Usefulness of verbal selective reminding in distinguishing frontal lobe memory disorders in epilepsy.
Frontal lobe memory disorders are distinguished from hippocampal memory disorders by poor organization of encoding and retrieval, among other things. Because the verbal Selective Reminding Test (SRT) has a metamemory ("remembering-to-remember") component, it may be useful in distinguishing frontal from temporal lobe memory disorders in patients with intractable epilepsy. Thirty-four patients with frontal lobe epilepsy (FLE) and 34 with temporal lobe epilepsy (TLE) underwent a comprehensive neuropsychological evaluation that included multiple memory and executive function tests. Patients with FLE performed significantly worse than those with TLE on SRT measures and Wechsler Memory Scale, Third Edition, Logical Memory (LM II), but not on other verbal and nonverbal memory tests. Furthermore, SRT and LM-II were significantly correlated with executive function measures. These findings have both theoretical and practical implications: (1) the memory impairment observed in frontal lobe disorders may be due, in part, to deficits in organizational strategy, monitoring, and remembering-to-remember, and (2) SRT and LM-II may be useful tests to differentiate frontal from temporal lobe memory disorders.


Occurrence and Predictors of Postoperative Preauricular and Masticatory Muscle Pain Symptoms After Surgical Removal of Third Molars: A Single-Blind Randomized Controlled Trial Comparing Dental Assistants Supporting the Mandible and the Restful Jaw Device.
During third molar removal, the mandible is supported by a dental assistant (DA) to counter downward forces during surgery, and with sedation, to maintain airway patency. The Restful Jaw device (PEP Design; Saint Paul) provides this support instead of the DA. This study compared the occurrence of postoperative preauricular and masticatory muscle pain symptoms (PMMPS) between the device and DAs providing mandibular support, using two outcome measures. Secondary aims identify predictors of outcome and providers' opinions of the device. In this multisite, single-blind, two-arm parallel randomized trial, participants without preoperative PMMPS had surgical removal of third molars, with sedation and bite blocks were randomly assigned to manual support or the device. The exposed group was randomly assigned to the device and the nonexposed group to manual support. The primary outcome was patient-reported PMMPS. Two secondary outcomes were pain assessed with the temporomandibular disorder Pain Screener and providers' views on the device. Outcomes were assessed at 1-, 3-, and 6-month postsurgery. The covariates are baseline demographics (eg, sex), clinical characteristics (eg, eruption status), and third molar surgeries. For occurrence of pain, generalized estimating equations assessed differences between groups. Logistic regression analysis assessed predictors of pain at 1 month, per the Screener. The level for statistical significance was 5%. Enrollment was 86 and 83 participants in the device and DA groups, respectively. The average age was 20.8 years; the majority were female (65%) and Caucasian (66%). The retention rate was ≥95.9%. The groups did not differ significantly for occurrence of pain using the primary and secondary outcome measures at any follow-up (P ≥ .46). Fully impacted molars were associated with occurrence of pain (odds ratio = 3.44; 95% confidence interval 1.49-7.92; P = .004). Occurrence of pain using the primary and secondary outcome measures did not differ significantly between groups at any follow-up and was associated with removal of fully impacted third molars. Four out of five surgeons reported wanting to use the device on a regular basis when performing this procedure in sedated patients.


[Could patients who underwent hepatic resection due to hepatocellular carcinoma with high alpha-fetoprotein be monitored for recurrence by alpha-fetoprotein level?].
The follow-up strategy after hepatectomy for hepatocellular carcinoma (HCC) usually depends on the experience of physician, resulting in frequent imaging studies, which leads to increased cost. Hence, we investigated the role of monitoring alpha-fetoprotein (AFP) levels after hepatectomy in patients with preoperative high AFP. From January 2000 to December 2004, 66 patients who underwent curative hepatectomy due to HCC with preoperative AFP level > 400 ng/mL were reviewed. Changes in AFP level after the operation were investigated. The recurrence was suspected in case of two consecutive increase of AFP over cut-off value. Cut-off value was determined by ROC curve. All patients were divided into 2 groups: patients who met the definition (Group S) and those who didn't (Group D). AFP level of 20 ng/ml was proposed as the cut-off value for diagnosis of recurrence by ROC curve. Thirty two patients who didn't have the AFP level decreased below 20 ng/ml after the resection had HCC recurred, whereas 16 out of 34 patients who had AFP decreased had tumor recurrence. The AFP level of patients without recurrence was kept below 20 ng/ml during the follow-up. The AFP level of 44 out of 48 recurred patients increased over 20 ng/ml upon recurrence. By definition, group D were 5 patients. In 4 patients of group D, the AFP level didn't increase above 20 ng/ml upon recurrence. These patients had HCC and they recurred 1 year after the surgery. In patients with preoperative AFP level > 400 ng/ml, the AFP level tended to increase above 20 ng/ml at recurrence mostly within 1 year. Hence, we proposed that these patients could be monitored by only AFP until 1 year after surgery.


Curcumin protects against testis-specific side effects of irinotecan.
Irinotecan (IR/CPT-11) is a semisynthetic, water-soluble derivative of the alkaloid camptothecin. It is a topoisomerase I group antineoplastic drug commonly used for the treatment of many cancer types, although it has side effects in tissues such as the testis. Curcumin (CRC) is a polyphenol compound produced from the Indian saffron root; it is used as food colouring and food flavouring. This study examined the testis-specific side effects of IR and the ability of CRC to protect against these side effects. Forty male Sprague-Dawley rats were used in our study (n = 10). The rats were randomly divided into the following four groups: control, IR, IR + CRC, and CRC. IR 10 mg/kg/day was administered intraperitoneally and CRC 100 mg/kg was administered orally. Blood and testicular samples were collected from rats in all four groups on day 30 after drug administration. Histological, biochemical, and spermatological analyses were conducted. Testis tissue and blood samples were collected from the four groups. Tissue samples from the control and CRC groups demonstrated normal histological appearance on light microscopy. The IR group exhibited the following findings: vascular congestion in the tunica albuginea layer; tubular degeneration and vascular congestion in the interstitial area; oedema, vacuolisation, and luminised cells in the seminiferous tubule; and cells that temporarily stopped dividing at any stage of division in the seminiferous tubule epithelium. In the IR+CRC group, histopathological damage was significantly reduced by CRC treatment. Biochemical analysis showed that the level of thiobarbituric acid reactive substance (TBARS) was significantly increased in the IR group, compared with the other groups. CRC treatment significantly decreased this IR-mediated increase in TBARS level, and the TBARS level in the IR + CRC group approached the level observed in the control group. IR treatment caused significant decreases in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) levels. However, CRC administration tended to ameliorate the decreases in GSH, SOD, CAT, and GPx levels. In this study, IR had some toxic effects in rat testis tissue; these effects were ameliorated by CRC treatment. Further studies are warranted to confirm our results.


Women's perception of cervical cancer and its prevention in rural Laos.
Cervical cancer is the second most common cancer of women in the world, and it becomes a major cause of cancer mortality in low-income countries. Currently, little is known regarding cervical cancer incidence in Laos, although it is anticipated to be high like in neighboring countries. To be able to develop a screening program in the country, it is essential to explore women's perception of the disease. The purpose of this study was therefore to describe knowledge, awareness, and attitudes regarding cervical cancer among rural women of Laos. In a descriptive cross-sectional study, women were interviewed using a structured questionnaire covering sociodemographic factors, knowledge of the disease and its risk factors, awareness, and attitudes toward cervical cancer and its prevention. Eight hundred women were included in the study, and 58% claimed to know about cervical cancer. Approximately one third (38%) considered themselves to be at risk, but less than 5% had ever had a Papanicolau test. Sixty-two percent believed it was possible to prevent cervical cancer and that vaccination may be a suitable method, but only 14% know about risk factors. Another method for prevention was frequent vaginal douching, which was suggested by 70% of the women. Symptoms like bleeding and discharge were correctly identified as possible indicators of cervical cancer, but only 57 women (7%) knew that an early stage of the disease could be symptom-free. Lack of subjective symptoms was the main reason for women to refrain from gynecological examinations. This study indicates that rural women in Laos have limited knowledge about cervical cancer and even less about screening and prevention. There is a need to educate the general community about the disease and its prevention.


Long noncoding RNAs in cancer: From discovery to therapeutic targets.
Long noncoding RNAs (lncRNAs) have recently gained considerable attention as key players in biological regulation; however, the mechanisms by which lncRNAs govern various disease processes remain mysterious and are just beginning to be understood. The ease of next-generation sequencing technologies has led to an explosion of genomic information, especially for the lncRNA class of noncoding RNAs. LncRNAs exhibit the characteristics of mRNAs, such as polyadenylation, 5' methyl capping, RNA polymerase II-dependent transcription, and splicing. These transcripts comprise more than 200 nucleotides (nt) and are not translated into proteins. Directed interrogation of annotated lncRNAs from RNA-Seq datasets has revealed dramatic differences in their expression, largely driven by alterations in transcription, the cell cycle, and RNA metabolism. The fact that lncRNAs are expressed cell- and tissue-specifically makes them excellent biomarkers for ongoing biological events. Notably, lncRNAs are differentially expressed in several cancers and show a distinct association with clinical outcomes. Novel methods and strategies are being developed to study lncRNA function and will provide researchers with the tools and opportunities to develop lncRNA-based therapeutics for cancer.


Histopathological characterization and fluorescence in situ hybridization of Cyprinid herpesvirus 2 in cultured Prussian carp, Carassius auratus gibelio in China.
Cyprinid herpesvirus 2 (CyHV-2) is an emerging pathogen in the commercially exploited fish, Prussian carp (Carassius auratus gibelio), which has caused huge economic loss in China and appears to be spreading worldwide. In this article, CyHV-2 infection of Prussian carp was confirmed for the first time by polymerase chain reaction (PCR), which gave positive results from the tissue samples dissected from moribund fish including kidney, spleen, liver, and gill. Histological examination showed systemic inflammatory reactions in the infected tissues, with infiltration of hemocytes, hypertrophied nuclei, marginal chromatin and karyorrhexis, epithelial cell shedding, vacuolar degeneration and focal necrosis. Tissue alterations were also evaluated semi-quantitatively by the degree of tissue change. The values of degree of tissue change determined for kidney, spleen, liver, and gill were significantly greater than respective controls and kidney was the most severely damaged organ, with highest degree of tissue change value. In addition, a fluorescence in situ hybridization (FISH) based on oligonucleotide probes to detect the pathogen directly in the tissue, allowing pathogen-lesion correlation, was established. With the advantages of better tissue penetration, potentially more specific and stable, three oligonucleotide probes were designed. Positive reactions to the probes with intense green fluorescence were observed within the infected tissues where PCR and H&E analysis had suggested previously the presence of the virus within these lesions. The probes did not hybridize with host tissues of uninfected fish, nor did they cross-react with 3 other virus samples tested. The current research could facilitate the study of CyHV-2 infection mechanism in Prussian carp, and enhance the early diagnosis of the novel virus.


[Serum ferritin in iron overload].
Even with uncomplicated iron overload, serum ferritin which can be identified in the circulating blood by sensitive immunochemical methods has a direct and quantitative correlation to the iron stored in the organism. The relation of stored iron and serum ferritin is not linear, but has an exponential character. The diagnostic function of serum ferritin as an indicator of stored iron, however, is virtually not influenced by it. The indications listed in Tab. 3 can be demarcated for diagnostic application in cases of iron overload. Hitherto, the molecular microheterogenicity of serum ferritin has exercised no essential impact on its diagnostic application. High ferritin concentrations may arise in the circulating blood by a number of disease processes listed in Tab. 4, without the simultaneous existence of a respective iron overload of the tissue. These correlations have to be observed in the diagnostic application of determining serum ferritin as well as in methodical possibilities of fault (high dose hook effect), thus limiting the use of serum ferritin as an indicator of stored iron both in case of iron overload and iron deficiency. As in all isolated laboratory investigations, all other clinical and chemical laboratory information available about the individual patient has to be taken into account in each case for interpreting the serum ferritin concentration.


Phylogenomic and functional analysis of pterin-4a-carbinolamine dehydratase family (COG2154) proteins in plants and microorganisms.
Pterin-4a-carbinolamine dehydratases (PCDs) recycle oxidized pterin cofactors generated by aromatic amino acid hydroxylases (AAHs). PCDs are known biochemically only from animals and one bacterium, but PCD-like proteins (COG2154 in the Clusters of Orthologous Groups [COGs] database) are encoded by many plant and microbial genomes. Because these genomes often encode no AAH homologs, the annotation of their COG2154 proteins as PCDs is questionable. Moreover, some COG2154 proteins lack canonical residues that are catalytically important in mammalian PCDs. Diverse COG2154 proteins of plant, fungal, protistan, and prokaryotic origin were therefore tested for PCD activity by functional complementation in Escherichia coli, and the plant proteins were localized using green fluorescent protein fusions. Higher and lower plants proved to have two COG2154 proteins, a mitochondrial one with PCD activity and a noncanonical, plastidial one without. Phylogenetic analysis indicated that the latter is unique to plants and arose from the former early in the plant lineage. All 10 microbial COG2154 proteins tested had PCD activity; six of these came from genomes with no AAH, and six were noncanonical. The results suggested the motif [EDKH]-x(3)-H-[HN]-[PCS]-x(5,6)-[YWF]-x(9)-[HW]-x(8,15)-D as a signature for PCD activity. Organisms having a functional PCD but no AAH partner include angiosperms, yeast, and various prokaryotes. In these cases, PCD presumably has another function. An ancillary role in molybdopterin cofactor metabolism, hypothesized from phylogenomic evidence, was supported by demonstrating significantly lowered activities of two molybdoenzymes in Arabidopsis thaliana PCD knockout mutants. Besides this role, we propose that partnerless PCDs support the function of as yet unrecognized pterin-dependent enzymes.


Polysaccharide utilization loci and nutritional specialization in a dominant group of butyrate-producing human colonic Firmicutes.
Firmicutes and Bacteroidetes are the predominant bacterial phyla colonizing the healthy human large intestine. Whilst both ferment dietary fibre, genes responsible for this important activity have been analysed only in the Bacteroidetes, with very little known about the Firmicutes. This work investigates the carbohydrate-active enzymes (CAZymes) in a group of Firmicutes, Roseburia spp. and Eubacterium rectale, which play an important role in producing butyrate from dietary carbohydrates and in health maintenance. Genome sequences of 11 strains representing E. rectale and four Roseburia spp. were analysed for carbohydrate-active genes. Following assembly into a pan-genome, core, variable and unique genes were identified. The 1840 CAZyme genes identified in the pan-genome were assigned to 538 orthologous groups, of which only 26 were present in all strains, indicating considerable inter-strain variability. This analysis was used to categorize the 11 strains into four carbohydrate utilization ecotypes (CUEs), which were shown to correspond to utilization of different carbohydrates for growth. Many glycoside hydrolase genes were found linked to genes encoding oligosaccharide transporters and regulatory elements in the genomes of Roseburia spp. and E. rectale, forming distinct polysaccharide utilization loci (PULs). Whilst PULs are also a common feature in Bacteroidetes, key differences were noted in these Firmicutes, including the absence of close homologues of Bacteroides polysaccharide utilization genes, hence we refer to Gram-positive PULs (gpPULs). Most CAZyme genes in the Roseburia/E. rectale group are organized into gpPULs. Variation in gpPULs can explain the high degree of nutritional specialization at the species level within this group.


Treatment of abdominal cellulite and circumference reduction with radiofrequency and dynamic muscle activation.
Cellulite is a frequent skin condition for which treatment remains a challenge. A wide variety of treatments are available but most procedures offer suboptimal clinical effect and/or delayed therapeutic outcome. Only few therapeutic options have proven efficacy in the treatment of cellulite. To determine the efficacy and the safety profiles of radiofrequency and dynamic muscle activation technology in treatment of abdominal cellulite and circumference reduction. Twenty-five females with abdominal cellulite received 6 weekly radiofrequency and dynamic muscle activation treatments. Treatment areas included the abdomen and both sides of flanks. Subjects were evaluated using standardized photographs, and measurements of body weight and abdominal circumference at baseline, before every treatment visit, and 1 week and four weeks after the final treatment. Subcutaneous tissue thickness was recorded by ultrasound at baseline and 4 weeks after completion of treatment protocol. Physicians' evaluation and patient's satisfaction of clinical improvement were also measured. All subjects completed the treatment protocol and attended every follow-up visits. There was significant abdominal circumference reduction of 2.96 and 2.52 cm at 1-, and 4-week follow-up visits (p < 0.05), respectively. At four weeks after the last treatment, the average circumferential reduction was sustained. Most of the patients were rated to have 25-49% improvement at 5th treatment, and 1- and 4-week follow-up visits. Ninety-two percent of the patients were satisfied with the treatment outcome. Radiofrequency provided beneficial effects on the reduction of abdomen and cellulite appearance. The benefit of muscle activation is yet to be determined.


The disease entity in psychiatry: fact or fiction?
The current debate concerning the forthcoming revisions of the International Classification of Diseases (ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM) lacks sufficient historical perspective on groundwork concepts in psychiatry, such as the nature of the disease entity, categorical typologies, dimensional models and their validity and utility. To offer an overview of the evolution and metamorphoses of the conceptual basis of classification in psychiatry, with particular focus on psychotic disorders. Discursive, proceeding from history of ideas to a critique of present dilemmas. Much of the present-day discussion of basic issues concerning the classification of mental disorders is a replay of debates that took place in the earlier periods of scientific psychiatry. CONCLUSION; The mainstream nosological paradigm adopted in psychiatry since early 20th century is in need to be critically examined and transcended with the help of concepts and methodological tools available today.


The initiation of haemoglobin synthesis in rabbit reticulocytes.
1. The incorporation of labelled valine by rabbit reticulocytes into the N-terminal position of nascent haemoglobin was investigated by deaminating the nascent peptides with nitrous acid and isolating labelled alpha-hydroxyisovaleric acid and valine after acid hydrolysis. 2. The amount of radioactivity in alpha-hydroxyisovaleric acid relative to that in valine indicated the presence of 12.3% N-terminal valine having a free amino group. This high value suggests that most if not all nascent peptides contain valine in the N-terminal position. 3. Cell-free preparations containing reticulocyte ribosomes and pH5 enzymes incorporated alpha-hydroxy-[(14)C]isovaleryl-tRNA (where tRNA refers to transfer RNA), which was obtained by deamination of [(14)C]valyl-tRNA from yeast or liver with nitrous acid, into both soluble and nascent protein. 4. When the soluble protein was chromatographed on CM-cellulose, radioactivity was found to be associated with both the alpha-and beta-globin chains. 5. The kinetics of hydrolysis of [(14)C]valine, was also investigated. Most of the material was hydrolysed rapidly at pH10, but a minor component that was relatively stable appeared to be present to the extent of about 10% of the total valyl-tRNA. Valine was, however, the only hydrolysis product detected by paper chromatography. 6. It is concluded that chain initiation in haemoglobin synthesis involves valine as the N-terminal amino acid and that the amino group of nascent protein is probably not substituted.


Effect of Tethered Swimming as Postactivation Potentiation on Swimming Performance and Technical, Hemophysiological, and Psychophysiological Variables in Adolescent Swimmers.
To investigate whether tethered swimming (TS) performed 8 minutes before a 50-m freestyle swimming sprint could be an effective postactivation potentiation method to improve performance in young swimmers. Fourteen regional-level male adolescent swimmers (age 13.0 [2.0] y; height 161.1 [12.4] cm; body mass 52.5 [9.5] kg) underwent 2 trial conditions in a randomized and counterbalanced order (1 experimental [TS], 1 control) on different days. During the experimental session, the participants performed a standard warm-up of 1200 m followed by a TS exercise, which consisted of 3 × 10-second maximal efforts of TS with 1-minute rests between bouts. In the control condition, the warm-up phase was immediately followed by 200 m at a moderate pace (same duration as the TS in the experimental session). Performance (time trial); biomechanical (stroke length), physiological (blood lactate concentrations), and psychophysiological (ratings of perceived exertion) variables; and countermovement-jump (CMJ) flight time were collected. TS warm-up had no significant effect on 50-m swimming performance (P = .27), postexercise ratings of perceived exertion, stroke length, or CMJ flight time (P ≥ .05). Blood lactate concentrations significantly increased at the end of the warm-up in the TS condition only (interaction effect: F1.91,29.91 = 4.91, P = .01, η2 = .27) and after the 50-m trial in both conditions (F1.57,20.41 = 62.39, P = .001, η2 = .82). The present study demonstrated that 3 × 10-second TS exercises performed 8 minutes prior to the event did not affect ratings of perceived exertion, stroke length, or CMJ flight time. In addition, tethered swimming did not affect 50-m freestyle sprint performance in young swimmers.


[Clinical study on tension-free vaginal tape and tension-free vaginal tape obturator for surgical treatment of severe stress urinary incontinence].
To investigate the clinical efficacy and improvement of patients' quality of life in tension-free vaginal tape (TVT) and tension-free vaginal tape obturator (TVT-O) for surgical treatment of severe female stress urinary incontinence. This study was a randomized, single-blinded, controlled trial. Patients were randomized by a computer-generated randomization schedule with allocation to either TVT or TVT-O procedure. TVT procedure was performed in 35 cases and TVT-O in 34 cases. None had received surgery for urinary incontinence or was in pregnancy. Transvaginal hysterectomy and prolapse reparation were done simultaneously in some of the patients. All patients were requested to complete the Urinary Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) as part of their pre- and postoperative assessment. All patients were evaluable and the mean follow-up was 14.5 months. The mean operative time was (18 +/- 5) min in the TVT-O group, significantly shorter than in the TVT group (27 +/- 5) min (P < 0.01). The two groups did not differ significantly in perioperative blood loss, postoperative complications (including tape erosion, pain in thigh or behind pubis), postvoid residual volume, hospital stays or expenses (all P > 0.05). Sixty patients were successfully treated for stress urinary incontinence (88.6% and 85.3% for TVT and TVT-O groups, respectively). There were significant improvements in postoperative scores for both the IIQ-7 and the UDI-6 (P < 0.01), except in subscale measuring symptoms of voiding dysfunction (P > 0.05). Both techniques appear to be equally effective in the surgical treatment of severe stress urinary incontinence in a short term review. Significant improvements could also be seen in patients' quality of life. However, TVT-O has a shorter operative time. No evidence of increasing risk of urethral obstruction after the operation could be found. Long term follow-ups are necessary to evaluate outcomes of different types of surgery for stress urinary incontinence.


Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults.
Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged (P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% (P < 0.05) and stiffness, modulus, and stress were unchanged (P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% (P < 0.05) and stiffness (-17%, P < 0.05) and modulus (-20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans.


Stress fractures of ankle and wrist in childhood: nature and frequency.
Stress fractures of many etiologies are found not infrequently in various tarsal bones but are less commonly recognized in carpal bones. To assess the distribution of tarsal and carpal stress fractures. During the last three decades, the senior author collected locations of tarsal and carpal bone stress fracture callus seen on plain radiographs. 527 children with tarsal and carpal stress fractures were identified (88 children had multiple bones involved). The totals were: calcaneus 244, cuboid 188, talus 121, navicular 24, cuneiforms 23, capitate 18, lunate 1, and scaphoid 1. Stress fractures were more frequently seen once we became aware each particular bone could be involved. Tarsal and carpal stress fractures in children are not rare. Careful perusal of these bones is urged in all susceptible children with limping or wrist pain.


A framework and tools for authoring, editing, documenting, sharing, searching, navigating, and executing computer-based clinical guidelines.
With the spread of managed care and integrated delivery networks, an increased emphasis has been placed on the cost-effectiveness of clinical practices. The need has been recognized to use guidelines to support education, and to integrate them into clinical practice. A specification for guideline representation that would facilitate computer-based clinical guideline sharing has been developed by the InterMed Collaboratory. Called GLIF (GuideLine Interchange Format), this specification and its proposed extensions have been the basis for our implementation of a framework and suite of integrated software tools for guideline authoring and editing, packaging in XML, Internet distribution, navigation, eligibility determination, and automatic execution.


Utility of human induced pluripotent stem cell-derived small intestinal epithelial cells for pharmacokinetic, toxicological, and immunological studies.
The small intestine, which plays a crucial role in the absorption and metabolism of drugs and foods, serves as a target organ for drug-induced toxicity and immune interactions with functional foods and intestinal bacteria. Current alternative models of the human small intestine, such as Caco-2 cells and experimental animals, have limitations due to variations in the expression levels of metabolic enzymes, transporters, and receptors. This study presents investigations into the utility of human induced pluripotent stem cell-derived small intestinal epithelial cells (hiSIECs) for pharmacokinetic, toxicological, and immunological studies, respectively. While hiSIECs displayed small intestinal epithelial cell characteristics and barrier function, they demonstrated pharmacokinetic properties such as cytochrome P450 3A4/5 activity equivalent to human primary enterocytes and stable P-glycoprotein activity. These cells also demonstrated potential for assessing two forms of intestinal toxicity caused by anticancer drugs and gamma-secretase inhibitors, displaying immune responses mediated by toll-like and fatty acid receptors while serving as an inflammatory gut model through the addition of tumor necrosis factor alpha and interferon gamma. Overall, hiSIECs hold promise as an in vitro model for assessing pharmacokinetics, toxicity, and effects on the intestinal immunity of pharmaceuticals, functional foods, supplements, and intestinal bacteria.


[Energy requirements of workers engaged in the underground repair of oil wells in the Azerbaijan SSR].
The energy requirement of workers engaged in the underground repair of oil wells has been evaluated. The energy expenditure during the 8-hour shift with the use of manual and mechanized labor was determined on the basis of the 7-day chronometric charts of their labor activity. The power consumption of 32 descending-lifting and preparative-conclusive operations was evaluated by the indirect calorimetry. Energy expenditure in the time off was studied by the questionnaire method during a week. It was established that, as it was calculated for standard body mass (70 kg), the daily energy expenditure of an operator comprised 3190 kcal (fluctuations depended on the use of mechanization means, 3125-3398 kcal), of his assistant--3487 kcal (3434-3644 kcal), machine driver of the tractor-elevator--3013 kcal (2965-3100 kcal). On the basis of the data obtained the work of the operator and machine driver has been referred to the III, and that of the operator's assistant to the IV occupational group with respect to the intensity of their labor.


Risk of second cancers in Waldenström macroglobulinemia.
An increased incidence of second cancers has been reported in lymphoproliferative disorders. We assessed the frequency, characteristics and predictive factors of second cancers in 230 patients with Waldenström macroglobulinemia (WM) and compared the incidence of second cancers in WM with that of an age- and sex-matched control population. Twenty-two patients (10%) developed solid cancers and 10 (4%) second hematologic malignancies. In a competing risk model, the cumulative incidence of solid cancers was 12% at 10 years and 17% at 15 years while the incidence of hematologic malignancies was 6% and 8%, respectively. The overall risk of second cancer in WM was 1.69 times higher than expected (P = 0.002). WM patients were at increased risk for diffuse large B-cell lymphoma [standardized incidence ratio (SIR) 9.24, P < 0.0001], myelodisplastic syndrome/acute myeloid leukemia (SIR 8.4, P < 0.0001), brain cancer (SIR 8.05, P = 0.0004). The risk of a second hematologic malignancy was fourfold higher in patients previously treated, though not reaching statistical significance (P = 0.19). WM patients are at higher risk of second cancers as compared with the general population. The sample size does not allow firm conclusions about the effect of therapy on the development of second cancers.


Proteomic analysis of the site specificity of glycation and carboxymethylation of ribonuclease.
Proteomic analysis using electrospray liquid chromatography-mass spectrometry (ESI-LC-MS) has been used to compare the sites of glycation (Amadori adduct formation) and carboxymethylation of RNase and to assess the role of the Amadori adduct in the formation of the advanced glycation end-product (AGE), N(epsilon)-(carboxymethyl)lysine (CML). RNase (13.7 mg/mL, 1 mM) was incubated with glucose (0.4 M) at 37 degrees C for 14 days in phosphate buffer (0.2 M, pH 7.4) under air. On the basis of ESI-LC-MS of tryptic peptides, the major sites of glycation of RNase were, in order, K41, K7, K1, and K37. Three of these, in order, K41, K7, and K37 were also the major sites of CML formation. In other experiments, RNase was incubated under anaerobic conditions (1 mM DTPA, N2 purged) to form Amadori-modified protein, which was then incubated under aerobic conditions to allow AGE formation. Again, the major sites of glycation were, in order, K41, K7, K1, and K37 and the major sites of carboxymethylation were K41, K7, and K37. RNase was also incubated with 1-5 mM glyoxal, substantially more than is formed by autoxidation of glucose under experimental conditions, but there was only trace modification of lysine residues, primarily at K41. We conclude the following: (1) that the primary route to formation of CML is by autoxidation of Amadori adducts on protein, rather than by glyoxal generated on autoxidation of glucose; and (2) that carboxymethylation, like glycation, is a site-specific modification of protein affected by neighboring amino acids and bound ligands, such as phosphate or phosphorylated compounds. Even when the overall extent of protein modification is low, localization of a high proportion of the modifications at a few reactive sites might have important implications for understanding losses in protein functionality in aging and diabetes and also for the design of AGE inhibitors.


Probing the Proton-Gated ASIC Channels Using Tetraalkylammonium Ions.
The action of tetraalkylammonium ions, from tetrametylammonium (TMA) to tetrapentylammonium (TPtA), on the recombinant and native acid-sensing ion channels (ASICs) was studied using the patch-clamp approach. The responses of ASIC1a, ASIC2a, and native heteromeric ASICs were inhibited by TPtA. The peak currents through ASIC3 were unaffected, whereas the steady-state currents were significantly potentiated. This effect was characterized by an EC50 value of 1.22 ± 0.12 mM and a maximal effect of 3.2 ± 0.5. The effects of TPtA were voltage-independent but significantly decreased under conditions of strong acidification, which caused saturation of ASIC responses. Molecular modeling predicted TPtA binding in the acidic pocket of closed ASICs. Bound TPtA can prevent acidic pocket collapse through a process involving ASIC activation and desensitization. Tetraethylammonium (TEA) inhibited ASIC1a and native ASICs. The effect was independent of the activating pH but decreased with depolarization, suggesting a pore-blocking mechanism.


LRG1 predicts the prognosis and is associated with immune infiltration in thyroid cancer: a bioinformatics study.
The diagnostic and prognostic value of the leucine-rich alpha-2-glycoprotein 1 (LRG1) gene in thyroid cancer remains unclear. Using the Cancer Genome Atlas (TCGA) database, we conducted a bioinformatics analysis to determine the role of LRG1 in thyroid cancer. Data from 512 patients with thyroid cancer and 59 normal individuals were collected from TCGA database. The Kruskal-Wallis test and logistic analysis were used to examine the relationship between LRG1 expression and clinicopathologic characteristics. Cox regression and Kaplan-Meier analysis were used to determine the predictive value of LRG1 on clinical outcomes. Single-sample gene set enrichment analysis (ssGSEA) was used to reveal associations between LRG1 expression and immune infiltration levels in thyroid cancer. LRG1 was highly expressed in thyroid cancer (P < 0.001) and could effectively distinguish tumor tissue (area under the curve = 0.875) from normal tissue. Moreover, LRG1 was significantly correlated with pathological N stage (odds ratio (OR) = 2.411 (1.659-3.505), P < 0.001). Kaplan-Meier survival analysis revealed that patients with high LRG1 expression had better overall survival (hazard ratio (HR) = 0.30, P = 0.038). Cox regression analysis indicated that pathological M stage was a risk factor for progression-free interval (HR = 5.964 (2.010-17.694), P < 0.001). Using ssGSEA, we found that LRG1 expression was positively correlated with the number of T helper 1 cells (R = 0.435, P < 0.001), dendritic cells (R = 0.442, P < 0.001), and macrophages (R = 0.459, P < 0.001). LRG1 may be an important biomarker for predicting the prognosis of thyroid cancer and represent a suitable target for immunotherapy associated with immune infiltration.


Activation of Toll-like receptor 7 regulates the expression of IFN-λ1, p53, PTEN, VEGF, TIMP-1 and MMP-9 in pancreatic cancer cells.
Toll-like receptors (TLRs) are critical in the induction of the immune response in tumor development. TLR7 has previously been demonstrated to be associated with the development of pancreatic cancer, and the release of cytokines and chemokines from other types of cancer cell; however, the specific expression induced by TLR7 agonists in pancreatic cancer cells remains to be elucidated. The present study aimed to investigate the effects of the TLR7 agonist, gardiquimod, on ERK1/2 signaling pathway, and on the expression of genes involved in the pathogenesis of cancer, including phosphatase and tensin homolog deleted on chromosome 10 (PTEN), p53, type Ⅲ interferon (IFN-λ1), vascular endothelial growth factor (VEGF), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1). The results demonstrated that activation of TLR7 upregulated the expression levels of certain genes to varying degrees; the expression levels of IFN-λ1 and MMP-9 were increased by ~3 fold, whereas other genes (p53, PTEN, TIMP-1) were upregulated by ~2 fold, and VEGF was marginally upregulated after 10 min. Furthermore, gardiquimod increased the expression levels of phosphorylated-extracellular signal-regulated kinase (ERK)1/2. In addition, PD98059, a specific inhibitor of ERK phosphorylation, inhibited the ability of gardiquimod to activate ERK1/2; consequently weakening the effect of gardiquimod on gene regulation. These findings indicated that the effect of TLR7 agonists, including gardiquimod, on gene expression in BxPC-3 pancreatic cancer cells was partly associated with the mitogen-activated protein kinase-ERK1/2 signaling pathway.


[Method for electrodiagnosis of the necrotic zone in skeletal muscles].
A simple new method for determination of necrosis of the skeletal muscles is suggested. Stimulation of the muscle and the recording of the contraction is made via a needle electrode. The contraction is recorded as a characteristic drop of the muscle resistance to high-frequency current which per se does not cause any stimulation. The zone of necrosis does not demonstrate any characteristic changes in the resistance. The presence of necrosis in the areas under exploration was proved histologically.


Wind Gates Search States in Free Flight.
For any organism tracking a chemical cue to its source, the motion of its surrounding fluid provides crucial information for success. For both swimming and flying animals engaged in olfactory search, turning into the direction of oncoming wind or water current is often a critical first step [Marsh et al., 1978, Carton and Montgomery, 2003]. However, in nature, fluid flow may be turbulent or very still [Crall et al., 2017, Houle and van Breugel, 2023, Carvalho and Gonçalves, 2020], and it is unclear how organisms adjust their search strategies accordingly due to the challenges of separately controlling flow and chemical encounters. Here, we use the genetic toolkit of Drosophila melanogaster , a model organism for olfaction [Benton, 2022], to develop an optogenetic paradigm to deliver temporally precise "virtual" olfactory experiences in free-flying animals while independently manipulating the wind conditions. We show that in free flight, Drosophila melanogaster adopt distinct search routines that are gated by whether they are flying in laminar wind or in still air. We first confirm that in laminar wind flies turn upwind, and further, we show that they achieve this using a rapid ballistic turn. In still air, flies adopt remarkably stereotyped "sink and circle" search state characterized by ∼60°turns at 3-4 Hz, biased in a consistent direction. In both laminar wind and still air, immediately after odor onset, flies decelerate and often perform a rapid turn. Both maneuvers are consistent with predictions from recent control theoretic analyses for how insects may estimate properties of wind while in flight [van Breugel, 2021, van Breugel et al., 2022]. We suggest that flies may use their deceleration and "anemometric" turn as active sensing maneuvers to rapidly gauge properties of their wind environment before initiating a proximal or upwind search routine.


Role of the equilibrative and concentrative nucleoside transporters in the intestinal absorption of the nucleoside drug, ribavirin, in wild-type and Ent1(-/-) mice.
Ribavirin is frontline treatment for hepatitis C virus infection. To determine the role of nucleoside transporters in the intestinal absorption of orally administered ribavirin, we perfused the intestines of Ent1(-/-) and wild-type mice, in situ, with [(3)H] ribavirin (20, 200, and 5000 μM) in the presence and absence of sodium. The decrease in luminal ribavirin concentration over 30 min was measured at 5 min intervals. Blood samples were collected approximately every 10 min. Ribavirin plus phosphorylated metabolite concentrations (hereafter referred to as ribavirin) were determined in tissue, blood, and plasma by HPLC fractionation and scintillation counting. There was no significant difference between wild-type and Ent1(-/-) mice in intestinal loss of ribavirin at any ribavirin concentration studied. Perfusions without sodium drastically reduced the intestinal loss of ribavirin in both wild-type and Ent1(-/-) mice. After 20 μM ribavirin perfusions, Ent1(-/-) intestinal tissue contained 8-fold greater ribavirin than wild-type mice (p < 0.01). Ribavirin concentrations in the wild-type intestinal tissue were 70-fold higher after 200 vs 20 μM perfusions (p < 0.001), indicating saturation of intestinal ribavirin efflux and possibly other processes as well. Ribavirin plasma concentrations were significantly higher in wild-type mice (2.7-fold) vs Ent1(-/-) mice at 30 min after the 20 μM perfusion (p < 0.01). These results suggest that, at lower intestinal concentrations of ribavirin, concentrative and equilibrative nucleoside transporters are important in the intestinal absorption of ribavirin. At higher intestinal concentrations, these transporters are saturated and other processes in the intestine (transport and/or metabolism) play an important role in the absorption of ribavirin.


Evaluation of skin erythema by use of chromametry and image analysis of digital photographs after intradermal administration of histamine in dogs.
To investigate whether the degree of erythema during an induced erythematous reaction, the histamine skin test reaction, can be assessed objectively by use of chromametry and image analysis of digital photographs. 9 pet dogs (6 Golden Retrievers and 3 yellow Labrador Retrievers). Histamine phosphate was injected intradermally, and erythema of the wheal reaction was evaluated during the hour that followed. This was done by use of clinical scores, chromametry, and image analysis of digital photographs. Method reproducibility was tested for visual evaluation of printouts of digital photographs and for image analysis of the same photographs. The coefficient of variation of the technically derived erythema values was < 10%. The reproducibility of image analysis was high and the range of agreement between observers narrow. Using chromametry, it was not possible to differentiate between various degrees of erythema intensity as visually perceived. In contrast, use of image analysis of digital photographs enabled discrimination of slight erythema from moderate and marked erythema. The dynamics of reaction measured by chromametry followed the clinical observation. Chromametric values are comparable to those obtained by visual inspection. As the result of standardized conditions, chromametry is preferred over digital photography.


Automatic Detection of Chronic Insomnia from Polysomnographic and Clinical Variables Using Machine Learning.
Insomnia is defined subjectively by the presence and frequency of specific clinical symptoms and an association with distress. Although sleep study data has shown some weak associations, no objective test can currently be used to predict insomnia. The purpose of this study was to use previously reported and relatively crafted insomnia-related polysomnographic variables in machine learning models to classify groups with and without insomnia. Demographics, diagnosed depression, Epworth Sleepiness Scale (ESS), and features derived from electroencephalography (EEG), arousals, and sleep stages from 3,407 sleep clinic patients (2,617 without insomnia and 790 insomnia patients based on responses to a set of questions) were included in this analysis. The number of features were reduced using pair-wise correlation and recursive feature elimination. Predictive value of three machine learning models (logistic regression, neural network, and support vector machine) was investigated, and the best performance was achieved with logistic regression, yielding a balanced accuracy of 71%. The most important features in predicting insomnia were depression, age, sex, duration of longest arousal, ESS score, and EEG power in theta and sigma bands across all sleep stages. Results indicate potential of machine learning-based screening for insomnia using clinical variables and EEG.


Aging effects on the Achilles tendon moment arm during walking.
The Achilles tendon (AT) moment arm transforms triceps surae muscle forces into a moment about the ankle which is critical for functional activities like walking. Moreover, the AT moment arm changes continuously during walking, as it depends on both ankle joint rotation and triceps surae muscle loading (presumably due to bulging of the muscle belly). Here, we posit that aging negatively effects the architecturally complex AT moment arm during walking, which thereby contributes to well-documented reductions in ankle moment generation during push-off. We used motion capture-guided ultrasound imaging to quantify instantaneous variations in the AT moment arms of young (23.9 ± 4.3 years) and older (69.9 ± 2.6 years) adults during walking, their dependence on triceps surae muscle loading, and their association with ankle moment generation during push-off. Older adults walked with 11% smaller AT moment arms and 11% smaller peak ankle moments during push-off than young adults. Moreover, as hypothesized, these unfavourable changes were significantly and positively correlated (r2 = 0.38, p < 0.01). More surprisingly, aging attenuated load-dependent increases in the AT moment arm (i.e., those between heel-strike and push-off at the same ankle angle); only young adults exhibited a significant increase in their AT moment arm due to triceps surae muscle-loading. Age-associated reductions in triceps surae volume or activation, and thus muscle bulging during force generation, may compromise the mechanical advantage of the AT during the critical push-off phase of walking in older adults. Thus, strategies to restore and/or improve locomotor performance in our aging population should consider these functionally important changes in musculoskeletal behavior.


Procollagen type III amino-terminal propeptide and insulin-like growth factor I as biomarkers of growth hormone administration.
The acceptance in 2012 by the World Anti-Doping Agency (WADA) of the biomarker test for human growth hormone (hGH) based on procollagen type III amino-terminal propeptide (P-III-NP) and insulin-like growth factor I (IGF-I) was perhaps the first time that such a method has been used for forensic purposes. Developing a biomarker test to anti-doping standards, where the strict liability principle applies, is discussed. An alternative WADA-accepted approach is based on the measurement of different hGH isoforms, a method that suffers from the very short half-life of hGH limiting the detection period. Modification or withdrawal of the immunoassays, on which the biomarker measurements largely depend, has necessitated revalidation of the assays, remeasurement of samples and adjustment of the decision limits above which an athlete will be assumed to have administered hGH. When a liquid chromatography coupled mass spectrometry (LC-MS) method became a reality for the measurement of IGF-I, more consistency of results was assured. Measurement of P-III-NP is still dependent on immunoassays although work is underway to develop an LC-MS method. The promised long-term detection time for the biomarker assay does not appear to have been realised in practice, and this is perhaps partly the result of decision limits being set too high. Nevertheless, more robust assays are needed before a further adjustment of the decision limit is warranted. In the meantime, WADA is considering using P-III-NP and IGF-I as components of a biomarker passport system recording data from an individual athlete, rather than the population. Using this approach, smaller perturbations in the growth hormone (GH) score would mandate an investigation and possible action for hGH administration.


Thyroid hormone ligands and metabolic diseases.
Thyroid hormones regulate fundamental genes involved in the metabolism, development and homeostasis of vertebrates. The endogenous hormones, L-3, 5, 3'-triiodo-L-thyronine (T(3)) and L-3, 5, 3', 5'-tetraiodo-L-thyronine (T(4)), are of limited use in pharmacological intervention, mainly due to cardiovascular liabilities. There exist two subtypes of thyroid hormone receptors (TR), alpha and beta, unequally distributed in the body. As TRalpha is most abundant in the heart and most effects of thyroid hormones on the heart are mediated through TRalpha, a reasonable strategy is the development of TR agonists that either are tissue selective or that interact selectively with TRbeta. The prospects for the treatment of metabolic diseases with such ligands are considerable and this review describes the massive efforts of the academic and industrial communities during the last decade. It is, however, the author's view that the development of selective ligands only is in its infancy, an opinion highlighted by the limited chemical structural variation of TR ligands as well as the present lack of TR ligands for the treatment of metabolic diseases in clinical phases.


Understanding the first-offer conundrum: How buyer offers impact sale price and impasse risk in 26 million eBay negotiations.
How low is the ideal first offer? Prior to any negotiation, decision-makers must balance a crucial tradeoff between two opposing effects. While lower first offers benefit buyers by anchoring the price in their favor, an overly ambitious offer increases the impasse risk, thus potentially precluding an agreement altogether. Past research with simulated laboratory or classroom exercises has demonstrated either a first offer's anchoring benefits or its impasse risk detriments, while largely ignoring the other effect. In short, there is no empirical answer to the conundrum of how low an ideal first offer should be. Our results from over 26 million incentivized real-world negotiations on eBay document (a) a linear anchoring effect of buyer offers on sales price, (b) a nonlinear, quartic effect on impasse risk, and (c) specific offer values with particularly low impasse risks but high anchoring benefits. Integrating these findings suggests that the ideal buyer offer lies at 80% of the seller's list price across all products-although this value ranges from 33% to 95% depending on the type of product, demand, and buyers' weighting of price versus impasse risk. We empirically amend the well-known midpoint bias, the assumption that buyer and seller eventually meet in the middle of their opening offers, and find evidence for a "buyer bias." Product demand moderates the (non)linear effects, the ideal buyer offer, and the buyer bias. Finally, we apply machine learning analyses to predict impasses and present a website with customizable first-offer advice configured to different products, prices, and buyers' risk preferences.


Short communication: survey of fresh cow management practices of dairy cattle on small and large commercial farms.
The objective was to conduct a survey of current fresh cow management practices that have an effect on health and diseases postpartum considering different herd sizes of commercial dairy farms. A mail survey regarding aspects of the fresh cow program including general management issues, calving, diseases, and veterinary service was conducted utilizing a convenience sample. A total of 429 survey forms were returned (12.0% response rate) and could be used for final analysis. Only 21.6% of the farms had a designated fresh cow pen. Almost every farm executed some type of fresh cow examination. Only 18.5% of farm managers documented the observations. Most of the dairy managers used more or less subjective criteria such as general appearance (97.0%) and appetite (69.7%). Only a minority of the responding dairy managers monitored their fresh cows using objective (fever 33.6%) or semiquantitative measures (subclinical ketosis 2.8%; body condition score 36.4%). On most farms, the veterinarian visited the herd only if needed (72.6%). Most cases of retained fetal membranes were treated by manual removal (72.3%) and antibiotic pills (89.5%). Several challenges and opportunities were identified to improve cow management practices.


Basic ultrasound head-to-toe skills for intensivists in the general and neuro intensive care unit population: consensus and expert recommendations of the European Society of Intensive Care Medicine.
To provide consensus, and a list of experts' recommendations regarding the basic skills for head-to-toe ultrasonography in the intensive care setting. The Executive Committee of the European Society of Intensive Care (ESICM) commissioned the project and supervised the methodology and structure of the consensus. We selected an international panel of 19 expert clinicians-researchers in intensive care unit (ICU) with expertise in critical care ultrasonography (US), plus a non-voting methodologist. The panel was divided into five subgroups (brain, lung, heart, abdomen and vascular ultrasound) which identified the domains and generated a list of questions to be addressed by the panel. A Delphi process based on an iterative approach was used to obtain the final consensus statements. Statements were classified as a strong recommendation (84% of agreement), weak recommendation (74% of agreement), and no recommendation (less than 74%), in favor or against. This consensus produced a total of 74 statements (7 for brain, 20 for lung, 20 for heart, 20 for abdomen, 7 for vascular Ultrasound). We obtained strong agreement in favor for 49 statements (66.2%), 8 weak in favor (10.8%), 3 weak against (4.1%), and no consensus in 14 cases (19.9%). In most cases when consensus was not obtained, it was felt that the skills were considered as too advanced. A research agenda and discussion on training programs were implemented from the results of the consensus. This consensus provides guidance for the basic use of critical care US and paves the way for the development of training and research projects.


Acidic phosphoprotein complex of the 60S ribosomal subunit of maize seedling roots. Components and changes in response to flooding.
We determined that ribosomes of seedling roots of maize (Zea mays L.) contain the acidic phosphoproteins (P-proteins) known to form a flexible lateral stalk structure of the 60S subunit of eukaryotic ribosomes. The P-protein stalk, composed of P0, P1, and P2, interacts with elongation factors, mRNA, and tRNA during translation. Acidic proteins of 13 to 15.5 kD were released as a complex from ribosomes with 0.4 M NH4Cl/50% ethanol. Protein and cDNA sequence analysis confirmed that maize ribosomes contain one type of P1, two types of P2, and a fourth and novel P1/P2-type protein. This novel P-protein, designated P3, has the conserved C terminus of P1 and P2. P1, P2, and P3 are similar in deduced mass (11.4-12.2 kD) and isoelectric point (4.1-4.3). A 35.5- to 36-kD acidic protein was released at low levels from ribosomes with 1.0 M NH4Cl/50% ethanol and identified as P0. Labeling of roots with [32P]inorganic phosphate confirmed the in vivo phosphorylation of the P-proteins. Flooding caused dynamic changes in the P-protein complex, which affected the potential of ribosome-associated kinases and casein kinase II to phosphorylate the P-proteins. We discuss possible alterations of the ribosomal P-protein complex and consider that these changes may be involved in the selective translation of mRNA in flooded roots.


Prognostic role of sensitive-to-apoptosis gene expression in rectal cancer.
To investigate the association between prognosis of rectal cancer treated with chemoradiotherapy (CRT) and expression of sensitive-to-apoptosis (SAG), B-cell lymphoma-extra large (Bcl-X(L)) and Bcl-2 homologous antagonist/killer (Bak). Real-time quantitative polymerase chain reaction was used to determine the expression of proteins of interest, namely SAG, Bcl-X(L), Bak and β-actin, in rectal carcinoma patients who had a follow-up period of 3 years after CRT. Biopsy specimens were excised from the rectal tumor preceding CRT. SAG, Bcl-X(L) and Bak proteins showed significant correlations with each other. In multivariate analysis, patients with high vs low SAG expression showed a statistically significant difference in 2-year survival rates: 56% vs 73%, respectively (P = 0.056). On the other hand, there were no significant correlations between the expression levels of all three genes and metastatic rates or tumor responses to CRT. Mean overall survival in the patients with elevated SAG expression was 27.1 mo ± 3.9 mo [95% confidence interval (CI): 19.3-34.9], and in patients with reduced expression, it was 32.1 mo ± 2.5 mo (95% CI: 27.3-36.9). The corresponding values for Bcl-X(L) were 28.0 mo ± 4.1 mo (95% CI: 19.9-36.1) and 31.7 mo ± 2.9 mo (95% CI: 26.0-37.5), and those for Bak were 29.8 mo ± 3.7 mo (95% CI: 22.5-37.2) and 30.6 mo ± 2.4 mo (95% CI: 25.5-35.0), respectively. Two-year survival rates significantly correlated with low SAG expression, and SAG may be a candidate gene for good prognosis, independent of therapeutic response of different individuals.


Insights into the disparate action of osmolytes and macromolecular crowders on amyloid formation.
It is widely recognized that amyloid formation sensitively responds to conditions set by myriad cellular solutes. These cosolutes include two important classes: macromolecular crowders and compatible osmolytes. We have recently found that addition of macromolecular PEG only slightly affects fibril formation of a model peptide in vitro. Polyol osmolytes, in contrast, lengthen the lag time for aggregation, and lead to larger fibril mass at equilibrium. To further hypothesize on the molecular underpinnings of the disparate effect of the two cosolute classes, we have further analyzed the experiments using an available kinetic mechanism describing fibril aggregation. Model calculations suggest that all cosolutes similarly lengthen the time required for nucleation, possibly due to their excluded volume effect. However, PEGs may in addition promote fibril fragmentation, leading to lag times that are overall almost unvaried. Moreover, polyols effectively slow the monomer-fibril detachment rates, thereby favoring additional fibril formation. Our analysis provides first hints that cosolutes act not only by changing association or dissociation rates, but potentially also by directing the formation of fibrils of varied morphologies with different mechanical properties. Although additional experiments are needed to unambiguously resolve the action of excluded cosolutes on amyloid formation, it is becoming clear that these compounds are important to consider in the search for ways to modulate fibril formation.


Actual Role of Platelet Glycoprotein IIb/IIIa Receptor Inhibitors as Adjunctive Pharmacological Therapy to Primary Angioplasty in Acute Myocardial Infarction: In the Light of Recent Randomized Trials and Observational Studies with Bivalirudin.
Strategies for preventing ischemic complications during percutaneous coronary interventions (PCI) in the setting of acute myocardial infarction (AMI) have focused on the platelet surface-membrane glycoprotein (GP) IIb/IIIa receptor. The platelet GP IIb/IIIa receptor inhibitors, by blocking the final common pathway of platelet aggregation, have become a breakthrough in the management of acute coronary syndromes. Current adjuvant pharmacological therapy of AMI with aspirin, clopidogrel, unfractionated heparin (UH), and platelet GP IIb/IIIa inhibitors provides useful therapeutic benefits. Although the use of more potent antithrombin and antiplatelet agents during PCI in AMI has reduced the rate of ischemic complications, in parallel, the rate of bleeding has increased. Several studies have reported an association between bleeding after PCI and an increase in morbidity and mortality. Therefore, investigational studies have focused in pharmacological agents that would reduce bleeding complications without compromising the rate of major adverse cardiovascular events. Based on the results of several randomized trials, abciximab with UH, aspirin and clopidogrel have become a standard adjunctive therapy with primary PCI for AMI. However, some of the trials were done before the use of stents and the widespread use of thienopyridines. In addition, GP IIb/IIIa inhibitors use have been associated with thrombocytopenia, high rates of bleeding, and the need for transfusions, which increase costs, length of hospital stay, and mortality. On the other hand, in the stent era, bivalirudin, a semi-synthetic direct thrombin inhibitor, has recently been shown to provide similar efficacy with less bleeding compared with unfractionated heparin plus platelet GP IIb/IIIa inhibitors in AMI patients treated with primary PCI. The impressive results of this recent randomized trial and other observational studies make a strong argument for the use of bivalirudin rather than heparin plus GP IIb/IIIa inhibitors for the great majority of patients with AMI treated with primary PCI. However, some controversial results and limitations in the studies with bivalirudin exert some doubts in the future widespread use of this drug.


Mitogen-activated protein kinase is a functional component of the autonomous circadian system in the suprachiasmatic nucleus.
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker driving behavioral and physiological rhythms in mammals. Circadian activation of mitogen-activated protein kinase [MAPK; also known as ERK (extracellular signal-regulated kinase)] is observed in vivo in the SCN under constant darkness, although the biological significance of this remains unclear. To elucidate this question, we first examined whether MAPK was autonomously activated in ex vivo SCN slices. Moreover, we investigated the effect of MAPK inhibition on circadian clock gene expression and neuronal firing rhythms using SCN-slice culture systems. We show herein that MAPK is autonomously activated in the SCN, and our data demonstrate that inhibition of the MAPK activity results in dampened rhythms and reduced basal levels in circadian clock gene expression at the SCN single-neuron level. Furthermore, MAPK inhibition attenuates autonomous circadian neuronal firing rhythms in the SCN. Thus, our data suggest that light-independent MAPK activity contributes to the robustness of the SCN autonomous circadian system.


Cardiovascular disease risk factors in 65-84 year old men and women: results from the Auckland University Heart and Health Study 1993-4.
To describe the distribution of the major cardiovascular risk factors among older men and women in the Auckland region, New Zealand. Means and prevalences of the major cardiovascular risk factors were estimated for non-Maori, non-Pacific Islands men and women in the age groups 65-74 and 75-84 years using data from the 1993-4 survey of the University of Auckland Heart and Health Study, a cross-sectional, population-based study of cardiovascular risk factors. 996 people aged 65-84 years participated, with men and women and the two ten-year age groups almost equally represented. Fewer than half engaged in regular leisure time physical activity; around 35% were overweight (BMI 25-30) and 10% were obese (BMI > 30). Total mean cholesterol levels were higher in women and 46% of women had a cholesterol level > or = 6.5 mmol/L compared with only 17% of men. However, total cholesterol:HDL ratios were higher among men. Age and sex differences in blood pressure were small. Around 50% had raised blood pressure (BP > 150/90) or were currently on antihypertensive medication; only 8% smoked; around 6% were diabetic. Almost 8% had three or all of four major modifiable cardiovascular risk factors (elevated blood pressure, total cholesterol:HDL ratio > or = 6.5, current smoking and physical inactivity). These results are broadly comparable to those from other Western populations. Differences between 65-74 and 75-84 year age groups are few but important differences in cholesterol, smoking and physical activity between older men and women are noted. These findings indicate that there is considerable potential for prevention of cardiovascular disease among older people.


Concomitant Aspergillus Species Infection and Squamous Cell Carcinoma Diagnosed on Pap Smear.
Concomitant infection with Aspergillus species and cervical squamous cell carcinoma in the female genital tract is a rare occurrence and attributed to the opportunistic nature of infection in the immunocompromised state due to the underlying malignancy. The contamination of smears with Aspergillus species should be excluded. The diagnosis of Aspergillus species infection along with squamous cell carcinoma was established on cervicovaginal pap smears in a 62-year-old female presented to gynecological clinic with complaints of stress urinary incontinence. Speculum examination revealed first-degree cervical descent. Smears showed features of squamous cell carcinoma along with fungal spores and fruiting body with hyphae of Aspergillus species. The presence of fruiting bodies and hyphae of Aspergillus species with coexisting squamous cell carcinoma is rare in routine pap smears. True infection needs to be distinguished from contamination by Aspergillus species. Early diagnosis can be established on routine cervicovaginal Pap smear examination.


Inline Spectroscopy: From Concept to Function.
The field of applied spectroscopy is strongly dominated by publications presenting proof-of-concepts, lab set-ups, and demonstrations. In contrast, the corresponding number of commercial successes of inline spectroscopy is surprisingly lower. This article discusses inline spectroscopy from an instrumentation perspective. It is the authors' firm belief that the success of inline spectroscopy lies in the understanding of how the design and implementation of the optical instrumentation affects the data quality, and how this in turn will limit or enhance the performance of the prediction model. This article emphasizes the need for a strong, multidisciplinary design team, whose design process is rooted in first principles, to bridge the technology "valley of death" and convert research in applied spectroscopy into commercially successful solutions.


Diagnostic points and possible origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a radiographic study of 77 mandibular osteomyelitis cases.
To find diagnostic points and to identify the origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome. Fifty-two patients with mandibular suppurative osteomyelitis and 25 patients with mandibular osteomyelitis in SAPHO syndrome were included in the study. Radiographic patterns of the lesion, types of periosteal reaction and the presence of external bone resorption and bone enlargement were investigated in each case and compared between the two entities. Suppurative osteomyelitis demonstrated an osteolytic pattern and a lamellated type of periosteal reaction, whereas SAPHO syndrome revealed a mixed-pattern, solid-type periosteal reaction, external bone resorption and bone enlargement. Radiographic examination is suggested to be convenient and a useful diagnostic method of differentiating osteomyelitis in SAPHO syndrome from suppurative osteomyelitis. The periosteum is suspected to be the original site of osteomyelitic lesions in SAPHO syndrome.


Reliability and Validity for Neuroscience Nurses.
The concepts of reliability and validity are important for neuroscience nurses to understand, particularly because they evaluate existing literature and integrate common scales or tools into their practice. Nurses must ensure instruments measuring specified concepts are both reliable and valid. This article will review types of reliability and validity-sometimes referred to collectively as a psychometric testing-of an instrument. Relevant examples in neuroscience are included to illustrate the importance of reliability and validity to neuroscience nurses.


Congenital lung lesions--underlying molecular mechanisms.
Congenital lung lesions comprise a broad spectrum of rare but clinically significant developmental abnormalities, including congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts, which are commonly surgically treated. Although the terms congenital cystic adenomatoid malformation, bronchopulmonary sequestrations, congenital lobar emphysema, and bronchogenic cysts are entrenched in clinical usage and comfortably correspond to rigid pathologic definitions, there is a considerable overlap in the findings. Disregarding the controversy about lesion nomenclature and classification, it is widely accepted that congenital lung lesions result from perturbations in lung and airway embryogenesis. It is generally accepted that both place (level in the tracheobronchial tree) and timing (gestational age) of the embryologic insult correlates with the type of lesion and histopathology that is manifested. The objective of this review is to briefly review normal lung development and to analyze the known molecular mechanisms underlying those diseases.


Health services and rehabilitation for active duty service members and veterans with mild TBI.
We review health services and reintegration practices that contribute to the rehabilitation of US active duty service members (ADSMs) and Veterans who experienced traumatic brain injury (TBI), especially mild TBI (mTBI), as discussed at the 2015 Department of Veterans Affairs (VA) TBI State-of-the-Art (SOTA) Conference. We reviewed the state-of-the-art at the time of the previous 2008 TBI SOTA Conference, advances in the field since then, and future directions to address gaps in knowledge. We reviewed: (1) mTBI and its comorbid conditions documented in ADSMs and Veterans, and recognized the need for additional healthcare utilization, health cost and quality of care studies; (2) VA vocational rehabilitation programmes and the effectiveness of supported employment for helping those with workplace difficulties; (3) the application of technology to assist in TBI rehabilitation, including mobile device applications for self-management, videoconferencing with providers, and virtual reality to help with behavioural and cognitive challenges, and (4) Department of Defense (DoD)-VA partnerships on identification, evaluation and dissemination of TBI best practices. There have been significant advances in TBI rehabilitation, but multiple areas across the DoD and VA care continuum need further exploration and development to meet the needs of ADSMs and Veterans.


Donor Human Milk and Fortifier Use in United States Level 2, 3, and 4 Neonatal Care Hospitals.
In 2011, the United States Surgeon General issued a call to action to "identify and address obstacles to greater availability of safe banked donor milk for fragile infants." The purpose of the present study is to analyze patterns in donor human milk (DHM) and fortifier use in level 2, 3, and 4 neonatal facilities in 2015 and to identify factors associated with nonuse. Data from the 2015 Maternity Practices in Infant Nutrition and Care survey, conducted by the Center for Disease Control and Prevention, were analyzed for questions about feeding practices within neonatal hospitals. The percentage of neonatal facilities that reported using DHM in 2015 was 38.3%, up 74% from 2011. The majority of level 3 and level 4 facilities reported using DHM (65.7% and 73.3%, respectively) and fortifiers (96.1% and 91.9%, respectively). Within DHM-using facilities, a wide range of DHM feeding patterns was reported. The prevalence of DHM use was higher in facilities that had the highest rates of mother's own milk feedings (P < 0.001), in facilities that were participating in the Baby Friendly Hospital Initiative (P < 0.001), and in facilities that were in a state with an operating milk bank (P < 0.001). DHM use continues to increase in advanced care neonatal settings, with significant difference based on acuity level, facility size, breast-feeding culture, and proximity to a milk bank. Geographic gaps in DHM use provide the opportunity for targeted efforts to improve access.


Composition, antibacterial, antioxidant and antiproliferative activities of essential oils from three Origanum species growing wild in Lebanon and Greece.
The essential oils from Origanum dictamnus, Origanum libanoticum and Origanum microphyllum were analysed by GC-MS, finding carvacrol, p-cymene, linalool, γ-terpinene and terpinen-4-ol as major components. The antioxidant activity by the DPPH and FRAP tests and the antiproliferative activity against two human cancer cell lines, LoVo and HepG2, were investigated, showing that the essential oil of O. dictamnus was statistically the most inhibitory on both the cell lines, while all the oils exerted a weak antioxidant activity. Furthermore, the samples were tested against 10 Gram-negative and Gram-positive bacteria; all the oils were active on Gram-positive bacteria but O. dictamnus essential oil was the most effective (MIC = 25-50 μg/mL), showing also a good activity against the Gram-negative Escherichia coli (MIC = 50 μg/mL). Data suggest that these essential oils and particularly O. dictamnus oil could be used as valuable new flavours with functional properties for food or nutraceutical products.


Inhibition of histone deacetylation augments dihydrotestosterone induction of androgen receptor levels: an explanation for trichostatin A effects on androgen-induced chromatin remodeling and transcription of the mouse mammary tumor virus promoter.
The integrated mouse mammary tumor virus (MMTV) promoter has provided an excellent model system with which to study the impact of steroid hormones on transcriptional activation in the context of a defined chromatin structure. The hormone response element (HRE) of this promoter is positioned on a phased nucleosome which becomes remodeled in response to steroids. One possible mechanism of chromatin remodeling by steroid receptors could involve recruitment of coactivators which alter the histone acetylation status of the HRE nucleosome. To examine how the androgen receptor (AR) influences transcription and chromatin remodeling and to assess whether changes in histone acetylation are involved in these effects, we determined whether the specific histone deacetylase inhibitor trichostatin A (TSA) influenced basal- and androgen-mediated transcriptional activation of the integrated MMTV promoter in the mouse L-cell fibroblast cell line 29+. These cells harbor the MMTV promoter integrated in the genome and express only one steroid hormone receptor subtype, i.e., the AR. Surprisingly, we found that treatment of the cells with TSA alone had virtually no effect on transcription and chromatin remodeling of the MMTV promoter nor on AR levels. However, pretreatment with TSA augmented the DHT effects on all three parameters. These results suggest that histone acetylation changes at the MMTV B nucleosome per se are not alone sufficient to induce chromatin remodeling and subsequent induction of MMTV transcription. Rather, the histone deacetylase inhibitor TSA exerts a portion of its effect on MMTV chromatin remodeling and transcriptional activation indirectly through increases in AR levels.


Multi-break rearrangements and breakpoint re-uses: from circular to linear genomes.
Multi-break rearrangements break a genome into multiple fragments and further glue them together in a new order. While 2-break rearrangements represent standard reversals, fusions, fissions, and translocations, 3-break rearrangements represent a natural generalization of transpositions. Alekseyev and Pevzner (2007a, 2008a) studied multi-break rearrangements in circular genomes and further applied them to the analysis of chromosomal evolution in mammalian genomes. In this paper, we extend these results to the more difficult case of linear genomes. In particular, we give lower bounds for the rearrangement distance between linear genomes and for the breakpoint re-use rate as functions of the number and proportion of transpositions. We further use these results to analyze comparative genomic architecture of mammalian genomes.


Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion.
Recent studies in mice have challenged the ability of bone marrow cells (BMCs) to differentiate into myocytes and coronary vessels. The claim has also been made that BMCs acquire a cell phenotype different from the blood lineages only by fusing with resident cells. Technical problems exist in the induction of myocardial infarction and the successful injection of BMCs in the mouse heart. Similarly, the accurate analysis of the cell populations implicated in the regeneration of the dead tissue is complex and these factors together may account for the negative findings. In this study, we have implemented a simple protocol that can easily be reproduced and have reevaluated whether injection of BMCs restores the infarcted myocardium in mice and whether cell fusion is involved in tissue reconstitution. For this purpose, c-kit-positive BMCs were obtained from male transgenic mice expressing enhanced green fluorescence protein (EGFP). EGFP and the Y-chromosome were used as markers of the progeny of the transplanted cells in the recipient heart. By this approach, we have demonstrated that BMCs, when properly administrated in the infarcted heart, efficiently differentiate into myocytes and coronary vessels with no detectable differentiation into hemopoietic lineages. However, BMCs have no apparent paracrine effect on the growth behavior of the surviving myocardium. Within the infarct, in 10 days, nearly 4.5 million biochemically and morphologically differentiated myocytes together with coronary arterioles and capillary structures were generated independently of cell fusion. In conclusion, BMCs adopt the cardiac cell lineages and have an important therapeutic impact on ischemic heart failure.


PSMA Uptake in Mediastinal Sarcoidosis.
Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein which is frequently overexpressed on prostate cancer cells. Ga-PSMA PET/CT plays an increasing role in prostate cancer management. However, growing evidence suggests increased PSMA uptake in a variety of other malignant tumor entities and in some benign lesions. This report describes PSMA uptake in numerous thoracic lymph nodes in a patient with known mediastinal sarcoidosis. Knowledge and recognition of these possibilities are important to avoid scan misinterpretation.


The film tells the story: Physical-chemical characteristics of IgG at the liquid-air interface.
The presence of liquid-air interfaces in protein pharmaceuticals is known to negatively impact product stability. Nevertheless, the mechanisms behind interface-related protein aggregation are not yet fully understood. Little is known about the physical-chemical behavior of proteins adsorbed to the interface. Therefore, the combinatorial use of appropriate surface-sensitive analytical methods such as Langmuir trough experiments, Infrared Reflection-Absorption Spectroscopy (IRRAS), Brewster Angle Microscopy (BAM), and Atomic Force Microscopy (AFM) is highly expedient to uncover structures and events at the liquid-air interface directly. Concentration-dependent adsorption of a human immunoglobulin G (IgG) and characteristic surface-pressure/area isotherms substantiated the amphiphilic nature of the protein molecules as well as the formation of a compressible protein film at the liquid-air interface. Upon compression, the IgG molecules do not readily desorb but form a highly compressible interfacial film. IRRA spectra proved not only the presence of the protein at the interface, but also showed that the secondary structure does not change considerably during adsorption or compression. IRRAS experiments at different angles of incidence indicated that the film thickness and/or packing density increases upon compression. Furthermore, BAM images exposed the presence of a coherent but heterogeneous distribution of the protein at the interface. Topographical differences within the protein film after adsorption, compression and decompression were revealed using underwater AFM. The combinatorial use of physical-chemical, spectroscopic and microscopic methods provided useful insights into the liquid-air interfacial protein behavior and revealed the formation of a continuous but inhomogeneous film of native-like protein molecules whose topographical appearance is affected by compressive forces.


Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery. Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy control participants. CBT intervention led to a significant improvement in health status, physical activity and cognitive performance. Crucially, CFS patients showed a significant increase in grey matter volume, localized in the lateral prefrontal cortex. This change in cerebral volume was related to improvements in cognitive speed in the CFS patients. Our findings indicate that the cerebral atrophy associated with CFS is partially reversed after effective CBT. This result provides an example of macroscopic cortical plasticity in the adult human brain, demonstrating a surprisingly dynamic relation between behavioural state and cerebral anatomy. Furthermore, our results reveal a possible neurobiological substrate of psychotherapeutic treatment.


Modeling the mechanical behavior of vertebral trabecular bone: effects of age-related changes in microstructure.
Age-related reductions in the thickness and number of trabeculae in vertebral trabecular bone have been documented by several workers, yet the relative effects of these changes on mechanical properties are not known. We developed a two-dimensional model of human vertebral trabecular bone and investigated its mechanical behavior using finite element analysis. The stress-strain behavior, failure mode, and strain distributions predicted using the model were consistent with those observed for vertebral trabecular bone under compressive loading. Random reductions in the number of trabeculae reduced the modulus and strength of the models two to five times more than uniform reductions in the thickness of trabeculae that caused the same loss of bone volume. For example, randomly removing longitudinal trabeculae to achieve a reduction in density of 10% reduced the strength by approximately 70%, whereas removing the same amount of bone by uniformly reducing the thickness of the longitudinal trabeculae only reduced the strength by approximately 20%. For a simulation of aged bone, in which the thickness and number of trabeculae were reduced concurrently, the strength was 23% of its intact ("young") value. When the bone mass of the aged model was restored to its intact level by increasing the thickness but not the number of trabeculae, the strength increased by 60%, but was still only 37% of its intact value. These combined findings, based on a two-dimensional, idealized model of vertebral trabecular bone, illustrate the importance of maintaining trabecular number and suggest that it may not be possible to restore bone strength following a period of advanced bone loss if a substantial number of trabeculae have been resorbed. Thus, until treatments exist that can increase trabecular number, the most effective treatment strategy is to prevent the degradation of bone strength by maintaining the number of trabeculae at a healthy level.


Differential expression of seven alpha-expansin genes during growth and ripening of pear fruit.
Seven cDNAs, designated PcExp1 to PcExp7, encoding expansin homologues, were isolated from mature pear fruit and their expression profiles were investigated in ripening fruit and other tissues, and in response to ethylene. Accumulation of PcExp2, -3, -5 and -6 mRNA increased markedly with fruit softening and then declined at the over-ripe stage. Treatment of fruit at an early ripening stage with 1-methylcyclopropene (MCP), an inhibitor of ethylene action, suppressed ethylene biosynthesis, fruit softening and the accumulation of the expansin mRNAs. Conversely, propylene treatment at the preclimacteric stage induced accumulation of the same four expansin genes, as well as ethylene production and fruit softening. The expression patterns correlated with alteration in the rate and extent of fruit softening. The abundance of PcExp1 mRNA increased at the late expanding phase of fruit development and further increased during ripening, whereas PcExp4 mRNA levels were constant throughout fruit growth and ripening. The MCP and propylene treatments had little effect on PcExp1 and PcExp4 expression. PcExp7 was expressed in young but not mature fruit. PcExp4 and PcExp6 mRNA was also detected in flowers. The accumulation of PcExp4, -5, -6 and -7 mRNA was more abundant in young growing tissues, but not in fully expanded tissues, suggesting roles for these genes in cell expansion. These results demonstrate that characteristically, multiple expansin genes show differential expression and hormonal regulation during pear fruit development and at least six expansins show overlapping expression during ripening.


Brain natriuretic peptide and cardiac resynchronization therapy in patients with mildly symptomatic heart failure.
There are limited data on the prognostic implications of brain natriuretic peptide (BNP) assessment in patients with mildly symptomatic heart failure (HF) who receive cardiac resynchronization therapy with a defibrillator (CRT-D). The effect of elevated baseline and 1-year BNP levels (dichotomized at the upper tertile BNP of 120 pg/mL) on the risk of HF or death was assessed among the cohort of 1197 patients with baseline BNP data enrolled in MADIT (Multicenter Automated Defibrillator Implantation Trial)-CRT. Elevated baseline BNP was associated with a significant 68% (P=0.007) and 58% (P=0.02) increase in the risk of HF or death among MADIT-CRT patients allocated to CRT-D and implantable cardioverter defibrillator-only therapy, respectively. At 1 year of follow-up, patients allocated to CRT-D displayed significantly greater reductions in BNP (26% reduction) levels compared with implantable cardioverter defibrillator-only patients (8% increase; P=0.005). Patients with CRT-D in whom 1-year BNP levels were reduced or remained low experienced a significantly lower risk of subsequent HF or death as compared with patients in whom 1-year BNP levels were high. Similarly, the echocardiographic response to CRT-D was highest among those who maintained low BNP levels or in whom BNP level at 1-year was reduced. Our findings suggest that assessment of baseline and follow-up BNP provides important prognostic implications in patients with mildly symptomatic HF who receive CRT.


Use of eye movement monitoring to examine item and relational memory in schizophrenia.
Patients with schizophrenia may be impaired at remembering interitem and item-context relationships (relational memory), even when memory for items is intact. Here, we applied the novel approach of using eye movements to assess integrity of item and relational memory in schizophrenia. This method does not rely on introspection and may be more readily translated to animal models than traditional behavioral methods. Sixteen healthy control subjects and 16 patients were administered a scene memory task while eye movements were monitored. During testing, participants indicated whether the scenes were unchanged, contained a new item (item manipulation), had a change in item location (relational manipulation), or were new. It was predicted that memory would be disproportionately impaired when relational changes were made. Results confirmed that tasks were equally difficult and showed that patients were impaired identifying all scene types. These behavioral impairments were associated with more severe disorganization and negative symptoms. Eye movement results were more specific. Both groups looked disproportionately at critical regions of repeated versus novel scenes-an effect of scene repetition. However, in contrast with predictions, patients showed equivalent eye-movement-based memory impairment whether changes were relational or item-based. This is the first experiment to demonstrate that eye movements can be used to investigate item and relational memory in schizophrenia. The eye movement procedure was well tolerated and was more specific than behavioral measures with respect to memory impairment. Results suggest that eye movements may be of use in clinical trials and translational studies employing animal models.


Combination of microscopic techniques reveals a comprehensive visual impression of biofilm structure and composition.
Bacterial biofilms are imaged by various kinds of microscopy including confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). One limitation of CLSM is its restricted magnification, which is resolved by the use of SEM that provides high-magnification spatial images of how the single bacteria are located and interact within the biofilm. However, conventional SEM is limited by the requirement of dehydration of the samples during preparation. As biofilms consist mainly of water, the specimen dehydration might alter its morphology. High magnification yet authentic images are important to understand the physiology of biofilms. We compared conventional SEM, Focused Ion Beam (FIB)-SEM and CLSM with SEM techniques [cryo-SEM and environmental-SEM (ESEM)] that do not require dehydration. In the case of cryo-SEM, the biofilm is not dehydrated but kept frozen to obtain high-magnification images closer to the native state of the sample. Using the ESEM technique, no preparation is needed. Applying these methods to biofilms of Pseudomonas aeruginosa showed us that the dehydration of biofilms substantially influences its appearance and that a more authentic biofilm image emerges when combining all methods.


TMS-Evoked Prefrontal Perturbation as a Toy Model of Brain Resilience to Stress During the COVID-19 Pandemic.
Psychosocial hardships associated with the COVID-19 pandemic led many individuals to suffer adverse mental health consequences, however, others show no negative effects. We hypothesized that the electroencephalographic (EEG) response to transcranial magnetic stimulation (TMS) could serve as a toy-model of an individual's capacity to resist psychological stress, in this case linked to the COVID-19 pandemic. We analyzed data from 74 participants who underwent mental health monitoring and concurrent electroencephalography with transcranial magnetic stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) and left inferior parietal lobule (L-IPL). Within the following 19 months, mental health was reassessed at three time points during lock-down confinement and different phases of de-escalation in Spain. Compared with participants who remained stable, those who experienced increased mental distress showed, months earlier, significantly larger late EEG responses locally after L-DLPFC stimulation (but not globally nor after L-IPL stimulation). This response, together with years of formal education, was significantly predictive of mental health status during the pandemic. These findings reveal that the effect of TMS perturbation offers a predictive toy model of psychosocial stress resilience, as exemplified by the COVID-19 pandemic, and point to the L-DLPFC as a promising target for resilience promotion.


Comparing Tinnitus Tuning Curves and Psychoacoustic Tuning Curves.
Tinnitus masking patterns have long been known to differ from those used for masking external sound. In the present study, we compared the shape of tinnitus tuning curves (TTCs) to psychophysical tuning curves (PTCs), the latter using as a target, an external sound that mimics the tinnitus characteristics. A secondary goal was to compare sound levels required to mask tinnitus to those required to mask tinnitus-mimicking sounds. The TTC, PTC, audiometric thresholds, tinnitus pitch, and level matching results of 32 tinnitus patients were analyzed. Narrowband noise maskers were used for both PTC and TTC procedures. Patients were categorized into three groups based on a combination of individual PTC-TTC results. Our findings indicate that in 41% of cases, the PTC was sharp (V shape), but the TTC showed a flat configuration, suggesting that the tinnitus-related activity in that subgroup does not behave as a regular stimulus-induced activity. In 30% of cases, V-shape PTC and TTC were found, indicating that the tinnitus-related activity may share common properties with stimulus-induced activity. For a masker centered at the tinnitus frequency, the tinnitus was more difficult to mask than the mimicking tone in 72% of patients; this was particularly true for the subset with V-shape PTCs and flat TTCs. These results may have implications for subtyping tinnitus and acoustic therapies, in particular those targeting the tinnitus frequency.