Accelerating Brain 3D T1-Weighted Turbo Field Echo MRI Using Compressed Sensing-Sensitivity Encoding (CS-SENSE).
To evaluate the clinical application of the accelerated 3D T1-weighted turbo field echo (T1W-TFE) using the compressed sensing-sensitivity encoding (CS-SENSE) and identify the appropriate acceleration factor. 33 healthy controls (HC), 10 multiple sclerosis (MS) and 10 Alzheimer's disease (AD) patients were prospectively recruited. A conventional 3D T1W-TFE sequence and accelerated sequences with CS-SENSE factors of 3, 4.5, 6 and with SENSE factors of 3, 4.5 were acquired for all participants on a 3.0T MR system. The visual evaluation was independently assessed by two experienced radiologists. Quantitative image quality metrics and intraclass correlation coefficients (ICCs) between the conventional and the accelerated sequences were performed at the voxel level. Group comparisons were performed between HC and AD or MS patients. There were no significant differences in the visual image quality metrics between conventional sequence and CS-SENSE factor of 3. The sequences with CS-SENSE factor of 6 and SENSE factors of 3, 4.5 showed significantly decreased overall image quality. The ICC values based on the voxel level of each accelerated scan and conventional scan were high (>0.9, 85.2%). For different accelerated sequences, AD and MS patients showed consistent results with the conventional sequence in gray matter atrophy when compared to HC. CS-SENSE factor of 3 is the appropriate parameter to accelerate the 3D T1W-TFE (65% time reduction) with preserved visual image quality. The voxel-based analysis demonstrated high ICCs for brain volume measurements in the majority of brain regions, implying the feasibility of the accelerated technique.


Ethnobotanical observations on Paraguayan Myrtaceae. I.
A survey of myrtaceous plants used in traditional medicine in rural areas of eastern Paraguay was undertaken to identify the constituents of crude drugs traded by herbalists. The literature on the use of those plants dating back to colonial times in Paraguay has been examined. Some crude drugs were shown to be mixtures of several genera and species. Those findings put into doubt the outcome of some pharmacological research work carried out without botanical documentation.


Comment on Chiu et al. Health Promotion and Disease Prevention Interventions for the Elderly: A Scoping Review from 2015-2019. Int. J. Environ. Res. Public Health 2020, 17, 5335.
Chiu et al. report in their paper "Health Promotion and Disease Prevention Interventions for the Elderly: A Scoping Review from 2015-2019" [...].


The diagnostic contribution of the frontal lumbar spine radiograph in community referred low back pain--a prospective study of 1030 patients.
The diagnostic contribution of the anteroposterior (AP) view was studied to assess whether this view could be omitted safely, thus reducing the radiation burden received by patients undergoing lumbar spine radiography. Prospective analysis of 1030 consecutive referrals for lumbar spine radiography from general practice. In the majority of cases (90.5%) the AP view was non-contributory. In 4.2% the diagnosis was strengthened and it was altered in 4.6%. However, in the latter group only 1.3% of the total were considered significant alterations. These were cases of possible, but not definite, pars defects and sacroiliitis. Specific important conditions such as infection, malignancy and benign tumours were not missed on the lateral view alone, in our study population. The radiation burden is reduced by 75% by omitting the AP view. A single lateral view is an adequate examination, with the proviso that sacroiliac joint disease is not assessed on this view and some pars defects and facet joint degenerative changes may be overlooked. The radiation protection gains are considerable. A single lateral lumbar view is now our routine practice unless sacroiliitis is a specific clinical concern.


Mutagenicity of N-nitroso pyridinol carbamate with the Salmonella/mammalian microsome test.
Pyridinol carbamate was nitrosated to the N,N1-dinitroso derivative and the structure was proved by spectroscopic methods, including chemical ionization mass spectroscopy. By the Ames test, the dinitroso derivative showed a significant dose-dependent mutagenic response with Salmonella typhimurium strains TA 1535 and TA 100; the response became more pronounced in the presence of microsomes. As the dosage of N-nitroso pyridinol carbamate increased, the number of revertant colonies also increased. Pyridinol carbamate was not mutagenic.


A novel MEN1 pathogenic variant in an Italian patient with multiple endocrine neoplasia type 1.
The multiple endocrine neoplasia type 1 (MEN1) is a rare syndrome characterized by the predisposition to developing multiple endocrine and non-endocrine tumors, typically characterized by the association between parathyroid gland hyperplasia or tumors, gastroenteropancreatic tumors and pituitary adenomas. The MEN1 gene is located on the long arm of chromosome 11 (11q13) and it encodes for the protein "menin". We here reported the case of a MEN1-patient, affected by primary hyperparathyroidism, insulinoma, pituitary non-hyperfunctioning adenoma and bilateral adrenal masses, carrying a novel heterozygous pathogenic variant (c.1252_1254delGACinsAT), located in exon 9 of MEN1 gene.


Diagnostic Utility of Computed Tomography Perfusion in the Telestroke Setting.
Definitive diagnosis of acute ischemic stroke is challenging, particularly in telestroke settings. Although the prognostic utility of CT perfusion (CTP) has been questioned, its diagnostic value remains under-appreciated, especially in cases without an easily visible intracranial occlusion. We assessed the diagnostic accuracy of routine CTP in the acute telestroke setting. Acute and follow-up data collected prospectively from consecutive suspected patients with stroke assessed by a state-wide telestroke service between March 2020 and August 2021 at 12 sites in Australia were analyzed. All patients in the final analysis had been assessed with multimodal CT, including CTP, which was post-processed with automated volumetric software. Diagnostic sensitivity and specificity were calculated for multimodal CT and each individual component (noncontrast CT [NCCT], CT angiogram [CTA], and CTP). Final diagnosis determined by consensus review of follow-up imaging and clinical data was used as the reference standard. During the study period, complete multimodal CT examination was obtained in 831 patients, 457 of whom were diagnosed with stroke. Diagnostic sensitivity for ischemic stroke increased by 19.5 percentage points when CTP was included with NCCT and CTA compared with NCCT and CTA alone (73.1% positive with NCCT+CTA+CTP [95% CI, 68.8-77.1] versus 53.6% positive with NCCT+CTA alone [95% CI, 48.9-58.3], P<0.001). No difference was observed between specificities of NCCT+CTA and NCCT+CTA+CTP (98.7% [95% CI, 98.5-100] versus 98.7% [95% CI, 96.9-99.6], P=0.13). Multimodal CT, including CTP, demonstrated the highest negative predictive value (75.0% [95% CI, 72.1-77.7]). Patients with stroke not evident on CTP had small volume infarcts on follow-up (1.2 mL, interquartile range 0.5-2.7mL). Acquisition of CTP as part of a telestroke imaging protocol permits definitive diagnosis of cerebral ischemia in 1 in 5 patients with normal NCCT and CTA.


The efficacy of combined chemotherapy and radiotherapy in advanced non-metastatic breast cancer.
Thirty-five patients with locally advanced (inoperable) breast cancer have been treated based on a regimen of chemotherapy-radiotherapy-chemotherapy. At the completion of all treatment a complete remission rate of 86% was achieved with acceptable toxicity. At a median follow-up of 24 months (range 4-60), relapse at the site of bulk disease occurred in 17% (10% isolated loco-regional relapse) and relapse at distant sites in 34%. The median relapse-free survival was 36 months and the median survival has not yet been reached. Following initial promising results in terms of loco-regional disease control in this group of high-risk patients, the protocol was extended to include 34 patients defined as having locally extensive disease. All patients in this subgroup had undergone a modified radical mastectomy and were categorized as (a) patients in whom the pre-operative clinical findings merited (in our opinion) inclusion in the category of locally advanced (inoperable) disease, (b) patients in whom the primary was operable but in whom extensive involvement of axillary nodes was found (greater than 10 nodes positive or greater than or equal to 70% nodes positive if less than 10 nodes found) and (c) patients without the above characteristics with a primary tumor greater than 8 cm. At a median follow-up of 23 months (range 4-48), loco-regional recurrence occurred in one patient (3%) but distant relapse occurred in 21%. Relapse-free and overall survival was not significantly different to that found in patients with locally advanced disease who did not undergo mastectomy.


MRI manifestations of central nervous system leukaemia and cytological analysis of the cerebrospinal fluid.
To investigate the magnetic resonance imaging (MRI) features and explore the value of MRI in the diagnosis of central nervous system leukaemia (CNSL). A retrospective study was performed in 68 patients with leukaemia who underwent cranial MRI between January 2020 and June 2022 at Institute of Hematology and Blood Diseases Hospital. A total of 33 patients fulfilled the requirements for inclusion. The findings showed that 87.9% patients exhibited neurological symptoms, and 23 patients showed abnormal MRI findings. No differences were observed between the MRI+ and MRI- groups in terms of age, sex, neurological symptoms, glucose in the cerebrospinal fluid (CSF), chloride in the CSF, abnormal cells detected using conventional cytology (CC), bone marrow status at the diagnosis of CNSL, signal intensity ratio, and mortality, except for protein concentration and the number of leukaemic cells detected using flow cytometry (FCM) in the CSF. Kaplan-Meier survival analysis in patients with leukaemia revealed no statistical differences in the median survival times between the MRI+ group and MRI- group. Cox regression analysis and multivariate analysis showed no significant difference in survival rate between the MRI+ and MRI- groups. Kappa consistency test shows weak diagnostic consistency between MRI and CC, and weak diagnostic inconsistency between MRI and FCM. MRI could serve as an important complementary tool to CC and FCM in the diagnosis of CNSL, especially in patients without leptomeningeal involvement.


Development and evaluation of a calibrator material for nucleic acid-based assays for diagnosing aspergillosis.
Twelve laboratories evaluated candidate material for an Aspergillus DNA calibrator. The DNA material was quantified using limiting-dilution analysis; the mean concentration was determined to be 1.73 × 10(10) units/ml. The calibrator can be used to standardize aspergillosis diagnostic assays which detect and/or quantify nucleic acid.


Considerations after intraoperative monitoring of somatosensory evoked potentials during carotid endarterectomy.
Somatosensory evoked potentials (SEPs) following median nerve stimulation were used to monitor cerebral function during 26 carotid endarterectomies. The patients with minor SEP variations had no neurological deficits on regaining consciousness while the one with more serious SEP variations had a transient deficit. The method thus seems useful in the early detection of ischemic brain impairment.


[Clinical and immunological aspects of Lichen ruber planus].
Clinical and histopathologic features of lesions in lichen r. planus are characteristic of inflammatory reaction: this it is possible some pondering on immunologic performance related to uncertain etiology of the disease.


Injectable adhesive hemostatic gel with tumor acidity neutralizer and neutrophil extracellular traps lyase for enhancing adoptive NK cell therapy prevents post-resection recurrence of hepatocellular carcinoma.
Post-resection recurrence remains an intractable problem in hepatocellular carcinoma (HCC) management. Natural killer (NK) cell infusion is considered as a promising cancer therapy, but acidic tumor microenvironment (TME) and neutrophil extracellular traps (NETs) greatly counteract its efficacy. Recently, polymer hydrogels have aroused much interest in tumor combination therapy, since they load and controllably release therapeutic agents with high bioavailability and low systemic toxicity. Therefore, a biocompatible hydrogel with tumor acidity neutralizer and NETs lyase may show promise for enhancing NK infusion to prevent post-resection HCC recurrence. Herein, a dual pH-responsive hydrogel with tumor acidity neutralizer (mesoporous bioactive glass nanoparticles) and NETs lyase (Deoxyribonuclease I, DNase I) is developed and used in combination with NK cell infusion for preventing post-resection HCC recurrence. The hydrogel can be injected to surgical margin and form an adhesive gel with a rapid hemostasis. Besides, it neutralizes tumor acidity to reduce tumor infiltration of immunosuppressive cells, and releases DNase I in a pH-responsive manner to degrade NETs. Moreover, this combination therapy significantly enhances NK cell infusion to combat post-surgical HCC recurrence without systemic toxicity. This study provides proof of concept that combination of NK cell adoptive therapy and hydrogel-based delivery system can successfully prevent post-resection HCC recurrence.


Regulation, competition and network evolution in aviation.
Our focus is the evolution of business strategies and network structure decisions in the commercial passenger aviation industry. The paper reviews the growth of hub-and-spoke networks as the dominant business model following deregulation in the latter part of the 20th century, followed by the emergence of value-based airlines as a global phenomenon at the end of the century. The paper highlights the link between airline business strategies and network structures, and examines the resulting competition between divergent network structure business models. In this context we discuss issues of market structure stability and the role played by competition policy.


Characteristics of electrocardiographic repolarization in acute myocardial infarction complicated by ventricular fibrillation.
Some de- and re-polarization patterns can reflect an increased risk of ventricular tachyarrhythmias. We studied whether some electrocardiographic (ECG) patterns are able to predict the development of ventricular fibrillation (VF) during acute myocardial infarction (MI). We compared the patterns of ST-T segment of 78 patients who developed VF during acute MI (patient with VF) vs 170 comparable patients with acute MI but with no VF complications. Of the VF group, 47 developed out-of-hospital VF and 31 developed VF after their admission to the hospital. A steep downsloping ST segment toward a negative T wave with or without a short, flat, or rising portion at the initial portion was observed in 69.2% of the 78 patients: 61.3% in patients with pre-VF and 74.5% in patients with post-VF, vs 9.4% of patients who did not develop VF (P < .0001). In 90.6% of the latter, a typical upward-concave or convex "ischemic" pattern of the ST segment was observed. Thus, the characteristic ST-T patterns were highly associated with VF with a specificity greater than 90%. A steep downsloping ST segment may characterize the ECGs of patients who develop VF during acute MI.


How does mitochondrial import machinery fine-tune mitophagy? Different paths and one destination.
Given their polyvalent roles, an intrinsic challenge that mitochondria face is the continuous exposure to various stressors including mitochondrial import defects, which leads to their dysfunction. Recent work has unveiled a presequence translocase-associated import motor (PAM) complex-dependent quality control pathway whereby misfolded proteins mitigate mitochondrial protein import and subsequently elicit mitophagy without the loss of mitochondrial membrane potential.


Safety and efficacy of ciprofloxacin in paediatric patients--review.
Like all fluoroquinolones, ciprofloxacin causes articular damage in juvenile animals. Consequently, this drug was not recommended for children or pregnant women. However, due to its antibacterial effectiveness and convenience of oral administration, ciprofloxacin is now increasingly used for the treatment of certain infectious conditions in children and adolescents aged less than 18 years. In this paper the published literature on this subject is reviewed. Up to now, data are available on more than 1,500 paediatric patients who were given ciprofloxacin, two-thirds of whom were suffering from acute infectious bronchopulmonary exacerbations of cystic fibrosis, mainly due to Pseudomonas aeruginosa. The effectiveness of oral ciprofloxacin for this indication compared well to that of standard intravenous combination regimens. The majority of the remaining published trials was conducted in children with multiresistant typhoid fever; the administration of ciprofloxacin was successful in up to 100% of the cases. The safety profile of ciprofloxacin in children and adolescents was very similar to that observed in adult patients. Adverse events were noted in 5-15%, with gastrointestinal, skin and central nervous system reactions being the most common. Reversible arthralgia occurred in 36 out of 1,113 patients with cystic fibrosis, and in no case could cartilage damage be demonstrated by radiographic procedures. Thus, publication data clearly suggest that the administration of ciprofloxacin to children is effective and safe, but there is a need for further prospective, well-controlled clinical trials.


A study of ionic composition and inorganic nutrient fluxes from rivers discharging into the Cilician Basin, Eastern Mediterranean.
Present water quality of the perennial rivers; Göksu, Lamas, Efrenk, Tarsus and Seyhan discharging into the Cilician Basin have been investigated. Monthly surface samples collected from three stations downstream of the rivers during the period of October 2004-May 2005 were analyzed to determine ionic composition (Cl(-), SO(2-)(4), N(O-)(3), PO(3-)(4), N(H+)(4), Ca(2+), Mg(2+), Na(+) and K(+)), in addition to measurements of pH, electrical conductivity, alkalinity and total hardness. The results have been compared with recommended water quality standards. Excluding Göksu, Seyhan and Efrenk river mouths, values for almost all measured parameters, except N(H+)(4), were found to be lower than the desirable limits. In particular, inorganic ammonium, phosphate and nitrate concentrations for Göksu and Seyhan Deltas were 10(1) or 10(2) orders of magnitude higher than the concentrations of the rest of the samples. Temporal variation in levels, primarily observed in PO(3-)(4), suggest the impact of agricultural fertilizers intensively used around Göksu and Seyhan Rivers. According to Turkish National Water Pollution Control Regulations, all rivers were found to be unpolluted with respect to their nitrate, chloride, sulfate and sodium ion contents, while they all could be considered as slightly polluted with respect to their phosphate contents. In contrast to nitrate and phosphate, ammonium exceeded the maximum permissible limits of water quality criteria in almost all samples. Among the sampled rivers, Tarsus River was better in water quality, with the lowest electrical conductivity, alkalinity, total hardness and nutrient concentration values. Calculated values of elemental inorganic N and P fluxes suggest a substantial increase in nitrogen loads within the last decade, compared to a significant decrease in phosphorus loads of the rivers during the same period.


Short strides to important findings: A short interval longitudinal study of sleep quality, psychological distress and microstructure changes to the uncinate fasciculus in early adolescents.
Developmental studies have shown adolescence is a period of ongoing white matter (WM) development, reduced sleep quality and the onset of many mental disorders. Findings indicate the WM development of the uncinate fasciculus (UF), a WM tract suggested to play a key role in mental disorders, continues throughout adolescence. While these studies provide valuable information, they are limited by long intervals between scans (1 to 4 years) leaving researchers and clinicians to infer what may be occurring between time-points. To allow inferences to be made regarding the impact that sleep quality may be having on WM development, longitudinal studies with much shorter between-scan intervals are required. The current study reports longitudinal data of self-reported sleep quality (PSQI), diffusion tensor imaging (DTI) measures of WM development and psychological distress (K10) for n = 64 early adolescents spanning the first twelve months (four time-points; Baseline, 4, 8, & 12 months) of the Longitudinal Adolescent Brain Study (LABS) study currently underway at the Thompson Institute. Generalised Estimating Equation analysis showed a significant relationship between sleep quality and psychological distress over the four time-points. Reduced radial diffusivity and increased fractional anisotropy of the UF is also reported with increasing age suggesting that ongoing myelination is occurring. Adding sleep quality to the model, however, negatively impacted this myelination process. These findings represent an important step towards elucidating how sleep, psychological distress and maturation of the UF may co-develop during early adolescence.


Hematopoietic recovery following autologous bone marrow transplantation: role of cryopreservation, number of cells infused and nature of high-dose chemotherapy.
Twenty-nine patients were treated with single or combined high-dose melphalan therapy followed by autologous bone marrow transplantation. Hematopoietic recovery from these treatments was studied. No correlation was found between the number of GM-CFC infused and the time required for hematopoietic recovery. It is suggested that this correlation is only demonstrable for low 'doses' of infused bone marrow cell and/or GM-CFCs. The role of bone marrow cell preservation techniques was examined and results were similar for fresh and cryopreserved bone marrow. The erythrocyte, lymphocyte and granulocyte levels of the patients reported here reached a normal or subnormal hematological steady state 3 months after autograft. Our results confirm the value of cryopreservation techniques. Hematopoietic recovery was short and of the same duration whether the patients were given single or combined high-dose melphalan before autologous bone marrow transplantation. These results also demonstrate the value of such transplantation in shortening the myelosuppression caused by high-dose chemotherapy.


Phonozen-mediated photodynamic therapy comparing two wavelengths in a mouse model of peritoneal carcinomatosis.
This study assessed the therapeutic efficacy of intraperitoneal photodynamic therapy (PDT) using photosensitizer activation at two different wavelengths, 405 and 664 nm, in a mouse model of peritoneal carcinomatosis. The dark and light cytotoxicity of chlorin e6-polyvinylpyrrolidone (Phonozen) were measured in vitro under 402 ± 14 and 670 ± 18 nm LED activation in bioluminescent human gastric cancer cells, MKN45-luc. Cell viability was measured at 6 h after irradiation using the PrestoBlue assay. Corresponding in vivo studies were performed in athymic nude mice by intraperitoneal injection of 1 × 106 MKN45-luc cells. PDT was performed 10 d after tumor induction and comprised intraperitoneal injection of Phonozen followed by light irradiation at 3 h, delivered by a diffusing-tip optical fiber placed in the peritoneal cavity and coupled to a 405 or 664 nm diode laser to deliver a total energy of 50 J (20 mice per cohort). Whole-body bioluminescence imaging was used to track the tumor burden after PDT out to 130 days, and 5 mice in each cohort were sacrificed at 4 h post treatment to measure the acute tumor necrosis. Photosensitizer dose-dependent photocytotoxicity was higher in vitro at 405 than 664 nm. In vivo, PDT reduced the tumor growth rate at both wavelengths, with no statistically significant difference. There was substantial necrosis, and median survival was significantly prolonged at both wavelengths compared with controls (46 and 46 vs. 34 days). Phonozen-mediated PDT results in significant cytotoxicity in vitro as well as tumor necrosis and prolonged survival in vivo following intraperitoneal light irradiation. Blue light was more photocytotoxic than red in vitro and had marginally higher efficacy in vivo.


Ideal treatment for total colonic Hirschsprung's disease.
Five children were treated for total colonic Hirschsprung's disease between 1982 and 1986. Three girls and two boys underwent total colectomy and straight ileoanal endorectal pull-through, with creation of a suprapelvic side-to-side anastomosis of 10 cm of cecum and ascending colon to ileum (Boley procedure). All patients have been followed for periods of greater than 1 year, and they have been free of any postoperative complication. Stool frequency on an unrestricted diet has been between one and five semiformed per day. Their growth and development have been excellent. An advantage of this procedure is excellent water absorption without the risks of mechanical problems encountered with a variety of pelvic pouch creations in the young growing child.


Oral colorectal cleansing preparations in adults.
Bowel preparation has been a much-debated issue for both colonoscopy and for colorectal surgery. While bowel preparation for colonoscopy is clearly mandatory for optimal intraluminal visualization, bowel preparation for surgery has recently been challenged. This review evaluates oral bowel preparation, based on evidence in the literature, in order to provide a practical guide for physicians and practitioners about oral bowel cleansing preparations in current use for both colonoscopy and for colorectal surgery.A MEDLINE search, limited to publications in English language, was done through Ovid including articles published from 1966 to 2007 about bowel preparation using terms 'pre-operative care' and 'colonoscopy' or 'surgical procedure' associated with 'polyethylene glycol' and 'sodium phosphate'. The references lists from the identified articles were also included in the review. No bowel preparation method meets the ideal criteria for bowel cleansing prior to colonoscopy. However, polyethylene glycol-electrolyte lavage solution (PEG-ELS) and sodium phosphate are the most commonly used bowel preparations before colonoscopy and colon surgery. Both preparations are safely used and effective; however, some precautions should be considered, particularly with sodium phosphate. In addition, the efficacy of low-volume PEG-ELS can be improved by the addition of preparation adjuncts. Timing and dose are important considerations regardless of the method used. Mechanical bowel preparation for surgery has been questioned, and shown to have no extra benefits and possibly the association with increased morbidity. Regardless of the evidence, there are many randomized controlled trials showing the lack of benefit of mechanical bowel preparation.


Metal complexes of xanthine and its derivatives: Synthesis and biological activity.
Xanthine and its derivatives are considered an important class of N-heterocyclic purine compounds that have gained significant importance in medicinal chemistry. N-heterocyclic carbene (NHC) and N-coordinated metal complexes of xanthine and its derivatives have revealed a range of new possibilities for their use as therapeutic agents in addition to their established catalytic behavior. The metal complexes of xanthine and its derivatives have been designed and synthesized for the exploration of their potential therapeutic applications. These metal complexes based on the xanthine scaffold exhibited various potential medicinal applications including anticancer, antibacterial, and antileishmanial activity. The metal complexes of xanthine and its derivatives shall pave the way for the rational design and development of new therapeutic agents. In the present comprehensive review, we highlighted the recent advancements in the synthesis and medicinal applications of metal complexes based on N-heterocyclic carbene (NHC) derived from xanthine scaffolds.


The control of potassium concentration in the cerebrospinal fluid and brain interstitial fluid of developing rats.
1. In situ measurements of plasma, cerebrospinal fluid (CSF) and brain interstitial fluid (ISF) K+ concentrations have been made in anaesthetized rats aged between 19 days gestation and 30 days after birth using K+-selective micro-electrodes. 2. Under control conditions, plasma, CSF and ISF [K+] did not vary significantly with age, the over-all mean concentrations being 3.8, 3.1 and 3.2 mM respectively. The CSF and ISF [K+] were significantly lower than plasma [K+] at all ages. 3. It is concluded that young rats, from the age of 19 days gestation, can normally maintain plasma-to-CSF and plasma-to-ISF gradients similar to those in the adult, presumably by action of the blood-CSF and blood-brain barriers. 4. During acute plasma hyperkalaemia there was very little regulation of CSF [K+] at 21 days gestation, but after birth there was a gradual improvement in CSF K+ homeostasis until by 30 days after birth a normal CSF [K+] could be maintained. 4. There was no regulation of ISF [K+] during hyperkalaemia at 21 days gestation, although after birth there was a rapid improvement in ISF K+ homeostasis. 1-day-old neonates were able to maintain a normal forebrain ISF [K+] during hyperkalaemia. 6. It is concluded that the onset of both CSF and ISF K+ homeostasis takes place at around birth in rats. However, K+ homeostasis matures more rapidly in the ISF than in the CSF. This suggests that, at least in the neonatal period, the CSF is not essential for ISF [K+] regulation.


Pulmonary alveolar microlithiasis.
Three cases of pulmonary alveolar microlithiasis are reported at the symptom-free stage of this condition. Two were siblings.


Sex-Specific Considerations in the Presentation, Diagnosis, and Management of Ischemic Heart Disease: JACC Focus Seminar 2/7.
There are sex-related differences in the epidemiology, presentation, diagnostic testing, and management of ischemic heart disease in women compared with men. The adjusted morbidity and mortality are persistently higher, particularly in younger women and Blacks. Women have more angina but less obstructive coronary artery disease, which affects delays in presentation and diagnosis and testing accuracy. The nonbiological factors play a significant role in access to care, ischemic heart disease management, and guideline adherence. Future research focus includes sex-specific outcomes, characterization of the biological differences, and implementation science around quality of clinical care.


Changes in rates and severity of compensation claims for asthma due to diisocyanates: a possible effect of medical surveillance measures.
A medical surveillance programme was introduced into Ontario for workers exposed to diisocyanates in 1983, but no mandated surveillance programme is in effect in this province for other occupational respiratory sensitisers. This study assesses changes in incidence and severity of compensated claims for occupational asthma (OA) due to diisocyanates compared with other causes, which have occurred since the introduction of this surveillance programme. New claims for OA compensated by the Ontario Workers' Compensation Board (WCB) between 1980 and 1993 were retrospectively reviewed. Linkage was made between these data and an Ontario Ministry of Health database to assess hospital admissions for asthma from the date of onset of OA until the end of 1996. Numbers of claims for OA induced by diisocyanates ranged from 9-15/year in 1980-83, increased up to 55-58 claims/year in 1988-90, then fell to 19-20 claims/year by 1992-93. By contrast yearly numbers of claims for OA due to other causes increased up to 1985-87 then remained relatively stable. Duration of symptoms for OA induced by diisocyanates was shorter than for other claims and there were fewer hospital admissions among those with OA induced by diisocyanates than among those with OA induced by other causes. Occupational asthma from all causes was diagnosed earlier in claims for 1987-93 compared with 1980-86, and indicators of severity of asthma were also milder in accepted claims during 1987-93 than in earlier claims. Although engineering and industrial hygiene measures may have contributed to these changes, our findings are also consistent with a beneficial contribution from the medical surveillance programme for workers exposed to diisocyanates.


Association between sleep quality and inflammatory complement components in collegiate males.
An accumulating amount of evidence has linked humoral mediators of inflammation with sleep measures. Nevertheless, important details of this association, in particular the role of the complement components in the context of chronic sleep attributes, have remained largely uncharacterized. Fifty university students (age, 23.3 ± 3.8 years; BMI, 23.7 ± 2.9 kg/m(2)) completed the study. Four dichotomized sleep measures assessed by the Pittsburgh Sleep Quality Index (PSQI) were used in association analysis using binary logistic regression with complement component 3, 4, and complement factor I (CFI). The sleep measures were defined as sleep quality (good sleep/poor sleep; PSQI ≤5/PSQI >5), bedtime (early/late; before 00:00 h/after 0:00 h), sleep duration (short/normal ≤6 h/>6 h), and sleep onset latency (normal/disturbed; 0-1 score/2-3 score on the PSQI component of sleep latency). The complement component 4 was associated with sleep quality (unadjusted, OR = 1.025, p < 0.05; adjusted for age, OR = 1.025, p < 0.05; adjusted for BMI, OR = 1.027, p < 0.05) and sleep duration (unadjusted, OR = 1.041, p < 0.01; adjusted for age, OR = 1.041, p < 0.01; adjusted for BMI, OR = 1.046, p < 0.01). CFI was associated with bedtime (unadjusted, OR = 0.737, p < 0.01; adjusted for age, OR = 0.717, p < 0.01; adjusted for BMI, OR = 0.677, p < 0.01) and with sleep duration (unadjusted, OR = 0.796, p < 0.05; adjusted for age, OR = 0.796, p < 0.05). The findings indicate the importance of the role of complement components in the dynamics of sleep. Therefore, sleep should be assessed in conditions where complement components are affected.


Revisiting variable-foreperiod effects: evaluating the repetition priming account.
A warning signal preceding an imperative stimulus by a certain foreperiod can accelerate responses (foreperiod effect). When foreperiod is varied within a block, the foreperiod effect on reaction time (RT) is modulated by both the current and the prior foreperiods. Using a non-aging foreperiod distribution in a simple-reaction task, Capizzi et al. (Cognition, 134, 39-49, 2015) found equal sequential effects for different foreperiods, which they credited to repetition priming. The multiple-trace theory of Los et al. (Frontiers in Psychology, 5, Article 1058, 2014) attributes the slope of the foreperiod-RT function to the foreperiod distribution. We conducted three experiments that examined these predicted relations. Experiment 1 tested Capizzi et al.'s prediction in a choice-reaction task and found an increasing foreperiod-RT function but a larger sequential effect at the shorter foreperiod. Experiment 2 used two distinct short foreperiods with the same foreperiod distribution and found a decreasing foreperiod-RT function. By increasing the difference between the foreperiods used in Experiment 2, Experiment 3 yielded a larger sequential effect overall. The experiments provide evidence that, with a non-aging foreperiod distribution, the variable-foreperiod paradigm yields unequal sequential-effect sizes at the different foreperiods, consistent with the multiple-trace theory but contrary to Capizzi et al.'s repetition-priming account. The foreperiod-RT functions are similar to those of the fixed-foreperiod paradigm, which is not predicted by the multiple trace theory.


Review: Exploration of placentation from human beings to ocean-living species.
This review covers four topics. 1) Placental pathology in Himalayan mountain people. To determine morphological changes of the placenta at high altitude, pathological examination was made of 1000 Himalayan placentas obtained in Nepal and Tibet and the results compared with Japanese placentas delivered at sea level. Characteristic findings in the placental villi of the Himalayan group included high incidences of villous chorangiosis and chorangioma. These processes were clarified by ultrastructural observation. 2) Placentation in Sirenians. The giant Takikawa sea cow, which lived 5 million years ago, was discovered on Hokkaido, Japan. It was an ancestor of the dugong as well as the manatees. Sirenia, the sea cow group, shares a common ancestor with Proboscidea, the elephants, even though they now inhabit quite different environments. A comparison was made of their zonary endothelial type of placentation. 3) Placentation in sharks and rays. The remarkable placentation of hammerhead sharks and manta rays is described. 4) Placentation in the Antarctic minke whale. Placental tissue samples of this whale were obtained from the Japan Institute of Cetacean Research. In an ultrastructural study of the utero-placental junction, microfilamental processes of the allantochorionic zone and crypt formation were visualized.


Multimodal imaging of sarcoid choroidal granulomas.
Enhanced-depth imaging optical coherence tomography (EDI-OCT) provides high-resolution imaging of the choroid. Herein, we report multimodal imaging, including EDI-OCT, of a case of sarcoid choroidal granulomas. A 63-year-old female with biopsy-supported sarcoidosis presented with unilateral multifocal choroidal granulomas. Enhanced-depth imaging optical coherence tomography (EDI-OCT) demonstrated a homogenous hyporeflective choroidal lesion with choriocapillaris thinning and sparing of the surrounding choroid. The patient was started on oral steroids with a weekly taper schedule. Within 5 weeks, the choroidal lesions had clinically resolved with return of normal-appearing choroidal architecture on EDI-OCT. Indocyanine green angiography, however, demonstrated hypofluoresence at the sites of choroidal granulomas 11 months after the clinical resolution, suggesting a longstanding choroidal perfusion deficit undetected by OCT. Choroidal imaging via EDI-OCT provides detailed morphologic information of sarcoid granulomas and can accurately demonstrate structural resolution of the lesions.


Microarray expression analysis in delayed cardioprotection: the effect of exercise, AICAR, or metformin and the possible role of AMP-activated protein kinase (AMPK).
AMP-activated protein kinase (AMPK) is an enzyme which may be involved in cardioprotective mechanisms in the ischemic heart. Exercise, AICAR, and metformin, all known activators of AMPK, induce delayed cardioprotection which protects the heart against ischemia-reperfusion injury. The objective was to determine the effect of exercise, AICAR, and metformin on gene expression profile and to demonstrate possible interactions in different genes and functions. Rats were divided into either an exercise, AICAR, metformin, or control group. 3, 12, and 24 h after either a single bout of exercise training, a single injection of AICAR or a single dose of metformin, hearts were removed and gene expression profiles were analyzed in tissue from the left ventricle using Affymetrix gene chip probe arrays. Ingenuity Pathway Analysis (IPA) tool was used to analyze the regulated genes for relevant functions and diseases. Each gene chip identified up to 30,000 different probesets of which Ingenuity identified approximately up to 12,000 genes. A total of 147, 304, and 114 different genes in the left ventricle whose expressions were altered >2.0-fold were identified in the exercise, AICAR, and metformin group, respectively. Seventy eight different genes were overlapping the exercise and AICAR group at 24 h. Ingenuity identified six overlapping genes between the exercise, AICAR, and metformin groups including NR4A3, TNFRSF12A, HBB, PENK, PAP, and MAP4K4. IPA software revealed an overabundance of focus molecules in all three intervention groups involving functions related to cell death, cellular growth and proliferation, gene expression and cancer. Exercise, AICAR, and metformin regulate several genes in the rat myocardium with the majority of overlapping genes observed in the exercise and AICAR group. Changes in gene programming mainly involved inflammatory and opioid systems recognized as cardioprotective pathways. Some of these genes may represent possible candidate genes involved in the molecular mechanisms of AMPK-induced delayed PC.


Impaired Glucose Metabolism, Anti-Diabetes Medications, and Risk of Thyroid Cancer.
The prevalence of obesity is progressively increasing along with the potential high risk for insulin resistance and development of type 2 diabetes mellitus. Obesity is associated with increased risk of many malignancies, and hyperinsulinemia has been proposed to be a link between obesity and cancer development. The incidence of thyroid cancer is also increasing, making this cancer the most common endocrine malignancy. There is some evidence of associations between obesity, insulin resistance and/or diabetes with thyroid proliferative disorders, including thyroid cancer. However, the etiology of such an association has not been fully elucidated. The goal of the present work is to review the current knowledge on crosstalk between thyroid and glucose metabolic pathways and the effects of obesity, insulin resistance, diabetes, and anti-hyperglycemic medications on the risk of thyroid cancer development.


Stimulation of liver functions in hierarchical co-culture of bone marrow cells and hepatocytes.
A hierarchial co-culture, in which rat hepatocytes and non-parenchymal liver cells (NPLCs) were separated by a collagen layer and which was designed to mimic the in vivo microenvironment, was carried out with the aim of developing a module for bio-artificial liver support. Compared with a monolayer co-culture and hepatocytes cultured alone in a monolayer, higher urea synthesis activity was maintained for 6 d in the hierarchical co-culture. When a rat hepatoma cell line H4-II-E-C3, which retains the induction of tyrosine aminotransferase (TAT), was co-cultured in a monolayer with NPLCs, dose-dependent stimulation of TAT induction was observed. In a hierarchical co-culture, NPLCs further stimulated TAT induction in H4-II-E-C3 cells. Since peritoneal macrophages could stimulate TAT induction in hepatocytes in both monolayer and hierarchical co-cultures, bone marrow cells, which can proliferate and differentiate into macrophages in vitro, were investigated as a possible substitute for NPLCs. Bone marrow cells isolated from rat femurs were cultivated in the presence of IL-3 and macrophage colony-stimulating factor (M-CSF), and co-cultured with hepatocytes. Urea synthesis and TAT induction of hepatocytes were stimulated in the co-culture. The co-culture of bone marrow and H4-II-E-C3 cells, both of which have proliferation ability in vitro, was also shown to be effective in stimulating liver functions. The hierarchical configuration, in which two cell types can communicate with the soluble factor(s) through a collagen layer, was found to be more effective than a monolayer in long-term co-culture.


Effect analysis of a virtual simulation experimental platform in teaching pulpotomy.
The experimental teaching of pediatric dentistry is a bridge between theoretical study and clinical practice, and virtual simulation technology provides a new method of instruction. We built an experimental teaching platform using virtual simulation technology for vital pulpotomy that includes learning and examination modes. A total of 199 students majoring in stomatology in the fourth year at Sun Yat-Sen University were randomly divided into a control group (conventional teaching mode) and an experimental group (virtual simulation experimental teaching model). The teaching effect was evaluated by theoretical and experimental examination. We found that both the theoretical and experimental scores of the experimental group were higher than those of the control group, and the theoretical scores of the experimental group after exposure to the virtual simulation experimental teaching platform were also higher than those before the class, with significant differences (P < 0.05). Feedback from the experimental group after the class indicated that the platform reinforced their theoretical knowledge and greatly improved their mastery of operational skills. The application of a virtual simulation experimental teaching platform can effectively improve the teaching of pulpotomy.


Nanotechnology in hyperthermia cancer therapy: From fundamental principles to advanced applications.
In this work, we present an in-depth review of recent breakthroughs in nanotechnology for hyperthermia cancer therapy. Conventional hyperthermia methods do not thermally discriminate between the target and the surrounding normal tissues, and this non-selective tissue heating can lead to serious side effects. Nanotechnology is expected to have great potential to revolutionize current hyperthermia methods. To find an appropriate place in cancer treatment, all nanotechnology-based hyperthermia methods and their risks/benefits must be thoroughly understood. In this review paper, we extensively examine and compare four modern nanotechnology-based hyperthermia methods. For each method, the possible physical mechanisms of heat generation and enhancement due to the presence of nanoparticles are explained, and recent in vitro and in vivo studies are reviewed and discussed. Nano-Photo-Thermal Therapy (NPTT) and Nano-Magnetic Hyperthermia (NMH) are reviewed as the two first exciting approaches for targeted hyperthermia. The third novel hyperthermia method, Nano-Radio-Frequency Ablation (NaRFA) is discussed together with the thermal effects of novel nanoparticles in the presence of radiofrequency waves. Finally, Nano-Ultrasound Hyperthermia (NUH) is described as the fourth modern method for cancer hyperthermia.


Generation of foxn1/Casper Mutant Zebrafish for Allograft and Xenograft of Normal and Malignant Cells.
Cell transplantation into immunodeficient recipients is a widely used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a foxn1/Casper mutant zebrafish that is transparent and exhibits T cell deficiency. By employing the line for hematopoietic stem cell (HSC) transplantation (HSCT), we could achieve nonconditioned transplantation. Meanwhile, we found that fetal HSCs from 3 days post fertilization zebrafish embryos produce a better transplant outcome in foxn1/Casper mutants, compared with adult HSCs. In addition to HSCT, the foxn1/Casper mutant is feasible for allografts of myelodysplastic syndrome-like and muscle cells, as well as xenografts of medaka muscle cells. In summary, foxn1/Casper mutants permit the nonconditioned engraftment of multiple cell types and visualized characterization of transplanted cells in vivo.


Influence of decreased intracellular glutathione level on the mutagenicity of patulin in cultured mouse lymphoma cells.
The mutagenicity of the mycotoxin patulin was assessed by the thymidine kinase mutation assay, which is based on point mutations and deletions. Patulin was mutagenic in cultured mouse lymphoma cells and the mutagenicity was significantly increased in cells pretreated with buthionine sulfoximine, which reduces intracellular glutathione levels.


Fluorescent location of lung tumour cells.
Cells were collected on glass slides by touching tumour surfaces (A) and normal regions (B) of the lung. The slides were stained with a nuclear stain and a fluorescent probe for a tumour associated cell surface protein. The (B) slides from the normal regions lacked fluorescent epithelial cells. The tumour slides (A) contained typical tumour cells and dyskaryotic cells which exhibited cell surface fluorescence.


Control of grip force when tilting objects: effect of curvature of grasped surfaces and applied tangential torque.
When we manipulate objects in everyday tasks, there are variations in the shape of the grasped surfaces, and the loads that potentially destabilize the grasp include time-varying linear forces and torques tangential to the grasped surfaces. Previous studies of the control of fingertip forces for grasp stability have dealt principally with flat grip surfaces and linear force loads. Here, we studied the regulation of grip force with changes in curvature of grasped surfaces and changes in tangential torque applied by the index finger and thumb when humans lifted an object and rotated it about the horizontal grip axis through an angle of 65 degrees. The curvatures of the matched pair of spherical surfaces varied from -50 m-1 (concave with radius 20 mm) to 200 m-1 (convex with radius 5 mm). The applied tangential torque at the orientation of 65 degrees was varied sixfold. Regardless of the values of curvature and end torque, grip force and tangential torque were coordinated, increasing in parallel throughout the tilt with an approximately linear relationship; the slope of the line increased progressively with increasing surface curvature. This parametric scaling of grip force was directly related to the minimum grip force required to prevent rotational slip, resulting in an adequate safety margin against slip in all cases. We conclude that surface curvature parametrically influences grip force regulation when the digits are exposed to torsional loads. Furthermore, the sensorimotor programs that control the grip force apparently predict the effect of the total load comprising linear forces and tangential torques.


The Ins and Outs of TAPBPR.
Peptide presentation on MHC class I molecules (MHC-I) is central to mounting effective antiviral and antitumoral immune responses. The tapasin-related protein TAPBPR is an MHC-I peptide editor which shapes the final peptide repertoire displayed on the cell surface. Here, we review recent findings which further elucidate the mechanisms by which TAPBPR performs peptide editing on a molecular level, and how glycosylation on MHC-I influences the interaction with TAPBPR and the peptide loading complex. We also explore how the function of TAPBPR can be utilized to promote exogenous peptide loading directly onto plasma-membrane expressed MHC-I. This has led to the development of new assays to investigate TAPBPR-mediated peptide editing and uncovered translational opportunities of utilizing TAPBPR to treat human disease.


PEG-mediated hybrid hemostatic gauze with in-situ growth and tightly-bound mesoporous silicon.
Pre-hospital control of bleeding is critical to save lives, however the development of hemostatic agents with efficient and safe performance is still a challenge. In this study, a hybrid hemostatic gauze (MG-PEG) with in-situ growth and tightly bound mesoporous silicon (MSN) was prepared by template method for hemorrhage control. This material integrated meso-porosity, blood coagulation and stability into flexible gauze fiber. The PEG in MG-PEG was not only used as template for the in-suit MSN growth, but also acted as joint connection between the gauze fibers and MSN. The MSN particles were firmly bound to the surface of gauze fibers with extremely low leakage after 3 min of sonication and displayed a comparable coagulant activity to untreated sample. The results of animal experiments confirmed that MG-PEG possessed superior hemostatic performance over silicates-based inorganic hemostasis-Combat Gauze, in terms of higher coagulant activity (in vivo clotting time <200 s), minimized loss of active components (liquids OD was only 3 % of CG), well biocompatibility (hemolysis ratio < 5 %, no cytotoxicity) and wider indications range for practical application.


Endoscopic management of uterine fibroids.
Uterine fibroids are the most common benign tumours of the uterus. Management depends on the symptoms, location and size of the fibroids, and the patient's desire to conceive. Surgical management of uterine fibroids has changed from laparotomy to minimally invasive surgery. Uterine fibroids are usually asymptomatic and do not require treatment. Laparoscopic myomectomy is the best treatment option for symptomatic women with uterine fibroids who wish to maintain their fertility. The authors' criteria for laparoscopic myomectomy are a fibroid of <15 cm in size, and no more than three fibroids with a size of 5 cm. Compared with laparotomy, laparoscopic myomectomy has the advantages of small incisions, short hospital stay, less postoperative pain, rapid recovery and good assessment of other abdominal organs. Due to the concern of decreased ovarian reserve, uterine artery embolization is not advisable for these women. In addition, it is associated with high risks of miscarriages, preterm delivery and postpartum bleeding. Laparoscopic myolysis causes severe adhesion formation. Women with submucous fibroids receive myomectomy by hysteroscopy. For women who have completed their family, laparoscopic hysterectomy could be performed. Most fibroids can be managed endoscopically either by laparoscopy or hysteroscopy. Surgeon expertise, especially laparoscopic suturing, is crucial. Laparoscopic myomectomy is still the best treatment option for symptomatic women with uterine fibroids who wish to maintain their fertility. Hysteroscopic myomectomy is an established surgical procedure for women with excessive uterine bleeding, infertility or repeated miscarriages.


The relationship among restless legs syndrome (Willis-Ekbom Disease), hypertension, cardiovascular disease, and cerebrovascular disease.
Untreated sleep disorders may contribute to secondary causes of uncontrolled hypertension, cardiovascular disease (CVD), and stroke. Restless legs syndrome, or Willis-Ekbom Disease (RLS/WED), is a common sensorimotor disorder with a circadian rhythmicity defined by an uncontrollable urge to move the legs that worsens during periods of inactivity or at rest in the evening, often resulting in sleep disruptions. Sleep disorders such as insomnia and obstructive sleep apnea (OSA) are established risk factors for increased risk of hypertension and vascular diseases. This literature review outlines the lessons learned from studies demonstrating insomnia and OSA as risk factors for hypertension and vascular diseases to support the epidemiologic and physiologic evidence suggesting a similar increase in hypertension and vascular disease risk due to RLS. Understanding the relationships between RLS and hypertension, CVD, and stroke has important implications for reducing the risks associated with these diseases.


[Effect of strophanthin and cytochrome C on myocardial contraction and the incidence of shock and ventricular fibrillation in experimental myocardial infarct].
High ligation of the interventricular artery caused ventricular fibrillation in the first 2--4 minutes in 20% of cats. In the remaining animals myocardial contractility diminished to half its initial value. After that, contractility increased gradually. In cardiosclerosis myocardial contractility reduced by 20--30%. Ligation of the interventricular artery on the background of cardiosclerosis induced cardiogenic shock in half of the animals. Cytochrome C does not reduce the diminution of myocardial contractility after ligation and has a marked antifibrillatory effect. Strophantin does not affect the diminution of contractility of a healthy myocardium but reduces the decrease in contractility of a sclerosed myocardium and also promotes the development of ventricular fibrillation following ligation of the interventricular artery.


Radial Wicking of Biological Fluids in Paper.
In this study, we analyze stain growth kinetics from droplets of biological fluids such as blood, plasma, and protein solutions on paper both experimentally and numerically. The primary difference of biological fluids from a simple fluid is a significant wetting/dewetting hysteresis in paper. This becomes important in later stages of droplet wicking, after the droplet has been completely absorbed into paper. This is shown by anomalous power dependence of area with time in the later stages of radial wicking. At early stages, current numerical wicking models can predict stain growth of biological fluids. However, at later stages, the introduction of hysteresis complicates modeling significantly. We show that the cause of the observed hysteresis is due to contact angle effects and that this is the dominant mechanism that leads to the anomalous stain growth kinetics measured uniquely in biological fluids. Results presented will streamline the design process of paper-based diagnostics, allowing a modeling approach instead of a trial and error method.


Androgen regulation of an antigen expressed in regions of developing brainstem monoaminergic cell groups.
To examine the regulation of brain development by gonadal steroids we are using monoclonal antibodies obtained with neonatal rat brain homogenates as immunogens. One antibody, 3D10, binds selectively in regions of identified monoaminergic neuronal cell groups in the brainstem. Characterization of 3D10 immunoreactivity was carried out using free-floating 50 microns tissue sections from perinatal rats. The strongest reactivity was seen on postnatal day 1 in the locus coeruleus (A6) and in the regions of the A4 (dorsal) and A5 (ventral) noradrenergic cell groups. Immunoreactivity was also seen in the raphe magnus, pallidus and obscuris. Faint immunoreactivity was seen in the more rostral and median raphe nuclei and in the midbrain dopaminergic cell groups of the ventral tegmentum and substantia nigra. The number of 3D10 immunoreactive cells in all groups was greatest perinatally and decreased with age. The number of immunoreactive cells in the A4 region of males decreased at an earlier age than in females. Female offspring treated prenatally with testosterone propionate also had fewer immunoreactive cells in the A4 region at earlier ages, approximating the time course in the male. Thus, changes in the number of 3D10 immunoreactive cells reveal hormonal control of the time course of a developmental process in a selective population of neurons.


Pyramidamycins A-D and 3-hydroxyquinoline-2-carboxamide; cytotoxic benzamides from Streptomyces sp. DGC1.
Four new benzamides, pyramidamycins A-D (2-5) along with the new natural 3-hydroxyquinoline-2-carboxamide (6) were isolated from the crude extract of Streptomyces sp. DGC1. Additionally, five other known compounds, namely 2-aminobenzamide (anthranilamide) (1), 4',7-dihydroxyisoflavanone (7), 2'-deoxy-thymidine, 2'-deoxy-uridine and adenosine were also isolated and identified. The structures of the new compounds 2-6 were elucidated by 1D and 2D NMR studies along with HR MS analyses. The isolated compounds 1-6 contained the same amide side chain. The isolated compounds 1-7 were biologically evaluated in comparison with landomycin A against a prostate cancer cell line (PC3) and non-small cell lung cancer cell line (H460) for 48 h and against several bacterial strains. Pyramidamycin C (4) was the most active compound against both PC3 and H460 cell lines (GI(50)=2.473 and 7.339 μM, respectively). Benzamides (1-3) demonstrated inhibitory activity against Kocuria rosea B-1106 (a diameter halo of 13±2 mm for 1; 10±2 mm for 2 and 3). Compound 6 was slightly active against both Escherichia coli DH5α and Micrococcus luteus NRRL B-2618 (diameter halos 8±2 and 9±2 mm, respectively). Taxonomically, the amplified 500-bp 16 S rRNA fragment of the Streptomyces sp. DGC1 had 99% identity (BLAST search) to the 16S rRNA gene of Streptomyces atrovirens strain NRRL B-16357.


Applicability of continuous-flow fast atom bombardment liquid chromatography-mass spectrometry in bioanalysis. Dextromethorphan in plasma.
Continuous-flow fast atom bombardment (CF-FAB) is an interface for combined liquid chromatography-mass spectrometry using FAB as the ionization method. The applicability of CF-FAB for quantitative bioanalysis was studied for a model compound, dextromethorphan, in plasma samples using conventional high-performance liquid chromatography. The flow-rate reduction was achieved either by splitting or by the phase-system switching approach. The features of both systems are discussed.


Repair of lacerated intrapericardial inferior vena cava after cardiac massage.
We successfully undertook surgical treatment of intrapericardial laceration of the inferior vena cava caused by external cardiac massage in a patient with acute coronary syndrome. Injury to the inferior vena cava without blunt trauma is very rare, and diagnostic imaging does not show it clearly, making it difficult to diagnose. Rapid and accurate judgment and management are necessary, because the mortality due to this injury is very high.


Draft Genome Sequence of Agreia bicolorata Strain AC-1804, a Producer of Large Amounts of Carotenoid Pigments, Isolated from Narrow Reed Grass Infected by the Phytoparasitic Nematode.
Here, we report the draft genome sequence of Agreia bicolorata strain AC-1804, isolated from narrow reed grass galls induced by a plant-parasitic nematode which is able to produce large amounts of carotenoid pigments. The draft genome sequence of 3,919,485 bp provides a resource for carotenoid pathway research.


The effect of changes in lower limb pain on the rate of progression of locomotor disability in middle and old age: evidence from the NorStOP cohort with 6-year follow-up.
Locomotor disability (LMD) is common at older ages, and can lead to other significant disability and mortality. Prevalent pain has been shown to be associated with LMD. This article aimed to assess the association between changes in lower limb pain status (ascertained from a manikin) and changes in the level of self-reported LMD in a sample of UK adults age ≥ 50years, over a 6-year period (data collected at 3-year intervals). There was an average increase in the level of LMD over 6 years. Reports of an onset of lower limb pain were associated with a relative increase in LMD, independently of sociodemographic factors and the onset of selected comorbid diseases. A dose-response relationship was observed between the onset of multiple lower limb joint involvement and more frequent or intense pain and larger increases in LMD. Becoming free from lower limb pain was associated with a relative decrease in LMD, but did not return LMD scores to the level of those who had remained pain-free throughout. This is consistent with a cumulative effect on LMD of recurrent episodes of pain. Lower limb pain may be a key target for prevention and rehabilitation to reduce years lived with disability in later life.


Is heart failure with preserved systolic function an overlooked enigma?
Heart failure with preserved systolic function, or diastolic heart failure, represents the neglected other half of the pandemic of heart failure. Unlike previously held beliefs, diastolic heart failure carries with it the same connotation of morbidity and mortality as systolic heart failure, particularly in the elderly. Due to lack of standards in application of the diagnosis of diastolic heart failure, studies are difficult to interpret due to heterogeneity in the clinical criteria applied to the patient enrollment. It is imperative that preventive efforts be implemented in high-risk groups, and screening measures with newer biomarkers be considered for identifying underlying structural heart disease in order to employ preventive therapy early in the course of illness. No evidence-based therapeutic strategy to reduce morbidity and mortality has been established, even after the diagnosis of diastolic heart failure is manifest. Current therapy targets lusitropic abnormalities in the realm of impaired relaxation, abnormal diastolic compliance, avoidance of tachycardia, and restoration of atrial booster pump function. Outcomes-based placebo-controlled clinical trials are currently underway to define appropriate therapeutic strategies in diastolic heart failure.


1-Phenyl-3-(2-thiazolyl)-2-thiourea inhibits melanogenesis via a dual-action mechanism.
1-Phenyl-3-(2-thiazolyl)-2-thiourea (PTTU) is a well-characterized dopamine β-hydroxylase inhibitor that prevents 6-hydroxydopamine-induced degenerative neuronal disease. However, the effect of PTTU on melanogenesis has not been reported. In this study, we examined the effect of PTTU on melanogenesis and studied its mechanism of action. We found that PTTU decreased melanin biosynthesis in a dose-dependent manner in normal human epidermal melanocytes (NHEMs). PTTU also inhibited tyrosinase catalytic activity in NHEMs. Moreover, PTTU treatment led to reduced protein levels of tyrosinase in NHEMs, while the protein levels of tyrosinase-related protein-1, tyrosinase-related protein-2, and microphthalmia-associated transcription factor were not affected. However, PTTU treatment did not affect the mRNA expression of tyrosinase. We found that PTTU-accelerated tyrosinase degradation via the ubiquitin-dependent proteasome pathway. In summary, we found that PTTU decreased melanin biosynthesis by decreasing the enzymatic activity and stability of tyrosinase. Our results indicate that PTTU could be used as a depigmentation agent for hyperpigmentation disorder.


Systems biology approaches to study the molecular effects of caloric restriction and polyphenols on aging processes.
Worldwide population is aging, and a large part of the growing burden associated with age-related conditions can be prevented or delayed by promoting healthy lifestyle and normalizing metabolic risk factors. However, a better understanding of the pleiotropic effects of available nutritional interventions and their influence on the multiple processes affected by aging is needed to select and implement the most promising actions. New methods of analysis are required to tackle the complexity of the interplay between nutritional interventions and aging, and to make sense of a growing amount of -omics data being produced for this purpose. In this paper, we review how various systems biology-inspired methods of analysis can be applied to the study of the molecular basis of nutritional interventions promoting healthy aging, notably caloric restriction and polyphenol supplementation. We specifically focus on the role that different versions of network analysis, molecular signature identification and multi-omics data integration are playing in elucidating the complex mechanisms underlying nutrition, and provide some examples on how to extend the application of these methods using available microarray data.


Participatory Design, Project Clients, and Healthcare User Groups.
This study is the third in a series of investigations that explored the role of project user groups and how they impact on the design of a healthcare facility. Previous studies focused on a wide range of users, whereas this study sought the views of project clients. The "project client" represents the organization responsible for the procurement of a healthcare facility. "Users" will work in or "use" that building. With the input of project clients, this research focused on the user group process required for Australian and New Zealand publicly funded healthcare projects. It sought lessons to improve the process for future projects. Previous research findings, and an expanded literature review examining participatory design, were used to develop questions for semistructured interviews with selected project clients. Responses were transcribed and analyzed in terms of themes and subthemes using reflexive thematic analysis to develop a narrative that reports and discusses the findings. Although not all are recognized, many stakeholders influence design decisions. No history, rationale, terms of reference, or evaluations of the user group process were found, suggesting that although it is a "given," the process could be enhanced. Useful suggestions for improving the user group process are offered. Evaluating the user group process, and learning from alternative approaches, may improve its outcomes. A project charter and terms of reference would support more effective decision making, while best practice guidelines and education for user group participants should be considered.


Induction therapy with thymoglobulin after heart transplantation: impact of therapy duration on lymphocyte depletion and recovery, rejection, and cytomegalovirus infection rates.
This retrospective single-center study compared lymphocyte depletion in 144 heart transplant recipients using 2 different induction protocols with Thymoglobulin (Genzyme Transplant, Cambridge, MA). Thymoglobulin (1.5 mg/kg) was given to 105 patients for 7 days (Thymo7) and 39 patients for 5 days (Thymo5). Patient clinical characteristics were similar except that the Thymo7 group had a higher prevalence of women (33% vs 15%, p = 0.04), gender mismatch (35% vs 19%, p = 0.07), donor African American race (19% vs 2%, p = 0.008), older donor age (35 +/- 13 vs 31 +/- 12, p = 0.08), and higher pre-transplant creatinine (1.43 +/- 0.67 vs 1.25 +/- 0.48 mg/dl, p = 0.095). Seventy-five percent of the Thymo7 group reached target (absolute lymphocyte count <or=200) and 42% at 21 days (p = 0.002). Thymo7 patients had significantly lower rejection rates (>or=1B) within the first year (7% vs 22%, p = 0.02). No humoral rejection occurred. At 1 year, freedom from rejection was 93% in the Thymo7 group vs 80% in the Thymo5 group (p = 0.007), and cytomegalovirus disease (9% and 5%, p = 0.5) and bacterial infection (26% vs 32%, p = 0.5) were similar. One-year actuarial survival was 92% +/- 3% in the Thymo7 and 100% in the Thymo5 group (p = 0.07), and at 3 years, 85 +/- 4% and 90 +/- 6%, respectively (p = 0.4). Both Thymoglobulin regimens were well tolerated. The 7-day treatment led to more efficient and prolonged lymphocyte depletion and significantly less rejection at 1 year, without an increase in cytomegalovirus infection rate.


Spinal chondrosarcoma following adenocarcinoma of the breast: case report.
Chest wall chondrosarcomas have been reported rarely in breast cancer patients treated with chest wall radiation therapy. However, there are no prior reports of spinal chondrosarcomas arising in patients with a history of breast adenocarcinoma. A neurologically intact 53-year-old woman with breast adenocarcinoma and new onset back pain was evaluated. Magnetic resonance imaging of the spine revealed a tumor of the posterior elements of T7, impinging upon the spinal cord. A computed tomography guided needle biopsy of the spinal mass failed to yield diagnostic results. The patient underwent an open surgical biopsy and complete excision of a low-grade chondrosarcoma. The patient's thoracic pain resolved after surgical excision of her thoracic tumor. She remained neurologically intact. Pathological examination of the tumor revealed a low-grade chondrosarcoma. We present the first reported case of chondrosarcoma of the spine arising in a patient with a history of breast adenocarcinoma without prior irradiation. Solitary spinal tumors in patients with breast adenocarcinoma should not be assumed to be metastatic lesions, and chondrosarcoma should be included in the differential diagnosis of spinal lesions in this patient population. Experimentally, chondrosarcomas have been shown to be sensitive to circulating levels of estrogens, and this might explain an association with adenocarcinoma of the breast treated with tamoxifen.


Some dogmas related to prosthodontics, temporomandibular disorders and occlusion.
It is the aim of this paper to give a few examples of dogmas related to prosthodontics and oral implants and to discuss the controversial role of occlusion in the aetiology of temporomandibular disorders. New knowledge is developing at a rapidly increasing rate in dentistry, as in other areas of society. Our lecturers at university taught us many useful things. But, as time goes by, what is still relevant? Some methods are so well established that they deserve to be called dogmas. It is implied that a dogma is not supported by strong evidence, even though it has existed and been practised for a long time. In the era of evidence-based dentistry it is appropriate to scrutinize such issues. A review of the current literature indicates that conflicting opinions exist concerning a number of common procedures in clinical dentistry, mainly due to a scarcity of good studies with unambiguous results. There is therefore a need for more high-quality clinical research in attempting to reach the goal of evidence-based clinical practice. The dental community should take an active part in this process.


Impact of the Ultrasonic scalpel on the amount of drained lymph after axillary or inguinal lymphadenectomy.
Seroma formation and lymphoedema are frequently encountered complications after radical lymph node dissection (RLND). Attempts to reduce the lymphatic morbidity include the use of Ultrasonic Scalpel. The aim of the present analysis was to assess the impact of the ultrasonic scalpel on the amount of drained lymph after lymph node dissection. Patients listed for a RLND or completion lymph node dissection (CLND) were enrolled in a prospective randomized trial to compare the impact of two surgical dissection techniques (USS versus control) on the amount of drained lymph. The lymph drained in 24 h was collected. Our primary endpoint was to compare the daily amount of drained lymph between the two groups. Secondary endpoints were the comparison of drained lymph with the BMI of the patients, the gender and the surgical site (axilla, groin). Eighty patients were randomly assigned to the USS group or the Control (C) group. No difference was measured in the total amount of lymph drained (USS: 2908 ± 2453 ml vs. C: 3898 ± 5791 ml; p-value = 0.382). The result was also similar after adjusting for gender, age, and BMI. A significant higher amount of lymph was measured after inguinal dissection with USS compared to axillary (p < 0.001). The study suggests that the use of Harmonic scalpel did not influence the amount of lymph drained after RLND and not support the theory that USS induces oversealing of lymphatics. Clinical Trial NCT02476357 . Registered 20 of February 2015.


Systematic review with meta-analysis: Lactobacillus rhamnosus GG in the prevention of antibiotic-associated diarrhoea in children and adults.
The effects of probiotics are strain specific. The clinical effects of each strain need to be evaluated separately. To evaluate the efficacy of Lactobacillus rhamnosus GG (LGG) in the prevention of antibiotic-associated diarrhoea (AAD) in children and adults. The Cochrane Library, MEDLINE, and EMBASE databases were searched up to July 2015, with no language restrictions, for randomised controlled trials (RCTs). Reference lists of reviews and included studies were examined. The quality of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines. Twelve RCTs (1499 participants) were included. Treatment with LGG compared with placebo or no additional treatment reduced the risk of AAD in patients treated with antibiotics from 22.4% to 12.3% (11 RCTs, n = 1308, relative risk, RR: 0.49, 95% confidence interval, CI: 0.29-0.83, low QoE). However, when children and adults were evaluated separately, the difference was significant in children only (five RCTs, n = 445, RR 0.48, 95% CI 0.26-0.89; moderate QoE). In adults, the difference was not significant (six RCTs, n = 863, RR 0.48, 95% CI 0.20-1.15; low QoE), except for in a subset of patients receiving antibiotics as part of Helicobacter pylori eradication therapy (four RCTs, n = 280, RR 0.26, 95% CI 0.11-0.59; low QoE). This meta-analysis shows that Lactobacillus rhamnosus GG is effective in preventing antibiotic-associated diarrhoea in children and adults treated with antibiotics for any reason. However, the quality of evidence is moderate to low.


Atypical cleft hand with complex syndactyly: An unusual form of hand oligodactyly.
Hand oligodactyly refers to a developmental defect which results in the presence of less than 5 digits on a hand. It presents as a component of 4 main categories of congenital upper limb malformations. Herein, we present a 50-year-old man with an unusual form of hand oligodactyly which is characterized by atypical cleft hand accompanied by complex syndactyly between the thumb and the index finger. Accurate characterization of hand oligodacticity can sometimes be challenging due to unusual phenotypic appearances accompanying the abnormality. Radiological evaluation is of great importance for correct identification and classification of such complex hand anomalies, and the treatment should be highly individualized in these patients.


Isolation, characterization, and experimental infection of Streptococcus gallolyticus subspecies pasteurianus from commercial turkeys with acute septicemia: a pilot study.
Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between 1 and 3 wk of age. SG is associated with septicemia resulting in acute mortality with no premonitory signs in turkeys. Three SG isolates were obtained from clinical field cases of acute septicemia of commercial turkeys and used in three independent experiments. In Experiment 1, embryos were inoculated 25 d of embryogenesis with varying concentrations of SG1, SG2, or SG3. In Experiment 2, day of hatch, poults were inoculated with varying concentrations using different routes of administration of SG1, SG2, or SG3. In Experiment 3, day of hatch, poults were inoculated with only isolate SG1 using different paths. Poults were randomly selected for necropsy on d 8 and d 15 and sampled to collect spleen, heart, and liver for SG on d 21, the remaining poults were necropsied and cultured. Samples were plated on Columbia nalidixic acid and colistin agar (CNA) (40°C, 18-24 h). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed suspect colonies. Data were analyzed using the chi-square test of independence, testing all possible combinations to determine significance (P < 0.05). Weight data were subjected to ANOVA using JMP with significance (P < 0.05). No differences were found in BW or BWG on d 0, 8, 15, or 22. Splenomegaly, focal heart necrosis, and pericarditis were observed in all groups in experiments 1 through 3. In Experiment 3, only airsacculitis was observed in a negative control in separate isolation (P > 0.05). On d 21 of Experiment 3, increased (P < 0.05) recovery of SG from spleens were observed in co-housed negative controls, as well as poults challenged by oral gavage (P > 0.05 for d 7 and d 14). These results confirm numerous previous studies indicating that SG subsp. pasteurianus is a primary infectious microorganism that causes septicemia in young poults.


Elevation of serum lymphotactin levels in patients with systemic sclerosis.
To determine serum concentrations of lymphotactin, a Th1 chemokine, and their clinical association in patients with systemic sclerosis (SSc). Lymphotactin levels were examined in serum samples from patients with SSc (n = 68), systemic lupus erythematosus (SLE; n = 42), or dermatomyositis (DM; n = 29), and healthy controls (n = 18) by enzyme linked immunosorbent assay. Serum lymphotactin levels were significantly elevated in SSc patients compared to patients with SLE or DM as well as controls. Serum lymphotactin levels were similar in patients with limited cutaneous SSc and diffuse cutaneous SSc (dSSc). Clinical correlation of elevated lymphotactin levels was not detected in the total group of patients with SSc, while elevation of lymphotactin levels was significantly associated with higher percentage vital capacity and percentage diffusing capacity of carbon monoxide, lower lung severity grade and serum IgG levels, and less frequent presence of short sublingual frenulum in patients with dSSc. Our results indicate that elevated serum lymphotactin levels correlate with relatively milder manifestations in dSSc, especially lower severity of lung involvement, suggesting that lymphotactin may play a role in the development of dSSc.


Retinal nerve fiber layer and ganglion cell layer thickness in patients receiving systemic isotretinoin therapy.
To evaluate the effect of oral isotretinoin therapy on retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thickness by spectral domain optical coherence tomography (OCT). This prospective study included newly diagnosed nodulocystic acne patients about to receive isotretinoin treatment. Macular average GCL thickness and peripapillary average, temporal, nasal, inferior, and superior quadrant RNFL thickness were measured by OCT before and after isotretinoin treatment. Pre- and post-treatment measurements were compared with paired t test. Fifty-six eyes of 28 patients were included. The mean duration of the treatment was 6.5 ± 1.3 months. The mean average GCL thickness was 90.04 ± 5.87 (80-96) μm at baseline and 90.75 ± 6.34 (81-96) μm after treatment. The mean average RNFL thickness was 93.25 ± 6.06 μm (84-107) before treatment and 93.05 ± 5.54 μm (82-106) after treatment. There were no statistically significant differences between pre- and post-treatment values (all p > 0.05). A 6-month course of systemic isotretinoin therapy seems to have no unfavorable effect on retinal ganglion cells; however, larger studies with longer follow-up periods are needed to be conclusive.


Simple Versus Radical Resection for Duodenal Adenocarcinoma: A Propensity Score Matched Analysis of National Cancer Database.
Duodenal adenocarcinoma treatment consists of either simple or radical surgical resection. Existing evidence suggests similar survival outcomes between the two but is limited by small numbers and single-institution analysis. We aim to compare survival after partial versus radical resection for duodenal adenocarcinoma using the National Cancer Database (NCDB). Using NCDB results from 2004 to 2014, we compared patients with duodenal adenocarcinoma undergoing partial resection (n = 1247) and radical resection (n = 1240) by age, sex, facility type, facility location, cancer stage, cancer grade, lymph node sampling, node status, tumor size, margin status, neoadjuvant therapy, and adjuvant therapy using chi-square analysis. Survival was compared using propensity matching. Patients undergoing partial resection had overall earlier cancer stage, more favorable tumor grade, and were less likely to undergo lymph node sampling and neoadjuvant therapy. When overall survival was compared between the 2 propensity-matched groups, the median survival was 46.7 months after partial resection and 43.2 months after radical resection (P = .329), and overall survival was similar between the 2 groups (P = .894). The use of adjuvant therapy demonstrated improved survival over either surgery alone (P < .0001, P = .0037). Partial resection did not demonstrate worse survival outcomes than radical resection for duodenal adenocarcinoma. The use of adjuvant therapy in addition to surgery demonstrated improved survival regardless of surgery type and played a larger role in survival than the type of surgery. Our findings provide evidence to support the continued use of both partial and radical surgical resections to treat duodenal malignancy.


Elevated serum progesterone levels before frozen embryo transfer do not negatively impact reproductive outcomes: a large retrospective cohort study.
To evaluate whether patients with high-serum progesterone levels before frozen embryo transfer (FET) under hormonal replacement therapy present with worse reproductive outcomes. A cohort retrospective study. A university-affiliated fertility center. A total of 3,183 FET cycles in patients receiving hormonal replacement therapy between March 2009 and December 2020 were included. The luteal phase was covered with 200 mg per 8 hours of vaginal micronized progesterone either alone or in combination with a daily subcutaneous injection of 25 mg of progesterone. A total of 1,360 cycles corresponded to frozen homologous embryo transfer (ET) (hom-FET), 1,024 were euploid ET (eu-FET) after preimplantation genetic testing for aneuploidies, and 799 cycles were frozen heterologous ET (het-FET). All patients had adequate serum progesterone levels (≥10.6 ng/mL) before the procedure. Frozen embryo transfer cycles. Clinical pregnancy, miscarriage, and live birth rates (LBRs). Median (P25; P75) serum progesterone level before FET was 14.39 (12.43-17.49) ng/mL. Progesterone levels were significantly higher in the group under vaginal plus subcutaneous progesterone (15.96 [13.74-21.60] vs. 14.09 [12.19-16.95]). No differences in clinical pregnancy, miscarriage, and LBR were observed based on the use of vaginal or vaginal plus subcutaneous progesterone for each of the groups (hom-FET, eu-FET, and het-FET). Live birth rates were comparable among patients in the highest centile of serum progesterone levels (≥p90) (22.33 ng/mL) and the rest of the patients (p<90) (43.9% vs. 41.3%). Patients with progesterone levels ≥p90 presented lower body mass index than those in the lower centiles (<p90) (22.62 ± 3.82 vs. 23.32 ± 4.06). After dividing patients into deciles based on serum progesterone levels, no differences in LBRs were observed among the groups. No association was observed using a generalized additive model between progesterone levels and LBR. A multivariable logistic regression adjusted by oocyte age, type of treatment, body mass index, type of luteal phase support, and the number of embryos transferred was applied for centile 90 and centile 95 of progesterone and showed that serum progesterone in their highest levels did not negatively impact LBR. Elevated serum progesterone levels before FET do not impair reproductive outcomes in patients receiving artificially prepared cycles with vaginal or vaginal plus subcutaneous progesterone.


Key research questions for implementation of artificial intelligence in capsule endoscopy.
Artificial intelligence (AI) is rapidly infiltrating multiple areas in medicine, with gastrointestinal endoscopy paving the way in both research and clinical applications. Multiple challenges associated with the incorporation of AI in endoscopy are being addressed in recent consensus documents. In the current paper, we aimed to map future challenges and areas of research for the incorporation of AI in capsule endoscopy (CE) practice. Modified three-round Delphi consensus online survey. The study design was based on a modified three-round Delphi consensus online survey distributed to a group of CE and AI experts. Round one aimed to map out key research statements and challenges for the implementation of AI in CE. All queries addressing the same questions were merged into a single issue. The second round aimed to rank all generated questions during round one and to identify the top-ranked statements with the highest total score. Finally, the third round aimed to redistribute and rescore the top-ranked statements. Twenty-one (16 gastroenterologists and 5 data scientists) experts participated in the survey. In the first round, 48 statements divided into seven themes were generated. After scoring all statements and rescoring the top 12, the question of AI use for identification and grading of small bowel pathologies was scored the highest (mean score 9.15), correlation of AI and human expert reading-second (9.05), and real-life feasibility-third (9.0). In summary, our current study points out a roadmap for future challenges and research areas on our way to fully incorporating AI in CE reading.


Review of British Standard BS 4094-1:1966 Part 1: data on shielding from gamma radiation.
British Standard BS 4094-1:1966 Part 1 (entitled 'Data on Shielding from Ionizing Radiation Part 1: Shielding from Gamma Radiation') provides a series of transmission curves (the Figure 2 series) which illustrate the attenuation of gamma radiation from eleven isotopes through a variety of absorber media. As such it is widely utilised across the nuclear industry and other sectors. However, British Standard BS4094 1:1966 was collated over 50 years ago when both computer codes and nuclear data were significantly less advanced than they are today. This paper reproduces the British Standard Figure 2 series in order to benchmark it against modern computer codes (specifically MCNP 6.2 and RANKERN) and data taken from more modern nuclear data libraries. The results show good agreement in the majority of cases. However, there are some significant discrepancies in a number of isotope / absorber combinations and in some of these cases British Standard BS 4094-1:1966 Part 1 may not be conservative. This paper concludes that a modern revision to British Standard BS 4094 1:1966 Part 1 would be appropriate and timely.


Holographic interferometry in the biomechanical study of femoral behavior, with and without prosthesis.
The authors studied the strains acting on a normal femur, and on the same femur fitted with an uncemented screwed prosthesis, by means of the method of holographic interferometry. This modern optical method has the advantage of not requiring any preparation of the surfaces or modification of the bone to be studied. It is non-destructive and can be repeated. This study required 40 interferograms for each case, using two or even three views. Comparison of the images obtained showed major modifications: disappearance of the physiologic flexion of the diaphysis, overload of the upper third, and zones of excess constraint.


Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor.
Galectins are beta-galactoside binding proteins. This ability may have a bearing on cell adhesion and migration/proliferation in human colon cancer cells. In addition to galectins-1 and -3 studied to date, other members of this family not investigated in detail may contribute to modulation of tumour cell features. This evident gap has prompted us to extend galectin analysis beyond the two prototypes. The present study deals with the quantitative determination of immunohistochemical expression of galectin-8 in normal, benign, and malignant human colon tissue samples and in four human colon cancer models (HCT-15, LoVo, CoLo201, and DLD-1) maintained both in vitro as permanent cell lines and in vivo as nude mice xenografts. The role of galectin-8 (and its neutralising antibody) in cell migration was investigated in HCT-15, LoVo, CoLo201, and DLD-1 cell lines. Immunohistochemical expression of galectin-8 and its overall ability to bind to sugar ligands (revealed glycohistochemically by means of biotinylated histochemically inert carrier bovine serum albumin with alpha- and beta-D-galactose, alpha-D-glucose, and lactose derivatives as ligands) were quantitatively determined using computer assisted microscopy. The presence of galectin-8 mRNA in the four human colon cancer cell lines was examined by reverse transcriptase-polymerase chain reaction. In vitro, cellular localisation of exogenously added galectin-8 in the culture media of these colon cancer cells was visualised by fluorescence microscopy. In vitro galectin-8 mediated effects (and the influence of its neutralising antibody) on migration levels of living HCT-15, LoVo, CoLo201, and DLD-1 cells were quantitatively determined by computer assisted phase contrast microscopy. A marked decrease in immunohistochemical expression of galectin-8 occurred with malignancy development in human colon tissue. Malignant colon tissue exhibited a significantly lower galectin-8 level than normal or benign tissue colon cancers; those with extensive invasion capacities (T3-4/N+/M+) harboured significantly less galectin-8 than colon cancers with localised invasion capacities (T1-2/N0/M0). The four experimental models (HCT-15, LoVo, CoLo201, and DLD-1) had more intense galectin-8 dependent staining in vitro than in vivo. Grafting the four experimental human colon cancer models onto nude mice enabled us to show that the immunohistochemical expression of galectin-8 was inversely related to tumour growth rate. In vitro, galectin-8 reduced the migration rate of only those human experimental models (HCT-15 and CoLo201) that exhibited the lowest growth rate in vivo. Expression of galectin-8 correlated with malignancy development, with suppressor activity, as shown by analysis of clinical samples and xenografts. In vitro, only the two models with low growth rates were sensitive to the inhibitory potential of this galectin. Future investigations in this field should involve fingerprinting of these newly detected galectins, transcending the common focus on galectins-1 and -3.


[CT-guided sympathicolysis in peripheral artery disease - Indications, patient selection and long-term results].
Assessment of long-term results of CT-guided lumbar sympathicolysis (LSL) in advanced peripheral arterial vascular disease (pavd). Establishment of a suitable patient selection. LSL was performed in 138 cases with Fontaine stages III (13 %) and IV (87 %). 250 consecutive patients were examined with a radionuclide perfusion study of the feet prior to and during peridural anaesthesia (PDA) in order to select suitable patients for LSL. LSL was not performed in patients with impaired perfusion under PDA (n = 112). Early and long-term results after one to five years were evaluated. In 79 % an initial improvement was found after LSL. After more than one year success was established in 38 %. 49 % of the cases had a progression of the disease. This is significantly better compared to a control group with conservative treatment and an initial improvement of 36 %. After more than one year only12 % revealed an improvement. In 82 % the disease was progressive. Diabetics showed also a positive response to LSL. LSL has a positive influence on the course of pvad in patients selected by radionuclide perfusion studies. Diabetes and angiographic findings do not play any first role in patient selection for LSL.


Scanpaths: the path to understanding abnormal cognitive processing in neurological disease.
Scanpaths, the sequence of saccades and fixations during visual search, provide the means to study a range of cognitive activities: planning, visuospatial attention, and spatial working memory. By measuring scanpaths, we have been able to identify impairment of working memory in patients with spatial hemineglect. Scanpaths during cognitively demanding tasks indicate a defect of working memory in patients with Parkinson's disease. Studies of scanpaths in patients with homonymous hemianopia have provided the means to develop a new strategy for visual rehabilitation.


Microarrays bring new insights into understanding of breast cancer metastasis to bone.
Using a microarray approach, Kang and colleagues identified several genes involved in the generation of breast cancer metastasis in bone and demonstrated their roles in bone colonization in vivo. Their findings and interpretations are reviewed in the context of recent array studies that compared gene expression in primary tumors and metastases. RNA expression array results have already demonstrated value in predicting whether metastases will develop in patients. They have also shown that expression patterns are similar in primary tumors and metastases. The latter data have invited re-examination of long-held notions related to mechanisms of metastasis. While the arrays show promise for improving diagnostic capability in breast cancers, ascribing mechanistic interpretations to correlative data should be done with extreme caution. Kang and colleagues' paper in Cancer Cell elegantly reinforces the concepts that efficiency of the metastatic process is dependent on the coordinated expression of multiple genes and that the expression of metastasis-associated genes is sometimes dependent on the microenvironment in which cells find themselves.


Differential impact of flanking sequences on estradiol- vs 4-hydroxytamoxifen-liganded estrogen receptor binding to estrogen responsive element DNA.
The mechanism by which antiestrogens antagonize the ability of estrogen receptor (ER) to induce the transcription of estrogen-regulated genes is only partially understood. To examine the effect of estrogen responsive element (ERE) stereoalignment and flanking sequences on estradiol-liganded ER (E2-ER)-ERE and antiestrogen-liganded ER (4-hydroxytamoxifen-liganded ER or 4-OHT-ER)-ERE binding, several dimeric EREs, containing a perfect inverted repeat (5'-GGTCAgagTGACC-3') but lacking the AT-rich flanking sequences typical of highly estrogen-responsive promoters, were cloned into a plasmid vector. The ERE centers of symmetry were spaced 1.5, 2.0, 3.0, 6.4 and 6.7 helical turns apart. E2-ER and 4-OHT-ER binding to these constructs was specific and saturable, but orientation-independent and, in contrast to our earlier work with E2-ER binding to AT-rich EREs, not cooperative. The affinity of E2-ER binding decreased as the distance between adjacent EREs was increased, suggesting that E2-ER binding to closely spaced EREs is more stable (Kd = 0.38, 0.58, 0.83, 1.23, and 0.96 nM, respectively, for the above spacings). In contrast, the affinity of 4-OHT-ER binding increased with increased ERE spacing (Kd = 2.90, 4.79, 1.39, 1.77, and 0.92 nM, respectively). The presence of AT-rich sequences flanking the ERE increased the binding affinity of E2-ER and 4-OHT-ER, an increase reflected in slower dissociation rates of ER from these EREs. The AT-rich sequence also enhanced the binding capacity of E2-ER but not 4-OHT-ER. Since the binding capacity of 4-OHT-ER is identical with or without an AT-rich region, we suggest that flanking sequences are more important in stabilizing E2-ER binding and may be critical for cooperative binding to stereoaligned EREs.