Investigating international time trends in the incidence and prevalence of atopic eczema 1990-2010: a systematic review of epidemiological studies.
The prevalence of atopic eczema has been found to have increased greatly in some parts of the world. Building on a systematic review of global disease trends in asthma, our objective was to study trends in incidence and prevalence of atopic eczema. Disease trends are important for health service planning and for generating hypotheses regarding the aetiology of chronic disorders. We conducted a systematic search for high quality reports of cohort, repeated cross-sectional and routine healthcare database-based studies in seven electronic databases. Studies were required to report on at least two measures of the incidence and/or prevalence of atopic eczema between 1990 and 2010 and needed to use comparable methods at all assessment points. We retrieved 2,464 citations, from which we included 69 reports. Assessing global trends was complicated by the use of a range of outcome measures across studies and possible changes in diagnostic criteria over time. Notwithstanding these difficulties, there was evidence suggesting that the prevalence of atopic eczema was increasing in Africa, eastern Asia, western Europe and parts of northern Europe (i.e. the UK). No clear trends were identified in other regions. There was inadequate study coverage worldwide, particularly for repeated measures of atopic eczema incidence. Further epidemiological work is needed to investigate trends in what is now one of the most common long-term disorders globally. A range of relevant measures of incidence and prevalence, careful use of definitions and description of diagnostic criteria, improved study design, more comprehensive reporting and appropriate interpretation of these data are all essential to ensure that this important field of epidemiological enquiry progresses in a scientifically robust manner.


Interstitial granulomatous dermatitis and granulomatous arteritis in the setting of PD-1 inhibitor therapy for metastatic melanoma.
Checkpoint inhibition has become an important target in the management of malignant melanoma. As anti-CTLA4 inhibitors and anti-PD1 antibodies are increasingly utilized, reports of immune-related adverse events (IRAEs) are becoming more frequent. Common noted cutaneous IRAEs are morbilliform, lichenoid, bullous, granulomatous, psoriasiform, and eczematous eruptions. We report a case of interstitial granulomatous dermatitis and granulomatous arteritis in the setting of nivolumab (anti-PD1) monotherapy for metastatic melanoma. There are many different causes for granulomatous vasculitis, such as herpes virus infection, lymphoproliferative disorders, systemic vasculitis, and inflammatory bowel disease. This report adds to the growing literature on granulomatous IRAEs due to checkpoint inhibition.


Metastatic basal cell carcinoma.
Basal cell carcinoma (BCC) is the most common skin cancer with a high propensity for local recurrence. The incidence of metastases from BCC is rare. We report a 65-year-old man who had BCC of the medial canthus of the left eye. In the 10-year period, he had been operated on approximately 12 times because of local recurrences. Three years after the last operation, he had a suspicious lesion on the operated area and a lumbar pain. Radiologic examination showed multiple metastatic skeletal and liver lesions. He was referred to the oncology department for radiation therapy and chemotherapy.


Opioid Use Disorders: Perioperative Management of a Special Population.
Opioid-related overdose deaths have reached epidemic levels within the last decade. The efforts to prevent, identify, and treat opioid use disorders (OUDs) mostly focus on the outpatient setting. Despite their frequent overrepresentation, less is known about the inpatient management of patients with OUDs. Specifically, the perioperative phase is a very vulnerable time for patients with OUDs, and little has been studied on the optimal management of acute pain in these patients. The preoperative evaluation should aim to identify those with OUDs and assess factors that may interfere with OUD treatment and pain management. Efforts should be made to provide education and assistance to patients and their support systems. For those who are actively struggling with opioid use, the perioperative phase can be an opportunity for engagement and to initiate treatment. Buprenorphine, methadone, and naltrexone medication treatment for OUD and opioid tolerance complicate perioperative pain management. A multidisciplinary team approach is crucial to provide clinically balanced pain relief without jeopardizing the patient's recovery. This article reviews the existing literature on the perioperative management of patients with OUDs and provides clinical suggestions for the optimal care of this patient population.


Onion and Garlic Intake and Breast Cancer, a Case-Control Study in Puerto Rico.
Studies show an inverse association between onion and garlic intake and risk of cancers of the lung, prostate, and stomach. There is limited evidence on the association between onion and garlic intake and breast cancer. We assessed this association in a population-based, case-control study in Puerto Rico. Incident, primary breast cancer cases (n = 314) were identified among women aged 30-79 from hospital and clinic records. Controls (n = 346) were women with no history of cancer other than nonmelanoma skin cancer, residents of the same area. Dietary intake was estimated using a food frequency questionnaire. Total onion and garlic intake included sofrito (a popular garlic- and onion-based condiment) intake frequency. Unconditional logistic regression assessed the association between onion and garlic consumption and breast cancer adjusting for age, education, parity, family history, body mass index, age at menarche, total energy, and smoking. Inverse associations with breast cancer were observed for moderate (OR (odds ratio) = 0.59, 95% CI (confidence interval): 0.35, 1.01) and high consumption (OR = 0.51, 95% CI: 0.30, 0.87) compared to low consumption of onion and garlic (Ptrend = 0.02). Results were similar when stratified by menopausal status. Study results suggest that high onion and garlic consumption is protective against breast cancer in this population.


Centella asiatica Fraction-3 Suppresses the Nuclear Factor Erythroid 2-Related Factor 2 Anti-Oxidant Pathway and Enhances Reactive Oxygen Species-Mediated Cell Death in Cancerous Lung A549 Cells.
Centella asiatica is a tropical medicinal plant that is commonly used in traditional medicine. Medicinal properties of C. asiatica include anti-oxidant, anti-inflammatory, and anti-cancer activity. We investigated the anti-oxidant and anti-proliferative/cytotoxic effects of a semi-purified fraction of C. asiatica ethanolic leaf extract (C3) in cancerous lung A549 cells. C3 was obtained by silica column fractionation and identified by using thin-layer chromatography and gas chromatography mass spectrometry. Cytotoxicity of C3 in A549 cells was evaluated (cell viability assay-WST-1; 24 h; [0.2-3 mg/mL]) to determine an inhibitory concentration (IC50). Intracellular reactive oxygen species (IROS), mitochondrial membrane potential (flow cytometry), malondialdehyde (MDA), lactate dehydrogenase (LDH) (spectrophotometry), glutathione (GSH), oxidised glutathione (GSSG), adenosine triphosphate levels, caspase activity (luminometry), and DNA damage (comet assay) were evaluated. Protein expression (Nrf-2, p53, Bax, Bcl-2, and HSP-70) and gene expression (Nrf-2, GPx, SOD, CAT, c-myc, and OGG-1) were quantified by western blotting and quantitative polymerase chain reaction (qPCR), respectively. C3 dose dependently decreased A549 cell viability. The IC50 of C3 increased MDA, IROS, mitochondrial depolarization, LDH, caspase (-8, -9, -3/7) activity, DNA damage, GSH levels, Nrf-2 protein expression, HSP-70 protein expression, and OGG-1 gene expression (P < .05). GSSG levels, anti-oxidant (Nrf-2, GPx, SOD) gene expression, p53, Bax, and Bcl-2 protein expression were decreased by C3 (P < .02). C3 diminished the anti-oxidant gene expression and induced anti-proliferative/cytotoxic effects in A549 cells.


Flooding and low oxygen responses in plants.
The world is currently experiencing dramatic increases in flood events impacting on natural vegetation and crops. Flooding often results in low O2 status in root tissues during waterlogging, but sometimes also in shoot tissues when plants become completely submerged. Plants possess a suite of traits enabling tissue aeration and/or adjusted metabolism during hypoxia or even in the absence of O2. This special issue of Functional Plant Biology presents key papers for plant scientists on the quest to further address and improve flood tolerance of terrestrial plants. The papers address low O2 responses in roots, shoots or whole plants in controlled laboratory conditions or in the field situation using natural wetland plants as models as well as economically important crops, such as rice, wheat and barley. The studies advance our understanding of low O2 responses in plant tissues as caused by O2 shortage during flooding. However, in most instances, submergence not only leads to hypoxic or anoxic tissues, but inundation in water also results in accumulation of CO2 and the important plant hormone ethylene. Thus, carefully designed laboratory studies are often needed to unravel the mechanistic relationships between a combined decline in O2 followed by increases in CO2 and ethylene at tissue as well as on the cellular level.


Effect of penethamate hydriodide treatment on bacteriological cure, somatic cell count and milk production of cows and quarters with chronic subclinical Streptococcus uberis or Streptococcus dysgalactiae infection.
A randomized, controlled field trial was performed in The Netherlands to determine the therapeutic efficacy of parenteral penethamate hydriodide (Leocillin) against naturally occurring, chronic, streptococcal mastitis during lactation. Quarter milk samples were collected from subclinical cases of Streptococcus uberis or Streptococcus dysgalactiae mastitis to determine the effect of treatment on bacteriological cure and somatic cell count (SCC) at quarter level. A quarter was considered to be cured when the bacterial species, isolated prior to treatment, was not isolated from the quarter milk samples taken on days 10 and 20 post-treatment (bacteriological cure), or when a quarter milk SCC (QMSCC) was <250000 cells/ml on days 10 and 20 post-treatment (SCC cure). Longitudinal data analysis was performed to determine the effect of antibiotic therapy on SCC and milk yield at cow level. Bacteriological cure occurred in 59% of 29 treated quarters, while no cure was observed in any of the 21 untreated control quarters. Treatment resulted in a significant decrease in SCC at cow and quarter level in comparison with untreated controls. There was no significant effect of treatment on milk production. Antibacterial treatment of subclinical streptococcal infections during lactation also prevented clinical mastitis. Furthermore, the treatment may contribute to reduction of bulk milk SCC and to prevention of pathogen spread in dairy herds.


Surgery for glioblastomas in the elderly: an Association des Neuro-oncologues d'Expression Française (ANOCEF) trial.
The role of surgery in the treatment of malignant gliomas in the elderly is not settled. The authors conducted a randomized trial that compared tumor resection with biopsy only-both followed by standard therapy-in such patients. Patients ≥ 70 years of age with a Karnofsky Performance Scale (KPS) score ≥ 50 and presenting with a radiological suspicion of operable glioblastoma (GBM) were randomly assigned between tumor resection and biopsy groups. Subsequently, they underwent standard radiotherapy during the first years of the trial (2008-2017), with the addition of adjunct therapy with temozolomide when this regimen became standard (2017-2019). The primary endpoint was survival, and secondary endpoints were progression-free survival (PFS), cognitive status (Mini-Mental State Examination), autonomy (KPS), quality of life (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-BN20), and perioperative morbidity and mortality. Between 2008 and 2019, 107 patients from 9 centers were enrolled in the study; 101 were evaluable for analysis because a GBM was histologically confirmed (50 in the surgery arm and 51 in the biopsy arm). There was no statistically significant difference in median survival between the surgery (9.37 months) and the biopsy (8.96 months, p = 0.36) arms (adjusted HR 0.79, 95% CI 0.52-1.21, p = 0.28). However, the surgery group had an increased PFS (5.06 vs 4.02 months; p = 0.034) (adjusted HR 0.50, 95% CI 0.32-0.78, p = 0.002). Less deterioration of quality of life and KPS score evolution than in the biopsy group was observed. Surgery was not associated with increased mortality or morbidity. This study suggests that debulking surgery is safe, and-compared to biopsy-is associated with a less severe deterioration of quality of life and autonomy, as well as a significant although modest improvement of PFS in elderly patients suffering from newly diagnosed malignant glioma. Although resection does not provide a significant survival benefit in the elderly, the authors believe that the risk/benefit analysis favors an attempt at optimal tumor resection in this population, provided there is careful preoperative geriatric evaluation. Clinical trial registration no.: NCT02892708 (ClinicalTrials.gov).


Engineered Exosomes as Vehicles for Biologically Active Proteins.
Exosomes represent an attractive vehicle for the delivery of biomolecules. However, mechanisms for loading functional molecules into exosomes are relatively unexplored. Here we report the use of the evolutionarily conserved late-domain (L-domain) pathway as a mechanism for loading exogenous proteins into exosomes. We demonstrate that labeling of a target protein, Cre recombinase, with a WW tag leads to recognition by the L-domain-containing protein Ndfip1, resulting in ubiquitination and loading into exosomes. Our results show that Ndfip1 expression acts as a molecular switch for exosomal packaging of WW-Cre that can be suppressed using the exosome inhibitor GW4869. When taken up by floxed reporter cells, exosomes containing WW-Cre were capable of inducing DNA recombination, indicating functional delivery of the protein to recipient cells. Engineered exosomes were administered to the brain of transgenic reporter mice using the nasal route to test for intracellular protein delivery in vivo. This resulted in the transport of engineered exosomes predominantly to recipient neurons in a number of brain regions, including the olfactory bulb, cortex, striatum, hippocampus, and cerebellum. The ability to engineer exosomes to deliver biologically active proteins across the blood-brain barrier represents an important step for the development of therapeutics to treat brain diseases.


Important lessons learned from studies on the pharmacology of glucocorticoids in human airway smooth muscle cells: Too much of a good thing may be a problem.
Glucocorticoids (GCs) are the treatment of choice for chronic inflammatory diseases such as asthma. Despite proven effective anti-inflammatory and immunosuppressive effects, long-term and/or systemic use of GCs can potentially induce adverse effects. Strikingly, some recent experimental evidence suggests that GCs may even exacerbate some disease outcomes. In asthma, airway smooth muscle (ASM) cells are among the targets of GC therapy and have emerged as key contributors not only to bronchoconstriction, but also to airway inflammation and remodeling, as implied by experimental and clinical evidence. We here will review the beneficial effects of GCs on ASM cells, emphasizing the differential nature of GC effects on pro-inflammatory genes and on other features associated with asthma pathogenesis. We will also summarize evidence describing how GCs can potentially promote pro-inflammatory and remodeling features in asthma with a specific focus on ASM cells. Finally, some of the possible solutions to overcome these unanticipated effects of GCs will be discussed.


Natural pathogens of laboratory animals and their effects on research.
The natural fungal pathogens of laboratory animals such as rabbits and guinea pigs are mainly dermatophyte species, most commonly Trichophyton mentagrophytes and also, less frequently Microsporum gypseum and M. canis. However, the incidences of infection and clinical disease are low in well-managed animal facilities. Young or immunocompromised rabbits are thought to be most susceptible. Dermatophytes infect the epidermis and adnexal structures, including hair follicles and shafts, usually on or around the head, and cause pruritus, patchy alopecia, erythema and crusting. Histopathological changes in the underlying skin occur and these changes could confound histological studies involving the skin. Yeast infections usually due to Candida spp. have been reported occasionally in laboratory animals. In this paper, the role of rodents in the evaluation of topical antifungal agents, dermatophytosis and two species of Candida, which are natural pathogens of laboratory animals, are discussed in relation to their effects on research. Pneumocystis carinii, an inhabitant of the respiratory tract of laboratory mice and rats, is a pathogen only under conditions of induced or inherent immunodeficiency. Infected mice and rats are likely to develop severe pneumocystosis following immunosuppression and will be rendered unsuitable for most experimental purposes.


[Comparative effectiveness of levamisole and vaccine in the complex treatment of patients with brucellosis].
The clinical efficacy of levamisole was compared to that of vaccine in a controlled trial of a combined treatment performed in 311 patients with acute and subacute brucellosis. As compared with vaccine, levamisole appeared effective in the treatment of active forms of brucellosis both during the control of the active process and later in convalescence. The use of levamisole permitted reducing the percentage of the chronic forms of the disease. When administered for active forms of brucellosis vaccine did not turn superior to levamisole.


The occurrence of virus in leukocytes of vaccinated chickens following challenge with virulent Newcastle disease virus.
Chickens that had been vaccinated with a lentogenic strain 2 to 9 weeks before challenge with a virulent virus remained clinically normal following challenge and circulated virus within leukocytes for as long as ten days. The virulent virus was detected by inoculating embryonating eggs with leukocytes separated from blood shortly after drawing. Freezing the leukocytes before inoculating the eggs reduced isolation 64.8%. Virus was demonstrated most readily in chickens challenged when antibody was decreasing, about 9 weeks after vaccination. The observation that virus in blood may be contained within a cellular component and be readily demonstrable only if the cells are separated and washed is significant both to an understanding of the immunological responsiveness of vaccinated chickens exposed to field challenge and to an understanding of epizootiological events.


Risk, Timing, and Predictors of Disease Flare After Discontinuation of Anti-Tumor Necrosis Factor Therapy in Children With Polyarticular Forms of Juvenile Idiopathic Arthritis With Clinically Inactive Disease.
To determine the frequency, time to flare, and predictors of disease flare upon withdrawal of anti-tumor necrosis factor (anti-TNF) therapy in children with polyarticular forms of juvenile idiopathic arthritis (JIA) who demonstrated ≥6 months of continuous clinically inactive disease. In 16 centers 137 patients with clinically inactive JIA who were receiving anti-TNF therapy (42% of whom were also receiving methotrexate [MTX]) were prospectively followed up. If the disease remained clinically inactive for the initial 6 months of the study, anti-TNF was stopped and patients were assessed for flare at 1, 2, 3, 4, 6, and 8 months. Life-table analysis, t-tests, chi-square test, and Cox regression analysis were used to identify independent variables that could significantly predict flare by 8 months or time to flare. Of 137 patients, 106 (77%) maintained clinically inactive disease while receiving anti-TNF therapy for the initial 6 months and were included in the phase of the study in which anti-TNF therapy was stopped. Stopping anti-TNF resulted in disease flare in 39 (37%) of 106 patients by 8 months. The mean/median ± SEM time to flare was 212/250 ± 9.77 days. Patients with shorter disease duration at enrollment, older age at onset and diagnosis, shorter disease duration prior to experiencing clinically inactive disease, and shorter time from onset of clinically inactive disease to enrollment were found to have significantly lower hazard ratios for likelihood of flare by 8 months (P < 0.05). Over one-third of patients with polyarticular JIA with sustained clinically inactive disease will experience a flare by 8 months after discontinuation of anti-TNF therapy. Several predictors of lower likelihood of flare were identified.


[Calcinosis of the cardiac coronary arteries].
In patients who had died due to various diseases and also in practically healthy individuals aged from 10 to 79 years calcinosis of the coronary arteries was studied morphometrically and histologically. The incidence and the extend of calcinosis implicating the coronary arteries increased with growing age and were more pronounced in males than in females. In analysis of observations uncovered, irrespective of the cause responsible for death, a direct relationship between the area of calcinosis and that of atherosclerosis in grosso modo (correlation factor of 0.46) was noted; the diseased in consequence of diverse affections demonstrated considerable variations in the development of arterial calcinosis. More often than not calcinosis of the coronary arteries was definable in atherosclerotic plaques carrying an important fibrotic component, in cases of necrosis and in those marked by a low lipids content and poor vasculalarization of an altered wall of the coronary artery. Calcinosis of the coronary arteries occurred more often than did their stenosis on 50% or more of the lumen. There has been established a direct relation between the frequency of the coronary artery stenosis and the area of calcinosis. The latter usually appears as a sign of disseminated atherosclerosis rather than as that of a progressive atherosclerotic process.


Genetic polymorphisms of CYP2C9, CYP2C19, and CYP3A5 in Kosovar population.
Cytochrome P450 genetic polymorphisms are responsible for individual variations in drug metabolism and drug-drug interactions. They are very important for pharmacogenetics, and their frequency varies across different populations. There is a big gap in the knowledge about the CYP gene family polymorphisms in the population of Kosovo, and the aim of our study was to fill that gap by determining the frequency of the most important variant alleles of CYP2C9, CYP2C19, and CYP3A5 in 234 nonrelated Kosovars. The allele frequencies of CYP2C9*2 and 2C9*3 were 17.52 %, and 10.89 %, respectively. Sixteen participants (6.81 %) were CYP2C9 poor metabolisers. The CYP2C19*2 and *17 variant frequencies were 13.03 % and 19.01 %, respectively. There were 2.13 % CYP2C19 poor and 4.27 % ultra-rapid metabolisers (homozygous carriers of the *17 allele). With regard to CYP3A5, the frequency of the *3 variant allele was 98.29 % (non-expressors), while the remaining participants (1.70 %) were expressors of CYP3A5. These findings are comparable with other European ethnicities, specifically those of Southeast Europe.


Effects of exercise training on physical activity in heart failure patients treated with cardiac resynchronization therapy devices or implantable cardioverter defibrillators.
This study elucidated the effects of exercise training on physical activity, 6-min walk distance, and all-cause hospitalization rates in patients with chronic heart failure, and evaluated factors contributing to changes in physical activity. Prospective cohort observational study. Patients (n =62) who completed an exercise training programme after implantable cardioverter-defibrillator or cardiac resynchronization therapy treatment between May 2017 and May 2018 were included. Patients exercised for 20-50 min 3-5 times weekly for 3 months and were assigned to the active (≥ 10 min/day) or non-active (< 10 min/day) group based on changes in walking times between baseline and 3 months, as assessed by the International Physical Activity Questionnaire. The 6-min walk distance improved in both groups with exercise training. Physical activity level did not increase in some patients, despite improvements in exercise tolerance. Depression improved significantly in the active group, but no correlation was found with physical activity. Factors contributing to physical activity changes were not identified. The all-cause hospitalization rate was lower in the active group during follow-up (mean 10.5 months). Exercise training effectively increased 6-min walk distance regardless of physical activity. Non-active patients experienced increased all-cause hospitalizations. Increasing physical activity improves patient outcomes.


Mycobacterium haemophilum infections of zebrafish (Danio rerio) in research facilities.
In May 2005, a disease outbreak was investigated at a zebrafish (Danio rerio) research facility experiencing severe losses. Mycobacterium haemophilum was isolated from these fish and the disease was subsequently recreated in experimentally infected zebrafish. Fish exhibited signs characteristic of mycobacteriosis, including granuloma formation and severe, diffuse, chronic inflammation. Bacteria were observed in multiple tissues, including the central nervous system. Biofilm samples from the outbreak facility were PCR positive for M. haemophilum, suggesting biofilms might act as a reservoir for infection. Zebrafish appear to be particularly vulnerable to M. haemophilum, and measures such as quarantine and treatment of incoming water should be implemented to minimize the likelihood of introduction of this bacterium to zebrafish research facilities. Zebrafish are already a well-established laboratory animal model for genetics, toxicology and disease, their susceptibility to M. haemophilum may make them useful for the study of this bacterium in the future.


Fifty years of executive control research in attention-deficit/hyperactivity disorder:What we have learned and still need to know.
For 50 years, attention-deficit/hyperactivity disorder (ADHD) has been considered a disorder of executive control (EC), the higher-order, cognitive skills that support self-regulation, goal attainment and what we generally call "attention." This review surveys our current understanding of the nature of EC as it pertains to ADHD and considers the evidence in support of eight hypotheses that can be derived from the EC theory of ADHD. This paper provides a resource for practitioners to aid in clinical decision-making. To support theory building, I draw a parallel between the EC theory of ADHD and the common gene-common variant model of complex traits such as ADHD. The conclusion offers strategies for advancing collaborative research.


Management of ramsay hunt syndrome in an acute palliative care setting.
The Ramsay Hunt syndrome is characterized by combination of herpes infection and lower motor neuron type of facial nerve palsy. The disease is caused by a reactivation of Varicella Zoster virus and can be unrepresentative since the herpetic lesions may not be always be present (zoster sine herpete) and might mimic other severe neurological illnesses. A 63-year-old man known case of carcinoma of gall bladder with liver metastases, post surgery and chemotherapy with no scope for further disease modifying treatment, was referred to palliative care unit for best supportive care. He was on regular analgesics and other supportive treatment. He presented to Palliative Medicine outpatient with 3 days history of ipsilateral facial pain of neuropathic character, otalgia, diffuse vesciculo-papular rash over ophthalmic and maxillary divisions of left trigeminal nerve distribution of face and ear, and was associated with secondary bacterial infection and unilateral facial edema. He was clinically diagnosed to have Herpes Zoster with superadded bacterial infection. He was treated with tablet Valacyclovir 500 mg four times a day, Acyclovir cream for local application, Acyclovir eye ointment for prophylactic treatment of Herpetic Keratitis, low dose of Prednisolone, oral Amoxicillin and Clindamycin for 7 days, and Pregabalin 150 mg per day. After 7 days of treatment, the rash and vesicles had completely resolved and good improvement of pain and other symptoms were noted. Management of acute infections and its associated complications in an acute palliative care setting improves both quality and length of life.


Examination of transcriptional networks reveals an important role for TCFAP2C, SMARCA4, and EOMES in trophoblast stem cell maintenance.
Trophoblast stem cells (TS cells), derived from the trophectoderm (TE) of blastocysts, require transcription factors (TFs) and external signals (FGF4, INHBA/NODAL/TGFB1) for self-renewal. While many reports have focused on TF networks that regulate embryonic stem cell (ES cell) self-renewal and pluripotency, little is know about TF networks that regulate self-renewal in TS cells. To further understand transcriptional networks in TS cells, we used chromatin immunoprecipitation with DNA microarray hybridization (ChIP-chip) analysis to investigate targets of the TFs-TCFAP2C, EOMES, ETS2, and GATA3-and a chromatin remodeling factor, SMARCA4. We then evaluated the transcriptional states of target genes using transcriptome analysis and genome-wide analysis of histone H3 acetylation (AcH3). Our results describe previously unknown transcriptional networks in TS cells, including TF occupancy of genes involved in ES cell self-renewal and pluripotency, co-occupancy of TCFAP2C, SMARCA4, and EOMES at a significant number of genes, and transcriptional regulatory circuitry within the five factors. Moreover, RNAi depletion of Tcfap2c, Smarca4, and Eomes transcripts resulted in a loss of normal colony morphology and down-regulation of TS cell-specific genes, suggesting an important role for TCFAP2C, SMARCA4, and EOMES in TS cell self-renewal. Through genome-wide mapping and global expression analysis of five TF target genes, our data provide a comprehensive analysis of transcriptional networks that regulate TS cell self-renewal.


Charge carrier field emission determines the number of charges on native state proteins in electrospray ionization.
Although multiple charging in electrospray ionization (ESI) is essential to protein mass spectrometry, the underlying mechanism of multiple charging has not been explicated. Here, we present a new theory to describe ESI of native-state proteins and predict the number of excess charges on proteins in ESI. The theory proposes that proteins are ionized as charged residues in ESI, as they retain residual excess charges after solvent evaporation and do not desorb from charged ESI droplets. However, their charge state is not determined by the Rayleigh limit of a droplet of similar size to the protein; rather, their final charge state is determined by the electric field-induced emission of small charged solute ions and clusters from protein-containing ESI droplets. This theory predicts that the number of charges on a protein in ESI should be directly proportional to the square of the gas-phase protein diameter and to E*, the critical electric field strength at which ion emission from droplets occurs. This critical field strength is determined by the properties of the excess charge carriers (i.e., the solute) in droplets. Charge-state measurements of native-state proteins with molecular masses in the 5-76 kDa range in ammonium acetate and triethylammonium bicarbonate are in excellent agreement with theoretical predictions and strongly support the mechanism of protein ESI proposed here.


Calcitonin from ultimobranchial glands of dogfish and chickens.
Acid extracts of thyroid glands from a small shark Squalus suckleyi and domestic fowl Gallus domestica contained no detectable calcitonin activity, while very potent hypocalcemic responses were obtained in rats with similar extracts from the ultimobranchial glands of these two species. The calcitonin concentration was 4 to 40 times that present in hog thyroid, which, as in most other mammals, contains ultimobranchial tissue. The evidence suggests that calcitonin is a fundamental calcium-regulating hormone present in all higher vertebrates and that it is an ultimobranchial rather than a thyroid hormone. It also indicates an important and hitherto unrecognized function for the ultimobranchial glands.


Multidrug-resistant Staphylococcus pettenkoferi isolated from cat in India.
Coagulase-negative staphylococci (CoNS) are considered to be one of the emerging pathogens in human and animals in recent times. Staphylococcus pettenkoferi, a novel pathogen under CoNS, is discovered in 2002 in humans with multiple clinical manifestations in various patients. To date, the pathogens have not yet been reported from any animals. The present study reported the first ever isolation, identification, and characterization of multidrug-resistant S. pettenkoferi from a cat with peritonitis in India. Peritoneal fluid was collected aseptically from 3 years old cat processed for bacteriological culture by standard techniques. Isolates were confirmed by BD Phoenix™ automated bacterial identification system and were subjected to plate and tube coagulase tests. All the isolates were tested for antimicrobial sensitivity profile by disc diffusion assay, extended-spectrum β-lactamase production by double disc diffusion assay, in vitro biofilm production ability by microtiter plate assay, and detection of virulence genes and mecA gene by polymerase chain reaction assay. A total of five clonally expanded isolates of S. pettenkoferi were isolated from peritoneal fluid of the affected cat. All the isolates were resistant against 36 antimicrobial agents and were also methicillin-resistant staphylococci. Phenotypically, all the isolates were negative for biofilm production but were carrying multiple biofilm-producing genes (icaA, IS257, nuc, and mecA). Although S. pettenkoferi was previously reported once from animal (cat) environment, this is probably the first ever report of isolation of the organism directly from any animals. This is also probably the first report from any species in India.


Quantitative endothelial biomicroscopy.
Twenty patients were evaluated by quantitative endothelial biomicroscopy and the resulting endothelial cell densities compared with those from a specular microscope. Estimated cell densities by this technique, when compared with the specular microscope, demonstrated a Pearson correlation coefficient of +0.977, an average error of -7% and an absolute error of 12%. There were no errors greater than 26% except for one extremely low cell density of 318 cells/mm2 for which the estimate was 476 cells/mm2. This rapid, inexpensive technique requires counting the number of endothelial cells seen across the horizontal diameter of the 0.2-mm projected spot beam of a standard biomicroscope. From this count and the known spot size the endothelial cell density may be accurately calculated. A simplified four-step technique for performing specular microscopy using only the standard biomicroscope and a method for accurately measuring the size of the projected slit lamp spot beam are explained.


Functional analysis of the fructooligosaccharide utilization operon in Lactobacillus paracasei 1195.
The fosABCDXE operon encodes components of a putative fructose/mannose phosphoenolpyruvate-dependent phosphotransferase system and a beta-fructosidase precursor (FosE) that are involved in the fructooligosaccharide (FOS) utilization pathway of Lactobacillus paracasei 1195. The presence of an N-terminal signal peptide sequence and an LPQAG cell wall anchor motif in the C-terminal region of the deduced FosE precursor amino acid sequence predicted that the enzyme is cell wall associated, indicating that FOS may be hydrolyzed extracellularly. In this study, cell fractionation experiments demonstrated that the FOS hydrolysis activity was present exclusively in the cell wall extract of L. paracasei previously grown on FOS. In contrast, no measurable FOS hydrolysis activity was detected in the cell wall extract from the isogenic fosE mutant. Induction of beta-fructosidase activity was observed when cells were grown on FOS, inulin, sucrose, or fructose but not when cells were grown on glucose. A diauxic growth pattern was observed when cells were grown on FOS in the presence of limiting glucose (0.1%). Analysis of the culture supernatant revealed that glucose was consumed first, followed by the longer-chain FOS species. Transcription analysis further showed that the fos operon was expressed only after glucose was depleted in the medium. Expression of fosE in a non-FOS-fermenting strain, Lactobacillus rhamnosus GG, enabled the recombinant strain to metabolize FOS, inulin, sucrose, and levan.


Survey of medications for myelomeningocele patients over their lifetime in Japan.
This study aimed to investigate medication prescriptions for patients with myelomeningocele (MMC) across different age groups, particularly in adulthood and after middle age. The Japan Medical Data Center (JMDC) database, based on medical claims data, was utilized for this analysis. Patients were divided into 10-year age groups, and prescriptions for analgesics, anticonvulsants, psychotropic drugs, lifestyle disease-related drugs, drugs for urinary incontinence, and laxatives were examined. To compare the differences in the utilization of medications unrelated to lifestyle-related diseases across different age groups, the data was categorized into three age groups: 19 or under, 20-39, and 40 or older. Among the 556 MMC patients, the percentage of those regularly prescribed analgesics increased from 2.8% in patients ≤ 19 to 31.7% in patients 40 or older (p < 0.01). Psychotropic medication use also increased with age, rising significantly from 6.3% in patients ≤ 19 to 34.6% in patients 40 or older (p < 0.01). Patients with MMC showed an increasing trend in prescriptions for lifestyle-related disease medications compared to the normal control group. Notably, the percentage of patients in their 30 s taking hypertension medication was 4.9%, significantly higher than the 0.86% in the control group (p = 0.029). In their 40 s, 22.9% of MMC patients were prescribed hyperlipidemia medication, significantly higher than the 3.9% in the control group (p < 0.01). Comprehensive multidisciplinary support and follow-up are crucial to enhance the quality of life for MMC patients, with particular attention to pain management, psychological care, and treatment of lifestyle-related diseases.


Involvement of human left frontoparietal cortices in neural processes associated with task-switching between two sequences of skilled finger movements.
In this study, we demonstrate the involvement of left frontoparietal cortices in neural processes for task-switching between skilled movements. Functional magnetic resonance imaging was conducted while thirty-two right-handed healthy participants performed two sequential finger-movement tasks with their left hands. One group (n = 16) trained these tasks through random-practice (tasks were either switched or repeated trial by trial) on one day and blocked-practice (successive intensive practice of each task) on the next day, while the remaining participants practiced in the reverse order. On the first day, performance of both tasks improved in all participants, suggesting that the two skilful tasks can be learned in both practice schedules. However, during the random-practice, the performance in the switched trials initially deteriorated and gradually approached to that in the repeated trials as the practice proceeded. The left (mainly inferior) frontoparietal cortices showed greater preparatory activity for the switched trials compared with the repeated trials in a left-hemispheric dominant manner, and the left intraparietal activity decreased as the performance of the switched trials improved. The results indicate that neural processes for task-switching are associated with the greater preparatory activity in the left inferior frontoparietal cortices, and the efficient switching may proceed concomitantly with the left intraparietal activity reduction.


[Photodynamic diagnosis of neoplasms of the mouth cavity after local administration of 5-aminolevulinic acid].
The aim of photodynamic diagnosis (PDD) is the complete visualization of all neoplastic lesions in a tumorous organ after topical or systemic application of a tumor selective photosensitizer. In this investigation we performed semiquantitative fluorescence measurements following topical application of 5-aminolevulinic acid (5-ALA) in 11 patients with neoplastic lesions of the oral cavity. Time course and type of porphyrin accumulation were analyzed in neoplastic and surrounding normal tissue by measuring emission spectra of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence at regular intervals for up to three hours following 15 min continuous rinsing of a 0.4% 5-ALA solution. After excitation with violet light of a high pressure xenon arc lamp (375-440 nm), fluorescence images in the red spectral range from the tumor tissue and the corresponding macroscopic visible tumor were recorded with a CCD camera. A quantitative analysis of the fluorescence contrast in neoplastic and surrounding tissue was performed using an optical multichannel analyzer. PpIX fluorescence was detected in the oral mucosa of all patients after local application of 5-ALA. PpIX in neoplastic tissue accumulated earlier in comparison to the surrounding normal tissue. The fluorescence contrast between tumor and host tissue was 10:1 and the maximum fluorescence was measured 1-2 hours following 5-ALA application. Labeling of mucosal lesions of the oral cavity with PpIX fluorescence induced by the local application of 5-ALA seems to be a promising diagnostic procedure for neoplastic lesions. Further investigations are required to assess the value of this new diagnostic procedure as a non-invasive and sensitive method for patients with head and neck cancer not only in pre- and postoperative diagnostic studies but also for a fluorescence-guided resection of tumors.


Myeloid Cells in Intact Human Cervical Explants Capture HIV and Can Transmit It to CD4 T Cells.
The importance of myeloid cells in HIV transmission in the female genital tract is uncertain. Because it is difficult to study the early events in HIV transmission in humans, most of our knowledge is based on animal models of SIV infection in Rhesus macaques and more recently HIV infection in humanized mice. However, these models may not accurately recapitulate transmission in the human genital tract. CD14+ myeloid cells are the most abundant hematopoietic cells in the human cervical mucosa, comprising 40-50% of CD45+ mononuclear cells. Most CD14+ cells are CD14+CD11c- macrophages and about a third are CD14+CD11c+ tissue dendritic cells, which express the HIV-binding receptors, DC-SIGN and CX3CR1. To examine the role of mucosal myeloid cells in HIV transmission, we infected intact healthy human cervical explants with CCR5-tropic HIV-1 ex vivo and then sorted populations of cervical immune cells 20 h later to determine whether they took up virus and could transmit it to activated CD4 T cells. Viral RNA was detected in CD14+ myeloid cells in all but one of 10 donor tissue samples, even when HIV RNA was not detected in CD4+ T cells. HIV RNA was detected predominantly in CD14+CD11c+ dendritic cells rather than in CD14+CD11c- macrophages. The reverse transcriptase inhibitor, nevirapine, reduced HIV RNA in CD4+ T cells, but not in CD14+ cells. Moreover, integrated HIV DNA were not detected above background in myeloid cells but was detected in T cells. These data suggest that although HIV replicates in T cells, myeloid cells in the female genital mucosa capture viral particles, but do not replicate the virus at early timepoints. However, sorted CD14+ myeloid cells isolated 20 h post-infection from 5 HIV-infected cervical explants tested all transmitted HIV to activated CD4+ T cells, while only 1 sample of sorted CD4+ T cells did. Thus, myeloid cells in human cervical tissue capture HIV and are an important early cellular storage site of infectious virus.


Evaluation of in situ methods used to detect Mycobacterium avium subsp. paratuberculosis in samples from patients with Crohn's disease.
In common with other diagnostic tests, detection of mycobacteria in tissue by microscopic examination is susceptible to spectrum bias. Since Crohn's disease is defined by the absence of detectable pathogenic organisms, the use of in situ techniques to search for Mycobacterium avium subsp. paratuberculosis in Crohn's disease samples requires validation of methods in a paucibacillary setting. To generate paucibacillary infection, C57BL/6 mice were artificially infected with Mycobacterium avium subsp. paratuberculosis strain K10 and M. tuberculosis H37Rv, yielding tissues harboring fewer than one bacillus per oil immersion field. Serial sections of organs were then studied by cell wall-based staining techniques (Ziehl-Neelsen and auramine rhodamine) and nucleic acid-based staining techniques (in situ hybridization [ISH] and indirect in situ PCR [IS PCR]). Microscopic examination and measurement of morphometric parameters of bacilli revealed that for all methods, Mycobacterium avium subsp. paratuberculosis bacilli were observed to be shorter, smaller, and less rod shaped than M. tuberculosis bacilli. Ziehl-Neelsen, auramine rhodamine stains, ISH targeting rRNA, and IS-PCR targeting the IS900 element afforded comparable sensitivities, but for all methods, visualization of individual bacterial forms required magnification x1,000. Auramine rhodamine staining and IS-PCR generated positive signals in negative controls, indicating the nonspecificity of these assays. Together, our results indicate that detection of Mycobacterium avium subsp. paratuberculosis bacilli in tissue requires oil immersion microscopy, that rRNA-ISH provides sensitivity and specificity comparable to those of Ziehl-Neelsen staining, and that the microscopic detection limit for Mycobacterium avium subsp. paratuberculosis in tissue is governed more by bacterial burden than by staining method.


Fungal allergen sensitization: Prevalence, risk factors, and geographic variation in the United States.
Many fungal species are associated with the pathogenesis of allergic disease, yet most epidemiologic studies on IgE-mediated fungal sensitization have only included a few species. We investigated fungal allergen sensitization prevalence, risk factors, and geographic variation in the United States. From 2014 to 2019, a total of 7,912,504 serum-specific IgE (sIgE) test results for 17 fungal species were measured in 1,651,203 patients aged 0-85 years by a US-wide clinical laboratory. Fungal sensitization prevalence, patterns, and relationship with demographic characteristics, clinical diagnoses, and geographic regions were analyzed. Twenty-two percent of patients were positive (sIgE > 0.10 kUA/L) to at least 1 fungal allergen; 13.7% were positive to >2 fungal allergens. Fungal species-specific positivity rates ranged 7.4-18.6% and were highest for Candida albicans (18.6%), Alternaria alternata (16.6%), Stemphylium herbarum (14.9%), and Aspergillus fumigatus (14.2%). Other fungi that were frequently tested had relatively low positivity rates (eg, Cladosporium herbarum 11.1%, Penicillium chrysogenum 10.7%). Independent risk factors for test positivity for all fungal species included male sex, teen age (highest in those aged 10-19 years), atopic dermatitis, and asthma. Fungal sensitization was generally higher in urban areas and ecoregions composed predominantly of grasslands and prairies compared to woodlands and forest, although there was greater variation in sensitization risk to different fungi in different ecoregions. Independent risk factors for fungal sensitization include male sex, teen ages, atopic dermatitis, asthma, and ecoregion.


Na and K changes in animal virus-infected HeLa cells.
Na-K changes and cytotoxic effects were monitored in HeLa cells infected with encephalomyocarditis (EMC) virus, human rhinovirus or vesicular stomatitis virus (VSV). Whereas in all three cases Na-K changes followed viral inhibition of cellular protein synthesis, such changes preceded trypan blue staining of rhinovirus-infected or VSV-infected cells and paralleled trypan blue staining of EMC virus-infected cells. In each case a progressive reduction in cellular electrical volume was associated with Na-K changes. K leakage from EMC virus- or rhinovirus-infected cells clearly exceeded Na gain by these cells. These findings are basically similar to those previously reported for poliovirus-infected HeLa cells. It is concluded that Na-K changes induced by picornaviruses or VSV do not trigger shut-off of HeLa cell protein synthesis, but may contribute to late manifestations of cytotoxicity.


Implementation of Clinical Decision Support Services to Detect Potential Drug-Drug Interaction Using Clinical Quality Language.
Potential drug-drug interactions (PDDI) rules are currently represented without any common standard making them difficult to update, maintain, and exchange. The PDDI minimum information model developed by the Semantic Web in the Healthcare and Life Sciences Community Group describes PDDI knowledge in an actionable format. In this paper, we report implementation and evaluation of CDS Services which represent PDDI knowledge with Clinical Quality Language (CQL). The suggested solution is based on emerging standards including CDS Hooks, FHIR, and CQL. Two use cases are selected, implemented with CQL rules and tested at the Connectathon held at the 32nd Annual Plenary & Working Group Meeting of HL7.


DC-SIGN on B lymphocytes is required for transmission of HIV-1 to T lymphocytes.
Infection of T cells by HIV-1 can occur through binding of virus to dendritic cell (DC)-specific ICAM-3 grabbing nonintegrin (DC-SIGN) on dendritic cells and transfer of virus to CD4+ T cells. Here we show that a subset of B cells in the blood and tonsils of normal donors expressed DC-SIGN, and that this increased after stimulation in vitro with interleukin 4 and CD40 ligand, with enhanced expression of activation and co-stimulatory molecules CD23, CD58, CD80, and CD86, and CD22. The activated B cells captured and internalized X4 and R5 tropic strains of HIV-1, and mediated trans infection of T cells. Pretreatment of the B cells with anti-DC-SIGN monoclonal antibody blocked trans infection of T cells by both strains of HIV-1. These results indicate that DC-SIGN serves as a portal on B cells for HIV-1 infection of T cells in trans. Transmission of HIV-1 from B cells to T cells through this DC-SIGN pathway could be important in the pathogenesis of HIV-1 infection.


Aortic regurgitation severity after transcatheter aortic valve implantation is underestimated by echocardiography compared with MRI.
Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) is associated with a poor clinical outcome and its assessment therefore crucial. Quantification of AR by transthoracic echocardiography (TTE), however, remains challenging in this setting. The present study used quantitative flow measurement by cardiac MRI (CMR) with calculation of regurgitant fraction (RF) for the assessment of AR and compared the results with TTE. We included 65 patients with a mean age of 82.2±8.1 years (38 women) who underwent successful TAVI with Edwards SAPIEN valves (52 transfemoral, 13 transapical). The post-interventional degree of AR was assessed by CMR and by TTE. There was agreement between CMR and TTE with regards to the absence of severe AR. However, TTE significantly underestimated the presence of moderate AR classifying it to be mild in 38 and moderate in only 5 patients, whereas CMR found mild AR in 23 and moderate in 16 patients. Overall, there was only fair agreement between CMR and TTE regarding the grading of AR with a weighted κ of 0.33. The rate of detection of TTE for more than mild AR was only 19%. Using CMR for the quantification of AR in a sizeable group of TAVI patients, we demonstrate a strong tendency of TTE to underestimate AR compared with CMR. Since higher AR severity on echocardiography has been associated with worse patient outcome, the potential incremental prognostic value of CMR should be studied prospectively in this setting.


Consumer Acceptance of Brown and White Rice Varieties.
Rice is consumed as a staple food by more than half of the world's population. Due to a higher fibre and micronutrient content, brown rice is more nutritious than white rice, but the consumption of brown rice is significantly lower than that of white rice, primarily due to sensory attributes. Therefore, the present research aimed to identify the sensory attributes which drive liking of Australian-grown brown and white rice varieties. Participants (n = 139) tasted and scored (9-point hedonic scale) their liking (i.e., overall liking, aroma, colour and texture) of brown and white rice types of Jasmine (Kyeema), Low GI (Doongara), and Medium grain rice (Amaroo). In addition, participants scored aroma, colour, hardness, fluffiness, stickiness, and chewiness, on Just About Right Scales. A within-subjects crossover design with randomised order (William's Latin Square design) was used with six repeated samples for liking and Just About Right scales. Penalty analyses were applied to determine the relative influence of perception of sensory attributes on consumer liking of the rice varieties. Across all varieties, white rice was liked more than brown rice due to the texture and colour, and Jasmine rice was preferred over Low GI and Medium Grain. Rice texture (hardness and chewiness) was the most important sensory attribute among all rice varieties and aroma was important for driving of liking between white rice varieties.


Association of Glomerular Filtration Rate With Cardiometabolic Risk Factors in Iranian Adolescents: CASPIAN III Study.
This study aimed to assess the association of glomerular filtration rate (GFR) with cardiometabolic risk factors in Iranian adolescents. Data of the 3rd round of a school-based surveillance system entitled "Childhood and Adolescence Surveillance and PreventIon of Adult Non-communicable Disease (CASPIAN III)" study was used for this study. A sample of 367 adolescents aged between 10 and 18 years was randomly selected. Glomerular filtration rate was estimated using the original and the updated Schwartz equations. The association of GFR with anthropometric data, blood pressure, lipid profile, and blood glucose was assessed in boys and girls by age group. Of the participants, 50.4% were boys and 26.2% were from rural regions. In the age group of 14 to 18 years, the ratio of low- to high-density lipoprotein cholesterol was significantly lower in the girls than the boys (P < .001), and the girls had significantly higher triglyceride and FBG levels. Significant correlations were found between GFR and waist circumference (r = 0.150 and P = .009 with the original Schwartz; r = 0.190 and P < .001 with the updated Schwartz) and body mass index (r = 0.115 and P = .03 with the original Schwartz; r = 0.121 and P = .02 with the updated Schwartz). Conclusions. The above findings showed that obese and overweight Iranian adolescents were more likely to have lower kidney function. Strategies to decline impaired kidney function may include prevention of obesity and central obesity in this population.


Knowledge, Attitudes, Practices, and Acceptability of Medical Male Circumcision among Males in Traditionally Circumcising Rural Communities of Alfred Nzo District, Eastern Cape, South Africa.
Male circumcision (MC) reduces HIV transmission risk by up to 60% in heterosexual men. However, uptake of medical male circumcision (MMC) is low in traditionally circumcising communities of South Africa. We assessed knowledge, attitudes, and practices to identify factors predicting acceptability of MMC among males in the Alfred Nzo District. A cross-sectional study was conducted among males aged 15-49 years in this district. Logistic regression was used to identify factors predicting acceptability of MMC. We interviewed 343 males who had a median age of 19 years (interquartile range (IQR): 16-25 years). Of these, 77% (95% confidence interval (CI): 72-82) were circumcised: 77% (95% CI: 71-82) were circumcised in a traditional setting and 21% (95% CI: 16-26) in a medical setting. The median score of knowledge about the benefits of MMC was 62.5% (IQR: 37.5-75.0), with 59% (95% CI: 53-64) demonstrating a positive attitude towards MMC and 68% (95% CI: 63-73) accepting involvement of health workers in MC. Excellent knowledge (adjusted odds ratio (aOR): 3.07, 95% CI: 0.99-9.58, p = 0.053), awareness (aOR: 3.26, 95% CI: 1.08-9.86, p = 0.037), and positive attitude towards MMC (aOR: 2.35, 95% CI: 1.30-4.25, p = 0.005) were associated with acceptability of MMC. Participants demonstrated good knowledge and acceptance of the MMC programme. Knowledge, attitude, and awareness were significant predictors of MMC acceptability.


The Role of Antigen Presentation in Tumor-Associated Macrophages.
Macrophages are cells of the myeloid lineage with important roles not only in immune regulation and tissue repair, but also in pathological states such as autoimmune disease and cancer. A plethora of macrophage subtypes exist with distinct phenotypes and functions, not least within the tumor microenvironment (TME) of solid tumors. The abundant macrophages located within the TME are often referred to as tumor-associated macrophages (TAMs). TAMs may be pro-inflammatory with antitumor properties, or may have pro-tumor functions such as angiogenesis. Typically, TAMs are endowed with pro-tumor phenotypes, which has led to strategies to deplete or reprogram TAMs within the TME. Although historically recognized as professional antigen presenting cells (APCs), macrophages are often considered inferior in their abilities to process and present antigens in comparison with dendritic cells (DCs). Notwithstanding, this review gives an overview of the potential accessory role that macrophages might have in antigen processing and presentation to T cells within the TME, with implications for the design of novel immunotherapies.


The Role of Galectin-3 as a Marker of Cancer and Inflammation in a Stage IV Ovarian Cancer Patient with Underlying Pro-Inflammatory Comorbidities.
In this case study, I report on a patient with stage IV ovarian cancer and underlying pro-inflammatory comorbidities. Initially, the patient's inflammatory condition was treated with an intensive integrative anti-inflammatory protocol using a combination of oral and intravenous nutrients and botanicals along with pharmaceutical intervention. This was followed by a standard course of chemotherapy supported by an individualized integrative protocol - with excellent response. Galectin-3 levels as well as other inflammatory and tumor markers were monitored throughout the course of treatment. Correlation with other markers, the clinical course of the disease, and symptomatology are presented. Galectin-3, a novel marker with potential clinical importance in cancer progression as well as inflammation and fibrosis, has been extensively researched in multiple in vitro, in vivo, and epidemiological studies. In this paper, a case in which galectin-3 has been used to assess and monitor patient progress is presented for the first time. This case is of further interest because of its complexity, with the coexistence of acute inflammatory conditions combined with progressing metastatic cancer. Galectin-3 monitoring reflected this complexity; nevertheless, it provided useful information and correlation with other inflammatory markers. The results suggest that monitoring serum galectin-3 as a marker for both inflammatory processes and cancer progression to a higher probability of metastasis may have clinical relevance. Additional clinical research is warranted.


Trichromophoric systems from square-planar Pt-ethynylbipyridine and octahedral Ru- and Os-bipyridine centers: syntheses, structures, electrochemical behavior, and bipartition of energy transfer.
The synthetic approach, electrochemical behavior, and optical absorption and emission properties are reported of the Pt-bipyridine-acetylide/Ru-bipyridine complex [(dbbpy)Pt{(ebpy)Ru(bpy) 2} 2] (4+), PtRu 2, the Pt-bipyridine-acetylide/Os-bipyridine analogue, PtOs 2, and the Pt/Ru/Os complex [(dbbpy)Pt(ebpy) 2Ru(bpy) 2Os(bpy) 2] (4+), PtRuOs; ebpy is 5-ethynylbpy, dbbpy is 4,4'-ditertiobutylbpy, and bpy is 2,2'-bipyridine. These triads are investigated in acetonitrile solvent by comparing their electrochemical and spectroscopic properties with those of the mononuclear species [(dbbpy)Pt(ebpy) 2], Pt, [Ru(ebpy)(bpy) 2] (2+), Ru, and [Os(ebpy)(bpy) 2] (2+), Os. Results of X-ray analysis of Pt are reported, which show the planar arrangement of this unit that features two free bpy sites. The absorption spectra of the triads and the mononuclear species show that light at 452 or 376 nm can be employed to observe luminescence spectra of these complexes; for the observation of emission lifetimes, nanoled sources at 465 and 373 nm are employed. With lambda exc = 452 (and 465) nm, one selectively produces Ru --> bpy/ebpy CT (RuLCT) or Os --> bpy/ebpy CT states (OsLCT); MLCT is a metal-to-ligand charge-transfer. With lambda exc = 376 (and 373) nm, one populates Pt --> dbbpy CT and intraligand charge transfer (ILCT, involving the ebpy fragment) levels, in addition to Ru(II)- or Os(II)-centered excited states, in aliquots that are estimated from comparison of the absorption features of the components. Upon excitation with light at 376 (and 373) nm, the optical studies of PtRu 2, PtOs 2, and PtRuOs reveal full quenching of the Pt-based emission and occurrence of efficient photoinduced energy transfer, leading to exclusive MLCT emission from the ruthenium and osmium centers. In particular, PtRuOs is found to exhibit a Ru- and Os-based dual luminescence, whose intensities ratio is consistent with a Pt --> Os intramolecular energy transfer step being 3-6 times faster than the Pt --> Ru one.


Imagining HIV/AIDS: morality and perceptions of personal risk in Nigeria.
The disparity between people's knowledge about HIV/AIDS and the extent to which they take measures to protect themselves is one of the most vexing issues for public health workers and social science analysts. This paper aims to explain some of this discrepancy, using survey and ethnographic data collected among young rural-urban migrants in Aba and Kano, two cities in Nigeria. The paper argues that many young Nigerian migrants do not perceive significant personal risk because they construct the risk of AIDS in ethical and moral terms, projecting immorality and danger onto imaginary others. To understand the way young Nigerians interpret risk, the paper focuses on four related issues: (1) the organization and meaning of sexual relationships; (2) the intersection of gender and ideas about reproduction; (3) the perception of AIDS as a disease without hope; and (4) the importance of religion in young people's framing of moralities and ethical choices about sexuality and HIV/AIDS.


Investigation of morphological abnormalities in red blood cells among dental laboratory technicians.
A variety of materials are used in dental prosthesis laboratories (DPL), especially metal alloys and methyl methacrylate (MMA)-based monomers and polymers. These metal alloys contain elements such as cobalt, chromium, nickel, molybdenum, lead, and mercury that can have toxic effects on human health when excessive amounts of exposure occur. This study aims to investigate the cytotoxic effects of occupational exposure due to dental prosthesis manufacturing operations on erythrocyte cells. Thirty DPL workers were compared with the 30 control group and the questionnaire forms were applied including the symptoms due to their occupational exposure. Blood was taken from the experimental group and the control group into tubes with EDTA, and the erythrocyte morphologies were examined by the peripheral smear technique. Morphological anomalies determined from the experimental group and the control group are statistically significant (p < .005, p < .01). On the other hand, it was revealed that the sub-variables, namely age range, alcohol, and smoking, did not significantly affect the anomalies. With these results, it was concluded that DPL employees should strictly comply with occupational health precautions.


Mining Data Impressions From Deep Models as Substitute for the Unavailable Training Data.
Pretrained deep models hold their learnt knowledge in the form of model parameters. These parameters act as "memory" for the trained models and help them generalize well on unseen data. However, in absence of training data, the utility of a trained model is merely limited to either inference or better initialization towards a target task. In this paper, we go further and extract synthetic data by leveraging the learnt model parameters. We dub them Data Impressions, which act as proxy to the training data and can be used to realize a variety of tasks. These are useful in scenarios where only the pretrained models are available and the training data is not shared (e.g., due to privacy or sensitivity concerns). We show the applicability of data impressions in solving several computer vision tasks such as unsupervised domain adaptation, continual learning as well as knowledge distillation. We also study the adversarial robustness of lightweight models trained via knowledge distillation using these data impressions. Further, we demonstrate the efficacy of data impressions in generating data-free Universal Adversarial Perturbations (UAPs) with better fooling rates. Extensive experiments performed on benchmark datasets demonstrate competitive performance achieved using data impressions in absence of original training data.


Primary Thyroid Lymphoma: Clinical Factors Predicting the Possibility of Diffuse Large B-Cell Lymphoma.
Aims: Among primary thyroid lymphomas (PTLs), diffuse large B-cell lymphoma (DLBCL) has a poorer prognosis than other indolent lymphomas such as mucosa-associated lymphoid tissue (MALT) or follicular lymphoma (FL). However, the clinical differences between DLBCL and indolent lymphoma remain unclear. Therefore, this retrospective study on PTL was aimed at investigating the clinical differences between DLBCL and indolent lymphomas and identifying the factors differentiating DLBCL from indolent lymphomas. Materials and Methods: Medical records of 28 patients diagnosed with PTL and treated at our institution between 2005 and 2022 were retrospectively analyzed. Data on the following clinical variables were extracted: sex, age, symptoms (pain and dysphagia), ultrasonographic appearance patterns, the presence of airway stenosis on computed tomography and laryngeal endoscopy, blood test results, disease stage, and pathological diagnosis. Results: In all, 13 patients were histologically diagnosed with DLBCL, 12 with MALT lymphoma, and 3 with FL. Significant differences in disease-specific survival rates were evident between the DLBCL and indolent lymphoma groups (68.2 vs 100%, P = .043). High lactate dehydrogenase levels (>230 U/mL) and airway stenosis were observed only in patients with DLBCL. Multivariate analysis identified that the presence of a linear echoic strand pattern and the absence of an echoic nodular pattern on ultrasound were independently associated with DLBCL (P = .0497 and .012, respectively). Conclusion: DLBCL can cause airway stenosis. The linear echogenic strand pattern and the absence of a nodular pattern should be recognized as predictive factors of DLBCL.


Genetic Diversity of Hepatitis B and C Viruses Revealed by Continuous Surveillance from 2015 to 2021 in Gabon, Central Africa.
Viral hepatitis remains one of the largest public health concerns worldwide. Especially in Central Africa, information on hepatitis virus infections has been limited, although the prevalence in this region has been reported to be higher than the global average. To reveal the current status of hepatitis B and C virus (HBV and HCV) infections and the genetic diversity of the viruses, we conducted longitudinal surveillance in Gabon. We detected 22 HBV and 9 HCV infections in 2047 patients with febrile illness. Genetic analyses of HBV identified subgenotype A1 for the first time in Gabon and an insertion generating a frameshift to create an X-preC/C fusion protein. We also revealed that most of the detected HCVs belonged to the "Gabon-specific" HCV subtype 4e (HCV-4e), and the entire nucleotide sequence of the HCV-4e polyprotein was determined to establish the first reference sequence. The HCV-4e strains possessed resistance-associated substitutions similar to those of other HCV-4 strains, indicating that the use of direct-acting antiviral therapy may be complex. These results provide a better understanding of the current situation of hepatitis B and C virus infections in Central Africa and will help public health organizations develop effective countermeasures to eliminate chronic viral hepatitis in this region.


In Vivo Imaging of Retinal Hypoxia Using HYPOX-4-Dependent Fluorescence in a Mouse Model of Laser-Induced Retinal Vein Occlusion (RVO).
To demonstrate the utility of a novel in vivo molecular imaging probe, HYPOX-4, to detect and image retinal hypoxia in real time, in a mouse model of retinal vein occlusion (RVO). Retinal vein occlusion was achieved in adult mice by photodynamic retinal vein thrombosis (PRVT). One or two major retinal vein(s) was/were occluded in close proximity to the optic nerve head (ONH). In vivo imaging of retinal hypoxia was performed using, HYPOX-4, an imaging probe developed by our laboratory. Pimonidazole-adduct immunostaining was performed and used as a standard ex vivo method for the detection of retinal hypoxia in this mouse RVO model. The retinal vasculature was imaged using fluorescein angiography (FA) and isolectin B4 staining. Retinal thickness was assessed by spectral-domain optical coherence tomography (SD-OCT) analysis. By application of the standard ex vivo pimonidazole-adduct immunostaining technique, retinal hypoxia was observed within 2 hours post-PRVT. The observed hypoxic retinal areas depended on whether one or two retinal vein(s) was/were occluded. Similar areas of hypoxia were imaged in vivo using HYPOX-4. Using OCT, retinal edema was observed immediately post-PRVT induction, resolving 8 days later. Nominal preretinal neovascularization was observed at 10 to 14 days post-RVO. HYPOX-4 is an efficient probe capable of imaging retinal hypoxia in vivo, in RVO mice. Future studies will focus on its use in correlating retinal hypoxia to the onset and progression of ischemic vasculopathies.


The Effect of Telephone-Administered Psychotherapy on Symptoms of Depression and Attrition: A Meta-Analysis.
Increasingly, the telephone is being used to deliver psychotherapy for depression, in part as a means to reduce barriers to treatment. Twelve trials of telephone-administered psychotherapies, in which depressive symptoms were assessed, were included. There was a significant reduction in depressive symptoms for patients enrolled in telephone-administered psychotherapy as compared to control conditions (d = 0.26, 95% confidence interval [CI] = 0.14-0.39, p < .0001). There was also a significant reduction in depressive symptoms in analyses of pretreatment to posttreatment change (d = 0.81, 95% CI = 0.50-1.13, p < .0001). The mean attrition rate was 7.56% (95% CI = 4.23-10.90). These findings suggest that telephone-administered psychotherapy can produce significant reductions in depressive symptoms. Attrition rates were considerably lower than rates reported in face-to-face psychotherapy.


In vivo and in vitro inhibition of B16 melanoma growth by vitamin B6.
The effect of vitamin B6 on the growth of B16 melanoma cells in vivo and in vitro was studied. B16 melanoma cells grown for three days in medium supplemented with 5.0 mM pyridoxine or 0.5 mM pyridoxal showed an 80% reduction in cell proliferation compared with control culture. Cells cultured for six hours in medium supplemented with 0.5 mM pyridoxal took up and incorporated 13 and 32% less [3H]thymidine, respectively, than did control cultures. A 17% reduction in [3H]glucose uptake was observed at this time point. When the incubation time was decreased to three hours, an inhibition of cellular uptake of [3H]thymidine (22%), [3H]uridine (14%), and [3H]glucose (15%) was observed; however, little or no inhibition in incorporation was detected. In in vivo studies, mice pretreated with pyridoxal for two weeks and then injected with B16 melanoma cells had a 62% reduction in tumor weight compared with controls at the end of a three-week period. If tumors were first established in mice and then treated with pyridoxal for six days, a 39% reduction in tumor growth was observed. There were no differences observed in body weights or liver weights in any of the animal groups. These results indicate that supraphysiological doses of vitamin B6 can inhibit the growth of B16 melanoma cells both in vitro and in vivo. The exact mechanism by which pyridoxal exerts its inhibitory effect was not ascertained, but experiments suggest that the vitamer may be acting on the plasma membrane to reduce precursor transport into the cell.


Treatment of avascular necrosis of the femoral head in small dogs with micro total hip replacement.
To evaluate clinical outcome of small dogs with avascular necrosis (AVN) of the femoral head treated with Micro total hip replacement (THR). Nonrandomized, retrospective efficacy case series. Dogs (n = 7; 7 hips) that had Micro THR. Medical records (December 2005-March 2009) of dogs affected with AVN treated with Micro THR were reviewed. Data analysis included age, sex, breed, body weight, and body condition. All dogs were evaluated at least 6 months after Micro THR was performed on the affected AVN limb. Physical, orthopedic, and radiographic examination, owner questionnaire, thigh girth, and ground reaction force were evaluated. Seven dogs (7 Micro THR) met the inclusion criteria. Mean age at time of onset of clinical signs was 7.7 months and mean age at time of Micro THR was 9.6 months. Mean body weight was 4.2 kg. Median body condition score was 5.0 (range, 4-6). Mean cumulative functional scores from client questionnaires before (19.5; range, 11-25) and after Micro THR (8.2; range, 7-14) were significantly different (P = .004). There was no significant difference between thigh girths of the Micro THR (17.8 ± 2.6 cm; range, 14.5-21.5 cm) limbs when compared with contralateral (17.5 ± 2.9 cm; range, 14.5-22.0 cm) limbs (P = .38). Peak vertical force (P = .20), vertical impulse (P = .81), peak braking force (P = .91), braking impulse (P = .19), peak propulsion force (P = .32), and propulsion impulse (P = .19) were not significantly different in Micro THR limbs compared with contralateral limbs. There was no relationship between age, sex, and breed for development of AVN in this study. Dogs that received Micro THR for the treatment of AVN had no significant differences in thigh girth and ground reaction forces when Micro THR limb was compared with the contralateral limb.


A comparison of the effects of pioglitazone and rosiglitazone combined with glimepiride on prothrombotic state in type 2 diabetic patients with the metabolic syndrome.
To compare the effects of glimepiride plus pioglitazone or plus rosiglitazone in diabetic patients with the metabolic syndrome on coagulation and fibrinolysis parameters. 91 type 2 diabetic patients with the metabolic syndrome participated. All patients took a fixed dose of glimepiride, 4 mg/day. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We compared body mass index (BMI), glycemic control, coagulation and fibrinolysis parameters, and heart rate (HR) during 12 months of this treatment. A total of 87 completed the study (pioglitazone n=45 or rosiglitazone n=42). Body mass index increased after 12 months compared to baseline (p<0.05) in both groups. A significant decrease in glycated haemoglobin (HbA(1c)) was observed after 9 (p<0.05), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were lower in both groups (p<0.05 and 0.01, respectively), as were fasting plasma insulin (FPI) and postprandial plasma insulin (PPI) (p<0.05 and p<0.01, respectively). An improvement in the homeostasis model assessment index (HOMA index) was seen at 9 and 12 months (p<0.05 and 0.01, respectively) compared to the baseline value in both groups. Plasminogen activator inhibitor 1 (PAI-1) was significant lower (p<0.05) in both groups after 12 months compared to the baseline values. No changes in tissue-plasminogen activator (t-PA) and fibrinogen (Fg) were seen during the study nor were there any changes in transaminases. We conclude that the addition of a thiazolinedione to glimepiride treatment in type 2 diabetic subjects with the metabolic syndrome is associated with a slight but significant reduction of PAI-1 value, related to a similar reduction in insulinresistance.


Management of subtrochanteric fractures of the femur in children.
We report the results of treatment in 99 children with subtrochanteric fractures of the femur. Late reviews of 60 of the 65 children treated with traction and then a hip spica after stabilization of the fracture by callus, and of 20 of the 22 treated with early closed reduction and a hip spica yielded 80% satisfactory outcomes. However, 27% of the fractures treated with early closed reduction required remanipulation. The satisfactory outcomes in the traction and delayed spica group would be increased to nearly 100% by using only skin traction, as persistent lengthening of the femur and pin-site pain, the main long-term complications, were the result of skeletal traction. Late review of 10 of the 12 children treated surgically showed 100% satisfactory medical outcomes but only 60% satisfactory patient-determined outcomes. Persistent pain in the thigh incision used for open reduction was the main cause of patient dissatisfaction.


Immunotherapy in genitourinary malignancies.
Treatment of cancer patients involves a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Traditionally, patients with metastatic disease are treated with combination chemotherapies or targeted agents. These cytotoxic agents have good response rates and achieve palliation; however, complete responses are rarely seen. The field of cancer immunology has made rapid advances in the past 20 years. Recently, a number of agents and vaccines, which modulate the immune system to allow it to detect and target cancer cells, are being developed. The benefit of these agents is twofold, it enhances the ability the body's own immune system to fight cancer, thus has a lower incidence of side effects compared to conventional cytotoxic chemotherapy. Secondly, a small but substantial number of patients with metastatic disease are cured by immunotherapy or achieve durable responses lasting for a number of years. In this article, we review the FDA-approved immunotherapy agents in the field of genitourinary malignancies. We also summarize new immunotherapy agents being evaluated in clinical studies either as single agents or as a combination.


In Vitro and In Vivo Inhibition of the Infectivity of Human Enterovirus 71 by a Sulfonated Food Azo Dye, Brilliant Black BN.
Hand, foot, and mouth disease (HFMD), a highly contagious disease in children, is caused by human enteroviruses, including enterovirus 71 (EV71), coxsackievirus A16 (CVA16), and coxsackievirus A6 (CVA6). Although HFMD is usually mild and self-limiting, EV71 infection occasionally leads to fatal neurological disorders. Currently, no commercial antiviral drugs for HFMD treatment are available. Here, numerous sulfonated azo dyes, widely used as food additives, were identified as having potent antiviral activities against human enteroviruses. Among them, brilliant black BN (E151) was able to inhibit all EV71, CVA16, and CVA6 strains tested. In rhabdomyosarcoma cells, the 50% inhibitory concentrations of the dye E151 for various strains of EV71 ranged from 2.39 μM to 28.12 μM, whereas its 50% cytotoxic concentration was 1,870 μM. Food azo dyes, including E151, interacted with the vertex of the 5-fold axis of EV71 and prevented viral entry. Their efficacy in viral inhibition was regulated by amino acids at VP1-98, VP1-145, and/or VP1-246. Dye E151 not only prevented EV71 attachment but also eluted attached viruses in a concentration-dependent manner. Moreover, E151 inhibited the interaction between EV71 and its cellular uncoating factor cyclophilin A. In vivo studies demonstrated that E151 at a dose of 200 mg/kg of body weight/day given on the initial 4 days of challenge protected AG129 mice challenged with 10× the 50% lethal dose of wild-type EV71 isolates. Taken together, these data highlight E151 as a promising antiviral agent against EV71 infection.IMPORTANCE Human enterovirus 71 (EV71) is one of the causative agents of hand, foot, and mouth disease in children and is responsible for thousands of deaths in the past 20 years. Food azo dyes have been widely used since the nineteenth century; however, their biological effects on humans and microbes residing in humans are poorly understood. Here, we discovered that one of these dyes, brilliant black BN (E151), was particularly effective in inhibiting the infectivity of EV71 in both cell culture and mouse model studies. Mechanistic studies demonstrated that these sulfonated dyes mainly competed with EV71 attachment factors for viral binding to block viral attachment/entry to host cells. As no commercial antiviral drugs against EV71 are currently available, our findings open an avenue to exploit the development of permitted food dye E151 as a potential anti-EV71 agent.


Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?
Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent 'cancer immunoediting' has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy in metastatic lung cancer. To date, these treatments have shown impressive results of efficacy and tolerability in early clinical trials, leading to testing in several large, randomized Phase III trials. As these results will be confirmed, these drugs will be available in the near future, offering new exciting therapeutic options for lung cancer treatment.


Physiological proteins in resource-limited herbivores experiencing a population die-off.
Nutrient availability is predicted to interact with herbivore population densities. Competition for low quality food at high density may reduce summer food intake, and in turn winter survival. Conversely, low population density may favor physiological recovery through better access to better quality spring forage. Here, we take advantage of the long-term study of the Soay sheep population of St. Kilda (Scotland) to measure plasma protein markers and immunity in two consecutive summers with contrasting population densities. We show that, following a winter die-off resulting in a shift to low population density, albumin and total proteins increased, but only in adult sheep. The effect was not solely attributable to selective disappearance of malnourished sheep. Similarly, the concentration of antibodies was higher following the die-off, potentially indicating recovery of immune function. Overall, our results are consistent with the physiological recovery of surviving individuals after a harsh winter.


Perception of HIV/AIDS among the Igbo of Anambra State, Nigeria.
Perception is fundamental in the fight against stigmatization of people living with HIV/AIDS (PLHIV). Perception generally influences discriminatory attitudes towards PLHIV which exacerbates their problems and quickens the degeneration of the disease from HIV to AIDS. This study examined the Anambra people's perception and knowledge of HIV/AIDS with the goal of creating knowledge on these issues in order to design effective intervention programmes towards the reduction of social stigmatization associated with the pandemic. The study was carried out in Idemmili North and Oyi local government areas of Anambra State. Qualitative and quantitative methodologies were used to elicit information from respondents who were adult males and females of 18 years and above. The research instruments were questionnaires and in-depth interview schedule. Questionnaires were administered on 1000 respondents while 13 people were interviewed in-depth. Analysis of quantitative data were conducted by using the Statistical package for Social Sciences. Univariate analysis in the form of frequencies were conducted which generated the distribution of respondents across the research variables. Furthermore, multivariate analysis were conducted to test the hypotheses and sought for relationships among variables. The qualitative data were reported in themes based on the research objectives and were analysed jointly with the quantitative data. The findings were that majority of the respondents viewed HIV/AIDS as a disease that afflict immoral people and as a punishment from God. Only a handful of them saw the disease as a disease that could afflict anybody. Also, many of the respondents said that AIDS is real but showed a low level of knowledge. It was further indicated that there were significant relationships between educational level, sex, occupation, income influence perception and peoples' reactions to HIV positive status of a relative while there were no significant relationships between these variables and knowledge of HIV/AIDS. It was concluded that these negative perceptions were as a result of the people's low level of knowledge and cultural belief systems, which see a strange illness as punishment from God for disobedience. Furthermore, the fact that most of the socio-economic characteristics of the respondents had significant relationship with perception and reaction to HIV was an indication that most people in the study area had a uniform perception. It was also an indication that government HIV/AIDS awareness programmes were not effective. It was recommended that strategies for effective HIV educational programme should be sought and carried out in the study area. Effective intervention programme have the power to change behaviours and would likely change the people's negative perception and low level of knowledge of HIV/AIDS, thereby reducing stigmatization of people living with HIV/AIDS.


Factors related to perceived life satisfaction among the elderly in South Korea.
This study attempted to explore the aging phenomena that now characterize much of Korean society, and assessed issues associated with the life satisfaction experienced during the process of aging. By employing the National Survey on the State of Life and the Desire for Welfare of the Elderly, 2004 in South Korea this study attempted to identify the factors that determine subjective life satisfaction among the elderly. The data utilized herein consisted of 3278 elderly people aged 65 years or older, from 9308 households. The results of analysis from the final model after the introduction of 19 variables in 8 factors showed statistically similar explanatory power in men (adj. R²=0.320) and in women (adj. R²=0.346). We found that economic condition was the most influential factor in both men (B=0.278) and women (B=0.336) except perceived health condition variables. The second most influential variable in life satisfaction was health checkups in men (B=0.128) and degree of nutritional diet in women (B=0.145). Those who had experience with chronic diseases also reported significantly lower perceived life satisfaction and this was particularly true of women. The aging society requires an understanding of the lives of elderly individuals. This study explored factors associated with life satisfaction in old age by using a life satisfaction model. The success of an aging society begins with an accurate understanding of the elderly, and thus political attention will need to be focused on this matter.


Sato needling for pupillary membranes.
Dense pupillary membranes are resistant to needle-knife incision. Trauma to attached intraocular structures may be produced during discission techniques that stretch the membrane. The Sato discission technique produces membrane stabilization on a fixation needle. This allows controlled incision of the pupillary membrane at a right angle to the direction of the fibers without tension on surrounding structures. The Sato technique is not difficult, and surgical complications are minimal. Using this technique, adequate pupillary openings were produced in 62 of 65 eyes, with an average follow-up of 50 months. Postoperative visual acuity was 6/24 or better in 43 (74%) eyes. No long-term surgical complications were encountered.


Proteomic analysis of breast tissue and nipple aspirate fluid for breast cancer detection.
Clinical proteomics has great promise, but many hurdles. Proteomic approaches may prove to be the answer to decades of frustrating searches for markers that are specific and selective for breast cancer. In order to achieve this goal, the challenge arises that breast cancer is a heterogeneous disease and individual variations are enormous. To identify sensitive and specific breast cancer markers will require standardization of every method, from tissue collection through statistical analysis and diligence. Small pilot studies of tumors with varied characteristics will not suffice; large, homogeneous sample sets will be the most efficient route to identify breast cancer markers. Proteomic analysis of nipple aspirate fluid may identify markers that can be used for screening with this noninvasive technique. Proteomic analysis of breast biopsies will allow more detailed characterization of the individual's cancer, with therapy tailored to the disease based on this information.


Microcytotoxicity and serum blocking factors in malignant melanoma and halo nevus.
Microcytotoxicity assays of patients with malignant melanoma and halo nevi were performed. No good correlation could be found between percent cell inhibition and histopathological level of melanoma or the clinical staging. The percent cell inhibition was usually an index of response to vaccinia virus immunotherapy. Actively regressing halo nevi showed high levels of percent cell inhibition, whereas inactive halo nevi had low levels of percent cell inhibition and blocking factor. Immunologic reactivity to melanoma cells may be a common feature of melanoma and halo nevus.


Coronary Computed Tomography Angiography Predicts Guidewire Crossing and Success of Percutaneous Intervention for Chronic Total Occlusion: Korean Multicenter CTO CT Registry Score as a Tool for Assessing Difficulty in Chronic Total Occlusion Percutaneous Coronary Intervention.
We developed a model that predicts difficulty of percutaneous coronary intervention for coronary chronic total occlusion (CTO) using coronary computed tomographic angiography. A total of 684 CTO lesions with preprocedural computed tomographic angiography were enrolled from 4 centers. Data were randomly divided into derivation and validation datasets at 2:1 ratio. The end point was successful guidewire crossing ≤30 minutes, which was met in 50%. The KCCT (Korean Multicenter CTO CT Registry) score was developed based on independent predictors identified by multivariable analysis, which were proximal blunt entry, proximal side branch, bending, occlusion length ≥15 mm, severe calcification, whole luminal calcification, reattempt, and ≥12 months or unknown duration of occlusion. The KCCT score was compared with the other prediction scores, including angiography-based J-CTO, PROGRESS-CTO, CL-score, and CT-based CT-RECTOR. The probability of guidewire crossing ≤30 minutes declined consistently from 100% to 0% according to the KCCT score (P<0.01, all). The KCCT score showed higher discriminative performance compared with the other scoring systems (c-statistics=0.78 versus 0.65-0.72, P<0.001, all). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of a KCCT score of <4 for guidewire crossing ≤30 minutes was 70%, 68%, 72%, 73%, and 70%, respectively. The KCCT score also showed consistent results with procedural success (P<0.05, all). These results could be reproduced in validation data set (P<0.05, all). KCCT scoring could predict successful guidewire crossing ≤30 minutes and also procedural success. KCCT scoring may enable noninvasive grading difficulty of CTO percutaneous coronary intervention.


Cortical and thalamic connectivity of occipital visual cortical areas 17, 18, 19, and 21 of the domestic ferret (Mustela putorius furo).
The present study describes the ipsilateral and contralateral corticocortical and corticothalamic connectivity of the occipital visual areas 17, 18, 19, and 21 in the ferret using standard anatomical tract-tracing methods. In line with previous studies of mammalian visual cortex connectivity, substantially more anterograde and retrograde label was present in the hemisphere ipsilateral to the injection site compared to the contralateral hemisphere. Ipsilateral reciprocal connectivity was the strongest within the occipital visual areas, while weaker connectivity strength was observed in the temporal, suprasylvian, and parietal visual areas. Callosal connectivity tended to be strongest in the homotopic cortical areas, and revealed a similar areal distribution to that observed in the ipsilateral hemisphere, although often less widespread across cortical areas. Ipsilateral reciprocal connectivity was observed throughout the visual nuclei of the dorsal thalamus, with no contralateral connections to the visual thalamus being observed. The current study, along with previous studies of connectivity in the cat, identified the posteromedial lateral suprasylvian visual area (PMLS) as a distinct network hub external to the occipital visual areas in carnivores, implicating PMLS as a potential gateway to the parietal cortex for dorsal stream processing. These data will also contribute to a macro connectome database of the ferret brain, providing essential data for connectomics analyses and cross-species analyses of connectomes and brain connectivity matrices, as well as providing data relevant to additional studies of cortical connectivity across mammals and the evolution of cortical connectivity variation.


Self-compression of high-intensity femtosecond optical pulses and spatiotemporal soliton generation
Self-compression of high-intensity femtosecond pulses has been observed in a number of atomic and molecular gases and solid bulk material. The evolution of the femtosecond pulse parameters during the self-compression has been studied under a variety of experimental conditions. Generation of spatiotemporal solitons has been achieved by the combined action of self-compression and self-focusing.


Local auxotonic systolic force and work in canine right ventricular free wall.
Regional auxotonic force (F) and segment length (SL) were measured in the right ventricular (RV) free wall of 10 anesthetized dogs. F was obtained with a Feigl force gauge and SL with ultrasonic crystals positioned in the inflow or outflow region and in the longitudinal or transverse direction. Although the time courses of right ventricular pressure and force were almost identical, the timing of right ventricular ejection had little relationship to specific parts of the force-segment-length loop. Thus local F vs. SL loops were of irregular form signifying local lengthening or shortening in isovolumic periods. Local work, i.e., F vs. SL loop area, increased linearly with cardiac output (CO), which was varied by volume expansion or reduction. A predominant contribution to total RV work from any particular region and direction was not observed. A "local contribution factor" [eta, defined as (local work/local area)/(total RV work/free wall area)] fell with increased CO from 2.1 +/- 0.5 at 1.1 l/min to 0.7 +/- 0.2 at 4.8 l/min. This observation suggests that transformation of local into total work became more efficient at higher CO or that structures other than the free wall became increasingly important for RV pump function at higher output levels.