Mealtime problems predict outcome in clinical trial to improve nutrition in children with CF.
Better growth and nutritional status is strongly associated with better pulmonary function and survival in children with CF. Behavioral intervention is an efficacious treatment approach for improving calorie intake and weight gain in children with CF; and recently has been shown to facilitate maintenance of daily energy intake at 120% of the healthy population over a 2-year period. However, no study to date has examined factors that predict outcome with behavior intervention to promote weight gain in CF. The objectives of this study were to examine the influence of nutritional status, mealtime behavior problems, and maternal depressive symptoms on calorie intake and weight gain following participation in a randomized trial to improve nutritional status in cystic fibrosis. Sixty-seven children, aged 4-12 years with cystic fibrosis participated in a clinical trial targeting calorie and weight increases. Participants completed baseline measures of mealtime behavior problems, maternal depression, and fat absorption, and baseline and post-treatment caloric intake and weight. Assignment to behavioral group (R(2) change = 0.17), lower frequency of mealtime behavior problems (R(2) change = 0.11), and higher maternal depression (R(2) change = 0.06) predicted greater calorie increase baseline to post-treatment. Assignment to behavioral group (R(2) change = 0.09), higher baseline weight (R(2) change = 0.10), fat absorption (R(2) change = 0.02), and lower frequency of mealtime behavior problems (R(2) change = 0.06) predicted greater weight gain baseline to post-treatment. Less frequent mealtime behavior problems led to better calorie intake and weight gain in a 9-week clinical trial of behavior intervention and nutrition education to improve nutritional status in cystic fibrosis. The key implication from these findings is that early referral to behavioral intervention as soon as growth deficits become a concern will likely yield the best nutritional outcomes.


Evaluation of repeated or acute treatment with cannabidiol (CBD), cannabidiolic acid (CBDA) or CBDA methyl ester (HU-580) on nausea and/or vomiting in rats and shrews.
When acutely administered intraperitoneally, the non-psychoactive cannabinoid cannabidiol (CBD), its acidic precursor cannabidiolic acid (CBDA) and a stable methyl ester of CBDA (HU-580) reduce lithium chloride (LiCl)-induced conditioned gaping in male rats (a selective preclinical model of acute nausea) via activation of the serotonin 1A (5-HT1A) receptor. To utilise these compounds to manage nausea in the clinic, we must determine if their effectiveness is maintained when injected subcutaneously (s.c) and when repeatedly administered. First, we compared the effectiveness of each of these compounds to reduce conditioned gaping following repeated (7-day) and acute (1-day) pretreatments and whether these anti-nausea effects were mediated by the 5-HT1A receptor. Next, we assessed whether the effectiveness of these compounds can be maintained when administered prior to each of 4 conditioning trials (once per week). We also evaluated the ability of repeated CBD (7 days) to reduce LiCl-induced vomiting in Suncus murinus. Finally, we examined whether acute CBD was equally effective in male and female rats. Both acute and repeated (7 day) s.c. administrations of CBD (5 mg/kg), CBDA (1 μg/kg) and HU-580 (1 μg/kg) similarly reduced LiCl-induced conditioned gaping, and these effects were blocked by 5HT1A receptor antagonism. When administered over 4 weekly conditioning trials, the anti-nausea effectiveness of each of these compounds was also maintained. Repeated CBD (5 mg/kg, s.c.) maintained its anti-emetic efficacy in S. murinus. Acute CBD (5 and 20 mg/kg, s.c.) administration reduced LiCl-induced conditioned gaping similarly in male and female rats. When administered repeatedly (7 days), CBD, CBDA and HU-580 did not lose efficacy in reducing nausea and continued to act via agonism of the 5-HT1A receptor. When administered across 4 weekly conditioning trials, they maintained their effectiveness in reducing LiCl-induced nausea. Repeated CBD also reduced vomiting in shrews. Finally, CBD's anti-nausea effects were similar in male and female rats. This suggests that these cannabinoids may be useful anti-nausea and anti-emetic treatments for chronic conditions, without the development of tolerance.


Encoding specificity principle in motor short-term memory for movement extent.
The hypothesis was tested that, when the mode of presentation matches the mode of reproduction in memory for movement extent, there is less error in reproduction than when the modes are not matched. Female undergraduates (n = 24) were tested under active and passive criterion movements presented either under preselected or constrained conditions. All subjects underwent 36 trials involving the combination of three retention conditions (immediate, 20-sec unfilled, and 20-sec filled) and two reproduction conditions (active and passive). Results for absolute error showed that for constrained presentations, when the mode of presentation and the mode of reproduction were the same, accuracy was greater than when the modes of presentation and reproduction were different.


Parallel evolution of arborescent carrots (Daucus) in Macaronesia.
Despite intensive research, the pathways and driving forces behind the evolution of derived woodiness on oceanic islands remain obscure. The genus Daucus comprises mostly herbs (therophytes, hemicryptophytes) with few rosette treelets (chamaephytes) endemic to various Macaronesian archipelagos, suggesting their independent evolution. To elucidate the evolutionary pathways to derived woodiness, we examined phylogenetic relationships and the habit and secondary xylem evolution in Daucus and related taxa. Sixty taxa were surveyed for molecular markers, life history, and habit traits. Twenty-one species were considered for wood anatomical characters. A dated phylogeny was estimated using Bayesian methods. The evolution of selected traits was reconstructed using parsimony and maximum likelihood. Daucus dispersed independently to the Canary Islands (and subsequently to Madeira), Cape Verde, and the Azores in the late Miocene and Pleistocene. Life span, reproductive strategy, and life form were highly homoplastic; the ancestor of Daucus was probably a monocarpic, biennial hemicryptophyte. Rosette treelets evolved independently in the Canarian-Madeiran lineage and in Cape Verde, the latter within the last 0.13 Myr. Treelets and hemicryptophytes did not differ in wood anatomy. Pervasive axial parenchyma in wood occurred more often in polycarpic rather than monocarpic species. Life span and life form in Daucus are evolutionarily labile and may change independently of wood anatomy, which is related to plant reproductive strategy rather than to life form. Insular woodiness may evolve rapidly (as demonstrated in D. bischoffii), and in Daucus, it does not seem to be an adaptation to lower the risk of xylem embolism.


Inhibition of tyrosine Z photooxidation after formation of the S3 state in Ca(2+)-depleted and Cl(-)-depleted photosystem II.
Ca2+ and Cl- are obligatory cofactors in photosystem II (PS-II), the oxygen-evolving enzyme of plants. The sites of inhibition in both Ca(2+)- and Cl(-)-depleted PS-II were compared using EPR and flash absorption spectroscopies to follow the extent of the photooxidation of the redox-active tyrosine (TyrZ) and of the primary electron donor chlorophyll (P680) and their subsequent reduction in the dark. The inhibition occurred after formation of the S3 state in Ca(2+)-depleted PS-II. In Cl(-)-depleted photosystem II, the inhibition occurred after formation of the S3 state in about half of the centers and probably after S2TyrZ+ formation in the remaining centers. After the S3 state was formed in Ca(2+)- and Cl(-)-depleted photosystem II, electron transfer from TyrZ to P680 was inhibited. This inhibition is discussed in terms of electrostatic constraints resulting from S3 formation in the absence of Ca2+ and Cl-.


The role of carbon monoxide and heme oxygenase in the prevention of sickle cell disease vaso-occlusive crises.
Sickle Cell Disease (SCD) is a painful, lifelong hemoglobinopathy inherited as a missense point mutation in the hemoglobin (Hb) beta-globin gene. This disease has significant impact on quality of life and mortality, thus a substantial medical need exists to reduce the vaso-occlusive crises which underlie the pathophysiology of the disease. The concept that a gaseous molecule may exert biological function has been well known for over one hundred years. Carbon monoxide (CO), although studied in SCD for over 50 years, has recently emerged as a powerful cytoprotective biological response modifier capable of regulating a host of physiologic and therapeutic processes that, at low concentrations, exerts key physiological functions in various models of tissue inflammation and injury. CO is physiologically generated by the metabolism of heme by the heme oxygenase enzymes and is measurable in blood. A substantial amount of preclinical and clinical data with CO have been generated, which provide compelling support for CO as a potential therapeutic in a number of pathological conditions. Data underlying the therapeutic mechanisms of CO, including in SCD, have been generated by a plethora of in vitro and preclinical studies including multiple SCD mouse models. These data show CO to have key signaling impacts on a host of metallo-enzymes as well as key modulating genes that in sum, result in significant anti-inflammatory, anti-oxidant and anti-apoptotic effects as well as vasodilation and anti-adhesion of cells to the endothelium resulting in preservation of vascular flow. CO may also have a role as an anti-polymerization HbS agent. In addition, considerable scientific data in the non-SCD literature provide evidence for a beneficial impact of CO on cerebrovascular complications, suggesting that in SCD, CO could potentially limit these highly problematic neurologic outcomes. Research is needed and hopefully forthcoming, to carefully elucidate the safety and benefits of this potential therapy across the age spectrum of patients impacted by the host of pathophysiological complications of this devastating disease.


Tomato 14-3-3 protein TFT7 interacts with a MAP kinase kinase to regulate immunity-associated programmed cell death mediated by diverse disease resistance proteins.
Programmed cell death (PCD) associated with immunity is triggered when a plant disease resistance (R) protein recognizes a corresponding pathogen virulence protein. In tomato, detection by the host Pto kinase of the Pseudomonas syringae proteins AvrPto or AvrPtoB causes localized PCD. Previously, we reported that both MAPKKKα (mitogen-activated protein kinase kinase kinase) and the tomato 14-3-3 protein 7 (TFT7) positively regulate Pto-mediated PCD in tomato and Nicotiana benthamiana. In addition, in contrast to MAPKKKα, TFT7 is required for PCD mediated by four other R proteins. Here we investigate why TFT7 is required for PCD induced by diverse R proteins in plants. We discovered that a MAPKK, SlMKK2, which acts downstream of SlMAPKKKα, also interacts with TFT7 in plant cells. Gene silencing experiments revealed that the orthologous genes of both SlMKK2 and TFT7 in N. benthamiana are required for PCD mediated by the same set of R proteins. SlMKK2 and its orthologs contain a 14-3-3 binding site in their N terminus, and Thr(33) in this site is required for interaction with TFT7 in vivo. Like the structurally similar human 14-3-3ε protein, TFT7 forms a homodimer in vivo. Because TFT7 interacts with both SlMAPKKKα and SlMKK2 and also forms a homodimer, we propose that TFT7 may coordinately recruit these client proteins for efficient signal transfer, leading to PCD induction.


The formation of highly oxidized multifunctional products in the ozonolysis of cyclohexene.
The prompt formation of highly oxidized organic compounds in the ozonolysis of cyclohexene (C6H10) was investigated by means of laboratory experiments together with quantum chemical calculations. The experiments were performed in borosilicate glass flow tube reactors coupled to a chemical ionization atmospheric pressure interface time-of-flight mass spectrometer with a nitrate ion (NO3(-))-based ionization scheme. Quantum chemical calculations were performed at the CCSD(T)-F12a/VDZ-F12//ωB97XD/aug-cc-pVTZ level, with kinetic modeling using multiconformer transition state theory, including Eckart tunneling corrections. The complementary investigation methods gave a consistent picture of a formation mechanism advancing by peroxy radical (RO2) isomerization through intramolecular hydrogen shift reactions, followed by sequential O2 addition steps, that is, RO2 autoxidation, on a time scale of seconds. Dimerization of the peroxy radicals by recombination and cross-combination reactions is in competition with the formation of highly oxidized monomer species and is observed to lead to peroxides, potentially diacyl peroxides. The molar yield of these highly oxidized products (having O/C > 1 in monomers and O/C > 0.55 in dimers) from cyclohexene ozonolysis was determined as (4.5 ± 3.8)%. Fully deuterated cyclohexene and cis-6-nonenal ozonolysis, as well as the influence of water addition to the system (either H2O or D2O), were also investigated in order to strengthen the arguments on the proposed mechanism. Deuterated cyclohexene ozonolysis resulted in a less oxidized product distribution with a lower yield of highly oxygenated products and cis-6-nonenal ozonolysis generated the same monomer product distribution, consistent with the proposed mechanism and in agreement with quantum chemical modeling.


Frontline antibiotic therapy.
The need to use front-line antibiotics wisely has never been greater. Antibiotic resistance and multi-drug resistant infection, driven by antibiotic use, remain major public health and professional concerns. To overcome these infection problems, use of older antibiotics active against multi drug-resistant pathogens is increasing - for example, colistin, fosfomycin, pivmecillinam, pristinamycin, temocillin and oral tetracyclines. The number of new antibacterials reaching clinical practice has reduced significantly in the last 20 years, most being focused on therapy of Gram-positive infection - eg linezolid, daptomycin, telavancin and ceftaroline. Recent guidance on antibiotic stewardship in NHS trusts in England is likely to provide a backdrop to antibiotic use in hospitals in the next 5 years.


Cell swelling activates ATP-dependent voltage-gated chloride channels in M-1 mouse cortical collecting duct cells.
In the present study we used whole-cell patch clamp recordings to investigate swelling-activated Cl-currents (ICl-swell) in M-1 mouse cortical collecting duct (CCD) cells. Hypotonic cell swelling reversibly increased the whole-cell Cl- conductance by about 30-fold. The I-V relationship was outwardly-rectifying and ICl-swell displayed a characteristic voltage-dependence with relatively fast inactivation upon large depolarizing and slow activation upon hyperpolarizing voltage steps. Reversal potential measurements revealed a selectivity sequence SCN- > I- > Br- > Cl- > > gluconate. ICl-swell was inhibited by tamoxifen, NPPB (5-nitro-2(3-phenylpropylamino)-benzoate), DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid), flufenamic acid, niflumic acid, and glibenclamide, in descending order of potency. Extracellular cAMP had no significant effect. ICl-swell was Ca2+ independent, but current activation depended on the presence of a high-energy gamma-phosphate group from intracellular ATP or ATP gamma S. Moreover, it depended on the presence of intracellular Mg2+ and was inhibited by staurosporine, which indicates that a phosphorylation step is involved in channel activation. Increasing the cytosolic Ca2+ concentration by using ionomycin stimulated Cl- currents with a voltage dependence different from that of ICl-swell. Analysis of whole-cell current records during early onset of ICl-swell and during final recovery revealed discontinuous step-like changes of the whole-cell current level which were not observed under nonswelling conditions. A single-channel I-V curve constructed using the smallest resolvable current transitions detected at various holding potentials and revealed a slope conductance of 55, 15, and 8 pS at +120, 0, and -120 mV, respectively. The larger current steps observed in these recordings had about 2, 3, or 4 times the size of the putative single-channel current amplitude, suggesting a coordinated gating of several individual channels or channel subunits. In conclusion we have functionally characterized ICl-swell in M-1 CCD cells and have identified the underlying single channels in whole-cell current recordings.


Obesometric factors associated with increased skin-to-stone distances in renal stone patients.
Obese patients are at increased risk for renal stones as well as treatment failures due to increased skin-to-stone distances (SSD) and harder stone compositions. We investigated the relationships between obesometric parameters (body mass index [BMI], body fat distribution and obesity-related hormone levels) with SSD and stone hardness. We prospectively enrolled patients undergoing stone interventions at our institution. Computed tomography (CT) scans were analyzed; adipose tissue was identified according to Hounsfield units (HU) and separated into subcutaneous (SAT) and visceral (VAT) components. The pixels were averaged at three levels to calculate fat distribution: %VAT = (VAT)/(VAT + SAT). SSD was measured and HU were used as a surrogate for stone hardness. Obesity-related hormones leptin and adiponectin were measured by ELISA. Seventy-nine patients were prospectively enrolled. Mean BMI and %VAT were 30.02 kg/m2 and 40.13 kg/m2. Mean leptin and adiponectin levels were 17.5 ng/mL and 7.67 mcg/mL indicating high risk for metabolic consequences of obesity. Females had greater proportions of subcutaneous fat than males (%VAT 28.4 versus 46.94, p < 0.001) and greater SSD (11.26 cm versus 9.86 cm, p = 0.025). Among obese patients, subcutaneous fat correlated with SSD independently of BMI (r = 0.454, p = 0.008). Obese patients with %VAT > 40 versus < 40 had SSD of 11.35 cm versus 13.7 cm (p = 0.005). Diabetics had harder stone compositions as measured by HU than non-diabetics (982.86 versus 648.86, p = 0.001). Obesometric parameters such as BMI, body fat distribution, and the presence of diabetes mellitus are important considerations in the management of renal stone disease. A large proportion of subcutaneous fat, which can be estimated by physical examination, predicts SSD among obese patients and may aid treatment decisions in patients, particularly those without pre-treatment CT scans. Further studies are needed to refine the role of obesometrics in personalizing treatment decisions.


Variables affecting production of monocyte chemotactic factor 1 from human leukocytes stimulated with Cryptococcus neoformans.
The chemokine monocyte chemoattractant protein 1 (MCP-1) is produced predominantly by mononuclear phagocytes and stimulates recruitment into infected tissues of blood monocytes and T cells. These cell types are thought to be critical to host defenses against infections due to Cryptococcus neoformans, a major cause of disease in persons with AIDS and other disorders of cell-mediated immunity. Accordingly, in the present study, we examined the conditions under which human monocytes and bronchoalveolar macrophages (BAM) are stimulated by C. neoformans to produce MCP-1. C. neoformans was a potent inducer of MCP-1 release from monocytes, with levels of chemokine secreted similar to that seen following stimulation with lipopolysaccharide (LPS). BAM, in contrast, were stimulated by LPS, but not by C. neoformans, to secrete MCP-1. A peak in MCP-1 mRNA was seen 8 h following cryptococcal stimulation of monocytes. Nine strains of C. neoformans stimulated monocytes to release MCP-1, and there was only modest variation between strains. However, when an individual strain was used, the capacity of C. neoformans to stimulate monocyte MCP-1 release did vary, depending upon the conditions used to grow the fungal stimuli. Finally, C. neoformans stimulated comparable quantities of MCP-1 release in monocytes from donors with and without human immunodeficiency virus infection. These data establish C. neoformans as a potent stimulator of MCP-1 in monocytes, but not in BAM. The failure of C. neoformans to stimulate MCP-1 in BAM, if occurring in vivo, could result in a diminished cell-mediated inflammatory response following inhalation of airborne fungi.


Genetic and caregiving-based contributions to infant attachment: unique associations with distress reactivity and attachment security.
In the longitudinal study reported here, we examined genetic and caregiving-based contributions to individual differences in infant attachment classifications. For 154 mother-infant pairs, we rated mothers' responsiveness to their 6-month-old infants during naturalistic interactions and classified infants' attachment organization at 12 and 18 months using the Strange Situation procedure. These infants were later genotyped with respect to the serotonin-transporter-linked polymorphic region (5-HTTLPR). Maternal responsiveness uniquely predicted infants' attachment security. Infants' 5-HTTLPR variation uniquely predicted their subtype of attachment security at 12 months and their subtype of attachment insecurity at 12 and 18 months. The short allele for 5-HTTLPR was associated with attachment classifications characterized by higher emotional distress. These findings suggest that 5-HTTLPR variation contributes to infants' emotional reactivity and that the degree to which caregivers are responsive influences how effectively infants use their caregivers for emotion regulation. Theoretical implications for the study of genetic and caregiving influences are discussed.


[Significance of arterial stiffness parameters for predicting cardiovascular mortality in hemodialysis patients: a prospective cohort study].
Previous studies demonstrated that different parameters of arterial stiffness are related to cardiovascular mortality in hemodialysis patients. The relative prognostic value of these parameters has not previously been evaluated in one cohort. Carotid-femoral pulse wave velocity, carotid augmentation index, carotid pulse pressure and carotid-brachial pulse pressure amplification were measured in 98 patients before and after hemodialysis. Patients were followed for a median of 29 months (1-34) and the association of these parameters with cardiovascular mortality was assessed using log-rank tests and Cox proportional hazards regressions. During follow-up, 40 patients died (mortality rate 20.7/100 patient-year), of which 25 died of cardiovascular causes. Increasing pre- and postdialysis pulse wave velocity tertiles and decreasing predialysis pulse pressure amplification tertiles were significantly related to cardiovascular mortality (p-values are 0.012 and 0.011 for pre- and postdialysis pulse wave velocity, and <0.001 and 0,321 for pre- and postdialysis pulse pressure amplification, respectively). Neither the carotid augmentation index nor carotid pulse pressure was related to cardiovascular mortality. In the Cox-regression, the adjusted hazard ratios for 1 m/s higher pre- and postdialysis pulse wave velocity were 1.24 (1.07-1.44) and 1.17 (1.06-1.28), respectively. The hazard ratio for 10% lower predialysis pulse pressure amplification was 1.41 (1.03-1.92). When included in the same model, both predialysis pulse wave velocity and pulse pressure amplification remained significantly associated with cardiovascular mortality (relative risk: 1.23 [1.07-1.42] and 1.39 [1.02-1.89]). Among different stiffness parameters, pulse wave velocity is consistently related to cardiovascular mortality, irrespective of the timing of measurement. Predialysis pulse pressure amplification seems to provide additional prognostic information.


Multipotent, dedifferentiated cancer stem-like cells from brain gliomas.
In modern cancer biology, external factors and niches can act on differentiated tissue cells to cause cancer by inducing dedifferentiation of mature adult cells. Recently, we discovered that dedifferentiation of glioma cancer cells alters the expression of mature and neural stem cell (NSC)-related genes, in that cancer cells adjust to the serum-deprived environment and cell-to-cell interaction by down-regulating genes associated with neural mature markers and up-regulating genes that are primitive NSC markers. Neurogenesis of dedifferentiated glioma cancer cells also showed a highly increased neuronal marker associated with highly decreased glial and oligodendrocyte cell markers. After treatment with chemotherapeutic drugs, dedifferentiated cancer cells showed strong drug resistance and continued active cell growth. After grafting to severe combined immunodeficient (SCID) mouse brains, dedifferentiated cancer stem cells migrated and continued active proliferation for more than 4 weeks. We also performed microarray analysis and characterized the gene expression patterns in control cancer cells with dedifferentiated cancer stem-like cells. We delineated specific numbers of important proliferation signaling proteins, primitive neural lineage-related proteins, cancer genes, and transporter genes. In this report, we propose that the dedifferentiation process of brain tumor and normal tissue may contribute to the malignancy and aggressiveness of the brain cancer.


DynPeak: an algorithm for pulse detection and frequency analysis in hormonal time series.
The endocrine control of the reproductive function is often studied from the analysis of luteinizing hormone (LH) pulsatile secretion by the pituitary gland. Whereas measurements in the cavernous sinus cumulate anatomical and technical difficulties, LH levels can be easily assessed from jugular blood. However, plasma levels result from a convolution process due to clearance effects when LH enters the general circulation. Simultaneous measurements comparing LH levels in the cavernous sinus and jugular blood have revealed clear differences in the pulse shape, the amplitude and the baseline. Besides, experimental sampling occurs at a relatively low frequency (typically every 10 min) with respect to LH highest frequency release (one pulse per hour) and the resulting LH measurements are noised by both experimental and assay errors. As a result, the pattern of plasma LH may be not so clearly pulsatile. Yet, reliable information on the InterPulse Intervals (IPI) is a prerequisite to study precisely the steroid feedback exerted on the pituitary level. Hence, there is a real need for robust IPI detection algorithms. In this article, we present an algorithm for the monitoring of LH pulse frequency, basing ourselves both on the available endocrinological knowledge on LH pulse (shape and duration with respect to the frequency regime) and synthetic LH data generated by a simple model. We make use of synthetic data to make clear some basic notions underlying our algorithmic choices. We focus on explaining how the process of sampling affects drastically the original pattern of secretion, and especially the amplitude of the detectable pulses. We then describe the algorithm in details and perform it on different sets of both synthetic and experimental LH time series. We further comment on how to diagnose possible outliers from the series of IPIs which is the main output of the algorithm.


Recent progress in drying technologies for improving the stability and delivery efficiency of biopharmaceuticals.
Most biopharmaceuticals are developed in liquid dosage forms that are less stable than solid forms. To ensure the stability of biopharmaceuticals, it is critical to use an effective drying technique in the presence of an appropriate stabilizing excipient. Various drying techniques are available for this purpose, such as freeze drying or lyophilization, spray drying, spray freeze-drying, supercritical fluid drying, particle replication in nonwetting templates, and fluidized bed drying. In this review, we discuss drying technologies and their applications in the production of stable solid-state biopharmaceuticals, providing examples of commercially available products or clinical trial formulations. Alongside this, we also review how different analytical methods may be utilized in the evaluation of aerosol performance and powder characteristics of dried protein powders. Finally, we assess the protein integrity in terms of conformational and physicochemical stability and biological activity. With the aim of treating either infectious respiratory diseases or systemic disorders, inhaled biopharmaceuticals reduce both therapeutic dose and cost of therapy. Drying methods in the presence of optimized protein/stabilizer combinations, produce solid dosage forms of proteins with greater stability. A suitable drying method was chosen, and the process parameters were optimized based on the route of protein administration. With the ongoing trend of addressing deficiencies in biopharmaceutical production, developing new methods to replace conventional drying methods, and investigating novel excipients for more efficient stabilizing effects, these products have the potential to dominate the pharmaceutical industry in the future.


Female responses to ancestral advertisement calls in tungara frogs.
Phylogenetic techniques were used to estimate and reconstruct advertisement calls at ancestral nodes. These calls were used to investigate the degree of preference of female túngara frogs (Physalaemus pustulosus) for both extant and ancestral calls. Females did not discriminate between calls of males of their own species and calls at their most recent ancestral node. They also recognized calls of three extant species and at four ancestral nodes as the signals of appropriate mates. Both shared ancestral history, and call convergence might differentially influence call preferences.


Comparative potential therapeutic effect of sesame oil and peanut oil against acute monocrotaline (Crotalaria) poisoning in a rat model.
Many Crotalaria plant species contain hepatotoxic pyrrolizidine alkaloids (such as monocrotaline) that can cause acute and chronic poisoning in cattle and other animals. Peanut oil, atropine sulfate, and antidiarrheal agents are used to treat acute monocrotaline poisoning. The effect of sesame on acute monocrotaline poisoning has never been investigated. Fifty male Sprague-Dawley rats were used for toxicity studies. Experiment 1: Group I, control. Groups II-IV were given monocrotaline (205.2 mg/kg) and euthanized 6, 12, and 24 hours later. Experiment 2: Group I, control. Group II monocrotaline alone (205.2 mg/kg). Groups III-VI were given monocrotaline (205.2 mg/kg) and 1 hour later, Groups III and IV were given sesame oil (1 and 2 mL/kg) and Groups V and VI were given peanut oil (1 and 2 mL/kg). Monocrotaline significantly decreased (P < .05) serum amylase activity, but, over time, increased (P < .05) pancreatic and lung injury. AST and ALT activity and liver injury peaked at 24 hours. Sesame oil and peanut oil (P < .05) inhibited the changes in all tested parameters in acute monocrotaline poisoning. Although peanut oil inhibited acute monocrotaline poisoning, it induced steatosis, but sesame oil did not. We hypothesize that early pancreatic and lung injury and late liver injury contribute to acute monocrotaline poisoning and that sesame oil is more efficacious than peanut oil against acute monocrotaline poisoning in rats. However, additional studies are needed to confirm that these oils have the same effects in cattle and other animals.


Budget impact of bimonthly use of cetuximab in patients diagnosed with metastatic colorectal cancer.
Aim: Cetuximab is used for the treatment of RAS wild-type metastatic colorectal cancer patients. Standard administration schedule is once a week; however, the bioequivalence of an every-other-week (EOW) schedule was demonstrated. Methods: We compared a base case scenario of 100% weekly administration to an EOW at 50 or 100%. Medical examinations, patient management and loss of productivity were considered. Results: Base case was estimated at €100.6 million versus €92.8 million and €84.9 million of EOW 50 and 100%, which showed a cost reduction of 8 and 16%, respectively. Indirect costs accounted for 65% in both scenarios. Conclusion: The adoption of an EOW administration schedule of cetuximab reduced direct and indirect costs substantially.


Statins Are Associated With Increased Insulin Resistance and Secretion.
Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.


Nocardia paucivorans sp. nov.
Chemotaxonomic and 16S rDNA sequence analyses of an isolate from the sputa and bronchial secretions of a patient with chronic lung disease clearly demonstrated that it belongs to the genus Nocardia. DNA-DNA hybridization data, as well as the biochemical characteristics of the isolate, indicate that it belongs to a new species that differs from previously described members of the genus Nocardia. The name Nocardia paucivorans sp. nov. is proposed for this isolate and is represented by strain IMMIB D-1632T (= DSM 44386T).


Nonredundant role of CCRL2 in lung dendritic cell trafficking.
Chemokine CC motif receptor-like 2 (CCRL2) is a heptahelic transmembrane receptor that shows the highest degree of homology with CCR1, an inflammatory chemokine receptor. CCRL2 mRNA was rapidly (30 minutes) and transiently (2-4 hours) regulated during dendritic cell (DC) maturation. Protein expression paralleled RNA regulation. In vivo, CCRL2 was expressed by activated DC and macrophages, but not by eosinophils and T cells. CCRL2(-/-) mice showed normal recruitment of circulating DC into the lung, but a defective trafficking of antigen-loaded lung DC to mediastinal lymph nodes. This defect was associated to a reduction in lymph node cellularity and reduced priming of T helper cell 2 response. CCRL2(-/-) mice were protected in a model of ovalbumin-induced airway inflammation, with reduced leukocyte recruitment in the BAL (eosinophils and mononuclear cells) and reduced production of the T helper cell 2 cytokines, interleukin-4 and -5, and chemokines CCL11 and CCL17. The central role of CCRL2 deficiency in DC was supported by the fact that adoptive transfer of CCRL2(-/-) antigen-loaded DC in wild-type animals recapitulated the phenotype observed in knockout mice. These data show a nonredundant role of CCRL2 in lung DC trafficking and propose a role for this receptor in the control of excessive airway inflammatory responses.


Custom-fabricated masks for aeromechanical measures.
A technique is described for the construction of custom fabricated face masks designed for use in aeromechanical studies of individuals with speech disorders, such as those associated with craniofacial defects. The wax-elimination method of mask fabrication described herein is similar to routine dental laboratory procedures. Materials employed are heat-cured acrylic resin for the body of the mask and heat-cured resilient liner for the tissue contacting surface of the mask.


Current problems and future requirements for 5-hydroxytryptamine receptor classification.
The present scheme for classifying and naming 5-hydroxytryptamine (5-HT) receptors is being challenged by a growing number of reports that describe receptor types that fail to meet the criteria for admission into the "5-HT1-like," 5-HT2 or, 5-HT3 classes. Consequently, there is an increasing tendency for authors to make unilateral designations for new receptor classes in the absence of any formal criteria for their classification. This hinders rather than helps in establishing the minimum safe criteria for receptor definition and emphasizes the need to update the current scheme. In this article a number of factors are considered that might contribute to instability in 5-HT receptor classification and attention is drawn in particular to the generally unreliable behavior of available chemically heterogeneous antagonists. Experiments with tryptamine agonists and antagonists, although limited in number, suggest that close chemical analogs of the natural receptor agonist 5-HT provide a quantitatively stable and therefore more secure basis for classification, which usefully complements and extends the currently accepted proposals. Furthermore, an approach based on hormone analogs focuses attention on the objectives of the classification process as well as a definition for the term receptor. These issues are germane to the development of a unifying scheme for receptor taxonomy and have been considered here in terms of the current problems and future requirements of 5-HT receptor classification.


Genetic and ecological outcomes of Inga vera subsp. affinis (Leguminosae) tree plantations in a fragmented tropical landscape.
Planting of native trees for habitat restoration is a widespread practice, but the consequences for the retention and transmission of genetic diversity in planted and natural populations are unclear. Using Inga vera subsp. affinis as a model species, we genotyped five natural and five planted populations in the Atlantic forest of northeastern Brazil at polymorphic microsatellite loci. We studied the breeding system and population structure to test how much genetic diversity is retained in planted relative to natural populations. We then genotyped seedlings from these populations to test whether genetic diversity in planted populations is restored by outcrossing to natural populations of I. vera. The breeding system of natural I. vera populations was confirmed to be highly outcrossing (t = 0.92; FIS = -0.061, P = 0.04), with populations showing weak population substructure (FST = 0.028). Genetic diversity in planted populations was 50% less than that of natural populations (planted: AR = 14.9, HO = 0.865 and natural: AR = 30.8, HO = 0.655). However, seedlings from planted populations showed a 30% higher allelic richness relative to their parents (seedlings AR = 10.5, parents AR = 7.6). Understanding the processes and interactions that shape this system are necessary to provide ecologically sensible goals and successfully restore hyper-fragmented habitats. Future restoration plans for I. vera must consider the genetic diversity of planted populations and the potential for gene flow between natural populations in the landscape, in order to preserve ecological interactions (i.e. pollination), and promote opportunities for outcrossing.


Cerebral polygyria in the Chiari Type II (Arnold-Chiari) malformation.
Abnormalities of the cerebral cortical pattern have been observed in association with the Chiari Type II malformation and described as polymicrogyria, microgyria, stenogyria or polygyria. In order to characterize and quantify these abnormalities, the sulcal patterns of the brains of 15 patients with the Chiari Type II malformation were compared with those of 10 pediatric controls without cerebral malformations. In this analysis, sulci were grouped by anatomical characteristics into three categories. The first category, the fissures, were represented by the long, deep indentions in the cerebral cortex such as the Sylvian fissure. The second category, the principal sulci, were represented by the shorter, named, anatomically consistent sulci such as the superior frontal sulcus. The third category contained the minor sulci which were defined as those shallow grooves which depressed the cortical surface but were not recognizable as consistent anatomical landmarks. Subjectively all brains with Chiari Type II malformations demonstrated abnormal gyral patterns. These brains exhibited abnormalities in the number and distribution of principal and/or minor sulci. Sulcal density, defined as the length of sulcus per square millimeter of cortical area, was quantitated utilizing a computer assisted digitizer program. For the brains with the Chiari Type II malformations, the length of all sulci (principal and minor combined) per square mm was 0.238 +/- 0.045 mm-1 as compared with the control patients whose value was 0.182 +/ 0.021 mm-1 (t = .0015). Average length per square millimeter of principal sulci was 0.176 +/- 0.029 mm-1 as compared with 0.132 +/- 0.015 mm-1 (t = .0002) for the control brains.(ABSTRACT TRUNCATED AT 250 WORDS)


Access to Telepharmacy Services May Reduce Hospital Admissions in Outpatient Populations During the COVID-19 Pandemic.
Introduction: Avoidable hospital admissions put increased pressure on already strained health care resources, causing emotional and financial distress for patients and their families while taxing the health system. Pharmacist involvement in patient care has been shown to improve health care outcomes. Telepharmacy allows for personalized interaction and access to pharmacy services in a flexible format. The primary aim of this report is to explore the impact that access to a personalized telepharmacy service has on the hospital admission rate in an outpatient population before and during the COVID-19 pandemic. Materials and Methods: A retrospective, double-arm cohort study was performed. Hospital admission rates were analyzed in two similarly aged groups; one group (n = 2,242) had access to telepharmacy services through their primary care provider and another group did not (n = 1,540), from 2019 to 2020. Statistical analysis was performed to explore hospitalization rates in both groups. Results: An increase in hospitalization rates was observed in both groups of patients from 2019 to 2020. The patient group that had access to the telepharmacy service demonstrated a reduced rise in hospitalization rates versus the group without access to the telepharmacy service (access group +12.9% vs. nonaccess group +40.2%, p < 0.05, Student's t-test). Discussion: The patient group with access to telepharmacy services demonstrated a reduced increase in hospitalizations versus the group without access in 2020. While this represents a preliminary investigation into the potential impacts of telepharmacy on hospitalization rates, telepharmacy services may have a role in improving patient outcomes and cost savings.


Vaginal vs. sublingual misoprostol with mifepristone for cervical priming in second-trimester abortion by dilation and evacuation: a randomized clinical trial.
The study was conducted to assess the effectiveness of mifepristone 200 mg 48 h before administering misoprostol 600 mug, sublingual vs. vaginal route, prior to dilation and evacuation (D&E) in 12- to 20-week pregnancies. Randomized clinical trial. Clínica Mediterrania Médica, Valencia, Spain. Women with 12- to 20-week pregnancies wanting a voluntary abortion between July 9, 2004, and February 9, 2006. Nine hundred women were randomized to be included in one of the following four groups: (I) mifepristone 200 mg plus sublingual misoprostol 600 microg before D&E, (II) mifepristone 200 mg plus vaginal misoprostol 600 microg before D&E, (III) sublingual misoprostol 600 microg before D&E and (IV) vaginal misoprostol 600 microg before D&E. The degree of cervical dilation achieved before D&E, surgical time necessary to terminate the pregnancy and side effects of misoprostol. The average cervical dilation in the mifepristone groups was 12.5+/-2.8 mm (SD) [95% confidence interval (CI), 12.3-12.8] vs. 8.5+/-3.2 mm (SD) (95% CI, 8.2-8.8) in those receiving only misoprostol. Surgical time in the mifepristone sublingual misoprostol group was 11.9+/-4.3 min (SD) vs. 13.0+/-5.3 min (SD) in the sublingual misoprostol group without mifepristone (p=.007); in the mifepristone vaginal misoprostol group, the average surgical time was 12.3+/-5.0 min (SD) vs. 13.0+/-6.2 (SD) in the vaginal misoprostol group without mifepristone (p=.031). Administering mifepristone before D&E with misoprostol in second-trimester abortions makes surgery easier and shorter and, to a certain extent, lessens the risk of cervical injuries, especially in D&E in advanced gestational periods.


Early transferences and transference-like reactions.
Some patients manifest intense transferences or transference-like reactions in the earliest hours of psychotherapy. Although these reactions may actually represent transference, they may also arise from other sources, such as aspects of a patient's character, displacements from former therapists, impaired reality testing, information about the therapist, and therapist's behavior. Clinical examples are presented, and their management is discussed.


Characterizing End-of-Life Care after Geriatric Burns at a Verified Level I Burn Center.
End-of-life (EoL) care after geriatric burns (geri-burns) is understudied. To examine the practices of burn surgeons for initiating EoL discussions and the impact of decisions made on the courses of geri-burn patients who died after injury. This retrospective cohort study examined all subjects ≥65 years who died on our Level I burn service from April 1, 2009, to December 31, 2014. Measurements obtained were timing of first EoL discussion (EARLY <24 hours post-admission; LATE ≥24 hours post-admission), decisions made, age, total body surface area burned, and calculated probability of death at admission. The cohort consisted of 57 subjects, of whom 54 had at least one documented EoL care discussion between a burn physician and the patient/surrogate. No differences were seen between groups for the likelihood of an immediate decision for comfort care after the first discussion (p = 0.73) or the mean number of total discussions (p = 0.07). EARLY group subjects (n = 38) had significantly greater magnitudes of injury (p = 0.002), calculated probabilities of death at admission (p ≤ 0.001), shorter times to death (p ≤ 0.001), and fewer trips to the operating theater for burn excision and skin grafting (p ≤ 0.001) than LATE subjects (n = 16). LATE subjects' first discussion occurred at a mean of 9.3 ± 10.0 days. The vast majority of geri-burn deaths on our burn service occur after a discussion about EoL care. The timing of these discussions is driven by magnitude of injury, and it does not lead to higher proportions of an immediate decision for comfort care. The presence and timing of EoL discussions bears further study as a quality metric for geri-burn EoL care.


Autoimmune reactions as indicators of a harmful effect of industrial poisons (a review).
Literary data on the study of autoimmune reactions in the preclinical period of pathological processes developing after exposure to industrial chemical substances and also during convalescence, are presented. An analysis of these data showed the advisability of examining the state of autoimmune reactions for the earliest possible detection [during clinical well-being] of the harmful effect of chemical agents on the health state of workers being systematically in contact with these substances in industry. The observation of their dynamics in the period of convalescence may be used for the evaluation of effectiveness of the therapy employed and of completeness of restorative processes.


Multifocal infantile haemangiomatosis with hepatic involvement: two cases and treatment management.
Infantile haemangiomas (IHs) are the most common benign tumours of childhood; despite the benign histology, prognosis depends on severity of visceral involvement, with a mortality rate ranging from 50 to 90%. In this paper, we describe two infants with multifocal infantile haemangiomatosis and hepatic involvement. This condition should receive appropriate management as it can be potentially lethal due to the high risk of systemic complications such as cardiac or fulminant hepatic failure and abdominal compartment syndrome. Both cases presented with liver involvement, but only the infant who had an excellent response to propranolol is still alive. A review of current therapeutic approaches is also presented even though there are, at present, no uniform guidelines for treatment, despite the relative frequency of infantile haemangiomatosis and the potential severe complications.


Rare bioparticle detection via deep metric learning.
Recent deep neural networks have shown superb performance in analyzing bioimages for disease diagnosis and bioparticle classification. Conventional deep neural networks use simple classifiers such as SoftMax to obtain highly accurate results. However, they have limitations in many practical applications that require both low false alarm rate and high recovery rate, e.g., rare bioparticle detection, in which the representative image data is hard to collect, the training data is imbalanced, and the input images in inference time could be different from the training images. Deep metric learning offers a better generatability by using distance information to model the similarity of the images and learning function maps from image pixels to a latent space, playing a vital role in rare object detection. In this paper, we propose a robust model based on a deep metric neural network for rare bioparticle (Cryptosporidium or Giardia) detection in drinking water. Experimental results showed that the deep metric neural network achieved a high accuracy of 99.86% in classification, 98.89% in precision rate, 99.16% in recall rate and zero false alarm rate. The reported model empowers imaging flow cytometry with capabilities of biomedical diagnosis, environmental monitoring, and other biosensing applications.


Emotional Semantic Congruency based on stimulus driven comparative judgements.
A common cognitive process in everyday life consists in the comparative judgements of emotions given a pair of facial expressions and the choice of the most positive/negative among them. Results from three experiments on complete-facial expressions (happy/angry) and mixed-facial expressions (neutral/happy-or-angry) pairs viewed with (Experiment 1 and 3) or without (Experiment 2) foveation and performed in conditions in which valence was either task relevant (Experiment 1 and 2) or task irrelevant (Experiment 3), show that comparative judgements of emotions are stimulus driven. Judgements' speed increased as the target absolute emotion intensity grew larger together with the average emotion of the pair, irrespective of the compatibility between the valence and the side of motor response: a semantic congruency effect in the domain of emotion. This result undermines previous interpretation of results in the context of comparative judgements based on the lateralization of emotions (e.g., SNARC-like instructional flexibility), and is fully consistent with our formalization of emotional semantic congruency: the direct Speed-Intensity Association model.


Serum Calprotectin in Adolescents With Inflammatory Bowel Disease-A Pilot Investigation.
Fecal calprotectin (FC) is a well-integrated parameter in the monitoring of adolescent patients with inflammatory bowel disease (IBD). However, measurement of FC is limited by day-to-day-variation and by the feces consistency. Furthermore, adolescents are often noncompliant to deliver fecal sampling leading to suboptimal monitoring. Consequently, we see the need of a substitute biomarker whenever measurement of FC fails and aimed to investigate serum calprotectin (SC) in adolescents with IBD. In cross sectional data from 19 ulcerative colitis (UC) patients <18 years old, a Spearman correlation was used to analyze the correlation between SC, FC, C-reactive protein (CRP) and endoscopic and symptom scores. In longitudinal data collected from 20 UC and Crohn disease (CD) patients (10-17 years old), Mixed Effect Models (MEM) were used to analyze the association between SC, FC, CRP, and symptom scores. We found positive correlations between SC (19 samples) and the endoscopic score, symptom score, and CRP (r = 0.56, P = 0.01; r = 0.64, P = 0.003; r = 0.97, P < 0.0001). We found no significant correlation between SC and FC. In 27 samples from UC patients, the association of SC with FC and CRP were positive and significant (P = 0.004, estimate = 0.32; P = 0.0001, estimate = 0.002). The association between SC and symptom score was insignificant. In 49 samples from CD patients, the association between SC and CRP was significant (P = 0.02, estimate = 0.002) whereas associations between SC and FC and symptom score were insignificant. In the current pilot study, we found a correlation between SC and the endoscopically assessed inflammation in UC. SC may have the potential to improve disease monitoring of adolescent patients.


[Health in Andean regional integration].
Despite their shared history, the Andean countries are socially and politically diverse, with heterogeneous health realities and complex integration processes. General developments such as the Latin American Free Trade Association and Latin American Integration Association have existed for decades, along with others of a regional scope, like the Andean Community of Nations, Caribbean Community, and Central American Common Market. The health field has a specific instrument in the Andean Region called the Hipólito Unánue Agreement, created in 1971. Integration processes have concentrated on economic aspects, based on preferential customs agreements that have led to an important long-term increase in trade. Less progress has been made in the field of health in terms of sharing national experiences, knowledge, and capabilities. Analysis of experiences in health has shown that integration depends on the countries' respective strengths and to a major extent on national political processes.


Racial and ethnic disparities in acuity of presentation among children with newly diagnosed acute leukemia.
We evaluated disparities in disease burden, organ dysfunction, vital signs, and timing of therapy in children newly presenting with acute leukemia. Among 899 patients with acute leukemia diagnosed at two large children's hospitals, a priori lab-based definitions of high disease burden, infection risk, renal dysfunction, and coagulopathy were applied to electronic health record data. Black patients with acute myeloid leukemia had increased prevalence of elevated white blood cell count and uric acid; Black patients with acute lymphoblastic leukemia demonstrated increased prevalence of coagulopathy. Black patients' presentation more frequently included multiple lab abnormalities consistent with advanced physiologic dysfunction. No differences were found in days to therapy initiation.


New developments in Sjögren's syndrome.
Over the past months, noteworthy contributions to our understanding of the clinical manifestations of Sjögren's syndrome have been made. Scintigraphic and echographic techniques have been refined to document xerostomia. Various systemic complications, such as nervous system involvement, pulmonary lesions, gastric and pancreatic dysfunction, and Raynaud's phenomenon have been further described. Mast cells have been shown to participate in the salivary gland infiltration, together with T lymphocytes, of which the majority are of the memory helper/inducer phenotype. Antinuclear antibodies are directed to SS-A/Ro and SS-B/La particles. Two studies have been devoted to the cloning of the DNA encoding the 52-kD component of the former, and a series of SS-B/La DNA fragments have been generated to analyze the peptides of the latter. Virologic data have been provided, particularly the detection of anti-human immunodeficiency virus type 1 p24 protein in a number of Sjögren's syndrome patients, and the discovery of a human intracisternal A-type retroviral particle in lymphoblastoid cells exposed to homogenates of salivary tissue from patients with Sjögren's syndrome.


Cockroaches (Periplaneta americana) as carriers of agents of bacterial diarrhoea in Accra, Ghana.
Bodies and intestinal contents of 208 cockroaches (Periplaneta americana), collected from kitchens in Accra and some surrounding villages were cultured for enteric bacterial pathogens. Six of them harboured three different serogroups of Salmonella, one had Shigella dysenteriae, 64 had Coliforms, 13 had Proteus species, two had Pseudomonas species and the rest (122) carried none of the bacterial species mentioned above. The presence of Salmonella species Shigella dysenteriae and Coliforms in these insects, which were collected from kitchens where foods are kept, points to the facts that these insects could play an important role in the transmission of these pathogenic organisms, especially in our environment. Permanent solution to these bacterial diarrhoea disease problems could only be solved when food, animals and the environments are free of these microbes.


Biomechanical consequences of plantar fascial release or rupture during gait. Part II: alterations in forefoot loading.
With a model using feet from cadavers, we tested the hypothesis that plantar fascial release or rupture alters the loading environment of the forefoot during the latter half of the stance phase of gait. The model simulated the position and loading environment of the foot at two instants: early in terminal stance immediately after heel-off and late in terminal stance just preceding contralateral heel strike. Eight feet were loaded at both positions by simulated plantar flexor contraction, and the distribution of plantar pressure was measured before and after progressive release of the plantar fascia. Strain in the diaphysis of the second metatarsal was also measured, from which the bending moments and axial force imposed on the metatarsal were calculated. Cutting the medial half of the central plantar fascial band significantly increased peak pressure under the metatarsal heads but had little effect on pressures in other regions of the forefoot or on second metatarsal strain and loading. Dividing the entire central band or completely releasing the plantar fascia from the calcaneus had a much greater effect and caused significant shifts in plantar pressure and force from the toes to beneath the metatarsal heads. These shifts were accompanied by significantly increased strain and bending in the second metatarsal. Complete fasciotomy increased the magnitude of strain in the dorsal aspect of the second metatarsal by more than 80%, suggesting that plantar fascial release or rupture accelerates the accumulation of fatigue damage in these bones. Altered forefoot loading may be a potential complication of plantar fasciotomy.


Successful intrauterine pregnancy following salpingostomy; case report.
Ectopic pregnancy occurs more in young women who still desire children. Because of tubal rupture, salpingectomy which leads to tubal loss and reduced reproductive potentials is the commonest management option. This is a case report of a primipara who had ruptured left tubal ectopic pregnancy managed by salpingectomy and later had unruptured heterotopic pregnancy involving the contralateral tube and managed by salpingostomy, after which she had spontaneous abortion of the associated intrauterine pregnancy. Initial marital disharmony, followed by an uneventful intrauterine pregnancy carried to term with caesarean delivery of a live female baby. In well-selected cases, conservative tubal surgeries should be encouraged in preference to radical surgeries in the management of unruptured tubal pregnancies.


Automatic and controlled attentional processes in startle eyeblink modification: effects of habituation of the prepulse.
The effect of prehabituation of the prepulse on startle eyeblink modification was studied in two experiments. In Experiment 1, college student participants were either prehabituated or nonhabituated to a tone that served as a prepulse in a startle modification passive attention paradigm. Neither short lead interval (60 and 120 ms) prepulse inhibition (PPI) nor long lead interval (2,000 ms) prepulse facilitation (PPF) was affected by the prehabituation procedure. In Experiment 2, participants were presented with an active attention paradigm in which one of two tone prepulses was attended while the other was ignored. One group was prehabituated to the prepulses and the other was not. Unlike the results with the passive paradigm in Experiment 1, prehabituation did significantly diminish attentional modulation of PPI and PPF. These results are consistent with the hypothesis that passive PPI and PPF are primarily automatic processes, whereas attentional modulation involves controlled cognitive processing.


Why Does the Inflation Reduction Act Exclude Expensive Cancer Treatments in Price Negotiations?
The Inflation Reduction Act (IRA) includes provisions for price negotiations of certain high-spending drugs in Medicare Parts B and D. This provision received considerable attention from those interested in the costs of cancer care since Medicare covers most patients with cancer and many cancer drugs are expensive. We simulate how many cancer drugs may be eligible for IRA price negotiations and examine the reasons that many are likely to be excluded from negotiation. This study uses 2021 Medicare Fee-for-Service Part B and Part D prescription drugs expenditure data. Cancer drugs were identified using the SEER Program list of cancer medications. Our measures included total spending, beneficiary users, and spending-per-beneficiary for all cancer drugs covered under Medicare. Each drug was evaluated for eligibility on the basis of IRA negotiation provisions, including estimated loss of patent exclusivity, current competitors, and orphan drug designation. We found that very few cancer drugs will meet the IRA eligibility thresholds to be included in negotiations. We estimate that only 2.2% of beneficiaries with cancer will see lower costs because of the IRA negotiations. The main reason for this is that although novel cancer drug treatments are priced high, they generally treat relatively few beneficiaries and thus do not meet negotiation eligibility criteria, which are primarily based on a ranking of total spending. The IRA negotiation provisions will have limited impact on cancer drug prices and will likely leave most patients with cancer exposed to high drug costs.


Stakeholders in One Health.
The stakeholders in One Health include the ultimate beneficiaries (i.e. animals, people and the environment) and the organisations that work to protect them (i.e. research institutes, government ministries, international organisations and professional bodies). However, identifying these stakeholders who will contribute to One Health activities and develop solutions to complex health problems can be difficult, as these problems often affect all sectors of society. In addition, evolving concepts about health and its dependence on environmental resilience necessitate the inclusion of ministries, organisations and disciplines that may not have been traditionally considered to be related to health. The multilateral organisations with greatest responsibilities in the global health arena have recognised that the best way to protect health security and promote overall global well-being is to work together across disciplinary and jurisdictional boundaries. Permanent regional networks and ad hoc networks created to tackle specific issues (both of which require donor investment) are also facilitating improved disease surveillance and collaborative approaches to synchronised interventions across country borders. These networks necessarily involve the key ministries for One Health, those of health, agriculture/livestock, and natural resources/environment. Ministries play a critical role in the formulation and implementation of policies for the promotion of health and disease control. They contribute to all stages of the One Heath process, as do universities, which engage by generating knowledge and capacity through teaching, research and extension services. Similarly, non-governmental organisations have a key role in stewardship; resource mobilisation; generation of knowledge; capacity development; intervention design; and implementation. Finally, communities, including rural and indigenous peoples, particularly those that are in close proximity to natural areas, are at the heart of the One Health concept.


Comparison of Ponte Osteotomies and 3-Column Osteotomies in the Treatment of Congenital Spinal Deformity.
Congenital spinal deformity (CSD) has traditionally been treated with 3-column osteotomies [hemivertebrectomy (HV) or vertebral column resection (VCR)] to address rigid deformities. Alternatively, multiple Ponte osteotomies (PO) may provide correction while minimizing risk. The purpose of this study was to compare safety and outcomes of patients undergoing surgical treatment for CSD with these 3 procedures. Retrospective review of CSD patients treated with posterior spinal fusion between 1996 to 2013. Patients treated with multiple Ponte osteotomies (PO group) were compared with those managed with 3-column osteotomies (HV/VCR group). Patients with previous instrumentation, isolated cervical deformity, growing spine instrumentation, or <2 year follow-up were excluded. Deformity angular ratio (DAR) was calculated as curve magnitude divided by number of levels of the deformity. There were 49 patients [17 PO, 32 HV/VCR (26 HV, 6 VCR)]. For the PO group, mean age was 14 years, and they had an average of 4 ponte osteotomies and 11 levels fused. Mean total DAR was 25 and mean number of congenital anomalies was 1.8 in the PO group. The HV/VCR group had a mean age of 7 years and 5 levels fused. Mean total DAR was 28 and mean number of congenital anomalies was 2.1 in the HV/VCR group. Patients had a mean of 54.1% correction of coronal deformity in the PO group and 54.4% in the HV/VCR group (P=0.78). Signal changes were observed less frequently with PO (1/17) and HV (1/26) than with VCR (4/6), P=0.001. Revision rates were 17.6% (3/17) in the PO group and 37.5% (12/32) in the HV/VCR group (P=0.35). Patients with CSD and a mean total DAR of 25 treated with multiple PO and long fusions had correction comparable with the HV/VCR group. Patients treated with VCR had the highest incidence of signal changes and postoperative neurologic deficits. Level III.


Characterization of chondroitin sulfate in stem cells derived from umbilical cord blood in rats.
Chondroitin sulfate (CS) and its isomeric variant, dermatan sulfate (DS), are complex glycosaminoglycans (GAGs) which are ubiquitous components of the extracellular matrix in various tissues including the brain. CS and/or DS are known to bind to a variety of growth factors and regulate many cellular events such as proliferation and differentiation. Although the biological activities of CS and/or DS towards neural stem/progenitor cells (NSPCs) have been well investigated, the CS and/or DS of hematopoietic stem cells (HSCs) have not been fully characterized. Here, we analyzed GAGs on mononuclear cells of rat umbilical cord blood cells (UCB-MNCs). CS was detected in vascular intima and media of rat umbilical cord at embryonic day 19 (E19) by immunohistochemistry. The stem-cell-enriched-UCBCs (SCE-UCBCs), which were expanded from rat UCB-MNCs, expressed CS. CS chains are composed of repeating disaccharide units, which are classified into several types such as O-, A-, B-, C-, D-, and E-unit according to the number and positions of sulfation. A disaccharide composition analysis revealed that CS and/or DS were abundant in rat UCB-MNCs as well as in their expanded SCE-UCBCs, while the amount of heparan sulfate (HS) was less. The degree of sulfation of CS/DS was relatively low and the major component in UCB-MNCs and SCE-UCBCs was the A-unit. A colony-forming cell assay revealed that the percentage of colony-forming cells decreased in culture with CS degradation enzyme. The CS and/or DS of UCBCs may be involved in biological activities such as stem cell proliferation and/or differentiation.


Comparison of endoscopy and barium swallow with marshmallow in dysphagia.
Forty-four patients with dysphagia were examined both by endoscopy and by barium swallow with a marshmallow bolus. In these patients 36 stenoses were found: 34 by radiology and 30 by endoscopy. The radiologic criteria for stenosis included arrest of the marshmallow in a manner to support a column of barium and reproduction of the patient's symptoms at the time this occurred. Radiologic false negative findings were partly due to an inability by patients to swallow an adequate marshmallow bolus; endoscopic failures were associated with small endoscopes and mild stenoses.


Reverse vessel remodeling but not coronary plaque regression could predict future cardiovascular events in ACS patients with intensive statin therapy--the extended JAPAN-ACS study.
The JAPAN-ACS study demonstrated that statins significantly reduced coronary plaque volume in patients with acute coronary syndrome (ACS). The clinical implications of plaque regression for clinical outcomes in ACS patients has not been established. The Extended JAPAN-ACS study was conducted to evaluate the relationship between coronary plaque regression and long-term clinical outcome, and to explore the factors associated with cardiovascular events. Patients with intravascular ultrasound (IVUS) data at both enrollment and follow-up in the JAPAN-ACS study were enrolled and observed for at least 3 years. Patients were divided into lesser and greater coronary plaque regression groups. The primary endpoint was defined as a composite of the following events: cardiovascular death, nonfatal myocardial infarction, nonfatal cerebral infarction, and unstable angina. The median value of the percent change in plaque volume, 18.0%, was used as a cutoff point. There were 4 primary events (3.4%) in the lesser regression group, and 2 events (1.7%) in the greater regression group (P=0.4). Cumulative secondary cardiovascular events did not differ between the 2 groups. Multivariate analysis identified the high-density lipoprotein cholesterol (HDL-C) at baseline and the % change of the external elastic membrane volume as independent risk factors of cardiovascular events. Coronary plaque regression induced by an intensive statin regimen did not predict future cardiovascular events in ACS patients. Rather, the baseline HDL-C level and reverse vessel remodeling might serve as predictors for cardiovascular events.


Population-based study of vestibular symptoms in migraineurs.
The differences between migraineurs with vertigo or motion sickness or both, and migraineurs with neither might reflect differences in migraine pathophysiology. To assess vestibular symptoms in 871 definite migraineurs. Data were gathered using a structured questionnaire. We considered responses to only 2/150 questions: (1) 'have you had vertigo with or apart from your headaches?' and (2) 'have you experienced motion sickness most of your life?'. The target groups were: (a) migraineurs with either vertigo or motion sickness, 'migraine with vestibular symptoms' (MwVS), their control group being migraineurs with neither vertigo nor motion sickness, 'migraine without vestibular symptoms' (MwoVS); (b) migraineurs who reported vertigo, 'migraine with vertigo' (MwV); their control group being migraineurs without vertigo (MwoV). Among the 871 definite migraineurs, 534 had MwV, 337 had MwoV, 663 had MwVS, and 208 had MwoVS. The MwVS group had more headache, aura, nausea, vomiting, osmophobia, allergy, allodynia, headache increasing with head motion, noise as trigger for headache, days needing analgesics, and higher migraine disability scores than the MwoVS group. The pattern was the same in the MwV vertigo group as in the MwVS group, apart from migraine disability scores, which were no different.


An entropy-based approach to predict seizures in temporal lobe epilepsy using scalp EEG.
We describe a novel algorithm for the prediction of epileptic seizures using scalp EEG. The method is based on the analysis of the positive zero-crossing interval series of the EEG signal and its first and second derivatives as a measure of brain dynamics. In a moving-window analysis, we estimated the probability density of these intervals and computed the differential entropy. The resultant entropy time series were then inspected using the cumulative sum (CUSUM) procedure to detect decreases as precursors of upcoming seizures. In the next step, the alarm sequences resulting from analysis of the EEG waveform and its derivatives were combined. Finally, a seizure prediction index was generated based on the spatio-temporal processing of the combined CUSUM alarms. We evaluated our algorithm using a dataset of approximately 21.5 hours of multichannel scalp EEG recordings from four patients with temporal lobe epilepsy, resulting in 87.5% sensitivity, a false prediction rate of 0.28/hr, and an average prediction time of 25 min.


Mobile phone screen protector glass: A TL investigation of the intrinsic background signal.
Screen protector glasses are often used to protect the display screen surface of mobile phones against physical damage. Their dosimetric properties were recently studied by thermoluminescence with the aim of using these items as potential emergency dosimeters in the event of a radiological accident. They are sensitive to ionizing radiation and they could be easily removed and replaced without destroying the phone in case of a dose assessment. However, an intrinsic background signal that partially overlaps with the radiation-induced TL signal is observed. The reconstructed dose could be overestimated if not properly taken into account. The homogeneity of this confounding signal on the surface of several screen protectors was estimated and a chemical treatment with hydrofluoric acid (HF 40%) was tested to minimize its contribution. For most of the samples studied, the intrinsic background signal remained a serious issue for dose reconstruction. Additionally, the TL signals were measured in the red detector range using two different models of red-sensitive photomultiplier tubes. The homogeneity of the intrinsic background signal on the surface of screen protectors was examined and the results of the reduction of this signal by the chemical HF treatment were discussed.


DNA fingerprinting by infrequent-restriction-site amplification.
Identification of bacterial strains by DNA fingerprinting facilitates epidemiologic studies and improves disease control. For some species of organisms, no typing method is available; for others, typing methods are tedious. We developed a method of amplifying DNA sequences flanking infrequent restriction sites by PCR and used the method to produce strain-specific electrophoretic patterns from crude bacterial lysates. This method of fingerprinting is rapid, sensitive, and widely applicable. Identical enzymes, adaptors, primers, and PCR conditions were used to characterize 32 Mycobacterium avium-M. intracellulare isolates, 4 Pseudomonas aeruginosa isolates, and 4 Staphylococcus aureus isolates.


Strategic aspects of stomach cancer surgery.
The aim of the research is to study both immediate and long-term results of treatment in patients with gastric cancer after extended and expanded-combined gastrectomy; assessment of quality of life of patients, depending on the methods of reconstruction. 90 extensive and extensively-combined gastrectomies have been performed. 23 patients have been given operations with overlaying reservoirs at the reconstructive stage. The post-operational complications were observed among 18 (20%) patients in the main group, mortality was constituted 5 (5,6%). In the control group the above mentioned rates was constituted 14 (17,1%) and 3 (3,37%) correspondingly. The difference between the obtained data is statistically non-authentic (p>0,05). Reflux-oesophagitis was detected among 17 (25,37%) patients after standard reconstructions and 2 (7,69%) - after overlaying the reservoirs (p<0,01). In the main group an annual disease free period constituted 94,11%, 3-year - 58,82%, in the control group - 73,2% and 32,9%, respectively. 3- and 5-year survival rate in the main group constituted 70,59% and 37,65%, in the control group - 47,6% and 13,4% correspondingly (p<0,01). Extensive and extensively-combined gastrectomies improve distant results of the treatment among the patients with stomach cancer and aren't followed by increase in rate of post-operational complications and mortality. Overlaying the reservoirs decrease the rate and intensity of reflux pathology.


Cytogenetically unrelated clones in different histologic components of a Wilms tumor.
Wilms tumor (WT) is a triphasic malignant neoplasm comprised of variable proportions of epithelial, blastemal, and mesenchymal (stromal) elements. Cytogenetic analysis of these tumors has revealed a number of recurring abnormalities, including hyperdiploidy and structural abnormalities of chromosomes 1, 7, 11, and 16. We describe a WT in which apparently unrelated cytogenetic clones were detected at diagnosis, when the predominant histologic component was blastema, and after therapy, when the tumor was composed primarily of stroma. At diagnosis, a pseudodiploid karyotype was present, characterized by an X;14 insertion with concurrent deletion of 14q. In contrast, the post-therapy specimen had a hyperdiploid karyotype with a constellation of gains typical for WT. The presence of clonal abnormalities in both the blastemal and mesenchymal components of a WT supports the hypothesis that the stromal component is neoplastic, rather than reactive. The clonal abnormalities seen in different histologic components of the same WT are typically related or identical. The finding in this case of apparently unrelated clones is unusual. Possible etiologies for this biclonality, and clinical implications, are discussed.


Determining the frequency and level of task-sharing for hypertension management in LMICs: A systematic review and meta-analysis.
Low- and middle-income countries (LMICs) bear a disproportionately higher burden of Cardiovascular Disease (CVD). Team-based care approach adds capacity to improve blood pressure (BP) control. This updated review aimed to test team-based care efficacy at different levels of hypertension team-based care complexity. We searched PubMed, Embase, Cochrane, and CINAHL for newer articles on task-sharing interventions to manage hypertension in LMICs. Levels of tasks complexity performed by healthcare workers added to the clinical team in hypertension control programs were categorized as administrative tasks (level 1), basic clinical tasks (level 2), and/or advanced clinical tasks (level 3). Meta-analysis using an inverse variance weighted random-effects model summarized trial-based evidence on the efficacy of team-based care on BP control, compared with usual care. Forty-three RCT articles were included in the meta-analysis: 31 studies from the previous systematic review, 12 articles from the updated search. The pooled mean effect for team-based care was a -4.6 mm Hg (95% CI: -5.8, -3.4, I2 = 80.2%) decrease in systolic BP compared with usual care. We found similar comparative reduction among different levels of team-based care complexity, i.e., administrative and basic clinical tasks (-4.7 mm Hg, 95% CI: -6.8, -2.2; I2 = 79.8%); and advanced clinical tasks (-4.5 mmHg, 95%CI: -6.1, -3.3; I2 = 81%). Systolic BP was reduced most by team-based care involving pharmacists (-7.3 mm Hg, 95% CI: -9.2, -5.4; I2 = 67.2%); followed by nurses (-5.1 mm Hg, 95% CI: -8.0, -2.2; I2 = 72.7%), dieticians (-4.7 mmHg, 95%CI: -7.1, -2.3; I2 = 0.0%), then community health workers (-3.3 mm Hg, 95% CI: -4.8, -1.8; I2 = 77.3%). Overall, team-based hypertension care interventions consistently contributed to lower systolic BP compared to usual care; the effect size varies by the clinical training of the healthcare team members. Resolve To Save Lives (RTSL) Vital Strategies, Danielle Cazabon, Andrew E. Moran, Yvonne Commodore-Mensah receive salary support from Resolve to Save Lives, an initiative of Vital Strategies. Resolve to Save Lives is jointly supported by grants from Bloomberg Philanthropies, the Bill & Melinda Gates Foundation, and Gates Philanthropy Partners, which is funded with support from the Chan Zuckerberg Foundation.


[The current evidence-based guidelines regarding prophylaxis of venous thrombembolism and their relevance for plastic surgery].
In Germany, clinically and experimentally proven, evidence-based guidelines for the perioperative prophylaxis of thromboembolism in plastic surgery have not yet been developed. The ever-expanding complexity of microsurgical reconstructive procedures associated with the immense technical progress in the medical field have once more highlighted the urgent need for evidence-based guidelines. Moreover, this urgency is underlined by more and more complex reconstructive procedures needing to be performed in elderly patients presenting with grave comorbidities and the related high risk for thromboembolic events. These facts prompted us to review and discuss the relevance of the updated S3-guidelines on prophylaxis of venous thromboembolic events for the field of plastic and reconstructive surgery . The existing S3-guidelines represent the result of a consensus between 27 medical societies and organisations. Delegates of the German Society of Plastic, Reconstructive and Aesthetic Surgery (DGPRAEC) also participated in this consensus process and the development of the guidelines, which provide evidence-based and clinically oriented recommendations for the prophylaxis of venous thromboembolism for operative and non-operative as well as outpatient and inpatient settings. In the results section of this paper, general and specific recommendations with regard to plastic and reconstructive surgery are outlined. Indications for the pharmacological prophylaxis of thromboembolic events are oriented on the specific risk categories for surgical interventions with regard to the dispositional individual risk factors. Furthermore, the recommendations for the field of plastic and reconstructive surgery are subdivided into the various regions of the body. Evidence-based recommendations for perioperative prophylaxis of venous thromboembolism in plastic surgery are not available yet. The establishment of an algorithm to screen and estimate the procedure-associated risks for thromboembolism is needed. The discussed S3-guidelines of the AWMF Society on the prophylaxis of venous thromboembolism meet these formal requirements. Gathering of evidence-based data and the generation of recommendations leading to a reduction of the perioperative risk of thromboembolic events is a pivotal element to improve patient outcomes and safety in microsurgery.


Effect of annulus dimension and annuloplasty on bicuspid aortic valve repair.
We have recently shown that valve sparing reimplantation (VSR) improves the durability of bicuspid aortic valve repair in comparison with subcommissural annuloplasty. The aim of this study was to assess the degree of annular reduction provided by these techniques and to correlate these findings with repair durability. From 1995 to 2010, 161 patients underwent bicuspid valve repair. We included only patients with subcommissural annuloplasty or reimplantation having intraoperative pre- and post-repair transoesophageal echocardiography images. Pre- and post-repair ventriculo-aortic junction (VAJ) diameters were measured on long axis views. Inclusion criteria were met by 53 patients with subcommissual annuloplasty and 65 with reimplantation. Median follow-up was 53 months in the subcommissual annuloplasty group and 42 months in the reimplantation group. Follow-up completeness was 100% in subcommissural annuloplasty and 94% in reimplantation. There was no operative or late mortality. Mean preoperative VAJ was similar in both groups (reimplantation: 28 ± 3 mm vs subcommissural annuloplasty: 28 ± 3, P = 0.16). Preoperative VAJ was larger in patients <40 years and with aortic regurgitation (AR) ≥ 3+ (P < 0.01). Mean postoperative VAJ was smaller in reimplantation compared with subcommissural annuloplasty (21 ± 2 mm vs 24 ± 3 mm, P < 0.01). In univariate analyses, subcommissural annuloplasty, preoperative VAJ ≥ 30 mm, postoperative VAJ ≥ 25 mm and cusp repair with patch were predictive of recurrent AR > 1+. In the subcommissural annuloplasty group, VAJ≥ 30 mm preoperatively and ≥ 25 mm postoperatively were associated with decreased 6 years freedom from recurrent AR>1+ (<30 mm: 74% vs ≥ 30 mm: 39%, P = 0.01; <25 mm: 80% vs ≥ 25 mm 31%, P = 0.02) In the reimplantation group, VAJ dimension had no effect on recurrent AR >1+ (P = 0.93). In bicuspid aortic valve repair, the circumferential annuloplasty of VSR offers greater reduction of VAJ compared with the non-circumferential annuloplasty provided by the subcommissural annuloplasty. The degree and extent of VAJ reduction in reimplantation seem to be factors among others that positively influence repair durability particularly in patients with a large VAJ (≥ 30 mm).


In vivo target sites of nitric oxide in photosynthetic electron transport as studied by chlorophyll fluorescence in pea leaves.
The role of nitric oxide (NO) in photosynthesis is poorly understood as indicated by a number of studies in this field with often conflicting results. As various NO donors may be the primary source of discrepancies, the aim of this study was to apply a set of NO donors and its scavengers, and examine the effect of exogenous NO on photosynthetic electron transport in vivo as determined by chlorophyll fluorescence of pea (Pisum sativum) leaves. Sodium nitroprusside-induced changes were shown to be mediated partly by cyanide, and S-nitroso-N-acetylpenicillinamine provided low yields of NO. However, the effects of S-nitrosoglutathione are inferred exclusively by NO, which made it an ideal choice for this study. Q(A)(-) reoxidation kinetics show that NO slows down electron transfer between Q(A) and Q(B), and inhibits charge recombination reactions of Q(A)(-) with the S(2) state of the water-oxidizing complex in photosystem II. Consistent with these results, chlorophyll fluorescence induction suggests that NO also inhibits steady-state photochemical and nonphotochemical quenching processes. NO also appears to modulate reaction-center-associated nonphotochemical quenching.


[Protein Repeats Show Clade-Specific Volatility in Aves].
Protein repeats are a source of rapid evolutionary and functional novelty. Repeats are crucial in development, neurogenesis, immunity, and disease. Repeat length variability and purity can alter the outcome of a pathway by altering the protein structure and affecting the protein-protein interaction affinity. Such rampant alterations can facilitate species to rapidly adapt to new environments or acquire various morphological/physiological features. With more than 11000 species, the avian clade is one of the most speciose vertebrate clades, with near-ubiquitous distribution globally. Explosive adaptive radiation and functional diversification facilitated the birds to occupy various habitats. High diversity in morphology, physiology, flight pattern, behavior, coloration, and life histories make birds ideal for studying protein repeats' role in evolutionary novelty. Our results demonstrate a similar repeat diversity and proportion of repeats across all the avian orders considered, implying an essential role of repeats in necessary pathways. We detected positively selected sites (PSS) in the polyQ repeat of RUNX2 in the avian clade; and considerable repeat length contraction in the Psittacopasserae. The repeats show a species-wide bias towards a contraction in Galloanseriformes. Interestingly, we detected the length contrast of polyS repeat in PCDH20 between Galli-formes and Anseriformes. We speculate the length variability of serine repeat and its interaction with β-catenin in the Wnt/β-catenin signaling pathway could have facilitated fowls to adapt to their respective environmental conditions. We believe our study emphasizes the role of protein repeats in functional/morphological diversification in birds. We also provide an extensive list of genes with considerable repeat length contrast to further explore the role of length volatility in evolutionary novelty and rapid functional diversification.


Self-reported versus objectively assessed exercise adherence.
OBJECTIVE. We examined agreement of data between self-reported and objectively assessed exercise adherence among women with systemic lupus erythematosus. METHOD. Eleven participants completed weekly exercise logs on date and duration of exercise during a 10-wk Wii Fit™ home-based program. Afterward, exercise data from the log were compared with those recorded in the Wii console. RESULTS. Of the paired data, the mean duration of exercise recorded in the Wii was 29.5 min and that recorded in the log was 33.3 min. The composite intraclass correlation for exercise duration between exercise log and the Wii Fit was 0.4. The 95% limits of agreement indicated large between-subjects variability. CONCLUSION. Exercise logs exhibit a marginally acceptable agreement with Wii estimation of exercise duration at a group level. However, caution should be applied when using the exercise log as a measure of a person's exercise behavior because of the tendency to overreport.


Flexible multi-purpose integrated RF/shim coil array for MRI and localized B0 shimming.
To develop a flexible, lightweight, and multi-purpose integrated parallel reception, excitation, and shimming (iPRES) coil array that can conform to the subject's anatomy and perform MR imaging and localized B0 shimming in different anatomical regions with a high SNR, shimming performance, ease of positioning, and subject comfort. A four-channel flexible iPRES coil array was constructed by enabling RF and direct currents to flow on the same flexible coil elements for imaging and shimming, respectively. Shimming experiments were performed with the coil array wrapped around the knee or neck of healthy subjects to demonstrate its high shimming performance and versatility. Additionally, its SNR and shimming performance in the knee were compared to those obtained with the coil array wrapped around a larger rigid tube designed to fit most knee sizes. Shimming with the coil array wrapped around the knee or neck resulted in an average reduction in B0 RMSE of 50.1% and 40.5% relative to first-order and second-order spherical harmonic shimming, respectively, and substantially reduced distortions in DWI images. In contrast, shimming the knee with the coil array wrapped around the rigid tube only provided a 29.6% reduction in B0 RMSE, whereas the SNR was reduced by 58.7%. The flexible iPRES coil array can conform to different anatomical regions and perform imaging and localized B0 shimming with a higher SNR, shimming performance, ease of positioning, and comfort compared to a rigid iPRES coil array, which should be valuable for many applications throughout the human body.


Chemical cross-linking with a diazirine photoactivatable cross-linker investigated by MALDI- and ESI-MS/MS.
Crystallography and nuclear magnetic resonance are well-established methods to study protein tertiary structure and interactions. Despite their usefulness, such methods are not applicable to many protein systems. Chemical cross-linking of proteins coupled with mass spectrometry allows low-resolution characterization of proteins and protein complexes based on measuring distance constraints from cross-links. In this work, we have investigated cross-linking by means of a heterobifunctional cross-linker containing a traditional N-hydroxysuccinimide (NHS) ester and a UV photoactivatable diazirine group. Activation of the diazirine group yields a highly reactive carbene species, with potential to increase the number of cross-links compared with homobifunctional, NHS-based cross-linkers. Cross-linking reactions were performed on model systems such as synthetic peptides and equine myoglobin. After reduction of the disulfide bond, the formation of intra- and intermolecular cross-links was identified and the peptides modified with both NHS and diazirine moieties characterized. Fragmentation of these modified peptides reveals the presence of a marker ion for intramolecular cross-links, which facilitates identification.


Impact of Electronic Self-Assessment and Self-Care Technology on Adherence to Clinician Recommendations and Self-Management Activity for Cancer Treatment-Related Symptoms: Secondary Analysis of a Randomized Controlled Trial.
Patients undergoing cancer treatment experience symptoms that negatively affect their quality of life and adherence to treatment. The early identification and management of treatment-related symptoms are critical to prevent symptom distress due to unmanaged symptoms. However, the early identification and management of treatment-related symptoms are complex as most cancer treatments are delivered on an outpatient basis where patients are granted less face-to-face time with clinicians. The Electronic Symptom Assessment and Self-Care (ESRA-C) promotes participant self-management of treatment-related symptoms by providing participants with communication coaching and symptom self-report, education, and tracking features. While the ESRA-C intervention has been demonstrated to improve symptom distress significantly, little is known as to how the ESRA-C influenced participants' self-management practices and adherence to clinician recommendations for symptom/quality of life issues (SQIs). To compare participant adherence to clinician recommendations and additional self-management strategy use for SQIs between ESRA-C intervention and control (electronic symptom assessment and participant symptom reports alone) group participants. Secondarily, we explored the impact of participant adherence to clinician recommendations and additional self-management strategy use for SQIs on symptom control, symptom management satisfaction, and symptom distress. Lastly, we examined baseline predictors of participant adherence to clinician recommendations and additional self-management strategy use for SQIs. This study presents an analysis of a randomized controlled trial. Participants beginning a new chemotherapy or radiotherapy regimen were recruited from oncology outpatient centers and were randomized to receive the ESRA-C intervention or control during treatment. Patients were included in this analysis if they remained on study through the duration of treatment and self-reported at least one bothersome SQI three-to-six weeks after beginning treatment. The Symptom Distress Scale-15 and Self-Management of SQIs Questionnaire were completed two weeks later. Based on Self-Management of SQIs Questionnaire ratings, participants were placed into adherence to clinician recommendations (adhered/did not adhere/did not receive recommendations) and additional self-management strategy use (yes/no) categories. Most participants were adherent to clinician recommendations (273/370, 73.8%), while fewer used additional self-management strategies for SQIs (182/370, 49.2%). There were no differences in the frequency of participant adherence to clinician recommendations (chi-square test, P=.99) or self-management strategy use (chi-square test, P=.80) between intervention (n=182) and control treatment groups (n=188). Participants who received clinician recommendations reported the highest treatment satisfaction (n=355, P<.001 by analysis of variance; ANOVA), although lowest distress was reported by participants who did not follow clinician recommendations (n=322, P=.04 by ANOVA) for top 2 SQIs. Women (n=188) reported greater additional self-management strategy use than men (n=182, P=0.03 by chi-square test). ESRA-C intervention use did not improve participants' adherence to clinician recommendations or additional self-management strategy use for SQIs in comparison to the control. Future research is needed to determine which factors are important in improving patients' self-management practices and symptom distress following ESRA-C use. ClinicalTrials.gov NCT00852852; https://clinicaltrials.gov/ct2/show/NCT00852852 (Archived by WebCite at http://www.webcitation.org/73rEhNWkU).


Tuberculous peritonitis during infliximab therapy.
Reactivation of tuberculosis is a severe side effect of anti-TNF treatment. Especially extrapulmonary forms of tuberculosis may occur, which are difficult to diagnose. The diagnosis may be obtained by a thorough search for Mycobacterium tuberculosis. We describe two patients who developed tuberculous peritonitis after infliximab therapy that was prescribed for treatment of rheumatoid arthritis. These cases illustrate that tuberculous peritonitis has a nonspecific clinical manifestation and that Mycobacteria can be difficult to find in ascites fluid. For this reason, tuberculostatic therapy has to be started in case of clinical suspicion. Before starting infliximab therapy, the patient must be thoroughly screened for the presence of (latent) tuberculosis.