Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-alpha.
Mice lacking epidermal growth factor (EGF), transforming growth factor alpha, and amphiregulin were used to identify roles for these EGF receptor (EGF-R) ligands in gastrointestinal development and mucosal integrity. Gastrointestinal tract development was examined in knockout mice and correlated with expression of EGF-R protein and EGF family members throughout the gut. Crossfostering experiments addressed roles of maternal- and neonatal-derived ligands in pup growth and intestinal development. Cysteamine-induced ulceration in EGF(-/-) mice was used to examine its role in mucosal cytoprotection. Neonatal mice lacking all 3 ligands were growth retarded, even when reared by wild-type dams; conversely, lack of maternal ligands transiently impaired wild-type pup growth. Triple null neonates displayed spontaneous duodenal lesions, and ileal villi were truncated and fragile with reduced cellular proliferation in the crypts. However, maturation of digestive enzymes was unaffected. Adult EGF(-/-) mice displayed more severe lesions in response to cysteamine treatment compared with wild-type counterparts, although triple null mice were not more susceptible to dextran sulfate sodium-induced colitis, suggesting a differential role for these ligands in the injury response. EGF-R ligands are required for development and mucosal maintenance in mouse small intestine. Both maternal and neonatal sources of growth factors are required for optimal pup growth.


Conserved miRNAs modulate the expression of potential transcription factors of isoflavonoid biosynthetic pathway in soybean seeds.
Despite the significant importance of soybean isoflavone, the regulatory mechanism of miRNAs during its biosynthesis is highly unexplored. In the present work, nine existing miRNAs along with their ten corresponding target genes were identified and validated in soybean for their possible role during isoflavonoid biosynthesis and accumulation. Temporal expression analysis at four key stages of seed development (35, 45, 55 and 65DAF) of all the miRNA-target pairs showed varying degree of differential accumulation in two soybean genotypes (NRC37: high isoflavone; and NRC7: low isoflavone). Differential expression of MYB65-Gma-miR159, MYB96-Gma-miRNA1534, MYB176-Gma-miRNA5030, SPL9-Gma-miRNA156, TCP3, TCP4-Gma-miRNA319, WD40-Gma-miRNA162, UDP-glucose: flavonoid 3-O-glucosyltransferase-Gma-miRNA396, and CHI3-Gma-miRNA5434 showed an important relationship with their targets in both the soybean genotypes across all the stages. Therefore, the finding of the present work would certainly increase our understanding of molecular regulation of isoflavone biosynthetic pathway mediated by the miRNA which would guide molecular breeder to develop isoflavone rich soybean cultivars.


Vagus Nerve Stimulation for Patients in Residential Treatment Facilities.
THIS ANALYSIS COMPARED THE EFFECTIVENESS OF VAGUS NERVE STIMULATION (VNS) THERAPY AMONG PATIENTS WITH INTRACTABLE SEIZURES: a group living in residential treatment facilities (RTF) with a group not living in RTFs (non-RTF). Among a constant cohort of patients with baseline, 3-month, and 12-month data, the RTF group had significantly (P < 0.05) larger numbers of patients with generalized seizures, previous callosotomy, psychiatric disorders, behavioral problems, and Rett's syndrome. Median seizure reductions after 3 months were 33% in the RTF group and 49% in the non-RTF group (P < 0.001); after 12 months, 50% (RTF) and 56% (non-RTF). After both 3 and 12 months, alertness, mood, postictal recovery, and cluster seizures improved in more than a third of patients in both groups. Because VNS therapy does not interact with medications and is delivered automatically, it should be seriously considered for patients with intractable epilepsy who reside in RTFs.


Predicting the Clean Movement Technique in Crossfit® Athletes Using an Optimal Upper-Limb Range of Motion: A Prospective Cohort Study.
The aim of this study was to determine the optimal upper-limb range of motion (ROM) profile for the catch phase of the clean movement (CPCM) and to identify the key ROMs for performing the CPCM in CrossFit® athletes. A prospective cohort study of twenty CrossFit® athletes aged 20-36 years was conducted. Data were collected regarding age, anthropometrics, CrossFit® training experience and upper-limb ROM. The ROM was measured using the ROM-SPORT method. After 7 months, athletes performed a clean movement with a load of 80% one repetition maximum. A Bayesian Student's t-analysis, binary logistic regression analysis and Receiver Operating Characteristic analysis were performed. The optimal upper-limb ROM profile that predicted correct CPCM performance was 78° in shoulder extension, 173° in shoulder flexion, 107° in shoulder external rotation, 89° in shoulder internal rotation, 153° in elbow flexion, 99° in elbow pronation and 92° in wrist extension (area under the curve ≥ 651; positive predictive value ≥ 80%). Shoulder external rotation, elbow pronation and wrist extension were found to be the most important ROMs for the efficient and safe performance of CPCM (area under the curve ≥ 854; positive predictive value ≥ 85.7%). The upper-limb ROM profile is associated with proper clean performance. Further studies are warranted to determine whether improving flexibility on upper-limb ROM may improve proper clean movement performance.


Cebocephaly in an infant with trisomy 18.
An infant who died in the perinatal period with the unusual association of trisomy 18 and cebocephaly is described. It is suggested that this association may be more common than is generally recognised because the majority of such infants are stillborn or live only briefly and often do not have chromosome studies performed.


Diffuse varioliform gastritis.
During 8 years experience, 90 cases of diffuse varioliform gastritis were observed (0.3% of examinations). Symptoms suggest either the presence of a gastroduodenal ulcer or of a digestive carcinoma when weight loss is prevalent. The disease proceeds by subacute evolutive bouts with remissions and further relapses. At endoscopy, lesions associate large folds in the fundus and erosive mucosal bulgings disseminated in the fundus and antrum. Histological alterations correspond to a superficial hyperplasic gastritis. Cellular infiltration of the lamina propria includes increased immunocytes population with an abnormal distribution of immunoglobulin classes. An increased percentage of IgE cells characterizes the disease as compared to inflammation in atrophic gastritis. Therapy is based upon agent inhibiting mastocytes degranulation and histamine antagonists. Diffuse varioliform gastritis must be separated from antral varioliform gastritis, a lesion with a higher frequency but no symptomatic individuality.


In silico markers: an evolutionary and statistical approach to select informative genes of human breast cancer subtypes.
Recent advancement in bioinformatics offers the ability to identify informative genes from high dimensional gene expression data. Selection of informative genes from these large datasets has emerged as an issue of major concern among researchers. Gene functionality and regulatory mechanisms can be understood through the analysis of these gene expression data. Here, we present a computational method to identify informative genes for breast cancer subtypes such as Basal, human epidermal growth factor receptor 2 (Her2), luminal A (LumA), and luminal B (LumB). The proposed In Silico Markers method is a wrapper feature selection method based on Least Absolute Shrinkage and Selection Operator (LASSO), Covariance Matrix Adaptation Evolution Strategy (CMA-ES) and Support Vector Machine (SVM) as a classifier. Moreover, the composite measure consisting of relevance, redundancy, and rank score of frequently appeared genes are used to select informative genes. The informative genes are validated by statistical and biologically relevant criteria. For a comparative evaluation of the proposed approach, biological similarity score designed on semantic similarity measure of GO terms are investigated. Further, the proposed technique is evaluated with 7 existing gene selection techniques using two-class annotated breast cancer subtype datasets. The utilization of this method can bring about the discovery of informative genes. Furthermore, under multiple criteria decision-making set-up, informative genes selected by the In Silico Markers are found to be admirable than the compared methods selected genes.


Impact of depressed skull fracture surgery on outcome of head injury patients.
To assess outcomes in surgically managed patients with depressed skull fractures and associated moderate to severe head injury. The study was conducted in the Department of Neurosurgery Jinnah Postgraduate Medical Centre, Karachi, from January 2016 to December 2017. We analyzed 90 patients with depressed skull fracture managed surgically from January 2015 to December 2016. The patients selected for this study belonged to all age groups with clinically palpable depressed skull fracture confirmed by CT brain with bone window. Outcome was assessed by Glasgow outcome score. Total 90 patients were included in the study. Sixty (66.7%) were male and 30 (33.3%) were female with mean age of years 27.58+11.329. Among 90 patients, 38.8% were aged between 21 and 30 years. Road traffic accident was seen in 72 (80%) patients. The commonest site of fracture was frontal region in 50 patients (55.6%). GCS improved post operatively on comparison to preoperative. Five patients expired. Depressed skull fracture is common neuro surgical issue. Timely surgical management gives excellent results by decreasing morbidity and mortality.


The induction of pulmonary phospholipidosis and the inhibition of lysosomal phospholipases by amiodarone.
Administration of high doses of amiodarone to young adult rats leads to phospholipidosis of the lung, with extensive phospholipid storage by type II pneumonocytes and alveolar macrophages. Biochemical analysis reveals an increase in the total phospholipid content of the lung and in the proportion of phosphatidylcholine. The cause of the phospholipidosis is suggested to be the inhibition of lysosomal phospholipases, responsible for catabolizing phospholipids. It is shown that amiodarone is a potent inhibitor of phospholipases prepared from the soluble fraction of adult rabbit lung lysosomes.


Complications associated with clear corneal cataract wounds during vitrectomy.
The purpose of this study was to report the intraoperative surgical complications that occurred during vitrectomy surgery associated with clear corneal incisions from previous cataract surgery. Retrospective, multicenter, case series, and chart review of five patients. Five patients, 3 men and 2 women, with a median age of 75 years (range, 59-78 years), were followed up for a median of 7.5 months (range, 6 months to 5 years). In each eye, the patient had previously undergone cataract surgery and intraocular lens implantation through a clear corneal wound. Each patient developed a surgical complication during the subsequent vitrectomy related to leakage through the clear corneal wound. Vitrectomy was performed for retained lens fragments (three), macular hole (one), and repair of combined rhegmatogenous/tractional diabetic retinal detachment (one). Twenty-gauge vitrectomy was performed in 3 cases; 23-gauge in 1 case; and a combined 25- and 20-gauge vitrectomy was used in 1 case. Median time between cataract surgery and vitrectomy was 8 days (range, 0-14 days). Median preoperative visual acuity was 20/200 (20/50 to hand motions), and median postoperative visual acuity was hand motions (20/40 to light perception). In all five eyes, the clear corneal wound was found to leak extensively with minimal manipulation of the sclera at the pars plana. Leakage through clear corneal wounds occurred during marking of the sclerotomy site (Case 1), during placement of a 23-gauge infusion cannula (Case 2), during lens fragmentation (Case 3), during retinotomy and retinectomy (Case 4), and during scleral depression (Case 4). Four eyes developed choroidal detachment associated with hypotony caused by leakage through the clear corneal wound. Three of these eyes developed hemorrhagic choroidal detachment with subretinal and/or vitreous hemorrhage. One eye developed iris incarceration and anterior subluxation of a sulcus-placed intraocular lens associated with leakage through the clear corneal wound. In all five cases, extra sutures were placed to secure the clear corneal incision, and the cases were able to be completed. Two eyes underwent repeat vitrectomy to address complications associated with hemorrhagic choroidal detachments. Median final visual acuity was 20/400 (range, 20/40 to hand motions). The retina remained attached in all cases at the latest follow-up visit. Intraoperative complications related to clear corneal incisions can occur during pars plana vitrectomy. We recommend that cataract surgeons encountering complications during surgery should secure clear corneal wounds in anticipation of eventual vitrectomy surgery. It is incumbent on the retinal surgeon to carefully inspect the corneal wound at the start of the vitrectomy procedure and to close it with sutures if it appears to leak with minimal manipulation. This should help to minimize additional intraoperative and/or long-term complications.


The pathology of optic nerve aging.
The pathology of the optic nerve in the advanced elderly has been investigated at autopsy in a sample of 50 subjects (43 males, 7 females), aged 95-103 years. Septal fibrous thickness and slendering of nerve fibers were the most frequently encountered lesions as well as degenerative processes involving the cribriform lamina. Other significant features included gliosis, demyelination, and corpora amylacea. Complete arteriosclerotic disease was rarely observed. The results of the present study suggest that optic nerve pathology in aged people is almost the consequence of an inadequate blood supply; nevertheless, the degree of these lesions does not seem to parallel that usually observed in other sites particularly injured by ischemic disease.


Rudimentary horn pregnancy in the first trimester; importance of ultrasound and clinical suspicion in early diagnosis: A case report.
We aimed to present 7-8 weeks rudimentary horn pregnancy detected preoperatively. A 37-year-old woman, gravida 3, para 2, at 7-8 weeks' gestation referred to our clinic with a complaint of abdominal pain. The patient was primarily infertile, and she had unicornuate uterus detected during infertility investigation. Due to abnormal ultrasonographic image, rudimentary horn pregnancy was considered. Accurate diagnosis was made by laparoscopy, and rudimentary horn excision was performed. Prerupture diagnosis is very difficult in rudimentary horn pregnancies. The key role in preoperative diagnosis is suspicion. Ultrasonographic examination and clinical suspicion are sufficient in most cases.


Primary hyperparathyroidism due to parathyroid carcinoma associated with pulmonary embolism.
Parathyroid carcinoma (PC) is an uncommon disease affecting 0.5-5% of all patients with primary hyperparathyroidism. PC is characterized by the association of severe symptoms of hypercalcemia, high serum calcium and parathyroid hormone (PTH) concentrations and a palpable neck mass. Definitive diagnosis can only be made by histological study after surgery. We report the case of a 77-year-old man admitted to our hospital due to pulmonary embolism and hypercalcemia. The patient was initially diagnosed with primary hyperparathyroidism, but displayed the atypical clinical features described above. Due to clinical suspicion of PC, a surgical procedure was carried out. Diagnosis of parathyroid carcinoma was confirmed by histopathologic study.


Surgical correction of cubitus varus in children with a lateral closing-wedge osteotomy: a comparison between two different techniques.
The primary objective of the present study is to compare the radiographic outcomes and complications of two different techniques for lateral closing-wedge osteotomy in pediatric patients with cubitus varus. We retrospectively identified patients treated at five tertiary care institutions: 17 underwent the Kirschner-wire (KW) technique, and 15 patients were treated with the mini external fixator (MEF) technique. Demographic data, previous treatment, pre- and postoperative carrying angle (CA), complications and additional procedures were recorded. Radiographic evaluation included assessment of the humerus-elbow-wrist angle (HEW), and the lateral prominence index (LPI). Patients treated with both KW and MEF achieved significant improvements in clinical alignment (mean pre-op CA -16 ± 6.1 degrees to mean post-op 8.9 ± 5.3 degrees, P < 0.001). There were no differences in final radiographic alignment or radiographic union time; however, time to achieve full elbow motion was faster in the MEF group (13.6 versus 34.3 weeks, P = 0.4547). Two patients (11.8%) in the KW group experienced complications, including one superficial infection and one failed correction that required unplanned revision surgery. Eleven patients in the MEF group underwent a planned second surgical procedure for hardware removal. Both fixation techniques are effective at correcting cubitus varus in the pediatric population. The MEF technique may have the advantage of shorter recovery of elbow range of motion but may require sedation for hardware removal. The KW technique may present a slightly higher complication rate.


CD10, TDAG51, CK20, AR, INSM1, and Nestin Expression in the Differential Diagnosis of Trichoblastoma and Basal Cell Carcinoma.
Trichoblastoma (TB) and basal cell carcinoma (BCC) are 2 different neoplasms composed of basaloid cells and have overlapping histopathological features. We compared the immunoexpression of CD10, T-cell death-associated gene 51 (TDAG51), cytokeratin 20 (CK20), androgen receptor (AR), insulinoma-associated protein 1 (INSM1), and nestin for the differential diagnosis of these tumors. We assessed a total of 27 BCC and 27 TB cases, including 4 TB lesions in nevus sebaceous and 3 malignant TB lesions for CD10, TDAG51, CK20, AR, INSM1, and nestin expression. Staining for CK20, TDAG51, INSM1, and stromal CD10 was significantly more common in TB cases than in BCC cases ( P < .001). Epithelial CD10 and AR staining was significantly more common in BCC cases than in TB cases ( P < .001). The difference between the groups for nestin staining was not significant ( P > .05). Stromal CD10 staining was the most sensitive marker (96.3%) and INSM1 the least sensitive (55.6%) marker for TB. TDAG51 showed 100% specificity for TB. A larger number of CK20 positive cells was found in the cases associated with nevus sebaceous than in the other TBs. All the selected markers except nestin were useful for the differential diagnosis between TB and BCC. CD10 and TDAG51 were more useful than the other markers. The use of CK20 could be preferred in nevus sebaceous lesions. INSM1 was less effective in highlighting Merkel cells within the lesion than CK20.


Who Said Medicine Means Never Having to Say You're Sorry?
Your mother said it, your teachers reiterated it, and you've heard it countless times: Everyone makes mistakes. So why do we doctors have such difficulty admitting that? More important, how do we respond to our patients after we make mistakes?


Interlimb postural coordination in the standing cat.
The dorsal-side-up body posture in standing quadrupeds is maintained by coordinated activity of four limbs. We studied this coordination in the cat standing on the platform periodically tilted in the frontal plane. By suspending different body parts, we unloaded one, two, or three limbs. The activity of selected extensor muscles and the contact forces under the limbs were recorded. With all four limbs on the platform, extensors of the fore- and hindlimbs increased their activity in parallel during ipsilateral downward tilt. With two forelimbs on the platform, this muscular pattern persisted in the forelimbs and in the suspended hindlimbs. With two hindlimbs on the platform, the muscular pattern persisted only in the hindlimbs, but not in the suspended forelimbs. These results suggest that coordination between the two girdles is based primarily on the influences of the forelimbs upon the hindlimbs. However, these influences do not necessarily determine the responses to tilt in the hindlimbs. This was demonstrated by antiphase tilting of the fore- and hindquarters. Under these conditions, the extensors of the fore- and hindlimbs appeared uncoupled and modulated in antiphase, suggesting an independent control of posture in the fore- and hindquarters. With only one limb supporting the shoulder or hip girdle, a muscular pattern with normal phasing was observed in both limbs of that girdle. This finding suggests that reflex mechanisms of an individual limb generate only a part of postural corrections; another part is produced on the basis of crossed influences.


Derivatization Technique To Identify Specifically Carbonyl Groups by Infrared Spectroscopy: Characterization of Photooxidative Aging Products in Terpenes and Terpeneous Resins.
Analysis of bioorganic materials by infrared spectroscopy (FT-IR) is frequently limited due to overlapping of diagnostic bands from the various components, which poses a fundamental problem to this analytical technique. The distinction of oxidized di- and triterpenes, for example, is hindered by the superposition of similar absorption bands of carbonyl functional groups summing up to a broad, nondistinctive signal. This study presents a technique for selective fluorination of various carboxylic acids by exposure to gaseous sulfur tetrafluoride. The derivatization treatment leads to characteristic band shifts, allowing the separation of otherwise overlapping bands. Accordingly, the IR bands of primary acids, α,β-unsaturated acids, tertiary acids, peroxy acids, esters, ketones, and α,β-unsaturated ketones are split into distinct absorption bands. The capability of this method is demonstrated on the example of natural resins and their ingredients, which are commonly known to be susceptible to oxidation at ambient conditions. The derivatization method enables one to identify various carbonyl containing functional groups by infrared spectroscopy, even in complex mixtures of terpenes. It unveils previously hidden degradation reactions running in terpenes and natural resins exposed to artificial aging by irradiation with light. New insight is presented on the individual reaction pathways of the terpenes hydroxydammarenone and abietic acid as well as of natural resin varnishes made from dammar and colophony.


Effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing total hysterectomy.
To observe the effects of hydromorphone and morphine intravenous analgesia on plasma motilin and postoperative nausea and vomiting in patients undergoing a total hysterectomy. 80 patients who underwent hysterectomy from April 2015 to June 2016 were randomly divided into two groups, with 40 patients in each group. The two groups received an intravenous infusion of hydromorphone or morphine for analgesia. The VAS pain score and Ramsey sedation score were recorded 4, 8, 12, 24, and 48 hours after the first dose of analgesia. The scores of nausea and vomiting were recorded. The levels of motilin were determined by radioimmunoassay before anesthesia, after anesthesia, during hysterectomy and 1 day after the operation. The results showed that the analgesic effect of hydromorphone was more rapid than morphine. There were significant differences in VAS scores between the two groups at each time point (p<0.05), indicating that the analgesic effect of hydromorphone was better than morphine's one. The scores of Ramsay sedation were less than 6 points at each time point within 48 hours after the operation. The content of plasma motilin in the hydromorphone group was higher than that in the morphine group during the first day after anesthesia. There were 34 cases (85%) of mild nausea and vomiting within 24 hours after the operation in the hydromorphone group. In the morphine group, there were 16 cases (40%) of mild nausea and vomiting within 24 hours after the operation, 10 cases (25%) of severe nausea and vomiting. The occurrence of severe malignant vomiting after the use of morphine was more than that after the use of hydromorphone. Normal level and function of motilin is the basis of avoiding nausea and vomiting. Too fast or too slow gastrointestinal motility can induce postoperative nausea and vomiting.


Digitally supported HIV self-testing increases facility-based HIV testing capacity in Ekurhuleni, South Africa.
HIV testing is the first step for linkage to HIV prevention or treatment services. Facility-based HIV testing is the most utilised method, but faces challenges such as limited work space and human resources. Digitally supported HIV self-testing (HIVST) provided in clinics shifts testing to the client, potentially empowering the client, and addresses such constraints. The study primary objective was to determine the feasibility of integrating digitally supported HIVST into the clinic. Secondary objectives were to describe HIV testing volume, populations reached, and antiretroviral treatment (ART) initiation. We conducted an analysis of prospectively collected data during implementation of digitally supported HIVST in two healthcare facilities based in South Africa from June 2019 to September 2019. We described implementation and client characteristics using HIVST and compared testing before and during implementation. During the 4-month implementation period there were 35 248 client visits. A total of 6997 (19.9%) of these visits involved HIV testing. Of those testing, 2278 (32.5%) used HIVST. Of the 2267 analysed, 264 (11.6%) were positive: 182 (12%) women and 82 (11%) men. Of those, 230 (95.4%) were confirmed HIV positive and 150 (65%) initiated ART within 14 days. During a four-month pre-implementation period, 14.5% of the clients tested for HIV. Compared to the pre-implementation period, we observed a 25% increase in HIV testing. Digitally supported HIVST increased the number of clients completing HIV testing in the health facility, without a need to significantly increase staff or space. Facility-based digitally assisted HIVST has the potential to increase HIV testing in high HIV prevalence clinic populations.


Noble gas and major element constraints on the water dynamics in an alpine floodplain.
The hydrogeological system of an ecologically sensitive alpine floodplain in the Valle di Blenio, Switzerland, was investigated using hydrochemical and 3H-3He dating methods. Water samples from six wells and from different surface locations were analyzed. The analysis of the concentrations of major ions in conjunction with age determination by the 3H-3He-method allowed the main hydrological properties of the system to be consistently characterized. Two geochemically distinct water zones can be distinguished: Ca-SO4-dominated water from the main river and Ca-HCO3-dominated floodplain water. The floodplain water component characterizes the whole floodplain including the surficial hillslope drainage system. Within the ground water samples, two spatially and temporally different types of water can be determined. A younger (age < 1.5 years), less mineralized water is found in the upper part of the aquifer during the summer season. The underlying aquifer zone contains older and more highly mineralized water. However, the general hydrochemical characterization of both types of ground water is similar. In winter, the water ages increase with decreasing ground water levels. Because precipitation is stored temporarily in the snow cover, the contribution of the younger near-surface ground water decreases, resulting in higher apparent water ages and higher mineralization in the upper zone of the aquifer. Water exchange between the main river and the ground water system is limited to ground water exfiltration from the shallow aquifer zone, whereas the hydrochemical separation of the deeper aquifer zone indicates the isolation of the deeper ground water from the main river.


Structure-based pharmacophore modeling, virtual screening, and molecular dynamics simulation studies for identification of Plasmodium falciparum 5-aminolevulinate synthase inhibitors.
Plasmodium falciparum (Pf) 5-aminolevulinic acid synthase (5-ALAS) is an essential enzyme with high selectivity during liver stage development, signifying its potential as a prophylactic antimalarial drug target. The aim of this study was to identify important potential lead compounds which can serve as inhibitors of Pf 5-ALAS using pharmacophore modeling, virtual screening, qualitative structural assessment, in silico ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) evaluation and molecular dynamics simulation. The best model of the tertiary structure of Pf 5-ALAS was obtained using MolProbity, while the following databases were explored for the pharmacophore-based virtual screening: CHEMBL, ChemDiv, ChemSpace, MCULE, MCULE-ULTIMATE, MolPort, NCI Open Chemical Repository, LabNetwork and ZINC databases. 2,621 compounds were screened against the modeled Pf 5-ALAS using AutoDock vina. The post-screening analysis was carried out using Discovery Studio while molecular dynamics simulation was performed on the best hits using NAMD-VMD and Galaxy Europe platform. Compound CSMS00081585868 was observed as the best hit with a binding affinity of -9.9 kcal/mol and predicted Ki of 52.10 nM, engaging in seven hydrogen bonds with the target's active site amino acid residues. The in silico ADMET prediction showed that all ten best hits possessed relatively good pharmacokinetic properties. The qualitative structural assessment of the best hit, CSMS00081585868, revealed that the presence of two pyridine scaffolds bearing hydroxy and fluorine groups linked by a pyrrolidine scaffold contributed significantly to its ability to have a strong binding affinity with the receptor. The best hit also showed stability in the active site of Pf 5-ALAS as confirmed from the RMSD obtained during the MD simulation.


The Influence of Cement Removal Techniques on In Situ Bacterial Adhesion and Biodegradation at the Marginal Interface of Ceramic Laminates.
This in situ study aimed to analyze the influence of different resin cement removal techniques on bacterial adhesion and biodegradation at the marginal interface of ceramic laminates. Eighty feldspathic ceramic (F) blocks were prepared and cemented onto bovine enamel slabs (7×2.5×2 mm). Excess cement was removed using a microbrush (MBR), a scalpel blade (SCP), or a Teflon spatula (TSP). For the biodegradation analysis, 40 disc-shaped resin cement specimens were prepared (7×1.5 mm) using a Teflon mold. The specimens were randomly allocated into two groups: (1) No finishing procedure (only Mylar strip), and (2) with finishing and polishing procedures using the Jiffy system (Ultradent, South Jordan, UT, USA) (n=20). The in situ phase consisted of using an intraoral palatal device by 20 volunteers for 7 days. Each device contained five cylindrical wells (8×3 mm), where three dental blocks and two cement specimens were included in the wells. Surface roughness (Ra) was measured using a contact profilometer. A micromorphological analysis was performed under a stereomicroscope and a scanning electron microscope. Bacterial adhesion was quantitated based on the number of colony-forming units (CFU/mL) and their biofilm development potential. The cement removal techniques directly affected surface roughness at the marginal interface (p<0.001), and the SCP technique produced higher mean roughness, regardless of the surface area analyzed. Surface polishing protected cement specimens from further biodegradation (p=0.148). There were no differences in CFU counts between the groups after the in situ phase (p=0.96). All specimens showed CFU with a strong ability to develop a biofilm. The techniques used for cement removal increased the surface roughness of ceramic laminates, particularly SCP, but they did not affect bacterial adhesion at the marginal interface. Surface polishing of the resin cement is recommended to mitigate biodegradation.


[Late reconstructive surgery for cloaca malformations].
The rarity of cloacal anomalies, the wide range of anatomical variants, and the number of different operations mean that successful management of a patient (neonate or child) with this condition is one of the greatest challenges for paediatric surgeons. The authors describe the complex corrections of 3 patients with cloacal malformation (age 10-13 years). The cloacal malformations were not diagnosed at neonatal age and therefore only the anorectal agenesis was corrected at the first stage. The authors strongly recommend that all components of this anomaly (urethra, vagina and anorectum) should be managed in one step. Because of the rarity and complexity of cloacal malformations, the anomaly should be operated on only in specialised centres.


Immunologic aspects of human colostrum and milk. I. Distribution characteristics and concentrations of immunoglobulins at different times after the onset of lactation.
Human colostrum and milk collected at different times after the onset of lactation from 200 subjects were tested for the levels of IgG, IgA, and IgM classes of immunoglobulins. The technique of radial immunodiffusion was employed. The levels of IgG immunoglobulin ranged from 1.4 to 4.9 mg/gm of protein at different intervals after onset of lactation. No significant change was observed in the individual levels of IgG over 180 days of sequential testing. On the other hand, highest levels of IgM and IgA immunoglobulins in the colostrum and milk were observed during the first three to four days postpartum. The IgM levels ranged from 27 to 30 mg/gm protein and IgA levels, from 22 to 35 mg/gm protein. A 3- to 4-fold decline in the levels of IgM and IgA immunoglobulin was demonstrated in milk samples collected 15 to 180 days postpartum. These observations provide reference data on the levels of immunoglobulins in colostrum and milk at different stages of lactation.


Preanalytical factors affecting blood inorganic phosphate concentration in dairy cows.
Hypophosphatemia is a condition that affects feed intake and milk production in dairy cows, and, to assess it, a precise biological parameter is needed. Plasma inorganic phosphate (Pi) can be used as a potential indicator of bioavailability of feed phosphorus in dairy cows. The purpose of this study was to evaluate the effects of sample type (serum vs. plasma), blood sampling site (jugular vs. coccygeal), and morning feeding on blood Pi concentration in dairy cows. Blood samples from 28 clinically healthy multiparous Holstein cows were analyzed for Pi concentration. The animals were sampled twice by coccygeal vessel into Vacutainer tubes both with and without sodium heparin, 3 hours after the morning feeding. In 4 additional cows, the concentration of Pi was measured in blood samples obtained simultaneously by jugular and coccygeal venipuncture into heparinized tubes before the morning feeding and 2, 4, and 6 hours after the feeding. The results were analyzed using parametric statistical tests. Serum and plasma concentrations of Pi were correlated (r(2) = 0.999, P < .0001), but serum Pi concentration was higher than plasma Pi (P < .02). Plasma Pi concentration 2 hours after feeding tended to be higher than that before feeding in jugular samples, but the difference was not significant. There was no significant variation in plasma Pi during the morning postfeeding times, although jugular concentrations were 19% lower than coccygeal (P = .04). To increase the precision of plasma Pi measurements as an indicator of bioavailability of feed phosphorus, sample type, sampling time, and site must be taken into account, to correctly interpret plasma Pi concentrations.


Effect of deep surgical sepsis on protein-sparing therapies and nitrogen balance.
Four patients from a larger group of 18 patients receiving dextrose-free isotonic (3%) amino acid solution as nutritional support, form the basis of this report. An additional seven patients received intravenous isotonic (5%) dextrose as their sole support in the postoperative period following major elective surgery (average nitrogen balance = -12.3 +/- 2.7 g). All patients were well-nourished as determined by anthropometric measurements. The nonseptic patients receiving infusions of isotonic amino acids demonstrated an improvement in nitrogen balance (= delta 8.5 +2, P less than 0.001) when compared to the postoperative use of 100 to 150 g of glucose. However, sepsis produced a decreased net utilization of the infused crystalline amino acids such that nitrogen balance was similar to the intravenous glucose group (- 10.6 +/- 2.1). This septic response was associated with decreased plasma free fatty acid concentrations and the absence of starvation ketosis and ketonuria. While the nitrogen balance was not different in the septic and the dextrose control groups, deficiencies in plasma amino acid concentrations were observed in the group receiving intravenous infusion of glucose.


Five Draft Genome Sequences of Historical Yersinia pestis Strains of Phylogroups 2.MED4 and 2.MED1 of the Medieval Biovar.
We announce the genome sequences of five historical highly virulent Yersinia pestis strains of the phylogroups 2.MED4 and 2.MED1 of the medieval biovar. They were the etiological agents of plague outbreaks with high mortality rates in the Northern Caspian Sea region at the end of the 19th century and beginning of the 20th.


[Albinism: diagnosis by visual evoked potentials].
In albinism the majority of the nerve fibers of the optic nerve originating from an eye are innervating the contralateral hemisphere. As a result of the predominantly monocular innervation of the left and right hemispheres, the unilateral activation of the visual cortex (lateralization) can be detected with visual evoked potentials (VEP). The VEPs were elicited with pattern onset stimulation. Five channels were recorded (2 channels over the left and right occipital lobe and 1 in the midline). 22 Patients with pendular nystagmus and 15 normal volunteers were examined. 5 of the normal volunteers were also examined with simulated pendular nystagmus (5-10 degrees, 1 Hz). The nystagmus was simulated by a simple galvanometer scanner based optical system. Unilateral activation of the hemispheres (lateralisation) was never detectable by normal volunteers. The lateralization of the VEP was detectable in all patients with oculocutaneous albinism with pattern onset stimulation. The pathological crossing of the nerve fibres in the optic chiasm is always detectable in oculocutaneous and ocular albinism with multichannel pattern onset VEP. The lateralization of the VEP is a more sensitive indicator of ocular albinism than other symptoms like macular hypoplasia, hypopigmentation, iris transillumination, nystagmus, reduced visual acuity et cetera.


Nickel-catalyzed enantioselective cross-couplings of racemic secondary electrophiles that bear an oxygen leaving group.
To date, effective nickel-catalyzed enantioselective cross-couplings of alkyl electrophiles that bear oxygen leaving groups have been limited to reactions of allylic alcohol derivatives with Grignard reagents. In this Communication, we establish that, in the presence of a nickel/pybox catalyst, a variety of racemic propargylic carbonates are suitable partners for asymmetric couplings with organozinc reagents. The method is compatible with an array of functional groups and utilizes commercially available catalyst components. The development of a versatile nickel-catalyzed enantioselective cross-coupling process for electrophiles that bear a leaving group other than a halide adds a significant new dimension to the scope of these reactions.


Distribution and behaviour of 233Pa in 2LiF-BeF2 molten salt.
Distribution and behavior of 233Pa, essential in the thorium-uranium nuclear fuel cycle, were studied in 2LiF-BeF2 (66 : 34 mole%, FLiBe) molten salt by γ-ray spectrometry. The experiments showed that 233Pa deposited slightly on the surface of graphite crucible. The addition of Hastelloy and metallic lithium decreased the 233Pa specific activity in the salt by 1 to 2 orders of magnitude rapidly. Analysis indicated that reductive deposition of 233Pa was responsible for the rapid decrease of 233Pa specific activity in the salt. Additional experiments strongly supported the mechanism of reductive deposition of 233Pa induced by Hastelloy and metallic lithium. In view of the large deposition of 233Pa on Hastelloy, the possible influence of fissile nuclide 233U produced from 233Pa decay on the operation of thorium-based molten salt reactor was discussed.


The Lsktm1 locus modulates lung and skin tumorigenesis in the mouse.
Alleles derived from skin tumor-resistant Car-R mice provide resistance to both skin and lung tumorigenesis over the susceptibility of the SWR/J strain. In an effort to map tumor modifier loci affecting both tumor types, we carried out a genetic linkage analysis in backcross SWR/J x (SWR/J x Car-R) mice and identified a locus (Lsktm1) on chromosome 1 linked to both skin (LOD score = 3.93) and lung (LOD score = 8.74) tumorigenesis. Two genes, Igfbp5 and Igfbp2, residing in this locus and belonging to the insulin-like growth factor binding protein family were expressed at significantly greater levels in normal lung tissue from cancer-resistant Car-R mice than in cancer-susceptible SWR/J mice. Overexpression of the recombinant Igfbp5 and Igfbp2 genes in two lung cancer cell lines significantly inhibited clonogenicity (P < 0.0001). Collectively, we have identified a single polymorphic locus that affects skin and lung tumorigenesis and identify Igfbp5 and Igfbp2 as candidate modifier genes of lung tumorigenesis.


Cerebral malaria and developmental biology: making parasites grow-up.
Erythrocytes infected with the protozoan parasite Plasmodium falciparum, in the final stages of asexual development, sequester and adhere to the lining of capillaries in the brain; killing 1-3 million (mostly children under the age of 5) each year. I will argue here that the rapidly evolving tools of developmental biology be employed to find a way of inducing gametocytogenesis, thereby making the parasite 'grow-up' prematurely, and in large numbers alleviating the severe symptoms in the brain.


Quadruple mutation GCAC1809-1812TTCT acts as a biomarker in healthy European HBV carriers.
Many mutation analyses of the HBV genome have been performed in the search for new prognostic markers. However, the Kozak sequence preceding precore was covered only infrequently in these analyses. In this study, the HBV core promoter/precore region was sequenced in serum samples from European inactive HBV carriers. Quadruple mutation GCAC1809-1812TTCT was found with a high prevalence of 42% in the Kozak sequence preceding precore among all HBV genotypes. GCAC1809-1812TTCT was strongly associated with coexistence of basal core promoter (BCP) double mutation A1762T/G1764A and lower HBV DNA levels. In vitro GCAC1809-1812TTCT lead to drastically diminished synthesis of pregenomic RNA (pgRNA), precore mRNA, core, HBsAg, and HBeAg. Calculation of the pgRNA secondary structure suggests a destabilization of the pgRNA structure by A1762T/G1764A that was compensated by GCAC1809-1812TTCT. In 125 patients with HBV-related cirrhosis, GCAC1809-1812TTCT was not detected. While a strong association of GCAC1809-1812TTCT with inactive carrier status was observed, BCP double mutation was strongly correlated with cirrhosis, but this was only observed in absence of GCAC1809-1812TTCT. In conclusion, our data reveal that GCAC1809-1812TTCT is highly prevalent in inactive carriers and acts as a compensatory mutation for BCP double mutation. GCAC1809-1812TTCT seems to be a biomarker of good prognosis in HBV infection.


[Detection of macrophage activity in the blood and synovia of chronic polyarthritis patients using an activated oxygen microassay].
A microassay was developed for the estimation of macrophage (M phi)-activation by released activated oxygen. From peripheral blood or synovia M phi are isolated. O-2 which is released by activated M phi is photometrically detected by cytochrome c reduction. Differences in O-2-production do not exist between monocytes of rheumatoid arthritis patients and controls. In contrast synovial M phi from rheumatoid arthritis patients show increased levels of O-2-production.


[Characteristics of bacteriology and drug sensitivity in patients with COPD combined with pneumonia].
To investigate the characteristics of bacteriology and the drug resistance in the patients with chronic obstructive disease (COPD) combined with pneumonia at our respiratory intensive care unit(RICU) in 2001. The sputum of 543 patients with COPD combined with pneumonia was collected with a regular method, the bacteria were cultured, and then the drug sensitivity was analyzed with K-B method. There were 181 positive samples in the 543 patients with the positive rate 33.9%. The main bacteria in the G- bacillus were Pseudomonas (21.55%), Haemophilus influenza (14.36%), Enteric bacilli (13.26%), and Klebsiella (11.60%) which were sensitive to impipenem, amikacin, and ceftazidime. The main bacteria in G+ bacteria were Staphylococcus aureus (7.18%) and Staphylococcus epidermindis (4.42%) which were sensitive to vancomycin, imipenem, ceftazidime, and amikacin. The bacteria in the patients with COPD combined with pneumonia at RICU of the hospital in 2001 are mainly made up of G- bacillus and secondarily of G+ bacteria which are sensitive to imipenem, amikacin, and ceftazidime. The G+ bacteria are highly sensitive to vancomycin.


Defect self-doped TiO₂ for visible light activity and direct noble metal anchoring.
A facile approach was developed for preparing defective, self-doped TiO2, which shows remarkable visible light activity in the photocatalytic degradation of RhB and hydrogen liberation from water. Moreover, noble metal was directly deposited onto the TiO2 surface via an in situ redox reaction between surficial Ti(3+) and metal salt. The lack of involvement of foreign reducing agents or stabilizers permits intimate contact between metal nanoparticles and the TiO2 substrate, which ensures the facilitated interfacial charge transfer. The strategy presented in this work may be applied to design other defect and noble metal mediated visible-light-active photocatalysts.


Predictors of immunosuppressive regulatory T lymphocytes in healthy women.
Immunosuppressive regulatory T (Treg) cells play an important role in antitumor immunity, self-tolerance, transplantation tolerance, and attenuation of allergic response. Higher proportion of Treg cells has been observed in peripheral blood of cancer cases compared to controls. Little is known about potential epidemiological predictors of Treg cell levels in healthy individuals. We conducted a cross-sectional study including 75 healthy women, between 20 and 80 years of age, who participated in the Data Bank and BioRepository (DBBR) program at Roswell Park Cancer Institute (RPCI), Buffalo, NY, USA. Peripheral blood levels of CD4(+)CD25(+)FOXP3(+) Treg cells were measured using flow cytometric analysis. A range of risk factors was evaluated using Wilcoxon Rank-Sum test, Kruskal-Wallis test, and linear regression. Age, smoking, medications for treatment of osteoporosis, postmenopausal status, body mass index (BMI), and hormone replacement therapy (HRT) were found to be significant positive predictors of Treg cell levels in peripheral blood (P ≤ 0.05). Higher education, exercise, age at first birth, oral contraceptives, and use of Ibuprofen were found be significant (P < 0.05) negative predictors of Treg levels. Thus, various epidemiological risk factors might explain interindividual variation in immune response to pathological conditions, including cancer.


A new shallow water species of Artemisina Vosmaer, 1885 (Microcionidae, Demospongiae; Porifera) from Northeastern Brazil.
Artemisina is a microcionid characterized by lacking a distinctive choanosomal skeleton or definite spongin fibres, lacking also echinating spicules, and with a nearly radial ectosomal skeleton (Hooper 2002). The genus currently has 19 valid species, six of which are recorded from the Atlantic Ocean (Van Soest et al. 2016): A. erecta Topsent, 1904, A. incrustans van Soest et al., 2013, A. melana van Soest, 1984, A. melanoides van Soest et al., 2013, A. transiens Topsent, 1890 and A. vulcani Lévi, 1963. The present study describes a new species of Artemisina from Northeastern Brazil. Four specimens of Artemisina brasili sp. nov. were collected by snorkelling at Pernambuco State. All specimens were preserved in 80% ethanol and deposited in the Porifera Collections at the Universidade Federal de Pernambuco (UFPEPOR) and Museu Nacional of Universidade Federal do Rio de Janeiro (MNRJ).


Cystic fibrosis transmembrane regulator fragments with the Phe508 deletion exert a dual allosteric control over the master kinase CK2.
Cystic fibrosis mostly follows a single Phe508 deletion in CFTR (cystic fibrosis transmembrane regulator) (CFTRDeltaF508), thereby causing premature fragmentation of the nascent protein with concomitant alterations of diverse cellular functions. We show that CK2, the most pleiotropic protein kinase, undergoes allosteric control of its different cellular forms in the presence of short CFTR peptides encompassing the Phe508 deletion: these CFTRDeltaF508 peptides drastically inhibit the isolated catalytic subunit (alpha) of the kinase and yet up-regulate the holoenzyme, composed of two catalytic and two non-catalytic (beta) subunits. Remarkable agreement between in silico docking and our biochemical data point to different sites for the CFTRDeltaF508 peptide binding on isolated CK2alpha and on CK2beta assembled into the holoenzyme, suggesting that CK2 targeting may be perturbed in cells expressing CFTRDeltaF508; this could shed light on some pleiotropic aspects of cystic fibrosis disease.


Stentless heterograft conduits for pulmonic ventricle to pulmonary artery connection: is it the right option?
A variety of stentless heterograft conduits has been developed as alternatives for pulmonary outflow reconstruction. Herein are reported the authors' results with four different types of stentless heterograft conduit implanted during the past nine years. Between January 1996 and March 2005, stentless heterograft conduits were used in 54 patients (mean age 9.9 +/- 7.5 years; median age 7 years; range: 1-32 years) to reconstruct the pulmonary outflow tract. The main pathologies were tetralogy of Fallot, transposition of the great arteries and aortic valve disease (Ross operation). A Baxter-Edwards Prima valve (EP) was used in three patients, a Medtronic Freestyle bioprosthesis (MF) in 27, a Cryolife Ross pulmonic heterograft (CR) in 14, and a Medtronic Contegra bovine jugular vein conduit (MC) in 10. The mean conduit diameter was 20.4 +/- 1.7 mm (range: 16-23 mm). Early mortality was 5.5%. Mean intensive care unit and hospital stays were 4.3 +/- 4.8 days and 11.7 +/- 7.2 days, respectively. Clinical follow up was complete for 92.1% of patients; the mean follow up period was 45.6 +/- 20 months. Excluding early deaths, the probability of patient survival (Kaplan-Meier) was 97.9% and 74.6% at one and five years, respectively. Transconduit gradients increased significantly in all conduit types during follow up. Conduit failure occurred in 15 patients (two EP, nine MF, three CR, one MC) at a median duration of 70 +/- 7 months (range: 56-84 months). To date, nine patients have undergone conduit re-replacement, without mortality and major morbidity. The probability of freedom from conduit failure was 91.6%, 66.4% and 27.9% at three, five and seven years, respectively. Stentless heterograft conduits are suitable alternatives to homografts, with acceptable early and mid-term results. However, they do not offer any significant advantage over homografts or other conventional Dacron or pericardial conduits.


Melatonin reduces apoptosis and necrosis induced by ischemia/reperfusion injury of the pancreas.
The pancreas is highly susceptible to the oxidative stress induced by ischemia/reperfusion (IR) injury leading to the generation of acute pancreatitis. Melatonin has been shown to be useful in the prevention of the damage by ischemia-reperfusion in liver, brain, myocardium, gut and kidney. The aim of the study was to evaluate the cytoprotective properties of melatonin against injury induced by IR in pancreas. The obstruction of gastro-duodenal and inferior splenic arteries induced pancreatic IR in male Wistar rats. Melatonin was intraperitoneally administered before or/and after IR injury. The animals were killed at 24 and 48 hr after reperfusion and there were evaluated parameters of oxidative stress (lipoperoxides, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione), glandular endocrine and exocrine function (lipase, amylase, insulin) and cell injury (apoptosis and necrosis). The IR induced a marked enhancement of oxidative stress and impaired pancreatic function. The histological analysis showed that IR induced acute pancreatitis with the accumulation of inflammatory infiltrate, disruption of tissue structure, cell necrosis and hemorrhage. Melatonin administration before or after pancreatic IR prevented all tissue markers of oxidative stress, biochemical and histological signs of apoptosis and necrosis, and restored glandular function. No histological signs of pancreatitis were observed 48 hr after reperfusion in 80% of the animals treated with melatonin, with only a mild edematous pancreatitis being observed in the remaining rats. Preventive or therapeutic administration of melatonin protected against the induction of oxidative stress and tissue injury, and restored cell function in experimental pancreatic IR in rats.


Enteroclysis and small bowel series: comparison of radiation dose and examination time.
Respective radiation doses and total examination and fluoroscopy times were compared for 50 patients; 25 underwent enteroclysis and 25 underwent small bowel series with (n = 17) and without (n = 8) an examination of the upper gastrointestinal (GI) tract. For enteroclysis, the mean skin entry radiation dose (12.3 rad [123 mGy]) and mean fluoroscopy time (18.4 minutes) were almost 1 1/2 times greater than those for the small bowel series with examination of the upper GI tract (8.4 rad [84 mGy]; 11.4 minutes) and almost three times greater than those for the small bowel series without upper GI examination (4.6 rad [46 mGy]; 6.3 minutes). However, the mean total examination completion time for enteroclysis (31.2 minutes) was almost half that of the small bowel series without upper GI examination (57.5 minutes) and almost four times shorter than that of the small bowel series with upper GI examination (114 minutes). The higher radiation dose of enteroclysis should be considered along with the short examination time, the age and clinical condition of the patient, and the reported higher accuracy when deciding on the appropriate radiographic examination of the small bowel.


Nursing informatics: scope and standards of practice.
The American Nurses Association published the third iteration of its nursing informatics scope and standards of practice in 2008. This work reflects the significant evolution of the specialty from the original scope of practice statement published in 1994 and the first nursing informatics standards of practice in 1995. Although the definition of nursing informatics remains essentially unchanged from that presented in 2001, the inclusion of "wisdom" reflects today's emerging mandate for evidence-based practice and decision support resources for the knowledge worker.


Chemical Compounds and Antioxidant Activity of Volatile Oil from the White Jelly Mushroom, Tremella fuciformis (Tremellomycetes).
To fully analyze the composition of volatile oil extracted from Tremella fuciformis, hydrodistillation (HD) and solid phase microextraction (SPME) were adopted simultaneously. In both cases, the analysis was carried out using gas chromatography-mass spectrometry and the antioxidant activity of the volatile oil was determined by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method with rutin as a positive control. Nineteen components in HD and 68 components in SPME were identified, respectively. Moreover, the oil obtained from T. fuciformis by HD indicated that aromatic compounds were a major class (93.5%), followed by the terpenes (5.7%), alkanes (0.4%), and alcohols (0.3%). Among them, butylated hydroxytoluene was the highest concentration (92.5%) of the compounds. The compounds detected by SPME were different from those of HD, and the substances with the largest content were esters (57.7%), followed by alcohols (19.0%), acids (7.0%), and aldehydes (6.3%). Only three of the same substances were detected in both of them, namely borneol, (-)-α-terpineol, and acetic acid. In the DPPH assays, strong antioxidant activity (IC50 = 0.176 mg/mL) was evident in volatile oil from T. fuciformis. Antioxidant activity was positively correlated with the concentration of volatile oil.


Targeting DNA double-strand break repair: is it the right way for sensitizing cells to 5-fluorouracil?
Inhibition of the repair of 5-fluorouracil (FU)-induced DNA lesions may improve the response of many tumors to this anticancer agent. Despite the identified associations between DNA strand breaks and the lethality of thymidylate synthase inhibitors, the role of DNA double-strand break (DSB) repair pathways in a cellular response to 5-FU treatment has not been studied yet. Isogenic cell lines defective (irs1SF), wild type (AA8), or reconstituted (1SFK8) in the DSB repair protein XRCC3 were used to investigate the effect of defective DSB repair on the overall sensitivity of cells to 5-FU and to see how targeting DSB repair may affect other cellular responses to 5-FU. Treatment with 5-FU resulted in (i) similar induction of DSB in both cell lines as indicated by the formation of gamma-H2AX (a marker for DSB). The repair of these breaks was complete in AA8 but not in irs1SF cells. (ii) Concentration-dependent reduction in the survival of both cell lines. The AA8 cells were six times more sensitive to 5-FU than the irs1SF cells. (iii) An earlier and more prolonged G(1)/S phase arrest in AA8 compared with the irs1SF cells. (iv) Induction of apoptosis as indicated by sub-G(1) cells and caspase-3 activity in AA8 but not in irs1SF cells. XRCC3 complementation of irs1SF cells restored the wild-type phenotype. This result shows that targeting DSB repair is not always associated with increased sensitivity to DNA damaging agents such as 5-FU because it may affect other cellular responses such as cell cycle regulation and induction of apoptosis.


[Surgical treatment of cryptorchism in scrotal hypoplasia].
In the submitted paper the authors give an account of their experience with the treatment of a patient with severe scrotal hypoplasia which is a very rare inborn defect. In a group of 1403 boys operated in the last ten years on account of cryptorchism this anomaly recorded only once, i.e. in 0.071%. The authors recommend a two-stage operation. In the first stage they use a V-Y plastic operation to create a neoscrotum. In the second stage orchidopexy is performed. Collaboration with a child endocrinologist is important. The aim of endocrinological examination is not only evidence of the presence and function of the gonads by a hormonal test, but in case of associated anomalies, also the assessment of genetic, genital and gonadal sex.


Identification of a novel mutation in the ATP7A gene in a Korean patient with Menkes disease.
Menkes disease is an infantile-onset X-linked recessive neurodegenerative disorder caused by diverse mutations in a copper-transport gene, ATP7A. Affected patients are characterized by progressive hypotonia, seizures, failure to thrive and death in early childhood. Here, we report a case of Menkes disease presented by intractable seizures and infantile spasms. A 3-month-old male infant had visited our pediatric clinic for lethargy, floppy muscle tone, poor oral intake and partial seizures. His hair was kinky, brown colored and fragile. Partial seizures became more frequent, generalized and intractable to antiseizure medications. An EEG showed frequent posteriorly dominant generalized spikes that were consistent with a generalized seizure. From a genetic analysis, a c.2743C>T (p.Gln915X) mutation was detected and diagnosed as Menkes disease. The mutation is a novel one that has not been previously reported as a cause of Menkes disease.


Trends in Nutrition Research for Sarcopenia: A Bibliometric Analysis.
Sarcopenia is age-related, pathophysiological muscle atrophy. Research regarding nutrition treatment of sarcopenia has developed rapidly, particularly as populations age. We evaluated the development of trends in this field using a bibliometric analysis. Articles up to July 2022 were searched in the Scopus database. Bibliographic information from the selected publications, such as countries, citations, world maps, institutions, authors, journals, and keywords, were converted and analyzed automatically using the "bibliometrix" package in R environment (version 4.2.0). We identified 368 Scopus articles from 1998-2021. According to citation analyses, 27 documents received more than 100 citations. Bibliometric analysis based on the literature included in this study revealed that South Korea (61 publications), United States (50), Japan (35), China (30), and Italy (20) contributed the most publications. Tehran University of Medical Science (19 records, 2.55% of articles) contributed the most publications. The most productive author was Landi, with eight articles (2.17% of articles). The publications were located in 196 journals, with Nutrients having the most publications (30, 8.15% of articles). The curves representing keywords "sarcopenia" and "aged" were the most apparent. Our analysis suggested that global nutrition and sarcopenia-related research increased rapidly from 2001 to 2021, demonstrating that this was a promising area of future research that could benefit from continued advances. Future research may focus on the effects of age and sex as well as intervention effectiveness, particularly exercise and nutrition supplementation.


Effect of the probiotic strain Bifidobacterium animalis subsp. lactis, BB-12®, on defecation frequency in healthy subjects with low defecation frequency and abdominal discomfort: a randomised, double-blind, placebo-controlled, parallel-group trial.
The aim of the present study was to investigate the effect of Bifidobacterium animalis subsp. lactis, BB-12®, on two primary end points - defecation frequency and gastrointestinal (GI) well-being - in healthy adults with low defecation frequency and abdominal discomfort. A total of 1248 subjects were included in a randomised, double-blind, placebo-controlled trial. After a 2-week run-in period, subjects were randomised to 1 or 10 billion colony-forming units/d of the probiotic strain BB-12® or a matching placebo capsule once daily for 4 weeks. Subjects completed a diary on bowel habits, relief of abdominal discomfort and symptoms. GI well-being, defined as global relief of abdominal discomfort, did not show significant differences. The OR for having a defecation frequency above baseline for ≥50% of the time was 1·31 (95% CI 0·98, 1·75), P=0·071, for probiotic treatment overall. Tightening the criteria for being a responder to an increase of ≥1 d/week for ≥50 % of the time resulted in an OR of 1·55 (95% CI 1·22, 1·96), P=0·0003, for treatment overall. A treatment effect on average defecation frequency was found (P=0·0065), with the frequency being significantly higher compared with placebo at all weeks for probiotic treatment overall (all P<0·05). Effects on defecation frequency were similar for the two doses tested, suggesting that a ceiling effect was reached with the one billion dose. Overall, 4 weeks' supplementation with the probiotic strain BB-12® resulted in a clinically relevant benefit on defecation frequency. The results suggest that consumption of BB-12® improves the GI health of individuals whose symptoms are not sufficiently severe to consult a doctor (ISRCTN18128385).


Effects of rice husk diluted dietary switching on the phenotypic change of gastrointestinal tract in adult ganders.
1. An experiment was conducted to test the directionality, scaling and reversibility of phenotypic responses of the gastrointestinal tract (GIT) of adult ganders to rice husk (RH) diluted dietary switching. 2. A total of 96 140-d-old ganders were acclimatised to a basal diet for 2 weeks. The birds were randomly assigned to 4 treatments. On d 1, diets in the experimental groups were switched from the basal diet to diets which contained 200, 400 or 600 g/kg RH by mass, with no RH in the basal diet. After 21 d, the diet of all the experimental birds was switched back to the basal diet until d 42. 3. Increasing RH content significantly increased feed intake, and a decreased trend appeared after diet-switching. The weights of geese fed on the 600 g/kg RH diet for 21 d reduced, and were significantly less than those of the other three groups, while body weights (BW) of the geese in all groups increased after diet-switching back to the basal diet. At d 21, significantly heavier relative weights of proventriculus, gizzard and all gut components, except duodenum, were observed in birds fed on a 600 g/kg RH diet, and significantly heavier relative weights of gizzard were observed in birds given a 400 g/kg RH diet. Thickness of the two gastric walls, gizzard length and all gut components lengths increased significantly in birds given a 600 g/kg RH diet compared with the other three groups. At d 42, no significant differences were noted in the relative weights or lengths of GIT, except for the caeca, which were significantly heavier in birds fed on 600 g/kg RH diet. 4. The results of the experiment were in accordance with the predictions of the hypothesis that there is matching between loads and capacities. The observed phenotypic responses were directional and scaled to the demands.


[Environmental audits of high voltage objects from the viewpoint of investors].
The localization of high voltage objects, e.g., overhead transmission lines, under the spatial planning and environmental protection regulations is discussed. The most important elements of the localization procedure concerning high voltage overhead lines are presented. One of the elements of this procedure is the assessment of the investment environmental impact. The environmental audit is an essential document, in which this impact is described. It seems that its scope specified in the Environmental Protection Act is not adjusted to the specificity of line investments. This gives rise to some problems in preparing environmental audits for overhead lines, e.g., possible influence of high voltage lines on the Natura 2000 area zones. Several other related problems are also highlighted in this paper.


Human blink startle during aversive and nonaversive Pavlovian conditioning.
Potentiation of blink startle during aversive and nonaversive Pavlovian single-cue conditioning was assessed in human Ss. In Experiment 1 (N = 89), the conditioning group received paired presentations of a visual conditioned stimulus (CS) and an unconditioned stimulus (US), whereas the control group was presented with a random sequence. The US was an electric shock for half the Ss and a nonaversive reaction time task for the other half. Electrodermal conditioning was evident regardless of the nature of the US, but blink potentiation was found only in the conditioning group that had been trained with the aversive US. These results were replicated in Experiment 2 (N = 65), in which a nonaversive US of increased motivational significance was used. Thus, only aversive conditioning seems to affect the affective valence of the CS, at least as reflected by changes in a skeletal reflex.


Removal of nasal foreign bodies with a Fogarty biliary balloon catheter.
Twenty-five children with a range of nasal foreign bodies, which were not easily amenable to anterior instrumental extraction, were considered for this study. These foreign bodies were removed by the use of a Fogarty biliary balloon catheter (Intimax) successfully in 23 children. In two children no foreign body was found. None of the children had any complications. This is a safe procedure which can be performed as an out-patient. Whilst the cost of the catheter may appear expensive, in comparison to the cost of admission for removal of similarly sited foreign bodies under general anaesthesia, the catheter fares favourably.


Benzoate fermentation by the anaerobic bacterium Syntrophus aciditrophicus in the absence of hydrogen-using microorganisms.
The anaerobic bacterium Syntrophus aciditrophicus metabolized benzoate in pure culture in the absence of hydrogen-utilizing partners or terminal electron acceptors. The pure culture of S. aciditrophicus produced approximately 0.5 mol of cyclohexane carboxylate and 1.5 mol of acetate per mol of benzoate, while a coculture of S. aciditrophicus with the hydrogen-using methanogen Methanospirillum hungatei produced 3 mol of acetate and 0.75 mol of methane per mol of benzoate. The growth yield of the S. aciditrophicus pure culture was 6.9 g (dry weight) per mol of benzoate metabolized, whereas the growth yield of the S. aciditrophicus-M. hungatei coculture was 11.8 g (dry weight) per mol of benzoate. Cyclohexane carboxylate was metabolized by S. aciditrophicus only in a coculture with a hydrogen user and was not metabolized by S. aciditrophicus pure cultures. Cyclohex-1-ene carboxylate was incompletely degraded by S. aciditrophicus pure cultures until a free energy change (DeltaG') of -9.2 kJ/mol was reached (-4.7 kJ/mol for the hydrogen-producing reaction). Cyclohex-1-ene carboxylate, pimelate, and glutarate transiently accumulated at micromolar levels during growth of an S. aciditrophicus pure culture with benzoate. High hydrogen (10.1 kPa) and acetate (60 mM) levels inhibited benzoate metabolism by S. aciditrophicus pure cultures. These results suggest that benzoate fermentation by S. aciditrophicus in the absence of hydrogen users proceeds via a dismutation reaction in which the reducing equivalents produced during oxidation of one benzoate molecule to acetate and carbon dioxide are used to reduce another benzoate molecule to cyclohexane carboxylate, which is not metabolized further. Benzoate fermentation to acetate, CO(2), and cyclohexane carboxylate is thermodynamically favorable and can proceed at free energy values more positive than -20 kJ/mol, the postulated minimum free energy value for substrate metabolism.


Lasker Awards Honor Three Researchers.
Three top cancer researchers were among recipients of the prestigious Albert and Mary Lasker Foundation awards. Douglas R. Lowy, MD, and John T. Schiller, PhD, were honored for research leading to the development of the first human papillomavirus vaccine. The prize for basic medical research went to Michael N. Hall, PhD, who discovered the TOR signaling pathway and its role in regulating cell growth and metabolism.


Development of Antimicrobial Cellulose Nanofiber-Based Films Activated with Nisin for Food Packaging Applications.
The cellulose nanofiber (CNF) is characterized by the nano-sized (fibers with a diameter between 5 and 20 nm and a length between 2 and 10 μm), flexible and cross-linked structure that confer enhanced mechanical and gas barrier properties to cellulosic fiber-based packaging materials. The purpose of this work was to develop an antimicrobial packaging film by direct mixing nisin with CNF, followed by coating it onto polyethylene (PE), polypropylene (PP), and polylactic acid (PLA) films. The antimicrobial effectiveness of CNF-Nis+PE, CNF-Nis+PP, and CNF-Nis+PLA was investigated both in vitro end in ex vivo tests. In the latter case, challenge test experiments were carried out to investigate the antimicrobial activity of the coupled films of CNF-Nisin+PLA to inhibit the growth of Listeria innocua 1770 during the storage of a meat product. The films were active against the indicator microorganisms Brochothrix thermosphacta and Listeria innocua in in vitro test. Moreover, a reduction in the Listeria population of about 1.3 log cycles was observed immediately after the contact (T0) of the active films with hamburgers. Moreover, when the hamburgers were stored in active films, a further reduction of the Listeria population of about 1.4 log cycles was registered after 2 days of storage. After this time, even though an increase in Listeria load was observed, the trend of the Listeria population in hamburgers packed with active films was maintained significantly lower than the meat samples packed with control films during the whole storage period.


Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3.
The predicted amino acid sequence of the cDNA encoding the murine B-lymphocyte differentiation antigen BP-1/6C3 suggested that it is a member of the zinc-dependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [microsomal aminopeptidase; alpha-aminoacyl-peptide hydrolase (microsomal), EC 126.96.36.199]. In the present studies, we examined the enzymatic activity of this antigen. From brush border preparations of the small intestine, a rich source of many endopeptidases and exopeptidases, the BP-1 antibody selectively removed aminopeptidase A [APA; L-alpha-aspartyl(L-alpha-glutamyl)-peptide hydrolase, EC 184.108.40.206] activity. The APA activity of a panel of cell lines correlated in linear fashion with cell-surface levels of the BP-1/6C3 antigen. APA activity was demonstrated for the BP-1/6C3 antigen immunopurified from the pre-B-cell membrane. This activity was enhanced by alkaline earth metals such as Ca2+ and was abrogated by amastatin and angiotensin, which are known competitive inhibitors of APA. The data indicate that the murine BP-1/6C3 antigen is active APA, an enzyme that catalyzes specifically the removal of unsubstituted, N-terminal glutamic acid and aspartic acid residues from peptides.


Reactivity of the Oxytocinergic and Neuroendocrine System Following the Adult Attachment Projective Picture System in Men of Recent Fatherhood: Results from an Exploratory Pilot Study with a Cross-Sectional Design.
The attachment representation (AR) of individuals affects emotional and cognitive information processes and is considered an important modulating factor of neuroendocrine stress responses. The neuropeptide oxytocin is studied as one biomolecular component underpinning this modulation. A validated procedure used in attachment-related research is the Adult Attachment Projective Picture System (AAP). To date, only a limited number of studies investigated oxytocin and neuroendocrine reactivity in the context of an attachment-related stimulus similar to the APP. In this pilot study, N = 26 men of recent fatherhood were exposed to the AAP to classify AR and to investigate salivary changes in oxytocin, cortisol and dehydroepiandrosterone (DHEA) after AAP stimulation. We observed increased oxytocin levels in response to AAP exposure, and this increase was more pronounced in fathers with unresolved/disorganized AR. No significant changes in cortisol and DHEA concentrations were observed in response to AAP administration. Interestingly, differences in basal cortisol levels (before the AAP) also depended on AR classification. Here, the group of men with unresolved/disorganized AR showed higher levels of cortisol compared to fathers with organized AR. To conclude, the finding of increased salivary oxytocin levels in response to the AAP further indicates its validity as an instrument to stimulate the attachment system.


The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group.
Cycle length variability (CLV), defined as the standard deviation of normal cycle length intervals, has been found to be a powerful predictor of subsequent mortality in a population of 808 survivors of acute myocardial infarction. Decreased CLV is associated with a significant increase in mortality. CLV remained an independent predictor of outcome even after adjusting for left ventricular ejection fraction, clinical risk factors, heart rate and ventricular arrhythmias. In the same population of survivors of acute myocardial infarction, the results of exercise testing also strongly predicted outcome, with those failing to take the test having the worst survival, and those completing the low-level stress test taken before discharge having the best prognosis. The hypothesis that the status of stress test (completed; did not complete; failed to take) and CLV were measuring the same factor related to mortality was tested. Although the distribution of CLV was shifted to higher CLV in patients who completed the test and to lower CLV in those who failed to take the test, both predictors of mortality remained independent predictors of long-term mortality (average of 31 months of follow-up) after controlling for each other. Moreover, subgroups with an approximate 15-fold difference in mortality were defined using both variables (CLV less than 50 ms, did not take test had a 54% mortality; CLV greater than 100 ms, completed the test had a mortality of 3.5%). CLV is a measure of autonomic tone; it is not strongly related to exercise ability and using the results of both stress testing and CLV results in the identification of subgroups of postinfarction patients with markedly disparate risks of mortality.


[Postural reactions in cosmonauts after long flights aboard Salyut-6].
Tilt tests were used to study changes in cardiovascular responses to ortho- and antiorthostasis of four cosmonauts after their 96- and 140-day flights onboard Salyut-6. Preflight the cosmonauts were exposed to head-up and head-down tests in order to facilitate their readaptation to weightlessness. Postflight all cosmonauts exhibited a better cardiovascular capability to counteract cranial blood redistribution during antiorthostatic tilt tests. This can be considered as a result of their adaptation to weightlessness. After flight every crewmember showed a significant decrease of orthostatic tolerance. One of the factors responsible for the lower orthostatic tolerance is assumed to be inactivity of the vascular tone mechanisms. It is suggested that their better stimulation before reentry may improve the efficacy of countermeasures against postflight orthostatic disorders.


Screening hybridomas for anabolic androgenic steroids by steroid analog antigen microarray.
Currently, dozens of anabolic androgenic steroids (AAS) are forbidden in the World Anti-Doping Agency Prohibited List, however, despite extensive investigation, there are still lots of AAS without corresponding monoclonal antibodies. A steroid analog antigen microarray made up of ten AAS was fabricated to screen the hybridoma and it was found an original unsuccessful clone turned out to be a candidate anti-boldenone antibody, without any cross-reactions with endogenous AAS or 44 different AAS standard reference materials tested. Our findings suggested that steroid analog antigen microarray could be a promising tool to screen and characterize new applications of antibodies for structure analogs, and this also exhibits the potential to fast identify effective epitopes of hybridomas in a single assay.


[Laparoscopic living donor nephrectomy of kidneys with multiple renal vessels].
Due to the increasing waiting time for transplantation of a cadaveric kidney, living donor kidney transplantation is an increasingly oncoming issue. Laparoscopic donor nephrectomies (LDN) have been performed since 1995 and presently more than 100 transplant centers offer this minimally invasive surgical approach. The advantages for the donor of less pain, shorter hospital stay, earlier return to work, better cosmetic results in combination with an organ function equal to open donor nephrectomy are the reasons for an enormous increase in LDN. Since up to 30% of the donor kidneys have multiple vessels for blood supply, an increase of these organs for LDN can be expected. We performed a retrospective study of LDN at our center and compared donors with multiple vs single vessel supply. From February 1999 to September 2002, 63 LDN were performed at the department of Urology, Charité University Hospital, Berlin. A comparison between 18 donor kidneys with multiple vessel supply and 45 donor organs with single vessels showed no difference for the time of laparoscopic explantation (207 vs 201 min, p=0.4) or the warm (166 vs 148 s, p=0.2) and cold ischemic times (117 vs 103 min, p=0.66). As could be expected, the mixed ischemic time, i.e., the time for anastomosis of the kidney with the recipient's vessels, showed a significant difference (53 vs 46 min, p=0.02). Intra- and postoperative complication rates for donors and recipients were not different in both groups. Laparoscopic donor nephrectomy for kidneys with multiple vessels is feasible and safe for donor and recipient.


A thoracic surgeon's perspective on the elastofibroma dorsi: A benign tumor of the deep infrascapular region.
An elastofibroma is a benign, soft-tissue tumor and is important in the differential diagnosis of thoracic wall masses. Here, patients with elastofibromas who underwent thoracic surgery were retrospectively reviewed to elucidate elastofibroma formation and to facilitate the differential diagnosis. This is a retrospective and descriptive study of a series of 30 patients with elastofibroma dorsi. The data was obtained by review of the hospital records. There were 27 female and three male patients (mean age, 55.13 ± 8.7 years) with a total of 42 elastofibroma dorsi tumors (12 bilateral cases, 18 unilateral cases) diagnosed between January 2004 and October 2011. Twenty patients (67%) underwent surgery as a result of subscapular swelling and pain. In 10 (33%) asymptomatic patients, elastofibromas were found incidentally during a thoracotomy. Imaging methods in symptomatic patients included computerized tomography (15 cases), magnetic resonance (three), and ultrasonography (two). For five patients, fluorodeoxyglucose uptake values were available and revealed mild metabolic activity in the elastofibromas. Elastofibromas were significantly larger in symptomatic patients (8.15 ± 1.9 vs. 6.2 ± 2.3; P= 0.02). Exposure to long-term repetitive micro-trauma was a precipitating factor in 23 (77%) patients. Seroma formation, the most common surgical complication, was observed in 40% of patients. The differential diagnosis of elastofibroma dorsi is straightforward, and preoperative histology is unnecessary when the clinical, radiological, and metabolic characteristics are known. Repetitive micro-trauma may predispose to hyperproliferation of fibroelastic tissue, and genetics may also play a role. Surgical treatment can be reserved for cases with severe symptoms.


Constitutive Notch Signaling Causes Abnormal Development of the Oviducts, Abnormal Angiogenesis, and Cyst Formation in Mouse Female Reproductive Tract.
The Notch signaling pathway is critical for the differentiation of many tissues and organs in the embryo. To study the consequences of Notch1 gain-of-function signaling on female reproductive tract development, we used a cre-loxP strategy and Amhr2-cre transgene to generate mice with conditionally activated Notch1 (Rosa(Notch1)). The Amhr2-cre transgene is expressed in the mesenchyme of developing female reproductive tract and in granulosa cells in the ovary. Double transgenic Amhr2-cre, Rosa(Notch1) females were infertile, whereas control Rosa(Notch1) mice had normal fertility. All female reproductive organs in mutants showed hemorrhaging of blood vessels progressing with age. The mutant oviducts did not develop coiling, and were instead looped around the ovary. There were multiple blockages in the lumen along the oviduct length, creating a barrier for sperm or oocyte passage. Mutant females demonstrated inflamed uteri with increased vascularization and an influx of inflammatory cells. Additionally, older females developed ovarian, oviductal, and uterine cysts. The significant change in gene expression was detected in the mutant oviduct expression of Wnt4, essential for female reproductive tract development. Similar oviductal phenotypes have been detected previously in mice with activated Smo and in beta-catenin, Wnt4, Wnt7a, and Dicer conditional knockouts, indicating a common regulatory pathway disrupted by these genetic abnormalities.


Patient-Centered Paradigm for Managing Autonomic Long COVID Symptoms During Sports and Exercise.
This report highlights a new, patient-centered paradigm for managing post-COVID-19 dysautonomia symptoms during sports and exercise. The patient was a healthcare worker exposed before vaccination. She experienced postural orthostatic tachycardia plus exertional tachycardia, with postexertional fatigue, beginning a few weeks after testing positive for COVID-19. Stress test, echo, and an extensive dysautonomia evaluation were negative. Recommended nonpharmacological and pharmacological interventions were poorly tolerated. Prescription of a novel regimen of "basal-dose" ivabradine, plus very low-dose metoprolol according to an exertional "sliding scale" managed symptoms to an acceptable level for work and recreation.


Integrating clinical and biological information in a shanghai biobank: an introduction to the sample repository and information sharing platform project.
Biobanks are important resources and central tools for translational medicine, which brings scientific research outcomes to clinical practice. The key purpose of biobanking in translational medicine and other medical research is to provide biological samples that are integrated with clinical information. In 2008, the Shanghai Municipal Government launched the "Shanghai Tissue Bank" in an effort to promote research in translational medicine. Now a sharing service platform has been constructed to integrate clinical practice and biological information that can be used in diverse medical and pharmaceutical research studies. The platform collects two kinds of data: sample data and clinical data. The sample data are obtained from the hospital biobank management system, and mainly include the donors' age, gender, marital status, sample source, sample type, collection time, deposit time, and storage method. The clinical data are collected from the "Hospital-Link" system (a medical information sharing system that connects 23 tertiary hospitals in Shanghai). The main contents include donors' corresponding medication information, test reports, inspection reports, and hospital information. As of the end of September 2014, the project has a collection of 16,020 donors and 148,282 samples, which were obtained from 12 medical institutions, and automatically acquired donors' corresponding clinical data from the "Hospital-Link" system for 6830 occurrences. This project will contribute to scientific research at medical institutions in Shanghai, and will also support the development of the biopharmaceutical industry. In this article, we will describe the significance, the construction phases, the application prospects, and benefits of the sample repository and information sharing service platform.


'High' anorectal malformation in boys: need for clarity of definition and management.
Posterior sagittal anorectoplasty is purported to be the approach of choice for the treatment of both intermediate and high variety of anorectal malformations. The authors describe their devastating experiences with 2 cases of high variety of anorectal malformations in which defects were repaired thorough the posterior sagittal approach. In the first case, because of the high level of the rectal pouch, complete urethrovesical disconnection was done along with inadvertent mobilization and pull-through of urinary bladder. The patient subsequently required major reconstructive procedures. In another case, the bladder was partially mobilized before the mistake was realized; the high-lying rectum was later identified, and a pull-through was performed without any ill consequences. The authors infer that only the patients with rectal pouches ending caudal to the third sacral vertebra should have their definitive surgery performed through posterior sagittal approach. They suggest that PS3 line should be the watershed in management of anorectal malformation in boys.


Properties of renin-binding protein.
Hog renal renin-binding protein could bind homologous and non-homologous renin but could not bind human renal renin. Renin-binding protein was only detected in the kidney and pituitary in which renin is found in relatively high concentration. The renal binding protein had no interaction with renal acid proteases nor with extrarenal renins obtained from pituitary and submaxillary glands, indicating that the binding is specific for renal renin. Subcellular localization of the binding protein was studied using rat kidney by differential and density gradient centrifugation. Most renin-binding protein was recovered in the cytosol fraction and was not associated with sedimentable subcellular organelles. A renin-secreting tumor (Juxtaglomerular cell tumor) in human kidney produced not only renin but also renin-binding protein in a very large quantity.


L6 cells as a tissue culture model for thyroid hormone effects on skeletal muscle metabolism.
L6 cells have been investigated as a potential tissue culture model for the study of thyroid hormone effects on skeletal muscle metabolism. Differentiated L6 myotubes contained high-affinity triiodothyronine (T3) receptors with a Kd of 3 X 10(-10) M and a maximal binding capacity of 24 fmol T3/100 micrograms DNA. Undifferentiated cells contained receptors with the same Kd, but the binding capacity was reduced by at least a factor of three. Sarcoplasmic reticulum vesicle calcium pumping was demonstrated in L6 cell homogenates. The Vmax for calcium pumping was increased 2.5-fold when T3 was present in the culture medium, but the Kd was unchanged. L6 cells contained high affinity thyroid hormone receptors and were thyroid hormone responsive. These cells may be useful as a tissue culture model for studying the effects of thyroid hormones on skeletal muscle metabolism. In addition, the increase in T3 receptor number with the differentiated state suggests this as a model system for studying regulation of T3 receptor number and the role of T3 in the induction or maintenance of the differentiated state.


Study of CNS depressant and behavioral activity of an ethanol extract of Achyranthes Aspera (Chirchita) in mouse model.
Achyranthes Aspera Linn., known as Chirchira (Hindi), Agadha (Marathi) is an indigenous herb found in India. The herb has been reported to have variety of activities like antifertility, antihyperlipidemic, antidiabetic, immunomodulatory, anticarcinogenic, diuretic and cardiotonic, analgesic, anti-inflammatory, hypnotic, antifungal and antibacterial activity. It has been also reported to have central anti-nociceptive activity in thermal induced pain methods in our earlier studies. We wanted to study its neuropharmacological effects, which may throw light on understanding the underlying mechanism for its central activity. The present study was designed to evaluate CNS depressant and behavioral effects of A. Aspera extract and to study the phytochemical responsible for these activities with possible mode of action. The effects on behavioral activity was studied using open field test (OFT). The extract was given intraperitoneally at a dose of 400 mg/kg. Diazepam (2mg/kg body weight i.p.) was used as standard. Data was analyzed by ANOVA test followed by Dunnett's test. All the results were expressed as Mean (±SEM). P <0.05 was considered significant. Phytochemical screening revealed presence of triterpenoids, saponins, alkaloids (betaine, achyranthine) and steroids as major constituents. The result of the study demonstrated that ethanol extract of A. Aspera (400 mg/kg i.p.) decreased locomotor activity, produced muscle relaxation and showed antianxiety activity. Ethanols extract of A. Aspera exhibit CNS depressant action and significant anxiolytic activity comparable to diazepam.


Expression of neuregulin 4 splice variants in normal human tissues and prostate cancer and their effects on cell motility.
The neuregulin 4 gene encodes at least five different variants (designated A1, A2, B1, B2 and B3) produced as a result of alternative splicing. We have determined their sites of expression in normal human adult tissues using isoform-specific antibodies. Their expression is cell type specific and differs in subcellular location suggesting that they may have varied functions in these contexts. We have shown in a panel of prostate cancers that each form is present to differing degrees, and that principal component analysis indicates that there are three patterns of expression. Some isoforms were positively correlated with high prostate-specific antigen levels and others were inversely associated with Gleason score. Synthetic, refolded A forms promoted lamellipodia and filopodia formation in cells expressing the ErbB4 (CTa) receptor and stimulated cell motility in wound healing assays. The data suggest that the different forms have varied sites of expression and function, and this includes effects on cell architecture and motility.


Sex steroids are necessary in the second postnatal week for the expression of male alloparental behavior in prairie voles (Microtus ochragaster).
Sex steroids play a significant role in organizing male social behavior, which is associated with low levels of pro-social behavior and high levels of aggression. However, the role of steroids in organizing behavior in highly social males is unclear. The authors tested the hypothesis that low levels of sex steroids facilitate the expression of pro-social behavior in male prairie voles (Microtus ochragaster), predicting that inhibition of testosterone and estradiol would reduce spontaneous-alloparental behavior. Treatment with the aromatase inhibitor 1,4,6-androstatriene-3,17-dione (ATD) or the androgen receptor blocker flutamide, days 8-14, significantly reduced the expression of alloparental behavior in 21-day old males. While both treatments reduced alloparental behavior and increased pup-directed aggression, there were differential treatment effects. Flutamide altered initial response, increasing latency to enter the pup cage and the likelihood of retreat from initial contact. ATD-treated males that were alloparental showed increases in sniffing and latencies to lick and huddle. Results indicate that endogenous steroids play a role in the development of male pro-social behavior and the effects of estrogens and androgens differ.


Handwritten Geometrical Patterns in the Evaluation of Motor Symptoms in Psychotic Disorders.
The analysis of handwriting has been used in several contexts. For example, handwriting has shown to be of value in the study of motor symptoms in neurological and mental disorders. In the present work, the geometric analysis of handwriting patterns is proposed as a tool to evaluate motor symptoms in psychotic disorders. Specifically, we have employed the lacunarity, a measure of the heterogeneity of a spatial structure. Forty-two patients with a psychotic disorder and 35 matched healthy controls participated in the study. Participants were asked to copy some patterns with a pen on a white paper. The results showed that lacunarity was significantly higher in handwritten patterns from patients than from controls. In addition, we found higher values of lacunarity in handwritten patterns from patients with severe motor symptoms in comparison with patients with mild or absent motor symptoms. Lacunarity of handwritten patterns was significantly correlated with clinical scores of rigidity. In conclusion we argue that the heterogeneity of handwritten patterns could be used as a simple and objective measure of motor symptoms.


Anti-arthritic and gastroprotective activities of Ardisia crispa root partially mediated via its antioxidant effect.
Background Ardisia crispa Thunb A.DC (Myrsinaceae), commonly known as "hen's eyes", has been traditionally used in treating various inflammatory diseases. The present study evaluated anti-arthritic, gastroprotective and antioxidant activities of Ardisia crispa root hexane extract (ACRH) in various animal models. Methods Anti-arthritic activity was evaluated in complete Freund adjuvant (CFA)-induced adjuvant arthritis and gastroprotective effect was studied in the ethanol-induced ulcer model in rats. ACRH was further isolated to yield quinone-rich fraction (QRF) and both were analyzed for their total phenolic content, total flavonoid content and antioxidant activities in various antioxidant assays. Both ACRH and QRF were also analyzed for the quinone composition via gas chromatography analysis. Results ACRH exerted significant reduction of IL-1β and TNF-α at a lower dose range in CFA-induced arthritis, as well as exhibited its cytoprotective effect against ethanol-induced ulcer lesion via involvement of mucosal nonprotein sulfhydryl (NP-SH) groups. ACRH also showed higher phenolic and flavonoid contents, as well as better antioxidant activities than QRF. Conclusions These findings demonstrated the plant as a potential anti-inflammatory agent, with ACRH succeeded in inhibiting both arthritic and ulcerogenic effect, possibly mediated via its antioxidant effect.