Aerobic training improves exercise-induced lipolysis in SCAT and lipid utilization in overweight men.
The aim of this study was to investigate whether endurance training improves lipid mobilization and oxidation in overweight subjects. Eleven young men (25.6 +/- 1.4 yr and body mass index 27.7 +/- 0.2) performed a 4-mo training program consisting of practicing aerobic exercise 5 days/wk. Before and after the training period, lipid oxidation was explored during a 60-min exercise at 50% of peak O2 consumption by use of indirect calorimetry. Lipid mobilization and antilipolytic alpha2-adrenoceptor effect were also studied using the microdialysis method in abdominal subcutaneous adipose tissue (SCAT). After training, plasma nonesterified fatty acid (NEFA) levels, at rest and during exercise, were significantly lower than before (P < 0.001). Lipolysis in SCAT was significantly higher after than before training. An antilipolytic alpha2-adrenoceptor effect in SCAT was underlined during exercise before training and disappeared after. The respiratory exchange ratio was lower after training, i.e., the percentage of lipid oxidation was higher only at rest. The amount of lipid oxidized was higher after training, at rest, and during exercise. Although exercise power was higher after training, the relative intensity was equivalent, as suggested by a similar increase in plasma catecholamine concentrations before and after training. In conclusion, 4-mo training in overweight men improved lipid mobilization through a decrease of antilipolytic alpha2-adrenoceptor effect in SCAT and lipid oxidation during moderate exercise. Training induced a decrease of blood NEFA, predicting better prevention of obesity.


Cutaneous wound biofilm and the potential for electrical stimulation in management of the microbiome.
Infection contributes significantly to delayed cutaneous wound healing, which impacts patient care. External application of electrical stimulation (ES) has beneficial effects on wound repair and regeneration. The majority of studies to date have explored ES in relation to planktonic microorganisms, yet evidence indicates that bacteria in chronic wounds reside as antibiotic-resistant polymicrobial biofilms, which contribute to impairing wound healing. Culture-independent sequencing techniques have revolutionized our understanding of the skin microbiome and allowed a more accurate determination of microbial taxa and their relative abundance in wounds allowing a greater understanding of the host-microbial interface. Future studies combining the fields of ES, biofilm and microbiome research are necessary to fully elucidate the use of ES in the management of wound infection.


Short-term effects of fibrinolytic therapy on the hemodynamic parameters of patients with intermediate- and high-risk pulmonary embolism.
We aimed to determine the effect of fibrinolytic therapy on hemodynamic parameters at 4 hours after treatment and bleeding complications in patients with intermediate- and high-risk pulmonary embolism. This single-center, retrospective, cohort study included patients with intermediate- and high-risk pulmonary embolism treated with fibrinolytics. Their demographic and clinical characteristics, complications, and vital signs at the initiation of and 4 hours after fibrinolytic therapy were evaluated. The primary outcome was the change in the patients' vital signs at 4 hours after fibrinolytic therapy, compared by the Mann-Whitney U-test. Seventy-nine patients were included in this study. The systolic and diastolic blood pressures of the high-risk group at 4 hours after fibrinolytic therapy were higher than those at the initiation of fibrinolytic therapy (80 mmHg vs. 99 mmHg, P = 0.029; 49 mmHg vs. 67 mmHg, P = 0.011, respectively). In the intermediate-risk group, the oxygen saturation increased (94% vs. 96%, P = 0.004) and pulse rate decreased (104 beats/min vs. 91 beats/min, P < 0.001). Blood pressure at 4 hours after fibrinolytic therapy increased in patients with high-risk pulmonary embolism. Also, oxygen saturation and pulse rate improved in intermediate-risk patients.


Influence of altered CSF solute composition on parotid salivary secretion in goats.
Infusions of hypertonic NaCl solution into the CSF of the lateral cerebral ventricle of the goat caused a marked reduction in parotid salivary flow concomitant with a rise in salivary [Na+]. Corresponding infusions of iso- or hypertonic glucose and glycerol solutions affected salivary secretion in the opposite direction. The possibility is discussed that a periventricular sodium-sensitive mechanism, which is of importance in the central control of fluid balance, also may participate in the regulation of parotid secretion in the goat. This interpretation of the results is to some extent obscured by the observation of a high incidence of intermittent rumination during the intraventricular infusions of glucose and glycerol solution.


Roles of Matrix Metalloproteinases and Their Natural Inhibitors in Metabolism: Insights into Health and Disease.
Matrix metalloproteinases (MMPs) are a family of zinc-activated peptidases that can be classified into six major classes, including gelatinases, collagenases, stromelysins, matrilysins, membrane type metalloproteinases, and other unclassified MMPs. The activity of MMPs is regulated by natural inhibitors called tissue inhibitors of metalloproteinases (TIMPs). MMPs are involved in a wide range of biological processes, both in normal physiological conditions and pathological states. While some of these functions occur during development, others occur in postnatal life. Although the roles of several MMPs have been extensively studied in cancer and inflammation, their function in metabolism and metabolic diseases have only recently begun to be uncovered, particularly over the last two decades. This review aims to summarize the current knowledge regarding the metabolic roles of metalloproteinases in physiology, with a strong emphasis on adipose tissue homeostasis, and to highlight the consequences of impaired or exacerbated MMP actions in the development of metabolic disorders such as obesity, fatty liver disease, and type 2 diabetes.


Modeling genetic platelet disorders with human pluripotent stem cells: mega-progress but wanting more on our plate(let).
Megakaryocytes are rare hematopoietic cells that play an instrumental role in hemostasis, and other important biological processes such as immunity and wound healing. With the advent of cell reprogramming technologies and advances in differentiation protocols, it is now possible to obtain megakaryocytes from any pluripotent stem cell (PSC) via hematopoietic induction. Here, we review recent advances in PSC-derived megakaryocyte (iMK) technology, focusing on platform validation, disease modeling and current limitations. A comprehensive study confirmed that iMK can recapitulate many transcriptional and functional aspects of megakaryocyte and platelet biology, including variables associated with complex genetic traits such as sex and race. These findings were corroborated by several pathological models in which iMKs revealed molecular mechanisms behind inherited platelet disorders and assessed the efficacy of novel pharmacological interventions. However, current differentiation protocols generate primarily embryonic iMK, limiting the clinical and translational potential of this system. iMK are strong candidates to model pathologic mutations involved in platelet defects and develop innovative therapeutic strategies. Future efforts on generating definitive hematopoietic progenitors would improve current platelet generation protocols and expand our capacity to model neonatal and adult megakaryocyte disorders.


Analysis of surgical treatment for pulmonary aspergilloma.
Surgery for pulmonary aspergilloma is reputed to be risky. The results of surgical treatment of pulmonary aspergilloma in 41 patients between 1988 and 2003 were evaluated retrospectively. Hemoptysis occurred in 31 patients (75.6%) and it was massive (> 300 mL in 24 hr) in 3. The underlying lung disease was tuberculosis in 35, bullous lung disease in 2, hydatid cyst in 2, and lung carcinoma in 2 patients. Lobectomy, bilobectomy, wedge resection, and pneumonectomy were performed in 27, 4, 6, and 4 patients respectively. The postoperative complication rate was 24.4%. One patient, who had a right pneumonectomy, died due to respiratory failure; the mortality rate was 2.4%. Recurrent hemoptysis was observed in only one patient. Early surgical treatment of patients with pulmonary aspergilloma resulted in a satisfactory outcome with acceptable morbidity, low mortality, and effective prevention of recurrent hemoptysis. Pneumonectomy has a high morbidity, thus it should be avoided if possible.


Dermatological Implications of the Taqiyah and Imamah: Recommendations for Delivering Culturally Conscious Care.
Background and objective The growing cultural and religious diversity in healthcare settings necessitates clinicians to integrate cultural competence and sensitivity into their practice. Despite significant research focusing on the hijab worn by Muslim women, there is a gap in understanding the dermatological implications of the taqiyah and imamah, worn by Muslim men. In light of this, this study aimed to offer insights into delivering culturally conscious dermatological care for Muslim men wearing these garments, thereby bridging a crucial knowledge gap. Materials and methods The study employed a comprehensive research strategy that encompassed both medical literature and foundational Islamic texts. PubMed, Web of Science, and Scopus were used for medical literature searches, while al-Maktabah al-Shamela and Sunnah.com, along with Quranic and Hadith translations were consulted for religious insights. A thematic analysis was employed to identify patterns, challenges, and unique points, ensuring a holistic understanding of the subject. Results Our findings revealed that wearing a taqiyah or imamah has both beneficial and detrimental dermatological effects, depending on factors such as climate, fabric, and hygiene practices. While the garments are rooted in Islamic tradition, their use varies based on cultural context rather than strict religious guidelines. Moreover, gender dynamics and the concept of privacy ('awrah) within Islamic teachings have implications for healthcare interactions. The study offers practical guidelines for dermatological care tailored to Muslim men wearing a taqiyah or imamah. It emphasizes the importance of material choice, hygiene practices, and the willingness of many Muslim men to be accommodating in medical settings, albeit with some reservations. The paper also discusses the role of telemedicine in culturally sensitive healthcare delivery, recommending measures such as secure communication channels and self-imaging options. Conclusion The paper provides comprehensive recommendations aimed at delivering culturally and religiously sensitive dermatological care to Muslim men wearing a taqiyah or imamah. By integrating both medical best practices and a nuanced understanding of Islamic customs, healthcare providers can foster a more trusting and effective care relationship, thereby improving patient satisfaction and dermatological outcomes.


Influence of flexoelectricity above the nematic Fréedericksz transition.
Continuum theory is used to demonstrate that the presence of flexoelectricity significantly alters the response to an applied voltage of a homogeneous nematic liquid crystal cell above the ac Fréedericksz threshold voltage. In such a system there is a fitting degeneracy: we obtain very good fits between theory and experimental permittivity data using any value of the sum of flexoelectric coefficients, e(11)+e(33), between 0.0 C/m and 1.5 x 10(-11) C/m. The corresponding values of the nematic bend elastic constant show an inverse parabolic relationship with e(11)+e(33), with K33 being reduced down to 90% of its value when flexoelectricity is neglected.


[Trend of caesarean section rate and puerpera characteristics: based on Robson classification].
Objective: To analyze the trend in caesarean section rate and puerpera characteristics in hospital, and provide valuable information for maternal and child health policy making and clinical practice. Methods: A total of 12 041 women who delivered in the affiliated Chaohu Hospital of Anhui Medical University from October 1, 2010 to September 30, 2016 were selected. Based on Robson classification system, changes in the rate of caesarean delivery as well as its relationship with two-child policy and infant sex ratio were analyzed. Results: The overall caesarean section rate gradually decreased from 66.9% to 44.2% during the past six years. Respectively, the caesarean section rate in primiparae with singleton term babies decreased to 32.1% and the rate in multiparas without uterine scar decreased to 14.2%, and the rate in premature delivery decreased to 22.9%, the differences were significant (P<0.01). The proportion of vaginal delivery (R1, R3), multiparas with uterine scar (R5) and twins pregnancy (R8) increased. the differences were significant (P<0.01). The annual overall newly-born sex ratio ranged from 110∶100 to 128∶100. In group R1, more babies were girls, the proportion was stable, more women with premature delivery and multiparas had boy babies, but the boy babies by multiparas without uterine scar obviously decreased in the last 2 years. Conclusions: Primiparae with singleton head birth, multipara without uterine scar and women with premature deliveries are the key population in the effort of reduction of caesarean section rate. The caesarean section rate and proportion were unstable in multiparas with uterine scar, breech deliveries and twin deliveries. The application of Robson classification system can improve the comparability of the surveillance data.


[TRANSVERSE TESTICULAR ECTOPIA WITH INCIDENTAL TESTICULAR TUMOR, DISCOVERED UPON SYMPTOMATIC TESTICULAR TORSION].
Transverse testicular ectopia is a condition in which a testicle crosses the midline and descends through the contralateral inguinal canal, with both testes in the same scrotal compartment. It is reported to be present in about 2% of persons who present with non-palpable testicles. Most transverse testicular ectopia patients undergo orchiopexy in early childhood; however, in rare cases, they are diagnosed in adulthood upon detection of testicular tumors.A 40-year-old man visited our hospital complaining of right abdominal pain. His right testis was palpable in the right scrotum; however, the left scrotal compartment seemed empty and there was a painful mass on the upper part of the right scrotal compartment. Computed tomography showed that both spermatic cords traversed through the right inguinal canal, and transverse testicular ectopia was diagnosed. Ultrasonography showed absent left testicular circulation on the upper part of the right scrotum. Upon diagnosis of left testicular torsion, emergency surgery was conducted. In the right scrotum, there was a normal right testicle, and a necrotic left testicle which was twisted 180 degrees on its axis, towards the cranial side. Histopathology of the excised left testicle revealed an incidental seminoma, pT1. Tumor markers following surgery were negative, and there was no evidence of recurrence observed with two years and five months of follow-up.Non-palpable testicular torsion may also be a transverse testicular ectopia. Therefore, it is necessary to consider malignant tumors based on the patient's age.


Surface energy and wettability of spin-coated thin films of lignin isolated from wood.
The surface energy of lignin films spin-coated onto oxidized silicon wafer has been determined from contact angle measurements of different test liquids with varying polar and dispersive components. Three different lignin raw materials were used, a kraft lignin from softwood, along with milled wood lignin from softwood and hardwood. Infrared and (31)P NMR spectroscopy was used to identify any major functional group differences between the lignin samples. No significant difference in the total solid-vapor surface energy for the different lignin films was observed; however, the polar component for the kraft lignin was much greater than for either of the milled wood lignin samples consistent with the presence of carboxyl groups and higher proportion of phenolic hydroxyl groups as shown by quantitative (31)P NMR on the phosphitylated samples. Furthermore, the total surface energy of lignin of 53-56 mJ m(-2) is of a similar magnitude to cellulose, also found in the wood cell wall; however, cellulose has a higher polar component leading to a lower contact angle with water and greater wettability than the milled wood lignin. Although lignin is not hydrophobic according to the strictest definition of a water contact angle greater than 90 degrees, water may only be considered a partially wetting liquid on a lignin surface. This supports the long-held belief that one of the functions of lignin in the wood cell wall is to provide water-proofing to aid in water transport. Furthermore, these results on the solid-vapor surface energy of lignin will provide invaluable insight for many natural and industrial applications including in the design and manufacture of many sustainable products such as paper, fiberboard, and polymer composite blends.


Transcriptomic and physiological comparison of Shatangju (Citrus reticulata) and its late-maturing mutant provides insights into auxin regulation of citrus fruit maturation.
Previous studies have shown that abscisic acid (ABA) and ethylene are involved in pulp maturation and peel coloration in the nonclimacteric citrus fruits. There are also signs indicating that other plant hormones may play some roles in citrus fruit ripening. In this study, we compared profiles of genome-wide gene expression and changes in hormones and peel pigments between fruits of Shatangju mandarin (Citrus reticulata Blanco, designated WT) and its natural mutant, Yuenongwanju (designated MT). The MT fruit matures ~2 months later than the WT fruit. Significant differences in fruit diameter, total soluble solids, titratable acid content, chlorophylls and carotenoids were detected between the fruits of the two genotypes at the sampled time points. Genome-wide transcriptome profiling showed that many genes involved in auxin and ABA metabolism and/or signaling pathways were differentially expressed between the MT and the WT fruits. Importantly, the expression of CrYUCCA8 was significantly lower and the expression of CrNCED5 was significantly higher in WT than in MT fruits at 230 and 250 DPA, respectively. In addition, the indole-3-acetic acid (IAA) level in the MT fruit was significantly higher than that in the WT counterpart, whereas a significantly lower level of ABA was detected in the mutant. Treatment of the WT fruit with exogenous IAA significantly delayed fruit maturation. Our results provide experimental evidence supporting the notion that auxin is a negative regulator of fruit maturation in citrus.


The Chemical Profile, and Antidermatophytic, Anti-Inflammatory, Antioxidant and Antitumor Activities of Withania chevalieri A.E. Gonç. Ethanolic Extract.
Withania chevalieri, endogenous from Cape Verde, is a medicinal plant used in ethnomedicine with a large spectrum of applications, such as treating skin fungal infections caused by dermatophytes. The aim of this work was to chemically characterize the W. chevalieri crude ethanolic extract (WcCEE), and evaluate its bioactivities as antidermatophytic, antioxidant, anti-inflammatory and anticancer, as well as its cytotoxicity. WcCEE was chemically characterized via HPLC-MS. The minimal inhibitory concentration, minimal fungicidal concentration, time-kill and checkerboard assays were used to study the antidermatophytic activity of WcCEE. As an approach to the mechanism of action, the cell wall components, β-1,3-glucan and chitin, and cell membrane ergosterol were quantified. Transmission electron microscopy (TEM) allowed for the study of the fungal ultrastructure. WcCEE contained phenolic acids, flavonoids and terpenes. It had a concentration-dependent fungicidal activity, not inducing relevant resistance, and was endowed with synergistic effects, especially terbinafine. TEM showed severely damaged fungi; the cell membrane and cell wall components levels had slight modifications. The extract had antioxidant, anti-inflammatory and anti-cancer activities, with low toxicity to non-tumoral cell lines. The results demonstrated the potential of WcCEE as an antidermatophytic agent, with antioxidant, anti-inflammatory and anticancer activity, to be safely used in pharmaceutical and dermocosmetic applications.


Improving the Performance of Hybrid Functional-Based Molecular Dynamics Simulation through Screening of Hartree-Fock Exchange Forces.
Density functional theory-based molecular dynamics calculations of condensed phase systems often benefit from the use of hybrid functionals. However, their use is computationally very demanding and severely limits the system size and time scale that can be simulated. Several methods have been introduced to accelerate hybrid functional molecular dynamics including Schwarz screening and the auxiliary density matrix method (ADMM). Here we present a simple screening scheme that can be applied in addition to these methods. It works by examining Hartree-Fock exchange (HFX) integrals and subsequently excluding those that contribute very little to any nuclear force component. The resultant force error is corrected by a history-dependent extrapolation scheme. We find that for systems where the calculation of HFX forces is a major bottleneck, a large fraction of the integrals can be neglected without introducing significant errors in the nuclear forces. For instance, for a 2 × 2 × 2 unit cell of CoO, 92% of the HFX integrals that have passed Schwarz screening within the ADMM approach can be neglected leading to a performance gain of a factor of 3 at a negligible error in nuclear forces (≤5 × 10-4 H bohr-1). We also show that total energy conservation and solvation structures are not adversely affected by the screening method.


Repression of phosphatidylinositol transfer protein α ameliorates the pathology of Duchenne muscular dystrophy.
Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by X-linked inherited mutations in the DYSTROPHIN (DMD) gene. Absence of dystrophin protein from the sarcolemma causes severe muscle degeneration, fibrosis, and inflammation, ultimately leading to cardiorespiratory failure and premature death. Although there are several promising strategies under investigation to restore dystrophin protein expression, there is currently no cure for DMD, and identification of genetic modifiers as potential targets represents an alternative therapeutic strategy. In a Brazilian golden retriever muscular dystrophy (GRMD) dog colony, two related dogs demonstrated strikingly mild dystrophic phenotypes compared with those typically observed in severely affected GRMD dogs despite lacking dystrophin. Microarray analysis of these "escaper" dogs revealed reduced expression of phosphatidylinositol transfer protein-α (PITPNA) in escaper versus severely affected GRMD dogs. Based on these findings, we decided to pursue investigation of modulation of PITPNA expression on dystrophic pathology in GRMD dogs, dystrophin-deficient sapje zebrafish, and human DMD myogenic cells. In GRMD dogs, decreased expression of Pitpna was associated with increased phosphorylated Akt (pAkt) expression and decreased PTEN levels. PITPNA knockdown by injection of morpholino oligonucleotides in sapje zebrafish also increased pAkt, rescued the abnormal muscle phenotype, and improved long-term sapje mutant survival. In DMD myotubes, PITPNA knockdown by lentiviral shRNA increased pAkt and increased myoblast fusion index. Overall, our findings suggest PIPTNA as a disease modifier that accords benefits to the abnormal signaling, morphology, and function of dystrophic skeletal muscle, and may be a target for DMD and related neuromuscular diseases.


Random regression models using Legendre orthogonal polynomials to evaluate the milk production of Alpine goats.
The objective of this study was to identify the best random regression model using Legendre orthogonal polynomials to evaluate Alpine goats genetically and to estimate the parameters for test day milk yield. On the test day, we analyzed 20,710 records of milk yield of 667 goats from the Goat Sector of the Universidade Federal de Viçosa. The evaluated models had combinations of distinct fitting orders for polynomials (2-5), random genetic (1-7), and permanent environmental (1-7) fixed curves and a number of classes for residual variance (2, 4, 5, and 6). WOMBAT software was used for all genetic analyses. A random regression model using the best Legendre orthogonal polynomial for genetic evaluation of milk yield on the test day of Alpine goats considered a fixed curve of order 4, curve of genetic additive effects of order 2, curve of permanent environmental effects of order 7, and a minimum of 5 classes of residual variance because it was the most economical model among those that were equivalent to the complete model by the likelihood ratio test. Phenotypic variance and heritability were higher at the end of the lactation period, indicating that the length of lactation has more genetic components in relation to the production peak and persistence. It is very important that the evaluation utilizes the best combination of fixed, genetic additive and permanent environmental regressions, and number of classes of heterogeneous residual variance for genetic evaluation using random regression models, thereby enhancing the precision and accuracy of the estimates of parameters and prediction of genetic values.


Genicular nerve block for emergency department patient: a successful management of subacute osteoarthritic knee pain.
The genicular nerve block (GNB) performed under ultrasound is a common procedure in the perioperative and outpatient setting for the treatment of surgical knee pain and osteoarthritis. It provides motor-sparing analgesia to the knee, making it a potential alternative to other modes of pain management in the emergency department (ED). We present an elderly woman with acute-on-chronic osteoarthritic knee pain which was relieved for a week after a GNB during her ED visit. In patients with knee pain, the ultrasound guided GNB has the potential to provide short-term analgesia for patients with pain refractory to other modes of analgesia. The GNB shows promise as a reliable contribution to a multimodal approach to pain management in the ED setting.


When Gist and Familiarity Collide: Evidence From False Recognition in Younger and Older Adults.
Aging is associated with decreased recollection required to offset misleading effects of familiarity, as well as an increased mnemonic reliance on gist-based over detail-based information. We tested the novel hypothesis that age-related decrements in overriding familiarity can be eliminated under conditions in which gist-based information facilitates retrieval. Twenty-seven younger adults and 27 older adults viewed scenes from two categories in an incidental encoding phase. In a recognition phase, old scenes were intermixed with new scenes from the studied categories and an unstudied category, with each new scene reappearing after 4, 18, or 48 intervening scenes. Participants were to respond "yes" to old scenes, and "no" to new scenes, including their repetitions. Despite encoding the scenes similarly, older adults made more false endorsements of new and repeated new scenes from studied categories. Both groups, however, were equally unlikely to falsely recognize new and repeated new scenes from the unstudied category. When helpful gist and misleading familiarity collide, gist wins, and eliminates age-related increases in false recognition.


Role of major histocompatibility complex class I molecules in autoimmune myositis.
Recent work has continued to clarify the role of major histocompatibility complex class I in the pathogenesis of autoimmune myositis. In the past year, several new observations have been made in this area. This review describes these findings and discusses their relevance to the pathogenesis of autoimmune myositis. Recent studies have confirmed earlier observations of the up-regulation of major histocompatibility complex class I antigens in myositis. In particular, a recent study has strengthened the conclusion that major histocompatibility complex class I expression is highly specific to inflammatory myopathies and may be of diagnostic value. Two new studies have indicated that endoplasmic reticulum stress response pathway (the endoplasmic reticulum overload [NF-kB] and unfolded protein response [GRP78]) are highly activated in patients with myositis. One study using transgenic mice has further indicated that abnormal accumulation of major histocompatibility complex class I in the endoplasmic reticulum of muscle may be responsible for the initiation of this endoplasmic reticulum stress response. Furthermore, studies of normal muscle cells have shown that endoplasmic reticulum stress also plays an important role in skeletal muscle development. Investigations of autoantigen expression in myositis biopsies have revealed that regenerating muscle cells express high levels of autoantigens and major histocompatibility complex class I, indicating that these cells are the targets of cytotoxic T-cell attack and may participate in the initiation of a myositis-specific autoimmune response. Defining the role of major histocompatibility complex class I in autoimmune myositis may be useful not only for diagnosis of this group of diseases but also for therapeutic opportunities for these difficult disorders.


Effect of Prebiotic Dietary Supplement Acacia senegal on Hormonal and Metabolic Markers in Polycystic Ovary Syndrome Patients: A Pilot Study.
Background The most prevalent endocrine condition affecting women of reproductive age is polycystic ovarian syndrome (PCOS), which is linked to a variety of metabolic abnormalities. Although the pathogenesis of PCOS is not fully understood, it is known that oxidative stress, altered gut microbiome, and increased gonadotrophin-releasing hormone play a significant role. Gum arabic (GA) is an edible, dried, gummy exudate from the Acacia senegal tree, well-known for its prebiotic and antioxidant effects. The main objective of the study was to assess the changes in hormonal and metabolic profiles in PCOS patients after the ingestion of gum arabic. Method This was a clinical trial conducted on fifteen patients suffering from PCOS, with a mean age of 27.8 years (20-39 years). All patients experienced irregular cycles. Hormonal and metabolic markers (follicular stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), fasting insulin, total cholesterol (TC), and glycosylated hemoglobin (HBA1c) were measured before and after the ingestion of gum arabic (30 g/day of GA dissolved in 250 ml water for eight weeks) on the second day of the menstrual cycle after granting ethical approval from the National Medicine and Poisons Board and from the participants of the study. Results The study demonstrated a significant decrease in the luteinizing hormone level, FSH/LH ratio, and cholesterol pre- and post-gum arabic ingestion (p-values 0.001, 0.013, and 0.007, respectively). Follicular stimulating hormone slightly reduced post-ingestion with no significant difference (p-value 0.414). No significant changes were seen in the testosterone, insulin, or HBA1c levels. Conclusion The study concluded that gum arabic ingestion for eight weeks decreases the luteinizing hormone and LH/FSH ratio and improves the metabolic profile by reducing the cholesterol level in PCOS patients.


Vogt-Koyanagi-Harada's syndrome and its multisystem involvement.
Vogt-Koyanagi-Harada's syndrome is a rare disease that affects tissues containing melanocytes, such as the eyes, central nervous system, inner ear and skin. Some ethnic groups have a higher probability of developing the disease, including Asians, Indians and Latin Americans and females are affected more often. Literature was reviewed in books, articles published on the internet and papers available in the online databases MEDLINE, LILACS and SciELO. Texts were selected that focused on otorhinolaryngological symptoms. The disease probably has autoimmune etiology, with aggression occurring on the surface of melanocytes by promoting inflammatory reaction in which T lymphocytes predominate. The allele most often found in association with this disease is HLA DRB1*0405. Clinical manifestations are divided into four stages: prodromal, uveitic, chronic and recurrent. Otorhinolaryngological symptoms occur during the uveitic stage and are characterized by bilateral sensorineural hearing loss, tinnitus and vestibular symptoms. Diagnosis is made according to the diagnostic criteria for the disease. Treatment is primarily with corticosteroids. It is important that professionals in other specialties are able to recognize Vogt-Koyanagi-Harada's syndrome, because late diagnosis can lead to ocular and cutaneous sequelae.


Strategies for the Diversity-Oriented Synthesis of Macrocycles.
Macrocycles have long been recognized as useful chemical entities for medicine, with naturally occurring and synthetic macrocycles clinically approved for use as prescription drugs. Despite this promise, the synthesis of collections of macrocycles has been historically challenging due to difficulties in the formation of large rings. Diversity-Oriented Synthesis (DOS) emerged in the early 2000s as a powerful strategic solution to the construction of diverse molecular libraries. This review details the various strategies developed within the field of DOS for the synthesis of macrocycle libraries, utilizing modern synthetic methodology to deliver structurally diverse collections of macrocyclic molecules, and the exploration of their therapeutic potential. Section 1 of this work details the use of algorithmic strategies and is divided into Build/Couple/Pair, Advanced Build/Couple/Pair, Initiate/Propagate/Terminate, Fragment-Based Domain Shuffling, Two-Directional Synthesis, and Successive Ring Expansion. Section 2 covers strategies based on ring distortion reactions, including Sequential Cycloaddition/Fragmentation, Ring Expansions, and Miscellaneous.


How I treat gastrointestinal bleeding in congenital and acquired von Willebrand disease.
Gastrointestinal (GI) bleeding is distinctive of severe von Willebrand disease (VWD), generally arising in older patients; in most cases, blood transfusion and hospitalization are required. The presence of arteriovenous malformations is often described when endoscopic examinations are performed. Patients with congenital type 3, 2A, and 2B are those most frequently affected by this symptom, possibly due to the loss of high-molecular-weight multimers of von Willebrand factor (VWF). GI bleeding can also occur in patients affected by acquired von Willebrand syndrome. Endoscopic examination of the GI tract is necessary to exclude ulcers and polyps or cancer as possible causes of GI bleeding. In congenital VWD, prophylaxis with VWF/factor VIII concentrates is generally started after GI-bleeding events, but this therapy is not always successful. Iron supplementation must be prescribed to avoid chronic iron deficiency. Possible rescue therapies (high-dose statins, octreotide, thalidomide, lenalidomide, and tamoxifen) were described in a few case reports and series; however, surgery may be necessary in emergency situations or if medical treatment fails to stop bleeding. In this article, we present several clinical cases that highlight the clinical challenges of these patients and possible strategies for their long-term management.


The La autoantigen is a malignancy-associated cell death target that is induced by DNA-damaging drugs.
To evaluate the La autoantigen as a target for specific monoclonal antibody (mAb) binding in dead cancer cells after use of DNA-damaging chemotherapy. In vitro studies of La-specific 3B9 mAb binding to malignant and normal primary cells with and without cytotoxic drug treatment were done using immunoblotting and flow cytometry. Chromatin-binding studies and immunofluorescence detection of gammaH2AX as a marker of DNA double-stranded breaks together with 3B9 binding assays were done to measure DNA damage responses. Incorporation of a transglutaminase 2 (TG2) substrate and TG2 inhibition were studied to measure protein cross-linking in dead cells. La was overexpressed in human cancer cell lines with respect to normal primary cells. Within 3 h of the DNA-damaging stimulus, La became chromatin bound when it colocalized with gammaH2AX. Later, after the stimulus produced cell death, La-specific 3B9 mAb bound specifically and preferentially in the cytoplasm of dead cancer cells. Moreover, 3B9 binding to dead cancer cells increased with increasing DNA damage. Both La and 3B9 became cross-linked in dead cancer cells via TG2 activity. La autoantigen represents a promising cancer cell death target to determine chemotherapy response because its expression was selectively induced in dead cancer cells after DNA-damaging chemotherapy.


Overview of a system for the computer-assisted operation of a small animal inhalation facility.
Automatic monitoring of the concentration of test gases and other environmental variables in small animal inhalation exposure chambers, coupled with computing capability and feedback control of the concentration of test gas, allows almost fully automatic operation of the chambers with a minimal amount of human intervention. Time-varying exposure profiles may be generated repeatedly with great accuracy, thus allowing a more realistic simulation of real-life exposures than is approached by operating chambers manually at ostensibly constant concentrations of test gases. Carefully conducted, pre-experimental calibration procedures are performed, and daily calibration checks allow statistical control of daily chamber operation and longer term quality control. At the conclusion of each experiment the investigator is supplied with records that document chamber conditions that have been monitored throughout the entire experiment, with estimates of the accuracy that was achieved in creating the specified exposure profile. A purpose of this report is to help to bridge the gap between the practicing inhalation toxicologist and the engineer in order to encourage their cooperation and mutual understanding of the technical problems involved in developing computer-assistance packages for inhalation facilities.


Sialolith characterization by scanning electron microscopy and X-ray photoelectron spectroscopy.
The objective of this study has been to characterize sialolith, a calcium phosphate deposit that develops in the human oral cavity, by high-resolution field emission scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS). The morphological and chemical data obtained helped in the determination of their formation mechanism in salivary glands. Sialoliths in the submandibular salivary glands may arise secondary to sialodenitis, but not via a luminal organic nidus. We believe this is the first study that characterizes a sialolith by XPS.


Calcineurin inhibitors in liver transplantation - still champions or threatened by serious competitors?
Current strategies for immunosuppression in liver transplant (LT) recipients include the design of protocols targeting a more individualized approach to reduce risk factors such as renal failure, cardiovascular complications and malignancies. Renal injury in LT recipients may be often multifactorial and is associated with increased risk of post-transplant morbidity and mortality. The quest for low toxicity immunosuppressive regimens has been challenging and resulted in CNI minimization protocols or CNI withdrawal and conversion to mycophenolate mofetil (MMF) and/or mammalian target of rapamycin inhibitor-based immunosuppressive regimens. Use of antibody induction to delay CNI administration may be an option in particular in immunocompromized, critically ill patients with high MELD scores. Protocols including MMF introduction and concomitant CNI minimization have the potential to recover renal function even in the medium and long term after LT. We review on hot topics in the prevention and management of acute and chronic renal injury in LT patients. For this purpose, we present and critically discuss results from immunosuppressive studies published in the current literature or presented at recent LT meetings.


Barriers to effective cancer pain management: a survey of hospitalized cancer patients in Australia.
The purpose of this study was to examine attitudinal barriers to effective pain management in a consecutively recruited cohort of 114 cancer patients from four Australian hospitals. When surveyed, 48% of this sample reported experiencing pain within the previous 24 hours. Of these, 56% reported this pain to be "distressing, horrible or excruciating," with large proportions indicating that this pain had affected their movement, sleep and emotional well-being. Three factors were identified as potentially impacting on patients' responses to pain-poor levels of patient knowledge about pain, low perceived control over pain, and a deficit in communication about pain. A trend for older patients to experience more severe pain was also identified. These older patients reported being more willing to tolerate pain and perceive less control over their pain. Suggestions are made for developing patient education programs and further research using concepts drawn from broader social and behavioral models.


Induction of granuloma-dependent angiotensin-converting enzyme and eosinophil chemotactic factor in the skin of athymic nude mice.
Activities of angiotensin-converting enzyme (ACE), other proteinases, and eosinophil chemotactic factor (ECF-G) are known to be elevated in hepatic hypersensitivity granulomas of thymus intact (nu/+) mice after Schistosoma mansoni infection. The enzyme activities also increase, but to a lesser degree in hepatic granulomas of athymic nude (nu/nu) mice, and ECF-G is not detectable. In this study isolated hepatic granulomas from nu/+ mice were grafted into the skin of uninfected nu/nu mice, and changes in those cellular functions were determined to examine whether the newly formed granulomas by recipient nu/nu cells acquire the functional activities as well as the histological appearance of nu/+ granulomas. ACE and ECF-G rapidly disappeared from grafted sites during the first 5 days, corresponding to loss of nu/+ cells from the graft. Reduction in activities of arylsulfatases, lysozyme, and acid phosphatase also occurred, but to a lesser extent. Recovery of ACE and ECF-G activities to the levels seen in nu/+ hepatic granulomas was observed by 14 days after grafting when nu/nu cells had accumulated in the grafts and formed new granulomas. Other enzymes increased to approximately half the levels seen in grafted donor granulomas. Circulating eosinophilia also increased. The findings indicate that nu/nu cells that accumulated in the skin grafts not only morphologically mimicked nu/+ type granulomas but also demonstrated nu/+ levels of cellular function. Analysis of skin granulomas developing in nu/+ mice after grafting of nu/+ hepatic granulomas showed the similar histology and enzymatic changes, whereas the skin sites inoculated with purified schistosome eggs alone caused neither significant histological changes nor elevation of ACE activity.


Investigating the Mechanism of Reversible Lithium Insertion into Anti-NASICON Fe2(WO4)3.
The gram-scale preparation of Fe2(WO4)3 by a new solution-based route and detailed characterization of the material are presented. The resulting Fe2(WO4)3 undergoes a reversible electrochemical reaction against lithium centered around 3.0 V with capacities near 93% of the theoretical maximum. Evolution of the Fe2(WO4)3 structure upon lithium insertion and deinsertion is probed using a battery of characterization techniques, including in situ X-ray diffraction, neutron total scattering, and X-ray absorption spectroscopy (XAS). A structural transformation from monoclinic to orthorhombic phases is confirmed during lithium intercalation. XAS and neutron total scattering measurements verify that Fe2(WO4)3 consists of trivalent iron and hexavalent tungsten ions. As lithium ions are inserted into the framework, iron ions are reduced to the divalent state, while the tungsten ions are electrochemically inactive and remain in the hexavalent state. Lithium insertion occurs via a concerted rotation of the rigid polyhedra in the host lattice driven by electrostatic interactions with the Li+ ions; the magnitude of these polyhedral rotations was found to be slightly larger for Fe2(WO4)3 than for the Fe2(MoO4)3 analog.


Regulation of the Notch signaling pathway by natural products for cancer therapy.
The Notch signaling pathway is an evolutionarily conserved pathway that modulates normal biological processes involved in cellular differentiation, apoptosis, and stem cell self-renewal in a context-dependent fashion. Attributed to its pleiotropic physiological roles, both overexpression and silencing of the pathway are associated with the emergence, progression, and poorer prognosis in various types of cancer. To decrease disease incidence and promote survival, targeting Notch may have chemopreventive and anti-cancer effects. Natural products with profound historical origins have distinguished themselves from other therapies due to their easy access, high biological compatibility, low toxicity, and reliable effects at specific physiological sites in vivo. This review describes the Notch signaling pathway, particularly its normal activation process, and some main illnesses related to Notch signaling pathway dysregulation. Emphasis is placed on the effects and mechanisms of natural products targeting the Notch signaling pathway in diverse cancer types, including curcumin, ellagic acid (EA), resveratrol, genistein, epigallocatechin-3-gallate (EGCG), quercetin, and xanthohumol and so on. Existing evidence indicates that natural products are feasible solution to fight against cancer by targeting Notch signaling, either alone or in combination with current therapeutic agents.


Cell-cell communication in diabetic retinopathy.
In diabetic retinopathy, high glucose (HG)-mediated breakdown in cell-cell communication promotes disruption of retinal homeostasis. Several studies indicate that HG condition alters expression of connexin genes and subsequent gap junction intercellular communication (GJIC) in retinal vascular cells and non-vascular cells. A serious consequence of disrupted cell-cell communication is apoptosis and breakdown of the blood-retinal barrier (BRB). More recently, studies suggest adverse effects from HG on retinal Müller cells. This article focuses on HG-mediated changes in connexin expression and GJIC and their subsequent effects on the breakdown of retinal homeostasis, cell death, compromised vascular permeability, and interactions between endothelial cells, pericytes and retinal Müller cells in the pathogenesis of diabetic retinopathy. Additionally, options for rectifying disrupted homeostasis under HG condition associated with diabetic retinopathy are reviewed.


Selective activation of A3 adenosine receptors with N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide protects against myocardial stunning and infarction without hemodynamic changes in conscious rabbits.
To examine the cardioprotective role of A3 adenosine receptors during myocardial ischemia/reperfusion injury, we tested the effect of N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA), a potent and selective A3 adenosine receptor agonist, in models of myocardial stunning and infarction in chronically instrumented conscious rabbits. In phase I (studies of myocardial stunning), rabbits were subjected to six 4-minute coronary occlusions, each separated by 4-minute reperfusion periods, after which the recovery of systolic wall thickening was measured (ultrasonic crystals). In phase II (studies of myocardial infarction), rabbits were subjected to a 30-minute coronary occlusion followed by 3 days of reperfusion. In both phases, IB-MECA was administered as an intravenous bolus (100 micrograms/kg) 10 minutes before the first coronary occlusion. This dose of IB-MECA was determined in pilot studies to have no effect on heart rate, arterial blood pressure, or plasma histamine concentration in rabbits. In phase I, IB-MECA markedly improved the recovery of wall thickening after the six occlusion/reperfusion cycles, and this effect was sustained throughout the 5-hour observation period; the total deficit of wall thickening (a measure of the overall severity of myocardial stunning) was reduced by 68% (control, 129 +/- 16 arbitrary units, n = 7; IB-MECA, 41 +/- 6 arbitrary units, n = 6; P < .01). The protective effects of IB-MECA against stunning were completely blocked by pretreatment with the nonselective adenosine receptor antagonist 8-p-sulfophenyl theophylline or the specific protein kinase C inhibitor chelerythrine. In phase II, IB-MECA reduced myocardial infarct size by 61%; infarct size (tetrazolium staining) was 41 +/- 4% of the risk region in control animals (n = 8) and 16 +/- 6% in IB-MECA-treated animals (n = 8, P < .01). These results demonstrate that in conscious rabbits the A3 adenosine receptor agonist IB-MECA confers a powerful protection against both reversible (stunning) and irreversible (infarction) injury during acute myocardial ischemia and reperfusion by a protein kinase C-mediated pathway, suggesting that selective activation of A3 receptors is an effective means of protecting the ischemic myocardium without hemodynamic changes.


β-Carotene suppresses osteoclastogenesis and bone resorption by suppressing NF-κB signaling pathway.
β-Carotene is a natural anti-oxidant, which has been used for treatment of cancer and cardiovascular diseases. Recently, the ameliorating function of β-carotene in osteoporosis has been implicated. However, the precise mechanism of β-carotene in prevention and treatment of osteoporosis is largely unknown. In the present study, we aimed to elucidate how β-carotene affects osteoclast formation and bone resorption. Bone marrow-derived monocytes/-macrophages (BMM) were exposed to 0.05, 0.1, 0.2, 0.4 and 0.6μM β-carotene, followed by evaluation of cell viability, lactate dehydrogenase (LDH) release, receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and resorption pits formation. Key factors in nuclear factor kappa B (NF-ĸB) and mitogen-activated protein kinases (MAPK) pathways were evaluated with western blot after BMM cells were exposed to RANKL and β-carotene. The effects of β-carotene in nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos and cathepsin K (CTSK) expression were also evaluated. β-Carotene significantly inhibited BMM viability and promoted LDH release at concentrations of 0.4 and 0.6μM. A decrease in RANKL-induced osteoclastogenesis and resorption was also observed after β-carotene treatment. β-Carotene attenuated the NF-ĸB pathway activation by RANKL, with no effect on MAPK pathway. β-Carotene suppressed the upregulation of NFATc1 and c-Fos by RANKL. We clarified the anti-osteoclastogenic role of β-carotene, which is mediated by NF-κB signaling.


The significance of suicide notes in the elderly.
Suicide notes are traditionally considered as markers of the severity of the suicide attempt and are said to provide valuable insight into the thinking of suicide victims before the fatal act. Few studies have described the characteristics of elderly suicide note-writers and their final thoughts. This study is a retrospective view of suicide notes obtained from coroners' records of all elderly suicides in Cheshire over a period of 10 years, 1989-1998. Out of 125 suicides, 54 (43%) had suicide notes, which were reported in the coroner's records. Of these there were 31 (57%) male and 23 (43%) female subjects. Elderly suicide note-leavers were more likely to be unknown to psychiatric services (p < 0.01) and to have used a non-violent method of suicide (p < 0.01). Sex, marital status, social isolation, mental or physical morbidity did not appear to be linked with leaving a suicide note. More cases that took an overdose, used plastic bags, electrocuted themselves, or used car exhaust also left suicide notes. Those who died by more violent means such as hanging, drowning, jumping from height, immolation or wounding appeared less likely to have left a suicide note. No statistically significant difference in the content of the suicide notes was observed in relation to sex or age. Many elderly are isolated and may have no one to write a note to, while others have lost the ability to express themselves. Therefore, it is not possible to say that the different incidence of note leaving observed for suicide was due to differing levels of suicidal intent. Although only a proportion of elderly suicide victims leave suicide notes, the absence of a suicide note must not be considered an indicator of a less serious attempt.


Radiation-induced osteosarcoma of the maxilla.
Radiation-induced sarcomas are well-known though uncommon potential late sequelae of radiation therapy. We report irradiation-induced osteosarcoma involving the maxilla following treatment of nasopharyngeal carcinoma in a 44-year-old man who presented with painful cheek swelling. Radiographs and computed tomography showed a large destructive lesion of the left maxilla. Diagnosis of osteosarcoma was confirmed by excision biopsy.


Characterization of metabolite profiles of leaves of bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea L.).
Leaves of bilberry (Vaccinium myrtillus L.) and lingonberry (Vaccinium vitis-idaea L.) are potential raw materials for food and health care products. Targeted (HPLC-DAD, HPLC-MS, and GC-FID) and nontargeted ((1)H NMR) approaches were applied to study the metabolomic profiles of these leaves. Chlorogenic acid was the major phenolic compound in bilberry leaves and arbutin in lingonberry leaves. Flavonol glycosides were another major group of phenolics in bilberry [5-28 mg/g DM (dry mass)] and lingonberry (15-20 mg/g DM) leaves. Contents of fatty acids were analyzed using GC-FID. The changes in the metabolomics profile during the season were apparent in bilberry but not lingonberry leaves. Negative correlation was found between the contents of lipids and phenolics. The consistency between the key results obtained by targeted and nontargeted analyses suggests nontargeted metabolomic analysis is an efficient tool for fast screening of various leaf materials.


Optimization of the Extraction from Spent Coffee Grounds Using the Desirability Approach.
The purpose of this work was the optimization of the extraction from spent coffee grounds, specifically 100% Arabica coffee blends, using a desirability approach. Spent coffees were recovered after the preparation of the espresso coffee under the typical conditions used in coffee bars with a professional machine. Spent coffee was subjected to different extraction procedures in water: by changing the extraction temperature (60, 80, or 100 °C) and the solvent extraction volume (10, 20, 30 mL for 1 gram of coffee) and by maintaining constant the extraction time (30 minutes). The ranges of the process parameters, as well as the solvent to be used, were established by running preliminary experiments not reported here. The variables of interest for the experimental screening design were the content of caffeine, trigonelline, and nicotinic acid, quantitatively determined from regression lines of standard solutions of known concentrations by a validated HPLC-VWD method. Since solvent extraction volumes and temperatures were revealed to be the most significant process variables, for the optimization of the extraction process, an approach based on Response Surface Methodology (RSM) was considered. In particular, a Box-Wilson Central Composite Design, commonly named central composite design (CCD), was used to find the optimal conditions of the extraction process. Moreover, the desirability approach was then applied to maximize the extraction efficiency by searching the optimal values (or at least the best compromise solution) for all three response variables simultaneously. Successively, the best extract, obtained in a volume of 20 mL of water at an extraction temperature of 80 °C, was analyzed for total phenol content (TPC) through the Folin-Ciocalteu assay, and the antioxidant capacities (AC) through the trolox equivalent (TE) antioxidant capacity (DPPH), ferric-ion reducing antioxidant parameter (FRAP), and radical cation scavenging activity and reducing power (ABTS). The TPC and the AC for spent coffee were high and comparable to the results obtained in previous similar studies. Then, the extract was evaluated by inductively coupled plasma mass spectrometry (ICP-MS), revealing that potassium was the most abundant element, followed by phosphorus, magnesium, calcium, sodium, and sulfur, while very low content in heavy metals was observed. Preliminary in vitro assays in keratinocyte HaCaT cells were carried out to assess the safety, in terms of cytotoxicity of spent coffee, and results showed that cell viability depends on the extract concentration: cell viability is unmodified up to a concentration of 0.3 mg/mL, over which it becomes cytotoxic for the cells. Spent coffee extract at 0.03 and 0.3 mg/mL showed the ability to reduce intracellular reactive oxygen species formation induced by hydrogen peroxide in HaCaT cells, suggesting its antioxidant activity at intracellular levels.


Left-Sided Amyand's Hernia: A Rare Variant of Inguinal Hernia.
Inguinal hernia is the most commonly diagnosed hernia, with approximately one out of every three males eventually being diagnosed with an inguinal hernia. Amyand's hernia is a subtype of an inguinal hernia that occurs when the appendix is located within the hernia sac. It is an uncommon condition that is usually discovered as an incidental finding in less than 1% of all patients with inguinal hernia. The management options for this condition will vary depending on the presence or absence of appendicitis. This case report highlights a rare occurrence where a patient with a left-sided scrotal swelling was found to have a left-sided Amyand's hernia that was eventually managed without complications.


Pre-activation-based one-pot synthesis of an alpha-(2,3)-sialylated core-fucosylated complex type bi-antennary N-glycan dodecasaccharide.
Synthesis of N-glycans is of high current interests due to their important biological properties. A highly efficient convergent strategy based on the pre-activation method for assembly of the complex type core fucosylated bi-antennary N-glycan dodecasaccharide has been developed. Retrosynthetically, this extremely challenging target is broken down to three modules: a sialyl disaccharide, a glucosamine building block and a hexasaccharide diol acceptor. The sialyl disaccharide was easily obtained by selective activation of a new 5-N-trichloroacetyl protected sialyl donor in the presence of a thiogalactoside acceptor. The hexasaccharide diol module was produced by double mannosylation of a fucosylated tetrasaccharide acceptor, which in turn was generated by glycosylation of a alpha-fucosylated disaccharide with a beta-mannose containing disaccharide donor. The union of the three modules was performed in one-pot giving the fully protected dodecasaccharide in high yield. This synthesis is characterized by minimum protective group and aglycon adjustment on oligosaccharide intermediates, thus greatly enhancing the overall synthetic efficiency. The modular feature of this strategy suggests that this method can be readily adapted to the synthesis of a wide variety of N-glycan structures.


The influence of probiotics for preterm neonates on the incidence of atopic dermatitis-results from a historically controlled cohort study.
Probiotic supplementation is a promising preventive strategy for atopic dermatitis (AD). To help clarifying the significance of timing with respect to prevention of AD, we here evaluate the benefit of prophylactic use of probiotic supplementation in neonates younger than 30 weeks of gestation. Preterm children from the Department of Neonatology, Rigshospitalet, Denmark from two different admission periods were included in a historically controlled cohort study. Neonates from January 2007 to February 2010, not treated with and neonates from March 2010 to February 2013 treated with probiotic were enrolled. Main outcome was prevalence of AD, and secondary outcomes were use of topical corticosteroids, and number of skin-related visits to GPs and dermatologists. 527 preterm neonates were included in the study, 249 treated and 278 not treated with probiotics. Response rate for the two cohorts was 76.7 and 77.7% respectively. The prevalence of AD was similar in the two groups (20.9% in the probiotic treated group versus 17.1% in the not treated group, p = 0.33). No significant differences were found between the groups with respect to treatment with topical corticosteroids, or visits at GPs or dermatologist. We found no indication that probiotics may prevent AD when administered to neonates <30 gestation weeks from birth until discharge home. Factors influencing the early maturation of the immune system have been assumed to be of particular importance in atopic dermatitis, and hence, our unique cohorts contribute information on how probiotic supplementation may affect the extremely immature immune systems of preterm infants.


Cerebellar continuous theta burst stimulation in essential tremor.
The pathophysiological mechanisms of essential tremor (ET) are still not entirely clear. In the present study, we aimed to investigate the cerebello-thalamo-cortical connectivity in ET using the cerebellar continuous theta burst stimulation (cTBS) and possible effects on tremor and reaching movements. Sixteen patients with ET and 11 healthy subjects underwent two experimental sessions: (i) cTBS over the right cerebellar hemisphere (real cerebellar cTBS) and (ii) cTBS over the neck muscles (sham cerebellar cTBS). The two sessions were performed at least 1 week apart. The effects of real and sham cerebellar cTBS were quantified as excitability changes on contralateral primary motor cortex, as well as possible changes of postural tremor and reaching movements on the ipsilateral arm. Primary motor cortex excitability was assessed by recording the input/output curve of the motor-evoked potentials from the right first dorsal interosseous muscle. Tremor was rated clinically. Objective assessment of tremor and reaching movements was performed using kinematic techniques. Real cerebellar cTBS reduced the excitability in the contralateral primary motor cortex in healthy subjects though not in patients with ET. There was no significant change in tremor severity and reaching movements, as assessed by clinical examination or kinematic techniques, after real or sham cerebellar cTBS in patients with ET. Finally, there was no correlation between individual changes of M1 excitability and kinematic measures of tremor and reaching movement abnormalities in patients with ET. The results suggest that functional cerebello-thalamo-cortical connectivity tested by cTBS is abnormal in ET and that cerebellar cTBS does not ameliorate tremor in this condition.


Development, maturation, and growth of the myodural bridge within the posterior atlanto-axial interspace in the rat.
The myodural bridge (MDB) complex are fibrous bridges that functionally connect the spinal dura mater to the suboccipital musculature. Previously, we described the maturational sequence of the MDB within the posterior atlanto-occipital interspace of the rat. The present paper describes the morphology and developmental maturation of the MDB within the posterior atlanto-axial interspace of the rat. In the present study, E18 embryonic rats, newborn rats, and adult rats were selected to evaluate the development and growth of the MDB. Within the posterior atlanto-axial interspace of the rat, the fibers of the MDB and its associated muscles, in the embryonic rat, were observed to be scarce and lightly stained. In contrast, these same structures observed in the postnatal rat were quite apparent and robustly stained. After birth, it was observed that MDB originated from the rectus capitis dorsal major muscle, extended forward and downward, and finally merged with the posterior atlanto-axial membrane. As the rats developed and matured, the observed MDB fibers passing through the posterior atlanto-axial interspace appeared denser and more organized. This study evidenced that the MDB fibers within the posterior atlanto-axial interspace were primarily composed of type I collagen fibers in the postnatal rat. By observing the suboccipital region, we are able to hypothesize that the MDB complex plays a key role in maintaining the subdural space located within the upper cervical segment during growth and development. This study provides a morphological basis for future research on the function of the MDB complex.


Spin-singlet Quantum Ground State in Zigzag Spin Ladder Cu(CF3 COO)2.
The copper salt of trifluoroacetic acid, Cu(CF3 COO)2 , offers a new platform to investigate the quantum ground states of low-dimensional magnets. In practice, it realizes the ideal case of a solid hosting essentially isolated magnetic monolayers. These entities are constituted by well-separated two-leg half-integer spin ladders organized in a zigzag fashion. The ladders are comprised of dimeric units of edge-sharing tetragonal pyramids coupled through carbon ions. The spin-gap state in this compound was revealed by static and dynamic magnetic measurements. No indications of long range magnetic ordering down to liquid helium temperature were obtained in specific heat measurements. First principles calculations allow estimation of the main exchange interaction parameters, J⊥ =176 K and J∥ =12 K, consistent with the weakly interacting dimers model.


Psychological outcome of injured workers at 3 months after occupational injury requiring hospitalization in Taiwan.
After a traumatic event, a significant proportion of victims develop psychiatric disorders. Trauma has been an important ailment among workers. This study aimed to determine the prevalence of post-traumatic stress disorder (PTSD) and other psychiatric disorders at three months after occupational injuries. Our study candidates were injured workers in Taiwan who were hospitalized for 3 days or longer and received hospitalization benefits from the Labor Insurance program. A two-staged survey study was conducted. A self-reported questionnaire including the Brief Symptom Rating Scale (BSRS-50) and Post-traumatic Symptom Checklist (PTSC) was sent to workers at 3 months after injury. Those who met the criteria were recruited for the second stage phone interview with a psychiatrist using the Mini-international Neuropsychiatrie Interview (MINI). A total of 2001 workers completed the questionnaire (response rate 45.5%). Among them, 357 (17.8%) fulfilled the criteria for the MINI interview and were invited. A total of 148 (41.5%) completed the phone interview. The estimated rates of PTSD, partial PTSD (PPTSD), major depression, comorbid PTSD/PPTSD and major depression, and either PTSD/PPTSD or major depression were 2.7, 4.1, 3.0, 2.3, and 7.5%, respectively. The estimated rates of either PTSD/PPTSD or major depression among workers who suffered from intracranial injury, fracture, burn, crushing injury, and open wound of upper limbs were 10.4, 6.9, 5.9, 5.8 and 0%, respectively. At three months after occupational injuries, a significant proportion of workers suffered from psychiatric disorders. The rates of psychiatric disorders occurring after intracranial injuries were significantly higher than those occurring after non-intracranial injuries.


Intranasal Lidocaine for Acute Management of Primary Headaches: A Systematic Review.
Intranasal lidocaine has been studied and recommended as an alternative in the management of acute headache. The objective of this systematic review was to evaluate the efficacy and safety of intranasal lidocaine in the acute management of primary headaches. The MEDLINE (1946 to May 2018), EMBASE (1974 to May 2018), Cochrane Central Register of Controlled Trials (2008 to May 2018), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to May 2018), and ClincialTrials.gov online databases were searched. Studies conducted in patients with acute primary headache were included if lidocaine was compared with placebo or alternative treatments, lidocaine dosing was specified, and patients' pain before and after treatment were clearly reported. Six studies met the inclusion criteria. Intranasal lidocaine demonstrated potential benefit over placebo in acute pain reduction and need for rescue medication only in the four studies deemed to be of poor quality, not in the two fair-quality studies. No study reported benefit in preventing headache recurrence or repeat visits to the emergency department. Lidocaine was associated with significantly higher rates of adverse events compared with placebo and may result in lower rates of patient satisfaction. There is insufficient evidence to support the use of intranasal lidocaine in acute management of primary headaches. Further research is warranted to better elucidate whether intranasal lidocaine has a role in the management of specific primary headache subtypes and whether there is an optimal regimen.


Occurrence of HLA types in H. influenzae type B disease.
We have studied 50 Caucasoid children under 7 years of age with Haemophilus influenzae b disease. Half of the patients (Group A) had invasive disease shown by positive blood and/or spinal fluid culture. The other half (Group B) had noninvasive disease characterized by fever, nasopharyngitis, negative blood culture, and positive throat culture. Age, number of other siblings under 12 years old in the family, immune response, antibody production and genetic markers were compared in the two groups. Significant difference between the two groups was only seen in their genetic markers. HLA-B12 was present in 52% of Group A patients as opposed to 16% in Group B patients (P less than .01). HLA-Bw40 was present in 24% of group B patients and absent in all Group A patients (P less than .01). These findings would suggest that susceptibility and resistance towards developing invasive type b disease may be genetically determined.


The P2Y nucleotide receptors in the human genome.
Since the first identification of P2Y receptor sequences in 1993, it has quickly become apparent that this family of the G-protein coupled receptors is very diverse. Members of this receptor family are activated extra-cellularly by a wide variety of adenosine and uridine nucleotides including sugar-nucleotides. The recent decipherment of the Human Genome has enabled us to search for new, yet undiscovered P2Y receptor subtypes. In this article we examine the relationships of six orphan G-protein coupled receptor (GPCR) sequences which show considerable sequence homology to various P2Y receptors. The clustering at a few chromosomal loci of P2Y receptor genes and their related orphan genes further suggests that particular P2Y subsets were derived from the same ancestral gene during evolution.


Changes in fine structure and acid phosphatase localization in rat thyroid cells following thyrotropin administration.
Shortly after the administration of 1/40 unit thyrotropin to rats, 24 hours post-hypophysectomy, the following sequence of changes has been observed within thyroid follicular epithelial cells: (1) the appearance of apical cell surface activity consisting of pseudopods projecting into the follicular lumen; (2) apparent phagocytic engulfment of colloid droplets lacking indications of acid phosphatase activity; (3) close association and probable fusion of newly formed colloid droplets and dense granules, the latter cytochemically positive for acid phosphatase activity; (4) the appearance of presumptive acid phosphatase activity within colloid droplets; and, (5) further colloid droplet changes, viz., basipetal migration and decrease in size, accompanied by an increase in density and in demonstrable acid phosphatase activity. These changes appeared to represent the resorption and degradation of follicular colloid. Comparable results were obtained using intact and more heavily stimulated animals. Colloid biosynthesis was tentatively visualized in these cells as a separate mechanism involving small vesicles prominent in the Golgi region and beneath the apical plasma membrane of some, but not all, thyroid follicular cells in each specimen.


Systems biology and birth defects prevention: blockade of the glucocorticoid receptor prevents arsenic-induced birth defects.
The biological mechanisms by which environmental metals are associated with birth defects are largely unknown. Systems biology-based approaches may help to identify key pathways that mediate metal-induced birth defects as well as potential targets for prevention. First, we applied a novel computational approach to identify a prioritized biological pathway that associates metals with birth defects. Second, in a laboratory setting, we sought to determine whether inhibition of the identified pathway prevents developmental defects. Seven environmental metals were selected for inclusion in the computational analysis: arsenic, cadmium, chromium, lead, mercury, nickel, and selenium. We used an in silico strategy to predict genes and pathways associated with both metal exposure and developmental defects. The most significant pathway was identified and tested using an in ovo whole chick embryo culture assay. We further evaluated the role of the pathway as a mediator of metal-induced toxicity using the in vitro midbrain micromass culture assay. The glucocorticoid receptor pathway was computationally predicted to be a key mediator of multiple metal-induced birth defects. In the chick embryo model, structural malformations induced by inorganic arsenic (iAs) were prevented when signaling of the glucocorticoid receptor pathway was inhibited. Further, glucocorticoid receptor inhibition demonstrated partial to complete protection from both iAs- and cadmium-induced neurodevelopmental toxicity in vitro. Our findings highlight a novel approach to computationally identify a targeted biological pathway for examining birth defects prevention.


Dioxygen Activation by Non-Adiabatic Oxidative Addition to a Single Metal Center.
A chromium(I) dinitrogen complex reacts rapidly with O2 to form the mononuclear dioxo complex [Tp(tBu,Me)Cr(V)(O)2] (Tp(tBu,Me) = hydrotris(3-tert-butyl-5-methylpyrazolyl)borate), whereas the analogous reaction with sulfur stops at the persulfido complex [Tp(tBu,Me)Cr(III)(S2)]. The transformation of the putative peroxo intermediate [Tp(tBu,Me)Cr(III)(O2)] (S = 3/2) into [Tp(tBu,Me)Cr(V)(O)2] (S = 1/2) is spin-forbidden. The minimum-energy crossing point for the two potential energy surfaces has been identified. Although the dinuclear complex [(Tp(tBu,Me)Cr)2(μ-O)2] exists, mechanistic experiments suggest that O2 activation occurs on a single metal center, by an oxidative addition on the quartet surface followed by crossover to the doublet surface.


The combination of heteroduplex analysis and protein truncation test for exact detection of the APC gene mutations.
Familial adenomatous polyposis (FAP) is usually associated with mutation in the adenomatous polyposis coli (APC) gene. To examine the occurrence of these mutations in the number of FAP suspected families from the whole Slovakia effectively, we have applied heteroduplex analysis (HDA) and protein truncation test (PTT) for the analyses of 2-5 base pair deletions and point mutations of the APC gene. In the analyzed exon 15 of the APC gene determined by the primers 15Efor-15Grev for HDA and 15ET7-15J3 for PTT more than 70% of mutations should be deletions [3, 12], which are detectable by HDA. In our collection of 5 FAP families mutations in the APC gene were found in families 10, 27 and 41 using HDA. By PTT test the formation of truncated APC protein in FAP families 2, 10, 16 and 27 were revealed. The necessity of combination of at least HDA and PTT techniques for exact detection of APC mutations in analyzed APC region is discussed.


Effect of side and size of graft on surgical outcomes of adult-to-adult live donor liver transplantation.
By virtue of size, the right liver graft has become the workhorse of adult-to-adult live donor liver transplantation (ALDLT). Although favorable results of left liver ALDLT have also been reported, a head-to-head comparison of these 2 graft types both containing the middle hepatic vein had not been made. In this study, we compared the outcomes of 29 right liver and 16 left liver ALDLTs of comparable graft weight to recipient estimated standard liver volume ratio (GW/ESLV, 36.9% and 36.4%, respectively). All liver grafts contained the middle hepatic vein. The Model for End-Stage Liver Disease (MELD) score and urgency for transplantation of both groups were similar. Postoperatively, left liver donors had significantly lower international normalized ratios and serum total bilirubin levels and no complications. Although the rate of return of international normalized ratios for recipients of both groups were comparable, left liver recipients had significantly higher serum total bilirubin and serum aminotransferase levels. Intensive care unit stay of the left liver recipients was longer than that of the right liver recipients (8.5 days versus 4 days, P = 0.007). Hospital mortality was 6.9% (2/29) for the right liver group and 18.8% (3/16) for the left liver group (P = 0.330). Safety profile of donor left hepatectomy was higher. However, despite similar GW/ESLV, the more arduous recovery and higher mortality rate of left liver recipients raise the caution of assuming the gram-to-gram equivalence of right and left liver grafts.


A Kernel-Based Low-Rank (KLR) Model for Low-Dimensional Manifold Recovery in Highly Accelerated Dynamic MRI.
While many low rank and sparsity-based approaches have been developed for accelerated dynamic magnetic resonance imaging (dMRI), they all use low rankness or sparsity in input space, overlooking the intrinsic nonlinear correlation in most dMRI data. In this paper, we propose a kernel-based framework to allow nonlinear manifold models in reconstruction from sub-Nyquist data. Within this framework, many existing algorithms can be extended to kernel framework with nonlinear models. In particular, we have developed a novel algorithm with a kernel-based low-rank model generalizing the conventional low rank formulation. The algorithm consists of manifold learning using kernel, low rank enforcement in feature space, and preimaging with data consistency. Extensive simulation and experiment results show that the proposed method surpasses the conventional low-rank-modeled approaches for dMRI.


Expression patterns of superficial epidermal adhesion molecules in an experimental dog model of acute atopic dermatitis skin lesions.
The stratum corneum is critical for providing a functional skin barrier, especially in humans and dogs with atopic dermatitis. An effective barrier also depends upon intact corneodesmosomes and superficial epidermal tight junctions. To study the expression of selected corneodesmosome, desmosome, tight and adherens junction proteins in an experimental model of acute atopic dermatitis skin lesions in dogs. Control and house dust mite (HDM) allergen-containing patches (two types of patches) were applied to the skin of six Maltese-beagle atopic dogs hypersensitive to HDM. Patches were left on for 48 h, and biopsies were collected 24 h after removal. Frozen skin sections were stained by indirect immunofluorescence for corneodesmosin, desmoglein-1, desmocollin-1, claudin-1 and E-cadherin. Immunostains were assessed for their extent, intensity and patterns; they were compared between HDM and control patches on the same dogs. The immunostaining for E-cadherin, desmocollin-1 and desmoglein-1 was homogeneous, intercellular and continuous in all control and HDM patches. The immunoreactivity of corneodesmosin and claudin-1 was heterogeneous and reduced in intensity in 12 of 12 and eight of 12 HDM patches, respectively, in contrast to a normal expression seen in all control samples (Fisher's test, P < 0.001). These observations suggest that HDM allergens, via proteolytic digestion and/or because of induced allergic inflammation, affect the expression and possible function of corneodesmosomal and tight junction proteins. Ensuing intercellular junction alterations might promote an abnormally increased penetration of allergens through the epidermis.


Exponential Synchronization of Coupled Stochastic Memristor-Based Neural Networks With Time-Varying Probabilistic Delay Coupling and Impulsive Delay.
This paper deals with the exponential synchronization of coupled stochastic memristor-based neural networks with probabilistic time-varying delay coupling and time-varying impulsive delay. There is one probabilistic transmittal delay in the delayed coupling that is translated by a Bernoulli stochastic variable satisfying a conditional probability distribution. The disturbance is described by a Wiener process. Based on Lyapunov functions, Halanay inequality, and linear matrix inequalities, sufficient conditions that depend on the probability distribution of the delay coupling and the impulsive delay were obtained. Numerical simulations are used to show the effectiveness of the theoretical results.


NHC-promoted asymmetric β-lactone formation from arylalkylketenes and electron-deficient benzaldehydes or pyridinecarboxaldehydes.
A chiral NHC catalyzes the asymmetric formal [2 + 2] cycloaddition of alkylarylketenes with both electron-deficient benzaldehydes and 2- and 4-pyridinecarboxaldehydes to generate stereodefined β-lactones. In the benzaldehyde series, optimal product diastereo- and enantiocontrol is observed using 2-nitrobenzaldehyde (up to 93:7 dr (syn:anti) and 93% ee). Substituted 2- and 4-pyridinecarboxaldehydes are also tolerated in this process, generating the corresponding β-lactones in good yield and enantioselectivity, although the diastereocontrol in these processes is highly dependent upon the aldehyde substitution. These processes are readily scalable, allowing multigram quantities of the β-lactone products to be prepared. Derivatization of these products, either through ring opening into the corresponding stereodefined β-hydroxy and β-amino acid derivatives without loss of stereochemical integrity or via cross-coupling, is demonstrated.


N-cofilin is associated with neuronal migration disorders and cell cycle control in the cerebral cortex.
Many neuronal disorders such as lissencephaly, epilepsy, and schizophrenia are caused by the abnormal migration of neurons in the developing brain. The role of the actin cytoskeleton in neuronal migration disorders has in large part remained elusive. Here we show that the F-actin depolymerizing factor n-cofilin controls cell migration and cell cycle progression in the cerebral cortex. Loss of n-cofilin impairs radial migration, resulting in the lack of intermediate cortical layers. Neuronal progenitors in the ventricular zone show increased cell cycle exit and exaggerated neuronal differentiation, leading to the depletion of the neuronal progenitor pool. These results demonstrate that mutations affecting regulators of the actin cytoskeleton contribute to the pathology of cortex development.


Effects of HPV-16 infection on hypopharyngeal squamous cell carcinoma and FaDu cells.
Hypopharyngeal squamous cell carcinoma is a common type of malignant tumor among head and neck squamous cell carcinomas (HNSCCs). Heavy smoking and/or drinking is associated with the development of HNSCC. However, HNSCC also occurs in individuals that do not drink or smoke, possibly due to infection with the human papilloma virus (HPV). HPV-16 has been shown to be closely associated with the occurrence of several types of cancers. However, its role in hypopharyngeal squamous cell carcinoma remains unclear. In the present study, we investigated the effects of HPV-16 on hypopharyngeal squamous cell carcinoma and FaDu cells. Lentiviral vectors were used to establish FaDu cells that expressed the E6 and E7 proteins of HPV-16. We used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays and western blotting to detect and determine the levels of expression for E6-E7 mRNAs and proteins. Cell Counting Kit-8 (CCK-8) assays, enzyme-linked immunosorbent assays (ELISA), Transwell assays, and flow cytometry were used to assess the effects of HPV-16 E6-E7 on the proliferation, invasion, metastasis and apoptosis of FaDu cells. Expression of microRNAs was analyzed by qRT-PCR. We found that the expression levels of HPV-16 E6-E7 were increased in FaDu cells transfected with the lentiviral vector compared with that observed in the control cells. In addition, the rates of apoptosis were decreased in the transfected cells, while proliferation was increased. The average numbers of cells penetrating the Matrigel were significantly higher than those for the controls. We detected miR-363 and miR-15a, and their expression levels were significantly increased in the HPV-16-positive patients and in FaDu cells expressing HPV-16 E6-E7. We found that HPV-16 E6-E7 appeared to inhibit apoptosis, and to increase cell proliferation, invasion and metastasis. Furthermore, miR-363 and miR-15a were overexpressed in the hypopharyngeal squamous cell carcinoma samples infected with HPV-16, and in FaDu cells stably expressing HPV-16 E6-E7. These findings may provide a new clue of the mechanisms involved in the pathogenesis of HPV-16-positive hypopharyngeal squamous cell carcinoma.


Competitive kinetics in free radical reactions of cinnamic acid derivatives. Influence of phenoxyl radicals reactions.
Relative rates of consumption of caffeic, ferulic and sinapic acids by 2,2'-azobis(2-amidine propane) derived peroxyl radicals has been measured in parallel experiments employing a single substrate and in competitive experiments. Rates of consumption measured in independent experiments at low substrate concentrations (first order limit) follow the order: sinapic > ferulic > caffeic. In agreement with this, in competitive experiments employing simultaneously sinapic and caffeic acid the former compound is consumed considerably faster. On the other hand, in competitive experiments employing ferulic and caffeic acids over a wide range of experimental conditions, caffeic acid is consumed considerably faster than ferulic acid, a result that contrasts with that obtained when both compounds are reacted independently. These apparently anomalous results are interpreted in terms of secondary reactions of the phenol-derived radicals. In particular, hydrogen transfer among phenoxyl radicals and the phenols and fast reactions (disproportionation) of caffeic acid derived radicals could explain these discrepancies.


Orally administered emu oil decreases acute inflammation and alters selected small intestinal parameters in a rat model of mucositis.
Mucositis resulting from cancer chemotherapy is a serious disorder of the alimentary tract. Emu oil has demonstrated anti-inflammatory properties in animal models of arthritis and wound healing; however, its effects on the intestine remain unknown. We investigated emu oil for its potential to decrease the severity of mucositis in a rat model. Female Dark Agouti rats (110-150 g) were orogastrically gavaged with emu oil (0.5 or 1 ml) or water (1 ml) for 5 d before intraperitoneal injection of 5-fluorouracil (5-FU, 150 mg/kg) or saline (control), and this was continued up to the day of sacrifice (48, 72 and 96 h post 5-FU administration). Histological (villus height, crypt depth (CD) and disease severity score) and biochemical (myeloperoxidase (MPO) activity) parameters were determined in intestinal tissues collected at sacrifice. Sucrase activity in vivo was quantified by the sucrose breath test. Activated neutrophil activity (MPO) in the ileum was significantly decreased by emu oil (0.5 ml, 451 (sem 168) U/g and 1 ml, 503 (sem 213) U/g) compared with 5-FU-treated controls (1724 (sem 431) U/g) 96 h post 5-FU administration. There were also significant increases in CD (152 (sem 8) microm) in the ileum of rats that received 1 ml emu oil at 96 h compared with 5-FU-treated controls (CD (106 (sem 12) microm)). Emu oil did not affect sucrase activity. Emu oil decreased acute ileal inflammation, and improved mucosal architecture in the intestine during recovery from chemotherapy in rats. Further studies investigating the potential benefits of emu oil as a nutritional supplement for the treatment of intestinal disorders are indicated.


A WeChat mini-program-based approach to smoking cessation behavioral interventions: Development and preliminary evaluation in a single-arm trial.
This study sought to develop a WeChat mini-program for smoking cessation behavioral interventions (named the WQ mini-program) and evaluate its usability, acceptability, and preliminary efficacy among Chinese smokers. The WQ mini-program was designed based on behavioral change theories and clinical practice guidelines, and clinical smoking cessation experts participated in the development process. Fifty Chinese smokers and five software experts were involved in a single-arm trial. Smokers were asked to use the WQ mini-program at least once a day for 4 weeks and to complete a weekly online follow-up questionnaire. Software experts were asked to complete an online follow-up questionnaire after using all functions of the WQ mini-program. Primary outcomes were usability and acceptability of and satisfaction with the mini-program tested by the System Usability Scale (SUS) and the Mobile App Rating Scale (MARS). Self-reported 7-day point prevalence abstinence (PPA) was used to evaluate its preliminary efficacy for smoking cessation. Optimization suggestions for the mini-program were collected from all participants through an open-ended question at the last follow-up and were analyzed by thematic analysis. The mean SUS and MARS total scores for the WQ mini-program as evaluated by smokers were 82.1 ± 13.8 and 84.5 ± 3.3 and by software experts were 4.21 ± 0.32 and 4.27 ± 0.15, respectively. Most smokers reported being willing to recommend this mini-program to other smokers (85.4%) and would continue to use it (95.8%). The mean satisfaction score for the mini-program was 4.23 ± 0.69 (out of 5 points) among smokers. Self-reported 7-day PPA among smokers at the 4-week follow-up was 50% (25/50). This study demonstrated that the WQ mini-program would be a feasible and potentially effective method to encourage Chinese smokers to quit smoking. However, future research is needed to confirm its efficacy through a randomized controlled trial.


Testicular microlithiasis and antisperm antibodies following testicular biopsy in boys with cryptorchidism.
Testicular biopsy (TBx) performed during orchiopexy in boys with cryptorchidism can help to predict future semen analyses and possibly identify patients at risk for testicular cancer. It has been theorized that TBx can be detrimental to the long-term health of the testis. We examined testicular microlithiasis (TM) and antisperm antibody (ASA) production in cryptorchid TBx. A total of 112 males underwent fertility evaluation. These patients had previously undergone orchiopexy and bilateral TBx (mean age 8.6 years) for unilateral or bilateral undescended testis. At a mean age of 19.6 years all patients underwent physical examination and scrotal ultrasound for evaluation of testis size, echotexture and abnormalities. Of 112 patients 57 also underwent direct Immunobead(R) assay with positive controls. Moving sperm free and/or bound to IgG bead complex were counted in the preparation. A total of 29 patients had bilateral and 83 had unilateral undescended testis. Of the 112 patients 26 were black and 86 were white. Four black patients (15.4%) and 4 white patients (4.7%) had testicular microlithiasis. Three patients had bilateral and 5 had unilateral diffuse TM. No tunica albuginea scars or testis masses were noted. In the 57 patients who underwent direct Immunobead assay no semen sample demonstrated evidence of forming bead-sperm complex, ie none had direct ASA. No patient exhibited evidence of direct ASA. Prepubertal open TBx does not increase the rate of TM. We found no evidence of additive testicular damage associated with TBx at the time of orchiopexy.


Propagation of Polycomb-repressed chromatin requires sequence-specific recruitment to DNA.
Epigenetic inheritance models posit that during Polycomb repression, Polycomb repressive complex 2 (PRC2) propagates histone H3 lysine 27 trimethylation (H3K27me3) independently of DNA sequence. We show that insertion of Polycomb response element (PRE) DNA into the Drosophila genome creates extended domains of H3K27me3-modified nucleosomes in the flanking chromatin and causes repression of a linked reporter gene. After excision of PRE DNA, H3K27me3 nucleosomes become diluted with each round of DNA replication, and reporter gene repression is lost. After excision in replication-stalled cells, H3K27me3 levels stay high and repression persists. H3K27me3-marked nucleosomes therefore provide a memory of repression that is transmitted in a sequence-independent manner to daughter strand DNA during replication. In contrast, propagation of H3K27 trimethylation to newly incorporated nucleosomes requires sequence-specific targeting of PRC2 to PRE DNA.


Facile method to activate substrate for oxygen evolution by a galvanic-cell reaction.
NiFe layered double hydroxide (NiFe LDH) is a promising material with multiple functions. In this communication, a novel method is used to prepare NiFe LDH. This synthesis method is achieved via galvanic-cell corrosion between nickel and iron substrates in aqueous solutions containing a halogen group anion (e.g., Cl) at ambient temperature. The as-prepared NiFe LDH electrodes are developed as electrocatalysts for the oxygen evolution reaction (OER) and exhibit excellent catalytic activities and durability. This work provides an energy-efficient, cost-effective, and scaled-up corrosion engineering approach for manufacturing NiFe LDH materials.


[Definition, classification and diagnosis of fibromyalgia syndrome].
Interdisciplinary guidelines for the definition, classification and diagnosis of chronic widespread pain (CWP) and fibromyalgia syndrome (FMS) were developed by collaboration of 10 German medical and psychological associations and 2 patient self-help organizations. A systematic literature search was performed in the Cochrane Library (1993-12/2006). Medline (1980-2006), and Scopus (1980-12/2006). Levels of evidence were assigned according to the classification system of the Oxford Center for Evidence-Based Medicine. Grading of the strength of recommendation was done according to the German program for disease management guidelines. Standardized procedures to reach a consensus on recommendations were used. CWP is defined by the criteria of the American College of Rheumatology (ACR-strong consensus). FMS can be diagnosed for clinical purposes by symptom-based criteria (without tender point examination) as well as by the ACR criteria (strong consensus).


Hyperhomocysteinemia, methylenetetrahydrofolate reductase 677TT genotype, and the risk for schizophrenia: a Dutch population based case-control study.
Evidence for an involvement of aberrant homocysteine metabolism in the aetiology of schizophrenia is limited and controversial. A case-control study was performed to quantify the risk of schizophrenia in the presence of elevated homocysteine concentrations or homozygosity for the 677C --> T polymorphism (677TT) in the methylenetetrahydrofolate reductase (MTHFR) gene in subjects of Dutch ancestry. We determined the 677C --> T MTHFR genotype distribution in 254 well-defined patients and 414 healthy controls. Plasma homocysteine concentrations were measured in 62 patients with schizophrenia and 432 control subjects. When homocysteine concentrations were stratified into quartiles of the control distribution, we calculated an increased risk for schizophrenia in the fourth and third quartile versus the lowest quartile [odds ratio (OR) = 3.3; 95% confidence interval (CI): 1.2-9.2, and OR = 3.1; 95% CI: 1.2-8.0, respectively]. A significant dose-response relation of increasing homocysteine levels and increasing risk for schizophrenia was observed (P = 0.036). The 677TT genotype was associated with an OR of 1.6 [95% CI: 0.96-2.8] of having schizophrenia. Heterozygosity for the T allele compared to 677CC subjects accounted for an OR of 1.3 [95% CI: 0.91-1.8]. Elevated homocysteine levels and the MTHFR 677TT genotype are associated with an increased risk for schizophrenia. These observations support a causal relation between disturbed homocysteine metabolism and schizophrenia.


What can we expect from biomarkers for acute kidney injury?
Biomarkers for acute kidney injury have numerous potential roles to play both at the bedside and in the design and conduct of clinical trials. Given the heterogeneous nature of this disease and the difficulty, so far, in developing effective therapies, a strategy that deploys all of our available tools in the treatment and in study of treatments would seem prudent. In this review, we discuss how biomarkers will change the way we do we take care of patients with and do clinical trials in acute kidney injury and why, in fact, biomarkers are necessary.