Linear response approximation to reference interaction site model self-consistent field explicitly including spatial electron density distribution. Free energy.
We proposed linear response approximation to reference interaction site model self-consistent field explicitly including spatial electron density distribution (RISM-SCF-SEDD). Because the electrostatic potential induced by solvent molecules is approximated by linear response to the density change of solute molecule, new algorithm becomes significantly simple compared to the original RISM-SCF-SEDD. The present method was applied to simple molecules and p-nitroaniline (PNA). The maximum relative error of the linear response approximation is less than 1.0% in the solvation free energies of the simple molecules. The present method also achieved a stable calculation of PNA.


Freshwater as shared between society and ecosystems: from divided approaches to integrated challenges.
The paper has its focus on water's key functions behind ecosystem dynamics and the water-related balancing involved in a catchment-based ecosystem approach. A conceptual framework is being developed to address fundamental trade-offs between humans and ecosystems. This is done by paying attention to society's unavoidable landscape modifications and their unavoidable ecological effects mediated by water processes. Because the coevolution of societal and environmental processes indicates resonance rather than a cause-effect relationship, humanity will have to learn to live with change while securing ecosystem resilience. In view of the partial incompatibility of the social imperative of the millennium goals and its environmental sustainability goal, human activities and ecosystems have to be orchestrated for compatibility. To this end a catchment-based approach has to be taken by integrating water, land use and ecosystems. It is being suggested that ecosystem protection has to be thought of in two scales: site-specific biotic landscape components to be protected for their social value, and a catchment-based ecosystem approach to secure sustainable supply of crucial ecosystem goods and services on which social and economic development depends.


Immature monocyte-derived dendritic cells are productively infected with herpes simplex virus type 1.
Herpes simplex viruses (HSV) have developed several immunoevasive strategies. Here we demonstrate a novel mechanism by which HSV type 1 may interfere with the immune response through infection of immature dendritic cells (DC) and selective downmodulation of costimulatory molecules. In our study we show productive infection of immature monocyte-derived DC, which closely resemble sessile Langerhans cells, by sequential expression of immediate-early, early, and late viral proteins and of glycoprotein D mRNA, as well as production of infectious virus of moderate titers. Infection was cytopathic, with the progressive loss of 20 to 45% of cells from 24 to 48 h after infection, with no more than 80% of DC found to be infected. These results are in contrast to those of previous findings of nonpermissive or abortive infection of monocytes and mature monocyte-derived DC. Infection of immature DC also led to selective and asynchronous downregulation of CD1a, CD40, CD54 (ICAM-1) (12 h postinfection), CD80 (24 h postinfection), and CD86 (48 h postinfection) but not of CD11c or major histocompatibility complex class I and II molecules when compared to DC exposed to UV-inactivated virus. Thus, we propose that productive infection of epidermal Langerhans cells in vivo may lead to delayed activation of T cells, allowing more time for replication of HSV type 1 in epidermal cells.


Tumour differentiation grade is associated with TNM staging and the risk of node metastasis in colorectal cancer.
The tumour differentiation grade has been shown by numerous multivariate analyses to be a stage-independent prognostic factor in colorectal cancer. The aim of this study was to explore the importance of differentiation grading for the staging of colorectal cancer and how it relates to the components of the TNM system. The study was a retrospective single-centre analysis of all patients undergoing surgical resection for colorectal cancer during the period 2002-2007 (n = 1239). The clinical parameters and pathology data of overall stage, differentiation grade, local tumour (T)-stage and metastasis status (M-stage) were included as well as the lymph node count of both assessed and metastatic nodes. The differentiation grade was correlated with demography, overall stage and each component of the TNM staging system. The correlation between differentiation grade and N-stage was also explored for the separate T-stages. The tumour differentiation grade correlated significantly with the overall TNM stage (p < 0.0001). The grade significantly correlated with the T-stage and the risk of having lymph node metastasis (p < 0.0001). A high grade was associated with a higher positive lymph node count in stage III disease (p < 0.0002). For the T-stages, the risk of node metastasis was significantly linked to the tumour grade. A low grade (G1) T2 had a 17% risk of lymph node metastasis compared to a 44% risk for a high grade (G4) T2. Tumour differentiation is an important prognostic factor. It correlates significantly with the overall stage of the TNM system and also to each of its components. The risk of having lymph node metastasis for each T-stage also correlates with the tumour grade. The findings can be of importance in postoperative risk assessment or when considering local resection procedures like TEM.


Knowledge and Attitudes of Population Living in Rural and Semi-Rural Areas towards Covid-19 :Case of the Menoua Division, Cameroon.
The pandemic situation the world is facing caused by the new SARS-Cov-2 continues to evolve and still represent a real problem. With more than eight thousand reported cases infection, Cameroon stands as the seventh most affected country in Africa. Prevention remains the best way to fight against this zoonosis. However, the limited information available about this infection is a great barrier to stopping the propagation of the virus within the population, especially in rural and semi-rural areas, where the lack of financial and material resources is a reality. This study aimed to assessing Awareness and attitudes of the population of the Menoua Division on COVID-19 infection. A cross-sectional study was conducted from March 9 to April 15 2020 amongst the populations of rural and semi-rural areas of the Menoua Division. Data were collected using a questionnaire administered face to face to each participant. The analysis was carried out using the Statistical Analysis System software (SAS version 9.4). The significance threshold was set at a P value of less than 0.05. A total of 434 participants of which male majority (sex ratio 1.07) were included in this study. The most represented age group was [21 - 40] years old representing 40.29% of the participants. Approximately all participants (98.57%) were aware of the world emergency state due to Coronavirus. 75.56%, 91% and 90.93% of the participants knew respectively that having close contacts, kissing and touching the face with the hands could favor the transmission of the virus. However, nearly 91.14% were not aware of the clinical symptoms of the disease. Moreover, 85.02% responded that they would not be able to comply with the confinement measures if they were applied at national level. The level of awareness varied significantly according to the occupation (p=0.038) and the educational level (p<0.001)of the participants. The average level of awareness of the population of the Menoua Division on COVID-19 infection was relatively low. Overcoming this pandemic disease means ensuring the flow of the correct information towards the population. Community outreach activities focus on clinical manifestations and what to do in case of COVID-19 infection as well as material and financial support should be help the population to protect themselves effectively against pandemic, particularly in rural areas and surrounding.


My older sibling was drunk - younger siblings' drunkenness in relation to parental monitoring and the parent-adolescent relationship.
This study explored the links between having older siblings who get drunk, satisfaction with the parent-adolescent relationship, parental monitoring, and adolescents' risky drinking. Regression models were conducted based on a national representative sample of 3725 8th to 10th graders in Switzerland (mean age 15.0, SD = .93) who indicated having older siblings. Results showed that both parental factors and older siblings' drinking behaviour shape younger siblings' frequency of risky drinking. Parental monitoring showed a linear dose-response relationship, and siblings' influence had an additive effect. There was a non-linear interaction effect between parent-adolescent relationship and older sibling's drunkenness. The findings suggest that, apart from avoiding an increasingly unsatisfactory relationship with their children, parental monitoring appears to be important in preventing risky drinking by their younger children, even if the older sibling drinks in such a way. However, a satisfying relationship with parents does not seem to be sufficient to counterbalance older siblings' influence.


Keeping the Zika Virus Out of the Assisted Reproductive Technology Laboratory.
The Zika virus (ZIKV) epidemic spreading through South and Central America, as well as several U.S. territories has created worldwide concern as the linkage between ZIKV infection and microcephaly has been established. Both travel associated and sexually transmitted cases have put couples who live in nonendemic areas at risk of falling victim to effects of Zika. The presence of ZIKV within reproductive tissues may pose a significant threat to patients seeking fertility services and to safety of the tissues currently housed in assisted reproductive technology (ART) laboratories. There are still many unanswered questions regarding the mechanism of ZIKV sexual transmission. Just as strict guidelines have been set regarding the screening and handling of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus-positive patient tissues, similar recommendations are needed to prevent contamination and inadvertent transmission within the ART laboratory.


Withdrawal of ventricular assist device support.
Ventricular assist devices (VAD) are mechanical pumps implanted into patients with advanced heart failure who are at risk of imminent death. VADs are a treatment and not a cure, and mortality on device support remains high. Recognizing the dire nature of the decisions for patients and families and the associated high mortality rates, we actively included processes for device withdrawal as part of our program mandate. At Toronto General Hospital, from October 2001 to December 2004, 22 patients underwent implantation of a VAD. Seven patients died following device withdrawal. The average time spent on support prior to device withdrawal was seven days. In four of the seven cases, family members initiated discussions regarding device withdrawal. Family-initiated discussions were more likely to occur if patients were implanted electively, as a bridge to transplantation. Disagreements occurred between the ICU and the transplant teams regarding the timing of device withdrawal and responsibility for stopping the pump. Establishing a process for device withdrawal has been a key factor in the success of our VAD program. This process relies heavily on pre-implantation preparation, a strategy for resolving disagreements, and a process for withdrawing device support.


[The role of AGEs for the pathogenesis of osteopenia in diabetes mellitus].
Osteopenia was reported in patients with type I diabetes mellitus (DM). Also, serum levels of advanced glycation endproducts (AGEs) were reported to be elevated in DM. In this review, we showed the effect of AGEs on primary human osteoblasts, the precursor of human osteoclast like cells and parathyroid cells in culture. AGEs were made from incubating bovine serum albumin with glucose 6 phosphate for 8 weeks (AGEs-BSA). AGEs-BSA (1,000 microg/mL) showed inhibitory effect for human osteoblasts in terms of the productions of procolagen c propeptide and osteocalcin, which were regarded as bone forming parameters. On the other hand, the same concentration of AGEs-BSA inhibited the increase in the parathyroid hormone secretion from the cultured human parathyroid cells induced by low calcium medium concentration. AGEs-BSA increased time dependently intracellular calcium levels of HEK 293 cells, which expressed the wild type human calcium-sensing receptor. Also, AGEs-BSA increased IL-6 synthesis by primary human osteoblast. Our preliminary data also showed that AGEs-BSA increased osteoclast-like cells formation in number from the osteoclast precursor rich bone marrow cells. These data suggested the important role of AGEs for the pathogenesis of osteopenia in patients with DM through decreased bone formation and increased bone resorption.


Isolation of TGF-β-neutralizing single-domain antibodies of predetermined epitope specificity using next-generation DNA sequencing.
The epitope specificity of therapeutic antibodies is often critical to their efficacy and mode of action. Here, we report the isolation of single-domain antibodies (sdAbs) against a pre-specified epitope of TGF-β3: namely, the site of interaction between the cytokine and its cell-surface type II receptor. By panning a phage-displayed immune llama VhH library against TGF-β3 using competitive elution with soluble dimeric type II receptor ectodomain in tandem with next-generation DNA sequencing, we identified several sdAbs that competed with the receptor for TGF-β3 binding and neutralized TGF-β3 in in vitro cellular assays. In contrast, all other sdAbs identified using conventional panning approaches (i.e., without regard to epitope specificity) did not target the site of receptor:cytokine interaction. We expect this strategy to be generally applicable for identifying epitope-specific sdAbs when binding reagents directed against the epitope of interest are available. The sdAbs identified here are of potential interest as cancer immunotherapeutics.


Inflammatory breast cancer: MR imaging findings.
This paper describes the magnetic resonance (MR) imaging features of primary inflammatory breast cancer (IBC). Two radiologists reviewed the MR examinations of 14 women with a pathological diagnosis of IBC. Images were assessed for skin thickening, oedema, nipple retraction, architectural distortion, type and extent of parenchymal and cutaneous enhancement and enhancement kinetics over time, axillary and internal mammary lymphadenopathy, pectoral muscle enhancement and additional findings. Skin thickening was identified in eight patients (58%), oedema in nine (64%), nipple retraction in two (14%), architectural distortion in eight (58%), mass-like enhancement in five (36%), non-mass-like enhancement in nine (64%) with washout enhancement curve in 12 (86%) and plateau curve in two (14%), axillary lymphadenopathy in 12 (86%) and internal mammary artery lymphadenopathy in two (14%), and pectoral muscle enhancement in one (7%). Additional findings included increased breast volume in two patients (14%), prepectoral fluid in four (28%) and hypertrophic internal mammary artery in three (21%). The most characteristic MR findings of IBC are skin thickening, oedema, architectural distortion, mass-like enhancement with washout curve and axillary lymphadenopathy; less frequent ones are nipple retraction, mass-like enhancement and internal mammary lymphadenopathy. Prepectoral fluid is frequent but is not a sign of infiltration.


Results of Combined, Single-Session Arthrocentesis and Dextrose Prolotherapy for Symptomatic Temporomandibular Joint Syndrome: A Case Series.
Arthrocentesis and prolotherapy are nonsurgical treatments for temporomandibular joint (TMJ) diseases. This study aimed to evaluate the treatment of hypermobility, pain, and displacement of the TMJ by consecutively performing arthrocentesis and prolotherapy in the same session. In this study, 10 adults with disc displacement and painful, hypermobile TMJ were selected. Arthrocentesis and prolotherapy were consecutively performed using a 30% dextrose solution that was simultaneously injected into five areas: posterior disc attachment, superior joint space, superior and inferior capsular attachments, and stylomandibular ligament. Paired t-test, McNemar test, and chi-square test were used to assess the maximum mouth opening, clicking sounds, pain, and subluxation of the TMJ. Patients with rheumatoid arthritis and parafunctional habits such as teeth clenching and grinding and biting of the cheeks or any other objects and those who had undergone surgery were excluded from this study. A total of 10 participants (36.20 ± 7.06 years old, 7 women and 3 men) received a single treatment session of combined arthrocentesis and prolotherapy at the same office visit. Subluxation frequency and pain significantly decreased after the first week of treatment (p < 0.05). Subluxation also decreased at the 3-month follow-up (p < 0.05). Clicking sound values did not significantly change at any of the follow-up time points. Maximum mouth opening values decreased at all follow-up time points compared to baseline (p < 0.05). A single session of combined arthrocentesis and prolotherapy to treat symptomatic TMJ safely and significantly improved the subluxation and pain after 1 week and subluxation after 3 months compared to baseline status. The maximum mouth opening significantly decreased at all follow-up time points. Future studies assessing multiple treatment sessions are warranted.


Memory facilitation by posttraining and pretest ACTH, epinephrine, and vasopressin administration: two separate effects.
Rats were trained in a step-down inhibitory avoidance task using a 0.3-mA, 2-s, 60 Hz footshock and tested 24 hr later. The animals received, 1 min after training and/or 5 min before testing, an ip injection of saline, ACTH (0.2 microgram/kg), lysine-vasopressin (10 micrograms/kg), epinephrine (5 micrograms/kg), naloxone (0.4 mg/kg), or a combination of naloxone with one of the hormones. Both the posttraining and the pretest injection of the hormones enhanced retention test performance; the enhancement was larger in animals that received the two treatments. Posttraining, but not pretest, naloxone administration also caused an enhancement. However, posttraining naloxone potentiated, and pretest naloxone antagonized, the effect of the concomitantly injected hormones. These data show that the posttraining and the pretest effect of the hormones are independent, are due to different mechanisms, and can be additive. In addition, it does not seem possible to explain posttraining memory facilitation by the hormones as owing to an addition to the reinforcement.


Different Rates of Synthesis and Degradation of Two Chloroplastic Ammonium-Inducible NADP-Specific Glutamate Dehydrogenase Isoenzymes during Induction and Deinduction in Chlorella sorokiniana Cells.
The kinetics of accumulation (per milliliter of culture) of the alpha- and beta- subunits, associated with chloroplast-localized ammonium inducible nicotinamide adenine dinucleotide phosphate-specific glutamate dehydrogenase (NADP-GDH) isoenzymes, were measured during a 3 hour induction of synchronized daughter cells of Chlorella sorokiniana in 29 millimolar ammonium medium under photoautotrophic conditions. The beta-subunit holoenzyme(s) accumulated in a linear manner for 3 hours without an apparent induction lag. A 40 minute induction lag preceded the accumulation of the alpha-subunit holoenzyme(s). After 120 minutes, the alpha-subunit ceased accumulating and thereafter remained at a constant level (i.e. steady state between synthesis and degradation). From pulsechase experiments, using (35)SO(4) and immunochemical procedures, the rate of synthesis of the alpha-subunit was shown to be greater than the beta-subunit during the first 80 minutes of induction. The alpha- and beta-subunits had different rates of degradation during the induction period (t((1/2)) = 50 versus 150 minutes, respectively) and during the deinduction period (t((1/2)) = 5 versus 13.5 minutes) after removal of ammonium from the culture. During deinduction, total NADP-GDH activity decreased with a half-time of 9 minutes. Cycloheximide completely inhibited the synthesis and degradation of both subunits. A model for regulation of expression of the NADP-GDH gene was proposed.


Suicidal behaviors and childhood-onset depressive disorders: a longitudinal investigation.
In this longitudinal study, the rates and correlates of suicidal ideation and suicide attempts were determined among outpatient youths with depressive disorders and youths with other psychiatric disorders. At study entry, about 66% of the subjects evidenced suicidal ideation and 9% already attempted suicide. The rate of ideation remained fairly stable over time, whereas the rate of attempts reached 24% by the average age of 17 years. Major depressive and dysthymic disorders were associated with significantly higher rates of suicidal behaviors than were adjustment disorder with depressed mood and nondepressive disorders. In the presence of affective disorders, comorbid conduct and/or substance use disorders further increased the risk of suicide attempts.


Management of deep caries and the exposed pulp.
Caries prevalence remains high throughout the world, with the burden of disease increasingly affecting older and socially disadvantaged groups in Western cultures. If left untreated, caries will advance through dentine stimulating pulpitis and eventually pulp infection and necrosis; however, if conservatively managed, pulpal recovery occurs even in deep carious lesions. Traditionally, deep caries management was destructive with nonselective (complete) removal of all carious dentine; however, the promotion of minimally invasive biologically based treatment strategies has been advocated for selective (partial) caries removal and a reduced risk of pulp exposure. Selective caries removal strategies can be one-visit as indirect pulp treatment or two-visit using a stepwise approach. Management strategies for the treatment of the cariously exposed pulp are also shifting with avoidance of pulpectomy and the re-emergence of vital pulp treatment (VPT) techniques such as partial and complete pulpotomy. These changes stem from an improved understanding of the pulp-dentine complex's defensive and reparative response to irritation, with harnessing the release of bioactive dentine matrix components and careful handling of the damaged tissue considered critical. Notably, the development of new pulp capping materials such as mineral trioxide aggregate, which although not an ideal material, has resulted in more predictable treatments from both a histological and a clinical perspective. Unfortunately, the changes in management are only supported by relatively weak evidence with case series, cohort studies and preliminary studies containing low patient numbers forming the bulk of the evidence. As a result, critical questions related to the superiority of one caries removal technique over another, the best pulp capping biomaterial or whether pulp exposure is a negative prognostic factor remain unanswered. There is an urgent need to promote minimally invasive treatment strategies in Operative Dentistry and Endodontology; however, the development of accurate diagnostic tools, evidence-based management strategies and education in management of the exposed pulp are critical in the future.


Artificial Intelligence in hepatology, liver surgery and transplantation: Emerging applications and frontiers of research.
The integration of artificial intelligence (AI) and augmented realities into the medical field is being attempted by various researchers across the globe. As a matter of fact, most of the advanced technologies utilized by medical providers today have been borrowed and extrapolated from other industries. The introduction of AI into the field of hepatology and liver surgery is relatively a recent phenomenon. The purpose of this narrative review is to highlight the different AI concepts which are currently being tried to improve the care of patients with liver diseases. We end with summarizing emerging trends and major challenges in the future development of AI in hepatology and liver surgery.


The cyclic nucleotide-gated channels of vertebrate photoreceptors and olfactory epithelium.
Cation channels that are directly gated by guanosine 3', 5'-cyclic monophosphate (cGMP) control the flow of ions across the surface membrane of vertebrate rod and cone photoreceptor cells. A similar channel, gated by adenosine 3',5'-cyclic monophosphate (cAMP), exists in vertebrate olfactory sensory neurons. The channel polypeptide of rod photoreceptors has been identified and the amino acid sequence of the channel polypeptide in rod and olfactory cells has been determined by cloning cDNA. Although the cyclic nucleotide-gated channels functionally belong to the class of ligand-gated channels, they share some structural features with voltage-gated channels.


Mammalian GW182 contains multiple Argonaute-binding sites and functions in microRNA-mediated translational repression.
In mammalian cells, microRNAs (miRNAs) are incorporated into miRNA-induced silencing complexes (miRISCs), which regulate protein expression post-transcriptionally through binding to 3'-untranslated regions of target mRNAs. Argonaute2 (Ago2), a key component of the miRISC, recruits GW182, a component of the processing body (GW/P-body), to the target mRNAs. To elucidate the function of GW182 in an miRNA-mediated translational repression, we analyzed Argonaute-binding sites in GW182. We found that human GW182 contains three binding sites for Ago2, within the amino-terminal glycine tryptophan (GW/WG)-repeated region that is characteristic of the GW182 family proteins. We also found that the first and second Ago2-binding site is conserved within the amino-terminal half of TNRC6B, which is a paralog of GW182. Each of the Ago-binding sites is alone sufficient to bind Ago2. Furthermore, we demonstrated that multiple Argonaute proteins were connected via the GW182 protein. A GW182 fragment containing the Ago2-binding region partially relieved let-7-mediated repression of protein synthesis in a mammalian cell-free system. Coincidentally, let-7-directed target mRNA deadenylation was delayed. Together, these results strongly suggested that the interactions of GW182 with Argonautes may induce the formation of large complexes containing miRNA target mRNAs, and may be critical for miRNA-mediated translational repression.


Rosuvastatin reduces caspase-3 activity and up-regulates alpha-secretase in human neuroblastoma SH-SY5Y cells exposed to A beta.
An increasing number of studies suggest that disturbances in cholesterol homeostasis may promote the formation and deposition of beta-amyloid (A beta) and the progression of Alzheimer's disease (AD). In this paper, we have analyzed the effect of the lipid-lowering compound rosuvastatin on apoptosis and caspase-3 activity in human neuroblastoma SH-SY5Y cells. Exposure of SH-SY5Y cells to A beta(1-42) alone resulted in a significantly increased caspase-3 activity approximately by 35% (135+/-15%, p<0.05), and decreased alpha-secretase activity by 34% (67.4+/-2.7%, p<0.001) compared to the controls (100+/-18.1%). Rosuvastatin alone decreased caspase-3 activity by 15% (85.3+/-1.5%, p<0.0005) compared to the controls and by 50% to cells exposed to A beta alone (p<0.00005). Cells exposed to rosuvastatin alone had a higher alpha-secretase activity compared to cells exposed to A beta (76.4+/-23.8%, n.s.) but a slightly lower activity compared to the controls (n.s.). Pre-treatment of SY-SY5Y cells with rosuvastatin prior to incubation with A beta(1-42) resulted in decreased caspase-3 activity by approximately 15% compared to the controls and by approximately 48% (86.8+/-16.9%, p<0.05) compared to cells treated with A beta(1-42) alone. Also, alpha-secretase activity was increased by approximately 50% compared to the controls and by 84% (151.3+/-10.1%, p<0.05), compared to cells treated with A beta(1-42) alone. Mevalonate abrogated the effect of rosuvastatin in vitro. To our knowledge, this is the first study demonstrating that the hydrophilic compound rosuvastatin decreases caspase-3 activity and increases alpha-secretase activity in human neuroblastoma SH-SY5Y cells exposed to A beta in vitro. These effects are essential for modulation of the amyloidogenic pathway and mediators of apoptosis in AD.


Surgical Treatment of Bilateral Atrophic Mandible Fracture.
Poor proprioception, weakness, and impaired reflexes increase the incidence of facial fracture in the elderly. Mandibular fractures in these people range from 10.1% to 56%. Fragment reduction and fracture consolidation are difficult due to bone atrophy, decreased capacity for bone regeneration, and lack of anatomical landmarks to guide the alignment of the fragments. This study reports 2 patients with different conducts regarding the treatment of bilateral fractures in atrophic mandible. The first patient refers to the removal of plates of the 2.4 mm system with low profile, which failed during the mandibular function, being replaced by the 2.4 mm system with high profile. The 2nd clinical reports the use of the 2.0 mm system only to simplify the mandibular fracture, and then reconstructing that with a 2.4-mm system with high profile, using the load bearing principles. Regarding mandibular fractures, an important goal is to neutralize the muscle action aiming the bone stability. There are several methods to treat that the indication should consider the load bearing and load sharing concepts. The incorrect fixation choice in these patients can result in complications as bad union, material failure, infection, and consequent treatment failure.


Syntheses and biological activities of rebeccamycin analogues. Introduction of a halogenoacetyl substituent.
In the course of structure-activity relationships on rebeccamycin analogues, a series of compounds bearing a halogenoacetyl substituent were synthesized with the expectation of increasing the interaction with DNA, possibly via covalent reaction with the double helix. Two rebeccamycin analogues bearing an acetyl instead of a bromoacetyl substituent were prepared to gain an insight into the role of the halogen atom. The new compounds show very little effect on protein kinase C and no covalent reaction with DNA was detected. However, the drugs behave as typical topoisomerase I poisons, and they are significantly more toxic toward P388 leukemia cells than to P388/CPT5 cells resistant to camptothecin. The introduction of a bromo- or chloro-acetyl substituent does not affect the capacity of the drug to interfere with topoisomerase I either in vitro or in cells. One of the bromoacetyl derivatives, compound 8, is the most cytotoxic rebeccamycin derivative among the hundred of derivatives we have synthesized to date. In addition, we determined the antimicrobial activities against two Gram-positive bacteria, Bacillus cereus and Streptomyces chartreusis, and against the Gram-negative bacterium Escherichia coli. The effect of the drugs on Candida albicans yeast growth and their anti-HIV-1 activities were also measured.


Sensitivity and specificity analysis for somatic cell count (SCC) used to predict bacteriologically positive subclinical mastitis at calving in a dairy herd with low SCC.
Validate, by sensitivity and specificity analyses, use of somatic cell count (SCC) to predict bacteriologically positive subclinical mastitis in a California dairy herd with low SCC. Study of monthly dairy herd improvement SCC obtained from the immediate preceding lactation and individual cow composite milk sample microbiologic isolates collected at calving. 515 California dairy cows with SCC and culture data. Somatic cell count sensitivity and specificity analyses with combinations of SCC parameter and at various thresholds were done, using the bacterial isolates as the standard. Combination of SCC threshold and SCC parameters could not be developed that had sufficient sensitivity and specificity to be a useful predictor of cows that would calve with subclinical mastitis. Under the conditions at this particular dairy, SCC could not be used as a basis of prediction of cows that would calve with bacteriologically positive subclinical mastitis or require selective nonlactating-cow antibiotic treatment.


[Diagnosis and prevalence of sarcopenia in long-term care homes: EWGSOP2 versus EWGSOP1].
Background: the definition and methodology recommended for the diagnosis of sarcopenia has been changing. The mostly applied consensus is the one published by the European Working Group in Older People in 2010 (EWGSOP1), which was updated in 2019 (EWGSOP2). Objectives: assessing the prevalence of sarcopenia in institutionalized older adults using the EWGSOP2 algorithm and comparing these results with the EWGSOP1 algorithm results. Methods: in order to diagnose sarcopenia, muscle mass was assessed using an impedanciometer, muscle strength with a dynamometer and walking speed over a four-meter course. For the comparison of the results, a sensitivity and specificity analysis were performed with the version 20 of SPSS. Results: according to the EWGSOP2, 60.1% of the participants had sarcopenia and 58.1% had severe sarcopenia, results with no statistical differences when they are compared to the results according to the EWGSOP1 (63% had sarcopenia and 61.2%, severe sarcopenia). Neither were statistical differences found when comparing subjects with low muscle mass according to the formulas suggested by both consensus, while there were differences when comparing subjects with low muscle strength due to the variation of cut-off points. Conclusions: the prevalence of sarcopenia in institutionalized older adults is high, being remarkable that the majority of the participants had low muscle strength and low physical performance. The utilization of the methodology proposed by the EWGSOP2 did not have influence in the results of prevalence of sarcopenia obtained when the EWGSOP1 recommendations were applied.


Emergency anaesthetic management of a severely anaemic, chronic schizophrenic patient with history of neuroleptic malignant syndrome.
Administering anaesthesia to a patient with chronic schizophrenia is a challenge due to the increased risk of various perioperative complications. Neuroleptic agents are highly effective drugs used for the treatment of psychiatric disorders, but are rarely associated with neuroleptic malignant syndrome (NMS). Here, we describe the successful anaesthetic management of a patient of chronic schizophrenia with past history of NMS who presented in emergency with active bleeding per rectum and haemoglobin of 3 gm%.


Efficacy of prosthetic rehabilitation in rotationplasty following Ewing's sarcoma: A case study.
Restoration of functional mobility including gait and balance are fundamental to prosthetic rehabilitation in children with rotationplasty. The literature to characterize and investigate the correlation between postural balance and gait following rotationplasty are scarce. This study examines the characteristics of balance and prosthetic gait in a subject with rotationplasty and checks whether any association exists between them. A 14-year-old boy with rotationplasty following Ewing's sarcoma was fitted with a custom made prosthesis. Center of pressure (COP) measures using the HUMAC® Balance & Tilt System (CSMi, Stoughton, MA), temporal-spatial gait parameters, and energy expenditure measured by a 10 meter walk test were recorded using the new and old prosthesis. A control subject was used for comparison. The stability score, path length, and average velocity of COP improved in a new prosthesis for both standing conditions. Gait parameters were improved and energy expenditure was marginally reduced with the new prosthesis. However, overall prosthetic gait was significantly different compared to the control subject. This subject-centric approach successfully improved balance, gait parameters, and energy expenditure by providing better alignment, fit, and comfort with a custom prosthesis.


Clinical Significance of OX40 and OX40 Ligand in the Peripheral Blood of Patients with Myasthenia Gravis.
A previous study on thymomas in myasthenia gravis (MG) patients indicated that OX40 expression may be upregulated in thymic tissues adjacent to germinal centers (GCs) and thymomas, and OX40 may interact with OX40L in GCs to enhance anti-acetylcholine receptor antibody production. However, little is known about the clinical significance of the expression of OX40 and OX40L in the peripheral blood of patients with MG. We aimed to characterize the expression of membrane-bound and soluble OX40 and OX40L in the peripheral blood of patients with MG and to identify their clinical significance. For membrane molecules, we collected peripheral blood (PB) from 39 MG patients at baseline, 22 patients in relapse, and 42 patients in remission, as well as from 36 healthy participants as controls. For soluble molecules, plasma from 37 MG patients at baseline, 34 patients in relapse, and 30 patients in remission, as well as plasma from 36 healthy controls (HC), was retrospectively collected from the sample bank of the First Hospital of Soochow University. The expression of membrane-bound OX40 and OX40L (mOX40 and mOX40L) by immune cells was measured using flow cytometry. Plasma levels of soluble OX40 and OX40L (sOX40 and sOX40L) were measured by ELISA. (1) The expression of OX40 on CD4+ T cells and that of OX40L on B cells and monocytes were significantly increased, and the levels of sOX40 were significantly decreased in MG patients at baseline compared with HC, while the expression of sOX40L was not significantly different between the two groups. (2) Dynamic observation of the molecules showed significantly higher expression of OX40 on CD4+ T cells and higher levels of sOX40 in MG patients in relapse than in MG patients at baseline and MG patients in remission. Furthermore, the expression levels of sOX40 were significantly elevated in MG patients in remission compared with MG patients at baseline, and the expression of sOX40L was significantly lower in MG patients in remission than in MG patients at baseline and MG patients in relapse. (3) Plasma levels of sOX40 and sOX40L were significantly decreased in 13 patients with relapsed MG after immunosuppressive treatment compared with those before treatment. (4) Correlation analysis showed that the expression of OX40 on CD4+ T cells in patients with relapsed MG was positively correlated with the concentration of acetylcholine receptor antibodies (AchR-Ab), whereas the expression of OX40L on CD19+ B cells and CD14+ monocytes was negatively correlated with disease duration. (5) Binary regression analysis showed that patients with high CD4+ OX40 expression and high sOX40L levels had an increased risk of relapse. OX40 and OX40L are abnormally expressed in the peripheral blood of patients with MG and may be closely associated with disease status and treatment. The OX40/OX40L pathway may be involved in the immunopathological process of MG and may play a role mainly in the later stage of MG.


Prediction of COVID-19 - Pneumonia based on Selected Deep Features and One Class Kernel Extreme Learning Machine.
In this work, we propose a deep learning framework for the classification of COVID-19 pneumonia infection from normal chest CT scans. In this regard, a 15-layered convolutional neural network architecture is developed which extracts deep features from the selected image samples - collected from the Radiopeadia. Deep features are collected from two different layers, global average pool and fully connected layers, which are later combined using the max-layer detail (MLD) approach. Subsequently, a Correntropy technique is embedded in the main design to select the most discriminant features from the pool of features. One-class kernel extreme learning machine classifier is utilized for the final classification to achieving an average accuracy of 95.1%, and the sensitivity, specificity & precision rate of 95.1%, 95%, & 94% respectively. To further verify our claims, detailed statistical analyses based on standard error mean (SEM) is also provided, which proves the effectiveness of our proposed prediction design.


The AG dinucleotide terminating introns is important but not always required for pre-mRNA splicing in the maize endosperm
Previous RNA analysis of lesions within the 15 intron-containing Sh2 (shrunken2) gene of maize (Zea mays) revealed that the majority of these mutants affect RNA splicing. Here we decipher further two of these mutants, sh2-i (shrunken2 intermediate phenotype) and sh2-7460. Each harbors a G-to-A transition in the terminal nucleotide of an intron, hence destroying the invariant AG found at the terminus of virtually all nuclear introns. Consequences of the mutations, however, differ dramatically. In sh2-i the mutant site is recognized as an authentic splice site in approximately 10% of the primary transcripts processed in the maize endosperm. The other transcripts exhibited exon skipping and lacked exon 3. A G-to-A transition in the terminus of an intron was also found in the mutant sh2-7460, in this case intron 12. The lesion activates a cryptic acceptor site downstream 22 bp within exon 13. In addition, approximately 50% of sh2-7460 transcripts contain intron 2 and 3 sequences.


Meta-analysis of the relative sensitivity of semi-natural vegetation species to ozone.
This study identified 83 species from existing publications suitable for inclusion in a database of sensitivity of species to ozone (OZOVEG database). An index, the relative sensitivity to ozone, was calculated for each species based on changes in biomass in order to test for species traits associated with ozone sensitivity. Meta-analysis of the ozone sensitivity data showed a wide inter-specific range in response to ozone. Some relationships in comparison to plant physiological and ecological characteristics were identified. Plants of the therophyte lifeform were particularly sensitive to ozone. Species with higher mature leaf N concentration were more sensitive to ozone than those with lower leaf N concentration. Some relationships between relative sensitivity to ozone and Ellenberg habitat requirements were also identified. In contrast, no relationships between relative sensitivity to ozone and mature leaf P concentration, Grime's CSR strategy, leaf longevity, flowering season, stomatal density and maximum altitude were found. The relative sensitivity of species and relationships with plant characteristics identified in this study could be used to predict sensitivity to ozone of untested species and communities.


Efficient Anchoring of Polysulfides Based on Self-Assembled Ti3C2Tx Nanosheet-Connected Hollow Co(OH)2 Nanotubes for Lithium-Sulfur Batteries.
Designing sulfur host materials with unique functions such as physical constraint or chemical catalysis to suppress the shuttle effect and promote the fast conversion of polysulfides is a prerequisite for lithium-sulfur batteries (LSBs). Herein, we construct hollow Co(OH)2 nanotubes connected by Ti3C2Tx nanosheets (denoted as Co(OH)2@Ti3C2Tx) as host materials for sulfur through a simple self-assembly method at room temperature. The large void spaces of Co(OH)2 nanotubes not only confine higher sulfur loading but also mitigate the volumetric expansion in the process of lithiation. Moreover, the conductive Ti3C2Tx layers facilitate fast electron transfer and catalyze the transition of sulfur based on the terminations on the surface. Combining those two materials can also act as an efficient polysulfide anchor to enable outstanding electrochemical performance. The Co(OH)2@Ti3C2Tx@S cathode presents a high discharge capacity of 1400 mAh g-1 at 0.1C and long-cycling stability at 1C for 500 cycles. Moreover, the obtained capacity of Li2S precipitation and the dissolution capacity reach 193.3 and 291.1 mAh g-1, respectively. Consequently, this work demonstrates a facile strategy to design multifunctional materials that effectively confine the polysulfides and enhance the performance of LSBs.


Detection and identification of ACP-105 and its metabolites in equine urine using LC/MS/MS after oral administration.
ACP-105 is a novel nonsteroidal selective androgen receptor modulator (SARM) with a tissue-specific agonist effect and does not have side effects associated with the use of common androgens. This research reports a comprehensive study for the detection of ACP-105 and its metabolites in racehorses after oral administration (in vivo) and postulating its structures using mass spectrometric techniques. To obtain the metabolic profile of ACP-105, a selective and reliable LC-MS/MS method was developed. The chemical structures of the metabolites were determined based on their fragmentation pattern, accurate mass, and retention time. Under the current experimental condition, a total of 19 metabolites were detected in ACP-105 drug administered equine urine samples. The study results suggest the following: (1) ACP-105 is prone to oxidation, which gives corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (2) along with oxidation, there is a possibility of elimination of water molecule (dehydration) from the third position of the tropine moiety, resulting in the dehydrated analogs of corresponding monohydroxylated, dihydroxylated, and trihydroxylated metabolites; (3) from the study on the metabolites using LC-MS/MS, it is clear that the fragmentation pattern is identical and a great number of fragment ions are common in all the metabolites and the parent drug. (4) The ACP-105 and its metabolites were detected for up to 72 h; thus, the result is a valuable tool for evaluating its use and/or misuse in sport.


Immunotherapy for metastatic liver disease from colorectal carcinoma: case series from the Middle East.
Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis.


[Relationship between apoptosis of neurons and microglia activation in Alzheimer's disease].
To assess the relationship between microglia activation and apoptosis of neurons, and the significance of activated microglias in the formation and progression of senile plaques in Alzheimer's disease. IL-1alpha and beta-amyloid immunohistochemistry, combined with TUNEL assay were used to assess brain tissue samples from 10 patients with Alzheimer's disease and 4 negative control cases without neurological disease. The number of resting microglias in the brains of Alzheimer's disease patients was similar to that of the control group (P > 0.05), but the number of activated microglias was significant greater in the Alzheimer's disease patients than that of the controls (P < 0.01). The activated microglias displayed altered size and morphology, and was therefore, categorized into three subtypes as primed, enlarged and phagocytic microglias. The numbers of primed, enlarged and phagocytic microglias were 5.4 +/- 0.87, 11.5 +/- 1.25, and 3.4 +/- 0.32 microglia/mm2 and represented 26.6%, 56.65%, and 16.75% of all activated microglias respectively. The number of TUNEL positive apoptotic neurons was significantly greater in Alzheimer patients than that in the control group (P < 0.05). There was a close relationship between the apoptosis of neurons and the activation of microglias (P < 0.01). The activated microglias were differentially distributed among four different plaque types in Alzheimer patients. Many primed (42.3%) and most of the enlarged and phagocytic microglias (56.2% and 70.6%) were present in the diffuse neuritic plaques. Hyperplasia and activation of microglias are a common phenomena in AD and may play an important role in its pathogenesis. There is a close relationship between the apoptosis of neurons and activation of microglias. The activation of microglias may play a key pathogenic role in senile plaque formation and progression of Alzheimer disease.


Resveratrol directly affects ovarian cell sirtuin, proliferation, apoptosis, hormone release and response to follicle-stimulating hormone (FSH) and insulin-like growth factor I (IGF-I).
The objective of our study was to examine the influence of the plant polyphenol resveratrol (R) on the rapamycin signalling pathway (mammalian target of rapamycin; mTOR) and basic ovarian cell functions in mammalian targets, as well as on their response to the physiological hormonal stimulators follicle-stimulating hormone (FSH) and insulin-like growth factor I (IGF-I). Resveratrol was found to stimulate sirtuin 1 accumulation and apoptosis, inhibit proliferation, suppress P and promote T and E release. Alone, FSH promoted proliferation and had no effect on apoptosis, but had an inhibitory effect on these processes when combined with R. IGF-I alone stimulated proliferation and inhibited apoptosis and promoted P production but not that of T; however, in the presence of R, the addition of IGF-I switched from having an anti-apoptotic to a pro-apoptotic effect and stimulated T release, but it did not modify the effect of IGF-I on proliferation and P output. These observations: (1) demonstrate that R directly affects the basic ovarian cell functions of proliferation, apoptosis and steroidogenesis, (2) provide further evidence of the involvement of FSH and IGF-I in the regulation of these processes, (3) demonstrate the ability of R to prevent and even invert the effects of FSH and IGF-I on ovarian cells and (4) indicate that the effects of R may be mediated by the mTOR-sirtuin intracellular signalling system.


The crystal structure of a high affinity RNA stem-loop complexed with the bacteriophage MS2 capsid: further challenges in the modeling of ligand-RNA interactions.
We have determined the structure to 2.8 A of an RNA aptamer (F5), containing 2'-deoxy-2-aminopurine (2AP) at the -10 position, complexed with MS2 coat protein by soaking the RNA into precrystallised MS2 capsids. The -10 position of the RNA is an important determinant of binding affinity for coat protein. Adenine at this position in other RNA stem-loops makes three hydrogen bonds to protein functional groups. Substituting 2AP for the -10 adenine in the F5 aptamer yields an RNA with the highest yet reported affinity for coat protein. The refined X-ray structure shows that the 2AP base makes an additional hydrogen bond to the protein compared to adenine that is presumably the principal origin of the increased affinity. There are also slight changes in phosphate backbone positions compared to unmodified F5 that probably also contribute to affinity. Such phosphate movements are common in structures of RNAs bound to the MS2 T = 3 protein shell and highlight problems for de novo design of RNA binding ligands.


GPT-4 can pass the Korean National Licensing Examination for Korean Medicine Doctors.
Traditional Korean medicine (TKM) emphasizes individualized diagnosis and treatment. This uniqueness makes AI modeling difficult due to limited data and implicit processes. Large language models (LLMs) have demonstrated impressive medical inference, even without advanced training in medical texts. This study assessed the capabilities of GPT-4 in TKM, using the Korean National Licensing Examination for Korean Medicine Doctors (K-NLEKMD) as a benchmark. The K-NLEKMD, administered by a national organization, encompasses 12 major subjects in TKM. GPT-4 answered 340 questions from the 2022 K-NLEKMD. We optimized prompts with Chinese-term annotation, English translation for questions and instruction, exam-optimized instruction, and self-consistency. GPT-4 with optimized prompts achieved 66.18% accuracy, surpassing both the examination's average pass mark of 60% and the 40% minimum for each subject. The gradual introduction of language-related prompts and prompting techniques enhanced the accuracy from 51.82% to its maximum accuracy. GPT-4 showed low accuracy in subjects including public health & medicine-related law, internal medicine (2), and acupuncture medicine which are highly localized in Korea and TKM. The model's accuracy was lower for questions requiring TKM-specialized knowledge than those that did not. It exhibited higher accuracy in diagnosis-based and recall-based questions than in intervention-based questions. A significant positive correlation was observed between the consistency and accuracy of GPT-4's responses. This study unveils both the potential and challenges of applying LLMs to TKM. These findings underline the potential of LLMs like GPT-4 in culturally adapted medicine, especially TKM, for tasks such as clinical assistance, medical education, and research. But they also point towards the necessity for the development of methods to mitigate cultural bias inherent in large language models and validate their efficacy in real-world clinical settings.


Protein S-palmitoylation in cellular differentiation.
Reversible protein S-palmitoylation confers spatiotemporal control of protein function by modulating protein stability, trafficking and activity, as well as protein-protein and membrane-protein associations. Enabled by technological advances, global studies revealed S-palmitoylation to be an important and pervasive posttranslational modification in eukaryotes with the potential to coordinate diverse biological processes as cells transition from one state to another. Here, we review the strategies and tools to analyze in vivo protein palmitoylation and interrogate the functions of the enzymes that put on and take off palmitate from proteins. We also highlight palmitoyl proteins and palmitoylation-related enzymes that are associated with cellular differentiation and/or tissue development in yeasts, protozoa, mammals, plants and other model eukaryotes.


Orbital cellulitis with gas.
Orbital cellulitis due to presumed gas-producing organisms has been associated with poor visual prognosis. We report successful visual recovery in a 14-year-old boy with orbital cellulitis and gas in the orbit on CT scan. The patient was treated with intravenous antibiotics and prompt orbital decompression. Pus from the sinus aspirate and orbital drain grew H. influenzae and Gram-negative bacilli. Repeat orbital surgery with drainage of residual abscess was performed and the patient made a complete recovery.


Fabrication of syntactic foam fillers via manipulation of on-chip quasi concentric nanoparticle-shelled droplet templates.
Syntactic foams with fly ash cenospheres or commercial microballoons as fillers have been widely used in various applications ranging from aerospace to marine fields and the automotive industry. However, these two extensively adopted fillers possess multiple shortcomings, such as variations in the composition, material degeneration and distinct structural heterogeneity, which will inevitably hamper accurate prediction of the structure-property relationship and the corresponding design of the syntactic foams, reducing material utilization. Here, we present a microfluidic-based approach integrated with a subsequent heat treatment process to engineer syntactic foam fillers with a predefined composition, specified dimensional scope and reduced structural heterogeneity. These fillers are fully guaranteed by the synergy of the flexible and controllable generation of droplet templates with hydrodynamic regulation and rational selection of the nanoparticle dynamic response with respect to the heating temperature. In addition, two distinct surface morphologies have been observed with a temperature demarcation point of 1473 K, further endowing the fillers with multiplicity and optionality, simultaneously laying the foundation to regulate the properties of the syntactic foams through the diversity of the filler selection. Then, we fabricated a syntactic foam specimen by mold casting, and the integrity of the fillers inside was verified using an elaborate buoyancy comparison experiment, exhibiting its potential value in lightweight related applications. As the fillers derived from our approach show significant advantages over conventional ones, they will provide considerable benefits for the regulation and improvement of syntactic foam fillers in many practical applications.


Burch colposuspension for the treatment of coital urinary leakage secondary to genuine stress incontinence.
The efficacy of Burch colposuspension in treating the symptom of coital urinary leakage in women with genuine stress incontinence has to date never been reported. Women who presented to our clinic with regular coital urinary leakage and urodynamically proven genuine stress incontinence between 1993 and 1997, and who proceeded to a Burch colposuspension procedure, were reviewed to determine the outcome of surgery. Fifty-five women were identified (mean age 46.1 years) with a mean follow-up interval after surgery of 18 months (range 3-42 months). All 55 women had symptoms of stress, urge and coital incontinence preoperatively. Following colposuspension, the subjective cure rates for stress and urge incontinence were 84% and 85%, respectively. Of 52 women that were sexually active after surgery, 81% described no further coital incontinence. The success or failure of surgery was not influenced by whether leakage occurred with penetration or orgasm preoperatively.


Correlations of telomere length, P53 mutation, and chromosomal translocation in soft tissue sarcomas.
Soft tissue sarcomas (STSs) are a heterogeneous group of malignant tumors that can be divided into specific reciprocal translocation associated in STSs (SRTSs) and nonspecific reciprocal translocation associated in STSs (NRTSs). Telomeres play a key role in maintaining chromosomal stability; pathological telomere elongation is found in a number of cancers. In this study, we aimed to assess telomere lengths in the two types of sarcomas. Twenty formalin-fixed paraffin-embedded (FFPE) archival tissues, namely, 10 sarcomas with characteristic translocations and 10 without characteristic translocations, were included in this study. Expression levels of special fusion gene transcripts were detected in these tumors by reverse transcription polymerase chain reaction. Telomere lengths were assessed by fluorescence in situ hybridization. Results showed that in 10 of the 10 cases of SRTSs, telomere lengths were similar to or reduced compared with the surrounding normal cells. Telomere lengths were elongated in eight of 10 cases of NRTSs, but reduced in two cases. The difference in telomere length was statistically significant in the two types of sarcomas (P=0.001). Upon combining the P53 mutation status, we found that the telomere length was short in eight cases, and only one case demonstrated p53 mutation. However, the telomere length was long in eight cases, and p53 mutation was observed in five cases. These data suggested that p53 mutation was accompanied with long telomeres, and telomeres possibly play an important role in NRTSs. Therefore, telomere-targeting therapy may lead to novel therapeutic strategies to improve treatment of NRTS patients.


Cyclosporin A-induced gingival hyperplasia in psoriasis: review of the literature and case reports.
Cyslosporin A (CyA) treatment of psoriasis is warranted in severe cases where other, conventional antipsoriatic approaches have failed. Gingival hyperplasia is a rare side effect of cyclosporin A treatment in psoriasis patients. Previous studies in cyclosporin A-treated patients (mostly transplant recipients) have demonstrated correlation between cyclosporin A serum levels and oral hygiene status on the one hand, and the prevalence and severity of this overgrowth on the other hand. Severe cases of gingival overgrowth may call for radical treatments such as periodontal surgery. Our aim was to present a severe form of cyclosporin A-induced hyperplasia in two female patients and to give an overview of the current literature on the issue. High serum levels of cyclosporin A were observed in both patients. Moreover, high initial plaque accumulation was noted in both patients. Upon cessation of drug administration and a combined periodontal treatment, virtually complete reduction of the gingival enlargement and inflammation was observed. Consequently, early diagnosis and an all-inclusive treatment of cyclosporin A-induced hyperplasia can result in virtually complete remission of the symptoms and eliminate the need of aggressive treatments such as periodontal surgery.


Butyric Acid from Probiotic Staphylococcus epidermidis in the Skin Microbiome Down-Regulates the Ultraviolet-Induced Pro-Inflammatory IL-6 Cytokine via Short-Chain Fatty Acid Receptor.
The glycerol fermentation of probiotic Staphylococcus epidermidis (S. epidermidis) in the skin microbiome produced butyric acid in vitro at concentrations in the millimolar range. The exposure of dorsal skin of mice to ultraviolet B (UVB) light provoked a significant increased production of pro-inflammatory interleukin (IL)-6 cytokine. Topical application of butyric acid alone or S. epidermidis with glycerol remarkably ameliorated the UVB-induced IL-6 production. In vivo knockdown of short-chain fatty acid receptor 2 (FFAR2) in mouse skin considerably blocked the probiotic effect of S. epidermidis on suppression of UVB-induced IL-6 production. These results demonstrate that butyric acid in the metabolites of fermenting skin probiotic bacteria mediates FFAR2 to modulate the production of pro-inflammatory cytokines induced by UVB.


Transanal endoscopic microsurgery: exploring its indications and novel applications. A narrative review.
Featuring some advantages of endoscopy and microsurgery, transanal endoscopic microsurgery (TEM) was first introduced in treating local early-stage rectal lesions in 1983. However, its applications to rectal surgery have remained virtually unchanged over the past 38 years. This review aims to describe some well-accepted indications for TEM and showcase other novel but successful applications. In this review, we conducted a thorough English literature review on the applications of transanal endoscopic microsurgery in the PubMed database. Published original articles, case reports, and letters from 1983 to 2020 were included. Retrieved articles were discussed and conclusions were made. The results showed that applications of TEM could be more flexible and extended, namely, TEM's niche applications in advanced rectal cancer after neoadjuvant chemoradiotherapy, neuroendocrine tumor, gastrointestinal stromal tumor, fistula, solitary rectal ulcer syndrome, benign stricture, and transanal total mesorectal excision are promising, while prospective studies are needed.


The effect of centrifugal forces on viability of adipocytes in centrifuged lipoaspirates.
Standard protocols for autologous fat transfer involve centrifugation of the lipoaspirate for better separation. The effect of the centrifugal forces on cell viability and possible induction of apoptosis is discussed controversially in current literature. We have examined the vitality of adipocytes in lipoaspirates after centrifugation by 8 different accelerations up to 20.000g immediately after the respective centrifugation as well as 4 days later by staining. No significant alterations in the viability of differently centrifuged adipocytes were found. Cultivation of the samples after centrifugation revealed no apoptotic changes. Our results show that centrifugation, as a part of the protocol of lipofilling, has no effect on the survival rate of isolated adipocytes in the purified fat. In contrast, lipoaspirates centrifuged with higher accelerations seem to be better cleansed of oil and cell debris than samples treated with lower centrifugal forces.


Oxidative stress-induced activation of microsomal glutathione S-transferase in isolated rat liver.
The activation of microsomal glutathione (GSH) S-transferase in isolated rat liver by oxidative stress was investigated using both ischemia/reperfusion and perfusion with hydrogen peroxide. When the isolated liver was reperfused for 30 min and 60 min after 90 min ischemia, microsomal GSH S-transferase activity, but not cytosolic transferase activity, was increased 1.2-fold and 1.3-fold, respectively. In addition, microsomal GSH peroxidase activity was also significantly increased after 60 min reperfusion following ischemia. The increase in microsomal GSH S-transferase activity by ischemia/reperfusion was reversed by dithiothreitol. When N-ethylmaleimide, which activates microsomal GSH S-transferase by covalent binding to the cysteine residue of the enzyme, was incubated with microsomes, transferase activity was increased to 526% in control microsomes and to 399% in liver that underwent ischemia/reperfusion liver. These data indicate that microsomal GSH S-transferase is activated by ischemia/reperfusion of the liver by means of disulfide bond formation. When rats were pretreated with a catalase inhibitor 3-amino-1,2,4-triazole for 6 weeks, microsomal GSH S-transferase activity was increased 1.4-fold by ischemia/reperfusion, corresponding to a 1.8-fold increase as compared to the non-perfused liver of untreated rats. Perfusion of the isolated liver with hydrogen peroxide (1 mM, 15 min) also caused a significant increase in microsomal GSH S-transferase activity with a concomitant decrease in GSH content, confirming that liver microsomal GSH S-transferase in rats was activated in vivo by oxidative stress.


Modern issues of sugar beet (Beta vulgaris L.) hybrid breeding.
High efficiency of the cultivation of unfertilized sugar beet ovules and preparation of haploid regenerants (microclones) of pollinators - maintainers of О-type sterility and MS forms of the RMS 120 hybrid components has been shown. A technological method that accelerates the creation of new uniform starting material is proposed. It speeds up the breeding process two to threefold. The identification of haploid regenerants with sterile cytoplasm in initial populations is of great theoretical and practical importance for breeding, as it facilitates the production of homozygous lines with cytoplasmic male sterility and high-performance hybrids on sterile basis. As shown by molecular analysis, a single-nucleotide polymorphism never reported hitherto is present in the mitochondrial genome of the haploid plant regenerants. It allows identification of microclones as fertile and sterile forms. It has been found that DNA markers of the sugar beet mitochondrial genome belonging to the TR minisatellite family (TR1 and TR3) enable reliable enough identification of haploid microclonal plants as MS- or O-type forms. Fragments of 1000 bp in length have been detected in monogenic forms in the analysis of 11 sugar beet plants cultured in vitro by PCR with the OP-S4 random RAPD primer. Testing of the OP-S4 marker's being in the same linkage group as the genes responsible for expression of the economically valuable trait monogermity demonstrates its relative reliability. By the proposed method, dihaploid lines (DH) of the male-sterile form and the О-type sterility maintainer of the RMS 120 sugar beet hybrid have been obtained in in vitro culture. These lines are highly uniform in biomorphological traits, as proven under field conditions.


Cost-effectiveness comparison of manual and on-line retrospective bibliographic searching.
A study to compare the cost effectiveness of retrospective manual and on-line bibliographic searching is described. Forty search queries were processed against seven abstracting-indexing publications and the corresponding SDC/ORBIT data bases. Equivalent periods of coverage and searcher skill levels were used for both search models. Separate task times were measured for question analysis, searching, photocopying, shelving, and output distribution. Component costs were calculated for labor, information, reproduction, equipment, physical space, and telecommunications. Results indicate that on-line searching is generally faster, less costly, and more effective than manual searching. However, for certain query/information-source combinations, manual searching may offer some advantages in precision and turn-around time. The results of a number of related studies are reviewed.


Antisense strategies for oncogene inactivation.
Antisense oligonucleotides have been evaluated as antineoplastic agents in a series of clinical trials, with mixed results. However, phase III trials incorporating G3139, a phosphorothioate oligomer targeted to the initiation codon region of the bcl-2 mRNA, have recently been completed in advanced melanoma, myeloma, and chronic lymphocytic leukemia (CLL). This article discusses the mechanism of the antisense effect and its dependence on the cellular internalization of oligonucleotides and the activity of RNase H. It also describes the properties, specific and nonspecific, of phosphorothioate oligonucleotides, the predominant species in current clinical trials, and discusses pharmacokinetic data obtained from earlier phase I and II trials employing these molecules. While the application of antisense technology to the treatment of human cancer is conceptually straightforward, in practice there are many complicated, mechanistically based questions that must be considered.


CD8(+) T cell tolerance to a tumor-associated antigen is maintained at the level of expansion rather than effector function.
CD8+ T cell tolerance to self-proteins prevents autoimmunity but represents an obstacle to generating T cell responses to tumor-associated antigens. We have made a T cell receptor (TCR) transgenic mouse specific for a tumor antigen and crossed TCR-TG mice to transgenic mice expressing the tumor antigen in hepatocytes (gag-TG). TCRxgag mice showed no signs of autoimmunity despite persistence of high avidity transgenic CD8+ T cells in the periphery. Peripheral CD8+ T cells expressed phenotypic markers consistent with antigen encounter in vivo and had upregulated the antiapoptotic molecule Bcl-2. TCRxgag cells failed to proliferate in response to antigen but demonstrated cytolytic activity and the ability to produce interferon gamma. This split tolerance was accompanied by inhibition of Ca(2+) flux, ERK1/2, and Jun kinase phosphorylation, and a block in both interleukin 2 production and response to exogenous interleukin 2. The data suggest that proliferation and expression of specific effector functions characteristic of reactive cells are not necessarily linked in CD8+ T cell tolerance.


Molybdenum cofactor biosynthesis and molybdenum enzymes.
The molybdenum cofactor (Moco) forms the active site of all eukaryotic molybdenum (Mo) enzymes. Moco consists of molybdenum covalently bound to two sulfur atoms of a unique tricyclic pterin moiety referred to as molybdopterin. Moco is synthesized from GTP by an ancient and conserved biosynthetic pathway that can be divided into four steps involving the biosynthetic intermediates cyclic pyranopterin monophosphate, molybdopterin, and adenylated molybdopterin. In a fifth step, sulfuration or bond formation between Mo and a protein cysteine result in two different catalytic Mo centers. There are four Mo enzymes in plants: (1) nitrate reductase catalyzes the first and rate-limiting step in nitrate assimilation and is structurally similar to the recently identified, (2) peroxisomal sulfite oxidase that detoxifies excessive sulfite. (3) Aldehyde oxidase catalyzes the last step of abscisic acid biosynthesis, and (4) xanthine dehydrogenase is essential for purine degradation and stress response.


RNA sequencing profiling of mRNAs, long noncoding RNAs, and circular RNAs in Trigeminal Ganglion following Temporomandibular Joint inflammation.
Patients with temporomandibular joint disorders (TMD) have high levels of inflammatory pain-related disability, which seriously affects their physical and mental health. However, an effective treatment is yet to be developed. Both circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) contribute to regulating pain conduction. In our current study, we report the expression profiles of circRNAs, lncRNAs, and mRNAs in the trigeminal ganglion (TG) associated with complete Freund's adjuvant (CFA)-induced TMD inflammation pain. The collected TGs from the experimental (CFA) and control (saline) groups were processed for deep RNA sequencing. Overall, 1078,909,068 clean reads were obtained. A total of 15,657 novel lncRNAs were identified, where 281 lncRNAs were differentially expressed on CFA3D and 350 lncRNAs were differentially expressed on CFA6D. In addition, a total of 55,441 mRNAs and 27,805 circRNAs were identified, where 3,914 mRNAs and 91 circRNAs were found differentially expressed, between the CFA3D and saline groups, while 4,232 mRNAs and 98 DE circRNAs were differentially expressed between the CFA6D and saline groups. Based on functional analyses, we found that the most significant enriched biological processes of the upregulated mRNAs were involved in the immunity, neuron projection, inflammatory response, MAPK signaling pathway, Ras signaling pathway, chemokine signaling pathway, and inflammatory response in TG. Further analyses of Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathway suggest the involvement of dysregulated genes in the pain occurrence mechanism. Our findings provide a resource for expression patterns of gene transcripts in regions related to pain. These results suggest that apoptosis and neuroinflammation are important pathogenic mechanisms underlying TMD pain. Some of the reported differentially expressed genes might be considered promising therapeutic targets. The current research study revealed the expression profiles of circRNAs, lncRNAs, and mRNAs during TMD inflammation pain and sheds light on the roles of circRNAs and lncRNAs underlying the pain pathway in the trigeminal system of TMD inflammation pain.


Lighter and heavier initial loads yield similar gains in strength when employing a progressive wave loading scheme.
Progressive wave loading strategies are common within strength and conditioning practice. The purpose of this study was to contribute to the understanding of this strategy by evaluating the effectiveness of 2 wave loading bench press training programmes that differed only in the initial load that was used to start the first wave. Thirty-four resistance-trained men were divided into 2 groups and performed 2 training sessions each week for 20 weeks. One session consisted of 6 sets of 2 repetitions, while the other consisted of 5 sets of 5 repetitions. The load used was incremented by 2.5% of one repetition maximum (1RM) each week until the subject could no longer complete the programmed repetitions. At this point, the load was decreased, and then started to ascend again. The initial loads for the 2 sessions were 87.5% and 80% 1RM respectively for the heavier group, and for the lighter group were 82.5% and 75% 1RM. The subjects experienced a significant improvement in their bench press performance (higher load group: pre test = 106.5 kg ± 14.6, post test = 112.2 kg ± 12.4, p ≤ 0.05; lower load group: pre test = 105.7 kg ± 14.1, post test = 114.3 kg ± 11.0, p ≤ 0.05), but there was no difference in the magnitude of the improvment between the two groups. These results tend to support the common practical recommendation to start with a lighter load when employing a progressive wave loading strategy, as such a strategy yields similar improvements in performance with a lower level of exertion in training.


[Controversies concerning acute otitis media].
Acute otitis media is the subject of many unresolved points of controversy: 1) correct diagnosis; 2) whether or not bacteria are present in each case of acute otitis media; 3) spontaneous course; 4) indication of antibiotherapy; 5) treatment of recurrent acute otitis media; and 6) the place of alternative medicine, such as homeopathy. There is no ideal response. It is important, however, to take into account the knowledge of the different otoscopic stages of acute otitis media and the fact that the course of the disease is spontaneously favorable in the majority of cases. Selective prescription of an antibiotic in cases of purulent otitis only, and attention directed towards early recognition of complications, appear to be the most appropriate attitudes in the management of the disease, helping to reduce the alarmingly increasing numbers of resistant bacteria.


[Therapy of onychomycosis].
The most important data about etiology, clinical signs, diagnostic methods and the most frequent therapeutic modalities in the field of onychomycoses are presented in the introduction. In a 6-month clinical study 141 patients with onychomycosis were registered. The data on 88 patients, divided into 4 groups according to clinical findings and therapeutic regimen, were evaluated. The best therapeutic results in the treatment of onychomycoses were obtained using antifungal agents such as amorolfine and terabinafine, especially combining systemic and local therapy.


Clinical relevance of Mycobacterium malmoense isolation in The Netherlands.
Uncertainty exists about the clinical relevance of Mycobacterium malmoense isolation, especially in pulmonary samples. We therefore determined clinical relevance, treatment and outcome of M. malmoense isolation in The Netherlands. A retrospective medical file study was conducted for all patients in The Netherlands from whom Mycobacterium malmoense had been isolated between January 2002 and January 2006. Diagnostic criteria for nontuberculous mycobacterial (NTM) disease published by the American Thoracic Society (ATS) were used to determine clinical relevance. Treatment was compared with guidelines published by the British Thoracic Society. In total, 51 patients were found from whom M. malmoense was isolated. Of these, 40 (78%) patients had pulmonary isolates and 32 (80%) of them met the ATS diagnostic criteria. Cavitary disease was most common (n = 28; 88%). Patients with pulmonary disease were mostly males, with an average age of 56 yrs and pre-existing chronic obstructive pulmonary disease. Cervical lymphadenitis was the most common extrapulmonary disease type. Adherence to treatment guidelines was poor. A good clinical response to treatment was observed in 70% and 73% of patients treated for pulmonary and extrapulmonary disease, respectively. In conclusion, M. malmoense is a clinically highly relevant NTM in The Netherlands causing serious pulmonary morbidity. Adherence to treatment guidelines is not satisfactory.


Preparation and characterization of folate-chitosan-gemcitabine core-shell nanoparticles for potential tumor-targeted drug delivery.
For the purpose of achieving targeted chemotherapy of pancreatic cancer, we prepared core-shell nanoparticles by coaxial electrospray technology, with folate-chitosan as the polymeric coating material and gemcitabine as the encapsulated drug. The effects of various solution properties and processing parameters on nanoparticles formation were investigated. By optimizing the electrospray parameters, the diameter of the core-shell nanoparticles was in the range of 200-300 nm with drug loading and encapsulation efficiency of 3.91 +/- 0.12% and 85.37 +/- 4.9%. The drug release kinetics revealed a controlled initial burst release followed by a sustained release over a period of 72 h at pH 7.4 and pH 5.0, and at pH 5.0 the drug released more quickly. Moreover, the cellular uptake experiment confirmed that the folate conjugated core-shell nanoparticles had high pancreatic cancer (BXPC3) cells uptake efficiency. And the cell cytotoxicity test displayed that they had remarkable cytotoxicity towards BXPC3 cells. This study indicates that coaxial electrospray is a facile technique in producing core-shell nanoparticles encapsulating hydrophilic small molecule drugs, and clearly infers that the folate conjugated core-shell nanoparticles is very much effective to use as a pancreatic tumor-targeted delivery carrier for anticancer drugs.


Issues in community-based care among homeless minorities.
Homelessness is an increasing major public health problem in the United States. The homeless population consists of men, women, youth and families who live on the streets or in shelters. Minorities, especially African-Americans and Hispanics, are particularly at risk for homelessness due to their high rates of poverty. Homelessness predisposes persons to poor health, including a variety of acute and chronic physical and psychological diseases for which they often have difficulty obtaining healthcare. This article discusses common issues and challenges that homeless minorities and their health-care providers face in obtaining community-based healthcare, including issues in caring for homeless men and women, fragmentation of healthcare, perceived discrimination and provider bias, provider-patient trust issues, lack of access to care, and health literacy issues. Two programs designed to provide community-based experiential learning for nursing students to address these issues and the health-care needs of the homeless are described, i.e., the Men Achieving Self Health (MASH) and Women Inspired Self Health (WISH) Outreach Programs. Approaches used by faculty and students who are engaged in providing health-care services to the homeless via the MASH and WISH Programs are discussed.


Contact tracing of in-flight measles exposures: lessons from an outbreak investigation and case series, Australia, 2010.
To describe a 2010 outbreak of nine cases of measles in Australia possibly linked to an index case who travelled on an international flight from South Africa while infectious. Three Australian state health departments, Victoria, Queensland and New South Wales, were responsible for the investigation and management of this outbreak, following Australian public health guidelines. An outbreak of measles occurred in Australia after an infectious case arrived on a 12-hour flight from South Africa. Only one of four cases in the first generation exposed to the index case en route was sitting within the two rows recommended for contact tracing in Australian and other guidelines. The remaining four cases in subsequent generations, including two health care workers, were acquired in health care settings. Seven cases were young adults. Delays in diagnosis and notification hampered disease control and contact tracing efforts. Review of current contact tracing guidelines following in-flight exposure to an infectious measles case is required. Alternative strategies could include expanding routine contact tracing beyond the two rows on either side of the case's row or expansion on a case-by-case basis depending on cabin layout and case and contact movements in flight. Releasing information about the incident by press release or providing generic information to everyone on the flight using e-mail or text messaging information obtained from the relevant airline, may also be worthy of consideration. Disease importation, inadequately vaccinated young adults and health care-related transmission remain challenges for measles control in an elimination era.


Development of tools for the oral health and panoramic radiograph evaluation of head and neck cancer patients: a methodological study.
Describe the methodology used to construct tools for standardized data collection of head and neck cancer patients (HNCP). We constructed the Oral Health Evaluation Tool (OHET) and Panoramic Radiograph Evaluation Tool (PRET) for systematic collection of long-term oral clinical/radiographical complications, prevalence, and severity. Tools were pilot-tested in 50 chemoradiation-treated HNCP >6 months post-therapy. Tools allowed for collection of extensive clinical and radiographical data. A medium of 1.9 years had elapsed since chemoradiation completion. Patients had a median of 6 missing teeth, 32.7% had no decay and a medium of 30% had filled surfaces; 42.9% had moderate-to-severe decay. Reduced/thickened saliva was noted in 85.4% and dry mucosa in 93.9%. Gingival bleeding was present in 75.5% HNCP and attachment loss in 86%. Four patients had trismus. Tools were user friendly and provided comprehensive, reproducible, and inexpensive means to evaluate post-therapy oral health of HNCP. Validation testing is ongoing.


[A case of pedunculated intrathoracic chest wall type lipoma].
The case was a 52-year-old female. Though the abnormal shadow on the chest X ray film was pointed out in 1990, she had been observed as a benign intrathoracic tumor for one year and four months. But she was admitted to our hospital for further evaluation because the mass shadow enlarged subsequently. The mass shadow was suspected as intrathoracic lipoma by the CT and MRI. However, because the shadow enlarged and its inner part was not single density that was equal to subcutaneous adipose tissues, left thoracotomy was performed. The tumor was pedunculated from the fatty tissue of the fifth intercostal space near the tubercle of rib. It was easily resectable, encapsulated and measured 6.0 x 3.5 x 2.5 cm in size. It was histologically diagnosed as benign lipoma. Preoperative diagnosis of the present tumor became possible to a certain extent by means of CT and MRI. However, in view of imperfect differentiation between lipoma and liposarcoma, the surgical treatment should be considered.


The role of Langerhans cells in pathologies of the skin.
Langerhans cells (LCs) are epidermal immune cells of myeloid origin. Although these cells were primarily thought to play a defensive role in the skin, evidence now indicates a diverse range of LC-mediated effects including the relay of viral antigens in herpes simplex infection, recruitment of eosinophils in atopic dermatitis and promotion of a Th17 response in Candida infection. LCs may have a protective or suppressive function in pathologies of the skin, with differing functions being driven by the skin milieu. Understanding LC function will help guide the development of interventions that modulate these cells for therapeutic benefit.


[Exercise therapy of atherosclerosis].
The effect of exercise on the progression of atherosclerotic diseases is reviewed. Prospective studies have reported that a low daily physical activity is associated with a lower incidence of coronary artery disease. Mild aerobic exercise improves survival in patients with coronary artery disease, lowers blood pressure in patients with mild hypertension, improves insulin resistance in diabetes mellitus, lowers weight in obesity and increases HDL-cholesterol and decrease triglyceride in patients with dyslipidemia. Mild exercise therapy may be beneficial in the management of atherosclerotic diseases.


A model to guide the rehabilitation of high-functioning employees after mild brain injury.
Impairment in executive functioning can occur after mild stroke, mild Traumatic Brain Injury, and neurodegenerative disease, and this can have deleterious effects on employment outcomes, occupational functioning, and general quality of life. What is not as well identified is the symbiotic relationship between executive functioning and other important psychosocial constructs inherent in successful employees ("Employee Performance Enablers"), and how various aspects of the employment environment can enable or inhibit the success of the employee with executive functioning deficits in meeting their essential job functions ("Workplace Ecology"). From an extensive review of the literature and the author's practice experience, a clinical model was developed to elucidate these two critical variables, as well as to provide guidance for organizing, planning, and implementing interventions that will address both employee enablers and workplace ecology to affect positive return to work outcomes for individuals with mild brain injury.


Biochemical, Serological, Molecular and Natural Host Studies on Tomato Chlorosis Virus in Egypt.
Tomato Chlorosis Virus (ToCV) is a white fly-transmitted and phloem-limited crinivirus reported in this study for the first time in Egypt. ToCV caused drastic reduction in tomato yield since 2013. The aim of this study is to characterize the virus incidence using biological, serological and molecular tools. The B. tabaci MEAM1 white fly was used for virus isolation and propagation. Identity of ToCV , its natural hosts were confirmed with RT-PCR using a specific primer pair for ToCV-heat shock protein 70 homologue (HSP70h) gene, sequencing and phylogenetic studies. ToCV was purified using the innovative electro-elution technique. The induced antiserum for the Egyptian isolate of the virus (ToCV-Giza) was used for DAS-ELISA and dot blotting immuno-assays to evaluate the virus presence in tomato and other natural hosts. The ToCV-Giza isolate was donated an accession number "MH667315.1" from the GenBank. Blastx sequence analysis of the HSP70h gene indicated 97-99% of amino acid similarities with many tested ToCV isolates. Phylogenetic studies showed the clustering of all ToCV isolates including ToCV-Giza in a separate group from the other tested criniviruses. The virus had a UV spectrum of a nucleoprotein with Amax and Amin at 260 and 240 nm, respectively and A260/280 ratio of 1.33. Out of 52 different tested plant species within 22 families, 44 were positive hosts for ToCV. Thirty seven out of these 44 plant species were considered as new hosts for ToCV in the present study. These included Ammi majus and Coriandrum sativum (Apiaceae), cabbage (Brassicaceae), sweet potato (Convolvulaceae), melon, cucumber, luffa (Cucurbitaceae), soybean, cowpea, faba bean (Fabaceae), Egyptian and American Cotton (Malvaceae). Several ornamentals either herbal type or woody trees belonging to Acanthaceae, Amaranthaceae, Euophorbiaceae, Moraceae and Rubiaceae were also recognized for the first time as hosts for ToCV. The obtained results confirmed the wide distribution of ToCV in its natural hosts in Egypt. Hygienic measures including control of the virus vector and removing of natural hosts should be strictly implicated.


A minimax procedure in the context of sequential testing problems in psychodiagnostics.
The purpose of this paper is to derive optimal rules for sequential testing problems in psychodiagnostics. In sequential psychodiagnostic testing, each time a patient is exposed to a new treatment, the decision then is to declare this new treatment effective, ineffective, or to continue testing and exposing the new treatment to another random patient suffering from the same mental health problem. The framework of minimax sequential decision theory is proposed for solving such testing problems; that is, optimal rules are obtained by minimizing the maximum expected losses associated with all possible decision rules at each stage of testing. The main advantage of this approach is that costs of testing can be explicitly taken into account. The sequential testing procedure is applied to an empirical example for determining the effectiveness of a cognitive-analytic therapy for patients suffering from anorexia nervosa. For a given maximum number of patients to be tested, the appropriate action is indicated at each stage of testing for different numbers of positive reactions to the cognitive-analytic therapy. The paper concludes with a simulation study, in which the minimax sequential strategy is compared for the anorexia nervosa example with other procedures that exist for similar classification decision problems in the literature in terms of average number of patients to be tested, classification accuracy and average loss.


Pneumatosis intestinalis in a burn patient: case report and literature review.
Pneumatosis Intestinalis (PI) is a rare condition characterized by gas in the intestinal wall. PI is not a disease in itself but a sign of an underlying problem. It is associated with a wide variety of underlying disorders, ranging from benign to life-threatening. When found, it should prompt a search for the underlying cause. Diagnostic efforts should be aimed at ruling out catastrophic problems such as intestinal ischemia and necrosis. The presence of peritonitis, rectal bleeding, portomesenteric venous gas, and lactic acidosis are important factors to determine the best course of action. Burn patients have multiple risk factors for developing this condition. Despite this, PI is not well-described in the burn literature. We present here a case report, a brief review of the literature, and clinical considerations.


The role of autophagy in the pathogenesis of exposure keratitis.
Incomplete tear film spreading and eyelid closure can cause defective renewal of the ocular surface and air exposure-induced epithelial keratopathy (EK). In this study, we characterized the role of autophagy in mediating the ocular surface changes leading to EK. Human corneal epithelial cells (HCECs) and C57BL/6 mice were employed as EK models, respectively. Transmission electron microscopy (TEM) evaluated changes in HCECs after air exposure. Each of these models was treated with either an autophagy inhibitor [chloroquine (CQ) or 3-methyladenine (3-MA)] or activator [Rapamycin (Rapa)]. Immunohistochemistry assessed autophagy-related proteins, LC3 and p62 expression levels. Western blotting confirmed the expression levels of the autophagy-related proteins [Beclin1 and mammalian target of rapamycin (mTOR)], the endoplasmic reticulum (ER) stress-related proteins (PERK, eIF2α and CHOP) and the PI3K/Akt/mTOR signalling pathway-related proteins. Real-time quantitative PCR (qRT-PCR) determined IL-1β, IL-6 and MMP9 gene expression levels. The TUNEL assay detected apoptotic cells. TEM identified autophagic vacuoles in both EK models. Increased LC3 puncta formation and decreased p62 immunofluorescent staining and Western blotting confirmed autophagy induction. CQ treatment increased TUNEL positive staining in HCECs, while Rapa had an opposite effect. Similarly, CQ injection enhanced air exposure-induced apoptosis and inflammation in the mouse corneal epithelium, which was inhibited by Rapa treatment. Furthermore, the phosphorylation status of PERK and eIF2α and CHOP expression increased in both EK models indicating that ER stress-induced autophagy promoted cell survival. Taken together, air exposure-induced autophagy is indispensable for the maintenance of corneal epithelial physiology and cell survival.


Smart panel with active damping units. Implementation of decentralized control.
This paper contains the second part of a study on a smart panel with five decentralized velocity feedback control units using proof mass electrodynamic actuators [Gonzalez Diaz et al., J. Acoust. Soc. Am. 124, 886 (2008)]. The implementation of five decentralized control loops is analyzed, both theoretically and experimentally. The stability properties of the five decentralized control units have been assessed with the generalized Nyquist criterion by plotting the loci of the eigenvalues of the fully populated matrix of frequency response functions between the five error signals and five input signals to the amplifiers driving the actuators. The control performance properties have been assessed in terms of the spatially averaged response of the panel measured with a scanning laser vibrometer and the total sound power radiated measured in an anechoic room. The two analyses have shown that reductions of up to 10 dB in both vibration response and sound radiation are measured at low audio frequencies, below about 250 Hz.


Heated indoor swimming pools, infants, and the pathogenesis of adolescent idiopathic scoliosis: a neurogenic hypothesis.
In a case-control study a statistically significant association was recorded between the introduction of infants to heated indoor swimming pools and the development of adolescent idiopathic scoliosis (AIS). In this paper, a neurogenic hypothesis is formulated to explain how toxins produced by chlorine in such pools may act deleteriously on the infant's immature central nervous system, comprising brain and spinal cord, to produce the deformity of AIS. Through vulnerability of the developing central nervous system to circulating toxins, and because of delayed epigenetic effects, the trunk deformity of AIS does not become evident until adolescence. In mature healthy swimmers using such pools, the circulating neurotoxins detected are chloroform, bromodichloromethane, dibromochloromethane, and bromoform. Cyanogen chloride and dichloroacetonitrile have also been detected. In infants, the putative portals of entry to the blood could be dermal, oral, or respiratory; and entry of such circulating small molecules to the brain are via the blood-brain barrier, blood-cerebrospinal fluid barrier, and circumventricular organs. Barrier mechanisms of the developing brain differ from those of adult brain and have been linked to brain development. During the first 6 months of life cerebrospinal fluid contains higher concentrations of specific proteins relative to plasma, attributed to mechanisms continued from fetal brain development rather than immaturity. The hypothesis can be tested. If confirmed, there is potential to prevent some children from developing AIS.