Hypersensitivity of spinothalamic tract neurons associated with diabetic neuropathic pain in rats.
Diabetic neuropathic pain is often considered to be caused by peripheral neuropathy. The involvement of the CNS in this pathological condition has not been well documented. Development of hypersensitivity of spinal dorsal horn neurons is involved in neuropathic pain induced by traumatic nerve injury. In the present study, we determined the functional changes of identified spinothalamic tract (STT) neurons and their correlation to diabetic neuropathic pain. Diabetes was induced in rats by intraperitoneal injection of streptozotocin. Hyperalgesia and allodynia were assessed by the withdrawal responses to pressure, radiant heat, and von Frey filaments applied to the hindpaw. Single-unit activity of STT neurons was recorded from the lumbar spinal cord in anesthetized rats. The responses of STT neurons to mechanical and thermal stimuli and the sensitivity to intravenous morphine were determined in diabetic and normal rats. In 12 diabetic rats, mechanical allodynia and hyperalgesia, but not thermal hyperalgesia, developed within 2 wk after streptozotocin injection and lasted for >/=7 wk. Compared to the 32 STT neurons recorded in normal animals, the 37 STT neurons in diabetic rats displayed a higher spontaneous discharge activity and enlarged receptive fields. Also, the STT neurons in diabetic rats exhibited lower thresholds and augmented responses to mechanical stimulation. Intravenous injection of 2.5 mg/kg of morphine suppressed significantly the responses of STT neurons to noxious stimuli in 12 nondiabetic rats. However, such an inhibitory effect of morphine on the evoked response of STT neurons was diminished in 14 diabetic animals. This electrophysiological study provides new information that development of hypersensitivity of spinal dorsal horn projection neurons may be closely related to neuropathic pain symptoms caused by diabetes. Furthermore, the attenuated inhibitory effects of morphine on evoked responses of STT neurons in diabetes likely accounts for its reduced analgesic efficacy in this clinical form of neuropathic pain.


Polychlorobornane components of toxaphene: structure-toxicity relations and metabolic reductive dechlorination.
2,2,5-endo,6-exo,8,9,10-Heptachlorobornane and four derivatives of this heptachlorobornane, with an additional chlorine atom at position 3-exo,8,9, or 10, account for a major portion of the acute toxicity of toxaphene and for up to 23 percent of toxaphene composition as analyzed by open tubular column gas-liquid chromatography with an electron capture detector. Both in several organisms and model environmental systems and on photolysis, this heptachlorobornane undergoes facile reductive dechlorination at the geminal-dichloro group and sometimes dehydrochlorination.


Conformational flexibility of the glycosidase NagZ allows it to bind structurally diverse inhibitors to suppress β-lactam antibiotic resistance.
NagZ is an N-acetyl-β-d-glucosaminidase that participates in the peptidoglycan (PG) recycling pathway of Gram-negative bacteria by removing N-acetyl-glucosamine (GlcNAc) from PG fragments that have been excised from the cell wall during growth. The 1,6-anhydromuramoyl-peptide products generated by NagZ activate β-lactam resistance in many Gram-negative bacteria by inducing the expression of AmpC β-lactamase. Blocking NagZ activity can thereby suppress β-lactam antibiotic resistance in these bacteria. The NagZ active site is dynamic and it accommodates distortion of the glycan substrate during catalysis using a mobile catalytic loop that carries a histidine residue which serves as the active site general acid/base catalyst. Here, we show that flexibility of this catalytic loop also accommodates structural differences in small molecule inhibitors of NagZ, which could be exploited to improve inhibitor specificity. X-ray structures of NagZ bound to the potent yet non-selective N-acetyl-β-glucosaminidase inhibitor PUGNAc (O-(2-acetamido-2-deoxy-d-glucopyranosylidene) amino-N-phenylcarbamate), and two NagZ-selective inhibitors - EtBuPUG, a PUGNAc derivative bearing a 2-N-ethylbutyryl group, and MM-156, a 3-N-butyryl trihydroxyazepane, revealed that the phenylcarbamate moiety of PUGNAc and EtBuPUG completely displaces the catalytic loop from the NagZ active site to yield a catalytically incompetent form of the enzyme. In contrast, the catalytic loop was found positioned in the catalytically active conformation within the NagZ active site when bound to MM-156, which lacks the phenylcarbamate extension. Displacement of the catalytic loop by PUGNAc and its N-acyl derivative EtBuPUG alters the active site conformation of NagZ, which presents an additional strategy to improve the potency and specificity of NagZ inhibitors.


[Case report of severe multiple trauma. Anesthesiologic techniques].
The modern anaesthetic devices have now put an end to the sixties-fashioned aphorism: "Closed circuit=open coffin". The currently renewed interest in the recirculation systems is justified by the following reasons: economic benefit; environmental advantages; clinical features, such as: 1) better humidification of gases; 2) better preservation of warmth; 3) monitoring of O2 consume; 4) gas analysis on each respiratory act. This allows the use of fresh gases at low flow without the risk of hypoxia or overdosage in patients and it guarantees for safe anaesthesia. The following clinical case clearly shows the application of the above mentioned principles. An extremely serious case of head, chest and abdominal multiple trauma, personally observed, is described. The so called technics "partial rebreathing" was adopted thanks to the availability of a device which permits a punctual monitoring of SAO2, ETCO2, FI and FET, FLO2, VM, VT, VEmin, % of N2O, invasive SAP and body temperature. These are very important parameters for a safe anaesthesia and in conditions like those of the above described clinical case.


Effect of estrogen upon cyclic ADP ribose metabolism: beta-estradiol stimulates ADP ribosyl cyclase in rat uterus.
Cyclic ADP ribose (cADPR) has been shown to trigger Ca2+ release from intracellular stores through ryanodine receptor/channel. In our previous study we observed that all-trans-retinoic acid stimulates cADPR synthesis by ADP ribose cyclase (ADPR cyclase) in cultured epithelial cells. We have now investigated whether cADPR may play a signaling role in action of beta-estradiol (E2), an archetypal steroid superfamily hormone, upon its major target organ, uterus, in vivo. Administration of E2 to gonadectomized rats (0.2 mg/kg per day for 7 days) resulted in an approximately Delta + 300% increase of ADPR cyclase activity in extracts from uterus, but in liver, brain, or skeletal muscle ADPR cyclase was unchanged. Most of the E2-stimulated uterine ADPR cyclase was associated with membranes. The higher ADPR cyclase activity in response to E2 was due to the increase of VMAX without change in Km. Simultaneous administration of estrogen antagonist tamoxifen (8 mg/kg per day) with E2 (0.2 mg/kg per day) prevented an increase in ADPR cyclase. In uterine extracts from E2-treated rats, the rate of cADPR inactivation by cADPR hydrolase and the activity of NADase was increased, but to a much lesser degree than activity of ADPR cyclase. Our results indicate that E2, via action to its nuclear receptors in vivo, increases ADPR cyclase activity in uterus. We propose that some of the estrogen effects, and by extension the effects of other steroid superfamily hormones, upon specialized cellular functions and upon hormone-induced gene expression in target cells, are mediated by cADPR-Ca2+ release pathway.


Transvaginal native-tissue repair of vaginal vault prolapse.
Posthysterectomy vaginal vault prolapse repair is a challenge for pelvic floor surgeons. Native-tissue repair procedures imply lower costs and reduced morbidity. Our study aims to evaluate operative data, complications, objective, subjective and functional outcomes of transvaginal native-tissue repair for posthysterectomy vaginal vault prolapse. We also investigated differences among available techniques. Retrospective study including patients with symptomatic vaginal vault prolapse (≥stage 2), previously treated with transvaginal vault suspension through native-tissue repair. Objective recurrence was defined as the descent of at least one compartment ≥II stage according to Pelvic Organ Prolapse Quantification (POP-Q) system or need of reoperation. Subjective recurrence was defined as the presence of bulging symptoms. Patients satisfaction was evaluated with PGI-I Score. The study included 111 patients. Apical suspension was achieved either by uterosacral ligament suspension (16), levator myorrhaphy (17), iliococcygeus fascia fixation (65) or sacrospinous ligament fixation (13). No intraoperative complications were observed. Perioperative/postoperative complications occurred in 8 patients (7.2%). Mean follow-up was 24.5±12.1 months. Objective recurrence was observed in 28 patients (25.2%). Reintervention was required by 3 patients (2.7%). Subjective recurrence was referred by 6 patients (5.4%). Mean satisfaction evaluated with PGI-I Score was 1.2±0.6. No differences in terms of operative data, overall complications, objective, subjective cure rate and perceived satisfaction were found among different techniques. Transvaginal repair with native-tissue procedures is safe and effective in correcting posthysterectomy vaginal vault prolapse and represents a valid alternative to prosthetic procedures for vaginal vault prolapse treatment.


Survey of adult mosquitoes (Diptera: Culicidae) during irrigation development in the Mahaweli Project, Sri Lanka.
A survey of adult mosquitoes was done during 1986-1987 in an area undergoing irrigation development in the Mahaweli Project of Sri Lanka. The study encompassed two 12-mo phases of settlement and irrigation, respectively. Diurnal human bait catches yielded 1,427 female mosquitoes in 27 species. Nocturnal collections (human bait, CDC light traps, indoor resting catches) produced a total of 30,491 females in 67 species. Comparisons with an earlier survey in the predevelopment forest showed that the diurnal human biting abundance of Aedes albopictus (Skuse) remained stable, whereas the abundance of Ae. novalbopictus Barraud and Ae. w-albus Theobald declined drastically after development. Man-mosquito contact increased substantially for nocturnally active Anopheles annularis van der Wulp, An. subpictus Grassi, Mansonia uniformis (Theobald), Culex tritaeniorhynchus Giles, and Cx. quinefasciatus Say and decreased for Ma. annulifera (Theobald) and Cx. gelidus Theobald. A small increase occurred in An. culicifacies Giles, An. vagus Donitz, An. varuna lyengar, Cx. fuscocephala Theobald, and Cx. whitmorei (Giles); Cx. pseudovishnui Colless decreased. The effect of changes in mosquito abundance on the increased transmission of malaria and Japanese encephalitis is discussed.


Peptide inhibitor of complement C1 modulates acute intravascular hemolysis of mismatched red blood cells in rats.
Acute hemolytic transfusion reactions have a broad clinical presentation from mild and transitory signs and symptoms to shock, disseminated intravascular coagulation, renal failure, and death. We have recently developed a rat model of acute intravascular hemolysis showing that the classical complement pathway mediates antibody-dependent hemolysis. The objective of this study was to evaluate the role of the classical pathway inhibitor peptide inhibitor of complement C1 (PIC1) in this animal model. Male Wistar rats received a 15% transfusion of human red blood cells (RBCs) and blood was isolated from the animals up to 120 minutes. Animals received PIC1 either 2 minutes before or 0.5 minutes after transfusion. Sham-, vehicle-, and cobra venom factor (CVF)-treated animals were used as control groups with a subset of rats also receiving an equivalent dose of intravenous immunoglobulin (IVIG) before transfusion. Blood was analyzed for transfused RBC survival by flow cytometry and free hemoglobin (Hb) in isolated plasma by spectrophotometry. Vehicle-treated rats showed decreased human RBC survival and increased free Hb as expected. Rats receiving PIC1 before transfusion showed increased human RBC survival and decreased Hb similar to CVF-treated rats. Notably, rats receiving PIC1 after initiation of transfusion showed similar decreases in hemolysis as animals receiving PIC1 before transfusion. Compared to IVIG and saline controls, PIC1-treated animals demonstrated decreased hemolysis and protection from acute kidney injury. These results demonstrate that PIC1 has efficacy in an animal model of acute intravascular hemolysis in both prevention and rescue scenarios.


Microwave-assisted aqueous synthesis of new quaternary-alloyed CdSeTeS quantum dots; and their bioapplications in targeted imaging of cancer cells.
In this study, we report for the first time a one-pot approach for the synthesis of new CdSeTeS quaternary-alloyed quantum dots (QDs) in aqueous phase by microwave irradiation. CdCl2 was used as a Cd precursor during synthesis, NaHTe and NaHSe were used as Te and Se precursors and mercaptopropionic acid (MPA) was used as a stabilizer and source of sulfur. A series of quaternary-alloyed QDs of different sizes were prepared. CdSeTeS QDs exhibited a wide emission range from 549 to 709 nm and high quantum yield (QY) up to 57.7 %. Most importantly, the quaternary-alloyed QDs possessed significantly long fluorescence lifetimes > 100 ns as well as excellent photostability. Results of high-resolution transmission electron microscopy (HRTEM), energy dispersive X-ray spectroscopy (EDX) and powder X-ray diffraction (XRD) spectroscopy showed that the nanocrystals possessed a quaternary alloy structure with good crystallinity. Fluorescence correlation spectroscopy (FCS) showed that QDs possessed good water solubility and monodispersity in aqueous solution. Furthermore, CdSeTeS QDs were modified with alpha-thio-omega-carboxy poly(ethylene glycol) (HS-PEG-COOH) and the modified QDs were linked to anti-epidermal growth factor receptor (EGFR) antibodies. QDs with the EGFR antibodies as labeling probes were successfully applied to targeted imaging for EGFR on the surface of SiHa cervical cancer cells. We believe that CdSeTeS QDs can become useful probes for in vivo targeted imaging and clinical diagnosis.


Schizophrenia: update on genetics, cognitive behavioural therapy and early intervention.
There have been considerable advances in the understanding of schizophrenia in recent years. This educational review paper focuses on three areas of interest and relevance to trainees preparing for the membership examination of the Royal College of Psychiatrists (MRCPsych): (a) recent advances in the genetics of schizophrenia; (b) advances in cognitive behavioural therapy in schizophrenia; and (c) advances in early intervention strategies for schizophrenia. Relevant papers and systematic reviews are discussed, and recommendations for further reading are provided.


Effect of vitamin K2 treatment on carboxylation of osteocalcin in early postmenopausal women.
We examined the serum level of undercarboxylated osteocalcin (uc OC), which is a sensitive marker of vitamin K status, and levels of bone turnover markers in early postmenopausal women receiving vitamin K2 treatment with or without vitamin D3. Thirty-four postmenopausal women with a mean age of 53 years whose bone mineral density (BMD) was less than 0.809 g/cm2 (osteopenia and osteoporosis) were treated with vitamin K2 or with a combination of vitamin K2 and vitamin D3. Seventeen women received daily oral administration of 45 mg vitamin K2 and 17 women received daily oral administration of 45 mg vitamin K2 plus 0.75 microg 1alpha-hydroxyvitamin D3. Serum levels of uc OC, intact osteocalcin (OC) and bone alkaline phosphatase (BAP), urinary deoxypyridinoline (DPD) levels and BMD at the lumbar spine were measured before and at 1 and 2 years after the start of treatment. Serum uc OC levels in women treated with vitamin K2 alone and with both vitamin K2 and vitamin D3 decreased significantly (p < 0.05). Serum levels of intact OC and BAP in women treated with vitamin K2 did not show significant changes, while those in women who received the combined treatment decreased significantly (p < 0.05). On the other hand, urinary DPD level in women treated with vitamin K2 did not change, while that in women who received the combined treatment tended to decrease (p < 0.1). Serum uc OC levels in early postmenopausal women who received vitamin K2 decreased due to carboxylation of uc OC. Combined treatment with vitamin K2 and vitamin D3 may be effective for sustaining BMD in early postmenopausal women whose bone turnovers are highly activated.


Detection of abscisic-acid-binding proteins in the microsomal protein fraction of Arabidopsis thaliana with abscisic-acid-protein conjugates used as affinity probes.
A family of affinity probes has been generated to detect and purify abscisic-acid (ABA)-binding proteins, by coupling ABA onto carrier proteins (ovalbumin or BSA) through the C1 carboxyl group or the C4' carbonyl group of ABA. ELISA detection showed that these ABA-protein conjugates bound efficiently to the solubilized microsomal protein fraction of Arabidopsis thaliana, but not to the soluble protein fraction. Heat or proteolytic treatments inhibited the binding of the conjugates, indicating the protein nature of these binding sites. After membrane purification of the microsomes, the binding sites were found to be preferentially located in the plasma membrane fraction. The binding of the conjugates was independent of the nature of the carrier protein or the ABA-carrier protein linker, but was competitively inhibited with an anti-ABA mAb. Furthermore, the competitive inhibition of the binding of the conjugates with ABA, but not with the inactive ABA methyl ester analog, demonstrated the specificity of the binding and the saturability of the binding sites. The binding of the conjugates was strictly correlated to the ABA/carrier protein molar coupling ratio, confirming that the affinity of the conjugates to the ABA-binding proteins was enhanced by the increase in the probability of binding events. The experimental approach permits a new insight into the nature of membrane-associated ABA-binding proteins.


Successful long-term control with lamivudine against reactivated hepatitis B infection following intensive chemotherapy and autologous peripheral blood stem cell transplantation in non-Hodgkin's lymphoma: experience of 2 cases.
It is well documented that cytotoxic treatment in patients carrying the hepatitis B virus (HBV) enhances the risk of severe hepatic damage. Recently lamivudine has been reported to be effective in suppressing the replication of HBV under such conditions. Here we report two cases with HBV carrier status and with non-Hodgkin's lymphoma who were successfully treated with high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation with the administration of lamivudine to prevent HBV flare-up. The antiviral effect of lamivudine was fair, and no objective side effect was experienced during the transplant procedure. Both patients were followed carefully for more than a year without the appearance of the resistant virus. The rebound phenomenon in which HBV proliferates abruptly has not been experienced after withdrawal of lamivudine. We suggest that lamivudine is indicated both in the treatment of HBV viremia and in the prevention of proliferation of HBV in patients with HBV carrier status undergoing high-dose myeloablative chemotherapy.


The electronic structure of metal-molecule hybrids in charged interfaces: surface-enhanced Raman selection rules derived from plasmon-like resonances.
DFT calculations predict that plasmon-like excitations in small metal clusters are able to selectively modify the relative intensities of specific SERS bands of adsorbed molecules. These electronic resonances provide new kinds of SERS selection rules which can explain the huge enhancement of mode 9a of pyridine in the spectra recorded at negative electrode potentials.


Involvement of metalloproteinase and nitric oxide synthase/nitric oxide mechanisms in early decidual angiogenesis-vascularization of normal and experimental pathological mouse placenta related to maternal alcohol exposure.
Successful pregnancy for optimal fetal growth requires adequate early angiogenesis and remodeling of decidual spiral arterioles during placentation. Prior to the initiation of invasion and endothelial replacement by trophoblasts, interactions between decidual stromal cells and maternal leukocytes, such as uterine natural killer cells and macrophages, play crucial roles in the processes of early maternal vascularization, such as proliferation, apoptosis, migration, differentiation, and matrix and vessel remodeling. These placental angiogenic events are highly dependent on the coordination of several mechanisms at the early maternal-fetal interface, and one of them is the expression and activity of matrix metalloproteinases (MMPs) and endothelial nitric oxide synthases (NOSs). Inadequate balances of MMPs and nitric oxide (NO) are involved in several placentopathies and pregnancy complications. Since alcohol consumption during gestation can affect fetal growth associated with abnormal placental development, recently, we showed, in a mouse model, that perigestational alcohol consumption up to organogenesis induces fetal malformations related to deficient growth and vascular morphogenesis of the placenta at term. In this review, we summarize the current knowledge of the early processes of maternal vascularization that lead to the formation of the definitive placenta and the roles of angiogenic MMP and NOS/NO mechanisms during normal and altered early gestation in mice. Then, we propose hypothetical defective decidual cellular and MMP and NOS/NO mechanisms involved in abnormal decidual vascularization induced by perigestational alcohol consumption in an experimental mouse model. This review highlights the important roles of decidual cells and their MMP and NOS balances in the physiological and pathophysiological early maternal angiogenesis-vascularization during placentation in mice.


Fiducial markers coupled with 3D PET/CT offer more accurate radiation treatment delivery for locally advanced esophageal cancer.
The role of three-dimensional positron emission tomography/computed tomography (3 D PET/CT) in esophageal tumors that move with respiration and have potential for significant mucosal inflammation is unclear. The aim of this study was to determine the correlation between gross tumor volumes derived from 3 D PET/CT and endoscopically placed fiducial markers. This was a retrospective, IRB approved analysis of 40 patients with esophageal cancer with fiducials implanted and PET/CT. The centroid of each fiducial was identified on PET/CT images. Distance between tumor volume and fiducials was measured using axial slices. Image features were extracted and tested for pathologic response predictability. The median adaptively calculated threshold value of the standardized uptake value (SUV) to define the metabolic tumor volume (MTV) border was 2.50, which corresponded to a median 23 % of the maximum SUV. The median distance between the inferior fiducial centroid and MTV was - 0.60 cm (- 3.9 to 2.7 cm). The median distance between the superior fiducial centroid and MTV was 1.25 cm (- 4.2 to 6.9 cm). There was no correlation between MTV-to-fiducial distances greater than 2 cm and the gastroenterologist who performed the fiducial implantation. Eccentricity demonstrated statistically significant correlations with pathologic response. There was a stronger correlation between inferior fiducial location and MTV border compared to the superior extent. The etiology of the discordance superiorly is unclear, potentially representing benign secondary esophagitis, presence of malignant nodes, inflammation caused by technical aspects of the fiducial placement itself, or potential submucosal disease. Given the concordance inferiorly and the ability to more precisely set up the patient with daily image guidance matching to fiducials, it may be possible to minimize the planning tumor volume (PTV) margin in select patients, thereby, limiting dose to normal structures.


Real-Time Ultrasound-Assisted Thoracic Epidural Placement: A Feasibility Study of a Novel Technique.
The placement of thoracic epidural catheters is complicated by the layering of the vertebral lamina. Therefore, traditional blind palpation techniques require insertion of an epidural needle with likely contact of lamina with redirections into the epidural space. We discuss a safe and consistent technique using true real-time ultrasound visualization of the needle with a paramedian sagittal oblique view to improve the consistency of placing an epidural in the thoracic spine for postoperative analgesia. Successful epidural placement was achieved in every patient. All catheters were found to be effective for use in the postoperative phase.


Incidence, treatment, and in-hospital outcome of bifurcation lesions in patients undergoing percutaneous coronary interventions for chronic total occlusions.
Bifurcation lesions represent a distinct lesion subset associated with an increased risk of procedural complications. Data on the incidence, treatment, and outcome of bifurcation lesions associated with chronic total occlusions are limited. Among chronic total occlusion procedures performed by a single experienced operator, patients with a bifurcation lesion within the chronic total occlusion vessel and a side branch reference diameter greater than or equal to 2.0 mm were enrolled. A total of 905 patients (mean age 61.1±9.5 years, men 89.4%) were treated for 922 chronic total occlusion lesions. Among these, 244 bifurcation lesions were observed (26.5%). The procedural time was significantly longer in bifurcation lesions (139±67 vs. 124±68 min; P=0.003), with greater use of contrast load (470±193 vs. 436±227 ml; P=0.04) and higher number of stents (3.1±1.5 vs. 2.9±1.4; P=0.035). Overall, an angiographic success was achieved in 91.1% of cases with a higher rate in nonbifurcation lesions (92.5 vs. 87.3%; P=0.04). Coronary perforations were more often observed in bifurcation lesions (4.9 vs. 1.7%; P<0.001), resulting in more tamponades (2.4 vs. 0.2%; P<0.001). True bifurcations were encountered in the majority of cases (86.8%) and required more two-stent techniques than false bifurcations (50 vs. 18.8%; P=0.001). The incidence of bifurcation lesions in chronic total occlusions is higher than that reported in continuous lesions. The presence of a bifurcation lesion increases the complexity of the procedure and may lead to less angiographic success and more periprocedural complications.


Alzheimer's disease and the quest for its biological measures.
Alzheimer's disease (AD) is the most common neurodegenerative disorder associated with dementia in the elderly. Although the initiating events are still unknown, it is clear that AD results from a combination of genetic and environmental risk factors. Recently proposed diagnostic criteria, in addition to the clinical neuropsychological examination aimed at identifying the typical AD symptoms, include staging criteria based on AD biological measures related to its pathology. Despite the obvious benefits of these new criteria, an accurate diagnosis is not always easily reached because, particularly in its earliest stages, the symptoms of the disease are very variable. Biological measures, or biomarkers, of the disease should first facilitate an early and accurate diagnosis, have a prognostic and predictive value, and have the capacity to monitor therapeutic efficacy. While amyloid-β and tau represent the two key pathological features of the disease, other aspects of this complex disease are emerging as important mediators in its pathogenesis. Among them, oxidative stress is probably one of the most investigated, and so are biomarkers reflecting it. Intrinsic limitation of biomarkers is the fact that they do not define mechanism of disease, but by nature are associative and/or correlative and unable to prove causality. Longitudinal studies are helping us in this difficult task by providing a clearer picture of the dynamic relationship between biomarkers, AD neuropathology, and cognitive phenotype.


Voice restoration after total laryngectomy using provox 2 (generation II) prosthesis.
Voice restoration after total laryngectomy is of outmost importance for patient and a therapeutic challenge for the surgeon and speech pathologist. Among various rehabilitation methods prosthetic voice yields nowadays the best results. A total of 12 patients underwent laryngectomy at the Department of Otorhinolaryngology, University Hospital, Patras, Greece, between February 2006 and May 2007. All patients had advanced laryngeal squamous cell carcinoma. Eight patients had primary voice prosthesis inserted and four patients had a tracheo-esophageal puncture (TEP) carried out as a secondary procedure. The majority of the patients (80%) from both the primary insertion or the secondary insertion group, developed good and understood speech using the prosthesis. No significant difference in quality of speech was found between the two subgroups. Four patients required replacement of the prosthesis at intervals of 8 and 10 months after insertion, because of salivary leakage and granulation formation around the fistula, while 3 patients developed a mild mucositis and tracheitis due to postoperative radiotherapy. TEP puncture and prosthesis insertion is a relatively simple, safe and effective surgical procedure for voice restoration after laryngectomy. Provox 2 (generation II) voice prosthesis is a new and useful modified device that has overcome the previous prosthesis drawbacks, is well tolerated by the patients and can be easily changed via the front-loading technique.


Cecropin P1 inhibits porcine reproductive and respiratory syndrome virus by blocking attachment.
Porcine reproductive and respiratory syndrome virus (PRRSV) is a continuous threat to the pig industry, causing high economic losses worldwide. Current vaccines have specific limitations in terms of their safety and efficacy, so the development of novel antiviral drugs is urgently required. The aim of this study was to evaluate the inhibitory effects and underlying molecular mechanisms of the antimicrobial peptide cecropin P1 (CP1) against PRRSV infection in vitro. CP1 not only displayed extracellular virucidal activity against PRRSV, but also exerted a potent inhibitory effect when added either before, simultaneously with, or after viral inoculation. The inhibitory effect of CP1 occurred during viral attachment, but not at viral entry into Marc-145 cells. CP1 also inhibited viral particle release and attenuated virus-induced apoptosis during the late phase of infection. CP1 exerted similar inhibitory effects against PRRSV infection in porcine alveolar macrophages, the cells targeted by the virus in vivo during its infection of pigs. The expression of interleukin 6 was elevated by CP1 in porcine alveolar macrophages, which might contribute to its inhibition of PRRSV infection. Collectively, our findings provide a new direction for the development of potential therapeutic drugs against PRRSV infection.


Smooth muscle neoplasms of the rectum and anal canal.
Forty-eight patients who presented to St. Mark's Hospital, London between 1948 and 1979 with smooth muscle neoplasms of the rectum or anal canal have been reviewed. Twenty-six tumours arose from the muscularis mucosae of the rectum. These lesions were small, asymptomatic and did not recur after local removal. Eighteen tumours arose from the muscularis externa of the rectum. Local excision of these resulted in a high local recurrence rate regardless of the degree of differentiation of the tumour but long-term survival figures were similar whether the tumours were treated by local or radical techniques. However, the prognosis did relate to the degree of tumour differentiation, being worst in the poorly differentiated group. In four cases the smooth muscle tumour arose from the internal sphincter of the anal canal.


Herpes simplex virus Us3(-) mutant as oncolytic strategy and synergizes with phosphatidylinositol 3-kinase-Akt targeting molecular therapeutics.
Oncolytic herpes simplex virus (HSV) vectors have shown safety in clinical trials, but efficacy remains unsatisfactory. Novel HSV vectors that possess tumor selectivity with enhanced potency are therefore needed. The gene product of HSV Us3 protects virus-infected cells from apoptosis, a cellular pathway frequently dysfunctional in tumors. We hypothesized that Us3 mutants, whose replication would be inhibited by apoptosis in normal cells, would be selective for tumor cells. HSV mutants G207 (ribonucleotide reductase-/gamma34.5-), R7041 (Us3-), and R7306 (Us3 revertant) were tested in normal and tumor cells for viral replication, antitumoral potency, apoptosis induction, and Akt activation. Safety and biodistribution after systemic administration and antitumoral efficacy after intratumoral (i.t.) or i.v. administration were examined. Us3 deletion results in up to 3-log replication inhibition in normal cells, which correlates with enhanced apoptosis induction. In contrast, R7041 replicates very well in tumor cells, showing 1 to 2 log greater yield than G207. In vivo, R7041 shows no signs of toxicity after systemic delivery in both immunocompetent and immunodeficient mice and shows preferential and prolonged replication in tumors compared with normal tissues. R7041 displays significant antitumoral efficacy after i.t. or i.v. administration. An additional feature of Us3 mutants is enhanced Akt activation compared with wild-type infection, which sensitizes cells to phosphatidylinositol 3-kinase-Akt inhibitors (LY294002, Akt inhibitor IV), shown by synergistic antitumoral activity in vitro and enhanced efficacy in vivo. Us3 deletion confers enhanced tumor selectivity and antitumoral potency on herpes simplex virus-1 and provides for a novel mechanism of combination therapy with phosphatidylinositol 3-kinase-Akt-targeting molecular therapeutics.


Etiology of Epiphora.
This study aimed to analyze the common causes of epiphora in Korean patients and their response to subsequent management. We retrospectively analyzed the medical records of 180 patients who visited Kim's Eye Hospital for epiphora between December 2017 and January 2019. This study included 320 eyes of 180 patients. In the 320 eyes of 180 patients, the most common etiology of epiphora was reflex tearing due to dry eye syndrome, which occurred in 167 eyes (52.19%). The other etiologies of epiphora included anatomical abnormality (68 eyes, 21.25%), multifactorial (60 eyes, 18.75%), functional epiphora (14 eyes, 4.38%), ocular surface disease (seven eyes, 2.19%), and eyelid abnormality (four eyes, 1.25%). The most common etiology of epiphora in Korean patients was reflex tearing due to dry eye syndrome, followed by lacrimal passage abnormality, multifactorial, functional epiphora, anterior segment disease, and eyelid malposition. Most patients with reflex tearing reported improvement in their symptoms after lubrication.


Effects of prophylactic or therapeutic application of bovine haemoglobin HBOC-200 on ischaemia-reperfusion injury following acute coronary ligature in rats.
Haemoglobin-based oxygen carriers (HBOCs) are assessed as blood substitutes in patients with perioperative anaemia including patients at risk for perioperative cardiac ischaemia. There is controversy as to whether HBOCs are beneficial or deleterious during ischaemia-reperfusion (I-R). Therefore the effects of HBOC-200 on I-R injury were evaluated in a randomized placebo-controlled animal trial. Animals were randomized to receive either placebo i.v. without I-R (sham group, n=9), placebo i.v. with I-R (control group, n=10), HBOC-200 0.4 g kg(-1) i.v. prior to I-R (prophylaxis group, n=12) or HBOC-200 0.4 g kg(-1) i.v. during I-R (therapy group, n=15). I-R consisted of 25 min of acute ligature of the left coronary artery followed by 120 min of reperfusion. Measurements included assessment of the area at risk and infarct size using triphenyl tetrazolium chloride (TTC) stain, DNA single-strand breaks (in situ nick translation with autoradiography/densitometry) and cardiac arrhythmias. Infarct size within the area at risk was 62 (sd 15)% (control), 46 (10)% (prophylaxis, P<0.025 vs control) and 61 (9)% (therapy, P<0.85 vs control). The frequency of DNA single-strand breaks was reduced vs control in the sham (P<0.01) and prophylaxis (P<0.04) groups and was almost the same in the therapy group (P<0.75). The severity of cardiac arrhythmias during ischaemia was lower compared with control in the sham (P<0.001) and prophylaxis (P<0.039) groups, but there was no difference in the therapy group. This study demonstrates that neither prophylactic nor therapeutic application of the cell-free haemoglobin solution HBOC-200 aggravates cardiac I-R injury. Furthermore, the prophylactic approach may offer a new opportunity for pretreatment of patients at risk for perioperative ischaemic cardiac events.


Mechanical properties of heel pads reconstructed with flaps.
We compared the mechanical properties of normal and reconstructed heel pads in seven patients. Four had latissimus dorsi flaps and one each an anterior thigh flap, a local dorsalis pedis flap and a sural arterial flap. The thickness of the heel pad was measured under serial incremental loads of 0.5 kg to a maximum of 3 kg and then relaxed sequentially. The load-displacement curve of the heel pad during a loading-unloading cycle was plotted and from this the unloaded heel-pad thickness (UHPT), compressibility index (CI), elastic modulus (Ep), and energy dissipation ratio (EDR) were calculated. The EDR was significantly increased in the reconstructed heels (53.7 +/- 18% v 23.4 +/- 6.5%, p = 0.003) indicating that in them more energy is dissipated as heat. Insufficient functional capacity in the reconstructed heel pad can lead to the development of shock-induced discomfort and ulceration.


Vitamin D in patients with renal failure: a summary of observational mortality studies and steps moving forward.
Although approximately half of patients undergoing hemodialysis receive activated forms of Vitamin D, the primary reason to initiate this therapy has rested solely on the management of secondary hyperparathyroidism. Secondary hyperparathyroidism is likely one of several consequences of Vitamin D deficiency, and only now have other consequences of Vitamin D deficiency emerged. Although previously viewed as a contributor to hypercalcemia and hyperphosphatemia, recent studies suggest Vitamin D may improve cardiovascular structure and function, improve vascular compliance, and reduce pro-inflammatory cytokines, all of which may contribute to the improved survival observed in retrospective studies examining the outcome of patients treated with activated Vitamin D compared to those who were not. The current review examines two recent large-scale studies of hemodialysis patients: one that demonstrated a survival advantage of paricalcitol over calcitriol, and a second that demonstrated a significant survival advantage of any intravenous Vitamin D formulation versus none. In both studies, the findings were independent of mineral and parathyroid hormone levels, suggesting "non-traditional" actions of Vitamin D contributed to the observed survival advantage. Potential steps moving forward in light of these observational studies are subsequently discussed.


Beta-Blocker Landiolol Hydrochloride in Preventing Atrial Fibrillation Following Cardiothoracic Surgery: A Systematic Review and Meta-Analysis.
The purpose of this article was to assess the benefit of perioperative administration of the intravenous beta-blocker landiolol hydrochloride in preventing atrial fibrillation (AF) after cardiothoracic surgery. We performed a systematic search in PubMed, Web of Science, CNKI, and OVID to identify randomized controlled trials (RCTs) and cohorts up to January 2021. Data regarding postoperative atrial fibrillation (POAF) and safety outcomes were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined using the Mantel-Haenszel method. Meanwhile, subgroup analyses were conducted according to surgery type including lung cancer surgery, esophageal cancer surgery, and cardiac surgery. Seventeen eligible articles involving 1349 patients within 13 RCTs and four cohorts were included in our meta-analysis. Compared with control group, landiolol administration was associated with a significant reduction of the occurrence of AF after cardiothoracic surgery (OR = 0.32, 95% CI 0.23-0.43, P <0.00001). In addition, the results demonstrated that perioperative administration of landiolol hydrochloride minimized the occurrence of postoperative complications (OR = 0.48, 95% CI 0.33-0.70, P = 0.0002). Funnel plots indicated no obvious publication bias. Considering this analysis, landiolol was effective in the prevention of AF after cardiothoracic surgery and did not increase the risk of major postoperative complications.


Temporal parameters of spontaneous speech in Alzheimer's disease.
This paper reports on four temporal parameters of spontaneous speech in three stages of Alzheimer's disease (mild, moderate, and severe) compared to age-matched normal controls. The analysis of the time course of speech has been shown to be a particularly sensitive neuropsychological method to investigate cognitive processes such as speech planning and production. The following parameters of speech were measured in Hungarian native-speakers with Alzheimer's disease and normal controls: articulation rate, speech tempo, hesitation ratio, and rate of grammatical errors. Results revealed significant differences in most of these speech parameters among the three Alzheimer's disease groups. Additionally, the clearest difference between the normal control group and the mild Alzheimer's disease group involved the hesitation ratio, which was significantly higher in the latter group. This parameter of speech may have diagnostic value for mild-stage Alzheimer's disease and therefore could be a useful aid in medical practice.


Mice deficient in oxytocin manifest increased saline consumption following overnight fluid deprivation.
Male mice (9-13 mo of age) in which the gene for oxytocin (OT) had been deleted (OT -/-) were administered 0.5 M sodium chloride (NaCl) solution or tap water as a two-bottle choice test following overnight fluid deprivation (1600 to 1000 the following day). Compared with wild-type cohorts (OT +/+), OT-deficient mice ingested sevenfold greater amounts of saline in the first hour following reintroduction of fluids, P < 0.001, and fourfold greater amounts at the end of 6 h, P < 0.02. No significant difference in total water ingested was noted between the two genotypes at the end of either 1 or 6 h. If food deprivation accompanied the overnight fluid deprivation and food was reintroduced 1 h after the reintroduction of both water and saline, OT -/- mice still ingested greater amounts of saline, but not water, than OT +/+ mice at both 1 h, P < 0.001, and 6 h, P < 0.02. No differences were noted between genotypes in the daily intake of 0.5 M NaCl solution or water during a 3-day observation period before the overnight fluid deprivation. The volume of saline consumed in each 24-h observation period represented about one-tenth of the total fluids ingested in each genotype. We conclude that OT -/- mice display an enhanced salt appetite compared with OT +/+ mice when fluid deprived overnight. The salt appetite was only apparent in the presence of a perturbation such as fluid deprivation, which predisposes the animal to moderate hypovolemia. The observations support an inhibitory role for OT in the control of sodium appetite in mice.


It took a pandemic: Perspectives on impact, stress, and telehealth from caregivers of people with autism.
Shelter in place mandates due to the COVID-19 pandemic left caregivers to determine how to best meet the therapeutic requirements of their children with autism spectrum disorder (ASD). Understanding the challenges faced by families, and their experiences using telehealth for the first time, may help make services sustainable in future public health emergencies. A sample of 70 caregivers of people with ASD from across the US completed an anonymous online survey. Results indicate that impaired emotion regulation was a primary contributor of parent-reported stress for persons with ASD during the pandemic, while loss of established structure and routine contributed to parental stress. Nearly half the sample reported using telehealth for the first time. Many caregivers were appreciative that telehealth permitted continuation of services, but expressed concerns about limited effectiveness due in part to their children's social communication problems.


l0 regularization based on a prior image incorporated non-local means for limited-angle X-ray CT reconstruction.
Restricted by the scanning environment in some CT imaging modalities, the acquired projection data are usually incomplete, which may lead to a limited-angle reconstruction problem. Thus, image quality usually suffers from the slope artifacts. The objective of this study is to first investigate the distorted domains of the reconstructed images which encounter the slope artifacts and then present a new iterative reconstruction method to address the limited-angle X-ray CT reconstruction problem. The presented framework of new method exploits the structural similarity between the prior image and the reconstructed image aiming to compensate the distorted edges. Specifically, the new method utilizes l0 regularization and wavelet tight framelets to suppress the slope artifacts and pursue the sparsity. New method includes following 4 steps to (1) address the data fidelity using SART; (2) compensate for the slope artifacts due to the missed projection data using the prior image and modified nonlocal means (PNLM); (3) utilize l0 regularization to suppress the slope artifacts and pursue the sparsity of wavelet coefficients of the transformed image by using iterative hard thresholding (l0W); and (4) apply an inverse wavelet transform to reconstruct image. In summary, this method is referred to as "l0W-PNLM". Numerical implementations showed that the presented l0W-PNLM was superior to suppress the slope artifacts while preserving the edges of some features as compared to the commercial and other popular investigative algorithms. When the image to be reconstructed is inconsistent with the prior image, the new method can avoid or minimize the distorted edges in the reconstructed images. Quantitative assessments also showed that applying the new method obtained the highest image quality comparing to the existing algorithms. This study demonstrated that the presented l0W-PNLM yielded higher image quality due to a number of unique characteristics, which include that (1) it utilizes the structural similarity between the reconstructed image and prior image to modify the distorted edges by slope artifacts; (2) it adopts wavelet tight frames to obtain the first and high derivative in several directions and levels; and (3) it takes advantage of l0 regularization to promote the sparsity of wavelet coefficients, which is effective for the inhibition of the slope artifacts. Therefore, the new method can address the limited-angle CT reconstruction problem effectively and have practical significance.


Enantioselective Palladium-Catalyzed Carbonylative Carbocyclization of Enallenes via Cross-Dehydrogenative Coupling with Terminal Alkynes: Efficient Construction of α-Chirality of Ketones.
An enantioselective PdII /Brønsted acid-catalyzed carbonylative carbocyclization of enallenes ending with a cross-dehydrogenative coupling (CDC) with a terminal alkyne was developed. VAPOL phosphoric acid was found as the best co-catalyst among the examined 28 chiral acids, for inducing the enantioselectivity of α-chiral ketones. As a result, a number of chiral cyclopentenones were easily synthesized in good to excellent enantiomeric ratio with good yields.


CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine ligand-18 (CCL18/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms.
Chemokines play an important role in atherogenesis and in ischemic injury and repair; however, prospective data on individual chemokines in unstable angina pectoris (UAP) are scarce. Therefore, we assessed chemokine patterns in a prospective cohort of patients with UAP. Plasma samples of 54 patients with Braunwald class IIIB UAP were examined at baseline for 11 chemokines and 5 inflammatory mediators via multiplex analysis. Levels of CC chemokine ligand (CCL)-5 (also known as RANTES [regulated on activation, normally T-cell expressed, and secreted]; 32.7 versus 23.1 ng/mL, P=0.018) and CCL18 (also known as PARC [pulmonary and activation-regulated chemokine]; 104.4 versus 53.7 ng/mL, P=0.011) were significantly elevated in patients with refractory ischemic symptoms versus stabilized patients. Temporal monitoring by ELISA of CCL5, CCL18, and soluble CD40 ligand (sCD40) levels revealed a drop in CCL5 and sCD40L levels in all UAP patients from day 2 onward (CCL5 12.1 ng/mL, P<0.001; sCD40L 1.35 ng/mL, P<0.05), whereas elevated CCL18 levels were sustained for at least 2 days, then were decreased at 180 days after inclusion (34.5 ng/mL, P<0.001). Peripheral blood mononuclear cells showed increased protein expression of chemokine receptors CCR3 and CCR5 in CD3+ and CD14+ cells at baseline compared with 180 days after inclusion, whereas mRNA levels were downregulated, which was attributable in part to a postischemic release of human neutrophil peptide-3-positive neutrophils and in part to negative feedback. Finally, elevated CCL5 and CCL18 levels predicted future cardiovascular adverse events, whereas C-reactive protein and sCD40L levels did not. We are the first to report that CCL18 and CCL5 are transiently raised during episodes of UAP, and peak levels of both chemokines are indicative of refractory symptoms. Because levels of both chemokines, as well as of cognate receptor expression by circulating peripheral blood mononuclear cells, are increased during cardiac ischemia, this may point to an involvement of CCL5/CCL18 in the pathophysiology of UAP and/or post-UAP responses.


Orthodontic treatment for the cleft palate patient.
This article is an overview of the treatment possibilities and the role of the orthodontist in the management of patients with cleft palate. Orthodontic intervention and treatment may be indicated soon after birth (infant orthopedics), in the deciduous, mixed, and permanent dentitions and also in the adult patient. This article focuses primarily on decision-making and procedural steps performed by the orthodontist during the permanent dentition stage. The need for coordinated interaction with other team members is emphasized.


Peripherally-inserted central catheter-related fungemia due to hansenula polymorpha in a patient with pancreatic cancer.
The methylotrophic yeast Hansenula polymorpha, used mainly as an industrial agent in the production of pharmaceuticals, has rarely been reported to cause disease. The case of a 47-year old Pilipino male with pancreatic cancer presented here is the second reported in the literature. Major risk factors for this infection included underlying malignancy, abdominal surgery and the use of a peripherally-inserted central catheter for total parenteral nutrition. He was successfully treated with a two-week's course of voriconazole.


Multiwavelength-Steerable Visible-Light-Driven Magnetic CoO-TiO2 Microswimmers.
While current light-driven microswimmers require high-intensity light, UV light, or toxic fuels to propel them, powering them with low-intensity UV-free visible light without fuels is essential to enable their potential high-impact applications. Therefore, in this study, a new material for light-driven microswimmers in the form of CoO is introduced. Janus CoO-TiO2 microswimmers powered with low-intensity, UV-free visible light inside water without using any toxic fuels like H2O2 is proposed. The microswimmers show propulsion under full spectrum of visible light with 17 times lower intensity than the mean solar intensity. They propel by breaking down water into oxygen and oxide radicals, which enables their potential applications for photocatalysis and drug delivery. The microswimmers are multiwavelength responsive, from the ultraviolet to the infrared region. The direction of swimming changes with the change in the illumination from the visible to UV light. In addition to being responsive, they are wavelength steerable and exhibit inherent magnetic properties enabling magnetic steering control of the CoO-TiO2 microswimmers. Thus, these microswimmers, which are propelled under low-intensity visible light, have direction-changing capability using light of different wavelengths, and have steering control capability by external magnetic fields, could be used in future potential applications, such as active and local cargo delivery, active photocatalysis, and hydrogen evolution.


Fostering an Internet-based work group in community health through action research.
In this article, we describe an action research study to foster an Internet-based work group as part of a two-year community health research training program in Alberta, Canada. The objectives of our study were to incorporate Internet-based technology into the program, establish a distributed work group over time, and reflect on the lessons learned. The participants represented seventeen health regions. There were thirty-five instructors and expert resource persons (varied over time), two training coordinators, four support staff, a program coordinator, two action researchers, and two independent consultants. The data collected included program documents, phone interviews, online surveys, meeting notes, online discussions, computer usage log, site visits, keystroke entry logs, help desk logs, and program evaluation reports. Content analysis was conducted with NUD*IST to identify concepts and themes from the data. Our findings suggest that role clarification, facilitative support, network linkages, and workplace learning are important aspects of fostering Internet-based work groups in a health setting, where members strive to establish themselves, seek meaning in their work, support each other, and add value to their organizations.


Fluvoxamine for stereotypic behavior in patients with dementia.
To describe the effects of treatment with the selective serotonin reuptake inhibitor fluvoxamine on three patients with advanced dementia who developed a stereotypic movement disorder. Three patients in a skilled nursing facility were referred by their primary physicians for psychiatric consultation to assist with the management of stereotypic behaviors. The patients received a standard medical, neurologic, and psychiatric workup for dementia. Two of the patients were diagnosed with dementia of the Alzheimer type and the other patient was diagnosed with vascular dementia. All three patients were started on fluvoxamine 25 mg/d; behaviors were monitored daily by the nursing staff and their primary care physicians and weekly by their psychiatrist using the Abnormal Involuntary Movement Scales. The dosage was titrated upward weekly to a maximum dosage of 150 mg/d. Two patients showed complete resolution of their stereotypic behaviors by week 6. The third patient showed noticeable improvement with some residual movements after 8 weeks of treatment. Fluvoxamine appeared effective in the control of stereotypic behaviors in three patients with advanced dementia.


Management of cardiogenic shock.
Despite the rapidly evolving evidence base in modern cardiology, progress in the area of cardiogenic shock remains slow, with short-term mortality still reaching 40-50%, relatively unchanged in recent years. Despite advances with an increase in the number of clinical trials taking place in this admittedly difficult-to-study area, the evidence base on which we make day-to-day decisions in clinical practice remains relatively sparse. With only definitive evidence for early revascularisation and the relative ineffectiveness of intra-aortic balloon pumping, most aspects of patient management are based on expert consensus, rather than randomised controlled trials. This updated 2020 review will outline the management of CS mainly after acute myocardial infarction with major focus on state-of-the-art treatment based on randomised clinical trials or matched comparisons if available.


MicroRNA-526a targets p21-activated kinase 7 to inhibit tumorigenesis in hepatocellular carcinoma.
MicroRNAs belong to a series of noncoding RNAs and have diverse roles in several biological processes. The association between aberrant microRNA expression and tumorigenesis is complex and remains to be fully elucidated. The present study investigated whether microRNA (miR) ‑526a can suppress the progression of hepatocellular carcinoma (HCC) in vitro and in vivo. Reverse transcription‑quantitative polymerase chain reaction, luciferase reporter assay, invasion assay, western blotting and in vivo implantation were used to investigate the potential function of miR‑526a. The present study observed that the level of miR‑526a was downregulated in HCC tissues and well‑established cell lines. In addition, the ectopic introduction of miR‑526a into Huh7 and HepG2 cells significantly attenuated HCC tumorigenesis, including proliferation, migration and invasion. The growth of tumor xenografts was also inhibited following transfection with miR‑526a. Using overlapping strategies, p21‑activated kinase 7 (PAK7) was predicted to be a target for miR‑526a, and this was verified experimentally. An inverse correlation was found between miR‑526a and PAK7 in HCC tissues. The results of the present study revealed a novel function of miR‑526a and may provide crucial insight into therapeutic interventions targeting microRNAs.


Dengue fever-associated necrotizing scleritis: A case report with long-term follow-up.
Dengue fever is a notable emerging infectious disease that is now seen worldwide, with an estimated incidence of approximately 390 million cases per year. Although ocular complications are uncommon among dengue fever-infected patients, caution is needed to prevent vision loss. Here we report a potentially serious sight-threatening complication of dengue fever, dengue fever-associated necrotizing scleritis. After being bitten by mosquitoes, a 60-year-old Japanese female exhibited positive serologic tests of immunoglobulin M and G enzyme immunoassays for dengue viral infection along with a decrease of leukocytes and platelets. These findings led to a dengue fever diagnosis. Slit lamp examination of her left eye revealed a conjunctival and scleral injection, elevation of the entire circumference of the sclera, and bulging of the sclera on the nasal upper side with a patch of avascular episcleral tissue. Since additional systemic examinations identified no autoimmune diseases such as rheumatism, we diagnosed the patient as dengue fever-associated scleritis. Intensive systemic and topical steroids were administrated during the initial acute phase. Over the next 15 months, the amount of steroid was tapered off. Initial findings for the scleritis gradually declined in response to steroid treatment. Although there was no recurrence of active scleritis, gradual thinning of the sclera continued to occur during the 18-year follow-up. To the best of our knowledge, this is the first reported case of dengue fever-associated necrotizing scleritis with long-term follow-up. This case suggests the existence of a long-term immune-mediated mechanism during the development of the dengue fever-associated necrotizing scleritis. Dengue fever virus patients found to have red eyes need to be carefully followed and treated, as these eyes might develop thinning of the sclera that could lead to rupture of the globe, thereby resulting in blindness.


Purification and Characterization of a Thermostable Trehalose Synthase from Thermus aquaticus.
Thermostable trehalose synthase, which catalyzes the conversion of maltose into trehalose by intramolecular transglucosylation, was purified from a cell-free extract of the thermophilic bacterium Thermus aquaticus ATCC 33923 to an electrophoretically homogeneity by successive column chromatographies. The purified enzyme had a molecular weight of 105,000 by SDS-polyacrylamide gel electrophoresis and a pI of 4.6 by gel isoelectrofocusing. The N-terminal amino acid of the enzyme was methionine. The optimum pH and temperature were pH 6.5 and 65°C, respectively. The enzyme was stable from pH 5.5 to 9.5 and up to 80°C for 60min. The trehalose synthase from Thermus aquaticus is more thermoactive and thermostable than that from Pimelobacter sp. R48. The yield of trehalose from maltose by the enzyme was independent of the substrate concentration, and tended to increase at lower temperatures. The maximum yield of trehalose from maltose by the enzyme reached 80-82% at 30-40°C. The activity was inhibited by Cu(2+) , Hg(2+), Zn(2+), and Tris.


Role of Preoperative Nerve Conduction Studies for Penetrating Hand Injuries Involving the Median Palmar Cutaneous Nerve.
Penetrating lacerations to the hand are a common cause of nerve injury and can lead to debilitating pain and numbness in the distribution of the nerve affected. Owing to an overlap in the cutaneous innervation from different sensory nerves, clinically identifying the injured nerve can be difficult. We present a novel case of isolated injury to the palmar cutaneous nerve from a penetrating knife injury which was detected using 'comparison waveform' nerve conduction studies. Using this technique, we can isolate injuries to the palmar cutaneous branch of the median nerve (PCBmdn) from the median nerve, dorsal radial sensory nerve, and lateral antebrachial cutaneous nerve. In addition, sensory nerve testing identified conduction block as the mechanism of injury, which resolved after surgery at 8 weeks postoperatively. Preoperative nerve conduction study can discern the level of nerve injury to PCBmdn only, thus eliminating the need for median and radial nerve exploration at the forearm, unnecessary incisions, pain, and scarring. The objective of this case report is to illustrate the value of preoperative comparison waveform nerve conduction study, particularly the PCBmdn, in patients presenting with neurologic deficits who have sustained penetrating lacerations to the hand.


Determination of the seroprevalence of Newcastle disease virus (avian paramyxovirus type 1) in Zambian backyard chicken flocks.
A cross-sectional study was conducted in five provinces and 11 districts of Zambia to determine the seroprevalence of Newcastle disease in Zambian backyard chicken flocks. Of the chickens sampled, 73.9% tested positive for avian paramyxovirus type 1 antibodies by means of an enzyme-linked immunosorbent assay. Seroprevalence varied amongst the five provinces sampled, ranging from 82.6% in the Eastern Province to 48.3% in Luapula Province. Seroprevalence also varied amongst the 11 districts sampled, ranging from 91.3% in Monze district of Southern Province to 22.8% in Mufulira district of the Copperbelt province. Overall, the seroprevalence of Newcastle disease in Zambian backyard chicken flocks has increased since the previous study conducted in 1994.


Blood neutrophil-lymphocyte ratio predicts survival after hepatectomy for hepatocellular carcinoma: A propensity score-based analysis.
To investigate whether an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) can predict poor survival in patients with hepatocellular carcinoma (HCC). We retrospectively reviewed 526 patients with HCC who underwent surgery between 2004 and 2011. Preoperative NLR ≥ 2.81 was an independent predictor of poor disease-free survival (DFS, P < 0.001) and overall survival (OS, P = 0.044). Compared with patients who showed a preoperative NLR < 2.81 and postoperative increase, patients who showed preoperative NLR ≥ 2.81 and postoperative decrease had worse survival (DFS, P < 0.001; OS, P < 0.001). Among patients with preoperative NLR ≥ 2.81, survival was significantly higher among those showing a postoperative decrease in NLR than among those showing an increase (DFS, P < 0.001; OS, P < 0.001). When elevated, alpha-fetoprotein (AFP) provided no prognostic information, and so preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS whenever AFP levels are low or high. Preoperative NLR ≥ 2.81 may be an indicator of poor DFS and OS in patients with HCC undergoing surgery. Preoperative NLR ≥ 2.81 may be a good complementary indicator of poor OS when elevated AFP levels provide no prognostic information.


Radiobiological effectiveness (RBE) of megavoltage X-ray and electron beams in radiotherapy.
Recent experiments indicate that significant differences exist in the microdosimetric properties (i.e., lineal energy distributions) of megavoltage X-ray and electron beams used in radiation therapy. In particular, dose averaged values of lineal energy for 18 MeV electrons are 10-30% lower than for 10 MeV bremsstrahlung X rays, which in turn are 30-60% lower than for 250 kVp X rays. Differences of this magnitude may manifest themselves in observable radiobiological effectiveness (RBE) differences between these radiations. Cell survival data have been obtained for line DLD-1 human tumor cells on all three of the above radiation sources. Results clearly demonstrate an RBE difference between orthovoltage and megavoltage radiation (P = 0.001). A small difference is also measured in RBE between megavoltage photons and megavoltage electrons, but the difference is not statistically significant (P = 0.25). All biological, dosimetric, and microdosimetric data were obtained under nearly identical geometric conditions. These data raise interesting questions vis à vis the applicability of microdosimetric theories in the interpretation of biological effects.


Gay-related stress and emotional distress among gay, lesbian, and bisexual youths: a longitudinal examination.
The longitudinal relations between gay-related stress (i.e., gay-related stressful events, negative attitudes toward homosexuality, and discomfort with homosexuality) and emotional distress (i.e., anxious symptoms, depressive symptoms, and conduct problems) were examined at 3 assessment periods (baseline, 6 months, and 12 months) among 140 gay, lesbian, and bisexual (GLB) youths. Although some findings were consistent with the hypothesis that stress would be associated with subsequent distress among GLB youths, the larger number of nonsignificant relations and the presence of relations between distress and subsequent gay-related stress indicate that the hypothesis was unsupported. The authors discuss the potential reasons for the lack of hypothesized relations and offer suggestions for future research.


THE TOPIC OF RESEARCH INTEGRITY IN LATINAMERICA.
Present article narrates the experience of trainees of the ethics of biomedical and psychosocial research program of the Interdisciplinary Center for studies on bioethics (CIEB) of the University of Chile on the topic of research integrity in Latin America. The following problems are covered: integrity of publications, reporting of scientific research misconduct, definitions of research integrity, scientific ethical review committees functioning, international multi-centric clinical trials monitoring and norms for scientific integrity and ethical oversight.


Evidence for enhancement of anisotropy persistence in kinematic magnetohydrodynamic turbulent systems with finite-time correlations.
Using the field-theoretic renormalization group approach and the operator product expansion technique in the second order of the corresponding perturbative expansion, the influence of finite-time correlations of the turbulent velocity field on the scaling properties of the magnetic field correlation functions as well as on the anisotropy persistence deep inside the inertial range are investigated in the framework of the generalized Kazantsev-Kraichnan model of kinematic magnetohydrodynamic turbulence. Explicit two-loop expressions for the scaling exponents of the single-time two-point correlation functions of the magnetic field are derived and it is shown that the presence of the finite-time velocity correlations has a nontrivial impact on their inertial-range behavior and can lead, in general, to significantly more pronounced anomalous scaling of the magnetic field correlation functions in comparison to the rapid-change limit of the model, especially for the most interesting three-dimensional case. Moreover, by analyzing the asymptotic behavior of appropriate dimensionless ratios of the magnetic field correlation functions, it is also shown that the presence of finite-time correlations of the turbulent velocity field has a strong impact on the large-scale anisotropy persistence deep inside the inertial interval. Namely, it leads to a significant enhancement of the anisotropy persistence, again, especially in three spatial dimensions.


Acute phencyclidine administration induces c-Fos-immunoreactivity in interneurons in cortical and subcortical regions.
Dysfunction of N-Methyl-d-aspartate receptors (NMDARs) is believed to underlie some of the symptoms in schizophrenia, and non-competitive NMDAR antagonists (including phencyclidine (PCP)) are widely used as pharmacological schizophrenia models. Furthermore, mounting evidence suggests that impaired γ-aminobutyric acid (GABA) neurotransmission contributes to the cognitive deficits in schizophrenia. Thus alterations in GABAergic interneurons have been observed in schizophrenia patients and animal models. Acute systemic administration of PCP increases levels of c-Fos in several cortical and subcortical areas, but whether such induction occurs in specific populations of GABAergic interneuron subtypes still remains to be established. We performed an immunohistochemical analysis of the PCP-induced c-Fos-immunoreactivity (IR) in parvalbumin (PV) and calbindin (CB) interneuron subtypes in the cortex and thalamus of rats. A single dose of PCP (10mg/kg, s.c.) significantly increased total number of c-Fos-IR in: (1) the prelimbic, infralimbic, anterior cingulate, ventrolateral orbital, motor, somatosensory and retrosplenial cortices as well as the nucleus accumbens (NAc), field CA1 of the hippocampus (CA1) field of hippocampus and mediodorsal thalamus (MD); (2) PV-IR cells in the ventrolateral orbitofrontal and retrosplenial cortices and CA1 field of hippocampus; and (3) CB-IR cells in the motor cortex. Overall, our data indicate that PCP activates a wide range of cortical and subcortical brain regions and that a substantial part of this activation is present in GABAergic interneurons in certain regions. This suggests that the psychotomimetic effect of PCP may be mediated via GABAergic interneurons.


Blood Pressure Levels and Associated Lifestyles Practices among Spouses of Patients with Hypertension Attending the General Outpatient Clinic of a Teaching Hospital in Lagos, Nigeria.
Hypertension is the commonest cardiovascular risk factor in the world. In Nigeria there have been rapid changes to a more western lifestyle and this is strongly associated with hypertension. Many spouses share similar lifestyle practices. The aim was to examine the association between elevated blood pressure and lifestyle practices among spouses of hypertensive patients. In a hospital based cross-sectional descriptive study at the General Outpatient Clinic of Lagos University Teaching Hospital, two hundred and thirty spouses of hypertensive patients were recruited by systematic sampling. An interviewer administered questionnaire adapted from WHO STEP instrument. Blood pressure was measured with a standardized mercury sphygmomanometer. The mean age of respondents was 52.3 ± 9.73 years. The mean systolic and diastolic blood pressures were 128.45 ± 19.47 mmHg and 82.68 ± 11.71 mmHg respectively. The proportion of respondents who had elevated systolic or diastolic blood pressure was 35.2 %. Proportion of current smokers was 3.9% and 3.5 % of respondents had excessive consumption of alcohol in the preceding seven days. Up to 43.9% of respondents had taken alcoholic beverage within the previous 12 months. About half (45.7%) of respondents engaged in moderate physical activity that lasted for at least 150 minutes per week. There was a statistically significant association between, the following factors and elevated systolic blood pressure among respondents; alcohol consumption within the past 12 months (c2= 6.738, p= 0.009); higher frequency of extra salt consumption (c2 = 4.816, p = 0.028); and red meat intake > 14times/week (c2 = 10.673, p = 0.014), with tobacco smoking (c2=6.202, p=0.037) and higher frequency of extra salt (c2 = 7.416, p=0.006) being significantly associated with elevated diastolic blood pressure. On the other hand, daily fruit intake (c2= 4.158, p=0.042) and vigorous physical activity >75min (c2=5.403, p=0.017)were significantly associated with non-elevated blood pressure among respondents. From this study, it can be concluded that more than one third of spouses of patients with hypertension are likely to have elevated blood pressure. It can also be concluded that elevated blood pressure among spouses of patients with hypertension is mostly associatedwithlack of vigorous physical activity >75min per week, recent consumption of alcohol, current smoking status, lack of daily fruit intake, higher salt consumption (addition of extra salt to served meal) and increased red meat consumption. Thus, this study has shown the importance of spousal case finding for both hypertension and adverse lifestyle practices, as a vital component of comprehensive care offered by family physicians caring for patients with hypertension.


Varicella Pneumonia in Otherwise Healthy 31-Year-Old Female Nonsmoker With No Prior Varicella Immunity.
Varicella pneumonia is a relatively rare but severe complication of primary varicella infection. It primarily affects adults and is exacerbated by risk factors such as smoking, immunocompromised status, and male gender. Left untreated, the mortality associated with varicella pneumonia is high and ranges from 10-30 percent in the literature. This is a case of an adult female patient with no prior immunity to varicella who presented with increased oxygen requirements approximately 5 days after the onset of cutaneous symptoms. Her symptoms quickly improved after 1-day post administration of valacyclovir, and on discharge, she was prescribed a 7-day course of valacyclovir. Early treatment with acyclovir is the mainstay of treatment and is essential as it has been shown to reduce long-term complications and decrease mortality. Despite the low incidence of varicella pneumonia among patients with primary varicella infection, the index of suspicion for varicella pneumonia among patients with primary varicella infection should be high in the setting of increased oxygen requirements due to the mortality and symptomatic benefits of early treatment.


Treatment Outcomes in Anaplastic Thyroid Cancer.
Anaplastic thyroid cancer (ATC) is rare, accounting for 1-2% of thyroid malignancies. Median survival is only 3-10 months, and the optimal therapeutic approach has not been established. This study aimed to evaluate outcomes in ATC based on treatment modality. Retrospective review was performed for patients treated at a single institution between 1990 and 2015. Demographic and clinical covariates were extracted from the medical record. Overall survival (OS) was modeled using Kaplan Meier curves for different treatment modalities. Univariate and multivariate analyses were conducted to assess the relationships between treatment and disease characteristics and OS. 28 patients with ATC were identified (n = 16 female, n = 12 male; n = 22 Caucasian, n = 6 African-American; median age 70.9). Majority presented as Stage IVB (71.4%). Most patients received multimodality therapy. 19 patients underwent local surgical resection. 21 patients received locoregional external beam radiotherapy (EBRT) with a median cumulative dose of 3,000 cGy and median number of fractions of 16. 14 patients received systemic therapy (n = 11 concurrent with EBRT), most commonly doxorubicin (n = 9). 16 patients were never disease free, 11 patients had disease recurrence, and 1 patient had no evidence of disease progression. Median OS was 4 months with 1-year survival of 17.9%. Regression analysis showed that EBRT (HR: 0.174; 95% CI: 0.050-0.613; p=0.007) and surgical resection (HR: 0.198; 95% CI: 0.065-0.598; p=0.004) were associated with improved OS. Administration of chemotherapy was not associated with OS. Anaplastic thyroid cancer patients receiving EBRT to the thyroid area/neck and/or surgical resection had better OS than patients without these therapies, though selection bias likely contributed to improved outcomes since patients who can undergo these therapies tend to have better performance status. Prognosis remains poor overall, and new therapeutic approaches are needed to improve outcomes.


Infection of CD127+ (interleukin-7 receptor+) CD4+ cells and overexpression of CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human immunodeficiency virus type 1 infection.
We recently found that human immunodeficiency virus (HIV)-specific CD4+ T cells express coreceptor CCR5 and activation antigen CD38 during early primary HIV-1 infection (PHI) but then rapidly disappear from the circulation. This cell loss may be due to susceptibility to infection with HIV-1 but could also be due to inappropriate apoptosis, an expansion of T regulatory cells, trafficking out of the circulation, or dysfunction. We purified CD38+++CD4+ T cells from peripheral blood mononuclear cells, measured their level of HIV-1 DNA by PCR, and found that about 10% of this population was infected. However, a small subset of HIV-specific CD4+) T cells also expressed CD127, a marker of long-term memory cells. Purified CD127+CD4+ lymphocytes contained fivefold more copies of HIV-1 DNA per cell than did CD127-negative CD4+ cells, suggesting preferential infection of long-term memory cells. We observed no apoptosis of antigen-specific CD4+ T cells in vitro and only a small increase in CD45RO+CD25+CD127dimCD4+ T regulatory cells during PHI. However, 40% of CCR5+CD38+++ CD4+ T cells expressed gut-homing integrins, suggesting trafficking through gut-associated lymphoid tissue (GALT). Furthermore, 80% of HIV-specific CD4+ T cells expressed high levels of the negative regulator CTLA-4 in response to antigen stimulation in vitro, which was probably contributing to their inability to produce interleukin-2 and proliferate. Taken together, the loss of HIV-specific CD4+ T cells is associated with a combination of an infection of CCR5+ CD127+ memory CD4+ T cells, possibly in GALT, and a high expression of the inhibitory receptor CTLA-4.


Differential modulation by Ca2+ of iodide transport processes in a cultured rat thyroid cell strain.
The interrelationship between the roles of Ca2+ and cyclic AMP (cAMP) in the control of intracellular iodide accumulation was investigated in the continuous rat thyroid cell strain FRTL-5. Using incubation conditions designed to allow independent study of iodide uptake and efflux into the incubation medium, dibutyryl cAMP (dbcAMP) mimicked the effect of TSH in enhancing iodide uptake, but the responses to both stimulators were decreased in the presence of the Ca2+ ionophore A23187, although the ionophore was ineffective when addition was delayed until after withdrawal of the stimulators. L-Adrenaline, an alpha-adrenergic agonist inactive with respect to cAMP accumulation in this cell strain, was also inactive with regard to iodide uptake. The rapid efflux of iodide from FRTL-5 cells seen in response to TSH was not mimicked by dbcAMP, but was reproduced by A23187, providing evidence for the involvement of Ca2+ in the release process. Under the latter conditions, no additional effect of TSH was obtained. L-Adrenaline also stimulated iodide efflux, in support of a possible role of alpha-adrenergic agonists in controlling the apical membrane p presentation of iodide in vivo. The observed differential effects of dbcAMP and alpha-adrenergic agonists on iodide uptake and efflux respectively, provide further evidence for the existence of two functionally distinct mechanisms controlling the available level of intracellular iodide. Opposing effects of free intracellular Ca2+ may, however, serve to control the activities of both influx and efflux processes since, whilst experimental increments in Ca2+ appear to promote iodide efflux through a non-cAMP-mediated pathway.(ABSTRACT TRUNCATED AT 250 WORDS)


Observation of elastic doublon decay in the Fermi-Hubbard model.
We investigate the decay of highly excited states of ultracold fermions in a three-dimensional optical lattice. Starting from a repulsive Fermi-Hubbard system near half filling, we generate additional doubly occupied sites (doublons) by lattice modulation. The subsequent relaxation back to thermal equilibrium is monitored over time. The measured absolute doublon lifetime covers 2 orders of magnitude. In units of the tunneling time h/J it is found to depend exponentially on the ratio of on-site interaction energy U to kinetic energy J. We argue that the dominant mechanism for the relaxation is a simultaneous many-body process involving several single fermions as scattering partners. A many-body calculation is carried out using diagrammatic methods, yielding fair agreement with the data.


Cumulative receipt of an anti-poverty tax credit for families did not impact tobacco smoking among parents.
The effect of anti-poverty tax credit interventions on tobacco consumption is unclear. Previous studies have estimated short-term effects, did not isolate the effects of cumulative dose of tax credits, produced conflicting results, and used methods with limited control for some time-varying confounders (e.g., those affected by prior treatment) and treatment regimen (i.e., study participants' tax credit receipt pattern over time). We estimated the longer-term, cumulative effect of New Zealand's Family Tax Credit (FTC) on tobacco consumption, using a natural experiment (administrative errors leading to exogenous variation in FTC receipt) and methods specifically for controlling confounding, reverse causation, and treatment regimen. We extracted seven waves (2002-2009) of the nationally representative Survey of Family, Income and Employment including 4404 working-age (18-65 years) parents in families. The exposure was the total numbers of years of receiving FTC. The outcomes were regular smoking and the average daily number of cigarettes usually smoked at wave 7. We estimated average treatment effects using inverse probability of treatment weighting and marginal structural modelling. Each additional year of receiving FTC affected neither the odds of regular tobacco smoking among all parents (odds ratio 1.02, 95% confidence interval 0.94-1.11), nor the number of cigarettes smoked among parents who smoked regularly (rate ratio 1.01, 95% confidence interval 0.99-1.03). We found no evidence for an association between the cumulative number of years of receiving an anti-poverty tax credit and tobacco smoking or consumption among parents. The assumptions of marginal structural modelling are quite demanding, and we therefore cannot rule out residual confounding. Nonetheless, our results suggest that tax credit programme participation will not increase tobacco consumption among poor parents, at least in this high-income country.


Effect of a long-acting contraceptive progestogen on lactation.
A prospective study was made on the duration of lactation in 406 mothers injected postpartum for contraception with medroxyprogesterone acetate (DMPA), 150 or 250-300 mg, IM, at 3- or 6-month intervals. Breast feedings up to 2 per day were recorded, and findings compared with those from 173 nontreated controls. Eighty percent of the DMPA group were nursing successfully at the sixth month and 42% at the 12th month postpartum. These figures are significant and compare favorably with the control group. No advantage was found in the administration of DMPA earlier than the second or third month after delivery. Amenorrhea persisted during lactation. No pathologic breast conditions were observed. The eventual mechanism of DMPA in galactopoiesis has yet to be clarified.


Preliminary efficacy of a Web-based family problem-solving treatment program for adolescents with traumatic brain injury.
Preliminary report of the efficacy of a Web-based treatment program to improve adolescent and family psychosocial functioning following traumatic brain injury (TBI). Families of 9 adolescents with TBI (2 severe and 7 moderate) injured less than 24 months ago participated in this study. A Web-based family treatment program designed to enhance family problem solving and adjustment, as well as reduce adolescent behavioral and social problems that are common sequelae of moderate-to-severe TBI was used as intervention. The program consisted of 10 core sessions and up to 4 supplemental sessions, each consisting of self-guided Web exercises followed by a videoconference therapy session. Significant improvements were found in parent-reported adolescent internalizing behaviors, self-reported adolescent depressive symptoms, parental depression, and parent-adolescent conflict. Effect sizes were in the medium-to-high range for these same contrasts. Exploratory analyses suggested that providing audio with the Web site may enhance some outcomes. This study provides preliminary evidence of the feasibility and efficacy of family-centered online intervention for improving adolescent and family adaptation following pediatric TBI.


[Treatment of gastric cancer].
Even though adjuvant systemic therapy significantly increases 5-year survival rates for resectable gastric or gastroesophageal carcinoma, quality assurance research has shown that in practice it is often not given. The European standard, perioperative chemotherapy, is based on results of the MAGIC trial (3 cycles of ECF - epirubicin, cisplatin, 5-FU as infusion before and after surgery). It is to be expected that oral capecitabine will replace infusional 5-FU in perioperative treatment, as in the palliative setting. This change has already taken place in many institutions. For metastatic and locally advanced esophageal and gastric carcinoma, the results of clinical trials over recent years have led to the following concrete changes: the importance of platinum has been confirmed. Oxaliplatin can replace cisplatin. Capecitabine can replace 5-FU. If docetaxel is given in addition to platinum/5-FU, this doubles 2-year survival (with significant toxicity). Targeted drugs such as cetuximab, panitumumab, and bevacizumab are currently undergoing clinical trials.


The effect of a Health Realization/Innate Health psychoeducational seminar on stress and anxiety in HIV-positive patients.
Chronic stress and depression have a negative impact on immune functioning and threaten the well-being of HIV-positive patients. Although therapy methods, such as Cognitive Behavioral Therapy, have been shown to reduce stress and depression in such patients, not all patients are willing or able to undergo therapy over time. The Health Realization/Innate Health (HR/IH) psychoeducational approach is a brief intervention alternative that can be presented in a classroom setting. It engages participants' innate capacity to realize peace of mind. Eight volunteer participants from patients in the Positive Health Clinic at West Virginia University School of Medicine attended a 1-1/2 day HR/IH seminar called "Finding Your Natural Peace of Mind". Shortly before the seminar started, the Brief Symptom Inventory (BSI) was administered by a Clinic staff member. The BSI was administered again immediately following the seminar. The BSI was mailed to the participants four weeks following the seminar with a return envelope. Participants' confidentiality was maintained through a coded ID. Pre-, post- and follow-up results were compared. Each case was evaluated individually. The participant who pre-tested in the "psychiatric inpatient" range of the BSI showed no change after the seminar or at follow-up. The participants who tested in the non-patient normal range before the seminar showed some improvement after and at follow-up. The participants who scored in the "psychiatric outpatient" range entering the seminar all showed improvement that was sustained upon follow-up. The HR/IH psychoeducational approach deserves further study as a brief intervention for stress-reduction in HIV-positive patients.


Alpha 1-receptor antagonists urapidil and prazosin inhibit neointima formation in rat carotid artery induced by balloon catheter injury.
Sympathetic nerves and catecholamines seem to have a trophic influence on vascular smooth muscle cells in vivo. We therefore tested whether alpha 1-antagonists would inhibit proliferation in arterial smooth muscle in vivo. Smooth muscle cells were stimulated to form a neointima in rat carotid arteries after deendothelialization by means of a 2F embolectomy catheter. The development of intimal lesions was determined 14 days after injury. The size of the neointima was measured using two parameters. Intimal DNA content was estimated from 5-mm segments of carotid arteries after DNA extraction and staining with Hoechst-stain. The size of the neointima was determined morphometrically as intimal area in histological cross-sections. Prazosin and urapidil were given orally once per day. Urapidil-treated rats showed significant inhibition of neointima formation for both parameters in a dose-dependent fashion. For prazosin a significant reduction could only be observed if DNA content was considered.


Isolation of the three grape sub-lineages of B-class MADS-box TM6, PISTILLATA and APETALA3 genes which are differentially expressed during flower and fruit development.
The B class of MADS-box floral homeotic genes specifies petal and stamen identity in angiosperms. While this group is one of the most studied in herbaceous plant species, it has remained largely uncharacterized in woody species such as grapevine. Although the B class PI/GLO and AP3/DEF clades have been extensively characterized in model species, the role of the TM6 subgroup within the AP3 clade is not completely understood, since it is absent in Arabidopsis thaliana. In this study, the coding regions of VvTM6 and VvAP3 and the genomic sequence of VvPI, were cloned. VvPI and AtPI were confirmed to be functional homologues by means of complementation of the pi Arabidopsis mutant. Expression analysis revealed that VvPI and VvAP3 transcripts are restricted almost exclusively to inflorescences, although VvPI was detected at low levels in leaves and roots. VvTM6 expresses throughout the plant, with higher levels in flowers and berries. A detailed chronological study of grape flower progression by light microscopy and temporal expression analysis throughout early and late developmental stages, revealed that VvPI expression increases during pollen maturation and decreases between the events of pollination and fertilization, before the cap fall. On the other hand, VvTM6 is expressed in the last stage of anther development. Specific expression of VvAP3 and VvPI was detected in petals and stamens within the flower, while VvTM6 was also expressed in carpels. Moreover, this work provides the first evidence for expression of a TM6-like gene throughout fruit growth and ripening. Even if these genes belong to the same genetic class they could act in different periods and/or tissues during reproductive organ development.


Expression and function of AIM, an activation inducer molecule of human lymphocytes, is dependent on the activation of protein kinase C.
AIM is an activation inducer molecule selectively expressed by activated lymphocytes through which agonistic proliferative signals can be triggered. The relationship between the expression of AIM with the activation of protein kinase C (PKC) has been studied. Different activators of PKC such as the active phorbol esters, phorbol myristate acetate and phorbol dibutyrate, or the phorbol-related ester mezerein were able to induce AIM expression on peripheral blood lymphocytes as assessed by immunofluorescence flow cytometry. Moreover, the expression of this activation antigen was also induced by treatment of peripheral blood lymphocytes either with dioctanoyl-rac-glycerol, a synthetic analogue of diacylglycerol, the physiological mediator of PKC activation. Further indirect evidence that AIM expression was dependent on the activation of PKC was obtained by blockade of the induction of its expression in cells treated with H7, an inhibitor of PKC. The AIM expression can be detected as early as 3 h after addition of phorbol esters and it requires active RNA and protein synthesis. The activation of PKC appears to be also required in the proliferative response induced by anti-AIM monoclonal antibody (mAb) in conjunction with phorbol esters. Agents such as phorbol myristate acetate, phorbol dibutyrate or mezerein but not the inactive phorbol ester methyl-phorbol myristate acetate induced a high proliferation of peripheral blood lymphocytes in the presence of anti-AIM mAb. In addition, we have demonstrated that the anti-AIM mAb is not sufficient by itself to induce cellular proliferation once the AIM antigen is expressed at the cell surface, requiring the simultaneous stimulation of the PKC to trigger high proliferative responses. Furthermore, the anti-AIM mAb did not appear to exert its effect on proliferation by rapidly increasing the intracytoplasmic Ca2+ levels. Taken together all these results indicate that the expression and function of AIM antigen is dependent on the activation of PKC.


Tissue Resident Foxp3+ Regulatory T Cells: Sentinels and Saboteurs in Health and Disease.
Foxp3+ regulatory T (Treg) cells are a CD4 T cell subset with unique immune regulatory function that are indispensable in immunity and tolerance. Their indisputable importance has been investigated in numerous disease settings and experimental models. Despite the extensive efforts in determining the cellular and molecular mechanisms operating their functions, our understanding their biology especially in vivo remains limited. There is emerging evidence that Treg cells resident in the non-lymphoid tissues play a central role in regulating tissue homeostasis, inflammation, and repair. Furthermore, tissue-specific properties of those Treg cells that allow them to express tissue specific functions have been explored. In this review, we will discuss the potential mechanisms and key cellular/molecular factors responsible for the homeostasis and functions of tissue resident Treg cells under steady-state and inflammatory conditions.


Pressure-Induced Confined Metal from the Mott Insulator Sr_{3}Ir_{2}O_{7}.
The spin-orbit Mott insulator Sr_{3}Ir_{2}O_{7} provides a fascinating playground to explore insulator-metal transition driven by intertwined charge, spin, and lattice degrees of freedom. Here, we report high-pressure electric resistance and resonant inelastic x-ray scattering measurements on single-crystal Sr_{3}Ir_{2}O_{7} up to 63-65 GPa at 300 K. The material becomes a confined metal at 59.5 GPa, showing metallicity in the ab plane but an insulating behavior along the c axis. Such an unusual phenomenon resembles the strange metal phase in cuprate superconductors. Since there is no sign of the collapse of spin-orbit or Coulomb interactions in x-ray measurements, this novel insulator-metal transition is potentially driven by a first-order structural change at nearby pressures. Our discovery points to a new approach for synthesizing functional materials.


Determinants of serum albumin concentration analyzed in a large cohort of patients on maintenance hemodialysis.
Serum albumin concentration is a powerful predictor of mortality in patients on chronic hemodialysis (CHD). This study sought to investigate variables associated with serum albumin concentration. Cross-sectional study in prevalent chronic hemodialysis patients treated at the Renal Research Institute between July 1, 2005 and October 31, 2005. A total of 4,798 (2,199 females) patients were studied. Univariate and multivariate relationships of serum albumin concentration with age, sex, race (black, white, other), vascular access type (arteriovenous fistula/graft, catheter), white blood cells, neutrophils, lymphocytes, equilibrated normalized protein catabolic rate (enPCR), dialysis efficacy (eKdrt/V), hemoglobin, phosphate, bio-intact parathyroid hormone [bioPTH], creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Age, access type, and variables of 3 domains, namely, nutrition (enPCR; creatinine), eKdrt/V, and inflammation (white blood cells; neutrophil:lymphocyte ratio; hemoglobin), were related to serum albumin. It is interesting to note that AST was the strongest negative predictor of albumin levels. In CHD patients, serum albumin concentration is defined by a complex interaction of inflammation, nutrition, and dialysis efficacy. The relationship between AST and albumin deserves additional study.


Nuclear stopping from 0.09A to 1.93A GeV and its correlation to flow.
We present a complete systematics (excitation functions and system-size dependences) of global stopping and side flow for heavy ion reactions in the energy range between 0.09A and 1.93A GeV. For the heaviest system, Au+Au, we observe a plateau of maximal stopping extending from about 0.2A to 0.8A GeV with a fast drop on both sides. The degree of stopping, which is shown to remain significantly below the expectations of a full stopping scenario, is found to be highly correlated to the amount of side flow.