Alternatively spliced exon 5 of the FERM domain of protein 4.1R encodes a novel binding site for erythrocyte p55 and is critical for membrane targeting in epithelial cells.
Direct physical linkage of MAGUKs to the actin cytoskeleton was first established by the interaction of erythrocyte p55 with the FERM domain of protein 4.1R. Subsequently, it was reported that p55 binds to a 51-amino acid peptide, encoded by exon 10, located within the FERM domain of protein 4.1R. In this study, we investigated the nature of the p55-FERM domain binding interface and show that p55 binds to a second 35-amino acid peptide, encoded by an alternatively spliced exon 5, located within the FERM domain of protein 4.1R. Competition and Surface Plasmon Resonance-binding measurements suggest that the peptides encoded by exons 5 and 10 bind to independent sites within the D5 domain of p55. Interestingly, the full length 135 kDa isoform of protein 4.1R containing both exons 5 and 10 was targeted exclusively to the plasma membrane of epithelial cells whereas the same isoform without exon 5 completely lost its membrane localization capacity. Together, these results indicate that p55 binds to two distinct sites within the FERM domain, and the alternatively spliced exon 5 is necessary for the membrane targeting of protein 4.1R in epithelial cells. Since sequences similar to the exon 5-peptide of protein 4.1R and D5 domain of p55 are conserved in many proteins, our findings suggest that a similar mechanism may govern the membrane targeting of other FERM domain containing proteins.


Outcomes of pessary fitting trials for patients with stage IV pelvic organ prolapse: a prospective study.
The objective was to evaluate the efficacy of pessaries in the treatment of stage IV pelvic organ prolapse (POP) and identify the influencing factors. One hundred and fifty-seven patients with stage IV symptomatic POP were admitted to the hospital for pessary fitting. A successful pessary fitting was defined as a patient fitted with a pessary at the initial fitting in whom use continued 2 weeks later. The rates of successful pessary fitting, patient satisfaction, remission of prolapse and urinary symptoms, and the occurrence of factors associated with successful pessary fitting were calculated and predictors of appropriate pessary type selection were analyzed. A total of 130 patients with stage IV POP had a successful pessary fitting (82.8%). The satisfaction rate associated with the two types of pessaries was more than 90%. The success rate among patients undergoing a ring pessary fitting trial was 44.6%, and 84.3% of the patients were self-managed. Prolapse symptoms significantly improved in 90% of cases, and urinary symptoms improved in 58-93% of cases from baseline. The number of vaginal deliveries, history of hysterectomy and vaginal introitus/total vaginal length (TVL) ratio were independent risk factors associated with unsuccessful pessary fitting. For patients with stage IV POP, the successful fitting rate is as high as 80% or more. More vaginal deliveries, a history of hysterectomy, and a larger vaginal introitus/TVL ratio (ratio >0.6) were predictors of unsuccessful pessary fitting.


Hand Doppler flowmetry for surgical planning of pedicled flap in extensive full-thickness scalp reconstruction.
Reconstruction of scalp defects can be performed with local flaps for medium to large defects (2-25 cm2) and microvascular free flaps for extensive full-thickness scalp reconstruction greater than 25 cm2. Doppler flowmetry with its ability to exactly mark the course of arteries on the overlying skin, is a useful tool for the surgical planning of large local flaps. In our retrospective study conducted on 38 patients (all patients had malignancies or post-traumatic scalp defects), consisting of 39 total surgical procedures, we studied the impact of doppler ultrasonic flowmetry in the surgical planning for pedicled flaps in extensive full-thickness scalp reconstruction (>25 cm2) by evaluating overall flap survival rate. Nine different types of local flaps were employed in the scalp reconstruction: Superficial temporal artery (STA) pedicled rotation flap, STA pedicled transposition flap, STA islanded flap, bipedicled STA flap, bipedicled fronto-occipital flap, Supraorbital/Supratrochlear artery rotation flap, Supraorbital/Supratrochlear artery transposition flap, Occipital artery (OA) pedicled rotation flap, OA pedicled transposition flap. Before each surgical procedure a hand held doppler Huntleigh Diagnostic flowmeter with a 8 MHz probe was used to identify and follow the course of the arteries. Flap survival rate was 100%. No postoperative complications related to the flap were reported, while in two patients a partial skin graft failure occurred.


[Andrew Lees «Mentored by a Madman: The William Burroughs Experiment»].
Andrew Lees «Mentored by a Madman: The William Burroughs Experiment».


Post-traumatic spinal stenosis.
A normal width of the peridural intracanal spinal space has been described as necessary for normal neural tissue mobility. This virtual functional space, called spinal reserve capacity (SRC) is measurable with the aid of computerized tomography. Aging and various lumbar pathological conditions have been described as leading to attenuation or obliteration of this reserve capacity, a phenomenon essential for a symptomatic lumbar canal stenosis. This article discusses delayed, post-traumatic obliteration of the SRC, and its symptoms and signs are illustrated with ten case histories.


Does arterial stiffness affect orthostatic hypotension among high-altitude Tibetans?
This study aimed to investigate the association between arterial stiffness and orthostatic hypotension (OH) and orthostatic blood pressure (BP) changes among Tibetans living at high altitude. A total of 630 high-altitude Tibetans were included (56.53 ± 10.16 years; 246 men). Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). OH was defined as a decrease in systolic BP (SBP) >20 mmHg or a decrease in diastolic BP (DBP) >10 mmHg after 1 min or 3 min of moving from supine to standing position. The prevalence of OH in this population was 6.3%. Compared with subjects without OH, the subjects with OH had a higher baPWV (P < 0.001). Multiple logistical regression found that baPWV was significantly associated with the occurrence of OH (OR 1.147, CI 95% 1.028-1.280, P = 0.014). Spearman correlation analysis showed that baPWV was negatively associated with orthostatic changes in SBP and DBP(r = -0.256, P < 0.001 and r = -0.194, P < 0.001, respectively). Further multiple stepwise linear regression analysis showed that baPWV was independently correlated with orthostatic BP changes (SBP: β = -0.599, P < 0.001; DBP: β = -0.333, P < 0.001). Moreover, increased baPWV was correlated with attenuation of orthostatic heart rate changes. No significant association was observed between hematocrit or hemoglobin concentration and OH. BaPWV was significantly associated with the occurrence of OH and orthostatic changes in the SBP and DBP, which suggests that arterial stiffness may be a potential mechanism of impaired hemodynamic response to orthostatic challenges among high-altitude Tibetans.


Rhythmicity, randomness and synchrony in climbing fiber signals.
The role of the climbing fiber input to the cerebellum has been enigmatic, with recent studies focusing on its temporal and spatial firing patterns. Debate remains as to whether climbing fibers provide a periodic clock for coordinating movements or lead to long-term modification of Purkinje cell activity as the basis of motor learning. Rhythmic and synchronous activity of climbing fibers can cause movements at the same frequency in some preparations, suggesting a role in motor timing. However, in awake monkeys climbing fiber signals have been reported to occur at random, presenting a problem for clock theories. Yet synchronous patterns of discharge are consistently observed among several Purkinje cells within a narrow parasagittal longitudinal band. Here, we review recent experimental and theoretical studies and attempt to provide a coherent account of the interplay between rhythmicity, randomness and synchrony in climbing fiber activity, with a particular reference to studies in chaos.


Role of endothelial dysfunction in heart failure.
Coronary artery disease is a major underlying etiology for heart failure. The role of coronary microvascular disease, and endothelial dysfunction, in the pathophysiology of heart failure is poorly appreciated. Endothelial dysfunction, induced by oxidative stress, contributes to the development of heart failure. Alterations of endothelial function and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway are involved in the pathophysiology of heart failure with both reduced and preserved ejection fraction. Indeed, an altered endothelium dependent vasodilatation, causing repeated episodes of ischemia/reperfusion, can induce a chronic stunned myocardium with systolic dysfunction and an increased diastolic stiffness with diastolic dysfunction. Moreover, the altered NO-cGMP pathway directly affects myocardial homeostasis. Endothelial dysfunction is associated with worse prognosis and higher rate of cardiovascular events. Potential therapeutic strategies targeting the NO-cGMP pathway in patients with HF will be discussed in this review article. Although clinical data are still inconclusive, the NO-cGMP pathway represents a promising target for therapy.


Prevalence of Taenia saginata cysticerci in Addis Ababa Abattoir Enterprise, Ethiopia.
An abattoir-based survey was conducted in Addis Ababa from December 2018 to April 2019 with the objectives of determining the prevalence of bovine cysticercosis and the viability of Taenia saginata cysticerci. Routine meat inspection was performed on the study animals. Palpation followed by incision of the heart, tongue, triceps muscle, masseter muscle and diaphragm were made to detect the presence of T. saginata cysts. From the detected cysts, 41 were randomly selected and subjected to viability test. From the total 500 study animals, 14(2.8%) had varying number of T. saginata cysts. The highest proportion of T. saginata cyst was observed in the triceps muscle 6(42.8%), followed by heart 3(21.4%), tongue 2(14.3%) and masseter muscle 2(14.3%). There was no cyst observed in the liver or diaphragm. Of the total randomly selected 41 cysticerci, 20(48.8%) were found to be viable while the rest 21(51.2%) cysticerci were found to be non-viable. Sex, breed, age, and body condition of the study animals were found to have no significant association with the occurrence of cysticerci (P > 0.05). Even though routine meat inspection has low sensitivity and usually under-estimates the prevalence of the disease, bovine cysticercosis was found to be prevalent in the study area. Therefore, an appropriate control program involving enforcement of meat inspection, promoting public awareness and improving personal and environmental hygiene should be designed and implemented.


Effect of cold storage on cholinergic responses induced by electrical field stimulation in human bronchi.
The aim of the present study was to examine the effects of cold storage on the responses induced by electrical field stimulation (EFS) in human bronchial preparations. Responses induced by EFS and acetylcholine were studied in human bronchial rings mounted in organ baths, either on the day of surgery or after storage at 4 degrees C in Krebs-Henseleit solution for 24 and 48 h, respectively. The responses induced by EFS were studied at different voltages (20, 40 and 60 V) and at a range of frequencies (2, 4, 8, 10, 30 and 60 Hz). EFS induced a triphasic response, consisting of a cholinergic contraction, followed by a relaxation and subsequently a slow sustained contraction. The amplitude of the EFS-induced response was enhanced with increasing voltages and increasing frequencies. None of the three EFS-induced phases were significantly altered by cold storage at 24h, whereas storage for 48 h significantly decreased the reactivity of the preparations. Likewise, the contractions induced by acetylcholine were unaltered after 24h, but significantly depressed after 48 h. These results suggest that the reactivity of human bronchial preparations to EFS is not altered when tissues are conserved for 24h, whereas prolonged storage should be avoided.


Successful pregnancy in a cystic fibrosis patient with a severe impairment of lung function receiving Elexacaftor-Tezacaftor-Ivacaftor.
Before the arrival of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators women with CF and impaired lung function were experiencing a high risk of complications and mortality during and the years after pregnancy. The arrival of the highly efficient CFTR modulator, Elexacaftor-Tezacaftor-Ivacaftor (ETI) resulted in an improvement of lung function, quality of life and fertility. Here we report a case of successful pregnancy and uncomplicated delivery for a CF patient with severely impaired lung function receiving ETI prior to conception.


Disruption of poly (3-hydroxyalkanoate) depolymerase gene and overexpression of three poly (3-hydroxybutyrate) biosynthetic genes improve poly (3-hydroxybutyrate) production from nitrogen rich medium by Rhodobacter sphaeroides.
Due to various environmental problems, biodegradable polymers such as poly (3-hydroxybutyrate) (PHB) have gained much attention in recent years. Purple non-sulfur (PNS) bacteria have various attractive characteristics useful for environmentally harmless PHB production. However, production of PHB by PNS bacteria using genetic engineering has never been reported. This study is the first report of a genetically engineered PNS bacterial strain with a high PHB production. We constructed a poly (3-hydroxyalkanoate) depolymerase (phaZ) gene-disrupted Rhodobacter sphaeroides HJ strain. This R. sphaeroides HJΔphaZ (pLP-1.2) strain showed about 2.9-fold higher volumetric PHB production than that of the parent HJ (pLP-1.2) strain after 5 days of culture. The HJΔphaZ strain was further improved for PHB production by constructing strains overexpressing each of the eight genes including those newly found and annotated as PHB biosynthesis genes in the KEGG GENES Database. Among these constructed strains, all of gene products exhibited annotated enzyme activities in the recombinant strain cells, and HJΔphaZ (phaA3), HJΔphaZ (phaB2), and HJΔphaZ (phaC1) showed about 1.1-, 1.1-, and 1.2-fold higher volumetric PHB production than that of the parent HJΔphaZ (pLP-1.2) strain. Furthermore, we constructed a strain that simultaneously overexpresses all three phaA3, phaB2, and phaC1 genes; this HJΔphaZ (phaA3/phaB2/phaC1) strain showed about 1.7- to 3.9-fold higher volumetric PHB production (without ammonium sulfate; 1.88 ± 0.08 g l-1 and with 100 mM ammonium sulfate; 0.99 ± 0.05 g l-1) than those of the parent HJ (pLP-1.2) strain grown under nitrogen limited and rich conditions, respectively. In this study, we identified eight different genes involved in PHB biosynthesis in the genome of R. sphaeroides 2.4.1, and revealed that their overexpression increased PHB accumulation in an R. sphaeroides HJ strain. In addition, we demonstrated the effectiveness of a phaZ disruption for high PHB accumulation, especially under nitrogen rich conditions. Furthermore, we showed that PNS bacteria may have some unidentified genes involved in poly (3-hydroxyalkanoates) (PHA) biosynthesis. Our findings could lead to further improvement of environmentally harmless PHA production techniques using PNS bacteria.


Immunolocalization of cathepsins B, H and L in skeletal muscle of X-linked muscular dystrophy (mdx) mouse.
The amounts of non-collagen proteins (muscle structural proteins) and the activity of creatine kinase were significantly decreased in muscles of 28-day-old mdx mice. The activities of lysosomal thiol proteases such as cathepsins B and L were increased in muscles of mdx mice at as early as 10 days of age. Endogenous thiol proteinase inhibitor and various lysosomal hydrolases also showed increased activities. The localization of cathepsins B, H and L, and endogenous thiol proteinase inhibitor was investigated using the respective specific antibodies. While only invading macrophages were stained strongly with anticathepsin B and H, and anti-thiol proteinase inhibitor antibodies, cathepsin L was localized in muscle cells as well as in invading macrophages. Cathepsin L in muscle cells itself may initially degrade muscle structural proteins, before lysosomal thiol proteases, mainly derived from macrophages, degrade them in skeletal muscles of mdx mice.


Funnel Shaped Anterior Communicating Artery Fenestration Mistaken for an Aneurysm: A Cautionary Tale.
This report portrays a case of a funnel shaped anterior communicating artery (ACoA) fenestration which was mistaken as a small A1 aneurysm in a subarachnoid hemorrhage case. Although tridimensional rotational digital subtraction angiography improves aneurysm diagnosis specially at the ACoA complex, current spatial resolution might leave behind a considerable percentage of ACoA fenestrations. This may lead to diagnostic errors and unnecessary treatments risking iatrogenic complications. Luckily for our patient, a concomitant aneurysm warranted clipping and subsequent surgical exploration of the ACoA complex revealed the pitfall, thus preventing further action. Interestingly, another group of authors who reported similar misdiagnosis with ACoA aneurysms were able to prevent a third error, thanks to the experience acquired with 2 prior cases. Therefore, this clinical image aims to raise wider awareness of the need for very cautious consideration of imaging depicting small and/or atypical aneurysms in the ACoA complex.


Instituting patient interviewing team simulation assessments into the curriculum.
Literature demonstrates that the primary concerns for entry-level graduates relate to standards covering professional competencies and outcome expectations; knowledge, skills, attitudes, and values; and pharmacy practice experiences. Implementing patient interviewing team simulation assessments (PITSA) into the curriculum is an option to address these concerns. PITSA are formative or summative assessment tools that can measure student's ability to communicate with a healthcare provider in addition to evaluating the student's clinical knowledge and skills during scheduled class time. At the University of Texas at Tyler Fisch College of Pharmacy, PITSA were implemented into an OSCE remediation course as an alternative strategy to allow students to review past content and practice counseling and interviewing techniques. Students identified the PITSA as a strength of the OSCE remediation course. Students reported the PITSA allowed them to improve their pharmacy practice skills. In addition, students stated the PITSA were beneficial to have prior to starting advanced pharmacy practice experiences. Although PITSA have some limitations, it can be a cost-effective instrument to prepare students for capstone OSCE assessments as well as advanced pharmacy practice experiences.


In the arena: contesting disaster creation in cities.
Space is a feature of all disasters, and it is through decisions on how space is developed, used, and reproduced that disasters manifest themselves. Critical urban theory sees urban space-cities-as an arena of contestation expressed through the relationship between people, power, and the built environment. Cities allow for an unpacking of this process of contestation through the interpretation of various temporal, spatial, social, and physical elements that together create complex issues and 'wicked problems'. In these urban spaces in all their complexity, disasters reveal both the worst injustices and inequalities present in a society. By drawing on three well-known cases-Hurricane Katrina in 2010; the Haiti earthquake in 2010; and the Great East Japan Earthquake and Tsunami in 2011-this paper not only explores the opportunities that critical urban theory presents for gaining a deeper understanding of disaster risk creation, but also it encourages disaster scholars to engage with it.


Clinical application of decision analysis: a detailed illustration.
The clinician must always optimize the patient's chance for the best possible outcome, but the complex task of deciding which diagnostic study to perform and which therapeutic agent to administer is usually carried out using imperfect information. These critical decisions are usually made in a covert fashion without explicit consideration of the multiple factors that impact on the outcome. Decision analysis is a quantitative method for making such diagnostic and therapeutic judgments, incorporating both probabilistic data and value judgments in the analysis of clinical problems. This article presents a brief overview of decision analysis and a detailed illustration of its use in an actual complex clinical situation. The clinical problem described consists of the management of suspected pulmonary embolism in a patient with a high risk of complications from both pulmonary arteriography and long-term anticoagulation. The example chosen also points up the virtue of decision analysis in considering prospectively both the information content and the attendant risks of contemplated diagnostic procedures.


Kinetics of dimerization of the Bence-Jones protein Au.
The dimerization reactions of complete Bence-Jones protein Au (VC-Au) and of its variable fragment (V-Au) were compared in 0.2 M (ionic strength) sodium phosphate buffer, pH 6.8 at 20 degrees C. The dimerization constant for VC-Au (6.6 X 10(4) M-1) was slightly smaller than a previously published value for the fragment (1.1 X 10(5) M-1). The reaction enthalpies were positive for both processes. Temperature jump experiments exhibited two kinetic phases. The relaxation time of the fast phase as well as its concentration dependence and amplitude were almost identical for VC-Au and V-Au. Only small differences were observed in the slow phase. These close similarities between the reactions of the two proteins demonstrate that dimerization occurs mainly via interactions between the variable domains and that the constant domains interfere very little. From the observation of two relaxation times it follows that the dimerization mechanism for both VC-Au and A-Au must include at least three reacting species. Mechanisms with an isomerization between monomers in two conformational states and a single dimer species are excluded by the data. Alternative mechanisms with a single monomeric species but isomerization between dimers give a rather unsatisfactory fit. A good fit can be obtained if it is assumed that both monomers and dimers can exist in two states. Rate constants of the association and dissociation steps are of the order of 10(7) M-1 s-1 and 10(2) s-1. Isomerization rate constants are in the range of 10 s-1.


Prevalence of atrial fibrillation and the HATCH score: Intensified monitoring of patients with high HATCH score.
The HATCH score [hypertension, age > 75 years, previous transient ischemic attack (TIA) or stroke (doubled), chronic obstructive pulmonary disease, heart failure (doubled)] has been established to identify patients who are at risk of developing persistent forms of AF. We investigated whether this score is associated with the prevalence of AF in order to guide diagnostic efforts and therapy. The data of 150,408 consecutive patients who were hospitalized at the University Hospital of Rostock between 2007 and 2012 were analyzed. Factors constituting the HATCH score and the presence of AF were prospectively documented using ICD-10 admission codes. Patients were 67.6 ± 13.6 years of age with a mean HATCH score of 1.48 ± 1.02; 16 % had a history of AF and 4 % suffered a TIA or stroke. The prevalence of AF increased significantly with the HATCH score up to 60.0 % (p < 0.001). In all, 63 % of the patients had a HATCH score of 0 and 1 without any history of stroke. The HATCH score correlates with the occurrence of AF, since the prevalence of AF rises with rising score values. Therefore, the HATCH score may be used to select patients for intensified ECG monitoring. Moreover, the score may also be used for stroke risk assessment, as none of the patients with a low HATCH score suffered a stroke.


Analysis of cellular migration using a two-chamber methodology.
Directed cell migration is fundamental to both physiological and pathophysiological processes such as embryogenesis, wound healing, and cancer metastasis. A complex series of events are required for directional cell migration, which is initiated by a migration-promoting or chemotactic stimulus, resulting in cellular polarization and entry into a cyclical pattern of leading edge protrusion, adhesion, and retraction of the trailing edge allowing cell movement. Heat shock proteins such as Hsp27, Hsp90, alphaB-crystallin, as well as heat shock transcription factors, are important players in both physiological and pathophysiological cell migration. A variety of techniques are currently available to assess cell migration, and among the most commonly utilized are those that employ a two-chamber methodology, such as that developed by Stephen Boyden in the early 1960s. Herein, we describe the use of a multiwell microchemotaxis migration assay that has the advantages of being reusable, inexpensive, highly reproducible, and requiring only a small volume of reagents.


Serum periostin and TNF-α levels in patients with obstructive sleep apnea-hypopnea syndrome.
Obstructive sleep apnea-hypopnea syndrome (OSAHS) may cause pulmonary diseases, and periostin plays an important role on the development of pulmonary diseases. In addition, periostin and pro-inflammatory cytokine TNF-α can regulate each other in vivo. This study aimed to observe the changes of serum periostin and TNF-α levels in patients with OSAHS compared with healthy volunteers and to investigate their correlation. A convenience sample of 67 patients with OSAHS in our hospital from December 2018 to December 2019 was selected and categorized into mild, moderate, and severe groups according to apnea-hypopnea index by polysomnography. In addition, 21 healthy volunteers were selected as the control group. Serum levels of periostin and TNF-α were determined by enzyme-linked immunosorbent assay (ELISA). Results were analyzed using the SPSS software. Both serum periostin and TNF-α levels in all the three OSAHS groups were higher than those of the control group and increased with severity of OSAHS. The severe group had significantly higher serum periostin and TNF-α levels than the mild and moderate groups (p < 0.05). For patients with OSAHS, serum periostin and TNF-α levels positively correlated with the apnea-hypopnea index (AHI) (p < 0.01) and negatively correlated with the lowest saturation oxygen (LSaO2) and mean saturation oxygen (MSaO2) (both p < 0.01). In addition, there was a positive correlation between serum periostin and TNF-α levels in patients with OSAHS (p < 0.001). Serum periostin and TNF-α levels were significantly increased in patients with OSAHS and may serve as a potential biomarker for severity of OSAHS. These findings suggest that it may be fruitful to study the role of periostin and TNF-α in OSAHS-induced pulmonary diseases.


Interactive video game-based approaches improve mobility and mood in older adults: A nonrandomized, controlled tri̇al.
Recently, technology-based approaches have become more frequently used in the field of rehabilitation. The aim of this study was to evaluate the effectiveness of interactive video games on mobility, general mood, and quality of life and compare them with physical activity approaches in older adults. Ninety-one residents of a nursing home were assessed and 58 volunteers who met the criteria were included in the study. Participants in Group I (n = 16) participated in a 30-min exercise program using the "Nintendo Wii Fit Plus" twice a week for 8 weeks. Group II (n = 14) participated in a physical activity program consisting of a bicycle ergometer and treadmill for the same duration. Participants were assessed pre- and post-intervention for functional mobility, general depression, and quality of life. The "Wilcoxon Signed-Rank" test was used to compare the pre- and post-treatment outcomes. The Kruskal-Wallis analysis of variance (post hoc Tukey's HSD test) was used to evaluate differences between the groups. and Discussion: Post-intervention, the scores in the Berg Balance Scale increased significantly for GI and GII compared to the control group (p = 0.001, p = 0.002) Timed Up and Go Test improved for GI (p = 0.001) and 10-Meter Walk Test improved for GI (p = 0.003). Although there was a significant change in Hamilton depression score for GI and GII (p < 0.005), between-group differences were not significant. Both programs demonstrated significant improvement in in all parameters. However, video-based program was more effective than physical activity, especially in mobility and balance parameters.


Applying different mathematical variability methods to identify older fallers and non-fallers using gait variability data.
The clinical assessment of gait variability may be a particularly powerful tool in the screening of older adults at risk of falling. Measurement of gait variability is important in the assessment of fall risk, but the variability metrics used to evaluate gait timing have not yet been adequately studied. The aims of this study were (1) to identify the best mathematical method of gait variability analysis to discriminate older fallers and non-fallers and (2) to identify the best temporal, kinematic parameter of gait to discriminate between older fallers and non-fallers. Thirty-five physically active volunteers participated in this study including 16 older women fallers (69.6 ± 8.1 years) and 19 older women non-fallers (66.1 ± 6.2 years). Volunteers were instructed to walk for 3 min on the treadmill to record the temporal kinematic gait parameters including stance time, swing time and stride time by four footswitches sensors placed under the volunteers' feet. Data analysis used 40 consecutive gait cycles. Six statistical methods were used to determine the variability of the stance time, swing time and stride time. These included: (1) standard deviation of all the time intervals; (2) standard deviation of the means of these intervals taken every five strides; (3) mean of the standard deviations of the intervals determined every five strides; (4) root-mean-square of the differences between intervals; (5) coefficient of variation calculated as the standard deviation of the intervals divided by the mean of the intervals; and (6) a geometric method calculated based on the construction of a histogram of the intervals. The standard deviation of 40 consecutive gait cycles was the most sensitive (100 %) and specificity (100 %) parameter to discriminate older fallers and non-fallers. The standard deviation of stance time is the kinematic gait variability parameter that demonstrated the best ability to discriminate older fallers from non-fallers. RBR-6rytw2.


High genetic diversity and low differentiation retained in the European fragmented and declining Greater Spotted Eagle (Clanga clanga) population.
Characterising genetic diversity and structure of populations is essential for effective conservation of threatened species. The Greater Spotted Eagle (Clanga clanga), a large and globally vulnerable raptor, is extinct or in severe decline in most of its previous range in Europe. We assessed whether the remnants of European population are genetically impoverished, and isolated from each other. We evaluated levels of genetic diversity and population structuring by sequencing mitochondrial pseudo-control region and 10 introns from various nuclear genes, and estimated length diversity in 23 microsatellite markers. The European population has expanded since the late Pleistocene, and does not exhibit signs of a recent population bottleneck. The global genetic diversity in Europe was rather similar to that detected in other similar species. Microsatellites suggested shallow but significant differentiation between the four extant populations in Estonia, Poland, Belarus and Russia (Upper Volga region) populations, but introns and mtDNA showed that only the Estonian population differed from the others. Mitochondrial diversity was highest in the northernmost Estonian population, introns suggested lower diversity in Upper Volga, microsatellites indicated equal diversity among populations. A recent bottleneck was detected in Poland, which is consistent with the observed repopulation of the region. We conclude that significant gene flow and high genetic diversity are retained in the fragmented Greater Spotted Eagle populations; there is currently no need for genetic augmentation in Europe.


Label-free in-situ real-time DNA hybridization kinetics detection employing microfiber-assisted Mach-Zehnder interferometer.
A label-free DNA biosensor based on microfiber-assisted Mach-Zehnder interferometer (MAMZI) for in-situ real-time DNA hybridization kinetics detection has been proposed and experimentally demonstrated. A microfiber of hundreds of microns in length is fabricated by tapering a segment of standard single-mode fiber (SMF) to construct the U-shaped microcavity between the lead-in and lead-out SMFs. Thanks to the mode field mismatching between the SMF and microfiber, the incident guided mode light would separate into two beams that respectively propagate in the air microcavity and the microfiber. Consequently, interference between different light modes would occur at the joint between the microfiber and the lead-out SMF. Experimental results indicate that owing to the participation of opening cavity modes in the modal interference process, the interferometric spectrum of our proposed microcavity sensor is highly sensitive to the variation of environmental refractive index (RI), especially for the RI range around 1.34 which is useful for most biological applications. The microfiber functionalization is achieved by stepwise modifying the microfiber with monolayer Poly-l-lysine (PLL) and single-stranded DNA (ssDNA) probes to produce the sensitive surface that could uniquely attach specific target ssDNAs. The fiber surface functionalization as well as DNA hybridization processes have been experimentally investigated for different target ssDNA solutions in real time. The interferometric transmission spectrum shows large wavelength shift for different biological phases, and a detection limit conservatively down to 0.0001pmol/μL has been acquired by employing the U-shaped microcavity of 176.88μm in length. Our proposed DNA biosensor possesses several advantages such as compact size, ease of fabrication, and strong response for DNA hybridization, which make it a promising candidate for potential applications in such rapidly expanding areas as medical diagnosis, cancer screenings, medicine examination and environmental engineering, etc.


Abnormal pulmonary aeration in infants and children.
There are many intrinsic and extrinsic, and congenital or acquired lesions that cause aeration disturbances in infants and children. The radiographic diagnosis of these entities and the pathophysiologic mechanisms by which they produce overinflation or underinflation are discussed. Longstanding airway compression may have serious effects on the developing lung and its vascular supply.


Development of doubly porous composite adsorbent for the extraction of fluoroquinolones from food samples.
A doubly porous microcomposite polyaniline/graphene oxide/octadecyl-bonded silica magnetite (PANI/GOx/C18-SiO2-Fe3O4) alginate adsorbent was developed and employed to extract fluoroquinolones. The Fe3O4 facilitated rapid and convenient for the separation of the adsorbent from sample solutions. The double porosity of the alginate hydrogel enhanced the surface area of the polyaniline coating. The developed method exhibited good linearity of 0.0010-50 μg L-1 for danofloxacin; 0.0050-50 μg L-1 for norfloxacin, ciprofloxacin and enrofloxacin; and 0.010-50 μg L-1 for sarafloxacin and difloxacin. The limits of detection were between 0.001 and 0.010 μg L-1 with RSD below 9.0%. The PANI/GOx/C18-SiO2-Fe3O4 adsorbent was utilized to extract fluoroquinolones from honey, milk and egg samples and satisfactory extraction recoveries were achieved ranged from 80 to 98%. The developed adsorbent has good stability which can be reused up to 7 times, is simple to prepare and convenient to use for the extraction fluoroquinolones.


Effects of vorticity on solitary waves.
The vorticity effect on solitary wave profiles has not been solved experimentally; previous studies theoretically and numerically showed that when a solitary wave progressed in the positive direction, the effective wavelength of a solitary wave with positive vorticity increased. Using laboratory experiments and fully nonlinear numerical simulations, we here show that the effective wavelength is extended more when positive vorticity is given to a progressive wave in the positive direction. We further show that the total energy increases with increasing positive vorticity, demonstrating that a wave with positive vorticity propagates with less attenuation and lasts longer than a solitary wave with no vorticity. We anticipate that our outcomes will provide a starting point for more sophisticated methods to investigate the effect of vorticity on solitary waves in laboratory experiments and numerical simulations.


Oxidized Low-Density Lipoprotein (Ox-LDL)-Triggered Double-Lock Probe for Spatiotemporal Lipoprotein Oxidation and Atherosclerotic Plaque Imaging.
Low-density lipoprotein (LDL), especially oxidative modified LDL (Ox-LDL), is the key risk factor for plaque accumulation and the development of cardiovascular disease. Herein, a highly specific Ox-LDL-triggered fluorogenic-colorimetric probe Pro-P1 is developed for visualizing the oxidation and aggregation progress of lipoproteins and plaque. A series of green fluorescent protein chromophores with modified donor-acceptor structures, containing carbazole as an electron donor and various substituents including pyridine-vinyl (P1), phenol-vinyl (P2), N, N-dimethylaniline-vinyl (P3), and thiophene-vinyl (P4), have been synthesized and evaluated. Emission spectroscopy and theoretical calculations of P1-P4 indicate that P1 shows enhanced green fluorescence (λem = 560 nm) by inhibiting its twisted intramolecular charge transfer in the presence of Ox-LDL. This feature allows the selection of P1 as a sensitive probe to directly visualize ferroptosis and Cu2+ -mediated LDL oxidative aggregation via in situ formation of fluorophore-bound Ox-LDL in living cells. The red-emissive probe Pro-P1 (λem = 660 nm) is prepared via borate protection of P1, which can be cleaved into P1 under high expression of HOCl and Ox-LDL condition at the lesion site, resulting in enhanced green emission. The plaque area and size with clear boundaries can be delineated by colorimetric fluorescence imaging and fluorescence lifetime imaging with precise differentiation.


Expression and characterization of human antithrombin III synthesized in mammalian cells.
Antithrombin III (ATIII) has been expressed in transiently transfected COS-1 monkey cells and in stably transformed Chinese hamster ovary cells, and the resultant protein has been characterized for biological activity. Both cell types efficiently secrete high levels of heterogeneous molecular weight forms of ATIII antigen. The heterogeneity results from differences in post-translational modifications. However, only a small percentage (5-10%) of the total antigen expressed is biologically active. The fraction of biologically active ATIII has been purified from total ATIII by affinity fractionation on heparin-Sepharose. This fractionation indicates that the differences in the active and inactive forms of expressed ATIII result from differences in their ability to bind heparin. Purified ATIII has a specific activity very similar to that of plasma-derived ATIII and exhibits typical heparin-accelerated ATIII activity. The biologically active fraction of ATIII appears to represent the higher molecular weight forms of the ATIII expressed and is likely not a result of altered asparagine-linked glycosylation; however, the nature of the post-translational modification required for ATIII activity remains unclear. The ability to express biologically active ATIII at such high levels should allow further investigations of the structural requirements for ATIII activity.


[Blood pressure variability and neuroplasticity in patients with type 2 diabetes mellitus].
Analysis of the role of blood pressure (BP) variability in the formation of neuroplasticity in patients with type 2 diabetes mellitus (DM). 100 patients with type 2 DM were examined, which were divided into groups depending on the presence of cognitive impairment (CI), the control group consisted of 25 people. All examined patients underwent a clinical examination, a standard set of biochemical blood tests, plasma osteopontin levels, 24-hour blood pressure monitoring (ABPM) for 24-26 h MRI of the brain (dynamic contrast and arterial spin marks, proton spectroscopy, tractography). Patients with type 2 diabetes and CI had higher body mass index, blood levels of glycated hemoglobin, glucose, alanine aminotransferase, low-density lipoprotein, triglycerides, total cholesterol, osteopontin, and lower levels of high-density lipoprotein (p≤0.05). The level of osteopontin was higher in patients with overweight, hyperglycemia, dyslipidemia, and in patients with CI in patients with BP variability. When assessing 24-hour blood pressure monitoring (ABPM), a significant difference was found in all standard indicators, while patients with type 2 diabetes were referred to as «non-dipper», in the presence of CI they noted significantly higher values of the index of time and area of stay in the suprathreshold state. BP and variability in SBP and DBP at night, as well as the risk of occult hypertension. A decrease in cerebral blood flow was revealed according to the data of contrast and non-contrast assessment of perfusion in cortical (especially in the frontal lobe) and subcortical (mainly in the putamen) structures, associated with changes in ABPM parameters. Mean SBP and DBP day and night, as well as the index of BP variability, also affect the integrity of the corticospinal, uncinate, lower longitudinal tracts, and arcuate fasciculus. The same parameters change the metabolism of the hippocampus in terms of choline (Cho), creatine (Cr), creatine phosphate (Cr2), as well as the ratio of N-acetylaspartate (NAA)/Cho, NAA/Cr, Cho/Cr. In patients with type 2 diabetes, BP variability contributes to the formation of CI through a pro-inflammatory mechanism (osteopontin), leading to impaired brain vascularization in general, white matter structure, and hippocampal metabolism.


Overcoming regulatory and economic challenges facing pharmacogenomics.
The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place.


JNK signaling in apoptosis.
Jun N-terminal kinases or JNKs play a critical role in death receptor-initiated extrinsic as well as mitochondrial intrinsic apoptotic pathways. JNKs activate apoptotic signaling by the upregulation of pro-apoptotic genes through the transactivation of specific transcription factors or by directly modulating the activities of mitochondrial pro- and antiapoptotic proteins through distinct phosphorylation events. This review analyses our present understanding of the role of JNK in apoptotic signaling and the various mechanisms by which JNK promotes apoptosis.


Development of an improved and accessible diet for western corn rootworm larvae using response surface modeling.
The western corn rootworm (WCR), Diabrotica virgifera virgifera LeConte, is an important pest of maize (Zea mays L.). Published WCR diets contain corn root powder, which is not available for purchase, thereby limiting the practical use of diets containing this ingredient. We applied response surface modeling combined with mixture designs to formulate a WCR diet that does not require corn root powder. We developed the new formulation by systematically exploring eight protein ingredients from animal, plant, and yeast sources based on simultaneous evaluation of three life history parameters (weight, molting, and survival). This formulation (WCRMO-2) without corn root powder supported approximately 97% of larval survival and successful molting. Larval weight gain after 10 days of feeding on WCRMO-2 was 4-fold greater than that of larvae feeding on the current best published WCR diet. Additionally, there was no significant difference in these larval performance traits when larvae were reared on WCRMO-2 and the best proprietary WCR diet. A commercial version of WCRMO-2 was tested and found to perform comparably for these traits. These improvements met our goal of a diet comprised of available ingredients that supports performance of WCR larvae equal to or better than publicly available formulations and proprietary formulations.


Synthesis of isoindolin-1-one derivatives via multicomponent reactions of methyl 2-formylbenzoate and intramolecular amidation.
Four series of heterocyclic compounds were obtained using Ugi-type multicomponent reactions (MCRs) with methyl 2-formylbenzoate as one of the starting materials. A facile and efficient one-pot procedure was suitable for all the MCRs under acidic conditions. This process provided access to four series of complex and potentially biologically active scaffolds.


In silico design of small molecules.
Computational methods now play an integral role in modern drug discovery, and include the design and management of small molecule libraries, initial hit identification through virtual screening, optimization of the affinity and selectivity of hits, and improving the physicochemical properties of the lead compounds. In this chapter, we survey the most important data sources for the discovery of new molecular entities, and discuss the key considerations and guidelines for virtual chemical library design.


Diastereomers of lithospermic acid and lithospermic acid B from Monarda fistulosa and Lithospermum erythrorhizon.
Monardic acids A (1) and B (2), which are (7R,8R) diastereomers of lithospermic acid (LA) and lithospermic acid B, respectively, were isolated from Monarda fistulosa. A (7S,8R) isomer (3) of LA was also isolated from this plant, and a (7R,8S) isomer (7) of LA was obtained from Lithospermum erythrorhizon. The absolute configuration of 1 was confirmed by analysis of its hydrolysates, 7-epiblechnic acid and 2R-3-(3,4-dihydroxyphenyl)-2-hydroxypropanoic acid. The configuration in the dihydrobenzofuran moieties of 2, 3, and 7 was extrapolated by using the phenylglycine methyl ester method and a Cotton effect at approximately 250-260 nm in their electronic circular dichroism spectra. Diastereomers (1-3 and 7) displayed moderate hyaluronidase inhibitory and histamine release inhibitory activities.


Nanoflower-Like Bi2 WO6 Encapsulated in ORMOSIL as a Novel Photocatalytic Antifouling and Foul-Release Coating.
Herein, the first multi-purpose antifouling and foul-release photocatalytic coating based on ORMOSIL thin films doped with nanoflower-like Bi2 WO6 is described. Irradiation with visible light of the new films immersed in water produces significant amounts of H2 O2 by photocatalytic oxidation of water, and allows the degradation of (bio)organic pollutants at the outer surface of the xerogel film.


Statins and the risk of idiopathic venous thromboembolism.
To evaluate the association between current statin use and the risk of idiopathic venous thromboembolism (VTE). A population-based retrospective follow-up with a nested case-control analysis using the General Practice Research Database. There were 72 cases of idiopathic VTE. Using normolipidaemic nonuse as the reference group, the adjusted relative risks for idiopathic VTE for current/recent statin use, past statin use, past other lipid-lowering drug use, and hyperlipidaemic nonuse were 0.8 (0.3, 2.7), 2.4 (0.6, 10.0), 1.8 (0.4, 7.4), and 0.9 (0.4, 2.0) in the follow-up analysis, and were 1.1 (0.3, 4.3), 3.7 (0.6, 24.1), 2.0 (0.3, 11.6), and 0.4 (0.2, 1.2) in the case-control analysis. Current statin use was not associated with a reduced risk of idiopathic VTE.


Oestrogen and noradrenaline modulate endogenous GABA release from slices of the rat medial preoptic area.
Endogenous gamma-aminobutyric acid (GABA) release from the rat medial preoptic area (MPOA) was measured in an in vitro slice technique with sensitive HPLC analysis. Oestrogen is demonstrated to increase GABA activity in the ovariectomised, oestrogen-primed (OVX-EB) rat prior to the luteinising hormone (LH) surge compared with ovariectomised (OVX) animals. Noradrenaline (NA) at a concentration of 10 microM was found to significantly enhance GABA release in response to 30 mM potassium stimulation in both OVX and OVX-EB animals. A significantly greater response to NA was observed in the OVX-EB animal. No effect of NA on basal GABA release was detected. The effects of NA were blocked by the alpha-adrenergic receptor blocker phenoxybenzamine (PB). These data suggest that GABA activity is modulated both by oestrogens and noradrenergic-mediated input in the MPOA.


Robust multisensory deviance detection in the mouse parietal associative area.
Context modulates how information is processed in the mammalian brain. For example, brain responses are amplified to contextually unusual stimuli. This phenomenon, known as "deviance detection,"1,2 is well documented in early, primary sensory cortex, where large responses are generated to simple stimuli that deviate from their context in low-order properties, such as line orientation, size, or pitch.2,3,4,5 However, the extent to which neural deviance detection manifests (1) in broader cortical networks and (2) to simple versus complex stimuli, which deviate only in their higher-order, multisensory properties, is not known. Consistent with a predictive processing framework,6,7 we hypothesized that deviance detection manifests in a hierarchical manner across cortical networks,8,9 emerging later and further downstream when stimulus deviance is complex. To test this, we examined brain responses of awake mice to simple unisensory deviants (e.g., visual line gratings, deviating from context in their orientation alone) versus complex multisensory deviants (i.e., audiovisual pairs, deviating from context only in their audiovisual pairing but not visual or auditory content alone). We find that mouse parietal associative area-a higher cortical region-displays robust multisensory deviance detection. In contrast, primary visual cortex exhibits strong unisensory visual deviance detection but weaker multisensory deviance detection. These results suggest that deviance detection signals in the cortex may be conceptualized as "prediction errors," which are primarily fed forward-or downstream-in cortical networks.6,7.


Physiological and anatomical responses to drought stress differ between two larch species and their hybrid.
Hybrid saplings were more reactive to soil water deficit than Japanese and European larch. European larch had hydraulically safer wood and anisohydric behavior, Japanese and hybrid larch showed isohydric strategy. Deciduous larch species could be an alternative to evergreen conifers in reforestation, but little is known about drought sensitivity of their saplings. The effect of an experimental drought on hydraulics and quantitative wood anatomy was tested on saplings of European larch (EL, Larix decidua), Japanese larch (JL, Larix kaempferi) and their hybrid (HL). Across species, biomass, transpiration rate and relative water content were higher in controls than in drought stressed trees, but transpiration efficiency was lower. JL had the highest transpiration efficiency under drought, and EL the lowest, coinciding with slower growth of EL. Wood of EL formed before drought was hydraulically safer as shown by higher wall/lumen ratio and lower pit cavity area. EL neither had a significant increase in transpiration efficiency nor a reduction in transpiration rate under drought, suggesting that the stomata remained open under soil water deficit. HL saplings were the most reactive to water shortage, indicated by intra-annual density fluctuations and a decrease in relative water content of the sapwood. Significant reduction in transpiration by HL suggested a higher stomatal sensitivity, while the same leaf surface area was maintained and radial growth was still similar to its best parent, the JL. The latter showed a significantly lower leaf surface area under drought than controls. EL, with its hydraulically safer wood, followed an anisohydric behavior, while JL and HL revealed an isohydric strategy. Altogether, our results suggest species dependent acclimations to drought stress, whereby HL followed the strategy of JL rather than that of EL. The online version contains supplementary material available at 10.1007/s00468-021-02129-4.


A Quinoxaline-Naphthaldehyde Conjugate for Colorimetric Determination of Copper Ion.
This work facilitates detection of bivalent copper ion by a simple Schiff base probe QNH based on a quinoxaline-naphthaldehyde framework. The detailed study in absorption spectroscopy and theoretical aspects and crystal study of the probe and probe-copper complex has been discussed. The detection limit of the probe in the presence of Cu2+ is 0.45 µM in HEPES-buffer/acetonitrile (3/7, v/v) medium for absorption study. The reversibility of the probe-copper complex has been investigated by EDTA. The selective visual detection of copper has been established also in gel form.


Comparative in vitro study of single and four layer graphene oxide nanoflakes - Cytotoxicity and cellular uptake.
In recent years, graphene and its derivatives have been extensively investigated because of their unique properties, which can be used in many fields including biomedical applications. Therefore, detailed biological study is required. In the current paper the detailed toxicological studies on single and four layer graphene oxide (GO) nanoflakes is presented. The morphology and size of the nanomaterials were characterized via atomic force microscopy. Cytotoxicity, proliferation and internalization study were performed using various methods, including optical, confocal and Raman microscopy imaging, flow cytometry analysis, colorimetric and luminescent cell assays. Our first findings undeniably show that the nanomaterials' functionalization has a considerable impact on their behavior in a biological environment. The cytotoxicity assay confirmed comparable, dose dependent cytotoxicity of single and four layers GO flakes. The differences between these two nanomaterials became more distinct during cell proliferation study and ROS detection. Namely, markedly stronger inhibition of cell proliferation and higher ROS generation by one-layer GO-PEG than four-layer GO-PEG were observed. Cell imaging revealed efficient internalization of the both GO nanoflakes in a time dependent manner. These findings emphasize the role of number of layer and functionalization in GO toxicological characteristics and may provide helpful information for their further biomedical applications.


Understanding interactions between urban development policies and GHG emissions: A case study in Stockholm Region.
Human-induced urban growth and sprawl have implications for greenhouse gas (GHG) emissions that may not be included in conventional GHG accounting methods. Improved understanding of this issue requires use of interactive, spatial-explicit social-ecological systems modeling. This paper develops a comprehensive approach to modeling GHG emissions from urban developments, considering Stockholm County, Sweden as a case study. GHG projections to 2040 with a social-ecological system model yield overall greater emissions than simple extrapolations in official climate action planning. The most pronounced difference in emissions (39% higher) from energy use single-residence buildings resulting from urban sprawl. And this difference is not accounted for in the simple extrapolations. Scenario results indicate that a zoning policy, restricting urban development in certain areas, can mitigate 72% of the total emission effects of the model-projected urban sprawl. The study outcomes include a decision support interface for communicating results and policy implications with policymakers.


Shaping risky choices: Ethics and the effects of organizational decisions.
Choices to live "at risk" are complex and challenging and can be structured by organizational policy. Some individuals genuinely wish to live in situations that are, or are perceived to be, high risk because this affords them an important benefit. However, it is likely that these choices are significantly affected by context and might not be made under different circumstances. The following argues for a responsibility to be attentive to the effects of organizational decisions on choices to live at risk and the overall distribution of risk.


Reciprocal expression of cell-cell coupling and voltage-dependent Na current during embryogenesis of rat telencephalon.
Using whole-cell patch-clamp techniques in situ (whole-tissue and tissue slices), we have studied two aspects of rat telencephalic cell development during the period of embryogenesis starting at E12. The first aspect was related to junctional coupling as revealed by low input resistance, intercellular dye spread and pharmacologic blockade. Coupling appeared to decrease with time, both in extent and occurrence. The second aspect dealt with cell excitability as revealed by voltage-dependent Na current (INa) expression. Immature action potentials and their underlying INaS were present in a small proportion of E12 cells. These currents were blocked 36% and 78% by 10(-7) M and 10(-6) M tetrodotoxin (TTX), respectively. From then onward, INaS got larger and more prevalent while no obvious changes in kinetics were observed. At E21, INaS were abolished by 10(-7) M TTX and channel density apparently was sufficient to support overshooting yet still immature action potentials.


Dealing with missing data by EM in single-case studies.
Single-case experimental design (SCED) research plays an important role in establishing and confirming evidence-based practices. Due to multiple measures of a target behavior in such studies, missing information is common in their data. The expectation-maximization (EM) algorithm has been successfully applied to deal with missing data in between-subjects designs, but only in a handful of SCED studies. The present study extends the findings from Smith, Borckardt, and Nash (2012) and Velicer and Colby (2005b, Study 2) by systematically examining the performance of EM in a baseline-intervention (or AB) design under various missing rates, autocorrelations, intervention phase lengths, and magnitudes of effects, as well as two fitted models. Three indicators of an intervention effect (baseline slope, level shift, and slope change) were estimated. The estimates' relative bias, root-mean squared error, and relative bias of the estimated standard error were used to assess EM's performance. The findings revealed that autocorrelation impacted the estimates' qualities most profoundly. Autocorrelation interacted with missing rate in impacting the relative bias of the estimates, impacted the root-mean squared error nonlinearly, and interacted with the fitted model in impacting the relative bias of the estimated standard errors. A simpler model without autocorrelation can be used to estimate baseline slope and slope change in time-series data. EM is recommended as a principled method to handle missing data in SCED studies. Two decision trees are presented to assist researchers and practitioners in applying EM. Emerging research directions are identified for treating missing data in SCED studies.


A summary-statistics-based approach to examine the role of serotonin transporter promoter tandem repeat polymorphism in psychiatric phenotypes.
In genetic studies of psychiatric disorders in the pre-genome-wide association study (GWAS) era, one of the most commonly studied loci is the serotonin transporter (SLC6A4) promoter polymorphism, a 43-base-pair insertion/deletion polymorphism in the promoter region (5-HTTLPR). The genetic association signals between 5-HTTLPR and psychiatric phenotypes, however, have been inconsistent across many studies. Since the polymorphism cannot be tested via available SNP arrays, we had previously proposed an efficient machine learning algorithm to predict the genotypes of 5-HTTLPR based on the genotypes of eight nearby SNPs, which requires access to individual-level genotype and phenotype data. To utilize the advantage of publicly available GWAS summary statistics obtained from studies with very large sample sizes, we develop a GWAS summary-statistics-based approach for testing the variable number of tandem repeat (VNTR) associations with various phenotypes. We first cross-verify the accuracy of the summary-statistics-based approach for 61 phenotypes in the UK Biobank. Since we observed a strong similarity between the predicted individual-level 5-HTTLPR genotype-based approach and the summary-statistics-based approach, we applied our method to the available neurobehavioral GWAS summary statistics data obtained from large-scale GWAS. We found no genome-wide significant evidence for association between 5-HTTLPR and any of the neurobehavioral traits. We did observe, however, genome-wide significant evidence for association between this locus and human adult height, BMI, and total cholesterol. Our summary-statistics-based approach provides a systematic way to examine the role of VNTRs and related types of genetic polymorphisms in disease risk and trait susceptibility of phenotypes for which large-scale GWAS summary statistics data are available.


Dosimetric evaluation of high-Z inhomogeneity with modern algorithms: A collaborative study.
To evaluate modern dose calculation algorithms with high-Z prosthetic devices used in radiation treatment. A bilateral hip prosthetic patient was selected to see the effect of modern algorithms from the commercial system for plan comparisons. The CT data with dose constraints were sent to various institutions for dose calculations. The dosimetric parameters, D98%, D90%, D50% and D2% were compared. A water phantom with an actual prosthetic device was used to measure the dose using a parallel plate ionization chamber. Dosimetric variability in PTV coverage was significant (>10%) among various treatment planning algorithms. The comparison of PTV dosimetric parameters, D98%, D90%, D50% and D2% as well as organs at risk (OAR) have large discrepancies compared to our previous publication with older algorithms (https://doi.org/10.1016/j.ejmp.2022.02.007) but provides realistic dose distribution with better homogeneity index (HI). Backscatter and forward scatter attenuation of the prosthesis was measured showing differences <15.7% at the interface among various algorithms. Modern algorithms dose distributions have improved greatly compared to older generation algorithms. However, there is still significant differences at high-Z-tissue interfaces compared to the measurements. To ensure accuracy, it's important to take precautions avoiding placing any prosthesis in the beam direction and using type C algorithms.


Small G protein RAC-2 regulates forgetting via the JNK-1 signalling pathway in Caenorhabditis elegans.
Although forgetting was once regarded as a passive decline in memory and an occasional source of embarrassment, recent research suggests that it is an active biological process of removing outdated or irrelevant memories via activation of specific genes and signal transduction pathways. Rho family G proteins are known to have a role in synaptic plasticity mediated by the actin cytoskeleton. However, the current study reveals that another Rho guanosine triphosphate enzyme (GTPase), RAC-2, facilitates the occurrence of forgetting in Caenorhabditis elegans independent of actin dynamics. Functioning downstream of RAC-2 in the same signalling pathway, JNK-1 and its phosphorylated protein are required to positively regulate forgetting. The pan-neuronal rescue of RAC-2 or JNK-1, instead of AWC neuron-specific expression, reverses the delayed forgetting caused by the rac-2 mutation, which indicates that the involvement of RAC-2/JNK-1 in more than AWCs must be required. In summary, our work elucidates the action of the Rho GTPase RAC-2 and downstream JNK-1 as a potential novel pathway in forgetting in C. elegans.


Diagnostic accuracy of periostin in predicting asthma: a systematic review and Meta-analysis.
We sought to evaluate the accuracy of periostin for the diagnosis of asthma through a systematic review and meta-analysis. we searched the electronic databases (PubMed, EMBASE, Web of science) to find relevant studies through December 31, 2018. Studies selecting, data extraction and quality assessment were conducted by two researchers independently according to inclusion and exclusion criteria. We used bivariate mixed effects model to conduct the meta-analysis. A total of 9 studies including 1448 subjects with asthma were analyzed. The pooled sensitivity, specificity, diagnostic odds ratio (DOR) were 0.68 (95% CI, 0.42-0.86), 0.87 (95% CI, 0.76-0.93) and 13.78 (95% CI, 4.64-40.93) respectively. The area under the summary receiver operating curves (SROC) was 0.87 (95% CI, 0.84-0.90). The Spearman correlation coefficient indicated that no threshold effect existed in the included studies. The study design had statistical significance for sensitivity results (p < 0.001) through regression analysis. Heterogeneity might be caused by non-threshold effect. Periostin has moderate accuracy in the diagnosis of asthma.


The impact of Paenibacillus polymyxa HY96-2 luxS on biofilm formation and control of tomato bacterial wilt.
The focus of this study was to investigate the effects of luxS, a key regulatory gene of the autoinducer-2 (AI-2) quorum sensing (QS) system, on the biofilm formation and biocontrol efficacy against Ralstonia solanacearum by Paenibacillus polymyxa HY96-2. luxS mutants were constructed and assayed for biofilm formation of the wild-type (WT) strain and luxS mutants of P. polymyxa HY96-2 in vitro and in vivo. The results showed that luxS positively regulated the biofilm formation of HY96-2. Greenhouse experiments of tomato bacterial wilt found that from the early stage to late stage postinoculation, the biocontrol efficacy of the luxS deletion strain was the lowest with 50.70 ± 1.39% in the late stage. However, the luxS overexpression strain had the highest biocontrol efficacy with 75.66 ± 1.94% in the late stage. The complementation of luxS could restore the biocontrol efficacy of the luxS deletion strain with 69.84 ± 1.09% in the late stage, which was higher than that of the WT strain with 65.94 ± 2.73%. Therefore, we deduced that luxS could promote the biofilm formation of P. polymyxa HY96-2 and further promoted its biocontrol efficacy against R. solanacearum.


Performance evaluation of disinfectant formulations using poloxamer-hydrogel biofilm-constructs.
Poloxamer F127 is a di-block co-polymer of polyoxyethylene and polyoxypropylene. Aqueous solutions show thermo-reversible gelation, being liquid at temperatures < 15 degrees C and robust gels at temperatures > 15 degrees C. Chilled poloxamer solutions (30% w/v) were inoculated with approximately 10(4-5) cfu ml-1 of stationary phase cultures of Pseudomonas aeruginosa, Ps. fluorescens, Pantoea agglomerans, Micrococcus luteus, Staphylococcus epidermidis, Bacillus subtilis or Listeria innocua. Drops (200 microliters) of the inoculated poloxamers were placed on stainless steel coupons held in Petri dishes containing moistened cotton wool and incubated at 30 degrees C for 5 h. All strains grew well giving between 10(6-7) cfu ml-1 at 5-6 h. The cultured gels were readily applied to tests of biocide effectiveness as the stainless steel coupons could be removed and flooded with biocide solution for fixed exposure times. Provided that the temperature of the biocide solutions was > 15 degrees C, the integrity of the gels could be maintained during exposure. After exposure, the gels and their supports were removed to separate tubes containing neutralizer solution (< 15 degrees C). The gels rapidly dispersed within 5 min to ensure a complete recovery of the sample population. Biofilm-constructs and cell suspensions (10(7) cfu ml-1) were exposed to four commercial disinfectant formulations, based on hypochlorite, alcohol, hydrogen peroxide and a tenside, at recommended use levels. Cell suspensions, in the presence of bovine serum albumen (BSA; 0.03% w/v), were subject to a > 5-log kill within 5 min while the killing effected against the biofilm-constructs varied between 0.4 and 2-log reductions. The results indicate a high degree of reproducibility between replicate samples, with patterns of susceptibility varying both as a function of organism, biocide type and concentration. The experiments strongly support the view that poloxamer-constructs are suitable for application in trials and testing of disinfectant formulations.


Scanning microfluorometric measurement of immunofluorescently labelled microtubules in cultured cells. Dependence of microtubule content on cell density.
A method for evaluation of microtubule content in cultured cells has been developed. The method is based on scanning microfluorometric measurement of immunofluorescently labelled microtubules. The method has been applied to the comparison of microtubule content in epithelial XTH-2 cells grown in culture at various cell densities. The results have shown that the microtubule content in the cells is not dependent on their proliferative state rather than it depends on cellular contacts.


Stimulation of dendritogenesis in the epidermal melanocytes of newborn mice by melanocyte-stimulating hormone.
The number of dendrites and the total length of dendrites in the epidermal melanocytes positive for the dopa reaction were shown to increase when newborn mice were injected with alpha-MSH or DBc-AMP. Moreover, both indices of the degree of dendritogenesis increased when skin explants of newborn mice were cultured in medium containing alpha-MSH or DBc-AMP. Electron-microscopic observation showed that the number of melanosomes was also increased by alpha-MSH treatment. Many mature melanosomes were observed in the dendrites of the epidermal melanocytes of alpha-MSH-injected mice. Highly dendritic melanocytes seem to be the cells stimulated by MSH to form melanosomes and translocate them to dendrites. Dendritogenesis stimulated by the hormone was suppressed by actinomycin D or cycloheximide, suggesting that the dendritogenesis in the epidermal melanocytes requires de novo transcription and translation.


Chromatography-based purification of adeno-associated virus.
Virus-mediated gene transfer shows great potential as a therapeutic strategy for the management of various inherited and acquired human diseases. Among the current viral vectors, adeno-associated virus (AAV) has become the vector of choice for numerous gene therapy applications. As AAV-based vectors approach the clinic, the need for scalable methods of production and purification is steadily increasing. In this chapter, we present a column chromatography-based protocol for the purification of recombinant AAV type 1 (AAV-1) to near homogeneity. The protocol, which can be completed within one working day, employs three major purification steps: (1) polyethylene glycol-mediated vector precipitation, (2) anion-exchange chromatography, and (3) gel filtration chromatography. This method provides a basic strategy, or "platform," that can be adapted to the purification of other recombinant AAV vector serotypes.


Combined chitosan and Cympobogon citratus (D.C. ex Nees) Stapf. essential oil to inhibit the fungal phytopathogen Paramyrothecium roridum and control crater rot in melon (Cucumis melo L.).
This study evaluated the efficacy of combined chitosan (Chi) and Cymbopogon citratus (DC) Stapf. essential oil (CCEO) to inhibit the fungal phytopathogen Paramyrothecium roridum L. Lombard & Crous and control crater rot in melon (Cucumis melo L.). Effects of several Chi and CCEO concentrations to inhibit the growth of four P. roridum isolates in vitro, as well as the type of interaction of some combined concentrations of Chi and CCEO was evaluated. Effects of coatings with combined concentrations of Chi and CCEO on development of crater rot lesions in melon artificially inoculated with P. roridum during storage (15 days, 25 °C) were measured. Chi (2.5, 3.75, 5, and 6.75 mg/mL) and CCEO (0.3 and 0.6 μL/mL) led to growth inhibition of the four examined P. roridum isolates. Combinations of Chi (5 mg/mL) and CCEO (0.15 and 0.3 μL/mL) had additive interaction to inhibit P. roridum. Coatings with additive combined concentrations of Chi and CCEO decreased the development and severity of carter rot lesions in melon during room storage regardless of the inoculated P. roridum isolate. Therefore, application of coatings formulated with combined concentrations of Chi and CCEO could be alternative strategies to control crater rot caused by P. roridum in melon and decrease synthetic fungicide use in this fruit.


Voltage-dependent calcium and potassium ion conductances: a contingency mechanism for an associative learning model.
Persistent light-induced depolarization results from Ca2+ influx across a photoreceptor membrane. The marked dependence on potential of this Ca2+ influx and a Ca+-dependent K+ efflux accounts for enhancement of the light-induced depolarization when light is paired with rotation. A positive feedback cycle between light-induced depolarization and synaptic depolarization due to stimulus pairing can explain long-lasting behavioral changes produced by associative training but not control paradigms. The sensitivity of this Ca2+ influx to intracellular levels of adenosine 3'-5'-monophosphate suggests biochemical steps for this model of associative learning.


Relationship between interleukin-1β gene expression in epicardial adipose tissue and coronary atherosclerosis based on computed tomographic analysis.
Anti-inflammatory therapy targeting interleukin (IL)-1β reduced cardiovascular events in a randomized trial. We evaluated the relationship between IL-1β mRNA expression in epicardial adipose tissue (EAT) and clinically-assessed coronary atherosclerosis on computed tomography (CT). We studied 45 patients before cardiac surgery (coronary artery bypass grafting [CABG], n = 18; non-CABG, n = 27). EAT volume, the coronary calcium score (CCS), and the presence of non- and/or partially-calcified coronary plaques (NCPs) and high-risk coronary plaques (HRPs; minimum CT density <30 Hounsfield units and vascular remodeling index >1.1) on CT angiography were assessed. EAT samples were obtained during cardiac surgery. IL-1β mRNA expression in EAT was measured using quantitative real-time PCR and normalized to that of β-actin in each patient. There was no difference in IL-1β mRNA levels between patients who were scheduled for CABG and non-CABG surgery or among subgroups based on the CCS. However, patients with NCPs (median [interquartile range], 4.1[2.0-11.6]E-4 versus 1.8[0.6-4.5]E-4, p = 0.024) and HRP (7.6[3.0-20.4]E-4 versus 1.9[0.7-4.3]E-4, p = 0.0023) had higher IL-1β mRNA levels than those without these plaques. On multivariate analysis adjusted for age, sex, coronary risk factors, statin therapy, CCS, and EAT volume, the presence of HRPs was significantly correlated with elevated IL-1β mRNA levels in EAT (β = 0.39, p = 0.047). Our data suggest a contribution of EAT to coronary atherosclerosis through molecular behavior, such as IL-1β gene expression, which may be a new therapeutic target.


Glypican-5 is a novel metastasis suppressor gene in non-small cell lung cancer.
Glypican-5 (GPC5) may be a potential tumor suppressor gene in non-small cell lung cancer (NSCLC). The present study aimed to clarify the GPC5 expression pattern and to explore its potential functions in NSCLC. The expression of GPC5 gene was lower in lung cancer tissues compared with adjacent noncancerous tissues. The GPC5 gene expression in the lymph node metastasis group was remarkably lower than that in the non-metastasis group. The tissue microarray (TMA) study found that the overall survival rate of GPC5-positive group was significantly higher than that of GPC5-negative group in AC subgroup. Overexpressing GPC5 in NSCLC cell lines significantly suppressed their migration, invasion, and proliferation activities and also induced G1/S phase arrest of the cells in vitro. Our data suggest that GPC5 is a novel metastasis suppressor gene in NSCLC and may be a potential biomarker that predicts NSCLC metastasis.


Treatment Patterns and Outcomes in Early-stage Hodgkin Lymphoma in the Elderly: A National Cancer Database Analysis.
The outcome for early-stage (I/II) Hodgkin lymphoma (HL) has improved significantly during the past few decades. However, older age (≥ 60 years) has continued to be associated with poor outcomes, and a paucity of data is available defining the optimal treatment regimens. In the present study, we sought to identify the practice patterns and outcomes in elderly patients with early-stage HL using the National Cancer Database. We performed a retrospective study of patients aged 60 years with early-stage classic HL diagnosed from 2004 to 2012. The overall survival (OS) of patients undergoing chemotherapy (CT), radiation therapy (RT), or CT plus RT were compared. Kaplan-Meier curves of OS for individual therapy were constructed and compared using the log-rank test. Multivariate analysis for predictors of mortality was conducted using the Cox proportional hazard method. A total of 3795 patients were included in the analysis. At baseline, 41% patients had stage I disease. Of the 3795 patients, 51% underwent CT, 16% underwent RT, and 33% underwent CT plus RT. With a median follow-up duration of 40.4 months, the unadjusted OS rates for patients receiving CT, RT, or CT plus RT were 58.1%, 54%, and 77.7%, respectively (P < .0001). On multivariate analysis, CT plus RT improved OS compared with monotherapy. In older patients (age ≥ 60 years) with stage I/II HL, the combination of CT plus consolidative RT resulted in improved OS compared with monotherapy. However, the use of combination therapy in this age group seems suboptimal. This could be, in part, secondary to comorbidities limiting the use of CT plus RT in the elderly.


An artificial interfacial layer with biomimetic ionic channels towards highly stable Li metal anodes.
Lithium (Li) metal with low electrochemical potential and high theoretical capacity is a promising anode material for next-generation batteries. However, the low reversibility and safety problems caused by the notorious dendrite growth significantly impede the development of high-energy-density lithium metal batteries (LMBs). Here, to enable a dendrite-free and highly reversible Li metal anode (LMA), we develop a cytomembrane-inspired artificial layer (CAL) with biomimetic ionic channels using a scalable spread coating method. The negatively charged CAL with uniform intraparticle and interparticle ionic channels facilitates the Li-ion transport and redistributes the Li-ion flux, contributing to stable and homogeneous Li stripping and plating. Furthermore, a robust underneath transition layer with abundant lithiophilic inorganic components is in-situ formed through the transformation of CAL during cycling, which promotes Li-ion diffusion and suppresses the continuous side reactions with the electrolyte. Additionally, the resulting cytomembrane-inspired artificial Janus layer (CAJL) displays an ultrahigh Young's modulus (≥10.7 GPa) to inhibit the dendrite growth. Consequently, the CAJL-protected LMA (Li@CAJL) is stably cycled with a high areal capacity of 10 mAh cm-2 at a high current density of 10 mA cm-2. More importantly, the effective CAJL modification realizes the stable operation of a practical 429.2 Wh kg-1 lithium-sulfur (Li-S) pouch cell using a low electrolyte/sulfur (E/S) ratio of 3 μL mg-1. The facile yet effective protection strategy of LMAs can promote the practical application of LMBs.


Exposure-response analysis of the association of maternal smoking and use of electronic cigarettes (vaping) in relation to preterm birth and small-for-gestational-age in a national US sample, 2016-2018.
The US experienced a surge in use of e-cigarettes. Smoking women may consider e-cigarettes during pregnancy as an alternative to smoking. E-cigarettes typically contain nicotine, an established cause of reduction in fetal growth in animal studies. This cohort study included 99,201 mothers who delivered live singletons in 2016-2018 from the Pregnancy Risk Assessment Monitoring System. We created exposure categories based on self-reported number of cigarettes smoked per day and vaping frequency and evaluated their associations with preterm birth and small-for-gestational-age (SGA) birth (two established cigarette smoking-related risks). Dual users in late pregnancy were a heterogeneous group: 29% lightly smoked and occasionally vaped; 19% lightly smoked and frequently vaped; 36% heavily smoked and occasionally vaped; and 15% heavily smoked and frequently vaped. While dual users who heavily smoked and occasionally vaped had the highest adjusted OR for SGA (3.4, 95% CI 2.0, 5.7), all the dual users had, on average, about twice the odds of having SGA than non-users. While the risks of preterm birth were higher among sole light smokers (adjusted OR 1.3, 95% CI 1.1, 1.5) and sole heavy smokers (adjusted OR 1.5. 95% CI 1.2, 1.8) than non-users, the adjusted odds of preterm birth for dual users were not noticeably higher than those of non-users. Relative to non-users, both smoking and vaping during pregnancy appear to increase risk of SGA, but excess risk of preterm birth appears to be primarily attributable to smoking alone. Higher levels of exposure tended to confer more risk.


A 6-year survey of road traffic accidents in Southwest China: Emphasis on traumatic brain injury.
The objective of this study is to provide an up-to-date overview of the patterns of injuries, especially traumatic brain injury (TBI) caused by RTAs and to discuss some of the public health consequences. A scientific team was established to collect road traffic accidents occurring between 2013 and 2018 in Chongqing, Southwest China. For each accident, the environment-, vehicle-, and person- variables were analyzed and determined. The overall injury distribution and TBI patterns of four types of road users (driver, passenger, motorcyclist and pedestrian) were compared. The environmental and time distribution of accidents with TBI were shown by bar and pie chart. The risks of severe brain injury whether motorcyclist wearing helmets or not were compared and the risk factors of severe TBI in pedestrian were determined by odds ratio analysis. This study enrolled 2131 accidents with 2741 persons of all kind of traffic participants, 1149 of them suffered AIS1+ head injury and 1598(58%) died in 7 days. The most common cause of deaths is due to head injury with 714(85%) and 1266(79%) persons died within 2 hours. Among 423 persons suffered both skull fracture and intracranial injury, 102 (24.1%) have an intracranial injury but no skull fractures, while none of the skull fractures without intracranial injury was found. Besides, motorcyclists without a helmet were at higher risks for all the brain injury categories. The risk of pedestrian suffering severe TBI at an impact speed of more than 70 km/h is 100 times higher than that with an impact speed of less than 40 km/h. It is urgently needed to develop a more reliable brain injury evaluation criterion for better protection of the road users. We believe that strengthening the emergency care to head injury at the scene is the most effective way to reduce traffic fatality.


Entrapment of an atrial tined pacemaker electrode in the tricuspid valve--a case report.
A rare complication is described in which an atrial tined pacemaker electrode was trapped in the chordae of the tricuspid valve and could not be removed. A possible method for avoiding this complication is discussed.


Synapses as associative memory elements in the hippocampal formation.
This report analyzes long term potentiation (LTP) and associative interactions between synapses of the ipsilateral and crossed entorhinal cortical (EC) pathways to the dentate gyrus (DG). In the anesthetized rat, conditioning stimulation to one EC-DG pathway reliably elicits LTP at the ipsilateral synapses, while the synapses of the collateral, crossed pathway to the contralateral DG do not exhibit LTP. Furthermore, in the DG ipsilateral to the conditioning stimulation the convergent crossed pathway from the contralateral side, which had not been itself conditioned, failed to exhibit heterosynaptic LTP. These results are consistent with a specific 'synaptic' localization of the changes responsible for LTP, and suggest that some critical number of synapses must be activated in order to observe LTP. While the crossed EC-DG projection never exhibited LTP when conditioned alone, the crossed input could be potentiated under certain circumstances. Specifically, paired conditioning of ipsi- and contralateral inputs by nearly simultaneous conditioning stimulation of the EC bilaterally results in LTP in the crossed system. Furthermore, this associatively induced LTP of the crossed system can be reversed by subsequent conditioning of the ipsilateral system alone. Successive potentiating and depotentiating sequences are possible using paired and non-paired stimulation procedures even after lesions which prevent neural loops through the EC. The results are interpreted as evidence for a 'Hebb' type synapse which has the capability for erasure. This synaptic type is not appropriate for classical conditioning without appendant circuitry, but is suited for other forms of associative learning.


Presentation, diagnostic features and glucose handling in a monocentric series of insulinomas.
New aspects have emerged in the clinical and diagnostic scenarios of insulinoma: current guidelines have lowered the diagnostic insulin threshold to 3 μU/ml in the presence of hypoglycemia (<55 mg/dl); post-prandial hypoglycemia has been reported as the only presenting symptom; preexisting diabetes mellitus (DM) was recognized in some patients. To evaluate clinical features, diagnostic criteria and glucose metabolic profile in a monocentric series of patients affected by insulinomas including two subgroups: sporadic and multiple endocrine neoplasia type-1 syndrome (MEN-1). Clinical, pathological and biochemical data regarding 33 patients were analyzed. following the current guidelines the 72-h fasting test was initially positive in all cases but one. In this case the test, initially negative, became positive after a 2-yr follow-up. Nadir insulin level was ≥ 3 μU/ml but <6 μU/ml in 3 patients and ≥ 6 μU/ml in the remaining 30 cases. At presentation, 27 patients (82%) reported only fasting symptoms, 3 (9%) only post-prandial and 3 (9%) both. Seven cases (21%) had previously been affected by type 2 DM or impaired glucose metabolism. In our series the new cut-off of insulin increased the sensitivity of the 72-h fasting test from 87% to 97%. The absence of hypoglycemia during the test cannot definitively rule out the diagnosis and the test should be repeated in every highly suspicious case. Post-prandial hypoglycemia can be the only presenting symptom. DM may be associated with the occurrence of insulinoma. So that a possible diagnosis of insulinoma must not be ignored if previous impaired glucose handling is evident.


Differences in tocopherol-lipid ratios in ARDS and non-ARDS patients.
Plasma tocopherol, plasma total lipid levels and tocopherol-lipid ratio were measured every 6 h during 48 h in 12 critically ill patients and compared with those of a control group. The patients were divided into two groups. Group I comprised 6 critically ill patients with ARDS and group II comprised 6 severely ill patients without ARDS. The means for all observations of plasma tocopherol, total lipid levels and tocopherol-lipid ratio in groups I and II were significantly depressed relative to a control group (p less than 0.0001). The difference in the average tocopherol-lipid ratio between the three groups (p less than 0.0001) and between the groups I and II was statistically significant (p less than 0.0001). Our results indicated: (1) a decrease of vitamin E concentrations in the critically ill patients, particularly in ARDS patients; (2) the importance of the relationship between plasma tocopherol and plasma lipids levels in evaluating the deficiency in vitamin E which was evident in ARDS patients.


Significance of left posterior extension of early repolarization in patients with J-wave syndrome.
J waves in the inferior or lateral leads are characteristic electrocardiographic (ECG) changes in patients with early repolarization syndrome (ERS). However, the presence of J waves in the left posterior region has not yet been evaluated. The purpose of this study was to clarify the significance of J waves in the posterior left ventricle using leads V7-V9 and a body surface mapping (BSM) system. Forty patients diagnosed with ERS were included. All patients exhibited J waves in either the contiguous inferior, lateral, or posterior leads. We evaluated the incidence of J waves in the inferolateral and posterior leads using a 15-lead ECG with synthesized V7-V9 and an 87-lead BSM. Additionally, we assessed the arrhythmogenicity of the posterior regions based on the morphology of the premature ventricular complexes (PVCs) associated with ventricular fibrillation (VF). J waves were observed in the lateral, inferior, and posterior leads of 26 (65%), 31 (78%), and 39 (97%) patients, respectively. J waves were found only in the posterior leads of 5 patients. BSM was evaluated in 9 patients, all of whom exhibited a positive area on the posterior region. PVCs associated with VF were recorded in 5 patients. Among patients with inferolateral and posterior J waves, all except 1 patient who displayed left bundle branch block morphology showed PVCs originating from the posterior left ventricular region. Posterior J waves are common in ERS patients. This abnormality can be detected using leads V7-V9 and the BSM system and may be associated with arrhythmogenesis.


Determining the symptoms and coping methods of patients at home after hematopoietic stem cell transplantation.
This descriptive study was conducted to determine symptoms experienced at home in the early period by patients who received hematopoietic stem cell transplantation (HSCT), identify coping behaviors used by the patients in the management of symptoms and assess the quality of life of these patients. The study included 200 patients who had received HSCT at a private hospital in Kocaeli in Turkey between October 2017 and November 2018 and been discharged. The data of the study were collected by using a patient information and interview form developed by the researcher, the Memorial Symptom Assessment Scale and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. The mean age of the patients was approximately 51, 39% (n = 78) of the patients were female, 61% (n = 122) were male, and the vast majority (82%) were married. The three most frequently experienced symptoms among the patients after being discharged were identified as pain (63%), weakness (48%), and loss of appetite (43%). It was found that the vast majority of the patients complied with coping behaviors reported in the literature, but these behaviors were partially effective. Clinical diagnosis, type of transplant, status of re-hospitalization of the being discharged, and number of problems experienced were identified as variables that were significantly effective on the treatment-related symptom experiences and many dimensions of the quality of life of the patients (p < 0.05). It was determined that the patients who were included in this study experienced various symptoms on different levels and at different frequencies. Regarding the effectiveness of the approaches used by the patients in coping with the symptoms they experienced, it was determined that the approaches they used to cope with nausea-vomiting, fever and insomnia were effective, and those they used for weight loss and anxiety were ineffective.


Evaluation of the combined measurement uncertainty in isotope dilution by MC-ICP-MS.
The combination of metrological weighing, the measurement of isotope amount ratios by a multicollector inductively coupled plasma mass spectrometer (MC-ICP-MS) and the use of high-purity reference materials are the cornerstones to achieve improved results for the amount content of lead in wine by the reversed isotope dilution technique. Isotope dilution mass spectrometry (IDMS) and reversed IDMS have the potential to be a so-called primary method, with which close comparability and well-stated combined measurement uncertainties can be obtained. This work describes the detailed uncertainty budget determination using the ISO-GUM approach. The traces of lead in wine were separated from the matrix by ion exchange chromatography after HNO(3)/H(2)O(2) microwave digestion. The thallium isotope amount ratio ( n((205)Tl)/ n((203)Tl)) was used to correct for mass discrimination using an exponential model approach. The corrected lead isotope amount ratio n((206)Pb)/ n((208)Pb) for the isotopic standard SRM 981 measured in our laboratory was compared with ratio values considered to be the least uncertain. The result has been compared in a so-called pilot study "lead in wine" organised by the CCQM (Comité Consultatif pour la Quantité de Matière, BIPM, Paris; the highest measurement authority for analytical chemical measurements). The result for the lead amount content k(Pb) and the corresponding expanded uncertainty U given by our laboratory was:k(Pb)=1.329 x 10-10mol g-1 (amount content of lead in wine)U[k(Pb)]=1.0 x 10-12mol g-1 (expanded uncertainty U=kxuc, k=2)The uncertainty of the main influence parameter of the combined measurement uncertainty was determined to be the isotope amount ratio R(206,B) of the blend between the enriched spike and the sample.


Correlation between cow's milk protein allergy and otitis media: a systematic review.
To review the evidence pertaining to the association between cow's milk protein allergy and recurrent acute otitis media and otitis media with effusion. The CENTRAL, Web of Science, EMBASE, MEDLINE, LILACS databases, and gray literature were searched. Four studies were included, identifying the prevalence rates: 0.2% of delayed speech due to chronic otitis media with effusion in 382 children with cow's milk protein allergy, 10.7% of cow's milk protein allergy in 242 children who underwent ENT procedures, 40% of cow's milk protein allergy in 25 children with recurrent otitis media with effusion and higher tendency to otitis media in children with cow's milk protein allergy of 186 children (1.5 + 0.6 vs. 0.4 + 0.1; p < 0.1). Considering the characteristics and methodological variations of the identified studies, it is not possible to state that there is reliable evidence of an association between cow's milk protein allergy and otitis media.


Erythrocyte magnesium fluxes in mice with nutritionally and genetically low magnesium status.
Low intracellular magnesium (Mg) contents may be observed in case of severe Mg insufficient intake or because of genetic regulation. This work was conducted to investigate the influence of intracellular Mg content on erythrocyte Mg(2+) influx and efflux in mice with low nutritionally and genetically (MGL and MGH mice) Mg status. C57BL6 mice were fed for 2 wks a diet containing 1000 mg Mg/kg diet Mg (control group), 100 mg Mg/kg diet (Mg-marginal group) or 30 mg Mg/kg diet (Mg deficient group), while mice with low (MGL) and high (MGH) Mg levels were fed a control diet for 2 wks. The quantification of erythrocyte Mg(2+) influx and efflux was performed using a stable isotope of Mg. Our results showed that erythrocyte Mg(2+) influx and efflux were respectively increased and decreased in nutritional Mg deficiency; while in genetically determined Mg status Mg(2+) fluxes were lower in MGL mice compared to MGH mice. Moreover Mg(2+) efflux was significantly correlated to Mg level in erythrocytes in all the mice studied (p < 0.001). In conclusion, erythrocyte Mg(2+) influx and efflux are modulated by low Mg status, namely decreased Mg(2+) efflux compensate for nutritional Mg deficiency, while the genetic regulation of erythrocyte Mg(2+) content depends on modification of Mg(2+) influx.