The problem of the origin of fibroblasts in the postnatal ontogenesis of mammals.
An analysis is made of the author's data and the literature information on the origin and patterns of differentiation of the fibroblasts of connective tissue during the postnatal ontogenesis of mammals. The hypothesis of the existence of two types of collagen-producing cells (fibroblasts) - protective-trophic (short-lived population) and supporting (long-lived population) - is substantiated. Hypotheses are advanced on the biological role of these types of fibroblasts and their origin in phylogenesis.


Is Pain Harder To Withstand Than Tinnitus?
The object of the study was to compare the perception of tinnitus with the perception of pain and to find specific factors that could influence the perception of both pain and tinnitus. A retrospective analysis of 124 patients with tinnitus as main complaint and 300 patients with cervical pain as main complaint who visited our clinic in a two-year period. This study indicates that it is harder to withstand cervical pain than tinnitus with a higher prevalence of fatigue and impaired work performance in cervical pain patients. Our analyses highlight the importance of fatigue as a potential mediator of the deleterious effects of pain and tinnitus on individual functioning. Female gender and the presence of cervical pain makes patients more accessible for fatigue. Tolerance against tinnitus depends on the perceived maximal intensity of tinnitus, but also of the presence of cervical pain. Cervical pain may reinforce the irritating awareness of tinnitus. Tinnitus and chronic pain are related to structural and functional brain changes that show a striking overlap between both conditions. The tolerance, the ability to withstand the "unpleasantness" of the percept, for tinnitus and pain depends on the perceived intensity of the sensation. However, the perceived intensity of pain provoked annoyance earlier compared to the perceived intensity of tinnitus. Cervical pain may reinforce and maintain the negative awareness of tinnitus. For a better withstanding of tinnitus, we advise to reduce the perceived maximal intensity of tinnitus and to treat cervical pain and fatigue.


Adjudicative Competence and the Criminalization of Intellectual Disability.
Wood and colleagues effectively argue that Title II of the Americans with Disabilities Act applies to securing accommodations for persons with intellectual/disability disorder so that such persons can meaningfully participate in the criminal adjudicative process. This invited commentary further discusses the challenges in identifying, assisting, and fully accommodating persons with intellectual/disability disorder in the criminal justice system. It also highlights ongoing problems with stereotypes within this population, which may affect the outcome of criminal proceedings. This commentary argues that persons with intellectual/disability disorder will likely continue to be treated unequally in the criminal justice system until better supports, treatments, and services are provided in community settings because treatment and placement options are often closely linked with case disposition.


Actinide arene-metalates: ion pairing effects on the electronic structure of unsupported uranium-arenide sandwich complexes.
Addition of [UI2(THF)3(μ-OMe)]2·THF (2·THF) to THF solutions containing 6 equiv. of K[C14H10] generates the heteroleptic dimeric complexes [K(18-crown-6)(THF)2]2[U(η6-C14H10)(η4-C14H10)(μ-OMe)]2·4THF (118C6·4THF) and {[K(THF)3][U(η6-C14H10)(η4-C14H10)(μ-OMe)]}2 (1THF) upon crystallization of the products in THF in the presence or absence of 18-crown-6, respectively. Both 118C6·4THF and 1THF are thermally stable in the solid-state at room temperature; however, after crystallization, they become insoluble in THF or DME solutions and instead gradually decompose upon standing. X-ray diffraction analysis reveals 118C6·4THF and 1THF to be structurally similar, possessing uranium centres sandwiched between bent anthracenide ligands of mixed tetrahapto and hexahapto ligation modes. Yet, the two complexes are distinguished by the close contact potassium-arenide ion pairing that is seen in 1THF but absent in 118C6·4THF, which is observed to have a significant effect on the electronic characteristics of the two complexes. Structural analysis, SQUID magnetometry data, XANES spectral characterization, and computational analyses are generally consistent with U(iv) formal assignments for the metal centres in both 118C6·4THF and 1THF, though noticeable differences are detected between the two species. For instance, the effective magnetic moment of 1THF (3.74 μ B) is significantly lower than that of 118C6·4THF (4.40 μ B) at 300 K. Furthermore, the XANES data shows the U LIII-edge absorption energy for 1THF to be 0.9 eV higher than that of 118C6·4THF, suggestive of more oxidized metal centres in the former. Of note, CASSCF calculations on the model complex {[U(η6-C14H10)(η4-C14H10)(μ-OMe)]2}2- (1*) shows highly polarized uranium-arenide interactions defined by π-type bonds where the metal contributions are primarily comprised by the 6d-orbitals (7.3 ± 0.6%) with minor participation from the 5f-orbitals (1.5 ± 0.5%). These unique complexes provide new insights into actinide-arenide bonding interactions and show the sensitivity of the electronic structures of the uranium atoms to coordination sphere effects.


[TREATMENT COMPLIANCE IN PATIENTS WITH CHRONIC HEART FAILURE AND COMORBIDITIES].
Treatment compliance determines to a large degree the effectiveness of therapy of chronic heart failure (CHF). However; individual characteristics of a patient, such as comorbidities and personality status are frequently disregarded. This work was aimed to study clinical and psychological peculiarities of patients with CHF determining treatment compliance taking account of comorbidity. The study included 203 patients (130 men and 73 women) of mean age 61.8 ± 9.6 yr. The following features were evaluated: comorbidity psychological status, compliance with medicamental and non-medicamental treatment of CHF. Charlson comorbidity index corrected for age was 5.0 ± 2.1. Compliance with non-medicamental (recommendations on self-control and changes in the lifestyle) and medicamental therapy was documented in 37 (18.2%) and 61 (30%) patients respectively. Patients with poor compliance were characterised by disadaptive type of responsiveness, emotional lability and indecisiveness (p < 0.04). Poor treatment compliance is to a large extent determined by peculiarities of the personality status.


Amebic infection in the human colon induces cyclooxygenase-2.
We sought to determine if infection of the colon with Entamoeba histolytica induces the expression of cyclooxygenase-2 and, if it does, to determine the contribution of prostaglandins produced through cyclooxygenase-2 to the host response to amebic infection. Human fetal intestinal xenografts were implanted subcutaneously in mice with severe combined immunodeficiency and allowed to grow; the xenografts were then infected with E. histolytica trophozoites. Infection with E. histolytica resulted in the expression of cyclooxygenase-2 in epithelial cells and lamina propria macrophages. Infection with E. histolytica increased prostaglandin E(2) (PGE2) levels 10-fold in the xenografts and resulted in neutrophil infiltration, as manifested by an 18-fold increase in myeloperoxidase activity. Amebic infection also induced an 18-fold increase in interleukin 8 (IL-8) production and a >100-fold increase in epithelial permeability. Treatment of the host mouse with indomethacin, an inhibitor of cyclooxygenase-1 and cyclooxygenase-2, or with NS-398, a selective inhibitor of cyclooxygenase-2, resulted in (i) decreased PGE(2) levels, (ii) a decrease in neutrophil infiltration, (iii) a decrease in IL-8 production, and (iv) a decrease in the enhanced epithelial permeability seen with amebic infection. These results indicate that amebic infection in the colon induces the expression of cyclooxygenase-2 in epithelial cells and macrophages. Moreover, prostaglandins produced through cyclooxygenase-2 participate in the mediation of the neutrophil response to infection and enhance epithelial permeability.


Body mass index and parasympathetic nervous system reactivity and recovery following graded exercise.
The present study sought to expand upon prior investigations examining patterns of vagally mediated heart rate variability (vmHRV) and perceived exertion as a function of body mass index (BMI) in response to and recovery from exercise. Participants underwent a resting (baseline) period, followed by a graded exercise protocol on an ergometer with ascending difficulty stages, and finally another resting (recovery) period. Individuals were stratified into three BMI groups: low, moderate, and high. Individuals in the high BMI group exhibited a significantly greater decrease in vmHRV from baseline to graded exercise in comparison to the moderate BMI group. Individuals in the high BMI group also showed significantly lower vmHRV at recovery compared with baseline than individuals with moderate BMI; indicating that the high BMI group's vmHRV did not recover to the degree of those in the moderate BMI group. No significant results regarding vmHRV were found in the low BMI group. Of note, BMI and perceived exertion during the recovery period were positively associated. Results also showed a significant negative association between vmHRV and perceived exertion at each grade of exercise. There was no significant association between vmHRV and perceived exertion during baseline or recovery. This report extends prior research studying BMI and patterns of vmHRV reactivity in the domain of physical exercise. Our data contribute to previous reports suggesting that high BMI can lead to maladaptive patterns of vmHRV reactivity to and recovery from physical exercise.


Centrioles are freed from cilia by severing prior to mitosis.
Cilia are necessary for normal tissue development and homeostasis and are generally present during interphase, but not in mitosis. The precise mechanism of premitotic ciliary loss has been controversial, with data supporting either sequential disassembly through the transition zone or, alternatively, a severing event at the base of the cilia. Here we show by live cell imaging and immunofluorescence microscopy that resorbing flagella of Chlamydomonas leave remnants associated with the mother cell wall. We postulated that the remnants are the product of severing of doublet microtubules between the basal bodies and the flagellar transition zone, thereby freeing the centrioles to participate in spindle organization. We show via TEM that flagellar remnants are indeed flagellar transition zones encased in vesicles derived from the flagellar membrane. This transition zone vesicle can be lodged within the cell wall or it can be expelled into the environment. This process is observable in Chlamydomonas, first because the released flagellar remnants can remain associated with the cell by virtue of attachments to the cell wall, and second because the Chlamydomonas transition zone is particularly rich with electron-dense structure. However, release of basal bodies for spindle-associated function is likely to be conserved among the eukaryotes.


Differential uptake and transport of trivalent and hexavalent chromium by tumbleweed (Salsola kali).
Experiments were conducted to determine the differential absorption of Cr species by tumbleweed (Salsola kali) as well as the effect of this heavy metal on plant growth and nutrient uptake. Tumbleweed seeds were grown in an agar-based media containing different concentrations of either Cr(III) or Cr(VI). The results demonstrated that the uptake of Cr was influenced by the Cr concentration in the growth medium and the speciation of this heavy metal. When supplied in the hexavalent form, the concentration of Cr in the different plant parts (2900, 790, and 600 mg kg(-1) for roots, stems, and leaves, respectively) was between 10 and 20 times higher than the amounts found when Cr was supplied in the trivalent form. In addition, it was found that in most of the experiments, Cr(III) exhibited more toxic effects on tumbleweed plants than Cr(VI). The size of roots of plants grown in 20 mg L(-1) Cr(III) were significantly smaller (p < 0.05) than those grown in 20 mg L(-1) Cr(VI). Plants exposed to 20 mg L(-1) Cr(III) produced shoots significantly shorter (p < 0.05) compared with the size of control plants and with those grown in 20 mg L(-1) Cr(VI). In addition, the absorption of macronutrients and microelements was in general lower when the plants were grown in the medium containing Cr(III). The amounts of Cr concentrated in the aerial plant parts under experimental conditions may indicate tumbleweed as a new option for the phytoremediation of Cr-contaminated soil.


Pulsed radiofrequency treatment of complex regional pain syndrome: a case series.
Various forms of sympathetic chain neurolysis (sympathectomy) have, at one time or another, held promise as effective treatment options for complex regional pain syndrome (CRPS). Complications, such as worsening pain and the development of new pain syndromes, have prevented sympathectomy from emerging as a standard intervention. In an effort to avoid poor outcomes associated with neurolysis, pulsed radiofrequency (PRF) has been proposed as a potential treatment alternative for a number of chronic neuropathic pain states, including some forms of CRPS. The present report describes three cases in which patients diagnosed with lower extremity CRPS type I obtained substantial and lasting intervals of pain relief following PRF of the lumbar sympathetic chain. Over a period of four years, 14 fluoroscopically guided procedures using PRF lesioning of the lumbar sympathetic chain at L2, L3 and L4 were performed in three individuals with CRPS type I of the lower limb. Outcome measures included pre- and post-treatment self-reported pain and medication requirements. Substantial pain relief (>50%) was achieved in 91.7% of PRF applications at three months and 83.3% at six months, with some treatments resulting in persistent relief well beyond 12 months. Medication use decreased to a comparable degree, with discontinuation of opiates after all but three treatments. PRF lesioning of the lumbar sympathetic chain can be an effective treatment for patients with CRPS type I of the lower extremity, with the potential to provide ≥6 months of substantial pain relief.


Indoor-biofilter growth and exposure to airborne chemicals drive similar changes in plant root bacterial communities.
Due to the long durations spent inside by many humans, indoor air quality has become a growing concern. Biofiltration has emerged as a potential mechanism to clean indoor air of harmful volatile organic compounds (VOCs), which are typically found at concentrations higher indoors than outdoors. Root-associated microbes are thought to drive the functioning of plant-based biofilters, or biowalls, converting VOCs into biomass, energy, and carbon dioxide, but little is known about the root microbial communities of such artificially grown plants, how or whether they differ from those of plants grown in soil, and whether any changes in composition are driven by VOCs. In this study, we investigated how bacterial communities on biofilter plant roots change over time and in response to VOC exposure. Through 16S rRNA amplicon sequencing, we compared root bacterial communities from soil-grown plants with those from two biowalls, while also comparing communities from roots exposed to clean versus VOC-laden air in a laboratory biofiltration system. The results showed differences in bacterial communities between soil-grown and biowall-grown plants and between bacterial communities from plant roots exposed to clean air and those from VOC-exposed plant roots. Both biowall-grown and VOC-exposed roots harbored enriched levels of bacteria from the genus Hyphomicrobium. Given their known capacities to break down aromatic and halogenated compounds, we hypothesize that these bacteria are important VOC degraders. While different strains of Hyphomicrobium proliferated in the two studied biowalls and our lab experiment, strains were shared across plant species, suggesting that a wide range of ornamental houseplants harbor similar microbes of potential use in living biofilters.


Invasion of Solanum tuberosum L. by Aspergillus terreus: a microscopic and proteomics insight on pathogenicity.
Aspergillus terreus is one of the most harmful filamentous fungal pathogen of humans, animals and plants. Recently, researchers have discovered that A. terreus can cause foliar blight disease in potato (Solanum tuberosum L.). We used light and scanning electron microscopy, and performed proteomics analysis in an attempt to dissect the invasion process of A. terreus in this important crop. Microscopic study revealed that invasion of leaf tissue is marked by rapid germination of A. terreus phialidic conidia (PC) by 4 h after inoculation. By 8 h after inoculation, primary germ tubes from PC differentiated into irregular protuberance, often displayed stomata atropism, and failed to penetrate via the epidermal cells. Colonization of leaf tissues was associated with high rate of production of accessory conidia (AC). These analyses showed the occurrence of a unique opposing pattern of AC, tissue-specific and produced on melanized colonizing hyphae during the infection of leaf tissue. A significant proteome change hallmarked by differential expression of class I patatin, lipoxygenase, catalase-peroxidase complex, and cysteine proteinase inhibitor were observed during tuber colonization. These proteins are often involved in signal transduction pathways and crosstalk in pathogenic responses. A. terreus abundantly produced AC and multipolar germinating PC to invade potato leaf tissue. Additionally, A. terreus differentially induced enzymes in potato tuber during colonization which facilitates rapid disease development.


IL-17 Augments B Cell Activation in Ocular Surface Autoimmunity.
Accumulating evidence shows that IL-17 is critically involved in diverse autoimmune diseases. However, its effect on the induction and progression of the humoral immune response is not fully understood. Using a preclinical model of IL-17-mediated dry eye disease, we demonstrate that upon encountering both the BCR and a secondary T cell signal, IL-17 can enhance B cell proliferation and germinal center formation in dry eye disease mice, suggesting that a stable Ag-dependent T-B cell interaction is required. Additionally, IL-17 also promotes the differentiation of B cells into isotype-switched B cells and plasma cells. Furthermore, we show that Th17 cells are more effective than Th1 cells to provide B cell help. Reduced B cell response correlates with significant reduction in clinical disease after in vivo IL-17A neutralization. In conclusion, our findings demonstrate a new role of IL-17 in promoting autoimmunity in part through directly enhancing B cell proliferation, differentiation, and plasma cell generation.


Identification of T-DNA structure and insertion site in transgenic crops using targeted capture sequencing.
The commercialization of GE crops requires a rigorous safety assessment, which includes a precise DNA level characterization of inserted T-DNA. In the past, several strategies have been developed for identifying T-DNA insertion sites including, Southern blot and different PCR-based methods. However, these methods are often challenging to scale up for screening of dozens of transgenic events and for crops with complex genomes, like potato. Here, we report using target capture sequencing (TCS) to characterize the T-DNA structure and insertion sites of 34 transgenic events in potato. This T-DNA is an 18 kb fragment between left and right borders and carries three resistance (R) genes (RB, Rpi-blb2 and Rpi-vnt1.1 genes) that result in complete resistance to late blight disease. Using TCS, we obtained a high sequence read coverage within the T-DNA and junction regions. We identified the T-DNA breakpoints on either ends for 85% of the transgenic events. About 74% of the transgenic events had their T-DNA with 3R gene sequences intact. The flanking sequences of the T-DNA were from the potato genome for half of the transgenic events, and about a third (11) of the transgenic events have a single T-DNA insertion mapped into the potato genome, of which five events do not interrupt an existing potato gene. The TCS results were confirmed using PCR and Sanger sequencing for 6 of the best transgenic events representing 20% of the transgenic events suitable for regulatory approval. These results demonstrate the wide applicability of TCS for the precise T-DNA insertion characterization in transgenic crops.


FEFsem neuronal response during combined volitional and reflexive pursuit.
Although much is known about volitional and reflexive smooth eye movements individually, much less is known about how they are coordinated. It is hypothesized that separate cortico-ponto-cerebellar loops subserve these different types of smooth eye movements. Specifically, the MT-MST-DLPN pathway is thought to be critical for ocular following eye movements, whereas the FEF-NRTP pathway is understood to be vital for volitional smooth pursuit. However, the role that these loops play in combined volitional and reflexive behavior is unknown. We used a large, textured background moving in conjunction with a small target spot to investigate the eye movements evoked by a combined volitional and reflexive pursuit task. We also assessed the activity of neurons in the smooth eye movement subregion of the frontal eye field (FEFsem). We hypothesized that the pursuit system would show less contribution from the volitional pathway in this task, owing to the increased involvement of the reflexive pathway. In accordance with this hypothesis, a majority of FEFsem neurons (63%) were less active during pursuit maintenance in a combined volitional and reflexive pursuit task than during purely volitional pursuit. Interestingly and surprisingly, the neuronal response to the addition of the large-field motion was highly correlated with the neuronal response to a target blink. This suggests that FEFsem neuronal responses to these different perturbations-whether the addition or subtraction of retinal input-may be related. We conjecture that these findings are due to changing weights of both the volitional and reflexive pathways, as well as retinal and extraretinal signals.


Changes to colour vision on exposure to high altitude.
Several studies have shown deterioration in colour vision at altitudes above 3,000m. These studies have been conducted in photopic (bright daylight) conditions, whereas many military operations take place in mesopic (dim light) conditions. Data suggests that the tritan colour vision axis (blue cones, TA) are more susceptible to hypoxic insult than protan axis (red cones, PA). The objective of this study was to examine colour vision at high altitude, in mesopic conditions, and using a novel method of assessment to discriminate between the tritan and protan axis. We examined 42 eyes (21 subjects, mean age 44, range 22-71), at sea level and within 12-36 hours of exposure to 3300m. This was done in a darkened room, with refractive error correction. Colour vision was studied using ChromaTest, a software programme that analyzes colour contrast threshold (CCT) of both TA and PA. We planned to repeat CCT measurement at 4,392m, but technology failure prevented this. Non-parametric paired data was examined using the Wilcoxon signed rank test. There was found to be no change to either the PA (p = 0.409) or the TA (p = 0.871) upon ascent. Within the PA 16 eyes had a lower CCT at high altitude, whilst 26 were higher. In the TA 20 eyes had a lower CCT and 22 were higher. At sea level, mean CCT for PA was 4.21 (SD 2.29) TA was 7.06 (SD 1.77). At 3,300m mean CCT for PA was 4.36 (SD 2.86) and TA was 6.93 (SD 2.39). This experiment revealed no changes to colour vision with exposure to 3,300m. This may be below the threshold altitude for cone dysfunction, alternatively colour vision deterioration may be less significant in mesopic conditions.


Nature of sulphated macromolecules in mouse Reichert's membrane. Evidence for tyrosine O-sulphate in basement-membrane proteins.
Seven different sulphated macromolecules were detected in 6 M-guanidinium chloride extracts of metabolically [35S]sulphate-labelled mouse Reichert's membrane and were partially separated. Polypeptide bands of apparent Mr 50 000, 150 000 (tentatively identified as entactin) and 170 000 contained essentially tyrosine O-sulphate as the labelled component. Most of the radioactive sulphate was incorporated into three different proteoglycans, which could be separated by chromatography and density-gradient centrifugation before and after enzymic degradation. Enzymic analysis of glycosaminoglycans and of protein cores by immunoassays identified these components as low-density and high-density forms of heparan sulphate proteoglycan and a high-density form of chondroitin sulphate or dermatan sulphate proteoglycan.


TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2.
Transcriptional factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, is generally regarded as a pro-survival factor. Here, we identify that besides its effect on autophagy induction, TFEB exerts a pro-apoptotic effect in response to the cyclopentenone prostaglandin 15-deoxy-∆-12,14-prostaglandin J2 (15d-PGJ2). Specifically, 15d-PGJ2 promotes TFEB translocation from the cytoplasm into the nucleus to induce autophagy and lysosome biogenesis via reactive oxygen species (ROS) production rather than mTORC1 inactivation. Surprisingly, TFEB promotes rather than inhibits apoptosis in response to 15d-PGJ2. Mechanistically, ROS-mediated TFEB translocation into the nucleus transcriptionally upregulates the expression of ATF4, which is required for apoptosis elicited by 15d-PGJ2. Additionally, inhibition of TFEB activation by ROS scavenger N-acetyl cysteine or inhibition of protein synthesis by cycloheximide effectively compromises ATF4 upregulation and apoptosis in response to 15d-PGJ2. Collectively, these results indicate that ROS-induced TFEB activation exerts a novel role in promoting apoptosis besides its role in regulating autophagy in response to 15d-PGJ2. This work not only evidences how TFEB is activated by 15d-PGJ2, but also unveils a previously unexplored role of ROS-dependent activation of TFEB in modulating cell apoptosis in response to 15d-PGJ2.


Chemical synthesis of a polypeptide backbone derived from the primary sequence of the cancer protein NY-ESO-1 enabled by kinetically controlled ligation and pseudoprolines.
The cancer protein NY-ESO-1 has been shown to be one of the most promising vaccine candidates although little is known about its cellular function. Using a chemical protein strategy, the 180 amino acid polypeptide, tagged with an arginine solubilizing tail, was assembled in a convergent manner from four unprotected peptide α-thioester peptide building blocks and one cysteinyl polypeptide, which were in turn prepared by Boc and Fmoc solid phase peptide synthesis (SPPS) respectively. To facilitate the assembly by ligation chemistries, non-native cysteines were introduced as chemical handles into the polypeptide fragments; pseudoproline dipeptides and microwave assisted Fmoc SPPS were crucial techniques to prepare the challenging hydrophobic C-terminal fragment. Three sequential kinetically controlled ligations, which exploited the reactivity between peptide arylthioesters and peptide alkylthioesters, were then used in order to assemble the more tractable N-terminal region of NY-ESO-1. The ensuing 147 residue polypeptide thioester then underwent successful final native chemical ligation with the very hydrophobic C-terminal polypeptide bearing an N-terminal cysteine affording the 186 residue polypeptide as an advanced intermediate en route to the native NY-ESO-1 protein.


The value of using top-down and bottom-up approaches for building trust and transparency in biobanking.
With the domestic and international proliferation of biobanks and their associated connections to health information databases, scholarly attention has been turning from the ethical issues arising from the construction of biobanks to the ethical issues that emerge in their operation and management. Calls for greater transparency in governance structures, coupled with stern reminders of the value of maintaining public trust, are seen as critical components in the success of these resources. Two different approaches have been adopted for addressing these types of ethical issues: the first is a 'top-down' approach which focuses on developing policy, procedures, regulations and guidelines to aid decision-makers. The second is a 'bottom-up' approach, which begins with those who are most affected by the issues and attempts to inductively develop consensus recommendations and policy. While both approaches have merit, I argue that more work needs to be done on 'bottom-up' strategies if trust and transparency are to be more than mere slogans. Using 2 case examples from Indiana, the paper summarizes data from a set of surveys we recently conducted that address issues arising from biobanks that provide some insight into issues associated with trust and transparency.


A retrospective comparison of endoscopic stenting alone with stenting and radiotherapy in non-resectable cholangiocarcinoma.
Radiotherapy has been reported to be of benefit in prolonging the survival of patients with cholangiocarcinoma. This study examined whether radiotherapy in addition to endoscopic stenting improved survival. 56 patients with obstructive jaundice due to histologically confirmed non-resectable cholangiocarcinoma. A retrospective analysis of these patients who were treated either with endoscopic biliary stenting followed by external beam radiotherapy and internal iridium-192 brachytherapy (n = 28) or with stenting alone (control group; n = 28). The two groups were well matched in age, sex, and stricture type. Eighteen patients had a type I stricture (control group: 11; radiotherapy group: 7) at the time of diagnosis and 38 had a type II or III stricture (control group: 17; radiotherapy group: 21). The median (range) overall survival from diagnosis was seven (1-29) and 10 (4-75) months in the control and radiotherapy groups respectively: This difference did not reach statistical significance (p = 0.06), but survival plots indicated a survival advantage in the radiotherapy group in the first nine months after diagnosis. Approximately one third survived longer than one year in both groups. More patients in the radiotherapy group required a stent change (1.9 v 0.9: p = 0.05), and also had a longer overall inpatient stay (42 days v 19: p < 0.001). When examined on the basis of stricture type, there was a survival advantage in the first 10 months after diagnosis in those with a type II/III stricture (seven and 11 months in the radiotherapy and control groups respectively: 0.01 < p < 0.05). There was no difference in survival between the groups in those with a type I stricture. Numbers surviving longer than one year, stent survival, and number of stent changes were all similar between the two groups when examined on the basis of stricture type, but length of hospital stay remained considerably longer in all patients receiving radiotherapy. The survival advantage of radiotherapy in those with a type II/III stricture is seen only in the first 10 months after diagnosis. The costs of radiotherapy and significantly increased time spent in hospital, however, raise doubts over its routine use in the management of non-resectable cholangiocarcinoma.


Angiotensin-converting enzyme 2-independent action of presumed angiotensin-converting enzyme 2 activators: studies in vivo, ex vivo, and in vitro.
Angiotensin (Ang)-converting enzyme 2 (ACE2) is a key enzyme in the metabolism of Ang II. XNT (1-[(2-dimethylamino)ethylamino]-4-(hydroxymethyl)-7-[(4-methylphenyl) sulfonyl oxy]-9H-xanthene-9-one) and diminazene have been reported to exert various organ-protective effects, which are attributed to the activation of ACE2. To test the effect of these compounds, we studied Ang II degradation in vivo and in vitro as well as their effect on ACE2 activity in vivo and in vitro. In a model of Ang II-induced acute hypertension, blood pressure (BP) recovery was markedly enhanced by XNT (slope with XNT, -3.26±0.2 versus -1.6±0.2 mm Hg/min without XNT; P<0.01). After Ang II infusion, neither plasma nor kidney ACE2 activity was affected by XNT. Plasma Ang II and Ang (1-7) levels also were not significantly affected by XNT. The BP-lowering effect of XNT seen in wild-type animals was also observed in ACE2 knockout mice (slope with XNT, -3.09±0.30 versus -1.28±0.22 mm Hg/min without XNT; P<0.001). These findings show that the BP-lowering effect of XNT in Ang II-induced hypertension cannot be because of the activation of ACE2. In vitro and ex vivo experiments in both mice and rat kidney confirmed a lack of enhancement of ACE2 enzymatic activity by XNT and diminazene. Moreover, Ang II degradation in vitro and ex vivo was unaffected by XNT and diminazene. We conclude that the biological effects of these compounds are ACE2-independent and should not be attributed to the activation of this enzyme.


The network of calcium regulation in muscle.
In this review the molecular characteristics and reaction mechanisms of different Ca(2+) transport systems associated with various membranes in muscle cells will be summarized. The following topics will be discussed in detail: a brief history of early observations concerning maintenance and regulation of cellular Ca(2+) homeostasis, characterization of the Ca(2+) pumps residing in plasma membranes and sarco(endo)plasmic reticulum, mitochondrial Ca(2+) transport, Ca(2+)-binding proteins, coordinated expression of Ca(2+) transport systems, a general background of muscle excitation-contraction coupling with emphasis to the calcium release channels of plasma membrane and sarcoplasmic reticulum, the structure and function of dihydropyridine and ryanodine receptors of skeletal and cardiac muscles, and finally their disposition in various types of muscles.


Changes in lung cancer histological types in Varese Cancer Registry, Italy 1976-1992.
Shifts in histological tumour type distribution, chiefly an increase in adenocarcinoma, have been reported to accompany changes in lung cancer incidence in the last two decades in the United States and several other developed countries. To elucidate this phenomenon further, we analysed population-based lung cancer incidence rates in the period 1976-1992 from the Varese province, an area with 788,000 inhabitants in Northern Italy. Rates were age-standardised on the world standard population. Overall, lung cancer had stopped increasing in males since the late 1980s, and had started declining in middle-aged men. Conversely, upward trends persisted in females up to 1991-1992. Although it decreased from 13 to 9, the male-to-female incidence ratio was, in 1991-1992 still substantially higher than in the U.S. and North Europe. Specific trends emerged according to histological type(s), with declines (males) or stabilisation (females) for squamous-cell carcinoma and gradual increases for small-cell carcinoma in males. Adenocarcinoma was the only lung cancer type whose incidence rates increased similarly (2.5-fold) in males and females thus approaching, in 1991-1992, in the two sexes combined, the rate for squamous-cell carcinoma. Although advances in diagnostic techniques may have played a role, the absolute and relative increases in the adenocarcinoma rate reflect changes in cigarette manufacture (i.e. spread of filter tips and low-nicotine low-tar cigarettes) and the decrease in smokers.


On the association between apathy and deficits of social cognition and executive functions in Huntington's disease.
To investigate if executive and social cognitive dysfunction was associated with apathy in a large cohort of Huntington's disease gene expansion carriers. Eighty premanifest and motor-manifest Huntington's disease gene expansion carriers (Mini-Mental State Examination score ≥ 24 and Montreal Cognitive Assessment score ≥ 19) and thirty-two controls were examined with the Lille Apathy Rating Scale (LARS), a tailored and quantitative measure of apathy, and a comprehensive cognitive battery on executive functions and social cognition (emotion recognition, theory of mind and sarcasm detection), as well as general correlates like demographic variables, and neuropsychiatric and cognitive screening tests. The motor-manifest Huntington's disease gene expansion carriers had significantly different scores on most measures of social cognition and executive functions, compared to premanifest and control participants. Apathy was significantly correlated with most executive test scores, but the Emotion Hexagon was the only social cognitive test score significantly correlated with apathy. We found that the motor score and the depression score were the only significant predictors of the apathy score, when the social cognitive and executive tests with the strongest association with the global LARS score were entered into a multiple stepwise regression model. No cognitive test score could significantly predict apathy. The model explained 21 % of the total variance. Despite being significantly correlated with apathy neuropsychological variables did not have a significant impact on apathy when variables as depression and motor symptoms were taken into account. Apathy should be considered an independent symptom of Huntington's disease that requires specific examination.


Development of an in vitro model to measure bioactivity of botulinum neurotoxin A in rat bladder muscle strips.
Botulinum toxin A (BoNT-A) is a new treatment modality in various causes of bladder dysfunction; like neurogenic detrusor overactivity and overactive bladder. The best technique of administrating BoNT-A in patients is unknown. A validated in vitro model could be used to investigate newer intravesical administration techniques of BoNT-A. In this study, we describe the development and validation of in vitro model to measure inhibitory effects of BoNT-A on bladder strip contractions. Rat bladder strips were mounted in organ baths filled with Krebs' solution. The strips were stimulated chemically (80 mM potassium chloride, 1 μM carbachol) and electrically (Electrical Field Stimulation (EFS) 100 shocks, 50 V, 20 Hz, every 3 minutes). The viability of the strips was measured by carbachol stimulation at the beginning and at the end of the experiments. The strips were incubated in various concentrations of BoNT-A (0.03, 0.2, 0.3 nM). Controls were incubated in Krebs' solution only. The inhibition of strip contraction induced by EFS was measured. These measurements were statistically analyzed with a log-logistic model representing diffusion. All strips remained viable during the experiments. Inhibition of strip contraction was observed after incubation with 0.3 nM BoNT-A. The measurements fitted to a log-logistic model describing diffusion of BoNT-A in the bladder strip. The parameters of the log-logistic model representing diffusion were significant for 0.3 nM BoNT-A. Incubation with 0.2 nM BoNT-A showed insignificant results for 2 out of 3 runs. Incubation with 0.03 nM BoNT-A did not result in significant inhibition of strip contractions. An in vitro model was developed and validated in which the inhibitory effect of low concentrations of BoNT-A on bladder strip contractions can be measured.


A flow-through nanoporous alumina trypsin bioreactor for mass spectrometry peptide fingerprinting.
Mass spectrometry-based proteomics benefits from efficient digestion of protein samples. In this study, trypsin was immobilized on nanoporous anodized alumina membranes to create an enzyme reactor suitable for peptide mass fingerprinting. The membranes were derivatized with 3-aminopropyltriethoxysilane and the amino groups were activated with carbonyldiimidazole to allow coupling of porcine trypsin via ε-amino groups. The function was assessed using the artificial substrate Nα-Benzoyl-L-arginine 4-nitroanilide hydrochloride, bovine ribonuclease A and a human plasma sample. A 10-membrane flow-through reactor was used for fragmentation and MS analysis after a single pass of substrate both by collection of product and subsequent off-line analysis, and by coupling on-line to the instrument. The peptide pattern allowed correct identification of the single target protein in both cases, and of >70 plasma proteins in single pass mode followed by LC-MS analysis. The reactor retained 76% of the initial activity after 14days of storage and repeated use at room temperature. This manuscript describes the design of a stable enzyme reactor that allows efficient and fast digestion with negligible leakage of enzyme and enzyme fragments. The high stability facilitates the use in an online-setup with MS detection since it allows the processing of multiple samples within an extended period of time without replacement.


Responsiveness of C neurons in rat dorsal root ganglion to 5-hydroxytryptamine-induced pruritic stimuli in vivo.
Itching is a common symptom in dermatologic diseases and causes restless scratching of the skin, which aggravates the condition. The mechanism of the itch sensation, however, is enigmatic. The present study included behavioral tests and electrophysiological recordings from rat dorsal root ganglion (DRG) neurons in vivo to analyze the response to pruritic stimuli induced by topical application of 5-hydroxytryptamine (5-HT) to the skin. Topically applied 5-HT to the rostral back evoked scratching, whereas application of the vehicle did not. Following subcutaneous injection of the opioid receptor antagonist naloxone, the number of scratches decreased, suggesting that the scratching was preferentially mediated by itch but not pain sensation. To elucidate the firing properties of DRG neurons in response to topically applied 5-HT, intracellular recordings were made from DRG neurons in vivo. None of the Abeta and Adelta neurons responded to 5-HT; in contrast, 25 of 91 C neurons (27%) exhibited repetitive firing in response to 5-HT, which could be classified into two firing patterns: one was a transient type, characterized by low firing frequency that decreased within 5 min; the other was a long-lasting type, having high firing frequency that continued increasing after 5 min. The time course of the firing pattern of long-lasting C neurons was comparable to the scratching behavior. Intriguingly, the long-lasting-type neurons had a significantly smaller fast afterhyperpolarization than that of the 5-HT-insensitive neurons. These observations suggest that the long-lasting-firing C neurons in rat DRG sensitive to 5-HT are responsible for conveying pruritic information to the spinal cord.


Secondary holocord syringomyelia with spinal hemangioblastoma: a report of two cases.
Intramedullary spinal hemangioblastoma is well known to be accompanied by syringomyelia. However, holocord secondary syringomyelia is uncommon. We present 2 cases of spinal hemangioblastoma, one in the conus medullaris and the other in midthoracic region, accompanied by holocord syrinx. In both the cases the secondary syrinx resolved following successful total tumor excision with good neurological recovery.


Prospective study of the accuracy of EGFR mutational analysis by high-resolution melting analysis in small samples obtained from patients with non-small cell lung cancer.
Epidermal growth factor receptor (EGFR) mutations, especially in-frame deletions in exon 19 (DEL) and a point mutation in exon 21 (L858R), predict gefitinib sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we verified the accuracy of EGFR mutation analysis in small samples by high-resolution melting analysis (HRMA), which is a rapid method using PCR amplification with a dye to analyze the melting curves in NSCLC. We designed a prospective study to compare the sensitivity and specificity of HRMA and DNA sequencing with laser capture microdissection. Eligible patients with lung lesions were screened by bronchoscopy or percutaneous needle biopsy to histologically confirm the diagnosis, followed by surgical resection of the NSCLC. Small diagnostic specimens were analyzed for EGFR mutations by HRMA, and the surgically resected specimens were examined for mutations by HRMA and DNA sequencing. The analyses for EGFR mutations were conducted in 52 eligible cases of the 92 enrolled patients. EGFR mutations were detected in 18 (34.6%) patients. The results of HRMA from surgically resected specimens as well as DNA sequencing revealed 100% sensitivity and specificity. On the other hand, the sensitivity and specificity of HRMA from the small diagnostic specimens were 83.3% and 100%, respectively. In this study, we showed that HRMA is a highly accurate method for detecting DEL and L858R mutations in patients with NSCLC, although it is necessary to consider the identification of patients with a false-negative result when the analysis is conducted using small samples.


Perception of Cancer Risk and Its Associated Risk Factors among Young Iraqis living in Baghdad.
Cancer is responsible for substantial burden on communities and more specifically on less developed countries. The incidence of cancer is on the rise due to population growth and aging, also due to increment of the risk factors such as smoking, increasing weight, low physical activity associated with adoption of western lifestyle. Around 14 million cases of new cancer and 8 million deaths from cancer is estimated to occur by 2012. This cross-sectional study was conducted in Baghdad from June 2016 to October 2016. Participants were selected according to our inclusion criteria, namely aged between 18 to 40 years and not being diagnosed with any chronic diseases. Those who fulfilled the inclusion criteria were 700 participants who completed the questionnaire. Results showed that most of our participants had low perceived susceptibility to cancer risk (62.4%), low perceived severity (59.8%), but good perceived benefits of screening (56.6%). Hierarchal linear regression analysis showed that sociodemographic factors of gender, marital status, and education level were statistically significant. Moreover, factors of health behaviour such as practice towards health and preventive behaviour were associated with the outcome. Finally, treatment control and emotional factors were mostly predicting the outcome. Perceived susceptibility to cancer along with its psychological factors and behaviour were important contributors to self-perceived health in this study. Hence there is association between perception and future morbidity and mortality, thus it is crucial for public health policy. Comprehensive health programs that include health promotion campaigns and proper health care services that deals with secondary prevention.


European Association of Nuclear Medicine and European Academy of Neurology recommendations for the use of brain 18 F-fluorodeoxyglucose positron emission tomography in neurodegenerative cognitive impairment and dementia: Delphi consensus.
Recommendations for using fluorodeoxyglucose positron emission tomography (FDG-PET) to support the diagnosis of dementing neurodegenerative disorders are sparse and poorly structured. Twenty-one questions on diagnostic issues and on semi-automated analysis to assist visual reading were defined. Literature was reviewed to assess study design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiver operating characteristic curve, and positive/negative likelihood ratio of FDG-PET in detecting the target conditions. Using the Delphi method, an expert panel voted for/against the use of FDG-PET based on published evidence and expert opinion. Of the 1435 papers, 58 papers provided proper quantitative assessment of test performance. The panel agreed on recommending FDG-PET for 14 questions: diagnosing mild cognitive impairment due to Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) or dementia with Lewy bodies (DLB); diagnosing atypical AD and pseudo-dementia; differentiating between AD and DLB, FTLD or vascular dementia, between DLB and FTLD, and between Parkinson's disease and progressive supranuclear palsy; suggesting underlying pathophysiology in corticobasal degeneration and progressive primary aphasia, and cortical dysfunction in Parkinson's disease; using semi-automated assessment to assist visual reading. Panellists did not support FDG-PET use for pre-clinical stages of neurodegenerative disorders, for amyotrophic lateral sclerosis and Huntington disease diagnoses, and for amyotrophic lateral sclerosis or Huntington-disease-related cognitive decline. Despite limited formal evidence, panellists deemed FDG-PET useful in the early and differential diagnosis of the main neurodegenerative disorders, and semi-automated assessment helpful to assist visual reading. These decisions are proposed as interim recommendations.


Arginine, scurvy and Cartier's "tree of life".
Several conifers have been considered as candidates for "Annedda", which was the source for a miraculous cure for scurvy in Jacques Cartier's critically ill crew in 1536. Vitamin C was responsible for the cure of scurvy and was obtained as an Iroquois decoction from the bark and leaves from this "tree of life", now commonly referred to as arborvitae. Based on seasonal and diurnal amino acid analyses of candidate "trees of life", high levels of arginine, proline, and guanidino compounds were also probably present in decoctions prepared in the severe winter. The semi-essential arginine, proline and all the essential amino acids, would have provided additional nutritional benefits for the rapid recovery from scurvy by vitamin C when food supply was limited. The value of arginine, especially in the recovery of the critically ill sailors, is postulated as a source of nitric oxide, and the arginine-derived guanidino compounds as controlling factors for the activities of different nitric oxide synthases. This review provides further insights into the use of the candidate "trees of life" by indigenous peoples in eastern Canada. It raises hypotheses on the nutritional and synergistic roles of arginine, its metabolites, and other biofactors complementing the role of vitamin C especially in treating Cartier's critically ill sailors.


[Medical insurance in the light of social informatics].
Analyzes the experience gained in cooperative studies aimed at the development and introduction of automated data processing systems, carried out by the Institute of Informatics, Russian Academy of Sciences, and the Krasnodar Territorial Foundation for Obligatory Medical Insurance and its branches.


Atypical hyperplasia of the breast: the black hole of routine breast cancer screening.
Determination of the prevalence, of the radiological and clinical characteristics, and outcome of atypical hyperplasia (AH) of the breast within a population subjected to routine screening (double-view mammography with double reading, performed every two years between 50 and 75 years of age). The clinical and radiological records and histological findings of percutaneous and surgical biopsy specimens of sixty-eight patients presenting with AH were reviewed together with patient follow-up data after percutaneous and surgical biopsy. AH incidence in the population was 0.19‰ with the following distribution of lesions: atypical epithelial hyperplasia (AEH, 53%), columnar cell metaplasia with atypia (CCMA, 32%), and lobular intraepithelial neoplasia (LIN, 8%). The mean patient age was 58 years and 24% of patients were receiving hormone replacement therapy. The main radiological finding was the presence of microcalcifications for AEH and CCMA lesions in particular, and the mammograms were valid (correlation between American College of Radiology score and risk of lesion, only 3% of lesions were recognized on the second reading). A total of 13.7% of AH cases were underestimated and a real risk of AH progression was observed, regardless of whether or not surgical biopsy had been performed. The clinical and radiological characteristics of AH observed in a population subjected to routine breast cancer screening are identical to those for patients with the same lesions referred to specialist centers. Surgical biopsy remains the recommended option due to the risk of underestimation of lesions by percutaneous biopsy and the risk of progression justifies the need for continued close monitoring.


[The taxonomic status of Leishmania garnhami, indicated by its pattern of development in the vector].
Under experimental conditions, the developmental pattern of Leishmania garnhami in its vector Lutzomyia townsendi, was established following daily dissections between the 1st and the 12th day post-infection. L. garnhami succeeded in establishing initial infections in any of the gut regions and in the Malpighian tubules of infected sandflies. Similar behavior was observed in infected Lu. longipalpis. The distribution of L. garnhami in the digestive tract of infected flies, is different to that observed in species of the L. mexicana and L. braziliensis complexes. The susceptibility of Lu. townsendi to infection by L. mexicana, L. braziliensis and L. garnhami is discussed. It is concluded that L. garnhami, according to its behaviour in the vector, must be considered different from the l. mexicana complex, and that its developmental pattern differs from that of the Suprapylaria, because it invades the hind triangle and also from the species of the Peripylaria by its invasion of the Malpighian tubules.


Dynamics of glycolipid domains in the plasma membrane of living cultured neurons, following protein kinase C activation: a study performed by excimer-formation imaging.
Dynamic changes of glycolipid domains within the plasma membranes of cultured rat cerebellar granule cells have been investigated. For this purpose, a pyrene-labelled derivative of G(M1) ganglioside has been incorporated in the cell plasma membrane, and the rate of excimer formation, directly related to the formation of domains, has been studied by a fluorescence imaging technique (excimer-formation imaging). Fluorescence imaging showed that upon addition of 100 microM glutamate, indirectly inducing the activation of protein kinase C (PKC), glycolipid concentration within domains increases in cell bodies. Comparable effects were exerted by the addition of PMA, directly inducing the activation of PKC. On the contrary, the phorbol ester was not effective in the presence of the specific PKC inhibitor, bisindolylmaleimide. These results suggest that glycolipid-enriched domains are dynamic supramolecular structures affected by membrane-associated events, such as PKC activation. Dynamic changes of domains could be important in modulating their postulated participation in a series of functions, including signal transduction and lipid/protein sorting.


A Comment on the Efficacy of Unilateral Versus Bilateral ECT.
Ten studies comparing the efficacy of unilateral versus bilateral electroconvulsive therapy (ECT) were reexamined. Three different methods of meta-analysis applied to the combined results revealed statistical significance in favor of bilateral ECT for the relief of depression. The recognition that bilateral ECT has some advantage over unilateral is in sharp contrast to an overly strong conclusion to the contrary previously reached by Janicak et al. (1985), in reviewing the same studies. Alternative statistical methods for evaluating the significance of combined results from several independent studies are illustrated with reference to previously published ECT research.


Metastatic glioblastoma multiforme in cervical lymph nodes. Report of a case with diagnosis by fine needle aspiration.
Metastatic glioblastoma multiforme is a rare event usually seen in patients with previous and repeated surgery. Fine needle aspiration from enlarged lymph nodes in a patient with cerebral glioblastoma multiforme showed a highly cellular smear with dispersed single cells and cell clusters. The cells had marked pleomorphism, hyperchromasia, coarse chromatin, prominent nucleoli and occasional intranuclear cytoplasmic inclusions. Multinucleate giant cells and marked endothelial proliferation were also seen. The diagnosis of metastatic glioblastoma multiforme was supported by immunohistochemistry, which showed many cells with thick and large cytoplasmic processes with intense immunoreactivity to glial fibrillary acid protein. The differential diagnosis with other metastatic small cell tumors is discussed.


Establishing Obstetric Anesthesiology Practice Guidelines in the Republic of Armenia: A Global Health Collaboration.
Disparity exists in anesthesia practices between high- and low-to-middle income countries, and awareness has been raised within the global health community to improve the standards of anesthesia care and patient safety. The establishment of international collaborations and appropriate practice guidelines may help address clinical care deficiencies. This report's aim was to assess the impact of a multiyear collaboration on obstetric anesthesia practices in the Republic of Armenia. An invited multinational team of physicians conducted six visits to Armenia between 2006 and 2015 to observe current practice and establish standards of obstetric anesthesia care. The Armenian Society of Anaesthesiologists and Intensive Care specialists collected data on the numbers of vaginal delivery, cesarean delivery, and neuraxial anesthesia use in maternity units during the period. Data were analyzed with the Fisher exact or chi-square test, as appropriate. Neuraxial anesthesia use for cesarean delivery increased significantly (P < 0.0001) in all 10 maternity hospitals within the capital city of Yerevan. For epidural labor analgesia, there was sustained or increased use in only two hospitals. For hospitals located outside the capital city, there was a similar increase in the use of neuraxial anesthesia for cesarean delivery that was greater in hospitals that were visited by an external team (P < 0.0001); however, use of epidural labor analgesia was not increased significantly. Over the course of the collaboration, guidelines for obstetric anesthesia were drafted and approved by the Armenian Ministry of Health. Collaboration between Armenian anesthesiologists and dedicated visiting physicians to update and standardize obstetric anesthesia practices led to national practice guidelines and sustained improvements in clinical care in the Republic of Armenia.


Retinoic Acid Receptor Alpha Represses a Th9 Transcriptional and Epigenomic Program to Reduce Allergic Pathology.
CD4+ T helper (Th) differentiation is regulated by diverse inputs, including the vitamin A metabolite retinoic acid (RA). RA acts through its receptor RARα to repress transcription of inflammatory cytokines, but is also essential for Th-mediated immunity, indicating complex effects of RA on Th specification and the outcome of the immune response. We examined the impact of RA on the genome-wide transcriptional response during Th differentiation to multiple subsets. RA effects were subset-selective and were most significant in Th9 cells. RA globally antagonized Th9-promoting transcription factors and inhibited Th9 differentiation. RA directly targeted the extended Il9 locus and broadly modified the Th9 epigenome through RARα. RA-RARα activity limited murine Th9-associated pulmonary inflammation, and human allergic inflammation was associated with reduced expression of RA target genes. Thus, repression of the Th9 program is a major function of RA-RARα signaling in Th differentiation, arguing for a role for RA in interleukin 9 (IL-9) related diseases.


G Protein-Coupled Estrogen Receptor: Rapid Effects on Hippocampal-Dependent Spatial Memory and Synaptic Plasticity.
In the hippocampus, estrogen regulates gene transcription linked to neuronal growth, neuroprotection, and the maintenance of memory function (1-3). The mechanism is likely to involve genomic regulation through classic estrogen receptor (ER) signaling cascades that influence transcription. Estrogens binding to classic nuclear ERs, alpha (ERα) and beta (ERβ), and have pleotropic effects on development, behavior, and neurophysiological functions, including synaptic plasticity and memory consolidation (4-7). In addition to ERα and ERβ, estrogen can also initiate activation of classical second messenger signaling cascades to influence the activity of G-proteins and a host of kinases, resulting in rapid changes in physiology (8-14). These rapid effects of estrogen are commonly mediated by membrane receptors. In the late 90s, multiple laboratories cloned cDNA/gene for an orphan G-protein-coupled receptor with very low homology with other G-protein-coupled receptors and named it G-protein-coupled receptor 30 (GPR30) (15-20). Later in 2007, the International Union of Basic and Clinical Pharmacology designated GPR30 as G protein-coupled estrogen receptor (GPER) (21); GPER is a seven-transmembrane G-protein-coupled receptor, predominantly expressed on the cell membrane (22). Interestingly, GPER is reported to mediate many of the rapid responses of estradiol in the adult brain, and is widely distributed in the mammalian brain including the plasma membrane of hippocampal neurons (23-31). GPER modulates second messenger signaling cascades involving Gαs- and Gαi/o-associated increase in cyclic adenosine monophosphate and phosphoinositide 3-kinase or Src protein kinase respectively (32, 33). Activation of GPER is also associated with phospholipase C, and the inositol receptor and ryanodine receptor-mediated increase in intracellular calcium (24, 34). This commentary is concentrated specifically on the possible rapid effects of GPER in hippocampal-dependent spatial memory function and synaptic plasticity.


Cup Safe Zone and Optimal Stem Anteversion in Total Hip Arthroplasty for Patients with Highly Required Range of Motion.
To avoid dislocation after total hip arthroplasty (THA), it is desirable to avoid implant impingement during activities of daily living. Numerous simulation studies have been performed at 30° of internal rotation (IR) with 90° of flexion. However, these studies may not reflect the impingement that occurs during activities such as floor sitting, which require a larger IR during flexion. The purpose of this study was to assess the impact of varying internal rotation angles during flexion on the impingement-free safe zone and optimal stem anteversion. In this study, implant impingement simulation was evaluated in computer simulation. The prosthesis used a flat liner, and a 32-mm or 40-mm femoral head and stem. Three patterns of required IR angle (30° IR/40° IR/50° IR with 90° flexion) combined with 13 directions of required ROM were simulated. The optimal stem anteversion to maximize the safe zone was analysed. Increasing the required IR at 90° flexion decreased the safe zone, particularly with small stem anteversion angles. With a 32-mm head, the desirable stem anteversion at 40° of cup inclination was 15°/25°/35° in required 30° IR/40° IR/50° IR with 90° flexion, respectively. The safe zone area of the 32-mm head was smaller than that of the 40-mm head. For patients who require a larger IR with 90° flexion, the stem and cup target anteversion should be adjusted according to the implant design, head diameter, patient's required IR at flexion in their lifestyle. This article is protected by copyright. All rights reserved.


[Structure of thromboembolic complications (based on prosection data of the Department of Pathological Anatomy of the I. M. Sechenov I Moscow Medical Institute from 1962 to 1979)].
Based on the study of the materials of 13,000 autopsies made in 1962--1979 at the Pathology Department of the Chair of Pathological Anatomy of the I. M. Sechenov First Medical Institute, an increase in the rate of thromboembolic complications (TEC) was established predominantly in diseases of the cardiovascular system (atherosclerosis, hypertension, ischemic heart disease, rheumatic disease, protracted bacterial endocarditis). The analysis of 8157 autopsies with TEC revealed general regularities of changes in TEC structure in different diseases irrespective of their pathogenetic differences: predominance in the last two decades of venous thrombs, thromboemboly of the pulmonary artery and pulmonary infarction; prevalence of senescent and senile people among patients with TEC, and women among them (with the exception of protracted bacterial endocarditis).


Copeptin and peroxiredoxin-4 independently predict mortality in patients with nonspecific complaints presenting to the emergency department.
Patients presenting to emergency departments (ED) with nonspecific complaints (NSCs) such as "not feeling well,""feeling weak,""being tired,""general deterioration," or other similar chief complaints that do not have a readily identifiable probable etiology are a common patient group at risk for adverse outcomes. Certain biomarkers, which have not yet been tested for prognostic value when applied to ED patients with NSCs, have emerged as useful tools for predicting prognosis in patients with a variety of diseases. This study tested the hypothesis that two of these novel markers, copeptin (a C-terminal portion of provasopressin) and/or peroxiredoxin-4 (Prx4), an enzyme that degrades hydrogen peroxide, singly or together are helpful in predicting death in the near term among patients presenting to the ED with NSCs. The Basel Non-specific Complaints (BANC) study is a delayed type cross-sectional diagnostic study with a prospective 30-day follow-up. ED patients with NSCs were consecutively enrolled. Patients with vital parameters out of the normal range were excluded. The primary endpoint of this study was the predictive value of copeptin and Prx4 for 30-day mortality in patients with NSCs. Measurement of both copeptin and Prx4 was performed in serum samples with sandwich immunoluminometric assays. On follow-up at 30 days after ED presentation, 28 of 438 patients with NSC had died. Copeptin and Prx4 concentrations were significantly higher in nonsurvivors than in survivors (Kruskal-Wallis test, p = 0.0001 and p < 0.0001, respectively). In univariate models, Prx4 (likelihood ratio [LR] χ(2) = 22.24, p < 0.00001, concordance index [C-index] = 0.749) and copeptin (LR χ(2) = 16.98, p = 0.00004, C-index = 0.724) were both predictive of 30-day mortality, and elevated levels were associated with an increased mortality. The bivariable model, which included both Prx4 and copeptin (LR χ(2) = 28.22, p < 0.00001, C-index = 0.783), allows a significantly better prediction than the univariate Prx4 (p = 0.00025) and copeptin models (p = 0.00099), respectively. Both biomarkers provided independent and additional information to clinical risk scores (Katz Activities of Daily Living [ADL] and Charlson Comorbidity Index [CCI], all p < 0.0005). Copeptin and Prx4 are new prognostic markers in patients presenting to the ED with NSCs. Copeptin and Prx4 might be valuable tools for risk stratification and decision-making in this patient group.


Deep brain stimulation of the lateral cerebellar nucleus produces frequency-specific alterations in motor evoked potentials in the rat in vivo.
The cerebral cortex is tightly and reciprocally linked to the cerebellum and the ascending dentato-thalalmo-cortical pathway influences widespread cortical regions. Using a rodent model of middle cerebral artery stroke, we showed previously that chronic, 20 Hz stimulation of the contralateral lateral cerebellar nucleus (LCN) improved motor recovery, while 50 Hz stimulation did not. Using motor evoked potentials (MEP) elicited by intracortical microstimulation, we now show the effect of LCN stimulation on motor cortex excitability as a function of pulse frequency in propofol-anesthetized rats. MEPs were recorded serially, at 15-s intervals, with cerebellar stimulation delivered in 10-min blocks at rates of 20, 30, 40, 50 or 100 Hz. Stimulation at 20, 30, 40 or 50 Hz enhanced the average MEP response across the block, with the maximal overall increase observed during 30 Hz stimulation. However, the effect varied as a function of both repeated trials within the block and LCN stimulation frequency, such that 40 Hz and 50 Hz stimulation showed a reduced effect over time. Stimulation at 100 Hz produced a transient increase in MEP amplitude in some animals; however the overall effect across the block was a trend towards reduced cortical excitability. These results suggest that direct stimulation of the LCN can yield frequency-dependent changes in cortical excitability and may provide a therapeutic approach to modulating cortical activity for the treatment of strokes or other focal cortical lesions, movement disorders and epilepsy.


A Diamond-Based Electrode for Detection of Neurochemicals in the Human Brain.
Deep brain stimulation (DBS), a surgical technique to treat certain neurologic and psychiatric conditions, relies on pre-determined stimulation parameters in an open-loop configuration. The major advancement in DBS devices is a closed-loop system that uses neurophysiologic feedback to dynamically adjust stimulation frequency and amplitude. Stimulation-driven neurochemical release can be measured by fast-scan cyclic voltammetry (FSCV), but existing FSCV electrodes rely on carbon fiber, which degrades quickly during use and is therefore unsuitable for chronic neurochemical recording. To address this issue, we developed durable, synthetic boron-doped diamond-based electrodes capable of measuring neurochemical release in humans. Compared to carbon fiber electrodes, they were more than two orders-of-magnitude more physically-robust and demonstrated longevity in vitro without deterioration. Applied for the first time in humans, diamond electrode recordings from thalamic targets in patients (n = 4) undergoing DBS for tremor produced signals consistent with adenosine release at a sensitivity comparable to carbon fiber electrodes. (Clinical trials # NCT01705301).


Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes.
The World Health Organization classification of myelodysplastic syndromes (MDS) is based on morphological evaluation of marrow dysplasia. We performed a systematic review of cytological and histological data from 1150 patients with peripheral blood cytopenia. We analyzed the frequency and discriminant power of single morphological abnormalities. A score to define minimal morphological criteria associated to the presence of marrow dysplasia was developed. This score showed high sensitivity/specificity (>90%), acceptable reproducibility and was independently validated. The severity of granulocytic and megakaryocytic dysplasia significantly affected survival. A close association was found between ring sideroblasts and SF3B1 mutations, and between severe granulocytic dysplasia and mutation of ASXL1, RUNX1, TP53 and SRSF2 genes. In myeloid neoplasms with fibrosis, multilineage dysplasia, hypolobulated/multinucleated megakaryocytes and increased CD34+ progenitors in the absence of JAK2, MPL and CALR gene mutations were significantly associated with a myelodysplastic phenotype. In myeloid disorders with marrow hypoplasia, granulocytic and/or megakaryocytic dysplasia, increased CD34+ progenitors and chromosomal abnormalities are consistent with a diagnosis of MDS. The proposed morphological score may be useful to evaluate the presence of dysplasia in cases without a clearly objective myelodysplastic phenotype. The integration of cytological and histological parameters improves the identification of MDS cases among myeloid disorders with fibrosis and hypocellularity.


Solution structure of the Ca2+-Binding EGF3-4 pair from vitamin K-dependent protein S: identification of an unusual fold in EGF3.
Vitamin K-dependent protein S is a cofactor of activated protein C, a serine protease that regulates blood coagulation. Deficiency of protein S can cause venous thrombosis. Protein S has four EGF domains in tandem; domains 2-4 bind calcium with high affinity whereas domains 1-2 mediate interaction with activated protein C. We have now solved the solution structure of the EGF3-4 fragment of protein S. The linker between the two domains is similar to what has been observed in other calcium-binding EGF domains where it provides an extended conformation. Interestingly, a disagreement between NOE and RDC data revealed a conformational heterogeneity within EGF3 due to a hinge-like motion around Glu186 in the Cys-Glu-Cys sequence, the only point in the domain where flexibility is allowed. The dominant, bent conformation of EGF3 in the pair has no precedent among calcium-binding EGF domains. It is characterized by a change in the psi angle of Glu186 from 160 degrees +/- 40 degrees , as seen in ten other EGF domains, to approximately 0 degrees +/- 15 degrees . NOESY data suggest that Tyr193, a residue not conserved in other calcium-binding EGF domains (except in the homologue Gas6), induces the unique fold of EGF3. However, SAXS data, obtained on EGF1-4 and EGF2-4, showed a dominant, extended conformation in these fragments. This may be due to a counterproductive domain-domain interaction between EGF2 and EGF4 if EGF3 is in a bent conformation. We speculate that the ability of EGF3 to adopt different conformations may be of functional significance in protein-protein interactions involving protein S.


Geochemical evidence for atmospheric pollution derived from prehistoric copper mining at Copa Hill, Cwmystwyth, mid-Wales, UK.
This paper presents geochemical data from a blanket peat located close to a Bronze Age copper mine on the northern slopes of the Ystwyth valley, Ceredigion, mid-Wales, UK. The research objective was to explore the possibility that the peat contained a geochemical record of the pollution generateD by mining activity. Four peat monoliths were extracted from the blanket peat to reconstruct the pollution history of the prehistoric mine. Three different geochemical measurement techniques were employed and four copper profiles have been reconstructed, two of which are radiocarbon-dated. The radiocarbon dates at one profile located close to the mine confirm that copper enrichment occurs in the peat during the known period of prehistoric mining. Similar enrichment of copper concentrations is shown in one adjacent profile and a profile within 30 m away. In contrast, copper was not enriched in the other radiocarbon-dated monolith, collected approximately 1.35 km to the north of the mine. Whilst other possible explanations to explain the copper concentrations are discussed, it is argued that the high copper concentrations represent evidence of localised atmospheric pollution caused by Bronze Age copper mining in the British Isles. The results of this study suggest that copper may be immobile in blanket peat and such deposits can usefully be used to reconstruct atmospheric pollution histories in former copper mining areas.


Resettable Microfluidics for Broad-Range and Prolonged Sweat Rate Sensing.
Wearable sweat sensors are emerging as promising platforms for personalized and real-time tracking of evolving health and fitness parameters. While most wearable sweat sensors focus on tracking biomarker concentration profiles, sweat secretion rate is a key metric with broad implications for assessing hydration, cardiac, and neural conditions. Here we present a wearable microfluidic sensor for continuous sweat rate measurement. A discrete impedimetric sensing scheme relying on interdigitated electrodes within a microfluidic sweat collector allows for precise and selective sweat rate measurement across a broad physiological range. Integration of a manually activated pressure pump to expel sweat from the device prevents sensor saturation and enables continuous sweat rate tracking over hours. By enabling broad range and prolonged sweat rate measurement, this platform tackles a key obstacle to realizing meaningful and actionable sweat sensing for applications in exercise physiology and medicine.


Possible UIP pattern on high-resolution computed tomography is associated with better survival than definite UIP in IPF patients.
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease of unknown etiology. Inter-society consensus guidelines on IPF diagnosis and management outline radiologic patterns including definite usual interstitial pneumonia (UIP), possible UIP, and inconsistent with UIP. We evaluate these diagnostic categories as prognostic markers among patients with IPF. Included subjects had biopsy-proven UIP, a multidisciplinary team diagnosis of IPF, and a baseline high-resolution computed tomography (HRCT). Thoracic radiologists assigned the radiologic pattern and documented the presence and extent of specific radiologic findings. The outcome of interest was lung transplant-free survival. IPF patients with a possible UIP pattern on HRCT had significantly longer Kaplan-Meier event-free survival compared to those with definite UIP pattern (5.21 and 3.57 years, respectively, p = 0.002). In a multivariable Cox proportional hazards model adjusted for baseline age, gender, %-predicted FVC, and %-predicted DLCO via the GAP Stage, extent of fibrosis (via the traction bronchiectasis score) and ever-smoker status, possible UIP pattern on HRCT (versus definite UIP) was associated with reduced hazard of death or lung transplant (HR = 0.42, CI 95% 0.23-0.78, p = 0.006). Radiologic diagnosis categories outlined by inter-society consensus guidelines is a widely-reported and potentially useful prognostic marker in IPF patients, with possible UIP pattern on HRCT associated with a favorable prognosis compared to definite UIP pattern, after adjusting for relevant covariates.


Characterization and ACE Inhibitory Activity of Fermented Milk with Probiotic Lactobacillus plantarum K25 as Analyzed by GC-MS-Based Metabolomics Approach.
Addition of probiotics to yogurt with desired health benefits is gaining increasing attention. To further understand the effect of probiotic Lactobacillus plantarum on the quality and function of fermented milk, probiotic fermented milk (PFM) made with probiotic L. plantarum K25 and yogurt starter (L. delbrueckii ssp. bulgaricus and Streptococcus thermophilus) was compared with the control fermented milk (FM) made with only the yogurt starter. The probiotic strain was shown to survive well with a viable count of 7.1 ± 0.1 log CFU/g in the PFM sample after 21 days of storage at 4°C. The strain was shown to promote formation of volatiles such as acetoin and 2,3-butanediol with milk fragrance, and it did not cause post-acidification during refrigerated storage. Metabolomics analysis by GC-MS datasets coupled with multivariate statistical analysis showed that addition of L. plantarum K25 increased formation of over 20 metabolites detected in fermented milk, among which γ-aminobutyric acid was the most prominent. Together with several other metabolites with relatively high levels in fermented milk such as glyceric acid, malic acid, succinic acid, glycine, alanine, ribose, and 1,3-dihydroxyacetone, they might play important roles in the probiotic function of L. plantarum K25. Further assay of the bioactivity of the PFM sample showed significant (p < 0.05) increase of ACE inhibitory activity from 22.3% at day 1 to 49.3% at day 21 of the refrigerated storage. Therefore, probiotic L. plantarum K25 could be explored for potential application in functional dairy products.


A novel DNA vaccine expressing the Ag85A-HA2 fusion protein provides protection against influenza A virus and Staphylococcus aureus.
Secondary pneumonia due to Staphylococcus aureus (S. aureus) causes significant morbidity and mortality. The aim of the research was designed a novel DNA vaccine encoding the Mycobacterium tuberculosis secreted antigen Ag85A fused with the influenza A virus (IAV) HA2 protein to provide protection against both influenza and secondary infection with S. aureus. The DNA vaccine vector efficiently expressed the encoded antigen in mammalian cells, as determined by RT-PCR, Western blotting and immunofluorescence analysis. Mice were immunized with the vaccine by intramuscular injection before challenge with IAV and S. aureus. The pulmonary and the splenocyte culture IFN-γ levels were significant higher in immunized mice than their respective controls. Although the antibody titer in the HI test was low, the sera of mice immunized with the novel vaccine vector were effective in neutralisation assay in vitro. The vaccine could reduce the loss of body weight in mice during IAV challenge. Both Western blotting and RT-PCR showed that the vaccine markedly enhanced toll like receptor 2 (TLR2) expression in splenocytes after the secondary infection with S. aureus. The survival rate of mice with high TLR2 expression (pEGFP/Ag85A-HA2 or iPR) was significantly increased compared with mice immunized with pEGFP/HA2 after challenge with S. aureus. However, the pulmonary IL-10 concentration and S. aureus titer were significantly decreased in immunized mice, and expression of TLR2 was increased after challenge with S. aureus. These results demonstrated that Ag85A could strengthen the immune response to IAV and S. aureus, and TLR2 was involved in the host response to S. aureus.


Spontaneous Pregnancy Loss in Denmark Following Economic Downturns.
An estimated 11%-20% of clinically recognized pregnancies result in spontaneous abortion. The literature finds elevated risk of spontaneous abortion among women who report adverse financial life events. This work suggests that, at the population level, national economic decline-an ambient and plausibly unexpected stressor-will precede an increase in spontaneous abortion. We tested this hypothesis using high-quality information on pregnancy and spontaneous loss for all women in Denmark. We applied time-series methods to monthly counts of clinically detected spontaneous abortions (n = 157,449) and the unemployment rate in Denmark beginning in January 1995 and ending in December 2009. Our statistical methods controlled for temporal patterns in spontaneous abortion (e.g., seasonality, trend) and changes in the population of pregnancies at risk of loss. Unexpected increases in the unemployment rate preceded by 1 month a rise in the number of spontaneous abortions (β = 33.19 losses/month, 95% confidence interval: 8.71, 57.67). An attendant analysis that used consumption of durable household goods as an indicator of financial insecurity supported the inference from our main test. Changes over time in elective abortions and in the cohort composition of high-risk pregnancies did not account for results. It appears that in Denmark, ambient stressors as common as increasing unemployment may precede a population-level increase in spontaneous abortion.


A matter of classes: stratifying health care populations to produce better estimates of inpatient costs.
To stratify traditional risk-adjustment models by health severity classes in a way that is empirically based, is accessible to policy makers, and improves predictions of inpatient costs. Secondary data created from the administrative claims from all 829,356 children aged 21 years and under enrolled in Georgia Medicaid in 1999. A finite mixture model was used to assign child Medicaid patients to health severity classes. These class assignments were then used to stratify both portions of a traditional two-part risk-adjustment model predicting inpatient Medicaid expenditures. Traditional model results were compared with the stratified model using actuarial statistics. The finite mixture model identified four classes of children: a majority healthy class and three illness classes with increasing levels of severity. Stratifying the traditional two-part risk-adjustment model by health severity classes improved its R(2) from 0.17 to 0.25. The majority of additional predictive power resulted from stratifying the second part of the two-part model. Further, the preference for the stratified model was unaffected by months of patient enrollment time. Stratifying health care populations based on measures of health severity is a powerful method to achieve more accurate cost predictions. Insurers who ignore the predictive advances of sample stratification in setting risk-adjusted premiums may create strong financial incentives for adverse selection. Finite mixture models provide an empirically based, replicable methodology for stratification that should be accessible to most health care financial managers.


White matter cerebral blood flow is inversely correlated with structural and functional connectivity in the human brain.
White matter provides anatomic connections among brain regions and has received increasing attention in understanding brain intrinsic networks and neurological disorders. Despite significant progresses made in characterizing the white matter's structural properties using post-mortem techniques and in vivo diffusion-tensor-imaging (DTI) methods, its physiology remains poorly understood. In the present study, cerebral blood flow (CBF) of the white matter was investigated on a fiber tract-specific basis using MRI (n=10, 25-33 years old). It was found that CBF in the white matter varied considerably, up to a factor of two between fiber groups. Furthermore, a paradoxically inverse correlation was observed between white matter CBF and structural and functional connectivities (P<0.001). Fiber tracts that had a higher CBF tended to have a lower fractional anisotropy in water diffusion, and the gray matter terminals connected to the tract also tended to have a lower temporal synchrony in resting-state BOLD signal fluctuation. These findings suggest a clear association between white matter perfusion and gray matter activity, but the nature of this relationship requires further investigations given that they are negatively, rather than positively, correlated.


Methods for obtaining and analyzing unattended polysomnography data for a multicenter study. Sleep Heart Health Research Group.
This paper reviews the data collection, processing, and analysis approaches developed to obtain comprehensive unattended polysomnographic data for the Sleep Heart Health Study, a multicenter study of the cardiovascular consequences of sleep-disordered breathing. Protocols were developed and implemented to standardize in-home data collection procedures and to perform centralized sleep scoring. Of 7027 studies performed on 6697 participants, 5534 studies were determined to be technically acceptable (failure rate 5.3%). Quality grades varied over time, reflecting the influences of variable technician experience, and equipment aging and modifications. Eighty-seven percent of studies were judged to be of "good" quality or better, and 75% were judged to be of sufficient quality to provide reliable sleep staging and arousal data. Poor submental EMG (electromyogram) accounted for the largest proportion of poor signal grades (9% of studies had <2 hours artifact free EMG signal). These data suggest that with rigorous training and clear protocols for data collection and processing, good-quality multichannel polysomnography data can be obtained for a majority of unattended studies performed in a research setting. Data most susceptible to poor signal quality are sleep staging and arousal data that require clear EEG (electroencephalograph) and EMG signals.


Voluntary activation and decreased force production of the quadriceps femoris muscle after total knee arthroplasty.
Quadriceps femoris muscle weakness as manifested by a decrease in force-generating capability is a persistent problem after total knee arthroplasty (TKA). The authors hypothesized that (1) patients with a TKA would have decreased quadriceps femoris muscle performance (weakness) and impaired volitional activation when compared with a group of older adults without knee pathology, (2) pain and age would account for a large portion of the variability in volitional activation after surgery, and (3) volitional activation in the TKA group would account for a large portion of the variability in force production. Comparison subjects were 52 volunteers (mean age=72.2 years, SD=5.34, range=64-85). The TKA group comprised 52 patients (mean age=64.9 years, SD=7.72, range=49-78) with a diagnosis of osteoarthritis who had undergone a tricompartmental, cemented TKA. Knee extension force was measured using a burst superimposition technique, where a supramaximal burst of electrical stimulation was superimposed on a maximal voluntary isometric contraction (MVIC). The amount of failure of volitional activation is determined by the amount of electrical augmentation of force beyond a person's MVIC at the instant of the application of the electrical burst. The average normalized knee extension force of the TKA group was 64% lower than that of the comparison group. The average volitional activation deficit in the TKA group (26%) was 4 times as great as the comparison group's deficit (6%). Age did not correlate with quadriceps femoris muscle activation, and knee pain explained only a small portion of the variance in knee extension force (r2=.17). Volitional activation was highly correlated with knee extension force production (r2=.65). Considerable quadriceps femoris muscle inhibition after surgery has several implications for recovery. Rehabilitation programs that focus on volitional exercise alone are unlikely to overcome this pronounced failure of activation. Early interventions focused at improving quadriceps femoris muscle voluntary activation may improve efforts to restore muscle force.


Surface acoustic wave two resonator filter using synchronous coupling interdigital transducers.
A surface acoustic wave (SAW) two resonator filter with coupling interdigital transducers (IDTs) located inside the reflectors, was designed, fabricated, and tested. In the filter, electrodes of the coupling IDTs are in spatial synchronism with the reflectors' electrodes. The filter, fabricated on ST-cut quartz, had a center frequency of 302.6 MHz, insertion loss about 13 dB, and minimum rejection in the stopbands of about 40 dB.


The Dynamics of Avian Influenza: Individual-Based Model with Intervention Strategies in Traditional Trade Networks in Phitsanulok Province, Thailand.
Avian influenza virus subtype H5N1 is endemic to Southeast Asia. In Thailand, avian influenza viruses continue to cause large poultry stock losses. The spread of the disease has a serious impact on poultry production especially among rural households with backyard chickens. The movements and activities of chicken traders result in the spread of the disease through traditional trade networks. In this study, we investigate the dynamics of avian influenza in the traditional trade network in Phitsanulok Province, Thailand. We also propose an individual-based model with intervention strategies to control the spread of the disease. We found that the dynamics of the disease mainly depend on the transmission probability and the virus inactivation period. This study also illustrates the appropriate virus disinfection period and the target for intervention strategies on traditional trade network. The results suggest that good hygiene and cleanliness among household traders and trader of trader areas and ensuring that any equipment used is clean can lead to a decrease in transmission and final epidemic size. These results may be useful to epidemiologists, researchers, and relevant authorities in understanding the spread of avian influenza through traditional trade networks.


Determination of total, saturated, and monounsaturated fats in foodstuffs by hydrolytic extraction and gas chromatographic quantitation: collaborative study.
Using gas chromatography (GC), 10 collaborating laboratories measured total, saturated, and monounsaturated fats in 8 blind duplicate pairs of foodstuffs. The method involves a hydrolysis/ether extraction of fat followed by quantitative GC analysis versus an internal standard. Calculations were designed to comply with federal regulations as specified in the Nutrition Labeling and Education Act of 1990. The range of fat contents was about 1-50%. Collaborators received and analyzed (in triplicate) a pre-collaborative sample of known fat content as a practice sample. After satisfactory results were obtained, participants received the 16-sample set. The repeatability standard deviations (RSDr) for total fat ranged from 2.04 to 10.6%; the reproducibility standard deviations (RSDR) for total fat ranged from 3.74 to 15.8%. The hydrolytic extraction-GC method for determination of fat (total, saturated, and monounsaturated) in foodstuffs has been adopted first action by AOAC INTERNATIONAL.


Is the Iliac Cortical Density Similarly Positioned in the Developing Pediatric Pelvis?
The iliac cortical density (ICD) is a critical fluoroscopic landmark for pelvic percutaneous screw placement. Our purpose was to evaluate the ICD as a landmark in pediatrics and quantify the diameter of osseous pathways for 3 screw trajectories: iliosacral (IS) at S1 and transiliac-transsacral (TSTI) at S1 and S2. Two hundred sixty-seven consecutive pelvic CT scans in children 0-16 years of age were analyzed. ICD and S1 vertebral heights were measured at multiple regions along S1. Their height and corresponding ratios, as well as osseous screw corridor dimensions were compared between age groups and by the dysmorphic status. In the nondysmorphic pelvises, S1 height, ICD height, and the ICD to S1 height ratio increased across age groups for all locations (P < 0.001). All 3 screw pathway diameters increased with age (P < 0.001). In the dysmorphic group, there was no increase in ICD to S1 height ratio with age. Except for the age 0-2 group, the ICD to S1 height ratios were significantly larger in the nondysmorphic group. In the dysmorphic group, S1 TSTI pathway remained narrow with age, whereas IS at S1 and TSTI at S2 had a significant increased diameter with age (P < 0.001). The ICD is a useful fluoroscopic landmark for percutaneous screw placement in the pediatric pelvis. For nondysmorphic pelvises, the ICD to S1 height ratio, as well as osseous corridors for IS, TSTI at S1, and TSTI at S2 screw trajectories increase significantly with age. The margin for safe screw placement in S1 is smaller for younger and dysmorphic pelvises.


Family planning for urban slums in low- and middle-income countries: a scoping review of interventions/service delivery models and their impact.
Although evidence suggest that many slum dwellers in low- and middle-income countries have the most difficulty accessing family planning (FP) services, there are limited workable interventions/models for reaching slum communities with FP services. This review aimed to identify existing interventions and service delivery models for providing FP services in slums, and as well examine potential impact of such interventions and service delivery models in low- and middle-income settings. We searched and retrieved relevant published studies on the topic from 2000 to 2020 from e-journals, health sources and six electronic databases (MEDLINE, Global Health, EMBASE, CINAHL, PsycINFO and Web of Science). Grey and relevant unpublished literature (e.g., technical reports) were also included. For inclusion, studies should have been published in a low- and middle-income country between 2000 and 2020. All study designs were included. Review articles, protocols or opinion pieces were excluded. Search results were screened for eligible articles and reports using a pre-defined criterion. Descriptive statistics and narrative syntheses were produced to summarize and report findings. The search of the e-journals, health sources and six electronic databases including grey literature and other unpublished materials produced 1,260 results. Following screening for title relevance, abstract and full text, nine eligible studies/reports remained. Six different types of FP service delivery models were identified: voucher schemes; married adolescent girls' club interventions; Willows home-based counselling and referral programme; static clinic and satellite clinics; franchised family planning clinics; and urban reproductive health initiatives. The urban reproductive health initiatives were the most dominant FP service delivery model targeting urban slums. As regards the impact of the service delivery models identified, the review showed that the identified interventions led to improved targeting of poor urban populations, improved efficiency in delivery of family planning service, high uptake or utilization of services, and improved quality of family planning services. This review provides important insights into existing family planning service delivery models and their potential impact in improving access to FP services in poor urban slums. Further studies exploring the quality of care and associated sexual and reproductive health outcomes as a result of the uptake of these service delivery models are essential. Given that the studies were reported from only 9 countries, further studies are needed to advance knowledge on this topic in other low-middle income countries where slum populations continue to rise.