Fluoride in low concentration modifies expression and activity of 15 lipoxygenase in human PBMC differentiated monocyte/macrophage.
Epidemiological and experimental evidences demonstrate positive correlation between environmental and occupational fluoride exposure and risk to various cardio-respiratory disorders. That fore we decided to examine the effect of fluorides on activity and expression of 15LOX enzyme which is implicated in biosynthesis of inflammatory mediators. Expression of 15LOX-1 and -2 enzymes mRNA and protein was analyzed using RT PCT and immunoblotting methods respectively whereas HPLC method was used to measure the levels of 15 lipoxygenases end products. Additionally AA and LA concentration in cells was measured using GC method. We observed that fluoride in small concentration may significantly decrease activity of 15LOX-1 and -2 in human PBMC macrophages and then concentration of its end products: 15-HETE, 12-HETE and 9+13-HODE, what may cause development of inflammation through the cholesterol arrest into the macrophages and its differentiation to foam cell. Noted by our team overexpression of the 15LOX-1 enzyme in macrophages after addition of lowest fluoride concentrations (1 and 3 μM) may be aimed at fighting inflammation development and excessive intracellular lipid accumulation. But highest fluoride concentrations (6 and 10 μM) added to cell culture slowly declined expression of this enzyme probably because of developing inflammation. Additional 15LOX-2 expression in macrophages after fluoride addition was low in 1 and 3 μM concentrations, but increased significantly after 10 μM fluoride addition what may suggest developing acute inflammation, because 15LOX-2 is associated to increased local hypoxia. This study indicated that even in small concentrations fluorides changes the amounts and activity of 15 LOX-1 and -2 enzymes taking part in the development of inflammatory process.


The ED50 and ED95 of intrathecal isobaric bupivacaine with opioids for cesarean delivery.
The ideal intrathecal isobaric bupivacaine dose for cesarean delivery anesthesia is uncertain. While small doses (5-9 mg) of bupivacaine may reduce side effects such as hypotension, they potentially increase spinal anesthetic failures. This study determined the ED50 and ED95 of intrathecal isobaric bupivacaine (with adjuvant opioids) for cesarean delivery. After institutional review board approval and written informed consent were obtained, 48 parturients undergoing elective cesarean delivery under combined spinal-epidural anesthesia were enrolled in this double-blind, randomized, dose-ranging study. Patients received a 5-, 6-, 7-, 8-, 9-, 10-, 11-, or 12-mg intrathecal isobaric bupivacaine dose with 10 microg fentanyl and 200 microg morphine. Overall anesthetic success was recorded when no intraoperative epidural supplement was required during the cesarean delivery. ED50 and ED95 values for overall anesthetic success were determined using a logistic regression model. ED50 and ED95 values for overall anesthetic success were 7.25 and 13.0 mg, respectively. No advantages for low doses could be demonstrated with regard to hypotension, nausea, vomiting, pruritus, or maternal satisfaction, although this study was underpowered to detect significant differences in secondary outcome variables. The ED50 and ED95 values (7.25 and 13.0 mg, respectively) for intrathecal isobaric bupivacaine in this circumstance are similar to values the authors determined recently for hyperbaric bupivacaine using similar methodology. These ED50 and ED95 values are significantly higher than those advocated in previous reports in which success was claimed using lower intrathecal bupivacaine doses. The current study used stricter criteria to define "successful" anesthesia and support the use of larger bupivacaine doses to ensure adequate patient comfort.


Long-term association of N-(phosphonacetyl)-L-aspartate with bone.
By means of enzymatic and autoradiographic techniques, it has been demonstrated that, 24 hr after a single dose of the antitumor amino acid N-phosphonacetyl-L-aspartic acid (PALA), (400 mg/kg i.p.; 1.15 mmol/kg) to C57BL x DBA/2 F1 mice, the agent accumulates in bone to a concentration of approximately 400 microM; this is 3000 times greater than the Ki of PALA for its target enzyme, aspartate carbamoyltransferase. However, disproportionately low inhibition of enzyme activity was demonstrated in homogenates of bone from these recipients, suggesting that the drug was sequestered from its target in this tissue. Autoradiography of sections of femoral shafts from mice treated with 14C-labeled drug demonstrated that autoradiogram density due to [14C]PALA equivalents was confined to the bony matrix, with no label above background resolvable in bone marrow. Following in vivo administration of PALA (400 mg/kg i.p.), the half-life of the drug in the bone was approximately 23 days. In vitro, with equilibrium dialysis at pH 7.4, it was demonstrated that: (a) normal pulverized and decalcified bone bound PALA with capacities of 3.5 nmol/mg and 0.1 nmol/mg bone, respectively, at a PALA concentration of 5 mM; (b) binding of PALA to normal bone reached saturation at a concentration of 200 mM; and (c) PALA functions as a solubilizer of bone at concentrations above this. Since administration of PALA was shown to produce long-lasting inhibition of aspartate carbamoyltransferase in liver and tumor and since its ultimate half-life in the plasma of mice, following a single 400-mg/kg administration of the drug, is 8 days, it is suggested that bone serves as a reservoir from which PALA is released at a slow rate into plasma and other tissues.


Profile of a BMET (biomedical equipment technician) in small hospitals.
A survey was done of biomedical engineering programs in hospitals of under 100 beds. A random sampling of 400 hospitals was selected from the American Hospital Association Guidebook. Questions were asked with regard to the size, educational background and experience of the biomedical engineering staff. The organizational location of the program was surveyed, and most programs were part of facility engineering. Programs are discussed as full-time, part-time and outside service contracts. An in-depth analysis of the educational and training background of BMETs has been done. This part of the study covered the type of training and what additional training they felt they required.


[Epidemiology of cancer of the pancreas. Current data].
In view of the poor prognosis of pancreatic cancer, improvements in our knowledge of its epidemiology are desirable. The present study describes its main geographical and chronological features and presents an up-to-date view of the principal risk factors associated with that disease. Mortality from pancreatic cancer is characterized by its increase with age, its predominance among males and its preferential ethnic and geographical distribution. The most striking point, however, is the increase of incidence noted since 1950, with an as yet unexplained tendency to stabilization. Among the various risk factors suspected of being associated with pancreatic cancer, only tobacco smoking seems to be well established. The methodological problems encountered in analytical studies explain that the role of nutritional, occupational and associated pathological factors remains hypothetical in the present state of our knowledge.


Nerve independent limb induction in axolotls.
Urodele amphibians can regenerate their limbs. During limb regeneration, dermal fibroblasts are transformed into undifferentiated cells called blastema cells. These dermis-blastema cells show multipotency. Such so-called endogenous reprogramming of cell differentiation is one of the main targets of amphibian limb regeneration studies. It is well recognized that nerve presence controls the initiation of limb regeneration. Accordingly, nerve factors have been sought in amphibian limb regeneration. To investigate it, a relatively new study system called the accessory limb model (ALM) was developed. Using ALM, two signaling cascades (Fgf and Gdf5 signaling) came under focus. In the present study, Growth and differentiation factor-5 (Gdf5) application to wounded skin initiated limb regeneration responses and resulted in induction of a blastema-like structure in the absence of a nerve. However, the Gdf5-induced structure showed defects as a regeneration blastema, such as absence of detectable Prrx1 expression by in situ hybridization. The defects could be remedied by additional Fibroblasts growth factor (Fgf) inputs. These two inputs (Gdf5 and Fgfs) were sufficient to substitute for the nerve functions in the induction of limb regeneration. Indeed, Fgf2, Fgf8, and Gdf5 applications with the contralateral skin graft resulted in limb formation without nerve supply. Furthermore, acquisition of cartilage differentiation potential of dermal fibroblasts was tested in an in vivo and in vitro combination assay. Dermal fibroblasts cultured with Gdf5 were difficult to participate in cartilage formation when the cultured cells were grafted into cartilage forming region. In contrast, dermal fibroblasts cultured with Fgf2 and Fgf8 became easier to participate into cartilage formation in the same procedure. These results contribute to our understanding of molecular mechanisms of the early phase of amphibian limb regeneration.


Anterolateral Ligament Reconstruction Practice Patterns Across the United States.
A proposed mechanism for recurrent instability following anterior cruciate ligament (ACL) reconstruction is failure of the anterolateral ligament (ALL). Presently, there are a number of approaches to treating ALL pathology. To determine practice patterns among orthopaedic surgeons regarding ALL during ACL reconstruction. Cross-sectional study. An online 7-question survey was sent to all physicians registered with the American Orthopaedic Society for Sports Medicine between June and July 2017. Results were analyzed with the survey website. Overall, 225 of 3467 surgeons responded to the survey, 86 of whom performed ALL reconstruction and completed each question in the survey. Eighty-six (38.2%) surgeons who responded to the questionnaire stated that they perform ALL reconstruction/lateral extra-articular tenodesis in conjunction with ACL reconstruction. The most common indications for ALL reconstruction were grade III pivot-shift test (46.0%) on physical examination and revision ACL reconstruction (46.0%). The most common technique used to perform ALL reconstruction was hamstring autograft (48.2%). The majority of participating surgeons (87.5%) stated that they do not make any alterations to their postoperative rehabilitation protocol after they perform ALL reconstruction. In addition, most surgeons responding to the survey (91.3%) anticipated either an increase in or the same number of ALL procedures performed in the coming year. The majority of surgeons who responded to the survey did not routinely reconstruct the ALL. Revision procedures and grade III pivot shift were the most cited indications for performing lateral augmentation. Anatomic reconstruction with hamstring was the most commonly used procedure, although there was no consensus among surgeons responding to the survey. Understanding the ALL and its contribution to knee stability is essential. For a community of physicians, it is useful to discover how fellow sports orthopaedic surgeons address ALL pathology to integrate effective and efficient treatment strategies into practice.


Ferromagnetic and Half-Metallic FeC2 Monolayer Containing C2 Dimers.
Ferromagnetism and half-metallicity are two vital properties of a material for realizing its potential in spintronics applications. However, none of the two-dimensional (2D) pristine metal-carbide sheets synthesized experimentally exhibits half-metallicity with ferromagnetic coupling. Here, a ferromagnetic and half-metallic FeC2 sheet containing isolated C2 dimers rather than individual carbon atoms is predicted to be such a material. Based on state-of-the-art theoretical calculations, we show that the FeC2 sheet is dynamically, thermally, and mechanically stable and can be chemically exfoliated from the bulk phase of layered ThFeC2. Due to its unique atomic configuration, the FeC2 sheet exhibits ferromagnetism with a Curie temperature of 245 K. This is in contrast to its bulk counterpart, ThFeC2, which is paramagnetic. We also find that, unlike the metallic metal-carbide sheets, the FeC2 sheet is half-metallic with semiconducting spin-up and metallic spin-down channels. Moreover, half-metallicity can remain until an equi-biaxial strain of 10%. In addition, we provide the Raman and infrared spectra which can be used to identify this new 2D structure experimentally in the future.


Oxygen dependency of hydrogen sulfide-mediated vasoconstriction in cyclostome aortas.
Hydrogen sulfide (H(2)S) has been proposed to mediate hypoxic vasoconstriction (HVC), however, other studies suggest the vasoconstrictory effect indirectly results from an oxidation product of H(2)S. Here we examined the relationship between H(2)S and O(2) in isolated hagfish and lamprey vessels that exhibit profound hypoxic vasoconstriction. In myographic studies, H(2)S (Na(2)S) dose-dependently constricted dorsal aortas (DA) and efferent branchial arteries (EBA) but did not affect ventral aortas or afferent branchial arteries; effects similar to those produced by hypoxia. Sensitivity of H(2)S-mediated contraction in hagfish and lamprey DA was enhanced by hypoxia. HVC in hagfish DA was enhanced by the H(2)S precursor cysteine and inhibited by amino-oxyacetate, an inhibitor of the H(2)S-synthesizing enzyme, cystathionine beta-synthase. HVC was unaffected by propargyl glycine, an inhibitor of cystathionine lambda-lyase. Oxygen consumption (M(O(2))) of hagfish DA was constant between 15 and 115 mmHg P(O(2)) (1 mmHg=0.133 kPa), decreased when P(O(2)) <15 mmHg, and increased after P(O(2)) exceeded 115 mmHg. 10 micromol l(-1) H(2)S increased and > or =100 micromol l(-1) H(2)S decreased M(O(2)). Consistent with the effects on HVC, cysteine increased and amino-oxyacetate decreased M(O(2)). These results show that H(2)S is a monophasic vasoconstrictor of specific cyclostome vessels and because hagfish lack vascular NO, and vascular sensitivity to H(2)S was enhanced at low P(O(2)), it is unlikely that H(2)S contractions are mediated by either H(2)S-NO interaction or an oxidation product of H(2)S. These experiments also provide additional support for the hypothesis that the metabolism of H(2)S is involved in oxygen sensing/signal transduction in vertebrate vascular smooth muscle.


Rural health care worker wellness during COVID-19: Compassion fatigue, compassion satisfaction & utilization of wellness resources.
The goal of this study was to identify factors associated with compassion fatigue (CF) and compassion satisfaction (CS) among rural health care workers (HCWs) during the COVID-19 pandemic. The secondary purpose was to assess utilization of wellness resources and preferences for new resources. A survey was distributed (October-December 2020) and completed by faculty, clinicians and staff (n = 406) at a rural university. Measures included a modified version of the Professional Quality of Life Scale (PROQOL-21), the Patient Health Questionnaire-4 and the Brief Resilience Coping Scale. Respondents reported their use of wellness resources and their preferences for new resources. The mean CF score was 21.1, the mean CS score was 26.8 and 42.0% screened positive for depression or anxiety. Few of the existing wellness resources were utilized and respondents' preferences for new wellness resources included time off (70.7%), onsite food trucks (43.0%) and support animals (36.5%). Younger age, depression and anxiety were associated with higher CF. Older age, better mental health and resilience were associated with higher CS. Rural HCWs have high CF, yet few utilize wellness resources. Rural health care organizations may foster wellness by providing time off for self-care, expanding mental health services and building resilience.


[Dolichol-coupled biosynthesis of an oligosaccharide precursor for N-glycosylated proteins in the rough endoplasmic reticulum].
Data from literature concerning the structure and function of enzymes, taking part in dolichol-coupled biosynthesis of oligosaccharide precursor, which is used for N-glycosylation of protein in endoplasmic reticulum of eukaryotic cells, are summarized and analyzed in the review. The mechanisms of translocation of dolichol and its derivatives through membrane are discussed. The data about topography of reactions of "dolichol cycle", taking place on cytoplasmic and luminal surfaces of endoplasmic reticulum membrane, are considered.


Regional variations in the prevalence of migraine and tension-type headache applying the new IHS criteria: the German DMKG Headache Study.
The prevalence of migraine and tension-type headache (TTH) varies considerably with respect to gender, age group and geographic regions. Methodological differences in the assessment and classification of cases are a major cause of this variability across studies, limiting the ability to perform true regional comparisons. We conducted three population-based studies in different German regions and assessed headache prevalence and headache characteristics in face-to-face interviews, applying standardized methods. We analysed the 6-month prevalence of migraine, TTH and their probable subtypes based on the new criteria of the International Headache Society (IHS). Among the 7417 participants in all three regions, the pooled 6-month prevalence of migraine, probable migraine, TTH and probable TTH was 6.75, 4.40, 19.86 and 11.61%, respectively. Despite the application of standardized classification methods, regional variations between 4.39 and 8.00% for migraine and 15.44 and 23.64% for TTH were observed, indicating differences in the local headache burden. Application of the new IHS criteria yielded headache categories that were not mutually exclusive, indicating a need for further discussion about the value of probable headache types in epidemiological studies.


Comparison of microscopy and culture in the detection of Leishmania donovani from splenic aspirates.
Three culture media were compared with Giemsa-stained smears for the detection of Leishmania in splenic aspirates from Kenyan patients with visceral leishmaniasis. Ninety-nine splenic aspirates obtained from 26 patients at various times before, during, and after treatment were cultured in Schneider's Drosophila medium and RPMI medium 1640 (each supplemented with 20% fetal bovine serum) and McConnell's modification of Senekje's medium overlayed with 0.9% saline. From 13 splenic aspirates obtained before treatment, amastigotes were identified microscopically in all and promastigotes were cultured in 12. During and after treatment, Schneider's medium was the most sensitive method for detecting parasites, followed by microscopic examination of stained smears which was more sensitive than either of the other two media tested. Results indicate that, for initial diagnosis, both culture and direct microscopy of aspirates should be employed.


Can tissue transglutaminase antibody titers replace small-bowel biopsy to diagnose celiac disease in select pediatric populations?
The use of screening tests for celiac disease has increased the number of patients referred for evaluation. We proposed that the subgroup of patients with very high tissue transglutaminase antibody (TTG) titers is positive for celiac disease and a small-bowel biopsy is not necessary to make the diagnosis. A gluten-free diet should be attempted and, if the patient's symptoms do not improve, then a biopsy should be performed to confirm the diagnosis. A chart review of data for 103 patients who underwent both TTG testing and a small-bowel biopsy was performed. We examined the impact of using TTG values of >100 U and <20 U as cutoff values and suggested performing biopsies for patients with TTG values of 20 to 100 U, as is current practice. Fifty-eight of 103 patients demonstrated positive biopsy results. Forty-nine of 103 patients had TTG levels of >100 U, with 48 of 49 exhibiting positive biopsy results. Only 7 of 16 patients with TTG values of 20 to 100 U exhibited positive biopsy results. Three patients with TTG levels of <20 U had positive biopsies; 2 were IgA negative and 1 had a duodenal ulcer. With the cutoff values of >100 U and <20 U with known IgA status, the sensitivity was 0.980 (48 of 49 cases) and the specificity was 0.972 (35 of 36 cases). An incremental cost analysis found that this proposal could potentially decrease the costs of investigation and diagnosis by almost 30%. When the cutoff values were changed to >100 and <20 U and IgA levels were verified, the sensitivity and specificity were very high. Patients with mid-range TTG values (20-100 U) or values of <20 U with negative IgA status should continue to undergo biopsies for diagnosis of celiac disease.


Tolerability and Acceptability of an Exogenous Ketone Monoester and Ketone Monoester/Salt Formulation in Humans.
Exogenous ketone ester and ketone ester mixed with ketone free acid formulations are rapidly entering the commercial marketspace. Short-term animal and human studies using these products suggest significant potential for primary or secondary prevention of a number of chronic disease conditions. However, a number of questions need to be addressed by the field for optimal use in humans, including variable responses among available exogenous ketones at different dosages; frequency of dosing; and their tolerability, acceptability, and efficacy in long-term clinical trials. The purpose of the current investigation was to examine the tolerability, acceptability, and circulating R-beta-hydroxybutyrate (R-βHB) and glucose responses to a ketone monoester (KME) and ketone monoester/salt (KMES) combination at 5 g and 10 g total R-βHB compared with placebo control (PC). Fourteen healthy young adults (age: 21 ± 2 years, weight: 69.7 ± 14.2 kg, percent fat: 28.1 ± 9.3%) completed each of the five study conditions: placebo control (PC), 5 g KME (KME5), 10 g KME (KME10), 5 g (KMES5), and 10 g KMES (KMES10) in a randomized crossover fashion. Circulating concentrations of R-βHB were measured at baseline (time 0) following an 8-12 h overnight fast and again at 15, 30, 60, and 120 min following drink ingestion. Participants also reported acceptability and tolerability during each condition. Concentrations of R-βHB rose to 2.4 ± 0.1 mM for KME10 after 15 min, whereas KMES10 similarly peaked (2.1 ± 0.1 mM) but at 30 min. KME5 and KMES5 achieved similar peak R-βHB concentrations (1.2 ± 0.7 vs. 1.1 ± 0.5 mM) at 15 min. Circulating R-βHB concentrations were similar to baseline for each condition by 120 min. Negative correlations were observed between R-βHB and glucose at the 30 min time point for each condition except KME10 and PC. Tolerability was similar among KME and KMES, although decreases in appetite were more frequently reported for KMES. Acceptability was slightly higher for KMES due to the more frequently reported aftertaste for KME. The results of this pilot investigation illustrate that the KME and KMES products used increase circulating R-βHB concentrations to a similar extent and time course in a dose-dependent fashion with slight differences in tolerability and acceptability. Future studies are needed to examine variable doses, frequency, and timing of exogenous ketone administration for individuals seeking to consume ketone products for health- or sport performance-related purposes.


Site-specific incorporation of photo-cross-linker and bioorthogonal amino acids into enteric bacterial pathogens.
Enteric bacterial pathogens are known to effectively pass through the extremely acidic mammalian stomachs and cause infections in the small and/or large intestine of human hosts. However, their acid-survival strategy and pathogenesis mechanisms remain elusive, largely due to the lack of tools to directly monitor and manipulate essential components (e.g., defense proteins or invasive toxins) participating in these processes. Herein, we have extended the pyrrolysine-based genetic code expansion strategy for encoding unnatural amino acids in enteric bacterial species, including enteropathogenic Escherichia coli , Shigella , and Salmonella . Using this system, a photo-cross-linking amino acid was incorporated into a Shigella acid chaperone HdeA (shHdeA), which allowed the identification of a comprehensive list of in vivo client proteins that are protected by shHdeA upon acid stress. To further demonstrate the application of our strategy, an azide-bearing amino acid was introduced into a Shigella type 3 secretion effector, OspF, without interruption of its secretion efficiency. This site-specifically installed azide handle allowed the facile detection of OspF's secretion in bacterial extracellular space. Taken together, these bioorthogonal functionalities we incorporated into enteric pathogens were shown to facilitate the investigation of unique and important proteins involved in the pathogenesis and stress-defense mechanisms of pathogenic bacteria that remain exceedingly difficult to study using conventional methodologies.


[Sinusotrabeculectomy with regulated filtration in the treatment of secondary glaucoma].
A new method for surgical treatment of secondary glaucoma (neovascular, postuveal, traumatic, and aphakic) is described. The aims of the new method are as follows: regulation of ophthalmic tone in the postoperative period, pain relief, organ preservation, stabilization of the process, and creation of reliable routes of intraocular fluid discharge with formation of a stable diffuse functional pad. Seven patients (8 eyes) aged 13-70 years were operated on and followed up for up to 6 months. Preliminary results are presented. Positive shifts were observed in all cases.


[Rhythm disorders and infarction].
Ventricular arrhythmias are a frequent complication of myocardial infarction. In either the acute or the late stage, ventricular tachycardia and ventricular fibrillation represent the most common cause of cardiac death. About 15% of the patients with acute myocardial infarction die before entering the hospital, the majority due to ventricular fibrillation. Another 10 to 15% of the survivors of an acute myocardial infarction die suddenly within the subsequent year, again mostly due to ventricular arrhythmias. Independent risk factors for sudden cardiac death consist of depressed left ventricular function, persistent electrical instability (e.g. repetitive and complex VPB's, documented 'late potentials', inducibility of arrhythmias at programmed electrical stimulation), new onset complete-bundle branch block and large aneurysm of the left anterior ventricular wall. Bradyarrhythmias (i.e. high-degree AV-Block, asystole) are a far less common etiology of sudden cardiac death caused by an ischemic lesion to the conduction system. Betablockers have a well-known benefit in secondary prevention, whereas antiarrhythmic agents (with the exception of amiodarone) are ineffective in asymptomatic patients or may even increase the risk for sudden death due to a proarrhythmic effect (class IC); therefore, the latter are not recommended in asymptomatic patients with documented VPB's and preserved left ventricular function. The prognosis of patients with sustained VT and VF is poor. Their outcome is improved in responders to an individual antiarrhythmic therapy with serial drug testing or with subendocardial resection of localized areas and by implantation of a cardioverter defibrillator.


Bile duct injury with formation of right hepatic duct-duodenal fistula after cholecystectomy: A case report.
The management of bile duct injury (BDI) remains a considerable challenge in the department of hepatobiliary and pancreatic surgery. BDI is mainly iatrogenic and mostly occurs in laparoscopic cholecystectomy (LC). After more than 2 decades of development, with the increase in experience and technological advances in LC, the complications associated with the procedure have decreased annually. However, bile duct injuries (BDI) still have a certain incidence, the severity of BDI is higher, and the form of BDI is more complex. We report the case of a patient who presented with bile duct injury and formation of a right hepatic duct-duodenal fistula after LC. Based on the diagnosis, a dissection was performed to relieve bile duct obstruction, suture the duodenal fistula, and anastomose the right and left hepatic ducts to the jejunum. Based on the diagnosis, a dissection was performed to relieve bile duct obstruction, suture the duodenal fistula, and anastomose the right and left hepatic ducts to the jejunum. Postoperative recovery was uneventful, with normal liver function and no complications, such as anastomotic fistula or biliary tract infection. The patient was hospitalized for 11 days postoperatively and discharged. The successful diagnosis and treatment of this case and the summarization of the imaging features and diagnosis of postoperative BDI have improved the diagnostic understanding of postoperative BDI and provided clinicians with a particular clinical experience and basis for treating such diseases.


Biogenic synthesis of gold nanoparticles using dual extract of tulsi-Vinca for breast cancer tumor regression in mice.
Aim: This work aims to synthesize the gold nanoparticles (GNPs) using a dual extract of tulsi and Vinca (T+V-Gold) for breast cancer tumor regression. Methods: The GNPs were synthesized and characterized for their microscopic, spectroscopic and crystalline properties. Further, the GNPs were investigated for in vitro and in vivo studies for the treatment of the 4T1-induced triple-negative breast cancer murine model. Results: The GNPs for 4T1 tumor-challenged mice resulted in delayed tumor development and lower tumor burden, with T+V-Gold demonstrating the highest prevention of tumor spread. The antitumor effect of T+V-Gold is highly significant in the glutathione family antioxidants glutathione S-transferase and glutathione in tumor tissue samples. Conclusion: The bioefficacy and anticancer outcomes of T+V-Gold nanoformulation can be used as therapeutic agents, and drug-delivery vehicles.


Coenzyme Q10 and neuropsychiatric and neurological disorders: relevance for schizophrenia.
Objective: Mitochondrial dysfunction has been implicated in the pathophysiology of schizophrenia and other neuropsychiatric disorders. Though the exact mechanisms and clinical implications for this dysfunction are not fully determined, there is a hypothesis that deficiency in coenzyme Q10 (CoQ10) may contribute to mitochondrial impairments and be reflected in cognitive, affective, and energy disturbances in the disorders. CoQ10 is a critical component of the mitochondrial respiratory chain and an essential free radical scavenger, necessary for mitochondrial function. Here, we review the results of CoQ10 supplementation interventions for adults with various neurological and neuropsychiatric disorders and consider the therapeutic potential of CoQ10 supplementation for schizophrenia in light of these studies. Methods: A literature review of randomised controlled trials and open-label studies investigating the effect of CoQ10 as a single intervention in adults with neurological and neuropsychiatric disorders was conducted. Results: CoQ10 supplementation has some positive effects on fatigue, cognitive impairment and affective difficulties in several neurological and neuropsychiatric conditions with associated mitochondrial dysfunction. Discussion: CoQ10 may be of therapeutic value to schizophrenia given evidence of mitochondrial dysfunction in the disorder.


Abdominal Compartment Syndrome as a Multidisciplinary Challenge. A Literature Review.
Abdominal Compartment Syndrome (ACS), despite recent advances in medical and surgical care, is a significant cause of mortality. The purpose of this review is to present the main diagnostic and therapeutic aspects from the anesthetical and surgical points of view. Intra-abdominal hypertension may be diagnosed by measuring intra-abdominal pressure and indirectly by imaging and radiological means. Early detection of ACS is a key element in the ACS therapy. Without treatment, more than 90% of cases lead to death and according with the last reports, despite all treatment measures, the mortality rate is reported as being between 25 and 75%. There are conflicting reports as to the importance of a conservative therapy approach, although such an approach is the central to treatment guidelines of the World Society of Abdominal Compartment Syndrome, Decompressive laparotomy, although a backup solution in ACS therapy, reduces mortality by 16-37%. The open abdomen management has several variants, but negative pressure wound therapy represents the gold standard of surgical treatment.


Microhabitat preferences of Biomphalaria pfeifferi and Lymnaea natalensis in a natural and a man-made habitat in southeastern Tanzania.
Schistosoma mansoni is an important human parasitic disease which is widespread throughout Africa. As Biomphalaria pfeifferi snails act as intermediate host, knowledge of their population ecology is an essential prerequisite towards understanding disease transmission. We conducted a field study and assessed the density and microhabitat preferences of B.pfeifferi in a natural habitat which was a residual pool of a river. Repeated removal collecting revealed a density of 26.6 [95% confidence interval (CI): 24.9-28.3] snails/m2. B. pfeifferi showed microhabitat preferences for shallow water (depths: 0-4cm). They were found most abundantly close to the shoreline (distances: 0-40cm), and preferred either plant detritus or bedrock as substratum. Lymnaea natalensis, a snail which may act as a host for human Fasciola gigantica, also occurred in this habitat with a density of 34.0 (95% CI: 24.7-43.3) snails/m2, and preferred significantly different microhabitats when compared to B.pfeifferi. Microhabitat selection by these snail species was also investigated in a man-made habitat nearby, which consisted of a flat layer of concrete fixed on the riverbed, covered by algae. Here, B.pfeifferi showed no preference for locations close to the shoreline, probably because the habitat had a uniform depth. We conclude that repeated removal collecting in shallow habitats provides reliable estimates of snail densities and that habitat changes through constructions may create favourable microhabitats and contribute to additional disease transmission.


Clavulanic acid-potentiated activity of amoxicillin against Bacteroides fragilis.
Seventy-seven clinical isolates of Bacteroides fragilis from animal sources were examined for beta-lactamase production and resistance to amoxicillin. Sixty-five (84%) of the isolates produced detectable amounts of beta-lactamase. Concentrations of amoxicillin greater than 8 micrograms/ml were required to inhibit all but 13 (17%) of the isolates evaluated. Clavulanic acid, a beta-lactamase inhibitor, minimally inhibited growth of B fragilis when used alone. However, a synergistic effect was found when amoxicillin and clavulanic acid were used together against B fragilis. Ninety-nine percent of the isolates were inhibited by concentrations of 1 microgram of amoxicillin/ml in combination with 0.5 microgram of clavulanic acid/ml.


Neurotensin signaling stimulates glioblastoma cell proliferation by upregulating c-Myc and inhibiting miR-29b-1 and miR-129-3p.
Neurotensin (NTS) and its primary receptor NTSR1 are implicated in cancer progression. Aberrant expression of NTS/NTSR1 contributes to the proliferation of glioblastoma cells; however, the mechanism is not fully understood. Microarray and real-time PCR were performed to identify the NTS-regulated micro (mi)RNAs. The targets of the miRNAs were identified by luciferase assays and immunoblot analysis. The c-Myc binding sites in the miR-29b-1 and cyclin-dependent kinase (CDK)4 promoters were identified through chromatin immunoprecipitation assay. Cell proliferation was evaluated by Cell Counting Kit-8 assay and flow cytometry analysis. An orthotopic xenograft model demonstrated the role of NTS/NTSR1 and miRNAs in glioblastoma growth in vivo. Pharmacological inhibition or small interfering NTSR1 treatment blocked glioblastoma cell cycle progression in the G1 phase with a concomitantly decreased expression of CDK6, CDK4, and c-Myc. Knockdown of NTSR1 increased the expression of miR-29b-1 and miR-129-3p, which were responsible for the decreased CDK6 expression. NTS/NTSR1 signaling activated the transcription factor c-Myc in U87 cells, leading to increased CDK4 expression and repressed miR-29b-1 expression. Knockdown of NTSR1 decreased the glioblastoma growth in vivo and significantly prolonged the survival time of the tumor-bearing mice, an effect that can be largely reversed by antagomir. Our study showed a novel regulatory mechanism of NTS/NTSR1, an upstream signaling of miRNAs and c-Myc, in glioblastoma progression. The inhibition of the NTSR1 function or the upregulation of miR-29b-1 and miR-129-3p expression impaired glioma cell proliferation. These results suggested that the NTS/NTSR1/c-Myc/miRNA axis may be a potential therapeutic target for glioblastoma therapy.


Latent effects of prenatal malnutrition on adult health: the example of schizophrenia.
It is well established that malnutrition in children has adverse effects on development. Only recently, however, has it become possible to examine the full scope of adverse effects of malnutrition across the life course, which would include latent effects of fetal or childhood malnutrition on health and disease in adult life. We review here a series of studies which have linked early prenatal famine to the risk of schizophrenia in the offspring. Thus we aim to draw attention to the need to look beyond the concurrent effects of malnutrition and consider also the effects that may become apparent decades later.


[Wilhelm Krücke (1911-1988): on the occasion of the 100th birthday of the great neuropathologist on December 26, 2011].
A short summary is presented on the life, professional development, research work, especially concerning peripheral nervous system, and personality of the former director of the Department of Neuropathology at the Max-Planck-Institute of Brain Research and Edinger Institute of the Johann Wolfgang Goethe-University, both in Frankfurt/Main.


Vegetation type and grazing intensity jointly shape grazing effects on grassland biodiversity.
In the Palaearctic steppe zone, overgrazing was identified as one of the key drivers of declining grassland biodiversity, which underlines the necessity of the functional evaluation of increased grazing pressure on grassland vegetation. We tested the following hypotheses: (a) The effect of grazing intensity on species and functional diversity is strongly dependent on grassland type. (b) The magnitude of diet selectivity of grazers decreases with increasing grazing intensity. (c) Increasing grazing intensity increases evenness and functional evenness of the subjected grasslands. We analyzed vegetation patterns in four types of grasslands (Dry alkali short-grass steppes, Dry loess steppes, Non-alkali wet and Alkali wet grasslands) along an intensity gradient of beef cattle grazing at 73 sites in Hungary. Species richness, Shannon diversity, evenness, and four leaf traits were analyzed. We calculated community-weighted means for each single trait, and multi-trait functional richness, functional evenness, and divergence for all leaf traits. All species and functional diversity metrics were significantly affected by the grassland type, except leaf dry matter content. The effect of interaction between grazing intensity and grassland type was also significant for functional richness, functional evenness, community-weighted means of leaf area, and for species richness and evenness. An upward trend of specific leaf area was detected in all grasslands with the highest scores for the overgrazed sites, but the change was also grassland type dependent. The detected trend suggests that with increased intensity the overall selectivity of grazing decreased. We found that evenness was affected but functional evenness was not affected by grazing intensity. Functional evenness scores were more related to the grassland type than to changes in grazing intensity, and displayed a high variability. We stress that one-size-fits-all strategies cannot be recommended and actions should be fine-tuned at least at the level of grassland type.


A novel genotype of Hantaan orthohantavirus harbored by Apodemus agrarius chejuensis as a potential etiologic agent of hemorrhagic fever with renal syndrome in Republic of Korea.
Orthohantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome, pose a significant public health threat worldwide. Despite the significant mortality and morbidity, effective antiviral therapeutics for orthohantavirus infections are currently unavailable. This study aimed to investigate the prevalence of HFRS-associated orthohantaviruses and identify the etiological agent of orthohantavirus outbreaks in southern Republic of Korea (ROK). We collected small mammals on Jeju Island during 2018-2020. We detected the Hantaan virus (HTNV)-specific antibodies and RNA using an indirect immunofluorescence assay test and reverse transcription-polymerase chain reaction on Apodemus agrarius chejuensis (A. chejuensis). The prevalence of anti-HTNV antibodies among rodents was 14.1%. A total of six seropositive mouse harbored HTNV RNA. The amplicon-based next-generation sequencing provided nearly full-length tripartite genomic sequences of six HTNV harbored by A. chejuensis. Phylogenetic and tanglegram analyses were conducted for inferring evolutionary relationships between orthohantaviruses with their reservoir hosts. Phylogenetic analysis showed a novel distinct HTNV genotype. The detected HTNV genomic sequences were phylogenetically related to a viral sequence derived from HFRS patient in southern ROK. Tanglegram analysis demonstrated the segregation of HTNV genotypes corresponding to Apodemus spp. divergence. Our results suggest that A. chejuensis-borne HTNV may be a potential etiological agent of HFRS in southern ROK. Ancestral HTNV may infect A. chejuensis prior to geological isolation between the Korean peninsula and Jeju Island, supporting the co-evolution of orthohantaviruses and rodents. This study arises awareness among physicians for HFRS outbreaks in southern ROK.


Donation After Circulatory Death for Liver Transplantation: A Meta-Analysis on the Location of Life Support Withdrawal Affecting Outcomes.
Liver transplantation using donation after circulatory death (DCD) donors is associated with inferior outcomes compared to donation after brain death (DBD). Prolonged donor warm ischemic time has been identified as the key factor responsible for this difference. Various aspects of the donor life support withdrawal procedure, including location of withdrawal and administration of antemortem heparin, are thought to play important roles in mitigating the effects of warm ischemia. However, a systematic exploration of these factors is important for more confident integration of these practices into a standard DCD protocol. Medline, EMBASE, and Cochrane libraries were systematically searched and 23 relevant studies identified for analysis. Donation after circulatory death recipients were stratified according to location of life support withdrawal (intensive care unit or operating theater) and use of antemortem heparin. Donation after circulatory death recipients had comparable 1-year patient survival to DBD recipients if the location of withdrawal of life support was the operating theater, but not if the location was the intensive care unit. Likewise, the inferior 1-year graft survival and higher incidence of ischemic cholangiopathy of DCD compared with DBD recipients were improved by withdrawal in operating theater, although higher rates of ischemic cholangiopathy and worse graft survival were still observed in DCD recipients. Furthermore, administering heparin before withdrawal of life support reduced the incidence of primary nonfunction of the allograft. Our evidence suggests that withdrawal in the operating theater and premortem heparin administration improve DCD liver transplant outcomes, thus allowing for the most effective usage of these valuable organs.


Adsorption and Dissociation of CO2 on Ru(0001).
The adsorption and dissociation of carbon dioxide on a Ru(0001) single crystal surface was investigated by reflection-absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD) spectroscopy for CO2 adsorbed at 85 K. RAIRS spectroscopy shows that the adsorption of CO2 on a Ru(0001) single crystal is partially dissociative, resulting in CO2 and CO. The CO vibrational mode was also observed to split into two distinct modes, indicating two general populations of CO present at the surface. Furthermore, a time-dependent blue-shift is observed, which is characteristic of increasing CO surface coverage. TPD showed that coverages of up to 0.3 ML were obtained, and no evidence for chemisorption of oxygen on ruthenium was found.


The Effects of Cold Saponification on the Unsaponified Fatty Acid Composition and Sensory Perception of Commercial Natural Herbal Soaps.
Saponification is the process in which triglycerides are combined with a strong base to form fatty acid metal salts during the soap-making process. The distribution of unsaturated and saturated fatty acid determines the hardness, aroma, cleansing, lather, and moisturizing abilities of soaps. Plant extracts, such as rosemary, vegetable, and essential oils are frequently added to soaps to enhance quality and sensory appeal. Three natural soaps were formulated using cold saponification to produce a base or control bar (BB), hibiscus rosehip bar (H), and a forest grove bar (FG). Rosemary extract (R) or essential oil (A) blends were added as additives to each formulation prior to curing to evaluate the effects of natural plant additives on the lipid composition and sensory characteristics of these natural herbal soaps. A total of seven natural soaps, three without additives (BB, H, FG) and four with additives (BBR, HA, FGR, FGA), were manufactured and studied. The majority (86⁻99%) of the polyunsaturated fatty acids (5.0⁻7.0 µg/mg) remained unsaponified in the manufactured natural soaps regardless of feedstock used. Principal component analysis (PCA) analyses showed the unsaponifiable fatty acids were different in the hibiscus bar compared to the other bars. There was a very strong correlation between the content of unsaponified C18:3n3 and C18:1n9 in all natural soaps. These results indicate that unsaponified fatty acids are important contributors to the quality and overall sensory perception and preference of natural herbal soaps following manufacturing by cold saponification.


Uncertainty in delivered dose resulting from the distribution of source activities in a Selectron LDR afterloader.
The uncertainty in the delivered dose resulting from the distribution of 137Cs source activity in a clinical Selectron LDR unit has been studied. A comparison is made of the dose delivered to a point 'A' in an implant with sources of equal activity to the actual dose delivered in the same implant with source activities randomly chosen from the population in the afterloader.


[Opinions and expectations of patients with health problems associated to asbestos exposure].
The prevalence of diseases related to asbestos exposure requires the development of monitoring programs and specific health care protocols. The aim of this study is to determine the opinions and expectations of former workers of an asbestos factory, in order to adapt the care process to the needs of the affected population, and to learn about the activity of the association that represents them. Qualitative study. Focus groups with former employees of a corrugated asbestos factory, members of the association AVIDA (Seville). Recording and transcription of interviews. Discourse analysis with Nudist Vivo 1.0. All respondents have health problems, including asbestosis, lung cancer and mesothelioma. Through the association, they are involved in an ongoing process of negotiation with the public administration, to improve healthcare, achieve recognition as having an occupational disease and the payment of compensation. The lack of monitoring and continuity in care is designated as the major problem in the current care process. They welcome the creation of special care units, the good treatment received and the quality of technical instruments in the public health system. On the contrary, they criticize the difficulties in finding an accurate diagnosis, the lack of continuity of care, and the bureaucratic difficulties and lack of specific care directed to affected relatives. The participants' expectations highlight their intention to participate in the development of future programs and protocols. This study confirms the multifactor nature of diseases related to asbestos exposure and the importance of determining the needs and demands of the affected population in order to improve health care.


[One patient - many faces of myocardial ischaemia].
We present the case of a woman treated with coronary angioplasty due to non-ST segment elevation myocardial infarction,then again because of restenosis, who continued to complain of chest pain and syncope. Holter electrocardiogram recording revealed atrioventricular block related to ST-segment elevations and variant angina was diagnosed. Despite administered medications, the patient required pacemaker implantation.


Presence of CpG DNA and the local cytokine milieu determine the efficacy of suppressive DNA vaccination in experimental autoimmune encephalomyelitis.
We here study the adjuvant properties of immunostimulatory DNA sequences (ISS) and coinjected cytokine-coding cDNA in suppressive vaccination with DNA encoding an autoantigenic peptide, myelin basic protein peptide 68-85, against Lewis rat experimental autoimmune encephalomyelitis (EAE). EAE is an autoaggressive, T1-mediated disease of the CNS. ISS are unmethylated CpG motifs found in bacterial DNA, which can induce production of type 1 cytokines in vertebrates through the innate immune system. Because ISS in the plasmid backbone are necessary for efficient DNA vaccination, we studied the effect of one such ISS, the 5'-AACGTT-3' motif, in our system. Treatment with a DNA vaccine encoding myelin basic protein peptide 68-85 and containing three ISS of 5'-AACGTT-3' sequence suppressed clinical signs of EAE, while a corresponding DNA vaccine without such ISS had no effect. We further observed reduced proliferative T cell responses in rats treated with the ISS-containing DNA vaccine, compared with controls. We also studied the possible impact of coinjection of plasmid DNA encoding rat cytokines IL-4, IL-10, GM-CSF, and TNF-alpha with the ISS-containing DNA vaccine. Coinjection of IL-4-, IL-10-, or TNF-alpha-coding cDNA inhibited the suppressive effect of the DNA vaccine on EAE, whereas GM-CSF-coding cDNA had no effect. Coinjection of cytokine-coding cDNA with the ISS-deficient DNA vaccine failed to alter clinical signs of EAE. We conclude that the presence of ISS and induction of a local T1 cytokine milieu is decisive for specific protective DNA vaccination in EAE.


An integrated direct loop-mediated isothermal amplification microdevice incorporated with an immunochromatographic strip for bacteria detection in human whole blood and milk without a sample preparation step.
We have developed an integrated direct loop-mediated isothermal amplification (Direct LAMP) microdevice incorporated with an immunochromatographic strip (ICS) to identify bacteria contaminated in real samples. The Direct LAMP is a novel isothermal DNA amplification technique which does not require thermal cycling steps as well as any sample preparation steps such as cell lysis and DNA extraction for amplifying specific target genes. In addition, the resultant amplicons were colorimetrically detected on the ICS, thereby enabling the entire genetic analysis process to be simplified. The two functional units (Direct LAMP and ICS) were integrated on a single device without use of the tedious and complicated microvalve and tubing systems. The utilization of a slidable plate allows us to manipulate the fluidic control in the microchannels manually and the sequential operation of the Direct LAMP and ICS detection could be performed by switching the slidable plate to each functional unit. Thus, the combination of the direct isothermal amplification without any sample preparation and thermal cycling steps, the ICS based amplicon detection by naked eyes, and the slidable plate to eliminate the microvalves in the integrated microdevice would be an ideal platform for point-of-care DNA diaganotics. On the integrated Direct LAMP-ICS microdevice, we could analyze Staphylococcus aureus (S. aureus) and Escherichia coli O157:H7 (E. coli O157:H7) contaminated in human whole blood or milk at a single-cell level within 1h.


Tocopherols and polyunsaturated fatty acids in human tissues.
Five tissues from three adults who died suddenly and three adult cancer victims were analyzed for alpha- and gamma-tocopherols and fatty acids. When compared with two reports in 1949 and 1958, the three presumably normal subjects had alpha-tocopherol concentrations in liver, muscle and adipose tissue in about the same range as earlier, but heart was twice as high and lung was three times higher than earlier. The content of gamma-tocopherol in all tissues was considerably higher than in 1949 or 1958. Tissues from cancer patients were no lower in alpha-tocopherol than tissues from normal subjects. Adipose tissue from three of the six subjects contained linoleic acid exceeding 15 per cent of total fatty acids. Tocopherols in these subjects, expressed on a tissue weight or tissue lipid basis, were not remarkable. The molar ratio of polyunsaturated fatty acids to alpha-tocopherol in heart and lung was calculated and its possible use in evaluating vitamin E status is discussed.


TET2 as a tumor suppressor and therapeutic target in T-cell acute lymphoblastic leukemia.
Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy resulting from overproduction of immature T-cells in the thymus and is typified by widespread alterations in DNA methylation. As survival rates for relapsed T-ALL remain dismal (10 to 25%), development of targeted therapies to prevent relapse is key to improving prognosis. Whereas mutations in the DNA demethylating enzyme TET2 are frequent in adult T-cell malignancies, TET2 mutations in T-ALL are rare. Here, we analyzed RNA-sequencing data of 321 primary T-ALLs, 20 T-ALL cell lines, and 25 normal human tissues, revealing that TET2 is transcriptionally repressed or silenced in 71% and 17% of T-ALL, respectively. Furthermore, we show that TET2 silencing is often associated with hypermethylation of the TET2 promoter in primary T-ALL. Importantly, treatment with the DNA demethylating agent, 5-azacytidine (5-aza), was significantly more toxic to TET2-silenced T-ALL cells and resulted in stable re-expression of the TET2 gene. Additionally, 5-aza led to up-regulation of methylated genes and human endogenous retroviruses (HERVs), which was further enhanced by the addition of physiological levels of vitamin C, a potent enhancer of TET activity. Together, our results clearly identify 5-aza as a potential targeted therapy for TET2-silenced T-ALL.


Influence of pretransplant transfusions on kidney graft survival.
A study was made to elucidate the influence of transfusions on graft survival in 42 transplanted patients. In this series of multitransfused patients the number of units given was without significance, whereas transfusions given before onset of renal disease deteriorated graft prognosis. Possible explanations are discussed and a restrictive transfusion policy is advocated for patients, for instance with malformation of the urinary tract, who may be future candidates for transplantation.


Turing, von Neumann, and the computational architecture of biological machines.
In the mid-1930s, the English mathematician and logician Alan Turing invented an imaginary machine which could emulate the process of manipulating finite symbolic configurations by human computers. His machine launched the field of computer science and provided a foundation for the modern-day programmable computer. A decade later, building on Turing's machine, the American-Hungarian mathematician John von Neumann invented an imaginary self-reproducing machine capable of open-ended evolution. Through his machine, von Neumann answered one of the deepest questions in Biology: Why is it that all living organisms carry a self-description in the form of DNA? The story behind how two pioneers of computer science stumbled on the secret of life many years before the discovery of the DNA double helix is not well known, not even to biologists, and you will not find it in biology textbooks. Yet, the story is just as relevant today as it was eighty years ago: Turing and von Neumann left a blueprint for studying biological systems as if they were computing machines. This approach may hold the key to answering many remaining questions in Biology and could even lead to advances in computer science.


Highlights from the 2012 Schizophrenia International Research Society Conference, April 14-18, 2012.
The 2012 Schizophrenia International Research Society (SIRS) Conference, held in Florence, Italy, attracted more than 1,600 attendees from 53 countries to the stately Firenze Fiera Conference Center from April 14-18, 2012. Providing four major plenary sessions, thirty-five symposia sessions and six workshops, this 3rd Biennial SIRS Conference was jointly sponsored by Vanderbilt University School of Medicine, Department of Psychiatry and SIRS. In conjunction with the Schizophrenia Research Forum, a Web project of the Brain and Behavior Research Foundation, and with our thanks to the SIRS organizers and staff, we bring you the following report on the meeting's discussions concerning drug therapy development for schizophrenia, psychological and social treatment for schizophrenia, and the challenges of predicting psychosis with brain imaging.


Routine DNA analysis based on 12S rRNA gene sequencing as a tool in the management of captive primates.
Automated DNA sequencing of a fragment of the relatively slowly evolving mitochondrial 12S rRNA gene was used to distinguish primate species, and the method was compared with species determination based upon classical taxonomy. DNA from blood from 53 monkeys housed at the Stichting AAP Shelter for Exotic Animals, all Old World monkeys, was amplified by polymerase chain reaction (PCR) with a primer set spanning approximately 390 nucleotides of the mitochondrial 12S rRNA gene. The products were directly sequenced and compared with our database of primate 12S sequences. Many individuals were found to harbor a 12S sequence identical to one of the reference sequences. For others, phylogenetic methods were used for species estimation, which was especially informative in Cercopithecus species.


Antistaphylococcal activity of Zataria multiflora essential oil and its synergy with vancomycin.
Staphylococcus aureus is recognized as one of the major cause of infections in communities and hospitals. In this study, the chemical composition and antistaphylococcal activity of Zataria multiflora Boiss essential oil were evaluated, along with its synergistic activity with vancomycin. The essential oil was obtained by hydrodistillation from aerial parts of the plant and analyzed using GC and GC-MS. Thymol (38.7%), carvacrol (15.3%) and rho-cymene (10.2%) were the main components of the oil. Antibacterial activity of the oil was evaluated by microbroth dilution assay against clinical isolates of methicillin -resistant (MR) and methicillin-sensitive (MS) strains of S. aureus. The oil showed high antibacterial activity against MRSA and MSSA with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values in the range of 0.25-1 and 0.5-2microl/ml, respectively. The synergistic action was evaluated by microtiter assay. The essential oil exhibited synergism with vancomycin and displayed the ability to enhance the activity of vancomycin. This study showed that Z. multiflora oil has significant antimicrobial activity against clinical isolates of S. aureus, especially MRSA, and might be useful in controlling MRSA infections.


Black male college students and hypertension: a qualitative investigation.
Qualitative research was used to determine what young black male college students do and believe in the hypertension related areas of nutrition, stress and exercise. Black female college students also were asked about their perception of the men's beliefs and behaviors in regard to the above mentioned areas. The study identified stress, especially the stress of being a black male in the US, as the most important concern of both male and female students. There was also agreement in both gender groups that relatives and close friends, especially females, had more influence on men's health behavior than professionals or celebrities. The study discusses the implications of these findings for hypertension prevention programs targeted at young black male college students.


Influence of topography on the endemicity of Kala-azar: a study based on remote sensing and geographical information system.
Kala-azar, a fatal infectious disease in many Indian states, particularly in Bihar, West Bengal, Uttar Pradesh, and Jharkhand, is caused by the protozoan parasite Leishmania donovani and transmitted by the sandfly vector Phlebotomus argentipes. The vector is distributed all over the country but the disease is confined to particular zones since before the last century. In this study, parameters such as altitude, temperature, humidity, rainfall and the normalized difference vegetation index (NDVI) were investigated for correlation with the distribution of the disease in the northeastern corner of the Indian sub-continent. Data analysis on Kala-azar prevalence during the period 2005-2007 in the four states showed that the highest prevalence was below 150 m of altitude with very few cases located above the 300 m level. Low NDVI value ranges (0.03-0.015) correlated with a high occurrence of the disease. The maximum temperatures in the affected sites varied between an upper level of 25-29 degrees C and a minimum of 16-20 degrees C. The rainfall in these areas fluctuated between 1154 and 1834 mm. As the disease showed a high correlation with the prevailing topographic conditions, an attempt was made to improve the relative strength of the approach to predict the potential for endemicity of leishmaniasis by introducing satellite imagery complemented with a geographical information system database.


Construction and Validation of a Prognostic Model Based on Novel Senescence-Related Genes in Non-Small Cell Lung Cancer Patients with Drug Sensitivity and Tumor Microenvironment.
Cellular senescence contributes to cancer pathogenesis and immune regulation. Using the LASSO Cox regression, we developed a 12-gene prognostic signature for lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) and a Gene Expression Omnibus (GEO) dataset. We assessed gene expression, drug sensitivity, immune infiltration, and conducted cell line experiments. High-risk LUAD patients showed increased mortality risk and shorter survival (P < 0.001). Senescence-related gene analysis indicated differences in protein phosphorylation and DNA methylation between normal individuals and LUAD patients. The high-risk group showed a positive association with PD-L1 expression (P = 0.003). Single-cell sequencing data suggested PEBP1 might significantly impact T cell infiltration. We predicted potential sensitive compounds for 12 senescence genes and found GAPDH promoted cell line proliferation. We established a novel prognostic system based on a newly identified senescence gene. High-risk patients had elevated immunosuppressive markers, and PEBP1 might influence T cell infiltration significantly. GAPDH, expressed at higher levels in tumors, could affect cancer progression. Our drug prediction model may guide treatment selection.


Demonstration and characterization of motilin-binding sites in the rabbit cerebellum.
This is the first report on central motilin receptors. Autoradiography on cerebellar slices revealed specific motilin-binding sites in the molecular layer of the cortex. Scatchard analysis of cold saturation studies showed the existence of a high-(pKd,hi = 9.07 +/- 0.09, where pKd is the negative logarithm of the dissociation constant) and a low-affinity binding site (pKd,lo = 6.56 +/- 0.09). Similar affinities were found with rabbit motilin and with the porcine (po) antagonist [Phe3, Leu13]po-motilin. Feline and canine motilin had a markedly lower affinity for the low-affinity site (pKd,lo = 5.29 and 4.58, respectively); chicken motilin had a lower affinity for both sites (pKd,hi = 8.36, pKd,lo = 3.97). Erythromycin A and its derivative N-trimethyl erythromycin A cnol ether also bound to cerebellar motilin receptors (pKd,hi = 7.29 and 8.91, respectively). Structure-activity studies with motilin fragments and the potency ranking of agonists suggest that a novel subtype receptor of motilin may exist in the brain. Guanosine 5'-O-(3-thiotriphosphate) (0.1 mM) reduced the number and the affinity for the high-affinity binding sites, which is evidence for G protein-coupled receptors. Our findings open new perspectives for the study of the physiological role of motilin.


Lipoproteins as targets and markers of lipoxidation.
Lipoproteins are essential systemic lipid transport particles, composed of apolipoproteins embedded in a phospholipid and cholesterol monolayer surrounding a cargo of diverse lipid species. Many of the lipids present are susceptible to oxidative damage by lipid peroxidation, giving rise to the formation of reactive lipid peroxidation products (rLPPs). In view of the close proximity of the protein and lipid moieties within lipoproteins, the probability of adduct formation between rLPPs and amino acid residues of the proteins, a process called lipoxidation, is high. There has been interest for many years in the biological effects of such modifications, but the field has been limited to some extent by the availability of methods to determine the sites and exact nature of such modification. More recently, the availability of a wide range of antibodies to lipoxidation products, as well as advances in analytical techniques such as liquid chromatography tandem mass spectrometry (LC-MSMS), have increased our knowledge substantially. While most work has focused on LDL, oxidation of which has long been associated with pro-inflammatory responses and atherosclerosis, some studies on HDL, VLDL and Lipoprotein(a) have also been reported. As the broader topic of LDL oxidation has been reviewed previously, this review focuses on lipoxidative modifications of lipoproteins, from the historical background through to recent advances in the field. We consider the main methods of analysis for detecting rLPP adducts on apolipoproteins, including their advantages and disadvantages, as well as the biological effects of lipoxidized lipoproteins and their potential roles in diseases.


Cutting Edge: Bach2 Integrates Cytokine Signals to Arbitrate Differentiation Decisions between T Follicular Helper and Th17 Lineages.
CXCR5 is a hallmark of T follicular helper (Tfh) cells. The mechanism of CXCR5 induction, however, is still incompletely understood. In this study, we report that in mice with the absence of transcription factor Bach2, the Th17-inducing cytokines IL-6 and TGF-β together induced CXCR5 expression in vitro. Mechanistically, IL-6/STAT3 drove Cxcr5 promoter activity via the upstream site 1 regulatory element, whereas TGF-β enhanced permissive histone modifications, and the STAT3 binding to the site 1 regulatory element was higher in the absence of Bach2. Subsequently, despite previous studies showing enhanced Th17 cell differentiation in the absence of Bach2 in vitro, we found that in vivo, the Bach2 deficiency led to an enhanced Tfh cell response at the expense of the Th17 cell response. These findings suggest that Bach2 helps integrate cytokine signals to arbitrate differentiation decisions between Tfh and Th17 lineages.


Causes and pattern of fracture of acrylic dentures among patients seen in a Nigerian teaching hospital.
There is little information on the causes and pattern of fracture of acrylic dentures in Nigerian patients despite being the most frequently employed design in Nigeria. The aim of this study was to determine the average life span of acrylic dentures before fracture, the causes and pattern of fracture of acrylic dentures in a Nigerian population. All consecutive patients that presented with fractured acrylic dentures at the Dental Centre, University College Hospital, Ibadan between January and July 2006 and were willing to participate were recruited into the study. A structured interviewer-administered questionnaire was used to record data from the patients. The questionnaire focused on patients' demographic data, age of acrylic denture as at the time of fracture, causes and pattern of fractures. The data were analysed using SPSS Version 11. A total of sixty-two patients were included in the study. They presented with sixty-nine fractured dentures. Five were complete dentures while 64 were partial dentures. The average life span was 7.4 years +/- 6.6 (SD) years. Early fracture was seen in 9 (13.4%), intermediate fracture in 29 (42%), and late fracture in 31 (44.9%) cases. The commonest cause of fracture was mastication as seen in 30.4% of the cases while the least cause was fight (4.3%). The commonest site of fracture (34.8%) was the palatal plate around the crest of the edentulous ridge while fracture of wrought metal clasps was the least, occurring in 1.4% of cases. We recommend proper design with balanced articulation and more emphasis on compliance to post insertion instructions by patients to prevent early fracture of acrylic dentures. Also, reinforcing the acrylic denture base especially in stress bearing area may prolong the life span of these prostheses.


[Debridement of burn wounds: rationale and options].
Debridement describes the removal of devitalised tissue and debris (to reduce the toxic and bacterial burden) from a wound. In thermally injured tissue, the adoption of excisional strategies has been shown to improve both morbidity as well as mortality, albeit at the expense of creating new donor wounds. Tangential debridement is performed with surgical steel (i.e., Humby or Goulian knife). Other modalities like enzymatic ointments and hydrosurgical systems have shown promise in refining the debridement process, affording a measure of control with respect to the depth of debridement.


Experimental renal osteodystrophy. The response to 25-hydroxycholecalciferol and dicholomethylene diphosphate therapy.
Bone mineral and matrix maturation in chronically uremic, nonacidotic rats were investigated after 25-hydroxcholecalciferol (25OHD) and/or dichloromethylene diphosphonate (C12MDP) therapy utilizing bromoform-toluene density gradient fractionation and X-ray diffraction analyses. The bromoform-toluene density gradient analyses demonstrated that the progressive accumulation of less dense, more immature bone characteristic of progressive uremia was reversed by 25OHD and/or C12MDP therapy for a 2-wk period, and that after 4 wk of therapy the maturational profile of bones from chronically uremic animals treated with 250HD and/or C12MDP was comparable to that from nonuremic littermates. X-ray diffraction analysis revealed that by the 4th wk of therapy with 25OHD and C12MDP both the degree of crystallinity and the crystal size/perfection parameters in the uremic bones were comparable to those of nonuremic, pair-fed control littermates. Treatment for 4 wk with 25OHD resulted in enlarged and/or more perfect apatite crystallites, while C12MDP alone slightly inhibited crystal growth and/or perfection after 2 wk of treatment. Soft tissue calcification was diminished in uremic animals treated for 4 wk with C12MDP or a combined C2MDP/25OHD regimen, the latter being much more effective in this regard. The accumulated data in this study support the premise that the attendant accelerated bone resorption, soft tissue calcification, and abnormal mineralization and maturation of the skeletal tissue, well documented to characterize experimental ranal insufficiency, may be alleviated with therapeutic dosages of 25OHD and/or C12MDP.


Personal health information management system and its application in referral management.
We developed a web-based personal health record (PHR) that can be used by patients to collect and manage their health information (e.g., medical history, past surgeries, medications, and allergies), to request self-referrals, and to store a record of their consultations. The PHR also includes a messaging system that can be structured into the workflow of referral management as well as allowing more general communications. A preliminary study was conducted with 61 patients. Thirty-two patients completed a survey in which 85% of respondents were satisfied with the usability and 94% were satisfied with the overall online referral process. The consulting physicians were satisfied with the content of subjects' personal health information and referral problem descriptions and found the information detailed enough to triage all requested referrals. Patients, physicians, and patient care coordinators reported that their communications were enhanced by the system and found the messaging component convenient to use.


Velocity invariance of receptive field structure in somatosensory cortical area 3b of the alert monkey.
This is the second in a series of studies of the neural representation of tactile spatial form in cortical area 3b of the alert monkey. We previously studied the spatial structure of 330 area 3b neuronal receptive fields (RFs) on the fingerpad with random dot patterns scanned at one velocity (40 mm/sec; ). Here, we analyze the temporal structure of 84 neuronal RFs by studying their spatial structure at three scanning velocities (20, 40, and 80 mm/sec). As in the previous study, most RFs contained a single, central, excitatory region and one or more surrounding or flanking inhibitory regions. The mean time delay between skin stimulation and its excitatory effect was 15.5 msec. Except for differences in mean rate, each neuron's response and the spatial structure of its RF were essentially unaffected by scanning velocity. This is the expected outcome when excitatory and inhibitory effects are brief and synchronous. However, that interpretation is consistent neither with the reported timing of excitation and inhibition in somatosensory cortex nor with the third study in this series, which investigates the effect of scanning direction and shows that one component of inhibition lags behind excitation. We reconcile these observations by showing that overlapping (in-field) inhibition delayed relative to excitation can produce RF spatial structure that is unaffected by changes in scanning velocity. Regardless of the mechanisms, the velocity invariance of area 3b RF structure is consistent with the velocity invariance of tactile spatial perception (e.g., roughness estimation and form recognition).


Ayurvedic formulations: Potential COVID-19 therapeutics?
While Molnupiravir and Paxlovid have recently been approved for use in some countries, there are no widely available treatments for COVID-19, the disease caused by SARS-CoV-2 infection. Herbal extracts have been used to treat respiratory clinical indications by Ayurvedic medicine practitioners with minimal adverse reactions and intense research efforts are currently under way to develop some of these formulations for COVID-19 treatment. Literature search for in silico, in vitro, in vivo, and clinical studies on the topic of Ayurvedic formulations for potential COVID-19 treatment, in order to present the current state of current knowledge by integrating information across all systems. The search yielded 20 peer reviewed articles on in silico studies examining the interaction of phytoconstituents of popular Ayurvedic formulations with SARS-CoV-2 components and its receptors; five articles on preclinical investigations of the ability of selected Ayurvedic formulations to inhibit functions of SARS-CoV-2 proteins; and 51 completed clinical trials on the efficacy of using Ayurvedic formulations for treatment of mild to moderate COVID-19. Clinical data was available from 17 of the 51 trials. There was a considerable overlap between formulations used in the in silico studies and the clinical trials. This finding was unexpected as there is no clearly stated alignment between studies and the traditional pathway to drug discovery- basic discovery leading to in vitro and in vivo proof of concept, followed by validation in clinical trials. This was further demonstrated in the majority of the in silico studies where focus was on potential antiviral mechanisms, while the clinical trials were focused on patient recovery using oral treatments. In all 17 clinical trials where data was available, Ayurvedic treatments lead to a shorter period to recovery in participants with COVID-19. The most commonly used Ayurvedic treatments for management of respiratory symptoms associated with SARS-CoV-2 infection appear to have prophylactic and/or therapeutic properties. It would be of particular interest to assess synergistic and concomitant systemic effects and antiviral activities of individual phytoconstituents and their combinations in the Ayurvedic treatments.


Unfair treatment, racial/ethnic discrimination, ethnic identification, and smoking among Asian Americans in the National Latino and Asian American Study.
We examined the relations of self-report of general unfair treatment and self-report of race/ethnicity-specific discrimination with current smoking among Asian Americans. We investigated whether ethnic identification moderated either association. Weighted logistic regressions were performed among 1977 Asian Americans recruited to the National Latino and Asian American Study (2002-2003). In weighted multivariate logistic regression models including both general unfair treatment and racial/ethnic discrimination, odds of current smoking were higher among Asian Americans who reported high levels of unfair treatment (odds ratio [OR]=2.80; 95% confidence interval [CI]=1.13, 6.95) and high levels of racial/ethnic discrimination (OR=2.40; 95% CI=0.94, 6.12) compared with those who reported no unfair treatment and discrimination, respectively. High levels of ethnic identification moderated racial/ethnic discrimination (F(3) =3.25; P =.03). High levels of ethnic identification were associated with lower probability of current smoking among participants reporting high levels of racial/ethnic discrimination. Our findings suggest that experiences of unfair treatment and racial/ethnic discrimination are risk factors for smoking among Asian Americans. Efforts to promote ethnic identification may be effective in mitigating the influence of racial/ethnic discrimination on smoking in this population.


Excited state intramolecular proton transfer in hydroxyanthraquinones: Toward predicting fading of organic red colorants in art.
Compositionally similar organic red colorants in the anthraquinone family, whose photodegradation can cause irreversible color and stability changes, have long been used in works of art. Different organic reds, and their multiple chromophores, suffer degradation disparately. Understanding the details of these molecules' degradation therefore provides a window into their behavior in works of art and may assist the development of improved conservation methods. According to one proposed model of photodegradation dynamics, intramolecular proton transfer provides a kinetically favored decay pathway in some photoexcited chromophores, preventing degradation-promoting electron transfer (ET). To further test this model, we measured excited state lifetimes of substituted gas-phase anthraquinones using high-level theory to explain the experimental results. The data show a general structural trend: Anthraquinones with 1,4-OH substitution are long-lived and prone to damaging ET, while excited state intramolecular proton transfers promote efficient quenching for hydroxyanthraquinones that lack this motif.


Distribution of insertion sequence ISRm1 in Rhizobium meliloti and other gram-negative bacteria.
An internal 0.9 kb segment of Rhizobium meliloti insertion sequence ISRm1 was used as a probe to determine the distribution of ISRm1 in strains of R. meliloti and other Gram-negative bacteria. The insertion sequence was detected in 80% (12/15) of R. meliloti strains from different parts of the world. Its copy number ranged from one to at least eleven. The ISRm1 copies detected showed variation in their internal restriction sites and their degree of homology to the probe. ISRm1 was found in a variety of genomic restriction fragments, and was detected in plasmids, including the nod and exo megaplasmids of R. meliloti. Other rhizobia found to contain ISRm1 were a strain of R. leguminosarum biovar phaseoli and two Rhizobium isolates capable of nodulating both Medicago sativa and Phaseolus vulgaris. It was also found in a diazotrophic soil bacterium isolated from the roots of wetland rice.


Measles virus infection in rhesus macaques: altered immune responses and comparison of the virulence of six different virus strains.
Measles remains a major cause of childhood mortality, with questions about virus virulence and pathogenesis still requiring answers. Rhesus macaques were infected with 5 different culture-adapted strains of measles virus, including 2 from patients with progressive vaccine-induced disease, and a sixth nonculture-adapted strain, Bilthoven. All caused infection detectable by reverse transcriptase-polymerase chain reaction and induction of antibody. Chicago-1 and Bilthoven induced viremias detectable by leukocyte cocultivation. Bilthoven induced Koplik's spots, conjunctivitis, and rash. Lymphopenia and depressed interleukin (IL)-2 production were followed by monocytosis and eosinophilia. All monkeys, including 41 involved in a primate facility outbreak, showed suppressed responses to phytohemagglutinin. As the rash resolved production of IL-2, IL-1beta, tumor necrosis factor-alpha, IL-6, and IL-5 mRNA increased. Monkeys are useful for studies of measles immunopathogenesis, but virus strains must be carefully chosen. Increased virulence of vaccine strains isolated from immunocompromised infants with fatal infections was not evident.


Effect of calcitonin treatment on the natural course of bone demineralization in Paget's disease.
Numerous studies have been done to determine the effects of long term calcitonin (CT) treatment on Paget's disease of bone, but very few studies have been undertaken to determine the long term CT effect on nonpagetic bone in man. Because of conflicting results of the CT effect on osteoporosis and also for further understanding of the role of CT on normal bone, we conducted a longitudinal prospective study on the effect of CT treatment on nonpagetic bone in patients with Paget's disease using monoenergetic photon absorptionmetry method. Patients with Paget's disease were given salmon CT daily for a period of 3 yr, the bone mineral content (BMC) in the nonpagetic distal radius was measured periodically for 3 yr, and the data were compared with those of the control group of patients with Paget's disease not receiving CT treatment. It was found that the control group showed a persistent gradual decrease in BMC during the study period of 3 yr, but the CT-treated group showed no decrease in BMC during the 3-yr period of treatment. Our study suggests that CT treatment may delay the natural course of bone demineralization with aging in patients with Paget's disease.


Prognostic significance of neutrophil/lymphocyte ratio (NLR) and correlation with PET-CT metabolic parameters in small cell lung cancer (SCLC).
The aim of this study is to detect the prognostic significance of neutrophil/lymphocyte ratio (NLR) in SCLC and to evaluate the relation with 18F-FDG PET-CT metabolic parameters (PET-CT MPs). Demographic parameters, laboratory values including NLR and other clinical variables were analyzed in 112 patients with small cell lung cancer (SCLC) and 54 of these patients had results of metabolic parameters detected with 18 FDG PET-CT [including SUVmax, SUVmean, metabolic tumor volume (MTV), whole body MTV (WBMTV), TLG (total lesion glycolysis), whole body TLG (WBTLG)] were evaluated for survival analyses. Mean and median overall survival (OS) and progression-free survival (PFS) were found to be significantly longer in cases with NLR < 4 compared with NLR > 4 in totally. Also stage, performance status, response to first-line therapy, LDH, and lymphocyte count were found to be prognostic for OS and PFS. MTV, WBMTV and WBTLG were found to be prognostic for both OS and PFS, while SUVmax found to be significant for OS. Patients with NLR ≥ 4, MTV ≥ 60.1, WBMTV ≥ 120 and WBTLG ≥ 1000 points had lower OS and PFS. A moderate positive correlation was found between NLR and SUVmean (r: 0.36), SUVmax (r: 0.34), TLG (r: 0.39), MTV (r: 0.51), WBMTV (r: 0.40), and WBTLG (r: 0.46). There is relationship between PET-CT metabolic parameters and NLR in SCLC. Highest correlation was found with NLR and MTV, WBMTV, and WBTLG, and evaluation of NLR together with these parameters predicts survival times and tumor biology more clearly in SCLC.


[Surgical tactics in patients with multi-stage occlusions].
Reconstructive operations on the vessels proved to be possible in 275 of 330 patients with "multi-stage occlusions": in 227 patients profound femoral arteries were included into the main blood flow, in 48 patients the blood flow was reestablished in the aorto-iliac and femoro-popliteal segments. Good results were obtained in 81.2% of the patients. Secondary amputation was performed in 9.1%, 8.7% of the patients died. In the postoperative period repeated interventions proved to be necessary in 46 (16.7%) patients.


Energy metabolites in pre- and postpartum dairy cattle as predictors of reproductive disorders.
This study aimed to determine values for selected energy metabolites (non-esterified fatty acid [NEFA], β-hydroxybutyrate [BHB], urea or urea:BHB ratio), together with a body condition score, associated with an increased risk of cows developing a reproductive disorder and to investigate temporal relationships between predictors and reproductive outcome. A cohort of 98 cows on one farm was monitored weekly from four weeks before to 10 weeks after calving; 89 cows provided sufficient data to calculate commencement of luteal activity (C-LA). Cows with high NEFA × urea (Nu; product of NEFA and urea) values one and three weeks after calving were twice as likely to develop cystic ovarian disease (risk ratio 2). Cows that developed endometritis had high NEFA values one (P=0.02) or four weeks (P=0.04) before calving, or low urea:BHB ratios two weeks before calving, at calving or three weeks after calving (P=0.024, P=0.031 and P=0.001, respectively). Cows that had delayed C-LA had high NEFA values one week after calving (P=0.05) or low urea:BHB ratios three or four weeks after calving (P=0.004 and P=0.003, respectively).


Distance Electronic Learning Strategy in Medical Teaching During the COVID-19 Pandemic: Cross-Sectional Survey Study.
Teaching hospitals have been regarded as the primary settings where doctors teach and practice high-quality medicine, as well as where medical students learn the profession and acquire their initial clinical skills. A percentage of instruction is now done over the internet or via electronic techniques. The present COVID-19 epidemic has pushed distance electronic learning (DEL) to the forefront of education at all levels, including medical institutions. This study aimed to observe how late-stage medical students felt about DEL, which was put in place during the recent COVID-19 shutdown in Jordan. We conducted a prospective, cross-sectional, web-based, questionnaire-based research study during the COVID-19 pandemic lockdown between March 15 and May 1, 2020. During this period, all medical schools in Jordan shifted to DEL. A total of 380 students responded to a request to fill out the questionnaire, of which 256 completed the questionnaire. The data analysis showed that 43.6% (n=112) of respondents had no DEL experience, and 53.1% (n=136)of respondents perceived the DEL method as user-friendly. On the other hand, 64.1% (n=164) of students strongly believed that DEL cannot substitute traditional clinical teaching. There was a significant positive correlation between the perception of user-friendliness and the clarity of the images and texts used. Moreover, there was a strong positive correlation between the perception of sound audibility and confidence in applying knowledge gained through DEL to clinical practice. DEL is a necessary and important tool in modern medical education, but it should be used as an auxiliary approach in the clinical setting since it cannot replace conventional personal instruction.


Clinical characteristics and quality of life, depression, and anxiety in adults with neurofibromatosis type 1: A nationwide study.
Neurofibromatosis type 1 (NF1) is a genetic condition characterized by numerous somatic manifestations. The psychosocial burden in adults has rarely been studied. We examined the prevalence of self-reported impairment of quality of life (QoL), symptoms of anxiety and depression and need for support, associated with disease severity and visibility. We conducted a nationwide cross-sectional study of all 467 adults with NF1 diagnosed between 1977 and 2016 at one of the two national centers for rare diseases in Denmark. A total of 244 (56% response rate) completed a questionnaire that included standard measures of QoL, symptoms of depression and anxiety, indicators of disease-related severity, visibility, and need for professional support. Associations between disease severity and visibility and psychosocial burden were analyzed in descriptive and multivariate models. We observed impaired QoL (mean = 81.3; 95% CI, 76.2; 86.4); 19% reported symptoms of depression (mean = 5.7; SD = 5.4), and 15% reported anxiety (mean = 5.1; SD = 5.2) at a clinical level. Adults with NF1 also reported requiring professional support for physical, psychological, and work-related problems. Disease severity and (partly) visibility were significantly (p < .0001) associated with psychosocial well-being and a requirement for support. This study provides new understanding of the factors associated with impaired QoL, indicating that follow-up care should be optimized into adult life.


The Effects of Both Recent and Long-Term Selection and Genetic Drift Are Readily Evident in North American Barley Breeding Populations.
Barley was introduced to North America ∼400 yr ago but adaptation to modern production environments is more recent. Comparisons of allele frequencies among growth habits and spike (inflorescence) types in North America indicate that significant genetic differentiation has accumulated in a relatively short evolutionary time span. Allele frequency differentiation is greatest among barley with two-row vs. six-row spikes, followed by spring vs. winter growth habit. Large changes in allele frequency among breeding programs suggest a major contribution of genetic drift and linked selection on genetic variation. Despite this, comparisons of 3613 modern North American cultivated barley breeding lines that differ for spike-type and growth habit permit the discovery of 142 single nucleotide polymorphism (SNP) outliers putatively linked to targets of selection. For example, SNPs within the Cbf4, Ppd-H1, and Vrn-H1 loci, which have previously been associated with agronomically adaptive phenotypes, are identified as outliers. Analysis of extended haplotype sharing identifies genomic regions shared within and among breeding populations, suggestive of a number of genomic regions subject to recent selection. Finally, we are able to identify recent bouts of gene flow between breeding populations that could point to the sharing of agronomically adaptive variation. These results are supported by pedigrees and breeders' understanding of germplasm sharing.


[Intensified therapy of severe lupus erythematosus].
14 female patients (mean age 28 [18-56] years) with severe systemic lupus erythematosus (SLE) were treated after discontinuing previous immunosuppressive therapy, according to an intensified protocol, with three plasmaphereses (days 1-3), followed by pulse cyclophosphamide (12 mg/kg i.v. each on days 3-5) and then oral immunosuppression (cyclophosphamide 1-5 mg/kg daily, depending on white blood cell count; prednisone equivalent 2.0 decreasing to 0.1 mg/kg, according to response, for 6 months). The aim of "synchronization" of plasmaphereses with subsequent cyclophosphamide pulse-therapy is to damage pathogenic lymphocyte clones during maximal compensatory activation induced by plasmapheresis. In all patients there was rapid improvement from the nephritis, pneumonitis, cytopenia, CNS abnormalities and polyserositis. The lupus activity index (SLAM) fell clearly, from initially 28.4 (13-37) points to 8.9 (2-13) after 6 months. Treatment was discontinued after this fall in 12 patients. A recurrence was observed in two patients, at 12 and 39 months respectively. Another patient died from liver cirrhosis of unknown aetiology. Nine patients are under observation but without treatment at present, in essential remission after 2 years (5-51 months), with a SLAM of 2.8 (0-7) points. "Synchronization" of plasmaphereses with subsequent pulse cyclophosphamide achieved rapid improvement and it resulted, for the first time, repeatedly in long-term treatment-free clinical remissions.


Asthma in light of patient documents. A factor analytic study.
The aims of the study were to elucidate the disease spectrum of asthma in clinical practice, the interplay of symptoms, tests and background factors in the diagnosis of asthma and the applicability of exploratory factor analysis in analysing patient documents. The data in this retrospective cross-sectional study included 195 suspect asthma patients from a systematic sample of 2877 outpatients examined in the Pulmonary Clinic of the Tampere University Hospital from 1983 to 1993 and some statistics on the place of residence and place of birth of the patients. The materials on 73 variables were reduced to 9 factors explaining 40% of the variance in a rotated principal component analysis. The factorial description of the patient documents revealed four types of asthma: "allergic", "seasonal", "nasal" and "obstructive" asthma. These phenotypes became more dominant in this order with increasing age. Skin prick reactions to pollen diminished, whereas reactions to epithelia and house dust mite increased from allergic to obstructive asthma. Some slight differences in the patient characteristics were also found with respect to place of residence and place of birth. The use of factor analysis in clinical practice and organisation was demonstrated.


Performance Evaluation of SeisTutor Using Cognitive Intelligence-Based "Kirkpatrick Model".
The classroom learning environment facilitates human tutors to interact with every learner and get the opportunity to understand the learner's psychology and then provide learning material (access learner prior knowledge and well align the learning material as per learner requirement) to them accordingly. Implementing this cognitive intelligence in intelligent tutoring system is quite tricky. This research has focused on mimicking human tutor cognitive intelligence in the computer-aided system of offering an exclusive curriculum to the learners. The prime focus of this research article is to evaluate the proposed SeisTutor using Kirkpatrick's four-phase evaluation model. Experimental results depicting the enhanced learning gain through intelligence incorporated SeisTutor as against the intelligence absence are demonstrated.


Antiplatelet Use in Ischemic Stroke.
A literature review of antiplatelet agents for primary and secondary stroke prevention, including mechanism of action, cost, and reasons for lack of benefit. Articles were gathered from MEDLINE, Cochrane Reviews, and PubMed databases (1980-2021). Abstracts from scientific meetings were considered. Search terms included ischemic stroke, aspirin, clopidogrel, dipyridamole, ticagrelor, cilostazol, prasugrel, glycoprotein IIb/IIIa inhibitors. English-language original and review articles were evaluated. Guidelines from multiple countries were reviewed. Articles were evaluated independently by 2 authors. An abundance of evidence supports aspirin and clopidogrel use for secondary stroke prevention. In the acute phase (first 21 days postinitial stroke), these medications have higher efficacy for preventing further stroke when combined, but long-term combination therapy is associated with higher hemorrhage rates. Antiplatelet treatment failure is influenced by poor adherence and genetic polymorphisms. Antiplatelet agents such as cilostazol may provide extra benefit over clopidogrel and aspirin, in certain racial groups, but further research in more diverse ethnic populations is needed. This review presents the data available on the use of different antiplatelet agents poststroke. Dual therapy, recurrence after initiation of secondary preventative therapy, and areas for future research are discussed. Although good evidence exists for the use of certain antiplatelet agents postischemic stroke, there are considerable opportunities for future research to investigate personalized therapies. These include screening patients for platelet polymorphisms that confer antiplatelet resistance and for randomized trials including more racially diverse populations.