In-hospital medical complication in older people after spine surgery: A scoping review.
Worldwide, older people are suffering from lumbar degenerative disease at an annual rate of 266 million. Although spine surgeries restore mobility, reduce pain and resolve neurological damage, these procedures can place older persons at high-risk for medical complications due to multiple comorbid conditions that are often present in this population. However, the prevalence of complications occurring in older people prior to discharge is unknown. Postoperative medical complications lead to increased healthcare costs as well as pain and potential harm for the patient. Hence, this scoping review aimed to provide an overview of the current knowledge state regarding in-hospital medical postoperative complications in older people (≥65 years) after elective spine surgery. A scoping review was conducted following Arksey and O'Malley's framework. Four databases (PubMed, Cochrane, Scopus and CINAHL) were systematically searched. Inclusion criteria were medical complication(s) after elective spine surgery prior to discharge, age ≥65 years and English language. Co-occurrence analysis was used to examine how often each complication was examined in the literature and how often the complications co-occur. Twenty-six studies met inclusion criteria. The most frequently examined postoperative medical complications after spine surgery are delirium and urinary tract infection, followed by gastrointestinal and pulmonary embolus. Despite the list of in-hospital medical complications, definitions or criteria for measurement of any identified complication were sparse and inconsistent. There is a lack of definition or instruments to comprehensively assess medical complications incurred by older people following spine surgery, including characteristics, classification methodology and temporality. To date, no research has been conducted on how older people experience or perceive a medical complication after elective spine surgery. The findings highlight the importance to develop comprehensive instruments to assess co-occurrence of postoperative medical complications and design interventions to mitigate the negative impacts of medical complications incurred by older people after spine surgery.


Intraoperative cone-beam computed tomography and multi-slice computed tomography in temporal bone imaging for surgical treatment.
Conventional computed tomography (CT) imaging is the standard imaging technique for temporal bone diseases, whereas cone-beam CT (CBCT) imaging is a very fast imaging tool with a significant less radiation dose compared with conventional CT. We hypothesize that a system for intraoperative cone-beam CT provides comparable image quality to diagnostic CT for identifying temporal bone anatomical landmarks in cadaveric specimens. Cross-sectional study. University tertiary care facility. Twenty cadaveric temporal bones were affixed into a head phantom and scanned with both a prototype cone-beam CT C-arm and multislice helical CT. Imaging performance was evaluated by 3 otologic surgeons and 1 head and neck radiologist. Participants were presented images in a randomized order and completed landmark identification questionnaires covering 21 structures. CBCT and multislice CT have comparable performance in identifying temporal structures. Three otologic surgeons indicated that CBCT provided statistically equivalent performance for 19 of 21 landmarks, with CBCT superior to CT for the chorda tympani and inferior for the crura of the stapes. Subgroup analysis showed that CBCT performed superiorly for temporal bone structures compared with CT. The radiologist rated CBCT and CT as statistically equivalent for 18 of 21 landmarks, with CT superior to CBCT for the crura of stapes, chorda tympani, and sigmoid sinus. CBCT provides comparable image quality to conventional CT for temporal bone anatomical sites in cadaveric specimens. Clinical applications of low-dose CBCT imaging in surgical planning, intraoperative guidance, and postoperative assessment are promising but require further investigation.


[Decimeter radiothermometry in the diagnosis of brain tumors].
The authors used a new noninvasive method, decimeter radiothermometry, to measure cerebrocranial temperature in 68 patients with brain tumors. It made it possible to study the mean temperature of a tissue layer situated at a depth of 3-5 cm from the surface to an accuracy of up to +/- 0.1 degrees C. Temperature anomaly at the site of the tumor projection was revealed in three fourths of cases, mainly when it was localized laterally. Cerebrocranial temperature was compared with the morphological structure of the tumor. The diagnostic value of the method in tumors of the brain is demonstrated.


Nontarget Impacts of Herbicides on Spiders in Orchards.
Spiders are key predators in many agroecosystems, including orchards. Despite the importance of spiders in biological control, pesticide nontarget effects on this group are poorly described. This is especially true for herbicides, which spiders frequently encounter as they move between the ground cover and tree canopy. We sought to determine the nontarget effects of seven herbicides used in orchards on three species of spiders that are commonly found in Washington state (USA) orchards: Pelegrina aeneola (Curtis) (Araneae: Salticidae), Philodromus cespitum (Walckenaer) (Araneae: Philodromidae), and Phanias watonus (Chamberlin & Ivie) (Araneae: Salticidae). Immature spiders were collected from orchards and used in laboratory assays. Single spiders were placed in vials with dried herbicide residues and mortality was evaluated after 1, 2, and 5 d. We also evaluated herbicide impacts on prey consumption rates and on spider movement using motion-tracking software. Only oxyfluorfen caused significant spider mortality. P. cespitum seemed to be less acutely sensitive to oxyfluorfen than the two salticid species. Several herbicide treatments significantly increased locomotion in P. cespitum, whereas rimsulfuron numerically decreased movement of P. aeneola. Sulfonylurea herbicides (rimsulfuron, halosulfuron) decreased prey consumption of P. aeneola. Our work indicates that although spiders may be less acutely sensitive to some pesticides than beneficial insects, they can be affected by sublethal effects of herbicides. Future work should determine if herbicide applications impact spider abundance in the field and reduce biological control services. In general, more work is needed on the impacts of herbicides on natural enemies.


Assessment of emerging and traditional halogenated contaminants in Guillemot (Uria aalge) egg from North-Western Europe and the Baltic Sea.
Persistent organic pollutants (POPs) are readily detected in biological samples at remote sites in the Arctic and sub-Arctic due to long-range transport from source areas. The aim of this study was to investigate the presence of POPs, polybrominated contaminants and their metabolites in guillemot (Uria aalge) eggs from Iceland, the Faroe Islands, Norway and Sweden to assess spatial trends of these compounds in the Arctic and sub-Arctic areas of Europe. Egg samples were extracted, and cleaned for chemical analysis. Concentrations of PCBs, 4,4'-DDE and beta-HCH were an order of magnitude higher in eggs from the Baltic Proper compared to eggs from the North Atlantic. Concentrations of HCB were of the same magnitude at all sites, ranging from 160 to 520 ng/g fat. Concentration of BCPS was 100 times higher in eggs from the Baltic compared to eggs from the North Atlantic and seems therefore to be special regional problem. Concentrations of PBDEs were lower in eggs from the North Atlantic compared to eggs from the Baltic Proper but the difference was not as large as for PCBs and 4,4'-DDE. HBCDD showed the same spatial trend as PCBs, where the concentrations in eggs from the Baltic Proper were an order of magnitude higher than in eggs from the North Atlantic. OH-PCB and MeSO(2)-PCB metabolites of PCBs, showed the same trend as the parent compounds while spatial trends of MeSO(2)-DDE and OH-PBDEs, metabolites of 4,4'-DDE and PBDEs, respectively, differed from the trend of the parent compounds. This may be due to two factors; firstly, the limited ability of birds to metabolise DDT, and secondly, to natural production of OH-PBDE, respectively. Guillemot is suggested as a monitoring species for circumpolar monitoring.


UVB-induced decreased resistance to Trichinella spiralis in the rat is related to impaired cellular immunity.
Our laboratory has demonstrated in preliminary experiments that UVB exposure using the Kromayer lamp can induce increased numbers of Trichinella spiralis larvae in carcasses of infected Wistar rats, without affecting specific antibody titers to this parasite. In this study, orally T. spiralis-infected Wistar rats were exposed to suberythemal doses of UVB radiation using FS40 lamps during different time periods before or after infection. A significant increase in the number of T. spiralis larvae was found in the carcasses of rats that were UVB irradiated daily for 7 consecutive days in the second week after infection. Additionally, increased numbers of larvae were also detected histologically in the tongue of rats that were exposed the first and the second week after infection. Lymphocyte stimulation assays using mesenteral lymph node cells indicated that UVB exposure also impaired the specific lymphocyte response to T. spiralis. Moreover, DTH responses to T. spiralis were severely impaired in rats that were UVB irradiated daily for 7 consecutive days in the second week after infection. Thus, these data combined with the data of the Kromayer study indicate that exposure of rats to FS40 irradiation following oral infection with T. spiralis leads to increased numbers of larvae in systemic sites and impaired T-cell immunity to the parasite.


An in vitro biomechanical investigation: variable positioning of leopard carbon fiber interbody cages.
This study is a biomechanical analysis of intervertebral cage placement, using a biomechanical model that has the appropriate matching geometry of the lumbar spine at the level of L4-L5 based upon prior morphometric studies. The goal of this in vitro biomechanical analysis of interbody cages is to determine the effect of interbody cage position on the mechanics of posterior spinal instrumentation. This biomechanical analysis can potentially be used to guide surgical technique for placement of interbody cage devices. Lumbar interbody spinal fusion cages are increasingly being used to promote spinal fusion and improve sagittal alignment in patients with degenerative disk disease. The transforaminal approach for placement of these cages has become popular, although the actual position of the cage that will provide optimal mechanical support in the intervertebral space is not known. Leopard carbon fiber interbody cages (DepuySpine, Raynham, MA) were placed in a spinal fusion model simulating the L4-L5 disk space in one of 3 positions-anterior, middle, or anterolateral. We tested 5 constructs in each of the 3 positions, applying cyclic axial loads of 500 N at a rate of 4 Hz for 100,000 cycles. Strain on the posterior instrumentation and displacement of the cages was measured at periodic intervals. Load to failure of each construct was tested after 100,000 cycles were complete. Statistical analysis of biomechanical indicators show more strain in the anterolateral position as compared with the anterior position (P=0.002) and middle position (P=0.02). No difference was noted between anterior and middle positions (P=1.00). Interval analysis reveals differences in strain at 500 cycles in anterior versus anterolateral (P=0.01) and middle versus anterolateral (P=0.02). At 10,000 cycles, anterolateral strain was significantly higher (P=0.02) than anterior. No significant difference in strain was noted at 50,000 or 100,000 cycles between any of the positions. No significant differences were noted in displacement of the cages between each of the positions. Ultimate load to failure was lower (nonsignificant) in the anterolateral versus anterior position (P=0.06), but no difference was noted between anterior versus middle (P=0.57) or anterolateral versus middle (P=0.69) positions. Linear regression analysis of load-displacement curves shows significance at 500 cycles (P=0.02), approaching significance at 10,000 cycles (P=0.07), and no significant difference at 50,000 (P=0.28) or 100,000 (P=0.28) cycles. Positioning of interbody cages in an offset position shows higher strain upon posterior instrumentation than a central position, and quicker load to failure than an anteriorly placed cage. Biomechanical studies using shear loading, and testing of adjacent spinal levels, are necessary to further elucidate the biomechanical consequences of variable positioning of interbody cages.


[Nosocomial outbreak of scabies from a Norwegian scabies case].
To describe a nosocomial outbreak of scabies occurred in August 1999, resulting from exposure to an undiagnosed Norwegian scabies case, in Mexico City. After reviewing the index case, we isolated the patient and identified secondary scabies cases among employees working in the affected ward, their relatives, and inpatients. Only individuals complaining from skin lesions and pruritus were included as infested cases. Control measures as contact isolation, proper handling of contaminated clothes, and topical treatment were implemented. A patient with AIDS (index case) with a severe water and electrolyte imbalance was admitted to the Hospital de Infectologia (Infectious Diseases Hospital) of the Centro Medico Nacional La Raza (La Raza National Medical Center) in Mexico City from July 19 to August 20, 1999. Twenty-eight days after the index case admission, scabies cases occurred among health workers. Norwegian scabies was suspected and confirmed by microscopic evidence of the mites on a specimen of scabs from the index case. We identified 48 secondary cases with clinical scabies: 71% health workers, mainly nurses (79%); 23% health workers' relatives; and 6% inpatients. The mean incubation period was 15 days (range 12 to 27). Skin rashes commonly involved the upper extremities (60%) but not the hands. This paper highlights the difficulties in diagnosing Norwegian scabies in an immunosuppressed host, as well as the importance of ensuring that health workers follow standard precautions at all times. The English version of this paper is available at: http://www.insp.mx/salud/index.html.


Mechanism for benzyl alcohol-induced aggregation of recombinant human interleukin-1 receptor antagonist in aqueous solution.
Benzyl alcohol, an antimicrobial preservative, accelerates aggregation and precipitation of recombinant human interleukin-1 receptor antagonist (rhIL-1ra) in aqueous solution. The loss of native monomer during incubation at 37 degrees C was determined by analysis of sample aliquots with size exclusion high performance liquid chromatography (SE-HPLC). Benzyl alcohol caused minor perturbation of the tertiary structure of the protein without changing its secondary structure, documenting that the preservative caused a minor shift in the protein molecular population toward partially unfolded species. Consistent with this conclusion, in the presence of benzyl alcohol the rate of H-D exchange was accelerated and the fluorescence of 1-anilinonaphthalene-8-sulfonic acid in the presence of rhIL1ra was increased. Benzyl alcohol did not alter the free energy of unfolding based on unfolding experiments in urea or guanidine HCl. With differential scanning calorimetry it was determined that benzyl alcohol reduced the apparent Tm of rhIL-1ra, but this effect occurred because the preservative lowered the temperature at which the protein aggregated during heating. Isothermal calorimetry documented that the interaction of benzyl alcohol with rhIL-1ra is relatively weak and hydrophobically driven. Thus, benzyl alcohol accelerates protein aggregation by binding to the protein and favoring an increase in the level of partially unfolded, aggregation-competent species. Sucrose partially inhibited benzyl alcohol-induced aggregation and tertiary structural change. Sucrose is preferentially excluded from the surface of the protein, favoring most compact native state species over expanded aggregation-prone forms.


Insight on ALPPS - Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy - mechanisms: activation of mTOR pathway.
ALPPS procedure has been introduced to increase the volume of future liver remnant. The mechanisms underlying the accelerated regeneration observed with ALPPS are unknown. It was hypothesized that AMPK/mTOR is activated as an integrating pathway for metabolic signals leading to proliferation and cell growth. Our aim was to analyze increase in liver volume, proliferation parameters and expression of AMPK/mTOR pathway-related molecules in patients undergoing ALPPS. A single center prospective study of patients undergoing ALPPS was performed from 2013 to 2015. Liver and serum samples, clinical laboratory results and CT-scan data were obtained. ELISA, Ki-67 immunostaining and qRT-PCR were performed in deportalized and remnant liver tissue in both stages of the procedure. 11 patients were enrolled. Remnant liver volume increased 112 ± 63% (p < 0.05) in 9.1 ± 1.6 days. Proliferation-related cytokines IL-6, TNF-α, HGF and EGF significantly increased, while higher Ki-67 immunostaining and cyclin D expression were observed in remnant livers after ALPPS. mTOR, S6K1, 4E-BP1, TSC1 and TSC2 expression were significantly increased in remnant livers at second stage, while AMPK and Akt increased only in deportalized liver samples. Rapid liver regeneration with ALPPS might be associated with hepatocyte proliferation induced by mTOR pathway activation.


Melatonin: a clinical perspective.
Over the last several decades the pineal gland has emerged as an active neuroendocrine transducer of important environmental information. However, the current understanding of the function of its major hormone, melatonin, in humans remains ill defined and based exclusively on correlative observations. In a similar manner, the multitude of phenomenological descriptions of the effects of exogenous melatonin is contrasted by the limited understanding of the underlying mechanisms and the lack of firmly established clinical applications for the hormone. Future randomized, double-blind, placebo-controlled clinical studies will be necessary to determine the precise indications, treatment regimens, and safety of melatonin in clinical practice. The recent rapid progress in the area of melatonin research should lead to a better understanding of its role in human health and disease.


Long-term effects of ileal conduit urinary diversion on upper urinary tract in bladder cancer.
To evaluate the functional and morphologic changes of the upper urinary tract after radical cystectomy and ileal conduit urinary diversion for bladder cancer. Radical cystectomy and ileal conduit urinary diversion were performed in a total of 249 patients with bladder cancer at our hospital from 1980 to 1999. Of the 249 patients, 67 were excluded because of the presence of preoperative lesions in the upper urinary tract or elevated serum creatinine (greater than 1.4 mg/dL). Of the remaining 182 patients, 82 were also excluded because of incomplete follow-up or death less than 5 years after surgery. Of the 249 patients, a total of 100 (40.2%) who had no preoperative lesions in upper urinary tract and normal renal function and survived 5 years or longer were included in this analysis. The median follow-up period was 91 months (range 60 to 193). The serum creatinine was greater than the normal range in 10 patients (10.0%), and radiologic changes in the upper urinary tract were observed in 14 patients (14.0%). They had diabetes mellitus nephropathy (4.0%) or specific comorbidities that could contribute to the deterioration of the upper urinary tract, such as ureteroileal anastomotic stricture (4.0%), chronic pyelonephritis (4.0%), urinary stones (1.0%), and upper urinary tract tumor (1.0%). The results of our study have shown that the functional and morphologic changes in the upper urinary tract after radical cystectomy and ileal conduit urinary diversion occur in patients with specific comorbidities that could contribute to those changes. Different from previous reports, none of the upper urinary tract changes developed without an obvious cause.


Monkey prefrontal cortical pyramidal and putative interneurons exhibit differential patterns of activity between prosaccade and antisaccade tasks.
Previous studies have shown that prefrontal cortex (PFC) neurons carry task-related activity; however, it is largely unknown how this selectivity is implemented in PFC microcircuitry. Here, we exploited known differences in extracellular action potential waveforms, and antidromic identification, to classify PFC neurons as putative pyramidal or interneurons, and investigate their relative contributions to task-selectivity. We recorded the activity of prefrontal neurons while monkeys performed a blocked pro/antisaccade task in which they were required to look either toward or away from a peripheral visual stimulus. We found systematic differences in activity between neuron classes. Putative pyramidal neurons had higher stimulus-related activity on antisaccade trials, whereas putative interneurons exhibited greater activity for prosaccades. These findings suggest that task-selectivity in the PFC may be shaped by interactions between these neuronal classes. They are also consistent with the robust deficits in antisaccade performance frequently observed in disease states associated with PFC dysfunction.


Late Side Effects in Normal Mouse Brain Tissue After Proton Irradiation.
Radiation-induced late side effects such as cognitive decline and normal tissue complications can severely affect quality of life and outcome in long-term survivors of brain tumors. Proton therapy offers a favorable depth-dose deposition with the potential to spare tumor-surrounding normal tissue, thus potentially reducing such side effects. In this study, we describe a preclinical model to reveal underlying biological mechanisms caused by precise high-dose proton irradiation of a brain subvolume. We studied the dose- and time-dependent radiation response of mouse brain tissue, using a high-precision image-guided proton irradiation setup for small animals established at the University Proton Therapy Dresden (UPTD). The right hippocampal area of ten C57BL/6 and ten C3H/He mice was irradiated. Both strains contained four groups (nirradiated = 3, ncontrol = 1) treated with increasing doses (0 Gy, 45 Gy, 65 Gy or 85 Gy and 0 Gy, 40 Gy, 60 Gy or 80 Gy, respectively). Follow-up examinations were performed for up to six months, including longitudinal monitoring of general health status and regular contrast-enhanced magnetic resonance imaging (MRI) of mouse brains. These findings were related to comprehensive histological analysis. In all mice of the highest dose group, first symptoms of blood-brain barrier (BBB) damage appeared one week after irradiation, while a dose-dependent delay in onset was observed for lower doses. MRI contrast agent leakage occurred in the irradiated brain areas and was progressive in the higher dose groups. Mouse health status and survival corresponded to the extent of contrast agent leakage. Histological analysis revealed tissue changes such as vessel abnormalities, gliosis, and granule cell dispersion, which also partly affected the non-irradiated contralateral hippocampus in the higher dose groups. All observed effects depended strongly on the prescribed radiation dose and the outcome, i.e. survival, image changes, and tissue alterations, were very consistent within an experimental dose cohort. The derived dose-response model will determine endpoint-specific dose levels for future experiments and may support generating clinical hypotheses on brain toxicity after proton therapy.


Alcohol seeking by rats: action or habit?
In two experiments, we examined the relative susceptibility to outcome devaluation of lever pressing by rats for either a 10% ethanol solution or food pellets. The rats were trained to press different levers for these two reinforcers using a sucrose-substitution procedure. An aversion was then conditioned from either the ethanol solution or the food pellets by pairing consumption with illness induced by lithium chloride. When instrumental performance was subsequently tested in extinction, the rats pressed less on the pellet lever if the pellets, rather than the ethanol, had been devalued by aversion conditioning. By contrast, performance on the ethanol lever was unaffected by whether the ethanol or pellets were devalued. Moreover, noncontingent presentations of the devalued reinforcer had no impact on test performance. The differential resistance to outcome devaluation suggests that, in contrast to food seeking, alcohol seeking is a stimulus-response habit rather than a goal-directed action mediated by a representation of the action-outcome contingency.


Evaluation of relapse with thermoplastic retainers equipped with microsensors.
To examine relapse with thermoplastic retainers equipped with microsensors 1 year after treatment. A total of 42 patients (29 females, 13 males) treated with four premolar extractions were included in this study. Thermoplastic appliances equipped with TheraMon microsensors (Handelsagentur Gschladt, Hargelsberg, Austria) were used to assess daily wear time (DWT), and the patients were monitored at 2-month intervals for a period of 12 months. At the end of the follow-up, the following two groups were formed based on the mean DWT: short wear time (SWT; <9 h/d) and long wear time (LWT; ≥9 h/d). Digital models were constructed before treatment (T0), at debonding (T1), and 6 months (T2) and 12 months (T3) after debonding. Little's Irregularity Index (LII) and the intercanine and intermolar widths, arch lengths, overjet, and overbite were calculated based on the digital models. Data were analyzed statistically. Irregularity and overjet increased, whereas transverse measurements and arch lengths decreased with time in both groups. During the retention period, overbite decreased in the SWT group but increased in the LWT group. There were significant differences between groups only in mandibular irregularity. The LII values of the SWT group were significantly higher than those of the LWT group for the T1-T2 and T1-T3 time intervals (P < .05). A mean DWT less than 9 hours/day was inadequate for controlling irregularity within clinically acceptable limits. A wear time of at least 9 h/d is recommended for the maintenance of mandibular anterior alignment.


Sarcocystis falcatula-like derived from opossum in Northeastern Brazil: In vitro propagation in avian cells, molecular characterization and bioassay in birds.
Most reported isolates of Sarcocystis spp. derived from Brazilian opossums (Didelphis sp.) have genetic characteristics distinct from the known species of Sarcocystis, but behave similarly as Sarcocystis falcatula, as they are infective to budgerigars. In previous studies, these Brazilian isolates, classified as Sarcocystis falcatula-like, were originated from South and Southeast regions of Brazil. In the current work, we aimed to culture and to perform multilocus sequence analysis of Sarcocystis sp. derived from a Brazilian opossum (D. aurita/D. marsupialis) that inhabited the city of Salvador, Bahia, in the Northeast of Brazil. The parasite was isolated in Vero cells, referred here as Sarco-BA1, and propagated in avian cells (DF-1). Molecular analysis of Sarco-BA1 revealed that the nucleotide sequence of the internal transcribed spacer 1 (ITS1) of the rDNA was identical to all isolates (n = 19) of Sarcocystis spp. reported in two studies from South and Southeast regions of the country. Two budgerigars were inoculated with 10 and 1000 sporocysts of Sarco-BA1, respectively, and developed acute sarcocystosis, showing that the parasite behaves like S. falcatula. It was interesting to observe that Sarco-BA1 had almost identical ITS1 and SAG sequences to all 16 isolates of S. falcatula-like recently described in Magellanic penguins (Spheniscus magellanicus) rescued on the coast of Espírito Santo state, Brazil. Our results suggest that Sarco-BA1 and S. falcatula-like may represent a single species of Sarcocystis. Propagation of the parasite in a permanent avian cell line significantly improved the yield of merozoites in cell culture. To our knowledge, this is the first molecular study and in vitro isolation of S. falcatula-like derived from Northeastern Brazil. Studies are under way to determine the infectivity of Sarco-BA1 to other animal species, as well as to investigate serological cross-reactivity among Sarco-BA1, S. neurona and related species.


Rapid differential endogenous plasminogen activator expression after acute middle cerebral artery occlusion.
During focal cerebral ischemia, the microvascular matrix (ECM), which participates in microvascular integrity, is degraded and lost when neurons are injured. Loss of microvascular basal lamina antigens coincides with rapid expression of select matrix metalloproteinases (MMPs). Plasminogen activators (PAs) may also play a role in ECM degradation by the generation of plasmin or by MMP activation. The endogenous expressions of tissue-type plasminogen activator (tPA), urokinase (uPA), and PA inhibitor-1 (PAI-1) were quantified in 10-microm frozen sections from ischemic and matched nonischemic basal ganglia and in the plasma of 34 male healthy nonhuman primates before and after middle cerebral artery occlusion (MCA:O). Within the ischemic basal ganglia, tissue uPA activity and antigen increased significantly within 1 hour after MCA:O (2P<0.005). tPA activity transiently decreased 2 hours after MCA:O (2P=0.01) in concert with an increase in PAI-1 antigen (2P=0.001) but otherwise did not change. The transient decrease in free tPA antigen was marked by an increase in the tPA-PAI-1 complex (2P<0.001). No significant relations to neuronal injury or intracerebral hemorrhage were discerned. The rapid increase in endogenous PA activity is mainly due to significant increases in uPA, but not tPA, within the ischemic basal ganglia after MCA:O. This increase and an increase in PAI-1 coincided with latent MMP-2 generation and microvascular ECM degeneration but not neuronal injury.


Quantum stabilization of the 1/3-magnetization plateau in Cs2CuBr4.
We consider the phase diagram of a spatially anisotropic 2D triangular antiferromagnet in a magnetic field. Classically, the ground state is umbrellalike for all fields, but we show that the quantum phase diagram is much richer and contains a 1/3-magnetization plateau, two commensurate planar states, two incommensurate chiral umbrella phases, and, possibly, a spin density wave state separating the two chiral phases. Our analysis sheds light on several recent experimental findings for Cs2CuBr4.


Long non-coding RNA SNHG16 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer via sponging miR-200a-3p.
Previous study has explored that SNHG16, a long non-coding RNA (lncRNA), mediated cell growth and proliferation. Yet, the role of SNHG16 in human colorectal cancer (CRC) still remains to be explored. Therefore, we conducted the present study to explore the functions of SNHG16 in CRC. In the present study, SNHG16 was significantly up-regulated in CRC tissues and cell lines. Gain- and loss-of-function of SNHG16 further presented that SNHG16 promoted the progression of CRC cells, including proliferation, migration, and invasion. Further, in vivo study also revealed that overexpression of SNHG16 could promote tumor growth. Bioinformatics analysis and luciferase reporter assay showed that SNHG16 was a direct target of miR-200a-3p. MiR-200a-3p was inversely correlated with SNHG16 expression in CRC tissues. In brief, the above results elucidate the important role of SNHG16 in CRC tumorigenesis, suggesting that SNHG16 might be quite vital for the diagnosis and development of CRC.


Identifying seedling root architectural traits associated with yield and yield components in wheat.
Plant roots growing underground are critical for soil resource acquisition, anchorage and plant-environment interactions. In wheat ( Triticum aestivum ), however, the target root traits to improve yield potential still remain largely unknown. This study aimed to identify traits of seedling root system architecture (RSA) associated with yield and yield components in 226 recombinant inbred lines (RILs) derived from a cross between the bread wheat Triticum aestivum 'Forno' (small, wide root system) and spelt Triticum spelta 'Oberkulmer' (large, narrow root system). A 'pouch and wick' high-throughput phenotyping pipeline was used to determine the RSA traits of 13-day-old RIL seedlings. Two field experiments and one glasshouse experiment were carried out to investigate the yield, yield components and phenology, followed by identification of quantitative trait loci (QTLs). There was substantial variation in RSA traits between genotypes. Seminal root number and total root length were both positively associated with grains m -2 , grains per spike, above-ground biomass m -2 and grain yield. More seminal roots and longer total root length were also associated with delayed maturity and extended grain filling, likely to be a consequence of more grains being defined before anthesis. Additionally, the maximum width of the root system displayed positive relationships with spikes m -2 , grains m -2 and grain yield. Ten RILs selected for the longest total roots exhibited the same effects on yield and phenology as described above, compared with the ten lines with the shortest total roots. Genetic analysis revealed 38 QTLs for the RSA, and QTL coincidence between the root and yield traits was frequently observed, indicating tightly linked genes or pleiotropy, which concurs with the results of phenotypic correlation analysis. Based on the results from the Forno × Oberkulmer population, it is proposed that vigorous early root growth, particularly more seminal roots and longer total root length, is important to improve yield potential, and should be incorporated into wheat ideotypes in breeding.


[Keep initiative mind to save burn crisis and strive hard to reach the summit of the burn discipline].
The Department of Burns and Plastic Surgery in Guangzhou Red Cross Hospital of Medical College of Ji'nan University grew up along with the development of burn discipline in China. In the past 60 years, it has developed into a burn specialty with three wards, 100 beds, and nearly 100 medical staff from several beds and surgeons. It is characterized by the treatment of severe burns and is a medical burn center integrating medical treatment, teaching and scientific research. In recent ten years or more, the subject development has closely followed the changes of burn discipline and society and has carried out the construction of sub-specialties. It has formed obvious speciality features in the network construction for severe burn rescue, the construction and management of burn intensive care unit and the comprehensive prevention and treatment of multiple organ dysfunction syndrome for severe burn patients and has enjoyed a good reputation in our speciality. We will continue to maintain the professional spirit of burn medicine workers for emergency and disaster relief for burned patients, keep initiative mind, strive hard to continuously improve the professional and technical level, and strive to establish a regional burn treatment center to make more contributions to the development of burn discipline.


Rapid and protracted phases of retinal ganglion cell loss follow axotomy in the optic nerve of adult rats.
To investigate the short- and long-term effects of axotomy on the survival of central nervous system (CNS) neurons in adult rats, retinal ganglion cells (RGCs) were labelled retrogradely with the persistent marker diI and their axons interrupted in the optic nerve (ON) by intracranial crush 8 or 10 mm from the eye or intraorbital cut 0.5 or 3 mm from the eye. Labelled RGCs were counted in flat-mounted retinas at intervals from 2 weeks to 20 months after axotomy. Two major patterns of RGC loss were observed: (1) an initial abrupt loss that was confined to the first 2 weeks after injury and was more severe when the ON was cut close to the eye; (2) a slower, persistent decline in RGC densities with one-half survival times that ranged from approximately 1 month after intraorbital ON cut to 6 months after intracranial ON crush. A small population of RGCs (approximately 5%) survived for as long as 20 months after intraorbital axotomy. The initial loss of axotomized RGCs presumably results from time-limited perturbations related to the position of the ON injury. A persistent lack of terminal connectivity between RGCs and their targets in the brain may contribute to the subsequent, more protracted RGC loss, but the differences between intraorbital cut and intracranial crush suggest that additional mechanisms are involved. It is unclear whether the various injury-related processes set in motion in both the ON and the retina exert random effects on all RGCs or act preferentially on subpopulations of these neurons.


A comparison of the pH, urea, and temperature-denatured states of barnase by heteronuclear NMR: implications for the initiation of protein folding.
The denatured states of barnase that are induced by urea, acid, and high temperature and acid have been assigned and characterised by high resolution heteronuclear NMR. The assignment was completed using a combination of triple-resonance and magnetisation-transfer methods. The latter was facilitated by selecting a suitable mutant of barnase (Ile-->Val51) which has an appropriate rate of interconversion between native and denatured states in urea. 3J NH-C alpha H coupling constants were determined for pH and urea-denatured barnase and intrinsic "random coil" coupling constants are shown to be different for different residue types. All the denatured states are highly unfolded. But, a consistent series of weak correlations in chemical shift, NOESY and coupling constant data provides evidence that the acid-denatured state has some residual structure in regions that form the first and second helices and the central strands of beta-sheet in the native protein. The acid/temperature-denatured states has less structure in these regions, and the urea-denatured state, less still. These observations may be combined with detailed analyses of the folding pathway of barnase from kinetic studies to illuminate the relevance of residual structure in the denatured states of proteins to the mechanism of protein folding. First, the folding of barnase is known to proceed in its later stages through structures in which the first helix and centre of the beta-sheet are extensively formed. Thus, embryonic initiation sites for these do exist in the denatured states and so could well develop into true nuclei. Second, it has been clearly established that the second helix is unfolded in these later states, and so residual structure in this region of the protein is non-productive. These data fit a model of protein folding in which local nucleation sites are latent in the denatured state and develop only when they make interactions elsewhere in the protein that stabilise them during the folding process. Thus, studies of the structure of denatured states pinpoint where nucleation sites may be, and the kinetic and protein engineering studies show which ones are productive.


Implications of Glycosylation in Alzheimer's Disease.
Alzheimer's disease (AD) is the most common cause of dementia, affecting millions of people worldwide, and no cure is currently available. The major pathological hallmarks of AD are considered to be amyloid beta plaques and neurofibrillary tangles, generated by respectively APP processing and Tau phosphorylation. Recent evidence imply that glycosylation of these proteins, and a number of other AD-related molecules is altered in AD, suggesting a potential implication of this process in disease pathology. In this review we summarize the understanding of glycans in AD pathogenesis, and discuss how glycobiology can contribute to early diagnosis and treatment of AD, serving as potential biomarkers and therapeutic targets. Furthermore, we look into the potential link between the emerging topic neuroinflammation and glycosylation, combining two interesting, and until recent years, understudied topics in the scope of AD. Lastly, we discuss how new model platforms such as induced pluripotent stem cells can be exploited and contribute to a better understanding of a rather unexplored area in AD.


Vanadate catalyzes photocleavage of adenylate kinase at proline-17 in the phosphate-binding loop.
Irradiation of adenylate kinase (AK) from chicken muscle with 300-400-nm light in the presence of 0.25 mM vanadate ion first inactivated the enzyme and then cleaved the polypeptide chain near the NH2 terminus. The addition of the multisubstrate analogue, P1,P5-bis(5'-adenosyl) pentaphosphate, prevented both effects. ATP, but not AMP, blocked both inactivation and cleavage in a saturable manner, suggesting that both effects were due to modification at the ATP-binding site. The polypeptide products of the photocleavage were isolated by HPLC and characterized by amino acid composition, peptide sequencing, and mass spectral analyses. The predominant (greater than 90%) small peptide fragment contained the first 16 amino acids from the amino terminus of the enzyme. The amino terminus of this peptide contained an acetylated serine, and the "carboxy" terminus was modified by a cyclized gamma-aminobutyric acid which originated from photooxidation and decarboxylation of proline-17 by vanadate. Edman sequencing indicated that the majority of the large peptide fragment (Mr approximately 19,500) was amino-terminal blocked, but a small portion was sequenceable starting at either glycine-18 (7%) or serine-19 (2%). These studies indicate that in the ATP-AK complex proline-17 is close to the phosphate chain of ATP but not AMP, consistent with the latest evaluation of nucleotide-binding sites on mitochondrial matrix AK by X-ray crystallography [Diederichs, K., & Schulz, G.E. (1991) J. Mol. Biol. 217, 541-549]. Furthermore, this is the first report that an amino acid other than serine can be involved in vanadate-promoted photocleavage reactions.


Thrombin attenuates neuronal cell death and modulates astrocyte reactivity induced by beta-amyloid in vitro.
beta-Amyloid protein has been implicated as a potential causative agent in the neuropathology associated with Alzheimer's disease. This possibility is supported by observations that beta-amyloid induces neuronal degeneration and astrocyte reactivity in vitro by as yet undefined mechanism(s). In this report, we present data demonstrating that the pathological effects of beta-amyloid on cultured cells are modulated by activation of the thrombin receptor. At concentrations between 50 and 500 nM, thrombin pretreatment significantly attenuates neurotoxicity mediated by fibrillar aggregates of beta 1-42 and beta 25-35 peptides. In cultured astrocytes, the stellate morphology induced by beta 1-42 and beta 25-35 aggregates can be prevented and reversed by thrombin exposures between 10 pM and 1 microM. In contrast, thrombin potentiates rather than attenuates the beta-amyloid-induced increased expression of basic fibroblast growth factor, suggesting that thrombin differentially modulates the effects of beta-amyloid on astrocytes. Thrombin's effects on both neurons and astrocytes are mimicked by thrombin receptor-activating peptide and inhibited by two potent thrombin inhibitors, hirudin and protease nexin-1. These data provide both new insight into the signaling pathways underlying the cellular effects of beta-amyloid and additional support for the role of thrombin as an important mediator of neuropathological events.


Enteroenteric fistula of the duodenum in a patient with AIDS and Mycobacterium avium-intracellulare infection.
Upper gastrointestinal endoscopy revealed a double lumen in the second portion of the duodenum in a 39-year-old man with advanced acquired immunodeficiency syndrome (AIDS). The lesion was not lined with an epithelium and improved with antituberculous therapy. These findings, as well as both an extensive transmural inflammation with foamy macrophages laden with acid-fast microorganisms and the destruction of the bowel wall, were consistent with Mycobacterium avium-intracellulare infection, but not with congenital duplication. An upper gastrointestinal series was falsely negative. Deep, penetrating lesions and double-barreled lumen are not infrequent in AIDS-related esophageal disease. We propose that similar lesions related to M avium-intracellulare occur in the bowel, especially when immune impairment and mycobacterial infection are severe. Awareness of mycobacterial infections of the gut is important in the era of AIDS.


Aluminum Partitioning in Intact Roots of Aluminum-Tolerant and Aluminum-Sensitive Wheat (Triticum aestivum L.) Cultivars.
Aluminum (Al) partitioning in intact roots of wheat (Triticum aestivum L.) cultivars that differ in sensitivity to Al was investigated. Roots of intact seedlings were exposed to Al for up to 24 hours and distribution of Al was assessed visually by hematoxylin staining or by direct measurement of concentration of Al by atomic absorption spectrophotometry or ion chromatography. Major differences in Al accumulation between Al-tolerant (Atlas 66) and Al-sensitive (Tam 105) cultivars were found in the growing regions 0 to 2 and 2 to 5 millimeters from the root apex. Al content was 9 to 13 times greater in the 0 to 2 millimeters root tips of cv Tam 105 than in the tips of cv Atlas 66 when exposed to 50 micromolar Al for 19 to 24 hours. The oxidative phosphorylation inhibitor carbonyl cyanide m-chlorophenylhydrazone and the protein synthesis inhibitor cycloheximide increased Al uptake by intact root tips of cv Atlas 66. Also, loss of Al from the roots of both cultivars was measured after the roots were "pulsed" with 50 micromolar Al for 2 hours and then placed in an Al-free nutrient solution for 6 hours. The 0 to 2 millimeter root tips of cv Tam 105 lost 30% of the absorbed Al, whereas the tips of cv Atlas 66 lost 60%. In light of these results, we conclude that the differential Al sensitivity in wheat correlates with the concentration of Al in the root meristems. The data support the hypothesis that part of the mechanism for Al tolerance in wheat is based on a metabolism-dependent exclusion of Al from the sensitive meristems.


Analysis of a salt stable mutant of cowpea chlorotic mottle virus.
An understanding of virion assembly and disassembly requires a detailed understanding of the protein-protein and protein-nucleic acid interactions which stabilize the virion. We have characterized a mutant of cowpea chlorotic mottle virus (CCMV) that is altered in virion stability. The mutant virions resist disassembly in 1.0 M NaCl, pH 7.5, whereas the wild-type virions completely disassociate into RNA and capsid protein components. Sequence analysis of the mutant coat protein gene identified a single A to G nucleotide change at position 1484 of RNA 3 (position 134 of RNA 4), which results in a lysine to arginine change at position 42 of the coat protein. Introduction of the K42R mutation into wild-type CCMV coat protein results in a salt stable virion phenotype. Likewise, expression of the K42R mutant coat protein in Escherichia coli followed by in vitro assembly produces virions that exhibit the salt stable phenotype. Analysis of this mutation demonstrates how a single amino acid change in the primary structure of the coat protein leads to tertiary interactions which stabilize the virion.


Molecular-Level Insights into the Notorious CO Poisoning of Platinum Catalyst.
Carbon monoxide (CO) is notorious for its strong adsorption to poison platinum group metal catalysts in the chemical industry. Here, we conceptually distinguish and quantify the effects of the occupancy and energy of d electrons, emerging as the two vital factors in d-band theory, for CO poisoning of Pt nanocatalysts. The stepwise defunctionalization of carbon support is adopted to fine-tune the 5d electronic structure of supported Pt nanoparticles. Excluding other promotional mechanisms, the increase of Pt 5d band energy strengthens the competitive adsorption of hydrogen against CO for the preferential oxidation of CO, affording the scaling relationship between Pt 5d band energy and CO/H2 adsorption energy difference. The decrease of Pt 5d band occupancy lowers CO site coverage to promote its association with oxygen for the total oxidation of CO, giving the scaling relationship between Pt 5d occupancy and activation energy. The above insights outline a molecular-level understanding of CO poisoning.


Ligation and cut as a method for bile duct division in living donor right hepatectomy.
The importance of bile duct division cannot be overemphasized in living donor surgery. Ligation and cut (LC) as a method for bile duct division in living donor right hepatectomy (LDRH) has never been reported. The purpose of this study was to introduce the LC method of bile duct division in LDRH. All LDRH donors were identified through a prospectively maintained database at the authors' institution between September 2009 and March 2013, and the 2 methods, LC and cut and oversewing (CO), were compared both in terms of donor and recipient outcomes of right lobe living donor liver transplantation. In the LC method, after complete parenchymal transection, the right hepatic duct was dissected in the Glisson's sheath and ligated just at the right side of the confluence, and then the right side of the ligature was cut. The LC and CO methods were performed in 109 and 134 donors, respectively. Bile duct division time (P < 0.001) and operative time (P < 0.001) were significantly shorter in the LC group than in the CO group. With a median follow-up of 60.2 months, biliary complication rate was lower in the LC group than in the CO group (0% versus 5.2%; P = 0.01), but with no significant difference between the recipient groups. All donors made a complete recovery. In conclusion, the bile ducts of living donors can be dissected safely from the Glisson's sheath, and the LC method facilitates bile duct division and has a lower incidence of biliary complication in LDRH without compromising the recipient outcomes. Liver Transplantation 23 448-456 2017 AASLD.


Transcriptional activation of homologous viral long terminal repeats by the human immunodeficiency virus type 1 or the human T-cell leukemia virus type I tat proteins occurs in the absence of de novo protein synthesis.
The genomes of human retroviruses [human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus (HTLV-I)] encode positive trans-activator proteins, named tat. In the presence of tat, the transcriptional activity of the homologous HIV-1 or HTLV-I long terminal repeat (LTR) promoter is markedly increased. We have constructed mammalian cell lines that contain stably integrated copies of a HIV-1 or a HTLV-I LTR-chloramphenicol acetyltransferase (CAT) gene. When presynthesized HIV-1 or HTLV-I tat proteins were separately introduced into these cells in the presence of cycloheximide, we found a strong increase in the steady-state expression of the homologous viral LTR. Nuclear "run-on" assays verified that this tat-mediated enhancement, occurring in the absence of de novo cellular protein synthesis, was due to increased transcriptional initiation at the LTR promoter. We conclude that one aspect of transcriptional trans-activation of viral LTR by the HIV-1 and HTLV-I tat proteins does not require the production of new cellular proteins.


Basics: Excipients Used in Nonsterile Compounding, Part 2.
The July-August 2019 issue of the International Journal of Pharmaceutical Compounding includes part 1 of a 3-part article on the topic of excipients used in nonsterile compounding. This article, which discusses dosage form design and excipients related to appearance, palatability, flavoring, sweetening, and coloring, represents part 2 of this 3-part series. Part 3 will discuss preservatives used in nonsterile preparations. The topics presented in part 2 are very important for patient compliance. The colors, flavors, sweetening, appearance, and other dosage form characteristics can often be modified to enhance compliance by the patient, which can aid in therapeutic effectiveness.


Transcriptional regulation of the gene coding for human protein C.
The promoter for the gene coding for human protein C has been characterized as to nucleotide sequences that regulate the synthesis of mRNA. The major transcription start site was found 65 nucleotides upstream from the first intron/exon boundary along with two minor sites. Functional characterization of 1528 base pairs at the 5'-end of the gene was then carried out by chloramphenicol acetyltransferase reporter assays, protection from DNase I digestion, and electrophoretic mobility shift assays employing HepG2 and HeLa cells. One of the upstream regions (nucleotides -25 to +9) contained binding sites for at least two different transcription factors, including a hepatic nuclear factor 1-binding site (-10 to +9) and two overlapping and oppositely oriented hepatic nuclear factor 3-binding sites (-25 to -11). A second major region (PCE1) (+12 to +30) appeared to be a unique, liver-specific regulatory sequence. An Sp1-binding site in exon I (+58 to +65) was also recognized by cotransfection experiments with an Sp1 expression plasmid. Specific mutations in these promoter elements reduced transcriptional activity and abolished the binding of hepatic nuclear proteins. Finally, a strong silencer element (PCS1) (between -162 and -82) and two possible liver-specific enhancer regions (PCE2 and PCE3), which interact coordinately with the promoter elements, were also found (between -1462 and -162).


Inadequacy of visual alarms in helicopter air medical transport.
Air medical programs use medical equipment primarily designed for hospital and/or ground transport settings. Many of these medical devices are equipped with auditory alarms of malfunction or deteriorating clinical status. The high ambient noise requires visual scanning of medical devices to detect alarm conditions in the helicopter cabin. To evaluate the adequacy of visual scanning for alarm conditions in the helicopter air medical environment. The helicopter transport program used in this study is staffed with two medical crewmembers. Flight nurse response time (RT) to a visual alarm was assessed during 25 air medical patient flights. RT was measured using a battery powered dual timer device with a red LED visual alarm placed in a fixed position among the medical instruments. The device was activated at a random time point unknown to the medical crew during each patient flight. RT was defined as the elapsed time from activation of the alarm until it was physically switched off by the flight nurse. RT was surprisingly lengthy for the study population with a mean RT of 81.2 +/- 78.4 s (95% CI 48.8-113.5 s). The variability of RT was also surprising ranging from 3 s to > 5 min. RT to visual alarms in the air medical environment is lengthy and quite variable. Recognition of malfunction of medical equipment or early signs of clinical instability prior to clinical deterioration cannot be assured by visual scanning for alarm conditions. Alternative alarming systems should be considered and investigated for air medical transport.


The evolution of multiple mating: Costs and benefits of polyandry to females and of polygyny to males.
Polyandry is a paradox: why do females mate multiple times when a single ejaculate often provides enough sperm for lifetime egg production? Gowaty et al. addressed explanations for polyandry in Drosophila pseudoobscura from the perspective of hypotheses based on sex differences in costs of reproduction (CoR). Contrary to CoR, Gowaty et al. showed that (1) a single ejaculate was inadequate for lifetime egg production; (2) polyandry provided fitness benefits to females beyond provision of adequate sperm and (3) fitness benefits of polyandry were not offset by costs. Here, I discuss predictions of the ad hoc hypotheses of CoR and three alternative hypotheses to CoR to facilitate a discussion and further development of a strong inference approach to experiments on the adaptive significance of polyandry for females. Each of the hypotheses makes testable predictions; simultaneous tests of the predictions will provide a strong inference approach to understanding the adaptive significance of multiple mating. I describe a sex-symmetric experiment meant to evaluate variation in fitness among lifelong virgins (V); monogamous females and males with one copulation (MOC); monogamous females and males with multiple copulations (MMC); PAND, polyandrous females; and PGYN, polygynous males. Last, I recommend the study of many different species, while taking care in choice of study species and attention to the assumptions of specific hypotheses. I particularly urge the study of many more Drosophila species both in laboratory and the wild to understand the "nature of flies in nature," where opportunities and constraints mold evolutionary responses.


Selecting the Right Tool: Comparison of the Analytical Performance of Infrared Attenuated Total Reflection Accessories.
The analytical performance of four commercially available infrared attenuated total reflection (IR-ATR) accessories with various ATR waveguide materials has been analyzed and evaluated using acetate, CO2, and CO3 (2-) solutions. Calibration functions have been established to determine and compare analytically relevant parameters such as sensitivity, signal-to-noise ratio (SNR), and efficiency. The obtained parameters were further analyzed to support conclusions on the differences in performance of the individual IR-ATR accessories.


A Systematic Approach to Diagnosing Arthritis Based on Radiological Imaging.
Radiology plays a key role in the diagnosis of arthritis. We herein suggest an algorithmic approach to diagnosing arthritis. First, the number of joint involvements is reviewed. Monoarticular arthritis includes septic arthritis, pigmented villonodular synovitis, and synovial chondromatosis. Second, polyarticular arthritis can be categorized by its characteristics: erosive, productive, and mixed. Erosive disease includes rheumatoid arthritis, hemophilia, and amyloidosis, while productive disease includes osteoarthritis and hemochromatosis. Third, mixed diseases are subcategorized by symmetricity. Ankylosing spondylitis and inflammatory bowel disease related arthritis affect joints symmetrically, while psoriatic arthritis, reactive arthritis, and crystalline arthropathy are asymmetric. Adjacent soft tissue density, periostitis, and bone density are ancillary findings that can be used as additional differential diagnostic clues. The final step in identifying the type of arthritis is to check whether the location is a site frequently affected by one particular disease over another. This systematic approach would be helpful for radiologists in diagnosing arthritis.


Do We Finally Know Whether CPAP Improves Quality of Life in Non-Sleepy Patients?
Weaver TE. Do we finally know whether CPAP improves quality of life in non-sleepy patients? J Clin Sleep Med. 2019;15(9):1193-1194.


Clinical efficacy of farcosolvin syrup (ambroxol-theophylline-guaiphenesin mixture) in the treatment of acute exacerbation of chronic bronchitis.
Acute exacerbations of chronic bronchitis (AECB) are defined as recurrent attacks of worsening bronchial inflammation that are marked by an increase in the volume of daily sputum produced, a change in color of the expectorated sputum, and worsening dyspnea. Farcosolvin (Pharco Pharmaceuticals, Alexandria, Egypt) is a mixture of ambroxol (15 mg); theophylline (50 mg); and guaiphenesin (30 mg), per 5 mL syrup. To test the clinical efficacy of Farcosolvin in the treatment of AECB in a randomized, single-blinded, controlled study design. One hundred patients with AECB were randomized to either Farcosolvin or guaiphenesin treatment groups, in addition to the standard medical treatment for their cases. Baseline clinical symptomatolgy of breathlessness, cough, and sputum severity scoring were compared before and after 3 and 7 days of treatment in both groups and the differences compared between groups. Changes in perceived improvement were also compared between groups using the Clinical Global Impression of Improvement or Change Scale (CGIC). There were statistically significant improvements in breathlessness and cough scores in both groups (pretreatment versus posttreatment at day 3 and at day 7; P < 0.05). There were highly statistically significant differences between groups in improvement in breathlessness and cough scores, after 3 and 7 days treatment, in favor of the Farcosolvin treatment group (P < 0.001). Out of 50 patients, 48 (96%) in the Farcosolvin-treated group rated their improvement on the CGIC scale as "much" and "very much" improved, while only 41 patients (82%) reported such a degree of improvement in the control group. The difference was statistically significant (P < 0.05). We concluded from our study that Farcosolvin syrup might be safe and effective in improving symptoms in cases of acute exacerbation of chronic bronchitis.


Developmentally regulated expression of pfs16, a marker for sexual differentiation of the human malaria parasite Plasmodium falciparum.
Sexual differentiation is essential for the transmission of Plasmodium to mosquitoes and therefore, for the spread of malaria. The molecular mechanisms underlying sexual differentiation are poorly understood but may be elucidated by a detailed study of the regulation of expression of sexual stage specific genes. In the present work we describe the differential expression of the gene encoding the sexual stage specific protein, Pfs16. We have conducted a comparative analysis of pfs16 promoter activity, RNA levels and the rate of de novo protein synthesis during development of Plasmodium falciparum. Furthermore, we have determined the pattern of expression of pfs16 transcripts at the single cell level by in situ hybridisation. We show that the expression of pfs16 is induced immediately following the invasion of a red blood cell in sexually committed ring stage parasites and continues throughout gametocytogenesis and in macrogametes. The expression of pfs16 is regulated at the level of transcription initiation and modulated by a post-transcriptional process. These results demonstrate that the expression of the pfs16 gene is the earliest event in the sexual differentiation process of P. falciparum described to date.


Amelioration of hypoxia and LPS-induced intestinal epithelial barrier dysfunction by emodin through the suppression of the NF-κB and HIF-1α signaling pathways.
Intestinal barrier dysfunction occurs in critical illnesses and involves the inflammatory and hypoxic injury of intestinal epithelial cells. Researchers are still defining the underlying mechanisms and evaluating therapeutic strategies for restoring intestinal barrier function. The anti-inflammatory drug, emodin, has been shown to exert a protective effect on intestinal barrier function; however, its mechanisms of action remain unknown. In this study, we investigated the protective effects of emodin on intestinal barrier function and the underlying mechanisms in intestinal epithelial cells challenged with lipopolysaccharide (LPS) and hypoxia/reoxygenation (HR). To induce barrier dysfunction, Caco-2 monolayers were subjected to HR with or without LPS treatment. Transepithelial electrical resistance and paracellular permeability were measured to evaluate barrier function. The expression of the tight junction (TJ) proteins, zonula occludens (ZO)-1, occludin, and claudin-1, as well as that of hypoxia-inducible factor (HIF)-1α, phosphor-IκB-α, phosphor-nuclear factor (NF)-κB p65 and cyclooxygenase (COX)-2 was determined by western blot analysis. The results revealed that emodin markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS and subjected to HR. Emodin also markedly alleviated the damage caused by LPS and HR (manifested by a decrease in the expression of the TJ protein, ZO-1), and inhibited the expression of HIF-1α, IκB-α, NF-κB and COX-2 in a dose-dependent manner. In conclusion, our data suggest that emodin attenuates LPS- and HR-induced intestinal epithelial barrier dysfunction by inhibiting the HIF-1α and NF-κB signaling pathways and preventing the damage caused to the TJ barrier (shown by the decrease in the expression of ZO-1).


Second surgical treatment of retroperitoneal persistent disease in epithelial ovarian cancer.
This report retrospectively analyzes 9 cases of epithelial ovarian cancer with persistent retroperitoneal metastasis after intraperitoneal surgery (without systematic lymphadenectomy) and chemotherapy. All 9 patients were diagnosed as FIGO stage I to IV at the time of primary surgery. They received combined postoperative chemotherapy (8 cases with a cisplatin-based regimen and 1 with adriamycin and endoxan). They were submitted to pelvic and paraaortic lymphadenectomy at the National Cancer Institute of Milan during the period 1990-1994. All patients presented no evidence of disease in the abdominal cavity but retroperitoneal metastasis, which was the unique metastatic site. Chemotherapy was administered as adjuvant therapy after lymphadenectomy. Six patients were free of disease for 14 to 61 months. One patient with vaginal recurrence at the 18th month was treated with radiotherapy and chemotherapy, but died of widespread disease 25 months after lymphadenectomy. Two patients with massive positive lymph nodes dies of brain and lung metastasis 20 and 6 months later, respectively. We conclude that retroperitoneal metastasis may be the only site of persistent disease and that systematic lymphadenectomy technically feasible in this situation to increase the opportunity for local disease control and to obtain a good result.


Choice of Unmanipulated T Cell Replete Graft for Haploidentical Stem Cell Transplant and Posttransplant Cyclophosphamide in Hematologic Malignancies in Adults: Peripheral Blood or Bone Marrow-Review of Published Literature.
Allogeneic hematopoietic stem cell transplantation (SCT) is often the only curative option for many patients with malignant and benign hematological stem cell disorders. However, some issues are still of concern regarding finding a donor like shrinking family sizes in many societies, underrepresentation of the ethnic minorities in the registries, genetic variability for some races, and significant delays in obtaining stem cells after starting the search. So there is a considerable need to develop alternate donor stem cell sources. The rapid and near universal availability of the haploidentical donor is an advantage of the haploidentical SCT and an opportunity that is being explored currently in many centers especially using T cell replete graft and posttransplant cyclophosphamide. This is probably because it does not require expertise in graft manipulation and because of the lower costs. However, there are still lots of unanswered questions, like the effect of use of bone marrow versus peripheral blood as the source of stem cells on graft-versus-host disease, graft versus tumor, overall survival, immune reconstitution, and quality of life. Here we review the available publications on bone marrow and peripheral blood experience in the haploidentical SCT setting.


Synthetic polymer nanoparticle-polysaccharide interactions: a systematic study.
The interaction between synthetic polymer nanoparticles (NPs) and biomacromolecules (e.g., proteins, lipids, and polysaccharides) can profoundly influence the NPs fate and function. Polysaccharides (e.g., heparin/heparin sulfate) are a key component of cell surfaces and the extracelluar matrix and play critical roles in many biological processes. We report a systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides by ITC, SPR, and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications. The interaction between acrylamide nanoparticles (~30 nm) and heparin is mainly enthalpy driven with submicromolar affinity. Hydrogen bonding, ionic interactions, and dehydration of polar groups are identified to be key contributions to the affinity. It has been found that high charge density and cross-linking of the NP can contribute to high affinity. The affinity and binding capacity of heparin can be significantly diminished by an increase in salt concentration while only slightly decreased with an increase of temperature. A striking difference in binding thermodynamics has been observed when the main component of a polymer nanoparticle is changed from acrylamide (enthalpy driven) to N-isopropylacryalmide (entropy driven). This change in thermodynamics leads to different responses of these two types of polymer NPs to salt concentration and temperature. Select synthetic polymer nanoparticles have also been shown to inhibit protein-heparin interactions and thus offer the potential for therapeutic applications.


Breast cancer: magnitude of the problem and descriptive epidemiology.
Breast cancer is the most common cancer among women in the United States. Knowledge of the descriptive epidemiology of breast cancer is useful both in suggesting etiologic hypotheses and, if preventive measures can be identified, in delineating high-risk groups to be targeted for preventive efforts. Demographic risk factors include increasing age (in Western countries), being white for breast cancer diagnosed at age 45 years or more, being black for breast cancer diagnosed at less than 40 years of age, high socioeconomic status, having never married, being of the Jewish faith, urban residence, and residence in the northern (as compared with the southern) United States. Incidence rates are generally highest in North American and Northern European countries, intermediate in Southern and Eastern European and South American countries, and lowest in Asia and Africa. The most notable characteristic of the descriptive epidemiology of breast cancer in recent years is perhaps the rapidly increasing incidence rates in developing countries. Identification of specific reasons for these increasing rates would contribute substantially to our understanding of the epidemiology of breast cancer.


Proximal Tibiofibular Joint Inclination Angle and Associated Meniscal Tear in Patients with Discoid Lateral Meniscus.
Background and objectives:Discoid lateral meniscus (DLM) is the most common congenital variant of a meniscus with a high prevalence meniscal tear due to abnormal shape and behavior. The proximal tibiofibular joint (PTFJ) has an important role during knee extension and ankle dorsiflexion. The aim of this research is to study the association between PTFJ morphology in MRI and DLM and its pathologies as compared with the normal lateral meniscus in Iranian population. Materials and methods:Totally, 1729 MRI scans were reviewed, and 69 scans were selected based on inclusion/exclusion criteria. A group of aged-matched control patients without DLM were also included in this study. MRI scans were studied for DLM, meniscal tear and PTFJ inclination angle (horizontal or oblique). Findings were compared with those of patients without DLM. Results:The frequency of horizontal-type PTFJ was significantly higher in the DLM group than in the control group. We also found a strong association (p value=0.018) between horizontal-type PTFJ and meniscal tear as compared with oblique-type in patients with DLM. Conclusion:Horizontal-type PTFJ is more prevalent in patients with DLM. The meniscal tear is also more frequently seen in patients with DLM and horizontal-type PTFJ. Larger prospective studies are needed to confirm these results.


Implementing the Americans with Disabilities Act. 1996 follow-up report on Sears, Roebuck and Co.
This article is the second in a series examining the employment practices of Sears, Roebuck and Co. in light of its compliance with the Americans with Disabilities Act of 1990. Sears employs approximately 20,000 persons with disabilities, nearly 7000 individuals with orthopedic disabilities. The article describes findings from two major areas of inquiry relevant for spine professionals: 1) the costs and benefits of workplace accommodations, and 2) the ways in which Sears and other companies informally and formally resolve Americans with Disabilities Act Title I disputes.


Timing of Urinary Pad Exchanges Was the Most Important Factor Affecting Quality of Life in the Early Postoperative Period After Robot-Assisted Laparoscopic Radical Prostatectomy.
The aim of the present study is to investigate the effect of pad use for postprostatectomy incontinence on urinary quality of life (QoL) after robot-assisted laparoscopic radical prostatectomy (RARP) in the early postoperative period. Ninety patients underwent RARP simultaneously completed International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and modified pad use questionnaire that evaluated pad use and urinary QoL and a 24-hour pad test. Pad use was also assessed by pad form, pad size, the number of pad exchanges per day, and the timing of pad exchanges (i.e., to what extent the pad was wet when the patients exchanged it.). The investigation involved patients visiting the outpatient clinic for the first time after RARP. The association between pad use and urinary QoL was investigated. The mean frequency of pad exchanges was 2±2/day. The mean 24-hour pad test was 139±193 g/day. Multivariate analyses revealed the timing of pad exchanges was significantly associated with QoL on the ICIQ-SF and the modified pad use questionnaire (P=0.007 and P<0.001, respectively) and the number of pad exchanges per day was significantly associated with QoL on the ICIQ-SF (P=0.01); QoL worsened with pad wetness and increasing frequency of pad exchange. The other factors relating to pad use were not significantly associated with aggravation of QoL. In the early postoperative period after RARP, the timing of pad exchanges was the most important factor affecting QoL. Namely, patients with postprostatectomy incontinence should wear the appropriate size of pad according to the volume of urinary incontinence and exchange pads when the pad is not too wet. On the other hand, pad form, pad size, and volume of urinary incontinence were not associated with decreased QoL.


Ventilator-associated pneumonia using a heated humidifier or a heat and moisture exchanger: a randomized controlled trial [ISRCTN88724583].
Some guidelines to prevent ventilator-associated pneumonia (VAP) do not establish a recommendation for the preferential use of either heat and moisture exchangers (HMEs) or heated humidifiers (HHs), while other guidelines clearly advocate the use of HMEs. The aim of this study was to determine the incidence of VAP associated with HHs or HMEs. A randomized study was conducted in the intensive care unit of a university hospital involving patients expected to require mechanical ventilation for >5 days. Patients were assigned to two groups; one group received HH and the other group received HME. Tracheal aspirate samples were obtained on endotracheal intubation, then twice a week, and finally on extubation, in order to diagnose VAP. Throat swabs were taken on admission to the intensive care unit, then twice a week, and finally at discharge from the intensive care unit in order to classify VAP as primary endogenous, secondary endogenous, or exogenous. A total of 120 patients were assigned to HMEs (60 patients) and HHs (60 patients); 16 patients received mechanical ventilation for less than five days and were excluded from the analysis. Data analysis of the remaining 104 patients (53 HMEs and 51 HHs) showed no significant differences between groups regarding sex, age, Acute Physiology and Chronic Health Evaluation II score, pre-VAP use of antibiotics, days on mechanical ventilation, and diagnosis group. VAP was found in eight of 51 (15.69%) patients in the HH group and in 21 of 53 (39.62%) patients in the HME group (P = 0.006). The median time free of VAP was 20 days (95% confidence interval, 13.34-26.66) for the HH group and was 42 days (95% confidence interval, 35.62-48.37) for the HME group (P <0.001). Cox regression analysis showed the HME as a risk factor for VAP (hazard rate, 16.2; 95% confidence interval, 4.54-58.04; P < 0.001). The patients mechanically ventilated during more than 5 days developed a lower incidence of VAP with a heated humidifier than heat and moisture exchanger.


Trends in the home management of non-fatal acute myocardial infarction in Perth, Western Australia between 1984 and 1993.
Trends in the incidence of acute myocardial infarction (AMI) that are based on admissions to hospital would be misleading if the proportion of non-fatal infarctions treated at home changed over time. To estimate trends in the management at home of cases of non-fatal AMI in Perth between 1984 and 1993 in order to determine if the number of such cases has remained consistently small and can be neglected in studies of the incidence of AMI. In 1989, 251 general practitioners in Perth responded to a postal questionnaire asking about management of cases of AMI at home in the preceding 12 months. In 1993, 288 general practitioners and 174 physicians responded to the same questionnaire. We estimate that 1.5% of all patients less than 65 years of age diagnosed with non-fatal AMI were managed at home in 1989. The corresponding figure for 1993 was 4.1%. A previous study in Perth in 1984 found that 3.9% of cases of non-fatal AMI in patients less than 65 years of age were managed at home. The management at home of cases of non-fatal AMI in people of working age in Perth has remained at a negligible level from 1984 to 1993. Thus a register based on admissions to hospital for AMI will accurately reflect trends in AMI in people of working age.


Brain-computer interface in stroke: a review of progress.
Brain-computer interface (BCI) technology has been used for rehabilitation after stroke and there are a number of reports involving stroke patients in BCI-feedback training. Most publications have demonstrated the efficacy of BCI technology in post-stroke rehabilitation using output devices such as Functional Electrical Stimulation, robot, and orthosis. The aim of this review is to focus on the progress of BCI-based rehabilitation strategies and to underline future challenges. A brief history of clinical BCI-approaches is presented focusing on stroke motor rehabilitation. A context for three approaches of a BCI-based motor rehabilitation program is outlined: the substitutive strategy, classical conditioning and operant conditioning. Furthermore, we include an overview of a pilot study concerning a new neuro-forcefeedback strategy. This pilot study involved healthy participants. Finally we address some challenges for future BCI-based rehabilitation.


Management of gastrointestinal failure in the adult critical care setting.
Gastrointestinal failure is a polymorphic syndrome with multiple causes. Managing the different situations from a practical, metabolic, and nutritional point of view is challenging, which the present review will try to address. Acute gastrointestinal injury (AGI) has been defined and has evolved into a concept of gastrointestinal dysfunction score (GIDS) built on the model of Sequential Organ Failure Assessment (SOFA) score, and ranging from 0 (no risk) to 4 (life threatening). But there is yet no specific, reliable and reproducible, biomarker linked to it. Evaluating the risk with the Nutrition Risk Screening (NRS) score is the first step whenever addressing nutrition therapy. Depending on the severity of the gastrointestinal failure and its clinical manifestations, nutritional management needs to be individualized but always including prevention of undernutrition and dehydration, and administration of target essential micronutrients. The use of fibers in enteral feeding solutions has gained acceptance and is even recommended based on microbiome findings. Parenteral nutrition whether alone or combined to enteral feeding is indicated whenever the intestine is unable to process the needs. The heterogeneity of gastrointestinal insufficiency precludes a uniform nutritional management of all critically ill patients but justifies its early detection and the implementation of individualized care.


Long-term Follow-up of a Patient with Portal Hypertension and Hepatic Failure Due to Hepatic Hydatid Disease.
We observed liver failure with a presumed etiology of echinococcosis in an 89-year-old woman. Our patient had been born and then resided on Rebun Island until she was 12 years old. At 46 years old, she had been referred to our hospital due to right abdominal pain. Ultrasound had revealed multilocular cysts in the right lobe of the liver. At 84 years old, the hepatic cyst occupied nearly the entire liver with ring-shaped calcification along the cyst wall. The patient was diagnosed with decompensated cirrhosis and hepatic hydatid disease based on typical imaging and the long-term natural clinical course.


Characteristic systemic cytokine responses in children with human bocavirus-positive lower respiratory tract infection.
To investigate systemic cytokine responses in human bocavirus (HBoV)-associated lower respiratory tract infection, serum cytokine profiles were analyzed in HBoV positive-children (n=14) using multiplex immunoassay. Concentrations of TNF-a, IL-2, IL-5 and IL-8 on admission were significantly different from those of respiratory syncytial virus-positive children (n=28). This unique cytokine response might partly explain some characteristic clinical features of HBoV-associated respiratory infection.


Clinical use of a low-dose medetomidine infusion in healthy dogs undergoing ovariohysterectomy.
Eight healthy dogs undergoing elective ovariohysterectomy were anesthetized with a standard protocol and received a low-dose medetomidine constant rate infusion during surgery. Cardiorespiratory parameters, including non-invasive cardiac output, were measured at various times. This protocol resulted in acceptable and stable cardiovascular performance, allowed low isoflurane concentrations, and provided smooth recoveries.


Long-term effects of pharmacological inhibition of anaplastic lymphoma kinase in neurofibromatosis 1 mutant mice.
Neurofibromatosis type 1 (NF1) is associated with behavioral alterations and cognitive impairments. There is a genetic interaction between NF1 and the receptor tyrosine kinase Alk. Short-term pharmacological Alk inhibition, with a compound FDA-approved for cancer starting 10 days prior to cognitive testing, was shown to improve cognitive performance of NF1 heterozygous (HET) mice. However, effects of long-term Alk inhibition on behavioral cognitive performance are not known. Therefore, in the study described below we determine the effects of prolonged pharmacological Alk inhibition for 24 weeks on behavioral and cognitive performance of NF1 HET mice. As these studies have the ultimate objective of developing a treatment for humans with neurofibromatosis and acceptable side effects in the context of cancer are not acceptable in the context of long-term treatment of patients with neurofibromatosis, we included additional behavioral tests of anxiety-like and depressive-like behaviors as well. Long-term effects of Alk inhibition had genotype-dependent effects, consistent with a specific interaction between Alk and NF1. Beneficial effects of long-term Alk inhibition in NF1 HET mice included rescue of impairments in object recognition in NF1 HET males and females, and improved cognitive performance of NF1 HET males and females in the water maze test. In contrast, long-term Alk inhibition had detrimental effects in WT mice not seen after short-term treatments. As longer treatments are translationally more relevant for NF1 patients, these data highlight the important to assess long-term effects of drugs, especially of repurposed drugs used originally as part of cancer therapy.


Inducing heat shock protein 70 expression provides a robust antithrombotic effect with minimal bleeding risk.
Antithrombotic medications target coagulation factors. Their use is associated with an increased bleeding risk. Safer drugs are needed. The heat shock protein 70 (Hsp70) exhibits antithrombotic properties that do not influence bleeding. By using murine models, we aimed to test the hypothesis that overexpressing Hsp70 with CM-695, a first in class dual inhibitor of HDAC6 and phosphodiesterase 9, protects against thrombosis while leaves bleeding tendency unaltered. CM-695 was used to induce Hsp70 overexpression. Hsp70 overexpressing mice were submitted to three thrombosis-triggering procedures. The ferric chloride carotid artery model was used to compare the antithrombotic role of CM-695 and rivaroxaban, a direct oral anticoagulant. The mouse tail transection model was used to compare the bleeding tendency upon CM-695 or rivaroxaban administration. Intraperitoneal (i. p.) 20 mg/kg CM-695 increased Hsp70 expression markedly in the murine aortic tissue. This treatment delayed thrombosis in the collagen/epinephrine [p=0.04 (Log-Rank test), n=10], Rose Bengal/laser [median vessel occlusion time (OT): 58.6 vs 39.0 minutes (min) in the control group (CG), p=0.008, n≥10] and ferric chloride (OT: 14.7 vs 9.2 min in the CG, p=0.032, n≥10) models. I.p. 80 mg/kg CM-695 (n≥9) and intravenous 3 mg/kg rivaroxaban (n≥8) significantly delayed thrombosis. CM-695 did not induce bleeding [median bleeding time (BT): 8.5 vs 7.5 min in the CG, n≥10]. However, BT was dramatically increased by rivaroxaban (30.0 vs 13.7 min in the CG, p=0.001, n=10). In conclusion, CM-695 is a new antithrombotic small molecule devoid of bleeding risk that may be envisioned as a useful clinical tool.


Glenohumeral arthroplasty: indications and preoperative considerations.
The indications for glenohumeral arthroplasty are severe pain and restricted range of motion associated with radiographic evidence of advanced glenohumeral arthritis. Nonsurgical management consisting of rest, physical therapy, and antiinflammatory medication should be tried before considering surgical management. It is important that each patient be evaluated on the basis of the clinical disease and radiographic characteristics of the underlying diagnosis. Preoperative considerations should include a careful assessment of bone quality and quantity and associated deformity. Evaluation of the soft tissues, particularly the rotator cuff and deltoid muscles, is essential because the success of total shoulder arthroplasty depends greatly on the integrity of these structures. Associated upper and lower extremity degenerative arthritis should be evaluated and carefully considered, particularly with respect to the timing of surgical management. Careful consideration of these factors is invaluable in obtaining successful outcomes of total shoulder arthroplasty.


The histochemical structure of the deep fascia and its structural response to surgery.
The histochemical structure of the deep fascia and its interface with the underlying muscle was examined in ten pigs. This structure was also evaluated after it had been raised as a fascial flap and in another site after the underlying muscle surface had been disrupted. The deep fascial is a simple structure of densely-packed collagen bundles and elastin fibres, and has hyaluronic acid concentrated on its inner surface, which is in contact with the underlying muscle. There is no specialised lining of this surface of the fascia to account for its gliding properties. The post-surgical specimens demonstrated preservation of the structure of the interface between fascia and muscle, including the retention of the hyaluronic acid lining, if the epimysium was intact. However, if the epimysium was disrupted, the structure of the interface was obliterated.


Cholelithiasis in hepatic cirrhosis: evaluating the role of risk factors.
To determine the role of risk factors, which promote cholelithasis in Hepatic Cirrhosis (HC). A prospective study was conducted on indoor cases with advanced HC. Outpatients with compensated Chronic Liver Disease were used as control. The subjects with history of cholecystectomy and diabetes mellitus were excluded from the study. Conventional ultrasound was used for the detection of gallstones, ascites and portal hypertension. Sonography also furnished pertinent information about the portal vein diameter, size of the spleen, gallbladder wall thickness and echogenecity of the liver. The number of registered cases was 206: (age: 30-85 years): 121 (58.7%) males and 85 (41.3%) females. Hepatitis C (HCV) was the cause of HC in 187 (90.88%) cases. Of 50 (24.30%) patients with detectable gallstones, 27(54.00%) were males. We observed correlation of several risk factors with cholelithasis in our patients (n = 50): advanced age: mean 57.3 +/- 9.7 years (100%); prolonged duration of HC: 3.5 years (100%); Child-Pughs' class C: 34 (68%); increased thickness of gallbladder wall: 45 (90%); gross ascites: 39 (78%); splenic enlargement: 17.3 cm (100%); increased portal vein diameter: 13.4mm (100%). The results were statistically significant when compared with the control group (p = < 0.001). Gallstones tend to occur more frequently in patients with decompensated CLD due to interaction of several risk factors in these patients.


CGDV: a webtool for circular visualization of genomics and transcriptomics data.
Interpretation of large-scale data is very challenging and currently there is scarcity of web tools which support automated visualization of a variety of high throughput genomics and transcriptomics data and for a wide variety of model organisms along with user defined karyotypes. Circular plot provides holistic visualization of high throughput large scale data but it is very complex and challenging to generate as most of the available tools need informatics expertise to install and run them. We have developed CGDV (Circos for Genomics and Transcriptomics Data Visualization), a webtool based on Circos, for seamless and automated visualization of a variety of large scale genomics and transcriptomics data. CGDV takes output of analyzed genomics or transcriptomics data of different formats, such as vcf, bed, xls, tab limited matrix text file, CNVnator raw output and Gene fusion raw output, to plot circular view of the sample data. CGDV take cares of generating intermediate files required for circos. CGDV is freely available at https://cgdv-upload.persistent.co.in/cgdv/ . The circular plot for each data type is tailored to gain best biological insights into the data. The inter-relationship between data points, homologous sequences, genes involved in fusion events, differential expression pattern, sequencing depth, types and size of variations and enrichment of DNA binding proteins can be seen using CGDV. CGDV thus helps biologists and bioinformaticians to visualize a variety of genomics and transcriptomics data seamlessly.


Case illustration of the self-psychological treatment of eating disorders.
The theoretical conceptualization of self-psychology and the implications for the therapist's stance open up new opportunities for the treatment of anorexia and bulimia. The major contributions of self-psychology to the treatment of anorexia and bulimia are centered upon the following principles: 1) the conceptualization of food, its consumption and avoidance as fulfilling selfobject needs, 2) the unique therapeutic stance of the therapist as selfobject who tries to empathize with the patient from an experience-near position, and 3) the respect that the theory attributes to the significance of the symptoms for the patient. This paper presents a case which can exemplify some of the principles which underlie the self-psychological understanding of eating disorders and their cure.


Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: U.S. Department of Health and Human Services interim public health recommendations, November 1997.
Fenfluramine and dexfenfluramine are appetite suppressants that were in widespread use in the United States. On July 8, 1997, 24 cases of valvular heart disease in women who had been treated with fenfluramine and phentermine were publicly reported. Although valvular lesions were observed on both sides of the heart, a left-sided valve was affected in all cases. The histopathologic features were similar to those observed in carcinoid-induced valvular disease, a serotonin-related syndrome. Based on these data, the Food and Drug Administration (FDA) issued a public health advisory on July 8, followed by letters from FDA to 700,000 U.S. health-care practitioners and institutions requesting information about any additional similar patients. Subsequently, reports of fenfluramine- or dexfenfluramine-associated valvulopathy increased. This report summarizes the data used by FDA in its decision to request voluntary withdrawal of these drugs from the market and presents interim public health recommendations for persons exposed to these drugs.


MsFLASH analysis of diurnal salivary cortisol and palpitations in peri- and postmenopausal women.
To evaluate the relationship between diurnal salivary cortisol patterns and distress from heart palpitations in midlife women. We analyzed baseline data from 293 women who were eligible for a 3 × 2 factorial trial of exercise or yoga versus routine activity, and omega-3 fish oil versus placebo for vasomotor symptoms. Women self-collected salivary cortisol using swabs at four time points over 2 consecutive days and reported distress from heart racing or pounding during the past 2 weeks using a single item. Sample description and covariate data included demographics, clinical data, vasomotor symptom frequency from daily diaries, medication use, and validated questionnaires on depression, stress, and insomnia (Patient Health Questionnaire-8, Perceived Stress Scale, and Insomnia Severity index). Data were analyzed using descriptive statistics, chi-square and t tests, and repeated measure linear regression models. Participants were on average 54.6 (SD = 3.6) years old, most were White (67%) postmenopausal (84%), and 26% reported distress related to palpitations. In adjusted models, the morning (wake plus 30-min) geometric mean daily salivary cortisol concentrations were significantly more blunted in those with distress from palpitations compared with those without distress (P ≤ 0.03). When all covariates were controlled, distress from palpitations was the sole significant predictor of wake plus 30-minute cortisol (-0.25 [-0.45 to -0.04], P = 0.02). Palpitations among midlife women may be associated with blunted morning cortisol, and this relationship is not explained by demographics, clinical variables, vasomotor symptoms, medications, depression, stress, or insomnia.


The Effect of Electroporation of a Lyotroic Liquid Crystal Genistein-Based Formulation in the Recovery of Murine Melanoma Lesions.
A lamellar lyotropic liquid crystal genistein-based formulation (LLC-Gen) was prepared in order to increase the aqueous solubility of the lipophilic phytocompound genistein. The formulation was applied locally, in a murine model of melanoma, with or without electroporation. The results demonstrated that, when the formulation was applied by electroporation, the tumors appeared later. During the 21 days of the experiment, the LLC-Gen formulation decreased the tumor volume, the amount of melanin and the degree of erythema, but when electroporation was applied, all these parameters indicated a better prognosis even (lower tumor volume, amount of melanin and degree of erythema). Although hematoxylin-eosin (HE) staining confirmed the above events, application of the LLC-Gen formulation by electroporation did not lead to a significant effect in terms of the serum concentrations of the protein S100B and serum neuron specific enolase (NSE), or the tissue expression of the platelet-derived growth factor receptor β (PDGFRβ) antibody.


Impact of pre-event testing and quarantine on reducing the risk of COVID-19 epidemic rebound: a modelling study.
With the evolving growth of the COVID-19 epidemic, travel restriction policies would need to be adjusted accordingly. Prohibition of mass event may be relaxed for social and economic benefits when virus transmission stops but could bear the risk of epidemic rebound. Against the background of the varied SARS-CoV-2 prevalence internationally, we modelled the potential impacts of pre-event interventions on epidemic risk of holding a mass event when COVID-19 is under control. We developed a mathematical model of SARS-CoV-2 transmission in Guangdong Province, China, where local virus transmission ceased to occur. A large-scale international trade fair was assumed to be held, with influx of people from overseas and rest of China over a short period of time, who participated for 2-week. Scenarios of pre-event intervention (none, quarantine arrangement and polymerase chain reaction (PCR) testing for participants) were compared. The influence of contact pattern, SARS-CoV-2 prevalence outside the province and China, and testing coverage were examined in sensitivity analyses. In basecase scenario (no event), the epidemic has been under control since March 2020. The event would lead to the detection of 1% more confirmed cases by 31 July when community contact rate increases to pre-epidemic level. In event scenario without additional interventions, there would be 599 (93%) more new infections comparing with basecase scenario. To avert new infections, quarantining all participants before the event would be the most effective strategy, followed by quarantining all overseas participants and testing all other participants, and testing all participants before the event and on day 7. However, testing strategy is likely to be affected by the SARS-CoV-2 prevalence outside the event province. Pre-event interventions are effective for reducing the risk of epidemic rebound caused by an international large-scale event. Universal testing for participants is likely to be an effective and feasible intervention.