Portable Sensor for the Detection of Choline and Its Derivatives Based on Silica Isoporous Membrane and Gellified Nanointerfaces.
A portable amperometric ion sensor was fabricated by integrating silica isoporous membrane (SIM) and organogel composed of polyvinyl chloride and 1,2-dichloroethane (PVC-DCE) on a 3D-printed polymer chip. The detection of ionic species in aqueous samples could be accomplished by adding a microliter of sample droplet to the sensor and by identifying the ion-transfer potential and current magnitude at the water/organogel interface array templated by SIM. Thanks to the ultrasmall channel size (2-3 nm in diameter), high channel density (4 × 108 μm-2), and ultrathin thickness (80 nm) of SIM, the ensemble of nanoscopic water/organogel (nano-W/Gel) interface array behaved like a microinterface with two back-to-back hemispherical mass diffusion zones. So, the heterogeneous ion-transfer across the nano-W/Gel interface array generated a steady-state sigmoidal current wave. The detection of choline (Ch) and its derivatives, including acetylcholine (ACh), benzoylcholine (BCh), and atropine (AP), in aqueous samples was examined with this portable sensor. Using differential pulse stripping voltammetry (DPSV), the quantification of these analytes was achieved with a limit of detection (LOD) down to 1 μM. Moreover, the portable ion sensor was insensitive to various potential interferents that might coexist in vivo, owing to size-/charge-based selectivity and antifouling capacity of SIM. With this priority, the portable ion sensor was able to quantitatively determine Ch and its derivatives in diluted urine and blood samples. The LODs for Ch, ACh, AP, and BCh in urine were 1.12, 1.30, 1.08, and 0.99 μM, and those for blood samples were 3.61, 3.38, 2.32, and 1.81 μM, respectively.


Decreased microviscosity of membrane lipids in leukemic cells: two possible mechanisms.
Steady-state fluorescence polarization studies with the fluorescent lipid probe 1,6-diphenyl 1,3,5-hexatriene were done to determine the degree of microviscosity of cellular membrane lipids and serum lipoproteins in human normal donors and leukemic patients. The results show a marked decrease in microviscosity of cellular membrane lipids in both intact lymphocytes and isolated cellular plasma membranes obtained from leukemic patients in clinical relapse as compared to intact lymphocytes and isolated cellular plasma membranes obtained from normal donors and leukemic patients in complete clinical remission. Concomitant to these dynamic changes in cellular membrane lipids, the degree of microviscosity of lipids in the blood serum of leukemic patients in clinical relapse is markedly reduced as compared to serum obtained from normal donors and leukemic patients in complete clinical remission. Moreover, an in vitro incubation of leukemic lymphocytes with normal low density lipoproteins results in an increased microviscosity of cellular membrane lipids. In addition to the interrelation between cellular membrane lipids and serum lipoproteins, plasma membrane vesicles with a high degree of lipid microviscosity were isolated from the blood serum and pleural effusion of leukemic patients in clinical relapse. Such membrane vesicles could not be detected in normal serum. Therefore, we suggest that the two major mechanisms associated with the decreased microviscosity of membrane lipids in human leukemic cells are an abnormal exchange in lipids between the leukemic cell surface membrane and leukemic serum lipoproteins and an exfoliation of plasma membrane vesicles with a high degree of microviscosity from the cell surface of leukemic cells.


A Comprehensive Approach to Deep Brain Stimulation for Movement Disorders.
Deep brain stimulation (DBS) is a well-established form of neuromodulation, used primarily for movement disorders such as Parkinson's disease (PD) and Essential Tremor (ET). The selection of patients who will benefit most from DBS depends on a team of clinicians from various disciplines, including neurology, neurosurgery, psychiatry, neuropsychology and rehabilitation specialists. The actual surgical procedure can take many forms. We apply a combination of multidisciplinary, team-based evaluations and intra-operative neurophysiology, test stimulation and imaging to optimize DBS therapy for individual patients. [Full article available at http://rimed.org/rimedicaljournal-2017-06.asp].


Impact of Compression Stockings vs. Continuous Positive Airway Pressure on Overnight Fluid Shift and Obstructive Sleep Apnea among Patients on Hemodialysis.
Obstructive sleep apnea (OSA) is common in edematous states, notably in hemodialysis patients. In this population, overnight fluid shift can play an important role on the pathogenesis of OSA. The effect of compression stockings (CS) and continuous positive airway pressure (CPAP) on fluid shift is barely known. We compared the effects of CS and CPAP on fluid dynamics in a sample of patients with OSA in hemodialysis, through a randomized crossover study. Each participant performed polysomnography (PSG) at baseline, during CPAP titration, and after 1 week of wearing CS. Neck circumference (NC) and segmental bioelectrical impedance were done before and after PSG. Fourteen patients were studied (53 ± 9 years; 57% men; body mass index 29.7 ± 6.8 kg/m2). Apnea-hypopnea index (AHI) decreased from 20.8 (14.2; 39.6) at baseline to 7.9 (2.8; 25.4) during CPAP titration and to 16.7 (3.5; 28.9) events/h after wearing CS (CPAP vs. baseline, p = 0.004; CS vs. baseline, p = 0.017; and CPAP vs. CS, p = 0.017). Nocturnal intracellular trunk water was higher after wearing CS in comparison to baseline and CPAP (p = 0.03). CS reduced the fluid accumulated in lower limbs during the day, although not significantly. Overnight fluid shift at baseline, CPAP, and CS was -183 ± 72, -343 ± 220, and -290 ± 213 ml, respectively (p = 0.006). Overnight NC increased at baseline (0.7 ± 0.4 cm), decreased after CPAP (-1.0 ± 0.4 cm), and while wearing CS (-0.4 ± 0.8 cm) (CPAP vs. baseline, p < 0.0001; CS vs. baseline, p = 0.001; CPAP vs. CS, p = 0.01). CS reduced AHI by avoiding fluid retention in the legs, favoring accumulation of water in the intracellular component of the trunk, thus avoiding fluid shift to reach the neck. CPAP improved OSA by exerting local pressure on upper airway, with no impact on fluid redistribution. CPAP performed significantly better than CS for both reduction of AHI and overnight reduction of NC. Complementary studies are needed to elucidate the mechanisms by which CPAP and CS reduce NC.


Association between frontal plane knee control and lower extremity injuries: a prospective study on young team sport athletes.
Poor frontal plane knee control can manifest as increased dynamic knee valgus during athletic tasks. The purpose of this study was to investigate the association between frontal plane knee control and the risk of acute lower extremity injuries. In addition, we wanted to study if the single-leg squat (SLS) test can be used as a screening tool to identify athletes with an increased injury risk. A total of 306 basketball and floorball players participated in the baseline SLS test and a 12-month injury registration follow-up. Acute lower extremity time-loss injuries were registered. Frontal plane knee projection angles (FPKPA) during the SLS were calculated using a two-dimensional video analysis. Athletes displaying a high FPKPA were 2.7 times more likely to sustain a lower extremity injury (adjusted OR 2.67, 95% CI 1.23 to 5.83) and 2.4 times more likely to sustain an ankle injury (OR 2.37, 95% CI 1.13 to 4.98). There was no statistically significant association between FPKPA and knee injury (OR 1.49, 95% CI 0.56 to 3.98). The receiver operating characteristic curve analyses indicated poor combined sensitivity and specificity when FPKPA was used as a screening test for lower extremity injuries (area under the curve of 0.59) and ankle injuries (area under the curve of 0.58). Athletes displaying a large FPKPA in the SLS test had an elevated risk of acute lower extremity and ankle injuries. However, the SLS test is not sensitive and specific enough to be used as a screening tool for future injury risk.


A Microporous Aluminosilicate with 12-, 12-, and 8-Ring Pores and Isolated 8-Ring Channels.
Synthesis of new zeolites with controlled pore architectures is important in the field of catalysis and separation related to chemical transformation, environmental protection, and energy-saving. Zeolites containing channels of different sizes in the same framework have been desirable. We report here the synthesis and structure of a novel aluminosilicate zeolite (designated as YNU-5), the first zeolite containing interconnected 12-, 12-, and 8-ring pores, as well as independent straight 8-ring channels. The synthesis procedure is quite simple and consists of conventional hydrothermal conditions as well as readily available starting materials. The framework structure is stable enough and Si/Al ratio is controllable between 9 and 350. Determination of the crystal structure is performed by utilizing X-ray diffraction-based techniques, revealing 9 independent tetrahedrally coordinated atoms. This robust structure is expected to be industrially valuable and several unusual combinations of composite building units are of considerable interest in an academic sense. The new zeolite YNU-5 is promising catalyst for the production of useful light olefins such as propylene and butylenes in the dimethyl ether-to-olefin reaction, when the Si/Al ratio is properly tuned by dealumination through simple acid treatments.


Number needed to treat (NNT) in clinical literature: an appraisal.
The number needed to treat (NNT) is an absolute effect measure that has been used to assess beneficial and harmful effects of medical interventions. Several methods can be used to calculate NNTs, and they should be applied depending on the different study characteristics, such as the design and type of variable used to measure outcomes. Whether or not the most recommended methods have been applied to calculate NNTs in studies published in the medical literature is yet to be determined. The aim of this study is to assess whether the methods used to calculate NNTs in studies published in medical journals are in line with basic methodological recommendations. The top 25 high-impact factor journals in the "General and/or Internal Medicine" category were screened to identify studies assessing pharmacological interventions and reporting NNTs. Studies were categorized according to their design and the type of variables. NNTs were assessed for completeness (baseline risk, time horizon, and confidence intervals [CIs]). The methods used for calculating NNTs in selected studies were compared to basic methodological recommendations published in the literature. Data were analyzed using descriptive statistics. The search returned 138 citations, of which 51 were selected. Most were meta-analyses (n = 23, 45.1%), followed by clinical trials (n = 17, 33.3%), cohort (n = 9, 17.6%), and case-control studies (n = 2, 3.9%). Binary variables were more common (n = 41, 80.4%) than time-to-event (n = 10, 19.6%) outcomes. Twenty-six studies (51.0%) reported only NNT to benefit (NNTB), 14 (27.5%) reported both NNTB and NNT to harm (NNTH), and 11 (21.6%) reported only NNTH. Baseline risk (n = 37, 72.5%), time horizon (n = 38, 74.5%), and CI (n = 32, 62.7%) for NNTs were not always reported. Basic methodological recommendations to calculate NNTs were not followed in 15 studies (29.4%). The proportion of studies applying non-recommended methods was particularly high for meta-analyses (n = 13, 56.5%). A considerable proportion of studies, particularly meta-analyses, applied methods that are not in line with basic methodological recommendations. Despite their usefulness in assisting clinical decisions, NNTs are uninterpretable if incompletely reported, and they may be misleading if calculating methods are inadequate to study designs and variables under evaluation. Further research is needed to confirm the present findings.


Comparison of Nonspherical Polyvinyl Alcohol Particles and Microspheres for Prostatic Arterial Embolization in Patients with Benign Prostatic Hyperplasia.
To report early results following prostatic artery embolization (PAE) and compare outcomes between nonspherical polyvinyl alcohol (PVA) particles and microspheres to treat lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). PAE was performed in nine patients (mean age: 78.1 years) with symptomatic BPH. Embolization was performed using nonspherical PVA particles (250-355 μm) in four patients and microspheres (300-500 μm) in five patients. PAE was technically successful in all nine patients (100%). During a mean follow-up of 10.1 months, improvements in mean International Prostate Symptom Score (IPSS), Quality of Life (QoL), prostatic volume (total volume and transition zone), and peak urinary flow (Qmax) were 9.8 points, 2.3 points, 28.1 mL, 17.8 mL, and 4.5 mL/s, respectively. Clinical success was obtained in seven of nine patients (78%). Patients in the microsphere group showed greater improvement in IPSS, QoL, prostatic volume, and Qmax compared to patients in the nonspherical PVA particle group. However, significant difference was noted only in the prostatic volume. PAE is a feasible, effective, and safe treatment option for BPH with LUTS. Use of microspheres showed greater prostatic volume reduction compared to nonspherical PVA particles.


The Incidence, Clinical Features, and a Comparison Between Early and Delayed Onset of Postoperative Spinal Epidural Hematoma.
A retrospective observational study. To investigate the incidence and clinical features of symptomatic postoperative spinal epidural hematoma (PSEH) with regard to spinal level and to compare early and delayed onset cases. PSEH is a serious complication of spinal surgeries. The difference in clinical manifestations between early and delayed PSEH remains unclear. Patients who underwent spinal surgeries between 1999 and 2013 at our institution, were reviewed through their medical records. For patients with PSEH, the incidence, duration to onset, duration from onset to evacuation, symptoms, recovery rate (American Spinal Injury Association grade), neurological outcomes, comorbidities, and preoperative use of anticoagulant drugs were examined. We next compared patients with early onset PSEH (onset until day 3) versus delayed onset (onset day 4 or later) regarding these clinical factors. Fourteen patients (0.42%, 14/3371) developed symptomatic PSEH. Initial symptoms were observed between 0 and 7 days (mean 2.6 ± 2.4 d) and almost half (43%, 6/14) occurred during the delayed phase (mean 5.0 ± 1.1 d postsurgery). Paralysis was the predominant symptom in patients with cervical and thoracic surgeries (100%, 6/6), whereas severe pain was most frequent in patients with lumbar procedures (63%, 5/8) (P = 0.019). No significant differences were identified between early and delayed groups. Neurological outcome was good in 10 cases, partial in two cases, and poor in two cases. The frequency was consistent in every spinal region, and the symptoms due to PSEH were correlated with spinal level. Almost half the cases were diagnosed after a delay (day 4 or later), which supports the necessity to follow up patients with spinal surgeries more carefully for a week or so and to educate patients and comedical staff about the possibility of delayed hematoma disorders in order not to defer timely intervention. 4.


[Prevention of epilepsy in children following birth trauma].
In a group of 120 children with prenatal and postnatal trauma 31 children with epileptic seizures were found who accounted for 25.8% of neuropsychiatric complications in this group. Epilepsy was more frequent in children with a history of asphyxia than after other forms of perinatal trauma. Seizures were observed either immediately after birth or up to the age of 100 months. In children with delayed onset of seizures evidence of abnormal behaviour with excessive motor agitation, sleep and appetite disturbances was found from the very birth. Besides prophylactic measures applied to avoid complications of pregnancy and labour it is indispensable to separate the children with perinatal trauma and group them for further neuropsychiatric observation in outpatient clinics and to begin treatment which may prevent development of frank epilepsy in at least a part of these children and may contribute to better rehabilitation of brain-damaged children.


[PAX4 gene polymorphism and islet autoantibody-negative ketosis-prone diabetes].
To investigate PAX4 gene polymorphism and its association with islet autoantibody-negative patients with ketosis-prone diabetes in Chinese Han population. We screened the variation of exon 3 and 9 within PAX4 gene by denaturing high performance liquid chromatography(DHPLC) in 112 non-diabetes control subjects (NC group) and 141 patients with ketosis-prone diabetes (KPD group), who were both negative for glutamic acid decarboxylase antibody (GAD-Ab) as well as protein tyrosine phosphatase antibody (IA-2Ab). The sequences of abnormal peaks were analyzed by DNA-sequencing. The A1168C single nucleotide polymorphism in PAX4 gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 308 non-diabetic control subjects and 141 KPD patients. No variation was discovered in PAX4 gene exon 3 both in the patients and in the controls. There was a single nucleotide polymorphism locus A1168C in the PAX4 gene exon 9, which induced missence mutation P321H (rs712701). No significant difference was observed in the genotype and allele frequencies of A1168C polymorphism between KPD patients and control subjects (P=0.532, 0.426). The difference was detected in the CC genotype and C allele frequencies in the KPD group when patients were stratified by gender (P=0.009,0.028). According to age at diagnosis, the difference was observed in the CC genotype and C allele frequencies between <20 years old and > or = 20 years old in the KPD group (P=0.034,0.032). The level of FCP in the CC genotype group was significantly higher than that of FCP in AA genotype group (P=0.005). A1168C polymorphism in PAX4 gene may not play an essential role in the genetic susceptibility of the islet autoantibody-negative KPD in Chinese Han population. However, A1168C variation may contribute to the predisposition to the male or < 20 years old patients with islet autoantibody-negative KPD.


Diversity of inhibitory responses to beta2-stimulants shown by term-pregnant human myometria in vitro is partly due to differences in receptor density.
The aims of this study were (1) to evaluate the usefulness of the new beta2-adrenergic stimulant KUR-1246 as a tocolytic agent and (2) to clarify the mechanisms that underlie the diverse inhibitory effects of beta2-stimulants that are seen in human myometria in vitro. The displacement of tritiated ([3H]) (-)CGP 12177 (0.4 nmol/L) by KUR-1246 and other beta2-stimulants was examined with human beta(1)- and beta2-receptors present on membrane fractions. The inhibitory effects of these beta2-stimulants on the term-pregnant human myometrium were compared with the use of isometric tension recording and microelectrode methods. Finally, the relationship between [3H]dihydroaloprenolol binding and the magnitude of the tocolytic effect of isoproterenol was examined. KUR-1246 was approximately 80 times and 7 times more selective for beta2-receptors than isoproterenol and ritodrine, respectively. The inhibitory effect of KUR-1246 was as strong as the inhibitory effect of the conventional beta2-adrenergic stimulants. A wide range of inhibitory effects was observed, even when high concentrations of isoproterenol or KUR-1246 were applied. There was a correlation between the degree to which isoproterenol suppressed contractions and the number of [3H]dihydroaloprenolol binding sites on the membrane in each muscle strip. KUR-1246 should be a very useful beta2-adrenergic stimulant for use as a tocolytic agent because of its high selectivity for the beta2-receptor and its potent inhibitory effect. The diversity of the inhibitory effects that are induced by beta2-stimulants is at least partly due to differences in beta2-receptor density among term-pregnant human myometria.


[A study of the cytochrome composition of microorganisms by their absorption spectra and first derivative spectra].
The cytochrome composition of Candida mycoderma and Torulopsis candida was studied by means of absorption spectra and spectra of the first derivative which were recorded at the temperature of liquid nitrogen and room temperature. The spectrum of the first derivative provided more information concerning the cytochrome composition than absorption spectra; data obtained with the aid of this spectrum at room temperature corresponded to those provided by means of absorption spectra at low temperatures.


Small cell carcinoma of the bladder.
Small cell carcinoma of the urinary bladder is an extremely aggressive and rare tumor. Even though small cell carcinoma most commonly arises from the lungs there are several reports of small cell carcinoma in extrapulmonary sites. Due to its low frequency there is no well-established management for this disease. We report the case of a 61 year-old man with small cell carcinoma of the bladder who underwent radical cystectomy following neoadjuvant chemotherapy. We also reviewed the literature for the optimal treatment strategy.


Clusterin protects hepatocellular carcinoma cells from endoplasmic reticulum stress induced apoptosis through GRP78.
Clusterin (CLU) is a stress-activated chaperone, which plays an important role in cancer development and progression through promoting cell survival. However, the exact mechanism of how CLU exerts its cell protective role under ER stress condition is still unclear. Therefore, in order to explore the molecular mechanisms by which CLU inhibited ER stress-induced apoptosis, HCC cell lines were treated with tunicamycin (TN), an ER stress inducer. We found that the expressions of both CLU and GRP78 were increased after TN treatment. Knockdown of CLU expression in SMMC7721 and HCCLM3 cells inhibited GRP78 expression after TN treatment and enhanced ER stress-induced apoptosis, whereas over-expression of CLU in HepG2 cells increased GRP78 expression after TN induction and abolished the effect of TN on cell apoptosis. Furthermore, knockdown of GRP78 expression in CLU-HepG2 cells abrogated the protective role of CLU under ER stress condition. Co-immunoprecipitation (co-IP) and confocal microscopy experiments confirmed the direct interaction between CLU and GRP78 under ER stress condition. The effect of CLU knockdown on GRP78 expression and cell apoptosis in HCC tumors were further determined in orthotopic xenograft tumor model. Knockdown of CLU expression in HCCLM3 cells inhibited GRP78 expression in tumor tissues, accompanied with increased number of apoptotic cancer cells. Moreover, the correlation between CLU and GRP78 expression was further determined in clinical HCC specimens. Taken together, these findings reveal that CLU protects HCC cells from ER stress induced apoptosis at least partially through interacting with GRP78.


Evaluating the tobacco settlement damage awards: too much or not enough?
This study compared the present economic value of the 1998 tobacco settlement with the present economic value of the damages attributable to tobacco. The 1987 National Medical Expenditure Survey was used to estimate the smoking attributable fraction (SAF) of medical expenditures. SAFs were then applied to Medicaid and other expenditures. Settlement payments covered only 40% of Medicaid treatment costs already incurred and only 30% of past and projected future Medicaid costs. Excess medical expenditures for all other payment sources were roughly comparable to those incurred by Medicaid. Although the settlement may reduce future smoking prevalence rates by limiting the ability of tobacco companies to promote smoking and by raising cigarette prices, euphoria over the huge settlement funds should be balanced by a sober comparison with the even larger damage amounts.


Purification and characterization of nicotinamide deamidase from yeast.
Nicotinamide deamidase (YNDase) has been purified from yeast through the use of a six-step procedure that includes molecular-sieve high performance liquid chromatography. The final preparation was homogeneous by the criteria of sodium dodecyl sulfate-gel electrophoresis, and the enzyme specific activity was determined to be 175 mumol of nicotinate formed per min/mg enzyme. Gel electrophoresis and molecular-sieve high performance liquid chromatography were employed also to characterize YNDase as a monomeric protein with a molecular weight of 34,000. A Km value for nicotinamide of 33 microM was determined for the deamidase activity at pH 6, and a pH range for optimal stability of 6-8.5 was established for this enzyme. The YNDase activity was also examined over a pH range at several substrate concentrations and both the log Vmax and log Vmax/Km plots versus pH suggested that a protonated amino acid residue with an apparent pKb value of 7.8 was essential to this activity. During an in vitro assay of the YNDase-catalyzed formation of nicotinate, ammonia was generated and detected chemically. Inhibition of the YNDase activity by nicotinaldehyde suggested the presence of either an essential lysine (Schiff's base formation) or cysteine residue (thiohemiacetal intermediate) at the YNDase active site. The relatively large value of the nicotinaldehyde inhibition constant (Ki = 68 microM), the observation that this analogue is a noncompetitive inhibitor of nicotinate formation, and the fact that this inhibition can be rendered irreversible through incubation with sodium borohydride, indicates that a Schiff's base intermediate is more likely to occur upon incubation of YNDase with nicotinaldehyde. However, YNDase is inactivated completely and irreversibly by N-ethylmaleimide at pH 6, and the enzyme is protected against this modification by either nicotinamide or nicotinate. These results suggest that both nicotinate and nicotinamide bind to YNDase, even though the enzymatic reaction is essentially irreversible, and that a cysteine residue may be present at the YNDase active site.


Healthcare microenvironments define multidrug-resistant organism persistence.
Multidrug-resistant organisms (MDROs) colonizing the healthcare environment have been shown to contribute to risk for healthcare-associated infections (HAIs), with adverse effects on patient morbidity and mortality. We sought to determine how bacterial contamination and persistent MDRO colonization of the healthcare environment are related to the position of patients and wastewater sites. We performed a prospective cohort study, enrolling 51 hospital rooms at the time of admitting a patient with an eligible MDRO in the prior 30 days. We performed systematic sampling and MDRO culture of rooms, as well as 16S rRNA sequencing to define the environmental microbiome in a subset of samples. The probability of detecting resistant gram-negative organisms, including Enterobacterales, Acinetobacter spp, and Pseudomonas spp, increased with distance from the patient. In contrast, Clostridioides difficile and methicillin-resistant Staphylococcus aureus were more likely to be detected close to the patient. Resistant Pseudomonas spp and S. aureus were enriched in these hot spots despite broad deposition of 16S rRNA gene sequences assigned to the same genera, suggesting modifiable factors that permit the persistence of these MDROs. MDRO hot spots can be defined by distance from the patient and from wastewater reservoirs. Evaluating how MDROs are enriched relative to bacterial DNA deposition helps to identify healthcare micro-environments and suggests how targeted environmental cleaning or design approaches could prevent MDRO persistence and reduce infection risk.


Combining biomechanical stimulation and chronobiology: a novel approach for augmented chondrogenesis?
The unique structure and composition of articular cartilage is critical for its physiological function. However, this architecture may get disrupted by degeneration or trauma. Due to the low intrinsic regeneration properties of the tissue, the healing response is generally poor. Low-grade inflammation in patients with osteoarthritis advances cartilage degradation, resulting in pain, immobility, and reduced quality of life. Generating neocartilage using advanced tissue engineering approaches may address these limitations. The biocompatible microenvironment that is suitable for cartilage regeneration may not only rely on cells and scaffolds, but also on the spatial and temporal features of biomechanics. Cell-autonomous biological clocks that generate circadian rhythms in chondrocytes are generally accepted to be indispensable for normal cartilage homeostasis. While the molecular details of the circadian clockwork are increasingly well understood at the cellular level, the mechanisms that enable clock entrainment by biomechanical signals, which are highly relevant in cartilage, are still largely unknown. This narrative review outlines the role of the biomechanical microenvironment to advance cartilage tissue engineering via entraining the molecular circadian clockwork, and highlights how application of this concept may enhance the development and successful translation of biomechanically relevant tissue engineering interventions.


Evaluation of clinical effect of transabdominal sonography and transvaginal sonography in early diagnosis of ectopic gestation.
To analyze the application of transabdominal sonography and transvaginal sonography in early diagnosis of pregnancy and to provide a reference for the selection of diagnosis methods in clinic. One hundred and eighty patients who were admitted into the hospital from February 2013 to February 2014, received clinical diagnosis and were confirmed as ectopic gestation by surgery were selected as research objects. They were examined by transabdominal sonography, transvaginal sonography, and transabdominal sonography in combination with transvaginal sonography respectively. Besides, the ultrasonic performance was observed and compared with surgical pathological results to analyze and compare diagnostic accordance rate. The positive rate of transabdominal sonography in combination with transvaginal sonography was much higher than that of transabdominal sonography and transvaginal sonography and the differences had statistical significance (P<0.05). The detection rate of different positive characteristics using the combined examination was much higher than that of transabdominal sonography and transvaginal sonography, and the differences had statistical significance (P<0.05). The detection rates of different types of ectopic gestation and different sizes of mass using transabdominal sonography in combination of transvaginal sonography were higher than that of transabdominal sonography and transvaginal sonography (P<0.05). Transabdominal sonography in combination with transvaginal sonography can complement information, improve detection rate, and reduce or avoid misdiagnosis and missed diagnosis, which provides a scientific basis for the formulation of clinical treatment scheme.


IoT Speech Recognition Application in Mass Sports Data Monitoring Based on Dynamic Adaptive Recommendation Algorithm.
In this paper, the existing dynamic adaptive recommendation methods are studied, which combine the practical application scheme of transforming the actual dynamic adaptive recommendation problem into user microblog information. After that, a dynamic adaptive weight fusion method is proposed and based on experimental verification, a real-time dynamic adaptive recommendation system is finally designed. The speech recognition of the Internet of Things takes natural language problems as the research object for a long time and takes the sound signal as the research topic. This paper analyzes the application of dynamic adaptive recommendation and Internet of Things speech recognition in mass sports data monitoring. The simulation results show that the system in this paper is convenient for users to monitor the exercise indicators in real time through the mobile client, and at the same time query the exercise historical data and compare the exercise data through the network terminal, thereby improving the exercise method and exercise load. Users can access the motion monitoring module and see the past floating state of motion parameters more intuitively than graphs, contains queries for metrics such as heart rate, body temperature, kinetic energy, pulse, and weight. Due to the diversity and complexity of people's differences, personal characteristics and business environments, sports data monitoring systems also need to be designed according to the scope of use. This paper analyzes the requirements for a motion data monitoring system and provides the system architecture design and basic data for producing detailed information for the system.


Rh-Catalyzed N-O Bond Cleavage of Anthranil: A C-H Amination Reagent for Simultaneous Incorporation of Amine and a Functional Group.
A novel Rh(III)-catalyzed C-H bond amination with the simultaneous release of a formyl group at distal positions is realized employing anthranil as a new type of C-H amination reagent. This chemistry provides an efficient protocol for the synthesis of 2-acyl diarylamines, which are important structural motifs in many bioactive compounds. This new type of C-H amination reagent possesses the advantages of high atom economy, avoids the use of external oxidants, and enables further transformation of the amination products.


Involvement of autonomic nervous system in gastric mucosal defense mechanism.
This article describes the histochemical, immunohistochemical, radioautographic, and ultrastructural localizations of aminergic and peptidergic nerves, neurotransmitter receptors, and their binding sites in the stomach wall. Cholinergic and vasoactive intestinal polypeptide (VIP)-ergic nerve fibers are distributed along the gastric microvasculature, within the myenteric and submucosal plexuses, and in the muscularis mucosae and circular muscle layer. In the mucosa, both nerve fibers evenly extend along the capillaries in association with the epithelial cells up to the mucosal surface. In particular, cholinergic nerves are proved to doubly innervate the mucosal capillaries and nonmuscular venules as well as the parietal cells. Adrenergic and neuropeptide Y (NPY)-containing nerves are distributed primarily along the arterioles of the gastric microvasculature, within the myenteric plexuses, and in the circular muscle layer. These nerve fibers extend up to the basal portion of the mucosa in close association with small arterioles, capillaries, and epithelial cells. Some of the adrenergic nerve axons are coexistent with the cholinergic nerve axons within the Schwann cell. Histamine H1 receptors are widely located on the walls of arterioles, capillaries and venules, while H2 receptors are evident not only on the parietal cells but also on the walls of the collecting venules and surrounding capillaries in the mucosa. Dopamine D1 receptors are predominantly located on the smooth muscle cells of the arterioles near the muscularis mucosae, while D2 receptors are present on the walls of postcapillary venules and collecting venules. Functional coordination of both intramural peptidergic nerves as intrinsic origin and aminergic nerves as extrinsic origin is considered to be essential for maintaining the gastric mucosal defense mechanism against a variety of aggressive factors.


[Solid pseudopapillary neoplasms of the pancreas].
Solid pseudopapillary neoplasm (SPN) is a very rare neoplasm that occurs in girls and young women in 90% of cases; the range is 779 years of age, and the median is 28 years of age. This tumour was first described by Virginia Frantz in 1959 as a papillary cystic tumour of the pancreas. The aim of this retrospective study was to analyse the incidence of SPN in all patients with a pancreatic tumour operated at the 1st Dept. of Surgery, University Hospital Olomouc between years 2006 and 2015. Clinical symptoms, imaging methods used, tumour marker positivity, histological findings, postoperative complications and disease-free interval were all evaluated. Of the 454 patients operated on between 20062015, the diagnosis of SPN was made in five female patients. The following imaging methods were used in the preoperative diagnostic process: CT, MRI, PET/CT and endosonography. In four patients the tumour was localised in the tail of the pancreas; these women underwent left-sided pancreatectomy. In one patient, the tumour was located in the pancreatic head and a pylorus-preserving pancreaticoduodenectomy was performed. Complications were seen only in one patient who underwent revision on the first postoperative day for bleeding from the pancreatic cut surface. Pancreatic fistula was not observed in any of the patients. The procedures were considered as sufficient from the oncological viewpoint due to the radical resection procedure and negative resection margin, and therefore no adjuvant oncological treatment was indicated in any of the patients. During the follow-up period, recurrence was not observed in any one of the patients. Solid pseudopapillary neoplasm of the pancreas is a rare disorder with a low malignant potential occurring primarily in young women. Generally, SPN has a good prognosis; however, advanced stages of the disease with distant metastases may be encountered in rare cases. The only curative treatment is radical surgical resection.Key words: solid pseudopapillary neoplasm Frantzs tumour pancreas.


Hip Fractures: The St Ann's Bay Regional Hospital Experience.
To study the outcome of hip fractures in a cohort of patients from two different time periods (2002-2003 and 2006-2008). Patients treated for hip fractures at the St Ann's Bay Regional Hospital (SABRH), which provides orthopaedic care for the parishes of St Ann, St Mary and Portland, were retrospectively analysed between 2002-2003 and 2006-2008. A significant increase in the recorded incidence of hip fractures, from 19 in the 2002-2003 time period to 101 in the 2006-2008 time period was noted. There was a drastic fall in the in-hospital mortality rate (43% in the 2002-2003 time period compared to 4.5% in the 2006-2008 time period). In the 2006-2008 period, 82.9% of patients were ambulant at discharge compared to 36% from the 2002-2003 time period. Early surgical fixation is necessary to allow rapid mobilization in these patients for whom the consequences of bed rest would otherwise be devastating.


Poly(hydroxyalkanoate)s-Based Hydrophobic Coatings for the Protection of Stone in Cultural Heritage.
Reversibility is a mandatory requirement for materials used in heritage conservation, including hydrophobic protectives. Nevertheless, current protectives for stone are not actually reversible as they remain on the surfaces for a long time after their hydrophobicity is lost and can hardly be removed. Ineffective and aged coatings may jeopardise the stone re-treatability and further conservation interventions. This paper aims at investigating the performance of PHAs-based coatings for stone protection, their main potential being the 'reversibility by biodegradation' once water repellency ended. The biopolymer coatings were applied to three different kinds of stone, representative of lithotypes used in historic architecture: sandstone, limestone and marble. Spray, poultice and dip-coating were tested as coating techniques. The effectiveness and compatibility of the protectives were evaluated in terms of capillary water absorption, static and dynamic contact angles, water vapour diffusion, colour alteration and surface morphology. The stones' wettability after application of two commercial protectives was investigated too, for comparison. Finally, samples were subjected to artificial ageing to investigate their solar light stability. Promising results in terms of efficacy and compatibility were obtained, although the PHAs-based formulations developed here still need improvement for increased durability and on-site applicability.


Plasmapheresis vs Conventional Insulin Therapy in Hypertriglyceridemia-Induced Acute Pancreatitis.
Hypertriglyceridemia is a rare yet firm etiology of pancreatitis, with an incidence of 2-4% in the general population. The etiology of hypertriglyceridemia itself consists of both primary and secondary causes. We discuss the case of a 37-year-old female with a strong family history of hypertriglyceridemia (primary cause) along with daily alcohol consumption (secondary cause) who initially presented to the emergency department with tingling and numbness of her bilateral upper extremities, bilateral lower extremity cramping and spasm and pins, and needles sensation in all extremities. She was found to have acute pancreatitis (AP) as a cause of hypocalcemia with elevated triglycerides of 5,823 mg/dl responsive to plasmapheresis combined with insulin drip. We explore the pathophysiology of hypertriglyceridemia-induced acute pancreatitis and the different modalities used to treat it which are still largely debated. The choice of therapy has been influenced by the cost, perceived effectiveness, and availability.


Cerebral ischemia during surgery: an overview.
Cerebral ischemia is the pathophysiological condition in which the oxygenated cerebral blood flow is less than what is needed to meet cerebral metabolic demand. It is one of the most debilitating complications in the perioperative period and has serious clinical sequelae. The monitoring and prevention of intraoperative cerebral ischemia are crucial because an anesthetized patient in the operating room cannot be neurologically assessed. In this paper, we provide an overview of the definition, etiology, risk factors, and prevention of cerebral ischemia during surgery.


Prioritizing outcome preferences in patients with ocular hypertension and open-angle glaucoma using best-worst scaling.
To quantify patients' preferences for glaucoma outcomes and use this information to prioritize outcomes that are important to patients. A cross-sectional study using best-worst scaling object case (BWS). Two hundred seventy-four participants newly diagnosed with ocular hypertension or mild to moderate open angle glaucoma from three private practices and one academic medical center in the United States. We designed a preference-elicitation survey based on findings from 25 semi-structured, qualitative interviews with patients with glaucoma (reported elsewhere). The survey asked participants to rate the importance of 13 glaucoma outcomes on a Likert scale as a warm-up exercise followed by completion of 13 BWS tasks. For each task, we presented participants a subset of four outcomes from the possible thirteen, and participants chose the most important and least important outcome. Outcomes included in the survey pertain to maintaining ability to perform vision-dependent activities of daily living (e.g., driving), maintaining visual function and perception (e.g., depth perception), minimizing need to take glaucoma drops, not experiencing ocular surface symptoms (e.g., red eyes, teary eyes), and having adequate control of intraocular pressure (IOP). We administered the survey online and analyzed response patterns using conditional logistic regression to determine the relative importance of different outcomes. Ordinal ranking of glaucoma outcomes based on preference weights. Between September 1, 2017 and February 28, 2018, we invited 1035 patients to complete our survey, among whom 274 (26%) responded. Most participants were older than 65 years of age (146/274, 53%) and currently on IOP-lowering drops (179/274, 65%). Participants identified that outcomes with the largest relative importance weight were having "adequate IOP control" and ability to "drive a car during the day," and the outcomes with the smallest relative importance weights were "maintaining appearance of the eye" and "reducing the number of IOP-lowering drops". Determining the relative importance of glaucoma outcomes to patients can help researchers design studies that may better inform clinical and regulatory decision-making. Although IOP is an outcome that researchers often measure in glaucoma clinical trials, patients also prioritized outcomes related to the ability to perform vision-dependent activities such as driving.


Priming Before In Vitro Maturation Cycles in Cancer Patients Undergoing Urgent Fertility Preservation: a Randomized Controlled Study.
In vitro maturation (IVM) of oocytes retrieved at germinal vesicle stage, followed by vitrification of mature oocytes, has emerged as a fertility preservation (FP) option. This technique was first developed for patients with polycystic ovarian syndrome. In this population, providing LH activity prior to oocyte collection has been associated with better IVM outcomes. However, the benefit of this treatment in normo-ovulatory breast cancer (BC) patients undergoing IVM for FP purpose has never been investigated. To assess if the absence of therapeutic intervention prior to oocyte retrieval for IVM modifies IVM outcomes in BC patients undergoing urgent FP, we performed a non-inferiority, randomized controlled trial. The main outcome was the total number of mature oocytes obtained and cryopreserved after IVM. A total of 172 normo-ovulatory women, suffering from BC, 18 to 39 years of age received no injection or a subcutaneous injection of hCG or GnRH agonist (GnRHa) 36 h before oocytes retrieval according to randomized allocation. The total number of cryopreserved oocytes were 5.1 ± 3.8, 5.4 ± 3.8, and 6.0 ± 4.2 oocytes, respectively in the without, hCG and GnRHa groups. Mean differences were not significant between the three groups (- 0.5; CI 97.5% [- 2.03:1.02] and - 0.22; CI 97.5% [- 1.75:1.32], respectively). Intention to treat analyses failed to show non-inferiority in the "without injection group" in comparison with hCG or GnRHa groups. Our results are not conclusive enough to modify our practices and to stop administering hCG or GnRHa before IVM cycles for FP. The study was retrospectively registered to clinical trial (ID NCT03954197) in May 2019.


Human respiratory tract infections with mycoplasmas and their in vitro susceptibility to tetracyclines and some other antibiotics.
The role played by Mycoplasma pneumoniae and possibly by other species of mycoplasma in respiratory tract infections in man is considered. The in vitro sensitivity of human mycoplasmas, that is, M. hominis, M. fermentans, M. orale type 1, M. pneumoniae, M. salivarium and T-mycoplasmas to different tetracycline analogues and some other antibiotics was determined. The strains tested were often somewhat more susceptible to doxycycline than to methacycline, minocycline and tetracycline, while oxytetracycline, per unit of weight, was in most instances 8-16 times less effective than doxycycline. The difference between the minimum concentrations of the above-mentioned tetracyclines, that inhibited metabolism of M. pneumoniae in liquid medium, and the minimum lethal concentrations of these antibiotics was small. Variation of the inoculum size of this organism had comparatively little effect on the result of the susceptibility tests with doxycycline. The study indicates a cidal rather than static action of doxycycline on M. pneumoniae. This organism as well as T-mycoplasmas were sensitive to low concentrations of erythromycin, while the strains of the other species studied were resistant to even 100 mug/ml of this antibiotic. M. pneumoniae and T-mycoplasmas were resistant to 20-80 mg/ml lincomycin, while the other human mycoplasmas were moderately sensitive. Chloramphenicol and gentamycin were generally less effective, per unit of weight, than the tetracyclines against most of the strains of mycoplasma tested. Some known effects of antibiotic treatment of mycoplasma infections in man are also discussed.


Detecting brain tumor in pathological slides using hyperspectral imaging.
Hyperspectral imaging (HSI) is an emerging technology for medical diagnosis. This research work presents a proof-of-concept on the use of HSI data to automatically detect human brain tumor tissue in pathological slides. The samples, consisting of hyperspectral cubes collected from 400 nm to 1000 nm, were acquired from ten different patients diagnosed with high-grade glioma. Based on the diagnosis provided by pathologists, a spectral library of normal and tumor tissues was created and processed using three different supervised classification algorithms. Results prove that HSI is a suitable technique to automatically detect high-grade tumors from pathological slides.


Distinguishing benign from malignant liver tumours.
Liver masses are very common and most are benign. It is therefore important to avoid unnecessary interventions for benign lesions, while at the same time ensuring accurate diagnosis of hepatic malignancies. Many cancer patients, like the general population, have incidental benign liver lesions. In planning treatment for cancer patients, it is critical to avoid inappropriate treatment decisions based on misdiagnosis of a benign lesion as a metastasis or primary liver malignancy. This article describes the salient imaging features of the common benign liver masses and outlines a general approach to distinguishing between benign and malignant hepatic lesions.


A case of panniculitis caused by Mycobacterium massiliense mimicking erythema induratum.
Among nontuberculosis mycobacteria (NTM), rapidly growing mycobacteria (RGM) are the most common causative agents of soft tissue infection. Mycobacterium massiliense, a new species of NTM, was isolated in 2004. Due to the lower virulence of RGM, M. massiliense infection is rare in the general population. Here, we report a case of multiple infective panniculitis, due to M. massiliense, mimicking erythema induratum in a patient with Cushing syndrome. The organism was identified using traditional mycobacterial culturing and staining methods as well as molecular approaches, including erythromycin ribosome transferase gene polymerase chain reaction. The patient was treated with clarithromycin for 9 months, based on antibiotic susceptibility testing.


Reversible mode of binding of serum proteins to DOTAP/cholesterol Lipoplexes: a possible explanation for intravenous lipofection efficiency.
There are many indications that interaction of serum proteins with intravenously injected cationic lipoplexes disturbs lipofection in vitro and in vivo. However, transfection with certain lipid compositions such as N-[1- (2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTAP)/cholesterol appears to be more resistant to serum and more efficacious. We investigated the mechanism of interaction between fluorescently labeled lipoplexes of the above composition and fluorescently labeled serum proteins. Fluorescence resonance energy transfer measurements in vitro indicate that serum proteins interact instantly and closely with the DOTAP/cholesterol lipoplexes. In accord with this, preinjection of fluorescently labeled serum into mice before injection of lipoplexes showed an immediate association of proteins with lipoplexes. Serum proteins colocalized with the lipoplexes in the lung vasculature; however, they dissociated from the cationic lipid as soon as 1 hr postinjection, probably because of displacement of serum proteins from lipoplexes by extracellular proteoglycans. Indeed, this displacement was imitated by heparin, a typical glycosaminoglycan, and could be explained by the inability of weakly acidic serum proteins to neutralize the DOTAP/cholesterol electrical surface potential psi0. The stability of the cationic lipid psi0 in serum could be a key reason for the high lung association and transfection efficiency with this formulation.


Corneal perforation secondary to UV radiation from a tanning lamp.
To report the case of a patient with keratoconus who developed a corneal perforation secondary to UV radiation from a tanning lamp. We believe this to be the first case of a corneal perforation secondary to UV radiation. The presentation and management of the patient and the pathophysiology of UV keratitis are discussed. Our patient developed a full-thickness corneal perforation after 30 minutes of tanning lamp exposure without eye protection. The cornea was temporized with cyanoacrylate tissue adhesive until penetrating keratoplasty could be performed. With an increased understanding of the pathophysiology of UV damage, treatment should be aimed at modulating the disease to reduce the likelihood of a poor outcome.


Synthesis and spectral properties of cholesterol- and FTY720-containing boron dipyrromethene dyes.
Two analogues (1, 2) of free cholesterol and one analogue (3) of the immunosuppressive sphingolipid FTY720 containing a boron dipyrromethene chromophore (BODIPY) were synthesized. The synthetic routes involved preparation of boron dipyrromethene moieties (5, 11), bearing a phenylethynyl group at different positions of the chromophore, and lipids (13, 20) bearing an azido group. The dye was tethered to the lipid via a 1,2,3-triazole in the linker by the click reaction. Analogues derived from 11 [in which an (E)-styrylethynyl moiety is bonded to C-5 of BODIPY] exhibited a marked red shift (approximately 70-80 nm) compared with those derived from 5 (in which a phenylethynyl moiety is bonded to C-8 of BODIPY).


Molecular machinery governing GABAergic neuron specification in the cerebellum.
Although the cerebellum contains a relatively small variety of neurons, the molecular machinery governing neuronal generation and/or subtype specification is still poorly understood. We identified a novel mutant mouse, cerebelless, which lacks the entire cerebellar cortex but survives up to the adult stages. Analyses of its phenotypes and identification of its responsible gene clarified that Ptf1a (pancreas transcription factor 1a), which encodes a bHLH transcription factor, is involved in cerebellar GABAergic neuron production. Together with recently published papers describing another bHLH gene, Math1, our study proposes that two bHLH transcription factors, PTF1A and MATH1, may participate in regionalization of cerebellar neuroepithelium, defining two distinct areas, the ventricular zone and the rhombic lip, which generate GABAergic and glutamatergic neurons, respectively. Here I will describe a novel cerebellar mutant, cerebelless, review the role of Ptf1a in GABAergic neuron production, and discuss new insights into cerebellar development from the vantage point of regulation by bHLH transcription factors.


An exTREMe disruption in Alzheimer's cleanup.
Partial loss-of-function variants in the TREM2 immune receptor are associated with increased risk for Alzheimer's disease (AD) and other forms of neurodegenerative disease, but the molecular bases for these connections are unknown. Three new structures of WT and R47H mutant TREM2 immunoglobulin-like (Ig-like) domain now reveal that R47 functions to correctly position elements of the ligand-binding surface. Intriguingly, the authors also demonstrate a disruption of receptor oligomerization by the R47H mutation, suggesting a role for ligand-induced clustering in receptor signaling and resultant plaque clearance.


[Arterial transcatheter embolization in arterio-venous fistulae therapy (aithor's transl)].
In arterio-venous malformations, arterial trans-catheter embolization can be considered as a definitive treatment, a pre-operative devascularizing technique, and a palliative treatment of those not surgically operable malformations. A very important point is choosing the correct way where to introduce the catheter and the embolizing devices. The most known devices are: synthetic fibrin foam (Gelfoam, Spongostan), Gianturco coils, and among the non reabsorbable devices a polyvinylic alcohol foam (Ivalon), the isobutyl-2-cyanoacrylate and silicone. Furthermore detachable balloons and bristle-brushes can be used. Many parameters must be taken into consideration: hemodynamic fluxes of the lesion, type of vascularization, extension of the lesion, aim of the embolization, possible risks. When embolizing large territories, the protocol must foresee several performances for the control of the embolized vessels, the presence of collateral circulation, the extension of the embolization and other afferent arteries to the lesion. Regarding the permanent occlusions it is preferable to utilize fragments of Ivalon, small silicone spheres or liquid silicone; finally, reabsorbable device must be used in the distal embolizations and non reabsorptible in the proximal embolizations. The best results have been achieved in the traumatic lesions where a direct communication exists between an artery and a vein. Among the arterio-venous malformations the best results have been achieved in cranio-facial angiomas with low flux. The possible complications are consequences of ischemia: necrotic musculo-cutaneous, cerebral or troncular changes.


Neuroanatomy of Anxiety: A Brief Review.
Anxiety disorders are among the most prevalent psychological issues worldwide, displaying the youngest age of onset and greatest chronicity of any mood or substance abuse disorder. Given the high social and economic cost imposed by these disorders, developing effective treatments is of the utmost importance. Anxiety disorders manifest in a variety of symptomatic phenotypes and are highly comorbid with other psychological diseases such as depression. These facts have made unraveling the complex underlying neural circuity an ever-present challenge for researchers. We offer a brief review on the neuroanatomy of anxiety disorders and discuss several currently available therapeutic options.


Effects of iron deficiency on cognitive function in school going adolescent females in rural area of central India.
Iron deficiency anemia is most common nutritional deficiency disorder in India and remains a formidable health challenge. Girls in the period of later school age and early adolescence are prone to develop iron deficiency. Iron deficiency leads to many non-hematological disturbances which include growth and development, depressed immune function in infants; reduces physical work capacity; decreases the cognitive function in both infants and adolescents. Present study was done to know the prevalence of iron deficiency in both the anemic and non anemic school going adolescent girls, to assess the effect of iron deficiency on cognitive functions in anemic iron deficient and non-anemic iron deficient school girls in a village school situated in central India. Methods. A secondary school having girl students in the age group of 12-15 years studying in sixth to ninth standard was selected. Serum ferritin concentration was estimated by ELISA. For assessing the cognitive function mathematics score, one multi-component test for memory, attention and verbal learning and Intelligent Quotient scores of the students were used. Results. Scholastic Performance, IQ and Scores of Mental balance, Attention & Concentration, Verbal Memory and Recognition were decreased in iron deficient girls, both anemic and non anemic as compared to the non iron deficient girls.


Effects of a Novel Psychomotor Stabilizer, IRL790, on Biochemical Measures of Synaptic Markers and Neurotransmission.
The novel small-molecule psychomotor stabilizer, IRL790, is currently in clinical trial for treatment of levodopa-induced dyskinesia and psychosis in patients with Parkinson disease. Here, we used naïve mice to investigate the effects of acute systemic administration of IRL790 on protein levels and phosphorylation states of proteins relevant for synaptic plasticity and transmission. IRL790 increased pro-brain-derived neurotrophic factor protein levels and phosphorylation at Ser1303 of the N-methyl-D-aspartate (NMDA) subtype 2B glutamate receptor (NR2B) in prefrontal cortex. IRL790 also increased the phosphorylation states at Ser19, Ser31, and Ser40, respectively, of tyrosine hydroxylase in striatum. IRL790 reduced protein levels of the NR2B receptor in striatum but not in prefrontal cortex. Taken together, we report that systemically administered IRL790 rapidly elicits changes in protein level and phosphorylation state of proteins associated with a beneficial effect on synaptic markers and neurotransmission. SIGNIFICANCE STATEMENT: The novel small-molecule psychomotor stabilizer, IRL790, is currently in clinical trial for treatment of levodopa-induced dyskinesia and psychosis in patients with Parkinson disease. In this study, we report that systemically administered IRL790 rapidly elicits changes in protein level and phosphorylation state of proteins associated with a beneficial effect on synaptic markers and neurotransmission.


Prebiotic Chemistry of HCN Tetramerization by Automated Reaction Search.
HCN oligomerization is considered to be one of the important pathways in chemical evolution. Nucleobases, aminoacids, and many other complex organic molecules can evolve through this pathway. We report an explorative study based on an automated reaction search method that avoids the cognitive bias present when searching chemical reaction space. We discuss the chemical space of the HCN dimer in detail, and the important trimers and tetramers are discussed briefly. A component-wise molecular-fingerprint-based methodology is proposed to identify molecular similarity. We present four different thermal routes to cis/trans-2,3-diaminomaleonitrile and 4-amino-1H-imidazole-5-carbonitrile, which are important intermediates in prebiotic chemistry.


Removal of penalty for breaking appointments. Final rule.
The Department of Veterans Affairs (VA) amends its regulations to remove an outdated regulation that stated that a veteran who misses two medical appointments without providing 24 hours' notice and a reasonable excuse is deemed to have refused VA medical care. VA removes this penalty because we believe it is incompatible with regulatory changes implemented after the regulation was promulgated, is not in line with current practice, and is inconsistent with VA's patient-centered approach to medical care.


Moral maps and medical imaginaries: clinical tourism at Malawi's College of Medicine.
At an understaffed and underresourced urban African training hospital, Malawian medical students learn to be doctors while foreign medical students, visiting Malawi as clinical tourists on short-term electives, learn about "global health." Scientific ideas circulate fast there; clinical tourists circulate readily from outside to Malawi but not the reverse; medical technologies circulate slowly, erratically, and sometimes not at all. Medicine's uneven globalization is on full display. I extend scholarship on moral imaginations and medical imaginaries to propose that students map these wards variously as places in which—or from which—they seek a better medicine. Clinical tourists, enacting their own moral maps, also become representatives of medicine "out there": points on the maps of others. Ethnographic data show that for Malawians, clinical tourists are colleagues, foils against whom they construct ideas about a superior and distinctly Malawian medicine and visions of possible alternative futures for themselves.


Relationship between vitamin D deficiency and thrombus load in patients with ST-elevation myocardial infarction.
Clinical studies detecting the increase in thrombotic events with vitamin D deficiency note the relationship between vitamin D and thrombosis. This study aims at evaluating the relationship between serum vitamin D levels and coronary thrombus burden. We retrospectively evaluated 77 patients with ST-elevated myocardial infarction (STEMI). Serum vitamin D levels, degree of coronary thrombus, Thrombolysis in Myocardial Infarction (TIMI) frame count and the extent and severity of atherosclerosis in coronary arteries were also measured in all cases. Patients were divided into 2 groups, according to thrombus load. The rate of vitamin D deficiency in the study population was 79.22% (< 20 ng/mL). Vitamin D levels were significantly higher in patients with a mild thrombus load than in patients with a severe thrombus load (16 vs. 13.95 p = 0.018). Gensini scores were significantly higher in patients with a severe thrombus burden than in patients with a mild thrombus burden (42 vs. 54.5 p = 0.014). There was a low negative correlation between vitamin D levels and thrombus burden classification grades (r = -0.304, p = 0.007), Cx TIMI frame counts (r = -0.402, p < 0.001), and RCA TIMI frame counts (r = -0.479, p < 0.001). There was a moderate negative correlation between serum vitamin D levels and LAD TIMI frame count (r = -0.507, p < 0.001). The results of our study showed that low 25(OH)D3 levels are an independent predictor of high coronary artery thrombus load and post-procedural TIMI frame count increase in patients with STEMI undergoing primary percutaneous coronary intervention.


Effects of feeding a thermomechanical, enzyme-facilitated, coprocessed yeast and soybean meal on growth performance, organ weights, leg health, and gut development of broiler chickens.
The development of a healthy gut during prestarter and starter phases is crucial to drive chicken's productivity. This study aimed to evaluate the effects of a thermomechanical, enzyme-facilitated, coprocessed yeast and soybean meal (pYSM) on growth performance, organ weights, leg health, and gut development in broiler chickens. A total of 576 as-hatched broiler chicks were randomly allotted to 3 dietary treatments (8 replicates/treatment, 24 chickens/replicate): a control group (C) without the pYSM, a treatment group 1 (T1), in which the pSYM was included at 20, 10, 5, 0, and 0% levels in the prestarter, starter, grower, finisher I, and finisher II feeding phases, respectively, and a treatment group 2 (T2), in which the pSYM was included at 5, 5, 5, 0, and 0% levels in each feeding phase. On d 3 and 10, 16 broilers/treatment were euthanized. The T1 broilers tended to show higher live weight (d 3 and 7) and average daily gain (prestarter and starter phases) than the other groups (P ≤ 0.10). Differently, pYSM-based diets did not influence the growth performance of the other feeding phases and the whole experimental period (P > 0.05). Relative weights of pancreas and liver were also unaffected by pYSM utilization (P > 0.05). Litter quality tended to have higher average scores in C group (P = 0.079), but no differences were observed for leg health (P > 0.05). Histomorphometry of gut, liver, and bursa of Fabricius was not affected by diet (P > 0.05). Gut immunity was driven to an anti-inflammatory pattern, with the reduction of IL-2, INF-γ, and TNF-α in the duodenum of treated birds (d 3, P < 0.05). Also, MUC-2 was greater in the duodenum of C and T2 group when compared to T1 (d 3, P = 0.016). Finally, T1-fed chickens displayed greater aminopeptidase activity in the duodenum (d 3 and 10, P < 0.05) and jejunum (d 3, P < 0.05). Feeding high levels of pYSM (10-20%) to broilers in the first 10 d tended to improve growth performance in the prestarter and starter phases. It also positively downregulated proinflammatory cytokines during the first 3 d, as well as stimulated the aminopeptidase activity in the prestarter and starter periods.


An opponent model for agent-based shared decision-making via a genetic algorithm.
Shared decision-making (SDM) has received a great deal of attention as an effective way to achieve patient-centered medical care. SDM aims to bring doctors and patients together to develop treatment plans through negotiation. However, time pressure and subjective factors such as medical illiteracy and inadequate communication skills prevent doctors and patients from accurately expressing and obtaining their opponent's preferences. This problem leads to SDM being in an incomplete information environment, which significantly reduces the efficiency of the negotiation and even leads to failure. In this study, we integrated a negotiation strategy that predicts opponent preference using a genetic algorithm with an SDM auto-negotiation model constructed based on fuzzy constraints, thereby enhancing the effectiveness of SDM by addressing the problems posed by incomplete information environments and rapidly generating treatment plans with high mutual satisfaction. A variety of negotiation scenarios are simulated in experiments and the proposed model is compared with other excellent negotiation models. The results indicated that the proposed model better adapts to multivariate scenarios and maintains higher mutual satisfaction. The agent negotiation framework supports SDM participants in accessing treatment plans that fit individual preferences, thereby increasing treatment satisfaction. Adding GA opponent preference prediction to the SDM negotiation framework can effectively improve negotiation performance in incomplete information environments.


Evidence-based advances in transfusion practice in neonatal intensive care units.
Transfusions to neonates convey both benefits and risks, and evidence is needed to guide wise use. Such evidence is accumulating, but more information is needed to generate sound evidence-based practices. We sought to analyze published information on nine aspects of transfusion practice in neonatal intensive care units. We assigned 'categories of evidence' and 'recommendations' using the format of the United States Preventive Services Task Force of the Agency for Healthcare Research and Quality. The nine practices studied were: (1) delayed clamping or milking of the umbilical cord at preterm delivery - recommended, high/substantial A; (2) drawing the initial blood tests from cord/placental blood from very low birth weight (VLBW, <1,500 g) infants at delivery - recommended, moderate/moderate B; (3) limiting phlebotomy losses of VLBW infants - recommended, moderate/substantial B; (4) selected use of erythropoiesis-stimulating agents to prevent transfusions - recommended, moderate/moderate-moderate/small B, C; (5) using platelet mass, rather than platelet count, in platelet transfusion decisions - recommended, moderate/small C; (6) permitting the platelet count to fall to <20,000/µl in 'stable' neonates before transfusing platelets - recommended, low/small I; (8) permitting the platelet count to fall to <50,000/µl in 'unstable' neonates before transfusing platelets - recommended, moderate/small C, and (9) not performing routine coagulation test screening on every VLBW infant - recommended, moderate/small C. We view these recommendations as dynamic, to be revised as additional evidence becomes available. We predict this list will expand as new studies provide more information to guide best transfusion practices.


Studies on stimulation of cell-mediated cytotoxicity by skin test antigens. I. Candida antigen stimulation of cell-mediated cytotoxicity in vitro correlated with the skin test response to candida antigen in vivo.
The magnitude of the skin test response in a group of normal volunteers to intradermal Candida antigen correlated closely with the level of cytolytic activity stimulated by Candida antigen in vitro in the peripheral blood lymphocytes from those same individuals. The cytolytic activity stimulated by Candida antigen was cell mediated, and cold target inhibition studies demonstrated that Candida antigen-stimulated effector cells were capable of cross-species (i.e., nonspecific) killing. Analysis of the Candida antigen-induced effector cell population for various cell markers did not enable absolute identification of the cell responsible for the killing. The findings in this study indicate that the stimulation of cell-mediated cytolysis by Candida antigen may be related to the delayed-type hypersensitivity response produced by the same antigen.


Using pay for performance incentives (P4P) to improve management of suspected malaria fevers in rural Kenya: a cluster randomized controlled trial.
Inappropriate treatment of non-malaria fevers with artemisinin-based combination therapies (ACTs) is a growing concern, particularly in light of emerging artemisinin resistance, but it is a behavior that has proven difficult to change. Pay for performance (P4P) programs have generated interest as a mechanism to improve health service delivery and accountability in resource-constrained health systems. However, there has been little experimental evidence to establish the effectiveness of P4P in developing countries. We tested a P4P strategy that emphasized parasitological diagnosis and appropriate treatment of suspected malaria, in particular reduction of unnecessary consumption of ACTs. A random sample of 18 health centers was selected and received a refresher workshop on malaria case management. Pre-intervention baseline data was collected from August to September 2012. Facilities were subsequently randomized to either the comparison (n = 9) or intervention arm (n = 9). Between October 2012 and November 2013, facilities in the intervention arm received quarterly incentive payments based on seven performance indicators. Incentives were for use by facilities rather than as payments to individual providers. All non-pregnant patients older than 1 year of age who presented to a participating facility and received either a malaria test or artemether-lumefantrine (AL) were eligible to be included in the analysis. Our primary outcome was prescription of AL to patients with a negative malaria diagnostic test (n = 11,953). Our secondary outcomes were prescription of AL to patients with laboratory-confirmed malaria (n = 2,993) and prescription of AL to patients without a malaria diagnostic test (analyzed at the cluster level, n = 178 facility-months). In the final quarter of the intervention period, the proportion of malaria-negative patients in the intervention arm who received AL was lower than in the comparison arm (7.3% versus 10.9%). The improvement from baseline to quarter 4 in the intervention arm was nearly three times that of the comparison arm (ratio of adjusted odds ratios for baseline to quarter 4 = 0.36, 95% CI: 0.24-0.57). The rate of prescription of AL to patients without a test was five times lower in the intervention arm (adjusted incidence rate ratio = 0.18, 95% CI: 0.07-0.48). Prescription of AL to patients with confirmed infection was not significantly different between the groups over the study period. Facility-based incentives coupled with training may be more effective than training alone and could complement other quality improvement approaches. This study was registered with ClinicalTrials.gov (NCT01809873) on 11 March 2013.


Doppler ultrasonic detection of particulate release during hemodialysis with cellulose hollow-fiber and sorbent suspension reciprocating dialyzers.
Doppler ultrasound is a noninvasive technique for monitoring moving objects such as flowing blood while ignoring stationary objects such as shunt tubing. A Doppler system was investigated to determine its sensitivity in detecting particulate release in blood during hemodialysis. Seven hemodialysis procedures with dogs and six trials with humans were done using a sorbent suspension reciprocating dialyzer ( SSRD ). Two additional trials were done with humans using a cellulose acetate hollow-fiber dialyzer (HFD). A large increase (approximately twofold) was found in the reflected Doppler signal in outflowing blood from the SSRD and HFD in both dogs and humans. Numerous additional studies to characterize the nature of the particulate matter showed platelet aggregates in the dogs and fibrinogen-fibrin degradation products in the humans to be present in the outflowing blood. In vitro studies suggested microscopic air bubbles (less than 25 micron in diameter) may have contributed to the particulate matter detected during hemodialysis by this sensitive monitoring system.


MyoLoop: Design, development and validation of a standalone bioreactor for pathophysiological electromechanical in vitro cardiac studies.
Mechanical load is one of the main determinants of cardiac structure and function. Mechanical load is studied in vitro using cardiac preparations together with loading protocols (e.g., auxotonic, isometric). However, such studies are often limited by reductionist models and poorly simulated mechanical load profiles. This hinders the physiological relevance of findings. Living myocardial slices have been used to study load in vitro. Living myocardial slices (LMS) are 300-μm-thick intact organotypic preparations obtained from explanted animal or human hearts. They have preserved cellular populations and the functional, structural, metabolic and molecular profile of the tissue from which they are prepared. Using a three-element Windkessel (3EWK) model we previously showed that LMSs can be cultured while performing cardiac work loops with different preload and afterload. Under such conditions, LMSs remodel as a function of the mechanical load applied to them (physiological load, pressure or volume overload). These studies were conducted in commercially available length actuators that had to be extensively modified for culture experiments. In this paper, we demonstrate the design, development and validation of a novel device, MyoLoop. MyoLoop is a bioreactor that can pace, thermoregulate, acquire and process data, and chronically load LMSs and other cardiac tissues in vitro. In MyoLoop, load is parametrised using a 3EWK model, which can be used to recreate physiological and pathological work loops and the remodelling response to these. We believe MyoLoop is the next frontier in basic cardiovascular research enabling reductionist but physiologically relevant in vitro mechanical studies. NEW FINDINGS: What is the central question of this study? Can cardiac tissues be cultured under conditions that do not simulate the mechanical load the heart is exposed to in vivo? What is the main finding and its importance? A culture bioreactor was developed that can keep living heart tissue alive in vitro under continuous electromechanical stimulation. The device, MyoLoop, simulates the cardiac cycle on a beating slice during culture, recreating the in vivo workload of the heart in vitro. MyoLoop is a novel translational platform for cardiac studies.


Enhanced susceptibility of LDL to oxidative modification in a CTX patient:- role of chenodeoxycholic acid in xanthoma formation.
Cerebrotendinous xanthomatosis (CTX) is a rare familial sterol storage disease, causing multiple xanthomas in tendons and the brain. The underlying biochemical defect is a lack of the hepatic mitochondrial cholesterol 27-hydroxylase involved in the normal biosynthesis of bile acid, resulting in reduced biosynthesis of chenodeoxycholic acid (CDCA). It has been reported that administration of CDCA to CTX patients improves neurological disorders and xanthomas of the Achilles tendon. The present study investigated the effect of CDCA on the mechanism of cholesterol accumulation in macrophages, the major cells in xanthoma. The LDL from the patients in this study was significantly more susceptible to oxidative modification than normal LDL, and supplement therapy with CDCA resulted in an improvement in the susceptibility to oxidative modification. In the incubation of CDCA with plasma, 13% of the CDCA added to serum was recovered in the LDL fraction. In addition, supplementation with CDCA enhanced cholesteryl ester transfer protein (CETP) activity and reduced high-density-lipoprotein cholesterol levels in the plasma. This evidence suggests that the multiple xanthomas observed in CTX may be induced by increased oxidized LDL and the low activity of CETP, both of which are caused by a lack of CDCA.


Wnt signal specifies the intrathalamic limit and its organizer properties by regulating Shh induction in the alar plate.
The structural complexity of the brain depends on precise molecular and cellular regulatory mechanisms orchestrated by regional morphogenetic organizers. The thalamic organizer is the zona limitans intrathalamica (ZLI), a transverse linear neuroepithelial domain in the alar plate of the diencephalon. Because of its production of Sonic hedgehog, ZLI acts as a morphogenetic signaling center. Shh is expressed early on in the prosencephalic basal plate and is then gradually activated dorsally within the ZLI. The anteroposterior positioning and the mechanism inducing Shh expression in ZLI cells are still partly unknown, being a subject of controversial interpretations. For instance, separate experimental results have suggested that juxtaposition of prechordal (rostral) and epichordal (caudal) neuroepithelium, anteroposterior encroachment of alar lunatic fringe (L-fng) expression, and/or basal Shh signaling is required for ZLI specification. Here we investigated a key role of Wnt signaling in the molecular regulation of ZLI positioning and Shh expression, using experimental embryology in ovo in the chick. Early Wnt expression in the ZLI regulates Gli3 and L-fng to generate a permissive territory in which Shh is progressively induced by planar signals of the basal plate.


Identification of a subpopulation of marrow MSC-derived medullary adipocytes that express osteoclast-regulating molecules: marrow adipocytes express osteoclast mediators.
Increased marrow medullary adipogenesis and an associated decrease in bone mineral density, usually observed in elderly individuals, is a common characteristic in senile osteoporosis. In this study we investigated whether cells of the medullary adipocyte lineage have the potential to directly support the formation of osteoclasts, whose activity in bone leads to bone degradation. An in vitro mesenchymal stem cell (MSC)-derived medullary adipocyte lineage culture model was used to study the expression of the important osteoclast mediators RANKL, M-CSF, SDF-1, and OPG. We further assessed whether adipocytes at a specific developmental stage were capable of supporting osteoclast-like cell formation in culture. In vitro MSC-derived medullary adipocytes showed an mRNA and protein expression profile of M-CSF, RANKL, and OPG that was dependent on its developmental/metabolic stage. Furthermore, RANKL expression was observed in MSC-derived adipocytes that were at a distinct lineage stage and these cells were also capable of supporting osteoclast-like cell formation in co-cultures with peripheral blood mononuclear cells. These results suggest a connection between medullary adipocytes and osteoclast formation in vivo and may have major significance in regards to the mechanisms of decreased bone density in senile osteoporosis.


Strong in the Face of Adversity.
Palliative care provides holistic care to individuals in life-threatening or life-limiting conditions. This narrative describes the journey of Kanchan. A strong lady and a doting mother, she came to the hospital by choice, in immense pain and with swelling. Her narrative illustrates how the palliative approach draws out the inner strengths of individuals by focusing on their issues and needs. Kanchan was able to benefit from physiotherapy to reduce the risk of lymphoedema after surgery for breast cancer. Her narrative illustrates how she found comfort and relief, ably supported by the dedicated hospital team. Although a chance encounter led her to the hospital, her story emphasizes the need for greater awareness about palliative services to ensure early intervention.


The mathematical model for total pubertal growth in idiopathic growth hormone (GH) deficiency suggests a moderate role of GH dose.
The role of GH treatment during total pubertal growth (TPG) is still unclear. We developed a prediction model for TPG (centimeters) through a multiple regression analysis of various prepubertal parameters in 303 adolescents with idiopathic GH deficiency from the KIGS database. Prepubertal catch-up growth and near-adult height were achieved, and GH dose was kept constant at approximately 30 micro g/kg.d. The model was validated on a cohort of 36 patients from one center. Four TPG predictors explained 70% of the variability with an error SD of 4.2 cm: gender (TPG in males was >11.3 cm vs. that in females), age at onset of puberty (negative), height SD score minus midparental height SD score at puberty onset (negative), and mean GH dose during puberty (positive). Our analysis suggests that TPG in idiopathic GH deficiency is only moderately dependent on GH dose. The use of a higher GH dosage at the onset of puberty should thus depend on the individual's height development. The TPG model aids in the planning of individually optimized and cost-effective GH treatment.


The Molecule Sensitized Pattern of Atopic Dermatitis Patients Who Co-Sensitized to Shrimp, Cockroaches, Crab and House Dust Mites.
This study investigated the molecule sensitized pattern of atopic dermatitis patients who co-sensitized to shrimp, cockroaches, crab and house dust mites allergens and promoted the development of clinical accurate diagnosis and treatment.


High prevalence of vancomycin-resistant enterococci in Swedish sewage.
In Europe the use of the growth promoter avoparcin is considered to have selected for vancomycin-resistant enterococci (VRE). Sweden ceased using avoparcin in 1986, and only occasional cases of VRE from hospitals have been reported since 1995. Within the framework of a European study, samples from urban raw sewage, treated sewage, surface water, and hospital sewage in Sweden (n = 118) were screened for VRE. Surprisingly, VRE were isolated from 21 of 35 untreated sewage samples (60%), from 5 of 14 hospital sewage samples (36%), from 6 of 32 treated sewage samples (19%), and from 1 of 37 surface water samples. Thirty-five isolates from 33 samples were further characterized by geno- and phenotyping, MIC determination, and PCR analysis. Most isolates (30 of 35) carried the vanA gene, and the majority (24 of 35) of the isolates were Enterococcus faecium. Most of the VRE were multiresistant. The typing revealed high diversity of the isolates. However, one major cluster with seven identical or similar isolates was found. These isolates came from three different sewage treatment plants and were collected at different occasions during 1 year. All VRE from hospital sewage originated from one of the two hospitals studied. That hospital also had vancomycin consumption that was 10-fold that of the other. We conclude that VRE were commonly found in sewage samples in Sweden. The origin might be both healthy individuals and individuals in hospitals. Possibly, antimicrobial drugs or chemicals released into the sewage system may sustain VRE in the system.


Linking palaeoenvironmental data and models to understand the past and to predict the future.
Complex, process-based dynamic models are used to attempt to mimic the intrinsic variability of the natural environment, ecosystem functioning and, ultimately, to predict future change. Palaeoecological data provide the means for understanding past ecosystem change and are the main source of information for validating long-term model behaviour. As global ecosystems become increasingly stressed by, for example, climate change, human activities and invasive species, there is an even greater need to learn from the past and to strengthen links between models and palaeoecological data. Using examples from terrestrial and aquatic ecosystems, we suggest that better interactions between modellers and palaeoecologists can help understand the complexity of past changes. With increased synergy between the two approaches, there will be a better understanding of past and present environmental change and, hence, an improvement in our ability to predict future changes.


Overdiagnosis of heart failure in primary care: a cross-sectional study.
Access to echocardiography in primary care is limited, but is necessary to accurately diagnose heart failure (HF). To determine the proportion of patients with a GP's diagnosis of HF who really have HF. A cross-sectional study of patients in 30 general practices with a GP's diagnosis of heart failure, based on the International Classification of Primary Care (ICPC) code K77, between June and November 2011. Electronic medical records of the patients' GPs were scrutinised for information on the diagnosis. An expert panel consisting of two cardiologists and an experienced GP used all available diagnostic information, and established the presence or absence of HF according to the criteria of the European Society of Cardiology (ESC) HF guidelines. In total, 683 individuals had a GP's diagnosis of HF. The mean age was 77.9 (SD 11.4) years, and 42.2% were male. Of these 683, 79.6% received cooperative care from a cardiologist. In 73.5% of cases, echocardiography was available for panel re-evaluation. Based on consensus opinion of the panel, 434 patients (63.5%, 95% confidence interval [CI] = 59.9 to 67.1) had definite HF, of which 222 (32.5%, 95% CI = 30.9 to 34.1) had HF with a reduced ejection fraction (HFrEF), 207 (30.3%, 95% CI = 29.0 to 31.6) had HF with a preserved ejection fraction (HFpEF), and five (0.7%, 95% CI = 1.2 to 2.6) had isolated right-sided HF. In 17.3% of cases (95% CI = 14.4 to 20.0), the panel considered HF absent, and in 19.2% (95% CI = 16.3 to 22.2) the diagnosis remained uncertain. More than one-third of primary care patients labelled with HF may not have HF, and such overdiagnosis may result in inadequate patient management.


Disease Progression in Papillary Thyroid Cancer with Biochemical Incomplete Response to Initial Therapy.
Dynamic risk stratification is utilized in the follow-up of patients with papillary thyroid carcinoma (PTC). Analysis of outcomes after biochemical incomplete response (BIR) to initial therapy will allow better individualization of care. A total of 494 patients with PTC were followed prospectively. Immunohistochemistry (IHC) for BRAFV600E mutation was completed on all surgical specimens. After exclusion of patients with inadequate data, 353 patients were stratified into four categories of response to initial therapy: excellent, biochemical incomplete, structural incomplete, or indeterminate. Patients with BIR, defined as elevated stimulated thyroglobulin >2 µg/L with negative imaging, were analysed for progression of disease. The primary outcome measure was development of structural recurrence. Forty-nine of 353 (13.9%) patients had BIR. BRAFV600E mutation was present in 32 of 49 (65.3%) with BIR. Progression to structural recurrence occurred in 8 of 49 (16.3%) with BIR, all of whom were positive for the BRAFV600E mutation (p = 0.02). Nine patients (18%) with BIR remitted during follow-up to no evidence of disease (6 had additional RAI therapy). After mean follow-up of 35 months, 12 patients with BIR (24%) remained biochemically abnormal with no structural evidence of disease. Patients with BIR following initial treatment for PTC have generally favorable outcomes. Positive IHC for BRAFV600E identifies patients at risk of structural disease recurrence.


Experience with 122 consecutive liver transplant procedures at King Faisal Specialist Hospital and Research Center.
Saudi Arabia is a leading country in the Middle East in the field of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT). We present out experience with DDLT and LDLT at King Faisal Specialist Hospital and Research Center (KFSHRC) for the period from April 2001 to January 2007. We performed 122 LT procedures (77 DDLTs and 45 LDLTs) in 118 patients (4 re-transplants) during this period of time. The number of adult and pediatric procedures was 107 and 11, respectively. The overall male/female ratio was 66/52 and the median age of patients was 43 years (range, 2-63 years). In the DDLT group, the median operating time was 8 hours (range, 4-19), the median blood transfusion was 6 units (range, 0-40), and the median hospital stay was 13 days (range, 6-183). In the DDLT group, after a mean follow-up period of 760 days (range, 2-2085), the overall patient and graft survival rate was 86%. In the LDLT group, the median operating time was 11 hours (range, 7-17), the median blood transfusion was 4 units (range, 0-65), and the median hospital stay was 15 days (range, 7-127). In the LDLT group, and after a mean follow-up period of 685 days (range, 26- 1540), the overall patient and graft survival rates were 90% and 80%, respectively with no significant difference in patient and graft survivals between groups. Biliary complications were significantly higher in LDLT compared to DDLT (P<0.05). Vascular complications were also significantly higher in LDLT compared DDLT (P<0.05). Both DDLT and LDLT are being successfully performed at KFSHRC with early experience indicating a higher rate of biliary and vascular complications in the LDLT group.


Veracity in big data: How good is good enough.
Veracity, one of the five V's used to describe big data, has received attention when it comes to using electronic medical record data for research purposes. In this perspective article, we discuss the idea of data veracity and associated concepts as it relates to the use of electronic medical record data and administrative data in research. We discuss the idea that electronic medical record data are "good enough" for clinical practice and, as such, are "good enough" for certain applications. We then propose three primary issues to attend to when establishing data veracity: data provenance, cross validation, and context.


Outcome measurement in home health.
Home health occupational therapists, as well as their colleagues in other settings, cannot afford to ignore the need for clear, objective, and reliable outcome measurements. Such measurement will provide patients and payers with information on the value and quality of specific occupational therapy services and their overall value to various patient populations.


Improving transparency-A call to include social housing information in biomedical research articles involving nonhuman primates.
The social setting of animal subjects in the research environment has known effects on a variety of dependent measures used in biomedical research. Proper evaluation of the robustness of published research is dependent upon transparent, detailed, and accurate reporting of research methods, including the animals' social housing conditions. However, to date, most research articles utilizing nonhuman primates (NHPs) provide only partial data on this topic, hampering transparency, and reproducibility. Therefore, we call for the inclusion of information pertaining to the social aspects of the animals' housing conditions in publications involving NHPs to improve transparency. We argue that including this information in scientific publications is crucial for the interpretation of research findings in the appropriate context and for understanding unexplained variability in study findings. Finally, the inclusion of this information in publications will additionally familiarize scientists with how other researchers conducting similar studies are housing their animals and will encourage them to consider the implications of various housing conditions on their research outcomes.


Conformational changes in the membrane-bound hydrogenase of Bradyrhizobium japonicum. Evidence that the redox state of the enzyme affects its accessibility to protease and membrane-impermeant reagents.
The sensitivity of the membrane-bound hydrogenase of Bradyrhizobium japonicum to inactivation by proteases and membrane-impermeant protein modification reagents was compared under hydrogen versus oxygen. In membrane vesicles, the half-life of enzyme inactivation by trypsin of the H2-reduced enzyme was approximately 10 min, whereas O2-oxidized enzyme was much less sensitive to trypsin inactivation (half-life of over 90 min). Diazobenzene sulfonate (DABS) affected the enzyme activity in a manner similar to proteases. With DABS, the enzyme had a half-life of 2-3 min under H2 versus over 30 min under O2. Experiments in which the gas phase (containing either H2 or O2) available to the membranes was changed prior to the protease or chemical modification treatments indicated that it is the redox state of the enzyme at the time of the treatment which determines the sensitivity of the enzyme to inactivation. The redox-dependent differences in the behavior of the membrane-bound enzyme were attributed to changes in the accessibility of the small (33 kDa) subunit. The kinetics of enzyme inactivation by trypsin, under H2, correlated very well with the degradation of the intact 33-kDa subunit, whereas the large subunit (65 kDa) was rather resistant to proteolytic degradation. DABS treatment was found to decrease the reactivity of the small subunit to its antibody concomitant with enzyme inactivation under H2, but without such an effect on the O2-oxidized enzyme. In contrast to the results with the membrane-bound enzyme, purified dehydrogenase was found to be equally susceptible to inactivation by proteolysis or chemical modification irrespective of whether the treatments were performed under H2 or O2. These results indicate that, in the membrane, hydrogenase undergoes a redox-linked conformational change, whereby the small subunit of the enzyme becomes more accessible to external reagents when the enzyme is in its reduced form.


Histopathological findings in cochlear implants in cats.
This histopathological study on cats has shown that electrodes may be implanted into the cochlea through the round window or an opening drilled over the middle and apical turns without loss of the spiral ganglion cells or auditory nerve fibres. It has also shown that infection, leading to a labyrinthitis, was more likely to occur when an opening was drilled in the cochlea, and this could lead to a marked destruction of the cochlear structures, and loss of the spiral ganglion cells.