness.


[Isolated hepatocytes fixed on collagen, an accurate model for the the secretion of proteins in a minimal medium. Response to inflammation].
The albumin, orosomucoïd and alpha 2-macroglobulin secretion by isolated hepatocytes of normal and suffering from Turpentine-induced inflammation rats, is investigated for 4 hr. The model, stable over the whole duration of incubation, is a true reflect of hepatic secretion in vivo and can be used to measure it.


[Inflammatory pseudotumor in a five-year-old girl].
Inflammatory pseudotumor is the most common primary lung mass in children. In many cases, it mimics organizing pneumonia on imaging tests. Another site often affected by inflammatory pseudotumors is the orbit, although they can be found in any part of the body. Inflammatory pseudotumors are rare and quasi-neoplastic, as radiologically and clinically they behave like malignant tumors. Consensus about their pathogenesis, natural history, imaging findings, and treatment options has yet to be reached.


Voltage imaging and spinal circuits get along swimmingly.
Voltage imaging promises to unite optical and electrical approaches to accelerate circuit discovery. In this issue of Neuron, Böhm et al. (2022) use voltage imaging to explore the structure and functional dynamics of spinal excitatory interneurons in larval zebrafish and reveal the role of V3 neurons in adaptive locomotor control.


Bit-mapped colour imaging of the potential fields of propagated and segmental subcortical components of somatosensory evoked potentials in man.
Early somatosensory evoked potentials (SEPs) to median or ulnar nerve stimulation were recorded with non-cephalic reference from neck, oesophagus and scalp in normal young adults. Transit times and durations were estimated for different components. SEP fields were mapped with up to 24 skin electrodes around the neck or along the midline neck and scalp, and projected onto a 2-dimensional plane for bit-mapped colour imaging. The posterior neck N11 is a near-field potential propagated caudorostrally in the dorsal column, associated with a positive P11 far field beyond termination of the cuneate bundle. A true phase reversal of the posterior neck N13 into an anterior neck P13 is substantiated, identifying a segmental generator with horizontal axis in dorsal horn. The N13-P13 represents postsynaptic excitatory potentials in interneurones of layers IV-V of the dorsal horn. It is not reflected in any scalp far field. The duration and onset latency of N13-P13 are in line with this interpretation. A new montage of posterior-to-anterior neck can enhance this component without introducing extraneous potentials. The P14 far field does not extend below the inion and presents distinct features. Neck-to-front scalp montages confound the SEP components generated in the spinal cord and above the foramen magnum respectively, but may serve to estimate N11 onset latency.


Ligament-sparing lumbar microdiscectomy: technical note.
The prevention or inhibition of postoperative adhesions is a significant goal for successful lumbar discectomy, not only to reduce the probable risk of recurrent radiculopathy, but also to improve the likelihood of success of re-operation. We describe a new technique for sparing the ligamentum flavum in lumbar microdiscectomy. The superficial layer of the ligament is removed by horizontal splitting. Additional horizontal splitting of the ligament yields a paper-thin deep layer. Lateral vertical splitting and retraction is then carried out to provide a sufficient operative window. The split ligament returns to its original position after releasing the retraction, thereby closing the operative window. This method could preserve a layer of the ligamentum flavum to act as a physical barrier, which in turn greatly restricts the peridural fibrosis. This ligament-sparing technique enables surgeons to preserve the original anatomic plane and to reduce the extent of postoperative adhesion.


Thymic production of human FOXP3(+) regulatory T cells is stable but does not correlate with peripheral FOXP3 expression.
In humans functionally mature FOXP3(+) regulatory T (Treg) cells can be found already in the fetus, but the kinetics of their maturation is still unknown. Here, we show that from birth to until 10 years of age the thymic production of FOXP3(+) Treg cells is very stable and correlates with T-lymphopoiesis in general. The level of FOXP3 expression in the blood was also very stable, even when children and adults were compared, but there was no correlation between thymic and peripheral FOXP3 levels. Analysis of the cell cycle-associated marker Ki67 showed that a substantial fraction of peripheral FOXP3(+) cells is dividing. This characteristic was obtained in the periphery, since it was not observed in thymic CD4(+) FOXP3(+) cells. These data suggest that the thymic output of human Treg cells is intrinsically stable, while in the periphery the increased rate of proliferation severs the connection between production and homeostatic maintenance of the FOXP3(+) Treg cell population.


Immediate autonomic changes during right nostril breathing and left nostril breathing in regular yoga practitioners.
The ancient Indian science of Yoga makes use of voluntary regulation of breathing to make respiration rhythmic and calm the mind. This practice is called pranayama. Nadisuddhi pranayama means "purification of subtle energy paths," inhalation and exhalation are through alternative nostrils for successive respiratory cycles. Surya Anuloma-Viloma pranayama means "heat generating breathing particle" when the respiratory cycle of inhalation and exhalation is completed through the right nostril exclusively. When completed through the left nostril alone, the practice is called "Chandra Anuloma-Viloma pranayama," which means a heat-dissipating or cooling liberating practice. We compared the effect of right nostril breathing (RNA) and left nostril breathing (LNB) pranayama on heart rate variability. The study was conducted at the Department of Physiology at an institute of national importance, after obtaining necessary ethical approvals from the Institutional Ethics Committee. Twenty healthy kriya yogi volunteers (mean age: 44 years), who are regular practitioners for the last 10-20 years, were inducted into the study. RNB pranayama starts with closing the right nostril with the thumb of the left hand followed by exhalation through the right nostril and inhaling slowly through the same nostril. This forms one round of RNB pranayama. In contrast, inhalation through the left nostril and exhalation through the right nostril exclusively is called chandrabhedana pranayama (chandrabhedana means moon-piercing breath in Sanskrit) with a similar variation called Chandra Anuloma-Viloma pranayama in which inhalation, as well as exhalation, is performed through the left nostril exclusively. The recording of electrocardiogram (ECG) for heart rate variability (HRV) analysis was taken by heart rate variability (Dinamika HRV-Advanced Heart Rate Variability Test System, Moscow, Russia). The resting and during readings of heart rate variability parameters were compared and post hoc analysis was done using Bonferroni and Holm multiple comparisons for repeated measures. Time domain parameters: Standard deviation of normal to normal RR intervals (SDNN) and root mean square of successive NN interval differences (RMSSD) were increased at a high level of statistical significance during both pranayama maneuvres. Frequency domain parameters: LF, LF/HF ratio increased significantly. Parasympathetic activity is represented by LF when the respiration rate is lower than 7 breaths per min or during taking a deep breath. Thus, when the subject is in a state of relaxation with slow and even breathing in both RNB-right nostril and Chandra-LNB, the LF values can be very high, indicating an increase in parasympathetic activity rather than an increase in sympathetic regulation. Our study is an acute study, where changes in HRV were seen after 5 min of RNB and LNB. However, statistically, there is not much difference in the immediate effects of the two pranayamas on heart rate variability in regular yoga practitioners.


Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data.
Available diagnostic assays for Mycobacterium avium subsp. paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN-γ, ELISA-antibody and fecal shedding experimental sensitivity scores for MAP infection detection and disease progression. We used both statistical methods and dynamic mathematical models to (i) evaluate the empirical assays (ii) infer and explain biological mechanisms that affect the time evolution of the biomarkers, and (iii) predict disease stages of 57 animals that were naturally infected with MAP. This analysis confirms that the fecal test is the best marker for disease progression and illustrates that Th1/Th2 (IFN-γ/ELISA antibodies) assays are important for infection detection, but cannot reliably predict persistent infections. Our results show that the theoretical simulated macrophage-based assay is a potential good diagnostic marker for MAP persistent infections and predictor of disease specific stages. We therefore recommend specifically designed experiments to test the use of a based assay in the diagnosis of MAP infections.


Brief Behavioral Interventions for Substance Use in Adolescents: A Meta-analysis.
Adolescents with problematic substance use (SU) are at risk for far-reaching adverse outcomes. Synthesize the evidence regarding the effects of brief behavioral interventions for adolescents (12-20 years) with problematic SU. We conducted literature searches in Medline, the Cochrane Central Register of Controlled Trials, Embase, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo through October 31, 2019. We screened 33 272 records and citations for interventions in adolescents with at least problematic SU, retrieved 1831 articles, and selected 22 randomized controlled trials of brief interventions meeting eligibility criteria for meta-analysis. We followed Agency for Healthcare Research and Quality guidelines. We categorized brief interventions into components, including motivational interviewing (MI), psychoeducation, and treatment as usual. Outcomes included SU (abstinence, days used per month) for alcohol and cannabis, and substance-related problem scales. Strength of evidence (SoE) was assessed. Both pairwise and network meta-analyses were conducted by using random effects models. Compared to treatment as usual, the use of MI reduces heavy alcohol use days by 0.7 days per month (95% credible interval [CrI]: -1.6 to 0.02; low SoE), alcohol use days by 1.1 days per month (95% CrI -2.2 to -0.3; moderate SoE), and overall substance-related problems by a standardized net mean difference of 0.5 (95% CrI -1.0 to 0; low SoE). The use of MI did not reduce cannabis use days, with a net mean difference of -0.05 days per month (95% CrI: -0.26 to 0.14; moderate SoE). There was lack of consistently reported outcomes and limited available comparisons. The use of MI reduces heavy alcohol use, alcohol use days, and SU-related problems in adolescents but does not reduce cannabis use days.


[Radiotherapy for endometrial cancer: experience of the national institute of oncology with 52 cases].
Endometrial cancer is the most common gynecological cancer in the Western world. It affects mainly postmenopausal women. The aim of our study is to report the experience of the radiotherapy department of the National Oncology Institute (INO) in the treatment of endometrial cancer. We retrospectively analyzed 52 cases of endometrial cancer treated in the INO radiotherapy department between 2007-2009. Data obtained from the patient medical records were related to the epidemiologic, clinical, therapeutic and evolutionary aspects of this cancer. The median age of the patients was 57 years, 87% were postmenopausal. The median of consultation time was six months. The main symptom was metrorrhagia (51 patients). Histological diagnosis was based on biopsic curettage of uterine endometrium in 51% of the cases. Anatomo-pathological examination showed an endometrioid adenocarcinoma in 92% of the cases. After the assessment, 27% of the patients were stage I, 30% stage II, 20% stage III and 1% stage IVA, according to the International Federation of Gynecological and Obstetrics (FIGO) stage classification. After surgery, 51% of the patients received postoperative external radiotherapy. The delivered dose was 46 Gray (Gy). All patients received internal vaginal brachytherapy. From an evolutionary perspective, 83% of the patients had no recurrences during the follow-up period, 8% of patients had a local recurrence and 4% of patients had distant metastases. Therefore, surgery is the main treatment for endometrial cancer. Radiotherapy is the primary adjuvant treatment.


Indium-111 octreotide scintigraphy for the detection of non-functioning metastases from differentiated thyroid cancer: diagnostic and prognostic value.
In this prospective study, we evaluated the diagnostic and prognostic value of (111)In-octreotide scintigraphy (SRS) in papillary and follicular thyroid carcinoma (DTC) with increasing thyroglobulin (Tg) levels but no response to treatment with (131)I. Twenty-three consecutive patients (13 female, 10 male; mean age 55 years, range 13-81 years) with progressive DTC were selected for the study. All patients had non-functioning metastases, defined by no or slight uptake of (131)I in metastases. Diagnosis of tumour progression was based on rising Tg levels during follow-up and was confirmed by radiological examination. Uptake on SRS was scored from 0 to 4. Data on initial tumour stage, histology, age, gender, Tg values, TSH levels, (131)I treatment doses, intervals and survival were gathered. Seven patients died during follow-up. The overall sensitivity for the detection of metastases was 74%. The sensitivity was better in patients in whom (131)I whole-body scintigraphy did not show any abnormal uptake (82%; 14/17) than in patients with faint (131)I uptake (50%; 3/6). The 10-year survival rate was significantly different between patients with an uptake score of 0 or 1 (100%) and those with an uptake score of 2, 3 or 4 (33%) ( P=0.001). Gender, log Tg and uptake on SRS significantly correlated with survival, but in stepwise analysis, (111)In-octreotide uptake was selected as the most prognostic independent variable (hazard rate 6.25, P=0.006). We conclude that (111)In-octreotide scintigraphy is a valuable clinical tool for the detection of non-functioning DTC metastases. The uptake seems to correlate with prognosis and survival.


Biological principles of adult degenerative scoliosis.
The global aging population has led to an increase in geriatric diseases, including adult degenerative scoliosis (ADS). ADS is a spinal deformity affecting adults, particularly females. It is characterized by asymmetric intervertebral disc and facet joint degeneration, leading to spinal imbalance that can result in severe pain and neurological deficits, thus significantly reducing the quality of life. Despite improved management, molecular mechanisms driving ADS remain unclear. Current literature primarily comprises epidemiological and clinical studies. Here, we investigate the molecular mechanisms underlying ADS, with a focus on angiogenesis, inflammation, extracellular matrix remodeling, osteoporosis, sarcopenia, and biomechanical stress. We discuss current limitations and challenges in the field and highlight potential translational applications that may arise with a better understanding of these mechanisms.


Increasing doctors working in specific rural regions through selection from and training in the same region: national evidence from Australia.
'Grow your own' strategies are considered important for developing rural workforce capacity. They involve selecting health students from specific rural regions and training them for extended periods in the same regions, to improve local retention. However, most research about these strategies is limited to single institution studies that lack granularity as to whether the specific regions of origin, training and work are related. This national study aims to explore whether doctors working in specific rural regions also entered medicine from that region and/or trained in the same region, compared with those without these connections to the region. A secondary aim is to explore these associations with duration of rural training. Utilising a cross-sectional survey of Australian doctors in 2017 (n = 6627), rural region of work was defined as the doctor's main work location geocoded to one of 42 rural regions. This was matched to both (1) Rural region of undergraduate training (< 12 weeks, 3-12 months, > 1 university year) and (2) Rural region of childhood origin (6+ years), to test association with returning to work in communities of the same rural region. Multinomial logistic regression, which adjusted for specialty, career stage and gender, showed those with > 1 year (RRR 5.2, 4.0-6.9) and 3-12 month rural training (RRR 1.4, 1.1-1.9) were more likely to work in the same rural region compared with < 12 week rural training. Those selected from a specific region and having > 1-year rural training there related to 17.4 times increased chance of working in the same rural region compared with < 12 week rural training and metropolitan origin. This study provides the first national-scale empirical evidence supporting that 'grow your own' may be a key workforce capacity building strategy. It supports underserviced rural areas selecting and training more doctors, which may be preferable over policies that select from or train doctors in 'any' rural location. Longer training in the same region enhances these outcomes. Reorienting medical training to selecting and training in specific rural regions where doctors are needed is likely to be an efficient means to correcting healthcare access inequalities.


Ku70 modulation alleviates murine allergic asthma features and restores mitochondrial function in lungs.
The airway epithelium is continuously exposed to a variety of pollutants and allergens, thanks to both natural and manmade environmental pollution. With numerous protective mechanisms, the airway epithelium protects the lungs. DNA repair mechanism is one such protective response and its failure could lead to the accumulation of DNA mutations. Our lab had earlier demonstrated the dysfunctional mitochondria in airway epithelium of the asthmatic mice lungs. Here, we show that Ku70 modulation by the administration of Ku70 plasmid attenuates asthma features and reduces mitochondrial dysfunction in the lungs of allergen exposed mice. Ku70 is a key DNA repair protein with diverse roles including VDJ recombination, telomere maintenance, and maintenance of cell homeostasis. Recently, we found a reduction in Ku70 expression in asthmatic airway epithelium, and this was associated with mitochondrial dysfunction in asthmatic condition. In this study, we have shown that Ku70 over-expression in asthmatic mice attenuated airway hyperresponsiveness, airway inflammation, sub-epithelial fibrosis along with reduction in TGF-β with no effect in IL-13 levels and goblet cell metaplasia. Ku70 over-expression in asthmatic mice reduced 8-isoprostane, a marker of oxidative stress, and restored the mitochondrial function in asthmatic mice. We further found these roles of Ku70 to be independent of DNA damage as Ku70 overexpressed mice did not show any reduction in DNA tail, an index of DNA damage. Thus, our findings indicate that Ku70 can attenuate crucial features of asthma along with the restoration of mitochondrial function. This implies that Ku70 could be a therapeutic target for asthma without affecting DNA repair function.


Recent advances and applications of metabolomics to investigate neurodegenerative diseases.
Metabolomics is gaining an important role in the investigation of neurological pathologies such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis which are characterized by the absence of reliable diagnostic markers. The magnitude of emotional, physical, and financial burden related to these three devastating pathologies can be deduced considering that nearly 20 million people worldwide suffer from these three pathologies. In this chapter, an overview of the recent advances and applications of metabolomics to investigate these major neurodegenerative diseases will be presented. Metabolomics strategies are now being developed to map potential perturbations in biochemical pathways linked to neurodegeneration. Going further, there is more and more evidence supporting the concept that these pathologies can begin years or even decades before the onset of clinical symptoms, and thus, metabolomics is also increasingly being used to discover preclinical biomarkers of these neurological diseases.


Role of diffusion tensor imaging of sciatic nerve in symptomatic patients with inconclusive lumbar MRI.
To assess fractional anisotropy (FA) of sciatic nerve roots within the pelvis by using diffusion tensor imaging (DTI) in patients suffering from sciatica with inconclusive lumbar MRI. This IRB-approved prospective study included 32 consecutive subjects (11 males and 21 females; mean age 32.2 years) between September 2019 and February 2020. All patients underwent DTI (TR/TE 5800/97 ms; b = 1000; slice thickness 3,5 mm; directions = 20) on a 1.5 T scanner (Siemens Aera). Seventeen patients were symptomatic, whereas 15 patients served as control group. DTI data were analyzed by two radiologists (25 and 11 years of experience, respectively) blinded to clinical data. Each radiologist placed two ROIs on the nerve roots at three different levels. Diagnostic accuracy values of FA numbers were calculated by using receiver operator curves (ROC) and relative area under the curve (AUC), by using clinical findings as standard of reference. Inter-observer agreement was calculated with k-statistics. Paired T-test and Mann-Whitney test were used for comparison accordingly to data distribution. A value of p < 0.05 was considered statistically significant. Among the 17 symptomatic patients, FA values were significantly lower in the affected side at all levels (p < 0.05). The FA ratio (FA affected side/FA unaffected side) of symptomatic patients was significantly lower compared to control group at level 1 (p = 0.0005) and level 2 (p = 0.0006). Using a threshold of 0.90 for level 1 and 0.73 for level 2, 76 % and 71 % sensitivity and 100 % and 87 % specificity were achieved, respectively. DTI can quantitatively demonstrate sciatic nerve roots impairment within the pelvis.


Switch movements and the myosin crossbridge stroke.
The myosin II motor from Dictyostelium discoideum has been engineered to contain single tryptophan residues at strategic locations to probe movements of switch 1 and switch 2. The tryptophan residue at W501 probes movement of the relay helix and indirectly reports on switch 2 movement. This probe suggests that there is an equilibrium between the switch 2 open- and closed-states when the gamma-phosphate position is occupied. Actin does not appear to greatly affect this equilibrium directly, but has indirect influence via switch 1. The latter region has been probed by introducing tryptophan residues at positions 239 and 242. The kinetics of the actomyosin ATPase in solution is discussed with respect to recent crossbridge models based on high-resolution crystal structures.


The physiology and measurement of hot flushes.
Hot flushes occur in the vast majority of women at menopause or after bilateral oophorectomy. Yet only in the last decade have the physiologic changes associated with hot flushes been identified. It is now clear that hot flushes occur together with pulsatile release of luteinizing hormone. Available data implicate the anterior hypothalamus in the pathogenesis of the hot flush and suggest involvement of catecholamines and endogenous opiates. Estrogen withdrawal appears to be the stimulus to the development of hot flushes in susceptible women, and likewise estrogen is the most effective agent in reducing the frequency and intensity of the hot flush.


Human surfactant protein B promoter in transgenic mice: temporal, spatial, and stimulus-responsive regulation.
Surfactant protein B (SP-B) is a developmentally and hormonally regulated lung protein that is required for normal surfactant function. We generated transgenic mice carrying the human SP-B promoter (-1,039/+431 bp) linked to chloramphenicol acetyltransferase (CAT). CAT activity was high in lung and immunoreactive protein localized to alveolar type II and bronchiolar epithelial cells. In addition, thyroid, trachea, and intestine demonstrated CAT activity, and each of these tissues also expressed low levels of SP-B mRNA. Developmental expression of CAT activity and SP-B mRNA in fetal lung were similar and both increased during explant culture. SP-B mRNA but not CAT activity decreased during culture of adult lung, and both were reduced by transforming growth factor (TGF)-beta(1). Treatment of adult mice with intratracheal bleomycin caused similar time-dependent decreases in lung SP-B mRNA and CAT activity. These findings indicate that the human SP-B promoter fragment directs tissue- and lung cell-specific transgene expression and contains cis-acting elements involved in regulated expression during development, fetal lung explant culture, and responsiveness to TGF-beta and bleomycin-induced lung injury.


Sensory, olfactometric and chemical characterization of the aroma potential of Garnacha and Tempranillo winemaking grapes.
Reconstituted polyphenolic and aromatic fractions (PAFs) from 33 different Garnacha and Tempranillo grapes were incubated in strict anoxia (75 °C × 24 h). Obtained hydrolyzates were characterized by sensory analysis, gas chromatography-olfactometry (GC-O) and gas chromatography-mass spectrometry (GC-MS). Five different aroma categories emerged. Garnacha may develop specific tropical/citrus fruit, kerosene and floral and Tempranillo toasty-woody and red-fruit characteristics. Those notes seem to mask alcoholic and fruit-in-syrup descriptors and the common vegetal background. Twenty-seven odorants were detected by GC-O. GC-MS data showed a clustering closely matching the one found by sensory analysis, suggesting the existence of five specific metabolomic profiles behind the five specific sensory profiles. Overall results suggest that 3-mercaptohexanol is responsible for tropical/citrus fruit, TDN for kerosene, volatile phenols for woody/toasty, β-damascenone and massoia lactone, likely with Z-1,5-octadien-3-one for fruit-in-syrup and alcoholic notes. Nine lipid-derived unsaturated aldehydes and ketones may be responsible for the vegetal background.


Functional Characterization of MC4R Variants in Chinese Morbid Obese Patients and Weight Loss after Bariatric Surgery.
Mutations in MC4R are the most common genetic cause of obesity. In the reported Chinese morbid obesity cohort, 10 out of 59 harbor six MC4R variants, including Y35C, T53I, V103I, R165W, G233S, and C277X, among which V103I has a relatively high frequency, while other five variants are rare in the population. The prevalence of MC4R carriers in Chinese morbid obese patients (body mass index ≥ 45 kg m-2 ) is detected as 16.9% in this study. R165W and C277X are loss-of-function variants. The patient with R165W achieves excess weight loss (%EWL) as high as 20.6% and 50.3% at 1 and 8 months after surgery, respectively. G233S is reported for the first time in Asia obese population. The patient harboring G233S has a %EWL as 23.3% one month postsurgery. It is concluded that morbid obese patients with rare MC4R variants can benefit from metabolic surgery. More importantly, the choice of surgery procedure and MC4R variant should be taken into consideration for personalized treatment. In the future, a larger size cohort, accompanied with regular and longer follow-up, would be helpful.


Comparing Psoriatic Arthritis Low-field Magnetic Resonance Imaging, Ultrasound, and Clinical Outcomes: Data from the TICOPA Trial.
The Tight Control of inflammation in Psoriatic arthritis (TICOPA; isrctn.com: ISRCTN30147736) trial compared standard care (StdC) and tight control (TC) in early psoriatic arthritis (PsA), demonstrating better outcomes for TC. This substudy evaluated the performance metrics of modern imaging outcomes and compared them to the clinical data. Non-contrast 0.2T magnetic resonance imaging (MRI; single hand) was assessed using the Outcomes in Rheumatology (OMERACT) PsA MRI Scoring System (PsAMRIS) with an additional global inflammation score. Ultrasound (US; same hand) was scored for greyscale, power Doppler, and erosions at the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints and scores summated. Seventy-eight patients had paired (baseline and 48 weeks) US data and 61 paired MRI data; 50 had matched clinical, MR, and US data. Significant within-group changes were seen for the inflammatory PsAMRIS components at MCP level: MRI global inflammation [median difference (range), standardized response mean (SRM)]: 3.25 (-5.0 to 12.0), 0.68; 1.0 (-4.5 to 17.5), 0.45 for TC and StdC, respectively. Similar within-group differences were obtained for US: 1.0 (-13.0 to 23.0), 0.45; 3.0 (-6.0 to 21.0), 0.77 for TC and StdC, respectively. No differences were seen between treatment groups. Significant correlations were found between baseline and change MRI and US scores. A significant correlation was found between baseline PsA disease activity scores and MRI global inflammation scores (Spearman ρ for MCP, PIP: 0.46, 0.63, respectively). No differences in erosion progression were observed. The PsAMRIS and US inflammation scores demonstrated good responsiveness. No between-group differences were demonstrated, but this substudy was likely underpowered to determine differences between the 2 treatment strategies.


Rb regulates proliferation and rod photoreceptor development in the mouse retina.
The retinoblastoma protein (Rb) regulates proliferation, cell fate specification and differentiation in the developing central nervous system (CNS), but the role of Rb in the developing mouse retina has not been studied, because Rb-deficient embryos die before the retinas are fully formed. We combined several genetic approaches to explore the role of Rb in the mouse retina. During postnatal development, Rb is expressed in proliferating retinal progenitor cells and differentiating rod photoreceptors. In the absence of Rb, progenitor cells continue to divide, and rods do not mature. To determine whether Rb functions in these processes in a cell-autonomous manner, we used a replication-incompetent retrovirus encoding Cre recombinase to inactivate the Rb1(lox) allele in individual retinal progenitor cells in vivo. Combined with data from studies of conditional inactivation of Rb1 using a combination of Cre transgenic mouse lines, these results show that Rb is required in a cell-autonomous manner for appropriate exit from the cell cycle of retinal progenitor cells and for rod development.


5-Hydroxytryptamine depolarizes neonatal rat motorneurones through a receptor unrelated to an identified binding site.
Superfusion of hemisected lumbar spinal cord of the neonatal rat with solutions containing 10(-6) to 10(-3) M 5-hydroxytryptamine (5-HT) elicited depolarizations of graded amplitude which were recorded from motorneurons through a ventral root. Maximum responses (amplitude 1.0 +/- 0.1 mV, mean +/- SEM, n = 30) were evoked by 10(-4) M 5-HT. Repeated concentration-response curves could be determined from the same preparation. There was no involvement of 5-HT2 receptors in the depolarizing response to 5-HT, since neither ritanserin nor ICI 169, 369 showed any antagonist action. Amongst agents with activity at 5-HT1A sites, the selective 5-HT1A receptor agonist, 8-hydyroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), neither mimicked the action of 5-HT nor antagonised it, while spiperone (10(-8)-10(-7 M) antagonised responses to 5-HT in a concentration-related manner. Responses to 10(-4) M noradrenaline, used as a control depolarizing agent, were unaffected by spiperone. The onset of blockade by spiperone was slow, 1 hr being required for equilibration of the tissue with antagonist. The blockade was surmountable by larger concentrations of 5-HT. Concentration-response curves to 5-HT were shifted to the right in an approximately parallel manner by spiperone. The dose ratios measured from these curves at the EC50 level, yielded an apparent pA2 of 8.24 +/- 0.14 (mean +/- SEM, n = 15), although the Schild plot of the data had a slope less than unity. The lack of activity of the selective 5-HT1B receptor agonist, RU 24969, and the 5-HT1B receptor antagonists, (+/-) cyanopindolol and quipazine, indicated that 5-HT1B receptors were not involved in the 5-HT response of motorneurones to 5-HT. Mesulergine, metergoline and cyproheptadine also antagonised responses of motorneurones to 5-HT, producing a surmountable blockade. Mesulergine (10(-8), 3 x 10(-8) and 10(-7) M caused a progressive rightward shift of the concentration-response curves, but 10(-7) M depressed the maximum response to 5-HT. Responses to noradrenaline were not affected by these concentrations of mesulergine. The apparent pA2 for blockade of 5-HT responses by mesulergine, calculated from experiments in which there was a parallel displacement of the concentration-response curves, was 8.75 +/- 0.11 (mean +/- SEM, n = 10).(ABSTRACT TRUNCATED AT 400 WORDS)


Blind subacromial injection from the anterolateral approach: the ballooning sign.
Our aim was to verify the association of fullness over the skin distal to anterior acromion termed "ballooning" in relation to accuracy of subacromial injection and determine its accuracy in terms of sensitivity, specificity, and predictive value. We hypothesized that a positive ballooning was a sign of an accurately placed injection into the subacromial bursa. Data of 136 shoulders with impingement, which received subacromial steroid injections, were evaluated for presence of ballooning signs, pain, motion, and muscle strength. Injections were performed via anterolateral approach, followed by radiographs to locate the contrast. Data were compared between pre- and post-injections as well as between accurate and inaccurate groups to evaluate the correlations between targeting accuracy and immediate outcomes. Ballooning signs were positive in 104 shoulders (76.5%), of which majority were inaccurate (58.7%). The accuracy rate was 49.3% with sensitivity of 64.2%, specificity 11.6% and positive as well as negative predictive values of 41.3% and 25% consecutively. Dispersal rate to the surrounding structures was 86.6% with majority infiltrated the deltoid (29.4%). Significant improvement was noted between pre- and post-injections in all parameters except muscle strength, indicating equal pain relief regardless of locations. The ballooning sign is not a reliable indicator for or against subacromial injection. Blind subacromial injections are frequently inaccurate using the anterolateral approach. Nevertheless, immediate improvement of pain, motion, and muscle strength can be expected regardless of location.


Oxidative stress-induced phosphorylation of JIP4 regulates lysosomal positioning in coordination with TRPML1 and ALG2.
Retrograde transport of lysosomes is recognised as a critical autophagy regulator. Here, we found that acrolein, an aldehyde that is significantly elevated in Parkinson's disease patient serum, enhances autophagy by promoting lysosomal clustering around the microtubule organising centre via a newly identified JIP4-TRPML1-ALG2 pathway. Phosphorylation of JIP4 at T217 by CaMK2G in response to Ca2+ fluxes tightly regulated this system. Increased vulnerability of JIP4 KO cells to acrolein indicated that lysosomal clustering and subsequent autophagy activation served as defence mechanisms against cytotoxicity of acrolein itself. Furthermore, the JIP4-TRPML1-ALG2 pathway was also activated by H2 O2 , indicating that this system acts as a broad mechanism of the oxidative stress response. Conversely, starvation-induced lysosomal retrograde transport involved both the TMEM55B-JIP4 and TRPML1-ALG2 pathways in the absence of the JIP4 phosphorylation. Therefore, the phosphorylation status of JIP4 acts as a switch that controls the signalling pathways of lysosoma l distribution depending on the type of autophagy-inducing signal.


Thymus lineage commitment: a single switch.
In this issue of Immunity, He et al. (2008) establish the logic and circuitry that determine CD4-CD8 lineage specification. It all comes down to an eighty base pair silencer switch.


Unbiased Profiling of Isogenic Huntington Disease hPSC-Derived CNS and Peripheral Cells Reveals Strong Cell-Type Specificity of CAG Length Effects.
In Huntington disease (HD), the analysis of tissue-specific CAG repeat length effects has been challenging, given the difficulty in obtaining relevant patient tissues with a broad range of CAG repeat lengths. We used genome editing to generate an allelic panel of isogenic HD (IsoHD) human embryonic stem cell (hESC) lines carrying varying CAG repeat lengths in the first exon of HTT. Functional analyses in differentiated neural cells revealed CAG repeat length-related abnormalities in mitochondrial respiration and oxidative stress and enhanced susceptibility to DNA damage. To explore tissue-specific effects in HD, we differentiated the IsoHD panel into neural progenitor cells, neurons, hepatocytes, and muscle cells. Transcriptomic and proteomic analyses of the resultant cell types identified CAG repeat length-dependent and cell-type-specific molecular phenotypes. We anticipate that the IsoHD panel and transcriptomic and proteomic data will serve as a versatile, open-access platform to dissect the molecular factors contributing to HD pathogenesis.


BRCA1 mRNA expression as a predictive and prognostic marker in advanced esophageal squamous cell carcinoma treated with cisplatin- or docetaxel-based chemotherapy/chemoradiotherapy.
The molecular backgrounds that determine therapeutic effectiveness in esophageal cancer remain largely unknown. Breast cancer susceptibility gene 1 (BRCA1) expression has been found to switch the response to cisplatin- or paclitaxel-based chemotherapy. It remains unclear how variations in BRCA1 expression influence clinical outcomes in esophageal cancer. Quantitative real-time polymerase chain reaction (qPCR) was performed to examine BRCA1 mRNA expressions in paraffin-embedded specimens from 144 patients with advanced or metastatic esophageal squamous cell carcinoma who received cisplatin- or docetaxel-based first-line treatments. Low BRCA1 mRNA expression correlated with increased response rate (RR; P = 0.025 and 0.017, respectively) and median overall survival (mOS; P = 0.002 and P<0.001, respectively) in cisplatin-based chemotherapy or chemoradiotherapy group and also correlated with decreased RR (P = 0.017 and 0.024, respectively) and mOS (both P<0.001) in docetaxel-based chemotherapy or chemoradiotherapy group. Multivariate analysis revealed that low BRCA1 expression was an independent prognostic factor in cisplatin-based chemotherapy (HR 0.29; 95%CI 0.12-0.71; P = 0.007) or chemoradiotherapy (HR 0.12; 95%CI 0.04-0.37; P<0.001) group and higher risk for mortality in docetaxel-based chemotherapy (HR 5.02; 95%CI 2.05-12.28; P<0.001) or chemoradiotherapy (HR 7.02; 95%CI 2.37-27.77; P<0.001) group. BRCA1 mRNA expression could be used as a predictive and prognostic marker in esophageal cancer who underwent first-line cisplatin- or docetaxel-based treatments.


Targeting RET to induce medullary thyroid cancer cell apoptosis: an antagonistic interplay between PI3K/Akt and p38MAPK/caspase-8 pathways.
Mutations in REarranged during Transfection (RET) receptor tyrosine, followed by the oncogenic activation of RET kinase is responsible for the development of medullary thyroid carcinoma (MTC) that responds poorly to conventional chemotherapy. Targeting RET, therefore, might be useful in tailoring surveillance of MTC patients. Here we showed that theaflavins, the bioactive components of black tea, successfully induced apoptosis in human MTC cell line, TT, by inversely modulating two molecular pathways: (i) stalling PI3K/Akt/Bad pathway that resulted in mitochondrial transmembrane potential (MTP) loss, cytochrome-c release and activation of the executioner caspases-9 and -3, and (ii) upholding p38MAPK/caspase-8/caspase-3 pathway via inhibition of Ras/Raf/ERK. Over-expression of either constitutively active myristoylated-Akt-cDNA (Myr-Akt-cDNA) or dominant-negative-caspase-8-cDNA (Dn-caspase-8-cDNA) partially blocked theaflavin-induced apoptosis, while co-transfection of Myr-Akt-cDNA and Dn-caspase-8-cDNA completely eradicated the effect of theaflavins thereby negating the possibility of existence of other pathways. A search for the upstream signaling revealed that theaflavin-induced disruption of lipid raft caused interference in anchorage of RET in lipid raft that in turn stalled phosphorylation of Ras and PI3Kinase. In such anti-survival cellular micro-environment, pro-apoptotic signals were triggered to culminate into programmed death of MTC cell. These findings not only unveil a hitherto unexplained mechanism underlying theaflavin-induced MTC death, but also validate RET as a promising and potential target for MTC therapy.


Field trial evaluation of premilking teat disinfection.
Efficacy of premiliking teat disinfection (predipping) with good udder preparation was compared with good udder preparation alone on four well-managed, commercial dairy farms. Three teat dip formulations containing iodophor were used for predipping. Predipping reduced the rate of intramammary infection with major mastitis pathogens approximately 54%. Infection rate with esculin-positive streptococci and coliforms was reduced more than 51%. Udder infections with coagulase-negative staphylococci were not controlled by predipping.


The intention to exercise and the execution of exercise among persons with multiple sclerosis--a qualitative metasynthesis.
This review was designed as a qualitative metasynthesis aiming to identify factors influencing the intention to exercise and the execution of exercise among persons with multiple sclerosis (PwMS). Based on principles laid out by Sandelowski and Barroso, this qualitative metasynthesis started with a systematic literature search for studies of PwMS's experiences relating to exercise in the following databases: CINAHL, Rehabilitation and Sports Medicine Source, PubMed, Web of Science and Psychology & Behavioral Science. The metasynthesis procedure also included critical appraisal using the Consolidated Criteria for Reporting Qualitative Research checklist, and integrating synthesis of the articles' findings. The metasynthesis included nine articles. Factors identified as influencing intention to exercise and the execution of exercise included social support, professional support and outcome expectations. Strong relationships between these three themes were detected for the intention to exercise, the execution of exercise or both among PwMS. The present metasynthesis offers a comprehensive understanding of factors influencing the intention to exercise and the execution of exercise among PwMS. Our findings reveal that health professionals influence the part of the process where PwMS enter the exercise setting, as well as the PwMS's intention to exercise. Social support, professional support and outcome expectations are potential facilitators and barriers for the intention to exercise and the execution of exercise among PwMS. Health professionals specializing in MS rehabilitation can influence the intention and the execution of physical exercise among PwMS when there exists a personal and supportive patient-professional relationship. Outcome expectations may impact the motivational and volitional phases of physical exercise.


Relaxation phenomena of polyethyleneimine molecules within saturated homogeneous and heterogeneous layers adsorbed at a silica/water interface.
Surface area exclusion chromatography was used to investigate the adsorption characteristics of the highly branched polyethyleneimine (PEI) molecule and of a related molecule resulting from the grafting of PEI with C12 to C22 alkyl chains. The interfacial relaxation and surface affinity of the two polymers was determined in homogeneous and heterogeneous layers. The presence of hydrophobic moieties within the branched morphology of the grafted PEI molecule was found to modify the adsorption histogram as compared to bare PEI and to lead to greater interfacial stability. The relaxation of the bare and grafted macromolecules proved to be of equal extent but to develop at different rates within homogeneous layers. In heterogeneous layers composed of the two polymers, the slower relaxation of the grafted macromolecules decreased the rate of relaxation of the bare molecules, while the faster relaxation of the bare molecules strongly increased the rate and extent of the relaxation of the grafted macromolecules. The same technique was then used to determine the mode of establishment of the layers. The polymer coating profiles on successive glass fiber filters of the chromatography column were found to depend on the sequence of injection of the two polymers. Simultaneous and sequential adsorption processes were analyzed on the basis of the random sequential adsorption of macromolecules.


A new species of Trichodina (Ciliophora: Peritrichia) from the intestine of the surgeonfish Acanthurus xanthopterus.
A population of a trichodinid (Ciliophora: Peritrichia) was found in the gut of the surgeonfish Acanthurus xanthopterus collected from Hawaii, South Africa and New Guinea and described as a new species. This is only the second record of a trichodinid from the intestine of a marine fish. In all the fish specimens examined, the micro-fauna normally found in other species of the fish family. Acanthuridae was absent and replaced entirely by the trichodinid population.


Insulin administration protects from paraplegia in the rat aortic occlusion model.
The effect of insulin induced hypoglycemia was evaluated in a rat aortic occlusion model of ischemic paraplegia. One hour before aortic occlusion, 200-250 g Sprague-Dawley rats received either 1 cc of saline or 0.5 units regular insulin in 1 cc saline. Rats were then anesthetized, intubated, and ventilated with halothane (1-1.5%). The aortic arch was exposed and snares were placed on the right and left subclavian arteries and the aorta distal to the left subclavian. The three vessels were occluded for 10 min. Lower extremity neurologic deficit was evaluated at 1, 4, 18, and 24 hr postocclusion based on a 15-point scale (0 = normal, 15 = severe deficit). Lower extremity neurologic deficit was significantly decreased in the insulin-treated group at 18 and 24 hr postocclusion (P = 0.005 and 0.006, respectively, Student's test). Blood glucose concentration was significantly lower at the time of occlusion in the insulin-treated group when compared to the saline-treated group (P = 0.001). We conclude that in this rat model of paraplegia, insulin induced hypoglycemia is associated with a reduction in lower extremity neurologic deficit produced by temporary aortic occlusion.


Competitor mRNA fragments for quantitation of cytokine specific transcripts in cell lysates.
Synthetic RNAs (sRNAs) specific for four human cytokines were constructed and used as an exogenous internal standard in a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). The sequences of the sRNA and the target mRNA were identical except for a duplication or deletion of approximately 100 nucleotides. The size difference between these two templates permitted easy electrophoretic separation of their PCR products. The sRNA has polyadenylated sequences at the 3' end and can be added directly either to a cell lysate before RNA purification or to a reverse transcription reaction. One pair of primers is used to amplify the internal standard and the target simultaneously, and the ratio of the two PCR products remains constant throughout the amplification. This technique can be applied to quantitate specific mRNA in as few as 10 cells when the exogenous control is added directly to cell lysates. This method is sensitive, accurate and adaptable for quantitation of other transcripts.


Observation in inner ear of tree shrew using scanning electron microscope and the Atoh1 distribution in cochlea.
This study aimed to observe the ultrastructure on the surface of the inner ear of a normal tree shrew using scanning electron microscope (SEM). The specimens of cochlea, macula utriculi, macula sacculi, and crista ampullaris of the normal adult tree shrew were collected and observed by SEM. We used immunofluorescence for cochlear protein Atoh1 staining. We observed that cochlea of the tree shrew is centered on the cochlear axis, circling about 3.5 times from bottom to top of the cochlea. The organ of Corti is located between medial and lateral grooves, including inner and outer hair cells as well as supporting cells. Maculae staticae include macula of saccule and macula of utricle, and the surface of macula is covered with a large number of otoliths. We found a gelatinous layer below the otoliths, followed by the layer of the honeycomb structure. The hair cell cilia of macula and crista ampullaris include one kinocilium and more stereocilia. There is no obvious cross structure but numerous hair cell cilia on semicircular canal crista ampullaris. Immunofluorescence staining showed that protein Atoh1 is mainly distributed in the nucleus of the cochlea's inner and outer hair cells. The observation of the inner ear structure under SEM elucidate the fine surface morphological structure of the entire cochlea, the vestibular maculae staticae, and crista ampullaris, providing new insight into the structure and function of the inner ear of tree shrew. HIGHLIGHTS: This article is the first to describe the inner ear ultrastructure of a small primate tree shrew by scanning electron microscopy (SEM). Under an SEM, the phalangeal processes of Deiter cells in tree shrews were observed to be connected to the tip of a neighboring hair cell, which was different from that of Deiters' cells in guinea pigs, and this crossed one hair cell, and connected to the tip of the third hair cell. It was observed that the crista ampullaris of tree shrews were horseshoe-shaped, and similar to that of humans and monkeys, this had no obvious "cross-shaped hump" structure. Tree shrew's ABR threshold value curve conforms to the mammalian U-shaped curve, wave III is the main wave of ARB, its sensory frequency may be higher 8 kHz, and the characteristics of the stereocilia of tree shrew we have observed may be related to the perception of higher frequency hearing.


Propagation method for persistent high yield of diverse Listeria phages on permissive hosts at refrigeration temperatures.
The efficient production of a high concentration of bacteriophage in large volumes has been a limiting factor in the exploration of the true potential of these organisms for biotechnology, agriculture and medicine. Traditional methods focus on generating small volumes of highly concentrated samples as the end product of extensive mechanical and osmotic processing. To function at an industrial scale mandates extensive investment in infrastructure and input materials not feasible for many smaller facilities. To address this, we developed a novel, scalable, generic method for producing significantly higher titer psychrophilic phage (P < 2.0 × 10(-6)), 2- to 4-fold faster than traditional methods. We generate renewable high yields from single source cultures by propagating phage under refrigeration conditions in which Listeria, Yersinia and their phages grow in equilibrium. Diverse Yersinia and Listeria phages tested yielded averages of 3.49 × 10(8) to 3.36 × 10(12) PFU/ml/day compared to averages of 1.28 × 10(5) to 1.30 × 10(10) PFU/ml/day by traditional methods. Host growth and death kinetics made this method ineffective for extended propagation of mesophilic phages.


Synaptic alterations as a neurodevelopmental trait of Duchenne muscular dystrophy.
Dystrophinopaties, e.g., Duchenne muscular dystrophy (DMD), Becker muscular dystrophy and X-linked dilated cardiomyopathy are inherited neuromuscular diseases, characterized by progressive muscular degeneration, which however associate with a significant impact on general system physiology. The more severe is the pathology and its diversified manifestations, the heavier are its effects on organs, systems, and tissues other than muscles (skeletal, cardiac and smooth muscles). All dystrophinopaties are characterized by mutations in a single gene located on the X chromosome encoding dystrophin (Dp427) and its shorter isoforms, but DMD is the most devasting: muscular degenerations manifests within the first 4 years of life, progressively affecting motility and other muscular functions, and leads to a fatal outcome between the 20s and 40s. To date, after years of studies on both DMD patients and animal models of the disease, it has been clearly demonstrated that a significant percentage of DMD patients are also afflicted by cognitive, neurological, and autonomic disorders, of varying degree of severity. The anatomical correlates underlying neural functional damages are established during embryonic development and the early stages of postnatal life, when brain circuits, sensory and motor connections are still maturing. The impact of the absence of Dp427 on the development, differentiation, and consolidation of specific cerebral circuits (hippocampus, cerebellum, prefrontal cortex, amygdala) is significant, and amplified by the frequent lack of one or more of its lower molecular mass isoforms. The most relevant aspect, which characterizes DMD-associated neurological disorders, is based on morpho-functional alterations of selective synaptic connections within the affected brain areas. This pathological feature correlates neurological conditions of DMD to other severe neurological disorders, such as schizophrenia, epilepsy and autistic spectrum disorders, among others. This review discusses the organization and the role of the dystrophin-dystroglycan complex in muscles and neurons, focusing on the neurological aspect of DMD and on the most relevant morphological and functional synaptic alterations, in both central and autonomic nervous systems, described in the pathology and its animal models.


Assessment of the effectiveness of the post-Fukushima food monitoring campaign in the first year after the nuclear accident: A hypothesis.
The purpose of this study was to assess whether or not the food monitoring campaign after the Fukushima nuclear accident has been successful in reducing the number of above-limit-food from reaching the consumers. The hypothesis of this study is that the fraction of "post-market" food can be used for this purpose, when the post-market fraction in the above-limit (p') items is compared to the post-market fraction in the entity of food items (p) that have been screened for radionuclides ((134)Cs and (137)Cs). Indeed the post-market fraction in most vegetarian produce decreased significantly in the above-limit food items (p'/p < 1), indicating a high efficiency of the monitoring campaign. For tea, however, the analysis reveals a low efficiency of the campaign (p'/p ≈ 1). For beef, the fraction of post-market-foods within the above-limit samples was much higher than the respective fraction in the entity of measured samples (p'/p > 1), indicating a much lower effectiveness of the monitoring action for beef. The author speculates that, by following the governmental monitoring manual (which gives "meat" only second priority), the sudden exceedances caught the monitoring agencies unprepared and triggered a much higher density monitoring of beef with the delay of several weeks. Even then, many above limit items reached the market (mainly because the monitoring during this period had focused on the post-market). Therefore, it is likely that some above-limit beef has been consumed by the public. For other meat products, the fraction of post-market samples was very low, which does not allow for the validation of the effectiveness of the monitoring campaign. Overall, the monitoring seemed to have been more effective for vegetarian produce than for meat.


Ethnopharmacological survey of the Bunda district, Tanzania: plants used to treat infectious diseases.
An ethnobotanical study was carried out in six villages in the Bunda district, Mara Region, Tanzania, where the use of plants still has a special meaning to the society, in the treatment of various diseases. Information was obtained from the traditional healers and other experienced persons, having some knowledge on medicinal plants. Fifty-two plants were reported for use in the treatment of various infectious diseases. These plants belong to 29 families, with Papilionaceae being the most represented. Leaves ranked the highest, especially for use in topical preparations. Oral administration was the most frequently used route of administration. Twenty-one percent of the recorded plants were reported for treating venereal diseases, with syphilis and gonorrhea being the most commonly mentioned. Information providers requested feedback with regard to the plants proven scientifically to be toxic in order to avoid risks while offering their services. From this work it was found out that, people in this area commonly use medicinal plants with trust they have built on the curative outcome witnessed. As the first ethnobotanical study in Bunda district recording 52 plants in a small area covered, publication of this work is expected to open up more studies to record many useful medicinal plants unfolded.


Myeloid metaplasia of the central nervous system in patients with myelofibrosis and agnogenic myeloid metaplasia. Report of 3 cases and review of the literature.
Foci of meningeal myeloid metaplasia were found in 3 of 11 consecutive autopsied patients with myelofibrosis and agnogenic myeloid metaplasia. The clinical and pathological findings in an additional seven published patients with agnogenic myeloid metaplasia who developed neurological manifestations due to pressue of hemopoietic tumors in the central nervous system are reviewed.


Level and Relationships of Life Satisfaction with Cognitive Flexibility and Resilience in IT Professionals.
Information Technology (IT) professionals commonly encounter occupation-related issues that adversely affect psychological health and well-being. To study the level and relationships of life satisfaction with cognitive flexibility and resilience in IT professionals. In this cross-sectional study, 457 IT professionals were assessed with Sociodemographic proforma, Cognitive Flexibility Scale (CFS), Cognitive Resilience Scale (CRS), and Satisfaction with Life Scale (SWLS). Descriptive statistics, Student's t-test, ANOVA, and linear regression analysis. The mean score on CRS was high (4.5), whereas on CFS was low (49.36). The mean score on SWLS was also low (17.36) particularly with widowed and disrupted family status, positively linked to the scoring of CFS & CRS, and negatively linked to hours of work. Among Indian IT professionals, cognitive flexibility and life satisfaction are low and influenced by family. Life satisfaction is proportionately linked to cognitive flexibility and resilience.


Time-Resolved Decoding of Two Processing Chains during Dual-Task Interference.
The human brain exhibits fundamental limitations in multitasking. When subjects engage in a primary task, their ability to respond to a second stimulus is degraded. Two competing models of multitasking have been proposed: either cognitive resources are shared between tasks, or they are allocated to each task serially. Using a novel combination of magneto-encephalography and multivariate pattern analyses, we obtained a precise spatio-temporal decomposition of the brain processes at work during multitasking. We discovered that each task relies on a sequence of brain processes. These sequences can operate in parallel for several hundred milliseconds but beyond ∼ 500 ms, they repel each other: processes evoked by the first task are shortened, while processes of the second task are either lengthened or postponed. These results contradict the resource-sharing model and further demonstrate that the serial model is incomplete. We therefore propose a new theoretical framework for the computational architecture underlying multitasking.


Quantitative oxygen measurements before and after intravascular guanethidine blocks.
In 11 patients oxygen pressure was measured transcutaneously before and after treatment with regional intravascular sympathetic blocks in extremities with pain, impairment of function, and/or dystrophy. In 50 normal individuals PO2 levels were determined in the hand. All patients showed lower than normal values before treatment. Subjective complaints were registered by means of a questionnaire before and after treatment. Improvement of PO2 levels was observed after treatment in eight out of 11 patients while complaints disappeared. Three out of 11 patients showed no improvement of PO2 levels or any lessening of complaints. Control PO2 values in the contralateral limbs stayed on the same level as before treatment in all patients. From the results in this article it can be stated that TcPO2 measurements seem to be helpful in (1) evaluating the pretreatment microvascular state of the affected limb and (2) judging the efficacy of the block.


Langerhans cells from women with cervical precancerous lesions become functionally responsive against human papillomavirus after activation with stabilized Poly-I:C.
Human papillomavirus (HPV)-mediated suppression of Langerhans cell (LC) function can lead to persistent infection and development of cervical intraepithelial neoplasia (CIN). Women with HPV-induced high-grade CIN2/3 have not mounted an effective immune response against HPV, yet it is unknown if LC-mediated T cell activation from such women is functionally impaired against HPV. We investigated the functional activation of in vitro generated LC and their ability to induce HPV16-specific T cells from CIN2/3 patients after exposure to HPV16 followed by treatment with stabilized Poly-I:C (s-Poly-I:C). LC from patients exposed to HPV16 demonstrated a lack of costimulatory molecule expression, inflammatory cytokine secretion, and chemokine-directed migration. Conversely, s-Poly-I:C caused significant phenotypic and functional activation of HPV16-exposed LC, which resulted in de novo generation of HPV16-specific CD8(+) T cells. Our results highlight that LC of women with a history of persistent HPV infection can present HPV antigens and are capable of inducing an adaptive T cell immune response when given the proper stimulus, suggesting that s-Poly-I:C compounds may be attractive immunomodulators for LC-mediated clearance of persistent HPV infection.


DNA gyrase inhibitory activity of ellagic acid derivatives.
Ellagic acid was found to inhibit E. coli DNA gyrase supercoiling with approximately the same potency as nalidixic acid. Tricyclic analogs of ellagic acid, which vary in the number and position of the hydroxy groups as well as their replacement with halogens, have been synthesized. The biological activity of these analogs is discussed.


Non-selective afferent innervation develops in embryonic mouse spinal cord-dorsal root ganglia explants chronically exposed to GM1 ganglioside.
Projection patterns of dorsal root ganglion afferents within organotypic explants of fetal mouse spinal cord were examined histologically using a horseradish peroxidase staining method. All explants were also examined electrophysiologically and showed spontaneous and evoked bioelectric discharges, which were evenly distributed across the cord explants. Explants chronically grown in a serum-free medium containing the monosialoganglioside GM1 failed to develop dorsal cord selectivity as was previously observed when a mixture of gangliosides was used. It therefore appears that not all gangliosides can induce selectivity in this model.


Cellulose supported layered double hydroxides for the adsorption of fluoride from aqueous solution.
Cellulose supported layered double hydroxides (CSLDHs) were synthesized and tested for adsorption of fluoride in aqueous medium. Three samples of cellulose supported LDHs were synthesized by varying the LDH loading on cellulose. The raw cellulose, unsupported LDH and cellulose supported LDHs were characterized by XRD, SEM and BET surface area. Batch adsorption as well as fixed-bed column experiments were performed for determining the fluoride adsorption characteristics of CSLDHs. The fluoride adsorption properties of CSLDHs were found to be superior to that of reported adsorbents, including activated alumina and carbon nanotubes. Defluoridation capacity of the CSLDHs was 2-4 times higher than that of unsupported LDH. The cellulose supported LDH, CSLDH-50, having an LDH loading of 27% showed maximum fluoride uptake capacity (5.29 mg g(-1) of CSLDH, 25.18 mg g(-1) of LDH) in fixed-bed column study.


Pathogenic role of autoantibodies against inhibitory synapses.
Diverse neuropsychiatric diseases were recently linked to specific anti-neuronal autoantibodies targeting synaptic proteins. Symptoms can range from epileptic seizures to cognitive impairment to movement disorders, commonly responding to treatment with immunotherapy. Several of these autoantibodies target inhibitory synapses that use GABA or glycine as neurotransmitters. Despite their relatively low abundance, inhibitory neurons are extraordinarily diverse in anatomical, electrophysiological and molecular terms, reflecting the variable clinical phenotypes of affected patients. Indeed, data on the antibody effects in neuronal cultures or animals models suggest that most of these antibodies are directly pathogenic by down-regulating synaptic proteins, activating complement or antagonizing ligand binding. The present review summarizes the current achievements in the field of humoral autoimmunity related to inhibitory networks, state-of-the-art diagnostics and clinical characterization of patients. In many instances, the phenotypic spectrum of patients with GABA receptor, glycine receptor, amphiphysin or GAD65 antibodies mirror the experimental findings, suggesting that ongoing work will markedly contribute to the better understanding of pathophysiology in this exciting patient group and might pave the way for disease-specific immunotherapy.


Homage to an unknown photographer.
The Daguerreotype is an integral part of modern history as artifact and witness to great events and forms the basis on which the first surgical photograph of an amputation was taken in North America, during the Mexican-American War between 1846 and 1847; however, its photographer remains unknown.


Living donor liver transplantation for a child with recurrent pediatric adult-type hepatocellular carcinoma.
Pediatric hepatocellular carcinoma (HCC) is an uncommon disease with a poor prognosis. There are few reports about liver transplantation for pediatric adult-type HCC. We experienced a case of living donor liver transplantation (LDLT) for a child with recurrent pediatric adult-type HCC. A 12-year-old boy was admitted to the Department of Pediatrics in our institution due to HCC in May 2005. He underwent hepatectomy after 3 courses of chemotherapy in July 2005. After the operation, he had 2 more courses of the same chemotherapy. His posttheraputic course was uneventful for 1 year. However, his alpha-fetoprotein level increased and a computed tomography (CT) scan showed recurrent tumor in his remnant liver in October 2006. He underwent another chemotherapy session immediately. However, CT revealed multiple liver tumors after chemotherapy in December 2006. His mother requested to be an LDLT donor, which was performed on January 23, 2007. The donor operation was a right hepatic lobectomy. The postoperative course of the donor was unremarkable and she has now returned to work. The recipient's posttransplantation course was uneventful and he was discharged at postoperative day 53 and is currently doing well. Liver transplantation in conjunction with chemotherapy may have an increasing role in the management of pediatric HCC.


Curcumin combined with photodynamic therapy, promising therapies for the treatment of cancer.
Curcumin, a phytochemical derived from the rhizome of turmeric (Curcuma longa L.), has a broad group of substances with antibacterial, anti-inflammatory, anti-oxidant, anticancer activities. The anticancer activity of curcumin and its derivatives are mainly related to its regulation of signal transduction pathways. However, due to the low oral availability of curcumin, fast metabolism and other pharmacokinetic properties limit the application of curcumin in the treatment of cancer. Evidence suggests that curcumin combined with photodynamic therapy can overcome the limitation of curcumin's low bioavailability by acting on apoptosis pathways, such as B-cell lymphoma 2 (Bcl-2) and caspase family, and affecting cell cycle. This paper reviews the structure and pharmacokinetics of curcumin, focusing on the anticancer activity of curcumin combined with photodynamic therapy and the effects on cancer-related signal pathways.


Beta spectral power during sleep is associated with impaired recall of extinguished fear.
The failure to retain memory for extinguished fear plays a major role in the maintenance of posttraumatic stress disorder (PTSD), with successful extinction recall necessary for symptom reduction. Disturbed sleep, a hallmark symptom of PTSD, impairs fear extinction recall. However, our understanding of the electrophysiological mechanisms underpinning sleep's role in extinction retention remains underdetermined. We examined the relationship between the microarchitecture of sleep and extinction recall in healthy humans (n = 71, both male and females included) and a pilot study in individuals with PTSD (n = 12). Participants underwent a fear conditioning and extinction protocol over 2 days, with sleep recording occurring between conditioning and extinction. Twenty-four hours after extinction learning, participants underwent extinction recall. Power spectral density (PSD) was computed for pre- and post-extinction learning sleep. Increased beta-band PSD (~17-26 Hz) during pre-extinction learning sleep was associated with worse extinction recall in healthy participants (r = 0.41, p = .004). Beta PSD was highly stable across three nights of sleep (intraclass correlation coefficients > 0.92). Results suggest beta-band PSD is specifically implicated in difficulties recalling extinguished fear.


Electrophysiological and antiarrhythmic effects of UK 52,046-27 during ischaemia and reperfusion in the guinea-pig heart.
1. We studied the antiarrhythmic and electrophysiological effects of UK 52,046-27 (10(-8) M and 5 x 10(-8) M), a highly selective alpha 1-adrenoceptor antagonist, during global ischaemia (flow reduced to 10% of control for 30 min) and reperfusion, in isolated, buffer-perfused hearts of guinea-pigs. 2. The compound had few electrophysiological effects during normal perfusion, although action potential amplitude and Vmax were reduced with 10(-8) M (by 9% and 22%) and refractory period was increased with 5 x 10(-8) M (by 13%) compared to control hearts. 3. Perfusion with 5 x 10(-8) M UK 52,046-27 reduced the incidence of ventricular tachycardia during ischaemia from 67% to 25%, and during reperfusion reduced the incidence of ventricular tachycardia (from 83% to 17%) and ventricular fibrillation (from 67% to 8%). 4. The compound prolonged significantly action potential duration and refractory period during ischaemia and reperfusion. Vmax was reduced to a greater extent during reperfusion in the treated hearts, while greater increases in QRS width and stimulation threshold occurred during ischaemia in the treated group. 5. These results confirm that blockade of the alpha 1-adrenoceptor subpopulation during myocardial ischaemia and reperfusion decreases the incidence of arrhythmias and alters cellular electrophysiology during ischaemia and reperfusion.


Intentional mind-wandering as intentional omission: the surrealist method.
Mind-wandering seems to be paradigmatically unintentional. However, experimental findings have yielded the paradoxical result that mind-wandering can also be intentional. In this paper, we first present the paradox of intentional mind-wandering and then explain intentional mind-wandering as the intentional omission to control one's own thoughts. Finally, we present the surrealist method for artistic production to illustrate how intentional omission of control over thoughts can be deployed towards creative endeavors.


S-thiolation of cytoplasmic cardiac creatine kinase in heart cells treated with diamide.
Two methods for quantitation of protein S-thiolation, by isoelectric focusing or by enzyme activity, were used for studying S-thiolation of cytoplasmic cardiac creatine kinase. With these methods, creatine kinase was identified as a major S-thiolated protein in both bovine and rat heart. In rat heart cell cultures, creatine kinase became 10% S-thiolated during a 10 min incubation with 0.2 mM diamide. This enzyme became S-thiolated more slowly than other heart cell proteins and it also dethiolated more slowly. Two sequential additions of diamide at a 25 min interval caused twice as much S-thiolation after the second addition as compared to the first. This increased sensitivity to the second diamide treatment may have resulted from glutathione loss during the first addition which produced a higher GSSG-to-GSH ratio after the second treatment. The GSSG-to-GSH ratio was highest prior to the maximum S-thiolation of creatine kinase, but, in general, the time course of glutathione was similar to the S-thiolation of creatine kinase. This study demonstrates that cytoplasmic creatine kinase is S-thiolated and, therefore, inhibited during a diamide-induced oxidative stress in heart cells. Implications for regulation of cardiac metabolism during oxidative stress are discussed.


Good outcome of brain stem progressive multifocal leukoencephalopathy in an immunosuppressed renal transplant patient: Importance of early detection and rapid immune reconstitution.
Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis.


Progressive myopathy in an inducible mouse model of oculopharyngeal muscular dystrophy.
The genetic basis of oculopharyngeal muscular dystrophy (OPMD) is a short expansion of a polyalanine tract (normal allele: 10 alanines, mutant allele: 11-17 alanines) in the nuclear polyadenylate binding protein PABPN1 which is essential for controlling poly(A) tail length in messenger RNA. Mutant PABPN1 forms nuclear inclusions in OPMD muscle. To investigate the pathogenic role of mutant PABPN1 in vivo, we generated a ligand-inducible transgenic mouse model by using the mifepristone-inducible gene expression system. Induction of ubiquitous expression of mutant PABPN1 resulted in skeletal and cardiac myopathy. Histological changes of degenerative myopathy were preceded by nuclear inclusions of insoluble PABPN1. Downregulation of mutant PABPN1 expression attenuated the myopathy and reduced the nuclear burden of insoluble PABPN1. These results support association between mutant PABPN1 accumulation and degenerative myopathy in mice. Resolution of myopathy in mice suggests that the disease process in OPMD patients may be treatable.


Congenital long QT syndrome inducing 2:1 atrioventricular block: early detection in fetal life.
A case is reported of congenital long QT interval associated with fixed 2:1 atrioventricular block. The bradycardia was detected at 16 weeks of gestational age. The atrioventricular block was due to an extremely delayed ventricular repolarization. Early detection of bradycardia in fetal life and the demonstration of a normal positive correlation between QT duration and ventricular rate suggest that, in this case, the syndrome may be due to an anomaly of the myocardial cells rather than to imbalance of the sympathetic nervous system.


Tigecycline Lock Therapy for Catheter-Related Bloodstream Infection Caused by KPC-Producing Klebsiella pneumoniae in Two Pediatric Hematological Patients.
Catheter-related bacteremias carry high mortality rates in hematological patients. When a multidrug-resistant microorganism is involved, the catheter should ideally be removed; however, this approach is not always possible. Tigecycline lock therapy was used in two pediatric oncohematological patients with intravascular catheter-related infection due to KPC-producing Klebsiella pneumoniae. The catheter was salvaged in both cases, and the patients were later discharged. Our experience suggests the usefulness of this approach in treating this type of infection.


Neural stem cells over-expressing brain-derived neurotrophic factor (BDNF) stimulate synaptic protein expression and promote functional recovery following transplantation in rat model of traumatic brain injury.
Brain-derived neurotrophic factor (BDNF) plays an essential regulatory role in the survival and differentiation of various neural cell types during brain development and after injury. In this study, we used neural stem cells (NSCs) genetically modified to encode BDNF gene (BDNF/NSCs) and naive NSCs transplantation and found that BDNF/NSCs significantly improved neurological motor function following traumatic brain injury (TBI) on selected behavioral tests. Our data clearly demonstrate that the transplantation of BDNF/NSCs causes overexpression of BDNF in the brains of TBI rats. The number of surviving engrafted cells and the proportion of engrafted cells with a neuronal phenotype were significantly greater in BDNF/NSCs than in naive NSCs-transplanted rats. The expression of pre- and post-synaptic proteins and a regeneration-associated gene in the BDNF/NSCs-transplanted rats was significantly increased compared to that in NSCs-transplanted rats, especially at the early stage of post-transplantation. These data suggest that neurite growth and overexpression of synaptic proteins in BDNF/NSCs-transplanted rats are associated with the overexpression of BDNF, which is hypothesized to be one of the mechanisms underlying the improved functional recovery in motor behavior at the early stage of cell transplantation following TBI. Therefore, the protective effect of the BDNF-modified NSCs transplantation is greater than that of the naive NSCs transplantation.


Serum lipids and lipoproteins in the atherosclerosis prone LA/N corpulent rat.
The LA/N rat is one of two congenic strains bred from the original obese, hyperphagic and hypertensive rats of Koletsky. With the exception of hypertension the LA/N strain, when homozygous for the corpulent gene, is phenotypically similar to the parent Koletsky strain and prone to the development of vascular and myocardial lesions. Here we report a detailed analysis of the serum lipids, lipoproteins and apolipoproteins B, E and A-I levels in young adult homozygous corpulent (cp/cp) rats of both sexes and in lean males of the same age which were demonstrable non-carriers (+/+) of the cp gene. Both male and female cp/cp rats were hypertriglyceridemic (282-512 mg/100 ml) and moderately hypercholesterolemic (74-84 mg/100 ml). Elevations in these lipids reflected the presence of large (622 A), triacylglycerol-rich and apoprotein-poor VLDL containing both apolipoproteins Bh and B1 and increased phospholipid-rich HDL. Similar, but less pronounced, elevations in serum apolipoproteins B and E in the cp/cp rats when compared to the +/+ animals were also noted. Apolipoproteins A-I levels were 2.7-3-fold higher in cp/cp rats. The levels of VLDL were significantly higher in female cp/cp rats; however, the levels of IDL (intermediate-density lipoproteins), LDL and HDL were significantly lower than in the more atherosclerosis prone male cp/cp rats. Similarly, apolipoprotein A-I was higher and apolipoprotein B lower in the male cp/cp than in the female cp/cp rats. The LDL (d = 1.030-1.063 g/ml) in cp/cp rats, like that in normal animals, was heterogeneous and contained apolipoproteins Bh, E, A-I and C. This fraction was significantly elevated in male cp/cp rats when compared to females but still represented less than 13% of the total serum cholesterol and less than 6% of the total serum lipids in 3-month-old cp/cp animals. The ratio of cholesterol to phospholipids was significantly lower for all lipoproteins in cp/cp rats when compared to +/+ males and these ratios for female cp/cp rats were in all cases lower than those of male cp/cp animals.


Relationship between obesity-related colorectal tumors and the intestinal microbiome: an animal-based trial.
Obesity is a risk factor for colorectal cancer (CRC), and the intestinal microbiome is considered to contribute to CRC and obesity. Nonetheless, the role of the intestinal microbiome in obesity-related CRC is unclear. This study aimed to clarify the relationship between obesity-related CRC and the intestinal microbiome using a mouse model. We compared an obese and insulin-resistant type 2 diabetes mouse model [KKAy] to wild-type mice (WT) [C57BL/6 J]. Azoxymethane was intraperitoneally injected to develop a mouse model CRC. At 26 weeks, we compared the number of tumors and the intestinal microbiome. We also compared them across two models, namely, antibiotic cocktail and co-housing. In all models, KKAy mice had a significantly greater number of tumors than WT mice. Analysis showed that the distribution of the intestinal microbiome changed in both models; however, no difference in tumor development was observed. Tumor expression was suppressed only in the antibiotic cocktail model of WT, whereas KKAy mice bore tumors (C57Bl/6 J: KKAy, 0/9:8/8; p < 0.001). KKAy mice remained predominantly tumor-bearing in all treatments. Based on the results, the intestinal microbiome may not be associated with tumorigenesis in obesity-related CRC. It may be necessary to think of other facts linked to obesity-related CRC.


From playfulness and self-centredness via grand expectations to normalisation: a psychoanalytical rereading of the history of molecular genetics.
In this paper, I will reread the history of molecular genetics from a psychoanalytical angle, analysing it as a case history. Building on the developmental theories of Freud and his followers, I will distinguish four stages, namely: (1) oedipal childhood, notably the epoch of model building (1943-1953); (2) the latency period, with a focus on the development of basic skills (1953-1989); (3) adolescence, exemplified by the Human Genome Project, with its fierce conflicts, great expectations and grandiose claims (1989-2003) and (4) adulthood (2003-present) during which revolutionary research areas such as molecular biology and genomics have achieved a certain level of normalcy--have evolved into a normal science. I will indicate how a psychoanalytical assessment conducted in this manner may help us to interpret and address some of the key normative issues that have been raised with regard to molecular genetics over the years, such as 'relevance', 'responsible innovation' and 'promise management'.


Which older Brazilians will accept a COVID-19 vaccine? Cross-sectional evidence from the Brazilian Longitudinal Study of Aging (ELSI-Brazil).
Vaccine hesitancy may represent a barrier to effective COVID-19 immunisation campaigns. This study assesses individual, disease-specific and contextual factors associated with COVID-19 vaccine acceptance among a nationally representative sample of older Brazilian adults. Cross-sectional analysis of data from household interviews and a supplementary telephone survey. Brazil and its five geographic regions. Data are derived from 6584 individuals aged 50 years and over who participated in the second wave of the Brazilian Longitudinal Study of Aging. Survey-weighted multinomial logistic regression assesses factors associated with intending, not intending or being uncertain about one's intention to vaccinate against COVID-19. Seventy-one per cent of study participants intend to receive a COVID-19 vaccine once available, while 17% (representative of nearly 9 million people) have no intention to vaccinate, and 12% are still undecided. Besides age, demographic and health-related factors related to COVID-19 severity and complications were not associated with intention to vaccinate. Those who most trusted social media or friends and family for COVID-19 information and those who did not trust any information source were 68% and 78% more likely to refuse vaccination, respectively, as compared with those who trusted official information sources. People who inconsistently used face masks when outside were 3.4 times more likely than consistent face mask users to intend to refuse vaccination. Higher municipal COVID-19 fatality rates were negatively associated with vaccine refusal. Most national COVID-19 immunisation strategies identify older individuals as among those prioritised for early vaccination, given their increased risk of more severe symptoms and complications of the disease. Because individual, disease-specific, and contextual factors were associated with vaccine acceptance, there is a clear need for multilevel and multichannel information and outreach campaigns to increase COVID-19 vaccine acceptance among vulnerable older populations.


[Spatial-temporal structure of the primary evoked activity of visual cortex neurons].
The unit activity displayed a mosiac position of the activated neuronal ensembles with asymmetrically inhibited adjacent areas development of primary response. The average distance between the centers of these ensembles, the latter's diameter being less than 240 mcm, was not more than 300 mcm. The centers displayed the most intensive activity of the neurons ranged in a column, with the shortest latency, the greatest synchronization, and the diffuse peripheral area which might be asymmetrical in respect to the center.


Factors associated with scabies outbreaks in primary schools in Ethiopia: a case-control study.
Scabies is a neglected tropical disease affecting more than 200 million people worldwide every year. Scabies in school adolescents and young adults could affect their school performance. The current study investigates the factors associated with an outbreak of scabies at primary schools in southern Ethiopia. A team of health professionals investigated an outbreak of scabies that occurred in primary schools from May 1 to 30, 2018. An unmatched case-control study was employed to assess factors which predisposed for the scabies outbreak. Cases of scabies were individuals having a skin lesion compatible with the WHO case definitions of scabies. Controls were from the same locality with no skin lesions. Data on sociodemographic and behavioral variables were collected using questionnaires. Data on clinical presentations of scabies among cases were recorded by two trained and experienced health professionals. Factors associated with scabies were assessed using bivariate and multivariate logistic regression, and strength of association was described using odds ratio (OR) and 95% confidence intervals (CIs). A total of 711 (237 cases and 474 controls) study subjects participated in the study. The mean age of study participants was 17.56±2.66 years. Poor knowledge about scabies, adjusted odds ratio (AOR)=4.32 (95% CI: 2.93, 6.36); male sex, AOR=2.69 (95% CI: 1.82, 3.96); and parental illiteracy, AOR =3.49 (95% CI: 2.06, 5.94) predicted scabies infestation. Additionally, socioeconomic variables like sharing clothes/beds or contact with others, AOR=3.12 (95% CI: 2.12, 4.59); low household annual income, AOR=2.13 (95% CI: 1.32, 3.44); and family size greater than five, AOR=1.77 (95% CI: 1.04, 3.01) were significantly associated with scabies infestation. Inaccessibility and poor utilization of water, AOR=1.64 (95% CI: 1.12, 2.40) and poor personal hygiene, AOR=1.69 (95% CI: 1.14, 2.51) were also factors independently associated with scabies. Modifiable risk factors such as personal hygiene and literacy level were found to be independent predictors of scabies infestation. Access to and utilization of water were also important predictors. Strategies for poverty alleviation and awareness creation on personal hygiene and efficient use of water are recommended for effective prevention of scabies infestation in closed institutions.