Prospective phase I evaluation of radiation therapy, 5-fluorouracil, and levamisole in locally advanced gastrointestinal cancer.
A recent clinical trial in patients with resected node-positive colon cancer demonstrated a clear survival advantage for patients treated with adjuvant 5-fluorouracil and levamisole. This finding led to interest in development of a Phase III trial comparing 5-fluorouracil and levamisole with 5-fluorouracil, levamisole, and radiation therapy in colon cancer patients at high risk for local recurrence. A prospective evaluation of 5-fluorouracil, levamisole, and radiation therapy was undertaken with the goal of establishing a satisfactorily tolerated regimen. Fifteen patients were studied who had locally advanced or locally recurrent upper abdominal gastrointestinal cancer (11 patients) or large bowel cancer confined to the pelvis (4 patients). The tumor and regional lymph nodes received 45 Gy in 25 fractions. Patients with pelvic tumors subsequently were treated with a radiation boost of 5.4-9 Gy in 3-5 fractions. Systemic therapy consisted of 5-fluorouracil, 450 mg/m2, given intravenously for 3 consecutive days during the first and last weeks of radiation therapy. Levamisole, 50 mg, given orally 3 times daily was used for 3 consecutive days concurrent with initiation of radiation therapy and 5-fluorouracil, at the beginning of the third week of radiation therapy, and concurrent with the final 3-day course of 5-fluorouracil. Therapy was generally well tolerated. In two patients, > or = grade 3 nonhematologic toxicity developed and consisted of transient small bowel obstruction in one and severe nausea and vomiting related to levamisole administration in another. One patient experienced grade 3 hematologic toxicity with a leukocyte count nadir of 1,600 cells/microL. These results are similar to the toxicity profile reported elsewhere for radiation therapy and 5-fluorouracil. The addition of levamisole to radiation therapy and 5-fluorouracil does not appear to increase toxicity significantly.


Correction of orbital hypertelorism in Asian patients.
In this article, correction of orbital hypertelorism in Oriental patients is summarized. An orbital osteotomy is currently used to correct an abnormally wide interorbital distance. At present, associated deformities such as a short nose and a depression deformity in the temporal region following orbital osteotomy can be partially corrected. In Oriental patients, the Mongolian fold can be enhanced after correction of orbital hypertelorism. This fold can be easily corrected by epicantoplasty.


Regulation of gene expression by cis-acting long non-coding RNAs.
Long non-coding RNAs (lncRNAs) are diverse transcription products emanating from thousands of loci in mammalian genomes. Cis-acting lncRNAs, which constitute a substantial fraction of lncRNAs with an attributed function, regulate gene expression in a manner dependent on the location of their own sites of transcription, at varying distances from their targets in the linear genome. Through various mechanisms, cis-acting lncRNAs have been demonstrated to activate, repress or otherwise modulate the expression of target genes. We discuss the activities that have been ascribed to cis-acting lncRNAs, the evidence and hypotheses regarding their modes of action, and the methodological advances that enable their identification and characterization. The emerging principles highlight lncRNAs as transcriptional units highly adept at contributing to gene regulatory networks and to the generation of fine-tuned spatial and temporal gene expression programmes.


IFN-beta increases listeriolysin O-induced membrane permeabilization and death of macrophages.
Type I IFN (IFN-I) signaling is detrimental to cells and mice infected with Listeria monocytogenes. In this study, we investigate the impact of IFN-I on the activity of listeriolysin O (LLO), a pore-forming toxin and virulence protein released by L. monocytogenes. Treatment of macrophages with IFN-beta increased the ability of sublytic LLO concentrations to cause transient permeability of the plasma membrane. At higher LLO concentrations, IFN-beta enhanced the complete breakdown of membrane integrity and cell death. This activity of IFN-beta required Stat1. Perturbation of the plasma membrane by LLO resulted in activation of the p38MAPK pathway. IFN-beta pretreatment enhanced LLO-mediated signaling through this pathway, consistent with its ability to increase membrane damage. p38MAPK activation in response to LLO was independent of TLR4, a putative LLO receptor, and inhibition of p38MAPK neither enhanced nor prevented LLO-induced death. IFN-beta caused cells to express increased amounts of caspase 1 and to produce a detectable caspase 1 cleavage product after LLO treatment. Contrasting recent reports with another pore-forming toxin, this pathway did not aid cell survival as caspase 1-deficient cells were equally sensitive to lysis by LLO. Key lipogenesis enzymes were suppressed in IFN-beta-treated cells, which may exacerbate the membrane damage caused by LLO.


Psychometric evaluation of the perceived perioperative competence scale-revised among the Chinese operating room nurses: a methodological research.
Perioperative competence is necessary to evaluate operating room nurses. The Perceived Perioperative Competence Scale-Revised (PPCS-R) is the only available tool developed specifically for the perioperative setting. However, there is a lack of research on the reliability and validity of this scale among Chinese nurses. Thus, the aim of this study is to translate, culturally adapt, and evaluate the psychometric properties of the Perioperative competence Scale-Revised (PPCS-R) among operating room nurses in China. Instrument cultural adaptation was carried out through forward translation, back translation, expert panel evaluation and pretesting. The psychometric properties (content validation, item analysis, construct validation, and reliability coefficient) of the Chinese PPCS-R (C-PPCS-R) were examined. An online survey was completed from June to August 2020 by operating room nurses (N = 480) in five third-grade class-A hospitals in Beijing. The item analysis identified six items for scale reduction. Exploratory factor analysis showed the remaining 34 items loaded on six factors, which were named in accordance with the original scale. The six-factor model showed a good fit through confirmatory factor analysis. The item content validity index for the C-PPCS-R items ranged from 0.857 to 1.000, and that for the total scale was 0.875. Cronbach's alpha was showed 0.787. Together, the six factors explained 68.62% of the variance. The 34-item C-PPCS-R showed good validity and reliability to measure perceived competence among operating room nurses in the Chinese context. The scale can assist nurse managers to identify operating room nurses' perceived competence, and provides evaluation criteria for career planning, performance appraisal, job assignment, and continuing education.


Internal mammary artery graft fistulae to the pulmonary arteries as a cause of myocardial ischaemia after coronary artery bypass Graft.
Internal mammary artery (IMA) graft fistula to the pulmonary arteries is a cause of myocardial ischaemia after coronary artery bypass grafting (CABG). Surgical and percutaneous interventional treatments are available, both with their inherent risk and benefits. Optimised medical management is therefore essential. A pre CABG IMA angiographic image may assist surgeons to ligate identifiable accessory branches, which may contribute to fistula formation.


Strain dependence in mice of resistance and susceptibility to the testicular effects of cadmium: assessment of the role of testicular cadmium-binding proteins.
The nature of the cadmium (Cd)-binding proteins in the mouse testes is unknown, although some studies have implied metallothionein (MT) is responsible for the marked strain dependence of Cd-induced testicular necrosis in mice. This study attempted to define the role of MT in strain-dependent Cd resistance using NFS (susceptible) and BALB/c (resistant) mice. In all cases, testicular proteins were compared to hepatic MT isolated after treatment with zinc (Zn). A low-molecular-weight (Mr) Zn-, Cd-binding protein was detected in testicular and hepatic cytosol from both strains after gel filtration. These proteins were extractable by heat treatment and sequential acetone precipitation. When such extracts were further purified with reverse-phase HPLC, two forms of authentic MT were shown by amino acid analysis from both NFS and BALB/c livers. However, of two testicular forms separated by HPLC from NFS and BALB/c mice, neither could be classified as MT based on amino acid composition. Methylation of the MT-I gene was also studied in testicular and hepatic DNAs isolated from control mice or from mice made resistant to Cd-induced testicular necrosis by Zn treatment. Major differences in methylation between tissues were seen, as the testicular gene of both NFS and BALB/c mice was highly methylated, a condition often linked to genetic quiescence. Zn treatment had no effect on MT-I gene methylation in testes of either strain, although rendering the NFS strain resistant to Cd. Zn treatment did not alter levels of this testicular protein in either strain while causing a marked induction of hepatic MT in both. These results indicate the low-Mr Cd-, Zn-binding proteins present in the testes of both resistant and susceptible mice are not MTs and further that the MT gene may not be expressed in either strain.


Resolving diagnostic uncertainty in initially poorly localizable fevers: a prospective study.
Prospective, observational data collection of fever patients with regard to aetiology and means of detecting it particularly noting the factors, which quickly helped resolve diagnostic uncertainty. Prospective follow-up of patients with clinically non-localizable fever admitted to Manipal Teaching Hospital, Pokhara, Nepal, documenting their temperature response, clinical and lab findings and diagnoses with their response to treatment. Enteric fever 56.8% (25), urinary tract infection 15.9% (7), malaria 9% (4), TB (pulmonary) 4% (2), abscess 4% (2) and hydatid cyst 4% (2). Remaining 4% were due to some other systemic causes. Culture positive: Salmonella typhi positive 32% (8), S. paratyphi positive 20% (5) and culture negative 48%. Response to treatment: enteric fever--(i) first-line drugs (ampicillin/cotrimoxazole) 16% (4), (ii) second-line drugs (ciprofloxacin) 20% (5) and (iii) ceftriaxone 44% (11). Fever charting as a means to localize Salmonella vs other fevers is still an invaluable clinical tool in adult patients in Nepal. If used judiciously, it can be used as an effective means to diagnose and treat patients of initially non-localizable fevers. Patience must be exercised in starting antibiotics, not until the fever pattern of 2 days suggests enteric, and also while waiting for a response to first-line drugs for Salmonella before one switches over to costlier second-line drugs, with the possible exception of quinolones which may even be used first line owing to their reduced costs (at the danger of wielding a double-edged sword).


Effects of quinidine, verapamil, nifedipine and ouabain on hysteresis in atrial refractoriness in the conscious dog: an approach to ionic mechanisms.
1. This work determines the effects of quinidine, verapamil, nifedipine and ouabain on the hysteresis of the atrial effective refractory period (AERP) in the conscious dog. 2. AERP was always longer in the increasing phase than in the decreasing phase of the extrastimulus method, thus demonstrating the existence of AERP hysteresis. Calculated as the difference between the two values, hysteresis was between 8+/-0.8 and 11+/-1.0 msec. 3. Quinidine increased hysteresis from 9+/-0.7 to 13+/-0.7 msec, whereas verapamil decreased it from 10+/-0.9 to 5+/-0.5 msec and nifedipine did not affect it. Ouabain also lengthened hysteresis from 8+/-0.8 to 11+/-1.2 msec. 4. Thus, these results confirm the existence of a hysteresis phenomenon in the AERP in the conscious dog and are evidence that the fast sodium and slow calcium specific membrane currents participate in this phenomenon.


Identification of differentially expressed genes in mandibular condylar and tibial growth cartilages using laser microdissection and fluorescent differential display: chondromodulin-I (ChM-1) and tenomodulin (TeM) are differentially expressed in mandibular condylar and other growth cartilages.
Mandibular condylar cartilage can be distinguished from articular and growth cartilages of long bones based on several differences in morphology, physiology, and function between these structures. However, there is almost no information available on the types of genes that contribute to these differences. In this study, genes that were differentially expressed in mandibular condylar and growth cartilages in 1-week-old rats were investigated using fluorescent differential display (FDD) and laser microdissection (LMD). A number of genes were identified by FDD including chondromodulin-1 (ChM-1), which is known to be an angiogenesis inhibitor of endochondral ossification. ChM-1 expression was then compared with that of tenomodulin (TeM) in mandibular condylar and tibial cartilages of 1- and 5-week-old rats using real time PCR (RT-PCR), immunohistochemistry, and in situ hybridization. There was negligible detection of ChM-1 mRNA and protein in mandibular condylar cartilages compared to tibial cartilages of 1- and 5-week-old rats. On the other hand, TeM mRNA was more abundant in mandibular condylar cartilage than in tibial. These observations demonstrated that gene expression in mandibular condylar cartilage differed from other types of cartilage such as articular and growth ones.


The physical microenvironment of hematopoietic stem cells and its emerging roles in engineering applications.
Stem cells are considered the fundamental underpinnings of tissue biology. The stem cell microenvironment provides factors and elements that play significant roles in controlling the cell fate direction. The bone marrow is an important environment for functional hematopoietic stem cells in adults. Remarkable progress has been achieved in the area of hematopoietic stem cell fate modulation based on the recognition of biochemical factors provided by bone marrow niches. In this review, we focus on emerging evidence that hematopoietic stem cell fate is altered in response to a variety of microenvironmental physical cues, such as geometric properties, matrix stiffness, and mechanical forces. Based on knowledge of these biophysical cues, recent developments in harnessing hematopoietic stem cell niches ex vivo are also discussed. A comprehensive understanding of cell microenvironments helps provide mechanistic insights into pathophysiological mechanisms and underlies biomaterial-based hematopoietic stem cell engineering.


Expression of the second epidermal growth factor-like domain of human factor VII in Escherichia coli.
The second epidermal growth factor (EGF)-like domain of human coagulation factor VII is a potent inhibitor of the FVIIa/tissue factor complex, the predominant initiator of coagulation in vivo. This domain has now for the first time been cloned and expressed in Escherichia coli as an affinity fusion protein. The fusion protein was secreted into the periplasm of E. coli and purified by affinity chromatography. The purified protein consisted of a fusion protein with the expected molecular weight, and in addition, a significant fraction of oligomers cross-linked by intermolecular disulfide bonds. Despite the presence of oligomers, the purified protein was a potent inhibitor of the extrinsic blood coagulation pathway with an IC50 value of about 20 microM. The biological activity was retained after liberation of the EGF domain by proteolytic cleavage.


Structures of human Pumilio with noncognate RNAs reveal molecular mechanisms for binding promiscuity.
Pumilio is a founder member of the evolutionarily conserved Puf family of RNA-binding proteins that control a number of physiological processes in eukaryotes. A structure of human Pumilio (hPum) Puf domain bound to a Drosophila regulatory sequence showed that each Puf repeat recognizes a single nucleotide. Puf domains in general bind promiscuously to a large set of degenerate sequences, but the structural basis for this promiscuity has been unclear. Here, we describe the structures of hPum Puf domain complexed to two noncognate RNAs, CycB(reverse) and Puf5. In each complex, one of the nucleotides is ejected from the binding surface, in effect, acting as a "spacer." The complexes also reveal the plasticity of several Puf repeats, which recognize noncanonical nucleotides. Together, these complexes provide a molecular basis for recognition of degenerate binding sites, which significantly increases the number of mRNAs targeted for regulation by Puf proteins in vivo.


Improved meal presentation increases food intake and decreases readmission rate in hospitalized patients.
Reduced food intake is a frequent problem at a hospital setting, being a cause and/or consequence of malnutrition. Food presentation can affect food intake and induce nutritional benefit. To investigate the effect of improved meal presentation supported by gastronomy expertise on the food intake in adults hospitalized in internal medicine departments. Controlled before and after study. Two hundred and six newly hospitalized patients in internal medicine departments were included and divided in two groups, a) control: receiving the standard lunch from the hospital and b) experimental: receiving a lunch improved in terms of presentation by the advices received by the Institut Paul Bocuse, Ecully, Lyon, France together with the hospital kitchen of the Beilinson Hospital, without change in the composition of the meal. The amount of food left at the participants' plates was estimated using the Digital Imaging Method, which consisted in photographing the plates immediately to previous tray collection by the researcher. In addition, the nutritionDay questionnaire was used to measure other variables concerned to their food intake during hospitalization. Charlson Comorbidity Index was calculated. There was no significant difference between the groups regarding demography or Charlson Comorbidity Index. Patients who received the meal with the improved presentation showed significantly higher food intake than those who received the standard meal, despite reported loss in appetite. Participants from the experimental group left on their plate less starch (0.19 ± 0.30 vs. 0.52 + 0.41) (p < 0.05) and less from the main course than the control group (0.18 + 0.31 vs. 0.46 + 0.41) (p < 0.05). However, both of the groups left the same amount of vegetables (0.37 + 0.36 vs. 0.29 + 0.35) (p > 0.05). Both of the groups were asked how hungry they were before the meal and no significance was shown. More participants from the experimental group reported their meal to be tasty in comparison to those in the control group (49.5% vs. 33.7% p < 0.005). Length of stay was not different but readmission rate decreased significantly in the study group (p < 0.02) from 31.2% to 13.5%. Improvement of meal presentation at a hospital setting can increase food intake, reduce waste food substantially and reduce readmission rate to hospital.


Adolescent's self-reported weight and its association with media impact on decision to lose weight and body thinness perception.
This study investigated the accuracy of self-reported weight among Kuwaiti adolescents and the associations of self-reported weight and calculated BMI with the impact of media use on adolescent's decision to lose weight and body thinness perception. A total of 706 Kuwaiti adolescents (363 females) 15-18 year-olds were randomly selected from schools. Weight and height were self-reported by the adolescents and measured by the researchers. A specifically designed questionnaire reported the impact of media use on adolescent's decision to lose weight and body thinness perception. There were significant (p < 0.001) relationships between measured and reported weight (r = 0.947), height (r = 0.777), and calculated BMI (r = 0.623). Intraclass correlation coefficients (95% CI) between self-reported and measured weight and height were 0.973 (0.968-0.977) and 0.867 (0.839-0.891), respectively. The mean differences between self-reported and measured weight (1.26 kg) and BMI (0.478 kg/m2) were relatively small. Females under-reported their weight and the calculated BMI from estimated weight and height was underestimated by adolescents with overweight/obesity. The impact of media use on the adolescent's perception of being thin relative to the accuracy of the calculated BMI was significant (p = 0.043-0.001). The age-adjusted odds ratio of the calculated (underestimated) BMI in adolescents without overweight/obesity was 0.437 (95% CI = 0.257-0.741; p = 0.002). It was concluded that the validity of self-reported weight was high. Adolescents with overweight/obesity were more likely to underestimate their weight and calculated BMI. Educating adolescents about proper lifestyles and weight loss through media appears warranted.


hsa_circ_0092306 Targeting miR-197-3p Promotes Gastric Cancer Development by Regulating PRKCB in MKN-45 Cells.
Gastric cancer (GC) is one of the most common cancers worldwide and is thus a global cancer burden. Here, we focused on a novel circular RNA hsa_circ_0092306 and explored the potential molecular mechanism to provide a new target for and novel insights into GC treatment. The GEO microarray was mined and analyzed with R software. Sanger sequencing and RNase R assay were applied to verify the identification of hsa_circ_0092306. Quantitative real-time PCR and western blot were performed to measure the mRNA and protein levels. Pull-down and luciferase reporter assays were conducted to confirm the target relationships. Annexin V-PI apoptosis flow cytometry, 3-(4,5Dimethylthiazol- yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT), wound healing, and Transwell assays were applied to detect cell apoptosis, viability, migration, and invasion in MKN-45 cells, respectively. A xenograft in vivo experiment was conducted to confirm the cell experiment results. hsa_circ_0092306 was upregulated in GC tissues and GC cells, and promoted GC development in MKN-45 cells. hsa_circ_0092306 inhibited tumor suppressor miR-197-3p expression but promoted tumor promotor protein kinase C beta (PRKCB) expression in MKN-45 cells. hsa_circ_0092306 and PRKCB had a common target (miR-197-3p) and were negatively related to miR-197-3p expression. hsa_circ_0092306 promoted the development of GC by regulating the pathway of miR-197-3p/PRKCB in MKN-45 cells.


Real-World Treatment Patterns and Outcomes from an Electronic Medical Records Database for Patients with Rheumatoid Arthritis Treated with Repository Corticotropin Injection.
Repository corticotropin injection (RCI; Acthar® Gel) is a naturally sourced mixture of adrenocorticotropic hormone analogs and other pituitary peptides that exerts anti-inflammatory and immunomodulatory properties via melanocortin receptors. RCI is approved as a short-term adjunctive therapy for rheumatoid arthritis (RA) and is typically used in patients with refractory RA. The objective of this study was to describe real-world outcomes of RA patients treated with RCI by retrospective analysis of an electronic medical records (EMR) database. EMR data were obtained from the United Rheumatology-Normal Integrated Community Evidence (UR-NICETM) data repository for patients who used RCI for the treatment of RA. Demographics, comorbidities, disease history, medications, and laboratory evaluations 365 days prior to and 365 days after initiation of RCI were examined. The patient cohort was predominantly White females with a mean age of 60 years and high RA activity prior to RCI therapy. Clinical measures of disease severity indicated that patients had high RA activity before starting RCI therapy. Clinical Disease Activity Index (CDAI) scores were significantly reduced 365 days post-initiation of RCI. Swollen and tender joint counts and patient-reported outcomes, including Routine Assessment of Patient Index Data 3 (RAPID3), Physician Global Assessment, and patient assessment of pain severity were also significantly lower. The number of patients taking conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), biologic (b) DMARDs, nonsteroidal anti-inflammatory drugs (NSAIDS), and opioids decreased, as did the number of drugs tried within each class for csDMARDs, bDMARDs, NSAIDs, and glucocorticoids. These findings suggest that RCI significantly improves clinical outcomes of RA and decreases the need for concomitant medications for up to 1 year following initiation of therapy. The study provides valuable insights into the use of RCI and management of these difficult-to-treat RA patients during routine clinical practice.


The Relationship Between the Serum Level of Vitamin D and Vitiligo: A Controlled Study on 300 Subjects.
Low vitamin D levels have been associated with several autoimmune diseases. Vitiligo could be associated with low vitamin D levels. To determine the level of serum vitamin D in vitiligo patients compared to controls and reveal the possible association of vitamin levels with the pathogenesis of vitiligo. A case-controlled study was conducted. After excluding factors that may affect serum vitamin D levels, blood samples were taken from vitiligo patients and controls. The association between vitamin D levels and various vitiligo subgroups (duration of vitiligo, site of onset, age, etc) was measured and correlated. A total of 150 vitiligo patients, 90 (60%) males with a mean age of 30.6 ± 11.4 years, were recruited. The study also had 150 age- and gender-matched vitiligo-free control subjects. There was no significant difference in median serum vitamin D levels between the cases and the controls (P = .25). The serum levels of vitamin D of the vitiligo patients were found to be lower in males (P = .01), the younger age group (P = .01), and patients not treated with ultraviolet (UV) treatment (P = .01). There is no difference between the vitamin D levels of the vitiligo patients and the control subjects. However, deficiency of 25(OH)D levels within the vitiligo subgroups may be linked to younger age, male gender, short duration of vitiligo, and non-use of phototherapy.


Surgical treatment of vesicoureteral reflux in infants under 3 months of age.
Surgical treatment for vesicoureteral reflux (VUR) is controversial in infants, especially small infants because of technical difficulty and higher rate of spontaneous resolution. However, in some conditions, such as high-grade reflux, breakthrough infection, or severe renal scarring, early operation may be justified. This study is to evaluate the results of ureteral reimplantation in infants with VUR under 3 months of age. From January 1993 to July 1997, 13 boys and five girls (24 ureters) under 3 months of age (range, 18 days to 3 months; mean age, 2 months) received ureteral reimplantation for VUR. The initial symptoms were urinary tract infection (UTI) in 16 infants, hydronephrosis found by prenatal ultrasound scan in one, and early postnatal screening ultrasound scan in one. The indications for 24 ureter reimplantations were high-grade reflux (grade V, n = 7), breakthrough infection under medical treatment (n = 5), and severe renal scarring (n = 8) and contralateral low-grade refluxing ureters (n = 4). All patients had Glenn-Anderson's or Cohen's ureteral reimplantation. Ureteral stents were required in six ureters. All patients had renal sonogram 1 month after operation to rule out ureteral obstruction. Fifteen patients had voiding cystourethrogram (VCUG) after operation. Renal growth was evaluated in 15 patients (20 reflux renal units) using serial ultrasound or differential perfusion renal scan. The operative time, use of ureteral stent, complication rate, hospital stay, and time needed for clearing urine, were compared with those of 115 counterpart patients at age over 3 months. Data were analyzed using X(2) test or t test. All patients, except one, were free of UTI during the follow-up of 6 months to 5 years. In fifteen infants who had postoperative VCUG, 14 were free of reflux, and one had persistent lower-grade VUR. One patient had transient ureteral obstruction that resolved spontaneously. One patient had postoperative ileus for 2 weeks. Renal growth of 20 reflux renal units was similar to that of the contralateral nonreflux kidneys. The only significant difference when compared with the patients over 3 months of age, was the higher incidence of ureteral stenting (25% v 4.2%, P<.01). Ureteral reimplantation should be performed in infants under 3 months of age when it is indicated.


The effects of age on neural blockade and hemodynamic changes after epidural anesthesia with ropivacaine.
We studied the influence of age on the neural blockade and hemodynamic changes after the epidural administration of ropivacaine 1.0% in patients undergoing orthopedic, urological, gynecological, or lower abdominal surgery. Fifty-four patients were enrolled in one of three age groups (Group 1: 18-40 yr; Group 2: 41-60 yr; Group 3: > or=61 yr). After a test dose of 3 mL of prilocaine 1.0% with epinephrine 5 microg/mL, 15 mL of ropivacaine 1.0% was administered epidurally. The level of analgesia and degree of motor blockade were assessed, and hemodynamic variables were recorded at standardized intervals. The upper level of analgesia differed among all groups (medians: Group 1: T8; Group 2: T6; Group 3: T4). Motor blockade was more intense in the oldest compared with the youngest age group. The incidence of bradycardia and hypotension and the maximal decrease in mean arterial blood pressure during the first hour after the epidural injection (median of Group 1: 11 mm Hg; Group 2: 16 mm Hg; Group 3: 29 mm Hg) were more frequent in the oldest age group. We conclude that age influences the clinical profile of ropivacaine 1.0%. The hemodynamic effects in older patients may be caused by the high thoracic spread of analgesia, although a diminished hemodynamic homeostasis may contribute. Analgesia levels after the epidural administration of 15 mL of ropivacaine 1.0% increase with increasing age. This is associated with an increased incidence of hypotension in the elderly, although an effect of age on the hemodynamic homeostasis may have contributed. It appears that epidural doses should be adjusted for elderly patients.


[Endocervicoscopy].
The endocervicoscopy is particularly interesting with regard to the way of endoscopic observations and to the successful identification of praecarcinosis intercervicalis. The findings are of clinical importance in the early detection of praecarcinomatic dysplastic processes and of neoplastic disease of the uterine endocervix. It is a valuable source of information in early treatment, surgery and rehabilitation.


Effect of acute aerobic exercise before immunotherapy and chemotherapy infusion in patients with metastatic non-small-cell lung cancer: protocol for the ERICA feasibility trial.
Patients with metastatic non-small cell lung cancer (mNSCLC) suffer from numerous symptoms linked to disease and treatment which may further impair the patient's overall condition. In addition to its benefits on quality of life and fatigue, physical exercise may improve treatment response, notably due to its known effects on the immune system. The ERICA study is designed to assess the feasibility of a supervised acute physical exercise therapy realised immediately prior immune-chemotherapy infusion in patients with mNSCLC. Secondary objectives will examine the effects of acute exercise combined with an unsupervised home-walking programme on clinical, physical, psychosocial and biological parameters. ERICA is a prospective, monocentric, randomised controlled, open-label feasibility study conducted at the Centre Léon Bérard Comprehensive Cancer Center (France). Thirty patients newly diagnosed with mNSCLC will be randomised (2:1 ratio) to the 'exercise' or the 'control' group. At baseline and during the last treatment cycle, participants in both groups will receive Physical Activity recommendations, and two nutritional assessments. In the exercise group, participants will receive a 3-month programme consisting of a supervised acute physical exercise session prior to immune-chemotherapy infusion, and an unsupervised home-based walking programme with an activity tracker. The acute exercise consists of 35 min interval training at submaximal intensity scheduled to terminate 15 min prior to infusion. Clinical, physical, biological and psychosocial parameters will be assessed at baseline, 3 and 6 months after inclusion. Biological measures will include immune, inflammatory, metabolic, oxidative stress biomarkers and molecular profiling. The study protocol was approved by the French ethics committee (Comité de protection des personnes Ile de France II, N°ID-RCB 20.09.04.65226, 8 December 2020). The study is registered on ClinicalTrials.gov (NCT number:NCT04676009) and is at the pre-results stage. All participants will sign an informed consent form. The findings will be disseminated in peer-reviewed journals and academic conferences.


Are LRRK2 mysteries lurking in the gut?
Gut-brain axis and inflammation are two hot topics in Parkinson's disease (PD). In this setting, the leucine-rich repeat kinase 2 (LRRK2) gene, which encodes the eponym protein, has attracted much attention. LRRK2 is not only the gene most commonly associated with Parkinson's disease but also a susceptibility gene for Crohn's disease (CD), thereby suggesting that it may sit at the crossroads of gastrointestinal inflammation, Parkinson's, and Crohn's disease. In contrast to the accumulated data on LRRK2 in the central nervous system (CNS), research on LRRK2 in the digestive tract is still in its infancy, and the scope of the present review article is therefore to review existing studies on LRRK2 in the gastrointestinal tract in both physiological and pathological conditions. In light of current data on LRRK2 in the gastrointestinal tract, we discuss if LRRK2 could be or not regarded as a molecular link between gut inflammation, Parkinson's disease, and Crohn's disease, and we suggest directions for future research.


Gluococorticoid could influence extracellular matrix synthesis through Sox9 via p38 MAPK pathway.
Here, we used glucocorticoid as an apoptosis inducer to study how glucocorticoid could accelerate cartilage degeneration and the responsible signal pathway. Human chondrocytes were isolated from knee joints gave glucocorticoid of different concentrations for 24 h, 48 h, 72 h, or 1 week, and cell viability was determined. Next, Sox9, Collagen type II, Aggrecan protein expression and mRNA transcription were detected by western blot analysis and quantitative real-time PCR, respectively. Glucocorticoid could suppress chondrocyte growth at the concentration of 100 μM. When cultured with glucocorticoid, the expressions of Sox9, Col II, and Aggrecan were depressed time-dependent and dose-dependent, as well as the mRNA transcription. The glucocorticoid-induced p38 inactivation was one mechanism that may response for the inhibition of extracellular matrix synthesis, and these influences appeared earlier than the apoptosis effect.


Theophylline for the treatment of atrioventricular block after myocardial infarction.
To show that second- or third-degree atrioventricular block occurring as an early complication of acute inferior myocardial infarction is mediated by adenosine. Cardiac care unit. Uncontrolled, observational, hypothesis-driven study. Patients who developed clinically significant atrioventricular nodal blockade within 4 hours of admission for acute inferior myocardial infarction. Theophylline, 100 mg/min intravenously to a maximum of 250 mg. Continuous multilead electrocardiographic monitoring before and after administration of theophylline. During a 6-month period, eight men who had had acute inferior myocardial infarction developed clinically significant atrioventricular block. Three had third-degree block, and five had high-grade second-degree block. In all patients, 1:1 atrioventricular nodal conduction was restored and normal sinus rhythm reappeared within 3 minutes of the administration of theophylline. All patients remained free of arrhythmia for at least 24 hours. Adenosine produced by the ischemic myocardium may induce atrioventricular nodal block. In our patients, atrioventricular nodal block was resistant to conventional therapy such as atropine, but it responded to the adenosine antagonist theophylline.


Transitional cell carcinoma of the kidney 25-year experience.
Seventy patients with transitional cell carcinoma of the kidney operated upon at Barnes Hospital during the last 25 years are reviewed. The relationship of the pathologic stage, grade, findings on excretory urography and survival is studied. The stage and survival rates were predicted fairly accurately on the basis of the excretory urogram alone. Survival of patients was determined occasionally by the status of the associated bladder tumors more than by the renal cancer. Because of tumor multiplicity we recommend total nephroureterectomy as the treatment of choice. The role of radiation therapy is considered.


The prevalence of post-traumatic stress disorder in chronic pain patients.
Several of the more common causes of chronic pain include traumatic events such as motor vehicle accidents and work-related incidents. Therefore, it is not unusual for patients presenting with chronic pain to also describe significant levels of distress including post-traumatic symptomatology and, in the more severe cases, post-traumatic stress disorder (PTSD). Throughout the past few decades, the literature relating to chronic pain and PTSD has become progressively more sophisticated, resulting in well-supported theories and treatments for sufferers. However, only a handful of studies have specifically attended to the co-occurrence of these two disorders. This review presents a summary of the literature relating to the two disorders in terms of symptoms, prevalence, and comorbidity. It also briefly describes the main empirically supported psychologic theories of chronic pain and PTSD and briefly reviews the evidence regarding what factors maintain the disorders. Treatment implications and issues for future research are considered.


Multiplicity of genome equivalents in the radiation-resistant bacterium Micrococcus radiodurans.
The complexity of the genome of Micrococcus radiodurans was determined to be (2.0 +/- 0.3) X 10(9) daltons by DNA renaturation kinetics. The number of genome equivalents of DNA per cell was calculated from the complexity and the content of DNA. A lower limit of four genome equivalents per cell was approached with decreasing growth rate. Thus, no haploid stage appeared to be realized in this organism. The replication time was estimated from the kinetics and amount of residual DNA synthesis after inhibiting initiation of new rounds of replication. From this, the redundancy of terminal genetic markers was calculated to vary with growth rate from four to approximately eight copies per cell. All genetic material, including the least abundant, is thus multiply represented in each cell. The potential significance of the maintenance in each cell of multiple gene copies is discussed in relation to the extreme radiation resistance of M. radiodurans.


[Virus-induced dysregulation of programmed immunocompetent cell death: pathology or adaptation?].
The review summarizes information from recent literature and results of the authors' own investigations concerning dysbalance of programmed cell death in establishment of a long-term virus persistense. The article discusses molecular mechanisms of apoptosis modulation of immune cellls by persistent viruses.


Conceptual Tools to Inform Course Design and Teaching for Ethical Engineering Engagement for Diverse Student Populations.
Contemporary engineering education recognises the need for engineering ethics content in undergraduate programmes to extend beyond concepts that form the basis of professional codes to consider relationality and context of engineering practice. Yet there is debate on how this might be done, and we argue that the design and pedagogy for engineering ethics has to consider what and to whom ethics is taught in a particular context. Our interest is in the possibilities and challenges of pursuing the dual imperatives of socialization and critique. Socialization involves creating opportunities for all, in a diverse cohort of students, to access and engage with the dominant professional engineering ethics knowledge, while critique involves engaging with a range of ways of knowing, valuing, being and using language as relevant in contemporary engineering practice. We identify conceptual tools from engineering ethics and ethical pedagogy in education scholarship for our context. We illustrate how we use these tools systematically to strengthen our reflective practice in a first-year university engineering ethics module to a deeper form of reflexivity. Specifically, we explore the ways in which we attend to the dual imperatives and also highlight opportunities that we miss. We identify as key opportunities design choices such as how we formulated questions and prompts, and how we attended to content, context and language in selecting classroom texts. Other key opportunities were pedagogical choices of when and how to use student contributions in discussion, and what was made explicit in the classroom and assessment. We share our plans to take our learnings forward in our practice and consider the generative possibilities of these learnings and the concepts in other contexts.


Pattern of cancer deaths in the medical wards of a teaching hospital in South East Nigeria.
Cancers are emerging public health problems in developing countries like Nigeria. The epidemiological shift and aging population make cancers a challenge. We set out to describe the pattern of death due to cancer in our medical ward. The hospital is one of the premier hospitals covering the South East zone of Nigeria. We retrospectively reviewed the case notes and death certificates of all who died of cancer in our adult medical wards for 16 years (January 1995 to December 2010). Statistical Package for Social Sciences (SPSS Inc. Chicago, IL) version 17.0 was used. Twenty seven thousand, five hundred and fourteen patients were admitted into the medical wards. Six thousand, two hundred and fifty died. Out of the 6250 deaths, cancers accounted for 7.6%. Male to Female ratio was 2.4:1. The mean age at death was 43.7 ± 17.4 years. The mean age at death in both sexes was similar (42.9 ± 17.5 for men and 45.7 ± 17.0 years for women), P = 0.109. Primary liver cell carcinoma was the most common cause of death among men (40.8%), while cancer of hematopoietic organ was the most common in women (48.7%). The overall fatality rate was 1.7% (477/27 514) of medical admissions. Younger and middle age groups were most commonly affected in both sexes. Since the most productive age groups were affected, governments in developing countries should as a matter of urgency put in place adequate cancer preventive and curative services.


Elimination of antibacterial activities of non-peptide luteinizing hormone-releasing hormone (LHRH) antagonists derived from erythromycin A.
Antibacterial SAR for a series of macrolides derived from erythromycin A that are potent LHRH antagonists was developed in an attempt to eliminate the antibiotic activities of these compounds. Increasing the size of the alkyl substituents on the desosamine 3'-amine resulted in potent LHRH antagonists that were inactive against staphylococcal bacteria strains, and were significantly (>10-fold) less active against streptococcal bacteria strains. Complete elimination of antibacterial activities could be achieved by replacement of one or both methyl groups on the 3'-amine with a large alkyl substituent.


Draft Genome Sequence of Deinococcus indicus DR1, a Novel Strain Isolated from a Freshwater Wetland.
Deinococcus indicus strain DR1, a red-pigmented, arsenic- and radiation-resistant bacterium, was isolated from a water sample of the Dadri wetland, Uttar Pradesh, India. Here, we report a draft genome sequence of this strain, which may provide useful information regarding the genes and pathways involved in heavy-metal bioremediation.


Diagnosis of cytomegalovirus infections of the nervous system by immunocytochemical demonstration of infected cells in cerebrospinal fluid.
Infections caused by the cytomegalovirus (CMV) are frequent complications in patients with the acquired immunodeficiency syndrome. Diagnosis of CMV infections of the nervous system is still difficult. We evaluated immunocytochemical staining for a CMV early antigen in cells prepared from the cerebrospinal fluid of patients with clinical evidence for neural CMV infections and from controls. CMV positive cells were found in four samples of patients with clinical evidence of CMV infection. Three of these patients were suffering from myeloradicalitis, one had a severe brain stem encephalitis. No CMV positive were found in controls. Immunocytochemical staining of CSF cells may be helpful in the diagnosis of CMV infection of the central nervous system and of the nerve roots.


Angiotensin-(1-7) enhances anti-aggregatory effects of the nitric oxide donor sodium nitroprusside.
Patients with ischemic heart disease have platelets that are resistant to the anti-aggregatory effects of nitric oxide (NO) donors. This NO resistance is associated with increased whole blood superoxide radical (O2-) content. Angiotensin II (Ang II) has been shown to augment O2- formation. Recent studies have demonstrated that angiotensin-(1-7) [Ang-(1-7)] has opposite actions to those of Ang II in the vasculature. This study compares the effects of Ang-(1-7) and Ang II on platelet aggregation and platelet responsiveness to the NO donor sodium nitroprusside (SNP). Platelet aggregation was induced by the thromboxane A2 mimetic U46619 (1-5 micromol/L), and the inhibitory effects of SNP (10 micromol/L) on the rate and extent of aggregation were quantified. Ang II did not induce aggregation, but 10-100 nmol/L Ang II potentiated U46619-induced aggregation by 21+/-6% in the absence and by 26+/-9% in the presence of SNP (P<0.01 for both), in blood samples from 8 normal subjects. By contrast, Ang-(1-7) alone did not affect platelet aggregation, but 10-100 nmol/L Ang-(1-7) potentiated the anti-aggregatory effects of SNP in blood samples from both normal subjects (n=17) and patients with acute coronary syndromes (n=17). This effect of Ang-(1-7) was bimodal, and at higher concentrations of Ang-(1-7), potentiation was abolished. The maximum incremental effects of Ang-(1-7) on inhibition of aggregation were 25+/-4% and 28+/-5%, for rate and extent of aggregation respectively (P<0.01 for both), corresponding to a 2.3-fold potentiation of the anti-aggregatory effect of SNP. Platelets from patients were resistant to the anti-aggregatory effect of SNP, but potentiation of SNP effects by Ang-(1-7) was similar for patients and normal subjects. Thus, Ang-(1-7) potentiates the anti-aggregatory effects of NO donor, and may therefore counteract platelet NO resistance that accompanies cardiovascular disease.


Evidence for involvement of 17beta-estradiol in intestinal calcium absorption independent of 1,25-dihydroxyvitamin D3 level in the Rat.
The sex steroid 17beta-estradiol (17beta-E2) has a broad range of actions, including effects on calcium and bone metabolism. This study with 3-month-old Brown Norway rats was designed to investigate the role of 17beta-E2 in the regulation of calcium homeostasis. Rats were divided in four groups, sham-operated, ovariectomized (OVX), and OVX supplemented with either a 0.025-mg or 0.05-mg 17beta-E2 pellet implanted subcutaneously. After 4 weeks, in none of the groups was serum calcium, phosphate, or parathyroid hormone altered compared with the sham group, while only in the OVX rats was a significant reduction in urinary calcium found. Bone mineral density and osteocalcin were modified, as can be expected after OVX and 17beta-E2 supplementation. OVX resulted in a nonsignificant increase in serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Supplementation with either one of the 17beta-E2 dosages resulted in an 80% reduction of 1,25(OH)2D3 and only a 20% reduction in 25-hydroxyvitamin D3 levels. OVX, as well as supplementation with 17beta-E2, did not affect serum levels of vitamin D binding protein. As a consequence, the estimated free 1,25(OH)2D3 levels were also significantly decreased in the 17beta-E2-supplemented group compared with the sham and OVX groups. Next, the consequences for intestinal calcium absorption were analyzed by the in situ intestinal loop technique. Although the 1,25(OH)2D3 serum level was increased, OVX resulted in a significant decrease in intestinal calcium absorption in the duodenum. Despite the strongly reduced 1,25(OH)2D3 levels (18. 1 +/- 2.1 and 16.4 +/- 2.2 pmol/l compared with 143.5 +/- 29 pmol/l for the OVX group), the OVX-induced decrease in calcium absorption could partially be restored by supplementation with either 0.025 mg or 0.05 mg of 17beta-E2. None of the treatments resulted in a significant change in calcium handling in the jejunum, although the trends were similar as those observed in the duodenum. 17beta-E2 did not change the VDR levels in both the intestine and the kidney. In conclusion, the present study demonstrates that 17beta-E2 is positively involved in intestinal calcium absorption, and the data strengthen the assertion that 17beta-E2 exerts this effect independent of 1,25(OH)2D3. In general, 17beta-E2 not only affects bone turnover but also calcium homeostasis via an effect on intestinal calcium absorption. (J Bone Miner Res 1999;14:57-64)


Effect of BMI and binge eating on food reward and energy intake: further evidence for a binge eating subtype of obesity.
The psychological characteristics of binge eating have been proposed as a phenotype to further understanding of overconsumption and susceptibility to obesity. This study examined the influence of trait binge eating in lean and overweight or obese women on appetite, food reward and energy intake. 25 lean and 25 overweight or obese women were categorised as either 'binge type' or 'non-binge type' based on their scores on the Binge Eating Scale. Food reward and food intake were assessed in fasted and fed conditions. Overweight or obese binge types (O-B) consumed more energy than overweight or obese non-binge types (O-NB) and lean binge (L-B) and non-binge types (L-NB). Both L-B and O-B exhibited greater preference for sweet foods. In O-NB, L-B and L-NB, lower liking and wanting for sweet foods was exhibited in the fed condition compared to the fasted condition. However, in O-B wanting for sweet foods was greater when they were fed compared to when they were in a fasted state. These findings provide further support for trait binge eating as a hedonic subtype of obesity. Binge types were characterised by greater intake of high-fat sweet foods and increased wanting for these foods when satiated. Additionally, these findings highlight the potential for separation in liking and wanting for food as a marker of susceptibility to overeat.


Affixin activates Rac1 via betaPIX in C2C12 myoblast.
Affixin/beta-parvin is an integrin-linked kinase (ILK)-binding focal adhesion protein highly expressed in skeletal muscle and heart. To elucidate the possible role of affixin in skeletal muscle, we established stable C2C12 cell line expressing T7-tagged human affixin (C2C12-affixin cells). Exogenous expression of affixin promotes lamellipodium formation where affixin, ILK alphap21-activated kinase (PAK)-interactive exchange factor (PIX) and betaPIX accumulate. The association of affixin and betaPIX was confirmed by immunoprecipitation and pull down assay. In C2C12-affixin cells, an increased level of activated Rac1 but not Cdc42 was observed, and mutant betaPIX lacking guanine nucleotide exchange factor activity inhibited lamellipodium formation. These results suggest that affixin is involved in reorganization of subsarcolemmal cytoskeletal actin by activation of Rac1 through alpha and betaPIXs in skeletal muscle.


Effect of Structure Variations in the Inter-subunit Contact Zone on the Activity and Allosteric Regulation of Inorganic Pyrophosphatase from Mycobacterium tuberculosis.
Hexameric inorganic pyrophosphatase from Mycobacterium tuberculosis (Mt-PPase) has a number of structural and functional features that distinguish it from homologous enzymes widely occurring in living organisms. In particular, it has unusual zones of inter-subunit contacts and lacks the N-terminal region common for other PPases. In this work, we constructed two mutant forms of the enzyme, Ec-Mt-PPase and R14Q-Mt-PPase. In Ec-Mt-PPase, the missing part of the polypeptide chain was compensated with a fragment of PPase from Escherichia coli (Ec-PPase). In R14Q-Mt-PPase, a point mutation was introduced to the contact interface between the two trimers of the hexamer. Both modifications significantly improved the catalytic activity of the enzyme and abolished its inhibition by the cofactor (Mg2+ ion) excess. Activation of Mt-PPase by low (~10 μM) concentrations of ATP, fructose-1-phosphate, L-malate, and non-hydrolyzable substrate analogue methylene bisphosphonate (PCP) was observed. At concentrations of 100 μM and higher, the first three compounds acted as inhibitors. The activating effect of PCP was absent in both mutant forms, and the inhibitory effect of fructose-1-phosphate was absent in Ec-Mt-PPase. The effects of other modulators varied only quantitatively among the mutants. The obtained data indicate the presence of allosteric sites in Mt-PPase, which are located in the zones of inter-subunit contact or associated with them.


Production, purification, and characterization of the cecropin from Plutella xylostella, pxCECA1, using an intein-induced self-cleavable system in Escherichia coli.
Antimicrobial peptides (AMPs) are widely expressed and play an important role in innate immune defense against infectious agents such as bacteria, viruses, fungi, and parasites. Cecropins are a family of AMPs synthesized in the fat body of insects that have proven effective at killing specific pathogens. In order to fulfill their clinical potential as antimicrobial drugs, a simple, cost-effective method to express AMPs is sorely needed. In this study, we expressed and characterized the cecropin from Plutella xylostella (pxCECA1) using an intein-dependent expression system in Escherichia coli. We cloned the pxCECA1 gene from larva by RT-PCR and fused the encoding sequence of mature pxCECA1 with an intein gene and a chitin-binding domain gene (CBD) in pTWIN1 plasmid. The fusion protein CBD-intein-pxCECA1 was expressed in E. coli BL21 (DE3) and separated by flowing cell extracts through a chitin column. Subsequently, self-cleavage of the intein at its C-terminus was induced in a temperature- and pH-dependent manner, resulting in the release of mature pxCECA1. The optimal conditions for self-cleavage were determined to be pH 6.0 for 48 h at 4°C, under which 12.3 mg of recombinant pxCECA1 could be recovered from 1 l of E. coli culture. The purified pxCECA1 displayed antimicrobial activity against a broad variety of gram-positive and gram-negative bacteria. This preparation was especially effective against Staphylococcus aureus, including methicillin-resistant strains. Catalase release assays demonstrated that pxCECA1 acts as a microbicidal agent. These results show for the first time that the IMPACT-TWIN expression system is an efficient, cost-effective way to produce fully functional AMPs and that the AMP pxCECA1 is a novel microbicidal agent with promising therapeutic applications.


Downregulation of MGMT expression by targeted editing of DNA methylation enhances temozolomide sensitivity in glioblastoma.
Glioblastoma is the most common and aggressive primary tumor of the central nervous system with poor outcome. Current gold standard treatment is surgical resection followed by a combination of radio- and chemotherapy. Efficacy of temozolomide (TMZ), the primary chemotherapeutic agent, depends on the DNA methylation status of the O6-methylguanine DNA methyltransferase (MGMT), which has been identified as a prognostic biomarker in glioblastoma patients. Clinical studies revealed that glioblastoma patients with hypermethylated MGMT promoter have a better response to TMZ treatment and a significantly improved overall survival. In this study, we thus used the CRISPRoff genome editing tool to mediate targeted DNA methylation within the MGMT promoter region. The system carrying a CRISPR-deactivated Cas9 (dCas9) fused with a methyltransferase (Dnmt3A/3L) domain downregulated MGMT expression in TMZ-resistant human glioblastoma cell lines through targeted DNA methylation. The reduction of MGMT expression levels reversed TMZ resistance in TMZ-resistant glioblastoma cell lines resulting in TMZ induced dose-dependent cell death rates. In conclusion, we demonstrate targeted RNA-guided methylation of the MGMT promoter as a promising tool to overcome chemoresistance and improve the cytotoxic effect of TMZ in glioblastoma.


Pathogenesis and treatment of depression: Role of diet in prevention and therapy.
In recent years, there has been a significant increase in depression, which is related to, among other things, the COVID-19 pandemic. Depression can be fatal if not treated or if treated inappropriately. Depression is the leading cause of suicide attempts. The disease is multifactorial, and pharmacotherapy often fails to bring satisfactory results. Therefore, increasingly more importance is attached to the natural healing substances and nutrients in food, which can significantly affect the therapy process and prevention of depressive disorders. A proper diet is vital to preventing depression and can be a valuable addition to psychological and pharmacologic treatment. An inadequate diet may reduce the effectiveness of antidepressants or increase their side effects, leading to life-threatening symptoms. This study aimed to review the literature on the pathogenesis of the development and treatment of depression, with particular emphasis on dietary supplements and the role of nutrition in the prevention and treatment of depressive disorders.


Meta-analysis of the changes in correlations between depression instruments used in longitudinal studies.
Correlations between instruments measuring the same construct reflect their concurrent validity. Little is known about changes in correlations between such instruments employed in studies with repeated assessment. The aim of this meta-analysis was to examine the changes in correlations between depression instruments in the course of longitudinal studies. A literature search was conducted using MEDLINE and PsycINFO for the period from 1960 to 2013. The total number of collected articles was 3723, of which 61 were included. Three meta-analyses were performed for the changes in correlations between each pair of the three depression scales: Hamilton Rating Scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI). The effect size in these meta-analyses was obtained by the z-transformation of correlation coefficients. Correlations between depression scales increased over time in 52 studies. Significant changes in correlation coefficients were found for correlations between HAMD and BDI (p<0.001) and for correlations between HAMD and MADRS (p<0.001). An increase in correlations between the scales was associated with a decrease in depression scores and increase in their variability. Univariable and multivariable meta-regression models were not obtained in all three meta-analyses because of the lack of data. A finding that correlations between depression instruments tended to increase over time has significant implications for assessment of the concurrent validity of these instruments. In longitudinal designs it is important to estimate correlations between depression scales over time because different thresholds for scale correlations indicate acceptable concurrent validity at different times.


Effect of 1.2 mmol/l calcium, triamcinolone acetonide, and retinoids on low-calcium regulated keratinocyte differentiation.
Neonatal mouse keratinocytes cultured in low calcium (0.01 mmol/l) show rapid growth and little stratification when compared with cells grown in normal 1.2 mmol/l calcium. The effect of low calcium on the amount and synthesis of specific differentiation proteins was studied; additionally, the effect of 10(-8) mol/l triamcinolone acetonide, and 6 micrograms/ml of retinoic acid and of etretinate (Ro 10-9359) on low-calcium regulated keratinocyte hyperproliferation and differentiation was determined. Low-calcium regulated keratinocytes contained less non-covalently cross-linked and disulphide cross-linked keratins, less cell envelopes, much greater amounts of SDS-soluble viable cell proteins, and slightly more keratohyaline granule-related proteins than normal-calcium regulated keratinocytes. A 24 h switching time to 1.2 mmol/l calcium medium did not affect the amounts or synthesis of these proteins. Both retinoids and triamcinolone acetonide inhibited by approximately 50% the proliferation of the low-calcium regulated keratinocytes. Growth of low-calcium cells in these drugs for 9 days increased the amounts of both keratins and cell envelope proteins in the cultures. We concluded that calcium-dependent processes can regulate epidermal keratinocyte proliferation and differentiation. Our studies suggest that these calcium-regulated events may occur via changes in calcium-dependent proteins.


The direct and indirect impact of the COVID-19 pandemic on the care of patients with pituitary disease: a cross sectional study.
The coronavirus disease 2019 (COVID-19) pandemic is widely believed to have had a major impact on the care of patients with pituitary disease. The virus itself may directly result in death, and patients with adrenal insufficiency, often a part of hypopituitarism, are thought to represent a particularly susceptible subgroup. Moreover, even in patients that do not contract the virus, the diversion of resources by healthcare institutions to manage the virus may indirectly result in delays in their management. To this end, the aim of this study was to determine the direct and indirect impact of the COVID-19 pandemic on patients with pituitary disease. A cross-sectional study design was adopted, with all adult patients seen by our pituitary service in the year prior to the nationwide lockdown on March 23rd 2020 invited to participate in a telephone survey. In all, 412 patients (412/586; 70.3%) participated in the survey. 66 patients (66/412; 16.0%) reported having suspected COVID-19 infection. Of the 10 patients in this group tested for COVID-19 infection, three received a positive test result. No deaths due to COVID-19 were identified. 267 patients (267/412; 64.8%) experienced a delay or change in the planned care for their pituitary disease, with 100 patients (100/412; 24.3%) perceiving an impact to their care. Whilst only a small percentage of patients had confirmed or suspected COVID-19 infection, over half were still indirectly impacted by the pandemic through a delay or change to their planned care.


Effects of supplemental dietary calcium on the intestinal association of calcium, phosphate, and bile acids.
It has been suggested that supplemental dietary calcium decreases hyperproliferation of colonic epithelial cells because calcium precipitates and thus inactivates luminal bile acids. Therefore, 12 healthy men were studied before and after dietary calcium supplementation (35.5 mmol/day) to quantify intestinal associations of calcium, phosphate, and bile acids. The supplemental dietary calcium was almost completely (95%) recovered, mainly in feces. Calcium increased the fecal excretion of both phosphate (31%) and bile acids (53%) and decreased the ratio of dihydroxy to trihydroxy bile acids in duodenal bile almost twofold. In vitro studies showed that precipitation of glycodeoxycholic acid was caused by the formation of insoluble calcium phosphate. Water-soluble and calcium-associated amounts of phosphate and bile acids in feces were measured by resolubilization studies, using the calcium chelator ethylenediaminetetraacetate. In both the control and calcium periods, significant amounts of phosphate (80% and 90%) and bile acids (33% and 50%) were calcium-associated. Moreover, the calcium-induced increments in fecal phosphate and bile acids were completely calcium-associated. Calcium decreased the amount of water-soluble phosphate but not of bile acids. These results indicate that supplemental calcium stimulates formation of insoluble calcium phosphate in the intestinal lumen and thus increases binding of luminal bile acids.


Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration.
To investigate whether the benefit of Age-Related Eye Disease Study (AREDS) formula multivitamins and zinc in the progression of age-related macular degeneration (AMD) may occur through inhibiting inflammatory events in the choroid. Mouse C166 endothelial cells (ECs) and, for some experiments, human retinal pigment epithelium (RPE)-choroid organ cultures were treated with AREDS multivitamin solution (MVS) or ZnCl(2). The cytotoxicity of MVS was evaluated using a lactate dehydrogenase colorimetric assay. Cell motility was assessed using a scratch assay. Macrophage adhesion to EC monolayers or ICAM-1 protein was determined after MVS and zinc treatment and with or without lipopolysaccharide (LPS). Quantitative reverse transcription PCR and Western blot analysis were used to determine the effects of MVS on the expression of proinflammatory molecules in treated and untreated cells. AREDS MVS and zinc did not affect C166 EC viability until the 56th hour after treatment. Scratch assays showed partial inhibition of MVS and zinc on EC migration. In cell adhesion assays, MVS and zinc decreased the number of macrophages bound to EC and to ICAM-1 protein. Quantitative PCR showed that LPS increased the expression of ICAM-1 in both C166 and human RPE-choroid cultures, which was partially offset by MVS and zinc. MVS and zinc also mitigated LPS-induced ICAM-1 protein expression on Western blot analysis. Treatment with AREDS MVS and zinc may affect both angiogenesis and endothelial-macrophage interactions. These results suggest that AREDS vitamins and zinc ions may slow the progression of AMD, in part through the attenuation of EC activation.


Electrolyte Regulation towards Stable Lithium-Metal Anodes in Lithium-Sulfur Batteries with Sulfurized Polyacrylonitrile Cathodes.
Lithium-sulfur (Li-S) batteries are highly regarded as the next-generation energy-storage devices because of their ultrahigh theoretical energy density of 2600 Wh kg-1 . Sulfurized polyacrylonitrile (SPAN) is considered a promising sulfur cathode to substitute carbon/sulfur (C/S) composites to afford higher Coulombic efficiency, improved cycling stability, and potential high-energy-density Li-SPAN batteries. However, the instability of the Li-metal anode threatens the performances of Li-SPAN batteries bringing limited lifespan and safety hazards. Li-metal can react with most kinds of electrolyte to generate a protective solid electrolyte interphase (SEI), electrolyte regulation is a widely accepted strategy to protect Li-metal anodes in rechargeable batteries. Herein, the basic principles and current challenges of Li-SPAN batteries are addressed. Recent advances on electrolyte regulation towards stable Li-metal anodes in Li-SPAN batteries are summarized to suggest design strategies of solvents, lithium salts, additives, and gel electrolyte. Finally, prospects for future electrolyte design and Li anode protection in Li-SPAN batteries are discussed.


Mass fractions of 52 trace elements and zinc/trace element content ratios in intact human prostates investigated by inductively coupled plasma mass spectrometry.
Contents of 52 trace elements in intact prostate of 64 apparently healthy 13-60-year-old men (mean age 36.5 years) were investigated by inductively coupled plasma mass spectrometry. Mean values (M ± SΕΜ) for mass fraction (in milligrams per kilogram, on dry-weight basis) of trace elements were as follows: Ag 0.041 ± 0.005, Al 36 ± 4, Au 0.0039 ± 0.0007, B 0.97 ± 0.13, Be 0.00099 ± 0.00006, Bi 0.021 ± 0.008, Br 29 ± 3, Cd 0.78 ± 0.09, Ce 0.028 ± 0.004, Co 0.035 ± 0.003, Cs 0.034 ± 0.003, Dy 0.0031 ± 0.0005, Er 0.0018 ± 0.0004, Gd 0.0030 ± 0.0005, Hg 0.046 ± 0.006, Ho 0.00056 ± 0.00008, La 0.074 ± 0.015, Li 0.040 ± 0.004, Mn 1.53 ± 0.09, Mo 0.30 ± 0.03, Nb 0.0051 ± 0.0009, Nd 0.013 ± 0.002, Ni 4.3 ± 0.7, Pb 1.8 ± 0.4, Pr 0.0033 ± 0.0004, Rb 15.9 ± 0.6, Sb 0.040 ± 0.005, Se 0.73 ± 0.03, Sm 0.0027 ± 0.0004, Sn 0.25 ± 0.05, Tb 0.00043 ± 0.00009, Th 0.0024 ± 0.0005, Tl 0.0014 ± 0.0001, Tm 0.00030 ± 0.00006, U 0.0049 ± 0.0014, Y 0.019 ± 0.003, Yb 0.0015 ± 0.0002, Zn 782 ± 97, and Zr 0.044 ± 0.009, respectively. The upper limit of mean contents of As, Cr, Eu, Ga, Hf, Ir, Lu, Pd, Pt, Re, Ta, and Ti were the following: As ≤ 0.018, Cr ≤ 0.64, Eu ≤ 0.0006, Ga ≤ 0.08, Hf ≤ 0.02, Ir ≤ 0.0004, Lu ≤ 0.00028, Pd ≤ 0.007, Pt ≤ 0.0009, Re ≤ 0.0015, Ta ≤ 0.005, and Ti ≤ 2.6. In all prostate samples, the content of Te was under detection limit (<0.003). Additionally, ratios of the Zn content to other trace element contents as well as correlations between Zn and trace elements were calculated. Our data indicate that the human prostate accumulates such trace elements as Al, Au, B, Br, Cd, Cr, Ga, Li, Mn, Ni, Pb, U, and Zn. No special relationship between Zn and other trace elements was found.


Mechanisms for sensing fat in food in the mouth: Presented at the Symposium "The Taste for Fat: New Discoveries on the Role of Fat in Sensory Perception, Metabolism, Sensory Pleasure and Beyond" held at the Institute of Food Technologists 2011 Annual Meeting, New Orleans, LA, USA., June 12, 2011.
The brain areas that represent taste including the primary taste cortex and the orbitofrontal cortex also provide a representation of oral texture. Fat texture is represented by neurons independently of viscosity: some neurons respond to fat independently of viscosity, and other neurons encode viscosity. The neurons that respond to fat also respond to silicone and paraffin oil, indicating that the sensing is texture-specific not chemo-specific. This fat sensing is not related to free fatty acids such as linoleic acid, and a few other neurons that respond to free fatty acids typically do not respond to fat in the mouth. Complementary human functional neuroimaging studies show that the pleasantness of food texture is represented in the orbitofrontal cortex. These findings have implications for the design of foods that mimic the pleasant texture of fat in the mouth but have low energy content, and thus for the prevention and treatment of obesity.


Lymphoid involvement in a patient with acute myeloid leukemia: a direct phenotypic and genotypic study of single cells.
Lymphoid involvement in acute myeloid leukemia (AML) was studied using the morphology-antibody-chromosome (MAC) combination technique in one patient. The chromosomal aberration, trisomy 8, was demonstrated in AML blasts, glycophorin A-positive erythroblasts, and CD3- and CD20/22-positive small lymphocytes. This suggests that in this patient even lymphocytes belonged to the leukemic clone.


Injectable system and its potential application for the delivery of biomolecules by using thermosensitive poly(γ-glutamic acid)-based physical hydrogel.
Poly (γ-glutamic acid) (PGA) is a natural biomaterial with numerous good properties such as non-toxicity, non-immunogenicity, and water holding. So, various forms of PGA-based materials have been developed for bio-applications, including sheet, cross-linked hydrogel, and nanoparticle except injectable hydrogel type. Considering inherent advantages of injectable system, injectable hydrogel based on PGA can broaden the bio-application range of PGA. In this study, a PGA-based injectable hydrogel system was prepared by physically mixing it with a small amount of chitosan with two different water solubility and molecular weight. The prepared hydrogel system showed a thermo-sensitivity through sol-gel transition behavior in the body temperature change. The mechanical properties and in vitro stability could be modulated by varying the ratio of two types of chitosan. In vitro protein (human bFGF) delivery using this injectable formulation showed a sustained release for ∼2 weeks while preserving its bioactivity. In addition, the in situ formation of this PGA-based hydrogel formulation upon subcutaneous injection was demonstrated in vivo. The hydrogel formed in vivo also showed a long term (∼2 weeks) stability without noticeable inflammatory response. Therefore, the present formulation can be applied as a promising injectable hydrogel system for tissue engineering or drug delivery.


Methylation of a middle repetitive DNA sequence class during differentiation in Friend erythroleukemia cells.
We have examined the methylation patterns within middle repetitive sequences in Friend erythroleukemia cells. Mouse-interspersed-family-1 (MIF-1) and a group characterized by a 1350-bp Eco-Bam fragment cloned into pBR322 as plasmid pFS-13, are both less modified in Friend cell DNA than in normal tissue DNA. The pattern of methylation present in pFS-13 homologous sequences was found to be stable during cell division, i.e., somatically inherited, and stable during differentiation induced by HMBA.


Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration.
Cytochrome c (Cyt c) is part of the mitochondrial electron transport chain (ETC), accepting electrons from bc(1) complex and transferring them to cytochrome c oxidase (CcO). The ETC generates the mitochondrial membrane potential, which is used by ATP synthase to produce ATP. In addition, the release of Cyt c from the mitochondria often commits a cell to undergo apoptosis. Considering its central role in life (respiration) and death (apoptosis) decisions one would expect tight regulation of Cyt c function. Reversible phosphorylation is a main cellular regulatory mechanism, but the effect of cell signaling targeting the mitochondrial oxidative phosphorylation system is not well understood, and only a small number of proteins that can be phosphorylated have been identified to date. We have recently shown that Cyt c isolated from cow heart tissue is phosphorylated on tyrosine 97 in vivo, which leads to inhibition of respiration in the reaction with CcO. In this study we isolated Cyt c from a different organ, cow liver, under conditions preserving the physiological phosphorylation state. Western analysis with a phosphotyrosine specific antibody suggested that liver Cyt c is phosphorylated. Surprisingly, the phosphorylation site was unambiguously assigned to Tyr-48 by immobilized metal affinity chromatography/nano-liquid chromatography/electrospray ionization mass spectrometry (IMAC/nano-LC/ESI-MS), and not to the previously identified phospho-Tyr-97 in cow heart. As is true of Tyr-97, Tyr-48 is conserved in eukaryotes. As one possible consequence of Tyr-48 phosphorylation we analyzed the in vitro reaction kinetics with isolated cow liver CcO revealing striking differences. Maximal turnover of Tyr-48 phosphorylated Cyt c was 3.7 s(-1) whereas dephosphorylation resulted in a 2.2 fold increase in activity to 8.2 s(-1). Effects of Tyr-48 phosphorylation based on the Cyt c crystal structure are discussed.


In non-transformed cells Bak activates upon loss of anti-apoptotic Bcl-XL and Mcl-1 but in the absence of active BH3-only proteins.
Mitochondrial apoptosis is controlled by proteins of the B-cell lymphoma 2 (Bcl-2) family. Pro-apoptotic members of this family, known as BH3-only proteins, initiate activation of the effectors Bcl-2-associated X protein (Bax) and Bcl-2 homologous antagonist/killer (Bak), which is counteracted by anti-apoptotic family members. How the interactions of Bcl-2 proteins regulate cell death is still not entirely clear. Here, we show that in the absence of extrinsic apoptotic stimuli Bak activates without detectable contribution from BH3-only proteins, and cell survival depends on anti-apoptotic Bcl-2 molecules. All anti-apoptotic Bcl-2 proteins were targeted via RNA interference alone or in combinations of two in primary human fibroblasts. Simultaneous targeting of B-cell lymphoma-extra large and myeloid cell leukemia sequence 1 led to apoptosis in several cell types. Apoptosis depended on Bak whereas Bax was dispensable. Activator BH3-only proteins were not required for apoptosis induction as apoptosis was unaltered in the absence of all BH3-only proteins known to activate Bax or Bak directly, Bcl-2-interacting mediator of cell death, BH3-interacting domain death agonist and p53-upregulated modulator of apoptosis. These findings argue for auto-activation of Bak in the absence of anti-apoptotic Bcl-2 proteins and provide evidence of profound differences in the activation of Bax and Bak.


Misdiagnosis of African-Americans with Psychiatric Issues - Part I.
This article highlights issues of misdiagnosis in an African-American, adult clinical population by doing point prevalence, record review study within a comprehensive community mental health center. Psychiatric evaluations of 330 patients were reviewed and clinically identifiable variables of: a) childhood Intellectual Disability (ID), special education, Attention Deficit Hyperactive Disorder (ADHD), or Autism/Pervasive Developmental Disorder (PDD); b) head injury causing Organic Brain Syndrome (OBS) or Temporal Lobe Epilepsy (TLE); c) a history of chronic substance abuse prior to the development of psychiatric symptoms; or d) childhood trauma causing Anxiety, Depression, and Panic Disorders were tabulated. Two hundred and twenty patients, who were free of the four variables, had a single psychiatric diagnosis and 18 had multiple co-morbid diagnoses. More than 25% (92/330) of the patients had the four variables in their histories. Four of the 92 patients had more than one variable in their history. Of the remaining 88 cases, 42 had psychiatric issues beginning in childhood (28 had history of ID, 4 had history of learning disabilities, 3 had history of ADHD, 7 had histories of Autism/PDD); 9 had histories of OBS or TLE; 20 had histories of substance abuse; and 18 had histories of extensive childhood trauma). Careful attention to common issues in African-Americans can inform the psychiatric diagnostic process pointing to prevention or treatment considerations that would benefit the African-American community at large.


The primary sequence of the late region of polyoma virus DNA II. The expression of the late genes and comparison with DNA sequences of SV40 and BKV.
The nucleotide sequence of the late region of the polyoma virus genome has been deduced, which codes for the major capsid protein VP1 and the C-terminal region of the minor proteins VP2 and VP3. The amino acid sequence of VP1 predicted from the nucleotide sequence is in good agreement with the partial N-terminal sequence 1 and amino acid composition of VP1 2,3. When both nucleotide and amono acid sequences are compared with their counterparts in the related viruses, SV40 4,5 and BKV (R. Young, personal communication), extensive homologies are found along the entire regions of the viral genes. Maximum homologies appear to occur in the regions which code for the C-terminal of VP1, on the contrary of the result of heteroduplex analysis 6 with 6 with SV40 and polyoma virus DNAs.


Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif.
We identified a novel gene encoding a RING finger (C3HC4-type zinc finger) protein from a human neuroblastoma full-length enriched cDNA library. This cDNA clone consists of 1919 nucleotides with an open reading frame of a 485-amino acid protein. From reverse transcription (RT)-polymerase chain reaction (PCR) analysis, the messenger RNA was ubiquitously expressed in various human adult tissues. The chromosomal location of the gene was determined on the chromosome 6p21.3 region by PCR-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel.


Use of alkenylresorcinols from Ononis speciosa as synthetic precursors of compounds with potential biological activity.
Selective ozonization of the alkenylresorcinols isolated from Ononis speciosa was studied. The derivatives thus obtained were used as precursors in the synthesis of cannabinoids and macrocyclic lactones.


[Optimized programming during cardiac resynchronization therapy].
Cardiac resynchronization (CRT) has evolved as a therapeutic add-on tool in patients with refractory heart failure. Additional pacing of the left ventricle leads to relevant clinical and hemodynamic improvement. Optimized programming of these pacing systems may modulate therapeutic efficacy. Optimal atrio-ventricular (AV) and ventriculo-ventricular (VV) delay programming is documented to increase invasively and non-invasively determined parameters of cardiac hemodynamics. In this manuscript different options for determining optimal AV and VV delay are discussed and a pragmatic approach to optimize CRT programming is detailed. VV delay needs to be optimized as a first step of programming. Different techniques may estimate the individual need for sequential ventricular pacing. Especially electrocardiographic criteria during right and left ventricular pacing may approximate the time-delay for pre-excitation. Delay between aortic and pulmonic valve ejection can be determined using Doppler echocardiography may identify patients who benefit from sequential pacing. Optimizing AV delay is a domain of Doppler echocardiography where using a simple formula the AV delay that produces the best diastolic resynchronization of left atrial contraction and left ventricular ejection can be calculated.Using the above mentioned techniques a pragmatic, easy and fast method for increasing CRT performance can be established. In cases of worsening heart failure or relevant changes of left ventricular dimensions adaptions (re-optimization) of VV and AV delay may be needed.


Treatment of hypertension and other cardiovascular risk factors in patients with metabolic syndrome.
Metabolic syndrome (MetS), a concurrence of hypertension, abdominal obesity, impaired fasting glucose, and dyslipidemia, has been shown to be a risk factor for cardiovascular disease. Insulin resistance has been thought to be one of the pathophysiologies of the syndrome. Reduction of the underlying causes of MetS, such as obesity, physical inactivity, and atherogenic diet, is first-line therapy. Treatment of hypertension and other cardiometabolic risk factors of MetS is also required. This article reviews the treatment of the metabolic syndrome with a focus on the importance of lifestyle changes and treatment of hypertension.


Synthesis of conformationally restricted 1,3-dioxanes to analyze the bioactive conformation of 1,3-dioxane-based σ1 and PCP receptor antagonists.
The receptor binding profile of 2-phenyl-4-(aminoethyl)-1,3-dioxanes is dependent on the additional substituent in 2-position, the substituents at the amino moiety and the stereochemistry. Herein, conformationally restricted 1,3-dioxanes bearing an axially oriented phenyl moiety in 2-position were prepared and pharmacologically evaluated. Two subsequent intramolecular transacetalization reactions represent the key steps in the synthesis of the tricyclic system. The resulting alcohol 17 was transformed into amines 20-23 with axially (a-series) or equatorially oriented aminoethyl moiety (b-series). The primary amines 20a and 20b did not interact with the PCP binding site of the NMDA receptor, which is explained by the additional methylene moiety between the acetalic center and the phenyl moiety, the missing substituent at the acetalic position and/or a non-optimal three-dimensional arrangement of the pharmacophoric elements. The benzylamine 21b with an equatorially oriented aminoethyl moiety shows high σ1 affinity (Ki=5.9nM). Compared with the conformationally flexible 1,3-dioxane 5, the σ1 affinity of 21b is 3-fold and the σ1/σ2 selectivity is 5-fold increased.


Corrigendum: Spatial Patterns of Thalassia testudinum Immune Status and Labyrinthula spp. Load Implicate Environmental Quality and History as Modulators of Defense Strategies and Wasting Disease in Florida Bay, United States.
[This corrects the article DOI: 10.3389/fpls.2021.612947.].


Leprosy: uncommon presentations.
The uniqueness of the clinical-dermatologic elements of leprosy recommends that control programs worldwide should diagnose the disease based on the so-called main clinical signs: cutaneous-neurological lesions with sensitivity-motor alterations without obligatory bacteriologic or histopathologic examination. The recognition of initial signs and symptoms of Hansen disease sometimes presents difficulties for its diagnosis, especially considering the relevance of an early diagnosis and the present guidelines for performance of decentralized treatment of the patient in the basic health-care network. The clinical cases illustrating this article were selected because of the degree of difficulty found in the confirmation of their diagnoses that required a histopathologic and/or bacteriologic examination.


Oral Glucose Tolerance is Associated with Neuroelectric Indices of Attention Among Adults with Overweight and Obesity.
This study aimed to elucidate the relationship between glucose levels and insulin resistance and sensitivity obtained from oral glucose tolerance tests and neurophysiological indices of attention among adults with overweight and obesity. Forty adults with overweight or obesity (BMI ≥ 25 kg/m2 ) underwent dual-energy x-ray absorptiometry to assess visceral adipose tissue. Repeated venous blood samples were collected during an oral glucose tolerance test to measure insulin resistance (homeostatic model assessment of insulin resistance) and indices of insulin sensitivity (Matsuda index and Stumvoll metabolic clearance rate). Attention was assessed using event-related brain potentials recorded during a visual oddball task. Amplitude and latency of the P3 wave form in a central-parietal region of interest were used to index attentional resource allocation and information processing speed. Following adjustment for visceral adipose tissue, reduced values of Matsuda index and Stumvoll metabolic clearance rate (indicating poor insulin sensitivity) were correlated with longer peak latency, whereas insulin area under the curve was positively related to peak latency, indicating slower information processing. Individuals with decreased insulin sensitivity (Matsuda index < 4.3) had significantly longer P3 latencies compared with individuals with normal insulin sensitivity. Higher fasting glucose, but not homeostatic model assessment of insulin resistance, and reduced indices of glucose sensivity are associated with decrements in attention characterized by slower reaction time and slower information processing speed among adults with overweight and obesity.


Prognostic value of odor identification impairment in multiple sclerosis: 10-Years follow-up.
Olfactory dysfunction has been linked to clinical severity variables in multiple MS populations. Though, its prognostic value is still unknown. The aim of this study was to explore the long-term outcome associated with Brief-Smell Identification Test (B-SIT) performance in a cohort of MS patients. A retrospective review of the clinical records was conducted in 149 patients who participated in a previous study, with a median follow-up of 121 months. Demographic and clinical data regarding the last clinical appointment with EDSS measurement were collected. Multiple Sclerosis Severity Scale (MSSS) and Age-Related Multiple Sclerosis Severity (ARMSS) scores were calculated. Date of the last clinical contact or death was recorded. Among MS patients with progressive clinical course (n = 33), those with impaired B-SIT at baseline had greater change per month during follow-up (as measured by increases in MSSS and ARMSS scores) and a higher hazard of death. No significant associations were found among patients with relapsing and remitting MS (n = 116). The study results demonstrate that odor identification impairment has prognostic value in progressive MS, suggesting that a brief odor identification measure can be a marker of neurodegeneration in progressive MS.


Partial characterization of a low molecular weight proteoglycan isolated from bovine parietal pericardium.
Knowledge of the nature of pericardial connective tissue components is incomplete. To gain a better understanding of the composition of this tissue, bovine parietal pericardium was extracted with 4 M guanidine hydrochloride yielding a proteoglycan-containing protein mixture. This was fractionated by a three-step chromatographic procedure with the resultant purification of a 75-110 Kd proteoglycan. The purified proteoglycan was susceptible to chondroitinase ABC digestion but resistant to chondroitinase AC and nitrous acid degradation suggesting the presence of dermatan sulfate glycosaminoglycan(s). This is the first reported isolation of a proteoglycan from parietal pericardium.


Treatment of Bronchopleural Fistula with Carbolic Acid instilled through Bronchofiberscope in post-pulmonectomy patients.
To investigate the efficacy of carbolic acid treatment of bronchopleural fistula (BPF) using bronchofiberscope (BFS) in post-pulmonectomy patients. Twelve patients with post-pulmonectomy BPF were enrolled in this study at the Liaoning Tumor Hospital between February 2009 and March 2012. Three patients had BPF after the right pneumonectomy, six patients after left pneumonectomy, one patient after the right middle and low lobectomy and two patients after left upper lobectomy. BPF patients were instilled with 100 % carbolic acid (0.5-1 ml one time every week) through BFS on the mucosal surface around the fistula, and the bubble disappearance was monitored. Treatment was repeated if the bubble remained. No haemorrhage, severe dyspnea or SpO2 declines occurred in all the 12 patients during the bronchoscopic therapy. BPF orifices were closed in five patients after receiving 5 treatments with carbolic acid, 1 patient received 2 treatments, 1 patient was given 3 treatments, 2 patients received 4 treatments and 3 patients were given 7 treatments. Follow-up was conducted for six months following bronchoscopy. The average treatment and fistula closure time were calculated from the data collected as 20 min and 30 days, respectively, and the cure rate was 100 %. Hematoxylin-eosin (HE) staining results revealed that the white flat hyperplasia tissue after carbolic acid treatment was inflammatory granulation tissue. Our results revealed that instillation of 100 % carbolic acid with BFS to treat BPF was 100 % effective, which can be a support for post-pulmonectomy BPF.


Kinetics of bacterial adhesion--a stochastic analysis.
In a previous work (Hsu & Wang, 1986), a birth-death type of stochastic model was proposed to analyze bacterial adhesion onto the substrate surface. The model is based upon the assumption that the number of available active sites on the substrate surface is relatively large compared to that of the cells in the system. This assumption is relaxed in the present study, and thus, the problem is considered in a more rigorous manner. The transient behavior of bacterial adhesion is examined through simulation studies. It is found that the present stochastic model should be employed when the number of available active sites is less than or on the same order of magnitude as that of the cells.


3D Printable concentrated liquid metal composite with high thermal conductivity.
Heat dissipation materials in which fillers are dispersed in a polymer matrix typically do not exhibit both high thermal conductivity (k) and processability due to a trade-off. In this paper, we fabricate heat dissipation composites which overcome the trade-off using liquid metal (LM). By exceeding the conventional filler limit, ten times higher k is achieved for a 90 vol% LM composite compared with k of 50 vol% LM composite. Further, an even higher k is achieved by introducing h-BN between the LM droplets, and the highest k in this study was 17.1 W m-1 K-1. The LM composite is processable at room temperature and used as inks for 3D printing. This combination of high k and processability not only allows heat dissipation materials to be processed on demand under ambient conditions but it also increases the surface area of the LM composite, which enables rapid heat dissipation.


Use of Polyclonal Intravenous Immunoglobulin at a Paediatric Referral Hospital in South Africa Between 2009 and 2012.
Polyvalent intravenous immunoglobulin (IVIG) is registered for a limited number of specific indications in South Africa but is increasingly being used for unregistered uses. No guideline exists nationally to monitor and control IVIG prescription, which results in its use in many clinical situations with varying levels of evidence. This study describes the registered and unregistered use, and cost of IVIG at a tertiary paediatric hospital in South Africa. A cross sectional descriptive study design was employed. Data on all patients (0 to 18 years) who attended the hospital during a 39 month period from 2009 to 2012 as out- or inpatients and were dispensed IVIG, was obtained from the pharmacy dispensing and National Health Laboratory Service electronic databases, and supplemented by a patient record review. During the study period, 185 patients received at least one dose of IVIG and a total 916 issues (3641.5 g) were dispensed. In 70 (41 %) of the 171 patients (involving 398 IVIG issues, 46 %), the South African Medicines Control Council registered indications for its use were followed. IVIG accounted for between 1.6, 1.7 and 4.6 % of the annual pharmacy expenditure during this 3-year study period. More than half of all IVIG dispensed at this paediatric hospital was used for unregistered indications. Considering the pressures on supply and the pharmaceutical costs, a more standardized, protocol-driven approach to the prescription of IVIG is called for.


Metabolic effects of pretreatment with Escherichia coli J5 antiserum on guinea pig gram-negative bacterial sepsis.
Antiserum raised to a rough mutant Escherichia coli, termed J5 (anti-J5 RS), protected against lethal gram-negative bacterial sepsis in a guinea pig model when animals were pretreated with both antiserum and heparin. This same model was used to examine and compare the effects of pretreatment with anti-J5 RS, normal rabbit serum (NRS), or saline, each +/- heparin on physiologic and metabolic parameters during a septic insult. Results demonstrated that leukopenia and thrombocytopenia occurred to a similar degree in all pretreatment groups; no significant leuko- or thrombostasis was noted on examination of histologic specimens; complement activation was maximal in those animals receiving anti-J5 RS alone without heparin; the most abnormal amino acid profile was present in the NRS + heparin group; and only the anti-J5 RS + heparin group did not develop glomerular lesions indicative of disseminated intravascular coagulation. A complement-mediated cell aggregation-type injury does not appear to occur in this model. It is hypothesized that both excessive complement and coagulation system activation occur after bacterial challenge when antibody directed against the bacteria is present (anti-J5 RS) leading to antigen-antibody complex formation and complement and coagulation cascade activation. Heparin may block either or both these cascade systems allowing enhanced, antibody-mediated opsonization and clearance of blood-borne bacteria, thus preventing end-organ alterations and organ failure during sepsis when combined with anti-J5 RS.


The role of physiological noise in resting-state functional connectivity.
Functional connectivity between different brain regions can be estimated from MRI data by computing the temporal correlation of low frequency (<0.1Hz) fluctuations in the MRI signal. These correlated fluctuations occur even when the subject is "at rest" (not asked to perform any particular task) and result from spontaneous neuronal activity synchronized within multiple distinct networks of brain regions. This estimate of connectivity, however, can be influenced by physiological noise, such as cardiac and respiratory fluctuations. This brief review looks at the effect of physiological noise on estimates of resting-state functional connectivity, discusses ways to remove physiological noise, and provides a personal recollection of the early developments in these approaches. This review also discusses the importance of physiological noise correction and provides a summary of evidence demonstrating that functional connectivity does have a neuronal underpinning and cannot purely be the result of physiological noise.