Optimum conditions for high-speed solid-liquid separation by ballasted flocculation.
In the ballasted flocculation, high-speed sedimentation of suspensions is achieved using a microsand as a ballast material and a polymer flocculant combined with microflocs made of polyaluminum chloride (PAC) as an inorganic coagulant. In this study, three turbid water samples containing kaolin clay (kaolin concentration: 20, 200, and 500 mg/L) were treated by coagulation-sedimentation and ballasted flocculation. The effects of pH and PAC dosage, which are the controlling parameters for coagulation, and the microsand (silica sand) and polymer dosages, which are the controlling parameters for ballasted treatment, on the treatment efficiency and floc settling velocity were examined. The floc settling velocity under the optimum conditions was 17 times higher than that of the conventional coagulation-sedimentation process using PAC. The turbidity was 0.54 turbidity unit (TU) (TU as the kaolin standard), and its removal efficiency was 99.7%. Furthermore, turbid water samples with different kaolin concentrations (20 and 500 mg/L) were treated via the ballasted flocculation. In this study, fundamental information on the optimization of each dosage condition of coagulant, ballast, and polymer and pH condition in ballasted flocculation was obtained, and the removal mechanisms under optimal, underoptimistic and overoptimistic conditions were proposed.


Spontaneous Cerebrospinal Fluid Rhinorrhea from a Prolactin-Secreting Pituitary Macroadenoma.
Cerebrospinal fluid (CSF) rhinorrhea is a rare complication of macroprolactinomas that, in the vast majority of cases, is subsequent to either medical or surgical intervention. Here, we present the successful management of a rare case of spontaneous, noniatrogenic CSF rhinorrhea in a patient with an untreated macroprolactinoma. A 27-year-old man with no significant medical history presented with six months of persistent CSF rhinorrhea, which was confirmed by testing for beta-2-transferrin. He had had decreased libido since adolescence and impaired growth of secondary sexual characteristics. Workup revealed an elevated prolactin level, and imaging demonstrated erosion of the anterior sellar floor and soft tissue within the sphenoid sinus, concerning for tumor. The patient underwent surgical repair of the CSF leak via a transnasal transsphenoidal approach, with resection and biopsy of tumor material within the sinus. No tumor was noted within the sella itself. The patient tolerated the procedure well and had subsequent normalization of his prolactin level with no further CSF egress. Spontaneous noniatrogenic CSF rhinorrhea, although rare, should be considered in the differential diagnosis of invasive pituitary macroadenomas, especially prolactinomas. The mechanism of CSF leak from a prolactinoma is not completely understood, but the CSF leak should be urgently repaired through a transnasal transsphenoidal approach. Concurrently, tumor resection should be performed and a postoperative lumbar puncture or lumbar drain should be considered to reinforce the skull base reconstruction.


Setting a minimum age for juvenile justice jurisdiction in California.
Purpose Despite the existence of minimum age laws for juvenile justice jurisdiction in 18 US states, California has no explicit law that protects children (i.e. youth less than 12 years old) from being processed in the juvenile justice system. In the absence of a minimum age law, California lags behind other states and international practice and standards. The paper aims to discuss these issues. Design/methodology/approach In this policy brief, academics across the University of California campuses examine current evidence, theory, and policy related to the minimum age of juvenile justice jurisdiction. Findings Existing evidence suggests that children lack the cognitive maturity to comprehend or benefit from formal juvenile justice processing, and diverting children from the system altogether is likely to be more beneficial for the child and for public safety. Research limitations/implications Based on current evidence and theory, the authors argue that minimum age legislation that protects children from contact with the juvenile justice system and treats them as children in need of services and support, rather than as delinquents or criminals, is an important policy goal for California and for other national and international jurisdictions lacking a minimum age law. Originality/value California has no law specifying a minimum age for juvenile justice jurisdiction, meaning that young children of any age can be processed in the juvenile justice system. This policy brief provides a rationale for a minimum age law in California and other states and jurisdictions without one.


Characterizing the chloroplast genome of Mammillaria elongata DC. 1828 in the Cactaceae family and unveiling its phylogenetic affinities within the genus Mammillaria.
With its nearly 200 species, the Mammillaria genus is the most species-rich within the Cactaceae family, yet surprisingly, few of its chloroplast genomes have been studied. We focused on the species Mammillaria elongata DC. 1828, a petite cactus native to Mexico and favored by horticulturists, yet whose phylogenetic relationships remain uncertain due to a lack of genomic data. We extracted the DNA from a sample obtained in China, sequenced it using the NovaSeq 6000 platform, and assembled the chloroplast genome using GetOrganelle software. Our assembly resulted in a chloroplast genome of 110,981 base pairs with an overall GC content of 36.28%, which included 100 genes (95 unique). Notably, several protein-coding genes were absent. Phylogenetic analysis using 59 shared genes across nine Mammillaria species and one Obregonia species revealed that M. elongata and M. gracilis are closely related, suggesting a recent common ancestor and possible shared evolutionary pressures or ecological niches. This study provides crucial genomic data for M. elongata and hints at intriguing phylogenetic relationships within the Mammillaria genus.


Mild-moderate TBI: clinical recommendations to optimize neurobehavioral functioning, learning, and adaptation.
Traumatic brain injury (TBI) can result in functional deficits that persist long after acute injury. The authors present a case study of an individual who experienced some of the most common debilitating problems that characterize the chronic phase of mild-to-moderate TBI-difficulties with neurobehavioral functions that manifest via complaints of distractibility, poor memory, disorganization, poor frustration tolerance, and feeling easily overwhelmed. They present a rational strategy for management that addresses important domain-general targets likely to have far-ranging benefits. This integrated, longitudinal, and multifaceted approach first addresses approachable targets and provides an important foundation to enhance the success of other, more specific interventions requiring specialty intervention. The overall approach places an emphasis on accomplishing two major categories of clinical objectives: optimizing current functioning and enhancing learning and adaptation to support improvement of functioning in the long-term for individuals living with brain injury.


Changes in Radiographic Alignment Following Metatarsophalangeal Fusion, Distal Metatarsal Osteotomy, and Lapidus.
The purpose of this study is to evaluate the effect of the different surgical treatments for hallux valgus on various radiographic measures of bunion correction. A retrospective cohort study was conducted at a single academic medical center involving 2 fellowship-trained foot and ankle surgeons. One hundred and nineteen feet (110 patients) were included. Procedures included first metatarsophalangeal (MTP) arthrodesis (n = 88), Chevron and/or Scarf osteotomy (n = 23), and Lapidus (n = 8). Overall, 78.2% of patients were female, mean age was 60.49 (range, 16-81) years, and mean follow-up was 1.20 (range, 0.25-3.92) years. Hallux valgus angle (HVA) significantly differed preoperatively (MTP = 33.33°, Chevron/Scarf = 27.03°, Lapidus = 32.56°; P = .026). There was no difference in distal metatarsal articular angle (DMAA) preoperatively (MTP = 18.87°, Chevron/Scarf = 17.80°, Lapidus = 14.39°; P = .629). At final follow-up, DMAA was significantly greatest among the Lapidus bunionectomy cohort (MTP = 9.63°, Chevron/Scarf = 13.51°, Lapidus = 17.45°; P = .005). There was no difference in infection (MTP = 6.8%, Chevron/Scarf = 4.4%, Lapidus = 0.0%; P = 1.00) or reoperation (MTP = 19.3%, Chevron/Scarf = 21.7%, Lapidus = 12.5%; P = .921) rates between cohorts, although both rates were highest in the first MTP arthrodesis group. Among the 3 hallux valgus corrections studied, Lapidus bunionectomy fared the worst regarding DMAA correction at first follow-up and final follow-up, compared with MTP fusion and distal metatarsal osteotomies. Other radiographic measures showed no significant difference among the groups. Level III: Retrospective cohort study.


Mechanistic analysis of RNA polymerase III regulation by the retinoblastoma protein.
The tumour suppressor protein RB restricts cellular growth. This may involve inhibiting the synthesis of tRNA and 5S rRNA by RNA polymerase (pol) III. We have shown previously that RB can repress pol III transcription when overexpressed either in vitro or in vivo. We also demonstrated that pol III activity is elevated substantially in primary fibroblasts from RB-deficient mice. Here we address the molecular mechanism of this regulation. RB is shown to repress all types of pol III promoter. It can do this even if added after transcription complex assembly. Functional assays demonstrate that RB targets specifically the general pol III factor TFIIIB. A physical interaction between TFIIIB and RB is indicated by fractionation, pull-down and immunoprecipitation data. We show that TFIIIB activity is elevated in primary fibroblasts from RB-deficient mice. TFIIIB is a multisubunit complex that includes the TATA-binding protein (TBP) and a TFIIB-related factor called BRF. We show that RB itself contains regions of homology to both TBP and BRF and propose a model in which RB disrupts TFIIIB by mimicking these two components.


Non-X-linked hyper-IgM syndrome with systemic lupus erythematosus.
A 24-year-old woman had suffered from recurrent bacterial infections and clinical manifestations of systemic lupus erythematosus (SLE). Laboratory findings disclosed an elevated level of serum IgM, markedly decreased IgG, IgA, IgD and IgE levels, and low levels of serum complement. Both the CD40 and CD40 ligands appeared to be normally expressed. Assays of in vitro immunoglobulin production by lymphocytes showed that IgM was produced normally and that IgE but not IgG or IgA production was rescued by signaling through CD40 on B cells. The proliferative response of lymphocytes to phobol ester was markedly decreased, suggesting some impairment of signal transduction in the patient's lymphocytes.


Social comparison impacts stimulus evaluation in a competitive social learning task.
When we perform an action, the outcome that follows it can change the value we place on that behaviour, making it more or less likely to be repeated in the future. However, the values that we learn are not objective: we interpret the outcomes that we receive for ourselves relative to those that share our environment, i.e. we engage in social comparison. The temporal dynamics of physiological responses to stimulus valuation in social learning tasks are poorly understood, particularly in human participants. Therefore, we recorded stimulus-locked event-related potentials with 64-channel EEG to examine stimulus valuation, following the design of a study previously used in macaques. Pairs of participants performed a social learning task in which they received outcomes sequentially for a presented stimulus (partner first) by pressing a button in response to a cue. There were two conditions: one in which stimulus values varied for the participant but output a constant rate of reward for the partner (self-variable blocks), and another condition in which this payout was reversed (other-variable blocks). We then measured participants' self-reported competitiveness. Approximately 200 ms post-stimulus, an ERP related to stimulus evaluation and attentional processing appeared to encode own stimulus value in self-variable blocks. In other-variable blocks the same pattern of activity was reversed, even though the value of the stimulus for the participant did not depend on the stimulus presented. Outcome-locked analyses further showed that attention dedicated to the partner's outcome was greater in more competitive participants. We conclude that subjective stimulus value can be reflected in early stimulus-locked ERP responses and that competitive participants may be more invested in their own performance relative to the other player, hence their increased interest in the outcome of their partner.


Trans-2-hexenal downregulates several pathogenicity genes of Pseudogymnoascus destructans, the causative agent of white-nose syndrome in bats.
White-nose syndrome is an emergent wildlife disease that has killed millions of North American bats. It is caused by Pseudogymnoascus destructans, a cold-loving, invasive fungal pathogen that grows on bat tissues and disrupts normal hibernation patterns. Previous work identified trans-2-hexenal as a fungistatic volatile compound that potentially could be used as a fumigant against P. destructans in bat hibernacula. To determine the physiological responses of the fungus to trans-2-hexenal exposure, we characterized the P. destructans transcriptome in the presence and absence of trans-2-hexenal. Specifically, we analyzed the effects of sublethal concentrations (5 μmol/L, 10 μmol/L, and 20 μmol/L) of gas-phase trans-2-hexenal of the fungus grown in liquid culture. Among the three treatments, a total of 407 unique differentially expressed genes (DEGs) were identified, of which 74 were commonly affected across all three treatments, with 44 upregulated and 30 downregulated. Downregulated DEGs included several probable virulence genes including those coding for a high-affinity iron permease, a superoxide dismutase, and two protein-degrading enzymes. There was an accompanying upregulation of an ion homeostasis gene, as well as several genes involved in transcription, translation, and other essential cellular processes. These data provide insights into the mechanisms of action of trans-2-hexenal as an anti-fungal fumigant that is active at cold temperatures and will guide future studies on the molecular mechanisms by which six carbon volatiles inhibit growth of P. destructans and other pathogenic fungi.


Experimental acute pancreatitis in the rat--a new model.
A new experimental model of acute pancreatitis in the rat has been devised. It consists of a closed duodenal loop into which infected bile is injected under pressure; intestinal continuity is maintained by a plastic tube passed through the loop. Histological and biochemical evidence of acute pancreatitis in the rat model is presented. The model has been compared with that of Nevalainen and with control groups of rats undergoing bile duct ligation and sham operation. The model produces a consistently fatal acute pancreatitis, more severe than that produced by Nevalainen's model, with a survival time fo 28+/-12.8 (SD) hours. A combination of the reflux of infected bile under increased pressure into the pancreatic duct, at a known time, produces a model which may be suitable for the investigation of therapeutic agents.


Likely transmission of norovirus on an airplane, October 2008.
On 8 October 2008, members of a tour group experienced diarrhea and vomiting throughout an airplane flight from Boston, Massachusetts, to Los Angeles, California, resulting in an emergency diversion 3 h after takeoff. An investigation was conducted to determine the cause of the outbreak, assess whether transmission occurred on the airplane, and describe risk factors for transmission. Passengers and crew were contacted to obtain information about demographics, symptoms, locations on the airplane, and possible risk factors for transmission. Case patients were defined as passengers with vomiting or diarrhea (> or =3 loose stools in 24 h) and were asked to submit stool samples for norovirus testing by real-time reverse-transcription polymerase chain reaction. Thirty-six (88%) of 41 tour group members were interviewed, and 15 (41%) met the case definition (peak date of illness onset, 8 October 2008). Of 106 passengers who were not tour group members, 85 (80%) were interviewed, and 7 (8%) met the case definition after the flight (peak date of illness onset, 10 October 2008). Multivariate logistic regression analysis showed that sitting in an aisle seat (adjusted relative risk, 11.0; 95% confidence interval, 1.4-84.9) and sitting near any tour group member (adjusted relative risk, 7.5; 95% confidence interval, 1.7-33.6) were associated with the development of illness. Norovirus genotype II was detected by reverse-transcription polymerase chain reaction in stool samples from case patients in both groups. Despite the short duration, transmission of norovirus likely occurred during the flight.


Central Venous Interventions.
Central venous stenosis or occlusion is a common and vexing problem in patients undergoing hemodialysis. Typical presenting symptoms include arm swelling and prolonged bleeding after hemodialysis. Despite multiple treatment approaches, these stenoses tend to recur and progress over time. A thorough preprocedure evaluation, methodical procedural approach and awareness of potential complications are all essential to try to preserve vascular access and improve patients' quality of life.


Histamine contributes to increased RANKL to osteoprotegerin ratio through altered nuclear receptor 4A activity in human chondrocytes.
To elucidate histamine receptor-mediated signaling pathways, transcriptional events, and target gene expression in human cartilage. Histamine modulation of cartilage destruction was assessed by Safranin O staining and proteoglycan release. H(1) , H(2) , H(3) , and H(4) histamine receptor-dependent regulation of transcription factors (nuclear receptor 4A1 [NR4A1], NR4A2, and NR4A3), RANKL, and osteoprotegerin (OPG) messenger RNA (mRNA) levels were measured in primary and SW-1353 chondrocyte cells using quantitative polymerase chain reaction and selective histamine receptor antagonists. Soluble RANKL and OPG protein levels were determined using enzyme-linked immunosorbent assays. NR4A protein levels and transactivity were evaluated by Western blot analysis, immunocytochemistry, and luciferase reporter assays. Stable depletion of NR4A1-3 was achieved by lentiviral transduction of NR4A short hairpin RNA. Primary human chondrocyte cells expressed differential steady-state levels of H(1) -H(4) histamine receptor mRNA. In combination with tumor necrosis factor α, histamine significantly promoted cartilage proteoglycan depletion and release. Histamine modulated the expression of NR4A1-3 orphan receptors in primary and immortalized human chondrocyte cells in a time- and concentration-dependent manner. Histamine selectively signaled through H(1) and H(2) histamine receptors in chondrocytes to modulate RANKL and NR4A2 expression. The temporal effects of histamine on NR4A2 gene transcription were reduced in cells pretreated with inhibitors directed against protein kinase A, MAPK, and NF-κB signaling pathways. Histamine modulated the expression of RANKL with modest effects on OPG levels, leading to increased RANKL:OPG mRNA and protein ratios. Stable knockdown of NR4A1-3 expression resulted in reduced endogenous OPG levels and the loss of histamine-dependent regulation of RANKL expression. Our findings indicate that histamine, via H(1) and H(2) histamine receptors, contributes to joint disease by enhancing the ratio of RANKL to OPG expression through altered NR4A activity in human chondrocyte cells.


Histopathological effects of topical ophthalmic preservatives on rat corneoconjunctival surface.
Long term use of topical drugs has clearly been shown to induce toxic immunopathological changes in the ocular surface. However, little is known concerning the respective roles of active compounds and preservatives. Benzalkonium chloride (BAC) is the most used preservative and its cytotoxicity is well known, but other preservatives have not yet been clearly evaluated. We thus performed a comparative study to investigate toxic side effects induced in the rat ocular surface by applications of various preservatives, with special attention to inflammatory infiltrates. A total of 35 brown Norway rats were divided into seven groups of five each. They received, for one month, in both eyes, either 0.01% cetrimonium chloride, 0.01% benzalkonium chloride, 0.01% benzododecinium bromide, 0.004% thiomersal, 0.05% methyl parahydroxybenzoate or phosphate-buffered saline (PBS), the last group remaining untreated. Then, animals were sacrificed and eyes were processed for histological and immunological procedures with monoclonal antibodies to rat immunocompetent cells. When compared to controls, all preservative-treated eyes consistently showed corneal and conjunctival damage, including epithelial alterations, various degrees of keratinization and inflammatory infiltrates at the limbus and within the conjunctival stroma and epithelium. No difference was found between the five tested drugs. This study confirms that most preservatives used in ophthalmic eyedrops may similarly induce strong histopathological and inflammatory changes in the ocular surface after short term use. Although obtained in animal model, these results confirm strong toxic side effects in patients with preexisting ocular surface disorders and/or receiving topical drugs for long periods.


Trends of Do-Not-Resuscitate Orders, Hospice Care Utilization, and Late Referral to Hospice Care among Cancer Decedents in a Tertiary Hospital in Taiwan between 2008 and 2014: A Hospital-Based Observational Study.
Out of respect for terminal patients' dignity and to decrease end-of-life suffering, patients in Taiwan can choose to sign do-not-resuscitate (DNR) orders and use hospice care when they are in a terminal condition. To explore the trends and characteristics of hospice care utilization and DNR status among terminal cancer patients. Design and Setting/Subjects: A secondary data analysis was conducted to examine the rate of DNR orders, hospice care utilization, the survival time after DNR order, the duration of survival (DOS) after hospice care enrollment, and the rate of late referral to hospice care among patients who died from malignant cancers in a tertiary hospital in Taiwan between 2008 and 2014. Of the 7857 patients, 7392 (94.1%) had signed a DNR order and 3965 (50.5%) had received hospice care. The rates of DNR orders and hospice care utilization were significantly different across sexes, cancer types, and admission departments (p < 0.001). From 2008 through 2014, the overall hospice utilization rate grew from 39.9% to 57.9% (p < 0.001), with increasing trends among most departments. The survival time after DNR order significantly increased (p < 0.001), and the DOS showed no significant trend (p = 0.404) but late referral rate increased from 29.4% to 35.7% (p = 0.005). The hospice care utilization among terminal cancer patients increased in most specialty departments from 2008 through 2014. The DOS did not increase, but the rate of late referrals increased. Further research should be conducted to investigate the factors behind late referrals and non-growing DOS.


Peptide Solubility Limits: Backbone and Side-Chain Interactions.
We calculate the solubility limit of pentapeptides in water by simulating the phase separation in an oversaturated aqueous solution. The solubility limit order followed by our model peptides (GGRGG > GGDGG > GGGGG > GGVGG > GGQGG > GGNGG > GGFGG) is found to be the same as that reported for amino acid monomers from experiment (R > D > G > V > Q > N > F). Investigation of dynamical properties of peptides shows that the higher the solubility of a peptide is, the lower the time spent by the peptide in the aggregated cluster is. We also demonstrate that fluctuations in conformation and hydration number of peptide in monomeric form are correlated with the solubility of the peptide. We considered energetic mechanisms and dynamical properties of interbackbone CO-CO and CO···HN interactions. Our results confirm that CO-CO interactions more than the interbackbone H-bonds are important in peptide self-assembly and association. Further, we find that the stability of H-bonded peptide pairs arises mainly from coexisting CO-CO and CO···HN interactions.


Clinico-pathologic patterns of extremity liposarcoma.
Liposarcoma is a tumour derived from primitive cells that undergo adipose differentiation. To describe the clinico-pathological pattern of extremity liposarcoma in Lagos, Nigeria. This is a descriptive study of patients with histologically established liposarcoma affecting the extremities seen at the Oncology unit of the National Orthopaedic Hospital, Lagos Nigeria. Demographic and clinical data ( including age, gender, presenting complaints anatomic location of lesions ), histologic type, clinical stage and treatment outcome were collected using a prepared proforma and analysed. Liposarcoma accounted for 6 [27.3%] of 22 cases of soft tissue sarcomas seen within the study period. All 6 were males with a M:F of 6:0. The age range was 36- 59 years. Lesions were mostly located in the thigh 5/6 (83.3%). The most common histologic type was myxoid seen in 3/6 [50%]. All presented at stage T2bNoMo. Five (83.3%) had limb salvage surgery with adjuvant radiotherapy while one had ablative surgery. Survival and recurrent rates could not be determined as all patients were lost to follow-up soon after surgery. Liposarcoma is the commonest extremity soft tissue sarcoma seen in our centre, the myxoid type being the commonest histologic subtype.


Multisoliton propagation in a linear granular chain.
When m grains hit a linear Hertzian chain of identical grains, m solitons are generated. We studied the multisoliton propagation using a particle dynamic simulation. The speed of solitons depends not only on the number of colliding grains but also on the sequence of generation. We found the hierarchy and evolution of the solitons as well as the generation of secondary solitons. We also found the oscillation and beats in the kinetic energy of the chain, which come from the discreteness of the medium in comparison with the spatial spreading of the soliton.


The Calibration and Use of Capacitance Sensors to Monitor Stem Water Content in Trees.
Water transport and storage through the soil-plant-atmosphere continuum is critical to the terrestrial water cycle, and has become a major research focus area. Biomass capacitance plays an integral role in the avoidance of hydraulic impairment to transpiration. However, high temporal resolution measurements of dynamic changes in the hydraulic capacitance of large trees are rare. Here, we present procedures for the calibration and use of capacitance sensors, typically used to monitor soil water content, to measure the volumetric water content in trees in the field. Frequency domain reflectometry-style observations are sensitive to the density of the media being studied. Therefore, it is necessary to perform species-specific calibrations to convert from the sensor-reported values of dielectric permittivity to volumetric water content. Calibration is performed on a harvested branch or stem cut into segments that are dried or re-hydrated to produce a full range of water contents used to generate a best-fit regression with sensor observations. Sensors are inserted into calibration segments or installed in trees after pre-drilling holes to a tolerance fit using a fabricated template to ensure proper drill alignment. Special care is taken to ensure that sensor tines make good contact with the surrounding media, while allowing them to be inserted without excessive force. Volumetric water content dynamics observed via the presented methodology align with sap flow measurements recorded using thermal dissipation techniques and environmental forcing data. Biomass water content data can be used to observe the onset of water stress, drought response and recovery, and has the potential to be applied to the calibration and evaluation of new plant-level hydrodynamics models, as well as to the partitioning of remotely sensed moisture products into above- and belowground components.


Cardiac biomarkers - the old and the new: a review.
Biomarkers are biological parameters that can be objectively measured and quantified as indicators of normal biologic processes, pathogenic processes, or responses to a therapeutic intervention. Typically thought of as disease process screening, diagnosing, or monitoring tools, biomarkers may also be used to determine disease susceptibility and eligibility for specific therapies. Cardiac biomarkers are protein components of cell structures that are released into circulation when myocardial injury occurs. They play a pivotal role in the diagnosis, risk stratification, and treatment of patients with chest pain and suspected acute coronary syndrome and those with acute exacerbations of heart failure. Cardiac markers are central to the new definition of acute myocardial infarction put forward by the American College of Cardiology and the European Society of Cardiology. Active investigation has brought forward an increasingly large number of novel candidate markers but few have withstood the test of time and become integrated into contemporary clinical care because of their readily apparent diagnostic, prognostic, or therapeutic utility.


The anionic basis of fluid secretion by the rabbit mandibular salivary gland.
The role played by anions in salivary secretion has been studied in experiments on the isolated, perfused mandibular gland of the rabbit, in which perfusate Cl- and/or HCO3- were replaced by other anions. Replacement of Cl- with Br- had no significant effect on salivary secretion rate, but replacement with the other anions tested caused secretory rate to fall, by 38% (I-), 50% (NO3-), 61% (isethionate, ise -), and 66% ( CH3SO4 -), respectively. Replacement of perfusate Cl- with ise - or CH3SO4 - caused the salivary HCO3- concentration to rise up to 4-fold. Replacement with Br- or I- seemed to have little effect on salivary HCO3- concentration but, in contrast to ise -, Br- and I- entered the saliva in concentrations comparable to those of Cl- during control perfusion. In glands perfused with HCO3- and ise -, the addition of methazolamide, an inhibitor of carbonic anhydrase, caused a further 60% drop in secretory rate, but the saliva remained rich in HCO3-. Replacement of perfusate HCO3- with Cl- or ise - had no effect on salivary secretion or composition. Replacement of both HCO3- and Cl- in the perfusate with ise - reduced salivary secretion to less than 2% of control levels. In control glands (i.e. perfused with both HCO3- and Cl-), administration of furosemide, an inhibitor of Na+/Cl- co-transport, reduced the secretion rate and increased salivary HCO3- in a manner indistinguishable from that seen when perfusate Cl- was replaced with ise -. In control perfused glands, administration of SITS (4-acetamido-4'- isothio cyano-2,2'-disulphonic acid stilbene), an inhibitor of Cl-/HCO3- antiports , did not cause any change in salivary HCO3- concentration. Unexpectedly, it induced a significant increase in salivary secretory rate. The results show that salivary secretion depends on two independent transport systems. One is a Cl- -dependent, furosemide-sensitive system, probably a Na+/Cl- symport. The other is an HCO3- -dependent, methazolamide-sensitive system, and is probably an Na+/H+ antiport.


Experience-dependent shaping of hippocampal CA1 intracellular activity in novel and familiar environments.
The hippocampus is critical for producing stable representations of familiar spaces. How these representations arise is poorly understood, largely because changes to hippocampal inputs have not been measured during spatial learning. Here, using intracellular recording, we monitored inputs and plasticity-inducing complex spikes (CSs) in CA1 neurons while mice explored novel and familiar virtual environments. Inputs driving place field spiking increased in amplitude - often suddenly - during novel environment exploration. However, these increases were not sustained in familiar environments. Rather, the spatial tuning of inputs became increasingly similar across repeated traversals of the environment with experience - both within fields and throughout the whole environment. In novel environments, CSs were not necessary for place field formation. Our findings support a model in which initial inhomogeneities in inputs are amplified to produce robust place field activity, then plasticity refines this representation into one with less strongly modulated, but more stable, inputs for long-term storage.


Potential-modulation spectroscopy at solid/liquid and liquid/liquid interfaces.
Potential-modulation spectroelectrochemical methods at solid/liquid and liquid/liquid interfaces are reviewed. After a brief summary of the basic features and advantages of the methods, practical applications of potential-modulation spectroscopy are demonstrated using our recent studies of solid/liquid and liquid/liquid interfaces, including reflection measurements for a redox protein on a modified gold electrode and fluorescence measurements for various dyes at a polarized water/1,2-dichloroethane interface. For both interfaces, the use of linearly polarized incident light enabled an estimation of the molecular orientation. The use of a potential-modulated transmission-absorption measurement for an optically transparent electrode with immobilized metal nanoparticles is also described. The ability of potential-modulated fluorescence spectroscopy to clearly elucidate the charge transfer and adsorption mechanisms at liquid/liquid interfaces is highlighted.


Rare complication of needleless mini-sling procedure: Case report.
The mini-sling procedure is a widely used, minimally invasive treatment for stress urinary incontinence. While bladder perforation and stone formation over the mesh is not an expected complication of the mini-sling procedure, in this case, we report on the management of bladder calculi formed over the mesh, which was passed through the bladder while applying the mini-sling procedure, and was eventually removed using holmium laser. Performing cystoscopy in patients with irritative and obstructive symptoms after the sling procedure will help confirm bladder perforation, and an endoscopic approach using holmium laser is an effective treatment.


Applications of CRISPR-Cas in its natural habitat.
Key components of CRISPR-Cas systems have been adapted into a powerful genome-editing tool that has caught the headlines and the attention of the public. Canonically, a customized RNA serves to guide an endonuclease (e.g. Cas9) to its DNA target, resulting in precise genomic lesions that can be repaired in a personalized fashion by cellular machinery. Here, we turn to the microbes that are the source of this system to explore many of its other notable applications. These include mining the CRISPR 'memory' arrays for functional genomic data, generation of customized virus-resistant or plasmid-refractory bacterial cells, editing of previously intractable viral genomes, and exploiting the unique properties of a catalytically inactive Cas9, dCas9, to serve as a highly customizable anti-nucleic acid 'antibody'.


Holding equine oocytes in a commercial embryo-holding medium: New perspective on holding temperature and maturation time.
In the present study, we examined the effect of holding equine oocytes in Syngro embryo holding medium (EHM) overnight at either 4 °C, 17 °C, or 22 °C to 25 °C, on the time to maturation and developmental competence. We also examined the effect of placing denuded oocyte without extruded polar body back in maturation condition on subsequent maturation rate. In experiment 1, cumulus-oocyte complexes (COCs) were recovered postmortem and placed in EHM at 22 °C to 25 °C for 18 to 20 hours (OH) or placed directly in maturation (DM). The maturation rate was assessed after 22, 24, or 28 hours of culture. After denuding cumulus cells at 22 or 24 hours, oocytes without obvious polar body were placed back into culture and reassessed at subsequent time points. At 22 hours, a higher proportion of oocytes placed in OH achieved nuclear maturation than those placed in DM (63% and 37%, respectively, P = 0.008). At 24 and 28 hours, no significant differences in the % MII stage oocytes were observed between OH and DM. The nuclear maturation rate for OH oocytes was similar at 22, 24, and 28 hours, indicating that the maximum maturation rate was reached at an earlier time than that in DM. Oocytes fertilized by intracytoplasmic sperm injection resulted in a 7.1% and 6.3% blastocyst rate for OH and DM, respectively. Denuding oocytes after 22 hours or more of culture did not have an adverse effect on the final nuclear maturation rate. After 28 hours of culture, the same nuclear maturation rate (MII) was reached for nondenuded oocytes and oocytes denuded after 22 hours of 24 hours of culture. In experiment 2, COCs were held overnight at room temperature in EHM, then placed in maturation for 20, 22, and 28 hours. Nuclear maturation rate was significantly lower at 20 hours than 22 and 28 hours of culture and was similar at 22 and 28 hours, suggesting that at least 22 hours of culture is required to reach maximal maturation rate for stored oocytes (43%, 62%, and 65% at 20, 22, and 28 hours, respectively. P < 0.001). In experiment 3, COCs were either placed directly in culture or held at 22 °C to 25 °C, 17 °C, or 4 °C overnight. After 24 hours of culture, maturation rate was similar for all groups, suggesting that COCs can be stored in conventional 4 °C transport condition or 17 °C. In preliminary studies, COCs were held at 4 °C followed by 24 hours of culture, and mature oocytes were fertilized using intracytoplasmic sperm injection. Twenty-three injected oocytes yielded four blastocysts. In conclusion, we reported that oocytes can be placed in a commercial EHM and stored overnight without a detrimental effect on maturation rates or blastocyst development. Oocytes held in holding medium require less time to reach the MII stage than oocytes placed in culture directly. Removing the cumulus cells from oocytes that have been cultured for at least 22 hours does not seem to alter the final nuclear maturation rate. Finally, we observed no detrimental effect of storing oocytes at 4 °C for up to 18 hours, and oocytes appeared to maintain developmental competence and blastocyst potential.


HNRNPA1-mediated 3' UTR length changes of HN1 contributes to cancer- and senescence-associated phenotypes.
Cellular senescence has been regarded as a mechanism of tumor suppression. Studying the regulation of gene expression at various levels in cell senescence will shed light on cancer therapy. Alternative polyadenylation (APA) regulates gene expression by altering 3' untranslated regions (3' UTR) and plays important roles in diverse biological processes. However, whether APA of a specific gene functions in both cancer and senescence remains unclear. Here, we discovered that 3' UTR of HN1 (or JPT1) showed shortening in cancers and lengthening in senescence, correlated well with its high expression in cancer cells and low expression in senescent cells, respectively. HN1 transcripts with longer 3' UTR were less stable and produced less protein. Down-regulation of HN1 induced senescence-associated phenotypes in both normal and cancer cells. Patients with higher HN1 expression had lower survival rates in various carcinomas. Interestingly, down-regulating the splicing factor HNRNPA1 induced 3' UTR lengthening of HN1 and senescence-associated phenotypes, which could be partially reversed by overexpressing HN1. Together, we revealed for the first time that HNRNPA1-mediated APA of HN1 contributed to cancer- and senescence-related phenotypes. Given senescence is a cancer prevention mechanism, our discovery indicates the HNRNPA1-HN1 axis as a potential target for cancer treatment.


The choice of chromogen and reliability of contact rhinoscopy in the irradiated nasopharynx.
A cross-sectional randomised single blind study was conducted to assess how concentrations of chromogen (vital stain) and the characteristics of the assessors affect the assessment of contact rhinoscopy. Twenty-eight patients who had undergone external radiotherapy for nasopharyngeal carcinoma were assessed by contact rhinoscopy using 0.5 per cent and 1 per cent methylene blue stain on opposite sides of the nasopharynx. Three independent observers assessed the visual clarity of the 45 contact endoscopic images showing squamous metaplasia according to a visual analogue scale. The intraclass correlation coefficients were 0.916 to 0.957 and 0.839 to 0.964 for intra-observer reliability of assessors in the groups of 0.5 per cent and 1 per cent stains, respectively. The intraclass correlation coefficients for inter-observer reliability of assessors were 0.884 and 0.885 in the groups of 0.5 per cent and 1 per cent stains, respectively. The mean scores of clarity of the cellular details were statistically higher in the group of 1 per cent stain among all assessors. These results showed that the assessment of squamous metaplasia by contact endoscopy is highly reliable irrespective of the clinical experience and knowledge of histopathology of the assessors. One per cent methylene blue should be the vital stain of choice in contact endoscopy.


Faithful cleavage of the P1 packaging site (pac) requires two phage proteins, PacA and PacB, and two Escherichia coli proteins, IHF and HU.
The PacA and PacB subunits of the bacteriophage P1 DNA packaging enzyme (pacase) are necessary for cleavage of the phage packaging site (pac). In the accompanying paper, we show that the PacA subunit of the enzyme specifically binds to pac in the absence of PacB, but requires factors present in an Escherichia coli extract to do so. We show here that either of two E. coli DNA binding proteins, integration host factor (IHF) or HU, can replace this extract and promote the binding of PacA to pac. IHF binds to pac independently of PacA and DNase I footprinting experiments show that IHF protects approximately 40 bp of DNA around an IHF consensus sequence adjacent to the cleavage site. DNase I footprinting experiments also show that in the presence of either IHF or HU, PacA binds to the hexanucleotide sequences (5'-TGATCA/G) that flank the cleavage site and that have been previously shown to be essential for pac cleavage. The importance of IHF and HU in pac cleavage is further demonstrated by the severe reduction in both the fidelity and efficiency of pac cleavage in vitro with extracts lacking both IHF and HU. Addition of either IHF or HU to the deficient extracts renders them fully proficient for pac cleavage. Finally, we show that IHF bends DNA at the IHF site within pac. Based on these results, we propose a model that can account for the role of the various phage and host proteins, and for DNA bending in the pac cleavage reaction.


The joint capsule: structure, composition, ageing and disease.
The joint capsule is vital to the function of synovial joints. It seals the joint space, provides passive stability by limiting movements, provides active stability via its proprioceptive nerve endings and may form articular surfaces for the joint. It is a dense fibrous connective tissue that is attached to the bones via specialised attachment zones and forms a sleeve around the joint. It varies in thickness according to the stresses to which it is subject, is locally thickened to form capsular ligaments, and may also incorporate tendons. The capsule is often injured, leading to laxity, constriction and/or adhesion to surrounding structures. It is also important in rheumatic disease, including rheumatoid arthritis and osteoarthritis, crystal deposition disorders, bony spur formation and ankylosing spondylitis. This article concentrates on the specialised structures of the capsule--where capsular tissues attach to bone or form part of the articulation of the joint. It focuses on 2 joints: the rat knee and the proximal interphalangeal (PIP) joint of the human finger. The attachments to bone contain fibrocartilage, derived from the cartilage of the embryonic bone rudiment and rich in type II collagen and glycosaminoglycans. The attachment changes with age, when type II collagen spreads into the capsular ligament or tendon, or pathology--type II collagen is lost from PIP capsular attachments in rheumatoid arthritis. Parts of the capsule that are compressed during movement adapt by becoming fibrocartilaginous. Such regions accumulate cartilage-like glycosaminoglycans and may contain type II collagen, especially in aged material.(ABSTRACT TRUNCATED AT 250 WORDS)


Importance of an Interprofessional Team Approach in Achieving Improved Management of the Dizzy Patient.
Because of its multifaceted nature, dizziness is difficult for clinicians to diagnose and manage independently. Current treatment trends suggest that patients are often referred to the otolaryngologist for intervention despite having a nonotologic disorder. Additionally, many individuals with atypical presentations are often misdiagnosed and spend a significant amount of time waiting for consultation by the otolaryngologist. Few studies have alluded that implementation of an interprofessional team approach in the diagnosis and management of the dizzy patient can improve clinical decision-making. However, to the authors' knowledge, there is no information specifically quantifying the outcomes and potential benefits of using an interprofessional balance care team approach. To compare dizziness diagnoses trends and referral practices with and without the use of an interprofessional management approach within a university healthcare system. Over the course of a 3-yr period, a retrospective review of the diagnosis and management of dizziness was performed with and without implementation of an interprofessional team. To observe potential differences, year 3 incorporated the interprofessional management approach while years 1-2 did not. The two periods were then compared to each other. A total of 134 patients referred to a university hearing clinic for a vestibular and balance function evaluation. Diagnoses and management trends were examined with descriptive statistics (percentages and frequencies). Fisher's exact tests, analysis of contingency tables, were conducted to evaluate the influence of interprofessional management on dizziness diagnoses and treatment patterns. Results demonstrated that before implementation of an interprofessional team approach, (1) referring clinicians used unspecific dizziness diagnosis codes (e.g., dizziness and giddiness), (2) a low number of patients with dizziness were referred for balance function testing, (3) diagnoses remained unspecific following the balance function assessment, and (4) the most frequently occurring vestibular diagnoses were unilateral vestibular hypofunction and benign paroxysmal positional vertigo. Following the use of an interprofessional management approach, it was determined that (1) disease-specific diagnoses increased, (2) patients with dizziness were referred for balance function testing mainly by otolaryngologists, (3) dizziness was considered to be multifaceted for a greater number of patients, (4) a larger percentage of patients were referred to a specialist other than the otolaryngologist as a result of their diagnosis, and (5) patients reported reduction or resolution of their symptoms. An interprofessional management approach for the dizzy patient can lead to more specific diagnoses and provide alternative referral pathways to other health-care professionals (e.g., audiologists, physical therapists, and pharmacists) in an effort to reduce over-referral to one specialist. Future studies should address the utility of an interprofessional team approach in the overall management of patients with dizziness.


Predicting photoactivity in dithienylethene crystalline solids.
This commentary discusses the design of stimuli-responsive materials, specifically, light-responsive dithienylethene-based compounds. Recent progress in predicting photoactivity using a combination of theory and crystal structure landscape experiments is highlighted.


[Factor structure of coping behavior of curious elderly people.]
An increase in the share of elderly people in the total population of Russia determines the theoretical and practical significance of studies aimed at improving social adaptation and the productivity of a person's life in retirement age. The relevance of the study is due to the contradiction between the theoretical and practical significance of the problem of coping behavior of older people and its insufficient development in gerontopsychology. The purpose of the study was to establish the theoretical basis for conducting the factor analysis of coping behaviour in the elderly studying at the University and to analyse the findings. Some theoretical and empirical methods with psychodiagnostic techniques were used, such as Heim`s coping technique, Lazarus and Folkman's model of coping (adapted by T.Kryukova, E.Kuftyak), Maddi`s hardiness survey (adapted by D.Leontyev), and Vodopyanova and Stein`s scale of optimism and activity. We applied the following methods of the mathematical and statistical analysis: descriptive statistics, Pearson criterion χ2 (Chi-square test), exploratory factor analysis (EFA), principal component analysis with a Varimax rotation with Kaiser normalization using the statistical package program StatSoft Statistica for Windows 10.0 and IBM SPSS Statistics 23. The empirical research was conducted in the University for Elderly, the regional branch of the National Non-Governmental Organization «Znanie» in Chelyabinsk. The sample comprised 101 people with the median age of 68,2 years. The factor analysis detected and verified a latent structure of coping behaviour in the elderly consisting of 7 key components classified by the degree of preference. Adaptive and relatively adaptive behavioural and cognitive coping styles (based on 3 out of 7 factors) that are both problem and self-preservation oriented prevail in the factor structure of coping behaviour in the subjects.


Spatiotemporal Patterns of Impervious Surface Area and Water Quality Response in the Fuxian Lake Watershed.
The increase of urbanization level has led to the rapid increase of impervious surface area (ISA). The aim of this work is to clarify the relationship between the ISA and water quality and lay a foundation for the improvement and protection of the water quality in the basin. Taking the Fuxian Lake Basin in Yunnan Province as an example, based on the Landsat ETM+ remote sensing image and the Gram-Schmidt (GS) image fusion algorithm, the four-terminal model and the linear spectral mixture model (LSMM) were used to extract the impervious surface of the watershed from 2006 to 2015. And statistical methods were used to distinguish its relationship with water quality. The results show that the four-terminal model and the linear spectral mixture model can effectively extract the impervious surface information of the Fuxian Lake Basin. The average root mean square error (RMS) of the image decomposition results from 2006 to 2015 was less than 0.02. In the past 10 years, the ISA has changed significantly in the Fuxian Lake Basin. The ISA showed an overall upward trend from 2006 to 2015. It increased from 24.73 km2 in 2006 to 35.14 km2 in 2015, an increase of 10.81 km2. From the value anomaly, the ISA in 2006 and 2009 is lower than the multiyear average, and those in the other years are higher than the multiyear average. The percentage of ISA in the basin was significantly positively correlated with Chemical Oxygen Demand-Mn (CODMn) and total phosphorus (TP) (r is 0.772, 0.763), and the correlation in the flooding season was greater than that in the dry season. The ISA threshold for water quality deterioration is around 10% in the Fuxian Lake Basin. Reducing ISA coverage, controlling ISA to less than 10%, and preventing nonpoint source pollution during flooding season will be the best measures to effectively improve the water quality environment in the basin.


[Clinical course and pathophysiology of hyperthermia].
In 221 hyperthermic baths with 138 healthy volunteers thermoregulatory, circulatory, respiratory, renal, hematological, immunological, and endocrinological function values and sudomotoric activity have been determined. The endocrinological investigations demonstrate an increased glucocorticoidal activity (eosinopenia, T-lymphocytopenia) while plasmatic cortisole concentrations are slightly decreased. This discrepancy may be explained by an increased dissociation of biologically active cortisole and transcortin and by a more rapid activation of the steroid-receptor complex within the endocrine target cell. During a series of ten hyperthermic baths on ten consecutive days mineralocorticoidal activity during hyperthermia is increased (sudomotor activity, excretion of urine and sodium); urinary excretion of aldosterone does not change. These results indicate an increased sensitivity of the mineralocorticoidal target cell after adaptation to heat. The hypothesis can be confirmed by experiments with aldosterone i.v.


Xanthoma Disseminatum Presenting with Hoarseness.
Xanthoma disseminatum (XD) is a rare, benign, non-Langerhans cell histiocytic disorder with unknown etio-pathology. It manifests with multiple, grouped, red-brown to yellow papules and nodules involving the skin, mucous membranes, and internal organs with a predilection for flexures and the face. We report a patient who presented with disseminated xanthomatous papules and nodules involving the face, neck, trunk, axilla, groin, and oral cavity, along with hoarseness of voice. Video laryngoscopy revealed multiple yellowish nodules over the base of the tongue, vallecula, laryngeal surface of the epiglottis, ary-epiglottic folds, interarytenoid region, and subglottic region. Histopathology was suggestive of xanthoma disseminatum and the patient was treated with tablet acitretin 25mg daily for three months without any response. Following this, the patient was prescribed tablet thalidomide 100 mg daily without any significant improvement at the end of two months. Xanthoma disseminatum is a very rare form of non-Langerhans cell histiocytosis that classically presents with cutaneous xanthomas, mucosal xanthomas, and diabetes insipidus. Hoarseness of voice due to lesions involving the larynx is a rare symptom. Because the disease has punctated, numerous relapses and causes morbidity to the patient, its multisystem manifestations have to be known. Therefore, xanthoma disseminatum has to be kept in mind as a differential diagnosis for hoarseness of voice.


TrkB deficiency increases survival and regeneration of spinal motoneurons after axotomy in mice.
Persisting motor function deficit after peripheral nerve injury often results from axotomized motoneuron death. Brain-derived neurotrophic factor (BDNF) and its receptor, trkB, are known to promote peripheral nerve regeneration. However, the requirement of BDNF and trkB for adult motoneuron survival after peripheral nerve injury is not established. We studied the number of surviving and regenerating motoneurons after sciatic nerve transection in wild-type and heterozygous trkB-deficient mice. The nerve was either left cut or immediately sewed up or the gap injury model was performed. The gap was provided with an autologous or cross (obtained from other genetic group) graft. Sixteen weeks after surgery, the animals were sacrificed and histological evaluations were performed. In order to study the number of regenerating motoneurons, immunofluorescent tracer was applied to the distal stump of the operated nerve. We found that in wild type mice, the decrease in motoneurons after nerve transection was markedly higher than in trkB-deficient animals, regardless of the operation procedure. Nerve transection resulted in the highest decrease in motoneuron number in wild type mice. This decrease was lower if the nerve was re-joined using a cross-graft obtained from a trkB-deficient animal. Interestingly, in trkB-deficient animals, the decrease in motoneuron count did not depend on type of operation and was similar after nerve transection, re-joining or grafting. The number of regenerating motoneurons after nerve transection and re-joining in wild type animals was lower than in trkB-deficient mice. The number of regenerating motoneurons after nerve grafting did not differ between groups. These results provide further evidence for the role of trkB receptor in spinal motoneuron survival and regeneration.


Targeted nonviral gene therapy in prostate cancer.
Prostate cancer is the second-most widespread cancer in men worldwide. Treatment choices are limited to prostatectomy, hormonal therapy, and radiotherapy, which commonly have deleterious side effects and vary in their efficacy, depending on the stage of the disease. Among novel experimental strategies, gene therapy holds great promise for the treatment of prostate cancer. However, its use is currently limited by the lack of delivery systems able to selectively deliver the therapeutic genes to the tumors after intravenous administration without major drawbacks. To remediate this problem, a wide range of nonviral delivery approaches have been developed to specifically deliver DNA-based therapeutic agents to their site of action. This review provides an overview of the various nonviral delivery strategies and gene therapy concepts used to deliver therapeutic DNA to prostate cancer cells, and focuses on recent therapeutic advances made so far.


[Molecular basis for cardiac functions].
Cardiac functions are regulated by both contractile proteins and calcium regulatory proteins. Alterations of these are considered involved in impaired contractile and diastolic functions in hypertrophied hearts. In this study, we analyzed molecular changes during the development of cardiac hypertrophy. Cardiac hypertrophy was induced by constricting the pulmonary artery in rabbits or the aorta in rats. In rabbit right ventricular hypertrophy, protein synthesis was increased to 1.8 times the control 2-4 days after pulmonary constriction. This increase in protein synthesis could be classified as an increase in both capacity and efficiency of synthesis. beta-cardiac myosin heavy chain (beta-MHC) isoform was predominantly expressed and alpha-MHC was suppressed in pressure overload hypertrophy. The switch from alpha- to beta-MHC occurred at the mRNA level. Ca(2+)-ATPase of sarcoplasmic reticulum (SR) is important because it regulates intracellular Ca2+ levels during relaxation. In pressure-overload hypertrophy, the SR Ca(2+)-ATPase was markedly decreased in both the enzyme activities and mRNA levels, while in thyrotoxic hearts both were increased. Interstitial cells also undergo phenotypic modulation which was demonstrated by the induction of nonmuscle-type MHC in pressure-overload hypertrophy. The signal transduction system in cardiac hypertrophy was examined by stretching cardiac myocytes grown on deformable membranes. In our analysis, stretching myocytes stimulated protein kinase C, MAP-II kinase and S6 kinase, all of which may lead to the induction of fetal-type cardiac genes and accelerated protein synthesis. These analyses of subcellular adaptation in cardiac hypertrophy provide important insights into understanding molecular mechanisms of cardiac functions.


The PI3K/Akt/mTOR pathway is involved in CVB3-induced autophagy of HeLa cells.
Recent studies have found that viral myocarditis (VMC) associated with coxsackievirus B3 (CVB3) causes autophagy activation after infection, but the specific mechanism is not clear. The present study demonstrated that the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway participates in CVB3‑induced autophagy. We found that the light chain 3 (LC3)‑Ⅱ/LC3‑I ratio was increased and p62 and p‑mTOR were altered at different times during CVB3 infection. To further assess the effects of this signaling pathway on CVB3 infection and viral replication, we selected 24 h post‑inoculation (h.p.i.) as our research time point to conduct our next study. We inhibited the function of PI3K, Akt1 and mTOR. The outcome showed that inhibition of PI3K with ZSTK474 alleviated autophagy and decreased CVB3 mRNA replication and VP1 expression. Inhibition of mTOR with rapamycin promoted autophagy and viral mRNA replication but did not impact VP1 expression. Inhibition of Akt with MK2206 aggravated autophagy induced by viral infection. In our research, p62 exhibited a decrease at the beginning of infection but then increased as infection time increased. This finding may serve as a clue to elucidate the function of autophagy at different times of infection. However, the details merit further study. In conclusion, our findings suggest that the PI3K/Akt/mTOR signaling pathway participates in the process of autophagy induced by CVB3 infection. This finding may provide a new perspective of CVB3-induced autophagy.


In vitro and pathological investigations of MODY5 with the R276X-HNF1beta (TCF2) mutation.
Maturity-onset diabetes of the young type 5 (MODY5) is caused by mutation of hepatocyte nuclear factor 1beta (HNF1 beta) (TCF2) gene, resulting in a wide range of phenotypes including diabetes and renal abnormalities, but little is known about the pathogenesis of the clinical spectrum. We describe a 27-year-old Japanese male with the MODY phenotype including an atrophic kidney and multiple renal cysts. Genetic analysis revealed the patient to be heterozygous for a nonsense mutation in codon 276 of the HNF1beta gene (CGA or Arginine to TGA or stop codon; R276X). To clarify the pathophysiological relevance of this mutation, we conducted an in vitro study monitoring human C-peptide secretion after transfecting both the HNF1beta mutant cDNA and preproinsulin cDNA into a murine beta cell line, MIN6. Functional studies of the transformed MIN6 cells indicated that expression of the R276X caused a significant decrease in glucose-stimulated insulin secretion but no change in either KCl-stimulated or basal insulin secretion. These results suggest that the R276X functions in a negative manner in regard to metabolic responses of insulin secretion in beta cells. Analysis with light and electron microscopy on biopsied kidney specimens suggested that the origin of the cysts might be glomeruli but the primary lesion could be tubules.


Novel Therapeutic Approaches and Targets for the Treatment of Hidradenitis Suppurativa.
Hidradenitis Suppurativa (HS) is a chronic, recurrent and disabling inflammatory skin condition, clinically characterized by nodules, bullae, abscesses, fistulae, and draining sinus tracts mainly located in axillae, inguinal folds, inframammary region and buttocks, often leading to pain, scarring, disfigurement and decreased quality of life. Due to its complex nature, with still no completely elucidated etiology and pathogenesis, the management of HS can be challenging. In fact, many patients do not respond to the traditionally available systemic treatments, including antiinflammatories, antibiotics and surgery. Research has provided new insights into the mechanisms of HS, mainly investigating the inflammatory cytokine pathways underlying the disease. We review the current knowledge on newer therapeutic approaches and targets for the treatment of HS, through a PubMed-based literature search. In this setting, studies on tumor necrosis factor-α, IL-1β, IL-10, and the IL-23/T-helper (Th) 17 and IL12/Th1 axes in immune dysregulation in HS have helped in developing new regimens. Inhibitor of phosphodiesterase 4 and laser treatments have shown clinically meaningful efficacy with good short-term safety and tolerability. Target therapy has revolutionized the treatment of moderate to severe HS, based on the inhibition of specific molecular or cellular targets, directly involved in the pathogenesis of the condition.


[The method and influencing factors of alkalescency protein purification from bitter melon (Momordica charantia) seeds by polyacrylicacid precipitation].
In this study, polyacrylicacid precipitation alkalescence protein from Momordica charantia L. seeds was studied, and the effect of conditions on experiment was also evaluated. Isoelectric precipitation is achieved by adjusting the pH of a protein solution and is based on that a protein's solubility is at minimum at its pI. The sample was titrated to pH 6.0 with citric acid, and 14.62% proteins were precipitated. With hydrochloric acid to pH 4.0, 32.49% proteins were precipitated. With the acetic acid to pH 6.0 and pH 4.0, 26.17% and 38.72% proteins were precipitated, respectively. In the 1 mL Bitter melon seeds extraction(pH 4.0) adjusted by acetic acid, hydrochloric acid and citric acid, the optimum dosage of PAA (1%) precipiting alkalescency protein (pl 8.65-9.30) was 100 microL, 120 microL and 100 microL, respectively. The respective extraction (1mL) was titrated to pH 5.0, pH 4.0, and pH 3.0 by acetic acid. After isoelectric precipitation, the PAA precipitation protein was performed. When concentration of PAA (1%) was 160 microL/mL, the protein decreased in the supernatant was 33.77% at pH 5.0, and 43.56% at pH 3.0. When concentration of PAA (1%) was 120 microL/mL, the protein decreased in the supernatant was 30.83% at pH 4.0. PAA-Protein complex could redissolve in alkaline conditions (pH > 9.0) and the protein most easilly redissolved when the NaCL was 3.0%. The bitter melon seeds extraction after PAA purification flowed through the Sephadex G-75 columns. The peaks I and II were obtained after 175 min and 300 min, respectively. SDS-PAGE and IEF analysis showed that the molecule weight from peaks I was 30 kD with pI 9.5, peaks II 10 kD with pI 9.3.


Relationship between exhaled nitric oxide and airway hyperresponsiveness following experimental rhinovirus infection in asthmatic subjects.
Exhaled nitric oxide (NO) is elevated in asthmatics, and varies with disease severity. We postulated that a respiratory virus infection increases exhaled NO levels in asthma, and examined the relationship between the virus-induced changes in exhaled NO and in airway hyperresponsiveness to histamine. In a parallel study, seven patients underwent experimental rhinovirus 16 (RV16) inoculation at days 0 and 1, whilst seven patients received placebo. Exhaled NO was measured at baseline (day 0) and at days 1, 2 and 3 after inoculation. Histamine challenges were performed prior to (day -7) and after inoculation (day 3), and were expressed as provocative concentration causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20). Following RV16 infection there was a significant increase in NO at days 2 and 3 as compared to baseline (median change (range): 4.2 (7.5) parts per billion (ppb), p=0.03, and 3.0 (10.1) ppb, p=0.02, respectively). Furthermore, PC20 decreased significantly following RV16 infection (mean+/-SD change in doubling dose: -0.65+/-0.54, p=0.02), whereas PC20 did not change in the placebo group (p=0.1). There was a significant correlation between the RV16-induced changes in exhaled NO levels at day 2 and the accompanying changes in PC20 at day 3 (rank correlation coefficient (rs): 0.86, p=0.01). Hence, the greater the increase in exhaled NO, the smaller the decrease in PC20. We conclude that rhinovirus infection increases exhaled nitric oxide levels in asthmatics, and that this increase is inversely associated with worsening of airway hyperresponsiveness to histamine. These results suggest that viral induction of nitric oxide synthase within the airways may play a protective role in exacerbations of asthma.


How many Layers has the Adventitia? - Structure of the Arterial Tunica Externa Revisited.
Tunica adventitia or tunica externa is the outer layer of the blood vessel wall. It consists of connective tissue with vasa and nervi vasorum and plays a key role in vascular health. The aim of our study was to compare the wall layers beyond tunica media in arteries of different type and location. The following arteries of pig, dog and cat were processed histologically and analysed by light microscopy: aorta ascendens, arcus aortae, aorta thoracica, aorta abdominalis, arteria (a.) femoralis, a. tibialis cranialis, a. carotis communis, a. lingualis, a. basilaris, a. cerebralis media, a. testicularis and aa. jejunales. We found two layers of connective tissue outside the media: (1) a compact layer with many elastic fibres in muscular and few in elastic arteries and (2) an outer layer of loose connective tissue. The compact layer was missing in aorta ascendens, arcus aortae and intracranial vessels. Adventitial stripping removed only the loose connective tissue layer. In spite of the still present compact layer, stripped arteries were very flimsy. We suggest using the term 'tunica externa' for the compact connective tissue layer and 'tunica adventitia' for the outermost loose connective tissue layer as in other organs. The presence of the tunica externa differs between species, arteries and arterial side, as well as the removability of tunica adventitia and tunica externa by anatomical dissection.


Scanning electron microscopy of the cochlea in rats with Streptococcus pneumoniae otitis media.
This investigation was performed to determine the morphologic effects of bacterial otitis media on the organ of Corti. The middle ear cavities of rats were inoculated with Streptococcus pneumoniae or saline and the animals were killed on days 1, 4, 7, 10, 14, and 21 after inoculation. Middle ear cultures were obtained and the cochleas were examined using scanning electron microscopy. All animals killed on day 1 had positive cultures, but by day 21, all cultures were negative. Cochlear changes observed were (1) damage to supporting cells (Deiters' cells), (2) morphologic changes of hair cell stereocilia, and (3) loss of inner and outer hair cell stereocilia and cell bodies (to a lesser extent), especially in the lower middle and basal turns. These changes appeared to occur in a definite sequence; ie, damage to the supporting cells, changes in stereocilia, and, finally, hair cell loss. These data show that cochlear damage and hair loss can be associated with bacterial otitis media.


[Outcomes of surgical treatment for locally advanced gastric cancer].
Results of surgical treatment of 223 patients with locally advanced gastric cancer (2000-2005) are presented. Postoperative complications rate was 25.6 +/- 2.5%, mortality--5.8 +/- 0.7%, overall survival--17.9 +/- 2.6%, median survival--12 months. Survival rates were higher following palliative treatment. Groups of patients in which RO resections failed to improve the end results were identified. That in turn calls for working out differentiated surgical strategies.


Establishment of unresponsiveness in primed B lymphocytes in vivo.
As an approach to examine the influence of the state of cellular activation on the ability to tolerize B cells, the induction of unresponsiveness in human gamma-globulin-(HGG) primed B lymphocytes was studied in an adoptive transfer system. In contrast to transferred normal spleen cells, spleen cells from HGG-primed mice are not readily rendered unresponsive when exposed to the tolerogen, deaggregated HGG (DHGG), in irradiated recipients. A kinetic study showed that unfractionated primed spleen cells do not respond to an antigenic challenge given between 6 and 10 days after cell transfer and injection of DHGG, indicating that they are transiently depressed. In contrast, isolated primed B cells are tolerized when transferred to recipients and treated with DHGG in the absence of T cells. Furthermore, primed B cells exposed to tolerogen in the recipients do not recover the ability to respond to HGG either after a secondary challenge with AHGG given up to 14 days after transfer, or after 2 consecutive challenges given on days 14 and 24 after transfer. The presence of primed T cells at the time of tolerization interferes with the induction of unresponsiveness in these primed B cells. These studies suggest that the presence of primed T cells is responsible for the inability to tolerize unfractionated primed spleen cells populations and that primed B cells themselves are not intrinsically resistant to the induction of unresponsiveness.


Rationality/anti-emotionality personality and dietary habits in a community population in Japan.
There are no strong and consistent predictors of dietary habits although some associations have been shown with psychological factors. The purpose of the present study was to examine the relationships between the rationality and anti-emotionality (R/A) personality and dietary consumption in a Japanese community. The Takayama study is a community-based cohort study on diet and cancer in Gifu, Japan, and was initiated on September 1, 1992. Cross-sectional analyses were conducted on dietary and lifestyle data. The consumption of 169 food and beverage items was measured along with portion size by using a food frequency questionnaire. Questions regarding the R/A-personality scale and lifestyle habits were included in the questionnaire. The participants were 28077 adults (13082 males and 14995 females) aged 35 years and over. Both males and females with high R/A-personality scores (i.e., high degree of rational thought and emotional repression) consumed more soy products, green and yellow vegetables, other vegetables, and seaweed than the other participants. Males with high R/A-personality scores drank fewer alcoholic beverages, and females with high scores were found to snack less on sweet and salty foods than the other participants. Males with high R/A-personality scores showed higher consumption of meat and dairy products, and females with high scores showed higher consumption of fish, shellfish, and eggs than those with low R/A-personality scores. The R/A-personality scale may differentiate dietary habits in males and females in a Japanese community.


Integrative functional genomics identifies an enhancer looping to the SOX9 gene disrupted by the 17q24.3 prostate cancer risk locus.
Genome-wide association studies (GWAS) are identifying genetic predisposition to various diseases. The 17q24.3 locus harbors the single nucleotide polymorphism (SNP) rs1859962 that is statistically associated with prostate cancer (PCa). It defines a 130-kb linkage disequilibrium (LD) block that lies in an ∼2-Mb gene desert area. The functional biology driving the risk associated with this LD block is unknown. Here, we integrate genome-wide chromatin landscape data sets, namely, epigenomes and chromatin openness from diverse cell types. This identifies a PCa-specific enhancer within the rs1859962 risk LD block that establishes a 1-Mb chromatin loop with the SOX9 gene. The rs8072254 and rs1859961 SNPs mapping to this enhancer impose allele-specific gene expression. The variant allele of rs8072254 facilitates androgen receptor (AR) binding driving increased enhancer activity. The variant allele of rs1859961 decreases FOXA1 binding while increasing AP-1 binding. The latter is key to imposing allele-specific gene expression. The rs8072254 variant in strong LD with the rs1859962 risk SNP can account for the risk associated with this locus, while rs1859961 is a rare variant less likely to contribute to the risk associated with this LD block. Together, our results demonstrate that multiple genetic variants mapping to a unique enhancer looping to the SOX9 oncogene can account for the risk associated with the PCa 17q24.3 locus. Allele-specific recruitment of the transcription factors androgen receptor (AR) and activating protein-1 (AP-1) account for the increased enhancer activity ascribed to this PCa-risk LD block. This further supports the notion that an integrative genomics approach can identify the functional biology disrupted by genetic risk variants.


Association of vitamin A deficiency with decrease in TNF-α expressing CD3-CD56+ NK cells in Ghanaians.
Although low plasma vitamin A concentrations are associated with increased incidence or severity of infections such as respiratory tract infection and measles in children, there is a paucity of data on the effect of vitamin A deficiency on the distribution of, and cytokine production by, the different cellular immune subsets in humans. We conducted a cross-sectional study in a district in Ghana to characterize cellular subsets and functional capacity of peripheral blood mononuclear cells from vitamin A deficient and vitamin A sufficient (normal) individuals, and evaluated the relationships between vitamin A concentration in plasma and cellular immune status. We measured the percentages of selected cellular phenotypes and intracellular cytokine expression and describe the differential cellular subset distributions and alterations in cytokine expression in participants with normal and deficient vitamin A concentrations. The major change observed in the constitution of cellular subsets was a decrease in TNF-α expressing CD3-CD56+ NK cells in those with vitamin A deficiency compared with normal individuals. CD4+ T cell proliferation and production of IFN-γ and IL-4 were not statistically different between the two groups. These results support previous studies that demonstrated decreased NK cell activity in vitamin A deficient animals. The decrease in TNF-α expressing NK cells observed in vitamin A deficient individuals in this study could help to explain the decreased resistance to infections observed in those with vitamin A deficiency.


The Hippocratic Oath and clinical ethics.
Its obvious shortcomings aside, this study by H. Steven Moffic, John Coverdale, and Timothy Bayer is disquieting. It comes as no surprise that residents have lapses of cognitive recall. Every medical teacher knows this very well. What is worrisome is that their amnesia concerns the oldest, most revered, and most influential moral statement in the history of the profession... Purely apart from its content, the oath continues to have power as the solemnification of a physician's entry into the profession. It signifies a willingness to submit to a way of life that demands some suppression of self-interest. If studying the oath more explicitly reenforces this solemnification or strengthens the physician's dedication to the welfare of the patient, the effort will be worthwhile.


Effect of aluminium on the levels of some essential elements in occupationally exposed workers.
The mechanism of aluminium-induced cytotoxicity has not yet been defined. This study investigated possible changes in essential elements in workers occupationally exposed to Al fumes. It included 60 exposed workers and a matching control group of 60 employees not occupationally exposed to Al. Mean serum copper, calcium, zinc and iron were significantly lower in the exposed group than in controls. In addition, mean plasma and urine levels of Al were significantly higher in the exposed employees than in the controls. A statistically significant negative correlation was found between plasma and urinary Al and the studied essential elements. These findings corroborate the hypothesis that Al exposure has an adverse effect on essential elements in humans, with subsequent impact on the cellular enzymatic and metabolic processes.


The randomized shortened dental arch study: 5-year maintenance.
The scientific evidence concerning prosthodontic care for the shortened dental arch (SDA) is sparse. This randomized multicenter study aimed to compare two common treatment options: removable partial dental prostheses (RPDPs) for molar replacement vs. no replacement (SDA). One of the hypotheses was that the follow-up treatment differs between patients with RPDPs and patients with SDAs during the 5-year follow-up period. Two hundred and fifteen patients with complete molar loss in one jaw were included in the study. Molars were either replaced by RPDPs or not replaced according to the SDA concept. A mean number of 4.2 (RPDP) and 2.8 (SDA) treatments for biological or technical reasons occurred during the 5-year observation time per patient. Concerning the biological aspect, no significant differences between the groups could be shown, whereas treatment arising from technical reasons was significantly more frequent for the RPDP group. When the severity of treatment was analyzed, a change over time was evident. When, at baseline, only follow-up treatment with minimal effort is required, over time there is a continuous increase to moderate and extensive effort observed for both groups (Controlled-trials.com number ISRCTN97265367).


[Autophagy, ATG proteins and infectious diseases].
One of the main functions of the autophagy pathway is to control infections. Intracellular micro-organisms or their products once internalized in the host cell can be directly degraded by autophagy, a process called xenophagy. Autophagy is also involved in other innate immune responses and participates to the adaptive immune system. In addition, several autophagy proteins play a role in the development of infectious diseases independently of their role in the autophagy pathway. To replicate efficiently, pathogens have therefore evolved to counteract this process or to exploit it to their own profit. The review focuses on the relationship between autophagy and micro-organisms, which is highly diverse and complex. Many research groups are now working on this topic to find new therapeutics and/or vaccines. Given the large number of data, we have addressed this subject through some representative examples.


Exact and approximate unconditional confidence intervals for proportion difference in the presence of incomplete data.
Confidence interval (CI) construction with respect to proportion/rate difference for paired binary data has become a standard procedure in many clinical trials and medical studies. When the sample size is small and incomplete data are present, asymptotic CIs may be dubious and exact CIs are not yet available. In this article, we propose exact and approximate unconditional test-based methods for constructing CI for proportion/rate difference in the presence of incomplete paired binary data. Approaches based on one- and two-sided Wald's tests will be considered. Unlike asymptotic CI estimators, exact unconditional CI estimators always guarantee their coverage probabilities at or above the pre-specified confidence level. Our empirical studies further show that (i) approximate unconditional CI estimators usually yield shorter expected confidence width (ECW) with their coverage probabilities being well controlled around the pre-specified confidence level; and (ii) the ECWs of the unconditional two-sided-test-based CI estimators are generally narrower than those of the unconditional one-sided-test-based CI estimators. Moreover, ECWs of asymptotic CIs may not necessarily be narrower than those of two-sided-based exact unconditional CIs. Two real examples will be used to illustrate our methodologies.


Mechanisms of cytotoxicity of anticancer titanocenes.
The organometallic compound titanocene (bis(cyclopentadienyl)titanium(IV) dichloride) showed promising preclinical anticancer activity in generally resistant tumors in vitro and in vivo but failed in clinical trials. A broad range of analogs with modified cyclopentadienyl ligands conferring increased stability and higher cytotoxicity were developed. Titanium was found to accumulate in the nucleus and inhibit DNA replication and transcription. The active species causing irreversible damage and exact mechanisms of action resulting in cell cycle arrest and apoptosis have not been identified to date. Our group investigated changes in global gene expression of NCI-H526 small cell lung cancer cells in response to the novel analog titanocene C (bis-N,N-dimethylamino-2-(N-methylpyrrolyl) methyl) titanium (IV)). Differences observed in transcript levels indicated downregulation of DNA unwinding by topoisomerases I and II alpha and activation of responses to DNA damage and cellular stress as well as shutdown of energy metabolism and, finally, apoptosis. Besides direct interaction of Ti(2+) with DNA, induction of the MT1 family of metallothionein genes and downregulation of cellular Zn(2+) uptake in response to titanocene C pointed to disturbed Zn(2+) homeostasis, which triggers cell cycle arrest and apoptosis due to defective transcription factors and metalloenzymes. In particular, histone H4 genes dependent on Zn(2+)-containing transcription factors H4TF-1/2 were specifically downregulated, and accumulation of defective metalloproteins in the endoplasmatic reticulum seemed to activate unfolded protein response. In conclusion, according to these results, we propose a model of titanocene-induced cytotoxicity, comprising direct DNA damage and perturbation of Zn(2+) homeostasis with impairment of the functions of cellular metalloproteome.


The clinical leadership role of the CNS in the identification of nursing-sensitive and multidisciplinary quality indicator sets.
Within a team-oriented approach to healthcare, the demonstration of quality is challenging. Multidisciplinary quality indicators ideally represent all pertinent stakeholders and are preferred when evaluating the quality of care for specific patient populations. Recently, however, nursing-sensitive indicators have been developed that reflect the unique contribution of nursing to patient outcomes. Because nursing-sensitive quality indicators reflect nursings' accountability for patient care, they must also be considered when identifying indicators sets. Controversy exists concerning the appropriate definition, number, and approach to indicator identification. Many organizations are attempting to measure everything to ensure that all appropriate indicators are represented. To incorporate both nursing-sensitive and multidisciplinary quality indicators, a phased organization-wide approach is advocated. Through clinical leadership skills combined with the advanced practice roles of consultant, educator, and researcher, the clinical nurse specialist can facilitate the inclusion of relevant indicators, preserve both multidisciplinary and nursing-sensitive approaches, and maintain efficiency during the process. The clinical nurse specialist, with clinical expertise and advanced education has a unique leadership role in the identification of the resultant critical indicator matrix.


Peroxidised dietary lipids impair intestinal function and morphology of the small intestine villi of nursery pigs in a dose-dependent manner.
The objective of this study was to investigate the effect of increasing degrees of lipid peroxidation on structure and function of the small intestine of nursery pigs. A total of 216 pigs (mean body weight was 6·5 kg) were randomly allotted within weight blocks and sex and fed one of five experimental diets for 35 d (eleven pens per treatment with three to four pigs per pen). Treatments included a control diet without added lipid, and diets supplemented with 6 % soyabean oil that was exposed to heat (80°C) and constant oxygen flow (1 litre/min) for 0, 6, 9 and 12 d. Increasing lipid peroxidation linearly reduced feed intake (P<0·001) and weight gain (P=0·024). Apparent faecal digestibility of gross energy (P=0·001) and fat (P<0·001) decreased linearly as the degree of peroxidation increased. Absorption of mannitol (linear, P=0·097) and d-xylose (linear, P=0·089), measured in serum 2 h post gavage with a solution containing 0·2 g/ml of d-xylose and 0·3 g/ml of mannitol, tended to decrease progressively as the peroxidation level increased. Increasing peroxidation also resulted in increased villi height (linear, P<0·001) and crypt depth (quadratic, P=0·005) in the jejunum. Increasing peroxidation increased malondialdehyde concentrations (quadratic, P=0·035) and reduced the total antioxidant capacity (linear, P=0·044) in the jejunal mucosa. In conclusion, lipid peroxidation progressively diminished animal performance and modified the function and morphology of the small intestine of nursery pigs. Detrimental effects were related with the disruption of redox environment of the intestinal mucosa.


Correlates of mortality among hospital-born neonates with birth asphyxia.
Birth asphyxia is a major cause of neonatal mortality. An understanding of the determinants of mortality among asphyxiated neonates will help formulate effective management protocols. One hundred and fifty consecutive neonates with birth asphyxia (apnoea or gasping respiration at 1-minute of age) were prospectively studied. The association of the outcome variable, namely, mortality before discharge, was documented in relation to a number of clinically important risk factors. The neonatal mortality of 24.7% (37/150) among asphyxiated neonates was 34.5-times compared to that of the non-asphyxiated population (p < 0.001). The mortality rates in preterm-and term-asphyxiated neonates were 47.8% and 6%, respectively (p < 0.0001). The relative risk of mortality increased progressively with increased birth-weight. On univariate analysis, prematurity, low birth-weight, respiratory distress, severity of asphyxia, hypoxic-ischaemic encephalopathy, apnoea, acidosis and seizures were found to be significant risk factors of death. However, on step wise regression analysis, prematurity emerged as the most significant determinant of mortality. The highest positive predictive value (58.3%) for mortality was documented for hypoxic-ischaemic encephalopathy. A significant reduction in mortality among asphyxiated neonates will require aggressive management of prematurity-related neonatal complications and hypoxic-ischaemic encephalopathy.


Prognostic significance of Subjective Global Assessment (SGA) in advanced colorectal cancer.
To evaluate the prognostic significance of Subjective Global Assessment (SGA) in advanced colorectal cancer and create statistically distinct prognostic groups of colorectal cancer patients based on clinical and nutritional variables. A retrospective clinical epidemiologic study. A private tertiary care American Cancer Center. In total, 234 colorectal cancer patients aged 29-82 y treated at Cancer Treatment Centers of America at Midwestern Regional Medical Center between January 1995 and March 2001. SGA Questionnaire. SGA A-well nourished; SGA B-moderately malnourished; and SGA C-severely malnourished. Malnutrition was defined as either SGA B or SGA C. The prevalence of malnutrition in this patient population, as determined by SGA, was 52% (113/217). The median survival of patients with SGA A was 12.8 months (95% CI; 9.1-16.5), those with SGA B was 8.8 months (95% CI; 6.7-10.9) and those with SGA C was 6 months (95% CI; 3.9-8.1); the difference being statistically significant at P=0.0013. Regression tree analysis identified prior treatment history, lactate dehydrogenase (LDH) and SGA to be important predictors of survival for our patient cohort. Patients with no prior treatment history (newly diagnosed disease), low LDH scores, and SGA A had the best overall survival of 40.4 months (95% CI; 30.45-50.4), whereas patients with prior treatment history (progressive disease), high LDH scores, and SGA B/C had the worst overall survival of 4.5 months (95% CI; 2.22-6.76). The SGA provides useful prognostic information in patients with advanced colorectal cancer.


Lightweight and Amplitude-Free Ultrasonic Imaging Using Single-Bit Digitization and Instantaneous Phase Coherence.
In the field of ultrasonic nondestructive testing (NDT), the total focusing method (TFM) and its derivatives are now commercially available on portable devices and are getting more popular within the NDT community. However, its implementation requires the collection of a very large amount of data with the full matrix capture (FMC) as the worst case scenario. Analyzing all the data also requires significant processing power, and consequently, there is an interest in: 1) reducing the required storage capacity used by imaging algorithms, such as delay-and-sum (DAS) imaging and 2) allowing the transmission and postprocessing of inspection data remotely. In this study, a different implementation of the TFM algorithm is used based on the vector coherence factor (VCF) that is used as an image itself. This method, also generally known as phase coherence imaging, presents certain advantages, such as a better sensitivity to diffracting geometries, consistency of defect restitution among different views, and an amplitude-free behavior as only the instantaneous phase of the signal is considered. Some drawbacks of this method must also be mentioned, including the fact that it poorly reproduces planar reflectors and presents a lower signal-to-noise ratio (SNR) than amplitude-based methods. However, previous studies showed that it can be used as a reliable tool for crack-like defect sizing. Thus, a lightweight acquisition process is proposed through single-bit digitization of the signal, followed by a phase retrieval method based on the rising and falling edge locations, allowing to feed the phase coherence imaging algorithm. Simulated and experimental tests were first performed in this study on several side-drilled holes (SDHs) in a stainless steel block and then extended to an experimental study on angled notches in a 19.05-mm ( 3/4" )-thick steel sample plate through multiview imaging. Results obtained using the array performance indicator (API) and the contrast-to-noise ratio (CNR) as quantitative evaluation parameters showed that the proposed lightweight acquisition process, which relies on binary signals, allows a reduction of the data throughput of up to 47 times. This throughput reduction is achieved while still presenting very similar results to phase coherence imaging based on the instantaneous phase derived from the Hilbert transform of the full waveform. In an era of increasing wireless network speed and cloud computing, these results allow considering interesting perspectives for the reduction of inspection hardware costs and remote postprocessing.


Mindfulness on Symptom Control and Quality of Life in Patients in Palliative Care: A Systematic Review.
Palliative care is a medical and humanitarian approach that improves the quality of life of patients, and their families, who are facing problems associated with chronic and life-threatening illnesses. Few studies have evaluated the effectiveness of mindfulness-based interventions for terminally ill or incurable patients. The aim of this study was to systematically review the literature on the effect of mindfulness-based interventions on symptom control and quality of life in patients in palliative care. PubMed, Web of Science and Cochrane databases were searched for articles, published between January 2017 and December 2022, in English, including randomized controlled and clinical trials. Participants: terminally ill or incurable patients. Interventions: any mindfulness-based intervention. Comparators: any. Outcomes: symptom control and quality of life. The risk of bias was analysed through Cochrane's ROB-2 tool. Eight studies were included involving 609 patients and 75 dyads patients-spousal caregivers. The overall risk of bias was low to moderate. Mindfulness-based interventions are helpful in managing suffering, anxiety and depressive symptoms, fatigue, insomnia, drowsiness, appetite, and spiritual well-being. Mindfulness-based interventions control several symptoms and improve spiritual quality of life in patients in palliative care. Additionally, their informal caregivers also benefit from these interventions. Future trials are crucial to investigate other effects of mindfulness-based interventions, and their long-term benefits, in patients in palliative care.


An adapted algorithm for patient engagement in care for young people living with perinatal HIV in England.
Evidence suggests that engagement in care (EIC) may be worse in young people living with perinatal HIV (YPLPHIV) compared to adults or children living with HIV. We took a published EIC algorithm for adults with HIV, which takes patients' clinical scenarios into account, and adapted it for use in YPLPHIV in England, to measure their EIC. The adult algorithm predicts when in the next 6 months the next clinic visit should be scheduled, based on routinely collected clinical indicators at the current visit. We updated the algorithm based on the latest adult guidelines at the time, and modified it for young people in paediatric care using the latest European paediatric guidelines. Paediatric/adolescent HIV consultants from the UK reviewed and adapted the resulting flowcharts. The adapted algorithm was applied to the Adolescent and Adults Living with Perinatal HIV (AALPHI) cohort in England. Data for 12 months following entry into AALPHI were used to predicted visits which were then compared to appointment attendances, to measure whether young people were in care in each month. Proxy markers (e.g. dates of CD4 counts, viral loads (VL)) were used to indicate appointment attendance. Three hundred sixteen patients were in AALPHI, of whom 41% were male, 82% of black African ethnicity and 58% born abroad. At baseline (time of AALPHI interview) median [IQR] age was 17 [15-18] years, median CD4 was 597 [427, 791] cells/µL and 69% had VL ≤50c/mL. 10 patients were dropped due to missing data. 306 YPLPHIV contributed 3,585 person months of follow up across the 12 month study in which a clinic visit was recorded for 1,204 months (38/1204 dropped due to missing data). The remaining 1,166 months were classified into 3 groups: Group-A: on ART, VL ≤ 50c/mL-63%(734/1,166) visit months, Group-B: on ART, VL > 50c/mL-27%(320/1,166) Group-C: not on ART-10%(112/1,166). Most patients were engaged in care with 87% (3,126/3,585) of months fulfilling the definition of engaged in care. The adapted algorithm allowed the varying clinical scenarios of YPLPHIV to be taken into account when measuring EIC. However availability of good quality surveillance data is crucial to ensure that EIC can be measured well.