Orbital forcing of Cretaceous river discharge in tropical Africa and ocean response.
The tropics have been suggested as the drivers of global ocean and atmosphere circulation and biogeochemical cycling during the extreme warmth of the Cretaceous period; but the links between orbital forcing, freshwater runoff and the biogeochemistry of continental margins in extreme greenhouse conditions are not fully understood. Here we present Cretaceous records of geochemical tracers for freshwater runoff obtained from a sediment core off the Ivory Coast that indicate that alternating periods of arid and humid African climate were driven by orbital precession. Our simulations of the precession-driven patterns of river discharge with a global climate model suggest that ocean anoxia and black shale sedimentation were directly caused by high river discharge, and occurred specifically when the northern equinox coincided with perihelion (the minimum distance between the Sun and the Earth). We conclude that, in a warm climate, the oceans off tropical continental margins respond rapidly and sensitively to even modest changes in river discharge.


Design matters: A comparison of natural versus synthetic skin substitutes across benchtop and porcine wound healing metrics: An experimental study.
Skin substitutes, essential tools for helping close full thickness wounds with minimal scarring, are available in both collagen-based and synthetic polyurethane constructions. Here we explore fundamental differences between two frequently used skin substitutes and discuss how these differences may impact in vivo performance. Polyurethane- and collagen-based matrices were characterized in vitro for pore size via scanning electron microscopy, hydrophobicity via liquid contact angle, conformability via bending angle, and biocompatibility via fibroblast and keratinocyte adhesion and proliferation. These matrices were then evaluated in a full-thickness excisional pig wound study followed by histological analysis. Statistical analysis was performed using t-tests or one-way analysis of variances with Tukey's multiple post hoc comparisons, where appropriate. Average pore diameter in the tested polyurethane matrix was over four times larger than that of the collagen matrix (589 ± 297 µm vs. 132 ± 91 µm). Through liquid contact angle measurement, the collagen matrix (not measurable) was found to be hydrophilic compared to the hydrophobic polyurethane matrix (>90°). The collagen matrix was significantly more conformable than the polyurethane matrix (9 ± 2° vs. 84 ± 5° bending angle, respectively). Fibroblast and keratinocyte adhesion and proliferation assays elucidated a significantly greater ability of both cell types to attach and proliferate on collagen versus polyurethane. While the porcine study showed minimal contraction of either matrix material, histological findings between the two treatments were markedly different. Collagen matrices were associated with early fibroblast infiltration and fibroplasia, whereas polyurethane matrices elicited a strong multinucleated giant cell response and produced a network of comparatively aligned collagen fibrils. The more favorable in vitro properties of the collagen matrix led to less inflammation and better overall tissue response in vivo. Overall, our findings demonstrate how the choice of biomaterial and its design directly translate to differing in vivo mechanisms of action and overall tissue quality.


Impact of a multidimensional infection control approach on catheter-associated urinary tract infection rates in adult intensive care units in 10 cities of Turkey: International Nosocomial Infection Control Consortium findings (INICC).
We evaluate the effectiveness of a multidimensional infection control approach for the reduction of catheter-associated urinary tract infections (CAUTIs) in 13 intensive care units (ICUs) in 10 hospital members of the International Nosocomial Infection Control Consortium (INICC) from 10 cities of Turkey. A before-after prospective active surveillance study was used to determine rates of CAUTI. The study was divided into baseline (phase 1) and intervention (phase 2). In phase 1, surveillance was performed applying the definitions of the Centers for Disease Control and Prevention/National Healthcare Safety Network. In phase 2, we implemented a multidimensional approach that included bundle of infection control interventions, education, surveillance and feedback on CAUTI rates, process surveillance, and performance feedback. We used random effects Poisson regression to account for clustering of CAUTI rates across time periods. The study included 4,231 patients, hospitalized in 13 ICUs, in 10 hospitals, in 10 cities, during 49,644 patient-days. We recorded a total of 41,871 urinary catheter (UC)-days: 5,080 in phase 1 and 36,791 in phase 2. During phase 1, the rate of CAUTI was 10.63 per 1,000 UC-days and was significantly decreased by 47% in phase 2 to 5.65 per 1,000 UC-days (relative risk, 0.53; 95% confidence interval: 0.4-0.7; P value = .0001). Our multidimensional approach was associated with a significant reduction in the rates of CAUTI in Turkey.


Cockroach allergen serine proteinases: Isolation, sequencing and signalling via proteinase-activated receptor-2.
Allergy to the German cockroach (Blattella germanica) is a significant asthma risk factor for inner-city communities. Cockroach, like other allergens, contains trypsin-like enzyme activity that contributes to allergenicity and airway inflammation by activating proteinase-activated receptors (PARs). To date, the enzymes responsible for the proteolytic activity of German cockroach allergen have not been characterized. We aimed to identify, isolate and characterize the trypsin-like proteinases in German cockroach allergen extracts used for clinical skin tests. For each enzyme, we sought to determine (1) its substrate and inhibitor enzyme kinetics (Km and IC50), (2) its amino acid sequence and (3) its ability to activate calcium signalling and/or ERK1/2 phosphorylation via PAR2. Using a trypsin-specific activity-based probe, we detected three distinct enzymes that were isolated using ion-exchange chromatography. Each enzyme was sequenced by mass spectometery (deconvoluted with an expressed sequence tag library), evaluated kinetically for its substrate/inhibitor profile and assessed for its ability to activate PAR2 signalling. Each of the three serine proteinase activity-based probe-labelled enzymes isolated was biochemically distinct, with different enzyme kinetic profiles and primary amino acid sequences. The three enzymes showed a 57%-71% sequence identity with a proteinase previously cloned from the American cockroach (Per a 10). Each enzyme was found to activate both Ca++ and MAPK signalling via PAR2. We have identified three different serine proteinases from the German cockroach that may, via PAR2 activation, play different roles for allergen sensitization in vivo and may represent attractive therapeutic targets for asthma.


Changes in private psychiatric practice in Australia: An analysis of trends in claims for outpatient Medicare item numbers over 14 years.
The Better Health Access Initiative added 32 Medicare Benefits Schedule (MBS) item numbers in 2006 to increase the number of people with access to mental health care. We investigated trends in the provision of outpatient Medicare-subsidised psychiatric services since the introduction of these item numbers in 2006 through 2019. Medicare Benefits Schedule aggregated item-number claims data were obtained from the Services Australia Medicare website, between January 2006 and December 2019 inclusive, for face-to-face psychiatrist consultations. Item number rates were collated and graphed per 100,000 population according to year and item number. There has been an increase in the number of claims for new patient assessments (291-296) and a reduction in most ongoing care Medicare item numbers, especially longer appointments that are often associated with psychotherapy provision (306-308). There have been changes in private psychiatric practice in Australia over the past 14 years. There are several possible causes for these changes and further research is required to determine the impact on patient care.


Determination of 1-deoxynojirimycin in Morus alba L. leaves by derivatization with 9-fluorenylmethyl chloroformate followed by reversed-phase high-performance liquid chromatography.
A rapid and reliable method suitable for assays of a large number of Morus alba leaves for 1-deoxynojirimycin (DNJ) has been developed. DNJ in 0.1 g of freeze-dried leaves was double-extracted in 10 mL of aqueous 0.05 M HCl by vortexing for 15 s at room temperature, derivatized with 9-fluorenylmethyl chloroformate (FMOC-Cl), and analyzed by reversed-phase high-performance liquid chromatography (RP-HPLC) equipped with a fluorescence detector. The double extraction recovered > 99% of extractable DNJ from the leaves. Stabilization of FMOC-derivatized DNJ (DNJ-FMOC) was achieved by diluting the reactant with aqueous acetic acid after derivatization. DNJ-FMOC was stable for at least 16 days under acidic conditions at room temperature (24 degrees C). Linearity ranged between 0.3 and 30 microg mL(-1). The intra- and inter-day precision for DNJ-spiked biological samples was between 0.6 and 1.8% and between 3.7 and 4.5%, respectively.


Preliminary screening of anticholinergic effect of some new derivatives of glycolic and aminoacetic acids.
The anticholinergic effect of some new alkylaminoalkyl esters of benzilic, cyclohexyl, 1-hydroxycyclohexyl, piperidino-and morpholino acetic acids (Table 1) was evaluated. Only benzilic acid esters were active and the 2-N-piperidinoaminoethyl benzilate hydrochloride (ANC-30) has the highest pA2 value.


Incidence and case fatality after day 28 of first time myocardial infarction in Sweden 1987-2008.
We studied trends in first-time myocardial infarction (MI) incidence and case fatality after day 28 and to examine the role of sex, education as an indicator for socioeconomic position, and birth country on these events in Sweden. Nationwide cohort including 6,752,655 individuals aged 35-89 years living in Sweden between January 1987 and December 2008, of which, 6,464,968 individuals and 366,085 nonfatal first-time MI patients were classified according to their sex, birth country, and education and followed over two decades. Incidence and case-fatality rate after day 28 of first-time MI and their trends. A decreasing trend for first-time MI incidence and case fatality after day 28 for both sexes regardless of birth country was observed (p-trend<0.0001). The trend was, however, less pronounced among female and foreign-born. Men had higher incidence than women (incidence rate ratio, IRR 2.09, 95% CI 2.08-2.11). Men born in Southern and Western Asia had 50% (95% CI 40-60%) higher risk than men born in Sweden. Incidence was 50-80% higher in the least educated irrespective of sex and birth country (p-trend<0.0001). This association was stronger for female and foreign-born. We observed a 15% higher case fatality after day 28 among men than women (hazard ratio, HR 1.15, 95% CI 1.13-1.17) and 20-40% lower case fatality after day 28 among patients with no diabetes. Low education was associated with 50% higher case fatality after day 28 regardless of sex and birth country (p-trend <0.0001). Although incidence of, and fatality after, first-time MI continued to decrease, low socioeconomic position, independent of birth country and sex, remained an important risk indicator for both events.


Chiroptical spectroscopy of a freely diffusing single nanoparticle.
Chiral plasmonic nanoparticles can exhibit strong chiroptical signals compared to the corresponding molecular response. Observations are, however, generally restricted to measurements on stationary single particles with a fixed orientation, which complicates the spectral analysis. Here, we report the spectroscopic observation of a freely diffusing single chiral nanoparticle in solution. By acquiring time-resolved circular differential scattering signals we show that the spectral interpretation is significantly simplified. We experimentally demonstrate the equivalence between time-averaged chiral spectra observed for an individual nanostructure and the corresponding ensemble spectra, and thereby demonstrate the ergodic principle for chiroptical spectroscopy. We also show how it is possible for an achiral particle to yield an instantaneous chiroptical response, whereas the time-averaged signals are an unequivocal measure of chirality. Time-resolved chiroptical spectroscopy on a freely moving chiral nanoparticle advances the field of single-particle spectroscopy, and is a means to obtain the true signature of the nanoparticle's chirality.


Free and nanoencapsulated curcumin suppress β-amyloid-induced cognitive impairments in rats: involvement of BDNF and Akt/GSK-3β signaling pathway.
Alzheimer's disease (AD), a neurodegenerative disorder exhibiting progressive loss of memory and cognitive functions, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and β-amyloid (Aβ) peptide. Drug delivery to the brain still remains highly challenging for the treatment of AD. Several studies have been shown that curcumin is associated with anti-amyloidogenic properties, but therapeutic application of its beneficial effects is limited. Here we investigated possible mechanisms involved in curcumin protection against Aβ(1-42)-induced cognitive impairment and, due to its poor bioavailability, we developed curcumin-loaded lipid-core nanocapsules in an attempt to improve the neuroprotective effect of this polyphenol. Animals received a single intracerebroventricular injection of Aβ(1-42) and they were administered either free curcumin or curcumin-loaded lipid-core nanocapsules (Cur-LNC) intraperitoneally for 10days. Aβ(1-42)-infused animals showed a significant impairment on learning-memory ability, which was paralleled by a significant decrease in hippocampal synaptophysin levels. Furthermore, animals exhibited activated astrocytes and microglial cells, as well as disturbance in BDNF expression and Akt/GSK-3β signaling pathway, beyond tau hyperphosphorylation. Our findings demonstrate that administration of curcumin was effective in preventing behavioral impairments, neuroinflammation, tau hyperphosphorylation as well as cell signaling disturbances triggered by Aβ in vivo. Of high interest, Cur-LNC in a dose 20-fold lower presented similar neuroprotective results compared to the effective dose of free curcumin. Considered overall, the data suggest that curcumin is a potential therapeutic agent for neurocognition and nanoencapsulation of curcumin in LNC might constitute a promising therapeutic alternative in the treatment of neurodegenerative diseases such as AD.


Prognostic significance of the number of positive lymph nodes in gallbladder cancer.
The aim of this study was to assess the prognostic impact of the number of lymph node metastases. The medical records of 33 patients with node-positive gallbladder cancer (GBC) treated at our institution from January 1985 through December 2002 were reviewed. There were 10 cases with a single node metastasis. The sites were as follows: the cystic duct node, the pericholedochal node, the retroportal node, the hilar node, the lymph node around the common hepatic artery, and the paraaortic node. According to the International Union Against Cancer (UICC) 5th edition, 5-year survival rates for the patients with pN1, pN2, and greater than pN2 were 19.2%, 10%, and 0%, respectively (not significant). Patients with a single node metastasis had a higher 5-year survival rate (33%) than patients with two or more lymph node metastases (0%; P < 0.05). There were no lymph node recurrences in patients with a single node metastasis. Number of positive nodes and liver metastasis were factors predictive of significantly worse survival. Rather than using the topographic classification, or even simply classifying whether nodal involvement is positive or negative, classification according to the number of positive nodes will contribute to establishing a more practically useful staging system.


Carbon Sequestration Anticipation Response to land use change in a mountainous karst basin in China.
The present article reports an assessment of afforestation potential and anticipation of carbon sequestration in the Houzhai River Basin in Guizhou Province in southwestern China. Total of 2755 soil profiles consisting of 22,057 soil samples were collected according to a grid-sampling method at a 150 m scale in the Houzhai River basin, and the SOC contents in soil samples were analyzed using a titration method. General information regarding the geographic characteristics of each sampling grid was recorded in the field. The results indicate that land use in the Houzhai River Basin is very complex. Land use status and land use change in the study area were closely associated with local geographic characteristics and variations in economic structures. There were approximately 15.26 km2 of land that could or should be rearranged as afforestation land in the Houzhai River Basin. The increased SOC storage (0.00-1.00 m soil horizon) would be up to 5.48 × 104 Mg, 6.42 × 104 Mg, 4.77 × 104 Mg and 3.18 × 104 Mg when all of the calculated lands became shrub-grass lands, shrub lands, arbor-shrub forest lands and arbor forest lands, respectively. The increased SOC percentages would be 52.16%, 61.13%, 45.39% and 30.32%, respectively, in comparison with the present SOC storage in these lands.


CD11b(+) Gr1(+) bone marrow cells ameliorate liver fibrosis by producing interleukin-10 in mice.
Clinical trials and animal models suggest that infusion of bone marrow cells (BMCs) is effective therapy for liver fibrosis, but the underlying mechanisms are obscure, especially those associated with early effects of BMCs. Here, we analyzed the early impact of BMC infusion and identified the subsets of BMCs showing antifibrotic effects in mice with carbon tetrachloride-induced liver fibrosis. An interaction between BMCs and activated hepatic stellate cells (HSCs) was investigated using an in vitro coculturing system. Within 24 hours, infused BMCs were in close contact with activated HSCs, which was associated with reduced liver fibrosis, enhanced hepatic expression of interleukin (IL)-10, and expanded regulatory T cells but decreased macrophage infiltration in the liver at 24 hours after BMC infusion. In contrast, IL-10-deficient (IL-10(-/-) ) BMCs failed to reproduce these effects in fibrotic livers. Intriguingly, in isolated cells, CD11b(+) Gr1(high) F4/80(-) and CD11b(+) Gr1(+) F4/80(+) BMCs expressed more IL-10 after coculturing with activated HSCs, leading to suppressed expression of collagen and α-smooth muscle actin in HSCs. Moreover, these effects were either enhanced or abrogated, respectively, when BMCs were cocultured with IL-6(-/-) and retinaldehyde dehydrogenase 1(-/-) HSCs. Similar to murine data, human BMCs expressed more IL-10 after coculturing with human HSC lines (LX-2 or hTERT), and serum IL-10 levels were significantly elevated in patients with liver cirrhosis after autologous BMC infusion. Activated HSCs increase IL-10 expression in BMCs (CD11b(+) Gr1(high) F4/80(-) and CD11b(+) Gr1(+) F4/80(+) cells), which in turn ameliorates liver fibrosis. Our findings could enhance the design of BMC therapy for liver fibrosis.


T7 RNA polymerase can direct expression of influenza virus cap-binding protein (PB2) in Escherichia coli.
Influenza virus cap-binding protein (PB2; Mr 85,000) is made in Escherichia coli when the cloned cDNA is transcribed by T7 RNA polymerase. Translation begins at the probable natural start codon and also from at least five internal sites in the same reading frame. The eukaryotic initiation site is not typical of protein initiation sites of E. coli, in that the closest potential Shine-Dalgarno sequence is far (15 nucleotides) from the start codon. Nevertheless, protein synthesis initiates efficiently at this site even in competition with a strong upstream prokaryotic initiation site. PB2 is somewhat unstable in the cell, but accumulates to a level where it is easily detectable in electrophoresis patterns of total cell protein. The full-length protein and various subfragments of it are insoluble in crude extracts, but have been useful for producing antibodies.


ING2 as a novel mediator of transforming growth factor-beta-dependent responses in epithelial cells.
Members of the ING (inhibitor of growth) family of chromatin modifying proteins (ING1-ING5) have emerged as critical regulators of gene expression and cellular responses, suggesting that the ING proteins may impinge on specific signal transduction pathways and their mediated effects. Here, we demonstrate a role for the protein ING2 in mediating responses by the transforming growth factor (TGF)-beta-Smad signaling pathway. We show that ING2 promotes TGF-beta-induced transcription. Both gain-of-function and RNA interference-mediated knockdown of endogenous ING2 reveal that ING2 couples TGF-beta signals to the induction of transcription and cell cycle arrest. We also find that the Smad-interacting transcriptional modulator SnoN interacts with ING2 and promotes the assembly of a protein complex containing SnoN, ING2, and Smad2. Knockdown of endogenous SnoN blocks the ability of ING2 to promote TGF-beta-dependent transcription, and conversely expression of SnoN augments ING2 enhancement of the TGF-beta response. Collectively, our data suggest that ING2 collaborates with SnoN to mediate TGF-beta-induced Smad-dependent transcription and cellular responses.


Influence of lithium salt-induced phase separation on thermal behaviors of poly(vinylidene fluoride)/ionic liquid gels and pore/void formation by competition with crystallization.
The thermal behavior of poly(vinylidene fluoride)/1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide/lithium bis(trifluoromethylsulfonyl)amide (PVDF/[C2mim][TFSA]/LiTFSA) gels, prepared by cooling from the hot solution, was investigated with various concentrations of LiTFSA (C LiTFSA). The peak melting temperature (T m) of the gels shifted toward higher temperatures with increased C LiTFSA. However, the thickness of lamellar crystal was found to decrease with the increase in C LiTFSA, which meant that the increase in T m was not caused by the thickening of lamellar crystal. Furthermore, we found the appearance of domains above T m in the high C LiTFSA region (≥20 wt%), which was a lithium ion-rich phase caused by the phase separation. Therefore, it is considered on the basis of Nishi-Wang equation that an increase in the interaction parameter with increasing C LiTFSA toward the phase separation increased the T m. The phase-separated domains competed with the subsequent crystallization, which resulted in the formation of micrometer-sized pores and nanometer-sized voids in the spherulites. Spectral measurements revealed that PVDF was not specifically solvated in the solution state above the crystallization temperature, while [TFSA]- anion formed a complex with lithium ion irrespective of the PVDF content. These results led to the consideration that an increase in the interaction parameter might be caused by the strong interaction between lithium ion and [TFSA]- anion to form the complex, which would also lower the interaction between PVDF and [TFSA]- anion.


Middle fossa approach: Applications in temporal bone lesions.
The middle fossa approach is a surgical technique that is very useful for lateral skull base surgery. However, it is true that it has limited surgical indications and implementation due to its technical complexity. We present our experience in 10 patients in whom the middle fossa approach was the treatment of choice because of the extent of the injury and complexity of the lesion or process. Despite the complexity of the cases, there was no mortality associated with surgery. Postoperative complications were found in 2 patients who presented an epidural hematoma and a cortico-subcortical hematoma. Hearing function was preserved in 5 patients out of the 7 who had adequate hearing at the time of surgery. House/Brackmann I-II facial nerve function was achieved in 8 patients; the remaining 2 had no deterioration of the nerve function. In 9 out of 10 patients, the surgery achieved complete solution of the lesion. The middle fossa approach is a safe and reliable surgical technique. It gives us great control and exposure of different skull base processes. We consider its knowledge of great importance, because it may be the only viable surgical alternative in some specific patients. That is the reason why it is important to learn this approach and know about it in our specialty.


Changes in the expression of the potassium channels TASK1, TASK3 and TRESK in a rat model of oral squamous cell carcinoma and their relation to malignancy.
Potassium channels have been proposed to promote cancer cell proliferation and metastases. Thus, we investigated the expression pattern of three 2-pore domain potassium channels (K2Ps) TASK1, TASK3 and TRESK in advanced oral squamous cell carcinoma (OSCC), the commonest oral malignancy. We used 4-nitroquinoline-1-oxide (4-NQO) to induce high grade OSCC in male adult rats. We then used immunohistochemistry and Western blotting to study the distribution and expression pattern of TASK1, TASK3 and TRESK in normal versus cancerous tissue. We also examined the expression of β-tubulin III (β-tub3), a marker associated with resistance to taxane-based chemotherapy and poor patient prognosis, and its correlation with the K2Ps. Finally, we studied the expression of TASK1, TASK3 and TRESK in human samples of SCC of oral origin. We found that TASK3 was significantly up-regulated whereas TASK1 and TRESK were both significantly down-regulated in advanced, poorly differentiated OSCC. Both, rat and human SCC showed a significant increase in the expression of β-tub3. Interestingly, the expression of the latter correlated positively and significantly with TASK3 and TRESK but not TASK1 in rat OSCC. Our initial results showed a similar pattern of up and down regulation and correlation with β-tub3 for these three K2Ps in human SCC. The changes in expression and the co-localization with a marker of resistance to taxanes like β-tub3 turn TASK1, TASK3 and TRESK into potentially new prognostic tools and possibly new therapeutic targets for OSCC.


Decreasing the time to defibrillation: a comparative study of defibrillator electrode designs.
Time to defibrillation (T(defib)) is the most important modifiable factor affecting survival from cardiac arrest. Mortality increases by approximately 7--10% for each minute of defibrillation delay. The purpose of this study was to determine whether defibrillator electrode design complexity affects T(defib). This was a randomized sequential design study utilizing a standardized ventricular fibrillation cardiac arrest model for CPR mannequins. We evaluated two common types of defibrillator electrode models: a single connector design and a double connector design that requires an adaptor. We compared the time required by cardiac arrest team leaders to apply the two types of defibrillator electrodes to a manikin, connect them to a defibrillator, and then deliver a first defibrillatory shock. The primary outcome was time to defibrillation. The secondary outcome was difficulty of application as perceived by the physician participants on a 10 cm visual analog scale. Thirty-two residents performed a sequential assessment of both electrodes. The average T(defib) for the double connector model was 42.9s longer than that of the single connector model (87.5s versus 44.6s, p<0.001). As evaluated by the study participants, the single connector model was significantly easier to apply then the double connector model (1.3 cm versus 4.4 cm, p<0.001). The single connector defibrillator electrode design was associated with a significantly shorter T(defib) than the double connector design. It also was judged to be easier to apply in this model. Ergonomic design of defibrillator electrodes can significantly impact time to defibrillation.


Pseudogenes and the electron transport chain.
With the advent of easy access to the human genome sequence, molecular biology techniques to target respirome-specific genes have begun to be exploited in the study of human disorders and in particular human cancers. In some recent publications it would appear that some investigators have inappropriately targeted pseudogenes rather than functional genes. The high transcription level and generally small size of many of the genes in the respirome make them prone to duplications in the form of processed pseudogenes within the human genome. Such genes can be challenging to analyse using standard molecular genetics approaches. In this presentation, we offer an analysis of pseudogenes that have been identified to have significant homology with some elements of the respirome. Other sequence elements such as Alu repeats, which present similar research obstacles, are also discussed.


Primary cardiac rhabdomyosarcoma following a uterine leiomyosarcoma: double primary sarcomas.
Primary cardiac rhabdomyosarcoma is rare. A dismal prognosis is usually given due to its high propensity for distant metastases, with survival rarely exceeding 2 years. We report a case that was initially considered to be a cardiac metastatic tumor from a primary uterine leiomyosarcoma, but after morphological and immunohistochemical examinations was shown to be a primary cardiac rhabdomyosarcoma. The right atrium was filled with a mass that oscillated between the right atrium and ventricle through the tricuspid valve. To reduce the risk of sudden death from tumor embolism into the pulmonary arteries, the tumor was resected. Even though the surgery was not curative, it eliminated the risk of sudden death due to tumor embolism into the pulmonary arteries and improved short-term survival.


A review of medical school records to investigate the effectiveness of enrichment programs for "at risk" students.
Although considerable attention has been given to the establishment of enrichment programs, almost none has focused on evaluating their effectiveness. To assess whether or not skills acquired during enrichment programs contributed to students' academic success in medical school. Success in medical school, as characterized by lack of delaying events (DE), student status, and United States Medical Licensing Examination-Step I scores were analyzed using a general linear model procedure to determine the effect of participation in 1 or more enrichment programs. Proportional program participation was analyzed using a chi-square test of equal proportion. Participants from the "serious research" enrichment programs experienced significantly fewer DE (p <.01), which contributed to student success. Some enrichment programs had disproportionately higher attendance. Participation in research-based enrichment programs for matriculating students who are "at risk" may develop critical thinking and problem-solving skills that help students to minimize DE.


Providencial Progression: Time to be Intolerant.
How to cite this article: Gopal P. Providencial Progression: Time to be Intolerant. Indian J Crit Care Med 2022;26(4):409-410.


Perceptions of forensic scientists on statistical models, sequence data, and ethical implications for DNA evidence evaluations: A qualitative assessment.
With the introduction of next generation sequencing (NGS) technology in the forensic field, it will be of interest to assess if forensic scientists feel equipped to interpret and present DNA evidence for sequence data. Here, we describe perceptions of sixteen U.S.-based forensic scientists on statistical models, sequence data, and ethical implications for DNA evidence evaluations. To get an in-depth understanding of the current situation, we used a qualitative research approach with a cross-sectional study design. Semi-structured interviews (N = 16) were conducted with U.S. forensic scientists working with DNA evidence. Open-ended interview questions were used to explore participants' views and needs surrounding the use of statistical models and sequence data for forensic purposes. We conducted a conventional content analysis using ATLAS. ti software and employed a second coder to ensure reliability of our results. Eleven themes emerged: 1) a statistical model that maximizes the value of the evidence is preferred; 2) a high-level understanding of the statistical model used is generally sufficient; 3) transparency is key in minimizing the risk of creating black boxes; 4) training and education should be an ongoing effort; 5) the effectiveness of presenting results in court can be improved; 6) NGS has the potential to become revolutionary; 7) some hesitations surrounding the use of sequence data remain; 8) there is a need for a concrete plan to alleviate barriers to the implementation of sequencing techniques; 9) ethics plays a major part in the role of a forensic scientist; 10) ethical barriers for sequence data depend on the application; 11) DNA evidence has its limitations. The results of this study give insight into the perceptions of forensic scientists regarding the use of statistical models and sequence data, providing valuable information in the move towards implementing sequencing methods for DNA evidence evaluations.


[Joint-sparing mobilization of TMJ ankylosis].
The causes leading to ankylosis are reviewed and operative approaches to avoid "block-resection" are briefly outlined. 2 patients with fibrous ankylosis are presented, with the affected area visualized through computer-tomograms. Each patient underwent only resection of the lateral exostosis causing restricted movement. Follow-up tomograms of the 2 patients are offered.


Evaluation of Systemic Markers Related to Anemia in Aggressive Periodontitis Patients before and after Phase I Periodontal Therapy: An Interventional Study.
The main aim of the study was to evaluate the systemic markers related to anemia in generalized aggressive periodontitis (GAgP) patients before and after phase I therapy. Based on the inclusion criteria, 15 patients with GAgP were allocated to two groups, group A (before phase I periodontal therapy) and group B (after phase I periodontal therapy). After 3 months, clinical parameters and hematological parameters were reevaluated. The hematological parameters like hemoglobin (Hb) and red blood cell (RBC) counts were increased significantly after therapy in group B with a significant improvement in the plaque index score, gingival bleeding index score with a reduction of probing depth, and a gain in clinical attachment levels. Within the limitation of this study, it could be concluded that GAgP was associated with reduced RBC parameters suggesting that it may tend toward anemia of chronic disease (ACD). Nonsurgical periodontal therapy (NSPT) not only reverses the periodontal health by reducing the inflammation but also improves the anemic status. Based on several studies, it was concluded that chronic periodontitis is associated with ACD. This study results indicate that like chronic periodontitis, aggressive periodontitis is also associated with reduced RBC and Hb count suggesting the risk for ACD. So when a patient is diagnosed to have any chronic infectious disease that might lead to ACD, then it is mandatory to treat that particular disease in order to reduce the infection so as to reverse the anemic status of an individual.


Reversible Light-Induced Dimerization of Secondary Face Azobenzene-Functionalized β-Cyclodextrin Derivatives.
β-cyclodextrin (βCyD) derivatives equipped with aromatic appendages at the secondary face exhibit tailorable self-assembling capabilities. The aromatic modules can participate in inclusion phenomena and/or aromatic-aromatic interactions. Supramolecular species can thus form that, at their turn, can engage in further co-assembling with third components in a highly regulated manner; the design of nonviral gene delivery systems is an illustrative example. Endowing such systems with stimuli responsiveness while keeping diastereomeric purity and a low synthetic effort is a highly wanted advancement. Here, we show that an azobenzene moiety can be "clicked" to a single secondary O-2 position of βCyD affording 1,2,3-triazole-linked βCyD-azobenzene derivatives that undergo reversible light-controlled self-organization into dimers where the monomer components face their secondary rims. Their photoswitching and supramolecular properties have been thoroughly characterized by UV-vis absorption, induced circular dichroism, nuclear magnetic resonance, and computational techniques. As model processes, the formation of inclusion complexes between a water-soluble triazolylazobenzene derivative and βCyD as well as the assembly of native βCyD/βCyD-azobenzene derivative heterodimers have been investigated in parallel. The stability of the host-guest supramolecules has been challenged against the competitor guest adamantylamine and the decrease of the medium polarity using methanol-water mixtures. The collective data support that the E-configured βCyD-azobenzene derivatives, in aqueous solution, form dimers stabilized by the interplay of aromatic-aromatic and aromatic-βCyD cavity interactions after partial reciprocal inclusion. Photoswitching to the Z-isomer disrupts the dimers into monomeric species, offering opportunity for the spatiotemporal control of the organizational status by light.


Effects of hypoxia and cytidine (5') diphosphocholine on the concentrations of dopamine, norepinephrine and metabolites in rat hypothalamus and striatum.
Experiments were performed in order to determine whether exogenous cytidine (5') diphosphocholine (CDP-choline) opposes the effects of an acute hypobaric hypoxia on the metabolism of catecholamines in rat striatum and hypothalamus. Hypoxia decreased striatal HVA, DOPAC, 3 MT, hypothalamic norepinephrine (NE), and increased both striatal and hypothalamic dopamine (DA). CDP-choline (1000 mg X kg-1 p.o.; 1 or 3 days) was devoid of effects in normoxia, but partially reversed 3 MT, NE and DA changes, potentiated the HVA and DOPAC decrease in hypoxic rats. Our results suggest that hypoxia could impair neurotransmitter release and that treatment with CDP-choline (acute, and especially subacute administration) opposes this impairment.


Expression of the low affinity neurotrophin receptor, P75NGFR, in the rat forebrain, following unilateral bulbectomy.
It has been hypothesized that the main olfactory bulb, with its relatively rich source of neurotrophins, may provide trophic support for neurons that project to the bulb. We monitored expression of the common, low affinity receptor for neurotrophins, p75NGFR, in the olfactory bulb and basal forebrain of unilaterally bulbectomized and sham-treated rats, 1-16 weeks post-surgery, using the monoclonal antibody MAb192. An induction of p75NGFR-immunoreactivity was observed in both the glomerular and olfactory nerve layers of the right, contralateral main olfactory bulb of lesioned animals. The naturally occurring regeneration taking place in the olfactory neuroepithelium is known to be altered by olfactory bulbectomy, with subsequent changes in the sensory input to the remaining bulb. These changes in expression of p75NGFR in the olfactory bulb support the hypothesis we have developed in previous papers, that changes in the extent of the peripheral input from the olfactory neuroepithelium to the main olfactory bulb regulate p75NGFR expression in both the glomerular and the olfactory nerve layers. Expression of p75NGFR in the basal forebrain of bulbectomized animals was found to be no different than sham-treated controls and does not support the hypothesis that the olfactory bulb provides trophic support to this region of the central nervous system.


The estimation of PAH bioavailability in contaminated sediments using hydroxypropyl-beta-cyclodextrin and Triton X-100 extraction techniques.
A study was conducted to investigate whether cyclodextrins and surfactants can be used to predict polycyclic aromatic hydrocarbon (PAH) bioavailability in contaminated sediments. Two sediment samples were extracted with aqueous solutions of hydroxypropyl-beta-cyclodextrin (HPCD) and Triton X-100. PAH removal during extraction was compared with PAH removal during biodegradation and solid-phase extraction. The latter two methods were used as reference methods to establish which part of the PAHs could be biodegraded and to what extent biodegradation was governed by bioavailability limitations. It was demonstrated that HPCD extraction followed solid-phase extraction and removed primarily readily bioavailable PAHs, while Triton X-100 extracted both readily and poorly bioavailable PAHs. Moreover, HPCD did not affect the degradation of PAHs in biodegradation experiments, while Triton X-100 enhanced the degradation of low molecular weight PAHs. It was concluded that HPCD extraction may provide a good method for the prediction of PAH bioavailability. Triton X-100 extraction is unfit for the prediction of PAH bioavailability.


Genome-wide analysis of the serine carboxypeptidase-like protein family reveals Ga09G1039 is involved in fiber elongation in cotton.
The Gossypium is a model genus for understanding polyploidy and the evolutionary pattern of inheritance. This study aimed to investigate the characteristics of SCPLs in different cotton species and their role in fiber development. A total of 891 genes from one typical monocot and ten dicot species were naturally divided into three classes based on phylogenetic analysis. The SCPL gene family in cotton has undergone intense purifying selection with some functional variation. Segmental duplication and whole genome duplication were shown to be the two main reasons for the increase in the number of genes during cotton evolution. The identification of Gh_SCPL genes exhibiting differential expression in particular tissues or response to environmental stimuli provides a new measure for the in-depth characterization of selected genes of importance. Ga09G1039 was involved in the developmental process of fibers and ovules, and it is significantly different from proteins from other cotton species in terms of phylogenetic, gene structure, conserved protein motifs and tertiary structure. Overexpression of Ga09G1039 significantly increased the length of stem trichomes. Ga09G1039 may be a serine carboxypeptidase protein with hydrolase activity, according to functional region, prokaryotic expression, and western blotting analysis. The results provide a comprehensive overview of the genetic basis of SCPLs in Gossypium and further our knowledge in understanding the key aspects of SCPLs in cotton with their potential role in fiber development and stress resistance.


Biphasic release characteristics of dual drug-loaded alginate beads.
The dual drug-loaded alginate beads simultaneously containing drug in inner and outer layers were prepared by dropping plain (single-layered) alginate beads into CaCl2 solution. The release characteristics were evaluated in simulated gastric fluid for 2 h followed by intestinal fluids thereafter for 12 h. The surface morphology and cross section of dual drug-loaded alginate beads was also investigated using scanning electron microscope (SEM). The poorly water-soluble ibuprofen was chosen as a model drug. The surface of single-layered and dual drug-loaded alginate beads showed very crude and roughness, showing aggregated particles, surface cracks and rough crystals. The thickness of dual drug-loaded alginate beads surrounded by outer layer was ranged from about 57 to 329 microns. The distinct chasm between inner and outer layers was also observed. In case of single-layered alginate beads, the drug was not released in gastric fluid but was largely released in intestinal fluid. However, the release rate decreased as the reinforcing Eudragit polymer contents increased. When the plasticizers were added into polymer, the release rate largely decreased. The release rate of dual drug-loaded alginate beads was stable in gastric fluid for 2 h but largely increased when switched in intestinal fluid. The drug linearly released for 4 h followed by another linear release thereafter, showing a distinct biphasic release characteristics. There was a difference in the release profiles between single-layered and dual drug-loaded alginate beads due to their structural shape. However, this biphasic release profiles were modified by varying formulation compositions of inner and outer layer of alginate beads. The release rate of dual drug-loaded alginate beads slightly decreased when the outer layer was reinforced with Eudragit RS100 polymers. In case of dual drug-loaded alginate beads with polymer-reinforced outer layer only, the initial amount of drug released was low but the initial release rate (slope) was higher due to more swellable inner cores when compared to polymer-reinforced inner cores. The current dual drug-loaded alginate beads may be used to deliver the drugs in a time dependent manner.


Phosphorylation of human estrogen receptor-beta at serine 105 inhibits breast cancer cell migration and invasion.
Multiple phosphorylation sites on the human estrogen receptor (hER)α were identified and shown to influence mammary carcinogenesis. In contrast, functional phosphorylation sites of hERβ have yet to be experimentally identified and validated. Here, using mass spectrometry, we uncovered three serines (S75, S87, and S105) in the N-terminus of hERβ as targets of ERK1/2 and p38 kinases. We raised a specific antibody against phosphorylated S105 (pS105) and demonstrated that this site was endogenously phosphorylated in MDA-MB-231 and BT-474 cells. A phospho-mimetic mutant generated from hERβ1 was found to exhibit higher transactivation activity than hERβ1. Ectopic expression of this mutant inhibited cell migration and invasion, but did not affect cell growth and cell-cycle progression in these cell models. In breast cancer specimens, pS105-hERβ immunoreactivity was detected with a higher prevalence and intensity than that of hERβ1. These results underscore the functional importance of the first experimentally identified hERβ-phosphorylation site in breast cancer.


Rehabilitation Nutrition for Iatrogenic Sarcopenia and Sarcopenic Dysphagia.
Sarcopenia is a very important issue in rehabilitation medicine and nutritional care. The prevalence of sarcopenia in older people is approximately 50% in the rehabilitation setting, and also approximately 15% of inpatients without sarcopenia upon admission developed sarcopenia during hospitalization. There is a concern that secondary sarcopenia may occur iatrogenically during hospitalization. Iatrogenic sarcopenia is defined as sarcopenia caused by the activities of medical staff including doctors, nurses, or other health care professionals in healthcare facilities. Iatrogenic sarcopenia is categorized into activity-related, nutrition-related and disease-related-iatrogenic sarcopenia. Especially in acute phase hospitals, concentrating on the treatment of diseases with less attention to nutrition and activity is more likely to cause iatrogenic sarcopenia. Sarcopenic dysphagia is also an important aspect in rehabilitation medicine and nutritional care. Sarcopenic dysphagia is characterized by swallowing difficulty because of a loss of mass and function in whole-body skeletal and swallowing muscles. Sarcopenic dysphagia can be diagnosed using a 5-step algorithm for the condition. Iatrogenic sarcopenia and sarcopenic dysphagia are affected by nutrition, activity and diseases in a complex manner. Therefore, treatment of iatrogenic sarcopenia and sarcopenic dysphagia requires comprehensive interventions through nutrition management and rehabilitation. Rehabilitation nutrition is effective for preventing and treating iatrogenic sarcopenia and sarcopenic dysphagia. Rehabilitation nutrition can be practiced more effectively and comprehensively by using the rehabilitation nutrition care process, which is a systematic problem-solving method. Further research is required to verify the efficacy of rehabilitation nutrition for preventing or improving iatrogenic sarcopenia and/or sarcopenic dysphagia.


Training a quantum measurement device to discriminate unknown non-orthogonal quantum states.
Here, we study the problem of decoding information transmitted through unknown quantum states. We assume that Alice encodes an alphabet into a set of orthogonal quantum states, which are then transmitted to Bob. However, the quantum channel that mediates the transmission maps the orthogonal states into non-orthogonal states, possibly mixed. If an accurate model of the channel is unavailable, then the states received by Bob are unknown. In order to decode the transmitted information we propose to train a measurement device to achieve the smallest possible error in the discrimination process. This is achieved by supplementing the quantum channel with a classical one, which allows the transmission of information required for the training, and resorting to a noise-tolerant optimization algorithm. We demonstrate the training method in the case of minimum-error discrimination strategy and show that it achieves error probabilities very close to the optimal one. In particular, in the case of two unknown pure states, our proposal approaches the Helstrom bound. A similar result holds for a larger number of states in higher dimensions. We also show that a reduction of the search space, which is used in the training process, leads to a considerable reduction in the required resources. Finally, we apply our proposal to the case of the phase flip channel reaching an accurate value of the optimal error probability.


Dysphagia associated with gastroesophageal reflux disease is improved by proton pump inhibitor.
This study aimed to determine whether dysphagia associated with gastroesophageal reflux disease was effectively treated with rabeprazole, a proton pump inhibitor. Sixty-eight outpatients with gastroesophageal reflux-associated dysphagia were enrolled in this study. Endoscopic esophagitis was confirmed in 52 of 68 subjects. The proton pump inhibitor rabeprazole was administered at 20 mg daily for 8 weeks. Rabeprazole was administered for a further 6 months to 16 subjects whose dysphagia was improved (10 mg/day) and 5 of these underwent 24-hr esophageal pH monitoring before and after treatment. Dysphagia was completely resolved in 40 of 68 subjects, which were categorized in Group I. Dysphagia improved partially in 20 subjects and was unchanged in 8 subjects. These 28 subjects were categorized into Group II. Comparison was made between Group I and Group II and multivariate analysis demonstrated that the only factor that correlated with the effect of rabeprazole on dysphagia was "improvement in heartburn symptoms." There were no relapses of symptoms during the 6-month follow-up period, and pH monitoring showed sustained suppression of acid secretion. The results indicate that rabeprazole is effective in the treatment of dysphagia associated with gastroesophageal reflux disease. We were, however, unable to elicit any factors that could predict the therapeutic effect of rabeprazole before commencing treatment.


Association between red blood cell distribution width and non-valvular atrial fibrillation in hemodialysis patients: a single-center Chinese population study.
Red blood cell distribution width (RDW) has emerged as a prognostic marker of atrial fibrillation (AF) in various clinical settings. However, the relationship by which RDW was linked to AF in hemodialysis (HD) patients was not clear. We sought to reveal the relationship between RDW and AF occurrence in HD patients. We enrolled 170 consecutive maintenance HD patients, including 86 AF patients and 84 non-AF patients. All participants' medical history and detailed clinical workup were recorded before the first dialysis session of the week. Electrocardiography, laboratory and transthoracic echocardiography examination indices were compared between the AF group and non-AF group. Multivariable logistic regression analysis was performed to identify the independent predictors of AF occurrence in HD patients. There were all paroxysmal AF patients in AF group. Compared to the non-AF group, patients with AF group had a significantly older age (61.0 ± 1.48 vs. 49.71 ± 1.79, p < 0.001), lower BMI (24.3 ± 4.11 vs. 25.8 ± 3.87, p < 0.05), higher RDW (15.10 ± 0.96 vs. 14.26 ± 0.82, p < 0.001) and larger LAD (39.87 ± 3.66 vs. 37.68 ± 5.08, p < 0.05). Multivariable logistic regression analyses demonstrated that values of age (OR: 1.030, 95%CI: 1.004-1.057, per one- year increase), BMI (OR: 0.863, 95%CI: 0.782-0.952, per 1 kg/m2 increase), RDW (OR: 2.917, 95%CI: 1.805-4.715, per 1% increase) and LAD (OR: 1.097, 95%CI: 1.004-1.199, per 1 mm increase) were independently associated with AF occurrence (p < 0.05, respectively). The best cutoff value of RDW to predict AF occurrence was 14.65% with a sensitivity of 68.6% and a specificity of 72.6%. The increased RDW was significantly associated with the paroxysmal AF occurrence in HD patients.


Decision trees in selection of featured determined food quality.
The determination of food quality, authenticity and the detection of adulterations are problems of increasing importance in food chemistry. Recently, chemometric classification techniques and pattern recognition analysis methods for wine and other alcoholic beverages have received great attention and have been largely used. Beer is a complex mixture of components: on one hand a volatile fraction, which is responsible for its aroma, and on the other hand, a non-volatile fraction or extract consisting of a great variety of substances with distinct characteristics. The aim of this study was to consider parameters which contribute to beer differentiation according to the quality grade. Chemical (e.g. pH, acidity, dry extract, alcohol content, CO(2) content) and sensory features (e.g. bitter taste, color) were determined in 70 beer samples and used as variables in decision tree techniques. This pattern recognition techniques applied to the dataset were able to extract information useful in obtaining a satisfactory classification of beer samples according to their quality grade. Feature selection procedures indicated which features are the most discriminating for classification.


Clinically suspected myocarditis in COVID-19 patients: Case series and review of the literature.
This Study describes eleven patients positive for severe acute respiratory syndrome coronavirus 2. In our cases, females and younger patients developed more severe disease. In contrast, improvement in left ventricular ejection fraction and N-terminal prohormone brain natriuretic peptide within the first week of treatment contributed to promising outcomes.


Photoinduced doping in heterostructures of graphene and boron nitride.
The design of stacks of layered materials in which adjacent layers interact by van der Waals forces has enabled the combination of various two-dimensional crystals with different electrical, optical and mechanical properties as well as the emergence of novel physical phenomena and device functionality. Here, we report photoinduced doping in van der Waals heterostructures consisting of graphene and boron nitride layers. It enables flexible and repeatable writing and erasing of charge doping in graphene with visible light. We demonstrate that this photoinduced doping maintains the high carrier mobility of the graphene/boron nitride heterostructure, thus resembling the modulation doping technique used in semiconductor heterojunctions, and can be used to generate spatially varying doping profiles such as p-n junctions. We show that this photoinduced doping arises from microscopically coupled optical and electrical responses of graphene/boron nitride heterostructures, including optical excitation of defect transitions in boron nitride, electrical transport in graphene, and charge transfer between boron nitride and graphene.


Acetylcholinesterase molecular forms in the fast or slow muscles of the chicken and the pigeon.
Molecular forms of acetylcholinesterase (AChE) were examined in various skeletal muscles of the chicken and the pigeon. In chicken pectoralis m., AChE was found to be restricted to endplate containing segments, and no asymmetric form could be detected in aneural samples. In the chicken muscles studied, a relation has been established between globular (G1,G2,G4) forms or asymmetric (A8,A12) forms, and muscle fibre types. Asymmetric forms are preponderant in fast-twitch muscles, whereas in slow tonic muscles 80% of the AChE activity is due to globular forms. However, comparison with pigeon muscles shows that AChE chicken muscle patterns may not be generalized.


Counterregulatory hormone responses preserved after long-term intravenous insulin infusion compared to continuous subcutaneous insulin infusion.
The counterregulatory hormone responses of cortisol, growth hormone, glucagon, epinephrine, norepinephrine, and dopamine to a fixed hypoglycemic stimulus (50 mg/dl for 1 h) were studied in five type I (insulin-dependent) diabetic subjects during conventional insulin therapy (CT), after 3 mo of continuous subcutaneous insulin infusion (SC), and after 3 mo of continuous intravenous insulin infusion (IV). During the two infusion periods, the overall mean levels of preprandial blood glucose (116 +/- 6 SC vs. 114 +/- 5 mg/dl IV) and glycosylated hemoglobin (6.1 +/- 2 SC vs. 5.9 +/- 2% IV) were virtually identical, but there were more hypoglycemic episodes and greater variability of preprandial blood glucose levels during SC than with IV. During the last 30 min of the hypoglycemic clamps, the mean levels of epinephrine and cortisol were significantly lower after 3 mo of SC (epinephrine, 268 +/- 80 pg/ml; cortisol, 14 +/- 1 microgram/dl) than with both CT (epinephrine 485 +/- 80 pg/ml; cortisol, 20 +/- 2 micrograms/dl) and IV (epinephrine, 443 +/- 62 pg/ml; cortisol, 19 +/- 2 micrograms/dl)(P less than .05). The mean growth hormone level was significantly (P less than .05) lower after SC (37 +/- 9 ng/ml) than after IV (79 +/- 12 ng/ml), but it did not reach statistical significance compared with CT (66 +/- 12 ng/ml). The mean glucagon, dopamine, and norepinephrine levels during the same period of hypoglycemia were not different when all treatment regimens were compared. We conclude that intensified insulin therapy with SC leads to significant blunting of the counterregulatory hormone response to hypoglycemia, whereas IV does not.(ABSTRACT TRUNCATED AT 250 WORDS)


Research progress of pattern recognition receptors in red swamp crayfish (Procambarus clarkii).
Though Procambarus clarkii (red swamp crayfish) is a lower invertebrate, it has nonetheless developed a complex innate immune system. The crayfish farming industry has suffered considerable economic losses in recent years as a consequence of bacterial and viral diseases. Hence, perhaps the most effective ways to prevent microbial infections in P. clarkii are to examine and elucidate its innate immunity. The first step in the immune response is to recognize pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs). PRRs are expressed mainly on immune cell surfaces and recognize at least one PAMP. Thence, downstream immune responses are activated and pathogens are phagocytosed. To date, the PRRs identified in P. clarkii include Toll-like receptors (TLRs), lectins, fibrinogen-related proteins (FREPs), and β-1,3-glucan-binding proteins (BGRPs). The present review addresses recent progress in research on PRRs and aims to provide guidance for improving immunity and preventing and treating infectious diseases in P. clarkii.


Processes of beta-amyloid and intracellular cytoplasmic domain generation by presenilin/gamma-secretase.
Following extracellular shedding, transmembrane domains (TMs) of beta-amyloid precursor protein (betaAPP) and Notch-1 undergo proteolysis by presenilin (PS)/gamma-secretase at least at two sites, near the middle of the TM (gamma-/S4 cleavage) and at the interface between cytosol and the TM (epsilon-/S3 cleavage), releasing Alzheimer disease (AD)-associated beta-amyloid (Abeta)/Notch-1beta (Nbeta) and betaAPP intracellular cytoplasmic domain (AICD)/Notch-1 intracellular cytoplasmic domain (NICD). Inhibiting PS/gamma-secretase activity is an essential approach to AD treatment, but it also decreases NICD production, which may cause severe side effects. Therefore, it is important to investigate the differences between the cleavages at the two sites. Gamma-/S4 and epsilon-cleavages have diversity, and produce a number of Abeta/Nbeta and AICD species. S3 cleavage diversity has been recently identified. It is significant that each cleavage occurs with strict precision, not randomly. Biochemical analysis of cultured cells was performed to explore the processing mechanisms. Familial AD-associated PS1 mutations as well as a subset of nonsteroidal anti-inflammatory drugs cause similar changes in gamma-/S4 cleavage precision, suggesting a common process for these cleavages near the middle of the TM. While the precision of the epsilon-cleavage is drastically affected by physiological factors, that of epsilon-/S3 cleavage is not. The processes of the two cleavages occurring in different portions of TMs may be diverse, thus representing possible targets for anti-AD therapeutics to selectively reduce Abeta.


TLR4 haplotypes in multiple sclerosis: a case-control study in the Spanish population.
Our aim in the present study is to evaluate the variation present in the TLR4 gene and its relationship with multiple sclerosis susceptibility in the Spanish population. Three hundred and sixty-two multiple sclerosis patients and 467 healthy controls from the Spanish population were included in the present study. Twelve single nucleotide polymorphisms (SNPs) were selected, and analyzed by the TaqMan technique. No statistically significant differences for any polymorphism or haplotypes were observed when patients were compared with controls. In conclusion, TLR4 does not play a major role in the predisposition to suffer from multiple sclerosis in our population.


[Choroid metastasis consequence of breast neoplasm].
The paper presents a clinical case of a 46 years old woman with metastatic carcinoma the leading point being breast and the therapeutical modalities taken in this situation.


Urinary EPCR and dermcidin as potential novel biomarkers for severe adult OSA patients.
Due to low predictive values of obstructive sleep apnea (OSA) screening tools, there is a need for biomarker for screening of OSA patients at an early stage. The aim of the study was to evaluate differentially expressed proteins in blood and urine samples of OSA patients. In this study, we used isobaric tagging for relative and absolute quantification (iTRAQ) based proteomics approach to identify differentially expressed proteins, which were subsequently verified and validated using enzyme-linked immunosorbent assay (ELISA) technique in adult OSA patients. Seventeen differentially expressed proteins were selected from iTRAQ data for verification, based on their clinical significance and reproducibility among different iTRAQ experiment sets. Five of these proteins (plasma = 2; urine = 3) were further validated in plasma (non-OSA- = 42; OSA = 198) and urine samples (non-OSA = 46; OSA = 197). ROC curve analysis for all OSA vs. non-OSA subjects ensured optimal diagnostic utility of two urinary proteins: Endothelial protein c receptor (EPCR) (AUC = 73%, cut-off: 35 pg/ml) and dermcidin (AUC = 74%, cut-off: 4.6 pg/ml). For severe OSA, diagnostic accuracy significantly improved with AUC as 88% and 82% for EPCR (cut-off: 46 pg/ml) and dermcidin (cut-off: 5.2 pg/ml) respectively. Sensitivity and specificity of combined performance of both urinary proteins for severe OSA were 94% and 91% respectively. In this study, urinary EPCR and dermcidin emerged as novel biomarkers for screening severe OSA patients.


Learning visuomotor transformations for gaze-control and grasping.
For reaching to and grasping of an object, visual information about the object must be transformed into motor or postural commands for the arm and hand. In this paper, we present a robot model for visually guided reaching and grasping. The model mimics two alternative processing pathways for grasping, which are also likely to coexist in the human brain. The first pathway directly uses the retinal activation to encode the target position. In the second pathway, a saccade controller makes the eyes (cameras) focus on the target, and the gaze direction is used instead as positional input. For both pathways, an arm controller transforms information on the target's position and orientation into an arm posture suitable for grasping. For the training of the saccade controller, we suggest a novel staged learning method which does not require a teacher that provides the necessary motor commands. The arm controller uses unsupervised learning: it is based on a density model of the sensor and the motor data. Using this density, a mapping is achieved by completing a partially given sensorimotor pattern. The controller can cope with the ambiguity in having a set of redundant arm postures for a given target. The combined model of saccade and arm controller was able to fixate and grasp an elongated object with arbitrary orientation and at arbitrary position on a table in 94% of trials.


Social engagement within the facility increased life expectancy in nursing home residents: a follow-up study.
Social engagement (SE) has been consistently shown to improve survival among community-dwelling older people, but the evidence in nursing home residents is inconclusive and prone to short-term reverse causation and confounding by major health determinants. Our main objective was to study the potential causal effect of within-the-facility social engagement (SE) on long-term all-cause mortality in care home residents. A representative cohort of 382 nursing home residents in Madrid without severe physical and cognitive impairments at baseline was followed up for 10-year all-cause mortality. Standardized mortality curves for residents with low/null, moderate, and high levels of SE at baseline were estimated using Kaplan-Meier methods and spline-based survival models with inverse probability of exposure weights conditional on baseline sociodemographic characteristics, facility features, comorbidity, and disability. Standardized 5-year mortality risks and median survival times were compared across levels of SE. The baseline prevalences of low/null, moderate, and high SE were 36, 44, and 20%, respectively. Compared with residents with low/null SE at baseline, the standardized differences (95% confidence intervals) in 5-year mortality risk were - 2.3% (- 14.6 to 10.0%) for moderately engaged residents and - 18.4% (- 33.8 to - 2.9%) for highly engaged residents. The median survival time increased by 0.4 (- 1.4 to 2.2) and 3.0 (0.8 to 5.2) years, respectively. Residents with high SE within the nursing home had an 18% lower 5-year mortality risk and a 3-year increase in their median survival, as compared with residents with similar health determinants but low/null SE. The development of adequate tailored intervention programs, addressed to increase SE in nursing home residents, could improve their long-term survival, in addition to expected gains in quality of life.


Antitransforming growth factor-beta therapy in fibrosis: recent progress and implications for systemic sclerosis.
Transforming growth factor-beta (TGF-beta) is required for tissue homeostasis but is also implicated in disease processes including fibrosis, and thus represents a molecular target for therapy. Multiple strategies for inhibiting excessive TGF-beta function exist. The three principal platforms are RNA-based technologies, monoclonal antibodies and small molecules. Monoclonal antibodies targeting TGF-beta have been used in a small clinical trial, with disappointing results to date. Antibodies to the alphavbeta6 integrin prevent local activation of latent TGF-beta and show promise in preclinical studies. Over a dozen small molecules inhibit the kinase activity of TGF-beta receptors. Several commonly used drugs appear to have unanticipated anti-TGF-beta activity and may therefore have a role in antifibrotic therapy. Because TGF-beta has important physiological functions, inhibiting its activity might potentially lead to aberrant immune activation, epithelial hyperplasia and impaired wound healing; spontaneous autoimmunity in particular is a concern in an autoimmune disease such as systemic sclerosis. Novel insights from DNA microarray analysis and genetic polymorphisms in TGF-beta signaling will aid in defining patient populations most likely to respond to anti-TGF-beta treatment. Anti-TGF-beta therapies promise to have a major impact in systemic sclerosis. Significant concerns regarding efficacy and safety need to be addresed. The identification of optimal candidates for therapy, and of biomarkers of safety and efficacy, are critical challenges ahead.


Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial.
In a double-blind, randomized, crossover, placebo-controlled study, we investigated the effects of adding taurine to the conventional treatment in 14 patients with congestive heart failure for a 4-week period. Compared with placebo, taurine significantly improved the New York Heart Association functional class (p less than 0.02), pulmonary crackles (p less than 0.02), and chest film abnormalities (p less than 0.01). A benefit of taurine over placebo was demonstrated when an overall treatment response for each patient was evaluated on the basis of clinical examination (p less than 0.05). No patient worsened during taurine administration, but four patients did during placebo. Pre-ejection period (corrected for heart rate) decreased from 148 +/- 14 ms before taurine treatment to 137 +/- 12 ms after taurine (p less than 0.001), and the quotient pre-ejection period/left ventricular ejection time decreased from 47 +/- 9 to 42 +/- 8% (p less than 0.001). Side effects did not occur in the patients during taurine. The results indicate that addition of taurine to conventional therapy is safe and effective for the treatment of patients with congestive heart failure.


Interference by methionine on valine uptake in Acremonium chrysogenum.
The incorporation of L-[U-14C]valine into delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV), a direct biosynthetic precursor of penicillins and cephalosporins, was studied. When DL-methionine was added to Acremonium chrysogenum culture broths, no labeled ACV was found, while a large amount of radioactive ACV was detected when methionine was not present. DL-Norleucine, a nonsulfur analog of methionine, also inhibited the synthesis of radioactive ACV to some degree. This effect was due to the inhibition of valine transport by methionine and norleucine.


Movement behaviors in short versus adequate nocturnal sleepers: A compositional analysis of preschoolers.
Accruing adequate daily amounts of time spent on movement behaviors (physical activity (PA), sedentary behavior (SB), and sleep) in childhood has been associated with positive short and long-term health outcomes. Nonetheless, how waking time is distributed across PA and SB among preschoolers who are short and adequate sleepers at night is unknown. This study investigated: (1) if there are differences in a movement behaviors composition among adequate and short nocturnal sleepers; and (2) the association between preschoolers' time spent in PA, SB, and sleep among adequate and short nocturnal sleepers. A total of 270 preschoolers (132 boys; 3.97 ± 0.81 years old; 15.48 ± 1.62 kg/m2 ) participated in this study. PA and SB were assessed using accelerometry (model wGT3X). Sleep duration was assessed through a parental-proxy interview, and preschoolers were stratified as short and adequate sleepers, according to attendance to international sleep duration guidelines. Compositional data analysis was used to explore the time-use patterns of behaviors among adequate and short sleepers. Short sleepers spent 64 min less time asleep, accumulated 32 min in more sedentary time (p = .005, Cohen's d = 0.36, Bayes Factor: 6.17), and 24 min more in light PA (p = .0005, Cohen's d = 0.44, Bayes Factor: 46.37) compared to adequate sleepers. Being a short sleeper was associated with greater time spent in SB and light PA during their waking hours. The health implications of movement behaviors composition among short sleep preschoolers should be further investigated.


Treatment of infected calcific myonecrosis with chronically discharging sinus caused by iatrogenic aspiration: A case report.
Calcific myonecrosis (CM) is a rare, benign post-traumatic sequela which is often challenging to differentiate from soft tissue tumors. Infected CM is recalcitrant and sometimes requires invasive treatment despite its benign nature. We present a case of infected CM in which MRI and 201Tl scintigraphy proved useful for diagnosis and intralesional debridement with prolonged placement of a suction tube allowed for successful treatment. A 71-year-old man had undergone repeated aspiration for swelling of the lower leg and presented with a sustained pyogenic discharging wound. He underwent intralesional debridement of purulent necrotic tissue followed by prolonged suction tube placement. Enterobacter cloacae was detected in the discharge, and specific antibiotics were administered. Once the wound closed, a new sinus recurred four months after surgery, warranting reoperation with debridement of the remnant fascia and necrotic tissue with suction tube replacement. The wound healed eight months after the first surgery with no signs of recurrence. CM can be diagnosed based on its unique imaging features and a history of compartment syndrome. To avoid infection, CM must be treated conservatively without surgical invasions, such as biopsy or aspiration. Extensive debridement with a myocutaneous flap is nevertheless recommended for infected CM treatment, despite significant invasion including intraoperative bleeding being problematic. MRI and 201Tl scintigraphy can help diagnose CM and avoid biopsy to exclude malignancy. Intralesional debridement of necrotic tissue with prolonged suction tube placement could be a valid treatment alternative to reduce the invasiveness of infected CM.


Subcellular distribution of peptides associated with gastric mucosal healing and neoplasia.
The trefoil peptides pS2 and human spasmolytic peptide are putative growth factors, particularly associated with mucus-producing cells of the gastrointestinal tract including those of the stomach. The receptor for transforming growth factor alpha (TGF alpha) takes its name from one of its alternative ligands, epidermal growth factor, and is called the epidermal growth factor receptor. Although there is immunoreactive epidermal growth factor in the stomach, it is TGF alpha and the epidermal growth factor receptor that are abundant. Immunolabelling at electron microscope level allows for subcellular localisation of antigens; pS2 and human spasmolytic peptide co-localise to cytomembranes, including the Golgi apparatus, and thecae of surface/pit mucous cells. TGF alpha is abundant on the membranes of tubulovesicles of parietal cells and is also present in chief cells: in mucous producing cells it can be detected but not in association with mucous. The distribution of the epidermal growth factor receptor mimics that of TGF alpha but with preferential clustering on the basolateral membranes of gastric cells. The trefoil peptides are associated with healing and probably act, together with mucus, to protect the gastric mucosa and maintain a viable environment. TGF alpha, transduced via the epidermal growth factor receptor, inhibits gastric acid secretion, thus aids the trefoils in the maintenance of a gastric microenvironment conducive to healing after damage. TGF alpha, however, is also a potent mitogen; while this property plays a vital part in repairing mucosal defects, if this peptide or indeed its receptor are overexpressed, the result can be neoplasia.


Signaling through MyD88 regulates leukocyte recruitment after brain injury.
Injury to the CNS provokes an innate inflammatory reaction that engages infiltrating leukocytes with the capacity to repair and/or exacerbate tissue damage. The initial cues that orchestrate leukocyte entry remain poorly defined. We have used flow cytometry to investigate whether MyD88, an adaptor protein that transmits signals from TLRs and receptors for IL-1 and IL-18, regulates leukocyte infiltration into the stab-injured entorhinal cortex (EC) and into sites of axonal degeneration in the denervated hippocampus. We have previously established the kinetics of leukocyte entry into the denervated hippocampus. We now show that significant leukocyte entry into the EC occurs within 3-12 h of stab injury. Whereas T cells showed small, gradual increases over 8 days, macrophage infiltration was pronounced and peaked within 12-24 h. MyD88 deficiency significantly reduced macrophage and T cell recruitment to the stab-injured EC and the denervated hippocampus at 5 days post-injury. Whereas macrophage and T cell entry remained impaired into the denervated hippocampus of MyD88-deficient mice at 8 days, leukocyte infiltration into the stab-injured EC was restored to levels observed in wild-type mice. Transcripts for TNF-alpha, IL-1beta, and CCL2, which increased >50-fold after stab injury in C57BL/6 mice at the time of peak expression, were severely reduced in injured MyD88 knockout mice. Leukocyte recruitment and gene expression were unaffected in TLR2-deficient or TLR4 mutant mice. No significant differences in gene expression were observed in mice lacking IL-1R or IL-18R. These data show that MyD88-dependent signaling mediates proinflammatory gene expression and leukocyte recruitment after CNS injury.


Note on the formulation of thermosensitive and mucoadhesive vaginal hydrogels containing the miniCD4 M48U1 as anti-HIV-1 microbicide.
The miniCD4 M48U1 was formulated into thermosensitive and mucoadhesive pluronic(®) hydrogels as anti-HIV-1 microbicide. The release kinetics of M48U1 from F127/HPMC (20/1 wt%) and F127/F68/HPMC (22.5/2.5/1 wt%) studied during 24h by using Franz diffusion cells showed that HEC hydrogel (1.5 wt%) used as control released 93% of the peptide, while about 25% of M48U1 remained in pluronic(®) hydrogels. The formulation of M48U1 in pluronic(®) hydrogels ensures a local delivery because no diffusion of the peptide was detected through vaginal Cynomolgus macaque mucosa using Ussing chamber. Finally, toxicological studies showed no significant difference in the HeLa cell viability of the pluronic(®) hydrogels in comparison with HEC and phosphate buffer saline.


Management of an Unusual Penetrating Neck Injury with an Iron Rod in a Tertiary Care Centre.
The majority of the neck injuries are linked either to aggression or self inflicted cut throat or firearm injuries. Here we present a rare case of a penetrating neck injury by an iron rod, which was sustained due to accidental fall at home. A very long, rusted, iron TMT bar about 10 mm diameter, with entangled clothing with hooks on it, had penetrated the neck of the patient from below the mandible in the left side and exited through the oral cavity on the right angle of the mouth. The patient was under alcohol intoxication, however was stable as far as vital signs were concerned. There was no active bleeding or expanding haematoma neither there was any stridor or neurological deficit. The patient was further stabilised and after doing the necessary investigations he was taken up for surgery under general anaesthesia and the rod was successfully removed and the wound repaired. The patient recovered uneventfully and quickly and was discharged on the fifth post operative day. Accidental penetrating neck injuries are not very common and internet search did not reveal many published cases. Penetrating neck injuries are usually attached with high morbidity and mortality, because of damage to great vessels and nerves. A good knowledge of the anatomy and proper assessment of the injury before removal is a prerequisite before removal. With a little bit of courage and adopting a multidisciplinary approach and good computed tomography (CT) scan to assess the injury, such cases can be easily handled.


Description and Comparison of Acute Pain Characteristics After Laparoscope-Assisted Vaginal Hysterectomy, Laparoscopic Myomectomy and Laparoscopic Adnexectomy.
To determine the characteristics of the acute pain after laparoscopic-assisted vaginal hysterectomy (LAVH), laparoscopic myomectomy (LM), and laparoscopic adnexectomy (LA) and compare them with each other. Patients undergoing LAVH, LM, and LA under general anaesthesia at the First Affiliated Hospital of Wenzhou Medical University between December 2017 and December 2019 were selected. Their data were collected before, during, and after the surgery. We evaluated the degrees of pain in each group of patients and compared them. There were differences in the baseline characteristics of the patients in the LAVH, LM, and LA groups. The severity and incidence of postoperative pain were higher in the LAVH group than in the LM and LA groups, followed by the LM and LA groups. Compared with the LA group, the postoperative pain in the LAVH and LM groups was more complicated. The LA group had the lowest incidence of two or more types of moderate to severe pain. The LAVH and LM groups mainly had visceral pain and low back pain, and the LA group mainly had incisional pain. Shoulder pain had the lowest incidence in the three groups. There were different postoperative pain characteristics after the LAVH, LM, and LA, and we should clinically adjust analgesia programs for different gynaecological laparoscopic surgeries.


Caged probes: a novel tool in studying symplasmic transport in plant tissues.
Caged probes offer a novel approach to study plant cell-to-cell communication. Instead of introducing fluorescent molecules into cells by microinjection, their caged counterparts can be preloaded into the tissue by diffusion. Following spatially controlled photoactivation, movement of the uncaged fluorochrome can be followed in time and direction by confocal laser scanning microscopy. In the onion bulb scale epidermis used as a model system, symplasmic transport of the tracer out of a target cell was followed. Transport via the symplasmic pathway was challenged by plasmolysing the tissue. The experiments confirmed the symplasmic nature of tracer transport.


Significance of age-specific creatinine levels at presentation in posterior urethral valve patients.
Determination of prognostic factors is of great importance in decision making on therapies and informing parents about the probable outcome of disease. The present study aims to evaluate and assess the prognostic factors in posterior urethral valve (PUV) patients. The data of 68 patients treated between 1996 and 2004 were evaluated retrospectively. The mean age at diagnosis was 36.4 months. The serum creatinine levels were standardized using the age-specific creatinine reference (ASCR) levels. The age at diagnosis, clinical presentation, initial serum creatinine, method of treatment, presence of vesicoureteral reflux (VUR) and hydroureteronephrosis (HUN), all of which may effect the prognosis, were evaluated. The analysis revealed that, of the 36 patients whose initial serum creatinine levels were within ASCR, only one (2.8%) had a final serum creatinine higher than ASCR values. In contrast, of the 32 patients whose initial serum creatinine levels were not within ASCR, 19 (59.4%) had final serum creatinine levels higher than ASCR (P<0.001). The distribution of final serum creatinine according to treatment method, presence of UTI before treatment and age at diagnosis was not statistically significant; however, the difference in distribution for initial serum creatinine (P<0.001), mode of clinical presentation (0.016), presence of HUN (0.019) and state of VUR (0.037) before treatment was statistically significant. Final outcome with regard to renal function in PUV patients is affected by bilateral VUR and most significantly by serum creatinine levels higher than ASCR.


Knowledge and awareness level of healthcare professional candidate students on inherited metabolic diseases: a cross-sectional study.
Healthcare professionals play a key role in the diagnosis, treatment, and follow-up of inborn metabolic diseases. However, the level of inborn metabolic disease knowledge of prospective healthcare professional students in our country has not yet been determined. Therefore, this study aimed to evaluate the level of knowledge of healthcare professional candidate students about inborn metabolic diseases. The knowledge levels of 761 students enrolled in the Department of Nutrition and Dietetics, Child Development, Midwifery, Occupational Therapy, Audiology, Health Management and Social Work at Gülhane Faculty of Health Sciences, Health Sciences University, were evaluated through a questionnaire using a face-to-face interview technique. Correct answers to the questions measuring the level of knowledge were scored as "1", and incorrect answers were scored as "0". The mean knowledge-level score of the individuals was 14.23 ± 4.56. A total of 56.0% of individuals had heard about inborn metabolic diseases before, 37.8% had heard of rare disease organizations/platforms before, and 16.8% had encountered an awareness campaign about inborn metabolic diseases. The level of exposure to awareness-raising campaigns, department of education, and grade level were shown to be factors affecting knowledge levels. It is necessary to improve the awareness and knowledge levels of health professional candidates involved in the treatment of inborn metabolic diseases. Education curricula in health sciences faculties should be evaluated with this aspect.


The extent of environmental and body contamination through aerosols by hydro-surgical debridement in the lumbar spine.
Surgical site infections occur in 1-6% of spinal surgeries. Effective treatment includes early diagnosis, parenteral antibiotics and early surgical debridement of the wound surface. On a human cadaver, we executed a complete hydro-surgery debridement including a full surgical setup such as draping. The irrigation fluid was artificially contaminated with Staphylococcus aureus (ATCC 6538). Surveillance cultures were used to detect environmental and body contamination of the surgical team. For both test setups, environmental contamination was observed in an area of 6 × 8 m. Both test setups caused contamination of all personnel present during the procedure and of the whole operating theatre. However, the concentration of contamination for the surgical staff and the environment was lower when an additional disposable draping device was used. The study showed that during hydro-surgery debridement, contaminated aerosols spread over the whole surgical room and contaminate the theatre and all personnel.


The effects of intravitreal irrigation during vitrectomy on the electroretinogram.
Intravitreal irrigation with Balanced Salt Solution Plus (BSS Plus) produced less decrease in b-wave amplitude than either normal saline solution or Balanced Salt Solution. BSS Plus was more suitable for intravitreal irrigation because it contained the appropriate bicarbonate, pH, and ionic composition necessary for maintenance of normal retinal electrical activity, and it contained glutathione, which is necessary for maintenance of endothelial cell adenosine triphosphatase and for protection against free radical damage and oxidative stress.


Vision Rehabilitation with a Native Pintucci-type Keratoprosthesis.
To report visual rehabilitation with a native Pintucci keratoprosthesis (KPro) after a severe ocular surface chemical burn in a male patient. A 41-year-old man experienced a bilateral severe chemical burn 5 years previously. Earlier penetrating keratoplasty and keratolimbal allografts were unsuccessful in both eyes, and neither of the eyes had vision better than light perception. Both corneas were opaque and conjunctivalized. Because of severe dry eye and total limbal stem cell deficiency, the left eye was considered for a Pintucci-type KPro. In the first stage, the ocular surface was reconstructed with an oral mucus membrane graft, and a KPro was placed under the skin and orbicularis oculi muscle. Three months later, the KPro was removed and implanted in the left eye. During seven months after the KPro implantation, the anatomical position was acceptable, and his best corrected visual acuity was 2/10. Bearing in mind the successful results of the native Pintucci KPro in this case of severe acid burn, using this type of keratoprosthesis in patients with total limbal stem cell deficiency and severe dry eye is recommended.


An overview of the new frontiers in the treatment of atherogenic dyslipidemias.
Cardiovascular diseases (CVDs) are the leading cause of morbidity/mortality worldwide. Dyslipidemia is a major risk factor for premature atherosclerosis and CVD. Lowering low-density-lipoprotein cholesterol (LDL-C) levels is well established as an intervention for the reduction of CVDs. Statins are the first-line drugs for treatment of dyslipidemia, but they do not address all CVD risk. Development of novel therapies is ongoing and includes the following: (i) reduction of LDL-C concentrations using antibodies to proprotein convertase subtilisin/kexin-9, antisense oligonucleotide inhibitors of apolipoprotein B production, microsomal transfer protein (MTP) inhibitors, and acyl-coenzyme A cholesterol acyl transferase inhibitors; (ii) reduction in levels of triglyceride-rich lipoproteins with ω-3 fatty acids, MTP inhibitors, and diacylglycerol acyl transferase-1 inhibitors; and (iii) increase of high-density-lipoprotein (HDL) cholesterol levels, HDL particle numbers, and/or HDL functionality using cholesteryl ester transfer protein inhibitors, HDL-derived agents, apolipoprotein AI mimetic peptides, and microRNAs. Large prospective outcome trials of several of these emerging therapies are under way, and thrilling progress in the field of lipid management is anticipated.


Interpretation of Mohs micrographic frozen sections: a peer review comparison study.
The ability of the Mohs surgeon to interpret frozen sections generated during Mohs surgery has been questioned recently. In this study 1000 Mohs micrographic slides were interpreted by a Mohs surgeon and subsequently by a general pathologist. The disputed slides were then reviewed independently by two Mohs surgeons, two pathologists, and a dermatopathologist. Overall, there was a 98.9% agreement in interpretation among the Mohs surgeons, the pathologists, and the dermatopathologist. Results would indicate that a well-trained and experienced Mohs surgeon is competent to interpret slides prepared under his or her supervision during Mohs surgery.


Adverse events associated with intravenous phenytoin in children: a prospective study.
A prospective study was undertaken to assess the type and frequency of adverse side-effects following the use of intravenous phenytoin in children. Twenty-two children received a total of 100 doses over a 10-month period. Six patients (27%) experienced one or more side-effects, including extravasation of the drug, hypotension and cardiac arrhythmia. No patient developed skin necrosis, including the 'purple glove syndrome'. Recovery from all adverse side-effects was spontaneous and complete. It is possible that some or all of these side-effects may have been caused by an excessive rate of infusion of phenytoin or the saline 'flush' following administration of the drug. The overall frequency of side-effects was perhaps less than expected.


miRNA-363-3p Hinders Proliferation, Migration, Invasion and Autophagy of Thyroid Cancer Cells by Controlling SYT1 Transcription to affect NF-κB.
Thyroid cancer (TC) is a frequent endocrine malignant tumor with various pathologic types. miRNA-363-3p plays a pivotal part in the occurrence, development, prognosis, and treatment of cancer. To explore the mechanism of miRNA-363-3p in TC and provide a new idea for targeted therapy of TC. Differential miRNAs and downstream target mRNAs in TC tissues were predicted with bioinformatics analysis. Expression levels of miRNA-363-3p and Synaptotagmin I (SYT1) in TC cells were ascertained by qRT-PCR. Cell migration, invasion, and proliferation were detected by wound healing assay, transwell assay, colony formation assay, CCK-8, and BrdU fluorescence experiment, respectively. Flow cytometry was utilized to detect the levels of apoptosis and necrosis. Immunofluorescence assay was used for detecting autophagosome formation in cells, and the expression levels of autophagy-related proteins, as well as NF-κB related proteins, were measured by western blot. Dual-luciferase reporter gene assay was applied for detecting the interaction between miRNA-363-3p and SYT1. miRNA-363-3p was prominently down-regulated in TC cells. miRNA-363-3p overexpression suppressed migration, invasion, and proliferation, promoting apoptosis and necrosis of TC cells. As the downstream target of miRNA-363-3p, SYT1 was up-regulated in TC cells. SYT1 overexpression reversed the inhibition of TC cell proliferation, invasion, migration, and autophagy mediated by miRNA-363-3p overexpression. In addition, miRNA-363-3p overexpression inhibited the activation of the NF-κB pathway in cells, while further overexpression of SYT1 weakened the inhibition of miRNA-363-3p overexpression on the NF-κB pathway. miRNA-363-3p affected the NF-κB signaling pathway by down-regulating SYT1 expression to inhibit the malignant progression of TC cells, providing theoretical support for the treatment of TC.


Mask proteins are cofactors of Yorkie/YAP in the Hippo pathway.
The Hippo signaling pathway acts via the Yorkie (Yki)/Yes-associated protein (YAP) transcriptional coactivator family to control tissue growth in both Drosophila and mammals [1-3]. Yki/YAP drives tissue growth by activating target gene transcription, but how it does so remains unclear. Here we identify Mask as a novel cofactor for Yki/YAP. We show that Drosophila Mask forms a complex with Yki and its binding partner, Scalloped (Sd), on target-gene promoters and is essential for Yki to drive transcription of target genes and tissue growth. Furthermore, the stability and subcellular localization of both Mask and Yki is coregulated in response to various stimuli. Finally, Mask proteins are functionally conserved between Drosophila and humans and are coexpressed with YAP in a wide variety of human stem/progenitor cells and tumors.


Cost of status epilepticus in a tertiary care hospital in India.
Status epilepticus (SE) is one of the most important neurological emergencies. The present study evaluated both direct cost of SE and predictors of cost in an Indian tertiary care teaching hospital in Lucknow India. SE was defined as continuous seizure for ≥ 5 min or recurrent seizures without regaining consciousness. Etiologies of SE were categorized as acute central nervous system (CNS) pathology, acute non-CNS pathology, chronic CNS pathology, congenital disorders and others. Patients requiring mechanical ventilation (MV) received ventilators free of cost. Mortality and disability on discharge were noted. Fifty-five patients aged 8-90 years were included (males, 33). Fifty (89.3%) patients had generalized convulsive SE. The severity of SE as assessed by Status Epilepticus Scoring Scale was unfavorable (score, 3-6) in 41 (74.5%) patients. The etiology of SE was categorized as acute CNS pathology in 28 (51%) patients, non-CNS and chronic CNS pathology in 11 (19.6%) patients each, remote congenital pathology in 2 (3.6%), and others in 3 (5.6%). Thirty (53.6%) patients had comorbidities. Median duration of hospitalization was 7 (range, 1-72) days.Twenty six patients were hospitalized for >7 days. SE was controlled by 2 drugs in 47 (85.5%) patients and refractory to 2 intravenous antiepileptic drugs in 8 (14.5%). Nineteen (34.5%) patients died, and 29 (51.8%) showed favorable outcomes on discharge. Median hospital expenditure per case was INR 19,900 ($309.87; range, INR 1600-574,000). On multivariate analysis, SE hospitalization costs were determined by refractoriness of SE and mechanical ventilation (MV). Hospitalization cost of SE was lower than those of stroke. Acute non-CNS pathology is largely responsible for the high cost of SE, particularly refractory SE requiring mechanical ventilation.


Cerebellar Mild Iron Accumulation in a Subset of FMR1 Premutation Carriers with FXTAS.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles of the FMR1 gene. Iron is essential for many facets of cell metabolism in the brain but when altered is likely to contribute to the development of neurodegenerative diseases. We previously reported that iron accumulates in the choroid plexus and the putamen in FXTAS and that the level and distribution of key iron-binding proteins are also altered, suggesting a potential alteration of iron metabolism in the brain. Here, we hypothesize that iron metabolism is also altered in the FXTAS cerebellum. To test this hypothesis, we used cerebellum samples collected from FXTAS and control subjects and measured the amount of iron contained within the cerebellar cortex and dentate nucleus. We found that the number of iron deposits increased in the cerebellum only in a subset of cases of FXTAS. This accumulation is likely to be mediated by factors other than or in addition to CGG-repeat coupled pathology. Thus, iron deposition in the cerebellum cannot be used as a hallmark of FXTAS pathogenesis.