[Lymphoma of the oral cavity and face. Review of the last ten years literature].
The paper examines a series of patients with primary oral and maxillo-facial non-Hodgkin's lymphoma, reviewing cases and therapeutic protocols from 1977 to 1988.


Perceptual impact of astigmatism induction in presbyopes.
We investigated the effect of induced astigmatism on subjective best focus and on visual acuity in 28 subjects of different ages (pre-presbyopic and presbyopic) and with different refractive profiles (emmetropes and astigmats). Measurements were performed using a custom-developed Adaptive Optics system, which allowed correction of high order aberrations and induction of astigmatism (0.5, 1, 1.5 and 2.0 D; axis: 180°, 45° and 22.5°). Upon induction of astigmatism, best focus shifted towards negative values in pre-presbyopic emmetropic eyes (by -0.14 D for 0.5 D and by -0.33 D for 2.0 D), while it shifted towards positive values in presbyopes, both in emmetropic presbyopes (by +0.04 D for 0.50 D and by +0.16 D for 2.0 D) and in astigmatic presbyopes (by +0.23 D for 0.50 D and by +0.40 D for 2.0 D). Also, visual acuity was most sensitive to astigmatism induction in pre-presbyopic emmetropes and least sensitive in presbyopes, particularly when high order aberrations were corrected: visual acuity ratio with/without astigmatism was: 0.74/0.85/0.98 (for astigmatism induced at 180°) and 0.68/0.73/0.86 at 45°, for pre-presbyopic emmetropes/presbyopic emmetropes/presbyopic astigmats. These findings may be connected to long term exposure to astigmatism in astigmats and corrected presbyopes.


Traumatic bowing of forearm and lower leg in children.
Traumatic bowing of the forearm or lower leg is reported in 31 children. It is a relatively rare condition. Bowing occurs most frequently in combination with fracture of the other bone in the same extremity. In a minority of cases a bowing deformity is a single lesion. Age distribution, degree of deformity, mechanism of origin and therapy are presented and discussed.


Diffusion of ionic species in bentonite.
We present a macroscopic model of ionic diffusion in bentonites including the effect of the hydraulic-electrical-chemical couplings expected in such charged porous medium. The anomalous concentrations of the ions in the pore water of the bentonite are modeled with a modified Donnan model in which we account for the partition of the counterions between the Stern and Gouy-Chapman layers. This is accomplished using an electric triple layer (TLM) model combined with an explicit complexation model at the mineral/water interface. The porosity entering into the determination of the formation factor of the medium is an effective porosity obtained by removing the fraction of hydration water covering the surface of the clay minerals. We investigate two different cases of diffusion. In the first case, we consider a salinity gradient between two reservoirs in contact with a cylindrical sample of bentonite. The model predicts an increase of the diffusivity of the salt with the salinity of the solution in contact with the bentonite in agreement with experimental data. In the second case, we analyze a self-diffusion experiment of an ionic tracer. The model predicts an increase of the diffusivity of anions with the effective porosity and with the ionic strength. This is also in good agreement with experimental data.


Diagnostic accuracy of circulating thyrotropin receptor messenger RNA combined with neck ultrasonography in patients with Bethesda III-V thyroid cytology.
The aim of this study was to analyze the usefulness of thyrotropin receptor messenger RNA (TSHR-mRNA) combined with neck ultrasonography (US) in the management of thyroid nodules with Bethesda III-V cytology. Cytology slides of patients with a preoperative fine needle aspiration (FNA) and TSHR-mRNA who underwent thyroidectomy between 2002 and 2011 were recategorized based on the Bethesda classification. Results of thyroid FNA, TSHR-mRNA, and US were compared with the final pathology. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. There were 12 patients with Bethesda III, 112 with Bethesda IV, and 58 with Bethesda V cytology. The sensitivity of TSHR-mRNA in predicting cancer was 33%, 65%, and 79 %, and specificity was 67%, 66%, and 71%, for Bethesda III, IV, and V categories, respectively. For the same categories, the PPV of TSHR-mRNA was 25%, 33%, and 79%, respectively; whereas the NPV was 75%, 88%, and 71%, respectively. The addition of neck US to TSHR-mRNA increased the NPV to 100% for Bethesda III, and 86%, for Bethesda IV, and 82% for Bethesda V disease. This study documents the potential usefulness of TSHR-mRNA for thyroid nodules with Bethesda III-V FNA categories. TSHR-mRNA may be used to exclude Bethesda IV disease. A large sample analysis is needed to determine its accuracy for Bethesda category III nodules.


Ten years of paediatric airway foreign bodies in Western Australia.
Whenever a paediatric airway foreign body (PAFB) is suspected, decisions may be difficult without a clearly defined or accepted treatment algorithm. History and examination are commonly non-diagnostic and the risks associated with either watchful waiting or proceeding to MLB are significant. This paper reviews a 10 year cohort of suspected PAFBs for the predictive utility of history, examination and investigations and subsequent positive findings at MLB. STUDY DESIGN: The medical records of 127 children who underwent MLB for suspected PAFB between 2007 and 2016 were examined. The data was retrospectively reviewed for epidemiological details, history, examination, radiological findings and MLB outcomes. Sensitivity for PAFB on MLB with all three; history, examination and imaging (x-ray) positive for PAFB was 87.7%. Of the patients who were both symptom and sign positive (n = 96), chest x-ray findings did not significantly alter the chance of finding a PAFB. Chest x-ray had a low specificity (17%) in symptom and sign positive patients. Conversely, sensitivity of chest x-ray was high (88%), for symptom and sign positive patients. For a child with both signs and symptoms, xray is unlikely to assist in decision making around suspected PAFB. When only sign or symptom is present, positive imaging may significantly increase the chance that PAFB is the cause.For patients with a low suspicion of PAFB, consideration of a CT can be a helpful means of excluding a PAFB and avoiding an unnecessary general anaesthetic in this potentially high-risk group.A greater level of public awareness is needed with regards to appropriate food types for children and the importance of eating seated and supervised in order to reduce the risk of PAFB.


Purine enzyme activities in peripheral blood mononuclear cells: comparison of a new non-radiochemical high-performance liquid chromatography procedure and a radiochemical thin-layer chromatography procedure.
Purine enzyme activities are usually assayed by radiochemical procedures and often TLC is part of the separation method. In screening patients with rheumatic diseases, these procedures have shown disadvantages like a relatively large coefficient of variation (C.V.) and time-instability. We describe a non-radiochemical reversed-phase HPLC micro-method with UV detection for measurement of activities of purine 5'-nucleotidase (5'NT; EC 184.108.40.206), purine nucleoside phosphorylase (PNP; EC 22.214.171.124) and hypoxanthine guanine phosphoribosyltransferase (HGPRT; EC 126.96.36.199) in human peripheral blood mononuclear cells (PBMC). The HPLC procedure is compared with the radiochemical TLC procedure by testing both with a 5'NT and a PNP assay. Reproducibility is tested with 14 healthy controls in each procedure. Short-term and long-term time-stability is tested by comparing enzyme activities measured immediately after preparation of the PBMC (week 0) with those found after freezing and storage at -20 degrees C for a maximum of 10 weeks. The HPLC procedure is preferable to the radiochemical TLC procedure because it shows significantly better reproducibility and better time-stability and in addition is non-radiochemical and less time-consuming.


The role of perineural space invasion in the local spread of prostatic adenocarcinoma.
In 176 radical prostatectomy specimens areas of capsule penetration by cancer and positive surgical margins were quantified and located over the prostate surface. The presence of cancer within the perineural space was sought in these areas and compared to the normal distribution of prostatic nerve branches. Capsule penetration was found in 78 of 156 stage B carcinomas, and in 39 of these 78 (50 per cent) it occurred entirely by cancer extension through the capsule within perineural spaces. In the remaining 39 prostates capsule penetration by perineural space invasion predominated but direct spread also was found. Most often, perineural space invasion followed the oblique vertical course of nerve branches that extended superiorly to the superior pedicle near the prostate base. In such cases capsule penetration areas were localized near the superior margin of the cancer, and in 11 per cent positive superior pedicle margins resulted from continued perineural space invasion outside the capsule. In cancers near the prostate apex capsule penetration by perineural space invasion produced positive margins in 89 per cent of 18 cases because of the short inferior pedicle. The role of perineural space invasion by cancer was less prominent in 4 of 20 stage A cancers that showed capsule penetration.


Real-life efficacy and safety of omalizumab in Portuguese patients with persistent uncontrolled asthma.
The real life effectiveness, safety and the use of omalizumab for Portuguese patients with uncontrolled persistent allergic asthma are not sufficiently well known. The objective of this report was to make an evaluation, in a post-marketing, non-interventional, observational registry, of the Portuguese population included in the eXpeRience study. The methods used in this report are the same as the global eXpeRience ones, applied to a Portuguese sub-population. Patients with uncontrolled allergic asthma who had started omalizumab within the previous 15 weeks were enrolled and received omalizumab add-on therapy for 24 months. The physicians' global evaluation of treatment effectiveness (GETE), asthma symptoms and control (ACT score), quality of life (mini-AQLQ score), exacerbations, and serious adverse events (SAE) were reported. Of the 943 patients recruited in the eXpeRience registry, 62 patients were from Portugal. 62.1% of them were observed to be responders with good/excellent GETE assessment at Week 16. Clinically meaningful improvements in asthma control (ACT score) and quality of life (mini-AQLQ score) were observed with omalizumab therapy at Months 12 (mean change: +7.7 [n=35]; +2.1 [n=20], respectively) and 24 (mean change: +7.0 [n=26]; +2.7 [n=13], respectively). Asthma symptoms and rescue medication usage were reduced to ≤1 day/week at Month 24 from a baseline of ≥3.5 days/week. The proportion of patients with no clinically significant exacerbations increased from 6.5% during pre-treatment (n=62) to 50% at Month 12 (n=54) and 60% at Month 24 (n=45). The findings from the Portugal subpopulation of eXpeRience registry confirm that omalizumab add-on therapy is efficacious and well tolerated in the management of uncontrolled persistent allergic asthma. Another pertinent issue is the fact that the Portuguese subpopulation response is similar to the international population average of the study.


Mobility and cognitive correlates of dual task cost of walking in persons with multiple sclerosis.
Persons with multiple sclerosis (MS) often experience a decrease in walking performance while simultaneously performing a cognitive task. This decrease in walking performance is termed dual task cost (DTC). To examine if mobility and cognitive function are correlates of DTC in persons with MS. Participants were 96 persons with MS who had Expanded Disability Status Scale scores that ranged between 2.0 and 6.5. To determine DTC, participants walked at a self-selected pace with and without a cognitive task while gait velocity was recorded. The effect of the cognitive task was quantified as the percent change in walking velocity between conditions. Participants further completed the timed 25-foot walk (T25FW) and Symbol Digit Modalities Test (SDMT). Centered scores for the T25FW and SDMT, and the product of the center scores, were placed into a linear regression to determine the correlates of DTC. DTC averaged 12.5% (SD = 9.3) and ranged between -14.1 and 42.4%. Performance on the T25FW ranged between 3.1 and 24.5 s with an average of 6.8 s (SD = 3.1 s). SDMT scores ranged between 15 and 79 with an average of 45 items (SD = 12). Regression analysis revealed that age, disability, walking and cognitive performance explained 17% of the variance in DTC. The interaction between walking and cognition did not explain additional variance. Mobility and cognitive impairment were both independent predictors of DTC of walking in persons with MS. This raises the possibility that DTC could be reduced with modifications of either mobility or cognition.


Myocardial infarction unveiled: Key miRNA players screened by a novel lncRNA-miRNA-mRNA network model.
Myocardial infarction (MI) is a major contributor to global mortality, and microRNAs (miRNAs) are important in its pathogenesis. Identifying blood miRNAs with clinical application potential for the early detection and treatment of MI is crucial. We obtained MI-related miRNA and miRNA microarray datasets from MI Knowledge Base (MIKB) and Gene Expression Omnibus (GEO), respectively. A new feature called target regulatory score (TRS) was proposed to characterize the RNA interaction network. MI-related miRNAs were characterized using TRS, transcription factor (TF) gene proportion (TFP), and ageing-related gene (AG) proportion (AGP) via the lncRNA-miRNA-mRNA network. A bioinformatics model was then developed to predict MI-related miRNAs, which were verified by literature and pathway enrichment analysis. The TRS-characterized model outperformed previous methods in identifying MI-related miRNAs. MI-related miRNAs had high TRS, TFP, and AGP values, and combining the three features improved prediction accuracy to 0.743. With this method, 31 candidate MI-related miRNAs were screened from the specific-MI lncRNA-miRNA-mRNA network, associated with key MI pathways like circulatory system processes, inflammatory response, and oxygen level adaptation. Most candidate miRNAs were directly associated with MI according to literature evidence, except hsa-miR-520c-3p and hsa-miR-190b-5p. Furthermore, CAV1, PPARA and VEGFA were identified as MI key genes, and were targeted by most of the candidate miRNAs. This study proposed a novel bioinformatics model based on multivariate biomolecular network analysis to identify putative key miRNAs of MI, which deserve further experimental and clinical validation for translational applications.


The influence of gastric filling instructions on dose delivery in patients with oesophageal cancer: A prospective study.
To evaluate whether adaptive radiotherapy for unaccounted stomach changes in patients with adenocarcinoma of the gastroesophageal junction (GEJ) is necessary and whether dose differences could be prevented by giving patients food and fluid instructions before treatment simulation and radiotherapy. Twenty patients were randomly assigned into two groups: patients with and without instructions about restricting food and fluid intake prior to radiotherapy simulation and treatment. Redelineation and offline recalculation of dose distributions based on cone-beam computed tomography (n=100) were performed. Dose-volume parameters were analysed for the clinical target volume extending into the stomach. Four patients who did not receive instructions had a geometric miss (0.7-12 cm(3)) in only one fraction. With instructions, 3 out of 10 patients had a geometric miss (0.1-1.9 cm(3)) in one (n=2) or two (n=1) fractions. The V95% was reduced by more than 5% for one patient, but this underdosage was in an in-air region without further clinical importance. Giving patients food and fluid instructions for the treatment of GEJ cancer offers no clinical benefit. Using a planning target volume margin of 1cm implies that there is no need for adaptive radiotherapy for GEJ tumours.


Identification of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia.
Cachexia is a metabolic disorder characterised by muscle wasting, diminished response to anti-cancer treatments and poor quality of life. Our objective was to identify blood-based biomarkers of cachexia in advanced cancer patients. Hence, we characterised the plasma cytokine and blood cell mRNA profiles of patients grouped in three cohorts: patients with cachexia, pre-cachexia (no cachexia but high CRP levels: ⩾ 5 mg l⁻¹) and no cachexia (no cachexia and CRP: < 5 mg l⁻¹). A total of 122 newly diagnosed cancer patients with seven cancer types were studied prior to their initial therapy. Plasma levels of 22 cytokines were quantified using the bio-plex technology. mRNAs isolated from whole blood and expression profiles were determined by the chip array technology and Ingenuity Pathway Analysis (IPA) software. In comparison with non-cachectic individuals, both pre-cachectic and cachectic patients showed an increase (⩾ 1.5-folds) in mRNA expression of neutrophil-derived proteases (NDPs) and significantly elevated angiotensin II (Ang II) (P = 0.005 and P = 0.02, respectively), TGFβ1 (P = 0.042 and P < 0.0001, respectively) and CRP (both P < 0.0001) in the plasma. Moreover, cachectic patients displayed a significant increase in IL-6 (P = 0.005), IL-8 (P = 0.001) and absolute neutrophil counts (P = 0.007). Ang II, TGFβ1, CRP and NDP are blood biomarkers for cancer cachexia. These findings contribute to early diagnosis and prevention of cachexia.


Polyamines stimulate the binding of hexokinase type II to mitochondria.
Spermine and spermidine enhanced the binding of hexokinase isoenzyme type II to mitochondria, both of which were prepared from Ehrlich-Lettre hyperdiploid ascites tumor cells, at much lower concentrations than Mg2+. Chymotrypsin-treated hexokinase II could not bind to the mitochondrial membrane in the presence of either spermine or Mg2+, indicating that the effect of spermine is not a nonspecific action, since the treatment of chymotrypsin cleaves only the region essential for the binding without any significant effect of the catalytic activity. Both spermine and Mg2+ antagonized the glucose 6-phosphate-induced release of mitochondria-bound hexokinase, and promoted the binding of the solubilized hexokinase II even in the presence of glucose 6-phosphate. However, inhibition of the activity of soluble hexokinase by glucose 6-phosphate was not reversed by spermine and Mg2+. Hexokinase II rebound to mitochondria with spermine and Mg2+ produced glucose 6-phosphate using ATP generated inside the mitochondria, and no difference was observed between the spermine- and Mg2+-rebound systems. Significance of the binding of hexokinase to mitochondria, especially with polyamines, is discussed with reference to high glycolytic rate in tumor cells.


Lopinavir/ritonavir versus darunavir plus ritonavir for HIV infection: a cost-effectiveness analysis for the United States.
The ARTEMIS trial compared first-line antiretroviral therapy (ART) with lopinavir/ritonavir (LPV/r) to darunavir plus ritonavir (DRV + RTV) for HIV-1-infected subjects. In order to fully assess the implications of this study, economic modelling extrapolating over a longer term is required. The aim of this study was to simulate the course of HIV and its management, including the multiple factors known to be of importance in ART. A comprehensive discrete event simulation was created to represent, as realistically as possible, ART management and HIV outcomes. The model was focused on patients for whom clinicians believed that LPV/r or DRV + RTV were good options as a first regimen. Prognosis was determined by the impact of initial treatment on baseline CD4+ T-cell count and viral load, adherence, virological suppression/failure/rebound, acquired resistance mutations, and ensuing treatment changes. Inputs were taken from trial data (ARTEMIS), literature and, where necessary, stated assumptions. Clinical measures included AIDS events, side effects, time on sequential therapies, cardiovascular events, and expected life-years lost as a result of HIV infection. The model underwent face, technical and partial predictive validation. Treatment-naive individuals similar to those in the ARTEMIS trial were modelled over a lifetime, and outcomes with first-line DRV + RTV were compared with those with LPV/r, both paired with tenofovir and emtricitabine. Up to three regimen changes were permitted. Drug prices were based on wholesale acquisition cost. Outcomes were lifetime healthcare costs (in 2011 US dollars) from the US healthcare system perspective and quality-adjusted life-years (QALYs) (discounted at 3 % per annum). Choice of LPV/r over DRV + RTV as initial ART resulted in nearly identical clinical outcomes, but distinctly different economic consequences. Starting with an LPV/r regimen potentially results in approximately US$25,000 discounted lifetime savings. Accumulated QALYs for LPV/r and DRV + RTV were 12.130 and 12.083, respectively (a 19-day difference). In sensitivity analyses, net monetary benefit ranged from US$12,000 to US$31,000, favouring LPV/r (base case US$27,762). A comprehensive simulation of lifetime course of HIV in the USA indicated that using LPV/r as first-line therapy compared with DRV + RTV may result in cost savings, with similar clinical outcomes.


A randomised feasibility study of computerised cognitive training as a therapeutic intervention for people with Huntington's disease (CogTrainHD).
Huntington's disease (HD) is associated with a range of cognitive deficits including problems with executive function. In the absence of a disease modifying treatment, cognitive training has been proposed as a means of slowing cognitive decline; however, the impact of cognitive training in HD patient populations remains unclear. The CogTrainHD study assessed the feasibility and acceptability of home-based computerised executive function training, for people impacted by HD. Thirty HD gene carriers were recruited and randomised to either executive function training or non-intervention control groups. Participants allocated to the intervention group were asked to complete executive function training three times a week for 30 min for 12 weeks in their own homes. Semi-structured interviews were conducted with participants and friends, family or carers, to determine their views on the study. 26 out of 30 participants completed the baseline assessments and were subsequently randomised: 13 to the control group and 13 to the intervention group. 23 of the 30 participants were retained until study completion: 10/13 in the intervention group and 13/13 in the control group. 4/10 participants fully adhered to the executive function training. All participants in the control group 13/13 completed the study as intended. Interview data suggested several key facilitators including participant determination, motivation, incorporation of the intervention into routine and support from friends and family members. Practical limitations, including lack of time, difficulty and frustration in completing the intervention, were identified as barriers to study completion. The CogTrainHD feasibility study provides important evidence regarding the feasibility and acceptability of a home-based cognitive training intervention for people with HD. Variable adherence to the cognitive training implies that the intervention is not feasible to all participants in its current form. The study has highlighted important aspects in relation to both the study and intervention design that require consideration, and these include the design of games in the executive function training software, logistical considerations such as lack of time, the limited time participants had to complete the intervention and the number of study visits required. Further studies are necessary before computerised executive function training can be recommended routinely for people with HD. ClinicalTrials.gov, Registry number NCT02990676.


Thromboembolism in Children.
To study pediatric patients who were diagnosed with thrombosis between January 2009 and March 2020. Patients were evaluated with respect to thrombophilic risk factors, localization of the thrombus, response to treatment, and recurrence rates during the last 11 y. Among 84 patients, 59 (70%) had venous thrombosis and 20 (24%) had arterial thrombosis. The number of documented thrombosis amongst hospitalized children in authors' hospital has increased over the years. It has been observed that the annual incidence of thromboembolism has increased after 2014. Thirteen patients were recorded between 2009 and 2014 and 71 patients between 2015 and 2020 (until March 2020). Exact thrombosis localization could not be detected in 5 patients. The median age of patients was 8 ± 5.95 (range 0-18). Fourteen children (16.9%) had a history of familial thrombosis. Genetic and/or acquired risk factors were detected in 81 (96.4%) of the patients. Overall, 64 patients (76.1%) had acquired risk factors such as infection (20.2%), catheterization (13.1%), liver disease (11.9%), mastoiditis (8.3%), liver transplantation (6%), hypoxic-ischemic encephalopathy (4.8%), dehydration (3.6%), trauma (3.6%) and cancer (2.4%). As genetic risk factors, the most common genetic mutations were PAI-1 4G>5G, MTHFR C677T, and MTHFR A1298C mutations. Twenty-eight (41.2%) patients had at least one genetic thrombophilic mutation. At least one homozygous mutation in 37 patients (44%) and at least one heterozygous mutation in 55 patients (65.4%) were detected. The annual incidence of thrombosis has increased over the years. Genetic predisposition and acquired risk factors play an important role in etiology, treatment, and follow-up in children with thromboembolism. Especially, genetic predisposition is common. Thrombophilic risk factors should be investigated and optimal therapeutic and prophylactic measures should be promptly taken in children with thrombosis.


A comparative study of a theoretical neural net model with MEG data from epileptic patients and normal individuals.
The aim of this study was to compare a theoretical neural net model with MEG data from epileptic patients and normal individuals. Our experimental study population included 10 epilepsy sufferers and 10 healthy subjects. The recordings were obtained with a one-channel biomagnetometer SQUID in a magnetically shielded room. Using the method of x2-fitting it was found that the MEG amplitudes in epileptic patients and normal subjects had Poisson and Gauss distributions respectively. The Poisson connectivity derived from the theoretical neural model represents the state of epilepsy, whereas the Gauss connectivity represents normal behavior. The MEG data obtained from epileptic areas had higher amplitudes than the MEG from normal regions and were comparable with the theoretical magnetic fields from Poisson and Gauss distributions. Furthermore, the magnetic field derived from the theoretical model had amplitudes in the same order as the recorded MEG from the 20 participants. The approximation of the theoretical neural net model with real MEG data provides information about the structure of the brain function in epileptic and normal states encouraging further studies to be conducted.


Surface physicochemical analysis of natural Lactococcus lactis strains reveals the existence of hydrophobic and low charged strains with altered adhesive properties.
The cell surface physicochemical properties of 50 Lactococcus lactis strains of different subspecies and isolated from different origins (dairy, vegetal and animal) were examined. Cell surface hydrophobicity and Lewis acid-base properties were evaluated by affinity measurements to solvents in a partitioning test, while the global electrical charge of the cells was assessed by micro-electrophoresis using a laser zeta-meter. A global multivariate analysis of the results revealed a high natural diversity of L. lactis cell surface properties. While 52% of the strains present a hydrophilic and electronegative cell wall surface, a group of strikingly hydrophobic strains (12% of the strains) and a group of strains with unusual low charged surface (18%) were identified. Adhesion on polystyrene microtitre plates was evaluated for twelve strains selected from the multivariate analysis as representatives of the various observed cell wall surface physicochemical patterns. A significant correlation between adhesion, hydrophobicity and low electronegativity was observed when adhesion was performed in a low ionic strength suspending medium. The most adhesive strains were hydrophobic or low charged. The presence of repulsive electrostatic interactions led to a decrease in adhesion of the most negatively charged hydrophilic strains. The present study highlights the diversity of L. lactis cell surface physicochemical properties, diversity that could not be connected to the origin or to the subspecies of the strains.


Treatment of spinal cord injury with intravenous immunoglobulin G: preliminary evidence and future perspectives.
Neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and thus worsen recovery. Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in the production of cytotoxic substances that are harmful to the nervous tissue. Therefore, suppression of excessive inflammation in the spinal cord could serve as a therapeutic strategy to attenuate tissue damage. The immunosuppressant methylprednisolone has been used in the setting of SCI, but there are complications which have attenuated the initial enthusiasm. Hence, there is interest in other immunomodulatory approaches, such as intravenous Immunoglobulin G (IVIg). Importantly, IVIg is used clinically for the treatment of several auto-immune neuropathies, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIPD) and Kawasaki disease, with a good safety profile. Thus, it is a promising treatment candidate for SCI. Indeed, IVIg has been shown by our team to attenuate the immune response and result in improved neurobehavioral recovery following cervical SCI in rats through a mechanism that involves the attenuation of neutrophil recruitment and reduction in the levels of cytokines and cytotoxic enzymes Nguyen et al. (J Neuroinflammation 9:224, 2012). Here we review published data in the context of relevant mechanisms of action that have been proposed for IVIg in other conditions. We hope that this discussion will trigger future research to provide supporting evidence for the efficiency and detailed mechanisms of action of this promising drug in the treatment of SCI, and to facilitate its clinical translation.


A new hepatic encephalopathy model to monitor the change of neural amino acids and astrocytes with behaviour disorder.
To elucidate the pathogenesis of hepatic encephalopathy (HE), we developed a new HE model with behaviour disorder. Male Wistar rats were divided into four treatment groups: a HE model: acetaminophen (APAP)+3-methylcholanthrene (3-MC) group (APAP+MC group); control group: acetaminophen group; 3-methylcholanthrene group; and a no-treatment group. We monitored the changes of neural amino acids in the synaptic cleft and astrocytes in the brain during behaviour disorder. In the APAP+MC group, alanine amino transferase, blood ammonia and glucose increased from 3 h and total bilirubin increased at 6 h. Prothrombin time was prolonged from 3 h in the APAP+MC group. The APAP+MC group exhibited centrilobular necrosis in the liver after 8 h. In the APAP+MC group, rats jumped vertically and this vertical activity increased significantly from 4 to 7 h. During the behaviour disorder, we found that glutamate and aspartate increased in the synaptic cleft from 4 h after treatment with APAP+3-MC, glutamate increased 23.9-fold at 7 h and aspartate increased 16.1-fold at 4 h, whereas glutamine did not change. At that time, we observed morphological changes of the astrocytes by immunostaining for the glial fibrillary acidic protein. Our new HE model demonstrated that increased excitatory neural amino acids and morphological change in astrocytes were involved in the behaviour disorder that occurs with HE.


The isolation of the two electrophoretic forms of cowpea mosaic virus using fast protein liquid chromatography.
This report describes the first time entire viral capsids have been purified using fast protein liquid chromatography (FPLC) techniques. The FPLC is used here to separate the two electrophoretic forms of cowpea mosaic virus. The capsid forms are shown to be separated by the Mono-Q column without damaging the capsids.


Circular dichroism analysis of the secondary structure of Z protein and its complexes with bilirubin and other organic anions.
Circular dichroism (CD) methods were employed to study the conformation of Z protein and characterize its complexes with bilirubin and other organic anions. Z protein-bilirubin complexes exhibited a spectrum with overlapping ellipticity bands of opposite sign in the bilirubin absorption region. These results were compared with those obtained with ligandin, the other major organic anion binding protein of liver. Secondary structural differences between the two proteins were easily demonstrated since ligandin is predominantly an alpha-helical protein and Z features mainly beta-structure. Furthermore, the optical activity pattern generated by bilirubin binding to Z was virtually a mirror image of that of the ligandin bilirubin system. CD experiments were designed to study the direct transfer of bilirubin between Z protein and ligandin, and it was shown that both proteins have almost equal affinities for bilirubin. The bilirubin on Z was readily displaced by oleic acid and displaced to a lesser extent by sulfobromophthalein,


Is Irritable Bowel Syndrome out of date and misleading as a diagnosis?
This study aimed at assessing the efficacy of targeted interventions addressing common food sensitivities and lifestyle factors that commonly contribute to the presentation of gastrointestinal problems identified as Irritable bowel syndrome (IBS). IBS has served to cover the expression of multifactorial disorders with variable aetiology and pathophysiology. Food antigens implicated in the modern lifestyle, acting as strong epigenetic factors is strongly implicated in pathophysiology of conditions under IBS. Identifying and addressing food sensitivities in patients presenting with IBS like symptoms are currently underemphasised in clinical guidelines yet have the potential to provide major benefits for patients. Information was collected from the medical records of patients that were referred to the Gastroenterology Unit of Palmerston North DHB with unexplained gastrointestinal (GI) symptoms with or without other GI comorbidities between September 2018 and November 2021. The main management option offered to the 121 patients included in this study, was lifestyle adjustment and/or a trial of 6 weeks, eliminating gluten and lactose from the diet. The most prevalent symptoms were abdominal pain 96/121 (79%), diarrhoea 83/121 (69%), followed by bloating and constipation. Seventy-eight patients had the outcomes of their improvement available. A total of 42 out of 78 patients (54%) were treated exclusively with gluten and lactose-free diet, in this group of patients 86% (36/42) reported a significant improvement in their symptoms with a score in the range of 40-100%. Our study illustrates the importance of focusing on triggering factors when assessing patients with IBS. We suggest that careful identifying and eliminating the triggering food antigens as monotherapy or in addition to the lifestyle adjustment where appropriate should be the main objective in symptomatic patients fulfilling the IBS diagnostic criteria. These combinations and holistic approach in treating IBS' patients' symptoms are less expensive, non-toxic, and highly effective in achieving optimal outcomes and improving these patient's quality of life.


Cataract surgery in patients with Behçet's disease.
To evaluate the outcomes and complications of cataract surgery in patients with Behçet's disease. Department of Ophthalmology, Hacettepe University School of Medicine, Ankara, Turkey. Thirty-three eyes of 26 patients with Behçet's disease that had extracapsular cataract surgery between January 1993 and July 1999 were analyzed retrospectively. The mean age of the patients was 38.9 years (range 20 to 54 years). The mean postoperative follow-up was 22.9 months (range 6 to 66 months). Extracapsular cataract extraction (ECCE) was performed in 22 eyes with and in 6 eyes without intraocular lens (IOL) implantation. Phacoemulsification with IOL implantation was performed in 5 eyes. Postoperatively, the visual acuity was better in 29 eyes (87.8%) and was 0.5 or better in 14 eyes (42.4%). Posterior segment complications of Behçet's disease, mainly optic atrophy and macular alterations from preoperative inflammatory episodes, restricted final acuity. No significant difference was detected in postoperative inflammation among the types of surgery; that is, ECCE, ECCE with IOL implantation, and phacoemulsification with IOL implantation. A neodymium:YAG laser posterior capsulotomy was performed in 3 cases. In patients with Behçet's disease, inflammation after extracapsular surgery was mild when surgery was performed after at least 3 months of no inflammatory signs. The results show that the outcomes of extracapsular cataract surgery mainly depend on the degree of preoperative posterior segment involvement.


Divergent outcomes after percutaneous therapy for symptomatic renal artery stenosis.
Percutaneous intervention for symptomatic renal artery atherosclerosis is rapidly replacing surgery in many centers. This study evaluated the anatomic and functional outcomes of endovascular therapy for atherosclerotic renal artery stenosis on a combined vascular surgery and interventional radiology service at an academic medical center. This was a retrospective analysis of patients who underwent renal artery angioplasty with or without stenting between January 1990 and June 2002. Indications included hypertension (86%) and rising serum creatinine concentration (55%). One hundred forty-six patients (80 women; average age, 71 years [range, 44-89 years]) underwent 183 attempted interventions (64 to treat bilateral stenosis). Forty-five percent of patients had significant bilateral disease: 27% had greater than 50% bilateral stenosis, and the remainder had nonfunctioning, absent, or occluded vessels. Of 183 planned interventions, technical success (<30% residual stenosis) was achieved in 179 vessels (98%) with placement of 137 stents (75%). Thirty-day mortality was 0.7%. The major morbidity rate was 4%, and the procedure-related complication rate was 18%. Five-year cumulative patient mortality was 25%. Primary patency, assisted primary patency, and recurrent stenosis rates were 82% +/- 9%, 100% +/- 0%, and 30% +/- 7%, respectively, at 5 years. Within 3 months of the procedure, 52% of patients who received treatment of hypertension demonstrated clinical benefit (hypertension improved or cured), which was maintained in 68% of patients at 5 years. Serum creatinine concentration was lowered or stabilized in 87% of patients within 3 months of the procedure, but this benefit, including freedom from dialysis, was maintained in only 45% of patients at 5 years. Endovascular intervention for symptomatic atherosclerotic renal artery stenosis is technically successful. There were excellent patency and low recurrent stenosis rates. There is immediate clinical benefit for most patients, but divergent long-term functional outcomes. Endovascular interventions modestly enhance the care of the patient with hypertension, but poorly preserve long-term renal function in the patient with chronic renal impairment.


Influenza-associated outpatient visits among children less than 5 years of age in eastern China, 2011-2014.
The disease burden of influenza in China has not been well described, especially among young children. The aim of this study was to estimate the incidence of outpatient visits associated with influenza in young children in Suzhou, a city of more than 11 million residents in Jiangsu Province in eastern China. Influenza-like illness (ILI) was defined as the presence of fever (axillary temperature ≥38 °C) and cough or sore throat. We collected throat swabs for children less than 5 years of age with ILI who visited Suzhou University Affiliated Children's Hospital (SCH) outpatient clinic or emergency room between April 2011 and March 2014. Suzhou CDC, a national influenza surveillance network laboratory, tested for influenza viruses by real-time reverse transcription-polymerase chain reaction assay (rRT-PCR). Influenza-associated ILI was defined as ILI with laboratory-confirmed influenza by rRT-PCR. To calculate the incidence of influenza-associated outpatient visits, we conducted community-based healthcare utilization surveys to determine the proportion of hospital catchment area residents who sought care at SCH. The estimated incidence of influenza-associated ILI outpatient visits among children aged <5 years in the catchment area of Suzhou was, per 100 population, 17.4 (95 % CI 11.0-25.3) during April 2011-March 2012, 14.6 (95 % CI 5.2-26.2) during April 2012-March 2013 and 21.4 (95 % CI: 10.9-33.5) during April 2013-March 2014. The age-specific outpatient visit rates of influenza-associated ILI were 4.9, 21.1 and 21.2 per 100 children aged 0- <6 months, 6- <24 months and 24- <60 months, respectively. Influenza virus infection causes a substantial burden of outpatient visits among young children in Suzhou, China. Targeted influenza prevention and control strategies for young children in Suzhou are needed to reduce influenza-associated outpatient visits in this age group.


The novel HLA-B*27:267 allele, identified by Sanger dideoxy nucleotide sequencing in a Chinese individual.
HLA-B*27:267 differs from HLA-B*27:04:01 by one nucleotide in exon 2.


An evaluation of the antioxidant and potential pro-oxidant properties of food additives and of trolox C, vitamin E and probucol.
The food additives propyl gallate and vanillin inhibited iron ion-dependent lipid peroxidation in rat-liver microsomes, but stimulated formation of a deoxyribose degrading species, probably hydroxyl radical, from ferric-EDTA and hydrogen peroxide. Propyl gallate accelerated DNA damage by the anti-tumour antibiotic bleomycin, although vanillin did not. The water-soluble vitamin E analogue Trolox C also stimulated bleomycin-dependent DNA damage, but not hydroxyl radical generation from ferric-EDTA and H2O2. Indeed, Trolox C was found to be a powerful scavenger of hydroxyl radical (rate constant greater than 10(10) M-1s-1). Probucol did not stimulate oxidative damage in any of the systems tested, and is a powerful inhibitor of lipid peroxidation in rat liver microsomes. The ESR spectrum of the radical produced by one electron-oxidation of probucol in ethanol is described.


Chronic hemospermia due to müllerian duct cyst: diagnosis by magnetic resonance imaging.
Hemospermia usually is considered of minor consequence. It rarely is identified with a specific pathological disorder. A case of hemospermia secondary to a müllerian duct cyst diagnosed by magnetic resonance scanning is reported.


Lumbar disc reherniation prevention with a bone-anchored annular closure device: 1-year results of a randomized trial.
The risk of recurrent herniation after lumbar discectomy is highest during the first postoperative year. The purpose of this study was to determine whether implantation of a bone-anchored annular closure device (ACD) following limited lumbar discectomy reduced the risk of recurrent herniation and complications during the first year of follow-up compared to limited lumbar discectomy alone (Controls) and whether this risk was influenced by patient characteristics. In this randomized multicenter trial, patients with symptomatic lumbar disc herniation and with a large annular defect following limited lumbar discectomy were randomized to bone-anchored ACD or Control groups. The risks of symptomatic reherniation, reoperation, and device- or procedure-related serious adverse events were reported over 1 year of follow-up. Among 554 patients (ACD 276; Control 278), 94% returned for 1-year follow-up. Bone-anchored ACD resulted in lower risks of symptomatic reherniation (8.4% vs. 17.3%, P = .002) and reoperation (6.7% vs. 12.9%, P = .015) versus Controls. Device- or procedure-related serious adverse events through 1 year were reported in 7.1% of ACD patients and 13.9% of Controls (P = .009). No baseline patient characteristic significantly influenced these risks. Among patients with large annular defects following limited lumbar discectomy, additional implantation with a bone-anchored ACD lowered the risk of symptomatic reherniation and reoperation over 1 year follow-up. Device- or procedure-related serious adverse events occurred less frequently in the ACD group. These conclusions were not influenced by patient characteristics. ClinicalTrials.gov (NCT01283438).


High diagnostic yield of direct Sanger sequencing in the diagnosis of neuronal ceroid lipofuscinoses.
Neuronal ceroid lipofuscinoses are neurodegenerative disorders. To investigate the diagnostic yield of direct Sanger sequencing of the CLN genes, we reviewed Molecular Genetics Laboratory Database for molecular genetic test results of the CLN genes from a single clinical molecular diagnostic laboratory. We reviewed electronic patient charts. We used consent forms and Research Electronic Data Capture questionnaires for the patients from outside of our Institution. We reclassified all variants in the CLN genes. Six hundred and ninety three individuals underwent the direct Sanger sequencing of the CLN genes for the diagnosis of neuronal ceroid lipofuscinoses. There were 343 symptomatic patients and 350 family members. Ninety-one symptomatic patients had molecular genetic diagnosis of neuronal ceroid lipofuscinoses including CLN1 (PPT1) (n = 10), CLN2 (TPP1) (n = 33), CLN3 (n = 17), CLN5 (n = 7), CLN6 (n = 10), CLN7 (MFSD8) (n = 10), and CLN8 (n = 4) diseases. The diagnostic yield of direct Sanger sequencing of CLN genes was 27% in symptomatic patients. We report detailed clinical and investigation results of 33 NCL patients. Juvenile onset CLN1 (PPT1) and adult onset CLN6 diseases were nonclassical phenotypes. In our study, the diagnostic yield of direct Sanger sequencing was close to diagnostic yield of whole exome sequencing. Developmental regression, cognitive decline, visual impairment and cerebral and/or cerebellar atrophy in brain MRI are significant clinical and neuroimaging denominators to include NCL in the differential diagnosis.


1-Hy-droxy-11H-benzo[b]fluoren-11-one.
The title compound, C(17)H(10)O(2), is nearly planar, the maximum atomic deviation being 0.053 (2) Å. In the mol-ecule, an intra-molecular O-H⋯O hydrogen bond generates an S(6) ring motif. In the crystal, inversion-related mol-ecules are linked by pairs of weak C-H⋯O hydrogen bonds, forming dimers. π-π stacking is observed in the crystal structure, the closest centroid-centroid distance being 3.7846 (16) Å.


Total knee replacement following high tibial osteotomy versus total knee replacement without high tibial osteotomy: a systematic review and meta analysis.
Currently, there is no consensus as to whether total knee replacement(TKR) following high tibial osteotomy(HTO) provides similar postoperative outcomes as compared to TKR without previous HTO. Previous studies have provided limited evidence to small sample sizes and methodological inappropriateness. A systematic search process was conducted utilising PRISMA guidelines. Electronic, peer reviewed and published literatures were searched. Databases searched include Embase, Medline, Cochrane Library, PubMed and cross references. Methodological appropriateness was assessed with Papadokastakis system and Critical Appraisal Skills questionnaire. Data were analysed for both clinical and statistical homogeneity. Meta analytic pooling was subsequently performed. 11 studies including 2170 TKR procedures were analysed for systematic review. The study (TKR following previous HTO) and control (TKR without previous HTO) groups were adequately matched for age, sex ratio and follow-up. Meta analysis of six studies utilising KSS system and four studies utilising HSS system showed no significant (p > 0.05) difference between the two groups. Complications also showed no significant difference between the two groups. At an average follow-up of 7.2 years, with revision arthroplasty for any cause as the endpoint, survivorship for the study and control groups was 95 and 97 %, respectively. For revision arthroplasty with aseptic loosening as the end point, the survivorship was 98 % for both groups. Systematic review and meta analysis suggested that TKR following HTO provides similar outcomes as compared to TKR without previous HTO. Therefore, a previous HTO does not negatively influence a future TKR, though the conversion process of HTO to TKR is technically challenging. Systematic review also identified paucity in prospective and long term studies.


Nocardia elegans infection involving purulent arthritis in humans.
Nocardia elegans infection in humans is rare and is predominantly associated with pulmonary infections. We describe the first case of N. elegans infection associated with purulent arthritis in humans. The patient was a 66-year-old woman without underlying disease. She had swelling in her left ankle that was increasing in size, but it did not cause the patient substantial pain. Punctual discharge was collected for Gram staining and Kinyoun's acid-fast staining. The results of microscopic findings were suggestive of the genus Nocardia. The 16S rRNA sequence of the isolate was completely identical (100%) with that of N. elegans, indicating that the isolate was N. elegans. All the previously reported 4 cases of N. elegans infection in humans were associated with respiratory infections; we present the first case of the infection involving purulent arthritis.


[Inflammatory bowel disease and pregnancy: report of 76 cases and review of the literature].
Obstetrical prognosis for women suffering from Crohn's disease and from ulcerative colitis, and consequences of pregnancy on inflammatory bowel diseases (IBD). Retrospective study, of 76 pregnancies, after the diagnosis of IBD among 77 women (33 ulcerative colitis, 44 Crohn's disease). Pregnancy did not modify the evolutive profile of IBD. No particular gravity of IBD revealed during pregnancy or post-partum was noticed. The outcome of the 54 pregnancies associated with quiescent IBD was the same as in the general population. Five of ten pregnancies started during an active period of Crohn's disease or ulcerative colitis ended in fetal loss (3 spontaneous abortions, 2 medical terminations). In women with a first acute episode or IBD reactivation during pregnancy (n=12), one-third of the newborns were low weight for gestational age, one-third were born preterm and only one-third were term babies with normal weight. Vaginal delivery did not trigger development or exacerbation of perianal Crohn's disease (n=20). Cesarean section was performed in 2 with an ileal pouch-anal anastomosis (n=4) and 1 patient with an ileo-rectal anastomosis (n=3) to avoid injury to the anal sphincter. Ileostomy (n=2) did not contraindicate delivery. Control of IBD is the main obstetrical factor for prognosis. Starting pregnancy can be advised if the disease is quiescent, with rapid and efficient management of possible flare-ups. Delivery route must be determined on a case-by-case basis, each considering pregestational anal continence and the clinical presentation of the perineum.


Transcatheter aortic valve implantation improves outcome compared to open-heart surgery in kidney transplant recipients requiring aortic valve replacement.
Cardiovascular disease is the most frequent cause of mortality for kidney transplant recipients. Open heart surgery has particularly high mortality and morbidity. As an alternative to traditional aortic valve replacement (AVR) for patients with high-grade aortic stenosis, transcatheter aortic valve implantation (TAVI) was developed as an innovative therapy for patients considered at high surgical risk. We considered all kidney transplant recipients as high-risk patients, which are candidates for TAVI. In 2010 and 2011, eight kidney transplant recipients with severe aortic stenosis underwent TAVI (6 transfemoral; 2 transapical; group I). The outcome of these patients was compared retrospectively to 18 kidney transplant recipients with aortic stenosis, who underwent conventional AVR (group II). Both groups had similar baseline characteristics, including estimated perioperative risk (EuroSCORE group I vs. group II: 9.5±5.9 vs. 10.4±10.5; p=0.829). All TAVI procedures were performed successfully with excellent functional results. In the TAVI group (group I), all patients were alive at the 12-month follow-up with one cardiovascular event (stroke). In contrast, the surgical group experienced a 30-day-mortality of 11.1% (n=2) and a 1-year-mortality of 16.7% (n=3). Based on our center's experience, TAVI appears to be an effective and safe alternative to conventional surgery for AVR in patients with prior renal transplantation. Renal transplantation is not currently identified as a risk factor in our traditional scoring system, and may need to be considered independently when weighing alternatives for AVR.


The genetics of human ageing.
The past two centuries have witnessed an unprecedented rise in human life expectancy. Sustaining longer lives with reduced periods of disability will require an understanding of the underlying mechanisms of ageing, and genetics is a powerful tool for identifying these mechanisms. Large-scale genome-wide association studies have recently identified many loci that influence key human ageing traits, including lifespan. Multi-trait loci have been linked with several age-related diseases, suggesting shared ageing influences. Mutations that drive accelerated ageing in prototypical progeria syndromes in humans point to an important role for genome maintenance and stability. Together, these different strands of genetic research are highlighting pathways for the discovery of anti-ageing interventions that may be applicable in humans.


The structure of liquid N-methyl pyrrolidone probed by x-ray scattering and molecular simulations.
The structural properties of liquid N-methyl pyrrolidone have been investigated by combining energy dispersive x-ray diffraction experiments and molecular dynamics simulations with generalized AMBER force field. A very good agreement between theoretical and experimental diffraction patterns was achieved. The analysis of the radial distribution functions shows that the methyl-carbonyl H-bond network observed in the crystal structure is partly preserved in the liquid structure.


Dietary ingredient change induces a transient MyD88-dependent mucosal enteric glial cell response and promotes obesity.
Consumption of a modern Western-type high-fat low-fiber diet increases the risk of obesity. However, how a host responds to such a diet, especially during the early period of dietary transition from a previous low-fat and fiber-rich diet, remains poorly explored. Wild-type C57BL/6 mice were fed a normal chow diet or a high-fat diet. Enteric glial cell (EGC) activation was detected through quantitative real-time PCR (qRT-PCR), immunoblotting and immunohistology analysis. Fluorocitrate or genetic deletion of glial fibrillary acidic protein (GFAP)-positive glial-intrinsic myeloid differentiation factor 88 (Myd88) was used to inhibit EGC activation, and the effect of a high-fat diet on obesity was further investigated. The role of MYD88-dependent sensing of commensal products in adipocyte was observed to analyze the effect of obesity. A dietary shift from a normal chow diet to a high-fat diet in mice induced a transient early-phase emergence of a GFAP-positive EGC network in the lamina propria of the ileum, accompanied with an increase in glial-derived neurotrophic factor production. Inhibition of glial cell activity blocked this response. GFAP-positive glial Myd88 knockout mice gained less body weight after high-fat diet (HFD) feeding than littermate controls. In contrast, adipocyte deletion of Myd88 in mice had no effect on weight gain but instead exacerbated glucose intolerance. Furthermore, short-term fluorocitrate intervention during HFD feeding attenuated body weight gain. Our findings indicate that EGCs are early responders to intestinal ecosystem changes and the GFAP-positive glial Myd88 signaling participates in regulating obesity.


Basal Segmental Longitudinal Strain: A Marker of Subclinical Myocardial Involvement in Anderson-Fabry Disease.
Cardiac involvement in Anderson-Fabry disease (AFD) is associated with increased left ventricular (LV) wall thickness. The aim of this study was to evaluate if two-dimensional global and regional strain in patients with AFD can identify early myocardial involvement (when LV wall thickness and function are normal). Additionally, the association of altered strain with adverse cardiovascular events was evaluated. In a retrospective cross-sectional study, 43 patients with AFD, before enzyme replacement therapy (mean age, 44 ± 12 years; 58.1% men), were compared with age- and gender-matched healthy control subjects. The mean follow-up duration among patients with AFD for major adverse cardiovascular events (MACE) was 82 months. LV ejection fraction was similar between groups (patients with AFD vs control subjects, 61 ± 8% vs 61 ± 6%; P = .89). However, global longitudinal strain (LS) was impaired in patients with AFD compared with control subjects (-16.5 ± 3.8% vs -20.2 ± 1.7%, P < .001), with greater impairment in patients with AFD with increased LV wall thickness (-15.4 ± 3.9% vs -18.7 ± 2.3%, P < .006). Additionally, LS was most impaired in the basal segments in patients with AFD (-14.8 ± 3.7% vs -20.3 ± 1.1%, P < .001). MACE occurred in 19 of 43 patients (four women, 15 men), and Kaplan-Meier analysis demonstrated that MACE were associated with impaired basal LS. In patients with AFD, altered basal LS is present even in those with normal LV wall thickness and is associated with MACE. Therefore, basal LS should be considered when screening for cardiac involvement in AFD, particularly in female patients with AFD with normal LV wall thickness.


Localization of calcium ions in mixed synapses of Mauthner neurons during exposure to substances altering the conductivity of gap junctions.
The pyroantimonate method was used to study the distribution of calcium ions in the mixed synapses of Mauthner neurons after exposure to substances altering the electrotonic conductivity of these synapses mediated by gap junctions (GJ). Ecdysone, an agent which increases GJ conductivity, produced precipitates of calcium pyroantimonate coating the whole postsynaptic surface of the GJ area, making them strongly asymmetrical. Precipitate granules were also seen to appear in the clefts of desmosome-like contacts (DLC). Chlorpromazine, which decreases GJ conductivity, produced precipitates in GJ clefts and on the pre- and postsynaptic membranes. No precipitate formed in DLC clefts. These results demonstrate that ecdysone acts as an agent selectively increasing GJ conductivity without affecting DLC function. Chlorpromazine had a double action, blocking conduction through both GJ and DLC. Thus, studies of agents altering GJ permeability require consideration of the possibility that they may interact with actin-containing structures also involved in the transport of the electrotonic signal.


Identification and composition of types of granular urinary casts.
Granular urinary casts were analyzed by scanning electron microscopy and histochemistry. Three types were identified. They appear to have distinctly different origins and significance. Their clinical associations remain to be defined. One type can be misidentified by bright field microscopy. Bacterial casts also can be misidentified as granular casts unless the sediment is examined carefully.


Bone turnover and balance evaluated by a combined calcium balance and 47calcium kinetic study and dynamic histomorphometry.
Bone resorption and formation rates were evaluated at the organ level using calcium kinetic methods and at the trabecular bone tissue level using dynamic histomorphometry in 20 patients with various metabolic bone diseases (primary hyperparathyroidism (N = 9), hyperthyroidism (N = 6), and hypothyroidism (N = 5). Highly significant correlations were demonstrated between resorption and formation rates at organ level (r = .90, P less than .001) and at tissue level (volume referent) (r = .93, P less than .001), indicating a high degree of coupling between resorption and formation within the three disease states. Tissue level resorption rates (surface referent, as well as volume referent) both correlated significantly (P less than .01) to organ level resorption rate (r = .60 and r = .63, respectively). Fractional active resorption surface and cellular level resorption rate did not reveal significant correlations to calcium kinetic estimates. No correlation could be demonstrated between organ level mineralization rate and formative or labeled trabecular surfaces. However, all tetracycline based tissue level formation rates revealed highly significant correlations (P less than .01) to organ level mineralization rate (calcification rate, r = .71; surface referent bone formation rate, r = .59; volume referent bone formation rate, r = .68). Based on histomorphometric parameters for resorption and formation, actual and predicted tissue level trabecular bone balances were calculated. Both the actual and predicted bone balance correlated significantly to the organ level calcium balance (P less than .05). Correction for skeletal size based on BMC measurements did not improve any of the correlations significantly.(ABSTRACT TRUNCATED AT 250 WORDS)


Oncogenetic landscape of T-cell lymphoblastic lymphomas compared to T-cell acute lymphoblastic leukemia.
In the latest 2016 World Health Organization classification of hematological malignancies, T-cell lymphoblastic lymphoma (T-LBL) and lymphoblastic leukemia (T-ALL) are grouped together into one entity called T-cell lymphoblastic leukemia/lymphoma (T-LBLL). However, the question of whether these entities represent one or two diseases remains. Multiple studies on driver alterations in T-ALL have led to a better understanding of the disease while, so far, little data on genetic profiles in T-LBL is available. We sought to define recurrent genetic alterations in T-LBL and provide a comprehensive comparison with T-ALL. Targeted whole-exome next-generation sequencing of 105 genes, multiplex ligation-dependent probe amplification, and quantitative PCR allowed comprehensive genotype assessment in 818, consecutive, unselected, newly diagnosed patients (342 T-LBL vs. 476 T-ALL). The median age at diagnosis was similar in T-LBL and T-ALL (17 vs. 15 years old, respectively; p = 0.2). Although we found commonly altered signaling pathways and co-occurring mutations, we identified recurrent dissimilarities in actionable gene alterations in T-LBL as compared to T-ALL. HOX abnormalities (TLX1 and TLX3 overexpression) were more frequent in T-ALL (5% of T-LBL vs 13% of T-ALL had TLX1 overexpression; p = 0.04 and 6% of T-LBL vs 17% of T-ALL had TLX3 overexpression; p = 0.006). The PI3K signaling pathway was significantly more frequently altered in T-LBL as compared to T-ALL (33% vs 19%; p < 0.001), especially through PIK3CA alterations (9% vs 2%; p < 0.001) with PIK3CAH1047 as the most common hotspot. Similarly, T-LBL genotypes were significantly enriched in alterations in genes coding for the EZH2 epigenetic regulator and in TP53 mutations (respectively, 13% vs 8%; p = 0.016 and 7% vs 2%; p < 0.001). This genetic landscape of T-LBLL identifies differential involvement of recurrent alterations in T-LBL as compared to T-ALL, thus contributing to better understanding and management of this rare disease.


Network of inflammatory cytokines and correlation with disease activity in ulcerative colitis.
The inflammatory component of most human inflammatory chronic diseases implicates the production of proinflammatory cytokines. Tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL1beta) seem to play an important role in ulcerative colitis (UC) in relevant experimental models. Moreover, antiTNF therapy seems promising experimentally and clinically. However, these cytokines, and TNFalpha more particularly, are hardly seen in vivo in such patients. The mediators of choice, correlated with disease activities or drug efficacy, remain unclear. To characterize in vivo the network of colonic cytokines in patients with UC, and the contribution of the various cytokines to disease activity we performed this study, using the colonic perfusion method. A 20-cm colon length was perfused. Perfusate samples were collected for cytokine determination by enzyme-linked immnoassays. Nineteen perfusions were performed in mild to moderate UC, including two successive perfusions in four patients. Six healthy control patients and four having Crohn's disease (CD) with rectal involvement were studied. Endoscopic score, leukocyte scintigraphy, and systemic markers of inflammation were simultaneously quantified. Large amounts of IL1beta, TNFalpha, IL6, and IL8 were produced in UC patients with a highly significant correlation between TNFalpha, IL1beta and IL8 two by two. Multivariate factorial analysis indicated that IL1beta showed the best correlation with disease activity. Locally produced IL6 was strongly associated with circulating platelet counts. Moreover, production of inflammatory cytokines was associated with similar variations of disease activity in the four patients with two successive perfusions performed. The level of inflammatory cytokines in CD was lower than in UC; TNFalpha, IL1beta, and IL6 were not found in any control patients. UC appears to be a chronic inflammatory disease characterized by high production of all four proinflammatory cytokines (IL1beta, TNFalpha, IL6, and IL8). These results suggest that colonic perfusion may be a suitable method to evaluate the local anticytokine properties of new drugs, in correlation with disease activity and systemic markers of inflammation.


Investigation on the difference between biofilm morphologies of the vermifilter and conventional biofilter with the flow cytometer.
With the demand of new sludge reduction processes, a vermifilter (VF) was studied based on a conventional biofilter (BF). The biofilm morphology was investigated using a new technique, the flow cytometer (FCM), to find a way to optimize VF structure. VF was inoculated with Eisenia fetida, packed with ceramsites, and operated stably at the organic load of 1.2kg-VSSm(-3)d(-1) with BF as the control. Compared with BF, VF had about 13% more removal efficiency of excess sludge and 45% shorter biofilm update period. FCM profile showed the morphology of microbial cells in VF biofilms was significantly different from that in BF in upper layers, with decreases of average refractive index (about 72%) and size (about 22%), and suggested it was better to keep earthworms there to remove rod-shaped microorganisms with other filter media in lower layers to remove spherical ones combining the findings in SEM images and extracellular polymeric substances.


Population structure and genetic diversity of the endangered fish black shinner Pseudopungtungia nigra (Cyprinidae) in Korea: a wild and restoration population.
The black shinner Pseudopungtungia nigra Mori, 1935 is an endangered fish endemic to Korea. It lives in the narrow basin of the Geumgang River, Mangyeonggang River, and Ungcheoncheon Stream, which flow into the West Sea of Korea. One population of P. nigra in Ungcheoncheon Stream has been locally exterminated once; it is now inhabiting the upper reaches of the dam through a restoration program. Efforts to identify and understand the genetic structure of these populations are important for conservation planning. Here, we analyzed genetic diversity using 21 microsatellite markers for 9 populations. The mean number of alleles ranged from 4.4 to 8.1, mean allelic richness ranged from 4.6 to 7.8, mean observed heterozygosity ranged from 0.519 to 0.702, and mean expected heterozygosity ranged from 0.540 to 0.763. All groups had recent and historical bottlenecks (P < 0.05, M-ratio < 0.68). Three groups [YD (2019), OC and UC] had significant inbreeding index values, suggesting that they were engaged in inbreeding. We observed a moderate level of genetic differentiation between MG and the rest of the population (FST = 0.135 to 0.168, P < 0.05). The genetic structure exhibited a fitting constant K = 2, along with separation between MG and the remaining populations. With respect to genetic flow, YD (2019), OC, CG, and ND shifted to the UC population (0.263 to 0.278). The genetic flow of each population was transferred only within the population; there was no gene flow among populations, except for the Ungcheoncheon Stream population. This study shows that the Ungcheoncheon Stream population needs conservation efforts to increase its genetic diversity, and the Geumgang River populations needs a conservation plan that considers the possibility of conservation and evolution through gene exchange among the populations.


Sequences associated with intracisternal A particles are reiterated in the mouse genome.
Using a 3H-cDNA for RNA sequences specifically associated with murine intracisternal type A particles, we have found multiple copies of this information in high molecular weight nuclear DNA from tissues of both Mus muscules (BALB/c, NIH Swiss, A/Jax and feral) and Mus cervicolor. Reiteration frequencies varied from 1050-1800 per haploid genome, except that fewer copies (450) were found in BALB/3T3 cells. In the series studied, the reiteration frequencies in the DNA of A particle-rich tumor cells (myeloma and neuroblastoma) were not higher than those in normal tissues (liver and sperm). Multiple copies were retained when cellular DNAs were sedimented through alkaline sucrose gradients, indicating that the sequences are integrated in the mouse genome. In situ hybridization with cDNA showed that the sequences were associated with many chromosomes and were concentrated over certain regions of some chromosomes. Only low levels of homologous sequences were detected in rat, hamster and guinea pig DNA under stringent conditions of hybridization. The presence of reiterated sequence transcripts in poly(A) RNA from a neuroblastoma A particle fraction was confirmed by direct hybridization of the RNA with cellular DNA.


Rapid diagnosis of common deletional α-thalassemia in the Chinese population by qPCR based on identical primer homologous fragments.
In China, -(SEA), -α(3.7) and -α(4.2) are common deletional α-thalassemia alleles. Gap-PCR is the currently used detection method for these alleles, whose disadvantages include time-consuming procedure and increased potential for PCR product contamination. Therefore, this detection method needs to be improved. Based on identical-primer homologous fragments, a qPCR system was developed for deletional α-thalassemia genotyping, which was composed of a group of quantitatively-related primers and their corresponding probes plus two groups of qualitatively-related primers and their corresponding probes. In order to verify the accuracy of the qPCR system, known genotype samples and random samples are employed. The standard curve result demonstrated that designed primers and probes all yielded good amplification efficiency. In the tests of known genotype samples and random samples, sample detection results were consistent with verification results. In detecting αα, -(SEA), -α(3.7) and -α(4.2) alleles, deletional α-thalassemia alleles are accurately detected by this method. In addition, this method is provided with a wider detection range, greater speed and reduced PCR product contamination risk when compared with current common gap-PCR detection reagents.


Incremental Validity Of The Diagnostic Criteria For Psychosomatic Research - Revised (DCPR-R) To Clinical Assessment In Primary Care.
Psychosocial problems are highly prevalent among primary care (PC) patients, but they often remain undetected using traditional classification systems. The aim of the present study was to test the incremental validity of the revised version of the Diagnostic Criteria for Psychosomatic Research (DCPR-R), in addition to standard psychiatric assessment based on DSM-5, with regard to the prediction of psychosocial functioning of PC patients. Two-hundred PC patients were consecutively recruited. A comprehensive assessment was performed using two clinical interviews and three self-rating questionnaires (the PsychoSocial Index [PSI], the Short-Form Health Survey [SF-12] and the Illness Attitude Scales [IAS]) for the assessment of psychopathology and psychosocial functioning. Adding the DCPR-R to DSM-5, the amount of explained variance significantly increased by 9% to 16% in the PSI subscales, by 13% in the SF-12 mental component summary, and by 2% to 6% in the IAS scales. The joint use of DCPR-R and DSM-5 thus significantly increased the prediction of psychosocial functioning of primary care patients. These findings further support the use of the DCPR-R in PC settings, particularly in patients who do not satisfy DSM-5 criteria and yet present with high psychological distress, maladaptive illness behavior, impaired psychological well-being and quality of life.


Increased Body Mass Index (BMI) and Sunscreen Use Are Associated with Inadequate Vitamin D Status in Greek Adults in Winter : BMI, Sunscreen Use and Vitamin D Status in Greek Adults.
Vitamin D deficiency is common even in sunny countries like Greece, especially during winter and is associated with skeletal disorders and additionally with increased risk for chronic diseases and adipose metabolic diseases such as obesity and diabetes. The purpose of this pilot study was the determination of vitamin D status in Greek adults and the investigation of possible correlation with lifestyles and somatometric characteristics. The study was conducted during winter and included 36 members (20 women and 16 men) of a university community in central Greece (latitude 39.6° North). Their age was 36.2 ± 16.3 years, body mass index (BMI) 26.4 ± 4.8 (women 26.6 ± 5.6, men 26.3 ± 3.8), and waist circumference 85.7 ± 13.3 cm (women 81.5 ± 13.0, men 90.7 ± 12.4) (mean ± SD). Mean serum 25(OH)D concentration was 20.1 ± 7.3 ng/mL (women 19.7 ± 7.6, men 20.7 ± 7.1). More than half of the participants had 25(OH)D levels below the 20 ng/mL (50 nmol/L) threshold of deficiency. There was a significant negative association between the use of sunscreen during summer and serum 25(OH)D concentrations during winter and a significant positive association between physical exercise and serum 25(OH)D. Levels of 25(OH)D tended to decrease with increasing BMI in persons with a BMI over 25.0. There is a high prevalence of vitamin D insufficiency in Greek adults during winter. Serum 25(OH)D levels in winter are positively associated with exercise and negatively associated with high BMI and the use of sunscreen during summer.


The role of the oxytocinergic system in the antidepressant-like effect of swimming training in male mice.
Increasing evidence shows that higher physical activity such as running and swimming exercises is associated with decreased depression-related symptoms. However, underlying mechanisms are not fully understood. This study aimed to investigate whether oxytocinergic system can mediate the antidepressant effect of swimming exercises in mice. First, male NMRI mice were subjected to swimming training for eight weeks, then animals intraperitoneally received oxytocin antagonist (L-368899) 1 h before behavioral tests. We assessed anhedonia and social behavior and behavioral despair using the sucrose preference test, social interaction test, and tail suspension test. Oxytocin levels in the brain and serum were also measured. The results showed that swimming training decreased anhedonia and behavioral despair, whereas it increased social behavior and oxytocin levels in male mice. On the other hand, a subthreshold dose of oxytocin antagonist treatment in exercised mice prevented the antidepressant effect of swimming exercise via increased anhedonia and behavioral despair and decreased social behavior compared to the swimming training group. However, the blockade of oxytocin receptors did not affect oxytocin levels in exercised mice. Overall, these findings suggest that oxytocinergic system can play a role in mediating the antidepressant-like effect of swimming training in mice.


Radiology in early slipped femoral capital epiphysis.
In a study of 38 hips showing only minor abnormality on the AP radiograph, it was found that the most reliable sign of an early slip was blurring of the junction between the metaphysis and the growth plate. The diagnosis could not be made on the AP film alone in 11% of cases and it is recommended that a routine lateral radiograph is obtained when slipped epiphysis is a clinical possibility. The importance of the radiologist in the early diagnosis of the condition is stressed and the causes of diagnostic delay are considered.


Comparative study on the structure and cytopathogenic activity of HIV Vpr/Vpx proteins.
The three-dimensional (3-D) structure of human immunodeficiency virus type 2 (HIV-2) Vpr/Vpx was predicted by homology modeling based on the NMR structure of human immunodeficiency virus type 1 (HIV-1) Vpr. The three proteins similarly have three major amphipathic alpha-helices. In contrast to HIV-1 Vpr, Vpr/Vpx of HIV-2 have a long N-terminal loop and clustered prolines in the second half of the C-terminal loop. HIV-2 Vpx uniquely contains a long region between the second and third major helices, and bears several glycines in the first half of the C-terminal loop. Instead of the glycines, there is a group of hydrophilic amino acids and arginines in the corresponding regions of the two Vprs. To compare the cytopathogenic potentials of HIV-1 Vpr and HIV-2 Vpr/Vpx, we examined the production of luciferase as a marker of cell damage. We further analyzed the characteristics of cells transduced with vpr/vpx genes driven by an inducible promoter. The results obtained clearly show that structurally similar, but distinct, HIV Vpr/Vpx proteins are detrimental to target cells.


Resectability and outcome with anti-EGFR agents in patients with KRAS wild-type colorectal liver-limited metastases: a meta-analysis.
Cetuximab (C) and panitumumab (P) increase response rate and survival in KRAS wild-type metastatic colorectal cancer (mCRC). We performed a meta-analysis of randomised controlled trials (RCTs) to assess their effect on overall response rate (ORR), the rate of radical resection (R0) and survival in patients with liver-limited initially unresectable mCRC. We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials for RCTs comparing first-line chemotherapy plus or minus C or P and reporting data in patients with KRAS wild-type, unresectable liver-limited mCRC. Relative risks (RRs) with 95% confidence interval were calculated. Meta-analysis of hazard ratios (HRs) for progression-free and overall survival (PFS and OS) was also performed. Four RCTs involving 484 KRAS wild-type patients were included. Compared to chemotherapy alone, the addition of C or P significantly increased the ORR (RR 1.67, p = 0.0001), the R0 resection rate from 11% to 18% (RR 1.59, p = 0.04) and PFS (HR 0.68, p = 0.002), but not OS (p = 0.42). The addition of C and P increased the R0 resection rate by 60% and reduced the risk of progression by 32% in patients with mCRC and unresectable liver-limited disease. This combination represents one of the preferred choices as conversion therapy in KRAS wild-type patients with unresectable liver metastases.


Clinicopathological Significance of CD133 and ALDH1 Cancer Stem Cell Marker Expression in Invasive Ductal Breast Carcinoma.
Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We investigated the possible correlation between cancer stem cell (CSC) markers (CD133, and ALDH1) in invasive ductal breast carcinomas with some clinicopathological parameters. To assess the correlation between expression of cancer stem cell (CSC) markers (CD133, and ALDH1) and clinicopathological parameters of invasive ductal breast carcinomas. Immunohistochemical analysis of CD133 and ALDH1 was performed on a series of 120 modified radical mastectomy (MRM) specimens diagnosed as invasive ductal breast carcinoma. Expression of both CD133 and ALDH1 was significantly changed and related to tumor size, tumor stage (TNM), and lymph node metastasis. A negative correlation between CD133 and ALDH1 was found. Detecting the expression of CD133 and ALDH1 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties and determining the optimal treatment.


Case managers and physicians: communication and perceived problems.
To describe case managers' perceptions of the physician-case manager relationship. A qualitative field study using in-depth open-ended interviews was used to elicit case managers' experiences and practices. A multidisciplinary team analyzed transcripts using an adaptation of the "grounded theory" approach of Glaser and Strauss. Case managers were selected for interview using a maximum variation sampling strategy within an established state-wide case management agency. Transcript analysis allowed for the organization of observations into themes, which were merged across interviews to generate theses. Case managers report that: (1) The case manager role is poorly understood by physicians. (2) Physicians lack insight into the social and environmental aspects of home-bound elderly people. (3) Access to physician services is often difficult to obtain. (4) Power struggles occasionally surface in care planning. (5) Decisions by physicians and case managers regarding the care of frail elderly are often made from different agenda. From the perspective of case managers, gaps in interprofessional communication may hinder the optimal care of frail elderly individuals.


Uptake of liposomally entrapped adenosine-3'-5'-cyclic monophosphate in mouse brain.
[3H] Adenosine-3',5'-cyclic monophosphate (cAMP) could be entrapped efficiently into small unilamellar vesicles when bound to cAMP-dependent protein kinase. The leakage of [3H]cAMP protein kinase complex from liposomes was reduced by more than 60% as compared to free [3H]cAMP. Hyperosmolar mannitol increased the delivery of liposomally entrapped [3H]cAMP protein kinase to the brain with maximum uptake occurring at 10 min after mannitol administration. Optimal delivery to the brain was observed when vesicles composed of total brain lipids or phosphatidylcholine:cholesterol:sulfatides (7:2:1) were used. A slower clearance of liposomally entrapped material from brain tissue was seen under hyperosmolar conditions.


CDC's 60th anniversary: director's perspective--David J. Sencer, M.D., M.P.H., 1966-1977.
Change, national and international, was the engine that thrust CDC into its third decade (1966-1975). Starting the decade as the Communicable Disease Center, it ended the decade as the Center for Disease Control as part of the Public Health Service (PHS) under the U.S. Department of Health, Education, and Welfare (HEW).


Chemoenzymatic synthesis and utilization of a SAM analog with an isomorphic nucleobase.
SalL, an enzyme that catalyzes the synthesis of SAM from l-methionine and 5'-chloro-5'-deoxyoadenosine, is shown to accept 5'-chloro-5'-deoxythienoadenosine as a substrate and facilitate the synthesis of a synthetic SAM analog with an unnatural nucleobase. This synthetic cofactor is demonstrated to replace SAM in the DNA methylation reaction with M.TaqI.


Stage and region dependent expression of a radial glial marker in commissural fibers in kindled mice.
Amygdala kindling is regarded as a model of temporal lobe epilepsy in humans because of many points of similarity. In amygdala kindling, bilateralization of epileptic seizures follows from the accumulation of stimulation and commissural fibers may play a role in this process. However, new progenies of cells following amygdala kindling have not been reported and the precise nature of how bilateralization occurs is not clear. In the present study, we aim to clarify the emergence of radial glia during the progress of amygdala kindling in mouse brain. For this purpose, immunohistochemical staining for 3CB2, which is a specific marker of radial glia, was employed. Immunoreactivity for 3CB2 was observed in the forceps minor, radiation of trunk and forceps major regions at Clonus 3 and more strongly at Clonus 5. In the forceps major, the cingulate gyrus showed immunopositive staining at Clonus 3, but the corpus callosum and alveus hippocampi showed staining only at Clonus 5. In the fimbria hippocampus, the anterior commissure posterior showed staining at Clonus 5. However, the anterior commissure anterior was not stained at the stage progressed to Clonus 5. These findings indicate stage and region dependent expression of progenitor cells in commissural fibers and suggest that these changes may accompany the formation of new circuits in seizure progression during amygdala kindling.


Extraction of leucocytes from human decidua. A comparison of dispersal techniques.
Functional studies of human utero-placental tissues have been limited by poor characterisation of the morphology and antigenic phenotype of the cells under investigation. The present study documents the effect of dispersal methods on the viability and cellular composition of cell suspensions prepared from decidualised endometrium in early human pregnancy. First trimester decidua was subjected to both mechanical disaggregation and digestion with various enzyme combinations in an attempt to optimise the yield of infiltrating decidual leucocytes. Cell types were characterised with monoclonal antibodies using an alkaline phosphatase immunolabelling method. Mechanical disaggregation resulted in suspensions containing many large decidual cells and much cell debris but few leucocytic cells. Overall viability was low, although the viability of small leucocytes common antigen-bearing cells remained high. Enzymic digestion yielded cell suspensions rich in leucocytes with high viability and minimal contamination by other cell types. Collagenase produced a high yield of leucocytes with high viability and minimal disruption of surface antigens in contrast with pronase which caused extensive antigenic loss. The disaggregation method determines the yield of bone marrow derived cells in decidual cell suspensions and the extent of contamination by true decidual cells and epithelial cells.


Image quality of the human eye for eccentric entrance pupils.
The human eye has a considerable amount of chromatic aberration and a moderate amount of spherical aberration. If a small artificial pupil is placed in front of such optics and moved away from the centre towards the periphery the chromatic aberration will result in lateral colour shifting, and the spherical aberration will cause coma. Starting from available experimental data on the chromatic aberration and the spherical aberration, modulation transfer functions (MTF's) are calculated for central and eccentric positions of small pupils placed in front of the human eye. These calculations may help to separate optical and retinal contributions to the well-known reduction of visual acuity measured with eccentric pupils. It appears that measurements with pupils smaller than 1 mm in monochromatic light can be considered optically as diffraction limited. Changes of visual acuity found in this way must be assigned to the retina.


A procedure for culturing rat neocortex explants in a serum-free nutrient medium.
A procedure is described for long-term culturing of rat neocortex explants in a serum-free growth medium. Slices spanning the entire cortical depth from pial to ventricular side are prepared from 6-day-old rat pups. After preincubation in Hanks' balanced salt solution with extra glucose, the explants are placed on polyamide gauze carriers in plastic culture dishes containing serum-free medium. The dishes are continuously rocked during the culture period. After 3 weeks in vitro the explants consist of a three-dimensional network of neural tissue with a mean thickness above the gauze of ca. 100 micron which corresponds with about 8 cell layers. Central necrosis is either fully absent (in one-third of the explants) or restricted to a minimal strip or patch located close to the gauze. From pial to ventricular side, 5 layers can be distinguished which, with respect to cell size and cell density, reflect a histiotypic architecture. The dense neuropil shows abundant axo-dendritic synapses (both on shafts and spines), myelinated fibers, and spontaneous bioelectric activity.


High-normal TSH values in obesity: is it insulin resistance or adipose tissue's guilt?
Clinical evidences reported subclinical alterations of thyroid function in obesity, although the relationship between thyroid status and obesity remains unclear. We cross-sectionally investigated the influence of metabolic features on hypothalamic-pituitary-thyroid axis in obesity. We enrolled 60 euthyroid subjects with no history of type 2 diabetes mellitus and assessed the relationship of thyroid function with insulin resistance, measured using euglycemic clamp, and abdominal fat volume, quantified by computed tomography scan (CT scan). Thyroid stimulating hormone (TSH) correlated with BMI (r = 0.46; P = 0.02), both visceral (r = 0.58; P = 0.02) and subcutaneous adipose tissue volumes (r = 0.43; P = 0.03) and insulin resistance (inverse relationship with insulin sensitivity-glucose uptake: r = -0.40; P = 0.04). After performing multivariate regression, visceral adipose tissue volume was found to be the most powerful predictor of TSH (β = 3.05; P = 0.01), whereas glucose uptake, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, subcutaneous adipose tissue volume, and triglycerides were not. To further confirm the hypothesis that high-normal TSH values could be dependent on adipose tissue, and not on insulin resistance, we restricted our analyses to moderately obese subjects' BMI ranging 30-35 kg/m(2). This subgroup was then divided as insulin resistant and insulin sensitive according to the glucose uptake (≤ or >5 mg · kg(-1) · min(-1), respectively). We did not find any statistical difference in TSH (insulin resistant: 1.62 ± 0.65 µU/ml vs. insulin sensitive: 1.46 ± 0.48; P = not significant) and BMI (insulin resistant: 32.2 ± 1.6 kg/m(2) vs. insulin sensitive: 32.4 ± 1.4; P = not significant), thus confirming absence of correlation between thyroid function and insulin sensitivity per se. Our study suggests that the increase in visceral adipose tissue is the best predictor of TSH concentration in obesity, independently from the eventual concurrent presence of insulin resistance.


The effect of drug therapy without volume restoration in experimental traumatic shock. Part III. Glucocorticoid.
The effects of methylprednisolone in connexion with a standardized trauma was studied on 30 rabbits. The treatment with glucocorticoid accentuated the hemodilution due to the trauma. Intensified lactacidosis was also demonstrated.


[A holder for plain x-ray visualization of ulnar, volar and radial injuries of the capsule and ligaments of the basal thumb joint. A hyperextensometer for the determination of the ligamentous laxity of the index finger basal joint].
We have constructed a device for standardized radiodiagnostics of ulnar, volar, and radial capsulo-ligamentous lesions of the basal thumb joint. Used as hyperextensometer at the basal joint of the index finger, the device is of equal value in the diagnosis of ligamentous laxity.


[Specificity of tyrosine metabolism depending on the state of melaninogenesis].
The excretion of metabolites of tyrosine (p-hydroxypyruvic acid-p-HPA, homogentisinic acid-HGA, total keto acids-TKA) and the activity of tyrosine aminotransferase of the tissues of 36 albino and 36 black rabbits was measured. The initial level of tyrosine metabolites in the urine of black and albino rabbits differed but little from one another. With the introduction of L-tyrosine, the quantity of the excreted p-HPA increased sharply, and of the HGA decreased in the albino rabbits. Among black rabbits an increase of the HGA excretion with a comparatively stable level of the excreted p-HPA was noted. Among all the tissues investigated only in the skin and the liver of albino rabbits there was a sharp increase in the initial tyrosine aminotransferase activity after the feeding of L-tyrosine, which testified to a probable adaptive synthesis of the enzyme. Analysis of the data obtained showed that tyrosine metabolism probably depended on the state of melaninogenesis.


Early management and decision making for the treatment of myelomeningocele.
A program for early selection and treatment of the infant with myelomeningocele was developed at the University of Oklahoma Health Sciences Center in 1977. Over a 5-year period, 69 babies were evaluated, 36 babies were recommended for early vigorous treatment. Of the 33 babies for whom only supportive care was recommended, five were initially treated at the parents' request, two underwent delayed vigorous treatment, one was subsequently treated by "crisis management," one moved and did not return for follow-up, and 24 received only supportive care. All 24 babies died between 1 to 189 days of age (mean 37 days). The involvement of several physicians and paramedical support personnel is considered essential for this approach of early selection and treatment. Continued support and regular follow-up is necessary for any baby who receives only supportive care. Parents retain legal custody. Although ethical concerns make any approach difficult, the method presented is considered to be the best alternative available at this time.


[Clinical studies of the role of the fluorescent circulating antibody test in the diagnosis of active tuberculosis].
The value was studied, of the test of circulating fluorescent antibodies against M. tuberculosis in establishing the diagnosis of active tuberculosis in 610 patients classified in 4 groups: 1. active tuberculosis bacteriologically confirmed; 2. active tuberculosis with negative bacteriological examination, but confirmed by other methods of criteria; 3. stabilized tuberculosis; 4. non-tuberculous affections. The specificity of the test in active tuberculosis was of 80% in adults and of 91,5% in children. The test was negative in 80,3% of stabilized tuberculosis cases and in 69% of non-tuberculous affections. The sensitivity was lower in active tuberculosis with positive bacilloscopy (67%) against active tuberculosis with negative bacilloscopy (90,6%), a fact explained by a high consumption of anti-bacillary antibodies, demonstrated by positivation of the test when bacilloscopy becomes negative. The use of the test is indicated in establishing a therapeutic test, and in the context of clinical and radiologic explorations, as well as in the expertising of working capacities of previous tuberculosis patients.


How an aspirin, a throat swab from a chicken, and four Guinea pigs changed thoracic surgery.
The development of antituberculous drugs changed thoracic surgery and also markedly lowered the morbidity and mortality of a disease that had epidemic proportions. This article summarizes aspects from 3 important articles that led to the discovery of these drugs.


Recent patterns of drug use in newborn intensive care.
To better understand patterns of medication use in neonatal intensive care, we examined data collected prospectively over a recent 9-year period in the newborn intensive care units of two large teaching hospitals. Among 2690 infants studied, 91% received at least one drug; 99% of infants weighing less than 1500 gm were exposed to drugs, compared with 90% of infants weighing more than 1500 gm. Among treated infants, the median number of drugs received was eight; the number of drugs administered was inversely related to birth weight and directly related to both length of hospital stay and the complexity of the infant's clinical condition. Within categories of length of hospital stay, the number of drugs received per day was greatest during the first week in the neonatal intensive care unit and fell to a relatively stable lower level during the second week. The most commonly used single drug was gentamicin (71% exposed), followed by sodium chloride (60%), potassium chloride (59%), heparin (58%), and packed erythrocytes (45%). Between 1978-1979 and 1985-1986 the prevalence of use increased substantially for some drugs (ampicillin, morphine, calcium salts, and acetates of sodium and potassium) and decreased for others (kanamycin, sodium bicarbonate, and blood products). These data document the dynamic nature of drug therapy in the neonatal intensive care unit and provide information that can guide cost-benefit assessments in this setting.