Effect of head and body positioning on cerebral blood flow velocity in patients who underwent cranial surgery.
The aim of this study was to investigate the effects of head and neck positions on the cerebral blood flow velocity by transcranial Doppler ultrasound in patients who underwent cranial surgery. Inappropriate head elevation and body positioning in patients who undergo cranial surgery may affect cerebral blood flow and cerebral perfusion pressure. DESIGNED: Experimental clinical study. Our sample consisted of 38 patients who underwent cranial surgery between October 2009 and May 2010. The measurments of mean cerebral blood flow velocity were taken by the transcranial Doppler ultrasound through the temporal window. The mean cerebral blood flow velocity of the patients was measured in supine position with 0° and 30° head elevations, right and left lateral positions, right and left lateral positions with head flexion and extension. The measurements were taken before surgery and within 72 hours after surgery. The mean cerebral blood flow velocity of the middle cerebral arteries was increased in head elevations from 0° to 30°, in right and lateral positions with 30° head elevations, but the velocity was decreased in head flexion and extension positions in preoperative and postoperative periods. Head and body positioning, which is one of the nursing care activities, may affect intracranial pressure and cerebral perfusion pressure. Our results are similar with those of previous studies, which showed that head elevation did not affect the cerebral blood flow velocity. By the results of this study, the head elevation of the patients, who underwent cranial surgery, should be 30° during the nursing care to provide optimum cerebral blood flow. Right and left lateral positioning is safe and recommended for these patients if there is no medical contraindication.


A Simple Method for Removal of Particles from the Retinal Surface during Vitrectomy.
Removal of particulate materials from the retinal surface is somewhat difficult during small gauge vitrectomy. Simple injection of balanced salt solution into the vitreous cavity in a controlled manner using a connector tubing between the syringe and needle can produce enough turbulence to float the deposited material and remove it.


Syntheses of arabinose-derived pyrrolidine catalysts and their applications in intramolecular Diels-Alder reactions.
Six chiral hydroxylated pyrrolidine catalysts were synthesized from commercially available D-arabinose in seven steps. Various aromatic substituents α to the amine can be introduced readily by a Grignard reaction, which enables facile optimization of the catalyst performance. The stereoselectivities of these catalysts have been assessed by comparing with those of MacMillan's imidazolidinone in a known intramolecular Diels-Alder (IMDA) reaction of a triene. Two additional IMDA reactions of symmetrical dienals with concomitant desymmetrisation further established the potential use of these novel amine catalysts. These pyrrolidines are valuable catalysts for other synthetic transformations.


Video-Recorded Validation of Wearable Step Counters under Free-living Conditions.
The purpose of this study was to determine the accuracy of 14-step counting methods under free-living conditions. Twelve adults (mean ± SD age, 35 ± 13 yr) wore a chest harness that held a GoPro camera pointed down at the feet during all waking hours for 1 d. The GoPro continuously recorded video of all steps taken throughout the day. Simultaneously, participants wore two StepWatch (SW) devices on each ankle (all programmed with different settings), one activPAL on each thigh, four devices at the waist (Fitbit Zip, Yamax Digi-Walker SW-200, New Lifestyles NL-2000, and ActiGraph GT9X (AG)), and two devices on the dominant and nondominant wrists (Fitbit Charge and AG). The GoPro videos were downloaded to a computer and researchers counted steps using a hand tally device, which served as the criterion method. The SW devices recorded between 95.3% and 102.8% of actual steps taken throughout the day (P > 0.05). Eleven step counting methods estimated less than 100% of actual steps; Fitbit Zip, Yamax Digi-Walker SW-200, and AG with the moving average vector magnitude algorithm on both wrists recorded 71% to 91% of steps (P > 0.05), whereas the activPAL, New Lifestyles NL-2000, and AG (without low-frequency extension (no-LFE), moving average vector magnitude) worn on the hip, and Fitbit Charge recorded 69% to 84% of steps (P < 0.05). Five methods estimated more than 100% of actual steps; AG (no-LFE) on both wrists recorded 109% to 122% of steps (P > 0.05), whereas the AG (LFE) on both wrists and the hip recorded 128% to 220% of steps (P < 0.05). Across all waking hours of 1 d, step counts differ between devices. The SW, regardless of settings, was the most accurate method of counting steps.


Thrombotic thrombocytopenic purpura accompanied by transient pure red cell aplasia and thymoma.
We describe a 64-year-old man with thrombotic thrombocytopenic purpura (TTP), transient pure red cell aplasia (PRCA) and thymoma. TTP in this case was thought to be idiopathic and was accompanied by microangiopathic hemolytic anemia. The patient, therefore, had an aplastic crisis due to PRCA. He was treated with peritoneal dialysis, plasma exchange with plasma infusion, red blood cell transfusion, methylprednisolone pulse therapy followed by maintenance dosing with intravenous prednisolone, gamma-globulin, vincristine, and dipyridamol. As a result, the patient's mental disorder, acute renal failure, anemia and thrombocytopenia improved; however, the haptoglobin level remained low. The pathogenesis of PRCA and thymoma indicates that these are immunological disorders often associated with each other. To our knowledge, there are no reports of TTP with transient PRCA and thymoma. Although such a combination is considered relatively rare, this case suggests that there is an immunological contribution to the pathogenesis of the association of these disorders.


Distribution of behavioral science faculty in United States medical schools: 1968-1969 and 1978-1979.
The Association of American Medical Colleges' faculty profiles were analyzed for 117 U.S. medical schools for the years 1968/1969 and 1978/1979. The growth of behavioral science faculty more than matched that of all medical school faculty (i.e. 78 vs 65%) in full-time tenure-track positions over this 10-year period. Most behavioral science medical school faculty are psychologists. Although still small in numbers, faculty from other disciplines such as anthropology and sociology have gained increasing acceptance, and these 117 medical schools now employ at least 20 full-time economists and 13 who have earned degrees in political science. The growth of behavioral science faculty has been primarily in clinical departments, and those who are associated with independent departments of behavioral science remained virtually static (87 vs 88) over this 10 year period.


Performance characteristics of a new levetiracetam immunoassay and method comparison with a high-performance liquid chromatography method.
Although levetiracetam is recognized for ease of dosing and being well tolerated, therapeutic drug monitoring is potentially useful in certain clinical situations. High-performance liquid chromatography has been commonly used for measuring levetiracetam. Recently, a homogeneous immunoassay for levetiracetam measurement in serum and plasma was introduced by ARK Diagnostics, Inc. The goal of this work was to validate this assay on a random access instrument. This immunoassay was established on the Siemens ADVIA 1200 automated chemistry analyzer. The intraday precision was assessed by 10 replicates of two levels of quality control materials in a batch, whereas interday precision was estimated by assaying the same materials one set per day for 20 days. Linearity was evaluated by serially diluting the highest calibrator and a high patient specimen run in triplicate, whereas the lower limit of quantification was confirmed by 10 measurements of a low-level specimen diluted from a calibrator and another from a diluted patient specimen. This method was compared with a commercial high-performance liquid chromatography method (Chromsystems) using 63 specimens from patients who were on levetiracetam therapy. The assay cycle was 10 minutes with a theoretical throughput of 800 per hour. The intra- (n = 10) and interday (n = 20) coefficients of variation were 8.1% or less for the two levels tested. The manufacturer-claimed analytical measurable range (2.0-100.0 μg/mL) was confirmed by serial dilution and lower limit of quantification experiments. Among the 63 patient samples studies, four showed levetiracetam levels below 2.0 μg/mL by both methods. Deming regression using the remaining 59 paired patient results by ARK immunoassay and the high-performance liquid chromatography method showed a correlation coefficient of 0.9962, a linear regression slope of 0.98, and an intercept of 0.61 with a mean bias of 0.04%. The ARK immunoassay is suitable for clinical use of monitoring levetiracetam levels in serum/plasma on an automated chemistry analyzer (Siemens ADVIA 1200).


Correlations of Hemoglobin Level and Perioperative Blood Transfusion with the Prognosis of Gastric Cancer: A Retrospective Study.
BACKGROUND This study was designed to explore the correlations of hemoglobin level (Hb) and perioperative blood transfusion with the prognosis of gastric cancer (GC). MATERIAL AND METHODS Our study consisted of 210 patients with GC who all received a D2 radical operation. These patients were assigned into three groups: 68 cases in group A (blood transfusion >5 U); 59 cases in group B (blood transfusion <5 U); 83 cases in group C (without blood transfusion). A 5-year follow-up was conducted to evaluate the disease-free survival of the patients. Univariate analysis was performed to reveal the relationship between the indicators and the patients with GC. Kaplan-Meier method was employed to analyze the survival rate of patients, and Cox regression analysis was applied to determine the independent prognostic factors of GC. RESULTS The univariate analysis indicated that age, perioperative blood transfusion amount, TNM staging, maximal tumor diameter, differentiation degree and invasion degree were associated with the prognosis of GC. The Kaplan-Meier curve showed that the disease-free survival rate was declined in the patients who were older, those received more amount of blood transfusion, those in advanced TNM staging, those had larger tumor diameter, and those with decreased degree of differentiation and invasion. Cox regression analysis indicated that perioperative blood transfusion, maximal tumor diameter and invasion degree were the independent factors affecting disease-free survival of the GC. CONCLUSIONS Our study revealed that large amount of perioperative blood transfusion leads to poor prognosis of GC.


Ethical Considerations of Community-based Participatory Research: Contextual Underpinnings for Developing Countries.
The nature of community-based participatory research (CBPR) poses distinctive ethical challenges. In the absence of organized guidelines, a remarkable amount of researchers' time and energy will be spent tackling these ethical challenges. The study aimed to explore ethical issues and principles potentially arising when conducting CBPR. This qualitative study conducted in CBPR Center of Tehran University of Medical Sciences. Required data were gathered through systematic literature review and semi-structured interviews. Representatives of community, academia, and nongovernmental organizations (NGOs) participated in our study. Ten interviews with representatives of partner organizations, four group interviews with academic staff, and four with representatives of community were conducted. Repeated thematic analysis was used to elicit ethics-related overarching themes from transcribed interviews. As recommendations, these themes were then organized into a set of CBPR-related ethical issues and principles. Four CBPR ethical guidelines (including 173 articles) were selected from a systematic review. Overarching themes relating to ethical principles which emerged from interviews were as follows: Trust, transparency and accountability, equity and inclusion, power imbalance, tolerance and conflict management, and attention to cultural sensitivity. Practical principles that emerged included: Consensus rather than informed consent, ownership of data and research achievements, and sustainability and maintenance of relationships. According to findings and in comparison to international guidelines, the present study put more emphasis on cultural sensitivity and sustainability as CBPR ethical tangles. Community-based participatory research ethical challenges are of the same kind in most parts of the world. However, some discrepancies exist that calls for local scrutiny. Future use and critic of current explored ethical issues and principles are highly encouraged.


Profound hypoxemia during major abdominal surgery in a small infant with tetralogy of Fallot.
We report a protracted hypoxic event during Soave's endorectal pull-through for Hirschsprung's disease in a 2-month-old male infant with tetralogy of Fallot. After the bowel loops were delivered out of the abdominal cavity, profound hypoxemia occurred which persisted for about 120 min. The hypoxemia was completely resolved after the intestine was reduced back into the peritoneal cavity. The immediate cause was postulated to have been decreased systemic vascular resistance. Associated factors included hypothermia and acidosis leading to high pulmonary vascular resistance which further aggravated the right-to-left blood-shunting situation in this patient. Postoperative follow-up showed no neurological complications. Small infants with complex heart disease should be carefully evaluated before major abdominal surgery.


Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation.
Hyperinsulinaemic hypoglycaemia (HH) is the most common cause of severe and persistent hypoglycaemia in neonates. The treatment of severe diazoxide unresponsive HH involves near total pancreatectomy. Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cellular proliferation. mTOR inhibitors are used in cancer patients and recently found to be effective in the treatment of insulinoma and HH patients. A 36 weeks large for gestational age neonate presented with severe hypoglycaemia on day 1 of life. The hypoglycaemia screen confirmed HH and genetic testing revealed compound heterozygous ABCC8 mutation, confirming diffuse disease. He was unresponsive to the maximal dose of diazoxide (15 mg/kg/day), hence needed treatment with higher concentration of intravenous glucose (25 mg/kg/min), intravenous glucagon and subcutaneous octreotide (30 μg/kg/day) infusions to maintain normoglycaemia. Sirolimus, a mTOR inhibitor, was commenced at 9 weeks of age following which he showed a marked improvement in his glycaemic control. After 4 weeks of sirolimus therapy, he was discharged home on subcutaneous octreotide injection (20 μg/kg/day) and oral sirolimus, thereby avoiding the need for a near total pancreatectomy. We report the first case of compound heterozygous ABCC8 mutation causing severe diffuse HH that responded to therapy with a mTOR inhibitor.


Procoagulant microparticles: disrupting the vascular homeostasis equation?
Apoptosis and vascular cell activation are main contributors to the release of procoagulant microparticles (MPs), deleterious partners in atherothrombosis. Elevated levels of circulating platelet, monocyte, or endothelial-derived MPs are associated with most of the cardiovascular risk factors and appear indicative of poor clinical outcome. In addition to being a valuable hallmark of vascular cell damage, MPs are at the crossroad of atherothrombosis processes by exerting direct effects on vascular or blood cells. Under pathological circumstances, circulating MPs would support cellular cross-talk leading to vascular inflammation and tissue remodeling, endothelial dysfunction, leukocyte adhesion, and stimulation. Exposed membrane phosphatidylserine and functional tissue factor (TF) are 2 procoagulant entities conveyed by circulating MPs. At sites of vascular injury, P-selectin exposure by activated endothelial cells or platelets leads to the rapid recruitment of MPs bearing the P-selectin glycoprotein ligand-1 and blood-borne TF, thereby triggering coagulation. Within the atherosclerotic plaque, sequestered MPs constitute the main reservoir of TF activity, promoting coagulation after plaque erosion or rupture. Lesion-bound MPs, eventually harboring proteolytic and angiogenic effectors are additional actors in plaque vulnerability. Pharmacological strategies aimed at modulating the release of procoagulant MPs appear a promising therapeutic approach of both thrombotic processes and bleeding disorders.


Stimulation of μ-opioid receptors dilates retinal arterioles by neuronal nitric oxide synthase-derived nitric oxide in rats.
Opioids contribute to the regulation of cerebral vascular tone. The purpose of this study was to examine the effects of herkinorin, a non-opioid μ-opioid receptor agonist derived from salvinorin A, on blood vessels in the rat retina and to investigate the mechanism underlying the herkinorin-induced retinal vasodilatory response. Ocular fundus images were captured using an original high-resolution digital fundus camera in vivo. The retinal vascular responses were evaluated by measuring the diameter of retinal arterioles in the fundus images. Both systemic blood pressure and heart rate were continuously recorded. Herkinorin increased the retinal arteriolar diameter without significantly changing mean blood pressure and heart rate. The retinal vasodilator response to herkinorin was almost completely prevented following treatment with naloxone, a nonselective opioid receptor antagonist and H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), a selective μ-opioid receptor antagonist. Nω-nitro-L-arginine methyl ester, a nonselective nitric oxide (NO) synthase inhibitor, or indomethacin, a cyclooxygenase inhibitor, significantly attenuated the herkinorin-induced retinal vasodilator responses. In addition, Nω-propyl-L-arginine, an inhibitor of neuronal NO synthase, diminished the herkinorin-induced retinal vasodilator responses. Seven days after an intravitreal injection of N-methyl-D-aspartic acid, loss of inner retinal neurons and abolishment of the retinal vasodilator response to herkinorin were observed. These results suggest that herkinorin dilates rat retinal arterioles through stimulation of retinal μ-opioid receptors. The μ-opioid receptor-mediated retinal vasodilator response is likely mediated by NO generated by neuronal NO synthase. Retinal neurons play an important role in the retinal vasodilator mechanism involving μ-opioid receptors in rats.


Lamotrigine treatment in childhood drug resistant epilepsy.
The clinical response to lamotrigine has been evaluated in a group of 63 drug resistant epileptic children in an open add-on trial. A negative response was observed in 30 subjects. In 11 patients, after an initial improvement lasting a mean period of 8 months, seizures recurred with the same frequency present before the beginning of the treatment. Twenty-two patients responded to lamotrigine treatment. Period of observation in the responsive group ranged from 1 year to 3 years. Response was complete in 16 patients and in the other 6 a 50% to 90% decrease of seizures was obtained. A complete normalization of the electroencephalogram (EEG) was registered in 10 cases after a mean period of 5 months of therapy. Side effects were mild and limited to 12 patients. Improvement was obtained in social and academic performance. Writing ability improved in one case. Lamotrigine can be considered a useful drug in the therapeutic armamentarium for childhood drug resistant epilepsy.


A piece of wood in the hand diagnosed by ultrasonography.
A piece of wood in the hand of an 11-year-old girl was not visible on radiographs, but was diagnosed by ultrasonography. Ultrasonography is useful for disclosing radiographically silent foreign bodies.


Depression in people with epilepsy: How much do Asian colleagues acknowledge it?
The purpose of this review was to investigate the prevalence of depression in people with epilepsy (PWE) in different countries in Asia. We searched the electronic database PubMed on June 13, 2017 for articles in English that included the following search terms: "epilepsy" AND "depression" AND "country name" for all Asian countries since 1947. Relevant original studies from Asia were included if they reported the prevalence of depression in PWE. Papers studying special populations (e.g., elderly, veterans, etc.) were not included. In addition, experts in epilepsy field were invited from some Asian countries for an in-depth assessment. Six hundred eighty-seven papers were reviewed and 26 related studies were included in this study. Depression is highly prevalent in PWE in different countries in Asia and the prevalence rates are consistent with rates reported in the literature from other countries: overall, about 25% of PWE suffer from depression. In Asian countries, as elsewhere, depression is common in PWE. High quality data is scarce in many countries and validated screening tools [e.g., Neurological Disorders Depression Inventory for Epilepsy (NDDI-E)] to appropriately investigate the prevalence of depression in PWE are still lacking in many languages. Considering the high prevalence of depression among PWE, routine and periodic screening of all PWE for early detection and appropriate management of depression would be a reasonable approach.


Occurrence of Volcanogenic Inorganic Mercury in Wild Mice Spinal Cord: Potential Health Implications.
Mercury accumulation has been proposed as a toxic factor that causes neurodegenerative diseases. However, the hazardous health effects of gaseous elemental mercury exposure on the spinal cord in volcanic areas have not been reported previously in the literature. To evaluate the presence of volcanogenic inorganic mercury in the spinal cord, a study was carried out in São Miguel island (Azores, Portugal) by comparing the spinal cord of mice exposed chronically to an active volcanic environment (Furnas village) with individuals not exposed (Rabo de Peixe village), through the autometallographic silver enhancement histochemical method. Moreover, a morphometric and quantification analysis of the axons was carried out. Results exhibited mercury deposits at the lumbar level of the spinal cord in the specimens captured at the site with volcanic activity (Furnas village). A decrease in axon calibre and axonal atrophy was also observed in these specimens. Given that these are relevant hallmarks in the neurodegenerative pathologies, our results highlight the importance of the surveillance of the health of populations chronically exposed to active volcanic environments.


Graft position in arthroscopic anterior cruciate ligament reconstruction: anteromedial versus transtibial technique.
When treating anterior cruciate ligament (ACL) injuries, the position of the ACL graft plays a key role in regaining postoperative knee function and physiologic kinematics. In this study, we aimed to compare graft angle, graft position in tibial tunnel, and tibial and femoral tunnel positions in patients operated with anteromedial (AM) and transtibial (TT) methods to those of contralateral healthy knees. Forty-eight patients who underwent arthroscopic ACL reconstruction with ipsilateral hamstring tendon autograft were included. Of these, 23 and 25 were treated by AM and TT techniques, respectively. MRI was performed at 18.4 and 19.7 months postoperatively in AM and TT groups. Graft angles, graft positions in the tibial tunnel and alignment of tibial and femoral tunnels were noted and compared in these two groups. The sagittal graft insertion tibia midpoint distance (SGON) has been used for evaluation of graft position in tunnel. Sagittal ACL graft angles in operated and healthy knees of AM patients were 57.78° and 46.80° (p < 0.01). With respect to TT patients, ACL graft angle was 58.87° and 70.04° on sagittal and frontal planes in operated knees versus 47.38° and 61.82° in healthy knees (p < 0.001). ACL graft angle was significantly different between the groups on both sagittal and frontal planes (p < 0.001). Sagittal graft insertion tibia midpoint distance ratio was 0.51 and 0.48 % in the operated and healthy knees of AM group (p < 0.001) and 0.51 and 0.48 % in TT group (p < 0.001). Sagittal tibial tunnel midpoint distance ratio did not differ from sagittal graft insertion tibia midpoint distance of healthy knees in either group. Femoral tunnel clock position was better in AM [right knee 10:19 o'clock-face position (310° ± 4°); left knee 1:40 (50° ± 3°)] compared with TT group [right knee 10:48 (324° ± 5°); left knee 1:04 (32° ± 4°)]. With respect to the sagittal plane, the anterior-posterior position of femoral tunnel was better in AM patients. Lysholm scores and range of motion of operated knees in the AM and TT groups showed no significant difference (p > 0.05). Precise reconstruction on sagittal plane cannot be obtained with either AM or TT technique. However, AM technique is superior to TT technique in terms of anatomical graft positioning. Posterior-placed grafts in tibial tunnel prevent ACL reconstruction, although tibial tunnel is drilled on sagittal plane.


Evidence for subgenomic RNAs in leaves infected with an Andean strain of potato virus S.
The genomic RNA (7.5 kb) and two subgenomic RNA species (2.5 kb and 1.1 kb) were detected by Northern hybridization in leaves infected with an Andean strain of potato virus S (PVSA). The single-stranded RNAs contain a substantial poly-(A) tract as shown by oligo (dT)-cellulose chromatography and by an increased mobility on agarose gels following digestion with RNase H in the presence of oligo (dT). In rabbit reticulocyte lysates, the 1.1 kb RNA directed the synthesis of the 34 kD virus coat protein which was not translated efficiently from full length genomic RNA isolated by sucrose gradient fractionation.


Labral reconstruction using the ligamentum teres capitis: report of a new technique.
We have used the ligamentum teres capitis to reconstruct the deficient or absent labrum in five patients with femoroacetabular impingement at the time of surgical hip dislocation. Two had a deficient labrum overlying a sectorial retroverted acetabulum causing pincer-type impingement. Three patients had the labrum previously resected arthroscopically. The minimum followup from surgery was 5 months (average, 10 months; range, 5-20 months). There were no intraoperative or postoperative complications related to the reconstruction. All patients had improvement in their clinical function and one patient underwent total hip arthroplasty at last followup for unresolved pain without radiographic progression of arthritis. Reconstruction of the labrum in patients with deficient or resected labrums at the time of surgical hip dislocation provides the theoretical advantage of sealing and stabilizing the hip joint, restoring the fluid layer which could potentially prevent continued cartilage degeneration.


Assessment of iodine deficiency and goitre incidence in parts of Yewa Area of Ogun State, Southwestern Nigeria.
This study was carried out to determine the occurrence, prevalence and contributing factors to the incidence of goitre in Yewa north local government area of Ogun state, southwestern Nigeria. To achieve these objectives, soil, water, and cassava tubers were collected from four villages -- Igbogila, Egua, Sawonjo and Imoto and from Lagos (about 250 m to the ocean) as a reference location, in order to determine their iodine concentrations. The results of the analyses indicated a soil mean iodine range of 2.1-5.8 microg g(-1); a cassava mean iodine value of 2.3-3.5 mug g(-1) and a drinking water mean iodine value of generally <1.0 microg L(-1) in all the four villages. These values of iodine in soil and water of the four villages are considered low when compared with the soil iodine value of 7.4 microg g(-1) and water iodine value of 6.1 microg L(-1) obtained from Lagos. The limestone unit of the study area remains an inhibiting factor in the bioavailability of the iodine because of its alkalinity. Statistical analysis has shown that there was significant difference between iodine concentration in the soils and the drinking water, and a correlation between the soil iodine and organic matter content at p < 0.05. The correlation between soil iodine and granulometric fractions occurred at p < 0.01. Potential goitrogens in the commonly consumed cassava products might also have contributed to the prevalence of goitre in the study area. Both the females and the adults (i.e., less mobile groups) were found to be vulnerable to goitre development in these villages.


Biobanking and Privacy in India.
Biobank-based research is not specifically addressed in Indian statutory law and therefore Indian Council for Medical Research guidelines are the primary regulators of biobank research in India. The guidelines allow for broad consent and for any level of identification of specimens. Although privacy is a fundamental right under the Indian Constitution, courts have limited this right when it conflicts with other rights or with the public interest. Furthermore, there is no established privacy test or actionable privacy right in the common law of India. In order to facilitate biobank-based research, both of these lacunae should be addressed by statutory law specifically addressing biobanking and more directly addressing the accompanying privacy concerns. A biobank-specific law should be written with international guidelines in mind, but harmonization with other laws should not be attempted until after India has created a law addressing biobank research within the unique legal and cultural environment of India.


Individual variability in physiological adaptation to metabolic stress during early lactation in dairy cows kept under equal conditions.
This study was conducted to investigate individual metabolic and endocrine adaptation to lactation under conditions of identical housing and feeding conditions in high-yielding dairy cows. Forty-five cows were studied on a research farm under standardized but practical conditions. From wk 2 before calving until wk 14 postpartum, blood samples were collected at weekly intervals and assayed for blood chemistry and various metabolites and hormones. Body weight, BCS, and backfat thickness were also recorded weekly. Milk yield, milk composition, and feed intake and energy balance were accordingly measured during the postpartum phase. The animals were retrospectively classified according to their plasma concentration of beta-hydroxybutyrate (BHB): cows in which a BHB threshold of 1 mM was exceeded at least once during the experiment were classified as BHB positive (BHB+); cows with BHB values consistently below this threshold were classified as BHB negative (BHB -). Using this classification, differences for NEFA and glucose concentrations were observed, but the mean calculated energy balance did not differ between the groups during the experimental period (-22.2 MJ of NE(1)/d +/- 4.7 for BHB+ and -18.9 MJ of NE(1)/d +/- 4.9 for BHB-). In BHB+ cows, the peripartum decrease (P < 0.05) of BW, BCS, and backfat thickness was more pronounced than in BHB- cows. Mean milk yields did not differ between groups. However, BHB+ cows had greater milk fat and lesser milk protein contents (P < 0.05), resulting in a greater (P < 0.05) fat:protein ratio than in BHB- cows. Thus, to some extent, cows were able to compensate for the negative energy balance by adjustments in performance. Milk acetone concentrations followed BHB concentrations in blood. Insulin-like growth factor-I and leptin concentrations were greater (P < 0.05) in BHB- cows during the time of observation than in the BHB+ cows. Comparing the reproductive variables recorded (first increase of progesterone, first service conception rate, number of services per conception, interval from calving to first AI, interval from first AI to conception, and days open) between the 2 groups yielded no significant differences. Our findings imply that despite comparable energy balance, there is considerable individual variation of the adaptive ability of cows during early lactation based on a variety of metabolic and endocrine variables.


Influence of ionic crosslinkers (Ca2+/Ba2+/Zn2+) on the mechanical and biological properties of 3D Bioplotted Hydrogel Scaffolds.
Three dimensional (3D) bioplotting requires appropriate crosslinkers to crosslink the hydrogel precursor while simultaneously maintaining the viability of embedded cells. However, the evaluation and comparison of various types of crosslinkers in bioplotting remains underexplored to date. This paper presents our study of the influence of three ionic crosslinkers-calcium chloride (CaCl2), barium chloride (BaCl2), and zinc chloride (ZnCl2)-on the mechanical and biological properties of 3D bioplotted alginate scaffolds. The scaffold mechanical properties characterized included the elastic modulus, swelling, and degradation while the biological properties considered included Schwann cell viability and surface morphology. The mechanical and biological properties of the bioplotted scaffolds were both dependent on the crosslinkers used for fabrication; specifically, crosslinking ions resulted in the elastic modulus of the hydrogels decreasing in the order BaCl2>CaCl2>ZnCl2 over 42 days while Schwann cell viability decreased in the order CaCl2>BaCl2>ZnCl2 over 7 days. Taken together, these results offer insights that are effective in terms of manipulating the 3D bioplotting process so as to tune and optimize the mechanical and biological performance of the plotted scaffolds for tissue engineering applications.


Novel cytoprotective inhibitors for apoptotic endonuclease G.
Apoptotic endonuclease G (EndoG) is responsible for DNA fragmentation both during and after cell death. Previous studies demonstrated that genetic inactivation of EndoG is cytoprotective against various pro-apoptotic stimuli; however, specific inhibitors for EndoG are not available. In this study, we have developed a high-throughput screening assay for EndoG and have used it to screen a chemical library. The screening resulted in the identification of two potent EndoG inhibitors, PNR-3-80 and PNR-3-82, which are thiobarbiturate analogs. As determined by their IC₅₀s, the inhibitors are more potent than ZnCl₂ or EDTA. They inhibit EndoG at one or two orders of magnitude greater than another apoptotic endonuclease, DNase I, and do not inhibit the other five tested cell death-related enzymes: DNase II, RNase A, proteinase, lactate dehydrogenase, and superoxide dismutase 1. Exposure of natural EndoG-expressing 22Rv1 or EndoG-overexpressing PC3 cells rendered them significantly resistant to Cisplatin and Docetaxel, respectively. These novel EndoG inhibitors have the potential to be utilized for amelioration of cell injuries in which participation of EndoG is essential.


Inhibition of implantation in the golden hamster by zona-precipitating antibody.
Antisera prepared against saline extracts of hamster ovary, and made specific to ovary by absorption with small intestine, precipitated the zona pellucida of provulatory hamster ova and all early embryonic stages examined, including the pronuclear, 2-, 4-, 8-, and 16-cell, morula, and blastocyst stages; this indicates that (1) the zona antigen is present during oocyte maturation and early embryonic development and (2) the antigen does not change its ability to react with zonaprecipitating antibody. Embryos in the morula and blastocyst stages, treated in vitro with zona-precipitating antibody, pre-immunization rabbit serum, or control media were transferred into synchronized pseudopregnant recipients. Precipitation of zonae by specific antibody inhibited implantation by blocking the process known as zona shedding, and thereby prevented the embryo from making contact with the uterus.


Ipsilateral motor pathway without contralateral motor pathway in a stroke patient.
The ipsilateral motor pathway from the unaffected motor cortex to the affected extremity is one of the mechanisms of motor recovery following stroke. We report on a stroke patient who showed the ipsilateral motor pathway without the contralateral motor pathway on functional MRI and diffusion tensor tractography. A 53-year-old left hemiparetic patient with an infarct in the right middle cerebral artery territory was evaluated. During a period of three months after onset, motor function of the affected (left) hand had recovered slowly, to the extent that the patient was able to overcome gravity. FMRI showed that only the unaffected (left) primary sensorimotor cortex was activated by movements of the unaffected (right) hand or of the affected (left) hand. On diffusion tensor tractography, the corticospinal tract of the left hemisphere originated from the primary sensori-motor cortex and descended through the known corticospinal tract pathway. By contrast, the right corticospinal tract showed a disruption with Wallerian degeneration to the upper medulla. We conclude that the motor function of the affected (left) hand appeared to be controlled only by the ipsilateral motor pathway from the left motor cortex to the left hand. Motor function of the affected hand appeared to have been reorganized to the ipsilateral motor pathway from the unaffected motor cortex to the affected hand.


Development of a vaccine to prevent Japanese encephalitis: a brief review.
Japanese encephalitis (ICD 10: A83.0) is an important specific viral encephalitis caused by the Japanese encephalitis virus, a virus of the Flavivirus group. Millions of people, especially those in endemic areas of developing countries in Asia, are at high risk from this infection. Therefore proper management to deal with this virus is essential. There is no specific treatment for Japanese encephalitis virus. Supportive and symptomatic treatments are usually used, which emphasize the importance of prevention in this specific neurological disorder. Vector control or vaccination can be used to prevent the disease. Because the existing Japanese encephalitis vaccine poses some undesirable problems, a new vaccine is needed. The process of developing a new vaccine is briefly discussed.


Prediction of the potentially suitable areas of Leonurus japonicus in China based on future climate change using the optimized MaxEnt model.
Leonurus japonicus Houtt. is a traditional Chinese medicinal plant with high medicinal and edible value. Wild L. japonicus resources have reduced dramatically in recent years. This study predicted the response of distribution range of L. japonicus to climate change in China, which provided scientific basis for the conservation and utilization. In this study, 489 occurrence points of L. japonicus were selected based on GIS technology and spThin package. The default parameters of MaxEnt model were adjusted by using ENMeva1 package of R environment, and the optimized MaxEnt model was used to analyze the distribution of L. japonicus. When the feature combination in the model parameters is hing and the regularization multiplier is 1.5, the MaxEnt model has a higher degree of optimization. With the AUC of 0.830, our model showed a good predictive performance. The results showed that L. japonicus were widely distributed in the current period. The maximum temperature of warmest month, the min temperature of coldest month, the precipitation of wettest month, the precipitation of driest month, and altitude were the main environmental factors affecting the distribution of L. japonicus. Under the three climate change scenarios, the suitable distribution area of L. japonicus will range shift to high latitudes, indicating that the distribution of L. japonicus has a strong response to climate change. The regional change rate is the lowest under the SSP126-2090s scenario and the highest under the SSP585-2090s scenario.


[Mechanism of cleft palate in C57BL/6N mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin].
Objective: To explore the molecular mechanism of cleft palate in mice induced by 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). Methods: The pregnant mice were randomly divided into TCDD-treated group (n=42) and control group (n=42). TCDD-treated group was given by gavage a single dose of TCDD (64 μg/kg) at 8: 00 AM on gestation day 10 (GD10) and the control group was given by gavage the isopyknic corn oil. At GD13-GD15, the fetal mice palate development was observed by HE staining. The mouse embryonic palatal mesenchymal cell proliferation was detected by 5-bromo-2-deoxyuridine (BrdU) immunofluorescence. The localization and expression of maternally expressed gene3 (MEG3) in mouse embryonic palatal mesenchymal cells was detected by situ hybridization and real-time PCR (RT-PCR). The key protein expressions of transforming growth factor-β (TGF-β)/Smad signaling pathway in mouse embryonic palatal mesenchyme were analyzed by Western blotting. The interaction of MEG3 and TGF-β receptor Ⅰ (TGF-βRⅠ) was examined by RNA binding protein immunoprecipitation (RIP). Results: At GD13 and GD14, compared with the control group, the ratio of BrdU-positive cells in the palatal mesenchyme of TCDD-treated fetuses decreased significantly (GD13, t=6.66, P=0.003; GD14, t=6.56, P=0.003). However, at GD15, the ratio of BrdU-positive cells was significantly increased (t=-5.98, P=0.004). MEG3 was mainly expressed in the nuclei of fetal mouse palatal mesenchymal cells, and the expression of MEG3 in TCDD group was significantly increased at GD13, GD14 and GD15(GD13, t=39.28, P=0.012; GD14, t=18.75, P=0.042; GD15, t=28.36, P=0.045). At GD14, TCDD decreased the levels of p-Smad2 and Smad4 in embryonic palate mesenchymal cells (p-Smad2, t=9.48, P=0.001;Smad4, t=63.10, P=0.001), whereas the expression of Smad7 was significantly increased at GD14 (t=30.77, P<0.001). The results of the RIP experiment showed that the amount of TGF-βRⅠ-bound MEG3 in mouse embryonic palatal mesenchymal cells in the TCDD group (23.940±1.301) was higher than that in the control group (8.537±1.523)(t=24.55, P<0.001). Conclusions: MEG3 is involved in the suppression of mouse embryonic palatal mesenchymal cell proliferation, functioning at least in part via interacting with the TGF-βRⅠ protein and thereby suppressing Smad signaling in the context of TCDD induced cleft palate.


[Diagnostic and therapeutic problems occasioned by a voluminous cervical schwannoma (author's transl)].
A tumour of the nervous sheath, the schwannoma often entails difficult diagnostic problems linked to its anatomopathological polymorphism. A medical case of a benign schwannoma of the neck has been reported. In this case, it concerns a tumour moreworthy for its size, its adherence, elements which are unusual in a regular tumour which is well inserted in a capsule, and which has entailed difficult therapeutic problems. Its atypical histological shape brought up a debate between its diagnostic on the one of a fibro-myxoma.


Bloodstream Infections due to Carbapenem-Resistant Klebsiella pneumoniae: A Single-Center Retrospective Study on Risk Factors and Therapy Options.
We aimed to compare efficacy of different patterns of antibiotics and explore the risk factors related to mortality in patients with bloodstream infections (BSIs) due to carbapenem-resistant Klebsiella pneumoniae (CRKP). This study retrospectively included 89 patients with BSIs due to CRKP with complete data during the year of 2018 in the First Affiliated Hospital of Zhejiang University School of Medicine. Overall, the 28-day mortality was 47.2% (42/89). Multivariate analysis of Cox regression revealed that hematological malignancy (hazard ratio [HR] 5.698; 95% confidence interval [CI], 2.405-13.504; p < 0.001) and Pitt bacteremia score (HR per unit increase, 1.303; 95% CI, 1.109-1.532; p = 0.001) were identified as independent predictors for 28-day mortality. Among 70 patients with appropriate therapy, 35 received tigecycline (TGC)-based therapy, 20 received polymyxin B (PMB)-based therapy, 9 received ceftazidime/avibactam-based therapy, and 6 patients had other kinds of antibiotics, including ciprofloxacin, amikacin, and cotrimoxazole. By adjusting variables selected by crude analysis, it showed that receiving PMB-based therapy provided a survival benefit comparing with TGC-based therapy (HR, 0.068; 95% CI, 0.018-0.260; p < 0.001). Hematological malignancy and Pitt bacteremia score were independent risk factors of death in patients with BSIs due to CRKP and PMB-based therapy improved survival rate compared with TGC-based therapy.


Fetal loss after early detection of heart motion in infertility patients. Prognostic factors.
To evaluate the incidence and prognosticators of spontaneous abortion (< 20 weeks' gestation) in an infertile population after early documentation of fetal cardiac activity. Retrospective chart review. We examined the incidence of spontaneous abortion in 231 clinical pregnancies with 259 fetuses documented to be viable by transvaginal sonography 28-38 days after ovulation. The population was an unselected group of infertility patients with no history of recurrent pregnancy loss. Maternal age and presence of multiple gestations were analyzed as separate variables by chi 2 testing. The incidence of spontaneous abortion among all fetuses was 9.6% (95% confidence interval [CI], 6.1-13.2%) and among singleton gestations was 7.7% (95% CI, 4.0-11.3%). Women with multiple gestations were more likely to suffer spontaneous fetal loss as compared to women with singleton gestations (18 vs. 7.6%, P < .05). In addition, women aged 35 and above with singleton pregnancies showed a significantly increased rate of fetal loss (13.4 vs. 4.9%, P < .05) when compared with younger women. Women > or = 35 years old and those with multiple gestations were significantly more likely to suffer late first- or early second-trimester fetal loss even after detection of fetal cardiac activity. These patients should be counseled differently than younger women with singleton pregnancies, and increased monitoring may be indicated.


Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis.
In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = -20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021-173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes.


Typing of MNSs blood group specific sequences in the human genome and characterization of a restriction fragment tightly linked to S-s- alleles.
Human erythrocyte membrane alpha and delta glycophorins (glycophorins A and B) carry the antigens for the M,N,S,s blood group system. Synthetic oligonucleotides spanning coding regions for M,N,S, and s epitopes were used to examine DNAs from 50 individuals selected at random and from individuals known to exhibit S(-)s(-)U- or S(-)s(-)U+ blood group phenotypes. We showed that M,N,S,s, blood group-specific sequences occur as multicopies in the human genome and reside within the alpha and delta glycophorin genes and also within the third glycophorin gene (glycophorin E gene). DNA typing with M- and N-epitope-specific probes showed distinct patterns that allowed correlation of the genotypes with the blood group phenotypes. The correlation using S- and s-specific probes was less definite owing to cross-hybridization. An Mspl restriction fragment length polymorphism (RFLP) residing in the E gene was detected in the black population. This RFLP is also carried by all individuals tested who exhibit the S(-)s(-)U- and S(-)s(-)U+ blood groups phenotypes, thereby serving as a useful marker for the S-s- alleles. The site of cleavage resulting in this RFLP was localized to the second intron of the E gene, and cleavage could occur through differential methylation of its two alleles.


Single-strand conformation polymorphism of microsatellite for rapid strain typing of Candida albicans.
Single-strand conformation polymorphisms (SSCP) of Candida albicans' microsatellite CAI were characterized. Among the 76 clinical isolates recovered from different patients (independent strains), 60 distinct CAI SSCP patterns were recognized, resulting in a discriminatory power of 0.993. The multiple isolates recovered sequentially from the same or different body locations of the same patient showed exactly the same CAI SSCP pattern. The reliability of the SSCP analysis was confirmed by GeneScan and sequence analyses. From the same set of independent strains, 59 distinct CAI genotypes were identified by GeneScan analysis. Sequence comparison showed the advantage of SSCP over GeneSan analysis in the detection of point mutations in the microsatellite. The results indicated that PCR SSCP analysis of CAI microsatellite is a powerful and economical approach for rapid strain typing of C. albicans in clinical laboratories, especially in the detection of microevolutionary changes in microsatellites and in large-scale epidemiological investigation.


Ontogenetic Emergence of Cognitive Reference Comprehension.
Prelinguistic cognitive reference comprehension is foundational to language acquisition and higher cognitive functions. However, its ontogenetic origins in the first year of life are currently not well understood. The current study pitted cognitivist against social interactionist views. We worked with infants monthly from 10 to 13 months of age and observed their behavioral search during a reference comprehension task. Our goal was to first establish the age at which infants begin to cognitively expect an occluded object in one of two locations following a communicative pointing cue. We then tested whether infants' cognitive referential expectations would prospectively predict social interaction skills and experiences (as assessed by spontaneous infant and parent pointing) or, conversely, be predicted by social interaction skills and experiences. Results revealed a linear increase in cognitive reference comprehension, with clear above chance performance, individual stability in month-to-month correlations, and a synchronous correlation to referential pointing all emerging at 12 months but not earlier. Regarding developmental predictions, infants' cognitive referential expectations were not predictive of social interaction skills and experiences; on the contrary, they were predicted by social interaction skills and experiences. Findings suggest that a nonverbal cognitive understanding of reference to occluded entities is neither early emerging, hard wired, nor causal to infants' or caregivers' referential pointing. Instead, this foundational skill is predicted by earlier social interaction. Findings are consistent with the view that cognitive reference comprehension develops via a social construction process in the first year of life.


Perceived Prejudice and the Mental Health of Chinese Ethnic Minority College Students: The Chain Mediating Effect of Ethnic Identity and Hope.
As a multinational country incorporating 56 officially recognized ethnic groups, China is concerned with the mental health of members of minority ethnic groups, with an increasing focus on supporting Chinese ethnic minority college students. Nevertheless, in daily life, members of minority ethnic groups in China often perceive prejudice, which may in turn negatively influence their mental health, with respect to relative levels of ethnic identity and hope. To examine the mediating effects of ethnic identity and hope on the relationship between perceived prejudice and the mental health of Chinese ethnic minority college students, 665 students (18-26 years old; 207 males, 458 females; the proportion of participants is 95.38%) from nine colleges in the Guangxi Zhuang autonomous region and Yunnan and Guizhou provinces of China took part in our study, each completing adapted versions of a perceived prejudice scale, a multiethnic identity measure, an adult dispositional hope scale, and a general health questionnaire. Analysis of the results reveals that perceived prejudice negatively influences mental health through both ethnic identity and hope in Chinese ethnic minority college students. The total mediation effect was 54.9%. Perceived prejudice was found to negatively predict ethnic identity and hope, suggesting that perceived prejudice brings about a negative reconstruction of ethnic identity and hope mechanisms within the study's Chinese cultural context. The relationship between perceived prejudice and mental health was fully mediated by hope and the chain of ethnic identity and hope. Ethnic identity partially mediated the relationship between perceived prejudice and hope. The relationship between perceived prejudice and mental health mediated by ethnic identity was not significant, which suggests that the rejection-identification model cannot be applied to Chinese ethnic minority college students. This paper concludes by considering the limitations of our study and discussing the implications of its results for researchers and practitioners.


Characteristics attributed to individuals with dental fluorosis.
Previous investigations of the public perception of dental fluorosis have focused mainly on aesthetics. Other characteristics which could potentially be ascribed to fluorosis, such as perceived personality traits, have not been examined. This study aimed to identify personal characteristics (descriptors) attributed to people with fluorosis of varying degrees of severity, as depicted in standardised photographs viewed from different perspectives. Extra-oral (full face) and intra-oral images of male and female subjects were digitally manipulated to represent normal dental enamel, mild, moderate, and severe fluorosis. The images were then scored by 90 members of the public (45M, 45F), under different experimental conditions, which varied the level of cueing to the teeth. Participants were asked (i) to record their spontaneous descriptors, (ii) select relevant descriptors from a predefined list of 50 descriptors and traits. 170 different word or phrase descriptors were spontaneously attributed to the images. Characteristics used to describe fluorosis varied with the degree of severity. However, endorsements were significantly influenced by whether participants viewed extra or intraoral images and the degree of cueing. Conditions which most accurately mirrored everyday social interactions, that is viewing extraoral images without cueing to pay particular attention to the mouth, were least likely to result in the attribution of characteristics that varied with levels of fluorosis. While characteristics varying with severity of dental fluorosis were ascribed, more sophisticated attitudinal measures are required to ascertain the wider social impact of fluorosis beyond the aesthetic.


Chromatin effector Pygo2 regulates mammary tumor initiation and heterogeneity in MMTV-Wnt1 mice.
Little is known about chromatin mechanisms that regulate tumor-initiating cells that are proposed to be responsible for tumor recurrence and relapse. We have previously shown that Pygopus 2 (Pygo2), a chromatin effector and context-dependent Wnt signaling coactivator, regulates mammary gland development by expanding epithelial stem/progenitor cells. However, the role of Pygo2 in mammary tumorigenesis in vivo remains to be addressed. In this study, we show that epithelia-specific ablation of Pygo2 in MMTV-Wnt1 transgenic mice results in delayed mammary ductal elongation, but the hyperbranching phenotype, aberrant accumulation of stem/progenitor-like cells, and canonical Wnt signaling output are largely unaffected. Chronic loss of Pygo2 significantly delays mammary tumor onset in MMTV-Wnt1 females, whereas acute deletion of Pygo2 in MMTV-Wnt1 tumor cells leads to a significant decrease in their tumor-initiating capability upon transplantation. Finally, we provide evidence supporting a role for Pygo2 in modulating the lineage potential of MMTV-Wnt1 tumor initiating cells. Collectively, our results suggest that Pygo2 acts at a step downstream of mammary stem cell accumulation to facilitate transformation, and that it regulates the tumor initiating capacity and lineage preference of the already transformed mammary cells, in MMTV-Wnt1 mice. These findings offer valuable insights into our understanding of the molecular basis of heterogeneity within breast tumors.


Protective effects of luteolin on rat testis following exposure to 900 MHz electromagnetic field.
Increasing cell phone use calls for clarification of the consequences of long term exposure to electromagnetic fields (EMF). We investigated the effects of EMF on the testes of 12-week-old rats as well as possible protective effects of luteolin on testis tissue. Twenty-four Wistar albino rats were randomly divided into four groups: control, EMF, luteolin, and EMF + luteolin. The number of Leydig cells, primary spermatocytes and spermatids were reduced in the EMF group compared to the control group. In the EMF + luteolin group, the number of Leydig cells, primary spermatocytes and spermatids was significantly greater than the EMF group. We found an increase in superoxide dismutase (SOD) activity in the EMF group compared to the control group. In the EMF group, we found decreased wet weight of testes and serum testosterone levels compared to the control group. Decreased SOD enzyme activity, and increased serum testosterone levels and weight of the testes were observed in the EMF + luteolin group compared to the EMF group. EMF also affected sperm morphology. We found that in rat testis repeated exposure to 900 MHz EMF caused changes in testicular tissue and that the antioxidant, luteolin, substantially reduced the deleterious effects of EMF.


Oxoglaucine Suppresses Hepatic Fibrosis by Inhibiting TGFβ-Induced Smad2 Phosphorylation and ROS Generation.
Hepatic fibrosis is the first stage of liver disease, and can progress to a chronic status, such as cirrhosis or hepatocellular carcinoma. Excessive production of extracellular matrix (ECM) components plays an important role in the development of fibrosis. Mechanistically, transforming growth factor beta (TGFβ)-induced phosphorylation of Smad is thought to be a key signaling pathway in the development of liver fibrosis. Although the natural isoquinoline alkaloid oxoglaucine (1,2,9,10-tetramethoxy-7H-dibenzo(de,g)quinolin-7-one) exerts numerous beneficial effects, including anti-cancer, anti-inflammatory, and anti-osteoarthritic effects in diverse cell types, the effects of oxoglaucine on liver fibrosis and fibrogenic gene expression have not been fully elucidated. The aim of this study is to evaluate the signaling pathway and antifibrotic activity of isoquinoline alkaloid oxoglaucine in TFGβ-induced hepatic fibrosis in vitro. Using Hepa1c1c7 cells and primary hepatocytes, we demonstrated that oxoglaucine treatment resulted in inhibition of the expression of fibrosis markers such as collagen, fibronectin, and alpha-SMA. Subsequent experiments showed that oxoglaucine suppressed TGFβ-induced phosphorylation of Smad2 and reactive oxygen species (ROS) generation, without altering cell proliferation. We further determined that the increase in Smad7 by oxoglaucine treatment is responsible for the inhibition of Smad2 phosphorylation and the anti-fibrogenic effects. These findings indicate that oxoglaucine plays a crucial role in suppression of fibrosis in hepatocytes, thereby making it a potential drug candidate for treatment of liver fibrosis.


Resection of non-cystic adenocarcinoma in pancreatic body and tail.
To report the outcome of Chinese patents with non-cystic adenocarcinoma in pancreatic body and tail (NCAPBT) after resection and to discuss its surgical strategy. Resection of NCAPBT was performed in eight Chinese patients with complete clinical-pathological data in our hospital from January 2000 to May 2004. The surgical strategy was explored by analyzing the results of these patients. The resection rate of NCAPBT in patients without back pain was higher than that in patients with back pain (66.67% vs 20%, 2/3 vs 1/5). The prognosis in the group receiving palliative resection was poorer than that in the group receiving curative resection. The median survival time was 12 mo in the curative resection group and 6 mo in the palliative resection group, respectively. The overall survival time of the Chinese patients with NCAPBT is dismal. The Chinese patients after curative resection of NCAPBT have a longer survival time. The Chinese NCAPBT patients with back pain trend to have a lower curative resection rate, but back pain should not be considered a contraindication for curative resection.


Wound-Induced Polyploidy Is Required for Tissue Repair.
Significance: All organs suffer wounds to some extent during an animal's lifetime and to compensate for cell loss, tissues often rely on cell division. However, many organs are made up of differentiated cells with only a limited capacity to divide. It is not well understood how cells are replaced in the absence of cell division. Recent Advances: Recent studies in the model organism Drosophila melanogaster have proven that wound-induced polyploidy (WIP) is an essential mechanism to replace tissue mass and restore tissue integrity in the absence of cell division. In this repair mechanism, preexisting differentiated cells increase their DNA content and cell size by becoming polyploid. Critical Issues: Cells within mammalian organs such as the liver, heart, and cornea have also been observed to increase their DNA ploidy in response to injury, suggesting that WIP may be an evolutionarily conserved mechanism to compensate for cell loss. Future Directions: The Hippo signal transduction pathway is required for differentiated cells to initiate WIP in Drosophila. Continued studies in Drosophila will help to identify other signaling pathways required for WIP as well as the conserved mechanisms that polyploid cells may play during wound repair in all organisms.


Hepatic lobe torsion as a cause of colic in a horse.
A 14-year-old Arabian gelding was examined for colic. An exploratory celiotomy was subsequently performed and the left lobe of the liver was found to be twisted. The lobe was resected using a TA-90 surgical stapling instrument. Histologic examination of the resected liver indicated portal vein and sinusoid dilation and congestion with blood. There were focal areas of necrosis and bacterial cocci and rods throughout the section. The histologic findings were consistent with hepatic lobe torsion. After surgery, the horse was treated with broad spectrum antibiotics, anti-inflammatory drugs, heparin, and intravenous fluids. The horse recovered without complications, although serum liver enzymes remained elevated for more than 1 week after surgery. Seven months after surgery the horse showed no adverse affects from the disease.


Alteration in the biliary and urinary excretion of acetaminophen metabolites by nephrotoxicants in rats.
It has been shown that ureter ligation increases the biliary excretion of acetaminophen (AA) conjugates, mainly as the sulfate in rats. This study was conducted to examine the effect of nephrotoxicants-that induce renal damage without liver injury on the biliary and urinary excretion of AA metabolites. Renal damage was produced in male S.D. rats, 1 day after dosing with 200 mg/kg p.o. of hexachloro-1,3-butadiene (HCBD), or 3 day after the dosage of 7.5 mg/kg iv of cisplatin (CIS). Renal damage without liver injury was confirmed by measuring serum enzymes, creatinine and BUN levels. AA and its metabolites were measured for 3 hr by HPLC in rats injected iv with 150 mg/kg of AA. The excreted amounts of AA-glucuronide (AA-G), AA-sulfate (AA-S) and AA-glutathione into bile were reduced to 57, 18 and 73% of control rats, respectively, by HCBD. HCBD pretreatment also altered the urinary excretion of AA-G, AA-S and AA-mercapturate to 75, 14 and 118% of controls. CIS drastically reduced the urinary excretion of AA metabolites, whereas this compound significantly enhanced the biliary excretion of AA-S. However, CIS did not cause an increase in the percentage of the dose excreted as AA-G in bile. Both HCBD and CIS caused marked elevations in the blood concentrations of AA-G and AA-S. These findings suggest that: 1) not all renal malfunction results in increased biliary excretion of AA metabolites to compensate for the lack of renal elimination, and 2) the selective reduction in biliary and urinary excretion of AA-S by HCBD appears to occur by mechanism(s) other than through alteration of AA and its metabolites.


Molecular cloning and structural modelling of gamma-phospholipase A2 inhibitors from Bothrops atrox and Micrurus lemniscatus snakes.
Phospholipases A2 inhibitors (PLIs) produced by venomous and non-venomous snakes play essential role in this resistance. These endogenous inhibitors may be classified by their fold in PLIα, PLIβ and PLIγ. Phospholipases A2 (PLA2s) develop myonecrosis in snake envenomation, a consequence that is not efficiently neutralized by antivenom treatment. This work aimed to identify and characterize two PLIs from Amazonian snake species, Bothrops atrox and Micrurus lemniscatus. Liver tissues RNA of specimens from each species were isolated and amplified by RT-PCR using PCR primers based on known PLIγ gene sequences, followed by cloning and sequencing of amplified fragments. Sequence similarity studies showed elevated identity with inhibitor PLIγ gene sequences from other snake species. Molecular models of translated inhibitors' gene sequences resemble canonical three finger fold from PLIγ and support the hypothesis that the decapeptide (residues 107-116) may be responsible for PLA2 inhibition. Structural studies and action mechanism of these PLIs may provide necessary information to evaluate their potential as antivenom or as complement of the current ophidian accident treatment.


Universality in surface mixing rule of adsorption strength for small adsorbates on binary transition metal alloys.
Understanding the adsorption phenomena of small adsorbates involved in surface reactions on transition metals is important because their adsorption strength can be a descriptor for predicting the catalytic activity. To explore adsorption energies on a wide range of binary transition metal alloys, however, tremendous computational efforts are required. Using density functional theory (DFT) calculations, here we suggest a "surface mixing rule" to predict the adsorption energies of H, O, S, CO and OH on bimetallic alloys, based on the linear interpolation of adsorption energies on each pure surface. As an application, the activity of CO oxidation on various bimetallic alloys is predicted from the adsorption energies of CO and O easily obtained by the surface mixing rule. Our results provide a useful tool for rapidly estimating adsorption energies, and furthermore, catalytic activities on multi-component metal alloy surfaces.


Phosphate-binding capacities of calcium and aluminum formulations.
Calcium and aluminum phosphate binders are used to treat hyperphosphatemia which is responsible for the development of osteodystrophy commonly seen in patients with end-stage renal disease. The purpose of this study was to determine the phosphate binding capacities of several frequently used calcium and aluminum formulations. The effect of formulation types on phosphate binding was evaluated. Calcium and aluminum phosphate binders were administered to six healthy volunteers after phosphate load on separate study days. Total urine outflow was collected afterwards to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The amounts of urinary phosphate recovered were different after administration of the phosphate binders. Calcium acetate resulted in the least amount of phosphate excreted. Calcium carbonate suspension, when compared with the tablet formulation, caused a smaller amount of phosphate excreted in the urine. Different phosphate binders formulations were found to have different phosphate binding capacities. Patients should therefore be closely monitored for efficacy after switching from one phosphate binder to another.


A Completed Cycle Audit of Psychiatric Discharge Summaries.
Patients discharge summaries are important as they record a vital miles stone in patients' care. Their accurate record improves patients' care and clarifies communication between different health professionals. 60 Discharge summaries from different consultant psychiatrists' case load were audited. The results were analysed and presented with recommendations to improve them a format was suggested. A reaudit of 62 discharge summaries was carried out by the same team after three years in the same catchment area but the practice has changed to inpatient and community. Improvement in most of the areas audited occur in the reaudit which indicates the usefulness of audit in improving clinical practice which a pivotal part of clinical governance. This completed audit cycle has proven that clinical practice has been reviewed and methods of improving it have been implemented. It has been noted that more items were reviewed and added to the second cycle which should be condoned. Discharge summaries are important clinical documents in secondary and primary care communications. They are helpful for secondary care staff as they good references for people in out of hours services and Accident and Emergency. Good quality discharge summaries improve patients care and make it easy to manage clinical risk.


Intranasal erythropoietin therapy in nervous system disorders.
Erythropoietin (EPO) is a growth hormone and cytokine that plays an important role in erythropoiesis and neuroprotection. However, EPO treatment for neurological diseases requires repeated injections or high-dose systemic administration, which may cause systemic side effects. The lack of any effective treatment of acute and chronic neurodegenerative diseases and the promising outcome by EPO in animal models in vivo demand a critical evaluation of intranasal EPO delivery to the brain as an alternative administration method. The current use and intranasal administration of EPO and its derivatives in preclinical studies and recent clinical trials with EPO in neurological diseases. This paper gives an overview of the therapeutic considerations of intranasal EPO and EPO derivatives for neuroprotection. Intranasal delivery (ID) of neuroprotective drugs is an area of great interest. Among the administration strategies used at present, ID of EPO is the most promising. Further preclinical and clinical studies are needed to evaluate the potential significance of this alternative route for increasing EPO bioavailability and decreasing side effects.


Grouping of residues based on their contact interactions.
Based on the concept of energy landscape a grouping method of residues for reducing the sequence complexity in proteins is presented. For the Miyazawa and Jernigan matrix, rational groupings of 20 kinds of residues with minimal mismatches, under the consideration of local minima and statistics on correlation between the residues, are studied. A hierarchical tree of groupings relating to different numbers of groups N is obtained, and a plateau around N=8-10 is found, which may represent the basic degree of freedom of the sequence complexity in proteins.


Oxytocic effects of the aqueous leaf extract of Costus lucanusianus - family Costaceae on isolated non-pregnant rat uterus.
Costus lucanusianus J. Braun (Costaceae) is a climbing herb, found mainly in the Niger Delta region of Nigeria. This plant is locally used in situations of pains, inflammation, dysmenorrhoea and in pyrexia. The purpose of this study was to investigate this claim with view to validating scientifically the ethno-medicinal usage. The aqueous extract was subjected to pharmacological testing in vitro on a piece of isolated rat uterus previously pretreated with 1 mg/kg stilbestrol for 24 h. The dose response curves of oxytocin and that of the extract were first obtained. The effects of antagonists like atropine (1 mg) and salbutamol (2 microg) on the dose response curve of the extract were also investigated. Possible synergy was investigated via co-administration of the extract and oxytocin. Finally the proximate analysis of the extract was investigated. The aqueous extract of C. lucanusianus and oxytocin both produced a dose dependent contraction of the uterus. An effect of 0.63+/-0.06 g force of uterine contraction produced by 12.5 mg of the extract was increased to 1.37+/-0.09 g when 200 mg of the extract was administered. Oxytocin at 0.16 i.u was observed to produce a similar force of contraction with 200 mg of the aqueous extract. Synergy was established as co administration of the extract at 200 mg and oxytocin at 0.08 i.u, produced higher contractile effect, significantly higher (p<0.05) than when either the extract (200mg) or oxytocin (0.08 i.u) was administered alone. Both atropine and salbutamol significantly (p<0.0001) inhibited the contractile effect produced by the extract. The inhibitory effect showed by atropine on the contractile effect of the extract seems to suggest the involvement of muscarinic receptors. The proximate analysis carried out in this study is used to establish the identity of the crude drug sample. A moisture content of 10.047 % was obtained. The total ash is a measure of the non-volatile inorganic constituents remaining after ashing. The values of 3.42 % were obtained.


Utility, reliability and reproducibility of immunoassay multiplex kits.
Multiplex technologies are becoming increasingly important in biomarker studies as they enable patterns of biomolecules to be examined, which provide a more comprehensive depiction of disease than individual biomarkers. They are crucial in deciphering these patterns, but it is essential that they are endorsed for reliability, reproducibility and precision. Here we outline the theoretical basis of a variety of multiplex technologies: Bead-based multiplex immunoassays (i.e. Cytometric Bead Arrays, Luminex™ and Bio-Plex Pro™), microtitre plate-based arrays (i.e. Mesoscale Discovery (MSD) and Quantsys BioSciences QPlex), Slide-based Arrays (i.e. FastQuant™) and reverse phase protein arrays. Their utility, reliability and reproducibility are discussed.


Enabling Technology for Safe Robot-Assisted Retinal Surgery: Early Warning for Unsafe Scleral Force.
Retinal microsurgery is technically demanding and requires high surgical skill with very little room for manipulation error. During surgery the tool needs to be inserted into the eyeball while maintaining constant contact with the sclera. Any unexpected manipulation could cause extreme tool-sclera contact force (scleral force) thus damage the sclera. The introduction of robotic assistance could enhance and expand the surgeon's manipulation capabilities during surgery. However, the potential intra-operative danger from surgeon's misoperations remains difficult to detect and prevent by existing robotic systems. Therefore, we propose a method to predict imminent unsafe manipulation in robot-assisted retinal surgery and generate feedback to the surgeon via auditory substitution. The surgeon could then react to the possible unsafe events in advance. This work specifically focuses on minimizing sclera damage using a force-sensing tool calibrated to measure small scleral forces. A recurrent neural network is designed and trained to predict the force safety status up to 500 milliseconds in the future. The system is implemented using an existing "steady hand" eye robot. A vessel following manipulation task is designed and performed on a dry eye phantom to emulate the retinal surgery and to analyze the proposed method. Finally, preliminary validation experiments are performed by five users, the results of which indicate that the proposed early warning system could help to reduce the number of unsafe manipulation events.


Clinical significances of p27 in digestive tract cancers: a comprehensive analysis on immunohistochemistry staining, published literatures, microarray and RNA-seq data.
In the present study, we conducted a comprehensive analysis on the clinical roles of p27 protein and p27 gene in digestive tract cancers (DTCs). First, we performed immunohistochemistry staining and found that p27 protein was down-regulated in DTCs. Then we collected 62 publications and calculated the combined hazard ratios (HRs), odds ratios (ORs) and 95% confidence intervals (95% CIs) to clarify the relationships of p27 protein expression with prognoses and clinicopathological parameters. The overall HRs indicated that the down-regulated p27 protein was an independent prognostic biomarker for overall survival (HR: 1.58, 95% CI: 1.38-1.81, P < 0.0001) but not for disease-free survival and cancer-specific survival. The combined ORs indicated that a low expression of p27 protein was positively related to lymph node metastasis (OR: 2.15, 95% CI: 1.57-2.96, P < 0.0001), distant metastasis (OR: 2.02, 95% CI: 1.12-3.63, P = 0.019) and pathology grading (OR: 2.14, 95% CI: 1.75-2.62, P < 0.0001). Additionally, 60 DTCs-related microarray and RNA-seq datasets were obtained to investigate the expression level and clinical value of p27 gene in DTCs patients. We found that the expression level of p27 gene in DTCs was similar to that in normal controls. And no significant associations of p27 gene expression with prognoses and clinicopathological factors were observed. In conclusion, according to our results, it was p27 protein, but not p27 gene, that can function as an effective biomarker to predict the clinical outcome in patients with DTCs. The down-regulation of p27 protein in DTCs may not result from the altered expression of p27 gene.


Immunogenicity and safety of the inactivated hepatitis A vaccine in children with juvenile idiopathic arthritis on methotrexate treatment: a matched case-control study.
To describe the immunogenicity and side effects of immunisation against hepatitis A virus (HAV) in JIA patients on methotrexate treatment, who have not been previously exposed to HAV. Case-control study performed in JIA patients and healthy controls matched on age and gender. The subjects received two doses of inactivated anti-HAV vaccine (720 mIU/ml) intramuscularly at 0 and 6 months. Seroconversion, seroprotection rates and anti-HAV-IgG titres were measured at 1, 7 and 18 months. Children were monitored for adverse events. 83 JIA patients and 76 controls were enrolled in the study. At one month, seroprotection rates were lower in children with, as compared to those without JIA (48.2% vs. 65%; p=0.05). At 7 and 18 months, rates of seroprotection rose significantly and were similar in both groups. The titre of anti-HAV-IgG was lower in children with JIA than healthy children at all time points (p<0.001). Vaccines were well tolerated. Two doses of inactivated HAV vaccine were well tolerated and immunogenic in most immunosuppressed children with JIA; however, a single dose of HAV vaccine was insufficient to induce seroprotection in half of the patients. Further studies are required to analyse the long-term immunity against HAV in this population and optimal HAV immunisation regimen.


Race Differences in Resilience Among Older Adults with Chronic Low Back Pain.
Racial minorities are disproportionally affected by pain. Compared to non-Hispanic Whites (NHWs), non-Hispanic Blacks (NHBs) report higher pain intensity, greater pain-related disability, and higher levels of mood disturbance. While risk factors contribute to these disparities, little is known regarding how sources of resilience influence these differences, despite the growing body of research supporting the protective role of resilience in pain and disability among older adults with chronic pain. The current study examined the association between psychological resilience and pain, and the moderating role of race across these relationships in older adults with chronic low back pain (cLBP). This is a secondary analysis of the Adaptability and Resilience in Aging Adults (ARIAA). Participants completed measures of resilience (ie, gratitude, trait resilience, emotional support), as well as a performance-based measure assessing lower-extremity function and movement-evoked pain. There were 45 participants that identified as non-Hispanic White (NHW) and 15 participants that identified as non-Hispanic Black (NHB). Race was a significant correlate of pain outcomes with NHBs reporting greater movement-evoked pain (r = 0.27) than NHWs. After controlling for relevant sociodemographic characteristics, measures of movement-evoked pain were similar across both racial groups, F (1, 48) = 0.31, p = 0.57. Moderation analyses revealed that higher levels of gratitude (b = -1.23, p = 0.02) and trait resilience (b = -10.99, p = 0.02) were protective against movement-evoked pain in NHWs. In contrast, higher levels of gratitude were associated with lower functional performance in NHBs (b = -0.13, p =0.02). These findings highlight racial differences in the relationship between resilience and pain-related outcomes among older adults with cLBP. Future studies should examine the potential benefits of targeted interventions that improve resilience and ameliorate pain disparities among racial minorities.


Nigella sativa Oil Improves Motor Skill Learning of Albino Mice: In Vivo and In Silico Investigations.
Experimental evidences demonstrated that Nigella sativa oil (NSO) can restore neuronal integrities and processes by increasing the neuronal density, decreasing apoptosis, preventing inflammatory processes, and improving the neurogenic cells in the hippocampus. This refurbishment enhances the learning process and memory. The antioxidant defense mechanism of NSO slows down the process of neurodegeneration and motor deficit. The present study aimed to investigate the effects of NSO on motor skill learning using the single pellet reaching task method on Swiss albino mice, followed by in silico studies. Mice (total of 16) were randomly divided into the control group and treatment group (n = 8). The treatment group received 1 ml/kg b.w. NSO orally once daily for 7 days, and a control group received 1 ml/kg normal saline instead of NSO in a similar manner. The average success rate due to ingestion of NSO in the treatment group mice increased significantly (P < 0.05) compared to controlled mice. Molecular docking analysis revealed that thymoquinone, carvacrol, thymohydroquinone, p-cymene, and t-anethole have binding affinities for the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA-R) that ranges from (-5.1 to -6.2) kcal/mol, which is comparable to the reference ligand glutamic acid binding affinity with AMPA-R (-6.6 kcal/mol). Thymoquinone and carvacrol formed hydrogen bonds with AMPA receptor at TYR61, SER142, and SER143 residues, comparable to the binding affinity of glutamic acid. ADMET analysis reported that all the compounds have higher bioavailability (>90%) and can cross the BBB easily (logBB> 0.3). Based on our experimental data and in silico report, we concluded that the enhanced motor skill learning effects of NSO are due to presence of potent antioxidants-thymoquinone and carvacrol-which might serve as AMPA receptor agonists. These phytoconstituents may play role in synaptic strengthening and promote experience-dependent motor skill learning.


Conformational stability of six truncated cHMG1a proteins studied in their mixture by H/D exchange and electrospray ionization mass spectrometry.
The high mobility group (HMG) proteins are abundant non-histone components of eukaryotic chromatin. The presence of C-terminal acidic tails is a common feature of the majority of HMG proteins. Although the biological significance of the acidic domains is not clear, they are conferring conformational and metabolic stability to the proteins in vitro. Moreover, the length and net charge of the acidic tails affect the strength of HMG protein interaction with DNA. Synthesis of an insect HMG protein by standard recombinant technology in bacteria leads to a mixture of the intact protein (cHMG1a-(1-113) (I)) and a series of its degradation products truncated at the C tail: cHMG1a-(1-111) (II); cHMG1a-(1-110) (III); cHuMGla-(1-109) (IV); cHMG1a-(1-108) (V); cHMG1a-(1-107) (VI); cHMG1a-(1-106) (VII). The proteins differ from each other only by the number of amino-acid residues at the C-terminal tail. We used H/D exchange mass spectrometry to characterize the stability of the proteins directly in their mixture. The results show that the proteins I-V and VII have very similar conformations. The protein VI is less compact and exchanges its protons faster than the others. It may be concluded that the C-terminal tail influences the conformation of the cHMG1a protein and that individual residues in this part of the protein play a key role in its compactness.


Pretreatment with melatonin protects against cyclophosphamide-induced oxidative stress and renal damage in mice.
Cyclophosphamide (CP) is widely used in treatment of different cancers. Nephrotoxicity is one of the dose-limiting side effects of CP. This study was carried out to investigate the effect of melatonin (MEL) on CP-induced nephrotoxicity in mice. In this study, 50 Swiss albino mice (20-25 g) were randomly divided into five groups. Mice were pretreated with MEL intraperitoneally (i.p) in doses of 5, 10 and 20 mg/kg for five consecutive days, and CP (200 mg/kg, i.p) was administrated on the 5th day 1 h after the last dose of MEL. Then on day 6, blood samples were collected to determine serum creatinine (Cr) and blood urea nitrogen (BUN) levels. The kidneys were used for histological examination, biochemical assays and real-time PCR studies. Malondialdehyde (MDA), glutathione (GSH), protein carbonyl (PC), nitric oxide (NO) level, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and myeloperoxidase (MPO) activity were assessed in renal tissue. In addition, the expression of SOD2 and PGx1 was measured using real-time PCR method in renal tissue. Results showed that CP administration significantly increases Cr, BUN, MDA, PC, NO level and MPO activity. It also decreases renal GSH level, SOD, GPx and CAT activity. Pretreatment with MEL (especially 20 mg/kg, i.p.) for 5 days prevented these changes; however, it did not affect the SOD activity. Our results revealed that MEL might be useful for prevention of the nephrotoxicity induced by CP through ameliorative effects on biochemical indices and oxidative stress parameters.


Single-step affinity purification for fungal proteomics.
A single-step protein affinity purification protocol using Aspergillus nidulans is described. Detailed protocols for cell breakage, affinity purification, and depending on the application, methods for protein release from affinity beads are provided. Examples defining the utility of the approaches, which should be widely applicable, are included.


Alamandine protects against renal ischaemia-reperfusion injury in rats via inhibiting oxidative stress.
This study was to determine whether alamandine (Ala) could reduce ischaemia and reperfusion (I/R) injury of kidney in rats. Renal I/R was induced by an occlusion of bilateral renal arteries for 70 min and a 24-h reperfusion in vivo, and rat kidney proximal tubular epithelial cells NRK52E were exposed to 24 h of hypoxia and followed by 3-h reoxygenation (H/R) in vitro. The elevated serum creatinine (Cr), blood cystatin C (CysC) and blood urea nitrogen (BUN) levels in I/R rats were inhibited by Ala treatment. Tumour necrosis factor alpha (TNF)-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax were increased, and Bcl2 was reduced in the kidney of I/R rats, which were reversed by Ala administration. Ala reversed the increase of TNF-α, IL-1β, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax and the decrease of Bcl2 in the H/R NRK52E cells. Ala could also inhibit the increase of oxidative stress levels in the kidney of I/R rats. NADPH oxidase 1 (Nox1) overexpression reversed the improving effects of Ala on renal function, inflammation and apoptosis of I/R rats. These results indicated that Ala could improve renal function, attenuate inflammation and apoptosis in the kidney of I/R rats via inhibiting oxidative stress.


Advances in Therapeutic Approaches to Extend Healthspan: a perspective from the 2nd Scripps Symposium on the Biology of Aging.
The 2nd Scripps Florida Symposium on The Biology of Aging entitled 'Advances in Therapeutic Approaches to Extend Healthspan' was held on January 22nd -25th , 2017 at The Scripps Research Institute in Jupiter, Florida. The meeting highlighted a variety of therapeutic approaches in animal models of aging that either are or soon will be in clinic trials. For example, drugs targeting senescent cells, metformin, rapalogs, NAD precursors, young plasma, mitochondrial-targeted free radical scavengers, stem cells, and stem cell factors all have shown significant preclinical efficacy. This perspective, based on presentations and discussions at the symposium, outlines the current and future state of development of therapeutic approaches to extend human healthspan.


Stomoxys calcitrans, mechanical vector of virulent Besnoitia besnoiti from chronically infected cattle to susceptible rabbit.
Cattle besnoitiosis caused by Besnoitia besnoiti (Eucoccidiorida: Sarcocystidae) is a re-emerging disease in Europe. Its mechanical transmission by biting flies has not been investigated since the 1960s. The aim of this study was to re-examine the ability of Stomoxys calcitrans (Diptera: Muscidae) to transmit virulent B. besnoiti bradyzoites from chronically infected cows to susceptible rabbits. Three batches of 300 stable flies were allowed to take an interrupted bloodmeal on chronically infected cows, followed by an immediate bloodmeal on three rabbits (Group B). A control group of rabbits and a group exposed to the bites of non-infected S. calcitrans were included in the study. Blood quantitative polymerase chain reaction (qPCR) analyses, and clinical, serological and haematological surveys were performed in the three groups over 152 days until the rabbits were killed. Quantitative PCR analyses and histological examinations were performed in 24 tissue samples per rabbit. Only one rabbit in Group B exhibited clinical signs of the acute phase of besnoitiosis (hyperthermia, weight loss, regenerative anaemia and transient positive qPCR in blood) and was seroconverted. Parasite DNA was detected in four tissue samples from this rabbit, but no cysts were observed on histological examination. These findings indicate that S. calcitrans may act as a mechanical vector of B. besnoiti more efficiently than was previously considered.


Comparative pyrimidine- and purine-specific RNAse-gold labeling on pancreatic acinar cells and isolated hepatocytes.
We applied the enzyme-gold approach to investigate the potential of various ribonucleases displaying different affinities for ultrastructural localization of particular RNA molecules. Five specific ribonucleases were used: three from a pancreatic source, RNAses A, B, and S with affinities for pyrimidine bases; and two from Aspergillus oryzae, RNAses T1 and T2 specific for purine bases. Conditions required for preparing each RNAse-gold complex, as well as for obtaining specific labelings, were determined. Application of the probes on thin sections of pancreatic acinar cells yielded labeling patterns that differed according to the enzyme used. Pancreatic RNAses labeled mostly the rough endoplasmic reticulum and the nucleolus, whereas fungal RNAses labeled more intensely the interchromatin space and the nucleolus, the rough endoplasmic reticulum being labeled to a lesser extent. Areas rich in interchromatin granules were intensely labeled by the RNAses T1 and T2. This was confirmed on DRB-treated hepatocytes, which displayed large clusters of interchromatin granules. Perichromatin granules were labeled by the RNAse A- and T1-gold complexes. These results provide a strong indication for the presence of RNA molecules in both types of granules. Nuclear pores were labeled, particularly by the RNAses T1 and T2, thus supporting the hypothesis for the site of RNA transit between nucleus and cytoplasm. The differences in patterns of labeling among the various enzyme-gold complexes could be related to differences in affinities. The use of a panel of specific RNAses, displaying different affinities, could thus allow for the topographical distribution of particular RNA molecules according to their relative content of specific bases.


Initialization Parameter Sweep in ATHENA: Optimizing Neural Networks for Detecting Gene-Gene Interactions in the Presence of Small Main Effects.
Recent advances in genotyping technology have led to the generation of an enormous quantity of genetic data. Traditional methods of statistical analysis have proved insufficient in extracting all of the information about the genetic components of common, complex human diseases. A contributing factor to the problem of analysis is that amongst the small main effects of each single gene on disease susceptibility, there are non-linear, gene-gene interactions that can be difficult for traditional, parametric analyses to detect. In addition, exhaustively searching all multi-locus combinations has proved computationally impractical. Novel strategies for analysis have been developed to address these issues. The Analysis Tool for Heritable and Environmental Network Associations (ATHENA) is an analytical tool that incorporates grammatical evolution neural networks (GENN) to detect interactions among genetic factors. Initial parameters define how the evolutionary process will be implemented. This research addresses how different parameter settings affect detection of disease models involving interactions. In the current study, we iterate over multiple parameter values to determine which combinations appear optimal for detecting interactions in simulated data for multiple genetic models. Our results indicate that the factors that have the greatest influence on detection are: input variable encoding, population size, and parallel computation.


Radiation dose to newborns in neonatal intensive care units.
With the increase of X-ray use for medical diagnostic purposes, knowing the given doses is necessary in patients for comparison with reference levels. The concept of reference doses or diagnostic reference levels (DRLs) has been developed as a practical aid in the optimization of patient protection in diagnostic radiology. To assess the radiation doses to neonates from diagnostic radiography (chest and abdomen). This study has been carried out in the neonatal intensive care unit of a province in Iran. Entrance surface dose (ESD) was measured directly with thermoluminescent dosimeters (TLDs). The population included 195 neonates admitted for a diagnostic radiography, in eight NICUs of different hospital types. The mean ESD for chest and abdomen examinations were 76.3 µGy and 61.5 µGy, respectively. DRLs for neonate in NICUs of the province were 88 µGy for chest and 98 µGy for abdomen examinations that were slightly higher than other studies. Risk of death due to radiation cancer incidence of abdomens examination was equal to 1.88 × 10 (-6) for male and 4.43 × 10 (-6) for female. For chest X-ray, it was equal to 2.54 × 10 (-6) for male and 1.17 × 10 (-5) for female patients. DRLs for neonates in our province were slightly higher than values reported by other studies such as European national diagnostic reference levels and the NRPB reference dose. The main reason was related to using a high mAs and a low kVp applied in most departments and also a low focus film distance (FFD). Probably lack of collimation also affected some exams in the NICUs.


Cross-Sectional Imaging of Intrahepatic Cholangiocarcinoma: Development, Growth, Spread, and Prognosis.
Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor that arises from the intrahepatic bile ducts. Although the pathologic and imaging features of ICC have been clearly identified, recent updates have addressed the pathologic classification and imaging features of ICC using new imaging techniques. First, a proposed new pathologic ICC subclassification includes perihilar large duct and peripheral small duct ICCs. Second, advanced MR-based imaging features of ICC, such as hepatobiliary phase imaging using hepatocytespecific contrast material and DWI, have recently been described. These imaging features are important when differentiating ICCs from hepatocellular carcinomas. Finally, some imaging features of ICC, such as prominent arterial enhancement or degree of delayed enhancement, exhibit potential as prognostic imaging biomarkers. Comprehensive and updated knowledge of ICC is necessary for accurate diagnosis and could facilitate prediction of clinical outcomes for patients with ICC.